EXC 1003: Cells in Motion - CiM: Visualisierung und Verstehen zellulären Verhaltens in lebenden Organismen
Zusammenfassung der Projektergebnisse
Zellen sind die Grundbausteine aller Organismen und die Untersuchung zellulärer Plastizität und Dynamik ist elementar für das Verständnis von Entwicklung, Homöostase und Regeneration. Neuartige optische Bildgebungsstrategien, die dynamisches Zellverhalten in vivo darstellen, haben unser Wissen revolutioniert und eindrücklich die Notwendigkeit der Untersuchung zellulären Verhaltens in lebenden Organismen untermauert. In diesem Themenbereich hat der Exzellenzcluster ‘Cells in Motion – CiM‘ in den letzten Jahren einen national und international sichtbaren Forschungsschwerpunkt aufgebaut. Basierend auf der interfakultären Expertise in Münster hat unsere Forschung dazu beigetragen, Limitationen im Bereich der optischen und medizinischen Bildgebung zu überwinden und das Zellverhalten im Organismus durch Entwicklung und Anwendung neuartiger Bildgebungsstrategien besser zu verstehen. Unsere Vision bleibt unverändert die Schaffung eines interfakultären Umfelds, das die biomedizinische Grundlagenforschung, die klinische Translation sowie deren Interaktion nachhaltig befördert. Hierbei ist die Bildgebung verbindende Strategie zur Charakterisierung des Zellverhaltens, gleichgültig ob in Einzelzellen oder Geweben, in Tiermodellen oder Patienten. Um traditionelle Fakultätsgrenzen zu überwinden und den wissenschaftlichen Austausch zu fördern, wurden sieben neue interdisziplinäre Professuren und zwei neue klinisch-translationale Professuren eingerichtet, sowie das interfakultäre Cells in Motion Interfaculty Centre (CiMIC) gegründet. CiMIC verstetigt mit finanzieller Unterstützung der WWU das Konzept des Exzellenzclusters und wird zukünftig im Forschungsneubau Multiscale Imaging Centre – MIC verortet sein. Ein weiteres wichtiges Element unseres Konzepts ist eine neue interfakultäre Ausbildungsstruktur, die Gleichstellungsaspekte auf allen Ebenen integriert (Careers in Motion Centre) und Medizinern durch einen Master in ‘Experimental Medicine‘ erstmals den Zugang zu einem PhD-Programm ermöglicht. CiM bündelt erfolgreich die Exzellenzbereiche ‘Zellbiologie‘ und ‘Molekulare Bildgebung‘ der WWU und integriert kompetitiv geförderte interdisziplinäre Netzwerke zwischen den Fakultäten für Medizin, Naturwissenschaften und Mathematik sowie dem Max-Planck-Institut für Molekulare Biomedizin. Durch den Aufbau eines interaktiven und langfristigen Forschungs- und Ausbildungsnetzwerks zwischen den beteiligten Fakultäten hat CiM nachhaltige strukturelle Änderungen an der WWU bewirkt und die nationale und internationale Sichtbarkeit der WWU im Bereich der Lebens- und Naturwissenschaften signifikant erhöht. Unser Ziel ist es nun, mit der Unterstützung durch CiMIC und durch die Einrichtung von neuen Sonderforschungsbereichen und Forschungsnetzwerken die erfolgreiche Arbeit im Bereich der Anwendung innovativer Bildgebungstechnologien in der biomedizinischen Forschung, in Diagnostik und Therapie weiterzuführen.
Link zum Abschlussbericht
https://doi.org/10.2314/KXP:170112324X
Projektbezogene Publikationen (Auswahl)
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Bacteria tracking by in vivo magnetic resonance imaging. BMC Biol. 2013; 11: 63
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Blocking endocytosis enhances short-term synaptic depression under conditions of normal availability of vesicles. Neuron. 2013; 80: 343-349
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cAMP-induced secretion of endothelial von Willebrand factor is regulated by a phosphorylation/dephosphorylation switch in annexin A2. Blood. 2013; 122: 1042-1051
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Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS. Nat Med. 2013; 19: 1161-1165
Bittner S, Ruck T, Schuhmann MK, Herrmann AM, Moha ou Maati H, Bobak N, Göbel K, Langhauser F, Stegner D, Ehling P, Borsotto M, Pape H-C, Nieswandt B, Kleinschnitz C, Heurteaux C, Galla H-J, Budde T, Wiendl H, Meuth SG
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FIM, a novel FTIR-based imaging method for high throughput locomotion analysis. PLoS One. 2013; 8: e53963
Risse B, Thomas S, Otto N, Lopmeier T, Valkov D, Jiang X, Klämbt C
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Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity. Nat Commun. 2014; 5: 4593
Vogl T, Eisenblätter M, Völler T, Zenker S, Hermann S, van Lent P, Faust A, Geyer C, Petersen B, Roebrock K, Schäfers M, Bremer C, Roth J
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Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014; 507: 323-328
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Ena/VASP Proteins Cooperate with the WAVE Complex to Regulate the Actin Cytoskeleton. Dev Cell. 2014; 30: 569-584
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Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature. 2014; 507: 376-380
Ramasamy SK, Kusumbe AP, Wang L, Adams RH
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Fusing VE-Cadherin to alpha-Catenin Impairs Fetal Liver Hematopoiesis and Lymph but Not Blood Vessel Formation. Mol Cell Biol. 2014; 34: 1634-1648
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Large Scale RNAi Reveals the Requirement of Nuclear Envelope Breakdown for Nuclear Import of Human Papillomaviruses. PLoS Pathog. 2014; 10: e1004162
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Leukocyte extravasation and vascular permeability are each controlled in vivo by different tyrosine residues of VE-cadherin. Nat Immunol. 2014; 15: 223-230
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Serial F-18-FDG PET/CT distinguishes inflamed from stable plaque phenotypes in shear-stress induced murine atherosclerosis. Atherosclerosis. 2014; 234: 276-282
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The Drosophila FHOD1-like formin Knittrig acts through Rok to promote stress fiber formation and directed macrophage migration during the cellular immune response. Development. 2014; 141: 1366-1380
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Total variation regularization in measurement and image space for PET reconstruction. Inverse Probl. 2014; 30: 105003
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Ultraviolet B light attenuates the systemic immune response in central nervous system autoimmunity. Ann Neurol. 2014; 75: 739-758
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Viral suppressors of the RIG-I-mediated interferon response are pre-packaged in influenza virions. Nat Commun. 2014; 5: 5645
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VLA-4 blockade promotes differential routes into human CNS involving PSGL-1 rolling of T cells and MCAM- adhesion of TH17 cells. J Exp Med. 2014; 211: 1833-1846
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A Bio-Inspired, Catalytic E --> Z Isomerization of Activated Olefins. J Am Chem Soc. 2015; 137: 11254-11257
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A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis. Developmental Cell. 2015; 35: 553-567
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Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia. J Exp Med. 2015; 212: 1255-1266
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CD8+ T cell-mediated neuronal dysfunction and degeneration in limbic encephalitis. Front Neurol. 2015; 6: 163
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Differential phospholipase C-dependent modulation of TASK and TREK two-pore domain K+ channels in rat thalamocortical relay neurons. J Physiol. 2015; 593: 127-144
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Focal MMP-2 and MMP-9 Activity at the Blood-Brain Barrier Promotes Chemokine-Induced Leukocyte Migration. Cell Rep. 2015; 10: 1040-1054
Song J, Wu C, Korpos E, Zhang X, Agrawal SM, Wang Y, Faber C, Schäfers M, Körner H, Opdenakker G, Hallmann R, Sorokin L
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Influence of cell shape, inhomogeneities and diffusion barriers in cell polarization models. Phys Biol. 2015; 12: 066014
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Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin. J Exp Med. 2015; 212: 2267-2287
Frye M, Dierkes M, Küppers V, Vockel M, Tomm J, Zeuschner D, Rossaint J, Zarbock A, Koh GY, Peters K, Nottebaum AF, Vestweber D
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JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis. Nat Commun. 2015; 6: 8128
Tuncay H, Brinkmann BF, Steinbacher T, Schurmann A, Gerke V, Iden S, Ebnet K
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Multimodal imaging reveals temporal and spatial microglia and matrix metalloproteinase activity after experimental stroke. J Cereb Blood Flow Metab.2015; 35: 1711-1721
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Optimization of Codon Translation Rates via tRNA Modifications Maintains Proteome Integrity. Cell. 2015; 161: 1606-1618
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Puzzle Approach to Pose Tracking of a Rigid Object in a Multi Camera System. Lect Notes Comput Sc. 2015; 9256: 337-349
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The motorized RhoGAP myosin IXb (Myo9b) in leukocytes regulates experimental autoimmune encephalomyelitis induction and recovery. J Neuroimmunol. 2015; 282: 25-32
Liu Z, Xu Y, Zhang X, Song J, Sorokin L, Bähler M
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The Triple-Repeat Protein Anakonda Controls Epithelial Tricellular Junction Formation in Drosophila. Dev Cell. 2015; 33: 535-548
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A novel family of fluorescent hypoxia sensors reveal strong heterogeneity in tumor hypoxia at the cellular level. Embo J. 2016; 35: 102-113
Erapaneedi R, Belousov VV, Schäfers M, Kiefer F
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Age-dependent modulation of vascular niches for haematopoietic stem cells. Nature. 2016; 532: 380-384
Kusumbe AP, Ramasamy SK, Itkin T, Mäe MA, Langen UH, Betsholtz C, Lapidot T, Adams RH
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Cannabinoid Receptor 2 Modulates Susceptibility to Experimental Cerebral Malaria through a CCL17-dependent Mechanism. J Biol Chem. 2016; 291: 19517-19531
Alferink J, Specht S, Arends H, Schumak B, Schmidt K, Ruland C, Lundt R, Kemter A, Dlugos A, Kuepper JM, Poppensieker K, Findeiss M, Albayram O, Otte D-M, Marazzi J, Gertsch J, Forster I, Maier W, Scheu S, Hoerauf A, Zimmer A
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Combinatorial effects of doxorubicin and retargeted tissue factor by intratumoral entrapment of doxorubicin and proapoptotic increase of tumor vascular infarction. Oncotarget. 2016; 7: 82458-82472
Stucke-Ring J, Ronnacker J, Brand C, Höltke C, Schliemann C, Kessler T, Schmidt LH, Harrach S, Mantke V, Hintelmann H, Hartmann W, Wardelmann E, Lenz G, Wünsch B, Müller-Tidow C, Mesters RM, Schwöppe C, Berdel WE
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Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response. Nat Commun. 2016; 7: 13464
Rossaint J, Kühne K, Skupski J, Van Aken H, Looney MR, Hidalgo A, Zarbock A
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Equilibrium physics breakdown reveals the active nature of red blood cell flickering. Nat Phys. 2016; 12: 513-519
Turlier H, Fedosov DA, Audoly B, Auth T, Gov NS, Sykes C, Joanny J-F, Gompper G, Betz T
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FGF23 signaling impairs neutrophil recruitment and host defense during CKD. J Clin Invest. 2016; 126: 962-974
Rossaint J, Oehmichen J, Van Aken H, Reuter S, Pavenstädt H, Meersch M, Unruh M, Zarbock A
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Fluorinated matrix metalloproteinases inhibitors-Phosphonate based potential probes for positron emission tomography. Bioorg Med Chem. 2016; 24: 902-909
Beutel B, Daniliuc CG, Riemann B, Schäfers M, Haufe G
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Gemcitabine Mechanism of Action Confounds Early Assessment of Treatment Response by 3'-Deoxy-3'-[18F]Fluorothymidine in Preclinical Models of Lung Cancer. Cancer Res. 2016; 76: 7096-7105
Schelhaas S, Held A, Wachsmuth L, Hermann S, Honess DJ, Heinzmann K, Smith D-M, Griffiths JR, Faber C, Jacobs AH
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Imaging by Elemental and Molecular Mass Spectrometry Reveals the Uptake of an Arsenolipid in the Brain of Drosophila melanogaster. Anal Chem. 2016; 88: 5258-5263
Niehoff A-C, Schulz J, Soltwisch J, Meyer S, Kettling H, Sperling M, Jeibmann A, Dreisewerd K, Francesconi KA, Schwerdtle T, Karst U
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Imaging matrix metalloproteinase activity in multiple sclerosis as a specific marker of leukocyte penetration of the blood-brain barrier. Sci Transl Med. 2016; 8: 364ra152
Gerwien H, Hermann S, Zhang X, Korpos E, Song J, Kopka K, Faust A, Wenning C, Gross CC, Honold L, Melzer N, Opdenakker G, Wiendl H, Schäfers M, Sorokin L
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Impaired NK-mediated regulation of T-cell activity in multiple sclerosis is reconstituted by IL-2 receptor modulation. Proc Natl Acad Sci USA. 2016; 113: E2973-82
Gross CC, Schulte-Mecklenbeck A, Runzi A, Kuhlmann T, Posevitz-Fejfar A, Schwab N, Schneider-Hohendorf T, Herich S, Held K, Konjevic M, Hartwig M, Dornmair K, Hohlfeld R, Ziemssen T, Klotz L, Meuth SG, Wiendl H
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Labeling and Selective Inactivation of Gram-Positive Bacteria Employing Bimodal Photoprobes with Dual Readouts. Chemistry. 2016; 22: 5243-5252
Galstyan A, Block D, Niemann S, Grüner MC, Abbruzzetti S, Oneto M, Daniliuc CG, Hermann S, Viappiani C, Schäfers M, Löffler B, Strassert CA, Faust A
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Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease. Sci Transl Med. 2016; 8: 362ra146
Mykicki N, Herrmann AM, Schwab N, Deenen R, Sparwasser T, Limmer A, Wachsmuth L, Klotz L, Köhrer K, Faber C, Wiendl H, Luger TA, Meuth SG, Loser K
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Modifying the 5'-Cap for Click Reactions of Eukaryotic mRNA and To Tune Translation Efficiency in Living Cells. Angew Chem Int Ed Engl. 2016; 55: 10899-10903
Holstein JM, Anhäuser L, Rentmeister A
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Protection from septic peritonitis by rapid neutrophil recruitment through omental high endothelial venules. Nat Commun. 2016; 7: 10828
Buscher K, Wang H, Zhang X, Striewski P, Wirth B, Saggu G, Lütke-Enking S, Mayadas TN, Ley K, Sorokin L, Song J
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Repulsive cues combined with physical barriers and cell-cell adhesion determine progenitor cell positioning during organogenesis. Nat Commun. 2016; 7: 11288
Paksa A, Bandemer J, Hoeckendorf B, Razin N, Tarbashevich K, Minina S, Meyen D, Biundo A, Leidel SA, Peyrieras N, Gov NS, Keller PJ, Raz E
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Repulsive Epithelial Cues Direct Glial Migration along the Nerve. Dev Cell. 2016; 39: 696-707
Sasse S, Klämbt C
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Staccato/Unc-13-4 controls secretory lysosome-mediated lumen fusion during epithelial tube anastomosis. Nat Cell Biol. 2016; 18: 727-739
Caviglia S, Brankatschk M, Fischer EJ, Eaton S, Luschnig S
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A central region in the minor capsid protein of papillomaviruses facilitates viral genome tethering and membrane penetration for mitotic nuclear entry. PLoS Pathog. 2017; 13: e1006308
Aydin I, Villalonga-Planells R, Greune L, Bronnimann MP, Calton CM, Becker M, Lai K-Y, Campos SK, Schmidt MA, Schelhaas M
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A Novel Mouse Model of Staphylococcus aureus Vascular Graft Infection: Noninvasive Imaging of Biofilm Development in Vivo. Am J Pathol. 2017; 187: 268-279
Van de Vyver H, Bovenkamp PR, Hoerr V, Schwegmann K, Tuchscherr L, Niemann S, Kursawe L, Grosse C, Moter A, Hansen U, Neugebauer U, Kuhlmann MT, Peters G, Hermann S, Löffler B
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An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel Formation. Circ Res. 2017; 120: 1263-1275
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An FIM-Based Long-Term In-Vial Monitoring System for Drosophila Larvae. IEEE Trans Biomed Eng. 2017; 64: 1862-1874
Berh D, Risse B, Michels T, Otto N, Jiang X, Klämbt C
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Bleb Expansion in Migrating Cells Depends on Supply of Membrane from Cell Surface Invaginations. Dev Cell. 2017; 43: 577-587.e5
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Cell-matrix signals specify bone endothelial cells during developmental osteogenesis. Nat Cell Biol. 2017; 19: 189-201
Langen UH, Pitulescu ME, Kim JM, Enriquez-Gasca R, Sivaraj KK, Kusumbe AP, Singh A, Di Russo J, Bixel MG, Zhou B, Sorokin L, Vaquerizas JM, Adams RH
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Changing POU dimerization preferences converts Oct6 into a pluripotency inducer. EMBO Rep. 2017; 18: 319-333
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Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake. Cancer Res. 2017; 77: 1831-1841
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Dll4 and Notch signalling couples sprouting angiogenesis and artery formation. Nat Cell Biol. 2017; 19: 915-927
Pitulescu ME, Schmidt I, Giaimo BD, Antoine T, Berkenfeld F, Ferrante F, Park H, Ehling M, Biljes D, Rocha SF, Langen UH, Stehling M, Nagasawa T, Ferrara N, Borggrefe T, Adams RH
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Endoglin controls blood vessel diameter through endothelial cell shape changes in response to haemodynamic cues. Nat Cell Biol. 2017; 19: 653-665
Sugden WW, Meissner R, Aegerter-Wilmsen T, Tsaryk R, Leonard EV, Bussmann J, Hamm MJ, Herzog W, Jin Y, Jakobsson L, Denz C, Siekmann AF
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Endothelial basement membrane laminin 511 is essential for shear stress response. EMBO J. 2017; 36: 183-201
Di Russo J, Luik A-L, Yousif L, Budny S, Oberleithner H, Hofschröer V, Klingauf J, van Bavel E, Bakker E NTP, Hellstrand P, Bhattachariya A, Albinsson S, Pincet F, Hallmann R, Sorokin L
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Endothelial Notch signalling limits angiogenesis via control of artery formation. Nat Cell Biol. 2017; 19: 928-940
Hasan SS, Tsaryk R, Lange M, Wisniewski L, Moore JC, Lawson ND, Wojciechowska K, Schnittler H, Siekmann AF
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FIM2c : A Multicolour, Multipurpose Imaging System to Manipulate and Analyse Animal Behaviour. IEEE Trans Biomed Eng. 2017; 64: 610-620
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FIMTrack: An open source tracking and locomotion analysis software for small animals. PLoS Comput Biol. 2017; 13: e1005530
Risse B, Berh D, Otto N, Klämbt C, Jiang X
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Generic wound signals initiate regeneration in missing-tissue contexts. Nat Commun. 2017; 8: 2282
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Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. Nat Genet. 2017; 49: 1529-1538
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PAR-1 promotes microtubule breakdown during dendrite pruning in Drosophila. EMBO J. 2017; 36: 1981-1991
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Polarized actin and VE-cadherin dynamics regulate junctional remodelling and cell migration during sprouting angiogenesis. Nat Commun. 2017; 8 (1): 2210
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Radiolabeled Selective Matrix Metalloproteinase 13 (MMP-13) Inhibitors: (Radio)Syntheses and in Vitro and First in Vivo Evaluation. J Med Chem. 2017; 60: 307-321
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Reversible Stabilization of Vesicles: Redox-Responsive Polymer Nanocontainers for Intracellular Delivery. Angew Chem Int Ed Engl. 2017; 56: 9603-9607
de Vries WC, Grill D, Tesch M, Ricker A, Nüsse H, Klingauf J, Studer A, Gerke V, Ravoo BJ
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S100-alarmin-induced innate immune programming protects newborn infants from sepsis. Nat Immunol. 2017; 18: 622-632
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VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses. Nat Commun. 2017; 8: 2279
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VIPAR, a quantitative approach to 3D histopathology applied to lymphatic malformations. JCI Insight. 2017; 2
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Addressable Cholesterol Analogs for Live Imaging of Cellular Membranes. Cell Chem Biol. 2018; 25: 952-961.e12
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Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation. J Clin Invest. 2018; 128: 1852-1866
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CD99L2 deficiency inhibits leukocyte entry into the central nervous system and ameliorates neuroinflammation. J Leukoc Biol. 2018; 104: 787-797
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Codon-specific translation reprogramming promotes resistance to targeted therapy. Nature. 2018; 558: 605-609
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Collective Cell Migration in Embryogenesis Follows the Laws of Wetting. Biophys J. 2018; 114: 213-222
Wallmeyer B, Trinschek S, Yigit S, Thiele U, Betz T
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Distinct roles of VE‐cadherin for development and maintenance of specific lymph vessel beds. EMBO J. 2018: e98271
Hägerling R, Hoppe E, Dierkes C, Stehling M, Makinen T, Butz S, Vestweber D, Kiefer F
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Enzymatic or In Vivo Installation of Propargyl Groups in Combination with Click Chemistry for the Enrichment and Detection of Methyltransferase Target Sites in RNA. Angew Chem Int Ed Engl. 2018; 57: 6342-6346
Hartstock K, Nilges BS, Ovcharenko A, Cornelissen NV, Püllen N, Lawrence-Dörner A-M, Leidel SA, Rentmeister A
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