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https://www.readbyqxmd.com/read/29158498/activity-dependent-expression-of-channelrhodopsin-at-neuronal-synapses
#1
Francesco Gobbo, Laura Marchetti, Ajesh Jacob, Bruno Pinto, Noemi Binini, Federico Pecoraro Bisogni, Claudia Alia, Stefano Luin, Matteo Caleo, Tommaso Fellin, Laura Cancedda, Antonino Cattaneo
Increasing evidence points to the importance of dendritic spines in the formation and allocation of memories, and alterations of spine number and physiology are associated to memory and cognitive disorders. Modifications of the activity of subsets of synapses are believed to be crucial for memory establishment. However, the development of a method to directly test this hypothesis, by selectively controlling the activity of potentiated spines, is currently lagging. Here we introduce a hybrid RNA/protein approach to regulate the expression of a light-sensitive membrane channel at activated synapses, enabling selective tagging of potentiated spines following the encoding of a novel context in the hippocampus...
November 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29157358/rng105-caprin1-an-rna-granule-protein-for-dendritic-mrna-localization-is-essential-for-long-term-memory-formation
#2
Kei Nakayama, Rie Ohashi, Yo Shinoda, Maya Yamazaki, Manabu Abe, Akihiro Fujikawa, Shuji Shigenobu, Akira Futatsugi, Masaharu Noda, Katsuhiko Mikoshiba, Teiichi Furuichi, Kenji Sakimura, Nobuyuki Shiina
Local regulation of synaptic efficacy is thought to be important for proper networking of neurons and memory formation. Dysregulation of global translation influences long-term memory in mice, but the relevance of the regulation specific for local translation by RNA granules remains elusive. Here, we demonstrate roles of RNG105/caprin1 in long-term memory formation. RNG105 deletion in mice impaired synaptic strength and structural plasticity in hippocampal neurons. Furthermore, RNG105-deficient mice displayed unprecedentedly severe defects in long-term memory formation in spatial and contextual learning tasks...
November 21, 2017: ELife
https://www.readbyqxmd.com/read/29154771/in-vitro-blockade-of-the-cd4-receptor-co-signal-in-antigen-specific-t-cell-stimulation-cultures-induces-the-outgrowth-of-potent-cd4-independent-t-cell-effectors
#3
Sarah Vatter, Maximilian Schmid, Claudia Gebhard, Carina Mirbeth, Sebastian Klobuch, Michael Rehli, Wolfgang Herr, Simone Thomas
T-cell receptor (TCR) redirected T cells are promising tools for adoptive cancer immunotherapy. Since not only CD8 but also CD4 T cells are key players for efficient antitumor responses, the targeted redirection of both subsets with the same antigen-specific TCR comes more and more into focus. Although rapidly evolving technologies enable the reliable genetic re-programming of T cells, the limited availability of TCRs that induce T-cell activation in both T-cell subsets without CD4/CD8 co-receptor contribution hampers the broad application of this approach...
November 14, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29150602/tlr7-mediated-viral-recognition-results-in-focal-type-i-interferon-secretion-by-dendritic-cells
#4
Shin-Ichiroh Saitoh, Fumiko Abe, Atsuo Kanno, Natsuko Tanimura, Yoshiko Mori Saitoh, Ryutaro Fukui, Takuma Shibata, Katsuaki Sato, Takeshi Ichinohe, Mayumi Hayashi, Kazuishi Kubota, Hiroko Kozuka-Hata, Masaaki Oyama, Yorifumi Kikko, Toshiaki Katada, Kenji Kontani, Kensuke Miyake
Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC-pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7(+) lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29149906/forebrain-specific-conditional-silencing-of-staufen2-alters-synaptic-plasticity-learning-and-memory-in-rats
#5
Stefan M Berger, Iván Fernández-Lamo, Kai Schönig, Sandra M Fernández Moya, Janina Ehses, Rico Schieweck, Stefano Clementi, Thomas Enkel, Sascha Grothe, Oliver von Bohlen Und Halbach, Inmaculada Segura, José María Delgado-García, Agnès Gruart, Michael A Kiebler, Dusan Bartsch
BACKGROUND: Dendritic messenger RNA (mRNA) localization and subsequent local translation in dendrites critically contributes to synaptic plasticity and learning and memory. Little is known, however, about the contribution of RNA-binding proteins (RBPs) to these processes in vivo. RESULTS: To delineate the role of the double-stranded RBP Staufen2 (Stau2), we generate a transgenic rat model, in which Stau2 expression is conditionally silenced by Cre-inducible expression of a microRNA (miRNA) targeting Stau2 mRNA in adult forebrain neurons...
November 17, 2017: Genome Biology
https://www.readbyqxmd.com/read/29149607/classifying-drosophila-olfactory-projection-neuron-subtypes-by-single-cell-rna-sequencing
#6
Hongjie Li, Felix Horns, Bing Wu, Qijing Xie, Jiefu Li, Tongchao Li, David J Luginbuhl, Stephen R Quake, Liqun Luo
The definition of neuronal type and how it relates to the transcriptome are open questions. Drosophila olfactory projection neurons (PNs) are among the best-characterized neuronal types: different PN classes target dendrites to distinct olfactory glomeruli, while PNs of the same class exhibit indistinguishable anatomical and physiological properties. Using single-cell RNA sequencing, we comprehensively characterized the transcriptomes of most PN classes and unequivocally mapped transcriptomes to specific olfactory function for six classes...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29142232/tdp-43-misexpression-causes-defects-in-dendritic-growth
#7
Josiah J Herzog, Mugdha Deshpande, Leah Shapiro, Avital A Rodal, Suzanne Paradis
Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) share overlapping genetic causes and disease symptoms, and are linked neuropathologically by the RNA binding protein TDP-43 (TAR DNA binding protein-43 kDa). TDP-43 regulates RNA metabolism, trafficking, and localization of thousands of target genes. However, the cellular and molecular mechanisms by which dysfunction of TDP-43 contributes to disease pathogenesis and progression remain unclear. Severe changes in the structure of neuronal dendritic arbors disrupt proper circuit connectivity, which in turn could contribute to neurodegenerative disease...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29142061/effects-of-regulatory-bc1-rna-deletion-on-synaptic-plasticity-learning-and-memory
#8
Ain Chung, Nessy Dahan, Juan Marcos Alarcon, André A Fenton
Nonprotein coding dendritic BC1 RNA regulates translation of mRNAs in neurons. We examined two lines of BC1 knockout mice and report that loss of BC1 RNA exaggerates group I mGluR-stimulated LTD of the Schaffer collateral synapse, with one of the lines showing a much more enhanced DHPG-induced LTD than the other. When the animals were given the hippocampus-synaptic plasticity-dependent active place avoidance task, learning and memory were impaired in the BC1-KO line with the more severely altered DHPG-induced LTD...
December 2017: Learning & Memory
https://www.readbyqxmd.com/read/29141219/preventive-inhibition-of-liver-tumorigenesis-by-systemic-activation-of-innate-immune-functions
#9
Jin Lee, Rui Liao, Gaowei Wang, Bi-Huei Yang, Xiaolin Luo, Nissi M Varki, Shuang-Jian Qiu, Bing Ren, Wenxian Fu, Gen-Sheng Feng
Liver cancer has become the second most deadly malignant disease, with no efficient targeted or immune therapeutic agents available yet. While dissecting the roles of cytoplasmic signaling molecules in hepatocarcinogenesis using an inducible mouse gene targeting system, Mx1-cre, we identified a potent liver tumor-inhibitory effect of synthetic double-stranded RNA (dsRNA), polyinosinic-polycytidylic acid (pIC), an inducer of the Mx1-cre system. Injection of pIC at the pre-cancer stage robustly suppressed liver tumorigenesis either induced by chemical carcinogens or by Pten loss and associated hepatosteatosis...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29140992/transcriptome-profile-of-lung-dendritic-cells-after-in-vitro-porcine-reproductive-and-respiratory-syndrome-virus-prrsv-infection
#10
Maren Julia Pröll, Christiane Neuhoff, Karl Schellander, Muhammad Jasim Uddin, Mehmet Ulas Cinar, Sudeep Sahadevan, Xueqi Qu, Md Aminul Islam, Mikhael Poirier, Marcel A Müller, Christian Drosten, Dawit Tesfaye, Ernst Tholen, Christine Große-Brinkhaus
The porcine reproductive and respiratory syndrome (PRRS) is an infectious disease that leads to high financial and production losses in the global swine industry. The pathogenesis of this disease is dependent on a multitude of factors, and its control remains problematic. The immune system generally defends against infectious diseases, especially dendritic cells (DCs), which play a crucial role in the activation of the immune response after viral infections. However, the understanding of the immune response and the genetic impact on the immune response to PRRS virus (PRRSV) remains incomplete...
2017: PloS One
https://www.readbyqxmd.com/read/29128662/activation-of-innate-immunity-in-primary-human-cells-using-a-plant-virus-derived-nanoparticle-tlr7-8-agonist
#11
Damien Carignan, Sabine Herblot, Marie-Ève Laliberté-Gagné, Marilène Bolduc, Michel Duval, Pierre Savard, Denis Leclerc
Rod-shaped virus-like nanoparticles (VLNP) made of papaya mosaic virus (PapMV) coat proteins (CP) self-assembled around a single stranded RNA (ssRNA) were showed to be a TLR7 agonist. Their utilization as an immune modulator in cancer immunotherapy was shown to be promising. To establish a clinical relevance in human for PapMV VLNP, we showed that stimulation of human peripheral blood mononuclear cells (PBMC) with VLNP induces the secretion of interferon alpha (IFNα) and other pro-inflammatory cytokines and chemokines...
November 8, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29123946/tumor-cell-death-by-pattern-sensing-of-exogenous-rna-tumor-cell-tlr3-directly-induces-necroptosis-by-poly-i-c-in-vivo-independent-of-immune-effector-mediated-tumor-shrinkage
#12
Hiromi Takaki, Hiroaki Shime, Misako Matsumoto, Tsukasa Seya
Poly(I:C) acts on dendritic cells to induce potent antitumor effects through the production of cytokines/interferons, activation of natural killer cells and proliferation of cytotoxic T lymphocytes. In some tumor or myeloid lineages, poly(I:C) seemed to induce necroptosis in concert with a pan-caspase inhibitor by directly acting on toll-like receptor (TLR) 3 in both in vivo and in vitro models.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29121950/the-hiv-1-integrase-ledgf-allosteric-inhibitor-mut-a-resistance-profile-impairment-of-virus-maturation-and-infectivity-but-without-influence-on-rna-packaging-or-virus-immunoreactivity
#13
Céline Amadori, Yme Ubeles van der Velden, Damien Bonnard, Igor Orlov, Nikki van Bel, Erwann Le Rouzic, Laia Miralles, Julie Brias, Francis Chevreuil, Daniele Spehner, Sophie Chasset, Benoit Ledoussal, Luzia Mayr, François Moreau, Felipe García, José Gatell, Alessia Zamborlini, Stéphane Emiliani, Marc Ruff, Bruno P Klaholz, Christiane Moog, Ben Berkhout, Montserrat Plana, Richard Benarous
BACKGROUND: HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration. Recently a new class of IN inhibitors was described, the IN-LEDGF allosteric inhibitors (INLAIs). Designed to interfere with the IN-LEDGF interaction during integration, the major impact of these inhibitors was surprisingly found on virus maturation, causing a reverse transcription defect in target cells. RESULTS: Here we describe the MUT-A compound as a genuine INLAI with an original chemical structure based on a new type of scaffold, a thiophene ring...
November 9, 2017: Retrovirology
https://www.readbyqxmd.com/read/29119662/toxoplasma-gondii-infection-shifts-dendritic-cells-into-an-amoeboid-rapid-migration-mode-encompassing-podosome-dissolution-secretion-of-timp-1-and-reduced-proteolysis-of-extracellular-matrix
#14
Einar B Ólafsson, Manuel Varas-Godoy, Antonio Barragan
Dendritic cells (DCs) infected by Toxoplasma gondii rapidly acquire a hypermigratory phenotype that promotes systemic parasite dissemination by a 'Trojan horse' mechanism in mice. Recent paradigms of leukocyte migration have identified the amoeboid migration mode of DCs as particularly suited for rapid locomotion in extracellular matrix and tissues. Here, we have developed a microscopy-based high-throughput approach to assess motility and matrix degradation by Toxoplasma-challenged murine and human DCs. DCs challenged with T...
November 8, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29118245/mer-receptor-tyrosine-kinase-signaling-prevents-self-ligand-sensing-and-aberrant-selection-in-germinal-centers
#15
Stephanie L Schell, Chetna Soni, Melinda J Fasnacht, Phillip P Domeier, Timothy K Cooper, Ziaur S M Rahman
Mer tyrosine kinase (Mer) signaling maintains immune tolerance by clearing apoptotic cells (ACs) and inducing immunoregulatory signals. We previously showed that Mer-deficient mice (Mer(-/-)) have increased germinal center (GC) responses, T cell activation, and AC accumulation within GCs. Accumulated ACs in GCs can undergo necrosis and release self-ligands, which may influence the outcome of a GC response and selection. In this study, we generated Mer(-/-) mice with a global MyD88, TLR7, or TLR9 deficiency and cell type-specific MyD88 deficiency to study the functional correlation between Mer and TLRs in the development of GC responses and autoimmunity...
November 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29106738/an-experimental-miniature-piglet-model-for-the-infection-of-human-norovirus-gii
#16
Dong Joo Seo, Day Jung, Soontag Jung, Seung-Kwon Ha, Sang-Do Ha, In-Soo Choi, Jinjong Myoung, Changsun Choi
Ten Yucatan miniature piglets were challenged with the human norovirus (NoV) GII.12/GII.3 CAU140599 strain and five piglets were used as negative controls. Stool, serum, and organs were collected and processed from two NoV-infected piglets and one negative piglet at 1, 2, 3, 5, and 7 days post-inoculation (dpi). NoV was detected in stool and serum samples by real-time RT-PCR. Mild diarrhea was observed at 1-3 dpi. Fecal shedding and viremia were detected intermittently at 1, 3, and 7 dpi. While interferon-α was significantly elevated at 2-3 dpi, interferon-γ was not changed...
November 6, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29105068/activation-of-plasmacytoid-dendritic-cells-by-apoptotic-particles-mechanism-for-the-loss-of-immunologic-tolerance-in-sj%C3%A3-gren-s-syndrome
#17
Mari Ainola, Pauliina Porola, Yuya Takakubo, Beata Przybyla, Vesa-Petteri Kouri, Tuomas Aleksi Tolvanen, Arno Hänninen, Dan Christian Nordström
Sjögren's syndrome (SS) is a common autoimmune disease targeting salivary and lacrimal glands. It is strongly female-dominant characterized by low estrogen levels combined with a local intracrine dihydrotestosterone defect. We hypothesized that these hormonal deficits lead to increased apoptosis of the epithelial cells and plasmacytoid dendritic cell (pDC) mediated pro-inflammatory host responses. Expression of Toll-like receptors (TLRs) 7 and 9 and cytokine profile was studied in pDCs treated with apoptotic particles collected in consecutive centrifugation steps of media from apoptotic cells...
November 4, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29104533/cell-type-specific-mrna-dysregulation-in-hippocampal-ca1-pyramidal-neurons-of-the-fragile-x-syndrome-mouse-model
#18
Laura Ceolin, Nathalie Bouquier, Jihane Vitre-Boubaker, Stéphanie Rialle, Dany Severac, Emmanuel Valjent, Julie Perroy, Emma Puighermanal
Fragile X syndrome (FXS) is a genetic disorder due to the silencing of the Fmr1 gene, causing intellectual disability, seizures, hyperactivity, and social anxiety. All these symptoms result from the loss of expression of the RNA binding protein fragile X mental retardation protein (FMRP), which alters the neurodevelopmental program to abnormal wiring of specific circuits. Aberrant mRNAs translation associated with the loss of Fmr1 product is widely suspected to be in part the cause of FXS. However, precise gene expression changes involved in this disorder have yet to be defined...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29103909/rna-aptamers-recognizing-murine-ccl17-inhibit-t-cell-chemotaxis-and-reduce-contact-hypersensitivity-in%C3%A2-vivo
#19
Lorenz Fülle, Nancy Steiner, Markus Funke, Fabian Gondorf, Franziska Pfeiffer, Julia Siegl, Friederike V Opitz, Silvana K Haßel, Anna Belen Erazo, Oliver Schanz, H James Stunden, Michael Blank, Carsten Gröber, Kristian Händler, Marc Beyer, Heike Weighardt, Eicke Latz, Joachim L Schultze, Günter Mayer, Irmgard Förster
The chemokine CCL17, mainly produced by dendritic cells (DCs) in the immune system, is involved in the pathogenesis of various inflammatory diseases. As a ligand of CCR4, CCL17 induces chemotaxis and facilitates T cell-DC interactions. We report the identification of two novel RNA aptamers, which were validated in vitro and in vivo for their capability to neutralize CCL17. Both aptamers efficiently inhibited the directed migration of the CCR4(+) lymphoma line BW5147.3 toward CCL17 in a dose-dependent manner...
October 13, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29093005/dendritic-cells-enhance-polyfunctionality-of-adoptively-transferred-t-cells-which-target-cytomegalovirus-in-glioblastoma
#20
Elizabeth Reap, Carter M Suryadevara, Kristen A Batich, Luis Sanchez-Perez, Gary E Archer, Robert J Schmittling, Pamela K Norberg, James E Herndon, Patrick Healy, Kendra L Congdon, Patrick C Gedeon, Olivia C Campbell, Adam M Swartz, Katherine A Riccione, John S Yi, Mohammed K Hossain-Ibrahim, Anirudh Saraswathula, Smita K Nair, Anastasie M Dunn-Pirio, Taylor M Broome, Kent J Weinhold, Annick Desjardins, Gordana Vlahovic, Roger Mclendon, Allan H Friedman, Henry S Friedman, Darell D Bigner, Peter E Fecci, Duane A Mitchell, John H Sampson
Median survival for glioblastoma (GBM) remains <15 months. Human Cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recent trial in recurrent GBM patients demonstrated the potential clinical benefit of adoptive T cell therapy (ATCT) of CMV phosphoprotein 65 (pp65)-specific T cells. However, ex vivo analyses from this study found no change in the capacity of CMV pp65-specific T cells to gain multiple effector functions or polyfunctionality, which has been associated with superior antitumor efficacy...
November 1, 2017: Cancer Research
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