ALBERT

Description: In response to adenosine 5'-diphosphate, the P2Y1 receptor (P2Y1R) facilitates platelet aggregation, and thus serves as an important antithrombotic drug target. Here we report the crystal structures of the human P2Y1R in complex with a nucleotide antagonist MRS2500 at 2.7 A resolution, and with a non-nucleotide antagonist BPTU at 2.2 A resolution. The structures reveal two distinct ligand-binding sites, providing atomic details of P2Y1R's unique ligand-binding modes. MRS2500 recognizes a binding site within the seven transmembrane bundle of P2Y1R, which is different in shape and location from the nucleotide binding site in the previously determined structure of P2Y12R, representative of another P2YR subfamily. BPTU binds to an allosteric pocket on the external receptor interface with the lipid bilayer, making it the first structurally characterized selective G-protein-coupled receptor (GPCR) ligand located entirely outside of the helical bundle. These high-resolution insights into P2Y1R should enable discovery of new orthosteric and allosteric antithrombotic drugs with reduced adverse effects.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408927/" 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/PMC4408927/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Dandan -- Gao, Zhan-Guo -- Zhang, Kaihua -- Kiselev, Evgeny -- Crane, Steven -- Wang, Jiang -- Paoletta, Silvia -- Yi, Cuiying -- Ma, Limin -- Zhang, Wenru -- Han, Gye Won -- Liu, Hong -- Cherezov, Vadim -- Katritch, Vsevolod -- Jiang, Hualiang -- Stevens, Raymond C -- Jacobson, Kenneth A -- Zhao, Qiang -- Wu, Beili -- U54 GM094618/GM/NIGMS NIH HHS/ -- U54GM094618/GM/NIGMS NIH HHS/ -- Z01 DK031116-21/Intramural NIH HHS/ -- Z01DK031116-26/DK/NIDDK NIH HHS/ -- ZIA DK031116-26/Intramural NIH HHS/ -- England -- Nature. 2015 Apr 16;520(7547):317-21. doi: 10.1038/nature14287. Epub 2015 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China. ; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Bridge Institute, Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA. ; Bridge Institute, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA. ; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China. ; 1] Bridge Institute, Department of Chemistry, University of Southern California, Los Angeles, California 90089, USA [2] Bridge Institute, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA [3] iHuman Institute, ShanghaiTech University, 99 Haike Road, Pudong, Shanghai 201203, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25822790" target="_blank"〉PubMed〈/a〉

Description: Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1alpha and nuclear lamina-heterochromatin anchoring protein LAP2beta. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494668/" 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/PMC4494668/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Weiqi -- Li, Jingyi -- Suzuki, Keiichiro -- Qu, Jing -- Wang, Ping -- Zhou, Junzhi -- Liu, Xiaomeng -- Ren, Ruotong -- Xu, Xiuling -- Ocampo, Alejandro -- Yuan, Tingting -- Yang, Jiping -- Li, Ying -- Shi, Liang -- Guan, Dee -- Pan, Huize -- Duan, Shunlei -- Ding, Zhichao -- Li, Mo -- Yi, Fei -- Bai, Ruijun -- Wang, Yayu -- Chen, Chang -- Yang, Fuquan -- Li, Xiaoyu -- Wang, Zimei -- Aizawa, Emi -- Goebl, April -- Soligalla, Rupa Devi -- Reddy, Pradeep -- Esteban, Concepcion Rodriguez -- Tang, Fuchou -- Liu, Guang-Hui -- Belmonte, Juan Carlos Izpisua -- F32 AG047770/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):1160-3. doi: 10.1126/science.aaa1356. Epub 2015 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. ; Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ; State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. ; Diagnosis and Treatment Center for Oral Disease, the 306th Hospital of the PLA, Beijing, China. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; College of Life Sciences, Peking University, Beijing 100871, China. ; The Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Universidad Catolica San Antonio de Murcia, Campus de los Jeronimos s/n, 30107 Guadalupe, Murcia, Spain. ; Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu. ; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. The Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Beijing Institute for Brain Disorders, Beijing 100069, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25931448" target="_blank"〉PubMed〈/a〉

Description: Double-stranded RNA (dsRNA) viruses possess a segmented dsRNA genome and a number of RNA-dependent RNA polymerases (RdRps) enclosed in a capsid. Until now, the precise structures of genomes and RdRps within the capsids have been unknown. Here we report the structures of RdRps and associated RNAs within nontranscribing and transcribing cypoviruses (NCPV and TCPV, respectively), using a combination of cryo-electron microscopy (cryo-EM) and a symmetry-mismatch reconstruction method. The RdRps and associated RNAs appear to exhibit a pseudo-D3 symmetric organization in both NCPV and TCPV. However, the molecular interactions between RdRps and the genomic RNA were found to differ in these states. Our work provides insight into the mechanisms of the replication and transcription in dsRNA viruses and paves a way for structural determination of lower-symmetry complexes enclosed in higher-symmetry structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Hongrong -- Cheng, Lingpeng -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1347-50. doi: 10.1126/science.aaa4938.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉College of Physics and Information Science, Hunan Normal University, Changsha, Hunan 410081, China. hrliu@hunnu.edu.cn lingpengcheng@mail.tsinghua.edu.cn. ; School of Life Sciences, Tsinghua University, Beijing 100084, China. hrliu@hunnu.edu.cn lingpengcheng@mail.tsinghua.edu.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383954" target="_blank"〉PubMed〈/a〉

Description: Numerous natural systems contain surfaces or threads that enable directional water transport. This behaviour is usually ascribed to hierarchical structural features at the microscale and nanoscale, with gradients in surface energy and gradients in Laplace pressure thought to be the main driving forces. Here we study the prey-trapping pitcher organs of the carnivorous plant Nepenthes alata. We find that continuous, directional water transport occurs on the surface of the 'peristome'--the rim of the pitcher--because of its multiscale structure, which optimizes and enhances capillary rise in the transport direction, and prevents backflow by pinning in place any water front that is moving in the reverse direction. This results not only in unidirectional flow despite the absence of any surface-energy gradient, but also in a transport speed that is much higher than previously thought. We anticipate that the basic 'design' principles underlying this behaviour could be used to develop artificial fluid-transport systems with practical applications.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chen, Huawei -- Zhang, Pengfei -- Zhang, Liwen -- Liu, Hongliang -- Jiang, Ying -- Zhang, Deyuan -- Han, Zhiwu -- Jiang, Lei -- England -- Nature. 2016 Apr 7;532(7597):85-9. doi: 10.1038/nature17189.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Mechanical Engineering and Automation, Beihang University, Beijing 100191, China. ; Laboratory of Bio-inspired Smart Interface Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China. ; School of Chemistry and Environment, Beihang University, Beijing 100191, China. ; Key Laboratory for Bionic Engineering, Ministry of Education, Jilin University, Changchun 130022, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078568" target="_blank"〉PubMed〈/a〉

Description: G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a approximately 20 degrees rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521999/" 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/PMC4521999/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kang, Yanyong -- Zhou, X Edward -- Gao, Xiang -- He, Yuanzheng -- Liu, Wei -- Ishchenko, Andrii -- Barty, Anton -- White, Thomas A -- Yefanov, Oleksandr -- Han, Gye Won -- Xu, Qingping -- de Waal, Parker W -- Ke, Jiyuan -- Tan, M H Eileen -- Zhang, Chenghai -- Moeller, Arne -- West, Graham M -- Pascal, Bruce D -- Van Eps, Ned -- Caro, Lydia N -- Vishnivetskiy, Sergey A -- Lee, Regina J -- Suino-Powell, Kelly M -- Gu, Xin -- Pal, Kuntal -- Ma, Jinming -- Zhi, Xiaoyong -- Boutet, Sebastien -- Williams, Garth J -- Messerschmidt, Marc -- Gati, Cornelius -- Zatsepin, Nadia A -- Wang, Dingjie -- James, Daniel -- Basu, Shibom -- Roy-Chowdhury, Shatabdi -- Conrad, Chelsie E -- Coe, Jesse -- Liu, Haiguang -- Lisova, Stella -- Kupitz, Christopher -- Grotjohann, Ingo -- Fromme, Raimund -- Jiang, Yi -- Tan, Minjia -- Yang, Huaiyu -- Li, Jun -- Wang, Meitian -- Zheng, Zhong -- Li, Dianfan -- Howe, Nicole -- Zhao, Yingming -- Standfuss, Jorg -- Diederichs, Kay -- Dong, Yuhui -- Potter, Clinton S -- Carragher, Bridget -- Caffrey, Martin -- Jiang, Hualiang -- Chapman, Henry N -- Spence, John C H -- Fromme, Petra -- Weierstall, Uwe -- Ernst, Oliver P -- Katritch, Vsevolod -- Gurevich, Vsevolod V -- Griffin, Patrick R -- Hubbell, Wayne L -- Stevens, Raymond C -- Cherezov, Vadim -- Melcher, Karsten -- Xu, H Eric -- DK071662/DK/NIDDK NIH HHS/ -- EY005216/EY/NEI NIH HHS/ -- EY011500/EY/NEI NIH HHS/ -- GM073197/GM/NIGMS NIH HHS/ -- GM077561/GM/NIGMS NIH HHS/ -- GM095583/GM/NIGMS NIH HHS/ -- GM097463/GM/NIGMS NIH HHS/ -- GM102545/GM/NIGMS NIH HHS/ -- GM103310/GM/NIGMS NIH HHS/ -- GM104212/GM/NIGMS NIH HHS/ -- GM108635/GM/NIGMS NIH HHS/ -- P30EY000331/EY/NEI NIH HHS/ -- P41 GM103310/GM/NIGMS NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- P50 GM073197/GM/NIGMS NIH HHS/ -- P50 GM073210/GM/NIGMS NIH HHS/ -- R01 DK066202/DK/NIDDK NIH HHS/ -- R01 DK071662/DK/NIDDK NIH HHS/ -- R01 EY011500/EY/NEI NIH HHS/ -- R01 GM087413/GM/NIGMS NIH HHS/ -- R01 GM109955/GM/NIGMS NIH HHS/ -- S10 RR027270/RR/NCRR NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- U54 GM094599/GM/NIGMS NIH HHS/ -- U54 GM094618/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Jul 30;523(7562):561-7. doi: 10.1038/nature14656. Epub 2015 Jul 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Structural Sciences, Center for Structural Biology and Drug Discovery, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA. ; Department of Chemistry and Biochemistry, and Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, Arizona 85287-1604, USA. ; Department of Chemistry, Bridge Institute, University of Southern California, Los Angeles, California 90089, USA. ; Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron DESY, 22607 Hamburg, Germany. ; Joint Center for Structural Genomics, Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California 94025, USA. ; 1] Laboratory of Structural Sciences, Center for Structural Biology and Drug Discovery, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA [2] Department of Obstetrics &Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ; The National Resource for Automated Molecular Microscopy, New York Structural Biology Center, New York, New York 10027, USA. ; Department of Molecular Therapeutics, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA. ; Jules Stein Eye Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA. ; Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, USA. ; Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, Menlo Park, California 94025, USA. ; 1] Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, Menlo Park, California 94025, USA [2] BioXFEL, NSF Science and Technology Center, 700 Ellicott Street, Buffalo, New York 14203, USA. ; 1] Department of Chemistry and Biochemistry, and Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, Arizona 85287-1604, USA [2] Department of Physics, Arizona State University, Tempe, Arizona 85287, USA. ; 1] Department of Chemistry and Biochemistry, and Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, Arizona 85287-1604, USA [2] Beijing Computational Science Research Center, Haidian District, Beijing 10084, China. ; 1] Department of Chemistry and Biochemistry, and Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, Arizona 85287-1604, USA [2] Department of Physics, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, USA. ; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. ; Department of Obstetrics &Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ; Swiss Light Source at Paul Scherrer Institute, CH-5232 Villigen, Switzerland. ; Department of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, California 90089, USA. ; School of Medicine and School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland. ; 1] BioXFEL, NSF Science and Technology Center, 700 Ellicott Street, Buffalo, New York 14203, USA [2] Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA. ; Laboratory of Biomolecular Research at Paul Scherrer Institute, CH-5232 Villigen, Switzerland. ; Department of Biology, Universitat Konstanz, 78457 Konstanz, Germany. ; Beijing Synchrotron Radiation Facility, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China. ; 1] Center for Free Electron Laser Science, Deutsches Elektronen-Synchrotron DESY, 22607 Hamburg, Germany [2] Centre for Ultrafast Imaging, 22761 Hamburg, Germany. ; 1] Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; 1] Department of Chemistry, Bridge Institute, University of Southern California, Los Angeles, California 90089, USA [2] Department of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, California 90089, USA [3] iHuman Institute, ShanghaiTech University, 2F Building 6, 99 Haike Road, Pudong New District, Shanghai 201210, China. ; 1] Laboratory of Structural Sciences, Center for Structural Biology and Drug Discovery, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA [2] VARI-SIMM Center, Center for Structure and Function of Drug Targets, CAS-Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26200343" target="_blank"〉PubMed〈/a〉

Description: Astrocytic brain tumours, including glioblastomas, are incurable neoplasms characterized by diffusely infiltrative growth. Here we show that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances. The resulting network allows multicellular communication through microtube-associated gap junctions. When damage to the network occurred, tumour microtubes were used for repair. Moreover, the microtube-connected astrocytoma cells, but not those remaining unconnected throughout tumour progression, were protected from cell death inflicted by radiotherapy. The neuronal growth-associated protein 43 was important for microtube formation and function, and drove microtube-dependent tumour cell invasion, proliferation, interconnection, and radioresistance. Oligodendroglial brain tumours were deficient in this mechanism. In summary, astrocytomas can develop functional multicellular network structures. Disconnection of astrocytoma cells by targeting their tumour microtubes emerges as a new principle to reduce the treatment resistance of this disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Osswald, Matthias -- Jung, Erik -- Sahm, Felix -- Solecki, Gergely -- Venkataramani, Varun -- Blaes, Jonas -- Weil, Sophie -- Horstmann, Heinz -- Wiestler, Benedikt -- Syed, Mustafa -- Huang, Lulu -- Ratliff, Miriam -- Karimian Jazi, Kianush -- Kurz, Felix T -- Schmenger, Torsten -- Lemke, Dieter -- Gommel, Miriam -- Pauli, Martin -- Liao, Yunxiang -- Haring, Peter -- Pusch, Stefan -- Herl, Verena -- Steinhauser, Christian -- Krunic, Damir -- Jarahian, Mostafa -- Miletic, Hrvoje -- Berghoff, Anna S -- Griesbeck, Oliver -- Kalamakis, Georgios -- Garaschuk, Olga -- Preusser, Matthias -- Weiss, Samuel -- Liu, Haikun -- Heiland, Sabine -- Platten, Michael -- Huber, Peter E -- Kuner, Thomas -- von Deimling, Andreas -- Wick, Wolfgang -- Winkler, Frank -- England -- Nature. 2015 Dec 3;528(7580):93-8. doi: 10.1038/nature16071. Epub 2015 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, INF 400, 69120 Heidelberg, Germany. ; Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. ; Department of Neuropathology, Institute of Pathology, Ruprecht-Karls University Heidelberg, INF 224, 69120 Heidelberg, Germany. ; Clinical Cooperation Unit Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), INF 224, 69120 Heidelberg, Germany. ; Department of Functional Neuroanatomy, Institute of Anatomy and Cell Biology, Heidelberg University, INF 307, 69120 Heidelberg, Germany. ; Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar der Technischen Universitat Munchen, 81675 Munich, Germany. ; Neurosurgery Clinic, University Hospital Heidelberg, INF 400, 69120 Heidelberg, Germany. ; Department of Neuroradiology, University Hospital Heidelberg, INF 400, 69120 Heidelberg, Germany. ; Department of Neurophysiology, Institute of Physiology, University of Wurzburg, 97070 Wurzburg, Germany. ; Department of Medical Physics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. ; Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. ; Light Microscopy Facility, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. ; Department of Translational Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. ; Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway. ; Institute of Neurology, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, 1090 Vienna, Austria. ; Tools For Bio-Imaging, Max-Planck-Institute of Neurobiology, 82152 Martinsried, Germany. ; Institute of Physiology II, Eberhard Karls University of Tubingen, 72074 Tubingen, Germany. ; Department of Medicine I, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center, CNS Unit, Medical University of Vienna, 1090 Vienna, Austria. ; Hotchkiss Brain Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada. ; Department of Cell Biology and Anatomy, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4Z6, Canada. ; Clark Smith Brain Tumor Research Centre, Southern Alberta Cancer Research Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada. ; Helmholtz Young Investigator Group, Normal and Neoplastic CNS Stem Cells, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany. ; Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. ; CCU Molecular and Radiation Oncology, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany. ; Department of Radiation Oncology, University Hospital Heidelberg, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26536111" target="_blank"〉PubMed〈/a〉