Multi-sensory Gamma Stimulation Ameliorates Alzheimer’s-Associated Pathology and Improves Cognition
Publication date: Available online 14 March 2019Source: CellAuthor(s): Anthony J. Martorell, Abigail L. Paulson, Ho-Jun Suk, Fatema Abdurrob, Gabrielle T. Drummond, Webster Guan, Jennie Z. Young, David Nam-Woo Kim, Oleg Kritskiy, Scarlett J. Barker, Vamsi Mangena, Stephanie M. Prince, Emery N. Brown, Kwanghun Chung, Edward S. Boyden, Annabelle C. Singer, Li-Huei TsaiSummaryWe previously reported that inducing gamma oscillations with a non-invasive light flicker (gamma entrainment using sensory stimulus or GENUS) impacted pathology in the visual cortex of Alzheimer’s disease mouse models. Here, we designed auditory to...
Source: Cell - March 15, 2019 Category: Cytology Source Type: research

Structures of the Catalytically Activated Yeast Spliceosome Reveal the Mechanism of Branching
In this study, we assembled the B∗ complexes on two different pre-mRNAs from Saccharomyces cerevisiae and determined the cryo-EM structures of four distinct B∗ complexes at overall resolutions of 2.9–3.8 Å. The duplex between U2 small nuclear RNA (snRNA) and the branch point sequence (BPS) is discretely away from the 5′-splice site (5′SS) in the three B∗ complexes that are devoid of the step I splicing factors Yju2 and Cwc25. Recruitment of Yju2 into the active site brings the U2/BPS duplex into the vicinity of 5′SS, with the BPS nucleophile positioned ...
Source: Cell - March 15, 2019 Category: Cytology Source Type: research

Per-Nucleus Crossover Covariation and Implications for Evolution
Publication date: Available online 14 March 2019Source: CellAuthor(s): Shunxin Wang, Carl Veller, Fei Sun, Aurora Ruiz-Herrera, Yongliang Shang, Hongbin Liu, Denise Zickler, Zijiang Chen, Nancy Kleckner, Liangran ZhangSummaryCrossing over is a nearly universal feature of sexual reproduction. Here, analysis of crossover numbers on a per-chromosome and per-nucleus basis reveals a fundamental, evolutionarily conserved feature of meiosis: within individual nuclei, crossover frequencies covary across different chromosomes. This effect results from per-nucleus covariation of chromosome axis lengths. Crossovers can promote evolut...
Source: Cell - March 15, 2019 Category: Cytology Source Type: research

Innate Immune Signaling Organelles Display Natural and Programmable Signaling Flexibility
Publication date: Available online 7 March 2019Source: CellAuthor(s): Yunhao Tan, Jonathan C. KaganSummaryThe signaling organelles of the innate immune system consist of oligomeric protein complexes known as supramolecular organizing centers (SMOCs). Examples of SMOCs include myddosomes and inflammasomes, which respectively induce transcription-dependent and -independent inflammatory responses. The common use of oligomeric structures as signaling platforms suggests multifunctionality, but each SMOC has a singular biochemically defined function. Here, we report that the myddosome is a multifunctional organizing center. In a...
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

Magnesium Flux Modulates Ribosomes to Increase Bacterial Survival
Publication date: Available online 7 March 2019Source: CellAuthor(s): Dong-yeon D. Lee, Leticia Galera-Laporta, Maja Bialecka-Fornal, Eun Chae Moon, Zhouxin Shen, Steven P. Briggs, Jordi Garcia-Ojalvo, Gürol M. SüelSummaryBacteria exhibit cell-to-cell variability in their resilience to stress, for example, following antibiotic exposure. Higher resilience is typically ascribed to “dormant” non-growing cellular states. Here, by measuring membrane potential dynamics of Bacillus subtilis cells, we show that actively growing bacteria can cope with ribosome-targeting antibiotics through an alternative mecha...
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

Energetic Trade-Offs and Hypometabolic States Promote Disease Tolerance
We report here that activation of immunity causes an energetic trade-off with the homeothermy (the stable maintenance of core temperature), resulting in hypometabolism and hypothermia. This immunity-induced physiologic trade-off was independent of sickness behaviors but required hematopoietic sensing of lipopolysaccharide (LPS) via the toll-like receptor 4 (TLR4). Metabolomics and genome-wide expression profiling revealed that distinct metabolic programs supported entry and recovery from the energy-conserving hypometabolic state. During bacterial infections, hypometabolic states, which could be elicited by competition for ...
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

Optimal-Transport Analysis of Single-Cell Gene Expression Identifies Developmental Trajectories in Reprogramming
Publication date: 7 March 2019Source: Cell, Volume 176, Issue 6Author(s): Geoffrey Schiebinger, Jian Shu, Marcin Tabaka, Brian Cleary, Vidya Subramanian, Aryeh Solomon, Joshua Gould, Siyan Liu, Stacie Lin, Peter Berube, Lia Lee, Jenny Chen, Justin Brumbaugh, Philippe Rigollet, Konrad Hochedlinger, Rudolf Jaenisch, Aviv Regev, Eric S. Lander (Source: Cell)
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

Structural Principles in Robo Activation and Auto-inhibition
Publication date: Available online 7 March 2019Source: CellAuthor(s): Reut Barak, Galit Yom-Tov, Julia Guez-Haddad, Lital Gasri-Plotnitsky, Roy Maimon, Moran Cohen-Berkman, Andrew A. McCarthy, Eran Perlson, Sivan Henis-Korenblit, Michail N. Isupov, Yarden OpatowskySummaryProper brain function requires high-precision neuronal expansion and wiring, processes controlled by the transmembrane Roundabout (Robo) receptor family and their Slit ligands. Despite their great importance, the molecular mechanism by which Robos’ switch from “off” to “on” states remains unclear. Here, we report a 3.6 &A...
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

An Error-Prone Polymerase in the Fight against Cancer
Publication date: 7 March 2019Source: Cell, Volume 176, Issue 6Author(s): Yathish Jagadheesh Achar, Marco FoianiError-prone polymerases are alleged to induce mutations while replicating damaged DNA and to increase the risk of cancer. Using in vitro studies and mice models, Yoon et al. (2019) provide evidence that the error-prone Pol θ polymerase protects against ultraviolet light-induced skin cancer despite its mutagenic potential. (Source: Cell)
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

Some Like it HOT: Horizontal Operon Transfer
Publication date: 7 March 2019Source: Cell, Volume 176, Issue 6Author(s): Amelia R.I. Lindsey, Irene L.G. NewtonWhile horizontal gene transfer (HGT) is well documented in bacteria, the role and frequency of HGT across eukaryotes remains poorly understood. Kominek et al. identified a horizontal operon transfer (HOT) event, with clear evidence for selection to facilitate gene expression, that has allowed a group of yeasts to scavenge iron using bacterially derived genes. (Source: Cell)
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

Self-Assembling Nanoparticles Usher in a New Era of Vaccine Design
Publication date: 7 March 2019Source: Cell, Volume 176, Issue 6Author(s): Rino Rappuoli, Davide SerrutoIn this issue, Marcandalli et al. (2019) report a self-assembling nanoparticle bearing an antigen from respiratory syncytial virus. This is the first time the structure, stability, and adjuvanticity of an antigen have been rationally designed at the atomic level and incorporated in one vaccine. (Source: Cell)
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

VEGF in Signaling and Disease: Beyond Discovery and Development
Publication date: 7 March 2019Source: Cell, Volume 176, Issue 6Author(s): Rajendra S. Apte, Daniel S. Chen, Napoleone FerraraThe discovery of vascular endothelial-derived growth factor (VEGF) has revolutionized our understanding of vasculogenesis and angiogenesis during development and physiological homeostasis. Over a short span of two decades, our understanding of the molecular mechanisms by which VEGF coordinates neurovascular homeostasis has become more sophisticated. The central role of VEGF in the pathogenesis of diverse cancers and blinding eye diseases has also become evident. Elucidation of the molecular regulatio...
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

Characterizing Mutational Signatures in Human Cancer Cell Lines Reveals Episodic APOBEC Mutagenesis
Publication date: 7 March 2019Source: Cell, Volume 176, Issue 6Author(s): Mia Petljak, Ludmil B. Alexandrov, Jonathan S. Brammeld, Stacey Price, David C. Wedge, Sebastian Grossmann, Kevin J. Dawson, Young Seok Ju, Francesco Iorio, Jose M.C. Tubio, Ching Chiek Koh, Ilias Georgakopoulos-Soares, Bernardo Rodríguez–Martín, Burçak Otlu, Sarah O’Meara, Adam P. Butler, Andrew Menzies, Shriram G. Bhosle, Keiran Raine, David R. JonesSummaryMultiple signatures of somatic mutations have been identified in cancer genomes. Exome sequences of 1,001 human cancer cell lines and 577 xenografts revealed most...
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

A Genome-wide Framework for Mapping Gene Regulation via Cellular Genetic Screens
Publication date: 7 March 2019Source: Cell, Volume 176, Issue 6Author(s): Molly Gasperini, Andrew J. Hill, José L. McFaline-Figueroa, Beth Martin, Seungsoo Kim, Melissa D. Zhang, Dana Jackson, Anh Leith, Jacob Schreiber, William S. Noble, Cole Trapnell, Nadav Ahituv, Jay Shendure (Source: Cell)
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus
Publication date: 7 March 2019Source: Cell, Volume 176, Issue 6Author(s): Jessica Marcandalli, Brooke Fiala, Sebastian Ols, Michela Perotti, Willem de van der Schueren, Joost Snijder, Edgar Hodge, Mark Benhaim, Rashmi Ravichandran, Lauren Carter, Will Sheffler, Livia Brunner, Maria Lawrenz, Patrice Dubois, Antonio Lanzavecchia, Federica Sallusto, Kelly K. Lee, David Veesler, Colin E. Correnti, Lance J. StewartSummaryRespiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main targ...
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

Auto-regulation of Secretory Flux by Sensing and Responding to the Folded Cargo Protein Load in the Endoplasmic Reticulum
Publication date: 7 March 2019Source: Cell, Volume 176, Issue 6Author(s): Advait Subramanian, Anita Capalbo, Namrata Ravi Iyengar, Riccardo Rizzo, Antonella di Campli, Rosaria Di Martino, Matteo Lo Monte, Andrea R. Beccari, Amol Yerudkar, Carmen del Vecchio, Luigi Glielmo, Gabriele Turacchio, Marinella Pirozzi, Sang Geon Kim, Petra Henklein, Jorge Cancino, Seetharaman Parashuraman, Dario Diviani, Francesca Fanelli, Michele SalleseSummaryMaintaining the optimal performance of cell processes and organelles is the task of auto-regulatory systems. Here we describe an auto-regulatory device that helps to maintain homeostasis of...
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome
Publication date: 7 March 2019Source: Cell, Volume 176, Issue 6Author(s): Yongdae Shin, Yi-Che Chang, Daniel S.W. Lee, Joel Berry, David W. Sanders, Pierre Ronceray, Ned S. Wingreen, Mikko Haataja, Clifford P. Brangwynne (Source: Cell)
Source: Cell - March 8, 2019 Category: Cytology Source Type: research

Megabase Length Hypermutation Accompanies Human Structural Variation at 17p11.2
Publication date: Available online 28 February 2019Source: CellAuthor(s): Christine R. Beck, Claudia M.B. Carvalho, Zeynep C. Akdemir, Fritz J. Sedlazeck, Xiaofei Song, Qingchang Meng, Jianhong Hu, Harsha Doddapaneni, Zechen Chong, Edward S. Chen, Philip C. Thornton, Pengfei Liu, Bo Yuan, Marjorie Withers, Shalini N. Jhangiani, Divya Kalra, Kimberly Walker, Adam C. English, Yi Han, Ken ChenSummaryDNA rearrangements resulting in human genome structural variants (SVs) are caused by diverse mutational mechanisms. We used long- and short-read sequencing technologies to investigate end products of de novo chromosome 17p11.2 rea...
Source: Cell - March 4, 2019 Category: Cytology Source Type: research

Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity
In conclusion, we provide single-cell technologies and an atlas of AML cell states, regulators, and markers with implications for precision medicine and immune therapies.Video AbstractGraphical Abstract (Source: Cell)
Source: Cell - March 4, 2019 Category: Cytology Source Type: research

Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae
Publication date: Available online 28 February 2019Source: CellAuthor(s): Yuqian Ma, Jin Bao, Yuanwei Zhang, Zhanjun Li, Xiangyu Zhou, Changlin Wan, Ling Huang, Yang Zhao, Gang Han, Tian XueSummaryMammals cannot see light over 700 nm in wavelength. This limitation is due to the physical thermodynamic properties of the photon-detecting opsins. However, the detection of naturally invisible near-infrared (NIR) light is a desirable ability. To break this limitation, we developed ocular injectable photoreceptor-binding upconversion nanoparticles (pbUCNPs). These nanoparticles anchored on retinal photoreceptors as miniature...
Source: Cell - March 4, 2019 Category: Cytology Source Type: research

Lineage Tracing in Humans Enabled by Mitochondrial Mutations and Single-Cell Genomics
Publication date: Available online 28 February 2019Source: CellAuthor(s): Leif S. Ludwig, Caleb A. Lareau, Jacob C. Ulirsch, Elena Christian, Christoph Muus, Lauren H. Li, Karin Pelka, Will Ge, Yaara Oren, Alison Brack, Travis Law, Christopher Rodman, Jonathan H. Chen, Genevieve M. Boland, Nir Hacohen, Orit Rozenblatt-Rosen, Martin J. Aryee, Jason D. Buenrostro, Aviv Regev, Vijay G. SankaranSummaryLineage tracing provides key insights into the fate of individual cells in complex organisms. Although effective genetic labeling approaches are available in model systems, in humans, most approaches require detection of nuclear ...
Source: Cell - March 4, 2019 Category: Cytology Source Type: research

Phosphoinositide Interactions Position cGAS at the Plasma Membrane to Ensure Efficient Distinction between Self- and Viral DNA
Publication date: Available online 28 February 2019Source: CellAuthor(s): Katherine C. Barnett, Julia M. Coronas-Serna, Wen Zhou, Michael J. Ernandes, Anh Cao, Philip J. Kranzusch, Jonathan C. KaganSummaryThe presence of DNA in the cytosol of mammalian cells is an unusual event that is often associated with genotoxic stress or viral infection. The enzyme cGAS is a sensor of cytosolic DNA that induces interferon and inflammatory responses that can be protective or pathologic, depending on the context. Along with other cytosolic innate immune receptors, cGAS is thought to diffuse throughout the cytosol in search of its DNA l...
Source: Cell - March 4, 2019 Category: Cytology Source Type: research

Higher-Order Clustering of the Transmembrane Anchor of DR5 Drives Signaling
Publication date: Available online 28 February 2019Source: CellAuthor(s): Liqiang Pan, Tian-Min Fu, Wenbin Zhao, Linlin Zhao, Wen Chen, Chixiao Qiu, Wenhui Liu, Zhijun Liu, Alessandro Piai, Qingshan Fu, Shuqing Chen, Hao Wu, James J. ChouSummaryReceptor clustering on the cell membrane is critical in the signaling of many immunoreceptors, and this mechanism has previously been attributed to the extracellular and/or the intracellular interactions. Here, we report an unexpected finding that for death receptor 5 (DR5), a receptor in the tumor necrosis factor receptor superfamily, the transmembrane helix (TMH) alone in the rece...
Source: Cell - March 4, 2019 Category: Cytology Source Type: research

Quiescence Modulates Stem Cell Maintenance and Regenerative Capacity in the Aging Brain
Publication date: Available online 28 February 2019Source: CellAuthor(s): Georgios Kalamakis, Daniel Brüne, Srikanth Ravichandran, Jan Bolz, Wenqiang Fan, Frederik Ziebell, Thomas Stiehl, Francisco Catalá-Martinez, Janina Kupke, Sheng Zhao, Enric Llorens-Bobadilla, Katharina Bauer, Stefanie Limpert, Birgit Berger, Urs Christen, Peter Schmezer, Jan Philipp Mallm, Benedikt Berninger, Simon Anders, Antonio del SolSummaryThe function of somatic stem cells declines with age. Understanding the molecular underpinnings of this decline is key to counteract age-related disease. Here, we report a dramatic drop in the neur...
Source: Cell - March 4, 2019 Category: Cytology Source Type: research

Human Anti-fungal Th17 Immunity and Pathology Rely on Cross-Reactivity against Candida albicans
Publication date: Available online 21 February 2019Source: CellAuthor(s): Petra Bacher, Thordis Hohnstein, Eva Beerbaum, Marie Röcker, Matthew G. Blango, Svenja Kaufmann, Jobst Röhmel, Patience Eschenhagen, Claudia Grehn, Kathrin Seidel, Volker Rickerts, Laura Lozza, Ulrik Stervbo, Mikalai Nienen, Nina Babel, Julia Milleck, Mario Assenmacher, Oliver A. Cornely, Maren Ziegler, Hilmar WisplinghoffSummaryTh17 cells provide protection at barrier tissues but may also contribute to immune pathology. The relevance and induction mechanisms of pathologic Th17 responses in humans are poorly understood. Here, we identify th...
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

Structural Basis of Nav1.7 Inhibition by a Gating-Modifier Spider Toxin
Publication date: 21 February 2019Source: Cell, Volume 176, Issue 5Author(s): Hui Xu, Tianbo Li, Alexis Rohou, Christopher P. Arthur, Foteini Tzakoniati, Evera Wong, Alberto Estevez, Christine Kugel, Yvonne Franke, Jun Chen, Claudio Ciferri, David H. Hackos, Christopher M. Koth, Jian Payandeh (Source: Cell)
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity
Publication date: Available online 21 February 2019Source: CellAuthor(s): Jiang Dai, Yi-Jiao Huang, Xinhua He, Ming Zhao, Xinzheng Wang, Zhao-Shan Liu, Wen Xue, Hong Cai, Xiao-Yan Zhan, Shao-Yi Huang, Kun He, Hongxia Wang, Na Wang, Zhihong Sang, Tingting Li, Qiu-Ying Han, Jie Mao, Xinwei Diao, Nan Song, Yuan ChenSummaryThe presence of DNA in the cytoplasm is normally a sign of microbial infections and is quickly detected by cyclic GMP-AMP synthase (cGAS) to elicit anti-infection immune responses. However, chronic activation of cGAS by self-DNA leads to severe autoimmune diseases for which no effective treatment is availabl...
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

Eukaryotic Acquisition of a Bacterial Operon
Publication date: Available online 21 February 2019Source: CellAuthor(s): Jacek Kominek, Drew T. Doering, Dana A. Opulente, Xing-Xing Shen, Xiaofan Zhou, Jeremy DeVirgilio, Amanda B. Hulfachor, Marizeth Groenewald, Mcsean A. Mcgee, Steven D. Karlen, Cletus P. Kurtzman, Antonis Rokas, Chris Todd HittingerSummaryOperons are a hallmark of bacterial genomes, where they allow concerted expression of functionally related genes as single polycistronic transcripts. They are rare in eukaryotes, where each gene usually drives expression of its own independent messenger RNAs. Here, we report the horizontal operon transfer of a sidero...
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization
Publication date: Available online 21 February 2019Source: CellAuthor(s): Elizabeth H. Finn, Gianluca Pegoraro, Hugo B. Brandão, Anne-Laure Valton, Marlies E. Oomen, Job Dekker, Leonid Mirny, Tom MisteliSummarySeveral general principles of global 3D genome organization have recently been established, including non-random positioning of chromosomes and genes in the cell nucleus, distinct chromatin compartments, and topologically associating domains (TADs). However, the extent and nature of cell-to-cell and cell-intrinsic variability in genome architecture are still poorly characterized. Here, we systematically p...
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

A Watershed Finding for Heart Regeneration
Publication date: 21 February 2019Source: Cell, Volume 176, Issue 5Author(s): Evan S. Bardot, Nicole C. DuboisThe adult mammalian heart is minimally regenerative after injury, whereas neonatal hearts fully recover even after major damage. New work from the Red-Horse and Woo labs (Das et al., 2019) shows that collateral artery formation is a key mechanism contributing to successful regeneration in newborn mice and provides insights into how collateral arteries form. (Source: Cell)
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

Dissecting Cell Lineages: From Microscope to Kaleidoscope
Publication date: 21 February 2019Source: Cell, Volume 176, Issue 5Author(s): Unmesh Jadhav, Ramesh A. ShivdasaniSingle-cell transcriptomics coupled with dynamic two-color fluorescence are used by Gehart et al. (2019) to elucidate adult mammalian cell trajectories in real time. The authors’ close examination of intestinal enteroendocrine differentiation reveals new lineage features and shifting cell identities, and experiments in organoids uncover specific roles for transcriptional regulators identified by this approach. (Source: Cell)
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

Genomic Imprinting and Physiological Processes in Mammals
Publication date: 21 February 2019Source: Cell, Volume 176, Issue 5Author(s): Valter Tucci, Anthony R. Isles, Gavin Kelsey, Anne C. Ferguson-Smith, Valter Tucci, Marisa S. Bartolomei, Nissim Benvenisty, Déborah Bourc’his, Marika Charalambous, Catherine Dulac, Robert Feil, Juliane Glaser, Lisa Huelsmann, Rosalind M. John, Gráinne I. McNamara, Kim Moorwood, Francoise Muscatelli, Hiroyuki Sasaki, Beverly I. Strassmann, Claudius VincenzComplex multicellular organisms, such as mammals, express two complete sets of chromosomes per nucleus, combining the genetic material of both parents. However, epigenetic st...
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

FXR Regulates Intestinal Cancer Stem Cell Proliferation
Publication date: 21 February 2019Source: Cell, Volume 176, Issue 5Author(s): Ting Fu, Sally Coulter, Eiji Yoshihara, Tae Gyu Oh, Sungsoon Fang, Fritz Cayabyab, Qiyun Zhu, Tong Zhang, Mathias Leblanc, Sihao Liu, Mingxiao He, Wanda Waizenegger, Emanuel Gasser, Bernd Schnabl, Annette R. Atkins, Ruth T. Yu, Rob Knight, Christopher Liddle, Michael Downes, Ronald M. EvansSummaryIncreased levels of intestinal bile acids (BAs) are a risk factor for colorectal cancer (CRC). Here, we show that the convergence of dietary factors (high-fat diet) and dysregulated WNT signaling (APC mutation) alters BA profiles to drive malignant trans...
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury
Publication date: 21 February 2019Source: Cell, Volume 176, Issue 5Author(s): Mary T. Joy, Einor Ben Assayag, Dalia Shabashov-Stone, Sigal Liraz-Zaltsman, Jose Mazzitelli, Marcela Arenas, Nora Abduljawad, Efrat Kliper, Amos D. Korczyn, Nikita S. Thareja, Efrat L. Kesner, Miou Zhou, Shan Huang, Tawnie K. Silva, Noomi Katz, Natan M. Bornstein, Alcino J. Silva, Esther Shohami, S. Thomas CarmichaelSummaryWe tested a newly described molecular memory system, CCR5 signaling, for its role in recovery after stroke and traumatic brain injury (TBI). CCR5 is uniquely expressed in cortical neurons after stroke. Post-stroke neuronal kno...
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

SnapShot: Cancer Immunotherapy with Oncolytic Viruses
Publication date: 21 February 2019Source: Cell, Volume 176, Issue 5Author(s): Shashi Gujar, John Bell, Jean-Simon DialloOncolytic viruses (OVs) preferentially infect and kill cancer cells without harming normal cells. OVs can revert cancer-associated immune suppression and initiate clinically meaningful antitumor immune responses. OVs and their resultant immunological events can act at both primary and metastatic sites. Thus, OVs can be exploited for cancer gene therapies and immunotherapies alone or in combination with other interventions, including immune checkpoint blockade. (Source: Cell)
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

Regulation of MicroRNA Machinery and Development by Interspecies S-Nitrosylation
Publication date: 21 February 2019Source: Cell, Volume 176, Issue 5Author(s): Puneet Seth, Paishiun N. Hsieh, Suhib Jamal, Liwen Wang, Steven P. Gygi, Mukesh K. Jain, Jeff Coller, Jonathan S. StamlerSummaryBioactive molecules can pass between microbiota and host to influence host cellular functions. However, general principles of interspecies communication have not been discovered. We show here in C. elegans that nitric oxide derived from resident bacteria promotes widespread S-nitrosylation of the host proteome. We further show that microbiota-dependent S-nitrosylation of C. elegans Argonaute protein (ALG-1)&mda...
Source: Cell - February 22, 2019 Category: Cytology Source Type: research

A Hippocampus-Accumbens Tripartite Neuronal Motif Guides Appetitive Memory in Space
Publication date: Available online 14 February 2019Source: CellAuthor(s): Stéphanie Trouche, Vadim Koren, Natalie M. Doig, Tommas J. Ellender, Mohamady El-Gaby, Vítor Lopes-dos-Santos, Hayley M. Reeve, Pavel V. Perestenko, Farid N. Garas, Peter J. Magill, Andrew Sharott, David DupretSummaryRetrieving and acting on memories of food-predicting environments are fundamental processes for animal survival. Hippocampal pyramidal cells (PYRs) of the mammalian brain provide mnemonic representations of space. Yet the substrates by which these hippocampal representations support memory-guided behavior remain unknown. He...
Source: Cell - February 15, 2019 Category: Cytology Source Type: research

Sexually Dimorphic Control of Parenting Behavior by the Medial Amygdala
Publication date: Available online 14 February 2019Source: CellAuthor(s): Patrick B. Chen, Rongfeng K. Hu, Ye Emily Wu, Lin Pan, Shan Huang, Paul E. Micevych, Weizhe HongSummarySocial behaviors, including behaviors directed toward young offspring, exhibit striking sex differences. Understanding how these sexually dimorphic behaviors are regulated at the level of circuits and transcriptomes will provide insights into neural mechanisms of sex-specific behaviors. Here, we uncover a sexually dimorphic role of the medial amygdala (MeA) in governing parental and infanticidal behaviors. Contrary to traditional views, activation o...
Source: Cell - February 15, 2019 Category: Cytology Source Type: research

The Small Non-coding Vault RNA1-1 Acts as a Riboregulator of Autophagy
Publication date: Available online 14 February 2019Source: CellAuthor(s): Rastislav Horos, Magdalena Büscher, Rozemarijn Kleinendorst, Anne-Marie Alleaume, Abul K. Tarafder, Thomas Schwarzl, Dmytro Dziuba, Christian Tischer, Elisabeth M. Zielonka, Asli Adak, Alfredo Castello, Wolfgang Huber, Carsten Sachse, Matthias W. HentzeSummaryVault RNAs (vtRNA) are small non-coding RNAs transcribed by RNA polymerase III found in many eukaryotes. Although they have been linked to drug resistance, apoptosis, and viral replication, their molecular functions remain unclear. Here, we show that vault RNAs directly bind the autophagy r...
Source: Cell - February 15, 2019 Category: Cytology Source Type: research

Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity
Publication date: Available online 14 February 2019Source: CellAuthor(s): Peng Xia, Daniel Gütl, Vanessa Zheden, Carl-Philipp HeisenbergSummaryCell fate specification by lateral inhibition typically involves contact signaling through the Delta-Notch signaling pathway. However, whether this is the only signaling mode mediating lateral inhibition remains unclear. Here we show that in zebrafish oogenesis, a group of cells within the granulosa cell layer at the oocyte animal pole acquire elevated levels of the transcriptional coactivator TAZ in their nuclei. One of these cells, the future micropyle precursor cell (MPC), a...
Source: Cell - February 15, 2019 Category: Cytology Source Type: research

Error-Prone Replication through UV Lesions by DNA Polymerase θ Protects against Skin Cancers
Publication date: Available online 14 February 2019Source: CellAuthor(s): Jung-Hoon Yoon, Mark J. McArthur, Jeseong Park, Debashree Basu, Maki Wakamiya, Louise Prakash, Satya PrakashSummaryCancers from sun-exposed skin accumulate “driver” mutations, causally implicated in oncogenesis. Because errors incorporated during translesion synthesis (TLS) opposite UV lesions would generate these mutations, TLS mechanisms are presumed to underlie cancer development. To address the role of TLS in skin cancer formation, we determined which DNA polymerase is responsible for generating UV mutations, analyzed the relative con...
Source: Cell - February 15, 2019 Category: Cytology Source Type: research

The Root Cap Cuticle: A Cell Wall Structure for Seedling Establishment and Lateral Root Formation
Publication date: Available online 14 February 2019Source: CellAuthor(s): Alice Berhin, Damien de Bellis, Rochus B. Franke, Rafael A. Buono, Moritz K. Nowack, Christiane NawrathSummaryThe root cap surrounding the tip of plant roots is thought to protect the delicate stem cells in the root meristem. We discovered that the first layer of root cap cells is covered by an electron-opaque cell wall modification resembling a plant cuticle. Cuticles are polyester-based protective structures considered exclusive to aerial plant organs. Mutations in cutin biosynthesis genes affect the composition and ultrastructure of this cuticular...
Source: Cell - February 15, 2019 Category: Cytology Source Type: research

Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L
We report here cryo-EM structures of Dot1L bound to ubiquitinated nucleosome that show how H2B-Ub stimulates Dot1L activity and reveal a role for the histone H4 tail in positioning Dot1L. We find that contacts mediated by Dot1L and the H4 tail induce a conformational change in the globular core of histone H3 that reorients K79 from an inaccessible position, thus enabling this side chain to insert into the active site in a position primed for catalysis. Our study provides a comprehensive mechanism of cross-talk between histone ubiquitination and methylation and reveals structural plasticity in histones that m...
Source: Cell - February 12, 2019 Category: Cytology Source Type: research

Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease
Publication date: Available online 7 February 2019Source: CellAuthor(s): Toufic Mayassi, Kristin Ladell, Herman Gudjonson, James E. McLaren, Dustin G. Shaw, Mai T. Tran, Jagoda J. Rokicka, Ian Lawrence, Jean-Christophe Grenier, Vincent van Unen, Cezary Ciszewski, Matthew Dimaano, Hoda E. Sayegh, Vinod Kumar, Cisca Wijmenga, Peter H.R. Green, Ranjana Gokhale, Hilary Jericho, Carol E. Semrad, Stefano GuandaliniSummaryTissue-resident lymphocytes play a key role in immune surveillance, but it remains unclear how these inherently stable cell populations respond to chronic inflammation. In the setting of celiac disease (CeD), wh...
Source: Cell - February 8, 2019 Category: Cytology Source Type: research

Co-targeting RNA Polymerases IV and V Promotes Efficient De Novo DNA Methylation in Arabidopsis
Publication date: Available online 7 February 2019Source: CellAuthor(s): Javier Gallego-Bartolomé, Wanlu Liu, Peggy Hsuanyu Kuo, Suhua Feng, Basudev Ghoshal, Jason Gardiner, Jenny Miao-Chi Zhao, Soo Young Park, Joanne Chory, Steven E. JacobsenSummaryThe RNA-directed DNA methylation (RdDM) pathway in plants controls gene expression via cytosine DNA methylation. The ability to manipulate RdDM would shed light on the mechanisms and applications of DNA methylation to control gene expression. Here, we identified diverse RdDM proteins that are capable of targeting methylation and silencing in Arabidopsis when tethered to ...
Source: Cell - February 8, 2019 Category: Cytology Source Type: research

Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence
Publication date: Available online 7 February 2019Source: CellAuthor(s): Gabriel E. Neurohr, Rachel L. Terry, Jette Lengefeld, Megan Bonney, Gregory P. Brittingham, Fabien Moretto, Teemu P. Miettinen, Laura Pontano Vaites, Luis M. Soares, Joao A. Paulo, J. Wade Harper, Stephen Buratowski, Scott Manalis, Folkert J. van Werven, Liam J. Holt, Angelika AmonSummaryCell size varies greatly between cell types, yet within a specific cell type and growth condition, cell size is narrowly distributed. Why maintenance of a cell-type specific cell size is important remains poorly understood. Here we show that growing budding yeast and ...
Source: Cell - February 8, 2019 Category: Cytology Source Type: research

The Perfect Appetizer: A Pharmacological Strategy for a Non-biting Mosquito
Publication date: 7 February 2019Source: Cell, Volume 176, Issue 4Author(s): João S.M. Gesto, Luciano A. MoreiraNew possibilities for vector-borne disease control are revealed by Duvall et al. (2019), who link host-seeking behavioral modulation in Aedes aegypti to neuropeptide Y (NPY)-like receptor 7. Small-molecule screening yields agonist compounds able to activate NPYLR7 and suppress attraction to hosts. (Source: Cell)
Source: Cell - February 8, 2019 Category: Cytology Source Type: research

Replication Timing Becomes Intertwined with 3D Genome Organization
Publication date: 7 February 2019Source: Cell, Volume 176, Issue 4Author(s): Jian Ma, Zhijun DuanThrough dissecting the link between spatial genome organization and DNA replication timing, Sima et al. (2018) discover early replicating control elements (ERCEs), a new type of cis-acting elements that regulate replication timing, transcription, and multiple layers of three-dimensional features of genome organization. The study has important implications for unraveling control elements of high-order genome structure and function. (Source: Cell)
Source: Cell - February 8, 2019 Category: Cytology Source Type: research

Designer Assays for Your Sick, Subdivided Heart
Publication date: 7 February 2019Source: Cell, Volume 176, Issue 4Author(s): Kevin Kit ParkerUsing induced pluripotent stem cells and microelectromechanical device technology Zhao et al. have developed ‘organs on chips’ representing the different chambers of the heart and used them to replicate healthy and diseased tissues in vitro. These systems offer investigators and the pharmaceutical industry a new tool in testing the safety and efficacy of new medicinal therapeutics. (Source: Cell)
Source: Cell - February 8, 2019 Category: Cytology Source Type: research

Small-Molecule Agonists of Ae. aegypti Neuropeptide Y Receptor Block Mosquito Biting
Publication date: 7 February 2019Source: Cell, Volume 176, Issue 4Author(s): Laura B. Duvall, Lavoisier Ramos-Espiritu, Kyrollos E. Barsoum, J. Fraser Glickman, Leslie B. VosshallSummaryFemale Aedes aegypti mosquitoes bite humans to obtain blood to develop their eggs. Remarkably, their strong attraction to humans is suppressed for days after the blood meal by an unknown mechanism. We investigated a role for neuropeptide Y (NPY)-related signaling in long-term behavioral suppression and discovered that drugs targeting human NPY receptors modulate mosquito host-seeking. In a screen of all 49 predicted Ae. aegypti peptide rece...
Source: Cell - February 8, 2019 Category: Cytology Source Type: research