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Rxivist combines biology preprints from bioRxiv and medRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 119,227 papers from 514,060 authors.

Most tweeted biology preprints, last 24 hours

*There are gaps in historical Twitter data, most notably in spring 2020. This may result in some preprints appearing with less tweets than they should.

202 results found. For more information, click each entry to expand.

81: SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration-like effects
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Posted 20 May 2020

SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration-like effects
1 tweet bioRxiv cell biology

Anand Ramani, Lisa Müller, Philipp Niklas Ostermann, Elke Gabriel, Pranty Abida-Islam, Andreas Müller-Schiffmann, Aruljothi Mariappan, Olivier Goureau, Henning Gruell, Andreas Walker, Marcel Andrée, Sandra Hauka, Torsten Houwaart, Alexander Dilthey, Kai Wohlgemuth, Heymut Omran, Florian Klein, Dagmar Wieczorek, Ortwin Adams, Jörg Timm, Carsten Korth, Heiner Schaal, Jay Gopalakrishnan

COVID-19 pandemic caused by SARS-CoV-2 infection is a public health emergency. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Dusseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within two days of exposure. Using COVID-19 convalescent serum, we identified that SARS-CoV-2 preferably targets soma of cortical neurons but not neural stem cells, the target cell type of ZIKA virus. Imaging cortical neurons of organoids reveal that SARS-CoV-2 exposure is associated with missorted Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Surprisingly, SARS-CoV-2 co-localizes specifically with Tau phosphorylated at Threonine-231 in the soma, indicative of early neurodegeneration-like effects. Our studies, therefore, provide initial insights into the impact of SARS-CoV-2 as a neurotropic virus and emphasize that brain organoids could model CNS pathologies of COVID-19. ### Competing Interest Statement The authors have declared no competing interest.

82: Imaging cell lineage with a synthetic digital recording system
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Posted 25 Feb 2020

Imaging cell lineage with a synthetic digital recording system
1 tweet bioRxiv synthetic biology

Ke-Huan K Chow, Mark W Budde, Alejandro A Granados, Maria Cabrera, Shinae Yoon, Soomin Cho, Ting-hao Huang, Noushin Koulena, Kirsten L Frieda, Long Cai, Carlos Lois, Michael B. Elowitz

Multicellular development depends on the differentiation of cells into specific fates with precise spatial organization. Lineage history plays a pivotal role in cell fate decisions, but is inaccessible in most contexts. Engineering cells to actively record lineage information in a format readable in situ would provide a spatially resolved view of lineage in diverse developmental processes. Here, we introduce a serine integrase-based recording system that allows in situ readout, and demonstrate its ability to reconstruct lineage relationships in cultured stem cells and flies. The system, termed intMEMOIR, employs an array of independent three-state genetic memory elements that can recombine stochastically and irreversibly, allowing up to 59,049 distinct digital states. intMEMOIR accurately reconstructed lineage trees in stem cells and enabled simultaneous analysis of single cell clonal history, spatial position, and gene expression in Drosophila brain sections. These results establish a foundation for microscopy-readable clonal analysis and recording in diverse systems. ### Competing Interest Statement K.F., K.K.C., L.C., and M.B.E. are inventors on a patent application for recording technologies.

83: Massively parallel assessment of human variants with base editor screens
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Posted 17 May 2020

Massively parallel assessment of human variants with base editor screens
1 tweet bioRxiv genetics

Ruth E Hanna, Mudra Hegde, Christian R Fagre, Peter C DeWeirdt, Annabel K Sangree, Zsofia Szegletes, Audrey Griffith, Marissa N Feeley, Kendall R Sanson, Yossef Baidi, Luke W Koblan, David R. Liu, James T Neal, John G. Doench

Understanding the functional consequences of single-nucleotide variants is critical to uncovering the genetic underpinnings of diseases, but technologies to characterize variants are limiting. Here we leverage CRISPR-Cas9 cytosine base editors in pooled screens to scalably assay variants at endogenous loci in mammalian cells. We benchmark the performance of base editors in positive and negative selection screens and identify known loss-of-function mutations in BRCA1 and BRCA2 with high precision. To demonstrate the utility of base editor screens to probe small molecule-protein interactions, we conduct screens with BH3 mimetics and PARP inhibitors and identify point mutations that confer drug sensitivity or resistance. Finally, we create a library of 52,034 clinically-observed variants in 3,584 genes and conduct screens in the presence of cellular stressors, identifying loss-of-function variants in numerous DNA damage repair genes. We anticipate that this screening approach will be broadly useful to readily and scalably functionalize genetic variants. ### Competing Interest Statement

84: Need for speed: Examining protein behaviour during cryoEM grid preparation at different timescales
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Posted 15 May 2020

Need for speed: Examining protein behaviour during cryoEM grid preparation at different timescales
1 tweet bioRxiv biochemistry

David P. Klebl, Molly S. C. Gravett, Dimitrios Kontziampasis, David J. Wright, Robin S. Bon, Diana Monteiro, Martin Trebbin, Frank Sobott, Howard D. White, Michele Darrow, Rebecca F. Thompson, Stephen P. Muench

A host of new technologies are under development to improve the quality and reproducibility of cryoEM grid preparation. Here we have systematically investigated the preparation of three macromolecular complexes using three different vitrification devices (Vitrobot, chameleon and a time-resolved cryoEM device) on various timescales, including grids made within 6 ms, (the fastest reported to date), to interrogate particle behaviour at the air-water interface for different timepoints. Results demonstrate that different macromolecular complexes can respond to the thin film environment formed during cryoEM sample preparation in highly variable ways, shedding light on why cryoEM sample preparation can be difficult to optimise. We demonstrate that reducing time between sample application and vitrification is just one tool to improve cryoEM grid quality, but that it is unlikely to be a generic silver bullet for improving the quality of every cryoEM sample preparation. ### Competing Interest Statement The authors would like to acknowledge that MCD works for SPT Labtech, the company developing and manufacturing chameleon systems.

85: Multivariate Analyses of Codon Usage of SARS-CoV-2 and other betacoronaviruses
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Posted 20 Feb 2020

Multivariate Analyses of Codon Usage of SARS-CoV-2 and other betacoronaviruses
1 tweet bioRxiv evolutionary biology

Haogao Gu, Daniel Chu, J. S. Malik SM Peiris, Leo L.M. Poon

Coronavirus disease 2019 (COVID-19) is a global health concern as it continues to spread within China and beyond. The causative agent of this disease, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus Betacoronavirus which also includes severe acute respiratory syndrome related coronavirus (SARSr-CoV) and Middle East respiratory syndrome related coronavirus (MERSr-CoV). Codon usage of viral genes are believed to be subjected to different selection pressures in different host environments. Previous studies on codon usage of influenza A viruses can help identify viral host origins and evolution trends, however, similar studies on coronaviruses are lacking. In this study, global correspondence analysis (CA), within-group correspondence analysis (WCA) and between-group correspondence analysis (BCA) were performed among different genes in coronavirus viral sequences. The amino acid usage pattern of SARS-CoV-2 was generally found similar to bat and human SARSr-CoVs. However, we found greater synonymous codon usage differences between SARS-CoV-2 and its phylogenetic relatives on spike and membrane genes, suggesting these two genes of SARS-CoV-2 are subjected to different evolutionary pressures.

86: Variability in the analysis of a single neuroimaging dataset by many teams
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Posted 15 Nov 2019

Variability in the analysis of a single neuroimaging dataset by many teams
1 tweet bioRxiv neuroscience

Rotem Botvinik-Nezer, Felix Holzmeister, Colin F. Camerer, Anna Dreber, Juergen Huber, Magnus Johannesson, Michael Kirchler, Roni Iwanir, Jeanette A. Mumford, Alison Adcock, Paolo Avesani, Blazej Baczkowski, Aahana Bajracharya, Leah Bakst, Sheryl Ball, Marco Barilari, Nadège Bault, Derek Beaton, Julia Beitner, Roland Benoit, Ruud Berkers, Jamil Bhanji, Bharat Biswal, Sebastian Bobadilla-Suarez, Tiago Bortolini, Katherine Bottenhorn, Alexander Bowring, Senne Braem, Hayley Brooks, Emily Brudner, Cristian Calderon, Julia Camilleri, Jaime Castrellon, Luca Cecchetti, Edna Cieslik, Zachary Cole, Olivier Collignon, Robert Cox, William Cunningham, Stefan Czoschke, Kamalaker Dadi, Charles Davis, Alberto De Luca, Mauricio Delgado, Lysia Demetriou, Jeffrey Dennison, Xin Di, Erin Dickie, Ekaterina Dobryakova, Claire Donnat, Juergen Dukart, Niall W Duncan, Joke Durnez, Amr Eed, Simon Eickhoff, Andrew Erhart, Laura Fontanesi, G. Matthew Fricke, Adriana Galvan, Remi Gau, Sarah Genon, Tristan Glatard, Enrico Glerean, Jelle Goeman, Sergej Golowin, Carlos González-García, Krzysztof Gorgolewski, Cheryl Grady, Mikella Green, João Guassi Moreira, Olivia Guest, Shabnam Hakimi, J. Paul Hamilton, Roeland Hancock, Giacomo Handjaras, Bronson Harry, Colin Hawco, Peer Herholz, Gabrielle Herman, Stephan Heunis, Felix Hoffstaedter, Jeremy Hogeveen, S. Holmes, Chuan-Peng Hu, Scott Huettel, Matthew Hughes, Vittorio Iacovella, Alexandru Iordan, Peder Isager, Ayse Ilkay Isik, Andrew Jahn, Matthew Johnson, Tom Johnstone, Michael Joseph, Anthony Juliano, Joseph Kable, Michalis Kassinopoulos, Cemal Koba, Xiang-Zhen Kong, Timothy Koscik, Nuri Erkut Kucukboyaci, Brice Kuhl, Sebastian Kupek, Angela Laird, Claus Lamm, Robert Langner, Nina Lauharatanahirun, Hongmi Lee, Sangil Lee, Alexander Leemans, Andrea Leo, Elise Lesage, Flora Li, Monica Li, Phui Cheng Lim, Evan Lintz, Schuyler Liphardt, Annabel Losecaat Vermeer, Bradley Love, Michael Mack, Norberto Malpica, Theo Marins, Vanessa Sochat, Kelsey McDonald, Joseph McGuire, Helena Melero, Adriana Méndez Leal, Benjamin Meyer, Kristin Meyer, Paul Mihai, Georgios Mitsis, Jorge Moll, Dylan Nielson, Gustav Nilsonne, Michael Notter, Emanuele Olivetti, Adrian Onicas, Paolo Papale, Kaustubh Patil, Jonathan E. Peelle, Alexandre Pérez, Doris Pischedda, Jean-Baptiste Poline, Yanina Prystauka, Shruti Ray, Patricia Reuter-Lorenz, Richard Reynolds, Emiliano Ricciardi, Jenny Rieck, Anais Rodriguez-Thompson, Anthony Romyn, Taylor Salo, Gregory Samanez-Larkin, Emilio Sanz-Morales, Margaret Schlichting, Douglas Schultz, Qiang Shen, Margaret Sheridan, Fu Shiguang, Jennifer Silvers, Kenny Skagerlund, Alec Smith, David Smith, Peter Sokol-Hessner, Simon Steinkamp, Sarah Tashjian, Bertrand Thirion, John Thorp, Gustav Tinghög, Loreen Tisdall, Steven Tompson, Claudio Toro-Serey, Juan Torre, Leonardo Tozzi, Vuong Truong, Luca Turella, Anna E. van’t Veer, Tom Verguts, Jean Vettel, Sagana Vijayarajah, Khoi Vo, Matthew Wall, Wouter D. Weeda, Susanne Weis, David White, David Wisniewski, Alba Xifra-Porxas, Emily Yearling, Sangsuk Yoon, Rui Yuan, Kenneth Yuen, Lei Zhang, Xu Zhang, Joshua Zosky, Thomas Nichols, Russell A. Poldrack, Tom Schonberg

Data analysis workflows in many scientific domains have become increasingly complex and flexible. To assess the impact of this flexibility on functional magnetic resonance imaging (fMRI) results, the same dataset was independently analyzed by 70 teams, testing nine ex-ante hypotheses. The flexibility of analytic approaches is exemplified by the fact that no two teams chose identical workflows to analyze the data. This flexibility resulted in sizeable variation in hypothesis test results, even for teams whose statistical maps were highly correlated at intermediate stages of their analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Importantly, meta-analytic approaches that aggregated information across teams yielded significant consensus in activated regions across teams. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset. Our findings show that analytic flexibility can have substantial effects on scientific conclusions, and demonstrate factors related to variability in fMRI. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for multiple analyses of the same data. Potential approaches to mitigate issues related to analytical variability are discussed.

87: SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant
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Posted 12 May 2020

SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant
1 tweet bioRxiv microbiology

Yoriyuki Konno, Izumi Kimura, Keiya Uriu, Masaya Fukushi, Takashi Irie, Yoshio Koyanagi, So Nakagawa, Kei Sato

One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays revealed that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of more than 15,000 SARS-CoV-2 sequences identified a natural variant, in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients, but also describe a possibility of the emergence of natural SARS-CoV-2 quasispecies with extended ORF3b that may exacerbate COVID-19 symptoms. ### Competing Interest Statement The authors have declared no competing interest.

88: A statistical framework for assessing pharmacological response and biomarkers using uncertainty estimates
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Posted 03 May 2020

A statistical framework for assessing pharmacological response and biomarkers using uncertainty estimates
1 tweet bioRxiv cancer biology

Dennis Wang, James Hensman, Ginte Kutkaite, Tzen S. Toh, GDSC Screening Team, Jonathan R Dry, Julio Saez-Rodriguez, Mathew J Garnett, Michael P Menden, Frank Dondelinger

Drug high-throughput screenings across large molecular-characterised cancer cell line panels enable the discovery of biomarkers, and thereby, cancer precision medicine. The ability to experimentally generate drug response data has accelerated. However, this data is typically quantified by a summary statistic from a best-fit dose response curve, whilst neglecting the uncertainty of the curve fit and the potential variability in the raw readouts. Here, we model the experimental variance using Gaussian Processes, and subsequently, leverage this uncertainty for identifying associated biomarkers with a new statistical framework based on Bayesian testing. Applied to the Genomics of Drug Sensitivity in Cancer, in vitro screening data on 265 compounds across 1,074 cell lines, our uncertainty models identified 24 clinically established drug response biomarkers, and in addition provided evidence for 6 novel biomarkers. We validated our uncertainty estimates with an additional drug screen of 26 drugs, 10 cell lines with 8 to 9 replicates. Our method is applicable to drug high-throughput screens without replicates, and enables robust biomarker discovery for new cancer therapies. ### Competing Interest Statement Jonathan Dry is an employee of AstraZeneca.

89: Dragonfly Inspired Smart Soft Robot
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Posted 30 Apr 2020

Dragonfly Inspired Smart Soft Robot
1 tweet bioRxiv bioengineering

Vardhman Kumar, Ung Hyun Ko, Yilong Zhou, Jiaul Hoque, Gaurav Arya, Shyni Varghese

Recent advancements in soft robotics have led to the development of compliant robots that can exhibit complex motions driven by living cells(1, 2), chemical reactions(3), or electronics(4). Further innovations are however needed to create the next generation of soft robots that can carry out advanced functions beyond locomotion. Here we describe DraBot, a dragonfly-inspired, entirely soft, multifunctional robot that combines long-term locomotion over water surface with sensing, responding, and adaptation capabilities. By integrating soft actuators, stimuli-responsive materials, and microarchitectural features, we created a circuitry of pneumatic and microfluidic logic that enabled the robot to undergo user- and environment-controlled (pH) locomotion, including navigating hazardous (acidic) conditions. DraBot was also engineered to sense additional environmental perturbations (temperature) and detect and clean up chemicals (oil). The design, fabrication, and integration strategies demonstrated here pave a way for developing futuristic soft robots that can acclimatize and adapt to harsh conditions while carrying out complex tasks such as exploration, environmental remediation, and health care in complex environments. ### Competing Interest Statement The authors have declared no competing interest.

90: Transcriptional control of apical protein clustering drives de novo cell polarity establishment in the early mouse embryo
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Posted 10 Feb 2020

Transcriptional control of apical protein clustering drives de novo cell polarity establishment in the early mouse embryo
1 tweet bioRxiv developmental biology

Meng Zhu, Peizhe Wang, Charlotte E. Handford, Jie Na, Magdalena Zernicka-Goetz

The establishment of cell polarity de novo in the early mammalian embryo triggers the transition from totipotency to differentiation to generate embryonic and extra-embryonic lineages. However, the molecular mechanisms governing the timing of cell polarity establishment remain unknown. Here, we identify stage-dependent transcription of Tfap2c and Tead4 as well as Rho GTPase signaling as key for the onset of cell polarization. Importantly, advancing their activity can induce precocious cell polarization and ectopic lineage differentiation in a cell-autonomous manner. Moreover, we show that the asymmetric clustering of apical proteins, regulated by Tfap2c-Tead4, and not actomyosin flow, mediates apical protein polarization. These findings identify the long-sought mechanism for the onset of polarization and the first lineage segregation in the mouse embryo.

91: A Wnt-specific astacin proteinase controls head formation in Hydra
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Posted 13 Aug 2020

A Wnt-specific astacin proteinase controls head formation in Hydra
1 tweet bioRxiv developmental biology

Berenice Ziegler, Irene Yiallouros, Benjamin Trageser, Sumit Kumar, Moritz Mercker, Svenja Kling, Maike Fath, Uwe Warnken, Martina Schnölzer, Thomas W. Holstein, Markus Hartl, Anna Marciniak-Czochra, Jörg Stetefeld, Walter Stöcker, Suat Özbek

The Hydra head organizer acts as a signaling center that initiates and maintains the primary body axis in steady state polyps and during budding or regeneration. Wnt/beta-Catenin signaling functions as a primary cue controlling this process, but how Wnt ligand activity is locally restricted at the protein level is poorly understood. Here we report the identification of an astacin family proteinase as a Wnt processing factor. Hydra astacin-7 (HAS-7) is expressed from gland cells as an apical-distal gradient in the body column, peaking close beneath the tentacle zone. HAS-7 siRNA knockdown abrogates HyWnt3 proteolysis in the head tissue and induces a robust double axis phenotype, which is rescued by simultaneous HyWnt3 knockdown. Accordingly, double axes are also observed in conditions of increased Wnt levels as in transgenic actin::HyWnt3 and HyDkk1/2/4 siRNA treated animals. HyWnt3-induced double axes in Xenopus embryos could be rescued by co-injection of HAS-7 mRNA. Mathematical modelling combined with experimental promotor analysis indicate an indirect regulation of HAS-7 by beta-Catenin, expanding the classical Turing-type activator-inhibitor model. Our data suggest a negative regulatory function of Wnt processing astacin proteinases in the global patterning of the oral-aboral axis in Hydra. ### Competing Interest Statement The authors have declared no competing interest.

92: Ecological processes underlying the emergence of novel enzootic cycles—arboviruses in the neotropics as a case study
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Posted 29 Apr 2020

Ecological processes underlying the emergence of novel enzootic cycles—arboviruses in the neotropics as a case study
1 tweet bioRxiv ecology

Sarah Guth, Kathryn Hanley, Benjamin M. Althouse, Mike Boots

Pathogens originating from wildlife (zoonoses) pose a significant public health burden, comprising the majority of emerging infectious diseases. Efforts to control and prevent zoonotic disease have traditionally focused on animal-to-human transmission, or spillover. However, in the modern era, increasing international mobility and commerce facilitate the spread of infected humans, non-human animals (hereafter animals), and their products worldwide, thereby increasing the risk that zoonoses will be introduced to new geographic areas. Imported zoonoses can potentially spill back to infect local wildlife, a danger magnified by urbanization and other anthropogenic pressures that increase contacts between human and wildlife populations. In this way, humans can function as vectors, dispersing zoonoses from their ancestral enzootic systems to establish reservoirs elsewhere in novel animal host populations. Once established, these enzootic cycles are largely unassailable by standard control measures and have the potential to feed human epidemics. Understanding when and why translocated zoonoses establish novel enzootic cycles requires disentangling ecologically complex and stochastic interactions between the zoonosis, the human population, and the natural ecosystem. We address this challenge by delineating potential ecological mechanisms affecting each stage of enzootic establishment; wildlife exposure, enzootic infection, and persistence, applying existing ecological concepts from epidemiology, invasion biology, and population ecology. We ground our study in the neotropics, where four arthropod-borne viruses (arboviruses) of zoonotic origin; yellow fever, dengue, chikungunya, and Zika viruses, have separately been introduced into the human population. This paper is a step towards developing a framework for predicting and preventing novel enzootic cycles in the face of zoonotic translocations. ### Competing Interest Statement The authors have declared no competing interest.

93: Predicted Cellular Immunity Population Coverage Gaps for SARS-CoV-2 Subunit Vaccines and their Augmentation by Compact Peptide Sets
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Posted 06 Aug 2020

Predicted Cellular Immunity Population Coverage Gaps for SARS-CoV-2 Subunit Vaccines and their Augmentation by Compact Peptide Sets
1 tweet bioRxiv immunology

Ge Liu, Brandon Carter, David K Gifford

Subunit vaccines induce immunity to a pathogen by presenting a component of the pathogen and thus inherently limit the representation of pathogen peptides for cellular immunity based memory. We find that SARS-CoV-2 subunit peptides may not be robustly displayed by the Major Histocompatibility Complex (MHC) molecules in certain individuals. We introduce an augmentation strategy for subunit vaccines that adds a small number of SARS-CoV-2 peptides to a vaccine to improve the population coverage of pathogen peptide display. Our population coverage estimates integrate clinical data on peptide immunogenicity in convalescent COVID-19 patients and machine learning predictions. We evaluate the population coverage of 9 different subunits of SARS-CoV-2, including 5 functional domains and 4 full proteins, and augment each of them to fill a predicted coverage gap. ### Competing Interest Statement David Gifford is a founder and shareholder of ThinkTx.

94: Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin binding proteins
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Posted 04 Aug 2020

Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin binding proteins
1 tweet bioRxiv biochemistry

Víctor M. Hernández-Rocamora, Natalia Baranova, Katharina Peters, Eefjan Breukink, Martin Loose, Waldemar Vollmer

Peptidoglycan is an essential component of the bacterial cell envelope that surrounds the cytoplasmic membrane to protect the cell from osmotic lysis. Important antibiotics such as β-lactams and glycopeptides target peptidoglycan biosynthesis. Class A penicillin binding proteins are bifunctional membrane-bound peptidoglycan synthases that polymerize glycan chains and connect adjacent stem peptides by transpeptidation. How these enzymes work in their physiological membrane environment is poorly understood. Here we developed a novel FRET-based assay to follow in real time both reactions of class A PBPs reconstituted in liposomes or supported lipid bilayers and we demonstrate this assay with PBP1B homologues from Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii in the presence or absence of their cognate lipoprotein activator. Our assay allows unravelling the mechanisms of peptidoglycan synthesis in a lipid-bilayer environment and can be further developed to be used for high throughput screening for new antimicrobials.

95: A candidate culture-dependent form in apes, nut-cracking, can be individually learnt by naive orangutans (Pongo abelii)
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Posted 23 Apr 2020

A candidate culture-dependent form in apes, nut-cracking, can be individually learnt by naive orangutans (Pongo abelii)
1 tweet bioRxiv animal behavior and cognition

Elisa Bandini, Johannes Grossmann, Anna Albiach Serrano, Claudio Tennie

Several species of non-human apes have been suggested to rely on copying to acquire some of their behavioural forms. One of the most cited examples, and UN-protected, is nut-cracking in chimpanzees. However, copying might not be the most parsimonious explanation for nut-cracking, considering the lack of evidence for spontaneous copying in this species. The zone of latent solutions (ZLS) hypothesis argues instead that the behavioural form of nut-cracking is individually learnt, whilst non-copying social learning fosters frequency differences across populations. In order to differentiate between the copying and the ZLS hypothesis, four nut-cracking-naive orangutans (Mage=16; age range=10-19; 4F; at time of testing) were provided with nuts and hammers but were not demonstrated the behaviour. Whilst the adults in the group were able to open nuts with their teeth, one juvenile spontaneously expressed nut-cracking with a wooden hammer. We therefore show that the behavioural form of nut-cracking does not necessarily rely on copying in orangutans. ### Competing Interest Statement The authors have declared no competing interest.

96: Cities have a negative impact on navigation ability: evidence from 38 countries
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Posted 24 Jan 2020

Cities have a negative impact on navigation ability: evidence from 38 countries
1 tweet bioRxiv neuroscience

A. Coutrot, E. Manley, D. Yesiltepe, R.C. Dalton, J. M. Wiener, C. Hölscher, M. Hornberger, H. J. Spiers

Cultural and geographical properties of the environment have been shown to deeply influence cognition and mental health. However, how the environment experienced during early life impacts later cognitive abilities remains poorly understood. Here, we used a cognitive task embedded in a video game to measure non-verbal spatial navigation ability in 442,195 people from 38 countries across the world. We found that on average, people who reported having grown up in cities have worse navigation skills than those who grew-up outside cities, even when controlling for age, gender, and level of education. The negative impact of cities was stronger in countries with low average Street Network Entropy, i.e. whose cities have a griddy layout. The effect was smaller in countries with more complex, organic cities. This evidences the impact of the environment on human cognition on a global scale, and highlights the importance of urban design on human cognition and brain function.

97: A molecular cell atlas of the human lung from single cell RNA sequencing
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Posted 27 Aug 2019

A molecular cell atlas of the human lung from single cell RNA sequencing
1 tweet bioRxiv genomics

Kyle J. Travaglini, Ahmad N. Nabhan, Lolita Penland, Rahul Sinha, Astrid Gillich, Rene V Sit, Stephen Chang, Stephanie D Conley, Yasuo Mori, Jun Seita, Gerald J. Berry, Joseph B Shrager, Ross J Metzger, Christin S Kuo, Norma F. Neff, Irving L. Weissman, Stephen R. Quake, Mark A Krasnow

Although single cell RNA sequencing studies have begun providing compendia of cell expression profiles, it has proven more difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here we describe droplet- and plate-based single cell RNA sequencing applied to ∼75,000 human lung and blood cells, combined with a multi-pronged cell annotation approach, which have allowed us to define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 of 45 previously known cell types or subtypes and 14 new ones. This comprehensive molecular atlas elucidates the biochemical functions of lung cell types and the cell-selective transcription factors and optimal markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signaling interactions including sources and targets of chemokines in immune cell trafficking and expression changes on lung homing; and identifies the cell types directly affected by lung disease genes and respiratory viruses. Comparison to mouse identified 17 molecular types that appear to have been gained or lost during lung evolution and others whose expression profiles have been substantially altered, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions, and interactions are achieved in development and tissue engineering and altered in disease and evolution.

98: Critical Assessment of Protein Intrinsic Disorder Prediction
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Posted 12 Aug 2020

Critical Assessment of Protein Intrinsic Disorder Prediction
1 tweet bioRxiv bioinformatics

Marco Necci, Damiano Piovesan, CAID Predictors, DisProt Curators, Silvio C E Tosatto

Intrinsically disordered proteins defying the traditional protein structure-function paradigm represent a challenge to study experimentally. As a large part of our knowledge rests on computational predictions, it is crucial for their accuracy to be high. The Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment was established as a community-based blind test to determine the state of the art in predicting intrinsically disordered regions in proteins and the subset of disordered residues involved in binding other molecules. A total of 43 methods, 32 for disorder and 11 for binding regions, were evaluated on a dataset of 646 proteins. The best methods use modern machine learning techniques and significantly outperform widely used first-generation methods across different types of targets. Disordered binding regions remain hard to predict correctly, which offers significant potential for improvement. Intriguingly, some of the top performing methods are also among the fastest.

99: High prevalence of the antibody against Syncytin-1 in schizophrenia
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Posted 16 Feb 2018

High prevalence of the antibody against Syncytin-1 in schizophrenia
1 tweet bioRxiv neuroscience

Yurina Hibi, Kaori Asamitsu, Hiroyo Matsumura, Takaomi Sanda, Yuki Nakahira, Kenji Arimoto, Shinsuke Nakanishi, Kazunori Maekawa, Tatsuo Akechi, Noriyuki Matsukawa, Terutaka Fukaya, Yutaka Tomita, Nariaki Iijima, Hiroyuki Kato, Takashi Okamoto

Both genetic and environmental factors have been considered causative agents for schizophrenia (SZ). However, no single gene has been shown responsible for the development of SZ. Furthermore, the pathophysiological roles of environmental factors including psychological stress, autoimmunity, and microbial infection have not been fully understood. Previous studies have suggested the involvement of one of the human endogenous retroviruses (HERVs), HERV-W, in SZ. In this study, prevalence of antibodies against the HERV-W Syncytin-1 protein was examined using a newly developed ELISA test. Fifty percent of patients with SZ (24 out of 48 cases) were antibody-positive, with a specificity of greater than 95% (less than 5% of control cases, 3 out of 79). No significant effect of medication was evident, nor did any SZ cases become seropositive after diagnosis. These findings indicate a possible involvement of HERV-W expression in the development of SZ and support its applicability to laboratory diagnoses.

100: Glycomic analysis of host-response reveals high mannose as a key mediator of influenza severity
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Posted 23 Apr 2020

Glycomic analysis of host-response reveals high mannose as a key mediator of influenza severity
1 tweet bioRxiv microbiology

Daniel W Heindel, Sujeethraj Koppolu, Yue Zhang, Brian Kasper, Lawrence Meche, Christopher Vaiana, Stephanie J. Bissel, Chalise E. Carter, Alyson A. Kelvin, Bin Zhang, Bin Zhou, Tsui-Wen Chou, Lauren Lashua, Ted M. Ross, Elodie Ghedin, Lara K Mahal

Influenza virus infections cause a wide variety of outcomes, from mild disease to 3-5 million cases of severe illness and ~290,000-645,000 deaths annually worldwide. The molecular mechanisms underlying these disparate outcomes are currently unknown. Glycosylation within the human host plays a critical role in influenza virus biology. However, the impact these modifications have on the severity of influenza disease has not been examined. Herein, we profile the glycomic host responses to influenza virus infection as a function of disease severity using a ferret model and our lectin microarray technology. We identify the glycan epitope high mannose as a marker of influenza virus-induced pathogenesis and severity of disease outcome. Induction of high mannose is dependent upon the unfolded protein response (UPR) pathway, a pathway previously shown to associate with lung damage and severity of influenza virus infection. Also, the mannan-binding lectin (MBL2), an innate immune lectin that negatively impacts influenza outcomes, recognizes influenza virus-infected cells in a high mannose dependent manner. Together, our data argue that the high mannose motif is an infection-associated molecular pattern on host cells that may guide immune responses leading to the concomitant damage associated with severity. ### Competing Interest Statement The authors have declared no competing interest.

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