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Detecting Tumor Antigen-Specific T Cells via Interaction-Dependent Fucosyl-Biotinylation.

Zilei Liu, Jie P Li, Mingkuan Chen, Mengyao Wu, Yujie Shi, Wei Li, John R Teijaro, Peng Wu,

Re-activation and clonal expansion of tumor-specific antigen (TSA)-reactive T cells are critical to the success of checkpoint blockade and adoptive transfer of tumor-infiltrating lymphocyte (TIL)-based therapies. There are no reliable markers to specifically identify the repertoire of TSA-reactive T cells due to their heterogeneous composition. We introduce FucoID as a general platform ... Read more >>

Cell (Cell)
[2020, :]

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Co-option of Neutrophil Fates by Tissue Environments.

Iván Ballesteros, Andrea Rubio-Ponce, Marco Genua, Eleonora Lusito, Immanuel Kwok, Gabriel Fernández-Calvo, Tariq E Khoyratty, Erinke van Grinsven, Sara González-Hernández, José Ángel Nicolás-Ávila, Tommaso Vicanolo, Antonio Maccataio, Alberto Benguría, Jackson LiangYao Li, José M Adrover, Alejandra Aroca-Crevillen, Juan A Quintana, Sandra Martín-Salamanca, Francisco Mayo, Stefanie Ascher, Giulia Barbiera, Oliver Soehnlein, Matthias Gunzer, Florent Ginhoux, Fátima Sánchez-Cabo, Estanislao Nistal-Villán, Christian Schulz, Ana Dopazo, Christoph Reinhardt, Irina A Udalova, Lai Guan Ng, Renato Ostuni, Andrés Hidalgo,

Classically considered short-lived and purely defensive leukocytes, neutrophils are unique in their fast and moldable response to stimulation. This plastic behavior may underlie variable and even antagonistic functions during inflammation or cancer, yet the full spectrum of neutrophil properties as they enter healthy tissues remains unexplored. Using a new model ... Read more >>

Cell (Cell)
[2020, :]

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Chromatin Potential Identified by Shared Single-Cell Profiling of RNA and Chromatin.

Sai Ma, Bing Zhang, Lindsay M LaFave, Andrew S Earl, Zachary Chiang, Yan Hu, Jiarui Ding, Alison Brack, Vinay K Kartha, Tristan Tay, Travis Law, Caleb Lareau, Ya-Chieh Hsu, Aviv Regev, Jason D Buenrostro,

Cell differentiation and function are regulated across multiple layers of gene regulation, including modulation of gene expression by changes in chromatin accessibility. However, differentiation is an asynchronous process precluding a temporal understanding of regulatory events leading to cell fate commitment. Here we developed simultaneous high-throughput ATAC and RNA expression with ... Read more >>

Cell (Cell)
[2020, :]

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HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis.

Jian Wang, Ivan Jelcic, Lena Mühlenbruch, Veronika Haunerdinger, Nora C Toussaint, Yingdong Zhao, Carolina Cruciani, Wolfgang Faigle, Reza Naghavian, Magdalena Foege, Thomas M C Binder, Thomas Eiermann, Lennart Opitz, Laura Fuentes-Font, Richard Reynolds, William W Kwok, Julie T Nguyen, Jar-How Lee, Andreas Lutterotti, Christian Münz, Hans-Georg Rammensee, Mathias Hauri-Hohl, Mireia Sospedra, Stefan Stevanovic, Roland Martin,

The HLA-DR15 haplotype is the strongest genetic risk factor for multiple sclerosis (MS), but our understanding of how it contributes to MS is limited. Because autoreactive CD4+ T cells and B cells as antigen-presenting cells are involved in MS pathogenesis, we characterized the immunopeptidomes of the two HLA-DR15 allomorphs DR2a and ... Read more >>

Cell (Cell)
[2020, :]

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Targeting KRAS(G12C): From Inhibitory Mechanism to Modulation of Antitumor Effects in Patients.

Dongsung Kim, Jenny Yaohua Xue, Piro Lito,

KRAS mutations are among the most common genetic alterations in lung, colorectal, and pancreatic cancers. Direct inhibition of KRAS oncoproteins has been a long-standing pursuit in precision oncology, one established shortly after the discovery of RAS mutations in human cancer cells nearly 40 years ago. Recent advances in medicinal chemistry ... Read more >>

Cell (Cell)
[2020, :]

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Functional Long Non-coding RNAs Evolve from Junk Transcripts.

Alexander F Palazzo, Eugene V Koonin,

Transcriptome studies reveal pervasive transcription of complex genomes, such as those of mammals. Despite popular arguments for functionality of most, if not all, of these transcripts, genome-wide analysis of selective constraints indicates that most of the produced RNA are junk. However, junk is not garbage. On the contrary, junk transcripts ... Read more >>

Cell (Cell)
[2020, :]

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A MicroRNA Linking Human Positive Selection and Metabolic Disorders.

Lifeng Wang, Nasa Sinnott-Armstrong, Alexandre Wagschal, Abigail R Wark, Joao-Paulo Camporez, Rachel J Perry, Fei Ji, Yoojin Sohn, Justin Oh, Su Wu, Jessica Chery, Bahareh Nemati Moud, Alham Saadat, Simon N Dankel, Gunnar Mellgren, Divya Sri Priyanka Tallapragada, Sophie Madlen Strobel, Mi-Jeong Lee, Ryan Tewhey, Pardis C Sabeti, Anne Schaefer, Andreas Petri, Sakari Kauppinen, Raymond T Chung, Alexander Soukas, Joseph Avruch, Susan K Fried, Hans Hauner, Ruslan I Sadreyev, Gerald I Shulman, Melina Claussnitzer, Anders M Näär,

Positive selection in Europeans at the 2q21.3 locus harboring the lactase gene has been attributed to selection for the ability of adults to digest milk to survive famine in ancient times. However, the 2q21.3 locus is also associated with obesity and type 2 diabetes in humans, raising the possibility that ... Read more >>

Cell (Cell)
[2020, :]

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A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms.

Nazar Mashtalir, Hiroshi Suzuki, Daniel P Farrell, Akshay Sankar, Jie Luo, Martin Filipovski, Andrew R D'Avino, Roodolph St Pierre, Alfredo M Valencia, Takashi Onikubo, Robert G Roeder, Yan Han, Yuan He, Jeffrey A Ranish, Frank DiMaio, Thomas Walz, Cigall Kadoch,

Mammalian SWI/SNF complexes are ATP-dependent chromatin remodeling complexes that regulate genomic architecture. Here, we present a structural model of the endogenously purified human canonical BAF complex bound to the nucleosome, generated using cryoelectron microscopy (cryo-EM), cross-linking mass spectrometry, and homology modeling. BAF complexes bilaterally engage the nucleosome H2A/H2B acidic patch ... Read more >>

Cell (Cell)
[2020, :]

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The Geometry of Abstraction in the Hippocampus and Prefrontal Cortex.

Silvia Bernardi, Marcus K Benna, Mattia Rigotti, Jérôme Munuera, Stefano Fusi, C Daniel Salzman,

The curse of dimensionality plagues models of reinforcement learning and decision making. The process of abstraction solves this by constructing variables describing features shared by different instances, reducing dimensionality and enabling generalization in novel situations. Here, we characterized neural representations in monkeys performing a task described by different hidden and ... Read more >>

Cell (Cell)
[2020, :]

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Genomes of the Banyan Tree and Pollinator Wasp Provide Insights into Fig-Wasp Coevolution.

Xingtan Zhang, Gang Wang, Shengcheng Zhang, Shuai Chen, Yibin Wang, Ping Wen, Xiaokai Ma, Yan Shi, Rui Qi, Yang Yang, Zhenyang Liao, Jing Lin, Jishan Lin, Xiuming Xu, Xuequn Chen, Xindan Xu, Fang Deng, Lihua Zhao, Yi-Lun Lee, Rong Wang, Xiao-Yong Chen, Yann-Rong Lin, Jisen Zhang, Haibao Tang, Jin Chen, Ray Ming,

Banyan trees are distinguished by their extraordinary aerial roots. The Ficus genus includes species that have evolved a species-specific mutualism system with wasp pollinators. We sequenced genomes of the Chinese banyan tree, F. microcarpa, and a species lacking aerial roots, F. hispida, and one wasp genome coevolving with F. microcarpa, Eupristina verticillata. Comparative ... Read more >>

Cell (Cell)
[2020, :]

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Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques.

Malika Aid, Kathleen Busman-Sahay, Samuel J Vidal, Zoltan Maliga, Stephen Bondoc, Carly Starke, Margaret Terry, Connor A Jacobson, Linda Wrijil, Sarah Ducat, Olga R Brook, Andrew D Miller, Maciel Porto, Kathryn L Pellegrini, Maria Pino, Timothy N Hoang, Abishek Chandrashekar, Shivani Patel, Kathryn Stephenson, Steven E Bosinger, Hanne Andersen, Mark G Lewis, Jonathan L Hecht, Peter K Sorger, Amanda J Martinot, Jacob D Estes, Dan H Barouch,

The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of ... Read more >>

Cell (Cell)
[2020, :]

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Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques

Malika Aid, Kathleen Busman-Sahay, Samuel J. Vidal, Zoltan Maliga, Stephen Bondoc, Carly Starke, Margaret Terry, Connor A. Jacobson, Linda Wrijil, Sarah Ducat, Olga R. Brook, Andrew D. Miller, Maciel Porto, Kathryn L. Pellegrini, Maria Pino, Timothy N. Hoang, Abishek Chandrashekar, Shivani Patel, Kathryn Stephenson, Steven E. Bosinger, Hanne Andersen, Mark G. Lewis, Jonathan L. Hecht, Peter K. Sorger, Amanda J. Martinot, Jacob D. Estes, Dan H. Barouch,

The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world. Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined. In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of ... Read more >>

Cell (Cell)
[2020, :]

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Lactate Elicits ER-Mitochondrial Mg2+ Dynamics to Integrate Cellular Metabolism.

Cassidy C Daw, Karthik Ramachandran, Benjamin T Enslow, Soumya Maity, Brian Bursic, Matthew J Novello, Cherubina S Rubannelsonkumar, Ayah H Mashal, Joel Ravichandran, Terry M Bakewell, Weiwei Wang, Kang Li, Travis R Madaris, Christopher E Shannon, Luke Norton, Soundarya Kandala, Jeffrey Caplan, Subramanya Srikantan, Peter B Stathopulos, W Brian Reeves, Muniswamy Madesh,

Mg2+ is the most abundant divalent cation in metazoans and an essential cofactor for ATP, nucleic acids, and countless metabolic enzymes. To understand how the spatio-temporal dynamics of intracellular Mg2+ (iMg2+) are integrated into cellular signaling, we implemented a comprehensive screen to discover regulators of iMg2+ dynamics. Lactate emerged as ... Read more >>

Cell (Cell)
[2020, 183(2):474-489.e17]

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Single Residue Variation in Skeletal Muscle Myosin Enables Direct and Selective Drug Targeting for Spasticity and Muscle Stiffness.

Máté Gyimesi, Ádám I Horváth, Demeter Túrós, Sharad Kumar Suthar, Máté Pénzes, Csilla Kurdi, Louise Canon, Carlos Kikuti, Kathleen M Ruppel, Darshan V Trivedi, James A Spudich, István Lőrincz, Anna Á Rauscher, Mihály Kovács, Endre Pál, Sámuel Komoly, Anne Houdusse, András Málnási-Csizmadia,

Muscle spasticity after nervous system injuries and painful low back spasm affect more than 10% of global population. Current medications are of limited efficacy and cause neurological and cardiovascular side effects because they target upstream regulators of muscle contraction. Direct myosin inhibition could provide optimal muscle relaxation; however, targeting skeletal ... Read more >>

Cell (Cell)
[2020, 183(2):335-346.e13]

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Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4+ T Cells in COVID-19.

Benjamin J Meckiff, Ciro Ramírez-Suástegui, Vicente Fajardo, Serena J Chee, Anthony Kusnadi, Hayley Simon, Simon Eschweiler, Alba Grifoni, Emanuela Pelosi, Daniela Weiskopf, Alessandro Sette, Ferhat Ay, Grégory Seumois, Christian H Ottensmeier, Pandurangan Vijayanand,

The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present single-cell transcriptomic analysis of >100,000 viral antigen-reactive CD4+ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper cells and cytotoxic ... Read more >>

Cell (Cell)
[2020, :]

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Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4+ T Cells in COVID-19

Benjamin J. Meckiff, Ciro Ramírez-Suástegui, Vicente Fajardo, Serena J. Chee, Anthony Kusnadi, Hayley Simon, Simon Eschweiler, Alba Grifoni, Emanuela Pelosi, Daniela Weiskopf, Alessandro Sette, Ferhat Ay, Grégory Seumois, Christian H. Ottensmeier, Pandurangan Vijayanand,

The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present single-cell transcriptomic analysis of >100,000 viral antigen-reactive CD4+ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper cells and cytotoxic ... Read more >>

Cell (Cell)
[2020, :]

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TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS.

Chien-Hsiung Yu, Sophia Davidson, Cassandra R Harapas, James B Hilton, Michael J Mlodzianoski, Pawat Laohamonthonkul, Cynthia Louis, Ronnie Ren Jie Low, Jonas Moecking, Dominic De Nardo, Katherine R Balka, Dale J Calleja, Fiona Moghaddas, Erya Ni, Catriona A McLean, Andre L Samson, Shiraz Tyebji, Christopher J Tonkin, Christopher R Bye, Bradley J Turner, Genevieve Pepin, Michael P Gantier, Kelly L Rogers, Kate McArthur, Peter J Crouch, Seth L Masters,

Cytoplasmic accumulation of TDP-43 is a disease hallmark for many cases of amyotrophic lateral sclerosis (ALS), associated with a neuroinflammatory cytokine profile related to upregulation of nuclear factor κB (NF-κB) and type I interferon (IFN) pathways. Here we show that this inflammation is driven by the cytoplasmic DNA sensor cyclic ... Read more >>

Cell (Cell)
[2020, :]

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A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer.

Patrick A Ott, Siwen Hu-Lieskovan, Bartosz Chmielowski, Ramaswamy Govindan, Aung Naing, Nina Bhardwaj, Kim Margolin, Mark M Awad, Matthew D Hellmann, Jessica J Lin, Terence Friedlander, Meghan E Bushway, Kristen N Balogh, Tracey E Sciuto, Victoria Kohler, Samantha J Turnbull, Rana Besada, Riley R Curran, Benjamin Trapp, Julian Scherer, Asaf Poran, Dewi Harjanto, Dominik Barthelme, Ying Sonia Ting, Jesse Z Dong, Yvonne Ware, Yuting Huang, Zhengping Huang, Amy Wanamaker, Lisa D Cleary, Melissa A Moles, Kelledy Manson, Joel Greshock, Zakaria S Khondker, Ed Fritsch, Michael S Rooney, Mark DeMario, Richard B Gaynor, Lakshmi Srinivasan,

Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor immunity. Here, we report the first open-label, phase Ib clinical trial of a personalized neoantigen-based vaccine, NEO-PV-01, in combination with PD-1 blockade in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. This analysis ... Read more >>

Cell (Cell)
[2020, 183(2):347-362.e24]

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Africa Needs a New Public Health Order to Tackle Infectious Disease Threats.

John N Nkengasong, Sofonias K Tessema,

The SARS-CoV-2 pandemic has revealed that Africa needs a new public health order to be resilient, to adapt, and to cope with 21st-century disease threats. The new order will need strengthened continental and national public health institutions; local manufacturing of vaccines, therapeutics, and diagnostics; attraction, training, and retention of a ... Read more >>

Cell (Cell)
[2020, 183(2):296-300]

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Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition.

Barzin Y Nabet, Mohammad S Esfahani, Everett J Moding, Emily G Hamilton, Jacob J Chabon, Hira Rizvi, Chloe B Steen, Aadel A Chaudhuri, Chih Long Liu, Angela B Hui, Diego Almanza, Henning Stehr, Linda Gojenola, Rene F Bonilla, Michael C Jin, Young-Jun Jeon, Diane Tseng, Cailian Liu, Taha Merghoub, Joel W Neal, Heather A Wakelee, Sukhmani K Padda, Kavitha J Ramchandran, Millie Das, Andrew J Plodkowski, Christopher Yoo, Emily L Chen, Ryan B Ko, Aaron M Newman, Matthew D Hellmann, Ash A Alizadeh, Maximilian Diehn,

Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating ... Read more >>

Cell (Cell)
[2020, 183(2):363-376.e13]

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Passive Transfer of Vaccine-Elicited Antibodies Protects against SIV in Rhesus Macaques.

Galit Alter, Wen-Han Yu, Abishek Chandrashekar, Erica N Borducchi, Khader Ghneim, Ashish Sharma, Rebecca Nedellec, Katherine R McKenney, Caitlyn Linde, Thomas Broge, Todd J Suscovich, Tom Linnekin, Peter Abbink, Noe B Mercado, Joseph P Nkolola, Katherine McMahan, Esther A Bondzie, Venous Hamza, Lauren Peter, Nicole Kordana, Shant Mahrokhian, Michael S Seaman, Wenjun Li, Mark G Lewis, Douglas A Lauffenburger, Lars Hangartner, Rafick-Pierre Sekaly, Dan H Barouch,

Several HIV-1 and SIV vaccine candidates have shown partial protection against viral challenges in rhesus macaques. However, the protective efficacy of vaccine-elicited polyclonal antibodies has not previously been demonstrated in adoptive transfer studies in nonhuman primates. In this study, we show that passive transfer of purified antibodies from vaccinated macaques ... Read more >>

Cell (Cell)
[2020, 183(1):185-196.e14]

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Timeline: Vaccines.

Rino Rappuoli,

Infectious diseases killed hundreds of million people, made empires and civilizations vulnerable, and recently took away our freedom to go out, walk, work, travel, meet friends, and visit relatives during the Covid-19 lockdown. Vaccination freed humans from most of infectious diseases of the past. By starting with a virus grown ... Read more >>

Cell (Cell)
[2020, 183(2):552]

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Colonic Macrophages Combat Fungal Intoxication: Metchnikoff Would Be Pleased.

Gwendalyn J Randolph,

How the colon microenvironment confronts a breach of its epithelial border remains incompletely understood. In this issue, the laboratories of Lennon-Duménil and Vignjevic reveal a novel role for macrophages in sustaining epithelial integrity in the face of fungal metabolites. ... Read more >>

Cell (Cell)
[2020, 183(2):305-307]

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The Spanish 1918 Flu and the COVID-19 Disease: The Art of Remembering and Foreshadowing Pandemics.

Joseph L Goldstein,

Tragic events such as pandemics can be remembered as well as foreshadowed by works of art. Paintings by the artists Edvard Munch and John Singer Sargent (1918-19) tell us in real time what it was like to be stricken by the Spanish flu. Paintings by Edward Hopper (1940s and '50s) ... Read more >>

Cell (Cell)
[2020, 183(2):285-289]

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Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study.

Katri Korpela, Otto Helve, Kaija-Leena Kolho, Terhi Saisto, Kirsi Skogberg, Evgenia Dikareva, Vedran Stefanovic, Anne Salonen, Sture Andersson, Willem M de Vos,

Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom ... Read more >>

Cell (Cell)
[2020, 183(2):324-334.e5]

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