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  • 1
    Abstract: As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non-BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.
    Type of Publication: Journal article published
    PubMed ID: 29227286
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Expert systems 7 (1990), S. 0 
    ISSN: 1468-0394
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Computer Science
    Notes: NEXPERT OBJECT is an expert system shell developed by Neuron Data Inc. NEXPERT costs $5,000/£4,500 for the microcomputer version, and a VAX version is available for $8,000/£7,500. Neuron Data can be contacted in the USA at 444 High St., Palo Alto, CA 94301 (+1 (415) 321-4488) or in the UK at 34 S. Molton St., London, W1Y 1BP (+44 (0)1-408 2333). The version reviewed in this article was release 1.02 with Microsoft Windows. It was run on an AT&T 6386 microcomputer with 3 megabytes of RAM, an 80 megabyte hard disk, and a colour monitor.
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2011-04-12
    Description: Laboratory evolution has generated many biomolecules with desired properties, but a single round of mutation, gene expression, screening or selection, and replication typically requires days or longer with frequent human intervention. Because evolutionary success is dependent on the total number of rounds performed, a means of performing laboratory evolution continuously and rapidly could dramatically enhance its effectiveness. Although researchers have accelerated individual steps in the evolutionary cycle, the only previous example of continuous directed evolution was the landmark study of Wright and Joyce, who continuously evolved RNA ligase ribozymes with an in vitro replication cycle that unfortunately cannot be easily adapted to other biomolecules. Here we describe a system that enables the continuous directed evolution of gene-encoded molecules that can be linked to protein production in Escherichia coli. During phage-assisted continuous evolution (PACE), evolving genes are transferred from host cell to host cell through a modified bacteriophage life cycle in a manner that is dependent on the activity of interest. Dozens of rounds of evolution can occur in a single day of PACE without human intervention. Using PACE, we evolved T7 RNA polymerase (RNAP) variants that recognize a distinct promoter, initiate transcripts with ATP instead of GTP, and initiate transcripts with CTP. In one example, PACE executed 200 rounds of protein evolution over the course of 8 days. Starting from undetectable activity levels in two of these cases, enzymes with each of the three target activities emerged in less than 1 week of PACE. In all three cases, PACE-evolved polymerase activities exceeded or were comparable to that of the wild-type T7 RNAP on its wild-type promoter, representing improvements of up to several hundred-fold. By greatly accelerating laboratory evolution, PACE may provide solutions to otherwise intractable directed evolution problems and address novel questions about molecular evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084352/" 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/PMC3084352/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Esvelt, Kevin M -- Carlson, Jacob C -- Liu, David R -- R01 GM065400/GM/NIGMS NIH HHS/ -- R01 GM065400-01/GM/NIGMS NIH HHS/ -- R01 GM065400-02/GM/NIGMS NIH HHS/ -- R01 GM065400-03/GM/NIGMS NIH HHS/ -- R01 GM065400-04/GM/NIGMS NIH HHS/ -- R01 GM065400-05/GM/NIGMS NIH HHS/ -- R01 GM065400-06/GM/NIGMS NIH HHS/ -- R01 GM065400-07/GM/NIGMS NIH HHS/ -- R01 GM065400-08/GM/NIGMS NIH HHS/ -- R01 GM065400-09/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Apr 28;472(7344):499-503. doi: 10.1038/nature09929. Epub 2011 Apr 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21478873" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Bacteriophage T3/genetics ; Bacteriophage T7/enzymology/genetics ; Bacteriophages/enzymology/genetics/*physiology ; Cytidine Triphosphate/metabolism ; DNA-Directed RNA Polymerases/biosynthesis/chemistry/genetics/*metabolism ; Directed Molecular Evolution/*methods ; Escherichia coli/genetics/growth & development/*metabolism/*virology ; Guanosine Triphosphate/metabolism ; Promoter Regions, Genetic/genetics ; Viral Proteins/biosynthesis/chemistry/genetics/*metabolism
    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: 2015-10-28
    Description: Epigenetic silencing including histone modifications and DNA methylation is an important tumorigenic mechanism. However, its role in cancer immunopathology and immunotherapy is poorly understood. Using human ovarian cancers as our model, here we show that enhancer of zeste homologue 2 (EZH2)-mediated histone H3 lysine 27 trimethylation (H3K27me3) and DNA methyltransferase 1 (DNMT1)-mediated DNA methylation repress the tumour production of T helper 1 (TH1)-type chemokines CXCL9 and CXCL10, and subsequently determine effector T-cell trafficking to the tumour microenvironment. Treatment with epigenetic modulators removes the repression and increases effector T-cell tumour infiltration, slows down tumour progression, and improves the therapeutic efficacy of programmed death-ligand 1 (PD-L1; also known as B7-H1) checkpoint blockade and adoptive T-cell transfusion in tumour-bearing mice. Moreover, tumour EZH2 and DNMT1 are negatively associated with tumour-infiltrating CD8(+) T cells and patient outcome. Thus, epigenetic silencing of TH1-type chemokines is a novel immune-evasion mechanism of tumours. Selective epigenetic reprogramming alters the T-cell landscape in cancer and may enhance the clinical efficacy of cancer therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779053/" 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/PMC4779053/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peng, Dongjun -- Kryczek, Ilona -- Nagarsheth, Nisha -- Zhao, Lili -- Wei, Shuang -- Wang, Weimin -- Sun, Yuqing -- Zhao, Ende -- Vatan, Linda -- Szeliga, Wojciech -- Kotarski, Jan -- Tarkowski, Rafal -- Dou, Yali -- Cho, Kathleen -- Hensley-Alford, Sharon -- Munkarah, Adnan -- Liu, Rebecca -- Zou, Weiping -- 5P30CA46592/CA/NCI NIH HHS/ -- CA099985/CA/NCI NIH HHS/ -- CA123088/CA/NCI NIH HHS/ -- CA152470/CA/NCI NIH HHS/ -- CA156685/CA/NCI NIH HHS/ -- CA171306/CA/NCI NIH HHS/ -- CA190176/CA/NCI NIH HHS/ -- CA193136/CA/NCI NIH HHS/ -- R01 CA099985/CA/NCI NIH HHS/ -- R01 CA123088/CA/NCI NIH HHS/ -- R01 CA152470/CA/NCI NIH HHS/ -- R01 CA156685/CA/NCI NIH HHS/ -- R01 CA171306/CA/NCI NIH HHS/ -- R01 CA190176/CA/NCI NIH HHS/ -- R01 CA193136/CA/NCI NIH HHS/ -- England -- Nature. 2015 Nov 12;527(7577):249-53. doi: 10.1038/nature15520. Epub 2015 Oct 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA. ; Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Biostatistics, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA. ; Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA. ; The First Department of Gynecologic Oncology and Gynecology, Medical University in Lublin, Lublin 20-081, Poland. ; The University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Department of Women's Health Services, Henry Ford Health System, Detroit, Michigan 48202, USA. ; Department of Obstetrics and Gynecology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA. ; Graduate Program in Tumor Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26503055" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD274/metabolism ; CD8-Positive T-Lymphocytes/cytology/immunology ; Chemokine CXCL10/biosynthesis/genetics/immunology ; Chemokine CXCL9/biosynthesis/genetics/immunology ; Chemokines/biosynthesis/*genetics/immunology ; DNA (Cytosine-5-)-Methyltransferase/antagonists & inhibitors/metabolism ; DNA Methylation/drug effects ; *Epigenesis, Genetic/drug effects ; Female ; *Gene Silencing ; Histones/chemistry/metabolism ; Humans ; *Immunotherapy/methods ; Lymphocytes, Tumor-Infiltrating/immunology ; Lysine/metabolism ; Mice ; Ovarian Neoplasms/enzymology/*immunology/pathology/*therapy ; Polycomb Repressive Complex 2/antagonists & inhibitors/metabolism ; Prognosis ; Th1 Cells/immunology/*metabolism ; Tumor Cells, Cultured ; Tumor Escape/immunology ; Xenograft Model Antitumor Assays
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2012-11-16
    Description: Meiosis is a germ-cell-specific cell division process through which haploid gametes are produced for sexual reproduction. Before the initiation of meiosis, mouse primordial germ cells undergo a series of epigenetic reprogramming steps, including the global erasure of DNA methylation at the 5-position of cytosine (5mC) in CpG-rich DNA. Although several epigenetic regulators, such as Dnmt3l and the histone methyltransferases G9a and Prdm9, have been reported to be crucial for meiosis, little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. Using a loss-of-function approach in mice, here we show that the 5mC-specific dioxygenase Tet1 has an important role in regulating meiosis in mouse oocytes. Tet1 deficiency significantly reduces female germ-cell numbers and fertility. Univalent chromosomes and unresolved DNA double-strand breaks are also observed in Tet1-deficient oocytes. Tet1 deficiency does not greatly affect the genome-wide demethylation that takes place in primordial germ cells, but leads to defective DNA demethylation and decreased expression of a subset of meiotic genes. Our study thus establishes a function for Tet1 in meiosis and meiotic gene activation in female germ cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528851/" 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/PMC3528851/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamaguchi, Shinpei -- Hong, Kwonho -- Liu, Rui -- Shen, Li -- Inoue, Azusa -- Diep, Dinh -- Zhang, Kun -- Zhang, Yi -- R01GM097253/GM/NIGMS NIH HHS/ -- U01 DK089565/DK/NIDDK NIH HHS/ -- U01DK089565/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Dec 20;492(7429):443-7. doi: 10.1038/nature11709. Epub 2012 Nov 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Harvard Medical School, WAB-149G, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23151479" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Animals ; Cell Count ; DNA Breaks, Double-Stranded ; DNA Methylation/genetics ; DNA-Binding Proteins/deficiency/genetics/*metabolism ; Embryo, Mammalian/cytology/pathology ; Female ; Gene Expression Regulation/*genetics ; Infertility, Female/pathology ; Male ; Meiosis/*genetics ; Mice ; Mice, Knockout ; Oocytes/cytology/*metabolism/pathology ; Proto-Oncogene Proteins/deficiency/genetics/*metabolism ; Transcriptome
    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: 2014-04-11
    Description: By analogy to transistors in classical electronic circuits, quantum optical switches are important elements of quantum circuits and quantum networks. Operated at the fundamental limit where a single quantum of light or matter controls another field or material system, such a switch may enable applications such as long-distance quantum communication, distributed quantum information processing and metrology, and the exploration of novel quantum states of matter. Here, by strongly coupling a photon to a single atom trapped in the near field of a nanoscale photonic crystal cavity, we realize a system in which a single atom switches the phase of a photon and a single photon modifies the atom's phase. We experimentally demonstrate an atom-induced optical phase shift that is nonlinear at the two-photon level, a photon number router that separates individual photons and photon pairs into different output modes, and a single-photon switch in which a single 'gate' photon controls the propagation of a subsequent probe field. These techniques pave the way to integrated quantum nanophotonic networks involving multiple atomic nodes connected by guided light.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tiecke, T G -- Thompson, J D -- de Leon, N P -- Liu, L R -- Vuletic, V -- Lukin, M D -- England -- Nature. 2014 Apr 10;508(7495):241-4. doi: 10.1038/nature13188.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA [2] Department of Physics and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [3]. ; 1] Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA [2]. ; 1] Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA [2] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; Department of Physics, Harvard University, Cambridge, Massachusetts 02138, USA. ; Department of Physics and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717513" target="_blank"〉PubMed〈/a〉
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2014-05-23
    Description: Despite decades of speculation that inhibiting endogenous insulin degradation might treat type-2 diabetes, and the identification of IDE (insulin-degrading enzyme) as a diabetes susceptibility gene, the relationship between the activity of the zinc metalloprotein IDE and glucose homeostasis remains unclear. Although Ide(-/-) mice have elevated insulin levels, they exhibit impaired, rather than improved, glucose tolerance that may arise from compensatory insulin signalling dysfunction. IDE inhibitors that are active in vivo are therefore needed to elucidate IDE's physiological roles and to determine its potential to serve as a target for the treatment of diabetes. Here we report the discovery of a physiologically active IDE inhibitor identified from a DNA-templated macrocycle library. An X-ray structure of the macrocycle bound to IDE reveals that it engages a binding pocket away from the catalytic site, which explains its remarkable selectivity. Treatment of lean and obese mice with this inhibitor shows that IDE regulates the abundance and signalling of glucagon and amylin, in addition to that of insulin. Under physiological conditions that augment insulin and amylin levels, such as oral glucose administration, acute IDE inhibition leads to substantially improved glucose tolerance and slower gastric emptying. These findings demonstrate the feasibility of modulating IDE activity as a new therapeutic strategy to treat type-2 diabetes and expand our understanding of the roles of IDE in glucose and hormone regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142213/" 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/PMC4142213/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maianti, Juan Pablo -- McFedries, Amanda -- Foda, Zachariah H -- Kleiner, Ralph E -- Du, Xiu Quan -- Leissring, Malcolm A -- Tang, Wei-Jen -- Charron, Maureen J -- Seeliger, Markus A -- Saghatelian, Alan -- Liu, David R -- DP2 OD002374/OD/NIH HHS/ -- F30 CA174152/CA/NCI NIH HHS/ -- P30 DK057521/DK/NIDDK NIH HHS/ -- P41 GM111244/GM/NIGMS NIH HHS/ -- R00 GM080097/GM/NIGMS NIH HHS/ -- R01 GM065865/GM/NIGMS NIH HHS/ -- R01 GM081539/GM/NIGMS NIH HHS/ -- R01 GM81539/GM/NIGMS NIH HHS/ -- T32 GM007598/GM/NIGMS NIH HHS/ -- T32 GM008444/GM/NIGMS NIH HHS/ -- UL1 TR000430/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 3;511(7507):94-8. doi: 10.1038/nature13297. Epub 2014 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA. ; Department of Pharmacological Sciences, Stony Brook University, 1 Circle Road, Stony Brook, New York 11794, USA. ; Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. ; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, 3204 Biological Sciences III, Irvine, California 92697, USA. ; Ben-May Department for Cancer Research, University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA. ; 1] Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA [2] Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24847884" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Binding Sites ; Blood Glucose/metabolism ; Catalytic Domain ; Diabetes Mellitus, Type 2/drug therapy/genetics ; Disease Models, Animal ; Gastric Emptying/drug effects ; Genetic Predisposition to Disease ; Glucagon/*metabolism ; Glucose Tolerance Test ; Hypoglycemic Agents/chemistry/*pharmacology/therapeutic use ; Insulin/*metabolism ; Insulysin/*antagonists & inhibitors/chemistry/genetics/metabolism ; Islet Amyloid Polypeptide/*metabolism ; Macrocyclic Compounds/chemistry/*pharmacology/therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Models, Molecular ; Obesity/drug therapy/metabolism ; Signal Transduction/drug effects ; Thinness/drug therapy/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2015-02-18
    Description: Autophagy, an important catabolic pathway implicated in a broad spectrum of human diseases, begins by forming double membrane autophagosomes that engulf cytosolic cargo and ends by fusing autophagosomes with lysosomes for degradation. Membrane fusion activity is required for early biogenesis of autophagosomes and late degradation in lysosomes. However, the key regulatory mechanisms of autophagic membrane tethering and fusion remain largely unknown. Here we report that ATG14 (also known as beclin-1-associated autophagy-related key regulator (Barkor) or ATG14L), an essential autophagy-specific regulator of the class III phosphatidylinositol 3-kinase complex, promotes membrane tethering of protein-free liposomes, and enhances hemifusion and full fusion of proteoliposomes reconstituted with the target (t)-SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) syntaxin 17 (STX17) and SNAP29, and the vesicle (v)-SNARE VAMP8 (vesicle-associated membrane protein 8). ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain, and stabilizes the STX17-SNAP29 binary t-SNARE complex on autophagosomes. The STX17 binding, membrane tethering and fusion-enhancing activities of ATG14 require its homo-oligomerization by cysteine repeats. In ATG14 homo-oligomerization-defective cells, autophagosomes still efficiently form but their fusion with endolysosomes is blocked. Recombinant ATG14 homo-oligomerization mutants also completely lose their ability to promote membrane tethering and to enhance SNARE-mediated fusion in vitro. Taken together, our data suggest an autophagy-specific membrane fusion mechanism in which oligomeric ATG14 directly binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442024/" 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/PMC4442024/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diao, Jiajie -- Liu, Rong -- Rong, Yueguang -- Zhao, Minglei -- Zhang, Jing -- Lai, Ying -- Zhou, Qiangjun -- Wilz, Livia M -- Li, Jianxu -- Vivona, Sandro -- Pfuetzner, Richard A -- Brunger, Axel T -- Zhong, Qing -- 5P30CA142543/CA/NCI NIH HHS/ -- P41 GM103403/GM/NIGMS NIH HHS/ -- R01 CA133228/CA/NCI NIH HHS/ -- R01 R37-MH63105/MH/NIMH NIH HHS/ -- R37 MH063105/MH/NIMH NIH HHS/ -- T32 GM007232/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Apr 23;520(7548):563-6. doi: 10.1038/nature14147. Epub 2015 Feb 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA [2] Department of Structural Biology, Stanford University, Stanford, California 94305, USA [3] Department of Photon Science, Stanford University, Stanford, California 94305, USA [4] Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA [5] Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA. ; 1] Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [3] College of Food Science &Nutritional Engineering, China Agricultural University, Beijing 100083, China. ; 1] Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA [2] Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. ; Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25686604" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Vesicular Transport/*chemistry/*metabolism ; *Autophagy ; Endosomes/*metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Lysosomes/*metabolism ; *Membrane Fusion ; Phagosomes/chemistry/*metabolism ; Protein Binding ; Protein Multimerization ; Protein Structure, Tertiary ; Qa-SNARE Proteins/metabolism ; Qb-SNARE Proteins/metabolism ; Qc-SNARE Proteins/metabolism ; R-SNARE Proteins/metabolism ; SNARE Proteins/chemistry/metabolism
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2012-06-16
    Description: Active DNA demethylation is an important part of epigenetic regulation in plants and animals. How active DNA demethylation is regulated and its relationship with histone modification patterns are unclear. Here, we report the discovery of IDM1, a regulator of DNA demethylation in Arabidopsis. IDM1 is required for preventing DNA hypermethylation of highly homologous multicopy genes and other repetitive sequences that are normally targeted for active DNA demethylation by Repressor of Silencing 1 and related 5-methylcytosine DNA glycosylases. IDM1 binds methylated DNA at chromatin sites lacking histone H3K4 di- or trimethylation and acetylates H3 to create a chromatin environment permissible for 5-methylcytosine DNA glycosylases to function. Our study reveals how some genes are indicated by multiple epigenetic marks for active DNA demethylation and protection from silencing.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575687/" 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/PMC3575687/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qian, Weiqiang -- Miki, Daisuke -- Zhang, Heng -- Liu, Yunhua -- Zhang, Xi -- Tang, Kai -- Kan, Yunchao -- La, Honggui -- Li, Xiaojie -- Li, Shaofang -- Zhu, Xiaohong -- Shi, Xiaobing -- Zhang, Kangling -- Pontes, Olga -- Chen, Xuemei -- Liu, Renyi -- Gong, Zhizhong -- Zhu, Jian-Kang -- R01 GM059138/GM/NIGMS NIH HHS/ -- R01 GM070795/GM/NIGMS NIH HHS/ -- R01GM059138/GM/NIGMS NIH HHS/ -- R01GM070795/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2012 Jun 15;336(6087):1445-8. doi: 10.1126/science.1219416.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Shanghai Center for Plant Stress Biology and Shanghai Institute of Plant Physiology and Ecology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22700931" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Arabidopsis/*genetics/*metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Chromatin/metabolism ; DNA Glycosylases/metabolism ; *DNA Methylation ; DNA, Plant/*metabolism ; Gene Silencing ; Genes, Plant ; Histone Acetyltransferases/chemistry/genetics/*metabolism ; Histones/metabolism ; Methylation ; Mutation ; Nuclear Proteins/genetics/metabolism ; Protein Structure, Tertiary ; Transgenes
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2013-08-10
    Description: Sequence-controlled polymers are macromolecules in which monomer units of different chemical nature are arranged in an ordered fashion. The most prominent examples are biological and have been studied and used primarily by molecular biologists and biochemists. However, recent progress in protein- and DNA-based nanotechnologies has shown the relevance of sequence-controlled polymers to nonbiological applications, including data storage, nanoelectronics, and catalysis. In addition, synthetic polymer chemistry has provided interesting routes for preparing nonnatural sequence-controlled polymers. Although these synthetic macromolecules do not yet compare in functional scope with their natural counterparts, they open up opportunities for controlling the structure, self-assembly, and macroscopic properties of polymer materials.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lutz, Jean-Francois -- Ouchi, Makoto -- Liu, David R -- Sawamoto, Mitsuo -- R01GM065865/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):1238149. doi: 10.1126/science.1238149.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Precision Macromolecular Chemistry Group, Institut Charles Sadron, UPR22-CNRS, 23 rue du Loess, Boite Postale 84047, 67034 Strasbourg Cedex 2, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23929982" target="_blank"〉PubMed〈/a〉
    Keywords: Biopolymers/*chemistry ; Catalysis ; DNA-Directed DNA Polymerase/chemistry ; Directed Molecular Evolution/methods ; Nucleic Acids/biosynthesis/chemical synthesis/chemistry ; *Polymerization ; Polymers/chemical synthesis/chemistry ; Templates, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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