73 results match your criteria conserved charging

Detection and quantification of glycosylated queuosine modified tRNAs by acid denaturing and APB gels.

RNA 2020 09 21;26(9):1291-1298. Epub 2020 May 21.

Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA.

Queuosine (Q) is a conserved tRNA modification in bacteria and eukaryotes. Eukaryotic Q-tRNA modification occurs through replacing the guanine base with the scavenged metabolite queuine at the wobble position of tRNAs with UN anticodon (Tyr, His, Asn, Asp) by the QTRT1/QTRT2 heterodimeric enzyme encoded in the genome. In humans, Q-modification in tRNA and tRNA are further glycosylated with galactose and mannose, respectively. Read More

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September 2020

Crystal structure of the Schizosaccharomyces pombe U7BR E2-binding region in complex with Ubc7.

Acta Crystallogr F Struct Biol Commun 2019 Aug 2;75(Pt 8):552-560. Epub 2019 Aug 2.

Structural Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.

Endoplasmic reticulum (ER)-associated degradation (ERAD) is a protein quality-control pathway in eukaryotes in which misfolded ER proteins are polyubiquitylated, extracted and ultimately degraded by the proteasome. This process involves ER membrane-embedded ubiquitin E2 and E3 enzymes, as well as a soluble E2 enzyme (Ubc7 in Saccharomyces cerevisiae and UBE2G2 in mammals). E2-binding regions (E2BRs) that recruit these soluble ERAD E2s to the ER have been identified in humans and S. Read More

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Mutations in a conserved loop in the PSST subunit of respiratory complex I affect ubiquinone binding and dynamics.

Biochim Biophys Acta Bioenerg 2019 07 19;1860(7):573-581. Epub 2019 Jun 19.

Structural Bioenergetics Group, Institute of Biochemistry II, Medical School, Goethe-University, Frankfurt am Main, Germany; Centre for Biomolecular Magnetic Resonance, Institute for Biophysical Chemistry, University of Frankfurt, Frankfurt am Main, Germany; Cluster of Excellence Frankfurt "Macromolecular Complexes", Goethe-University, Frankfurt am Main, Germany. Electronic address:

Respiratory complex I catalyses the reduction of ubiquinone (Q) from NADH coupled to proton pumping across the inner membrane of mitochondria. The electrical charging of the inner mitochondrial membrane drives the synthesis of ATP, which is used to power biochemical reactions of the cell. The recent surge in structural data on complex I from bacteria and mitochondria have contributed to significant understanding of its molecular architecture. Read More

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Serine-Threonine Kinases Encoded by Split Homologs Inhibit Tryptophanyl-tRNA Synthetase.

mBio 2019 06 18;10(3). Epub 2019 Jun 18.

Centre for Bacterial Stress Response and Persistence, Section for Functional Genomics, Department of Biology, University of Copenhagen, Copenhagen, Denmark

Type II toxin-antitoxin (TA) modules encode a stable toxin that inhibits cell growth and an unstable protein antitoxin that neutralizes the toxin by direct protein-protein contact. of strain K-12 codes for HipA, a serine-threonine kinase that phosphorylates and inhibits glutamyl-tRNA synthetase. Induction of inhibits charging of glutamyl-tRNA that, in turn, inhibits translation and induces RelA-dependent (p)ppGpp synthesis and multidrug tolerance. Read More

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Metabolic models and gene essentiality data reveal essential and conserved metabolism in prokaryotes.

PLoS Comput Biol 2018 11 16;14(11):e1006556. Epub 2018 Nov 16.

Department of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal.

Essential metabolic reactions are shaping constituents of metabolic networks, enabling viable and distinct phenotypes across diverse life forms. Here we analyse and compare modelling predictions of essential metabolic functions with experimental data and thereby identify core metabolic pathways in prokaryotes. Simulations of 15 manually curated genome-scale metabolic models were integrated with 36 large-scale gene essentiality datasets encompassing a wide variety of species of bacteria and archaea. Read More

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November 2018

Expanding the clinical phenotype of IARS2-related mitochondrial disease.

BMC Med Genet 2018 11 12;19(1):196. Epub 2018 Nov 12.

Genetics and Molecular Cell Sciences Research Centre, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.

Background: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies. Read More

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November 2018

Translational Control through Differential Ribosome Pausing during Amino Acid Limitation in Mammalian Cells.

Mol Cell 2018 07;71(2):229-243.e11

Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology and Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address:

Limitation for amino acids is thought to regulate translation in mammalian cells primarily by signaling through the kinases mTORC1 and GCN2. We find that a selective loss of arginine tRNA charging during limitation for arginine regulates translation through ribosome pausing at two of six arginine codons. Surprisingly, limitation for leucine, an essential and abundant amino acid in protein, results in little or no ribosome pausing. Read More

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Structural basis of actin monomer re-charging by cyclase-associated protein.

Nat Commun 2018 05 14;9(1):1892. Epub 2018 May 14.

Institute of Biotechnology, University of Helsinki, 00014, Helsinki, Finland.

Actin polymerization powers key cellular processes, including motility, morphogenesis, and endocytosis. The actin turnover cycle depends critically on "re-charging" of ADP-actin monomers with ATP, but whether this reaction requires dedicated proteins in cells, and the underlying mechanism, have remained elusive. Here we report that nucleotide exchange catalyzed by the ubiquitous cytoskeletal regulator cyclase-associated protein (CAP) is critical for actin-based processes in vivo. Read More

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Two P-ATPases of With Distinct Properties in Cu/Ag Transport.

Front Microbiol 2018 23;9:747. Epub 2018 Apr 23.

Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Prague, Czechia.

As we have shown previously, the Cu and Ag concentrations in the sporocarps of Ag-hyperaccumulating are correlated, and both metals share the same uptake system and are sequestered by the same metallothioneins intracellularly. To further improve our knowledge of the Cu and Ag handling in cells, we searched its transcriptome for the P-ATPases, recognizing Cu and Ag for transport. We identified transcripts encoding 1097-amino acid (AA) AsCRD1 and 978-AA AsCCC2, which were further subjected to functional studies in metal sensitive . Read More

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Aminoacyl-tRNA synthetase evolution and sectoring of the genetic code.

Transcription 2018 30;9(4):205-224. Epub 2018 May 30.

c Department of Biochemistry and Molecular Biology , Michigan State University , 603 Wilson Rd, E. Lansing , MI 48824-1319, USA.

The genetic code sectored via tRNA charging errors, and the code progressed toward closure and universality because of evolution of aminoacyl-tRNA synthetase (aaRS) fidelity and translational fidelity mechanisms. Class I and class II aaRS folds are identified as homologs. From sequence alignments, a structurally conserved Zn-binding domain common to class I and class II aaRS was identified. Read More

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October 2018

Expression Pattern of the Aspartyl-tRNA Synthetase DARS in the Human Brain.

Front Mol Neurosci 2018 20;11:81. Epub 2018 Mar 20.

Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.

Translation of mRNA into protein is an evolutionarily conserved, fundamental process of life. A prerequisite for translation is the accurate charging of tRNAs with their cognate amino acids, a reaction catalyzed by specific aminoacyl-tRNA synthetases. One of these enzymes is the aspartyl-tRNA synthetase DARS, which pairs aspartate with its corresponding tRNA. Read More

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Lack of 2'-O-methylation in the tRNA anticodon loop of two phylogenetically distant yeast species activates the general amino acid control pathway.

PLoS Genet 2018 03 29;14(3):e1007288. Epub 2018 Mar 29.

Department of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester School of Medicine, Rochester, NY, United States of America.

Modification defects in the tRNA anticodon loop often impair yeast growth and cause human disease. In the budding yeast Saccharomyces cerevisiae and the phylogenetically distant fission yeast Schizosaccharomyces pombe, trm7Δ mutants grow poorly due to lack of 2'-O-methylation of C32 and G34 in the tRNAPhe anticodon loop, and lesions in the human TRM7 homolog FTSJ1 cause non-syndromic X-linked intellectual disability (NSXLID). However, it is unclear why trm7Δ mutants grow poorly. Read More

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New tRNA contacts facilitate ligand binding in a T box riboswitch.

Proc Natl Acad Sci U S A 2018 04 26;115(15):3894-3899. Epub 2018 Mar 26.

Molecular, Cellular, and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210;

T box riboswitches are RNA regulatory elements widely used by organisms in the phyla Firmicutes and Actinobacteria to regulate expression of amino acid-related genes. Expression of T box family genes is down-regulated by transcription attenuation or inhibition of translation initiation in response to increased charging of the cognate tRNA. Three direct contacts with tRNA have been described; however, one of these contacts is absent in a subclass of T box RNAs and the roles of several structural domains conserved in most T box RNAs are unknown. Read More

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Charging nanoparticles: increased binding of Gd@C(OH) derivatives to human MMP-9.

Nanoscale 2018 Mar 12;10(12):5667-5677. Epub 2018 Mar 12.

Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA and Department of Chemistry, Columbia University, New York, NY 10027, USA.

Unlike most matrix metalloproteinase (MMP) inhibitors, which target the conserved catalytic zinc site, Gd@C(OH) indirectly inhibits MMP-9 activity by binding at the ligand specificity S1' loop. The allosteric binding makes Gd@C(OH) a promising inhibitor selective for MMP-9. However, the hydrophobic nature of the aromatic carbon cage may cause Gd@C(OH) to self-aggregate in aqueous solutions, hence weakening the binding. Read More

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Consequences of Spin-Orbit Coupling at the Single Hole Level: Spin-Flip Tunneling and the Anisotropic g Factor.

Phys Rev Lett 2017 Apr 20;118(16):167701. Epub 2017 Apr 20.

Sandia National Laboratories, Albuquerque, New Mexico 87185, USA.

Hole transport experiments were performed on a gated double quantum dot device defined in a p-GaAs/AlGaAs heterostructure with a single hole occupancy in each dot. The charging diagram of the device was mapped out using charge detection confirming that the single hole limit is reached. In that limit, a detailed study of the two-hole spin system was performed using high bias magnetotransport spectroscopy. Read More

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Mistranslation: from adaptations to applications.

Biochim Biophys Acta Gen Subj 2017 Nov 30;1861(11 Pt B):3070-3080. Epub 2017 Jan 30.

Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada. Electronic address:

Background: The conservation of the genetic code indicates that there was a single origin, but like all genetic material, the cell's interpretation of the code is subject to evolutionary pressure. Single nucleotide variations in tRNA sequences can modulate codon assignments by altering codon-anticodon pairing or tRNA charging. Either can increase translation errors and even change the code. Read More

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November 2017

Mechanism of catalysis, E2 recognition, and autoinhibition for the IpaH family of bacterial E3 ubiquitin ligases.

Proc Natl Acad Sci U S A 2017 02 23;114(6):1311-1316. Epub 2017 Jan 23.

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5;

IpaH enzymes are secreted bacterial effectors that function within host cells as E3 ubiquitin (Ub) ligases. Catalytic activity is imparted by a conserved novel E3 ligase (NEL) domain that is unique to Gram-negative pathogens and whose activity is repressed by a flanking substrate-binding leucine-rich repeat (LRR) domain when substrate is absent. How the NEL domain catalyzes the conjugation of Ub onto substrates, recognizes host E2s, and maintains its autoinhibited state remain poorly understood. Read More

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February 2017

Maf1-mediated regulation of yeast RNA polymerase III is correlated with CCA addition at the 3' end of tRNA precursors.

Gene 2017 May 27;612:12-18. Epub 2016 Aug 27.

Department of Genetics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warsaw, Poland. Electronic address:

In eukaryotic cells tRNA synthesis is negatively regulated by the protein Maf1, conserved from yeast to humans. Maf1 from yeast Saccharomyces cerevisiae mediates repression of trna transcription when cells are transferred from medium with glucose to medium with glycerol, a non-fermentable carbon source. The strain with deleted gene encoding Maf1 (maf1Δ) is viable but accumulates tRNA precursors. Read More

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Aminoacyl-tRNA Synthetases in the Bacterial World.

EcoSal Plus 2016 05;7(1)

Université Paris Diderot, Sorbonne Cité, UPR9073 CNRS, IBPC, 75005 Paris, France.

Aminoacyl-tRNA synthetases (aaRSs) are modular enzymes globally conserved in the three kingdoms of life. All catalyze the same two-step reaction, i.e. Read More

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Degenerate connective polypeptide 1 (CP1) domain from human mitochondrial leucyl-tRNA synthetase.

J Biol Chem 2015 Oct 13;290(40):24391-402. Epub 2015 Aug 13.

From the State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, the Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai and the School of Life Science and Technology, ShanghaiTech University, 319 Yue Yang Road, Shanghai 200031, China

The connective polypeptide 1 (CP1) editing domain of leucyl-tRNA synthetase (LeuRS) from various species either harbors a conserved active site to exclude tRNA mis-charging with noncognate amino acids or is evolutionarily truncated or lost because there is no requirement for high translational fidelity. However, human mitochondrial LeuRS (hmtLeuRS) contains a full-length but degenerate CP1 domain that has mutations in some residues important for post-transfer editing. The significance of such an inactive CP1 domain and a translational accuracy mechanism with different noncognate amino acids are not completely understood. Read More

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October 2015

A conserved proline triplet in Val-tRNA synthetase and the origin of elongation factor P.

Cell Rep 2014 Oct 9;9(2):476-83. Epub 2014 Oct 9.

Gene Center and Department for Biochemistry, University of Munich, Feodor-Lynen-Straße 25, 81377 Munich, Germany; Center for Integrated Protein Science Munich (CiPSM) at the University of Munich, 80539 Munich, Germany. Electronic address:

Bacterial ribosomes stall on polyproline stretches and require the elongation factor P (EF-P) to relieve the arrest. Yet it remains unclear why evolution has favored the development of EF-P rather than selecting against the occurrence of polyproline stretches in proteins. We have discovered that only a single polyproline stretch is invariant across all domains of life, namely a proline triplet in ValS, the tRNA synthetase, that charges tRNA(Val) with valine. Read More

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October 2014

Impaired function is a common feature of neuropathy-associated glycyl-tRNA synthetase mutations.

Hum Mutat 2014 Nov;35(11):1363-71

Cellular and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, Michigan; Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, Michigan.

Charcot-Marie-Tooth disease type 2D (CMT2D) is an autosomal-dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D. GARS is a member of the ubiquitously expressed aminoacyl-tRNA synthetase (ARS) family and is responsible for charging tRNA with glycine. Read More

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November 2014

Rotor stability separates sustained ventricular fibrillation from self-terminating episodes in humans.

J Am Coll Cardiol 2014 Jun 30;63(24):2712-21. Epub 2014 Apr 30.

University of California San Diego, San Diego, California; Veterans Affairs San Diego Healthcare System, San Diego, California.

Objectives: This study mapped human ventricular fibrillation (VF) to define mechanistic differences between episodes requiring defibrillation versus those that spontaneously terminate.

Background: VF is a leading cause of mortality; yet, episodes may also self-terminate. We hypothesized that the initial maintenance of human VF is dependent upon the formation and stability of VF rotors. Read More

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Charging of graphene by a magnetic field and the mechanical effect of magnetic oscillations.

J Phys Condens Matter 2013 Dec 6;25(49):496007. Epub 2013 Nov 6.

Department of Physics, Loughborough University, Loughborough LE11 3TU, UK. Petersburg Nuclear Physics Institute, Russia.

We discuss the fact that the quantum capacitance of graphene-based devices leads to variation of graphene charge density under changes of external magnetic field. The charge is conserved, but redistributes to the substrate or other graphene sheets. We derive an exact analytic expression for charge redistribution in the case of ideal graphene in a strong magnetic field. Read More

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December 2013

Leucine-specific domain modulates the aminoacylation and proofreading functional cycle of bacterial leucyl-tRNA synthetase.

Nucleic Acids Res 2013 May 21;41(9):4988-98. Epub 2013 Mar 21.

State Key Laboratory of Molecular Biology, Center for RNA Research, Institute of Biochemistry and Cell Biology, the Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, PR China.

The leucine-specific domain (LSD) is a compact well-ordered module that participates in positioning of the conserved KMSKS catalytic loop in most leucyl-tRNA synthetases (LeuRSs). However, the LeuRS from Mycoplasma mobile (MmLeuRS) has a tetrapeptide GKDG instead of the LSD. Here, we show that the tetrapeptide GKDG can confer tRNA charging and post-transfer editing activity when transplanted into an inactive Escherichia coli LeuRS (EcLeuRS) that has had its LSD deleted. Read More

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Two novel mutations of GARS in Korean families with distal hereditary motor neuropathy type V.

J Peripher Nerv Syst 2012 Dec;17(4):418-21

Department of Biological Science, Kongju National University, Gongju, South Korea.

Glycyl-tRNA synthetase (GARS), which encodes the enzyme responsible for charging tRNA(Gly) with glycine in both the cytoplasm and mitochondria, is implicated to Charcot-Marie-Tooth disease 2D (CMT2D) and distal hereditary motor neuropathy type V (dHMN-V). We performed whole exome sequencing (WES) to identify the genetic defects in the two dHMN families. WES revealed several decades of non-synonymous variants in the CMT and aminoacyl-tRNA synthetase genes. Read More

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December 2012

Selection of tRNA charging quality control mechanisms that increase mistranslation of the genetic code.

Nucleic Acids Res 2013 Jan 6;41(2):1104-12. Epub 2012 Dec 6.

Department of Microbiology, Ohio State University, 484 West 12th Avenue, Columbus, OH 43210-1292, USA.

Mistranslation can follow two events during protein synthesis: production of non-cognate amino acid:transfer RNA (tRNA) pairs by aminoacyl-tRNA synthetases (aaRSs) and inaccurate selection of aminoacyl-tRNAs by the ribosome. Many aaRSs actively edit non-cognate amino acids, but editing mechanisms are not evolutionarily conserved, and their physiological significance remains unclear. To address the connection between aaRSs and mistranslation, the evolutionary divergence of tyrosine editing by phenylalanyl-tRNA synthetase (PheRS) was used as a model. Read More

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January 2013

Aminoacyl-tRNA Synthetases in the Bacterial World.

EcoSal Plus 2012 Nov;5(1)

Aminoacyl-tRNAsynthetases (aaRSs) are modular enzymesglobally conserved in the three kingdoms of life. All catalyze the same two-step reaction, i.e. Read More

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November 2012

Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy.

Hum Mol Genet 2012 Oct 23;21(20):4521-9. Epub 2012 Jul 23.

Research Programs Unit, Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, 00290 Helsinki, Finland.

Next-generation sequencing has turned out to be a powerful tool to uncover genetic basis of childhood mitochondrial disorders. We utilized whole-exome analysis and discovered novel compound heterozygous mutations in FARS2 (mitochondrial phenylalanyl transfer RNA synthetase), encoding the mitochondrial phenylalanyl transfer RNA (tRNA) synthetase (mtPheRS) in two patients with fatal epileptic mitochondrial encephalopathy. The mutations affected highly conserved amino acids, p. Read More

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October 2012

Loop 7 of E2 enzymes: an ancestral conserved functional motif involved in the E2-mediated steps of the ubiquitination cascade.

PLoS One 2012 18;7(7):e40786. Epub 2012 Jul 18.

Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.

The ubiquitin (Ub) system controls almost every aspect of eukaryotic cell biology. Protein ubiquitination depends on the sequential action of three classes of enzymes (E1, E2 and E3). E2 Ub-conjugating enzymes have a central role in the ubiquitination pathway, interacting with both E1 and E3, and influencing the ultimate fate of the substrates. Read More

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