9,249 results match your criteria truncated forms


Testosterone-induced increase in libido in a patient with a loss-of-function mutation in the AR gene.

Endocrinol Diabetes Metab Case Rep 2021 Jun 1;2021. Epub 2021 Jun 1.

Department of Service of Endocrinology, Diabetes, and Metabolism, Faculty of Biology and Medicine, University of Lausanne, Lausanne University Hospital, Lausanne, Vaud, Switzerland.

Summary: Complete androgen-insensitivity syndrome (CAIS), a disorder of sex development (46,XY DSD), is caused primarily by mutations in the androgen receptor (AR). Gonadectomy is recommended due to the increased risk of gonadoblastoma, however, surgical intervention is often followed by loss of libido. We present a 26-year-old patient with CAIS who underwent gonadectomy followed by a significant decrease in libido, which was improved with testosterone treatment but not with estradiol. Read More

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PB1-F2 amyloid-like fibers correlate with pro-inflammatory signaling and respiratory distress in influenza-infected mice.

J Biol Chem 2021 Jun 16:100885. Epub 2021 Jun 16.

Université Paris-Saclay, UVSQ, INRAE, VIM, 78350, Jouy-en-Josas, France. Electronic address:

PB1-F2 is a virulence factor of influenza A virus (IAV) known to increase viral pathogenicity in mammalian hosts. PB1-F2 is an intrinsically disordered protein displaying a propensity to form amyloid-like fibers. However, the correlation between PB1-F2 structures and the resulting inflammatory response is unknown. Read More

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Survival mediation analysis with the death-truncated mediator: The completeness of the survival mediation parameter.

Stat Med 2021 Jun 10. Epub 2021 Jun 10.

Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.

In medical research, the development of mediation analysis with a survival outcome has facilitated investigation into causal mechanisms. However, studies have not discussed the death-truncation problem for mediators, the problem being that conventional mediation parameters cannot be well defined in the presence of a truncated mediator. In the present study, we systematically defined the completeness of causal effects to uncover the gap, in conventional causal definitions, between the survival and nonsurvival settings. Read More

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RT-QuIC Using C-Terminally Truncated α-Synuclein Forms Detects Differences in Seeding Propensity of Different Brain Regions from Synucleinopathies.

Biomolecules 2021 May 31;11(6). Epub 2021 May 31.

Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha 974, Qatar.

Aggregated α-synuclein (αSyn) protein is a core pathological feature of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Both PD and DLB demonstrate the presence of diverse intracellular α-synuclein (αSyn) species, including C-terminally truncated αSyn (C-αSyn), although it is unknown how C-αSyn species contribute to disease progression. Using recombinant C-αSyn and PD and DLB brain lysates as seeds in the real-time quaking-induced conversion (RT-QuIC) assay, we explored how C-αSyn may be involved in disease stratification. Read More

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High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia.

Int J Mol Sci 2021 May 7;22(9). Epub 2021 May 7.

Department of Respiratory Medicine, Sendai City Hospital, Miyagi 982-8502, Japan.

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). Read More

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Sequence determinants of human junctophilin-2 protein nuclear localization and phase separation.

Biochem Biophys Res Commun 2021 Jul 29;563:79-84. Epub 2021 May 29.

Department of Pharmaceutical Sciences, North Dakota State University, 1401 Albrecht Blvd, Fargo, ND, 58102, USA.

Junctophilin-2 (JPH2) was conventionally considered as a structural membrane binding protein. Recently, it was shown that proteolytically truncated mouse JPH2 variants are imported into nucleus to exert alternative functions. However, the intranuclear behaviors of human JPH2 (hJPH2) and underlying molecular determinants have not been explored. Read More

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Structural modeling of a novel membrane-bound globin-coupled sensor in .

Comput Struct Biotechnol J 2021 26;19:1874-1888. Epub 2021 Mar 26.

Proteinchemistry, Proteomics and Epigenetic Signalling, Department of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Globin-coupled sensors (GCS) usually consist of three domains: a sensor/globin, a linker, and a transmitter domain. The globin domain (GD), activated by ligand binding and/or redox change, induces an intramolecular signal transduction resulting in a response of the transmitter domain. Depending on the nature of the transmitter domain, GCSs can have different activities and functions, including adenylate and di-guanylate cyclase, histidine kinase activity, aerotaxis and/or oxygen sensing function. Read More

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Crystal and solution structures reveal oligomerization of individual capsid homology domains of Drosophila Arc.

PLoS One 2021 14;16(5):e0251459. Epub 2021 May 14.

Department of Biomedicine, University of Bergen, Bergen, Norway.

Synaptic plasticity is vital for brain function and memory formation. One of the key proteins in long-term synaptic plasticity and memory is the activity-regulated cytoskeleton-associated protein (Arc). Mammalian Arc forms virus-like capsid structures in a process requiring the N-terminal domain and contains two C-terminal lobes that are structural homologues to retroviral capsids. Read More

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Glycosylation Regulates N-Terminal Proteolysis and Activity of the Chemokine CCL14.

ACS Chem Biol 2021 06 14;16(6):973-981. Epub 2021 May 14.

School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.

Chemokines are secreted proteins that regulate leukocyte migration during inflammatory responses by signaling through chemokine receptors. Full length CC chemokine ligand 14, CCL14(1-74), is a weak agonist for the chemokine receptor CCR1, but its activity is substantially enhanced upon proteolytic cleavage to CCL14(9-74). CCL14 is O-glycosylated at Ser7, adjacent to the site of proteolytic activation. Read More

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Calcium channelopathies and intellectual disability: a systematic review.

Orphanet J Rare Dis 2021 May 13;16(1):219. Epub 2021 May 13.

Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.

Background: Calcium ions are involved in several human cellular processes including corticogenesis, transcription, and synaptogenesis. Nevertheless, the relationship between calcium channelopathies (CCs) and intellectual disability (ID)/global developmental delay (GDD) has been poorly investigated. We hypothesised that CCs play a major role in the development of ID/GDD and that both gain- and loss-of-function variants of calcium channel genes can induce ID/GDD. Read More

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HBD1 protein with a tandem repeat of two HMG-box domains is a DNA clip to organize chloroplast nucleoids in .

Proc Natl Acad Sci U S A 2021 May;118(20)

Department of Botany, Graduate School of Science, Kyoto University, Kita-Shirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan;

Compaction of bulky DNA is a universal issue for all DNA-based life forms. Chloroplast nucleoids (chloroplast DNA-protein complexes) are critical for chloroplast DNA maintenance and transcription, thereby supporting photosynthesis, but their detailed structure remains enigmatic. Our proteomic analysis of chloroplast nucleoids of the green alga identified a protein (HBD1) with a tandem repeat of two DNA-binding high mobility group box (HMG-box) domains, which is structurally similar to major mitochondrial nucleoid proteins transcription factor A, mitochondrial (TFAM), and ARS binding factor 2 protein (Abf2p). Read More

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Structural and functional analysis of the MazEF toxin-antitoxin system.

IUCrJ 2021 May 5;8(Pt 3):362-371. Epub 2021 Mar 5.

The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul, 08826, Republic of Korea.

Bacterial toxin-antitoxin (TA) systems correlate strongly with physiological processes in bacteria, such as growth arrest, survival and apoptosis. Here, the first crystal structure of a type II TA complex structure of at 2.3 Å resolution is presented. Read More

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Linear Free Energy Relationships for Enzymatic Reactions: Fresh Insight from a Venerable Probe.

Acc Chem Res 2021 05 3;54(10):2532-2542. Epub 2021 May 3.

Department of Chemistry, University at Buffalo, SUNY, Buffalo, New York 14260-3000, United States.

Linear free energy relationships (LFERs) for substituent effects on reactions that proceed through similar transition states provide insight into transition state structures. A classical approach to the analysis of LFERs showed that differences in the slopes of Brønsted correlations for addition of substituted alkyl alcohols to ring-substituted 1-phenylethyl carbocations and to the β-galactopyranosyl carbocation intermediate of reactions catalyzed by β-galactosidase provide evidence that the enzyme catalyst modifies the curvature of the energy surface at the saddle point for the transition state for nucleophile addition. We have worked to generalize the use of LFERs in the determination of enzyme mechanisms. Read More

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Congenital asymmetric distal myopathy with hemifacial weakness caused by a heterozygous large de novo mosaic deletion in nebulin.

Neuromuscul Disord 2021 Jun 23;31(6):539-545. Epub 2021 Mar 23.

Folkhälsan Research Center, Helsinki, Finland; Department of Medical Genetics, Medicum, University of Helsinki, Finland.

We report the first mosaic mutation, a deletion of exons 11-107, identified in the nebulin gene in a Finnish patient presenting with a predominantly distal congenital myopathy and asymmetric muscle weakness. The female patient is ambulant and currently 26 years old. Muscle biopsies showed myopathic features with type 1 fibre predominance, strikingly hypotrophic type 2 fibres and central nuclei, but no nemaline bodies. Read More

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Mechanistic Insight into the Peptide Binding Modes to Two MazF Toxins.

Toxins (Basel) 2021 04 28;13(5). Epub 2021 Apr 28.

MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, The Sun Yat-Sen University, Guangzhou 510006, China.

Tuberculosis (TB) is a contagious disease caused by (). It is regarded as a major health threat all over the world, mainly because of its high mortality and drug-resistant nature. Toxin-antitoxin (TA) systems are modules ubiquitously found in prokaryotic organisms, and the well-studied MazEF systems (MazE means "what is it?" in Hebrew) are implicated in the formation of "persister cells" in the pathogen. Read More

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Conformational Plasticity-Rigidity Axis of the Coagulation Factor VII Zymogen Elucidated by Atomistic Simulations of the N-Terminally Truncated Factor VIIa Protease Domain.

Biomolecules 2021 Apr 8;11(4). Epub 2021 Apr 8.

Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology, University of Copenhagen, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark.

The vast majority of coagulation factor VII (FVII), a trypsin-like protease, circulates as the inactive zymogen. Activated FVII (FVIIa) is formed upon proteolytic activation of FVII, where it remains in a zymogen-like state and it is fully activated only when bound to tissue factor (TF). The catalytic domains of trypsin-like proteases adopt strikingly similar structures in their fully active forms. Read More

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Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

School of Life Sciences, Tianjin University, Tianjin, 300072, China;

Guanylate-binding proteins (GBPs) form a family of dynamin-related large GTPases which mediate important innate immune functions. They were proposed to form oligomers upon GTP binding/hydrolysis, but the molecular mechanisms remain elusive. Here, we present crystal structures of C-terminally truncated human GBP5 (hGBP5), comprising the large GTPase (LG) and middle (MD) domains, in both its nucleotide-free monomeric and nucleotide-bound dimeric states, together with nucleotide-free full-length human GBP2. Read More

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AKT/AMPK-mediated phosphorylation of TBC1D4 disrupts the interaction with insulin-regulated aminopeptidase.

J Biol Chem 2021 Apr 16:100637. Epub 2021 Apr 16.

Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Medical Faculty, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Düsseldorf, Germany. Electronic address:

TBC1D4 is a 160 kDa multi-domain Rab GTPase-activating protein (RabGAP), and a downstream target of the insulin- and contraction-activated kinases AKT and AMPK. Phosphorylation of TBC1D4 has been linked to translocation of GLUT4 from storage vesicles (GSVs) to the cell surface. However, its impact on enzymatic activity is not well understood, as previous studies mostly investigated the truncated GAP domain lacking the known phosphorylation sites. Read More

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A Heart Failure-Associated Splice Variant Leads to a Reduction in Sodium Current Through Coupled-Gating With the Wild-Type Channel.

Front Physiol 2021 22;12:661429. Epub 2021 Mar 22.

Department of Physiology and Cell Biology, Frick Center for Heart Failure and Arrhythmias, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, United States.

Na1.5, encoded by the gene , is the predominant voltage-gated sodium channel expressed in the heart. It initiates the cardiac action potential and thus is crucial for normal heart rhythm and function. Read More

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Direct Observation of the Self-Aggregation of R3R4 Bi-repeat of Tau Protein.

Chembiochem 2021 Jun 3;22(12):2093-2097. Epub 2021 May 3.

School of Chemistry, IISER Thiruvananthapuram, Maruthamala P.O, Thiruvananthapuram, Kerala, India.

Different cryo-EM derived atomic models of in vivo tau filaments from patients with tauopathies consisted of R3 and R4 repeats of the microtubule-binding domain. In comparison, only the R3 repeat forms the core of the heparin-induced fibrils of the three repeat tau isoforms. For developing therapeutics, it is desirable to have an in vitro tau aggregation system producing fibrils corresponding to the disease morphology. Read More

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The Arabidopsis thaliana chloroplast division protein FtsZ1 counterbalances FtsZ2 filament stability in vitro.

J Biol Chem 2021 Apr 1:100627. Epub 2021 Apr 1.

Department of Plant Biology, Michigan State University, East Lansing, Michigan 48824. Electronic address:

Bacterial cell and chloroplast division are driven by a contractile "Z ring" composed of the tubulin-like cytoskeletal GTPase FtsZ. Unlike bacterial Z rings, which consist of a single FtsZ, the chloroplast Z ring in plants is composed of two FtsZ proteins, FtsZ1 and FtsZ2. Both are required for chloroplast division in vivo, but their biochemical relationship is poorly understood. Read More

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A Novel Truncating Mutation in HOMER2 Causes Nonsyndromic Progressive DFNA68 Hearing Loss in a Spanish Family.

Genes (Basel) 2021 Mar 12;12(3). Epub 2021 Mar 12.

Servicio de Genética, Hospital Universitario Ramón y Cajal, IRYCIS, Carretera de Colmenar km 9.100, 28034 Madrid, Spain.

Nonsyndromic hereditary hearing loss is a common sensory defect in humans that is clinically and genetically highly heterogeneous. So far, 122 genes have been associated with this disorder and 50 of them have been linked to autosomal dominant (DFNA) forms like DFNA68, a rare subtype of hearing impairment caused by disruption of a stereociliary scaffolding protein (HOMER2) that is essential for normal hearing in humans and mice. In this study, we report a novel HOMER2 variant (c. Read More

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Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflect the Severity for the Acute and Chronic Infectious Diseases.

Biomolecules 2021 03 15;11(3). Epub 2021 Mar 15.

Department of Health Science and Social Welfare, Kibi International University, Takahashi 716-8508, Japan.

Galectin-9 (Gal-9) is a β-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. Read More

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From ELISA to Immunosorbent Tandem Mass Spectrometry Proteoform Analysis: The Example of CXCL8/Interleukin-8.

Front Immunol 2021 11;12:644725. Epub 2021 Mar 11.

Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium.

With ELISAs one detects the ensemble of immunoreactive molecules in biological samples. For biomolecules undergoing proteolysis for activation, potentiation or inhibition, other techniques are necessary to study biology. Here we develop methodology that combines immunosorbent sample preparation and nano-scale liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) for proteoform analysis (ISTAMPA) and apply this to the aglycosyl chemokine CXCL8. Read More

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Evaluation of transduced dendritic cells expressing HIV-1 p24-Nef antigens in HIV-specific cytotoxic T cells induction as a therapeutic candidate vaccine.

Virus Res 2021 Jun 26;298:198403. Epub 2021 Mar 26.

Hepatitis, AIDS and Blood borne diseases Department, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

Various approaches have been investigated to prevent or eliminate HIV-1 since 1981. However, the virus has been affecting human population worldwide with no effective vaccine yet. The conserved regions among the viral genes are suitable targets in mutable viruses to induce the immune responses via an effective delivery platform. Read More

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North polar trough formation due to in-situ erosion as a source of young ice in mid-latitudinal mantles on Mars.

Sci Rep 2021 Mar 25;11(1):6750. Epub 2021 Mar 25.

External Geodynamics and Hydrogeology Group, Department of Geology, Autonomous University of Barcelona, 08193, Bellaterra, Barcelona, Spain.

The clockwise spiral of troughs marking the Martian north polar plateau forms one of the planet's youngest megastructures. One popular hypothesis posits that the spiral pattern resulted as troughs underwent poleward migration. Here, we show that the troughs are extensively segmented into enclosed depressions (or cells). Read More

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Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer.

Mol Biol Rep 2021 Mar 24;48(3):2429-2436. Epub 2021 Mar 24.

Sahlgrenska University Hospital, Gothia Forum - for Clinical Research, Gothenburg, Sweden.

Prostate cancer (PCa) is a highly heterogeneous and unpredictable progressive disease. Sensitivity of PCa cells to androgens play a central role in tumor aggressiveness but biomarkers with high sensitivity and specificity that follow the progression of the disease has not yet been verified. The vitamin D endocrine system and its receptors, the Vitamin D Receptor (VDR) and the Protein Disulfide-Isomerase A3 (PDIA3), are related to anti-tumoral effects as well as carcinogenesis and have therefore been suggested as potential candidates for the prevention and therapy of several cancer forms, including PCa. Read More

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Identification of novel androgen receptor degrading agents to treat advanced prostate cancer.

Eur J Med Chem 2021 May 16;217:113376. Epub 2021 Mar 16.

Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Prostate cancer (PCa) is one of the most common malignancies affecting men worldwide. Androgen receptor (AR) has been a target of PCa treatment for nearly six decades. AR antagonists/degraders can effectively treat PCa caused by increased AR overexpression. Read More

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Biochemical characterization of Bombyx mori α-N-acetylgalactosaminidase belonging to the glycoside hydrolase family 31.

Insect Mol Biol 2021 Mar 20. Epub 2021 Mar 20.

Department of Agriculture, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka, Japan.

Horizontal gene transfer is an important evolutionary mechanism not only for bacteria but also for eukaryotes. In the domestic silkworm Bombyx mori, a model species of lepidopteran insects, some enzymes are known to have been acquired by horizontal transfer; however, the enzymatic features of protein BmNag31, belonging to glycoside hydrolase family 31 (GH31) and whose gene was predicted to be transferred from Enterococcus sp. are unknown. Read More

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Expression of an alternatively spliced variant of SORL1 in neuronal dendrites is decreased in patients with Alzheimer's disease.

Acta Neuropathol Commun 2021 03 16;9(1):43. Epub 2021 Mar 16.

Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000, Aarhus C, Denmark.

SORL1 is strongly associated with both sporadic and familial forms of Alzheimer's disease (AD), but a lack of information about alternatively spliced transcripts currently limits our understanding of the role of SORL1 in AD. Here, we describe a SORL1 transcript (SORL1-38b) characterized by inclusion of a novel exon (E38b) that encodes a truncated protein. We identified E38b-containing transcripts in several brain regions, with the highest expression in the cerebellum and showed that SORL1-38b is largely located in neuronal dendrites, which is in contrast to the somatic distribution of transcripts encoding the full-length SORLA protein (SORL1-fl). Read More

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