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https://www.readbyqxmd.com/read/28089597/magnesium-and-calcium-ions-differentially-affect-human-serine-racemase-activity-and-modulate-its-quaternary-equilibrium-toward-a-tetrameric-form
#1
Stefano Bruno, Marilena Margiotta, Francesco Marchesani, Gianluca Paredi, Valentina Orlandi, Serena Faggiano, Luca Ronda, Barbara Campanini, Andrea Mozzarelli
Serine racemase is the pyridoxal 5'-phosphate dependent enzyme that catalyzes both production and catabolism of d-serine, a co-agonist of the NMDA glutamate receptors. Mg(2+), or, alternatively, Ca(2+), activate human serine racemase by binding both at a specific site and - as ATP-metal complexes - at a distinct ATP binding site. We show that Mg(2+) and Ca(2+) bind at the metal binding site with a 4.5-fold difference in affinity, producing a similar thermal stabilization and partially shifting the dimer-tetramer equilibrium in favour of the latter...
January 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088785/the-igh-locus-3-cis-regulatory-super-enhancer-co-opts-aid-for-allelic-transvection
#2
Sandrine Le Noir, Brice Laffleur, Claire Carrion, Armand Garot, Sandrine Lecardeur, Eric Pinaud, Yves Denizot, Jane Skok, Michel Cogné
Immunoglobulin heavy chain (IgH) alleles have ambivalent relationships: they feature both allelic exclusion, ensuring monoallelic expression of a single immunoglobulin (Ig) allele, and frequent inter-allelic class-switch recombination (CSR) reassembling genes from both alleles. The IgH locus 3' regulatory region (3'RR) includes several transcriptional cis-enhancers promoting activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM) and CSR, and altogether behaves as a strong super-enhancer...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28087698/inhibition-of-trpml1-by-lysosomal-adenosine-involved-in-severe-combined-immunodeficiency-diseases
#3
Xi Zoë Zhong, Yuanjie Zou, Xue Sun, Gaofeng Dong, Qi Cao, Aditya Pandey, Jan K Rainey, Xiaojuan Zhu, Xian-Ping Dong
Impaired adenosine homeostasis has been associated with numerous human diseases. Lysosomes are referred to as the cellular recycling centers which generate adenosine by breaking down nucleic acids or ATP. Recent studies have suggested that lysosomal adenosine overload causes lysosome defects which phenocopy patients with mutations in TRPML1, a lysosomal Ca2+ channel, suggesting that lysosomal adenosine overload may impair TRPML1 and then lead to subsequent lysosomal dysfunction. In this study, we demonstrate that lysosomal adenosine is elevated by deleting adenosine deaminase (ADA), an enzyme responsible for adenosine degradation...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28077648/human-papillomavirus-16-e6-up-regulates-apobec3b-via-the-tead-transcription-factor
#4
Seiichiro Mori, Takamasa Takeuchi, Yoshiyuki Ishii, Takashi Yugawa, Tohru Kiyono, Hiroshi Nishina, Iwao Kukimoto
: The cytidine deaminase APOBEC3B (A3B) underlies the genetic heterogeneity of several human cancers including cervical cancer, which is caused by human papillomavirus (HPV) infection. We previously identified a region within the A3B promoter that is activated by the viral protein HPV16 E6 in human keratinocytes. Here, we discovered three sites recognized by the TEAD family of transcription factors within this region of the A3B promoter. Reporter assays in HEK293 cells showed that exogenously expressed TEAD4 induced A3B promoter activation through binding to these sites...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077417/aid-is-a-key-regulator-of-myeloid-erythroid-differentiation-and-dna-methylation-in-hematopoietic-stem-progenitor-cells
#5
Hiroyoshi Kunimoto, Anna Sophia McKenney, Cem Meydan, Kaitlyn Shank, Abbas Nazir, Franck Rapaport, Benjamin Durham, Francine E Garrett-Bakelman, Elodie Pronier, Alan H Shih, Ari Melnick, Jayanta Chaudhuri, Ross L Levine
Recent studies have reported activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 occur in myeloid malignancies and hematopoietic specific loss of Tet2 induces aberrant hematopoietic stem cell (HSC) self-renewal/differentiation, implicating TET2 as a master regulator of normal and malignant hematopoiesis. Despite the functional link between AID and TET in epigenetic gene regulation, the role of AID loss in hematopoiesis and myeloid transformation remains to be investigated...
January 11, 2017: Blood
https://www.readbyqxmd.com/read/28074903/alterations-in-the-brain-adenosine-metabolism-cause-behavioral-and-neurological-impairment-in-ada-deficient-mice-and-patients
#6
Aisha V Sauer, Raisa Jofra Hernandez, Francesca Fumagalli, Veronica Bianchi, Pietro L Poliani, Chiara Dallatomasina, Elisa Riboni, Letterio S Politi, Antonella Tabucchi, Filippo Carlucci, Miriam Casiraghi, Nicola Carriglio, Manuela Cominelli, Carlo Alberto Forcellini, Federica Barzaghi, Francesca Ferrua, Fabio Minicucci, Stefania Medaglini, Letizia Leocani, Giancarlo la Marca, Lucia D Notarangelo, Chiara Azzari, Giancarlo Comi, Cristina Baldoli, Sabrina Canale, Maria Sessa, Patrizia D'Adamo, Alessandro Aiuti
Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073404/isolation-and-characterization-of-hiv-1-envelope-glycoprotein-specific-b-cell-from-immortalized-human-na%C3%A3-ve-b-cell-library
#7
Zehua Sun, Shiqiang Lu, Zheng Yang, Jingjing Li, Meiyun Zhang
With the recent development of single B cell cloning techniques, an increasing number of HIV-1-specific broadly neutralizing antibodies (bNAbs) have been isolated since 2009. However, knowledge regarding HIV-1-specific B cells in vivo is limited. In this study, an HIV-1-specific B cell line has been established using healthy PBMC donors by the highly efficient EBV transformation method to generate immortalized human naïve B cell libraries. The enrichment of HIV-1 envelope-specific B cells was observed after four rounds of cell panning with the HIV-1 envelope glycoprotein...
January 10, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28069759/correction-regulation-of-adenosine-deaminase-on-induced-mouse-experimental-autoimmune-uveitis
#8
Dongchun Liang, Aijun Zuo, Ronglan Zhao, Hui Shao, Henry J Kaplan, Deming Sun
No abstract text is available yet for this article.
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28069372/rna-exosome-and-non-coding-rna-coupled-mechanisms-in-aid-mediated-genomic-alterations
#9
REVIEW
Brice Laffleur, Uttiya Basu, Junghyun Lim
The eukaryotic RNA exosome is a well-conserved protein complex with ribonuclease activity implicated in RNA metabolism. Various families of non-coding RNAs have been identified as substrates of the complex, underscoring its role as a non-coding RNA processing/degradation unit. However, the role of RNA exosome and its RNA processing activity on DNA mutagenesis/alteration events have not been investigated until recently. B lymphocytes use two DNA alteration mechanisms, class switch recombination (CSR) and somatic hypermutation (SHM), to re-engineer their antibody gene expressing loci until a tailored antibody gene for a specific antigen is satisfactorily generated...
January 6, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28065739/r-loop-depletion-by-over-expressed-rnase-h1-in-mouse-b-cells-increases-activation-induced-deaminase-access-to-the-transcribed-strand-without-altering-frequency-of-isotype-switching
#10
Robert W Maul, Hyongi Chon, Kiran Sakhuja, Susana M Cerritelli, Lina A Gugliotti, Patricia J Gearhart, Robert J Crouch
R-loops, three-strand structures consisting of mRNA hybridized to the complementary DNA and a single-stranded DNA loop, are formed in switch regions on the heavy-chain immunoglobulin locus. To determine if R-loops have a direct effect on any of the steps involved in isotype switching, we generated a transgenic mouse that over-expressed RNase H1, an enzyme that cleaves the RNA of RNA/DNA hybrids in B cells. R-loops in the switch μ region were depleted by 70% in ex vivo activated splenic B cells. Frequencies of isotype switching to IgG1, IgG2b, IgG2c, and IgG3 were the same as C57BL/6 control cells...
January 6, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28063995/activation-of-tnf-%C3%AE-aid-axis-and-co-inhibitory-signals-in-coordination-with-th1-type-immunity-in-a-mouse-model-recapitulating-hepatitis-b
#11
Tomonori Matsumoto, Ken Takahashi, Tadashi Inuzuka, Soo Ki Kim, Tomoaki Kurosaki, Shigeru Kawakami, Tsutomu Chiba, Hiroshi Seno, Hiroyuki Marusawa
Hepatitis B virus (HBV) infection evokes host immune responses that primarily determine the outcome of HBV infection and the clinical features of HBV-associated liver disease. The precise mechanisms by which host factors restrict HBV replication, however, are poorly understood due to the lack of useful animal models that recapitulate immune responses to HBV. Here, we performed comprehensive immunologic gene expression profiling of the liver of a mouse model recapitulating anti-HBV immune response using a high sensitivity direct digital counting system...
January 5, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28057604/biological-markers-in-the-diagnosis-of-tuberculous-pleural-effusion
#12
Bastien Mollo, Stéphane Jouveshomme, François Philippart, Benoît Pilmis
Tuberculosis is one of the main etiologies to evoke in the context of lymphocyte pleurisy. However, diagnosis is difficult and is based on mycobacteriology that is not enough sensitive and time-consuming, or on histology that requires invasive biopsy gesture. This literature review, carried out from Medline, summarizes the main meta-analyzes, reviews, and originator publications in English on biomarkers, classic and more innovative, studied for the diagnosis of tuberculous pleurisy. Among the immuno-biochemical markers, interferon-γ (IFN-γ), isoenzyme of adenosine deaminase 2 (ADA2) and total adenosine deaminase (ADA) seem the most relevant with respective sensitivities of 89% (87-91), 97...
January 5, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/28053137/activation-of-cecr1-in-m2-like-tams-promotes-paracrine-stimulation-mediated-glial-tumor-progression
#13
Changbin Zhu, Dana Mustafa, Ping-Pin Zheng, Marcel van der Weiden, Andrea Sacchetti, Maarten Brandt, Ihsan Chrifi, Dennie Tempel, Pieter J M Leenen, Dirk Jan Duncker, Caroline Cheng, Johan M Kros
BACKGROUND: The majority of glioma-associated microglia/macrophages have been identified as M2-type macrophages with immune suppressive and tumor supportive action. Recently, the extracellular adenosine deaminase protein Cat Eye Syndrome Critical Region Protein 1 (CECR1) was shown to regulate macrophage maturation. In this study, we investigate the role of CECR1 in the regulation of the glioma-associated macrophage response. METHODS: Expression of CECR1 was assessed in human glioma samples...
January 3, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28053121/adar2-regulates-rna-stability-by-modifying-access-of-decay-promoting-rna-binding-proteins
#14
Aparna Anantharaman, Vidisha Tripathi, Abid Khan, Je-Hyun Yoon, Deepak K Singh, Omid Gholamalamdari, Shuomeng Guang, Johan Ohlson, Helene Wahlstedt, Marie Öhman, Michael F Jantsch, Nicholas K Conrad, Jian Ma, Myriam Gorospe, Supriya G Prasanth, Kannanganattu V Prasanth
Adenosine deaminases acting on RNA (ADARs) catalyze the editing of adenosine residues to inosine (A-to-I) within RNA sequences, mostly in the introns and UTRs (un-translated regions). The significance of editing within non-coding regions of RNA is poorly understood. Here, we demonstrate that association of ADAR2 with RNA stabilizes a subset of transcripts. ADAR2 interacts with and edits the 3'UTR of nuclear-retained Cat2 transcribed nuclear RNA (Ctn RNA). In absence of ADAR2, the abundance and half-life of Ctn RNA are significantly reduced...
January 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28052578/ticagrelor-increased-adenosine-and-cyclic-adenosine-monophosphate-plasma-concentration-compared-with-clopidogrel-in-acute-coronary-syndromes-patients
#15
Xiao-Ye Li, Qi-Bing Wang, Ying Xue, Jia-Hui Chen, Qian-Zhou Lv
Ticagrelor produces a more potent antiplatelet effect than clopidogrel, and inhibits cellular uptake of adenosine, which is associated with several cardiovascular consequences. We aimed to explore the correlation between adenosine and cyclic adenosine monophosphate (cAMP) plasma concentration and antiplatelet effect by clopidogrel or ticagrelor in acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT). We conducted a prospective, observational and single-centre cohort study enrolling 68 patients with non-ST-segment elevation ACS from January 2016 to May 2016...
January 4, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28049429/jacusa-site-specific-identification-of-rna-editing-events-from-replicate-sequencing-data
#16
Michael Piechotta, Emanuel Wyler, Uwe Ohler, Markus Landthaler, Christoph Dieterich
BACKGROUND: RNA editing is a co-transcriptional modification that increases the molecular diversity, alters secondary structure and protein coding sequences by changing the sequence of transcripts. The most common RNA editing modification is the single base substitution (A→I) that is catalyzed by the members of the Adenosine deaminases that act on RNA (ADAR) family. Typically, editing sites are identified as RNA-DNA-differences (RDDs) in a comparison of genome and transcriptome data from next-generation sequencing experiments...
January 3, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28045133/calpain-dependent-disruption-of-nucleo-cytoplasmic-transport-in-als-motor-neurons
#17
Takenari Yamashita, Hitoshi Aizawa, Sayaka Teramoto, Megumi Akamatsu, Shin Kwak
Nuclear dysfunction in motor neurons has been hypothesized to be a principal cause of amyotrophic lateral sclerosis (ALS) pathogenesis. Here, we investigated the mechanism by which the nuclear pore complex (NPC) is disrupted in dying motor neurons in a mechanistic ALS mouse model (adenosine deaminase acting on RNA 2 (ADAR2) conditional knockout (AR2) mice) and in ALS patients. We showed that nucleoporins (Nups) that constituted the NPC were cleaved by activated calpain via a Ca(2+)-permeable AMPA receptor-mediated mechanism in dying motor neurons lacking ADAR2 expression in AR2 mice...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28043538/murine-model-of-tb-meningitis
#18
Umesh Datta Gupta, Ali Abbas, Raj Pal Singh Kashyap, Pushpa Gupta
BACKGROUND: Central nervous system (CNS) infections caused by Mycobacterium tuberculosis (MTB) are the most severe forms of extrapulmonary TB (EPTB) due to high levels of mortality and neurological morbidity. Limited studies are available on CNS-TB animal-model development, despite the steady rise in cerebral-TB cases in India over the past decade. This study describes the development of a murine model of CNS-TB using a clinical strain (C3) isolated from the cerebrospinal fluid (CSF) of CNS-TB patients...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28040796/role-of-rpl39-in-metaplastic-breast-cancer
#19
Bhuvanesh Dave, Daniel D Gonzalez, Zhi-Bin Liu, Xiaoxian Li, Helen Wong, Sergio Granados, Nadeer E Ezzedine, Douglas H Sieglaff, Joe E Ensor, Kathy D Miller, Milan Radovich, Agda KarinaEtrovic, Steven S Gross, Olivier Elemento, Gordon B Mills, Michael Z Gilcrease, Jenny C Chang
BACKGROUND: Metaplastic breast cancer is one of the most therapeutically challenging forms of breast cancer because of its highly heterogeneous and chemoresistant nature. We have previously demonstrated that ribosomal protein L39 (RPL39) and its gain-of-function mutation A14V have oncogenic activity in triple-negative breast cancer and this activity may be mediated through inducible nitric oxide synthase (iNOS). The function of RPL39 and A14V in other breast cancer subtypes is currently unknown...
June 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28036052/sugar-allocation-to-metabolic-pathways-is-tightly-regulated-and-affects-the-virulence-of-streptococcus-mutans
#20
REVIEW
Miki Kawada-Matsuo, Yuichi Oogai, Hitoshi Komatsuzawa
Bacteria take up and metabolize sugar as a carbohydrate source for survival. Most bacteria can utilize many sugars, including glucose, sucrose, and galactose, as well as amino sugars, such as glucosamine and N-acetylglucosamine. After entering the cytoplasm, the sugars are mainly allocated to the glycolysis pathway (energy production) and to various bacterial component biosynthesis pathways, including the cell wall, nucleic acids and amino acids. Sugars are also utilized to produce several virulence factors, such as capsule and lipoteichoic acid...
December 28, 2016: Genes
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