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The challenges of modeling and forecasting the spread of COVID-19.

Andrea L Bertozzi, Elisa Franco, George Mohler, Martin B Short, Daniel Sledge,

The coronavirus disease 2019 (COVID-19) pandemic has placed epidemic modeling at the forefront of worldwide public policy making. Nonetheless, modeling and forecasting the spread of COVID-19 remains a challenge. Here, we detail three regional-scale models for forecasting and assessing the course of the pandemic. This work demonstrates the utility of ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Extensive sequence and structural evolution of Arginase 2 inhibitory antibodies enabled by an unbiased approach to affinity maturation.

Denice T Y Chan, Lesley Jenkinson, Stuart W Haynes, Mark Austin, Agata Diamandakis, Daniel Burschowsky, Chitra Seewooruthun, Alexandra Addyman, Sebastian Fiedler, Stephanie Ryman, Jessica Whitehouse, Louise H Slater, Ellen Gowans, Yoko Shibata, Michelle Barnard, Robert W Wilkinson, Tristan J Vaughan, Sarah V Holt, Vincenzo Cerundolo, Mark D Carr, Maria A T Groves,

Affinity maturation is a powerful technique in antibody engineering for the in vitro evolution of antigen binding interactions. Key to the success of this process is the expansion of sequence and combinatorial diversity to increase the structural repertoire from which superior binding variants may be selected. However, conventional strategies are ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Premature termination codons in the DMD gene cause reduced local mRNA synthesis.

Raquel García-Rodríguez, Monika Hiller, Laura Jiménez-Gracia, Zarah van der Pal, Judit Balog, Kevin Adamzek, Annemieke Aartsma-Rus, Pietro Spitali,

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene leading to the presence of premature termination codons (PTC). Previous transcriptional studies have shown reduced DMD transcript levels in DMD patient and animal model muscles when PTC are present. Nonsense-mediated decay (NMD) has been suggested to be responsible ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Extracellular proteolytic cascade in tomato activates immune protease Rcr3.

Judith K Paulus, Jiorgos Kourelis, Selva Ramasubramanian, Felix Homma, Alice Godson, Anja C Hörger, Tram Ngoc Hong, Daniel Krahn, Laura Ossorio Carballo, Shuaishuai Wang, Joe Win, Matthew Smoker, Sophien Kamoun, Suomeng Dong, Renier A L van der Hoorn,

Proteolytic cascades regulate immunity and development in animals, but these cascades in plants have not yet been reported. Here we report that the extracellular immune protease Rcr3 of tomato is activated by P69B and other subtilases (SBTs), revealing a proteolytic cascade regulating extracellular immunity in solanaceous plants. Rcr3 is a ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators, and role in key physiological response.

Saugat Poudel, Hannah Tsunemoto, Yara Seif, Anand V Sastry, Richard Szubin, Sibei Xu, Henrique Machado, Connor A Olson, Amitesh Anand, Joe Pogliano, Victor Nizet, Bernhard O Palsson,

The ability of Staphylococcus aureus to infect many different tissue sites is enabled, in part, by its transcriptional regulatory network (TRN) that coordinates its gene expression to respond to different environments. We elucidated the organization and activity of this TRN by applying independent component analysis to a compendium of 108 ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Base rate neglect and neural computations for subjective weight in decision under uncertainty.

Yun-Yen Yang, Shih-Wei Wu,

Base rate neglect, an important bias in estimating probability of uncertain events, describes humans' tendency to underweight base rate (prior) relative to individuating information (likelihood). However, the neural mechanisms that give rise to this bias remain elusive. In this study, subjects chose between uncertain prospects where estimating reward probability was ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Male reproductive aging arises via multifaceted mating-dependent sperm and seminal proteome declines, but is postponable in Drosophila.

Irem Sepil, Ben R Hopkins, Rebecca Dean, Eleanor Bath, Solomon Friedman, Ben Swanson, Harrison J Ostridge, Lucy Harper, Norene A Buehner, Mariana F Wolfner, Rebecca Konietzny, Marie-Laëtitia Thézénas, Elizabeth Sandham, Philip D Charles, Roman Fischer, Josefa Steinhauer, Benedikt M Kessler, Stuart Wigby,

Declining ejaculate performance with male age is taxonomically widespread and has broad fitness consequences. Ejaculate success requires fully functional germline (sperm) and soma (seminal fluid) components. However, some aging theories predict that resources should be preferentially diverted to the germline at the expense of the soma, suggesting differential impacts of ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Nur77 controls tolerance induction, terminal differentiation, and effector functions in semi-invariant natural killer T cells.

Amrendra Kumar, Timothy M Hill, Laura E Gordy, Naveenchandra Suryadevara, Lan Wu, Andrew I Flyak, Jelena S Bezbradica, Luc Van Kaer, Sebastian Joyce,

Semi-invariant natural killer T (iNKT) cells are self-reactive lymphocytes, yet how this lineage attains self-tolerance remains unknown. iNKT cells constitutively express high levels of Nr4a1-encoded Nur77, a transcription factor that integrates signal strength downstream of the T cell receptor (TCR) within activated thymocytes and peripheral T cells. The function of ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Screen identifies DYRK1B network as mediator of transcription repression on damaged chromatin.

Chao Dong, Kirk L West, Xin Yi Tan, Junshi Li, Toyotaka Ishibashi, Cheng-Han Yu, Shirley M H Sy, Justin W C Leung, Michael S Y Huen,

DNA double-strand breaks (DSBs) trigger transient pausing of nearby transcription, an emerging ATM-dependent response that suppresses chromosomal instability. We screened a chemical library designed to target the human kinome for new activities that mediate gene silencing on DSB-flanking chromatin, and have uncovered the DYRK1B kinase as an early respondent to ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Cofactor-enabled functional expression of fruit fly, honeybee, and bumblebee nicotinic receptors reveals picomolar neonicotinoid actions.

Makoto Ihara, Shogo Furutani, Sho Shigetou, Shota Shimada, Kunihiro Niki, Yuma Komori, Masaki Kamiya, Wataru Koizumi, Leo Magara, Mai Hikida, Akira Noguchi, Daiki Okuhara, Yuto Yoshinari, Shu Kondo, Hiromu Tanimoto, Ryusuke Niwa, David B Sattelle, Kazuhiko Matsuda,

The difficulty of achieving robust functional expression of insect nicotinic acetylcholine receptors (nAChRs) has hampered our understanding of these important molecular targets of globally deployed neonicotinoid insecticides at a time when concerns have grown regarding the toxicity of this chemotype to insect pollinators. We show that thioredoxin-related transmembrane protein 3 ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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An engineered chimeric toxin that cleaves activated mutant and wild-type RAS inhibits tumor growth.

Vania Vidimar, Greg L Beilhartz, Minyoung Park, Marco Biancucci, Matthew B Kieffer, David R Gius, Roman A Melnyk, Karla J F Satchell,

Despite nearly four decades of effort, broad inhibition of oncogenic RAS using small-molecule approaches has proven to be a major challenge. Here we describe the development of a pan-RAS biologic inhibitor composed of the RAS-RAP1-specific endopeptidase fused to the protein delivery machinery of diphtheria toxin. We show that this engineered ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Dynamic neural and glial responses of a head-specific model for traumatic brain injury in Drosophila.

Janani Saikumar, China N Byrns, Matthew Hemphill, David F Meaney, Nancy M Bonini,

Traumatic brain injury (TBI) is the strongest environmental risk factor for the accelerated development of neurodegenerative diseases. There are currently no therapeutics to address this due to lack of insight into mechanisms of injury progression, which are challenging to study in mammalian models. Here, we have developed and extensively characterized ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Inner Workings: Was Jupiter born beyond the current orbits of Neptune and Pluto?

Ken Croswell,

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Time-dependent plasticity in silicon microbeams mediated by dislocation nucleation.

Mohamed Elhebeary, Tristan Harzer, Gerhard Dehm, M Taher A Saif,

Understanding deformation mechanisms in silicon is critical for reliable design of miniaturized devices operating at high temperatures. Bulk silicon is brittle, but it becomes ductile at about 540 °C. It creeps (deforms plastically with time) at high temperatures (∼800 °C). However, the effect of small size on ductility and creep ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Bioinspired nervous signal transmission system based on two-dimensional laminar nanofluidics: From electronics to ionics.

Yunfei Teng, Pei Liu, Lin Fu, Xiang-Yu Kong, Lei Jiang, Liping Wen,

Mammalian nervous systems, as natural ionic circuitries, stand out in environmental perception and sophisticated information transmission, relying on protein ionic channels and additional necessary structures. Prosperously emerged ionic regulated biomimetic nanochannels exhibit great potentialities in various application scenarios, especially signal transduction. Most reported direct current systems possess deficiencies in informational ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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The E3 ubiquitin ligase MARCH1 regulates antimalaria immunity through interferon signaling and T cell activation.

Jian Wu, Lu Xia, Xiangyu Yao, Xiao Yu, Keyla C Tumas, Wenxiang Sun, Yang Cheng, Xiao He, Yu-Chih Peng, Brajesh K Singh, Cui Zhang, Chen-Feng Qi, Silvia Bolland, Sonja M Best, Channe Gowda, Ruili Huang, Timothy G Myers, Carole A Long, Rong-Fu Wang, Xin-Zhuan Su,

Malaria infection induces complex and diverse immune responses. To elucidate the mechanisms underlying host-parasite interaction, we performed a genetic screen during early (24 h) Plasmodium yoelii infection in mice and identified a large number of interacting host and parasite genes/loci after transspecies expression quantitative trait locus (Ts-eQTL) analysis. We next ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface.

Uddhav K Shigdel, Seung-Joo Lee, Mathew E Sowa, Brian R Bowman, Keith Robison, Minyun Zhou, Khian Hong Pua, Dylan T Stiles, Joshua A V Blodgett, Daniel W Udwary, Andrew T Rajczewski, Alan S Mann, Siavash Mostafavi, Tara Hardy, Sukrat Arya, Zhigang Weng, Michelle Stewart, Kyle Kenyon, Jay P Morgenstern, Ende Pan, Daniel C Gray, Roy M Pollock, Andrew M Fry, Richard D Klausner, Sharon A Townson, Gregory L Verdine,

The vast majority of intracellular protein targets are refractory toward small-molecule therapeutic engagement, and additional therapeutic modalities are needed to overcome this deficiency. Here, the identification and characterization of a natural product, WDB002, reveals a therapeutic modality that dramatically expands the currently accepted limits of druggability. WDB002, in complex with ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Turning up the heat on HIV-1.

Irene P Chen, Melanie Ott,

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Stem cell lineage survival as a noisy competition for niche access.

Bernat Corominas-Murtra, Colinda L G J Scheele, Kasumi Kishi, Saskia I J Ellenbroek, Benjamin D Simons, Jacco van Rheenen, Edouard Hannezo,

Understanding to what extent stem cell potential is a cell-intrinsic property or an emergent behavior coming from global tissue dynamics and geometry is a key outstanding question of systems and stem cell biology. Here, we propose a theory of stem cell dynamics as a stochastic competition for access to a ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Intercepting second-messenger signaling by rationally designed peptides sequestering c-di-GMP.

Chee-Seng Hee, Judith Habazettl, Christoph Schmutz, Tilman Schirmer, Urs Jenal, Stephan Grzesiek,

The bacterial second messenger cyclic diguanylate (c-di-GMP) regulates a wide range of cellular functions from biofilm formation to growth and survival. Targeting a second-messenger network is challenging because the system involves a multitude of components with often overlapping functions. Here, we present a strategy to intercept c-di-GMP signaling pathways by ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Sir2 takes affirmative action to ensure equal opportunity in replication origin licensing.

Armelle Lengronne, Philippe Pasero,

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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X-ray processing of a realistic ice mantle can explain the gas abundances in protoplanetary disks.

Angela Ciaravella, Guillermo M Muñoz Caro, Antonio Jiménez-Escobar, Cesare Cecchi-Pestellini, Li-Chieh Hsiao, Chao-Hui Huang, Yu-Jung Chen,

The Atacama Large Millimeter Array has allowed a detailed observation of molecules in protoplanetary disks, which can evolve toward solar systems like our own. While CO, [Formula: see text], HCO, and [Formula: see text] are often abundant species in the cold zones of the disk, [Formula: see text] or [Formula: ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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An essential role for cardiolipin in the stability and function of the mitochondrial calcium uniporter.

Sagnika Ghosh, Writoban Basu Ball, Travis R Madaris, Subramanya Srikantan, Muniswamy Madesh, Vamsi K Mootha, Vishal M Gohil,

Calcium uptake by the mitochondrial calcium uniporter coordinates cytosolic signaling events with mitochondrial bioenergetics. During the past decade all protein components of the mitochondrial calcium uniporter have been identified, including MCU, the pore-forming subunit. However, the specific lipid requirements, if any, for the function and formation of this channel complex ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Acquirement of water-splitting ability and alteration of the charge-separation mechanism in photosynthetic reaction centers.

Hiroyuki Tamura, Keisuke Saito, Hiroshi Ishikita,

In photosynthetic reaction centers from purple bacteria (PbRC) and the water-oxidizing enzyme, photosystem II (PSII), charge separation occurs along one of the two symmetrical electron-transfer branches. Here we report the microscopic origin of the unidirectional charge separation, fully considering electron-hole interaction, electronic coupling of the pigments, and electrostatic interaction with ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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Active forces shape the metaphase spindle through a mechanical instability.

David Oriola, Frank Jülicher, Jan Brugués,

The metaphase spindle is a dynamic structure orchestrating chromosome segregation during cell division. Recently, soft matter approaches have shown that the spindle behaves as an active liquid crystal. Still, it remains unclear how active force generation contributes to its characteristic spindle-like shape. Here we combine theory and experiments to show ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2020, :]

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