Pallinti Purushotham, Ruoya Ho, Jochen Zimmer
Cellulose is an essential plant cell wall component and represents the most abundant biopolymer on Earth. Supramolecular plant cellulose synthase complexes organize multiple linear glucose polymers into microfibrils as load-bearing wall components. We determined the structure of a poplar cellulose synthase CesA homotrimer that suggests a molecular basis for cellulose microfibril formation. This complex, stabilized by cytosolic plant conserved regions and helical exchange within the transmembrane segment, forms three channels occupied by nascent cellulose polymers...
July 9, 2020: Science
Wei Deng, Linlin Bao, Jiangning Liu, Chong Xiao, Jiayi Liu, Jing Xue, Qi Lv, Feifei Qi, Hong Gao, Pin Yu, Yanfeng Xu, Yajin Qu, Fengdi Li, Zhiguang Xiang, Haisheng Yu, Shuran Gong, Mingya Liu, Guanpeng Wang, Shunyi Wang, Zhiqi Song, Ying Liu, Wenjie Zhao, Yunlin Han, Linna Zhao, Xing Liu, Qiang Wei, Chuan Qin
Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes...
July 2, 2020: Science
Gregor L Weiss, Jessica J Stanisich, Maximilian M Sauer, Chia-Wei Lin, Jonathan Eras, Dawid S Zyla, Johannes Trück, Olivier Devuyst, Markus Aebi, Martin Pilhofer, Rudi Glockshuber
Uromodulin is the most abundant protein in human urine and forms filaments that antagonize the adhesion of uropathogens; however, filament structure and mechanism of protection remain poorly understood. We used cryo-electron tomography to show that the uromodulin filament consists of a zigzag-shaped backbone with laterally protruding arms. N-glycosylation mapping and biophysical assays revealed that uromodulin acts as a multivalent ligand for the bacterial type 1 pilus adhesin, presenting specific epitopes on the regularly spaced arms...
July 2, 2020: Science
Vladislav Kamysbayev, Alexander S Filatov, Huicheng Hu, Xue Rui, Francisco Lagunas, Di Wang, Robert F Klie, Dmitri V Talapin
Versatile chemical transformations of surface functional groups in 2D transition-metal carbides (MXenes) open up a new design space for this broad class of functional materials. We introduce a general strategy to install and remove surface groups by performing substitution and elimination reactions in molten inorganic salts. Successful synthesis of MXenes with O, NH, S, Cl, Se, Br, and Te surface terminations, as well as bare MXenes (no surface termination) was demonstrated. These MXenes show distinctive structural and electronic properties...
July 2, 2020: Science
Hyun-Jae Lee, Minseong Lee, Kyoungjun Lee, Jinhyeong Jo, Hyemi Yang, Yungyeom Kim, Seung Chul Chae, Umesh Waghmare, Jun Hee Lee
Discovery of robust yet reversibly switchable electric dipoles at reduced dimensions is critical in advancing nanoelectronics devices. Energy bands flat in momentum space generate robust localized states that are activated independently of each other. We determined flat bands exist and induce robust yet independently switchable dipoles exhibiting a unique ferroelectricity in HfO2 Flat polar phonon bands in HfO2 cause extreme localization of electric dipoles within its irreducible half-unit-cell-widths (~3 Å)...
July 2, 2020: Science
Sebastian Z Oener, Marc J Foster, Shannon W Boettcher
Catalyzing water dissociation (WD) into protons and hydroxide ions is important both for fabricating bipolar membranes (BPMs) that can couple different pH environments into a single electrochemical device, and for accelerating electrocatalytic reactions that consume protons in neutral-to-alkaline media. We designed a BPM electrolyzer to quantitatively measure WD kinetics and show that, for metal nanoparticles, WD activity correlates with alkaline hydrogen-evolution-reaction activity. By combining metal-oxide WD catalysts efficient near the acidic proton-exchange layer with those efficient near the alkaline hydroxide-exchange layer, we demonstrate a BPM driving WD with overpotentials of < 10 mV at 20 mA·cm-2 and pure-water BPM electrolyzers that operate with an alkaline anode and acidic cathode at 500 mA·cm-2 with a total electrolysis voltage of ~ 2...
July 2, 2020: Science
M Kolmer, A K Steiner, I Izydorczyk, W Ko, M Engelund, M Szymonski, A-P Li, K Amsharov
Atomically precise graphene nanoribbons (GNRs) attract great interest because of their highly tunable electronic, optical, and transport properties. However, on-surface synthesis of GNRs is typically based on metal-surface assisted chemical reactions, where metallic substrates strongly screen their designer electronic properties and limit further applications. Here, we present an on-surface synthesis approach to forming atomically precise GNRs directly on semiconducting metal oxide surfaces. The thermally triggered multistep transformations preprogrammed in our precursors' design rely on highly selective and sequential activations of C-Br, C-F bonds and cyclodehydrogenation...
June 25, 2020: Science
Pengfei Lan, Bin Zhou, Ming Tan, Shaobai Li, Mi Cao, Jian Wu, Ming Lei
Ribonuclease (RNase) MRP is a conserved eukaryotic ribonucleoprotein complex that plays essential roles in pre-ribosomal RNA (pre-rRNA) processing and cell cycle regulation. In contrast to RNase P, which selectively cleaves tRNA-like substrates, it has remained a mystery how RNase MRP recognizes its diverse substrates. To address this question, we determined cryo-EM structures of Saccharomyces cerevisiae RNase MRP alone and in complex with a fragment of pre-rRNA. These structures combined with biochemical studies reveal that co-evolution of both protein and RNA subunits has transformed RNase MRP into a distinct ribonuclease that processes single-stranded RNAs by recognizing a short, loosely-defined consensus sequence...
June 25, 2020: Science
Tom Britton, Frank Ball, Pieter Trapman
Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups with low contact rates. We estimate that if R 0 = 2.5 in an age-structured community with mixing rates fitted to social activity then the disease-induced herd immunity level can be around 43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population...
June 23, 2020: Science
Xiangyang Chi, Renhong Yan, Jun Zhang, Guanying Zhang, Yuanyuan Zhang, Meng Hao, Zhe Zhang, Pengfei Fan, Yunzhu Dong, Yilong Yang, Zhengshan Chen, Yingying Guo, Jinlong Zhang, Yaning Li, Xiaohong Song, Yi Chen, Lu Xia, Ling Fu, Lihua Hou, Junjie Xu, Changming Yu, Jianmin Li, Qiang Zhou, Wei Chen
Developing therapeutics against SARS-CoV-2 could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein, but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from ten convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. An mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, but does not bind the RBD...
June 22, 2020: Science
Bing Yang, Hui Sun, Chun-Jiong Huang, Han-Yi Wang, Youjin Deng, Han-Ning Dai, Zhen-Sheng Yuan, Jian-Wei Pan
Scalable, coherent many-body systems can enable the realization of previously unexplored quantum phases and have a potential to exponentially speed up information processing. Here we report the cooling of a quantum simulator with ten thousand atoms and mass production of high-fidelity entangled pairs. In a two-dimensional plane, we cool Mott-insulator samples by immersing them into removable superfluid reservoirs, achieving an entropy per particle of [Formula: see text] The atoms are then rearranged into a two-dimensional lattice free of defects...
June 18, 2020: Science
Michael Heide, Christiane Haffner, Ayako Murayama, Yoko Kurotaki, Haruka Shinohara, Hideyuki Okano, Erika Sasaki, Wieland B Huttner
The neocortex has expanded during mammalian evolution. Overexpression studies in developing mouse and ferret neocortex have implicated the human-specific gene ARHGAP11B in neocortical expansion, but the relevance for primate evolution has been unclear. Here, we provide functional evidence that ARHGAP11B causes expansion of the primate neocortex. ARHGAP11B expressed in fetal neocortex of the common marmoset under control of the gene's own, human, promoter increased numbers of basal radial glia progenitors in the marmoset outer subventricular zone, increased numbers of upper-layer neurons, enlarged the neocortex, and induced its folding...
June 18, 2020: Science
Duanyang Kong, Patrick J Moon, Erica K J Lui, Odey Bsharat, Rylan J Lundgren
Many classical and emerging methodologies in organic chemistry rely on CO2 extrusion to generate reactive intermediates for bond-forming events. Synthetic reactions that involve the microscopic reverse, the carboxylation of reactive intermediates, have conventionally been undertaken using very different conditions. We report that chemically stable C(sp3 ) carboxylates, such as arylacetic acids and malonate half-esters, undergo uncatalyzed reversible decarboxylation in dimethylformamide solution. Decarboxylation/carboxylation occurs with substrates resistant to protodecarboxylation by Brønsted acids under otherwise identical conditions...
June 18, 2020: Science
Tianhao Le, Yuan Wang, Lang Liu, Jiani Yang, Yuk L Yung, Guohui Li, John H Seinfeld
The absence of motor vehicle traffic and suspended manufacturing during the COVID-19 pandemic in China produced a unique experiment to assess the efficiency of air pollution mitigation. Up to 90% reduction of certain emissions during the city-lockdown period can be identified from satellite and ground-based observations. Unexpectedly, extreme particulate matter levels simultaneously occurred in northern China. Our synergistic observation analyses and model simulations show that anomalously high humidity promoted aerosol heterogeneous chemistry, along with stagnant airflow and uninterrupted emissions from power plants and petrochemical facilities, contributing to severe haze formation...
June 17, 2020: Science
Alina Baum, Benjamin O Fulton, Elzbieta Wloga, Richard Copin, Kristen E Pascal, Vincenzo Russo, Stephanie Giordano, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S Atwal, Andrew J Murphy, Neil Stahl, George D Yancopoulos, Christos A Kyratsous
Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID19 pandemic; however, concerns remain that mutations can yield antibody resistance. We investigate the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails. These antibodies remain effective against spike variants that have arisen in the human population. However, novel spike mutants rapidly appeared following in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization; such escape also occurred with combinations of antibodies binding diverse but overlapping regions of the spike protein...
June 15, 2020: Science
Thomas F Rogers, Fangzhu Zhao, Deli Huang, Nathan Beutler, Alison Burns, Wan-Ting He, Oliver Limbo, Chloe Smith, Ge Song, Jordan Woehl, Linlin Yang, Robert K Abbott, Sean Callaghan, Elijah Garcia, Jonathan Hurtado, Mara Parren, Linghang Peng, Sydney Ramirez, James Ricketts, Michael J Ricciardi, Stephen A Rawlings, Nicholas C Wu, Meng Yuan, Davey M Smith, David Nemazee, John R Teijaro, James E Voss, Ian A Wilson, Raiees Andrabi, Bryan Briney, Elise Landais, Devin Sok, Joseph G Jardine, Dennis R Burton
Countermeasures to prevent and treat COVID-19 are a global health priority. We enrolled a cohort of SARS-CoV-2-recovered participants, developed neutralization assays to interrogate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen over 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein...
June 15, 2020: Science
Philip J M Brouwer, Tom G Caniels, Karlijn van der Straten, Jonne L Snitselaar, Yoann Aldon, Sandhya Bangaru, Jonathan L Torres, Nisreen M A Okba, Mathieu Claireaux, Gius Kerster, Arthur E H Bentlage, Marlies M van Haaren, Denise Guerra, Judith A Burger, Edith E Schermer, Kirsten D Verheul, Niels van der Velde, Alex van der Kooi, Jelle van Schooten, Mariëlle J van Breemen, Tom P L Bijl, Kwinten Sliepen, Aafke Aartse, Ronald Derking, Ilja Bontjer, Neeltje A Kootstra, W Joost Wiersinga, Gestur Vidarsson, Bart L Haagmans, Andrew B Ward, Godelieve J de Bree, Rogier W Sanders, Marit J van Gils
The rapid spread of SARS-CoV-2 has a significant impact on global health, travel and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent COVID-19 patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3 and VH1-24 gene usage. A subset of the antibodies were able to potently inhibit authentic SARS-CoV-2 infection as low as 0...
June 15, 2020: Science
Johanna Hansen, Alina Baum, Kristen E Pascal, Vincenzo Russo, Stephanie Giordano, Elzbieta Wloga, Benjamin O Fulton, Ying Yan, Katrina Koon, Krunal Patel, Kyung Min Chung, Aynur Hermann, Erica Ullman, Jonathan Cruz, Ashique Rafique, Tammy Huang, Jeanette Fairhurst, Christen Libertiny, Marine Malbec, Wen-Yi Lee, Richard Welsh, Glen Farr, Seth Pennington, Dipali Deshpande, Jemmie Cheng, Anke Watty, Pascal Bouffard, Robert Babb, Natasha Levenkova, Calvin Chen, Bojie Zhang, Annabel Romero Hernandez, Kei Saotome, Yi Zhou, Matthew Franklin, Sumathi Sivapalasingam, David Chien Lye, Stuart Weston, James Logue, Robert Haupt, Matthew Frieman, Gang Chen, William Olson, Andrew J Murphy, Neil Stahl, George D Yancopoulos, Christos A Kyratsous
Neutralizing antibodies have become an important tool in treating infectious diseases. Recently, two separate approaches yielded successful antibody treatments for Ebola - one from genetically-humanized mice, and the other from a human survivor. Here, we describe parallel efforts using both humanized mice and convalescent patients to generate antibodies against the SARS-CoV-2 spike protein, yielding a large collection of fully-human antibodies that were characterized for binding, neutralization and three dimensional structure...
June 15, 2020: Science
Anna Z Wec, Daniel Wrapp, Andrew S Herbert, Daniel P Maurer, Denise Haslwanter, Mrunal Sakharkar, Rohit K Jangra, M Eugenia Dieterle, Asparouh Lilov, Deli Huang, Longping V Tse, Nicole V Johnson, Ching-Lin Hsieh, Nianshuang Wang, Juergen H Nett, Elizabeth Champney, Irina Burnina, Michael Brown, Shu Lin, Melanie Sinclair, Carl Johnson, Sarat Pudi, Robert Bortz, Ariel S Wirchnianski, Ethan Laudermilch, Catalina Florez, J Maximilian Fels, Cecilia M O'Brien, Barney S Graham, David Nemazee, Dennis R Burton, Ralph S Baric, James E Voss, Kartik Chandran, John M Dye, Jason S McLellan, Laura M Walker
Broadly protective vaccines against known and pre-emergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) elicited by prior HCoV infections...
June 15, 2020: Science
Patrick G T Walker, Charles Whittaker, Oliver J Watson, Marc Baguelin, Peter Winskill, Arran Hamlet, Bimandra A Djafaara, Zulma Cucunubá, Daniela Olivera Mesa, Will Green, Hayley Thompson, Shevanthi Nayagam, Kylie E C Ainslie, Sangeeta Bhatia, Samir Bhatt, Adhiratha Boonyasiri, Olivia Boyd, Nicholas F Brazeau, Lorenzo Cattarino, Gina Cuomo-Dannenburg, Amy Dighe, Christl A Donnelly, Ilaria Dorigatti, Sabine L van Elsland, Rich FitzJohn, Han Fu, Katy A M Gaythorpe, Lily Geidelberg, Nicholas Grassly, David Haw, Sarah Hayes, Wes Hinsley, Natsuko Imai, David Jorgensen, Edward Knock, Daniel Laydon, Swapnil Mishra, Gemma Nedjati-Gilani, Lucy C Okell, H Juliette Unwin, Robert Verity, Michaela Vollmer, Caroline E Walters, Haowei Wang, Yuanrong Wang, Xiaoyue Xi, David G Lalloo, Neil M Ferguson, Azra C Ghani
The ongoing COVID-19 pandemic poses a severe threat to public health worldwide. We combine data on demography, contact patterns, disease severity, and health care capacity and quality to understand its impact and inform strategies for its control. Younger populations in lower income countries may reduce overall risk but limited health system capacity coupled with closer inter-generational contact largely negates this benefit. Mitigation strategies that slow but do not interrupt transmission will still lead to COVID-19 epidemics rapidly overwhelming health systems, with substantial excess deaths in lower income countries due to the poorer health care available...
June 12, 2020: Science
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