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https://www.readbyqxmd.com/read/28730145/prokaryotic-rna-associated-to-bacterial-viability-induces-polymorphonuclear-neutrophil-activation
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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, FMRP (fragile X mental retardation protein), 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
#8
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
#9
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
#10
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
#11
Wen Li Kelly 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 (enterocyte, 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
#12
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
https://www.readbyqxmd.com/read/28662698/mov10-suppresses-retroelements-and-regulates-neuronal-development-and-function-in-the-developing-brain
#13
Geena Skariah, Joseph Seimetz, Miles Norsworthy, Monica C Lannom, Phillip J Kenny, Mohamed Elrakhawy, Craig Forsthoefel, Jenny Drnevich, Auinash Kalsotra, Stephanie Ceman
BACKGROUND: Moloney leukemia virus 10 (Mov10) is an RNA helicase that mediates access of the RNA-induced silencing complex to messenger RNAs (mRNAs). Until now, its role as an RNA helicase and as a regulator of retrotransposons has been characterized exclusively in cell lines. We investigated the role of Mov10 in the mouse brain by examining its expression over development and attempting to create a Mov10 knockout mouse. Loss of both Mov10 copies led to early embryonic lethality. RESULTS: Mov10 was significantly elevated in postnatal murine brain, where it bound retroelement RNAs and mRNAs...
June 29, 2017: BMC Biology
https://www.readbyqxmd.com/read/28658614/a-critical-analysis-of-the-role-of-snare-protein-sec22b-in-antigen-cross-presentation
#14
S Julia Wu, Yashar S Niknafs, Stephanie H Kim, Katherine Oravecz-Wilson, Cynthia Zajac, Tomomi Toubai, Yaping Sun, Jayendra Prasad, Daniel Peltier, Hideaki Fujiwara, Israel Hedig, Nathan D Mathewson, Rami Khoriaty, David Ginsburg, Pavan Reddy
Cross-presentation initiates immune responses against tumors and viral infections by presenting extracellular antigen on MHC I to activate CD8(+) T cell-mediated cytotoxicity. In vitro studies in dendritic cells (DCs) established SNARE protein SEC22B as a specific regulator of cross-presentation. However, the in vivo contribution of SEC22B to cross-presentation has not been tested. To address this, we generated DC-specific Sec22b knockout (CD11c-Cre Sec22b(fl/fl)) mice. Contrary to the paradigm, SEC22B-deficient DCs efficiently cross-present both in vivo and in vitro...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28655636/diesel-exhaust-particulate-associated-chemicals-attenuate-expression-of-cxcl10-in-human-primary-bronchial-epithelial-cells
#15
Kirsty Meldrum, Timothy W Gant, Martin O Leonard
Air pollution affects a large proportion of the population particularly in urban areas, with diesel particulates recognised as particular causes for concern in respiratory conditions such as asthma. In this study we examined the response of human primary airway epithelial cells to diesel particulate chemical extracts (DE) and characterised gene expression alterations using RNA-SEQ. Using the antagonist CH223191, DE induced CYP1A1 and attenuation of CXCL10 among other genes were observed to be aryl hydrocarbon receptor dependent...
June 24, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28640917/human-hantavirus-infection-elicits-pronounced-redistribution-of-mononuclear-phagocytes-in-peripheral-blood-and-airways
#16
Saskia Scholz, Faezzah Baharom, Gregory Rankin, Kimia T Maleki, Shawon Gupta, Sindhu Vangeti, Jamshid Pourazar, Andrea Discacciati, Jonas Höijer, Matteo Bottai, Niklas K Björkström, Johan Rasmuson, Magnus Evander, Anders Blomberg, Hans-Gustaf Ljunggren, Jonas Klingström, Clas Ahlm, Anna Smed-Sörensen
Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs), including monocytes and dendritic cells (DCs), orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28638110/a-novel-and-effective-method-to-generate-human-porcine-specific-regulatory-t-cells-with-high-expression-of-il-10-tgf-%C3%AE-1-and-il-35
#17
Mingqian Li, Judith Eckl, Christiane Geiger, Dolores J Schendel, Heike Pohla
Organ transplantation remains the most effective treatment for patients with late stage organ failure. Transgenic pigs provide an alternative organ donor source to the limited availability of human organs. However, cellular rejection still remains to be the obstacle for xenotransplantation. Superior to other methods, antigen-specific regulatory T cells (Treg) alleviate cellular rejection with fewer side effects. Here we demonstrate the use of a fast method to provide tolerogenic dendritic cells (tolDC) that can be used to generate effective porcine-specific Treg cells (PSTreg)...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#18
Johan Mj Van den Bergh, Evelien Ljm Smits, Zwi N Berneman, Tim Ja Hutten, Hans De Reu, Viggo Fi Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DCs) is an appealing strategy to boost the GVT-response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
June 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28636433/immunogenicity-of-ags-004-dendritic-cell-therapy-in-patients-treated-during-acute-hiv-infection
#19
Cynthia L Gay, Mark A DeBenedette, Irina Y Tcherepanova, Alicia Gamble, Whitney E Lewis, Anna B Cope, JoAnn D Kuruc, Kara S McGee, Mary F Kearney, John M Coffin, Nancie M Archin, Charles B Hicks, Joseph J Eron, Charles A Nicolette, David M Margolis
AGS-004 consists of matured autologous dendritic cells co-electroporated with in vitro transcribed RNA encoding autologous HIV antigens. In an open-label, single arm sub-study of AGS-004-003, AGS-004 was administered monthly to suppressed participants who started antiretroviral therapy (ART) during acute HIV infection. HIV-1 specific T cell responses were measured by multicolor flow cytometry after 3-4 doses. The frequency of resting CD4(+) T-cell infection (RCI) was measured by quantitative viral outgrowth assay...
June 21, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28623238/a-normal-genetic-variation-modulates-synaptic-mmp-9-protein-levels-and-the-severity-of-schizophrenia-symptoms
#20
Katarzyna Lepeta, Katarzyna J Purzycka, Katarzyna Pachulska-Wieczorek, Marina Mitjans, Martin Begemann, Behnam Vafadari, Krystian Bijata, Ryszard W Adamiak, Hannelore Ehrenreich, Magdalena Dziembowska, Leszek Kaczmarek
Matrix metalloproteinase 9 (MMP-9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms has been missing. In the present study, we performed a phenotype-based genetic association study (PGAS) in > 1,000 schizophrenia patients from the Göttingen Research Association for Schizophrenia (GRAS) data collection and found an association between the MMP-9 rs20544 C/T single-nucleotide polymorphism (SNP) located in the 3'untranslated region (UTR) and the severity of a chronic delusional syndrome...
June 16, 2017: EMBO Molecular Medicine
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