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The Roborovski dwarf hamster – a highly susceptible model for a rapid and fatal course of SARS-CoV-2 infection

Jakob Trimpert, Daria Vladimirova, Kristina Dietert, Azza Abdelgawad, Dusan Kunec, Simon Dökel, Anne Voss, Achim D. Gruber, Luca D. Bertzbach, Nikolaus Osterrieder,

The COVID-19 pandemic caused by SARS-CoV-2 has precipitated an unprecedented and yet unresolved health crisis worldwide. Different mammals are susceptible to SARS-CoV-2; however, few species examined so far develop robust clinical disease that mirrors severe human cases or allows testing of vaccines and drugs under conditions of severe disease. Here, ... Read more >>

Cell Rep (Cell reports)
[2020, :]

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JAK1 Inhibition Blocks Lethal Immune Hypersensitivity in a Mouse Model of Down Syndrome.

Kathryn D Tuttle, Katherine A Waugh, Paula Araya, Ross Minter, David J Orlicky, Michael Ludwig, Zdenek Andrysik, Matthew A Burchill, Beth A J Tamburini, Colin Sempeck, Keith Smith, Ross Granrath, Dayna Tracy, Jessica Baxter, Joaquin M Espinosa, Kelly D Sullivan,

Individuals with Down syndrome (DS; trisomy 21) display hyperactivation of interferon (IFN) signaling and chronic inflammation, which could potentially be explained by the extra copy of four IFN receptor (IFNR) genes encoded on chromosome 21. However, the clinical effects of IFN hyperactivity in DS remain undefined. Here, we report that ... Read more >>

Cell Rep (Cell reports)
[2020, 33(7):108407]

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Myt1 Kinase Couples Mitotic Cell Cycle Exit with Differentiation in Drosophila.

Reegan J Willms, Jie Zeng, Shelagh D Campbell,

The Drosophila midgut is an excellent system for characterizing cell cycle regulation in the context of tissue homeostasis. Two major progenitor cell types populate the midgut: mitotic intestinal stem cells and their post-mitotic daughters, enteroblasts. Although regulatory networks that control stem cell proliferation are well characterized, how enteroblast mitotic-cell-cycle exit ... Read more >>

Cell Rep (Cell reports)
[2020, 33(7):108400]

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Poly(A)-Binding Protein Regulates the Efficiency of Translation Termination.

Chan Wu, Bijoyita Roy, Feng He, Kevin Yan, Allan Jacobson,

Multiple factors influence translation termination efficiency, including nonsense codon identity and immediate context. To determine whether the relative position of a nonsense codon within an open reading frame (ORF) influences termination efficiency, we quantitate the production of prematurely terminated and/or readthrough polypeptides from 26 nonsense alleles of 3 genes expressed ... Read more >>

Cell Rep (Cell reports)
[2020, 33(7):108399]

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Tau Pathology Drives Dementia Risk-Associated Gene Networks toward Chronic Inflammatory States and Immunosuppression.

Jessica E Rexach, Damon Polioudakis, Anna Yin, Vivek Swarup, Timothy S Chang, Tam Nguyen, Arjun Sarkar, Lawrence Chen, Jerry Huang, Li-Chun Lin, William Seeley, John Q Trojanowski, Dheeraj Malhotra, Daniel H Geschwind,

To understand how neural-immune-associated genes and pathways contribute to neurodegenerative disease pathophysiology, we performed a systematic functional genomic analysis in purified microglia and bulk tissue from mouse and human AD, FTD, and PSP. We uncover a complex temporal trajectory of microglial-immune pathways involving the type 1 interferon response associated with ... Read more >>

Cell Rep (Cell reports)
[2020, 33(7):108398]

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Inflammasomes within Hyperactive Murine Dendritic Cells Stimulate Long-Lived T Cell-Mediated Anti-tumor Immunity.

Dania Zhivaki, Francesco Borriello, Ohn A Chow, Benjamin Doran, Ira Fleming, Derek J Theisen, Paris Pallis, Alex K Shalek, Caroline L Sokol, Ivan Zanoni, Jonathan C Kagan,

Central to anti-tumor immunity are dendritic cells (DCs), which stimulate long-lived protective T cell responses. Recent studies have demonstrated that DCs can achieve a state of hyperactivation, which is associated with inflammasome activities within living cells. Herein, we report that hyperactive DCs have an enhanced ability to migrate to draining lymph ... Read more >>

Cell Rep (Cell reports)
[2020, 33(7):108381]

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A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest.

Michael Tsabar, Caroline S Mock, Veena Venkatachalam, Jose Reyes, Kyle W Karhohs, Trudy G Oliver, Aviv Regev, Ashwini Jambhekar, Galit Lahav,

Cell Rep (Cell reports)
[2020, 33(6):108392]

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TFEB Transcriptional Responses Reveal Negative Feedback by BHLHE40 and BHLHE41.

Kimberly L Carey, Geraldine L C Paulus, Lingfei Wang, Dale R Balce, Jessica W Luo, Phil Bergman, Ianina C Ferder, Lingjia Kong, Nicole Renaud, Shantanu Singh, Maria Kost-Alimova, Beat Nyfeler, Kara G Lassen, Herbert W Virgin, Ramnik J Xavier,

Transcription factor EB (TFEB) activates lysosomal biogenesis genes in response to environmental cues. Given implications of impaired TFEB signaling and lysosomal dysfunction in metabolic, neurological, and infectious diseases, we aim to systematically identify TFEB-directed circuits by examining transcriptional responses to TFEB subcellular localization and stimulation. We reveal that steady-state nuclear ... Read more >>

Cell Rep (Cell reports)
[2020, 33(6):108371]

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Intramacrophage ROS Primes the Innate Immune System via JAK/STAT and Toll Activation.

Sveta Chakrabarti, Sandhya S Visweswariah,

Tissue injury is one of the most severe environmental perturbations for a living organism. When damage occurs in adult Drosophila, there is a local response of the injured tissue and a coordinated action across different tissues to help the organism overcome the deleterious effect of an injury. We show a ... Read more >>

Cell Rep (Cell reports)
[2020, 33(6):108368]

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Restoration of Cingulate Long-Term Depression by Enhancing Non-apoptotic Caspase 3 Alleviates Peripheral Pain Hypersensitivity.

Yong-Jie Wang, Ming-Gang Liu, Jing-Hua Wang, Wei Cao, Cheng Wu, Zi-Yue Wang, Li Liu, Fan Yang, Zhi-Hui Feng, Li Sun, Fuxing Zhang, Yi Shen, Yu-Dong Zhou, Min Zhuo, Jian-Hong Luo, Tian-Le Xu, Xiang-Yao Li,

Nerve injury in somatosensory pathways may lead to neuropathic pain, which affects the life quality of ∼8% of people. Long-term enhancement of excitatory synaptic transmission along somatosensory pathways contributes to neuropathic pain. Caspase 3 (Casp3) plays a non-apoptotic role in the hippocampus and regulates internalization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) ... Read more >>

Cell Rep (Cell reports)
[2020, 33(6):108369]

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Rapid and Scalable Profiling of Nascent RNA with fastGRO.

Elisa Barbieri, Connor Hill, Mathieu Quesnel-Vallières, Avery J Zucco, Yoseph Barash, Alessandro Gardini,

Genome-wide profiling of nascent RNA has become a fundamental tool to study transcription regulation. Unlike steady-state RNA-sequencing (RNA-seq), nascent RNA profiling mirrors real-time activity of RNA polymerases and provides an accurate readout of transcriptome-wide variations. Some species of nuclear RNAs (i.e., large intergenic noncoding RNAs [lincRNAs] and eRNAs) have a ... Read more >>

Cell Rep (Cell reports)
[2020, 33(6):108373]

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AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF.

George K E Umanah, Mehdi Ghasemi, Xiling Yin, Melissa Chang, Jin Wan Kim, Jianmin Zhang, Erica Ma, Leslie A Scarffe, Yun-Il Lee, Rong Chen, Kavya Tangella, Amy McNamara, Leire Abalde-Atristain, Mohamad A Dar, Samuel Bennett, Marisol Cortes, Shaida A Andrabi, Paschalis-Thomas Doulias, Harry Ischiropoulos, Ted M Dawson, Valina L Dawson,

The regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking affects multiple brain functions, such as learning and memory. We have previously shown that Thorase plays an important role in the internalization of AMPARs from the synaptic membrane. Here, we show that N-methyl-d-aspartate receptor (NMDAR) activation leads to increased S-nitrosylation of Thorase ... Read more >>

Cell Rep (Cell reports)
[2020, 33(5):108329]

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G9a Promotes Breast Cancer Recurrence through Repression of a Pro-inflammatory Program.

Nathaniel W Mabe, Nina Marie G Garcia, Shayna E Wolery, Rachel Newcomb, Ryan C Meingasner, Brittany A Vilona, Ryan Lupo, Chao-Chieh Lin, Jen-Tsan Chi, James V Alvarez,

Dysregulated gene expression is a common feature of cancer and may underlie some aspects of tumor progression, including tumor relapse. Here, we show that recurrent mammary tumors exhibit global changes in gene expression and histone modifications and acquire dependence on the G9a histone methyltransferase. Genetic ablation of G9a delays tumor ... Read more >>

Cell Rep (Cell reports)
[2020, 33(5):108341]

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Human and Mouse Transcriptome Profiling Identifies Cross-Species Homology in Pulmonary and Lymph Node Mononuclear Phagocytes.

Sonia M Leach, Sophie L Gibbings, Anita D Tewari, Shaikh M Atif, Brian Vestal, Thomas Danhorn, William J Janssen, Tor D Wager, Claudia V Jakubzick,

The mononuclear phagocyte (MP) system consists of macrophages, monocytes, and dendritic cells (DCs). MP subtypes play distinct functional roles in steady-state and inflammatory conditions. Although murine MPs are well characterized, their pulmonary and lymph node (LN) human homologs remain poorly understood. To address this gap, we have created a gene ... Read more >>

Cell Rep (Cell reports)
[2020, 33(5):108337]

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Evaluation of Engineered CRISPR-Cas-Mediated Systems for Site-Specific RNA Editing.

Ryan J Marina, Kristopher W Brannan, Kevin D Dong, Brian A Yee, Gene W Yeo,

Site-directed RNA editing approaches offer great potential to correct genetic mutations in somatic cells while avoiding permanent off-target genomic edits. Nuclease-dead RNA-targeting CRISPR-Cas systems recruit functional effectors to RNA molecules in a programmable fashion. Here, we demonstrate a Streptococcus pyogenes Cas9-ADAR2 fusion system that uses a 3' modified guide RNA ... Read more >>

Cell Rep (Cell reports)
[2020, 33(5):108350]

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Airway Microbiota-Host Interactions Regulate Secretory Leukocyte Protease Inhibitor Levels and Influence Allergic Airway Inflammation.

Natalia Jaeger, Ryan T McDonough, Anne L Rosen, Ariel Hernandez-Leyva, Naomi G Wilson, Michael A Lint, Emilie V Russler-Germain, Jiani N Chai, Leonard B Bacharier, Chyi-Song Hsieh, Andrew L Kau,

Homeostatic mucosal immune responses are fine-tuned by naturally evolved interactions with native microbes, and integrating these relationships into experimental models can provide new insights into human diseases. Here, we leverage a murine-adapted airway microbe, Bordetella pseudohinzii (Bph), to investigate how chronic colonization impacts mucosal immunity and the development of allergic ... Read more >>

Cell Rep (Cell reports)
[2020, 33(5):108331]

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Atypical UV Photoproducts Induce Non-canonical Mutation Classes Associated with Driver Mutations in Melanoma.

Marian F Laughery, Alexander J Brown, Kaitlynne A Bohm, Smitha Sivapragasam, Haley S Morris, Mila Tchmola, Angelica D Washington, Debra Mitchell, Stephen Mather, Ewa P Malc, Piotr A Mieczkowski, Steven A Roberts, John J Wyrick,

Somatic mutations in skin cancers and other ultraviolet (UV)-exposed cells are typified by C>T and CC>TT substitutions at dipyrimidine sequences; however, many oncogenic "driver" mutations in melanoma do not fit this UV signature. Here, we use genome sequencing to characterize mutations in yeast repeatedly irradiated with UV light. Analysis of ... Read more >>

Cell Rep (Cell reports)
[2020, 33(7):108401]

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Gbx2 Identifies Two Amacrine Cell Subtypes with Distinct Molecular, Morphological, and Physiological Properties.

Patrick C Kerstein, Joseph Leffler, Benjamin Sivyer, W Rowland Taylor, Kevin M Wright,

Our understanding of nervous system function is limited by our ability to identify and manipulate neuronal subtypes within intact circuits. We show that the Gbx2CreERT2-IRES-EGFP mouse line labels two amacrine cell (AC) subtypes in the mouse retina that have distinct morphological, physiological, and molecular properties. Using a combination of RNA-seq, ... Read more >>

Cell Rep (Cell reports)
[2020, 33(7):108382]

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Early-Life Stress Regulates Cardiac Development through an IL-4-Glucocorticoid Signaling Balance.

Dilem C Apaydin, Paul A Morocho Jaramillo, Laura Corradi, Francesca Cosco, Fritz G Rathjen, Thomas Kammertoens, Alessandro Filosa, Suphansa Sawamiphak,

Stressful experiences early in life can increase the risk of cardiovascular diseases. However, it remains largely unknown how stress influences susceptibility to the disease onset. Here, we show that exposure to brain-processed stress disrupts myocardial growth by reducing cardiomyocyte mitotic activity. Activation of the glucocorticoid receptor (GR), the primary stress ... Read more >>

Cell Rep (Cell reports)
[2020, 33(7):108404]

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Essentiality of CENP-A Depends on Its Binding Mode to HJURP.

Tetsuya Hori, JingHui Cao, Kohei Nishimura, Mariko Ariyoshi, Yasuhiro Arimura, Hitoshi Kurumizaka, Tatsuo Fukagawa,

CENP-A incorporation is critical for centromere specification and is mediated by the chaperone HJURP. The CENP-A-targeting domain (CATD) of CENP-A specifically binds to HJURP, and this binding is conserved. However, the binding interface of CENP-A-HJURP is yet to be understood. Here, we identify the critical residues for chicken CENP-A or ... Read more >>

Cell Rep (Cell reports)
[2020, 33(7):108388]

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Pairwise Synchrony and Correlations Depend on the Structure of the Population Code in Visual Cortex.

Veronika Koren, Ariana R Andrei, Ming Hu, Valentin Dragoi, Klaus Obermayer,

In visual areas of primates, neurons activate in parallel while the animal is engaged in a behavioral task. In this study, we examine the structure of the population code while the animal performs delayed match-to-sample tasks on complex natural images. The macaque monkeys visualized two consecutive stimuli that were either ... Read more >>

Cell Rep (Cell reports)
[2020, 33(6):108367]

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The Deubiquitinating Enzyme Ataxin-3 Regulates Ciliogenesis and Phagocytosis in the Retina.

Vasileios Toulis, Sílvia García-Monclús, Carlos de la Peña-Ramírez, Rodrigo Arenas-Galnares, Josep F Abril, Sokol V Todi, Naheed Khan, Alejandro Garanto, Maria do Carmo Costa, Gemma Marfany,

Expansion of a CAG repeat in ATXN3 causes the dominant polyglutamine disease spinocerebellar ataxia type 3 (SCA3), yet the physiological role of ATXN3 remains unclear. Here, we focus on unveiling the function of Ataxin-3 (ATXN3) in the retina, a neurological organ amenable to morphological and physiological studies. Depletion of Atxn3 ... Read more >>

Cell Rep (Cell reports)
[2020, 33(6):108360]

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Prrx1 Fibroblasts Represent a Pro-fibrotic Lineage in the Mouse Ventral Dermis.

Tripp Leavitt, Michael S Hu, Mimi R Borrelli, Michael Januszyk, Julia T Garcia, Ryan C Ransom, Shamik Mascharak, Heather E desJardins-Park, Ulrike M Litzenburger, Graham G Walmsley, Clement D Marshall, Alessandra L Moore, Bryan Duoto, Sandeep Adem, Deshka S Foster, Ankit Salhotra, Abra H Shen, Michelle Griffin, Ethan Z Shen, Leandra A Barnes, Elizabeth R Zielins, Zeshaan N Maan, Yuning Wei, Charles K F Chan, Derrick C Wan, Hermann P Lorenz, Howard Y Chang, Geoffrey C Gurtner, Michael T Longaker,

Fibroblast heterogeneity has been shown within the unwounded mouse dorsal dermis, with fibroblast subpopulations being identified according to anatomical location and embryonic lineage. Using lineage tracing, we demonstrate that paired related homeobox 1 (Prrx1)-expressing fibroblasts are responsible for acute and chronic fibroses in the ventral dermis. Single-cell transcriptomics further corroborated ... Read more >>

Cell Rep (Cell reports)
[2020, 33(6):108356]

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A Leptin-Mediated Neural Mechanism Linking Breathing to Metabolism.

Jeehaeh Do, Zheng Chang, Gabriella Sekerková, Donald R McCrimmon, Marco Martina,

Breathing is coupled to metabolism. Leptin, a peptide mainly secreted in proportion to adipose tissue mass, increases energy expenditure with a parallel increase in breathing. We demonstrate that optogenetic activation of LepRb neurons in the nucleus of the solitary tract (NTS) mimics the respiratory stimulation after systemic leptin administration. We ... Read more >>

Cell Rep (Cell reports)
[2020, 33(6):108358]

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Prepronociceptin-Expressing Neurons in the Extended Amygdala Encode and Promote Rapid Arousal Responses to Motivationally Salient Stimuli.

Jose Rodriguez-Romaguera, Randall L Ung, Hiroshi Nomura, James M Otis, Marcus L Basiri, Vijay M K Namboodiri, Xueqi Zhu, J Elliott Robinson, Hanna E van den Munkhof, Jenna A McHenry, Louisa E H Eckman, Oksana Kosyk, Thomas C Jhou, Thomas L Kash, Michael R Bruchas, Garret D Stuber,

Motivational states consist of cognitive, emotional, and physiological components controlled by multiple brain regions. An integral component of this neural circuitry is the bed nucleus of the stria terminalis (BNST). Here, we identify that neurons within BNST that express the gene prepronociceptin (PnocBNST) modulate rapid changes in physiological arousal that ... Read more >>

Cell Rep (Cell reports)
[2020, 33(6):108362]

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