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Profile of Subra SureshDuring his long and distinguished career, Subra Suresh has made crucial contributions to the field of engineering. While finishing up high school in India in the 1970s, however, Suresh was not even sure of going to college, let alone becoming an engineer. Nonetheless, Suresh decided to take a shot at the entrance examination for the prestigious Indian Institutes of Technology. “A month before my exam, I bought a book to prepare and worked through some practice questions and just thought, go try it,” Suresh says. “To my surprise, I got in.” His degree in mechanical engineering from Indian Institutes of Technology Madras would turn out to be the starting point of a wide-ranging research career. Subra Suresh. Image credit: Nanyang Technological University, Singapore. Suresh’s research interests would eventually span engineering, basic science, and medicine. His multidisciplinary work led to elected memberships in all three US National Academies: The National Academy of Engineering in 2002, the National Academy of Sciences in 2012, and the National Academy of Medicine in 2013. Suresh has held several prestigious positions, from being dean of Massachusetts Institute of Technology’s School of Engineering and president of Carnegie Mellon University to leading the National Science Foundation (NSF) of the United States. Now President of Nanyang Technological University, Singapore, Suresh continues to push forward in research with his recent work on deforming nanoscale diamond. In his Inaugural Article (1), Suresh and his colleagues show computationally that it is possible to make nanoscale diamond behave like a metal with respect to select properties, which would open up a wide array of applications in microelectronics, optoelectronics, and solar energy. After obtaining his bachelor’s degree at Indian Institutes of Technology Madras, a scholarship offer led Suresh to attend Iowa State University for a Master’s degree in mechanical engineering. When he left for …
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QnAs with Janet CurrieMany mental illnesses arise in adolescence, and a study of national insurance claims in the United States finds a large variance in how adolescent patients are treated even within the same zip code. The findings, reported in Janet Currie’s Inaugural Article (IA) (1), reveal that 45% of adolescents receive first-line treatments that are not approved by the US Food and Drug Administration (FDA) (1). Currie, elected to the National Academy of Sciences in 2019, has studied children’s health for three decades. A professor of economics and public affairs at Princeton University, Currie has undertaken pioneering economic analysis of child development, including analysis of the effects of the Head Start program on children (2, 3) and the effects of expansions of the Medicaid program for pregnant women and children (4, 5). In her IA (1), Currie analyzes a large national dataset to reveal disparities in treatment that cannot be attributed to supply-side factors, such as limited availability of treatment providers. Janet Currie. Image credit: Princeton University/Denise Applewhite. > PNAS:What is the link between health and economics? > Currie:Health can have an impact on how much human capital, like education, people are able to acquire. Moreover, healthcare is a business, and it accounts for almost 20% of US GDP [gross domestic product]. So there are two strands: One is thinking about health as a business, and another is thinking about health as a form of wealth. My work generally focuses more on that second aspect of health as a form of human capital. The Inaugural Article (1) brings those two strands together to a certain extent because mental health problems in children are …
Remdesivir targets a structurally analogous region of the Ebola virus and SARS-CoV-2 polymerasesRemdesivir is a nucleotide analog prodrug that has been evaluated in humans against acute Ebola virus disease; it also recently received emergency use authorization for treating COVID-19. For antiviral product development, the Food and Drug Administration recommends the characterization of in vitro selected resistant viruses to define the specific antiviral mechanism of action. This study identified a single amino acid residue in the Ebola virus polymerase that conferred low-level resistance to remdesivir. The significance of our study lies not only in characterizing this particular mutation, but also in relating it to a resistance mutation observed in a similar structural motif of coronaviruses. Our findings thereby indicate a consistent mechanism of action by remdesivir across genetically divergent RNA viruses causing diseases of high consequence in humans. Remdesivir is a broad-spectrum antiviral nucleotide prodrug that has been clinically evaluated in Ebola virus patients and recently received emergency use authorization (EUA) for treatment of COVID-19. With approvals from the Federal Select Agent Program and the Centers for Disease Control and Prevention’s Institutional Biosecurity Board, we characterized the resistance profile of remdesivir by serially passaging Ebola virus under remdesivir selection; we generated lineages with low-level reduced susceptibility to remdesivir after 35 passages. We found that a single amino acid substitution, F548S, in the Ebola virus polymerase conferred low-level reduced susceptibility to remdesivir. The F548 residue is highly conserved in filoviruses but should be subject to specific surveillance among novel filoviruses, in newly emerging variants in ongoing outbreaks, and also in Ebola virus patients undergoing remdesivir therapy. Homology modeling suggests that the Ebola virus polymerase F548 residue lies in the F-motif of the polymerase active site, a region that was previously identified as susceptible to resistance mutations in coronaviruses. Our data suggest that molecular surveillance of this region of the polymerase in remdesivir-treated COVID-19 patients is also warranted. The raw data used for the manuscript figures has been submitted as [Dataset S1][1]. A master list of all SNVs detected at frequencies >15% across all lineages and all serial passages sequenced has been submitted as [Dataset S2][1]. NGS raw sequencing files are available upon request and have been deposited to National Center for Biotechnology Information Sequence Read Archive under BioProject number [PRJNA664887][2]. [1]: https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2012294117/-/DCSupplemental [2]: http://www.ncbi.nlm.nih.gov/bioproject?term=PRJNA664887