Versatile CRISPR/Cas9-mediated mosaic analysis by gRNA-induced crossing-over for unmodified genomes
by Sarah E. Allen, Gabriel T. Koreman, Ankita Sarkar, Bei Wang, Mariana F. Wolfner, Chun Han Mosaic animals have provided the platform for many fundamental discoveries in developmental biology, cell biology, and other fields. Techniques to produce mosaic animals by mitotic recombination have been extensively developed inDrosophila melanogaster but are less common for other laboratory organisms. Here, we report mosaic analysis by gRNA-induced crossing-over (MAGIC), a new technique for generating mosaic animals based on DNA double-strand breaks produced by CRISPR/Cas9. MAGIC efficiently produces mosaic clones in both somati...
Source: PLoS Biology: Archived Table of Contents - January 14, 2021 Category: Biology Authors: Sarah E. Allen Source Type: research

Identification of 3 ′ UTR motifs required for mRNA localization to myelin sheaths in vivo
by Katie M. Yergert, Caleb A. Doll, Rebecca O ’Rouke, Jacob H. Hines, Bruce Appel Myelin is a specialized membrane produced by oligodendrocytes that insulates and supports axons. Oligodendrocytes extend numerous cellular processes, as projections of the plasma membrane, and simultaneously wrap multiple layers of myelin membrane around target axons. Notably, myelin sheaths origi nating from the same oligodendrocyte are variable in size, suggesting local mechanisms regulate myelin sheath growth. Purified myelin contains ribosomes and hundreds of mRNAs, supporting a model that mRNA localization and local protein synthe...
Source: PLoS Biology: Archived Table of Contents - January 13, 2021 Category: Biology Authors: Katie M. Yergert Source Type: research

TMT-Opsins differentially modulate medaka brain function in a context-dependent manner
by Bruno M. Fontinha, Theresa Zekoll, Mariam Al-Rawi, Miguel Gallach, Florian Reithofer, Alison J. Barker, Maximilian Hofbauer, Ruth M. Fischer, Arndt von Haeseler, Herwig Baier, Kristin Tessmar-Raible Vertebrate behavior is strongly influenced by light. Light receptors, encoded by functional opsin proteins, are present inside the vertebrate brain and peripheral tissues. This expression feature is present from fishes to human and appears to be particularly prominent in diurnal vertebrates. Despi te their conserved widespread occurrence, the nonvisual functions of opsins are still largely enigmatic. This is even more appar...
Source: PLoS Biology: Archived Table of Contents - January 7, 2021 Category: Biology Authors: Bruno M. Fontinha Source Type: research

Ectoderm to mesoderm transition by down-regulation of actomyosin contractility
by Leily Kashkooli, David Rozema, Lina Espejo-Ramirez, Paul Lasko, Fran çois Fagotto Collective migration of cohesive tissues is a fundamental process in morphogenesis and is particularly well illustrated during gastrulation by the rapid and massive internalization of the mesoderm, which contrasts with the much more modest movements of the ectoderm. In theXenopus embryo, the differences in morphogenetic capabilities of ectoderm and mesoderm can be connected to the intrinsic motility of individual cells, very low for ectoderm, highly for mesoderm. Surprisingly, we find that these seemingly deep differences can be ac...
Source: PLoS Biology: Archived Table of Contents - January 6, 2021 Category: Biology Authors: Leily Kashkooli Source Type: research

Cell cycle-dependent and independent mating blocks ensure fungal zygote survival and ploidy maintenance
by Aleksandar Vje štica, Melvin Bérard, Gaowen Liu, Laura Merlini, Pedro Junior Nkosi, Sophie G. Martin To ensure genome stability, sexually reproducing organisms require that mating brings together exactly 2 haploid gametes and that meiosis occurs only in diploid zygotes. In the fission yeastSchizosaccharomyces pombe, fertilization triggers the Mei3-Pat1-Mei2 signaling cascade, which represses subsequent mating and initiates meiosis. Here, we establish a degron system to specifically degrade proteins postfusion and demonstrate that mating blocks not only safeguard zygote ploidy but also prevent lysis caused...
Source: PLoS Biology: Archived Table of Contents - January 6, 2021 Category: Biology Authors: Aleksandar Vje štica Source Type: research

Cyclin-dependent Kinase 1 and Aurora Kinase choreograph mitotic storage and redistribution of a growth factor receptor
by Christina D. Cota, Matthew S. Dreier, William Colgan, Anna Cha, Twan Sia, Brad Davidson Endosomal trafficking of receptors and associated proteins plays a critical role in signal processing. Until recently, it was thought that trafficking was shut down during cell division. Thus, remarkably, the regulation of trafficking during division remains poorly characterized. Here we delineate the role of mitotic kinases in receptor trafficking during asymmetric division. Targeted perturbations reveal that Cyclin-dependent Kinase 1 (CDK1) and Aurora Kinase promote storage of Fibroblast Growth Factor Receptors (FGFRs) by suppress...
Source: PLoS Biology: Archived Table of Contents - January 4, 2021 Category: Biology Authors: Christina D. Cota Source Type: research

< i > Borrelia burgdorferi < /i > infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart
by Diego Barriales, Itziar Mart ín-Ruiz, Ana Carreras-González, Marta Montesinos-Robledo, Mikel Azkargorta, Ibon Iloro, Iraide Escobés, Teresa Martín-Mateos, Estibaliz Atondo, Ainhoa Palacios, Monika Gonzalez-Lopez, Laura Bárcena, Ana R. Cortázar, Diana Cabrera, Ainize Peña-Cearra, Sebastiaan M. van Liempd, Juan M. Falcón- Pérez, Miguel A. Pascual-Itoiz, Juana María Flores, Leticia Abecia, Aize Pellon, Maria Luz Martínez-Chantar, Ana M. Aransay, Alberto Pascual, Felix Elortza, Edurne Berra, José Luis Lavín, Héctor Rodrí...
Source: PLoS Biology: Archived Table of Contents - January 4, 2021 Category: Biology Authors: Diego Barriales Source Type: research

Correlative light electron ion microscopy reveals in vivo localisation of bedaquiline in < i > Mycobacterium tuberculosis < /i > –infected lungs
by Antony Fearns, Daniel J. Greenwood, Angela Rodgers, Haibo Jiang, Maximiliano G. Gutierrez Correlative light, electron, and ion microscopy (CLEIM) offers huge potential to track the intracellular fate of antibiotics, with organelle-level resolution. However, a correlative approach that enables subcellular antibiotic visualisation in pathogen-infected tissue is lacking. Here, we develope d correlative light, electron, and ion microscopy in tissue (CLEIMiT) and used it to identify the cell type–specific accumulation of an antibiotic in lung lesions of mice infected withMycobacterium tuberculosis. Using CLEIMiT, we f...
Source: PLoS Biology: Archived Table of Contents - December 31, 2020 Category: Biology Authors: Antony Fearns Source Type: research

A comprehensive atlas of white matter tracts in the chimpanzee
by Katherine L. Bryant, Longchuan Li, Nicole Eichert, Rogier B. Mars Chimpanzees (Pan troglodytes) are, along with bonobos, humans ’ closest living relatives. The advent of diffusion MRI tractography in recent years has allowed a resurgence of comparative neuroanatomical studies in humans and other primate species. Here we offer, in comparative perspective, the first chimpanzee white matter atlas, constructed from in vivo chi mpanzee diffusion-weighted scans. Comparative white matter atlases provide a useful tool for identifying neuroanatomical differences and similarities between humans and other primate species. U...
Source: PLoS Biology: Archived Table of Contents - December 31, 2020 Category: Biology Authors: Katherine L. Bryant Source Type: research

Clustering of Tir during enteropathogenic < i > E < /i > . < i > coli < /i > infection triggers calcium influx –dependent pyroptosis in intestinal epithelial cells
by Qiyun Zhong, Theodoros I. Roumeliotis, Zuza Kozik, Massiel Cepeda-Molero, Luis Ángel Fernández, Avinash R. Shenoy, Chris Bakal, Gad Frankel, Jyoti S. Choudhary Clustering of the enteropathogenicEscherichia coli (EPEC) type III secretion system (T3SS) effector translocated intimin receptor (Tir) by intimin leads to actin polymerisation and pyroptotic cell death in macrophages. The effect of Tir clustering on the viability of EPEC-infected intestinal epithelial cells (IECs) is unknown. We show that EPEC induces pyroptosis in IECs in a Tir-dependent but actin polymerisation-independent manner, which was enha...
Source: PLoS Biology: Archived Table of Contents - December 30, 2020 Category: Biology Authors: Qiyun Zhong Source Type: research

Single-cell RNA-seq analysis of mouse preimplantation embryos by third-generation sequencing
by Xiaoying Fan, Dong Tang, Yuhan Liao, Pidong Li, Yu Zhang, Minxia Wang, Fan Liang, Xiao Wang, Yun Gao, Lu Wen, Depeng Wang, Yang Wang, Fuchou Tang The development of next generation sequencing (NGS) platform-based single-cell RNA sequencing (scRNA-seq) techniques has tremendously changed biological researches, while there are still many questions that cannot be addressed by them due to their short read lengths. We developed a novel scRNA-seq technology based on third-generation sequencing (TGS) platform (single-cell amplification and sequencing of full-length RNAs by Nanopore platform, SCAN-seq). SCAN-seq exhibited high...
Source: PLoS Biology: Archived Table of Contents - December 30, 2020 Category: Biology Authors: Xiaoying Fan Source Type: research

Structural analyses of the PKA RII β holoenzyme containing the oncogenic DnaJB1-PKAc fusion protein reveal protomer asymmetry and fusion-induced allosteric perturbations in fibrolamellar hepatocellular carcinoma
We report several differences in both structure and dynamics that could not be captured by the conventional crystallography approaches used to obtain prior structures. Most striking is the asymmetry caused by the absence of the second cyclic nucleotide binding (CNB) domain and the J-domain in one of the RIIβ:J-C protomers. Using molecular dynamics (MD) simulations, we discovered that this asymmetry is already present in the wild-type (WT) RIIβ2C2 but had been masked in the previous crystal structure. This asymmetry may link to the intrinsic allosteric regulation of all PKA holoenzymes and could also explain why m...
Source: PLoS Biology: Archived Table of Contents - December 28, 2020 Category: Biology Authors: Tsan-Wen Lu Source Type: research

Regulation of glial size by eicosapentaenoic acid through a novel Golgi apparatus mechanism
by Albert Zhang, Ziqiang Guan, Kyle Ockerman, Pengyuan Dong, Jiansheng Guo, Zhiping Wang, Dong Yan Coordination of cell growth is essential for the development of the brain, but the molecular mechanisms underlying the regulation of glial and neuronal size are poorly understood. To investigate the mechanisms involved in glial size regulation, we usedCaenorhabditis elegans amphid sheath (AMsh) glia as a model and show that a conservedcis-Golgi membrane proteineas-1/GOLT1B negatively regulates glial growth. We found thateas-1 inhibits a conserved E3 ubiquitin ligasernf-145/RNF145, which, in turn, promotes nuclear activation ...
Source: PLoS Biology: Archived Table of Contents - December 28, 2020 Category: Biology Authors: Albert Zhang Source Type: research

Delineating reef fish trophic guilds with global gut content data synthesis and phylogeny
by Valeriano Parravicini, Jordan M. Casey, Nina M. D. Schiettekatte, Simon J. Brandl, Chlo é Pozas-Schacre, Jérémy Carlot, Graham J. Edgar, Nicholas A. J. Graham, Mireille Harmelin-Vivien, Michel Kulbicki, Giovanni Strona, Rick D. Stuart-Smith Understanding species’ roles in food webs requires an accurate assessment of their trophic niche. However, it is challenging to delineate potential trophic interactions across an ecosystem, and a paucity of empirical information often leads to inconsistent definitions of trophic guilds based on expert opinion, especially when applied to hyperdiverse ecosys...
Source: PLoS Biology: Archived Table of Contents - December 28, 2020 Category: Biology Authors: Valeriano Parravicini Source Type: research

Increased prostaglandin-D < sub > 2 < /sub > in male STAT3-deficient hearts shifts cardiac progenitor cells from endothelial to white adipocyte differentiation
by Elisabeth Stelling, Melanie Ricke-Hoch, Sergej Erschow, Steve Hoffmann, Anke Katharina Bergmann, Maren Heimerl, Stefan Pietzsch, Karin Battmer, Alexandra Haase, Britta Stapel, Michaela Scherr, Jean-Luc Balligand, Ofer Binah, Denise Hilfiker-Kleiner Cardiac levels of the signal transducer and activator of transcription factor-3 (STAT3) decline with age, and male but not female mice with a cardiomyocyte-specific STAT3 deficiency conditional knockout (CKO) display premature age-related heart failure associated with reduced cardiac capillary den sity. In the present study, isolated male and female CKO-cardiomyocytes exhibi...
Source: PLoS Biology: Archived Table of Contents - December 28, 2020 Category: Biology Authors: Elisabeth Stelling Source Type: research

Long-term experimental evolution of HIV-1 reveals effects of environment and mutational history
by Eva Bons, Christine Leemann, Karin J. Metzner, Roland R. Regoes An often-returning question for not only HIV-1, but also other organisms, is how predictable evolutionary paths are. The environment, mutational history, and random processes can all impact the exact evolutionary paths, but to which extent these factors contribute to the evolutionary dynamics of a particular system is an open question. Especially in a virus like HIV-1, with a large mutation rate and large population sizes, evolution is expected to be highly predictable if the impact of environment and history is low, and evolution is not neutral. We invest...
Source: PLoS Biology: Archived Table of Contents - December 28, 2020 Category: Biology Authors: Eva Bons Source Type: research

CEP290 is essential for the initiation of ciliary transition zone assembly
by Zhimao Wu, Nan Pang, Yingying Zhang, Huicheng Chen, Ying Peng, Jingyan Fu, Qing Wei Cilia play critical roles during embryonic development and adult homeostasis. Dysfunction of cilia leads to various human genetic diseases, including many caused by defects in transition zones (TZs), the “gates” of cilia. The evolutionarily conserved TZ component centrosomal protein 290 (CEP29 0) is the most frequently mutated human ciliopathy gene, but its roles in ciliogenesis are not completely understood. Here, we report that CEP290 plays an essential role in the initiation of TZ assembly inDrosophila. Mechanistically, t...
Source: PLoS Biology: Archived Table of Contents - December 28, 2020 Category: Biology Authors: Zhimao Wu Source Type: research

Signatures of host –pathogen evolutionary conflict reveal MISTR—A conserved MItochondrial STress Response network
by Mahsa Sorouri, Tyron Chang, Palmy Jesudhasan, Chelsea Pinkham, Nels C. Elde, Dustin C. Hancks Host–pathogen conflicts leave genetic signatures in genes that are critical for host defense functions. Using these “molecular scars” as a guide to discover gene functions, we discovered a vertebrate-specific MItochondrial STress Response (MISTR) circuit. MISTR proteins are associated with e lectron transport chain (ETC) factors and activated by stress signals such as interferon gamma (IFNγ) and hypoxia. Upon stress, ultraconserved microRNAs (miRNAs) down-regulate MISTR1(NDUFA4) followed by replacement ...
Source: PLoS Biology: Archived Table of Contents - December 28, 2020 Category: Biology Authors: Mahsa Sorouri Source Type: research

Convergent evolution of diverse < i > Bacillus anthracis < /i > outbreak strains toward altered surface oligosaccharides that modulate anthrax pathogenesis
by Michael H. Norris, Alexander Kirpich, Andrew P. Bluhm, Diansy Zincke, Ted Hadfield, Jose Miguel Ponciano, Jason K. BlackburnBacillus anthracis, a spore-forming gram-positive bacterium, causes anthrax. The external surface of the exosporium is coated with glycosylated proteins. The sugar additions are capped with the unique monosaccharide anthrose. The West African Group (WAG)B.anthracis have mutations rendering them anthrose deficient. Through genome sequencing, we identified 2 different large chromosomal deletions within the anthrose biosynthetic operon ofB.anthracis strains from Chile and Poland. In silico analysis id...
Source: PLoS Biology: Archived Table of Contents - December 28, 2020 Category: Biology Authors: Michael H. Norris Source Type: research

Biparental contributions of the < i > H2A < /i > . < i > B < /i > histone variant control embryonic development in mice
by Antoine Molaro, Anna J. Wood, Derek Janssens, Selina M. Kindelay, Michael T. Eickbush, Steven Wu, Priti Singh, Charles H. Muller, Steven Henikoff, Harmit S. Malik Histone variants expand chromatin functions in eukaryote genomes.H2A.B genes are testis-expressed short histone H2A variants that arose in placental mammals. Their biological functions remain largely unknown. To investigate their function, we generated a knockout (KO) model that disrupts all 3H2A.B genes in mice. We show thatH2A.B KO males have globally altered chromatin structure in postmeiotic germ cells. Yet, they do not show impaired spermatogenesis or te...
Source: PLoS Biology: Archived Table of Contents - December 23, 2020 Category: Biology Authors: Antoine Molaro Source Type: research

< i > LSM12 < /i > - < i > EPAC1 < /i > defines a neuroprotective pathway that sustains the nucleocytoplasmic RAN gradient
by Jongbo Lee, Jumin Park, Ji-hyung Kim, Giwook Lee, Tae-Eun Park, Ki-Jun Yoon, Yoon Ki Kim, Chunghun Lim Nucleocytoplasmic transport (NCT) defects have been implicated in neurodegenerative diseases such asC9ORF72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Here, we identify a neuroprotective pathway of like-Sm protein 12 (LSM12) and exchange protein directly activated by cyclic AMP 1 (EPAC1) that sustains the nucleocytoplasmic RAN gradient and thereby suppresses NCT dysfunction by theC9ORF72-derived poly(glycine-arginine) protein. LSM12 depletion in human neuroblastoma cells aggrava...
Source: PLoS Biology: Archived Table of Contents - December 23, 2020 Category: Biology Authors: Jongbo Lee Source Type: research

Glycosylation generates an efficacious and immunogenic vaccine against H7N9 influenza virus
by Jin Il Kim, Sehee Park, Joon-Yong Bae, Sunmi Lee, Jeonghun Kim, Gayeong Kim, Kirim Yoo, Jun Heo, Yong Seok Kim, Jae Soo Shin, Mee Sook Park, Man-Seong Park Zoonotic avian influenza viruses pose severe health threats to humans. Of several viral subtypes reported, the low pathogenic avian influenza H7N9 virus has since February 2013 caused more than 1,500 cases of human infection with an almost 40% case-fatality rate. Vaccination of poultry appears to reduce human infections. However, the emergence of highly pathogenic strains has increased concerns about H7N9 pandemics. To develop an efficacious H7N9 human vaccine, we d...
Source: PLoS Biology: Archived Table of Contents - December 23, 2020 Category: Biology Authors: Jin Il Kim Source Type: research

Oligodendrocytes support axonal transport and maintenance via exosome secretion
by Carsten Fr ühbeis, Wen Ping Kuo-Elsner, Christina Müller, Kerstin Barth, Leticia Peris, Stefan Tenzer, Wiebke Möbius, Hauke B. Werner, Klaus-Armin Nave, Dominik Fröhlich, Eva-Maria Krämer-Albers Neurons extend long axons that require maintenance and are susceptible to degeneration. Long-term integrity of axons depends on intrinsic mechanisms including axonal transport and extrinsic support from adjacent glial cells. The mechanisms of support provided by myelinating oligodendrocytes to und erlying axons are only partly understood. Oligodendrocytes release extracellular vesicles (EVs) with proper...
Source: PLoS Biology: Archived Table of Contents - December 22, 2020 Category: Biology Authors: Carsten Fr ühbeis Source Type: research

Design of novel granulopoietic proteins by topological rescaffolding
by Birte Hernandez Alvarez, Julia Skokowa, Murray Coles, Perihan Mir, Masoud Nasri, Kateryna Maksymenko, Laura Weidmann, Katherine W. Rogers, Karl Welte, Andrei N. Lupas, Patrick M üller, Mohammad ElGamacy Computational protein design is rapidly becoming more powerful, and improving the accuracy of computational methods would greatly streamline protein engineering by eliminating the need for empirical optimization in the laboratory. In this work, we set out to design novel granulopoietic agents usin g a rescaffolding strategy with the goal of achieving simpler and more stable proteins. All of the 4 experimentally tes...
Source: PLoS Biology: Archived Table of Contents - December 22, 2020 Category: Biology Authors: Birte Hernandez Alvarez Source Type: research

Phosphorylation of seryl-tRNA synthetase by ATM/ATR is essential for hypoxia-induced angiogenesis
by Yi Shi, Ze Liu, Qian Zhang, Ingrid Vallee, Zhongying Mo, Shuji Kishi, Xiang-Lei Yang Hypoxia-induced angiogenesis maintains tissue oxygen supply and protects against ischemia but also enhances tumor progression and malignancy. This is mediated through activation of transcription factors like hypoxia-inducible factor 1 (HIF-1) and c-Myc, yet the impact of hypoxia on negative regula tors of angiogenesis is unknown. During vascular development, seryl-tRNA synthetase (SerRS) regulates angiogenesis through a novel mechanism by counteracting c-Myc and transcriptionally repressing vascular endothelial growth factor A (VEGFA) ...
Source: PLoS Biology: Archived Table of Contents - December 22, 2020 Category: Biology Authors: Yi Shi Source Type: research

Single-cell transcriptome landscape of ovarian cells during primordial follicle assembly in mice
by Jun-Jie Wang, Wei Ge, Qiu-Yue Zhai, Jing-Cai Liu, Xiao-Wen Sun, Wen-Xiang Liu, Lan Li, Chu-Zhao Lei, Paul W. Dyce, Massimo De Felici, Wei Shen Primordial follicle assembly in the mouse occurs during perinatal ages and largely determines the ovarian reserve that will be available to support the reproductive life span. The development of primordial follicles is controlled by a complex network of interactions between oocytes and ovarian som atic cells that remain poorly understood. In the present research, using single-cell RNA sequencing performed over a time series on murine ovaries, coupled with several bioinformatics ...
Source: PLoS Biology: Archived Table of Contents - December 22, 2020 Category: Biology Authors: Jun-Jie Wang Source Type: research

Expansion of RiPP biosynthetic space through integration of pan-genomics and machine learning uncovers a novel class of lantibiotics
by Alexander M. Kloosterman, Peter Cimermancic, Somayah S. Elsayed, Chao Du, Michalis Hadjithomas, Mohamed S. Donia, Michael A. Fischbach, Gilles P. van Wezel, Marnix H. Medema Microbial natural products constitute a wide variety of chemical compounds, many which can have antibiotic, antiviral, or anticancer properties that make them interesting for clinical purposes. Natural product classes include polyketides (PKs), nonribosomal peptides (NRPs), and ribosomally synthes ized and post-translationally modified peptides (RiPPs). While variants of biosynthetic gene clusters (BGCs) for known classes of natural products are ea...
Source: PLoS Biology: Archived Table of Contents - December 22, 2020 Category: Biology Authors: Alexander M. Kloosterman Source Type: research

Patterns of smallpox mortality in London, England, over three centuries
We describe and analyze smallpox mortality in London from 1664 to 1930. We digitized the weekly records published in the London Bills of Mortality (LBoM) and the Registrar General’s Weekly Returns (R GWRs). We annotated the resulting time series with a sequence of historical events that might have influenced smallpox dynamics in London. We present a spectral analysis that reveals how periodicities in reported smallpox mortality changed over decades and centuries; many of these changes in epidemi c patterns are correlated with changes in control interventions and public health policies. We also examine how the seasona...
Source: PLoS Biology: Archived Table of Contents - December 21, 2020 Category: Biology Authors: Olga Krylova Source Type: research

Telomeric TART elements target the piRNA machinery in < i > Drosophila < /i >
by Christopher E. Ellison, Meenakshi S. Kagda, Weihuan Cao Coevolution between transposable elements (TEs) and their hosts can be antagonistic, where TEs evolve to avoid silencing and the host responds by reestablishing TE suppression, or mutualistic, where TEs are co-opted to benefit their host. TheTART-A TE functions as an important component ofDrosophila telomeres but has also reportedly inserted into theDrosophila melanogaster nuclear export factor genenxf2. We find that, rather than inserting intonxf2,TART-A has actually captured a portion ofnxf2 sequence. We show thatTART-A produces abundant Piwi-interacting small R...
Source: PLoS Biology: Archived Table of Contents - December 21, 2020 Category: Biology Authors: Christopher E. Ellison Source Type: research

The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins
by Carina Conceicao, Nazia Thakur, Stacey Human, James T. Kelly, Leanne Logan, Dagmara Bialy, Sushant Bhat, Phoebe Stevenson-Leggett, Adrian K. Zagrajek, Philippa Hollinghurst, Michal Varga, Christina Tsirigoti, Matthew Tully, Chris Chiu, Katy Moffat, Adrian Paul Silesian, John A. Hammond, Helena J. Maier, Erica Bickerton, Holly Shelton, Isabelle Dietrich, Stephen C. Graham, Dalan Bailey SARS Coronavirus 2 (SARS-CoV-2) emerged in late 2019, leading to the Coronavirus Disease 2019 (COVID-19) pandemic that continues to cause significant global mortality in human populations. Given its sequence similarity to SARS-CoV, as wel...
Source: PLoS Biology: Archived Table of Contents - December 21, 2020 Category: Biology Authors: Carina Conceicao Source Type: research

Prediction error signaling explains neuronal mismatch responses in the medial prefrontal cortex
by Lorena Casado-Rom án, Guillermo V. Carbajal, David Pérez González, Manuel S. Malmierca The mismatch negativity (MMN) is a key biomarker of automatic deviance detection thought to emerge from 2 cortical sources. First, the auditory cortex (AC) encodes spectral regularities and reports frequency-specific deviances. Then, more abstract representations in the prefrontal cortex (PFC) all ow to detect contextual changes of potential behavioral relevance. However, the precise location and time asynchronies between neuronal correlates underlying this frontotemporal network remain unclear and elusive. Our s...
Source: PLoS Biology: Archived Table of Contents - December 21, 2020 Category: Biology Authors: Lorena Casado-Rom án Source Type: research

Infection-induced 5 ′-half molecules of tRNA < sup > HisGUG < /sup > activate Toll-like receptor 7
by Kamlesh Pawar, Megumi Shigematsu, Soroush Sharbati, Yohei Kirino Toll-like receptors (TLRs) play a crucial role in the innate immune response. Although endosomal TLR7 recognizes single-stranded RNAs, their endogenous RNA ligands have not been fully explored. Here, we report 5′-tRNA half molecules as abundant activators of TLR7. Mycobacterial infection and acc ompanying surface TLR activation up-regulate the expression of 5′-tRNA half molecules in human monocyte-derived macrophages (HMDMs). The abundant accumulation of 5′-tRNA halves also occur in HMDM-secreted extracellular vehicles (EVs); the abundan...
Source: PLoS Biology: Archived Table of Contents - December 17, 2020 Category: Biology Authors: Kamlesh Pawar Source Type: research

Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant < i > Enterococcus faecium < /i >
by Clare L. Kinnear, Elsa Hansen, Valerie J. Morley, Kevin C. Tracy, Meghan Forstchen, Andrew F. Read, Robert J. Woods The antimicrobial resistance crisis has persisted despite broad attempts at intervention. It has been proposed that an important driver of resistance is selection imposed on bacterial populations that are not the intended target of antimicrobial therapy. But to date, there has been limited quantit ative measure of the mean and variance of resistance following antibiotic exposure. Here we focus on the important nosocomial pathogenEnterococcus faecium in a hospital system where resistance to daptomycin is e...
Source: PLoS Biology: Archived Table of Contents - December 17, 2020 Category: Biology Authors: Clare L. Kinnear Source Type: research

Permeability of the HIV-1 capsid to metabolites modulates viral DNA synthesis
by Chaoyi Xu, Douglas K. Fischer, Sanela Rankovic, Wen Li, Robert A. Dick, Brent Runge, Roman Zadorozhnyi, Jinwoo Ahn, Christopher Aiken, Tatyana Polenova, Alan N. Engelman, Zandrea Ambrose, Itay Rousso, Juan R. Perilla Reverse transcription, an essential event in the HIV-1 life cycle, requires deoxynucleotide triphosphates (dNTPs) to fuel DNA synthesis, thus requiring penetration of dNTPs into the viral capsid. The central cavity of the capsid protein (CA) hexamer reveals itself as a plausible channel that allow s the passage of dNTPs into assembled capsids. Nevertheless, the molecular mechanism of nucleotide import into...
Source: PLoS Biology: Archived Table of Contents - December 17, 2020 Category: Biology Authors: Chaoyi Xu Source Type: research

Rapid detection of SARS-CoV-2 with CRISPR-Cas12a
In this study, we d eveloped a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated proteins (Cas) 12a-based diagnostic method that allows the results to be visualized by the naked eye. We also introduced a rapid sample processing method, and when combined with recombinase polymerase amp lification (RPA), the sample to result can be achieved in 50 minutes with high sensitivity (1–10 copies per reaction). This accurate and portable detection method holds a great potential for COVID-19 control, especially in areas where specialized equipment is not available. (Source: PLoS Biology: Archi...
Source: PLoS Biology: Archived Table of Contents - December 15, 2020 Category: Biology Authors: Dan Xiong Source Type: research

A sensitive and affordable multiplex RT-qPCR assay for SARS-CoV-2 detection
by Martin A. M. Reijns, Louise Thompson, Juan Carlos Acosta, Holly A. Black, Francisco J. Sanchez-Luque, Austin Diamond, David A. Parry, Alison Daniels, Marie O'Shea, Carolina Uggenti, Maria C. Sanchez, Alan O'Callaghan, Michelle L. L. McNab, Martyna Adamowicz, Elias T. Friman, Toby Hurd, Edward J. Jarman, Frederic Li Mow Chee, Jacqueline K. Rainger, Marion Walker, Camilla Drake, Dasa Longman, Christine Mordstein, Sophie J. Warlow, Stewart McKay, Louise Slater, Morad Ansari, Ian P. M. Tomlinson, David Moore, Nadine Wilkinson, Jill Shepherd, Kate Templeton, Ingolfur Johannessen, Christine Tait-Burkard, J ürgen G. Haas,...
Source: PLoS Biology: Archived Table of Contents - December 15, 2020 Category: Biology Authors: Martin A. M. Reijns Source Type: research

Self-limiting stem-cell niche signaling through degradation of a stem-cell receptor
by Sophia Ladyzhets, Matthew Antel, Taylor Simao, Nathan Gasek, Ann E. Cowan, Mayu Inaba Stem-cell niche signaling is short-range in nature, such that only stem cells but not their differentiating progeny receive self-renewing signals. At the apical tip of theDrosophila testis, 8 to 10 germline stem cells (GSCs) surround the hub, a cluster of somatic cells that organize the stem-cell niche. We have previously shown that GSCs form microtubule-based nanotubes (MT-nanotubes) that project into the hub cells, serving as the platform for niche signal reception; this spatial arrangement ensures the reception of the niche signal ...
Source: PLoS Biology: Archived Table of Contents - December 14, 2020 Category: Biology Authors: Sophia Ladyzhets Source Type: research

Neuroinflammation in the normal-appearing white matter (NAWM) of the multiple sclerosis brain causes abnormalities at the nodes of Ranvier
by Patricia Gallego-Delgado, Rachel James, Eleanor Browne, Joanna Meng, Swetha Umashankar, Li Tan, Carmen Picon, Nicholas D. Mazarakis, A. Aldo Faisal, Owain W. Howell, Richard Reynolds Changes to the structure of nodes of Ranvier in the normal-appearing white matter (NAWM) of multiple sclerosis (MS) brains are associated with chronic inflammation. We show that the paranodal domains in MS NAWM are longer on average than control, with Kv1.2 channels dislocated into the paranode. T hese pathological features are reproduced in a model of chronic meningeal inflammation generated by the injection of lentiviral vectors for the ...
Source: PLoS Biology: Archived Table of Contents - December 14, 2020 Category: Biology Authors: Patricia Gallego-Delgado Source Type: research

In silico APC/C substrate discovery reveals cell cycle-dependent degradation of UHRF1 and other chromatin regulators
by Jennifer L. Franks, Raquel C. Martinez-Chacin, Xianxi Wang, Rochelle L. Tiedemann, Thomas Bonacci, Rajarshi Choudhury, Derek L. Bolhuis, Taylor P. Enrico, Ryan D. Mouery, Jeffrey S. Damrauer, Feng Yan, Joseph S. Harrison, M. Ben Major, Katherine A. Hoadley, Aussie Suzuki, Scott B. Rothbart, Nicholas G. Brown, Michael J. Emanuele The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase and critical regulator of cell cycle progression. Despite its vital role, it has remained challenging to globally map APC/C substrates. By combining orthogonal features of known substrates, we predicted APC/C substrates ...
Source: PLoS Biology: Archived Table of Contents - December 11, 2020 Category: Biology Authors: Jennifer L. Franks Source Type: research

Distinct populations of crypt-associated fibroblasts act as signaling hubs to control colon homeostasis
by Michael David Br ügger, Tomas Valenta, Hassan Fazilaty, George Hausmann, Konrad Basler Despite recent progress in recognizing the importance of mesenchymal cells for the homeostasis of the intestinal system, the current picture of how these cells communicate with the associated epithelial layer remains unclear. To describe the relevant cell populations in an unbiased manner, we carr ied out a single-cell transcriptome analysis of the adult murine colon, producing a high-quality atlas of matched colonic epithelium and mesenchyme. We identify two crypt-associated colonic fibroblast populations that are demarcated by...
Source: PLoS Biology: Archived Table of Contents - December 11, 2020 Category: Biology Authors: Michael David Br ügger Source Type: research

Decoding the neural dynamics of free choice in humans
by Thomas Thiery, Anne-Lise Saive, Etienne Combrisson, Arthur Dehgan, Julien Bastin, Philippe Kahane, Alain Berthoz, Jean-Philippe Lachaux, Karim Jerbi How do we choose a particular action among equally valid alternatives? Nonhuman primate findings have shown that decision-making implicates modulations in unit firing rates and local field potentials (LFPs) across frontal and parietal cortices. Yet the electrophysiological brain mechanisms that un derlie free choice in humans remain ill defined. Here, we address this question using rare intracerebral electroencephalography (EEG) recordings in surgical epilepsy patients per...
Source: PLoS Biology: Archived Table of Contents - December 10, 2020 Category: Biology Authors: Thomas Thiery Source Type: research

Ensuring the quality and specificity of preregistrations
by Marjan Bakker, Coosje L. S. Veldkamp, Marcel A. L. M. van Assen, Elise A. V. Crompvoets, How Hwee Ong, Brian A. Nosek, Courtney K. Soderberg, David Mellor, Jelte M. Wicherts Researchers face many, often seemingly arbitrary, choices in formulating hypotheses, designing protocols, collecting data, analyzing data, and reporting results. Opportunistic use of “researcher degrees of freedom” aimed at obtaining statistical significance increases the likelihood of obtaini ng and publishing false-positive results and overestimated effect sizes. Preregistration is a mechanism for reducing such degrees of freedom by s...
Source: PLoS Biology: Archived Table of Contents - December 9, 2020 Category: Biology Authors: Marjan Bakker Source Type: research

The Venus flytrap trigger hair –specific potassium channel KDM1 can reestablish the K < sup > + < /sup > gradient required for hapto-electric signaling
by Anda L. Iosip, Jennifer B öhm, Sönke Scherzer, Khaled A. S. Al-Rasheid, Ingo Dreyer, Jörg Schultz, Dirk Becker, Ines Kreuzer, Rainer Hedrich The carnivorous plantDionaea muscipula harbors multicellular trigger hairs designed to sense mechanical stimuli upon contact with animal prey. At the base of the trigger hair, mechanosensation is transduced into an all-or-nothing action potential (AP) that spreads all over the trap, ultimately leading to trap closure and prey capture. To reveal the molecular basis for the unique functional repertoire of this mechanoresponsive plant structure, we determined the trans...
Source: PLoS Biology: Archived Table of Contents - December 9, 2020 Category: Biology Authors: Anda L. Iosip Source Type: research

TNF- α signaling: TACE inhibition to put out the burning heart
This study suggests that preventing tmTNF-α cleavage by targeting the TNF-α converting enzyme (TACE) rather than inhibiting TNF-α signaling altogether might b e a valuable therapeutic approach. (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - December 9, 2020 Category: Biology Authors: Gesine M. Dittrich Source Type: research

Correction: Planthopper bugs use a fast, cyclic elastic recoil mechanism for effective vibrational communication at small body size
by Leonidas-Romanos Davranoglou, Alice Cicirello, Graham K. Taylor, Beth Mortimer (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - December 9, 2020 Category: Biology Authors: Leonidas-Romanos Davranoglou Source Type: research

Correction: Low availability of code in ecology: A call for urgent action
by The PLOS Biology Staff (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - December 9, 2020 Category: Biology Authors: The PLOS Biology Staff Source Type: research

Correction: High-coverage plasma lipidomics reveals novel sex-specific lipidomic fingerprints of age and BMI: Evidence from two large population cohort studies
by Habtamu B. Beyene, Gavriel Olshansky, Adam Alexander T. Smith, Corey Giles, Kevin Huynh, Michelle Cinel, Natalie A. Mellett, Gemma Cadby, Joseph Hung, Jennie Hui, John Beilby, Gerald F. Watts, Jonathan E. Shaw, Eric K. Moses, Dianna J. Magliano, Peter J. Meikle (Source: PLoS Biology: Archived Table of Contents)
Source: PLoS Biology: Archived Table of Contents - December 9, 2020 Category: Biology Authors: Habtamu B. Beyene Source Type: research

The Drosophila amyloid precursor protein homologue mediates neuronal survival and neuroglial interactions
We report that APPL loss of function (LOF) results in the dysregulation of endolysosomal function in neurons, with a notable enlargement of early endosomal compartments followed by neuronal cell death and the accumulation of dead neurons in the brain during a critical period at a young age. These defects can be rescued by reduction in the levels of the early endosomal regulator Rab5, indicating a causal role of endosomal function for cell death. Finally, we show that the secreted extracellular domain of APPL interacts with glia and regulates the size of their endosomes, the expression of the Draper engulfment receptor, and...
Source: PLoS Biology: Archived Table of Contents - December 8, 2020 Category: Biology Authors: Irini A. Kessissoglou Source Type: research

Reoccurring neural stem cell divisions in the adult zebrafish telencephalon are sufficient for the emergence of aggregated spatiotemporal patterns
by Valerio Lupperger, Carsten Marr, Prisca Chapouton Regulation of quiescence and cell cycle entry is pivotal for the maintenance of stem cell populations. Regulatory mechanisms, however, are poorly understood. In particular, it is unclear how the activity of single stem cells is coordinated within the population or if cells divide in a purely rando m fashion. We addressed this issue by analyzing division events in an adult neural stem cell (NSC) population of the zebrafish telencephalon. Spatial statistics and mathematical modeling of over 80,000 NSCs in 36 brain hemispheres revealed weakly aggregated, nonrandom division...
Source: PLoS Biology: Archived Table of Contents - December 8, 2020 Category: Biology Authors: Valerio Lupperger Source Type: research

The actions of others act as a pseudo-reward to drive imitation in the context of social reinforcement learning
by Anis Najar, Emmanuelle Bonnet, Bahador Bahrami, Stefano Palminteri While there is no doubt that social signals affect human reinforcement learning, there is still no consensus about how this process is computationally implemented. To address this issue, we compared three psychologically plausible hypotheses about the algorithmic implementation of imitation in rei nforcement learning. The first hypothesis, decision biasing (DB), postulates that imitation consists in transiently biasing the learner’s action selection without affecting their value function. According to the second hypothesis, model-based imitation (...
Source: PLoS Biology: Archived Table of Contents - December 8, 2020 Category: Biology Authors: Anis Najar Source Type: research