WASHINGTON, DC – The Editorial Board of the Proceedings of the National Academy of Sciences (PNAS) has selected six papers published by PNAS in 2020 to receive the Cozzarelli Prize, an award that recognizes outstanding contributions to the scientific disciplines represented by the National Academy of Sciences (NAS). Papers were chosen from the more than 3,600 research articles that appeared in the journal last year and represent the six broadly defined classes under which the NAS is organized. Additionally, the Editorial Board has recognized six papers—one in each class—as finalists for the 2020 Cozzarelli Prize.

The annual Cozzarelli Prize acknowledges papers that reflect scientific excellence and originality. The award was established in 2005 as the Paper of the Year Prize and was renamed in 2007 to honor late PNAS Editor-in-Chief Nicholas R. Cozzarelli. The 2020 awardees will be recognized at a virtual awards ceremony during the NAS Annual Meeting on April 25, 2021.

2020 Cozzarelli Prize Recipients

Class I: Physical and Mathematical Sciences

Winner:

Universal free-energy landscape produces efficient and reversible electron bifurcation

J. L. Yuly, P. Zhang, C. E. Lubner, J. W. Peters, and D. N. Beratan

Electron bifurcation is an often-reversible and efficient two-electron transfer process encountered in biological reaction networks, such as nitrogen fixation and carbon dioxide reduction. However, the physical principles that suppress energy-dissipating and short-circuiting reactions that might occur in bifurcating networks were unclear. Of the possible free-energy landscapes for reversible electron bifurcation, the authors found, efficient bifurcation emerges naturally in a generic free-energy scheme with two steep electron-transfer pathways branching from the bifurcating site. The results reveal the intrinsic properties of this free-energy landscape, illustrate how electron bifurcation can be realized with efficiency, and could guide future efforts to create synthetic electron bifurcation systems.

https://doi.org/10.1073/pnas.2010815117

Finalist:

Evidence for aggregation-independent, PrP^C-mediated Aβ cellular internalization

Alejandro R. Foley, Graham P. Roseman, Ka Chan, Amanda Smart, Thomas S. Finn, Kevin Yang, R. Scott Lokey, Glenn L. Millhauser, and Jevgenij A. Raskatov

https://doi.org/10.1073/pnas.2009238117

Class II: Biological Sciences

Winner:

B2 and ALU retrotransposons are self-cleaving ribozymes whose activity is enhanced by EZH2

Alfredo J. Hernandez, Athanasios Zovoilis, Catherine Cifuentes-Rojas, Lu Han, Bojan Bujisic, and Jeannie T. Lee

Ribozymes are segments of RNA that act as enzymes, but their physiological functions are often unclear. Working with the mouse genome, the authors examined B2 elements, which are short interspersed nuclear elements that produce RNA that is cleaved during interaction with the protein EZH2 and that activate genes implicated in heat stress. EZH2 is not a known nuclease enzyme, and the authors found that RNAs made from B2—as well as its human analog ALU—are self-cleaving ribozymes whose cleavage activity is accelerated in the presence of EZH2. The results suggest that B2/ALU elements, which may represent the predominant ribozyme activity in mammalian cells, can be classified as epigenetic ribozymes, which are gene expression switches that can be activated during stress.

https://doi.org/10.1073/pnas.1917190117

Finalist:

USP7 regulates ALS-associated proteotoxicity and quality control through the NEDD4L–SMAD pathway

Tao Zhang, Goran Periz, Yu-Ning Lu, and Jiou Wang

https://doi.org/10.1073/pnas.2014349117

Class III: Engineering and Applied Sciences

Winner:

A scalable pipeline for designing reconfigurable organisms

Sam Kriegman, Douglas Blackiston, Michael Levin, and Josh Bongard

For biotechnological applications, living organisms offer advantages such as self-renewal and biocompatibility, compared with inanimate technologies. Using artificial intelligence, the authors developed a process for designing synthetic organisms for specified functions. Next, the authors used a cell-based construction kit and pluripotent stem cells from Xenopus frogs to create the organisms using living cells. Using this approach, the authors designed and evolved in silico structures capable of locomotion, object manipulation, object transport, and collective behavior. Fabricated cellular structures emulated not only the form but also the function of the in silico designs. The results suggest a wide array of applications, from precise drug delivery to environmental remediation.

https://doi.org/10.1073/pnas.1910837117

Finalist:

Bioinspired underwater locomotion of light-driven liquid crystal gels

Hamed Shahsavan, Amirreza Aghakhani, Hao Zeng, Yubing Guo, Zoey S. Davidson, Arri Priimagi, and Metin Sitti

https://doi.org/10.1073/pnas.1917952117

Class IV: Biomedical Sciences

Winner:

HIV-1 uncoats in the nucleus near sites of integration

Ryan C. Burdick, Chenglei Li, MohamedHusen Munshi, Jonathan M. O. Rawson, Kunio Nagashima, Wei-Shau Hu, and Vinay K. Pathak

During infection, the human immunodeficiency virus (HIV-1) must disassemble the capsid coating surrounding its viral DNA before incorporating the DNA into the host genome. However, the intracellular location and timing of viral uncoating have been unclear, with previous studies suggesting uncoating in the cytoplasm and outside the nucleus. The authors labeled the HIV-1 capsid protein and identified infectious virions, finding that viral cores enter the nucleus intact or nearly intact, and that uncoating occurs near the genomic integration site, within 1.5 hours of integration. The findings provide fundamental insights into HIV-1 behavior upon entering human cells and suggest that maintaining an intact core until shortly before integration may aid efficient viral replication and evasion of cellular immune responses.

https://doi.org/10.1073/pnas.1920631117

Finalist:

Uncoupling DNA damage from chromatin damage to detoxify doxorubicin

Xiaohang Qiao, Sabina Y. van der Zanden, Dennis P. A. Wander, Daniel M. Borràs, Ji-Ying Song, Xiaoyang Li, Suzanne van Duikeren, Noortje van Gils, Arjo Rutten, Tessa van Herwaarden, Olaf van Tellingen, Elisa Giacomelli, Milena Bellin, Valeria Orlova, Leon G. J. Tertoolen, Sophie Gerhardt, Jimmy J. Akkermans, Jeroen M. Bakker, Charlotte L. Zuur, Baoxu Pang, Anke M. Smits, Christine L. Mummery, Linda Smit, Ramon Arens, Junmin Li, Hermen S. Overkleeft, and Jacques Neefjes

https://doi.org/10.1073/pnas.1922072117

Class V: Behavioral and Social Sciences

Winner:

Physician–patient racial concordance and disparities in birthing mortality for newborns

Brad N. Greenwood, Rachel R. Hardeman, Laura Huang, and Aaron Sojourner

Studies showing racial disparities in infant mortality find that Black newborns die at three times the rate of White newborns; other studies have found that underrepresented minorities may benefit from racial concordance between patient and physician. The authors examined records of 1.8 million hospital births in Florida between 1992 and 2015 and found that when Black newborns received care from Black physicians, the mortality disparity with White newborns was reduced by half. Racial concordance did not significantly improve mortality outcomes among Black birthing mothers. The findings suggest that the benefits of patient–physician racial concordance may be enhanced in challenging birth scenarios and in hospitals that deliver high numbers of Black babies.

https://doi.org/10.1073/pnas.1913405117

Finalist:

Cross-level sociodemographic homogeneity alters individual risk for completed suicide

Bernice A. Pescosolido, Byungkyu Lee, and Karen Kafadar

https://doi.org/10.1073/pnas.2006333117

Class VI: Applied Biological, Agricultural, and Environmental Sciences

Winner:

Fast behavioral feedbacks make ecosystems sensitive to pace and not just magnitude of anthropogenic environmental change

Michael A. Gil, Marissa L. Baskett, Stephan B. Munch, and Andrew M. Hein

Human-driven environmental changes can alter animal behavior, which, in turn, can affect species demographics. However, behavioral patterns are often not considered in population models designed to evaluate ecosystem responses to environmental change. The authors used extensive data on foraging behavior of herbivorous fish in a coral reef, combined with empirical demographic estimates, to develop a coupled behavioral–demographic ecosystem model. Inclusion of behavioral feedbacks revealed that the ecosystem was susceptible not only to the magnitude of changes in fishing pressure but also to the pace of change. The findings suggest that rapid changes, such as quickly increasing fishing to a given level, can collapse an ecosystem that would persist under more gradual change.

https://doi.org/10.1073/pnas.2003301117

Finalist:

Nutrient dilution and climate cycles underlie declines in a dominant insect herbivore

Ellen A. R. Welti, Karl A. Roeder, Kirsten M. de Beurs, Anthony Joern, and Michael Kaspari

https://doi.org/10.1073/pnas.1920012117

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