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Richard a flavell

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https://www.readbyqxmd.com/read/28195328/visualization-of-xylem-embolism-by-x-ray-microtomography-a-direct-test-against-hydraulic-measurements
#1
Markus Nolf, Rosana Lopez, Jennifer M R Peters, Richard J Flavel, Leah S Koloadin, Iain M Young, Brendan Choat
X-ray microtomography (microCT) is becoming a valuable noninvasive tool for advancing our understanding of plant-water relations. Laboratory-based microCT systems are becoming more affordable and provide better access than synchrotron facilities. However, some systems come at the cost of comparably lower signal quality and spatial resolution than synchrotron facilities. In this study, we evaluated laboratory-based X-ray microCT imaging as a tool to nondestructively analyse hydraulic vulnerability to drought-induced embolism in a woody plant species...
February 14, 2017: New Phytologist
https://www.readbyqxmd.com/read/28167932/a-new-approach-to-modify-plant-microbiomes-and-traits-by-introducing-beneficial-bacteria-at-flowering-into-progeny-seeds
#2
Birgit Mitter, Nikolaus Pfaffenbichler, Richard Flavell, Stéphane Compant, Livio Antonielli, Alexandra Petric, Teresa Berninger, Muhammad Naveed, Raheleh Sheibani-Tezerji, Geoffrey von Maltzahn, Angela Sessitsch
The microbial component of healthy seeds - the seed microbiome - appears to be inherited between plant generations and can dynamically influence germination, plant performance, and survival. As such, methods to optimize the seed microbiomes of major crops could have far-reaching implications for plant breeding and crop improvement to enhance agricultural food, feed, and fiber production. Here, we describe a new approach to modulate seed microbiomes of elite crop seed embryos and concomitantly design the traits to be mediated by seed microbiomes...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28143932/dissection-of-neuronal-gap-junction-circuits-that-regulate-social-behavior-in-caenorhabditis-elegans
#3
Heeun Jang, Sagi Levy, Steven W Flavell, Fanny Mende, Richard Latham, Manuel Zimmer, Cornelia I Bargmann
A hub-and-spoke circuit of neurons connected by gap junctions controls aggregation behavior and related behavioral responses to oxygen, pheromones, and food in Caenorhabditis elegans The molecular composition of the gap junctions connecting RMG hub neurons with sensory spoke neurons is unknown. We show here that the innexin gene unc-9 is required in RMG hub neurons to drive aggregation and related behaviors, indicating that UNC-9-containing gap junctions mediate RMG signaling. To dissect the circuit in detail, we developed methods to inhibit unc-9-based gap junctions with dominant-negative unc-1 transgenes...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28129537/the-stromal-intervention-regulation-of-immunity-and-inflammation-at-the-epithelial-mesenchymal-barrier
#4
REVIEW
Roni Nowarski, Ruaidhrí Jackson, Richard A Flavell
The immune system safeguards organ integrity by employing a balancing act of inflammatory and immunosuppressive mechanisms designed to neutralize foreign invaders and resolve injury. Maintaining or restoring a state of immune homeostasis is particularly challenging at barrier sites where constant exposure to immunogenic environmental agents may induce destructive inflammation. Recent studies underscore the role of epithelial and mesenchymal barrier cells in regulating immune cell function and local homeostatic and inflammatory responses...
January 26, 2017: Cell
https://www.readbyqxmd.com/read/28077418/a-novel-humanized-mouse-model-with-significant-improvement-of-class-switched-antigen-specific-antibody-production
#5
Hua Yu, Chiara Borsotti, Jean-Nicolas Schickel, Shu Zhu, Till Strowig, Elizabeth E Eynon, Davor Frleta, Cagan Gurer, Andrew J Murphy, George D Yancopoulos, Eric Meffre, Markus G Manz, Richard A Flavell
Humanized mice are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, the existing models cannot support robust adaptive immune responses, especially the generation of class-switched, antigen-specific antibody responses. Here we describe a new mouse strain, in which human IL6 gene encoding the cytokine that is important for B and T cell differentiation was knocked into its respective mouse locus. The provision of human IL6 not only enhanced thymopoiesis and periphery T-cell engraftment, but also significantly increased class switched memory B cells and serum IgG...
January 11, 2017: Blood
https://www.readbyqxmd.com/read/28003377/il-10-receptor-signaling-is-essential-for-tr1-cell-function-in-vivo
#6
Leonie Brockmann, Nicola Gagliani, Babett Steglich, Anastasios D Giannou, Jan Kempski, Penelope Pelczar, Maria Geffken, Bechara Mfarrej, Francis Huber, Johannes Herkel, Yisong Y Wan, Enric Esplugues, Manuela Battaglia, Christian F Krebs, Richard A Flavell, Samuel Huber
IL-10 is essential to maintain intestinal homeostasis. CD4(+) T regulatory type 1 (TR1) cells produce large amounts of this cytokine and are therefore currently being examined in clinical trials as T cell therapy in patients with inflammatory bowel disease. However, factors and molecular signals sustaining TR1 cell regulatory activity still need to be identified to optimize the efficiency and ensure the safety of these trials. We investigated the role of IL-10 signaling in mature TR1 cells in vivo. Double IL-10(eGFP) Foxp3(mRFP) reporter mice and transgenic mice with impairment in IL-10 receptor signaling were used to test the activity of TR1 cells in a murine inflammatory bowel disease model, a model that resembles the trials performed in humans...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27917411/ptpn22-inhibition-resets-defective-human-central-b-cell-tolerance
#7
Jean-Nicolas Schickel, Marcel Kuhny, Alessia Baldo, Jason M Bannock, Christopher Massad, Haowei Wang, Nathan Katz, Tyler Oe, Laurence Menard, Pauline Soulas-Sprauel, Till Strowig, Richard Flavell, Eric Meffre
The 1858T protein tyrosine phosphatase nonreceptor type 22 (PTPN22 T) allele is one of the main risk factors associated with many autoimmune diseases and correlates with a defective removal of developing autoreactive B cells in humans. To determine whether inhibiting PTPN22 favors the elimination of autoreactive B cells, we first demonstrated that the PTPN22 T allele interfered with the establishment of central B cell tolerance using NOD-scid-common γ chain knockout (NSG) mice engrafted with human hematopoietic stem cells expressing this allele...
2016: Science Immunology
https://www.readbyqxmd.com/read/27913094/hematopoietic-stem-cell-niches-produce-lineage-instructive-signals-to-control-multipotent-progenitor-differentiation
#8
Ana Cordeiro Gomes, Takahiro Hara, Vivian Y Lim, Dietmar Herndler-Brandstetter, Erin Nevius, Tatsuki Sugiyama, Shizue Tani-Ichi, Susan Schlenner, Ellen Richie, Hans-Reimer Rodewald, Richard A Flavell, Takashi Nagasawa, Koichi Ikuta, João Pedro Pereira
Hematopoietic stem cells (HSCs) self-renew in bone marrow niches formed by mesenchymal progenitors and endothelial cells expressing the chemokine CXCL12, but whether a separate niche instructs multipotent progenitor (MPP) differentiation remains unclear. We show that MPPs resided in HSC niches, where they encountered lineage-instructive differentiation signals. Conditional deletion of the chemokine receptor CXCR4 in MPPs reduced differentiation into common lymphoid progenitors (CLPs), which decreased lymphopoiesis...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27846608/the-dna-sensing-aim2-inflammasome-controls-radiation-induced-cell-death-and-tissue-injury
#9
Bo Hu, Chengcheng Jin, Hua-Bing Li, Jiyu Tong, Xinshou Ouyang, Naniye Malli Cetinbas, Shu Zhu, Till Strowig, Fred C Lam, Chen Zhao, Jorge Henao-Mejia, Omer Yilmaz, Katherine A Fitzgerald, Stephanie C Eisenbarth, Eran Elinav, Richard A Flavell
Acute exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively proliferating cells, including bone marrow and the gastrointestinal tract. However, the cellular and molecular mechanisms underlying this pathology remain controversial. Here, we show that mice deficient in the double-stranded DNA sensor AIM2 are protected from both subtotal body irradiation-induced gastrointestinal syndrome and total body irradiation-induced hematopoietic failure. AIM2 mediates the caspase-1-dependent death of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks caused by ionizing radiation and chemotherapeutic agents...
November 11, 2016: Science
https://www.readbyqxmd.com/read/27846573/a-pathogenic-role-for-t-cell-derived-il-22bp-in-inflammatory-bowel-disease
#10
Penelope Pelczar, Mario Witkowski, Laura Garcia Perez, Jan Kempski, Anna G Hammel, Leonie Brockmann, Dörte Kleinschmidt, Sandra Wende, Cathleen Haueis, Tanja Bedke, Marco Witkowski, Susanne Krasemann, Stefan Steurer, Carmen J Booth, Philipp Busch, Alexandra König, Ursula Rauch, Daniel Benten, Jakob R Izbicki, Thomas Rösch, Ansgar W Lohse, Till Strowig, Nicola Gagliani, Richard A Flavell, Samuel Huber
Intestinal inflammation can impair mucosal healing, thereby establishing a vicious cycle leading to chronic inflammatory bowel disease (IBD). However, the signaling networks driving chronic inflammation remain unclear. Here we report that CD4(+) T cells isolated from patients with IBD produce high levels of interleukin-22 binding protein (IL-22BP), the endogenous inhibitor of the tissue-protective cytokine IL-22. Using mouse models, we demonstrate that IBD development requires T cell-derived IL-22BP. Lastly, intestinal CD4(+) T cells isolated from IBD patients responsive to treatment with antibodies against tumor necrosis factor-α (anti-TNF-α), the most effective known IBD therapy, exhibited reduced amounts of IL-22BP expression but still expressed IL-22...
October 21, 2016: Science
https://www.readbyqxmd.com/read/27798161/tlr8-couples-socs-1-and-restrains-tlr7-mediated-antiviral-immunity-exacerbating-west-nile-virus-infection-in-mice
#11
Amber M Paul, Dhiraj Acharya, Linda Le, Penghua Wang, Dobrivoje S Stokic, A Arturo Leis, Lena Alexopoulou, Terrence Town, Richard A Flavell, Erol Fikrig, Fengwei Bai
West Nile virus (WNV) is a neurotropic ssRNA flavivirus that can cause encephalitis, meningitis, and death in humans and mice. Human TLR7 and TLR8 and mouse TLR7 recognize viral ssRNA motifs and induce antiviral immunity. However, the role of mouse TLR8 in antiviral immunity is poorly understood. In this article, we report that TLR8-deficient (Tlr8(-/-)) mice were resistant to WNV infection compared with wild-type controls. Efficient WNV clearance and moderate susceptibility to WNV-mediated neuronal death in Tlr8(-/-) mice were attributed to overexpression of Tlr7 and IFN-stimulated gene-56 expression, whereas reduced expression of the proapoptotic gene coding Bcl2-associated X protein was observed...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27795421/interleukin-17a-promotes-cd8-t-cell-cytotoxicity-to-facilitate-west-nile-virus-clearance
#12
Dhiraj Acharya, Penghua Wang, Amber M Paul, Jianfeng Dai, David Gate, Jordan E Lowery, Dobrivoje S Stokic, A Arturo Leis, Richard A Flavell, Terrence Town, Erol Fikrig, Fengwei Bai
: CD8(+) T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8(+) T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a(-/-)) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8(+) T cells isolated from Il17a(-/-) mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in vivo Importantly, treatment of WNV-infected mice with recombinant IL-17A, as late as day 6 postinfection, significantly reduces the viral burden and increases survival, suggesting a therapeutic potential for IL-17A...
January 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27723723/microenvironment-dependent-growth-of-preneoplastic-and-malignant-plasma-cells-in-humanized-mice
#13
Rituparna Das, Till Strowig, Rakesh Verma, Srinivas Koduru, Anja Hafemann, Stephanie Hopf, Mehmet H Kocoglu, Chiara Borsotti, Lin Zhang, Andrew Branagan, Elizabeth Eynon, Markus G Manz, Richard A Flavell, Madhav V Dhodapkar
Most human cancers, including myeloma, are preceded by a precursor state. There is an unmet need for in vivo models to study the interaction of human preneoplastic cells in the bone marrow microenvironment with non-malignant cells. Here, we genetically humanized mice to permit the growth of primary human preneoplastic and malignant plasma cells together with non-malignant cells in vivo. Growth was largely restricted to the bone marrow, mirroring the pattern in patients with myeloma. Xenografts captured the genomic complexity of parental tumors and revealed additional somatic changes...
November 2016: Nature Medicine
https://www.readbyqxmd.com/read/27618552/glioma-induced-inhibition-of-caspase-3-in-microglia-promotes-a-tumor-supportive-phenotype
#14
Xianli Shen, Miguel A Burguillos, Ahmed M Osman, Jeroen Frijhoff, Alejandro Carrillo-Jiménez, Sachie Kanatani, Martin Augsten, Dalel Saidi, Johanna Rodhe, Edel Kavanagh, Anthony Rongvaux, Vilma Rraklli, Ulrika Nyman, Johan Holmberg, Arne Östman, Richard A Flavell, Antonio Barragan, Jose Luis Venero, Klas Blomgren, Bertrand Joseph
Glioma cells recruit and exploit microglia (the resident immune cells of the brain) for their proliferation and invasion ability. The underlying molecular mechanism used by glioma cells to transform microglia into a tumor-supporting phenotype has remained elusive. We found that glioma-induced microglia conversion was coupled to a reduction in the basal activity of microglial caspase-3 and increased S-nitrosylation of mitochondria-associated caspase-3 through inhibition of thioredoxin-2 activity, and that inhibition of caspase-3 regulated microglial tumor-supporting function...
September 12, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27617863/abc-transporters-and-nr4a1-identify-a-quiescent-subset-of-tissue-resident-memory-t-cells
#15
Chandra Sekhar Boddupalli, Shiny Nair, Simon M Gray, Heba N Nowyhed, Rakesh Verma, Joanna A Gibson, Clara Abraham, Deepak Narayan, Juan Vasquez, Catherine C Hedrick, Richard A Flavell, Kavita M Dhodapkar, Susan M Kaech, Madhav V Dhodapkar
Immune surveillance in tissues is mediated by a long-lived subset of tissue-resident memory T cells (Trm cells). A putative subset of tissue-resident long-lived stem cells is characterized by the ability to efflux Hoechst dyes and is referred to as side population (SP) cells. Here, we have characterized a subset of SP T cells (Tsp cells) that exhibit a quiescent (G0) phenotype in humans and mice. Human Trm cells in the gut and BM were enriched in Tsp cells that were predominantly in the G0 stage of the cell cycle...
October 3, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27581357/inv-16-and-npm1mut-amls-engraft-human-cytokine-knock-in-mice
#16
Jana M Ellegast, Philipp J Rauch, Larisa V Kovtonyuk, Rouven Müller, Ulrich Wagner, Yasuyuki Saito, Nicole Wildner-Verhey van Wijk, Christine Fritz, Anahita Rafiei, Veronika Lysenko, Ewa Dudkiewicz, Alexandre P Theocharides, Davide Soldini, Jeroen S Goede, Richard A Flavell, Markus G Manz
Favorable-risk human acute myeloid leukemia (AML) engrafts poorly in currently used immunodeficient mice, possibly because of insufficient environmental support of these leukemic entities. To address this limitation, we here transplanted primary human AML with isolated nucleophosmin (NPM1) mutation and AML with inv(16) in mice in which human versions of genes encoding cytokines important for myelopoiesis (macrophage colony-stimulating factor [M-CSF], interleukin-3, granulocyte-macrophage colony-stimulating factor, and thrombopoietin) were knocked into their respective mouse loci...
October 27, 2016: Blood
https://www.readbyqxmd.com/read/27562264/microbiome-ecology-of-eczema
#17
Ian D Odell, Richard A Flavell
No abstract text is available yet for this article.
2016: Nature Microbiology
https://www.readbyqxmd.com/read/27543436/peripheral-blood-cd34-cells-efficiently-engraft-human-cytokine-knock-in-mice
#18
Yasuyuki Saito, Jana M Ellegast, Anahita Rafiei, Yuanbin Song, Daniel Kull, Mathias Heikenwalder, Anthony Rongvaux, Stephanie Halene, Richard A Flavell, Markus G Manz
Human CD34(+) hematopoietic stem and progenitor cells (HSPCs) can reconstitute a human hemato-lymphoid system when transplanted into immunocompromised mice. While fetal liver- and cord blood-derived CD34(+) cells lead to high engraftment levels, engraftment of mobilized, adult donor-derived CD34(+) cells has remained poor. We generated so-called MSTRG and MISTRG hu-manized mice on a Rag2(-/-)Il2rg(-/-) background carrying a transgene for human SIRPα and human homologues of the cytokines macrophage-colony stimulating factor, thrombopoietin, with or without interleukin-3 and granulocyte-macrophage colony stimulating factor under murine promotors...
August 19, 2016: Blood
https://www.readbyqxmd.com/read/27525555/the-long-non-coding-rna-morrbid-regulates-bim-and-short-lived-myeloid-cell-lifespan
#19
Jonathan J Kotzin, Sean P Spencer, Sam J McCright, Dinesh B Uthaya Kumar, Magalie A Collet, Walter K Mowel, Ellen N Elliott, Asli Uyar, Michelle A Makiya, Margaret C Dunagin, Christian C D Harman, Anthony T Virtue, Stella Zhu, Will Bailis, Judith Stein, Cynthia Hughes, Arjun Raj, E John Wherry, Loyal A Goff, Amy D Klion, John L Rinn, Adam Williams, Richard A Flavell, Jorge Henao-Mejia
Neutrophils, eosinophils and 'classical' monocytes collectively account for about 70% of human blood leukocytes and are among the shortest-lived cells in the body. Precise regulation of the lifespan of these myeloid cells is critical to maintain protective immune responses and minimize the deleterious consequences of prolonged inflammation. However, how the lifespan of these cells is strictly controlled remains largely unknown. Here we identify a long non-coding RNA that we termed Morrbid, which tightly controls the survival of neutrophils, eosinophils and classical monocytes in response to pro-survival cytokines in mice...
September 8, 2016: Nature
https://www.readbyqxmd.com/read/27455420/apoptosis-in-response-to-microbial-infection-induces-autoreactive-th17-cells
#20
Laura Campisi, Gaetan Barbet, Yi Ding, Enric Esplugues, Richard A Flavell, J Magarian Blander
Microbial infections often precede the onset of autoimmunity. How infections trigger autoimmunity remains poorly understood. We investigated the possibility that infection might create conditions that allow the stimulatory presentation of self peptides themselves and that this might suffice to elicit autoreactive T cell responses that lead to autoimmunity. Self-reactive CD4(+) T cells are major drivers of autoimmune disease, but their activation is normally prevented through regulatory mechanisms that limit the immunostimulatory presentation of self antigens...
September 2016: Nature Immunology
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