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https://www.readbyqxmd.com/read/28794025/retrovirus-based-virus-like-particle-immunogenicity-and-its-modulation-by-toll-like-receptor-activation
#1
Fabien Pitoiset, Thomas Vazquez, Beatrice Levacher, Djamel Nehar-Belaid, Nicolas Dérian, James Vigneron, David Klatzmann, Bertrand Bellier
Retrovirus-derived virus-like particles (VLPs) are particularly interesting vaccine platforms as they trigger efficient humoral and cellular immune responses and can be used to display heterologous antigens. In this study, we characterized the intrinsic immunogenicity of VLPs and investigated their possible adjuvantization by incorporation of toll-like receptor (TLR) ligands. We designed a non-coding single-stranded RNA (ncRNA) that could be encapsidated by VLPs and induce TLR7/8-signaling. We found that VLPs efficiently induce in vitro dendritic cell activation, which can be improved by ncRNA encapsidation (ncRNAVLPs)...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768867/mechanism-of-interferon-stimulated-gene-induction-in-hiv-1-infected-macrophages
#2
Najla Nasr, Abdullateef A Alshehri, Thomas K Wright, Maryam Shahid, Bonnie M Heiner, Andrew N Harman, Rachel A Botting, Karla J Helbig, Michael R Beard, Kazuo Suzuki, Anthony D Kelleher, Paul Hertzog, Anthony L Cunningham
Viruses manipulate the complex interferon and interferon stimulated gene (ISG) system in different ways. We have previously shown that HIV inhibits type I and III interferons in its key target cells but directly stimulates a subset of >20 ISGs in macrophages and dendritic cells many of which are antiviral. Here we examined the mechanism of induction of ISGs and showed this occurred in two phases. The first phase was transient (0-24hpi) induced mainly by extracellular vesicles, and one of its component proteins HSP90α, contained within the HIV inoculum...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28767565/small-intestine-follicular-dendritic-cell-sarcoma-with-liver-metastasis-a-case-report
#3
Yun-Chen Chang, Ivy Yenwen Chau, Yi-Chen Yeh, Gar-Yang Chau
RATIONALE: Follicular dendritic cell sarcoma (FDCS) is a rare neoplasia composed of spindle or oval cells with follicular dendritic cell differentiation, usually occurring in lymphoid tissue. In this report, we present a case of FDCS of the small intestine with liver metastasis. PATIENT CONCERNS: A 19-year-old female presented with recent onset of left upper abdominal pain. Abdominal computed tomography scan showed a large tumor mass in the liver lateral segment with compression to the pancreas upper part, and a smaller mass in the terminal ileum, respectively...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28765142/a-retained-intron-in-the-3-utr-of-calm3-mrna-mediates-its-staufen2-and-activity-dependent-localization-to-neuronal-dendrites
#4
Tejaswini Sharangdhar, Yoichiro Sugimoto, Jacqueline Heraud-Farlow, Sandra M Fernández-Moya, Janina Ehses, Igor Ruiz de Los Mozos, Jernej Ule, Michael A Kiebler
Dendritic localization and hence local mRNA translation contributes to synaptic plasticity in neurons. Staufen2 (Stau2) is a well-known neuronal double-stranded RNA-binding protein (dsRBP) that has been implicated in dendritic mRNA localization. The specificity of Stau2 binding to its target mRNAs remains elusive. Using individual-nucleotide resolution CLIP (iCLIP), we identified significantly enriched Stau2 binding to the 3'-UTRs of 356 transcripts. In 28 (7.9%) of those, binding occurred to a retained intron in their 3'-UTR The strongest bound 3'-UTR intron was present in the longest isoform of Calmodulin 3 (Calm3L ) mRNA Calm3L 3'-UTR contains six Stau2 crosslink clusters, four of which are in this retained 3'-UTR intron...
August 1, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28763347/ex-vivo-induction-of-multiple-myeloma-specific-immune-responses-by-monocyte-derived-dendritic-cells-following-stimulation-by-whole-tumor-antigen-of-autologous-myeloma-cells
#5
Spyridoula Vasileiou, Ioannis Baltadakis, Sosanna Delimpasi, Maria-Helena Karatza, Konstantinos Liapis, Maria Garofalaki, Eirini Tziotziou, Zoe Poulopoulou, Dimitri Karakasis, Nicholas Harhalakis
The introduction of novel agents has significantly expanded treatment options for multiple myeloma (MM), albeit long-term disease control cannot be achieved in the majority of patients. Vaccination with MM antigen-loaded dendritic cells (DCs) represents an alternative strategy that is currently being explored. The aim of this study was to assess the immunogenic potential of ex vivo-generated monocyte-derived DCs (moDCs), following stimulation with the whole-antigen array of autologous myeloma cells (AMC). MoDCs were loaded with antigens of myeloma cells by 2 different methods: phagocytosis of apoptotic bodies from γ-irradiated AMC, or transfection with AMC total RNA by square-wave electroporation...
July 31, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28751858/distinct-localization-of-snap47-protein-in-gabaergic-and-glutamatergic-neurons-in-the-mouse-and-the-rat-hippocampus
#6
Agnieszka Münster-Wandowski, Heike Heilmann, Felix Bolduan, Thorsten Trimbuch, Yuchio Yanagawa, Imre Vida
Synaptosomal-associated protein of 47 kDa (SNAP47) isoform is an atypical member of the SNAP family, which does not contribute directly to exocytosis and synaptic vesicle (SV) recycling. Initial characterization of SNAP47 revealed a widespread expression in nervous tissue, but little is known about its cellular and subcellular localization in hippocampal neurons. Therefore, in the present study we applied multiple-immunofluorescence labeling, immuno-electron microscopy and in situ hybridization (ISH) and analyzed the localization of SNAP47 in pre- and postsynaptic compartments of glutamatergic and GABAergic neurons in the mouse and rat hippocampus...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28740074/cdkl5-localizes-at-the-centrosome-and-midbody-and-is-required-for-faithful-cell-division
#7
Isabella Barbiero, Davide Valente, Chetan Chandola, Fiorenza Magi, Anna Bergo, Laura Monteonofrio, Marco Tramarin, Maria Fazzari, Silvia Soddu, Nicoletta Landsberger, Cinzia Rinaldo, Charlotte Kilstrup-Nielsen
The cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with rare neurodevelopmental disorders characterized by the early onset of seizures and intellectual disability. The CDKL5 protein is widely expressed in most tissues and cells with both nuclear and cytoplasmic localization. In post-mitotic neurons CDKL5 is mainly involved in dendritic arborization, axon outgrowth, and spine formation while in proliferating cells its function is still largely unknown. Here, we report that CDKL5 localizes at the centrosome and at the midbody in proliferating cells...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733463/tlr4-and-c5ar-crosstalk-in-dendritic-cells-induces-a-core-regulatory-network-of-rsk2-pi3k%C3%AE-sgk1-and-foxo-transcription-factors
#8
Anouk Zaal, Benjamin Nota, Kat S Moore, Miranda Dieker, S Marieke van Ham, Anja Ten Brinke
Crosstalk between complement component 5a receptors (C5aRs) and TLRs in dendritic cells (DCs) occurs upon pathogen invasion; however, studies on C5aR and TLR crosstalk mainly focused on the modulating effect of C5a on TLR-induced cytokine production. To elucidate the breadth of C5aR and TLR4 crosstalk, the effect of simultaneous treatment with C5a and LPS was investigated in human monocyte-derived DCs (moDCs) 2 h after stimulation using whole transcriptome sequencing analysis. Although the effect of C5a on hallmark genes defining TLR4-induced DC maturation was limited at this time point, RNA sequencing analysis revealed a great variety of novel C5a targets, of which many interfere with TLR4-mediated immune activation...
July 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28730145/prokaryotic-rna-associated-to-bacterial-viability-induces-polymorphonuclear-neutrophil-activation
#9
Nahuel Rodriguez-Rodrigues, Luis A Castillo, Verónica I Landoni, Daiana Martire-Greco, M Ayelén Milillo, Paula Barrionuevo, Gabriela C Fernández
Polymorphonuclear neutrophils (PMN) are the first cellular line of antibacterial host defense. They sense pathogens through recognition of pathogen-associated molecular patterns (PAMPs) by innate pattern recognition receptors, such as Toll-like receptors (TLR). The aim of this study was to investigate whether PMN sense bacterial viability and explore which viability factor could be involved in this phenomenon. For this purpose, different functions were evaluated in isolated human PMN using live Escherichia coli (Ec) and heat-killed Ec (HK-Ec)...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28723570/dynamic-control-of-dendritic-mrna-expression-by-cnot7-regulates-synaptic-efficacy-and-higher-cognitive-function
#10
Rhonda L McFleder, Fernanda Mansur, Joel D Richter
Translation of mRNAs in dendrites mediates synaptic plasticity, the probable cellular basis of learning and memory. Coordination of translational inhibitory and stimulatory mechanisms, as well as dendritic transport of mRNA, is necessary to ensure proper control of this local translation. Here, we find that the deadenylase CNOT7 dynamically regulates dendritic mRNA translation and transport, as well as synaptic plasticity and higher cognitive function. In cultured hippocampal neurons, synaptic stimulation induces a rapid decrease in CNOT7, which, in the short-term, results in poly(A) tail lengthening of target mRNAs...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28717398/preclinical-evaluation-of-nf-%C3%AE%C2%BAb-triggered-dendritic-cells-expressing-the-viral-oncogenic-driver-of-merkel-cell-carcinoma-for-therapeutic-vaccination
#11
Kerstin F Gerer, Michael Erdmann, Sine R Hadrup, Rikke Lyngaa, Lena-Marie Martin, Reinhard E Voll, Beatrice Schuler-Thurner, Gerold Schuler, Niels Schaft, Stefanie Hoyer, Jan Dörrie
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but very aggressive skin tumor that develops after integration of a truncated form of the large T-antigen (truncLT) of the Merkel cell polyomavirus (MCV) into the host's genome. Therapeutic vaccination with dendritic cells (DCs) loaded with tumor antigens is an active form of immunotherapy, which intends to direct the immune system towards tumors which express the respective vaccination antigens. METHODS: Cytokine-matured monocyte-derived DCs of healthy donors and MCC patients were electroporated with mRNA encoding the truncLT...
July 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28713366/intratumoral-lentivector-mediated-tgf-%C3%AE-1-gene-downregulation-as-a-potent-strategy-for-enhancing-the-antitumor-effect-of-therapy-composed-of-cyclophosphamide-and-dendritic-cells
#12
Joanna Rossowska, Natalia Anger, Agnieszka Szczygieł, Jagoda Mierzejewska, Elżbieta Pajtasz-Piasecka
Vaccination with dendritic cells (DCs) stimulated with tumor antigens can induce specific cellular immune response that recognizes a high spectrum of tumor antigens. However, the ability of cancer cells to produce immunosuppressive factors drastically decreases the antitumor activity of DCs. The main purpose of the study was to improve the effectiveness of DC-based immunotherapy or chemoimmunotherapy composed of cyclophosphamide (CY) and DCs by application of lentivectors (LVs)-encoding short hairpin RNA specific for TGF-β1 (shTGFβ1 LVs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28697890/stress-induced-neuronal-colony-stimulating-factor-1-provokes-microglia-mediated-neuronal-remodeling-and-depressive-like-behavior
#13
Eric S Wohleb, Rosemarie Terwilliger, Catharine H Duman, Ronald S Duman
BACKGROUND: Chronic stress exposure causes neuronal atrophy and synaptic deficits in the medial prefrontal cortex (PFC), contributing to development of anxiety- and depressive-like behaviors. Concomitantly, microglia in the PFC undergo morphological and functional changes following stress exposure, suggesting that microglia contribute to synaptic deficits underlying behavioral consequences. METHODS: Male and female mice were exposed to chronic unpredictable stress (CUS) to examine the role of neuron-microglia interactions in the medial PFC during development of anxiety- and depressive-like behaviors...
June 12, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28694521/genome-wide-analysis-of-long-noncoding-rna-profiling-in-prrsv-infected-pam-cells-by-rna-sequencing
#14
Jing Zhang, Pu Sun, Lipeng Gan, Weijie Bai, Zhijia Wang, Dong Li, Yimei Cao, Yuanfang Fu, Pinghua Li, Xingwen Bai, Xueqing Ma, Huifang Bao, Yingli Chen, Zaixin Liu, Zengjun Lu
Porcine reproductive and respiratory syndrome (PRRS) is a major threat to the global swine industry and causes tremendous economic losses. Its causative agent, porcine reproductive and respiratory syndrome virus (PRRSV), primarily infects immune cells, such as porcine alveolar macrophages and dendritic cells. PRRSV infection results in immune suppression, antibody-dependent enhancement, and persistent infection. Highly pathogenic strains in China cause high fever and severe inflammatory responses in the lungs...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28685837/proteomic-analyses-of-nucleus-laminaris-identified-candidate-targets-of-the-fragile-x-mental-retardation-protein
#15
Hitomi Sakano, Diego A R Zorio, Xiaoyu Wang, Ying S Ting, William S Noble, Michael J MacCoss, Edwin W Rubel, Yuan Wang
The avian nucleus laminaris (NL) is a brainstem nucleus necessary for binaural processing, analogous in structure and function to the mammalian medial superior olive. In chickens (Gallus gallus), NL is a well-studied model system for activity-dependent neural plasticity. Its neurons have bipolar extension of dendrites, which receive segregated inputs from two ears and display rapid and compartment-specific reorganization in response to unilateral changes in auditory input. More recently, fragile X mental retardation protein (FMRP), an RNA-binding protein that regulates local protein translation, has been shown to be enriched in NL dendrites, suggesting its potential role in the structural dynamics of these dendrites...
July 7, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28683307/recruitment-of-staufen2-enhances-dendritic-localization-of-an-intron-containing-camkii%C3%AE-mrna
#16
Raúl Ortiz, Maya V Georgieva, Sara Gutiérrez, Neus Pedraza, Sandra M Fernández-Moya, Carme Gallego
Regulation of mRNA localization is a conserved cellular process observed in many types of cells and organisms. Asymmetrical mRNA distribution plays a particularly important role in the nervous system, where local translation of localized mRNA represents a key mechanism in synaptic plasticity. CaMKIIα is a very abundant mRNA detected in neurites, consistent with its crucial role at glutamatergic synapses. Here, we report the presence of CaMKIIα mRNA isoforms that contain intron i16 in dendrites, RNA granules, and synaptoneurosomes from primary neurons and brain...
July 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28681930/synthesis-and-biological-evaluation-of-ionizable-lipid-materials-for-the-in-vivo-delivery-of-messenger-rna-to-b-lymphocytes
#17
Owen S Fenton, Kevin J Kauffman, James C Kaczmarek, Rebecca L McClellan, Siddharth Jhunjhunwala, Mark W Tibbitt, Manhao D Zeng, Eric A Appel, Joseph R Dorkin, Faryal F Mir, Jung H Yang, Matthias A Oberli, Michael W Heartlein, Frank DeRosa, Robert Langer, Daniel G Anderson
B lymphocytes regulate several aspects of immunity including antibody production, cytokine secretion, and T-cell activation; moreover, B cell misregulation is implicated in autoimmune disorders and cancers such as multiple sclerosis and non-Hodgkin's lymphomas. The delivery of messenger RNA (mRNA) into B cells can be used to modulate and study these biological functions by means of inducing functional protein expression in a dose-dependent and time-controlled manner. However, current in vivo mRNA delivery systems fail to transfect B lymphocytes and instead primarily target hepatocytes and dendritic cells...
July 6, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28671760/tuning-the-ph-switch-of-supramolecular-polymer-carriers-for-sirna-to-physiologically-relevant-ph
#18
Patrick Ahlers, Hendrik Frisch, Regina Holm, Daniel Spitzer, Matthias Barz, Pol Besenius
The preparation of histidine enriched dendritic peptide amphiphiles and their self-assembly into multicomponent pH-switchable supramolecular polymers is reported. Alternating histidine and phenylalanine peptide synthons allow the assembly/disassembly to be adjusted in a physiologically relevant range of pH 5.3-6.0. Coassembly of monomers equipped with dendritic tetraethylene glycol chains with monomers bearing peripheral primary amine groups leads to nanorods with a tunable cationic surface charge density. These surface functional supramolecular polycations are able to reversibly bind short interfering RNA (siRNA)...
July 3, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28667746/integrated-gut-liver-microphysiological-systems-elucidates-inflammatory-inter-tissue-crosstalk
#19
Wen L K Chen, Collin Edington, Emily Suter, Jiajie Yu, Jeremy J Velazquez, Jason G Velazquez, Michael Shockley, Emma M Large, Raman Venkataramanan, David J Hughes, Cynthia L Stokes, David L Trumper, Rebecca L Carrier, Murat Cirit, Linda G Griffith, Douglas A Lauffenburger
A capability for analyzing complex cellular communication among tissues is important in drug discovery and development, and in vitro technologies for doing so are required for human applications. A prominent instance is communication between the gut and the liver, whereby perturbations of one tissue can influence behavior of the other. Here, we present a study on human gut-liver tissue interactions under normal and inflammatory contexts, via an integrative multi-organ platform comprising human liver (hepatocytes and Kupffer cells), and intestinal (enterocytes, goblet cells, and dendritic cells) models...
July 1, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28666759/a-short-hairpin-rna-based-adjuvant-targeting-nf-%C3%AE%C2%BAb-repressor-i%C3%AE%C2%BAb%C3%AE-promotes-migration-of-dermal-dendritic-cells-to-draining-lymph-nodes-and-antitumor-ctl-responses-induced-by-dna-vaccination
#20
Felipe Gálvez-Cancino, Jonathan Roco, Nicole Rojas-Colonelli, Camila Flores, Paola Murgas, Sebastián Cruz-Gómez, César Oyarce, Manuel Varas-Godoy, Daniela Sauma, Alvaro Lladser
DNA vaccination is an attractive approach to elicit tumor-specific cytotoxic CD8(+) T lymphocytes (CTL), which can mediate protective immunity against tumors. To initiate CTL responses, antigen-encoding plasmids employed for DNA vaccination need to activate dendritic cells (DC) through the stimulation of DNA-sensing innate immune receptors that converge in the activation of the master transcription factor NF-κB. To this end, NF-κB repressor IκBα needs to be degraded, allowing NF-κB to translocate to the nucleus and transcribe proinflammatory target genes, as well as its repressor IκBα...
June 27, 2017: Vaccine
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