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2-Photon Characterization of Optical Proteolytic Beacons for Imaging Changes in Matrix-Metalloprotease Activity in a Mouse Model of Aneurysm
- Darren G. Haskett, David Maestas, Stephen J. Howerton, Tyler Smith, D. Catalina Ardila, Tom Doetschman, Urs Utzinger, Dominic McGrath, J. Oliver McIntyre, Jonathan P. Vande Geest
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- Journal:
- Microscopy and Microanalysis / Volume 22 / Issue 2 / April 2016
- Published online by Cambridge University Press:
- 23 February 2016, pp. 349-360
- Print publication:
- April 2016
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Abdominal aortic aneurysm is a multifactorial disease that is a leading cause of death in developed countries. Matrix-metalloproteases (MMPs) are part of the disease process, however, assessing their role in disease initiation and progression has been difficult and animal models have become essential. Combining Förster resonance energy transfer (FRET) proteolytic beacons activated in the presence of MMPs with 2-photon microscopy allows for a novel method of evaluating MMP activity within the extracellular matrix (ECM). Single and 2-photon spectra for proteolytic beacons were determined in vitro. Ex vivo experiments using the apolipoprotein E knockout angiotensin II-infused mouse model of aneurysm imaged ECM architecture simultaneously with the MMP-activated FRET beacons. 2-photon spectra of the two-color proteolytic beacons showed peaks for the individual fluorophores that enable imaging of MMP activity through proteolytic cleavage. Ex vivo imaging of the beacons within the ECM revealed both microstructure and MMP activity. 2-photon imaging of the beacons in aneurysmal tissue showed an increase in proteolytic cleavage within the ECM (p<0.001), thus indicating an increase in MMP activity. Our data suggest that FRET-based proteolytic beacons show promise in assessing MMP activity within the ECM and will therefore allow future studies to identify the heterogeneous distribution of simultaneous ECM remodeling and protease activity in aneurysmal disease.
Contributors
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- By Mowaffaq Almikhlafi, Osama Al-muslim, Robert Arntfield, Ian M Ball, Sue Berney, Mohit Bhutani, Clay A Block, Ken Blonde, Rudi Brits, Ron Butler, Lois Champion, Chris Clarke, Linda Denehy, Joseph Dreier, A Ebersohn, Shane W English, Ari Ercole, Darren H Freed, John Fuller, Julio P Zavala Georffino, RT Noel Gibney, Jeff Granton, Donald EG Griesdale, Arun K Gupta, Wael Haddara, Ahmed F Hegazy, Umjeet Singh Jolly, Philip M Jones, Ilya Kagan, Kala Kathirgamanathan, Harneet Kaur, John Kellett, Bhupesh Khadka, Biniam Kidane, Carlos Kidel, Anand Kumar, Alejandro Lazo-Langner, David Leasa, W Robert Leeper, Stephen Y Liang, Tania Ligori, Jaimie Manlucu, Janet Martin, Ian McConachie, Alan McGlennan, Lauralyn McIntyre, Tina Mele, MJ Naisbitt, Raj Nichani, Daniel H Ovakim, Neil Parry, Daniel Castro Pereira, Thomas Piraino, Brian Pollard, Valerie Schulz, Michael D Sharpe, Rohit K Singal, Pierre Singer, Mark Soth, Christian P Subbe, Jaffer Syed, Ravi Taneja, Tom Varughese, Jennifer Vergel Del Dios, Jessie R Welbourne, Christopher W White, Rebecca P Winsett, Titus C Yeung, G Bryan Young, Shelley R Zieroth
- Edited by John Fuller, University of Western Ontario, Jeff Granton, University of Western Ontario, Ian McConachie, University of Western Ontario
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- Book:
- Handbook of ICU Therapy
- Published online:
- 05 February 2015
- Print publication:
- 04 December 2014, pp vii-xii
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Contributors
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- By Ghazi Al-Rawas, Vazken Andréassian, Tianqi Ao, Stacey A. Archfield, Berit Arheimer, András Bárdossy, Trent Biggs, Günter Blöschl, Theresa Blume, Marco Borga, Helge Bormann, Gianluca Botter, Tom Brown, Donald H. Burn, Sean K. Carey, Attilio Castellarin, Francis Chiew, François Colin, Paulin Coulibaly, Armand Crabit, Barry Croke, Siegfried Demuth, Qingyun Duan, Giuliano Di Baldassarre, Thomas Dunne, Ying Fan, Xing Fang, Boris Gartsman, Alexander Gelfan, Mikhail Georgievski, Nick van de Giesen, David C. Goodrich, Hoshin V. Gupta, Khaled Haddad, David M. Hannah, H. A. P. Hapuarachchi, Hege Hisdal, Kamila Hlavčová, Markus Hrachowitz, Denis A. Hughes, Günter Humer, Ruud Hurkmans, Vito Iacobellis, Elena Ilyichyova, Hiroshi Ishidaira, Graham Jewitt, Shaofeng Jia, Jeffrey R. Kennedy, Anthony S. Kiem, Robert Kirnbauer, Thomas R. Kjeldsen, Jürgen Komma, Leonid M. Korytny, Charles N. Kroll, George Kuczera, Gregor Laaha, Henny A. J. van Lanen, Hjalmar Laudon, Jens Liebe, Shijun Lin, Göran Lindström, Suxia Liu, Jun Magome, Danny G. Marks, Dominic Mazvimavi, Jeffrey J. McDonnell, Brian L. McGlynn, Kevin J. McGuire, Neil McIntyre, Thomas A. McMahon, Ralf Merz, Robert A. Metcalfe, Alberto Montanari, David Morris, Roger Moussa, Lakshman Nandagiri, Thomas Nester, Taha B. M. J. Ouarda, Ludovic Oudin, Juraj Parajka, Charles S. Pearson, Murray C. Peel, Charles Perrin, John W. Pomeroy, David A. Post, Ataur Rahman, Liliang Ren, Magdalena Rogger, Dan Rosbjerg, José Luis Salinas, Jos Samuel, Eric Sauquet, Hubert H. G. Savenije, Takahiro Sayama, John C. Schaake, Kevin Shook, Murugesu Sivapalan, Jon Olav Skøien, Chris Soulsby, Christopher Spence, R. ‘Sri’ Srikanthan, Tammo S. Steenhuis, Jan Szolgay, Yasuto Tachikawa, Kuniyoshi Takeuchi, Lena M. Tallaksen, Dörthe Tetzlaff, Sally E. Thompson, Elena Toth, Peter A. Troch, Remko Uijlenhoet, Carl L. Unkrich, Alberto Viglione, Neil R. Viney, Richard M. Vogel, Thorsten Wagener, M. Todd Walter, Guoqiang Wang, Markus Weiler, Rolf Weingartner, Erwin Weinmann, Hessel Winsemius, Ross A. Woods, Dawen Yang, Chihiro Yoshimura, Andy Young, Gordon Young, Erwin Zehe, Yongqiang Zhang, Maichun C. Zhou
- Edited by Günter Blöschl, Technische Universität Wien, Austria, Murugesu Sivapalan, University of Illinois, Urbana-Champaign, Thorsten Wagener, University of Bristol, Alberto Viglione, Technische Universität Wien, Austria, Hubert Savenije, Technische Universiteit Delft, The Netherlands
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- Book:
- Runoff Prediction in Ungauged Basins
- Published online:
- 05 April 2013
- Print publication:
- 18 April 2013, pp ix-xiv
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Adoption as an issue of local justice
- Monica Duffy Toft, David P. McIntyre
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- Journal:
- European Journal of Sociology / Archives Européennes de Sociologie / Volume 33 / Issue 1 / June 1992
- Published online by Cambridge University Press:
- 28 July 2009, pp. 83-105
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The focus of this paper is adoption, specifically adoption as an issue of local justice. Local justice, as conceived by Jon Elster, is a way of thinking about how scarce goods and burdens are allocated by local, low-level institutions; and encompasses such issues as military service, college admission, organs for transplantation, donation of sperm, child custody, and adoption. There are three principle elements to local justice: scarce goods, institutions that allocate them, and the individuals who step forward as allocative candidates. Over time, the individual will bring his or her needs before a succession of institutional providers, while the institutions will find before them a succession of individuals who need, want, or merit the scarce good being allocated. In many instances, such as the allocation of organs for transplantation, allocation may be a matter of life or death; while in other instances, the consequences of not receiving the good may not be life threatening, but nonetheless affect an individual's future life plans (e.g. admittance into Harvard). Thus allocative decisions can be evaluated according to their importance along two different axes. The first contains decisions which are ‘important’ because they involve life and death outcomes, such as the allocation of kidneys, while other decisions are ‘important’ not because they carry with them life-and-death outcomes, but because they influence the lives of a vast number of individuals. Selection choices for college admission are among this latter type of important decision.