Febrile temperature change modulates CD4 T cell differentiation via a TRPV channel-regulated Notch-dependent pathway [Immunology and Inflammation]
Fever is a conserved and prominent response to infection. Yet, the issue of how CD4 T cell responses are modulated if they occur at fever temperatures remains poorly addressed. We have examined the priming of naive CD4 T cells in vitro at fever temperatures, and we report notable fever-mediated modulation... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Danish Umar, Arundhoti Das, Suman Gupta, Somdeb Chattopadhyay, Debayan Sarkar, Gauri Mirji, Jeet Kalia, Gopalakrishnan Aneeshkumar Arimbasseri, Jeannine Marie Durdik, Satyajit Rath, Anna George, Vineeta Bal Tags: Biological Sciences Source Type: research

IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome [Immunology and Inflammation]
Cytokine release syndrome (CRS) is a life-threatening complication induced by systemic inflammatory responses to infections, including bacteria and chimeric antigen receptor T cell therapy. There are currently no immunotherapies with proven clinical efficacy and understanding of the molecular mechanisms of CRS pathogenesis is limited. Here, we found that patients diagnosed... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Sujin Kang, Toshio Tanaka, Hitomi Inoue, Chikako Ono, Shoji Hashimoto, Yoshiyuki Kioi, Hisatake Matsumoto, Hiroshi Matsuura, Tsunehiro Matsubara, Kentaro Shimizu, Hiroshi Ogura, Yoshiharu Matsuura, Tadamitsu Kishimoto Tags: Coronavirus (COVID-19) Biological Sciences Source Type: research

Conformational diversity facilitates antibody mutation trajectories and discrimination between foreign and self-antigens [Immunology and Inflammation]
Conformational diversity and self-cross-reactivity of antigens have been correlated with evasion from neutralizing antibody responses. We utilized single cell B cell sequencing, biolayer interferometry and X-ray crystallography to trace mutation selection pathways where the antibody response must resolve cross-reactivity between foreign and self-proteins bearing near-identical contact surfaces, but differing in... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Deborah L. Burnett, Peter Schofield, David B. Langley, Jennifer Jackson, Katherine Bourne, Emily Wilson, Benjamin T. Porebski, Ashley M. Buckle, Robert Brink, Christopher C. Goodnow, Daniel Christ Tags: Biological Sciences Source Type: research

CHD8 dosage regulates transcription in pluripotency and early murine neural differentiation [Genetics]
The chromatin remodeler CHD8 is among the most frequently mutated genes in autism spectrum disorder (ASD). CHD8 has a dosage-sensitive role in ASD, but when and how it becomes critical to human social function is unclear. Here, we conducted genomic analyses of heterozygous and homozygous Chd8 mouse embryonic stem cells... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Sabina Sood, Christopher M. Weber, H. Courtney Hodges, Andrey Krokhotin, Aryaman Shalizi, Gerald R. Crabtree Tags: Biological Sciences Source Type: research

Detecting selection with a genetic cross [Evolution]
Distinguishing which traits have evolved under natural selection, as opposed to neutral evolution, is a major goal of evolutionary biology. Several tests have been proposed to accomplish this, but these either rely on false assumptions or suffer from low power. Here, I introduce an approach to detecting selection that makes... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Hunter B. Fraser Tags: Biological Sciences Source Type: research

Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates [Evolution]
The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Joana Damas, Graham M. Hughes, Kathleen C. Keough, Corrie A. Painter, Nicole S. Persky, Marco Corbo, Michael Hiller, Klaus-Peter Koepfli, Andreas R. Pfenning, Huabin Zhao, Diane P. Genereux, Ross Swofford, Katherine S. Pollard, Oliver A. Ryder, Martin T. Tags: Coronavirus (COVID-19) Biological Sciences Source Type: research

Genome-wide analyses reveal drivers of penguin diversification [Evolution]
Penguins are the only extant family of flightless diving birds. They currently comprise at least 18 species, distributed from polar to tropical environments in the Southern Hemisphere. The history of their diversification and adaptation to these diverse environments remains controversial. We used 22 new genomes from 18 penguin species to... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Juliana A. Vianna, Flavia A. N. Fernandes, Maria Jose Frugone, Henrique V. Figueiro, Luis R. Pertierra, Daly Noll, Ke Bi, Cynthia Y. Wang–Claypool, Andrew Lowther, Patricia Parker, Celine Le Bohec, Francesco Bonadonna, Barbara Wienecke, Pierre Pisto Tags: Biological Sciences Source Type: research

Isotopic evidence for the timing of the dietary shift toward C4 foods in eastern African Paranthropus [Evolution]
New approaches to the study of early hominin diets have refreshed interest in how and when our diets diverged from those of other African apes. A trend toward significant consumption of C4 foods in hominins after this divergence has emerged as a landmark event in human evolution, with direct evidence... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Jonathan G. Wynn, Zeresenay Alemseged, Rene Bobe, Frederick E. Grine, Enquye W. Negash, Matt Sponheimer Tags: Social Sciences Source Type: research

Robust paths to net greenhouse gas mitigation and negative emissions via advanced biofuels [Environmental Sciences]
Biofuel and bioenergy systems are integral to most climate stabilization scenarios for displacement of transport sector fossil fuel use and for producing negative emissions via carbon capture and storage (CCS). However, the net greenhouse gas mitigation benefit of such pathways is controversial due to concerns around ecosystem carbon losses from... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: John L. Field, Tom L. Richard, Erica A. H. Smithwick, Hao Cai, Mark S. Laser, David S. LeBauer, Stephen P. Long, Keith Paustian, Zhangcai Qin, John J. Sheehan, Pete Smith, Michael Q. Wang, Lee R. Lynd Tags: Sustainability Science Physical Sciences Source Type: research

Elucidating the G'' overshoot in soft materials with a yield transition via a time-resolved experimental strain decomposition [Engineering]
Materials that exhibit yielding behavior are used in many applications, from spreadable foods and cosmetics to direct write three-dimensional printing inks and filled rubbers. Their key design feature is the ability to transition behaviorally from solid to fluid under sufficient load or deformation. Despite its widespread applications, little is known... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Gavin J. Donley, Piyush K. Singh, Abhishek Shetty, Simon A. Rogers Tags: Physical Sciences Source Type: research

The global value of water in agriculture [Economic Sciences]
Major environmental functions and human needs critically depend on water. In regions of the world affected by water scarcity economic activities can be constrained by water availability, leading to competition both among sectors and between human uses and environmental needs. While the commodification of water remains a contentious political issue,... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Paolo D’Odorico, Davide Danilo Chiarelli, Lorenzo Rosa, Alfredo Bini, David Zilberman, Maria Cristina Rulli Tags: Social Sciences Source Type: research

The allometry of movement predicts the connectivity of communities [Ecology]
Connectivity has long played a central role in ecological and evolutionary theory and is increasingly emphasized for conserving biodiversity. Nonetheless, connectivity assessments often focus on individual species even though understanding and preserving connectivity for entire communities is urgently needed. Here we derive and test a framework that harnesses the well-known... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Jack Hartfelder, Chevonne Reynolds, Richard A. Stanton, Muzi Sibiya, Ara Monadjem, Robert A. McCleery, Robert J. Fletcher Jr Tags: Biological Sciences Source Type: research

Shape, size, and quantity of ingested external abrasives influence dental microwear texture formation in guinea pigs [Ecology]
Food processing wears down teeth, thus affecting tooth functionality and evolutionary success. Other than intrinsic silica phytoliths, extrinsic mineral dust/grit adhering to plants causes tooth wear in mammalian herbivores. Dental microwear texture analysis (DMTA) is widely applied to infer diet from microscopic dental wear traces. The relationship between external abrasives... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Daniela E. Winkler, Thomas Tutken, Ellen Schulz–Kornas, Thomas M. Kaiser, Jacqueline Muller, Jennifer Leichliter, Katrin Weber, Jean–Michel Hatt, Marcus Clauss Tags: Biological Sciences Source Type: research

Animal body size distribution influences the ratios of nutrients supplied to plants [Ecology]
Nutrients released through herbivore feces have the potential to influence plant-available nutrients and affect primary productivity. However, herbivore species use nutrients in set stoichiometric ratios that vary with body size. Such differences in the ratios at which nutrients are used leads to differences in the ratios at which nutrients are... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Elizabeth le Roux, Laura S. van Veenhuisen, Graham I. H. Kerley, Joris P. G. M. Cromsigt Tags: Biological Sciences Source Type: research

Resolving the Dust Bowl paradox of grassland responses to extreme drought [Ecology]
During the 1930s Dust Bowl drought in the central United States, species with the C3 photosynthetic pathway expanded throughout C4-dominated grasslands. This widespread increase in C3 grasses during a decade of low rainfall and high temperatures is inconsistent with well-known traits of C3 vs. C4 pathways. Indeed, water use efficiency... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Alan K. Knapp, Anping Chen, Robert J. Griffin-Nolan, Lauren E. Baur, Charles J.W. Carroll, Jesse E. Gray, Ava M. Hoffman, Xiran Li, Alison K. Post, Ingrid J. Slette, Scott L. Collins, Yiqi Luo, Melinda D. Smith Tags: Biological Sciences Source Type: research

Genetic diversity of soil invertebrates corroborates timing estimates for past collapses of the West Antarctic Ice Sheet [Earth, Atmospheric, and Planetary Sciences]
During austral summer field seasons between 1999 and 2018, we sampled at 91 locations throughout southern Victoria Land and along the Transantarctic Mountains for six species of endemic microarthropods (Collembola), covering a latitudinal range from 76.0°S to 87.3°S. We assembled individual mitochondrial cytochrome c oxidase subunit 1 (COI) sequences (n... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Gemma E. Collins, Ian D. Hogg, Peter Convey, Leopoldo G. Sancho, Don A. Cowan, W. Berry Lyons, Byron J. Adams, Diana H. Wall, T. G. Allan Green Tags: Biological Sciences Source Type: research

Global variability in seawater Mg:Ca and Sr:Ca ratios in the modern ocean [Earth, Atmospheric, and Planetary Sciences]
Seawater Mg:Ca and Sr:Ca ratios are biogeochemical parameters reflecting the Earth–ocean–atmosphere dynamic exchange of elements. The ratios’ dependence on the environment and organisms' biology facilitates their application in marine sciences. Here, we present a measured single-laboratory dataset, combined with previous data, to test the assumption of limited seawater Mg:Ca and... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Mario Lebrato, Dieter Garbe–Schonberg, Marius N. Muller, Sonia Blanco–Ameiȷeiras, Richard A. Feely, Laura Lorenzoni, Juan–Carlos Molinero, Karen Bremer, Daniel O. B. Jones, Debora Iglesias–Rodriguez, Dana Greeley, Miles D. L Tags: Biological Sciences Source Type: research

Configurational entropy of basaltic melts in Earth’s mantle [Earth, Atmospheric, and Planetary Sciences]
Although geophysical observations of mantle regions that suggest the presence of partial melt have often been interpreted in light of the properties of basaltic liquids erupted at the surface, the seismic and rheological consequences of partial melting in the upper mantle depend instead on the properties of interstitial basaltic melt... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Sung Keun Lee, Jed L. Mosenfelder, Sun Young Park, A. Chim Lee, Paul D. Asimow Tags: Physical Sciences Source Type: research

Biomass combustion produces ice-active minerals in biomass-burning aerosol and bottom ash [Earth, Atmospheric, and Planetary Sciences]
Ice nucleation and the resulting cloud glaciation are significant atmospheric processes that affect the evolution of clouds and their properties including radiative forcing and precipitation, yet the sources and properties of atmospheric ice nucleants are poorly constrained. Heterogeneous ice nucleation caused by ice-nucleating particles (INPs) enables cloud glaciation at temperatures... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Leif G. Jahn, Michael J. Polen, Lydia G. Jahl, Thomas A. Brubaker, Joshua Somers, Ryan C. Sullivan Tags: Physical Sciences Source Type: research

News Feature: Foreseeing fires [Earth, Atmospheric, and Planetary Sciences]
To predict future wildfires, researchers are building models that better account for the vegetation that fans the flames. Wildfire ripped through the black spruce forests of Eagle Plains, Yukon Territory, Canada in 1990. Fire came again in 2005. By the time plant ecologist Carissa Brown arrived in the summer of... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Amy McDermott Tags: News Features, Earth, Atmospheric, and Planetary Sciences, Environmental Sciences Source Type: research

A noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis [Developmental Biology]
NOD-like receptors (NLRs) are traditionally recognized as major inflammasome components. The role of NLRs in germ cell differentiation and reproduction is not known. Here, we identified the gonad-specific Nlrp14 as a pivotal regulator in primordial germ cell-like cell (PGCLC) differentiation in vitro. Physiologically, knock out of Nlrp14 resulted in reproductive... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Yike Yin, Shiyu Cao, Huancheng Fu, Xueying Fan, Jingfei Xiong, Qiuyue Huang, Yu Liu, Kun Xie, Tie-Gang Meng, Yuliang Liu, Dan Tang, Tingting Yang, Biao Dong, Shiqian Qi, Ling Nie, Huiyuan Zhang, Hongbo Hu, Wenming Xu, Fuping Li, Lunzhi Dai, Qing-Yuan Sun, Tags: Biological Sciences Source Type: research

LIN28B/let-7 control the ability of neonatal murine auditory supporting cells to generate hair cells through mTOR signaling [Developmental Biology]
Mechano-sensory hair cells within the inner ear cochlea are essential for the detection of sound. In mammals, cochlear hair cells are only produced during development and their loss, due to disease or trauma, is a leading cause of deafness. In the immature cochlea, prior to the onset of hearing, hair... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Xiao-Jun Li, Angelika Doetzlhofer Tags: Biological Sciences Source Type: research

Spin cascade and doming in ferric hemes: Femtosecond X-ray absorption and X-ray emission studies [Chemistry]
The structure–function relationship is at the heart of biology, and major protein deformations are correlated to specific functions. For ferrous heme proteins, doming is associated with the respiratory function in hemoglobin and myoglobins. Cytochrome c (Cyt c) has evolved to become an important electron-transfer protein in humans. In its ferrous... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Camila Bacellar, Dominik Kinschel, Giulia F. Mancini, Rebecca A. Ingle, Jeremy Rouxel, Oliviero Cannelli, Claudio Cirelli, Gregor Knopp, Jakub Szlachetko, Frederico A. Lima, Samuel Menzi, Georgios Pamfilidis, Katharina Kubicek, Dmitry Khakhulin, Woȷ Tags: Physical Sciences Source Type: research

Achieving delafossite analog by in situ electrochemical self-reconstruction as an oxygen-evolving catalyst [Chemistry]
Development of novel and robust oxygen evolution reaction (OER) catalysts with well-modulated atomic and electronic structure remains a challenge. Compared to the well-known metal hydroxides or (oxyhydr)oxides with lamellar structure, delafossites (ABO2) are characterized by alternating layers of A cations and edge-sharing BO2 octahedra, but are rarely used in OER... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Juzhe Liu, Qi Hu, Yu Wang, Zhao Yang, Xiaoyu Fan, Li-Min Liu, Lin Guo Tags: Physical Sciences Source Type: research

Age-related loss of neural stem cell O-GlcNAc promotes a glial fate switch through STAT3 activation [Cell Biology]
Increased neural stem cell (NSC) quiescence is a major determinant of age-related regenerative decline in the adult hippocampus. However, a coextensive model has been proposed in which division-coupled conversion of NSCs into differentiated astrocytes restrict the stem cell pool with age. Here we report that age-related loss of the posttranslational... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Charles W. White III, Xuelai Fan, Jason C. Maynard, Elizabeth G. Wheatley, Gregor Bieri, Julien Couthouis, Alma L. Burlingame, Saul A. Villeda Tags: Biological Sciences Source Type: research

Transcriptome-wide analysis of PGC-1{alpha}-binding RNAs identifies genes linked to glucagon metabolic action [Cell Biology]
The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a transcriptional coactivator that controls expression of metabolic/energetic genes, programming cellular responses to nutrient and environmental adaptations such as fasting, cold, or exercise. Unlike other coactivators, PGC-1α contains protein domains involved in RNA regulation such as serine/arginine (SR) and RNA recognition... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Clint D. J. Tavares, Stefan Aigner, Kfir Sharabi, Shashank Sathe, Beste Mutlu, Gene W. Yeo, Pere Puigserver Tags: Biological Sciences Source Type: research

CAMSAP1 breaks the homeostatic microtubule network to instruct neuronal polarity [Cell Biology]
The establishment of axon/dendrite polarity is fundamental for neurons to integrate into functional circuits, and this process is critically dependent on microtubules (MTs). In the early stages of the establishment process, MTs in axons change dramatically with the morphological building of neurons; however, how the MT network changes are triggered... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Zhengrong Zhou, Honglin Xu, Yuejia Li, Mengge Yang, Rui Zhang, Aki Shiraishi, Hiroshi Kiyonari, Xin Liang, Xiahe Huang, Yingchun Wang, Qi Xie, Shuai Liu, Rongqing Chen, Lan Bao, Weixiang Guo, Yu Wang, Wenxiang Meng Tags: Biological Sciences Source Type: research

Ligand-induced gene activation is associated with oxidative genome damage whose repair is required for transcription [Cell Biology]
Among several reversible epigenetic changes occurring during transcriptional activation, only demethylation of histones and cytosine-phosphate-guanines (CpGs) in gene promoters and other regulatory regions by specific demethylase(s) generates reactive oxygen species (ROS), which oxidize DNA and other cellular components. Here, we show induction of oxidized bases and single-strand breaks (SSBs), but... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Shiladitya Sengupta, Haibo Wang, Chunying Yang, Bartosz Szczesny, Muralidhar L. Hegde, Sankar Mitra Tags: Biological Sciences Source Type: research

Human epidermal stem cell differentiation is modulated by specific lipid subspecies [Cell Biology]
While the lipids of the outer layers of mammalian epidermis and their contribution to barrier formation have been extensively described, the role of individual lipid species in the onset of keratinocyte differentiation remains unknown. A lipidomic analysis of primary human keratinocytes revealed accumulation of numerous lipid species during suspension-induced differentiation.... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Matteo Vietri Rudan, Ajay Mishra, Christian Klose, Ulrike S. Eggert, Fiona M. Watt Tags: Biological Sciences Source Type: research

The cochlear outer hair cell speed paradox [Cell Biology]
Cochlear outer hair cells (OHCs) are among the fastest known biological motors and are essential for high-frequency hearing in mammals. It is commonly hypothesized that OHCs amplify vibrations in the cochlea through cycle-by-cycle changes in length, but recent data suggest OHCs are low-pass filtered and unable to follow high-frequency signals.... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Richard D. Rabbitt Tags: Physical Sciences Source Type: research

Metabolic stress promotes stop-codon readthrough and phenotypic heterogeneity [Biophysics and Computational Biology]
Accurate protein synthesis is a tightly controlled biological process with multiple quality control steps safeguarded by aminoacyl-transfer RNA (tRNA) synthetases and the ribosome. Reduced translational accuracy leads to various physiological changes in both prokaryotes and eukaryotes. Termination of translation is signaled by stop codons and catalyzed by release factors. Occasionally,... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Hong Zhang, Zhihui Lyu, Yongqiang Fan, Christopher R. Evans, Karl W. Barber, Kinshuk Banerjee, Oleg A. Igoshin, Jesse Rinehart, Jiqiang Ling Tags: Biological Sciences Source Type: research

Structural impact of K63 ubiquitin on yeast translocating ribosomes under oxidative stress [Biophysics and Computational Biology]
Subpopulations of ribosomes are responsible for fine tuning the control of protein synthesis in dynamic environments. K63 ubiquitination of ribosomes has emerged as a new posttranslational modification that regulates protein synthesis during cellular response to oxidative stress. K63 ubiquitin, a type of ubiquitin chain that functions independently of the proteasome,... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Ye Zhou, Panagiotis L. Kastritis, Shannon E. Dougherty, Jonathan Bouvette, Allen L. Hsu, Laura Burbaum, Shyamal Mosalaganti, Stefan Pfeffer, Wim J. H. Hagen, Friedrich Forster, Mario J. Borgnia, Christine Vogel, Martin Beck, Alberto Bartesaghi, Gustavo M. Tags: Biological Sciences Source Type: research

Structural cavities are critical to balancing stability and activity of a membrane-integral enzyme [Biophysics and Computational Biology]
Packing interaction is a critical driving force in the folding of helical membrane proteins. Despite the importance, packing defects (i.e., cavities including voids, pockets, and pores) are prevalent in membrane-integral enzymes, channels, transporters, and receptors, playing essential roles in function. Then, a question arises regarding how the two competing requirements,... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Ruiqiong Guo, Zixuan Cang, Jiaqi Yao, Miyeon Kim, Erin Deans, Guowei Wei, Seung-gu Kang, Heedeok Hong Tags: Biological Sciences Source Type: research

An enumerative algorithm for de novo design of proteins with diverse pocket structures [Biophysics and Computational Biology]
To create new enzymes and biosensors from scratch, precise control over the structure of small-molecule binding sites is of paramount importance, but systematically designing arbitrary protein pocket shapes and sizes remains an outstanding challenge. Using the NTF2-like structural superfamily as a model system, we developed an enumerative algorithm for creating... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Benjamin Basanta, Matthew J. Bick, Asim K. Bera, Christoffer Norn, Cameron M. Chow, Lauren P. Carter, Inna Goreshnik, Frank Dimaio, David Baker Tags: Biological Sciences Source Type: research

Exploring the F-actin/CPEB3 interaction and its possible role in the molecular mechanism of long-term memory [Biophysics and Computational Biology]
Dendritic spines are tiny membranous protrusions on the dendrites of neurons. Dendritic spines change shape in response to input signals, thereby strengthening the connections between neurons. The growth and stabilization of dendritic spines is thought to be essential for maintaining long-term memory. Actin cytoskeleton remodeling in spines is a key... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Xinyu Gu, Nicholas P. Schafer, Qian Wang, Sarah S. Song, Mingchen Chen, M. Neal Waxham, Peter G. Wolynes Tags: Biological Sciences Source Type: research

How cholesterol stiffens unsaturated lipid membranes [Biophysics and Computational Biology]
Cholesterol is an integral component of eukaryotic cell membranes and a key molecule in controlling membrane fluidity, organization, and other physicochemical parameters. It also plays a regulatory function in antibiotic drug resistance and the immune response of cells against viruses, by stabilizing the membrane against structural damage. While it is... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Saptarshi Chakraborty, Milka Doktorova, Trivikram R. Molugu, Frederick A. Heberle, Haden L. Scott, Boris Dzikovski, Michihiro Nagao, Laura-Roxana Stingaciu, Robert F. Standaert, Francisco N. Barrera, John Katsaras, George Khelashvili, Michael F. Brown, Ra Tags: Physical Sciences Source Type: research

Target search and recognition mechanisms of glycosylase AlkD revealed by scanning FRET-FCS and Markov state models [Biophysics and Computational Biology]
DNA glycosylase is responsible for repairing DNA damage to maintain the genome stability and integrity. However, how glycosylase can efficiently and accurately recognize DNA lesions across the enormous DNA genome remains elusive. It has been hypothesized that glycosylase translocates along the DNA by alternating between a fast but low-accuracy diffusion... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Sijia Peng, Xiaowei Wang, Lu Zhang, Shanshan He, Xin Sheng Zhao, Xuhui Huang, Chunlai Chen Tags: Physical Sciences Source Type: research

Sequence-independent recognition of the amyloid structural motif by GFP protein family [Biochemistry]
Cnidarian fluorescent protein (FP) derivatives such as GFP, mCherry, and mEOS2 have been widely used to monitor gene expression and protein localization through biological imaging because they are considered functionally inert. We demonstrate that FPs specifically bind amyloid fibrils formed from many natural peptides and proteins. FPs do not bind... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Sherry C. S. Xu, Josephine G. LoRicco, Anthony C. Bishop, Nathan A. James, Welby H. Huynh, Scott A. McCallum, Nadia R. Roan, George I. Makhatadze Tags: Biological Sciences Source Type: research

A mutation in POLR3E impairs antiviral immune response and RNA polymerase III [Biochemistry]
RNA polymerase (Pol) III has a noncanonical role of viral DNA sensing in the innate immune system. This polymerase transcribes viral genomes to produce RNAs that lead to induction of type I interferons (IFNs). However, the genetic and functional links of Pol III to innate immunity in humans remain largely... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Aravind Ramanathan, Michael Weintraub, Natalie Orlovetskie, Raphael Serruya, Dhivakar Mani, Orly Marcu, Polina Stepensky, Yiska Weisblum, Esther Djian, Avraham Shaag, Shoshana Revel-Vilk, Iris Fried, Moshe Kotler, Alex Rouvinski, Dana Wolf, Orly Elpeleg, Tags: Biological Sciences Source Type: research

Calcium modulates the domain flexibility and function of an {alpha}-actinin similar to the ancestral {alpha}-actinin [Biochemistry]
The actin cytoskeleton, a dynamic network of actin filaments and associated F-actin–binding proteins, is fundamentally important in eukaryotes. α-Actinins are major F-actin bundlers that are inhibited by Ca2+ in nonmuscle cells. Here we report the mechanism of Ca2+-mediated regulation of Entamoeba histolytica α-actinin-2 (EhActn2) with features expected for the common... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Nikos Pinotsis, Karolina Zielinska, Mrigya Babuta, Joan L. Arolas, Julius Kostan, Muhammad Bashir Khan, Claudia Schreiner, Anita Salmazo, Luciano Ciccarelli, Martin Puchinger, Eirini A. Gkougkoulia, Euripedes de Almeida Ribeiro Jr, Thomas C. Marlovits, Al Tags: Biological Sciences Source Type: research

Intein-mediated cytoplasmic reconstitution of a split toxin enables selective cell ablation in mixed populations and tumor xenografts [Biochemistry]
The application of proteinaceous toxins for cell ablation is limited by their high on- and off-target toxicity, severe side effects, and a narrow therapeutic window. The selectivity of targeting can be improved by intein-based toxin reconstitution from two dysfunctional fragments provided their cytoplasmic delivery via independent, selective pathways. While the... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Vedud Purde, Elena Kudryashova, David B. Heisler, Reena Shakya, Dmitri S. Kudryashov Tags: Biological Sciences Source Type: research

Allosteric regulation of thioesterase superfamily member 1 by lipid sensor domain binding fatty acids and lysophosphatidylcholine [Biochemistry]
Nonshivering thermogenesis occurs in brown adipose tissue to generate heat in response to cold ambient temperatures. Thioesterase superfamily member 1 (Them1) is transcriptionally up-regulated in brown adipose tissue upon exposure to the cold and suppresses thermogenesis in order to conserve energy reserves. It hydrolyzes long-chain fatty acyl-CoAs that are derived... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Matthew C. Tillman, Norihiro Imai, Yue Li, Manoj Khadka, C. Denise Okafor, Puneet Juneja, Akshitha Adhiyaman, Susan J. Hagen, David E. Cohen, Eric A. Ortlund Tags: Biological Sciences Source Type: research

RNA-protein interaction mapping via MS2- or Cas13-based APEX targeting [Biochemistry]
RNA–protein interactions underlie a wide range of cellular processes. Improved methods are needed to systematically map RNA–protein interactions in living cells in an unbiased manner. We used two approaches to target the engineered peroxidase APEX2 to specific cellular RNAs for RNA-centered proximity biotinylation of protein interaction partners. Both an MS2-MCP... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Shuo Han, Boxuan Simen Zhao, Samuel A. Myers, Steven A. Carr, Chuan He, Alice Y. Ting Tags: Biological Sciences Source Type: research

Structural base for the transfer of GPI-anchored glycoproteins into fungal cell walls [Biochemistry]
The correct distribution and trafficking of proteins are essential for all organisms. Eukaryotes evolved a sophisticated trafficking system which allows proteins to reach their destination within highly compartmentalized cells. One eukaryotic hallmark is the attachment of a glycosylphosphatidylinositol (GPI) anchor to C-terminal ω-peptides, which are used as a zip code... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Marian Samuel Vogt, Gesa Felicitas Schmitz, Daniel Varon Silva, Hans–Ulrich Mosch, Lars–Oliver Essen Tags: Biological Sciences Source Type: research

Two-step release of kinase autoinhibition in discoidin domain receptor 1 [Biochemistry]
Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase with important functions in organogenesis and tissue homeostasis. Aberrant DDR1 activity contributes to the progression of human diseases, including fibrosis and cancer. How DDR1 activity is regulated is poorly understood. We investigated the function of the long intracellular juxtamembrane... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Douglas Sammon, Erhard Hohenester, Birgit Leitinger Tags: Biological Sciences Source Type: research

60Fe deposition during the late Pleistocene and the Holocene echoes past supernova activity [Astronomy]
Nuclides synthesized in massive stars are ejected into space via stellar winds and supernova explosions. The solar system (SS) moves through the interstellar medium and collects these nucleosynthesis products. One such product is 60Fe, a radionuclide with a half-life of 2.6 My that is predominantly produced in massive stars and... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: A. Wallner, J. Feige, L. K. Fifield, M. B. Froehlich, R. Golser, M. A. C. Hotchkis, D. Koll, G. Leckenby, M. Martschini, S. Merchel, S. Panjkov, S. Pavetich, G. Rugel, S. G. Tims Tags: Physical Sciences Source Type: research

Hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion is rate-limited by monocarboxylate transporter-1 in the plasma membrane [Applied Physical Sciences]
Hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging (MRSI) is a noninvasive metabolic-imaging modality that probes carbon flux in tissues and infers the state of metabolic reprograming in tumors. Prevailing models attribute elevated hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion rates in aggressive tumors to enhanced glycolytic flux and lactate dehydrogenase A (LDHA) activity (Warburg effect).... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Yi Rao, Seth Gammon, Niki M. Zacharias, Tracy Liu, Travis Salzillo, Yuanxin Xi, Jing Wang, Pratip Bhattacharya, David Piwnica-Worms Tags: Biological Sciences Source Type: research

Universal motion of mirror-symmetric microparticles in confined Stokes flow [Applied Physical Sciences]
Comprehensive understanding of particle motion in microfluidic devices is essential to unlock additional technologies for shape-based separation and sorting of microparticles like microplastics, cells, and crystal polymorphs. Such particles interact hydrodynamically with confining surfaces, thus altering their trajectories. These hydrodynamic interactions are shape dependent and can be tuned to guide... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Rumen N. Georgiev, Sara O. Toscano, William E. Uspal, Bram Bet, Sela Samin, Rene van Roiȷ, Huseyin Burak Eral Tags: Physical Sciences Source Type: research

Archetypal landscapes for deep neural networks [Applied Physical Sciences]
The predictive capabilities of deep neural networks (DNNs) continue to evolve to increasingly impressive levels. However, it is still unclear how training procedures for DNNs succeed in finding parameters that produce good results for such high-dimensional and nonconvex loss functions. In particular, we wish to understand why simple optimization schemes,... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Philipp C. Verpoort, Alpha A. Lee, David J. Wales Tags: Physical Sciences Source Type: research

Evaluating insecticide resistance across African districts to aid malaria control decisions [Applied Biological Sciences]
Malaria vector control may be compromised by resistance to insecticides in vector populations. Actions to mitigate against resistance rely on surveillance using standard susceptibility tests, but there are large gaps in the monitoring data across Africa. Using a published geostatistical ensemble model, we have generated maps that bridge these gaps... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - September 8, 2020 Category: Science Authors: Catherine L. Moyes, Duncan K. Athinya, Tara Seethaler, Katherine E. Battle, Marianne Sinka, Melinda P. Hadi, Janet Hemingway, Michael Coleman, Penelope A. Hancock Tags: Biological Sciences Source Type: research