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https://www.readbyqxmd.com/read/29775506/dyschromatosis-symmetrica-hereditaria-with-chilblains-due-to-a-novel-two-amino-acid-deletion-in-the-double-stranded-rna-binding-domain-of-adar1
#1
M Kono, M Suganuma, T Shimada, Y Ishikura, S Watanabe, T Takeichi, Y Muro, M Akiyama
Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant skin disease caused by a heterozygous mutation of ADAR1.1 DSH is characterized by a mixture of hyper- and hypo-pigmented small macules in the extremities. Among the mutations, the pathogenicity of in-frame deletion in regions other than the deaminase domain has not been clarified in DSH.2 This article is protected by copyright. All rights reserved.
May 18, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29770436/all-i-s-on-the-radar-role-of-adar-in-gene-regulation
#2
REVIEW
Galina Shevchenko, Kevin V Morris
Adenosine to inosine (A-to-I) editing is the most abundant form of RNA modification in mammalian cells, which is catalyzed by adenosine deaminase acting on the double-stranded RNA (ADAR) protein family. A-to-I editing is currently known to be involved in the regulation of the immune system, RNA splicing, protein recoding, microRNA biogenesis, and formation of heterochromatin. Editing occurs within regions of double-stranded RNA, particularly within inverted Alu repeats, and is associated with many diseases including cancer, neurological disorders, and metabolic syndromes...
May 16, 2018: FEBS Letters
https://www.readbyqxmd.com/read/29769532/aid-apobec-like-cytidine-deaminases-are-ancient-innate-immune-mediators-in-invertebrates
#3
Mei-Chen Liu, Wen-Yun Liao, Katherine M Buckley, Shu Yuan Yang, Jonathan P Rast, Sebastian D Fugmann
In the course of both innate and adaptive immunity, cytidine deaminases within the activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) family modulate immune responses by mutating specific nucleic acid sequences of hosts and pathogens. The evolutionary emergence of these mediators, however, seems to coincide precisely with the emergence of adaptive immunity in vertebrates. Here, we show a family of genes in species within two divergent invertebrate phyla-the echinoderm Strongylocentrotus purpuratus and the brachiopod Lingula anatina-that encode proteins with similarities in amino acid sequence and enzymatic activities to the vertebrate AID/APOBECs...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769310/tumor-associated-intronic-editing-of-hnrpll-generates-a-novel-splicing-variant-linked-to-cell-proliferation
#4
Yi-Tung Chen, Ian Yi-Feng Chang, Hsuan Liu, Chung-Pei Ma, Yu-Ping Kuo, Chieh-Tien Shih, Ying-Hsin Shih, Lin Kang, Bertrand Chin-Ming Tan
Processing of the eukaryotic transcriptome is a dynamic regulatory mechanism that confers genetic diversity, and splicing and A-to-I RNA editing are well-characterized examples of such processing. Growing evidence reveals the crosstalk between the splicing and RNA editing, but there is a paucity of substantial evidence for its mechanistic details and contribution in a physiological context. Here, our findings demonstrate that tumor-associated differential RNA editing, in conjunction with splicing machinery, regulates the expression of variants of HNRPLL, a gene encoding splicing factor...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29768381/tuberculous-pleurisy-mimicking-mycoplasma-pneumoniae-infection-in-a-previously-healthy-young-adult-a-case-report
#5
Daizo Yaguchi, Motoshi Ichikawa, Masato Shizu, Noriko Inoue, Daisuke Kobayashi, Naoyuki Imai, Masao Ito
RATONALE: Sometimes, pleural effusion accompanying an acute Mycoplasma pneumoniae infection or tuberculous pleurisy has similar analysis results. We report a case of tuberculous pleurisy which was initially diagnosed as acute M pneumoniae infection, which is of special interest because anti-Mycoplasma antibody results were positive, which served as a red herring. PATIENT CONCERNS: A 20-year-old woman visited the outpatient emergency romm of our hospital for chief complaints of high fever, dry cough, and pleuralgia persiting for 2 days...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29762717/durable-complete-responses-in-some-recurrent-high-grade-glioma-patients-treated-with-toca-511-toca-fc
#6
Timothy F Cloughesy, Joseph Landolfi, Michael A Vogelbaum, Derek Ostertag, James B Elder, Stephen Bloomfield, Bob Carter, Clark C Chen, Steven N Kalkanis, Santosh Kesari, Albert Lai, Ian Y Lee, Linda M Liau, Tom Mikkelsen, Phioanh Nghiemphu, David Piccioni, William Accomando, Oscar R Diago, Daniel J Hogan, Dawn Gammon, Noriyuki Kasahara, Thian Kheoh, Douglas J Jolly, Harry E Gruber, Asha Das, Tobias Walbert
Background: Vocimagene amiretrorepvec (Toca 511) is an investigational gamma-retroviral replicating vector encoding cytosine deaminase that, when used in combination with extended-release 5-fluorocytosine (Toca FC), results preclinically in local production of 5-fluorouracil, depletion of immune-suppressive myeloid cells, and subsequent induction of anti-tumor immunity. Recurrent high grade glioma (rHGG) patients have a high unmet need for effective therapies that produce durable responses lasting more than 6 months...
May 12, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29761620/polyserositis-a-diagnostic-challenge
#7
Inés Losada, Juan González Moreno, Nuria Roda, Lola Ventayol, Yolanda Borjas, Francisco Javier Domínguez, Victoria Fernández Vaca, Mercedes García Gasalla, Antoni Payeras
Polyserositis (PS) is the inflammation, with effusion, of different serous membranes. It has been associated with different aetiologiesbut the aetiology of PS remains unknown in a high percentage of patients. The general objective of this retrospective study was to analyse the aetiology of PS cases seen at Son Llàtzer Hospital in an eleven-year period. Other objectives were to determine epidemiological, clinical, and analytical characteristics of these patients. Ninety-two patients were included in the study...
May 14, 2018: Internal Medicine Journal
https://www.readbyqxmd.com/read/29760455/substrate-sequence-selectivity-of-apobec3a-implicates-intra-dna-interactions
#8
Tania V Silvas, Shurong Hou, Wazo Myint, Ellen Nalivaika, Mohan Somasundaran, Brian A Kelch, Hiroshi Matsuo, Nese Kurt Yilmaz, Celia A Schiffer
The APOBEC3 (A3) family of human cytidine deaminases is renowned for providing a first line of defense against many exogenous and endogenous retroviruses. However, the ability of these proteins to deaminate deoxycytidines in ssDNA makes A3s a double-edged sword. When overexpressed, A3s can mutate endogenous genomic DNA resulting in a variety of cancers. Although the sequence context for mutating DNA varies among A3s, the mechanism for substrate sequence specificity is not well understood. To characterize substrate specificity of A3A, a systematic approach was used to quantify the affinity for substrate as a function of sequence context, length, secondary structure, and solution pH...
May 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29760157/methyl-cpg-binding-protein-2-mediates-antifibrotic-effects-in-scleroderma-fibroblasts
#9
Ye He, Pei-Suen Tsou, Dinesh Khanna, Amr H Sawalha
OBJECTIVE: Emerging evidence supports a role for epigenetic regulation in the pathogenesis of scleroderma (SSc). We aimed to assess the role of methyl-CpG-binding protein 2 (MeCP2), a key epigenetic regulator, in fibroblast activation and fibrosis in SSc. METHODS: Dermal fibroblasts were isolated from patients with diffuse cutaneous SSc (dcSSc) and from healthy controls. MeCP2 expression was measured by qPCR and western blot. Myofibroblast differentiation was evaluated by gel contraction assay in vitro...
May 14, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29753815/neutropenia-among-patients-with-adenosine-deaminase-deficiency
#10
Vy Hong-Diep Kim, Anne Pham-Huy, Eyal Grunebaum
Neutropenia occurs frequently among adenosine deaminase-deficient patients, independent of infections, medications or chemotherapy, and might be among the presenting manifestations of the disease. Adenosine deaminase deficiency might directly affect myeloid development.
May 10, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29751245/paracetamol-toxicity-and-microbial-utilization-pseudomonas-moorei-kb4-as-a-case-study-for-exploring-degradation-pathway
#11
Joanna Żur, Danuta Wojcieszyńska, Katarzyna Hupert-Kocurek, Ariel Marchlewicz, Urszula Guzik
Paracetamol, a widely used analgesic and antipyretic drug, is currently one of the most emerging pollutants worldwide. Besides its wide prevalence in the literature only several bacterial strains able to degrade this compound have been described. In this study, we isolated six new bacterial strains able to remove paracetamol. The isolated strains were identified as the members of Pseudomonas, Bacillus, Acinetobacter and Sphingomonas genera and characterized phenotypically and biochemically using standard methods...
May 3, 2018: Chemosphere
https://www.readbyqxmd.com/read/29749052/exercise-testing-based-algorithms-to-diagnose-mcardle-disease-and-mad-defects
#12
J-B Noury, F Zagnoli, J-L Carré, I Drouillard, F Petit, C Le Maréchal, P Marcorelles, F Rannou
OBJECTIVE: As exercise intolerance and exercise-induced myalgia are commonly encountered in metabolic myopathies, functional screening tests are commonly used during the diagnostic work-up. Our objective was to evaluate the accuracy of isometric handgrip test (IHT) and progressive cycle ergometer test (PCET) to identify McArdle disease and myoadenylate deaminase (MAD) deficiency and to propose diagnostic algorithms using exercise-induced lactate and ammonia variations. METHODS: A prospective sample of 46 patients underwent an IHT and a PCET as part of their exercise-induced myalgia and intolerance evaluation...
May 10, 2018: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/29747747/tiger-nut-and-walnut-extracts-modulate-extracellular-metabolism-of-atp-and-adenosine-through-the-nos-cgmp-pkg-signalling-pathway-in-kidney-slices
#13
Ayodeji A Olabiyi, Fabiano B Carvalho, Nathieli B Bottari, Vera M Morsch, Ademir F Morel, Ganiyu Oboh, Maria Rosa Schetinger
BACKGROUND: Tiger nut (Cyperus esculentus L.) and walnut (Tetracarpidium conophorum Müll. Arg.) have been reportedly used in the treatment of inflammatory diseases such as atherosclerosis, prevent heart attack and improve blood circulation, reduce serum cholesterol level as well as inhibit oxidation reactions. PURPOSE: This study investigated the effect of tiger nut and walnut hydro-alcoholic extracts on extracellular metabolism of ATP through the NOS/cGMP/PKG signaling pathway induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) in kidney slices...
April 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29746834/characterization-of-bk-polyomaviruses-from-kidney-transplant-recipients-suggests-a-role-for-apobec3-in-driving-in-host-virus-evolution
#14
Alberto Peretti, Eileen M Geoghegan, Diana V Pastrana, Sigrun Smola, Pascal Feld, Marlies Sauter, Stefan Lohse, Mayur Ramesh, Efrem S Lim, David Wang, Cinzia Borgogna, Peter C FitzGerald, Valery Bliskovsky, Gabriel J Starrett, Emily K Law, Reuben S Harris, J Keith Killian, Jack Zhu, Marbin Pineda, Paul S Meltzer, Renzo Boldorini, Marisa Gariglio, Christopher B Buck
BK polyomavirus (BKV) frequently causes nephropathy (BKVN) in kidney transplant recipients (KTRs). BKV has also been implicated in the etiology of bladder and kidney cancers. We characterized BKV variants from two KTRs who developed BKVN followed by renal carcinoma. Both patients showed a swarm of BKV sequence variants encoding non-silent mutations in surface loops of the viral major capsid protein. The temporal appearance and disappearance of these mutations highlights the intra-patient evolution of BKV. Some of the observed mutations conferred resistance to antibody-mediated neutralization...
May 9, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29746667/a-fluorescent-reporter-for-quantification-and-enrichment-of-dna-editing-by-apobec-cas9-or-cleavage-by-cas9-in-living-cells
#15
Amber St Martin, Daniel Salamango, Artur Serebrenik, Nadine Shaban, William L Brown, Francesco Donati, Uday Munagala, Silvestro G Conticello, Reuben S Harris
Base editing is an exciting new genome engineering technology. C-to-T mutations in genomic DNA have been achieved using ribonucleoprotein complexes comprised of rat APOBEC1 single-stranded DNA deaminase, Cas9 nickase (Cas9n), uracil DNA glycosylase inhibitor (UGI), and guide (g)RNA. Here, we report the first real-time reporter system for quantification of APOBEC-mediated base editing activity in living mammalian cells. The reporter expresses eGFP constitutively as a marker for transfection or transduction, and editing restores functionality of an upstream mCherry cassette through the simultaneous processing of two gRNA binding regions that each contain an APOBEC-preferred 5'TCA target site...
May 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29745882/the-adenosinergic-system-a-potential-player-in-the-pathogenesis-of-anca-associated-vasculitis
#16
REVIEW
Lovis Kling, Bernhard K Krämer, Benito A Yard, Anna-Isabelle Kälsch
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially lethal autoimmune disease whose pathology comprises disturbed T cell differentiation and functionality accompanied by dysfunctional autoreactive immunoglobulin development, culminating in destructive innate immune response as well. Purines, adenine nucleotides and adenosine in particular, have been elucidated as potent extracellular mediators for fine adjustment of these pivotal processes establishing human immunity. Therefore, the extracellular purinergic microenvironment is under control of ectonucleotidases CD39 and CD73 degrading pro-inflammatory adenosine triphosphate (ATP) to anti-inflammatory adenosine as well as adenosine deaminase bound to CD26 deactivating adenosine...
May 3, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29744787/ada-deficiency-evaluation-of-the-clinical-and-laboratory-features-and-the-outcome
#17
Deniz Cagdas, Pınar Gur Cetinkaya, Betül Karaatmaca, Saliha Esenboga, Cagman Tan, Togay Yılmaz, Ersin Gümüş, Safa Barış, Barış Kuşkonmaz, Tuba Turul Ozgur, Pawan Bali, Ines Santisteban, Diclehan Orhan, Aysel Yüce, Duygu Cetinkaya, Kaan Boztug, Michael Hershfield, Ozden Sanal, İlhan Tezcan
INTRODUCTION: Adenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. The aim of this study was to evaluate the outcome of 13 ADA-deficient patients. We planned to evaluate their clinical and laboratory findings before and after enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (aHSCT), and hematopoietic stem cell gene therapy (HSCGT)...
May 9, 2018: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29744038/generating-and-repairing-genetically-programmed-dna-breaks-during-immunoglobulin-class-switch-recombination
#18
REVIEW
Laura Nicolas, Montserrat Cols, Jee Eun Choi, Jayanta Chaudhuri, Bao Vuong
Adaptive immune responses require the generation of a diverse repertoire of immunoglobulins (Igs) that can recognize and neutralize a seemingly infinite number of antigens. V(D)J recombination creates the primary Ig repertoire, which subsequently is modified by somatic hypermutation (SHM) and class switch recombination (CSR). SHM promotes Ig affinity maturation whereas CSR alters the effector function of the Ig. Both SHM and CSR require activation-induced cytidine deaminase (AID) to produce dU:dG mismatches in the Ig locus that are transformed into untemplated mutations in variable coding segments during SHM or DNA double-strand breaks (DSBs) in switch regions during CSR...
2018: F1000Research
https://www.readbyqxmd.com/read/29743394/-cerebrospinal-fluid-findings-in-chronic-active-epstein-barr-virus-infection-with-central-nervous-system-involvement
#19
Mayumi Yoshimori, Ken-Ichi Imadome, Shohei Tomii, Kouhei Yamamoto, Osamu Miura, Ayako Arai
As chronic active Epstein-Barr virus (EBV) infection (CAEBV) progresses, EBV-infected tumor cells invade the central nervous system (CNS). To establish a diagnostic procedure for CNS invasion, we retrospectively analyzed cerebrospinal fluid (CSF) obtained from eight patients. Two patients presented with consciousness disturbance and were diagnosed with CNS invasion based on scan and autopsy results, respectively. The remaining six patients were diagnosed without CNS invasion by clinical findings and scans. In the two patients with CNS invasion, the number of mononuclear cells and the protein concentration were increased, whereas the CSF to serum glucose ratio and the adenosine deaminase concentration were raised...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29743315/an-unmutated-igm-response-to-the-vi-polysaccharide-of-salmonella-typhi-contributes-to-protective-immunity-in-a-murine-model-of-typhoid
#20
Kalgi D Pandya, Isabel Palomo-Caturla, Justin A Walker, Vijay K Sandilya, Zhijiu Zhong, Kishore R Alugupalli
T cell-dependent B cell responses typically develop in germinal centers. Abs generated during such responses are isotype switched and have a high affinity to the Ag because of somatic hypermutation of Ab genes. B cell responses to purified polysaccharides are T cell independent and do not result in the formation of bona fide germinal centers, and the dominant Ab isotype produced during such responses is IgM with very few or no somatic mutations. Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and Ig isotype switching in humans and mice...
May 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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