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336 Pharmacologic Modulation of Endothelial Cell Autophagy During Hypoxic Cold Storage and Reperfusion: Harnessing the Power of 'Self-Eating,' as a Pre-Treatment Strategy for Donor Organs
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- Meredith E. Taylor, Dinesh Jaishankar, Ashley P. Strouse, Yu Min Lee, Satish N. Nadig
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 102
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OBJECTIVES/GOALS: Donor hearts are transported in cold storage (CS) and undergo ischemia-reperfusion injury (IRI) when transplanted. IRI injures microvascular endothelial cells (EC), heightens the immune response, and has been associated with increased autophagy. We aim to understand the changes in autophagy during CS and IRI and its impact on EC immunogenicity. METHODS/STUDY POPULATION: To study autophagy changes during IRI, immunoblotting for autophagy markers was performed in mouse cardiac ECs (MCECs) lysates. MCECs were in a cold preservation solution in a hypoxic chamber for 6 hours(h) and warm conditions with culture medium for 24 h. MCECs, under standard conditions, served as controls. Secreted interferon-gamma (IFN-γ) levels were quantified via ELISA to study autophagy and EC immunogenicity. MCEC-sensitized CD8+ T-cells were isolated from C57BL/6 spleens and co-cultured with MCECs pre-treated for 16 h with rapamycin or starvation, autophagy inducers, or chloroquine, an autophagy inhibitor under normal or IRI conditions. MCECs without any treatment served as controls. RESULTS/ANTICIPATED RESULTS: To determine autophagy levels in IRI, immunoblotting of MCEC lysates revealed a significant increase (P<0.01) in the established autophagy marker, LC3, at early time points post-reperfusion compared to NT conditions, indicating more autophagosome formation during CS and IRI. To assess the role of autophagy in EC immunogenicity, the co-culture experiment revealed that autophagy induction in MCECs under NT and HCS conditions with rapamycin had a 74.9-fold and 51.5-fold reduction of IFN-γ (pg/mL), resepectively, compared to the non-treated controls. In contrast, autophagy inhibition in MCECs with chloroquine resulted in 1.82-fold increase of IFN-γ compared to untreated controls. This suggests a protective role of autophagy in ECs during IRI. DISCUSSION/SIGNIFICANCE: We observed that autophagy may be protective during IRI by mitigating EC immunogenicity. Thus, pharmacologically modulating microvascular EC autophagy in donor hearts prior to transplantation may mitigate insults incurred during CS and IRI.
Marine geological investigation of Edward VIII Gulf, Kemp Coast, East Antarctica
- Isabel A. Dove, Amy Leventer, Meredith J. Metcalf, Stefanie A. Brachfeld, Robert B. Dunbar, Patricia Manley, Amelia E. Shevenell, Richard W. Murray, Matthew Hommeyer, Kelly A. Kryc, Natalie McLenaghan, Fiona Taylor, Bruce A. Huber
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- Journal:
- Antarctic Science / Volume 32 / Issue 3 / June 2020
- Published online by Cambridge University Press:
- 04 March 2020, pp. 210-222
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A physical oceanographic, geophysical and marine geological survey of Edward VIII Gulf, Kemp Coast, collected data from conductivity–temperature–depth casts, multi-beam bathymetric swath mapping and 3.5 kHz sub-bottom surveying. Modified circumpolar deep water (mCDW) is observed in Edward VIII Gulf, as well as notable bathymetric features including mega-scale glacial lineations and a 1750 m-deep trough. Sedimentological, geochemical, rock-magnetic and micropalaeontological analysis of two kasten cores document regional palaeoclimate and palaeo-oceanographic conditions over the past 8000 years, with a warm period occurring from c. 8 to 4 ka and a shift to cooler conditions beginning at c. 4 ka and persisting until at least 0.9 ka. Sediment packages > 40 m thick within deep troughs in Edward VIII Gulf present potential targets for higher-resolution Holocene and deglacial climate studies. Despite the presence of mCDW on the shelf, inland bed topography consisting of highland terrain suggests the likelihood of relative stability of this sector of the East Antarctic Ice Sheet.
Contributors
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- By Brittany L. Anderson-Montoya, Heather R. Bailey, Carryl L. Baldwin, Daphne Bavelier, Jameson D. Beach, Jeffrey S. Bedwell, Kevin B. Bennett, Richard A. Block, Deborah A. Boehm-Davis, Corey J. Bohil, David B. Boles, Avinoam Borowsky, Jessica Bramlett, Allison A. Brennan, J. Christopher Brill, Matthew S. Cain, Meredith Carroll, Roberto Champney, Kait Clark, Nancy J. Cooke, Lori M. Curtindale, Clare Davies, Patricia R. DeLucia, Andrew E. Deptula, Michael B. Dillard, Colin D. Drury, Christopher Edman, James T. Enns, Sara Irina Fabrikant, Victor S. Finomore, Arthur D. Fisk, John M. Flach, Matthew E. Funke, Andre Garcia, Adam Gazzaley, Douglas J. Gillan, Rebecca A. Grier, Simen Hagen, Kelly Hale, Diane F. Halpern, Peter A. Hancock, Deborah L. Harm, Mary Hegarty, Laurie M. Heller, Nicole D. Helton, William S. Helton, Robert R. Hoffman, Jerred Holt, Xiaogang Hu, Richard J. Jagacinski, Keith S. Jones, Astrid M. L. Kappers, Simon Kemp, Robert C. Kennedy, Robert S. Kennedy, Alan Kingstone, Ioana Koglbauer, Norman E. Lane, Robert D. Latzman, Cynthia Laurie-Rose, Patricia Lee, Richard Lowe, Valerie Lugo, Poornima Madhavan, Leonard S. Mark, Gerald Matthews, Jyoti Mishra, Stephen R. Mitroff, Tracy L. Mitzner, Alexander M. Morison, Taylor Murphy, Takamichi Nakamoto, John G. Neuhoff, Karl M. Newell, Tal Oron-Gilad, Raja Parasuraman, Tiffany A. Pempek, Robert W. Proctor, Katie A. Ragsdale, Anil K. Raj, Millard F. Reschke, Evan F. Risko, Matthew Rizzo, Wendy A. Rogers, Jesse Q. Sargent, Mark W. Scerbo, Natasha B. Schwartz, F. Jacob Seagull, Cory-Ann Smarr, L. James Smart, Kay Stanney, James Staszewski, Clayton L. Stephenson, Mary E. Stuart, Breanna E. Studenka, Joel Suss, Leedjia Svec, James L. Szalma, James Tanaka, James Thompson, Wouter M. Bergmann Tiest, Lauren A. Vassiliades, Michael A. Vidulich, Paul Ward, Joel S. Warm, David A. Washburn, Christopher D. Wickens, Scott J. Wood, David D. Woods, Motonori Yamaguchi, Lin Ye, Jeffrey M. Zacks
- Edited by Robert R. Hoffman, Peter A. Hancock, University of Central Florida, Mark W. Scerbo, Old Dominion University, Virginia, Raja Parasuraman, George Mason University, Virginia, James L. Szalma, University of Central Florida
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- Book:
- The Cambridge Handbook of Applied Perception Research
- Published online:
- 05 July 2015
- Print publication:
- 26 January 2015, pp xi-xiv
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Contributors
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- By Aakash Agarwala, Linda S. Aglio, Rae M. Allain, Paul D. Allen, Houman Amirfarzan, Yasodananda Kumar Areti, Amit Asopa, Edwin G. Avery, Patricia R. Bachiller, Angela M. Bader, Rana Badr, Sibinka Bajic, David J. Baker, Sheila R. Barnett, Rena Beckerly, Lorenzo Berra, Walter Bethune, Sascha S. Beutler, Tarun Bhalla, Edward A. Bittner, Jonathan D. Bloom, Alina V. Bodas, Lina M. Bolanos-Diaz, Ruma R. Bose, Jan Boublik, John P. Broadnax, Jason C. Brookman, Meredith R. Brooks, Roland Brusseau, Ethan O. Bryson, Linda A. Bulich, Kenji Butterfield, William R. Camann, Denise M. Chan, Theresa S. Chang, Jonathan E. Charnin, Mark Chrostowski, Fred Cobey, Adam B. Collins, Mercedes A. Concepcion, Christopher W. Connor, Bronwyn Cooper, Jeffrey B. Cooper, Martha Cordoba-Amorocho, Stephen B. Corn, Darin J. Correll, Gregory J. Crosby, Lisa J. Crossley, Deborah J. Culley, Tomas Cvrk, Michael N. D'Ambra, Michael Decker, Daniel F. Dedrick, Mark Dershwitz, Francis X. Dillon, Pradeep Dinakar, Alimorad G. Djalali, D. John Doyle, Lambertus Drop, Ian F. Dunn, Theodore E. Dushane, Sunil Eappen, Thomas Edrich, Jesse M. Ehrenfeld, Jason M. Erlich, Lucinda L. Everett, Elliott S. Farber, Khaldoun Faris, Eddy M. Feliz, Massimo Ferrigno, Richard S. Field, Michael G. Fitzsimons, Hugh L. Flanagan Jr., Vladimir Formanek, Amanda A. Fox, John A. Fox, Gyorgy Frendl, Tanja S. Frey, Samuel M. Galvagno Jr., Edward R. Garcia, Jonathan D. Gates, Cosmin Gauran, Brian J. Gelfand, Simon Gelman, Alexander C. Gerhart, Peter Gerner, Omid Ghalambor, Christopher J. Gilligan, Christian D. Gonzalez, Noah E. Gordon, William B. Gormley, Thomas J. Graetz, Wendy L. Gross, Amit Gupta, James P. Hardy, Seetharaman Hariharan, Miriam Harnett, Philip M. Hartigan, Joaquim M. Havens, Bishr Haydar, Stephen O. Heard, James L. Helstrom, David L. Hepner, McCallum R. Hoyt, Robert N. Jamison, Karinne Jervis, Stephanie B. Jones, Swaminathan Karthik, Richard M. Kaufman, Shubjeet Kaur, Lee A. Kearse Jr., John C. Keel, Scott D. Kelley, Albert H. Kim, Amy L. Kim, Grace Y. Kim, Robert J. Klickovich, Robert M. Knapp, Bhavani S. Kodali, Rahul Koka, Alina Lazar, Laura H. Leduc, Stanley Leeson, Lisa R. Leffert, Scott A. LeGrand, Patricio Leyton, J. Lance Lichtor, John Lin, Alvaro A. Macias, Karan Madan, Sohail K. Mahboobi, Devi Mahendran, Christine Mai, Sayeed Malek, S. Rao Mallampati, Thomas J. Mancuso, Ramon Martin, Matthew C. Martinez, J. A. Jeevendra Martyn, Kai Matthes, Tommaso Mauri, Mary Ellen McCann, Shannon S. McKenna, Dennis J. McNicholl, Abdel-Kader Mehio, Thor C. Milland, Tonya L. K. Miller, John D. Mitchell, K. Annette Mizuguchi, Naila Moghul, David R. Moss, Ross J. Musumeci, Naveen Nathan, Ju-Mei Ng, Liem C. Nguyen, Ervant Nishanian, Martina Nowak, Ala Nozari, Michael Nurok, Arti Ori, Rafael A. Ortega, Amy J. Ortman, David Oxman, Arvind Palanisamy, Carlo Pancaro, Lisbeth Lopez Pappas, Benjamin Parish, Samuel Park, Deborah S. Pederson, Beverly K. Philip, James H. Philip, Silvia Pivi, Stephen D. Pratt, Douglas E. Raines, Stephen L. Ratcliff, James P. Rathmell, J. Taylor Reed, Elizabeth M. Rickerson, Selwyn O. Rogers Jr., Thomas M. Romanelli, William H. Rosenblatt, Carl E. Rosow, Edgar L. Ross, J. Victor Ryckman, Mônica M. Sá Rêgo, Nicholas Sadovnikoff, Warren S. Sandberg, Annette Y. Schure, B. Scott Segal, Navil F. Sethna, Swapneel K. Shah, Shaheen F. Shaikh, Fred E. Shapiro, Torin D. Shear, Prem S. Shekar, Stanton K. Shernan, Naomi Shimizu, Douglas C. Shook, Kamal K. Sikka, Pankaj K. Sikka, David A. Silver, Jeffrey H. Silverstein, Emily A. Singer, Ken Solt, Spiro G. Spanakis, Wolfgang Steudel, Matthias Stopfkuchen-Evans, Michael P. Storey, Gary R. Strichartz, Balachundhar Subramaniam, Wariya Sukhupragarn, John Summers, Shine Sun, Eswar Sundar, Sugantha Sundar, Neelakantan Sunder, Faraz Syed, Usha B. Tedrow, Nelson L. Thaemert, George P. Topulos, Lawrence C. Tsen, Richard D. Urman, Charles A. Vacanti, Francis X. Vacanti, Joshua C. Vacanti, Assia Valovska, Ivan T. Valovski, Mary Ann Vann, Susan Vassallo, Anasuya Vasudevan, Kamen V. Vlassakov, Gian Paolo Volpato, Essi M. Vulli, J. Matthias Walz, Jingping Wang, James F. Watkins, Maxwell Weinmann, Sharon L. Wetherall, Mallory Williams, Sarah H. Wiser, Zhiling Xiong, Warren M. Zapol, Jie Zhou
- Edited by Charles Vacanti, Scott Segal, Pankaj Sikka, Richard Urman
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- Book:
- Essential Clinical Anesthesia
- Published online:
- 05 January 2012
- Print publication:
- 11 July 2011, pp xv-xxviii
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