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https://www.readbyqxmd.com/read/29774448/the-expression-alteration-of-bc1-rna-and-its-interaction-with-eukaryotic-translation-initiation-factor-eif4a-post-status-epilepticus
#1
Xiangchang Zeng, Wenjing Zong, Qing Gao, Siyu Chen, Lulu Chen, Guirong Zeng, Weihua Huang, Zhenyu Li, Chang Zeng, Yuanyuan Xie, Xiaohui Li, Bo Xiao, Dongsheng-Ouyang, Kai Hu
Abnormal dendritic sprouting and synaptic remodelling are important pathological features of temporal lobe epilepsy. BC1 RNA is a translation repressor involved in the regulation of the dendritic protein synthesis and mRNA transport, which is essential for dendritic development and plasticity. The expression alteration of BC1 RNA in the pilocarpine induced epilepsy model remains unknown. It is unclear if the interactions between BC1 RNA and eukaryotic initiation factor 4A (eIF4A) exists in this model. The purpose of this study was to investigate the expression changes of BC1 RNA and its interactions with eIF4A post-status epilepticus (SE)...
May 17, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29774215/importance-of-functional-loss-of-fus-in-ftld-als
#2
REVIEW
Shinsuke Ishigaki, Gen Sobue
Fused in sarcoma (FUS) is an RNA binding protein that regulates RNA metabolism including alternative splicing, transcription, and RNA transportation. FUS is genetically and pathologically involved in frontotemporal lobar degeneration (FTLD)/amyotrophic lateral sclerosis (ALS). Multiple lines of evidence across diverse models suggest that functional loss of FUS can lead to neuronal dysfunction and/or neuronal cell death. Loss of FUS in the nucleus can impair alternative splicing and/or transcription, whereas dysfunction of FUS in the cytoplasm, especially in the dendritic spines of neurons, can cause mRNA destabilization...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29773099/-toxoplasma-gondii-rop38-promotes-the-maturation-of-dendritic-cells-mediated-by-tlr4
#3
Heng Zhang, Shanghua Wu, Zhiqiang Shi, Shan Wang, Wei Lu, Yizhen Wu, Pei Sun, Qianming Xu
Objective To investigate the effect of rhoptry protein 38 (ROP38) from Toxoplasma gondii (T. gondii) on the maturation of dendritic cells (DCs) by Toll-like receptor 4 (TLR4) induction in vitro. Methods The total RNA from T. gondii RH strain was extracted by guanidine thiocyanate method, and then cDNA was synthesized with reverse transcription reaction. After ROP38 gene was amplified by PCR, the recombinant pGEX-4T-ROP38 was constructed and expressed under IPTG induction. The recombinant ROP38 protein was detected by SDS-PAGE and Western blot analysis...
March 2018: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29769269/trim29-negatively-regulates-the-type-i-ifn-production-in-response-to-rna-virus
#4
Junji Xing, Ao Zhang, Laurie J Minze, Xian Chang Li, Zhiqiang Zhang
The innate immunity is critically important in protection against virus infections, and in the case of RNA viral infections, the signaling mechanisms that initiate robust protective innate immunity without triggering autoimmune inflammation remain incompletely defined. In this study, we found the E3 ligase TRIM29 was specifically expressed in poly I:C-stimulated human myeloid dendritic cells. The induced TRIM29 played a negative role in type I IFN production in response to poly I:C or dsRNA virus reovirus infection...
May 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29766042/bc-rna-mislocalization-in-the-fragile-x-premutation
#5
Ilham A Muslimov, Taesun Eom, Anna Iacoangeli, Shih-Chieh Chuang, Renate K Hukema, Rob Willemsen, Dimitre G Stefanov, Robert K S Wong, Henri Tiedge
Fragile X premutation disorder is caused by CGG triplet repeat expansions in the 5' untranslated region of FMR1 mRNA. The question of how expanded CGG repeats cause disease is a subject of continuing debate. Our work indicates that CGG-repeat structures compete with regulatory BC1 RNA for access to RNA transport factor hnRNP A2. As a result, BC1 RNA is mislocalized in vivo, as its synapto-dendritic presence is severely diminished in brains of CGG-repeat knock-in animals (a premutation mouse model). Lack of BC1 RNA is known to cause seizure activity and cognitive dysfunction...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29753166/double-determination-of-long-noncoding-rnas-from-lung-cancer-via-multi-amplified-electrochemical-genosensor-at-sub-femtomole-level
#6
Xiaoyan Li, Gang Peng, Feng Cui, Qianying Qiu, Xiaojun Chen, He Huang
An ultrasensitive electrochemical genosensor has been fabricated for the double determination of two different specific sequences deduced from the maternally expressed gene3 (MEG3) lncRNA (long noncoding RNA), which was demonstrated by coupling RNase A-aided target recycling with DNA supersandwich-induced signal enhancement, based on a composite interface of graphene-like tungsten disulfide/dendritic gold nanostructures (WS2 /DGN). Firstly, duple target sequences of T1 and T2 were captured by the primer probes of P1 /P2 functionalized Fe3 O4 @C magnetic nanoparticles, via the DNA/RNA hybridization between T1 /T2 and P1 /P2 ...
May 2, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29752062/single-cell-rna-sequencing-of-lymph-node-stromal-cells-reveals-niche-associated-heterogeneity
#7
Lauren B Rodda, Erick Lu, Mariko L Bennett, Caroline L Sokol, Xiaoming Wang, Sanjiv A Luther, Ben A Barres, Andrew D Luster, Chun Jimmie Ye, Jason G Cyster
Stromal cells (SCs) establish the compartmentalization of lymphoid tissues critical to the immune response. However, the full diversity of lymph node (LN) SCs remains undefined. Using droplet-based single-cell RNA sequencing, we identified nine peripheral LN non-endothelial SC clusters. Included are the established subsets, Ccl19hi T-zone reticular cells (TRCs), marginal reticular cells, follicular dendritic cells (FDCs), and perivascular cells. We also identified Ccl19lo TRCs, likely including cholesterol-25-hydroxylase+ cells located at the T-zone perimeter, Cxcl9+ TRCs in the T-zone and interfollicular region, CD34+ SCs in the capsule and medullary vessel adventitia, indolethylamine N-methyltransferase+ SCs in the medullary cords, and Nr4a1+ SCs in several niches...
April 26, 2018: Immunity
https://www.readbyqxmd.com/read/29746296/pd-1-contributes-to-the-establishment-and-maintenance-of-hiv-1-latency
#8
Vanessa A Evans, Renée M Van Der Sluis, Ajantha Solomon, Ashanti Dantanarayana, Catriona McNeil, Roger Garsia, Sarah Palmer, Rémi Fromentin, Nicolas Chomont, Rafick-Pierre Sékaly, Paul U Cameron, Sharon R Lewin
OBJECTIVE: In HIV-infected individuals on antiretroviral therapy (ART), latent HIV is enriched in CD4 T-cells expressing immune checkpoint molecules (ICs), in particular programmed cell death-1 (PD-1). We therefore assessed the effect of blocking PD-1 on latency, both in vitro and in vivo. METHODS: HIV latency was established in vitro following co-culture of resting CD4 T-cells with myeloid dendritic cells. Expression of PD-1 was quantified by flow cytometry, and latency assessed in sorted PD-1 and PD-1 non-proliferating CD4 memory T-cells...
May 9, 2018: AIDS
https://www.readbyqxmd.com/read/29720240/integrative-analysis-reveals-cd38-as-a-therapeutic-target-for-plasma-cell-rich-pre-disease-and-established-rheumatoid-arthritis-and-systemic-lupus-erythematosus
#9
Suzanne Cole, Alice Walsh, Xuefeng Yin, Mihir D Wechalekar, Malcolm D Smith, Susanna M Proudman, Douglas J Veale, Ursula Fearon, Costantino Pitzalis, Frances Humby, Michele Bombardieri, Amy Axel, Homer Adams, Christopher Chiu, Michael Sharp, John Alvarez, Ian Anderson, Loui Madakamutil, Sunil Nagpal, Yanxia Guo
BACKGROUND: Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE. METHODS: RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target...
May 2, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29718193/transcriptional-profiling-of-age-associated-gene-expression-changes-in-human-circulatory-cd1c-myeloid-dendritic-cell-subset
#10
Farah Rahmatpanah, Sudhanshu Agrawal, Vanessa M Scarfone, Sameer Kapadia, Dan Mercola, Anshu Agrawal
Immune dysfunction is a hallmark of aging and is thought to be responsible for the age-associated diseases. Dendritic cells(DCs) of the immune system function as initiators and regulators of the immune responses. Recent studies have highlighted the division of labor between various DC subsets. CD1c+ DC subset has emerged as a major inducer of CD4 T cell response. There is a scarcity of information regarding the age-associated changes in the functions of DC subsets in the elderly. Here we investigated the changes in transcriptional profile of CD1c+ DC subset from healthy aged and young individuals using RNA-sequencing...
April 28, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29712715/nmdar-dependent-argonaute-2-phosphorylation-regulates-mirna-activity-and-dendritic-spine-plasticity
#11
Dipen Rajgor, Thomas M Sanderson, Mascia Amici, Graham L Collingridge, Jonathan G Hanley
MicroRNAs (miRNAs) repress translation of target mRNAs by associating with Argonaute (Ago) proteins to form the RNA-induced silencing complex (RISC), underpinning a powerful mechanism for fine-tuning protein expression. Specific miRNAs are required for NMDA receptor (NMDAR)-dependent synaptic plasticity by modulating the translation of proteins involved in dendritic spine morphogenesis or synaptic transmission. However, it is unknown how NMDAR stimulation stimulates RISC activity to rapidly repress translation of synaptic proteins...
April 30, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29695694/-maturation-and-antigen-loading-protocols-influence-activity-of-anticancer-dendritic-cells
#12
Zh K Nazarkina, A Zajakina, P P Laktionov
The practical use of dendritic cell-based vaccines in anticancer therapy is limited by a lack of standards for dendritic cell (DC) generation, as well as standard procedures for controlling their activation and the technique of DC loading with nucleic acids encoding tumor antigens. Analyzing the currently available data, the most promising cocktails for DC maturation were selected and a comparative study of the cocktails and time of maturation on the capacity of DC to activate T-cell immune response has been performed...
March 2018: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/29690903/ccl20-is-up-regulated-in-non-alcoholic-fatty-liver-disease-fibrosis-and-is-produced-by-hepatic-stellate-cells-in-response-to-fatty-acid-loading
#13
Xin Chu, Qunyan Jin, Hui Chen, G Craig Wood, Anthony Petrick, William Strodel, Jon Gabrielsen, Peter Benotti, Tooraj Mirshahi, David J Carey, Christopher D Still, Johanna K DiStefano, Glenn S Gerhard
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent complication of extreme obesity. Loading of the liver with fat can progress to inflammation and fibrosis including cirrhosis. The molecular factors involved in the progression from simple steatosis to fibrosis remain poorly understood. METHODS: Gene expression profiling using microarray, PCR array, and RNA sequencing was performed on RNA from liver biopsy tissue from patients with extreme obesity...
April 24, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29688101/the-efficiency-of-lipid-nanoparticles-with-an-original-cationic-lipid-as-a-sirna-delivery-system-for-macrophages-and-dendritic-cells
#14
Yasunori Uemura, Tomoyuki Naoi, Yasumasa Kanai, Katsuya Kobayashi
Small interfering of RNA (siRNA) technology has the potential to be a next-generation therapy. However, naked siRNA does not have high transfection efficiency and is rapidly degraded after systemic injection, so an appropriate drug delivery system (DDS) is required for clinical use. Several potential systems have been assessed, clinically focusing on hepatocyte or cancer tissue using siRNA. However, targeting immune cells using siRNA is still challenging, and a new DDS is required. In this study, we prepared lipid nanoparticles (LNP) composed of original cationic lipid, neutral lipid of DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and PEG2000-DMPE (N- (Carbonyl-methoxypolyethyleneglycol 2000) -1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, sodium salt)...
April 24, 2018: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29687651/tlr9-deficiency-breaks-tolerance-to-rna-associated-antigens-and-upregulates-tlr7-protein-in-sle1-mice
#15
Teja Celhar, Hiroko Yasuga, Hui-Yin Lee, Olga Zharkova, Shubhita Tripathi, Susannah I Thornhill, Hao K Lu, Bijin Au, Lina H K Lim, Thomas P Thamboo, Shizuo Akira, Edward K Wakeland, John E Connolly, Anna-Marie Fairhurst
OBJECTIVE: Toll-like receptors (TLRs) 7 and 9 are important innate signaling molecules with opposing roles in the development and progression of Systemic Lupus Erythematosus (SLE). While multiple studies support a dependency on TLR7 for disease development, genetic ablation of TLR9 results in severe disease with glomerulonephritis (GN) by a largely unknown mechanism. The present study was designed to examine the suppressive role of TLR9 in the development of severe lupus. METHODS: We crossed Sle1 lupus-prone mice with TLR9-deficient mice to generate Sle1TLR9-/- ...
April 24, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29679565/activation-of-tlr3-and-its-adaptor-ticam-1-increases-mir-21-levels-in-extracellular-vesicles-released-from-human-cells
#16
Yoshimi Fukushima, Masaaki Okamoto, Kana Ishikawa, Takahisa Kouwaki, Hirotake Tsukamoto, Hiroyuki Oshiumi
Pattern-recognition receptors (PRRs) recognizes viral RNAs and trigger the innate immune responses. Toll-like receptor 3 (TLR3), a PRR, recognizes viral double-stranded RNA (dsRNA) in endolysosomes, whereas cytoplasmic dsRNA is sensed by another PRR, MDA5. TLR3 and MDA5 utilize TICAM-1 and MAVS, respectively, to trigger the signal for inducing innate immune responses. Extracellular vesicles (EVs) include the exosomes and microvesicles; an accumulating body of evidence has shown that EVs delivers functional RNA, such as microRNAs (miRNAs), to other cells and thus mediate intercellular communications...
April 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29656876/alternative-3-utrs-modify-the-localization-regulatory-potential-stability-and-plasticity-of-mrnas-in-neuronal-compartments
#17
Georgi Tushev, Caspar Glock, Maximilian Heumüller, Anne Biever, Marko Jovanovic, Erin M Schuman
Neurons localize mRNAs near synapses where their translation can be regulated by synaptic demand and activity. Differences in the 3' UTRs of mRNAs can change their localization, stability, and translational regulation. Using 3' end RNA sequencing of microdissected rat brain slices, we discovered a huge diversity in mRNA 3' UTRs, with many transcripts showing enrichment for a particular 3' UTR isoform in either somata or the neuropil. The 3' UTR isoforms of localized transcripts are significantly longer than the 3' UTRs of non-localized transcripts and often code for proteins associated with axons, dendrites, and synapses...
April 9, 2018: Neuron
https://www.readbyqxmd.com/read/29648784/design-of-mannose-functionalized-curdlan-nanoparticles-for-macrophage-targeted-sirna-delivery
#18
Tsogzolmaa Ganbold, Huricha Baigude
6-Amino-6-deoxy-curdlan is a promising nucleic acid carrier that efficiently delivers plasmid DNA as well as short interfering RNA (siRNA) to various cell lines. The highly reactive C6-NH2 groups of 6-amino-6-deoxy-curdlan prompt conjugation of various side groups including tissue-targeting ligands to enhance cell-type-specific nucleic acid delivery to specific cell lines. Herein, to test the primary-cell-targeting efficiency of the curdlan derivative, we chemically conjugated a macrophage-targeting ligand, mannose, to 6-amino-6-deoxy-curdlan...
May 2, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29630061/fateid-infers-cell-fate-bias-in-multipotent-progenitors-from-single-cell-rna-seq-data
#19
Josip S Herman, Sagar, Dominic Grün
To understand stem cell differentiation along multiple lineages, it is necessary to resolve heterogeneous cellular states and the ancestral relationships between them. We developed a robotic miniaturized CEL-Seq2 implementation to carry out deep single-cell RNA-seq of ∼2,000 mouse hematopoietic progenitors enriched for lymphoid lineages, and used an improved clustering algorithm, RaceID3, to identify cell types. To resolve subtle transcriptome differences indicative of lineage biases, we developed FateID, an iterative supervised learning algorithm for the probabilistic quantification of cell fate bias in progenitor populations...
April 9, 2018: Nature Methods
https://www.readbyqxmd.com/read/29625118/fus-causes-synaptic-hyperexcitability-in-drosophila-dendritic-arborization-neurons
#20
James B Machamer, Brian M Woolums, Gregory Fuller, Thomas E Lloyd
Mutations in the nuclear localization signal of the RNA binding protein FUS cause both Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). These mutations result in a loss of FUS from the nucleus and the formation of FUS-containing cytoplasmic aggregates in patients. To better understand the role of cytoplasmic FUS mislocalization in the pathogenesis of ALS, we identified a population of cholinergic neurons in Drosophila that recapitulate these pathologic hallmarks. Expression of mutant FUS or the Drosophila homolog, Cabeza (Caz), in class IV dendritic arborization neurons results in cytoplasmic mislocalization and axonal transport to presynaptic terminals...
April 3, 2018: Brain Research
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