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2019 v.178 no.5
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- Author:
- El Khattabi, Laila; Zhao, Haiyan; Kalchschmidt, Jens; Young, Natalie; Jung, Seolkyoung; Van Blerkom, Peter; Kieffer-Kwon, Philippe; Kieffer-Kwon, Kyong-Rim; Park, Solji; Wang, Xiang; Krebs, Jordan; Tripathi, Subhash; Sakabe, Noboru; Sobreira, Débora R.; Huang, Su-Chen; Rao, Suhas S.P.; Pruett, Nathanael; Chauss, Daniel; Sadler, Erica; Lopez, Andrea; Nóbrega, Marcelo A.; Aiden, Erez Lieberman; Asturias, Francisco J.; Casellas, Rafael
- Source:
- Cell 2019 v.178 no.5 pp. 1145-1158.e20
- ISSN:
- 0092-8674
- Subject:
- CRISPR-Cas systems; DNA; cryo-electron microscopy; embryonic stem cells; enzymes; mammals; mechanism of action; models; topology; transcription factors
- Abstract:
- ... While Mediator plays a key role in eukaryotic transcription, little is known about its mechanism of action. This study combines CRISPR-Cas9 genetic screens, degron assays, Hi-C, and cryoelectron microscopy (cryo-EM) to dissect the function and structure of mammalian Mediator (mMED). Deletion analyses in B, T, and embryonic stem cells (ESC) identified a core of essential subunits required for Pol I ...
- DOI:
- 10.1016/j.cell.2019.07.011
- https://dx.doi.org/10.1016/j.cell.2019.07.011
- Author:
- Van de Weyer, Anna-Lena; Monteiro, Freddy; Furzer, Oliver J.; Nishimura, Marc T.; Cevik, Volkan; Witek, Kamil; Jones, Jonathan D.G.; Dangl, Jeffery L.; Weigel, Detlef; Bemm, Felix
- Source:
- Cell 2019 v.178 no.5 pp. 1260-1272.e14
- ISSN:
- 0092-8674
- Subject:
- Arabidopsis thaliana; alleles; disease resistance; immunologic receptors; infectious diseases; inventories; pathogens
- Abstract:
- ... Infectious disease is both a major force of selection in nature and a prime cause of yield loss in agriculture. In plants, disease resistance is often conferred by nucleotide-binding leucine-rich repeat (NLR) proteins, intracellular immune receptors that recognize pathogen proteins and their effects on the host. Consistent with extensive balancing and positive selection, NLRs are encoded by one of ...
- DOI:
- 10.1016/j.cell.2019.07.038
- https://dx.doi.org/10.1016/j.cell.2019.07.038
- Author:
- Jordan, Stefan; Tung, Navpreet; Casanova-Acebes, Maria; Chang, Christie; Cantoni, Claudia; Zhang, Dachuan; Wirtz, Theresa H.; Naik, Shruti; Rose, Samuel A.; Brocker, Chad N.; Gainullina, Anastasiia; Hornburg, Daniel; Horng, Sam; Maier, Barbara B.; Cravedi, Paolo; LeRoith, Derek; Gonzalez, Frank J.; Meissner, Felix; Ochando, Jordi; Rahman, Adeeb; Chipuk, Jerry E.; Artyomov, Maxim N.; Frenette, Paul S.; Piccio, Laura; Berres, Marie-Luise; Gallagher, Emily J.; Merad, Miriam
- Source:
- Cell 2019 v.178 no.5 pp. 1102-1114.e17
- ISSN:
- 0092-8674
- Subject:
- autoimmune diseases; bone marrow; chemokine CCL2; energy intake; fasting; food intake; glucose; hepatocytes; inflammation; liver; low calorie diet; monocytes; peroxisome proliferator-activated receptor alpha; protein content; protein kinases; tissue repair
- Abstract:
- ... Caloric restriction is known to improve inflammatory and autoimmune diseases. However, the mechanisms by which reduced caloric intake modulates inflammation are poorly understood. Here we show that short-term fasting reduced monocyte metabolic and inflammatory activity and drastically reduced the number of circulating monocytes. Regulation of peripheral monocyte numbers was dependent on dietary gl ...
- DOI:
- 10.1016/j.cell.2019.07.050
- https://dx.doi.org/10.1016/j.cell.2019.07.050
- Author:
- Choudhury, Saurav Roy; Babes, Liane; Rahn, Jennifer J.; Ahn, Bo-Young; Goring, Kimberly-Ann R.; King, Jennifer C.; Lau, Arthur; Petri, Björn; Hao, Xiaoguang; Chojnacki, Andrew K.; Thanabalasuriar, Ajitha; McAvoy, Erin F.; Tabariès, Sébastien; Schraeder, Christoph; Patel, Kamala D.; Siegel, Peter M.; Kopciuk, Karen A.; Schriemer, David C.; Muruve, Daniel A.; Kelly, Margaret M.; Yipp, Bryan G.; Kubes, Paul; Robbins, Stephen M.; Senger, Donna L.
- Source:
- Cell 2019 v.178 no.5 pp. 1205-1221.e17
- ISSN:
- 0092-8674
- Subject:
- adhesion; blood flow; endothelium; endotoxemia; enzyme activity; image analysis; in vitro culture; inflammation; integrins; liver; lungs; neutrophils; peptides; therapeutics
- Abstract:
- ... A hallmark feature of inflammation is the orchestrated recruitment of neutrophils from the bloodstream into inflamed tissue. Although selectins and integrins mediate recruitment in many tissues, they have a minimal role in the lungs and liver. Exploiting an unbiased in vivo functional screen, we identified a lung and liver homing peptide that functionally abrogates neutrophil recruitment to these ...
- DOI:
- 10.1016/j.cell.2019.07.017
- https://dx.doi.org/10.1016/j.cell.2019.07.017
- Author:
- Amezcua Vesely, Maria Carolina; Pallis, Paris; Bielecki, Piotr; Low, Jun Siong; Zhao, Jun; Harman, Christian C.D.; Kroehling, Lina; Jackson, Ruaidhrí; Bailis, Will; Licona-Limón, Paula; Xu, Hao; Iijima, Norifumi; Pillai, Padmini S.; Kaplan, Daniel H.; Weaver, Casey T.; Kluger, Yuval; Kowalczyk, Monika S.; Iwasaki, Akiko; Pereira, Joao P.; Esplugues, Enric; Gagliani, Nicola; Flavell, Richard A.
- Source:
- Cell 2019 v.178 no.5 pp. 1176-1188.e15
- ISSN:
- 0092-8674
- Subject:
- Klebsiella pneumoniae; T-lymphocytes; adaptive immunity; animal models; antibodies; bacterial infections; endothelial cells; immunization; interleukin-17; interleukin-7; lungs; mice; vaccine development
- Abstract:
- ... Adaptive immunity provides life-long protection by generating central and effector memory T cells and the most recently described tissue resident memory T (TRM) cells. However, the cellular origin of CD4 TRM cells and their contribution to host defense remain elusive. Using IL-17A tracking-fate mouse models, we found that a significant fraction of lung CD4 TRM cells derive from IL-17A-producing ef ...
- DOI:
- 10.1016/j.cell.2019.07.032
- https://dx.doi.org/10.1016/j.cell.2019.07.032
- Author:
- Nagai, Motoyoshi; Noguchi, Ryotaro; Takahashi, Daisuke; Morikawa, Takayuki; Koshida, Kouhei; Komiyama, Seiga; Ishihara, Narumi; Yamada, Takahiro; Kawamura, Yuki I.; Muroi, Kisara; Hattori, Kouya; Kobayashi, Nobuhide; Fujimura, Yumiko; Hirota, Masato; Matsumoto, Ryohtaroh; Aoki, Ryo; Tamura-Nakano, Miwa; Sugiyama, Machiko; Katakai, Tomoya; Sato, Shintaro; Takubo, Keiyo; Dohi, Taeko; Hase, Koji
- Source:
- Cell 2019 v.178 no.5 pp. 1072-1087.e14
- ISSN:
- 0092-8674
- Subject:
- B-lymphocytes; Peyer's patches; apoptosis; bone marrow; chemokine CXCL13; diarrhea; digestive system; fasting; homeostasis; immune response; immunoglobulin A; lymph nodes; mucosal immunity; nutritional status; oral vaccination; ovalbumin; refeeding; stromal cells
- Abstract:
- ... Nutritional status potentially influences immune responses; however, how nutritional signals regulate cellular dynamics and functionality remains obscure. Herein, we report that temporary fasting drastically reduces the number of lymphocytes by ∼50% in Peyer’s patches (PPs), the inductive site of the gut immune response. Subsequent refeeding seemingly restored the number of lymphocytes, but whose ...
- DOI:
- 10.1016/j.cell.2019.07.047
- https://dx.doi.org/10.1016/j.cell.2019.07.047
- Author:
- Luan, Harding H.; Wang, Andrew; Hilliard, Brandon K.; Carvalho, Fernando; Rosen, Connor E.; Ahasic, Amy M.; Herzog, Erica L.; Kang, Insoo; Pisani, Margaret A.; Yu, Shuang; Zhang, Cuiling; Ring, Aaron M.; Young, Lawrence H.; Medzhitov, Ruslan
- Source:
- Cell 2019 v.178 no.5 pp. 1231-1244.e11
- ISSN:
- 0092-8674
- Subject:
- body temperature; cardiac output; disease resistance; inflammation; lipid metabolism; pathogens; protective effect; sepsis (infection); triacylglycerols
- Abstract:
- ... Growth and differentiation factor 15 (GDF15) is an inflammation-associated hormone with poorly defined biology. Here, we investigated the role of GDF15 in bacterial and viral infections. We found that inflammation induced GDF15, and that GDF15 was necessary for surviving both bacterial and viral infections, as well as sepsis. The protective effects of GDF15 were largely independent of pathogen con ...
- DOI:
- 10.1016/j.cell.2019.07.033
- https://dx.doi.org/10.1016/j.cell.2019.07.033
- Author:
- Cheng, Chia-Wei; Biton, Moshe; Haber, Adam L.; Gunduz, Nuray; Eng, George; Gaynor, Liam T.; Tripathi, Surya; Calibasi-Kocal, Gizem; Rickelt, Steffen; Butty, Vincent L.; Moreno-Serrano, Marta; Iqbal, Ameena M.; Bauer-Rowe, Khristian E.; Imada, Shinya; Ulutas, Mehmet Sefa; Mylonas, Constantine; Whary, Mark T.; Levine, Stuart S.; Basbinar, Yasemin; Hynes, Richard O.; Mino-Kenudson, Mari; Deshpande, Vikram; Boyer, Laurie A.; Fox, James G.; Terranova, Christopher; Rai, Kunal; Piwnica-Worms, Helen; Mihaylova, Maria M.; Regev, Aviv; Yilmaz, Ömer H.
- Source:
- Cell 2019 v.178 no.5 pp. 1115-1131.e15
- ISSN:
- 0092-8674
- Subject:
- 3-hydroxybutyric acid; genes; histone deacetylase; homeostasis; hydroxymethylglutaryl-CoA synthase; ketogenic diet; ketone bodies; mammals; small intestine; stem cells
- Abstract:
- ... Little is known about how metabolites couple tissue-specific stem cell function with physiology. Here we show that, in the mammalian small intestine, the expression of Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthetase 2), the gene encoding the rate-limiting enzyme in the production of ketone bodies, including beta-hydroxybutyrate (βOHB), distinguishes self-renewing Lgr5+ stem cells (ISCs) from dif ...
- DOI:
- 10.1016/j.cell.2019.07.048
- https://dx.doi.org/10.1016/j.cell.2019.07.048
- Author:
- Sberro, Hila; Fremin, Brayon J.; Zlitni, Soumaya; Edfors, Fredrik; Greenfield, Nicholas; Snyder, Michael P.; Pavlopoulos, Georgios A.; Kyrpides, Nikos C.; Bhatt, Ami S.
- Source:
- Cell 2019 v.178 no.5 pp. 1245-1259.e14
- ISSN:
- 0092-8674
- Subject:
- genes; metagenomics; microbiome; proteins; translation (genetics)
- Abstract:
- ... Small proteins are traditionally overlooked due to computational and experimental difficulties in detecting them. To systematically identify small proteins, we carried out a comparative genomics study on 1,773 human-associated metagenomes from four different body sites. We describe >4,000 conserved protein families, the majority of which are novel; ∼30% of these protein families are predicted to b ...
- DOI:
- 10.1016/j.cell.2019.07.016
- https://dx.doi.org/10.1016/j.cell.2019.07.016
- Author:
- Suh, Jaehong; Romano, Donna M.; Nitschke, Larissa; Herrick, Scott P.; DiMarzio, Britt A.; Dzhala, Volodymyr; Bae, Jun-Seok; Oram, Mary K.; Zheng, Yuejiao; Hooli, Basavaraj; Mullin, Kristina; Gennarino, Vincenzo A.; Wasco, Wilma; Schmahmann, Jeremy D.; Albers, Mark W.; Zoghbi, Huda Y.; Tanzi, Rudolph E.
- Source:
- Cell 2019 v.178 no.5 pp. 1159-1175.e17
- ISSN:
- 0092-8674
- Subject:
- Alzheimer disease; animal models; ataxia (disorder); cerebellum; cerebrum; cognition; mice; microsatellite repeats; mutants; neurodegenerative diseases; neurogenesis; pathogenesis; patients; risk factors
- Abstract:
- ... Expansion of CAG trinucleotide repeats in ATXN1 causes spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disease that impairs coordination and cognition. While ATXN1 is associated with increased Alzheimer’s disease (AD) risk, CAG repeat number in AD patients is not changed. Here, we investigated the consequences of ataxin-1 loss of function and discovered that knockout of Atxn1 reduced CIC ...
- DOI:
- 10.1016/j.cell.2019.07.043
- https://dx.doi.org/10.1016/j.cell.2019.07.043
- Author:
- Soutourina, Julie
- Source:
- Cell 2019 v.178 no.5 pp. 1036-1038
- ISSN:
- 0092-8674
- Subject:
- genomics; mammals; mechanism of action; transcription (genetics)
- Abstract:
- ... In this issue of Cell, Casellas and colleagues provide insights into the structural and functional aspects of the mammalian multi-subunit Mediator complex, a conserved and essential transcriptional coregulator. Combining cryo-EM, genetic, and genomic analyses, the work sheds light on Mediator’s mode of action as a functional bridge between enhancers and promoters. ...
- DOI:
- 10.1016/j.cell.2019.07.040
- https://dx.doi.org/10.1016/j.cell.2019.07.040
- Author:
- Akera, Takashi; Trimm, Emily; Lampson, Michael A.
- Source:
- Cell 2019 v.178 no.5 pp. 1132-1144.e10
- ISSN:
- 0092-8674
- Subject:
- DNA; animal models; centromeres; eggs; females; histones; meiosis; mice; microtubules; phosphorylation
- Abstract:
- ... Asymmetric division in female meiosis creates selective pressure favoring selfish centromeres that bias their transmission to the egg. This centromere drive can explain the paradoxical rapid evolution of both centromere DNA and centromere-binding proteins despite conserved centromere function. Here, we define a molecular pathway linking expanded centromeres to histone phosphorylation and recruitme ...
- DOI:
- 10.1016/j.cell.2019.07.001
- https://dx.doi.org/10.1016/j.cell.2019.07.001
- Author:
- Jaeger, Kathrin; Bruenle, Steffen; Weinert, Tobias; Guba, Wolfgang; Muehle, Jonas; Miyazaki, Takuya; Weber, Martin; Furrer, Antonia; Haenggi, Noemi; Tetaz, Tim; Huang, Chia-Ying; Mattle, Daniel; Vonach, Jean-Marie; Gast, Alain; Kuglstatter, Andreas; Rudolph, Markus G.; Nogly, Przemyslaw; Benz, Joerg; Dawson, Roger J.P.; Standfuss, Joerg
- Source:
- Cell 2019 v.178 no.5 pp. 1222-1230.e10
- ISSN:
- 0092-8674
- Subject:
- CCR7 receptor; antagonists; automation; crystal structure; immunity; ligands; lymph nodes; metastasis; neoplasms; protein binding; screening; sialidase; therapeutics; thermal stability
- Abstract:
- ... The CC chemokine receptor 7 (CCR7) balances immunity and tolerance by homeostatic trafficking of immune cells. In cancer, CCR7-mediated trafficking leads to lymph node metastasis, suggesting the receptor as a promising therapeutic target. Here, we present the crystal structure of human CCR7 fused to the protein Sialidase NanA by using data up to 2.1 Å resolution. The structure shows the ligand Cmp ...
- DOI:
- 10.1016/j.cell.2019.07.028
- https://dx.doi.org/10.1016/j.cell.2019.07.028
14. Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells
- Author:
- Dong, Matthew B.; Wang, Guangchuan; Chow, Ryan D.; Ye, Lupeng; Zhu, Lvyun; Dai, Xiaoyun; Park, Jonathan J.; Kim, Hyunu R.; Errami, Youssef; Guzman, Christopher D.; Zhou, Xiaoyu; Chen, Krista Y.; Renauer, Paul A.; Du, Yaying; Shen, Johanna; Lam, Stanley Z.; Zhou, Jingjia J.; Lannin, Donald R.; Herbst, Roy S.; Chen, Sidi
- Source:
- Cell 2019 v.178 no.5 pp. 1189-1204.e23
- ISSN:
- 0092-8674
- Subject:
- CD8-positive T-lymphocytes; RNA helicases; breast neoplasms; cytokines; gene editing; genes; immune response; immunotherapy; mice; transcription factor NF-kappa B; transcriptomics
- Abstract:
- ... CD8 T cells play essential roles in anti-tumor immune responses. Here, we performed genome-scale CRISPR screens in CD8 T cells directly under cancer immunotherapy settings and identified regulators of tumor infiltration and degranulation. The in vivo screen robustly re-identified canonical immunotherapy targets such as PD-1 and Tim-3, along with genes that have not been characterized in T cells. T ...
- DOI:
- 10.1016/j.cell.2019.07.044
- https://dx.doi.org/10.1016/j.cell.2019.07.044
- Author:
- Collins, Nicholas; Han, Seong-Ji; Enamorado, Michel; Link, Verena M.; Huang, Bonnie; Moseman, E. Ashley; Kishton, Rigel J.; Shannon, John P.; Dixit, Dhaval; Schwab, Susan R.; Hickman, Heather D.; Restifo, Nicholas P.; McGavern, Dorian B.; Schwartzberg, Pamela L.; Belkaid, Yasmine
- Source:
- Cell 2019 v.178 no.5 pp. 1088-1101.e15
- ISSN:
- 0092-8674
- Subject:
- T-lymphocytes; adipocytes; adipogenesis; bone marrow; dietary restriction; energy conservation; erythropoiesis; food availability; glucocorticoids; immunologic memory; lymphatic system; malnutrition; mammals; neoplasms
- Abstract:
- ... Mammals evolved in the face of fluctuating food availability. How the immune system adapts to transient nutritional stress remains poorly understood. Here, we show that memory T cells collapsed in secondary lymphoid organs in the context of dietary restriction (DR) but dramatically accumulated within the bone marrow (BM), where they adopted a state associated with energy conservation. This respons ...
- DOI:
- 10.1016/j.cell.2019.07.049
- https://dx.doi.org/10.1016/j.cell.2019.07.049
- Author:
- Plichta, Damian R.; Graham, Daniel B.; Subramanian, Sathish; Xavier, Ramnik J.
- Source:
- Cell 2019 v.178 no.5 pp. 1041-1056
- ISSN:
- 0092-8674
- Subject:
- environmental exposure; genetic factors; homeostasis; immunity; inflammation; inflammatory bowel disease; intestines; metabolites; microbiome; microorganisms; pathogenesis; therapeutics
- Abstract:
- ... The current understanding of inflammatory bowel disease (IBD) pathogenesis implicates a complex interaction between host genetics, host immunity, microbiome, and environmental exposures. Mechanisms gleaned from genetics and molecular pathogenesis offer clues to the critical triggers of mucosal inflammation and guide the development of therapeutic interventions. A complex network of interactions be ...
- DOI:
- 10.1016/j.cell.2019.07.045
- https://dx.doi.org/10.1016/j.cell.2019.07.045
- Author:
- Mittelman, Karin; Burstein, David
- Source:
- Cell 2019 v.178 no.5 pp. 1034-1035
- ISSN:
- 0092-8674
- Subject:
- bacteria; genes; hosts; microbiome; proteins
- Abstract:
- ... Exploration of tiny protein-coding sequences within the human microbiome reveals thousands of conserved gene families that have been overlooked by traditional analyses. These small proteins may play key roles in the crosstalk among bacteria within the microbiome and in interactions with their human hosts. ...
- DOI:
- 10.1016/j.cell.2019.07.039
- https://dx.doi.org/10.1016/j.cell.2019.07.039
- Author:
- Grubaugh, Nathan D.; Saraf, Sharada; Gangavarapu, Karthik; Watts, Alexander; Tan, Amanda L.; Oidtman, Rachel J.; Ladner, Jason T.; Oliveira, Glenn; Matteson, Nathaniel L.; Kraemer, Moritz U.G.; Vogels, Chantal B.F.; Hentoff, Aaron; Bhatia, Deepit; Stanek, Danielle; Scott, Blake; Landis, Vanessa; Stryker, Ian; Cone, Marshall R.; Kopp, Edgar W.; Cannons, Andrew C.; Heberlein-Larson, Lea; White, Stephen; Gillis, Leah D.; Ricciardi, Michael J.; Kwal, Jaclyn; Lichtenberger, Paola K.; Magnani, Diogo M.; Watkins, David I.; Palacios, Gustavo; Hamer, Davidson H.; Gardner, Lauren M.; Perkins, T. Alex; Baele, Guy; Khan, Kamran; Morrison, Andrea; Isern, Sharon; Michael, Scott F.; Andersen, Kristian G.
- Source:
- Cell 2019 v.178 no.5 pp. 1057-1071.e11
- ISSN:
- 0092-8674
- Subject:
- Zika virus; genomics; islands; monitoring; mosquito control; travel; virus transmission; viruses; Caribbean; Cuba; North America; South America
- Abstract:
- ... The Zika epidemic in the Americas has challenged surveillance and control. As the epidemic appears to be waning, it is unclear whether transmission is still ongoing, which is exacerbated by discrepancies in reporting. To uncover locations with lingering outbreaks, we investigated travel-associated Zika cases to identify transmission not captured by reporting. We uncovered an unreported outbreak in ...
- DOI:
- 10.1016/j.cell.2019.07.018
- https://dx.doi.org/10.1016/j.cell.2019.07.018
- Author:
- Buono, Roberta; Longo, Valter D.
- Source:
- Cell 2019 v.178 no.5 pp. 1038-1040
- ISSN:
- 0092-8674
- Subject:
- autoimmunity; fasting; low calorie diet; neoplasm cells; neoplasms
- Abstract:
- ... Cycles of fasting reduce autoimmunity and activate lymphocyte-dependent killing of cancer cells, but the mechanisms remain poorly understood. Three studies in this issue of Cell begin to reveal the drastic and complex effects of fasting and severe calorie restriction on the levels and localization of different immune cells and the mechanisms responsible for them. ...
- DOI:
- 10.1016/j.cell.2019.07.052
- https://dx.doi.org/10.1016/j.cell.2019.07.052