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Richard a flavell

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https://www.readbyqxmd.com/read/29774952/plant-roots-redesign-the-rhizosphere-to-alter-the-three-dimensional-physical-architecture-and-water-dynamics
#1
Sheikh M F Rabbi, Matthew K Tighe, Richard J Flavel, Brent N Kaiser, Chris N Guppy, Xiaoxian Zhang, Iain M Young
The mechanisms controlling the genesis of rhizosheaths are not well understood, despite their importance in controlling the flux of nutrients and water from soil to root. Here, we examine the development of rhizosheaths from drought-tolerant and drought-sensitive chickpea varieties; focusing on the three-dimensional characterization of the pore volume (> 16 μm voxel spatial resolution) obtained from X-ray microtomography, along with the characterization of mucilage and root hairs, and water sorption. We observe that drought-tolerant plants generate a larger diameter root, and a greater and more porous mass of rhizosheath, which also has a significantly increased water sorptivity, as compared with bulk soil...
May 18, 2018: New Phytologist
https://www.readbyqxmd.com/read/29669929/antigen-mediated-regulation-in-monoclonal-gammopathies-and-myeloma
#2
Shiny Nair, Joel Sng, Chandra Sekhar Boddupalli, Anja Seckinger, Marta Chesi, Mariateresa Fulciniti, Lin Zhang, Navin Rauniyar, Michael Lopez, Natalia Neparidze, Terri Parker, Nikhil C Munshi, Rachael Sexton, Bart Barlogie, Robert Orlowski, Leif Bergsagel, Dirk Hose, Richard A Flavell, Pramod K Mistry, Eric Meffre, Madhav V Dhodapkar
A role for antigen-driven stimulation has been proposed in the pathogenesis of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) based largely on the binding properties of monoclonal Ig. However, insights into antigen binding to clonal B cell receptors and in vivo responsiveness of the malignant clone to antigen-mediated stimulation are needed to understand the role of antigenic stimulation in tumor growth. Lysolipid-reactive clonal Ig were detected in Gaucher disease (GD) and some sporadic gammopathies...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29625895/klrg1-effector-cd8-t-cells-lose-klrg1-differentiate-into-all-memory-t-cell-lineages-and-convey-enhanced-protective-immunity
#3
Dietmar Herndler-Brandstetter, Harumichi Ishigame, Ryo Shinnakasu, Valerie Plajer, Carmen Stecher, Jun Zhao, Melanie Lietzenmayer, Lina Kroehling, Akiko Takumi, Kohei Kometani, Takeshi Inoue, Yuval Kluger, Susan M Kaech, Tomohiro Kurosaki, Takaharu Okada, Richard A Flavell
Protective immunity against pathogens depends on the efficient generation of functionally diverse effector and memory T lymphocytes. However, whether plasticity during effector-to-memory CD8+ T cell differentiation affects memory lineage specification and functional versatility remains unclear. Using genetic fate mapping analysis of highly cytotoxic KLRG1+ effector CD8+ T cells, we demonstrated that KLRG1+ cells receiving intermediate amounts of activating and inflammatory signals downregulated KLRG1 during the contraction phase in a Bach2-dependent manner and differentiated into all memory T cell linages, including CX3 CR1int peripheral memory cells and tissue-resident memory cells...
March 31, 2018: Immunity
https://www.readbyqxmd.com/read/29449309/zeb1-zeb2-and-the-mir-200-family-form-a-counterregulatory-network-to-regulate-cd8-t-cell-fates
#4
Tianxia Guan, Claudia X Dominguez, Robert A Amezquita, Brian J Laidlaw, Jijun Cheng, Jorge Henao-Mejia, Adam Williams, Richard A Flavell, Jun Lu, Susan M Kaech
Long-term immunity depends partly on the establishment of memory CD8+ T cells. We identified a counterregulatory network between the homologous transcription factors ZEB1 and ZEB2 and the miR-200 microRNA family, which modulates effector CD8+ T cell fates. Unexpectedly, Zeb1 and Zeb2 had reciprocal expression patterns and were functionally uncoupled in CD8+ T cells. ZEB2 promoted terminal differentiation, whereas ZEB1 was critical for memory T cell survival and function. Interestingly, the transforming growth factor β (TGF-β) and miR-200 family members, which counterregulate the coordinated expression of Zeb1 and Zeb2 during the epithelial-to-mesenchymal transition, inversely regulated Zeb1 and Zeb2 expression in CD8+ T cells...
April 2, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29444161/a-3d-anatomical-atlas-of-appendage-musculature-in-the-chelicerate-arthropod-limulus-polyphemus
#5
Russell D C Bicknell, Ada J Klinkhamer, Richard J Flavel, Stephen Wroe, John R Paterson
Limulus polyphemus, an archetypal chelicerate taxon, has interested both biological and paleontological researchers due to its unique suite of anatomical features and as a useful modern analogue for fossil arthropod groups. To assist the study and documentation of this iconic taxon, we present a 3D atlas on the appendage musculature, with specific focus on the muscles of the cephalothoracic appendages. As L. polyphemus appendage musculature has been the focus of extensive study, depicting the muscles in 3D will facilitate a more complete understanding thereof for future researchers...
2018: PloS One
https://www.readbyqxmd.com/read/29398113/circuit-design-features-of-a-stable-two-cell-system
#6
Xu Zhou, Ruth A Franklin, Miri Adler, Jeremy B Jacox, Will Bailis, Justin A Shyer, Richard A Flavell, Avi Mayo, Uri Alon, Ruslan Medzhitov
Cell communication within tissues is mediated by multiple paracrine signals including growth factors, which control cell survival and proliferation. Cells and the growth factors they produce and receive constitute a circuit with specific properties that ensure homeostasis. Here, we used computational and experimental approaches to characterize the features of cell circuits based on growth factor exchange between macrophages and fibroblasts, two cell types found in most mammalian tissues. We found that the macrophage-fibroblast cell circuit is stable and robust to perturbations...
February 8, 2018: Cell
https://www.readbyqxmd.com/read/29369775/intestinal-ifn-%C3%AE-producing-type-1-regulatory-t-cells-coexpress-ccr5-and-programmed-cell-death-protein-1-and-downregulate-il-10-in-the-inflamed-guts-of-patients-with-inflammatory-bowel-disease
#7
Johanna Sophie Alfen, Paola Larghi, Federica Facciotti, Nicola Gagliani, Roberto Bosotti, Moira Paroni, Stefano Maglie, Paola Gruarin, Chiara Maria Vasco, Valeria Ranzani, Cristina Frusteri, Andrea Iseppon, Monica Moro, Maria Cristina Crosti, Stefano Gatti, Massimiliano Pagani, Flavio Caprioli, Sergio Abrignani, Richard A Flavell, Jens Geginat
BACKGROUND: IL-10 is an anti-inflammatory cytokine required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type 1 regulatory T (TR 1) cells but is also produced by CD25+ regulatory T (Treg) cells. OBJECTIVE: We aimed to identify and characterize human intestinal TR 1 cells and to investigate whether they are a relevant cellular source of IL-10 in patients with inflammatory bowel diseases (IBDs). METHODS: CD4+ T cells isolated from the intestinal lamina propria of human subjects and mice were analyzed for phenotype, cytokine production, and suppressive capacities...
January 31, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29343433/oxysterol-sensing-through-the-receptor-gpr183-promotes-the-lymphoid-tissue-inducing-function-of-innate-lymphoid-cells-and-colonic-inflammation
#8
Johanna Emgård, Hana Kammoun, Bethania García-Cassani, Julie Chesné, Sara M Parigi, Jean-Marie Jacob, Hung-Wei Cheng, Elza Evren, Srustidhar Das, Paulo Czarnewski, Natalie Sleiers, Felipe Melo-Gonzalez, Egle Kvedaraite, Mattias Svensson, Elke Scandella, Matthew R Hepworth, Samuel Huber, Burkhard Ludewig, Lucie Peduto, Eduardo J Villablanca, Henrique Veiga-Fernandes, João P Pereira, Richard A Flavell, Tim Willinger
Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs)...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29303144/m-6-a-mrna-methylation-sustains-treg-suppressive-functions
#9
Jiyu Tong, Guangchao Cao, Ting Zhang, Esen Sefik, Maria Carolina Amezcua Vesely, James P Broughton, Shu Zhu, Huabin Li, Bin Li, Lei Chen, Howard Y Chang, Bing Su, Richard A Flavell, Hua-Bing Li
No abstract text is available yet for this article.
February 2018: Cell Research
https://www.readbyqxmd.com/read/29281837/shaping-of-intestinal-microbiota-in-nlrp6-and-rag2-deficient-mice-depends-on-community-structure
#10
Eric J C Gálvez, Aida Iljazovic, Achim Gronow, Richard Flavell, Till Strowig
Contradicting observations have been made regarding the relative contributions of immune sensors to shaping the microbiome, yet the reasons for these discrepancies are not fully understood. Here, we investigated the contribution of environmental factors in shaping the microbiome in mice deficient in adaptive immunity (Rag2-/- ) and Nlrp6, an immune sensor proposed to be involved in regulation of microbiota composition. In conventionally housed Nlrp6-/- mice, familial transmission has a significant effect on microbiota composition, complicating the analysis of genotype-dependent effects...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29233972/irf8-dependent-molecular-complexes-control-the-th9-transcriptional-program
#11
Etienne Humblin, Marion Thibaudin, Fanny Chalmin, Valentin Derangère, Emeric Limagne, Corentin Richard, Richard A Flavell, Sandy Chevrier, Sylvain Ladoire, Hélène Berger, Romain Boidot, Lionel Apetoh, Frédérique Végran, François Ghiringhelli
Interferon regulatory factors (IRF) have critical functions in lymphoid development and in immune response regulation. Although many studies have described the function of IRF4 in CD4+ T cells, few have focused on the IRF4 homologue, IRF8. Here, we show that IRF8 is required for Th9 differentiation in vitro and in vivo. IRF8 functions through a transcription factor complex consisting of IRF8, IRF4, PU.1 and BATF, which binds to DNA and boosts Il9 transcription. By contrast, IRF8 deficiency promotes the expression of other genes such as Il4, as IRF8 dimerises with the transcriptional repressor ETV6 and inhibits Il4 expression...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29220023/corrigendum-development-and-function-of-human-innate-immune-cells-in-a-humanized-mouse-model
#12
Anthony Rongvaux, Tim Willinger, Jan Martinek, Till Strowig, Sofia V Gearty, Lino L Teichmann, Yasuyuki Saito, Florentina Marches, Stephanie Halene, A Karolina Palucka, Markus G Manz, Richard A Flavell
No abstract text is available yet for this article.
December 8, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/29158380/anti-sirp%C3%AE-antibody-immunotherapy-enhances-neutrophil-and-macrophage-antitumor-activity
#13
Nan Guo Ring, Dietmar Herndler-Brandstetter, Kipp Weiskopf, Liang Shan, Jens-Peter Volkmer, Benson M George, Melanie Lietzenmayer, Kelly M McKenna, Tejaswitha J Naik, Aaron McCarty, Yunjiang Zheng, Aaron M Ring, Richard A Flavell, Irving L Weissman
Cancer immunotherapy has emerged as a promising therapeutic intervention. However, complete and durable responses are only seen in a fraction of patients who have cancer. A key factor that limits therapeutic success is the infiltration of tumors by cells of the myeloid lineage. The inhibitory receptor signal regulatory protein-α (SIRPα) is a myeloid-specific immune checkpoint that engages the "don't eat me" signal CD47 expressed on tumors and normal tissues. We therefore developed the monoclonal antibody KWAR23, which binds human SIRPα with high affinity and disrupts its binding to CD47...
December 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29155454/harnessing-the-power-of-regulatory-t-cells-to-control-autoimmune-diabetes-overview-and-perspective
#14
REVIEW
Hua Yu, Ricardo Paiva, Richard A Flavell
Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease resulting in islet β-cell destruction, hypoinsulinaemia and severely altered glucose homeostasis. Although the mechanisms that initiate T1D still remain elusive, a breakdown of immune tolerance between effector T-cells (Teff ) and regulatory T-cells (Treg ) is considered to be the crucial component leading to autoimmunity. As such, strategies have been developed to boost the number and/or function of Treg in the hope of specifically hampering the pathogenic Teff activity...
February 2018: Immunology
https://www.readbyqxmd.com/read/29109123/a-protective-function-of-il-22bp-in-ischemia-reperfusion-and-acetaminophen-induced-liver-injury
#15
Dörte Kleinschmidt, Anastasios D Giannou, Heather M McGee, Jan Kempski, Babett Steglich, Francis Jessica Huber, Thomas Michael Ernst, Ahmad Mustafa Shiri, Claudia Wegscheid, Elena Tasika, Peter Hübener, Philipp Huber, Tanja Bedke, Niklas Steffens, Theodora Agalioti, Tobias Fuchs, Jill Noll, Hannelore Lotter, Gisa Tiegs, Ansgar W Lohse, Jonathan H Axelrod, Eithan Galun, Richard A Flavell, Nicola Gagliani, Samuel Huber
Acute liver injury can be secondary to a variety of causes, including infections, intoxication, and ischemia. All of these insults induce hepatocyte death and subsequent inflammation, which can make acute liver injury a life-threatening event. IL-22 is a dual natured cytokine which has context-dependent protective and pathogenic properties during tissue damage. Accordingly, IL-22 was shown to promote liver regeneration upon acute liver damage. However, other studies suggest pathogenic properties of IL-22 during chronic liver injury...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29078283/humanized-mouse-model-supports-development-function-and-tissue-residency-of-human-natural-killer-cells
#16
Dietmar Herndler-Brandstetter, Liang Shan, Yi Yao, Carmen Stecher, Valerie Plajer, Melanie Lietzenmayer, Till Strowig, Marcel R de Zoete, Noah W Palm, Jie Chen, Catherine A Blish, Davor Frleta, Cagan Gurer, Lynn E Macdonald, Andrew J Murphy, George D Yancopoulos, Ruth R Montgomery, Richard A Flavell
Immunodeficient mice reconstituted with a human immune system represent a promising tool for translational research as they may allow modeling and therapy of human diseases in vivo. However, insufficient development and function of human natural killer (NK) cells and T cell subsets limit the applicability of humanized mice for studying cancer biology and therapy. Here, we describe a human interleukin 15 ( IL15 ) and human signal regulatory protein alpha ( SIRPA ) knock-in mouse on a Rag2-/- Il2rg-/- background (SRG-15)...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29069606/distinct-microbial-communities-trigger-colitis-development-upon-intestinal-barrier-damage-via-innate-or-adaptive-immune-cells
#17
Urmi Roy, Eric J C Gálvez, Aida Iljazovic, Till Robin Lesker, Adrian J Błażejewski, Marina C Pils, Ulrike Heise, Samuel Huber, Richard A Flavell, Till Strowig
Inflammatory bowel disease comprises a group of heterogeneous diseases characterized by chronic and relapsing mucosal inflammation. Alterations in microbiota composition have been proposed to contribute to disease development, but no uniform signatures have yet been identified. Here, we compare the ability of a diverse set of microbial communities to exacerbate intestinal inflammation after chemical damage to the intestinal barrier. Strikingly, genetically identical wild-type mice differing only in their microbiota composition varied strongly in their colitis susceptibility...
October 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/29045905/transcriptional-reprogramming-during-effector-to-memory-transition-renders-cd4-t-cells-permissive-for-latent-hiv-1-infection
#18
Liang Shan, Kai Deng, Hongbo Gao, Sifei Xing, Adam A Capoferri, Christine M Durand, S Alireza Rabi, Gregory M Laird, Michelle Kim, Nina N Hosmane, Hung-Chih Yang, Hao Zhang, Joseph B Margolick, Linghua Li, Weiping Cai, Ruian Ke, Richard A Flavell, Janet D Siliciano, Robert F Siliciano
The latent reservoir for HIV-1 in resting memory CD4+ T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4+ T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/28930674/a-protein-scaffold-coordinates-src-mediated-jnk-activation-in-response-to-metabolic-stress
#19
Shashi Kant, Claire L Standen, Caroline Morel, Dae Young Jung, Jason K Kim, Wojciech Swat, Richard A Flavell, Roger J Davis
Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH2-terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930659/group-1-innate-lymphoid-cell-lineage-identity-is-determined-by-a-cis-regulatory-element-marked-by-a-long-non-coding-rna
#20
Walter K Mowel, Sam J McCright, Jonathan J Kotzin, Magalie A Collet, Asli Uyar, Xin Chen, Alexandra DeLaney, Sean P Spencer, Anthony T Virtue, EnJun Yang, Alejandro Villarino, Makoto Kurachi, Margaret C Dunagin, Gretchen Harms Pritchard, Judith Stein, Cynthia Hughes, Diogo Fonseca-Pereira, Henrique Veiga-Fernandes, Arjun Raj, Taku Kambayashi, Igor E Brodsky, John J O'Shea, E John Wherry, Loyal A Goff, John L Rinn, Adam Williams, Richard A Flavell, Jorge Henao-Mejia
Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. We identified a cis-regulatory element demarcated by a long non-coding RNA (lncRNA) that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s. The locus encoding this lncRNA, which we termed Rroid, directly interacted with the promoter of its neighboring gene, Id2, in group 1 ILCs...
September 19, 2017: Immunity
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