scholarly journals A novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hilal Eren Gozel ◽  
Kıvanç Kök ◽  
Fatma Ozlen ◽  
Cihan Isler ◽  
Sadrettin Pence
Keyword(s):  
Differential Expression ◽  
Cavernous Malformation ◽  
Expression Profiles ◽  
Cell Metabolism ◽  
Cell Structure ◽  
Epileptic Seizures ◽  
Vascular Lesion ◽  
Cerebral Cavernous Malformation ◽  
Differentially Expressed ◽  
Differential Expression Profile

AbstractCerebral cavernous malformation (CCM) is a vascular lesion of the central nervous system that may lead to distinct symptoms among patients including cerebral hemorrhages, epileptic seizures, focal neurologic deficits, and/or headaches. Disease-related mutations were identified previously in one of the three CCM genes: CCM1, CCM2, and CCM3. However, the rate of these mutations in sporadic cases is relatively low, and new studies report that mutations in CCM genes may not be sufficient to initiate the lesions. Despite the growing body of research on CCM, the underlying molecular mechanism has remained largely elusive. In order to provide a novel insight considering the specific manifested symptoms, CCM patients were classified into two groups (as Epilepsy and Hemorrhage). Since the studied patients experience various symptoms, we hypothesized that the underlying cause for the disease may also differ between those groups. To this end, the respective transcriptomes were compared to the transcriptomes of the control brain tissues and among each other. This resulted into the identification of the differentially expressed coding genes and the delineation of the corresponding differential expression profile for each comparison. Notably, some of those differentially expressed genes were previously implicated in epilepsy, cell structure formation, and cell metabolism. However, no CCM1-3 gene deregulation was detected. Interestingly, we observed that when compared to the normal controls, the expression of some identified genes was only significantly altered either in Epilepsy (EGLN1, ELAVL4, and NFE2l2) or Hemorrhage (USP22, EYA1, SIX1, OAS3, SRMS) groups. To the best of our knowledge, this is the first such effort focusing on CCM patients with epileptic and hemorrhagic symptoms with the purpose of uncovering the potential CCM-related genes. It is also the first report that presents a gene expression dataset on Turkish CCM patients. The results suggest that the new candidate genes should be explored to further elucidate the CCM pathology. Overall, this work constitutes a step towards the identification of novel potential genetic targets for the development of possible future therapies.

24 GLOBAL TRANSCRIPT PROFILING OF CLONED BOVINE BLASTOCYSTS USING AFFYMETRIX GENECHIP TECHNOLOGY

2006 ◽  
Vol 18 (2) ◽  
pp. 120
Author(s):  
Z. Beyhan ◽  
P. Ross ◽  
A. Iager ◽  
A. Kocabas ◽  
K. Cunniff ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Expression Profiles ◽  
Cell Structure ◽  
Donor Cell ◽  
Lipid Binding ◽  
Differentially Expressed ◽  
Gtp Binding ◽  
Cloned Bovine

Identification of genes implicated in the biological processes of somatic cell nuclear transfer will improve our understanding of reprogramming events, i.e. the transformation of a lineage-committed cell into a pluripotent one. In addition, the gene expression profile of cloned embryos can help explain the widely reported developmental failures in cloned animals. In this study, we investigated global gene expression profiles of bovine in vitro-fertilized and cloned embryos using Gene Chip Bovine Genome Arrays (Affymetrix, Inc., Santa Clara, CA, USA). For the generation of cloned bovine blastocysts from two adult fibroblast lines (C and D), we employed methods previously proven to generate live offspring and compared these offspring to in vitro-produced blastocysts. Total RNA isolated from groups of 10 blastocysts was amplified by a template-switching PCR. Amplified cDNAs were used to synthesize biotin-labeled antisense RNAs (aRNAs) during and in vitro transcription reaction. Labeled aRNAs were hybridized to microarrays as described by the manufacturer. Experiments were performed in four replicates. Expression data were analyzed using the Significance Analysis of Microarrays (SAM; Tusher et al. 2001 Proc. Natl. Acad. Sci. 98, 5116-5121) procedure and software. Overall, 48.4% and 46% of 23 000 bovine transcripts spotted on the arrays were present in cloned and in in vitro-produced control blastocysts, respectively. The SAM procedure identified 43 genes that changed at least 1.5-fold, with an estimated false discovery rate (FDR) of 20%. Comparison of gene expression between NT embryos produced from two different cell lines and IVF controls with the same criteria revealed 6 (clones from cell line C vs. IVF) and 46 (clones from cell line D vs. IVF) differentially expressed genes. The number of transcripts expressed differentially between the cloned embryos with different donor cell origin was 437. Of the 43 differentially expressed transcripts in cloned blastocysts, 13 have unknown functions and the rest of the genes related to cell structure (tuftelin, desmoplakin), cell cycle/mitosis (Kinesin like 4, katanin, stathmin, PCNA), energy metabolism (lactate dehydrogenase, ATPsynthase, lipid-binding protein, keto acid dehydrogenase E1, metallothionein), and cell signaling (GTP-binding protein1, GTP binding stimulatory protein). Our results indicate that expression profiles of cloned blastocysts could be affected by somatic donor cell.

scholarly journals Colony sectorization of Metarhizium anisopliae is a sign of ageing

Microbiology ◽  
2005 ◽  
Vol 151 (10) ◽  
pp. 3223-3236 ◽  
Author(s):  
Chengshu Wang ◽  
Tariq M. Butt ◽  
Raymond J. St Leger
Keyword(s):  
Oxidative Stress ◽  
Differentially Expressed Genes ◽  
Microarray Analysis ◽  
Stress Responses ◽  
Metarhizium Anisopliae ◽  
Cell Metabolism ◽  
Cell Structure ◽  
Pathogenic Fungus ◽  
Differentially Expressed ◽  
Physiological Adaptation

Spontaneous phenotypic degeneration resulting in sterile sectors is frequently observed when culturing filamentous fungi on artificial medium. Sterile sectors from two different strains of the insect pathogenic fungus Metarhizium anisopliae were investigated and found to contain reduced levels of cAMP and destruxins (insecticidal peptides). Microarray analysis using slides printed with 1730 clones showed that compared to wild-type, sterile sectors down-regulated 759 genes and upregulated 27 genes during growth in Sabouraud glucose broth or on insect cuticle. The differentially expressed genes are largely involved in cell metabolism (18·8 %), cell structure and function (13·6 %) and protein metabolism (8·8 %). Strong oxidative stress was demonstrated in sectorial cultures using the nitro blue tetrazolium assay and these cultures show other syndromes associated with ageing, including mitochondrial DNA alterations. However, genes involved in deoxidation and self-protection (e.g. heat-shock proteins, HSPs) were also upregulated. Further evidence of physiological adaptation by the degenerative sectorial cultures included cell-structure reorganization and the employment of additional signalling pathways. In spite of their very similar appearance, microarray analysis identified 181 genes differentially expressed between the two sectors, and the addition of exogenous cAMP only restored conidiation in one of them. Most of the differentially expressed genes were involved in catabolic or anabolic pathways, but the latter included genes for sporulation. Compared to the mammalian ageing process, sectorization in M. anisopliae showed many similarities, including similar patterns of cAMP production, oxidative stress responses and the involvement of HSPs. Thus, a common molecular machinery for ageing may exist throughout the eukaryotes.

Abstract P737: Human Homologs Of Differentially Expressed Plasma MicroRNAs In Preclinical Murine Models Target Fundamental Mechanisms Of Cerebral Cavernous Malformation

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sharbel Romanos ◽  
Abhinav Srinath ◽  
Thomas Moore ◽  
Ying Li ◽  
Janne Koskimaki ◽  
...  
Keyword(s):  
Mouse Models ◽  
Cavernous Malformation ◽  
Cerebral Cavernous Malformation ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Human Homolog ◽  
Murine Models ◽  
Putative Gene ◽  
Disease States ◽  
Plasma Mirnas

Introduction: There is a current need for sensitive and specific biomarkers of Cerebral Cavernous Malformation (CCM) that can be readily translated from preclinical to human models to accurately diagnose and monitor disease states and response to novel therapeutics. MiRNAs are small non-coding RNAs that influence gene expression and whose levels can be affected by disease states. We hypothesize that there are human homologs of differentially expressed (DE) miRNA in the plasma of CCM murine models that can be identified in CCM patients. We further hypothesize that these miRNAs have gene targets within previously published CCM transcriptomes, mechanistically linking them to CCM disease. Methods: Plasma miRNAs from homozygous and heterozygous Ccm1 and Ccm3 mice, as well as their respective wild type controls were sequenced and analyzed. Putative gene targets of DE miRNAs [p<0.05, false discovery rate (FDR) corrected] were queried in previously published mouse CCM transcriptomes. The human homologs of the DE miRNAs in the plasma of Ccm1 and Ccm3 mouse models were identified and assessed in the plasma of healthy controls (n=13), CCM1 (n=11), and CCM3 (n=11) patients using RT-qPCR. Results: 5 miRNAs in homozygous and 10 in heterozygous for Ccm1 , while 45 in homozygous and 2 in heterozygous for Ccm3 were DE in the plasma of mouse models (p<0.05, FDR corrected), had gene targets within CCM mouse transcriptomes, and have a human homolog. Preliminary results show mmu-miR-375-3p as DE in both Ccm1 +/- and Ccm3 -/- mice. RT-qPCR assays show that plasma relative quantification values of the human homolog hsa-miR-375-3p were higher in CCM3 than in CCM1 patients ( p <0.001) and in healthy controls ( p <0.05). Conclusion: DE plasma miRNAs identified in mouse models with human homologs and putative gene targets mechanistically implicated in CCM disease may be used as candidate biomarkers for specific clinical contexts.

scholarly journals Distinct Expression Profiles of lncRNAs Between Regressive and Mature Scars

2015 ◽  
Vol 35 (2) ◽  
pp. 663-675 ◽  
Author(s):  
Jingyun Li ◽  
Wei Long ◽  
Qian Li ◽  
Qing Zhou ◽  
Yu Wang ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Immune System ◽  
Differential Expression ◽  
Pathway Analysis ◽  
Expression Profiles ◽  
Molecular Targets ◽  
Differentially Expressed ◽  
Altered Expression ◽  
Qrt Pcr ◽  
Non Coding Rnas

Background: Recent studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in human diseases. The function of lncRNAs in abnormal scar pathogenesis remains poorly understood. Methods: In this study, we examined the lncRNAs expression profiles among regressive and mature scars following caesarean sections. A total of 30,586 lncRNAs and 26,109 mRNAs were analyzed by microarrays (Human LncRNA Array v3.0, Arraystar, Inc.). Results: In total, we identified 1,871 lncRNAs and 817 mRNAs with differential expression between regressive and mature scar individuals (fold change≥3, p≤0.001). A set of differentially expressed lncRNA transcripts, in particular, lncRNA8975-1, AC097662.2 and RP11-586K2.1, were confirmed using qRT-PCR. Gene ontology and pathway analysis revealed that compared to mature scars, many processes over-represented in regressive scars are related to the immune system. Conclusion: Our results show significantly altered expression profiles of lncRNAs and mRNAs between regressive and mature scars. These transcripts are potential molecular targets for inhibiting abnormal scar formation following caesarean sections.

Dead or alive: gene expression profiles of advanced atherosclerotic plaques from autopsy and surgery

2007 ◽  
Vol 30 (3) ◽  
pp. 335-341 ◽  
Author(s):  
Judith C. Sluimer ◽  
Natasja Kisters ◽  
Kitty B. Cleutjens ◽  
Oscar L. Volger ◽  
Anton J. Horrevoets ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Basal Cell ◽  
Protein Level ◽  
Expression Profiles ◽  
Cell Metabolism ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Expression Levels ◽  
Atherosclerotic Lesions

Since inclusion of atherosclerotic tissues from different sources is often indispensable to study the full atherogenic spectrum, we investigated to what extent the expression profiles of advanced, stable atherosclerotic lesions obtained during autopsy and surgery are comparable. The gene expression profiles of human carotids with advanced atherosclerosis obtained at autopsy and at vascular surgery were studied by microarray analysis. Expression analysis was performed both at the single gene (Rosetta, Gene Ontology) and at the pathway level using Ingenuity and Gene Set Enrichment Analysis. In addition, mRNA and protein expression levels were validated using quantitative (q) RT-PCR and immunohistochemistry on unrelated advanced carotid lesions from autopsy and surgery. Microarray analysis indicated that the 97.2% of genes showed similar expression levels in advanced atherosclerotic lesions from autopsy and surgery. While the expression data revealed no differences in common atherosclerotic related pathways such as lipid metabolism and inflammation, the differentially expressed genes were mainly involved in basal cell metabolism and hypoxia driven pathways. qRT-PCR confirmed the differential expression of hypoxia-driven genes VEGF-A (2.3-fold ↑), glucose transporter (GLUT)-1 (2.5-fold ↑), GLUT3 (8.3-fold ↑), and hexokinase 1 (2.4-fold ↑) in autopsy vs. surgical specimens. Immunohistochemistry revealed that the transcriptional differences in these hypoxia-related genes were not reflected at the protein level. The gene expression profiles of advanced atherosclerotic lesions from autopsy and surgery are largely similar. However, >500 genes, mostly involved in basal cell metabolism and hypoxia were differentially expressed at mRNA, but not at the protein level.

scholarly journals Differential expression of miRNAs involved in biological processes responsible for inflammation and immune response in lichen sclerosus urethral stricture disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261505
Author(s):  
Harjivan Kohli ◽  
Brandon Childs ◽  
Travis B. Sullivan ◽  
Artem Shevtsov ◽  
Eric Burks ◽  
...  
Keyword(s):  
Immune Response ◽  
Differential Expression ◽  
Urethral Stricture ◽  
Expression Profiles ◽  
Lichen Sclerosus ◽  
Differentially Expressed ◽  
P Value ◽  
Screening Analysis ◽  
Urethral Stricture Disease ◽  
False Discovery

Purpose To better understand the pathophysiology of lichen sclerosus (LS) urethral stricture disease (USD), we aimed to investigate expression profiles of microRNAs (miRNAs) in tissue samples from men undergoing urethroplasty. Methods Urethral stricture tissue was collected from 2005–2020. Histologic features diagnostic of LS were the basis of pathologic evaluation. Foci of areas diagnostic for LS or non-LS strictures were chosen for RNA evaluation. In an initial screening analysis, 13 LS urethral strictures and 13 non-LS strictures were profiled via miRNA RT-qPCR arrays for 752 unique miRNA. A validation analysis of 23 additional samples (9 LS and 14 non-LS) was performed for 15 miRNAs. Statistical analyses were performed using SPSS v25. Gene Ontology (GO) analysis was performed using DIANA-mirPath v. 3.0. Results In the screening analysis 143 miRNAs were detected for all samples. 27 were differentially expressed between the groups (false discovery p-value <0.01). 15 of these miRNAs individually demonstrated an area under the curve (AUC)>0.90 for distinguishing between between LS and non-LS strictures. 11-fold upregulation of MiR-155-5p specifically was found in LS vs. non-LS strictures (p<0.001, AUC = 1.0). In the validation analysis, 13 of the 15 miRNAs tested were confirmed to have differential expression (false discovery p-value <0.10). Conclusions To our knowledge this is the first study evaluating miRNA expression profiles in LS and non-LS USD. We identified several miRNAs that are differentially expressed in USD caused by LS vs other etiologies, which could potentially serve as biomarkers of LS USD. The top eight differentially expressed miRNAs have been linked to immune response processes as well as involvement in wound healing, primarily angiogenesis and fibrosis.

scholarly journals Detection and analysis of long noncoding RNA expression profiles related to epithelial–mesenchymal transition in keloids

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhixiong Chen ◽  
Xi Chu ◽  
Jinghong Xu
Keyword(s):  
Differential Expression ◽  
Noncoding Rna ◽  
Matrix Protein ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Normal Skin ◽  
Differentially Expressed ◽  
Extracellular Matrix Protein ◽  
Mesenchymal Transition ◽  
Promote Cell Proliferation

Abstract Background The role of epithelial-mesenchymal transition (EMT) in the pathogenesis of keloids is currently raising increasing attention. Long noncoding RNAs (lncRNAs) govern a variety of biological processes, such as EMT, and their dysregulation is involved in many diseases including keloid disease. The aim of this study was to identify differentially expressed EMT-related lncRNAs in keloid tissues versus normal tissues and to interpret their functions. Results Eleven lncRNAs and 16 mRNAs associated with EMT were identified to have differential expression between keloid and normal skin tissues (fold change > 1.5, P < 0.05). Gene Ontology (GO) analysis showed that these differentially expressed mRNAs functioned in the extracellular matrix, protein binding, the positive regulation of cellular processes, the Set1C/COMPASS complex and histone acetyltransferase activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that these mRNAs are involved in pathways in cancer. The lncRNA, XLOC_000587 may promote cell proliferation and migration by enhancing the expression of ENAH, while AF268386 may facilitate the invasive growth of keloids by upregulating DDR2. Conclusions We characterized the differential expression profiles of EMT-related lncRNAs and mRNAs in keloids, which may contribute to preventing the occurrence and development of keloids by targeting the corresponding signaling pathways. These lncRNAs and mRNAs may provide biomarkers for keloid diagnosis and serve as potential targets for the treatment of this disease.

Differential Expression Genes of CLL Subgroups Defined by Ki67 Expression Level Which Correlated with Clinical Outcome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2435-2435
Author(s):  
Xiao-Jie Yan ◽  
Daniel Kalenscher ◽  
Erin Boyle ◽  
Arrti Damle ◽  
Sophie Yancopoulos ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
Differential Expression ◽  
Cellular Proliferation ◽  
Conflicts Of Interest ◽  
Expression Profiles ◽  
Gene List ◽  
Differentially Expressed ◽  
Resting Cells ◽  
Ki67 Expression

Abstract Abstract 2435 Introduction: Chronic Lymphocyte Leukemia (CLL) is characterized by the slow clonal expansion of B-lymphocytes, which eventually overwhelm healthy immune cells, therefore hindering normal function. In order to determine the underlying mechanisms for this uncontrolled proliferation, gene expression data was gathered through cDNA microarray analysis of the B-cells from CLL patients. The data was split into two groups depending on expression levels of Ki67, a strong marker for cellular proliferation. In our study, high Ki67 expression only showed in 60% of unmutated CLL patients and higher in CD38+ CLL B cells. The expression of individuals with high levels of Ki67 was compared to the expression profiles of individuals with low levels of Ki67. This allowed for the determination of differences in gene expression correlated to an increase in proliferation of B-cells. Methods: 1) The RNA were purified from CLL B cells which were isolated by RosetteSep Human B cell Enrichment Cocktail (StemCell Technologies) during 4 hours after blood drawn from patients. Microarray assay was performed on Illumina HumanWG-6 expression beadchips. 2) The samples were devided to 2 groups according Ki67 surface expression, 9 samples with Ki67high (>5%) and 26 samples with Ki67low (<5%). 3) Differential expression of gene were first analyzed using Partek. 98 genes were selected as differentially expressed if the fold change was greater than 1.5-fold and p value is lower than <0.01. 4) This set of genes was further examined by pathway analysis (Ingenuity pathway analyses). Results: 1) Time to first time treatment (TTFT) were compared between Ki67high and Ki67low patients. Ki67high patients had a significantly shorter TTFT (2.76 yr) compared to Ki67low patients (23.46 years; P<0.0001). 2) 98 genes were selected as differentially expressed between Ki67high and Ki67low groups. 78 genes were upregulated and 20 genes downregulated in Ki67high group. For the location of these genes, Extracellular space: 9 genes; Plasma membrane: 22 genes; Cytoplasma: 21 genes and Nucleus: 18 genes. 3) Several networks, which involved in cell growth and proliferation, cell cycles and cellular development, has revealed in which there were significant changes in gene expression correlated to high levels of Ki-67 activity. 4) As would be expected, distinct changes in expression were those relating to cell proliferation (23 genes), cell movement and migration (14 genes) as well as, cell-signaling and interaction (20 genes) and cell death (23 genes). 5) To compare this gene list to another set microarray analyses in CLL patients. 28 genes were identified in both experiments. 6) One pathway which particular involved with NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) was selected. The genes precipitated in this pathway are CDKN2C, CRY1, DFNA5, FKBP5, HIST2H2AA3, IL15, LPL, MPSK, MYLK, PAK1, ZAP70. NF-κB is a transcription factor involved in the regulation of various genes relating to apoptosis, cell survival, and proliferation. Although unchanged in its own expression, various regulators of NF-κB displayed a significant change in expression. Conclusion and discussion: Ki67 is a nuclear protein which upregulated in G1, S, G2, and M phases of the cell cycle but is absent from resting cells (G0 phase1). We reported that Ki67+ cell is enriched in CD38+ cells regardless of the percentage of CD38+ cells in a patient's CLL clone2. To analyze gene expression profile in Ki67high and Ki67low groups will determine the possible interactions responsible for the proliferative nature of B-cells in CLL. Misregulation of the NF-κB complex has been implicated in the development of various immunological diseases as well as cancer, therefore identifying it as a candidate for further research in CLL development and treatment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Individualized lncRNA differential expression profile reveals heterogeneity of breast cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Zhangxiang Zhao ◽  
YingYing Guo ◽  
Yaoyao Liu ◽  
Lichun Sun ◽  
Bo Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Breast Cancer Subtype ◽  
Differential Expression Analysis ◽  
Differentially Expressed ◽  
Migration And Invasion ◽  
Response Analysis ◽  
Mesenchymal Transition

AbstractLong non-coding RNAs (lncRNAs) play key regulatory roles in breast cancer. However, population-level differential expression analysis methods disregard the heterogeneous expression of lncRNAs in individual patients. Therefore, we individualized lncRNA expression profiles for breast invasive carcinoma (BRCA) using the method of LncRNA Individualization (LncRIndiv). After evaluating the robustness of LncRIndiv, we constructed an individualized differentially expressed lncRNA (IDElncRNA) profile for BRCA and investigated the subtype-specific IDElncRNAs. The breast cancer subtype-specific IDElncRNA showed frequent co-occurrence with alterations of protein-coding genes, including mutations, copy number variation and differential methylation. We performed hierarchical clustering to subdivide TNBC and revealed mesenchymal subtype and immune subtype for TNBC. The TNBC immune subtype showed a better prognosis than the TNBC mesenchymal subtype. LncRNA PTOV1-AS1 was the top differentially expressed lncRNA in the mesenchymal subtype. And biological experiments validated that the upregulation of PTOV1-AS1 could downregulate TJP1 (ZO-1) and E-Cadherin, and upregulate Vimentin, which suggests PTOV1-AS1 may promote epithelial-mesenchymal transition and lead to migration and invasion of TNBC cells. The mesenchymal subtype showed a higher fraction of M2 macrophages, whereas the immune subtype was more associated with CD4 + T cells. The immune subtype is characterized by genomic instability and upregulation of immune checkpoint genes, thereby suggesting a potential response to immunosuppressive drugs. Last, drug response analysis revealed lncRNA ENSG00000230082 (PRRT3-AS1) is a potential resistance biomarker for paclitaxel in BRCA treatment. Our analysis highlights that IDElncRNAs can characterize inter-tumor heterogeneity in BRCA and the new TNBC subtypes indicate novel insights into TNBC immunotherapy.

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