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209 A CTS Team Approach to Modeling Migration and Suppression of CCR2+/CX3CR1+ Myeloid Cells in Glioblastoma
- Hannah Anderson, Gregory P. Takacs, Christian Kreiger, Defang Luo, Libin Rong, Jeffrey K. Harrison, Tracy Stepien
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- Journal:
- Journal of Clinical and Translational Science / Volume 6 / Issue s1 / April 2022
- Published online by Cambridge University Press:
- 19 April 2022, p. 32
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OBJECTIVES/GOALS: Evaluate the migration and immune suppressive functions of CCR2+/CX3CR1+ myeloid-derived suppressor cells (MDSCs). Integrate experimental data and biologically relevant mathematical models of infiltrating MDSCs in the context of glioblastoma (GBM). METHODS/STUDY POPULATION: CCR2+/CX3CR1+ cells were enriched from bone marrow obtained from CCR2(+/RFP)/CX3CR1(+/GFP) glioma-bearing mice to evaluate their immune-suppressive phenotype and ability to migrate to CCL2 and CCL7. Fluorescent imaging and quantification were performed on a range of tumor sizes to acquire vasculature, tumor, T cell, and MDSC densities. A system of ordinary differential equations was constructed to represent the temporal dynamics of glioma cells, T cells, and MDSCs within the tumor microenvironment. The Approximate Bayesian Computation method was used to determine probability distributions of important parameters, such as the suppression rate of T cells by MDSCs. RESULTS/ANTICIPATED RESULTS: CCR2+/CX3CR1+ M-MDSCs isolated from the bone marrow of tumor-bearing mice suppress CD8+ T cell proliferation and IFNγ production. CCR2+/CX3CR1+ cells migrate to recombinant and KR158B glioma sourced CCL2 and CCL7. Parameter values determined by the Approximate Bayesian Computation method agreed with parameter values from experimental data. This result further validated the structure and results of the mathematical model when performing computer simulations; thus, we can predict CCR2+/CX3CR1+ M-MDSC infiltration over time. DISCUSSION/SIGNIFICANCE: The immune-suppressive microenvironment in GBM contributes to poor outcomes despite standard of care. This study integrates biological and mathematical models to better understand infiltrating immune-suppressive cells, namely CCR2+/CX3CR1+ M-MDSCs. Future directions include modeling immunotherapies.
84357 A TL1 Team Approach to Integrating Mathematical and Biological Models to Target Myeloid-Derived Immune Cells in Glioblastoma
- Gregory P. Takacs, Hannah Anderson, Christian Kreiger, Defang Luo, Libin Rong, Tracy Stepien, Jeffrey K. Harrison
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- Journal:
- Journal of Clinical and Translational Science / Volume 5 / Issue s1 / March 2021
- Published online by Cambridge University Press:
- 30 March 2021, p. 20
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ABSTRACT IMPACT: Predicting therapeutic responses in GBM. OBJECTIVES/GOALS: The goal of this team approach is to integrate mathematical models of glioblastoma (GBM) infiltrating myeloid cells that contribute to the immunosuppressive phenotype in glioma with experimental data to predict therapeutic responses to combined chemokine receptor and immune checkpoint blockade. METHODS/STUDY POPULATION: Orthotopic murine KR158-luc gliomas were established in fluorescent reporter CCR2WT/RFP CX3CR1WT/GFP mice. Subsequently, an anti-CD31 injection was administered to label the vasculature. Fluorescent imaging and quantification of anti-CD3 stained sections were performed on a range of tumor sizes to acquire vasculature, tumor, T cell, and myeloid cell densities. In parallel, a system of ordinary differential equations was formulated based on biological assumptions to evaluate the change over time of tumor cells, T cells, and infiltrating myeloid cells. The model was then refined and validated by experimental results. RESULTS/ANTICIPATED RESULTS: Fluorescent imaging and quantification revealed a correlation between tumor size and abundance of (CX3CR1+, CCR2-) and (CX3CR1+, CCR2+) myeloid cell populations in the tumor microenvironment. The density of these cell populations and vasculature remained constant as the tumors increased in size. Computer simulations of the mathematical model will predict tumor, myeloid, and T cell dynamics. These simulations will be particularly useful to uncover information regarding myeloid cell dynamics, such as cell entry time into the tumor microenvironment. Parameter sensitivity analysis of the model will inform us of the biological processes driving these tumor-immune cell dynamics. DISCUSSION/SIGNIFICANCE OF FINDINGS: GBM is a challenge as current intervention are ineffective. This study improves the understanding of glioma infiltrating myeloid cells and their impact on tumor progression. The data will serve as a basis for quantitatively predicting therapeutic responses of a novel combination treatment.
Summary of the Snowmastodon Project Special Volume A high-elevation, multi-proxy biotic and environmental record of MIS 6–4 from the Ziegler Reservoir fossil site, Snowmass Village, Colorado, USA
- Ian M. Miller, Jeffrey S. Pigati, R. Scott Anderson, Kirk R. Johnson, Shannon A. Mahan, Thomas A. Ager, Richard G. Baker, Maarten Blaauw, Jordon Bright, Peter M. Brown, Bruce Bryant, Zachary T. Calamari, Paul E. Carrara, Michael D. Cherney, John R. Demboski, Scott A. Elias, Daniel C. Fisher, Harrison J. Gray, Danielle R. Haskett, Jeffrey S. Honke, Stephen T. Jackson, Gonzalo Jiménez-Moreno, Douglas Kline, Eric M. Leonard, Nathaniel A. Lifton, Carol Lucking, H. Gregory McDonald, Dane M. Miller, Daniel R. Muhs, Stephen E. Nash, Cody Newton, James B. Paces, Lesley Petrie, Mitchell A. Plummer, David F. Porinchu, Adam N. Rountrey, Eric Scott, Joseph J.W. Sertich, Saxon E. Sharpe, Gary L. Skipp, Laura E. Strickland, Richard K. Stucky, Robert S. Thompson, Jim Wilson
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- Journal:
- Quaternary Research / Volume 82 / Issue 3 / November 2014
- Published online by Cambridge University Press:
- 20 January 2017, pp. 618-634
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In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.
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- By Lenard A. Adler, Pinky Agarwal, Rehan Ahmed, Jagga Rao Alluri, Fawaz Al-Mufti, Samuel Alperin, Michael Amoashiy, Michael Andary, David J. Anschel, Padmaja Aradhya, Vandana Aspen, Esther Baldinger, Jee Bang, George D. Baquis, John J. Barry, Jason J. S. Barton, Julius Bazan, Amanda R. Bedford, Marlene Behrmann, Lourdes Bello-Espinosa, Ajay Berdia, Alan R. Berger, Mark Beyer, Don C. Bienfang, Kevin M. Biglan, Thomas M. Boes, Paul W. Brazis, Jonathan L. Brisman, Jeffrey A. Brown, Scott E. Brown, Ryan R. Byrne, Rina Caprarella, Casey A. Chamberlain, Wan-Tsu W. Chang, Grace M. Charles, Jasvinder Chawla, David Clark, Todd J. Cohen, Joe Colombo, Howard Crystal, Vladimir Dadashev, Sarita B. Dave, Jean Robert Desrouleaux, Richard L. Doty, Robert Duarte, Jeffrey S. Durmer, Christyn M. Edmundson, Eric R. Eggenberger, Steven Ender, Noam Epstein, Alberto J. Espay, Alan B. Ettinger, Niloofar (Nelly) Faghani, Amtul Farheen, Edward Firouztale, Rod Foroozan, Anne L. Foundas, David Elliot Friedman, Deborah I. Friedman, Steven J. Frucht, Oded Gerber, Tal Gilboa, Martin Gizzi, Teneille G. Gofton, Louis J. Goodrich, Malcolm H. Gottesman, Varda Gross-Tsur, Deepak Grover, David A. Gudis, John J. Halperin, Maxim D. Hammer, Andrew R. Harrison, L. Anne Hayman, Galen V. Henderson, Steven Herskovitz, Caitlin Hoffman, Laryssa A. Huryn, Andres M. Kanner, Gary P. Kaplan, Bashar Katirji, Kenneth R. Kaufman, Annie Killoran, Nina Kirz, Gad E. Klein, Danielle G. Koby, Christopher P. Kogut, W. Curt LaFrance, Patrick J.M. Lavin, Susan W. Law, James L. Levenson, Richard B. Lipton, Glenn Lopate, Daniel J. Luciano, Reema Maindiratta, Robert M. Mallery, Georgios Manousakis, Alan Mazurek, Luis J. Mejico, Dragana Micic, Ali Mokhtarzadeh, Walter J. Molofsky, Heather E. Moss, Mark L. Moster, Manpreet Multani, Siddhartha Nadkarni, George C. Newman, Rolla Nuoman, Paul A. Nyquist, Gaia Donata Oggioni, Odi Oguh, Denis Ostrovskiy, Kristina Y. Pao, Juwen Park, Anastas F. Pass, Victoria S. Pelak, Jeffrey Peterson, John Pile-Spellman, Misha L. Pless, Gregory M. Pontone, Aparna M. Prabhu, Michael T. Pulley, Philip Ragone, Prajwal Rajappa, Venkat Ramani, Sindhu Ramchandren, Ritesh A. Ramdhani, Ramses Ribot, Heidi D. Riney, Diana Rojas-Soto, Michael Ronthal, Daniel M. Rosenbaum, David B. Rosenfield, Durga Roy, Michael J. Ruckenstein, Max C. Rudansky, Eva Sahay, Friedhelm Sandbrink, Jade S. Schiffman, Angela Scicutella, Maroun T. Semaan, Robert C. Sergott, Aashit K. Shah, David M. Shaw, Amit M. Shelat, Claire A. Sheldon, Anant M. Shenoy, Yelizaveta Sher, Jessica A. Shields, Tanya Simuni, Rajpaul Singh, Eric E. Smouha, David Solomon, Mehri Songhorian, Steven A. Sparr, Egilius L. H. Spierings, Eve G. Spratt, Beth Stein, S.H. Subramony, Rosa Ana Tang, Cara Tannenbaum, Hakan Tekeli, Amanda J. Thompson, Michael J. Thorpy, Matthew J. Thurtell, Pedro J. Torrico, Ira M. Turner, Scott Uretsky, Ruth H. Walker, Deborah M. Weisbrot, Michael A. Williams, Jacques Winter, Randall J. Wright, Jay Elliot Yasen, Shicong Ye, G. Bryan Young, Huiying Yu, Ryan J. Zehnder
- Edited by Alan B. Ettinger, Albert Einstein College of Medicine, New York, Deborah M. Weisbrot, State University of New York, Stony Brook
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- Neurologic Differential Diagnosis
- Published online:
- 05 June 2014
- Print publication:
- 17 April 2014, pp xi-xx
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- By Krista Adamek, Ana Luisa K. Albernaz, J. Marcio Ayres†, Andrew J. Baker, Karen L. Bales, Adrian A. Barnett, Christopher Barton, John M. Bates, Jennie Becker, Bruna M. Bezerra, Júlio César Bicca-Marques, Richard Bodmer, Jean P. Boubli, Mark Bowler, Sarah A. Boyle, Christini Barbosa Caselli, Janice Chism, Elena P. Cunningham, José Maria C. da Silva, Lesa C. Davies, Nayara de Alcântara Cardoso, Manuella A. de Souza, Stella de la Torre, Ana Gabriela de Luna, Thomas R. Defler, Anthony Di Fiore, Eduardo Fernandez-Duque, Stephen F. Ferrari, Wilsea M.B. Figueiredo-Ready, Tracy Frampton, Paul A. Garber, Brian W. Grafton, L. Tremaine Gregory, Maria L. Harada, Amy Harrison-Levine, Walter C. Hartwig, Stefanie Heiduck, Eckhard W. Heymann, André Hirsch, Leandro Jerusalinsky, Gareth Jones, Richard F. Kay, Martin M. Kowalewski, Shawn M. Lehman, Laura Marsh, Jesús Martinez, William A. Mason, Hope Matthews, Wynlyn McBride, Shona McCann-Wood, W. Scott McGraw, D. Jeffrey Meldrum, Sally P. Mendoza, Nohelia Mercado, Russell A. Mittermeier, Mirjam N. Nadjafzadeh, Marilyn A. Norconk, Robert Gary Norman, Marcela Oliveira, Marcelo M. Oliveira, Maria Juliana Ospina Rodríguez, Erwin Palacios, Suzanne Palminteri, Liliam P. Pinto, Marcio Port-Carvalho, Leila Porter, Carlos Portillo-Quintero, George Powell, Ghillean T. Prance, Rodrigo C. Printes, Pablo Puertas, P. Kirsten Pullen, Helder L. Queiroz, Luis Reginaldo R. Rodrigues, Adriana Rodríguez, Alfred L. Rosenberger, Anthony B. Rylands, Ricardo R. Santos, Horacio Schneider, Eleonore Z.F. Setz, Suleima S.B. Silva, José S. Silva Júnior, Andrew T. Smith, Marcelo C. Sousa, Antonio S. Souto, Wilson R. Spironello, Masanaru Takai, Marcelo F. Tejedor, Cynthia L. Thompson, Diego G. Tirira, Raul Tupayachi, Bernardo Urbani, Liza M. Veiga, Marianela Velilla, João Valsecchi, Jean-Christophe Vié, Tatiana M. Vieira, Suzanne E. Walker-Pacheco, Rob Wallace, Patricia C. Wright, Charles E. Zartman
- Edited by Liza M. Veiga, Universidade Federal do Pará, Brazil, Adrian A. Barnett, Roehampton University, London, Stephen F. Ferrari, Universidade Federal de Sergipe, Brazil, Marilyn A. Norconk, Kent State University, Ohio
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- Evolutionary Biology and Conservation of Titis, Sakis and Uacaris
- Published online:
- 05 April 2013
- Print publication:
- 11 April 2013, pp xii-xv
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