A Well-Mixed E. coli Genome: Widespread Contacts Revealed by Tracking Mu Transposition
Publication date: Available online 13 February 2020Source: CellAuthor(s): David M. Walker, Peter L. Freddolino, Rasika M. HarsheySummaryThe three-dimensional structures of chromosomes are increasingly being recognized as playing a major role in cellular regulatory states. The efficiency and promiscuity of phage Mu transposition was exploited to directly measure in vivo interactions between genomic loci in E. coli. Two global organizing principles have emerged: first, the chromosome is well-mixed and uncompartmentalized, with transpositions occurring freely between all measured loci; second, several gene families/...
Source: Cell - February 15, 2020 Category: Cytology Source Type: research

Proteogenomic Characterization of Endometrial Carcinoma
Publication date: Available online 13 February 2020Source: CellAuthor(s): Yongchao Dou, Emily A. Kawaler, Daniel Cui Zhou, Marina A. Gritsenko, Chen Huang, Lili Blumenberg, Alla Karpova, Vladislav A. Petyuk, Sara R. Savage, Shankha Satpathy, Wenke Liu, Yige Wu, Chia-Feng Tsai, Bo Wen, Zhi Li, Song Cao, Jamie Moon, Zhiao Shi, MacIntosh Cornwell, Matthew A. WyczalkowskiSummaryWe undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/&beta...
Source: Cell - February 15, 2020 Category: Cytology Source Type: research

Cellular and Molecular Probing of Intact Human Organs
Publication date: Available online 13 February 2020Source: CellAuthor(s): Shan Zhao, Mihail Ivilinov Todorov, Ruiyao Cai, Rami AI -Maskari, Hanno Steinke, Elisabeth Kemter, Hongcheng Mai, Zhouyi Rong, Martin Warmer, Karen Stanic, Oliver Schoppe, Johannes Christian Paetzold, Benno Gesierich, Milagros N. Wong, Tobias B. Huber, Marco Duering, Oliver Thomas Bruns, Bjoern Menze, Jan Lipfert, Victor G. PuellesSummaryOptical tissue transparency permits scalable cellular and molecular investigation of complex tissues in 3D. Adult human organs are particularly challenging to render transparent because of the accumulation of dense a...
Source: Cell - February 15, 2020 Category: Cytology Source Type: research

Lymphoma Driver Mutations in the Pathogenic Evolution of an Iconic Human Autoantibody
Publication date: Available online 13 February 2020Source: CellAuthor(s): Mandeep Singh, Katherine J.L. Jackson, Jing J. Wang, Peter Schofield, Matt A. Field, David Koppstein, Timothy J. Peters, Deborah L. Burnett, Simone Rizzetto, Damien Nevoltris, Etienne Masle-Farquhar, Megan L. Faulks, Amanda Russell, Divya Gokal, Asami Hanioka, Keisuke Horikawa, Alexander D. Colella, Timothy K. Chataway, James Blackburn, Tim R. MercerSummaryPathogenic autoantibodies arise in many autoimmune diseases, but it is not understood how the cells making them evade immune checkpoints. Here, single-cell multi-omics analysis demonstrates a share...
Source: Cell - February 15, 2020 Category: Cytology Source Type: research

Click Chemistry in Proteomic Investigations
Publication date: Available online 13 February 2020Source: CellAuthor(s): Christopher G. Parker, Matthew R. PrattDespite advances in genetic and proteomic techniques, a complete portrait of the proteome and its complement of dynamic interactions and modifications remains a lofty, and as of yet, unrealized, objective. Specifically, traditional biological and analytical approaches have not been able to address key questions relating to the interactions of proteins with small molecules, including drugs, drug candidates, metabolites, or protein post-translational modifications (PTMs). Fortunately, chemists have bridged this ex...
Source: Cell - February 15, 2020 Category: Cytology Source Type: research

Mapping the Fine-Scale Organization and Plasticity of the Brain Vasculature
Publication date: Available online 13 February 2020Source: CellAuthor(s): Christoph Kirst, Sophie Skriabine, Alba Vieites-Prado, Thomas Topilko, Paul Bertin, Gaspard Gerschenfeld, Florine Verny, Piotr Topilko, Nicolas Michalski, Marc Tessier-Lavigne, Nicolas RenierSummaryThe cerebral vasculature is a dense network of arteries, capillaries, and veins. Quantifying variations of the vascular organization across individuals, brain regions, or disease models is challenging. We used immunolabeling and tissue clearing to image the vascular network of adult mouse brains and developed a pipeline to segment terabyte-sized multichann...
Source: Cell - February 15, 2020 Category: Cytology Source Type: research

Tissue Determinants of Human NK Cell Development, Function, and Residence
Publication date: Available online 13 February 2020Source: CellAuthor(s): Pranay Dogra, Chiara Rancan, Wenji Ma, Marta Toth, Takashi Senda, Dustin J. Carpenter, Masaru Kubota, Rei Matsumoto, Puspa Thapa, Peter A. Szabo, Maya Meimei Li Poon, Jacky Li, Janice Arakawa-Hoyt, Yufeng Shen, Lawrence Fong, Lewis L. Lanier, Donna L. FarberSummaryImmune responses in diverse tissue sites are critical for protective immunity and homeostasis. Here, we investigate how tissue localization regulates the development and function of human natural killer (NK) cells, innate lymphocytes important for anti-viral and tumor immunity. Integrating ...
Source: Cell - February 15, 2020 Category: Cytology Source Type: research

Single-Cell Transcriptome Atlas of Murine Endothelial Cells
Publication date: Available online 13 February 2020Source: CellAuthor(s): Joanna Kalucka, Laura P.M.H. de Rooij, Jermaine Goveia, Katerina Rohlenova, Sébastien J. Dumas, Elda Meta, Nadine V. Conchinha, Federico Taverna, Laure-Anne Teuwen, Koen Veys, Melissa García-Caballero, Shawez Khan, Vincent Geldhof, Liliana Sokol, Rongyuan Chen, Lucas Treps, Mila Borri, Pauline de Zeeuw, Charlotte Dubois, Tobias K. KarakachSummaryThe heterogeneity of endothelial cells (ECs) across tissues remains incompletely inventoried. We constructed an atlas of>32,000 single-EC transcriptomes from 11 mouse tissues and identified 7...
Source: Cell - February 15, 2020 Category: Cytology Source Type: research

Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains
Publication date: Available online 6 February 2020Source: CellAuthor(s): Tamta Arakhamia, Christina E. Lee, Yari Carlomagno, Duc M. Duong, Sean R. Kundinger, Kevin Wang, Dewight Williams, Michael DeTure, Dennis W. Dickson, Casey N. Cook, Nicholas T. Seyfried, Leonard Petrucelli, Anthony W.P. FitzpatrickSummaryTau aggregation into insoluble filaments is the defining pathological hallmark of tauopathies. However, it is not known what controls the formation and templated seeding of strain-specific structures associated with individual tauopathies. Here, we use cryo-electron microscopy (cryo-EM) to determine the structures of ...
Source: Cell - February 7, 2020 Category: Cytology Source Type: research

Co-incidence of Damage and Microbial Patterns Controls Localized Immune Responses in Roots
Publication date: 6 February 2020Source: Cell, Volume 180, Issue 3Author(s): Feng Zhou, Aurélia Emonet, Valérie Dénervaud Tendon, Peter Marhavy, Dousheng Wu, Thomas Lahaye, Niko GeldnerSummaryRecognition of microbe-associated molecular patterns (MAMPs) is crucial for the plant’s immune response. How this sophisticated perception system can be usefully deployed in roots, continuously exposed to microbes, remains a mystery. By analyzing MAMP receptor expression and response at cellular resolution in Arabidopsis, we observed that differentiated outer cell layers show low expression of pattern-recogn...
Source: Cell - February 7, 2020 Category: Cytology Source Type: research

Reconstructing Denisovan Anatomy Using DNA Methylation Maps
Publication date: 6 February 2020Source: Cell, Volume 180, Issue 3Author(s): David Gokhman, Nadav Mishol, Marc de Manuel, David de Juan, Jonathan Shuqrun, Eran Meshorer, Tomas Marques-Bonet, Yoel Rak, Liran Carmel (Source: Cell)
Source: Cell - February 7, 2020 Category: Cytology Source Type: research

Single-Cell Transcriptomic Atlas of Primate Ovarian Aging
This study provides a comprehensive understanding of the cell-type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.Graphical Abstract (Source: Cell)
Source: Cell - February 1, 2020 Category: Cytology Source Type: research

Identifying and Interpreting Apparent Neanderthal Ancestry in African Individuals
Publication date: Available online 30 January 2020Source: CellAuthor(s): Lu Chen, Aaron B. Wolf, Wenqing Fu, Liming Li, Joshua M. AkeySummaryAdmixture has played a prominent role in shaping patterns of human genomic variation, including gene flow with now-extinct hominins like Neanderthals and Denisovans. Here, we describe a novel probabilistic method called IBDmix to identify introgressed hominin sequences, which, unlike existing approaches, does not use a modern reference population. We applied IBDmix to 2,504 individuals from geographically diverse populations to identify and analyze Neanderthal sequences segregating in...
Source: Cell - February 1, 2020 Category: Cytology Source Type: research

Host-Specific Evolutionary and Transmission Dynamics Shape the Functional Diversification of Staphylococcus epidermidis in Human Skin
Publication date: Available online 30 January 2020Source: CellAuthor(s): Wei Zhou, Michelle Spoto, Rachel Hardy, Changhui Guan, Elizabeth Fleming, Peter J. Larson, Joseph S. Brown, Julia OhSummaryMetagenomic inferences of bacterial strain diversity and infectious disease transmission studies largely assume a dominant, within-individual haplotype. We hypothesize that within-individual bacterial population diversity is critical for homeostasis of a healthy microbiome and infection risk. We characterized the evolutionary trajectory and functional distribution of Staphylococcus epidermidis—a keystone skin micro...
Source: Cell - February 1, 2020 Category: Cytology Source Type: research

Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody
Publication date: Available online 30 January 2020Source: CellAuthor(s): Philipp Schommers, Henning Gruell, Morgan E. Abernathy, My-Kim Tran, Adam S. Dingens, Harry B. Gristick, Christopher O. Barnes, Till Schoofs, Maike Schlotz, Kanika Vanshylla, Christoph Kreer, Daniela Weiland, Udo Holtick, Christof Scheid, Markus M. Valter, Marit J. van Gils, Rogier W. Sanders, Jörg J. Vehreschild, Oliver A. Cornely, Clara LehmannSummaryBroadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits c...
Source: Cell - February 1, 2020 Category: Cytology Source Type: research

Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex
Publication date: Available online 30 January 2020Source: CellAuthor(s): Changrui Xing, Youwen Zhuang, Ting-Hai Xu, Zhiwei Feng, X. Edward Zhou, Maozi Chen, Lei Wang, Xing Meng, Ying Xue, Junmei Wang, Heng Liu, Terence Francis McGuire, Gongpu Zhao, Karsten Melcher, Cheng Zhang, H. Eric Xu, Xiang-Qun XieSummaryDrugs selectively targeting CB2 hold promise for treating neurodegenerative disorders, inflammation, and pain while avoiding psychotropic side effects mediated by CB1. The mechanisms underlying CB2 activation and signaling are poorly understood but critical for drug design. Here we report the cryo-EM structure of the ...
Source: Cell - February 1, 2020 Category: Cytology Source Type: research

Constant Sub-second Cycling between Representations of Possible Futures in the Hippocampus
Publication date: Available online 30 January 2020Source: CellAuthor(s): Kenneth Kay, Jason E. Chung, Marielena Sosa, Jonathan S. Schor, Mattias P. Karlsson, Margaret C. Larkin, Daniel F. Liu, Loren M. FrankSummaryCognitive faculties such as imagination, planning, and decision-making entail the ability to represent hypothetical experience. Crucially, animal behavior in natural settings implies that the brain can represent hypothetical future experience not only quickly but also constantly over time, as external events continually unfold. To determine how this is possible, we recorded neural activity in the hippocampus of r...
Source: Cell - February 1, 2020 Category: Cytology Source Type: research

DIX Domain Polymerization Drives Assembly of Plant Cell Polarity Complexes
Publication date: Available online 30 January 2020Source: CellAuthor(s): Maritza van Dop, Marc Fiedler, Sumanth Mutte, Jeroen de Keijzer, Lisa Olijslager, Catherine Albrecht, Che-Yang Liao, Marcel E. Janson, Mariann Bienz, Dolf WeijersSummaryCell polarity is fundamental for tissue morphogenesis in multicellular organisms. Plants and animals evolved multicellularity independently, and it is unknown whether their polarity systems are derived from a single-celled ancestor. Planar polarity in animals is conferred by Wnt signaling, an ancient signaling pathway transduced by Dishevelled, which assembles signalosomes by dyna...
Source: Cell - February 1, 2020 Category: Cytology Source Type: research

Activation and Signaling Mechanism Revealed by Cannabinoid Receptor-Gi Complex Structures
Publication date: Available online 30 January 2020Source: CellAuthor(s): Tian Hua, Xiaoting Li, Lijie Wu, Christos Iliopoulos-Tsoutsouvas, Yuxia Wang, Meng Wu, Ling Shen, Christina A. Johnston, Spyros P. Nikas, Feng Song, Xiyong Song, Shuguang Yuan, Qianqian Sun, Yiran Wu, Shan Jiang, Travis W. Grim, Othman Benchama, Edward L. Stahl, Nikolai Zvonok, Suwen ZhaoSummaryHuman endocannabinoid systems modulate multiple physiological processes mainly through the activation of cannabinoid receptors CB1 and CB2. Their high sequence similarity, low agonist selectivity, and lack of activation and G protein-coupling knowledge have hin...
Source: Cell - February 1, 2020 Category: Cytology Source Type: research

All-Optical Electrophysiology Reveals the Role of Lateral Inhibition in Sensory Processing in Cortical Layer 1
Publication date: Available online 23 January 2020Source: CellAuthor(s): Linlin Z. Fan, Simon Kheifets, Urs L. Böhm, Hao Wu, Kiryl D. Piatkevich, Michael E. Xie, Vicente Parot, Yooree Ha, Kathryn E. Evans, Edward S. Boyden, Anne E. Takesian, Adam E. CohenSummaryCortical layer 1 (L1) interneurons have been proposed as a hub for attentional modulation of underlying cortex, but the transformations that this circuit implements are not known. We combined genetically targeted voltage imaging with optogenetic activation and silencing to study the mechanisms underlying sensory processing in mouse barrel cortex L1. Whisker sti...
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

Astrocytic trans-Differentiation Completes a Multicellular Paracrine Feedback Loop Required for Medulloblastoma Tumor Growth
Publication date: Available online 23 January 2020Source: CellAuthor(s): Maojin Yao, P. Britten Ventura, Ying Jiang, Fausto J. Rodriguez, Lixin Wang, Justin S.A. Perry, Yibo Yang, Kelsey Wahl, Rowena B. Crittenden, Mariko L. Bennett, Lin Qi, Cong-Cong Gong, Xiao-Nan Li, Ben A. Barres, Timothy P. Bender, Kodi S. Ravichandran, Kevin A. Janes, Charles G. Eberhart, Hui ZongSummaryThe tumor microenvironment (TME) is critical for tumor progression. However, the establishment and function of the TME remain obscure because of its complex cellular composition. Using a mouse genetic system called mosaic analysis with double markers ...
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism
We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain devel...
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold
Publication date: 23 January 2020Source: Cell, Volume 180, Issue 2Author(s): David W. Vredevoogd, Thomas Kuilman, Maarten A. Ligtenberg, Julia Boshuizen, Kelly E. Stecker, Beaunelle de Bruijn, Oscar Krijgsman, Xinyao Huang, Juliana C.N. Kenski, Ruben Lacroix, Riccardo Mezzadra, Raquel Gomez-Eerland, Mete Yildiz, Ilknur Dagidir, Georgi Apriamashvili, Nordin Zandhuis, Vincent van der Noort, Nils L. Visser, Christian U. Blank, Maarten Altelaar (Source: Cell)
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

Science that Inspires
Publication date: 23 January 2020Source: Cell, Volume 180, Issue 2Author(s): The Cell Press Team (Source: Cell)
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

Establishing or Exaggerating Causality for the Gut Microbiome: Lessons from Human Microbiota-Associated Rodents
Publication date: 23 January 2020Source: Cell, Volume 180, Issue 2Author(s): Jens Walter, Anissa M. Armet, B. Brett Finlay, Fergus ShanahanHuman diseases are increasingly linked with an altered or “dysbiotic” gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer o...
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

Snake Venom Gland Organoids
This study extends organoid technology to reptilian tissues and describes an experimentally tractable model system representing the snake venom gland.Graphical Abstract (Source: Cell)
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

Widespread Transcriptional Scanning in the Testis Modulates Gene Evolution Rates
Publication date: 23 January 2020Source: Cell, Volume 180, Issue 2Author(s): Bo Xia, Yun Yan, Maayan Baron, Florian Wagner, Dalia Barkley, Marta Chiodin, Sang Y. Kim, David L. Keefe, Joseph P. Alukal, Jef D. Boeke, Itai YanaiSummaryThe testis expresses the largest number of genes of any mammalian organ, a finding that has long puzzled molecular biologists. Our single-cell transcriptomic data of human and mouse spermatogenesis provide evidence that this widespread transcription maintains DNA sequence integrity in the male germline by correcting DNA damage through a mechanism we term transcriptional scanning. We fi...
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk
Publication date: 23 January 2020Source: Cell, Volume 180, Issue 2Author(s): International Multiple Sclerosis Genetics Consortium (Source: Cell)
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle
We report that FAMIN phosphorolytically cleaves adenosine into adenine and ribose-1-phosphate. Such activity was considered absent from eukaryotic metabolism. FAMIN and its prokaryotic orthologs additionally have adenosine deaminase, purine nucleoside phosphorylase, and S-methyl-5′-thioadenosine phosphorylase activity, hence, combine activities of the namesake enzymes of central purine metabolism. FAMIN enables in macrophages a purine nucleotide cycle (PNC) between adenosine and inosine monophosphate and adenylosuccinate, which consumes aspartate and releases fumarate in a manner involving fatty acid o...
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

Cysteine Toxicity Drives Age-Related Mitochondrial Decline by Altering Iron Homeostasis
Publication date: 23 January 2020Source: Cell, Volume 180, Issue 2Author(s): Casey E. Hughes, Troy K. Coody, Mi-Young Jeong, Jordan A. Berg, Dennis R. Winge, Adam L. HughesSummaryMitochondria and lysosomes are functionally linked, and their interdependent decline is a hallmark of aging and disease. Despite the long-standing connection between these organelles, the function(s) of lysosomes required to sustain mitochondrial health remains unclear. Here, working in yeast, we show that the lysosome-like vacuole maintains mitochondrial respiration by spatially compartmentalizing amino acids. Defects in vacuole function result i...
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

Quantitative Proteomics of the Cancer Cell Line Encyclopedia
Publication date: 23 January 2020Source: Cell, Volume 180, Issue 2Author(s): David P. Nusinow, John Szpyt, Mahmoud Ghandi, Christopher M. Rose, E. Robert McDonald, Marian Kalocsay, Judit Jané-Valbuena, Ellen Gelfand, Devin K. Schweppe, Mark Jedrychowski, Javad Golji, Dale A. Porter, Tomas Rejtar, Y. Karen Wang, Gregory V. Kryukov, Frank Stegmeier, Brian K. Erickson, Levi A. Garraway, William R. Sellers, Steven P. GygiSummaryProteins are essential agents of biological processes. To date, large-scale profiling of cell line collections including the Cancer Cell Line Encyclopedia (CCLE) has focused primarily on genetic ...
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma
Publication date: 23 January 2020Source: Cell, Volume 180, Issue 2Author(s): Henry R. Maun, Janet K. Jackman, David F. Choy, Kelly M. Loyet, Tracy L. Staton, Guiquan Jia, Amy Dressen, Jason A. Hackney, Meire Bremer, Benjamin T. Walters, Rajesh Vij, Xiaocheng Chen, Neil N. Trivedi, Ashley Morando, Michael T. Lipari, Yvonne Franke, Xiumin Wu, Juan Zhang, John Liu, Ping Wu (Source: Cell)
Source: Cell - January 25, 2020 Category: Cytology Source Type: research

Evolutionary Persistence of DNA Methylation for Millions of Years after Ancient Loss of a De Novo Methyltransferase
We examined how methylation has persisted since the ancient loss of DnmtX. Experimental and comparative studies reveal efficient replication of methylation patterns in C. neoformans, rare stochastic methylation loss and gain events, and the action of natural selection. We propose that an epigenome has been propagated for>50 million years through a process analogous to Darwinian evolution of the genome.Graphical Abstract (Source: Cell)
Source: Cell - January 17, 2020 Category: Cytology Source Type: research

Cell-Surface Proteomic Profiling in the Fly Brain Uncovers Wiring Regulators
Publication date: Available online 16 January 2020Source: CellAuthor(s): Jiefu Li, Shuo Han, Hongjie Li, Namrata D. Udeshi, Tanya Svinkina, D.R. Mani, Chuanyun Xu, Ricardo Guajardo, Qijing Xie, Tongchao Li, David J. Luginbuhl, Bing Wu, Colleen N. McLaughlin, Anthony Xie, Pornchai Kaewsapsak, Stephen R. Quake, Steven A. Carr, Alice Y. Ting, Liqun LuoSummaryMolecular interactions at the cellular interface mediate organized assembly of single cells into tissues and, thus, govern the development and physiology of multicellular organisms. Here, we developed a cell-type-specific, spatiotemporally resolved approach to profile cel...
Source: Cell - January 17, 2020 Category: Cytology Source Type: research

Cerebellar Neurodynamics Predict Decision Timing and Outcome on the Single-Trial Level
Publication date: Available online 16 January 2020Source: CellAuthor(s): Qian Lin, Jason Manley, Magdalena Helmreich, Friederike Schlumm, Jennifer M. Li, Drew N. Robson, Florian Engert, Alexander Schier, Tobias Nöbauer, Alipasha VaziriSummaryGoal-directed behavior requires the interaction of multiple brain regions. How these regions and their interactions with brain-wide activity drive action selection is less understood. We have investigated this question by combining whole-brain volumetric calcium imaging using light-field microscopy and an operant-conditioning task in larval zebrafish. We find global, recurring dyn...
Source: Cell - January 17, 2020 Category: Cytology Source Type: research

Proteolysis-Targeting Chimeras as Therapeutics and Tools for Biological Discovery
We describe the PROTAC technology and its application to drug discovery and provide examples where PROTACs have enabled novel biological insights. Furthermore, we provide a workflow for PROTAC development and use and discuss the benefits and issues associated with PROTACs. Finally, we compare PROTAC-mediated protein-level modulation with other technologies, such as RNAi and genome editing. (Source: Cell)
Source: Cell - January 17, 2020 Category: Cytology Source Type: research

Cryo-EM Reveals Integrin-Mediated TGF-β Activation without Release from Latent TGF-β
Publication date: Available online 16 January 2020Source: CellAuthor(s): Melody G. Campbell, Anthony Cormier, Saburo Ito, Robert I. Seed, Andrew J. Bondesson, Jianlong Lou, James D. Marks, Jody L. Baron, Yifan Cheng, Stephen L. NishimuraSummaryIntegrin αvβ8 binds with exquisite specificity to latent transforming growth factor-β (L-TGF-β). This binding is essential for activating L-TGF-β presented by a variety of cell types. Inhibiting αvβ8-mediated TGF-β activation blocks immunosuppressive regulatory T cell differentiation, which is a potential therapeutic strategy i...
Source: Cell - January 17, 2020 Category: Cytology Source Type: research

Identification of a Master Regulator of Differentiation in Toxoplasma
Publication date: Available online 16 January 2020Source: CellAuthor(s): Benjamin S. Waldman, Dominic Schwarz, Marc H. Wadsworth, Jeroen P. Saeij, Alex K. Shalek, Sebastian LouridoSummaryToxoplasma gondii chronically infects a quarter of the world’s population, and its recrudescence can cause life-threatening disease in immunocompromised individuals and recurrent ocular lesions in the immunocompetent. Acute-stage tachyzoites differentiate into chronic-stage bradyzoites, which form intracellular cysts resistant to immune clearance and existing therapies. The molecular basis of this differentiation is unknown, despite ...
Source: Cell - January 17, 2020 Category: Cytology Source Type: research

Modulation of RNA Condensation by the DEAD-Box Protein eIF4A
Publication date: Available online 9 January 2020Source: CellAuthor(s): Devin Tauber, Gabriel Tauber, Anthony Khong, Briana Van Treeck, Jerry Pelletier, Roy ParkerSummaryStress granules are condensates of non-translating mRNAs and proteins involved in the stress response and neurodegenerative diseases. Stress granules form in part through intermolecular RNA-RNA interactions, and to better understand how RNA-based condensation occurs, we demonstrate that RNA is effectively recruited to the surfaces of RNA or RNP condensates in vitro. We demonstrate that, through ATP-dependent RNA binding, the DEAD-box protein eIF4...
Source: Cell - January 11, 2020 Category: Cytology Source Type: research

Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance
Publication date: 9 January 2020Source: Cell, Volume 180, Issue 1Author(s): Kimberly M. Cirelli, Diane G. Carnathan, Bartek Nogal, Jacob T. Martin, Oscar L. Rodriguez, Amit A. Upadhyay, Chiamaka A. Enemuo, Etse H. Gebru, Yury Choe, Federico Viviano, Catherine Nakao, Matthias G. Pauthner, Samantha Reiss, Christopher A. Cottrell, Melissa L. Smith, Raiza Bastidas, William Gibson, Amber N. Wolabaugh, Mariane B. Melo, Benjamin Cossette (Source: Cell)
Source: Cell - January 11, 2020 Category: Cytology Source Type: research

Structural Basis of Teneurin-Latrophilin Interaction in Repulsive Guidance of Migrating Neurons
Publication date: Available online 9 January 2020Source: CellAuthor(s): Daniel del Toro, Maria A. Carrasquero-Ordaz, Amy Chu, Tobias Ruff, Meriam Shahin, Verity A. Jackson, Matthieu Chavent, Miguel Berbeira-Santana, Goenuel Seyit-Bremer, Sara Brignani, Rainer Kaufmann, Edward Lowe, Rüdiger Klein, Elena SeiradakeSummaryTeneurins are ancient metazoan cell adhesion receptors that control brain development and neuronal wiring in higher animals. The extracellular C terminus binds the adhesion GPCR Latrophilin, forming a trans-cellular complex with synaptogenic functions. However, Teneurins, Latrophilins, and FLRT proteins ...
Source: Cell - January 11, 2020 Category: Cytology Source Type: research

Shinya Inoué (1921–2019)
Publication date: 9 January 2020Source: Cell, Volume 180, Issue 1Author(s): Timothy J. Mitchison (Source: Cell)
Source: Cell - January 11, 2020 Category: Cytology Source Type: research

Neural Control and Modulation of Thirst, Sodium Appetite, and Hunger
Publication date: 9 January 2020Source: Cell, Volume 180, Issue 1Author(s): Vineet Augustine, Sangjun Lee, Yuki OkaThe function of central appetite neurons is instructing animals to ingest specific nutrient factors that the body needs. Emerging evidence suggests that individual appetite circuits for major nutrients—water, sodium, and food—operate on unique driving and quenching mechanisms. This review focuses on two aspects of appetite regulation. First, we describe the temporal relationship between appetite neuron activity and consumption behaviors. Second, we summarize ingestion-related satiation signals that...
Source: Cell - January 11, 2020 Category: Cytology Source Type: research

Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity
Publication date: 9 January 2020Source: Cell, Volume 180, Issue 1Author(s): Abigail Jarret, Ruaidhrí Jackson, Coco Duizer, Marc E. Healy, Jun Zhao, Joseph M. Rone, Piotr Bielecki, Esen Sefik, Manolis Roulis, Tyler Rice, Kisha N. Sivanathan, Ting Zhou, Angel G. Solis, Hanna Honcharova-Biletska, Karelia Vélez, Saskia Hartner, Jun Siong Low, Rihao Qu, Marcel R. de Zoete, Noah W. PalmSummaryMucosal barrier immunity is essential for the maintenance of the commensal microflora and combating invasive bacterial infection. Although immune and epithelial cells are thought to be the canonical orchestrators of this compl...
Source: Cell - January 11, 2020 Category: Cytology Source Type: research

Adrenergic Signaling in Muscularis Macrophages Limits Infection-Induced Neuronal Loss
Publication date: 9 January 2020Source: Cell, Volume 180, Issue 1Author(s): Fanny Matheis, Paul A. Muller, Christina L. Graves, Ilana Gabanyi, Zachary J. Kerner, Diego Costa-Borges, Tomasz Ahrends, Philip Rosenstiel, Daniel MucidaSummaryEnteric-associated neurons (EANs) are closely associated with immune cells and continuously monitor and modulate homeostatic intestinal functions, including motility and nutrient sensing. Bidirectional interactions between neuronal and immune cells are altered during disease processes such as neurodegeneration or irritable bowel syndrome. We investigated the effects of infection-induced inf...
Source: Cell - January 11, 2020 Category: Cytology Source Type: research

Low-Fidelity Assembly of Influenza A Virus Promotes Escape from Host Cells
Publication date: 9 January 2020Source: Cell, Volume 180, Issue 1Author(s): Michael D. Vahey, Daniel A. Fletcher (Source: Cell)
Source: Cell - January 11, 2020 Category: Cytology Source Type: research

A Pathogen-Responsive Gene Cluster for Highly Modified Fatty Acids in Tomato
Publication date: 9 January 2020Source: Cell, Volume 180, Issue 1Author(s): Ju Eun Jeon, Jung-Gun Kim, Curt R. Fischer, Niraj Mehta, Cosima Dufour-Schroif, Kimberly Wemmer, Mary Beth Mudgett, Elizabeth SattelySummaryIn response to biotic stress, plants produce suites of highly modified fatty acids that bear unusual chemical functionalities. Despite their chemical complexity and proposed roles in pathogen defense, little is known about the biosynthesis of decorated fatty acids in plants. Falcarindiol is a prototypical acetylenic lipid present in carrot, tomato, and celery that inhibits growth of fungi and human cancer cell ...
Source: Cell - January 11, 2020 Category: Cytology Source Type: research

Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma
Publication date: 9 January 2020Source: Cell, Volume 180, Issue 1Author(s): David J. Clark, Saravana M. Dhanasekaran, Francesca Petralia, Jianbo Pan, Xiaoyu Song, Yingwei Hu, Felipe da Veiga Leprevost, Boris Reva, Tung-Shing M. Lih, Hui-Yin Chang, Weiping Ma, Chen Huang, Christopher J. Ricketts, Lijun Chen, Azra Krek, Yize Li, Dmitry Rykunov, Qing Kay Li, Lin S. Chen, Umut Ozbek (Source: Cell)
Source: Cell - January 11, 2020 Category: Cytology Source Type: research

A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity
Publication date: Available online 26 December 2019Source: CellAuthor(s): Fadi Jacob, Ryan D. Salinas, Daniel Y. Zhang, Phuong T.T. Nguyen, Jordan G. Schnoll, Samuel Zheng Hao Wong, Radhika Thokala, Saad Sheikh, Deeksha Saxena, Stefan Prokop, Di-ao Liu, Xuyu Qian, Dmitriy Petrov, Timothy Lucas, H. Isaac Chen, Jay F. Dorsey, Kimberly M. Christian, Zev A. Binder, MacLean Nasrallah, Steven BremSummaryGlioblastomas exhibit vast inter- and intra-tumoral heterogeneity, complicating the development of effective therapeutic strategies. Current in vitro models are limited in preserving the cellular and mutational diversity of ...
Source: Cell - December 28, 2019 Category: Cytology Source Type: research

Saltatory Conduction along Myelinated Axons Involves a Periaxonal Nanocircuit
Publication date: Available online 26 December 2019Source: CellAuthor(s): Charles C.H. Cohen, Marko A. Popovic, Jan Klooster, Marie-Theres Weil, Wiebke Möbius, Klaus-Armin Nave, Maarten H.P. KoleSummaryThe propagation of electrical impulses along axons is highly accelerated by the myelin sheath and produces saltating or “jumping” action potentials across internodes, from one node of Ranvier to the next. The underlying electrical circuit, as well as the existence and role of submyelin conduction in saltatory conduction remain, however, elusive. Here, we made patch-clamp and high-speed voltage-calibrated opt...
Source: Cell - December 28, 2019 Category: Cytology Source Type: research