Displaying publications 1 - 20 of 82 in total

Abstract:
Sort:
  1. Wong LM, Phoon LQ, Wei LK
    J Stroke Cerebrovasc Dis, 2021 Dec;30(12):106033.
    PMID: 34598837 DOI: 10.1016/j.jstrokecerebrovasdis.2021.106033
    OBJECTIVES: In recent years, the evidence of the relationship between epigenetics and acute ischemic stroke (AIS) were accumulating, however, the epigenetic characteristics that directs specifically towards the aetiology of large-artery atherosclerosis (LAA) remain ambiguous. The aim of this study was to highlight the overall evidence concerning the epigenetic mechanisms associated with the occurrence of LAA.

    MATERIALS AND METHODS: Studies that involve investigations related to epigenetic markers (DNA methylation and RNA modifications) and LAA were retrieved from eleven scientific publication databases. The studies were screened through the pre-set inclusion and exclusion criteria prior to the NOS evaluation.

    RESULTS: Eligible studies (n=25) were evaluated. Of which, six reported on DNA methylation and 19 studies assessed RNA modifications (16 on miRNAs, two on lncRNAs, and one study on circRNA). Hypomethylation of MTRNR2L8 and ERα promoters; microRNAs (miR-7-2-3p, miR-16, miR-34a-5p, miR-126, miR-143, miR-200b, miR-223, miR-503, miR-1908, miR-146a rs2910164 C/G, miR-149 rs2292832 T/C, miR-200b rs7549819 T/C, miR-34a rs2666433); lncRNA of ZFAS1; and circRNA of hsa_circRNA_102488 were associated with LAA significantly.

    CONCLUSION: Current systematic review highlighted hypomethylation of miRNAs and lncRNA might be the potential biomarkers for LAA.

    Matched MeSH terms: Epigenesis, Genetic
  2. Choo KB
    Malays J Pathol, 2011 Dec;33(2):61-70.
    PMID: 22299205
    Since the discovery of the double-helical structure of DNA, genetic regulation of gene expression has been well elucidated. More recently, another equally, if not more, important scheme of regulation of gene expression, called epigenetics, has emerged to explain the many biological observations that traditional genetic mechanisms have failed to decipher. Epigenetics is a discipline of study on the biological consequences of cellular alterations that do not involve nucleotide changes, as opposed to genetic mutations. Epigenetic changes are reversible and may lead to loss or gain of biological functions. The three most reported mechanisms of epigenetic regulation of gene expression involve changes in: (i) chromatin remodelling, (ii) DNA methylation and (iii) microRNA (miRNA). More importantly, many of the elucidated epigenetic changes are linked to the pathogenesis of human diseases and cancers. In this mini review, core concepts and basic experimental approaches in the study of epigenetic regulation of gene expression are briefly reviewed in relation to disease, with emphasis on cancer. This mini review also intends to highlight the fact that, besides genetics, epigenetics is now a discipline physicians and clinical research scientists can no longer ignore in their pursuit to understand disease and cancer and to develop new therapeutic strategies for treatment.
    Matched MeSH terms: Epigenesis, Genetic*
  3. Low HC, Chilian WM, Ratnam W, Karupaiah T, Md Noh MF, Mansor F, et al.
    Br J Biomed Sci, 2023;80:10884.
    PMID: 36866104 DOI: 10.3389/bjbs.2023.10884
    Type 2 Diabetes Mellitus is a major chronic metabolic disorder in public health. Due to mitochondria's indispensable role in the body, its dysfunction has been implicated in the development and progression of multiple diseases, including Type 2 Diabetes mellitus. Thus, factors that can regulate mitochondrial function, like mtDNA methylation, are of significant interest in managing T2DM. In this paper, the overview of epigenetics and the mechanism of nuclear and mitochondrial DNA methylation were briefly discussed, followed by other mitochondrial epigenetics. Subsequently, the association between mtDNA methylation with T2DM and the challenges of mtDNA methylation studies were also reviewed. This review will aid in understanding the impact of mtDNA methylation on T2DM and future advancements in T2DM treatment.
    Matched MeSH terms: Epigenesis, Genetic/genetics
  4. Hayakawa K
    Nihon Eiseigaku Zasshi, 2011 Jan;66(1):29-30.
    PMID: 21358129
    The importance of twin research in the field of preventive medicine is described from the viewpoint of gene-environment interaction. The recent advancements in twin research in Japan and other countries are the major topics in this paper. The historical background of the Japan Society for Twin Studies is described. The Center for Twin Research of Osaka University is also described as the first center of this kind in Japan. The advancement of epigenetic research is described as a new global trend of twin research, particularly in European countries. Other new trends in twin research in Asian countries, such as China, Indonesia, Russia, Iran, and Malaysia, are also described.
    Matched MeSH terms: Epigenesis, Genetic/physiology*
  5. Azizi P, Hanafi MM, Sahebi M, Harikrishna JA, Taheri S, Yassoralipour A, et al.
    Funct Plant Biol, 2020 05;47(6):508-523.
    PMID: 32349860 DOI: 10.1071/FP19077
    Chromatin modulation plays important roles in gene expression regulation and genome activities. In plants, epigenetic changes, including variations in histone modification and DNA methylation, are linked to alterations in gene expression. Despite the significance and potential of in vitro cell and tissue culture systems in fundamental research and marketable applications, these systems threaten the genetic and epigenetic networks of intact plant organs and tissues. Cell and tissue culture applications can lead to DNA variations, methylation alterations, transposon activation, and finally, somaclonal variations. In this review, we discuss the status of the current understanding of epigenomic changes that occur under in vitro conditions in plantation crops, including coconut, oil palm, rubber, cotton, coffee and tea. It is hoped that comprehensive knowledge of the molecular basis of these epigenomic variations will help researchers develop strategies to enhance the totipotent and embryogenic capabilities of tissue culture systems for plantation crops.
    Matched MeSH terms: Epigenesis, Genetic*
  6. Govender N, Senan S, Mohamed-Hussein ZA, Wickneswari R
    Sci Rep, 2018 Jun 15;8(1):9211.
    PMID: 29907786 DOI: 10.1038/s41598-018-27493-z
    The plant shoot system consists of reproductive organs such as inflorescences, buds and fruits, and the vegetative leaves and stems. In this study, the reproductive part of the Jatropha curcas shoot system, which includes the aerial shoots, shoots bearing the inflorescence and inflorescence were investigated in regard to gene-to-gene interactions underpinning yield-related biological processes. An RNA-seq based sequencing of shoot tissues performed on an Illumina HiSeq. 2500 platform generated 18 transcriptomes. Using the reference genome-based mapping approach, a total of 64 361 genes was identified in all samples and the data was annotated against the non-redundant database by the BLAST2GO Pro. Suite. After removing the outlier genes and samples, a total of 12 734 genes across 17 samples were subjected to gene co-expression network construction using petal, an R library. A gene co-expression network model built with scale-free and small-world properties extracted four vicinity networks (VNs) with putative involvement in yield-related biological processes as follow; heat stress tolerance, floral and shoot meristem differentiation, biosynthesis of chlorophyll molecules and laticifers, cell wall metabolism and epigenetic regulations. Our VNs revealed putative key players that could be adapted in breeding strategies for J. curcas shoot system improvements.
    Matched MeSH terms: Epigenesis, Genetic/physiology*
  7. Hussain MS, Afzal O, Gupta G, Altamimi ASA, Almalki WH, Alzarea SI, et al.
    Pathol Res Pract, 2023 Sep;249:154738.
    PMID: 37595448 DOI: 10.1016/j.prp.2023.154738
    Lung cancer (LC) continues to pose a significant global medical burden, necessitating a comprehensive understanding of its molecular foundations to establish effective treatment strategies. The mitogen-activated protein kinase (MAPK) signaling system has been scientifically associated with LC growth; however, the intricate regulatory mechanisms governing this system remain unknown. Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of diverse cellular activities, including cancer growth. LncRNAs have been implicated in LC, which can function as oncogenes or tumor suppressors, and their dysregulation has been linked to cancer cell death, metastasis, spread, and proliferation. Due to their involvement in critical pathophysiological processes, lncRNAs are gaining attention as potential candidates for anti-cancer treatments. This article aims to elucidate the regulatory role of lncRNAs in MAPK signaling in LC. We provide a comprehensive review of the key components of the MAPK pathway and their relevance in LC, focusing on aberrant signaling processes associated with disease progression. By examining recent research and experimental findings, this article examines the molecular mechanisms through which lncRNAs influence MAPK signaling in lung cancer, ultimately contributing to tumor development.
    Matched MeSH terms: Epigenesis, Genetic
  8. Aanniz T, Bouyahya A, Balahbib A, El Kadri K, Khalid A, Makeen HA, et al.
    Chem Biol Interact, 2024 Apr 01;392:110907.
    PMID: 38395253 DOI: 10.1016/j.cbi.2024.110907
    The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i.e. their abnormal expression or activity, can result in the repression or overactivation of gene expression. Consequently, this can generate cellular dysregulation leading to instability and tumor development. Several reports highlighted the involvement of DNMTs in human cancers. The inhibition or activation of DNMTs is a promising therapeutic approach in many human cancers. In the present work, we provide a comprehensive and critical summary of natural bioactive molecules as primary inhibitors of DNMTs in human cancers. The active compounds hold the potential to be developed as anti-cancer epidrugs targeting DNMTs.
    Matched MeSH terms: Epigenesis, Genetic
  9. Hashemi M, Daneii P, Asadalizadeh M, Tabari K, Matinahmadi A, Bidoki SS, et al.
    Int J Biochem Cell Biol, 2024 May;170:106566.
    PMID: 38513802 DOI: 10.1016/j.biocel.2024.106566
    Hepatocellular carcinoma (HCC), a significant challenge for public healthcare systems in developed Western countries including the USA, Canada, and the UK, is influenced by different risk factors including hepatitis virus infections, alcoholism, and smoking. The disruption in the balance of microRNAs (miRNAs) plays a vital function in tumorigenesis, given their function as regulators in numerous signaling networks. These miRNAs, which are mature and active in the cytoplasm, work by reducing the expression of target genes through their impact on mRNAs. MiRNAs are particularly significant in HCC as they regulate key aspects of the tumor, like proliferation and invasion. Additionally, during treatment phases such as chemotherapy and radiotherapy, the levels of miRNAs are key determinants. Pre-clinical experiments have demonstrated that altered miRNA expression contributes to HCC development, metastasis, drug resistance, and radio-resistance, highlighting related molecular pathways and processes like MMPs, EMT, apoptosis, and autophagy. Furthermore, the regulatory role of miRNAs in HCC extends beyond their immediate function, as they are also influenced by other epigenetic factors like lncRNAs and circular RNAs (circRNAs), as discussed in recent reviews. Applying these discoveries in predicting the prognosis of HCC could mark a significant advancement in the therapy of this disease.
    Matched MeSH terms: Epigenesis, Genetic
  10. Alam F, Islam MA, Gan SH, Mohamed M, Sasongko TH
    Curr Pharm Des, 2016;22(28):4398-419.
    PMID: 27229720
    DNA methylation, a major regulator of epigenetic modifications has been shown to alter the expression of genes that are involved in aspects of glucose metabolism such as glucose intolerance, insulin resistance, β-cell dysfunction and other conditions, and it ultimately leads to the pathogenesis of type 2 diabetes mellitus (T2DM). Current evidences indicate an association of DNA methylation with T2DM. This review provides an overview of how various factors play crucial roles in T2DM pathogenesis and how DNA methylation interacts with these factors. Additionally, an update on current techniques of DNA methylation analysis with their pros and cons is provided as a basis for the adoption of suitable techniques in future DNA methylation research towards better management of T2DM. To elucidate the mechanistic relationship between vital environmental factors and the development of T2DM, a better understanding of the changes in gene expression associated with DNA methylation at the molecular level is still needed.
    Matched MeSH terms: Epigenesis, Genetic*
  11. Kafle A, Suttiprapa S, Muhammad M, Tenorio JCB, Mahato RK, Sahimin N, et al.
    PLoS Negl Trop Dis, 2024 Sep;18(9):e0012477.
    PMID: 39236081 DOI: 10.1371/journal.pntd.0012477
    BACKGROUND: Epigenetic modifications, such as DNA methylation and histone modifications, are pivotal in regulating gene expression pathways related to inflammation and cancer. While there is substantial research on epigenetic markers in cholangiocarcinoma (CCA), Opisthorchis viverrini-induced cholangiocarcinoma (Ov-CCA) is overlooked as a neglected tropical disease (NTD) with limited representation in the literature. Considering the distinct etiological agent, pathogenic mechanisms, and pathological manifestations, epigenetic research plays a pivotal role in uncovering markers and potential targets related to the cancer-promoting and morbidity-inducing liver fluke parasite prevalent in the Great Mekong Subregion (GMS). Emerging studies highlight a predominant hypermethylation phenotype in Opisthorchis viverrini (O. viverrini) tumor tissues, underscoring the significance of abnormal DNA methylation and histone modifications in genes and their promoters as reliable targets for Ov-CCA.

    PRINCIPAL FINDINGS: Relevant published literature was identified by searching major electronic databases using targeted search queries. This process retrieved a total of 81 peer-reviewed research articles deemed eligible for inclusion, as they partially or fully met the pre-defined selection criteria. These eligible articles underwent a qualitative synthesis and were included in the scoping review. Within these, 11 studies specifically explored Ov-CCA tissues to investigate potential epigenetic biomarkers and therapeutic targets. This subset of 11 articles provided a foundation for exploring the applications of epigenetics-based therapies and biomarkers for Ov-CCA. These articles delved into various epigenetic modifications, including DNA methylation and histone modifications, and examined genes with aberrant epigenetic changes linked to deregulated signalling pathways in Ov-CCA progression.

    CONCLUSIONS: This review identified epigenetic changes and Wnt/β-catenin pathway deregulation as key drivers in Ov-CCA pathogenesis. Promoter hypermethylation of specific genes suggests potential diagnostic biomarkers and dysregulation of Wnt/β-catenin-modulating genes contributes to pathway activation in Ov-CCA progression. Reversible epigenetic changes offer opportunities for dynamic disease monitoring and targeted interventions. Therefore, this study underscores the importance of these epigenetic modifications in Ov-CCA development, suggesting novel therapeutic targets within disrupted signalling networks. However, additional validation is crucial for translating these novel insights into clinically applicable strategies, enhancing personalised Ov-CCA management approaches.

    Matched MeSH terms: Epigenesis, Genetic*
  12. Nour El Huda Abd Rahim, Mohd Nabil Fikri Rahim, Norsidah Ku Zaifah, Hanisah Mohd Noor, Kartini Abdullah, Norlelawati A. Talib
    MyJurnal
    The dopamine hypothesis has earlier dominated the theories for the
    development of schizophrenia based on the early pharmacologic evidence. The
    antipsychotic drugs, among others, is thought to interfere with the function of the
    dopamine D2 receptor (DRD2) resulting in clinical improvement. Accumulating evidence
    suggest the role of epigenetic mechanisms in the pathophysiology of schizophrenia.
    Despite this, specific evidence linking the DRD2 DNA methylation with schizophrenia is
    insufficient mainly due to the poor accessibility and limited brain samples. Of late, new
    data has suggested the global impact of DNA methylation in the development of
    schizophrenia, thus methylation in the peripheral blood could infer changes in the brain.
    The aim of this study was to assess the DRD2 DNA methylation in the peripheral blood of
    schizophrenia.
    Matched MeSH terms: Epigenesis, Genetic
  13. Abdul Manap AS, Madhavan P, Vijayabalan S, Chia A, Fukui K
    PeerJ, 2020;8:e10003.
    PMID: 33062432 DOI: 10.7717/peerj.10003
    Previously, we reported the synergistic effects of curcumin and piperine in cell cultures as potential anti-cholinesterase and anti-amyloidogenic agents. Due to limited findings on the enrolment of these compounds on epigenetic events in AD, we aimed at elucidating the expression profiles of Aβ42-induced SH-SY5Y cells using microarray profiling. In this study, an optimized concentration of 35 µM of curcumin and piperine in combination was used to treat Aβ42 fibril and high-throughput microarray profiling was performed on the extracted RNA. This was then compared to curcumin and piperine used singularly at 49.11 µM and 25 µM, respectively. Our results demonstrated that in the curcumin treated group, from the top 10 upregulated and top 10 downregulated significantly differentially expressed genes (p 
    Matched MeSH terms: Epigenesis, Genetic
  14. Elhassan SA, Wong YH, Bhattamisra SK, Candasamy M
    Minerva Med, 2022 Oct;113(5):896-897.
    PMID: 32683846 DOI: 10.23736/S0026-4806.20.06611-2
    Matched MeSH terms: Epigenesis, Genetic
  15. Abu N, Rus Bakarurraini NAA, Nasir SN, Ishak M, Baharuddin R, Jamal R, et al.
    Iran J Immunol, 2023 Mar 14;20(1):83-91.
    PMID: 36932973 DOI: 10.22034/iji.2023.92600.2171
    BACKGROUND: Cancer testis antigens (CTAs) are a class of immune-stimulating antigens often overexpressed in many types of cancers. The usage of the CTAs as immunotherapy targets have been widely investigated in different cancers including melanoma, hematological malignancies, and colorectal cancer. Studies have indicated that the epigenetic regulation of the CTAs such as the methylation status may affect the expression of the CTAs. However, the report on the methylation status of the CTAs is conflicting. The general methylation profile of the CTAs, especially in colorectal cancer, is still elusive.

    OBJECTIVE: To determine the methylation profile of the selected CTAs in our colorectal cancer patients.

    METHODS: A total of 54 pairs of colorectal cancer samples were subjected to DNA methylation profiling using the Infinium Human Methylation 450K bead chip.

    RESULTS: We found that most of the CTAs were hypomethylated, and CCNA1 and TMEM108 genes were among the few CTAs that were hypermethylated.

    CONCLUSION: Overall, our brief report has managed to show the overall methylation profile in over the 200 CTAs in colorectal cancer and this could be used for further refining any immunotherapy targets.

    Matched MeSH terms: Epigenesis, Genetic
  16. Mohamad Zamberi NN, Abuhamad AY, Low TY, Mohtar MA, Syafruddin SE
    CRISPR J, 2024 Apr;7(2):73-87.
    PMID: 38635328 DOI: 10.1089/crispr.2023.0078
    Clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing is evolving into an essential tool in the field of biological and medical research. Notably, the development of catalytically deactivated Cas9 (dCas9) enzyme has substantially broadened its traditional boundaries in gene editing or perturbation. The conjugation of dCas9 with various molecular effectors allows precise control over transcriptional processes, epigenetic modifications, visualization of chromosomal dynamics, and several other applications. This expanded repertoire of CRISPR-Cas9 applications has emerged as an invaluable molecular tool kit that empowers researchers to comprehensively interrogate and gain insights into health and diseases. This review delves into the advancements in Cas9 protein engineering, specifically on the generation of various dCas9 tools that have significantly enhanced the CRISPR-based technology capability and versatility. We subsequently discuss the multifaceted applications of dCas9, especially in interrogating the regulation and function of genes that involve in supporting cancer pathogenesis. In addition, we also delineate the designing and utilization of dCas9-based tools as well as highlighting its current constraints and transformative potentials in cancer research.
    Matched MeSH terms: Epigenesis, Genetic
  17. Nour El Huda AR, Norsidah KZ, Nabil Fikri MR, Hanisah MN, Kartini A, Norlelawati AT
    Psychiatry Clin Neurosci, 2018 Apr;72(4):266-279.
    PMID: 29160620 DOI: 10.1111/pcn.12622
    AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relations with the clinical variables of schizophrenia patients.

    METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays. The extracted DNA was bisulfite converted, and the percentage methylation ratio value was calculated based on the results following a MethyLight protocol analysis.

    RESULTS: The percentage methylation ratio of COMT was lower in schizophrenia than it was in the healthy controls (P 

    Matched MeSH terms: Epigenesis, Genetic/drug effects; Epigenesis, Genetic/physiology*
  18. Halim AS, Emami A, Salahshourifar I, Kannan TP
    Arch Plast Surg, 2012 May;39(3):184-9.
    PMID: 22783524 DOI: 10.5999/aps.2012.39.3.184
    Keloid disease is a fibroproliferative dermal tumor with an unknown etiology that occurs after a skin injury in genetically susceptible individuals. Increased familial aggregation, a higher prevalence in certain races, parallelism in identical twins, and alteration in gene expression all favor a remarkable genetic contribution to keloid pathology. It seems that the environment triggers the disease in genetically susceptible individuals. Several genes have been implicated in the etiology of keloid disease, but no single gene mutation has thus far been found to be responsible. Therefore, a combination of methods such as association, gene-gene interaction, epigenetics, linkage, gene expression, and protein analysis should be applied to determine keloid etiology.
    Matched MeSH terms: Epigenesis, Genetic
  19. Alhaji SY, Ngai SC, Abdullah S
    Biotechnol Genet Eng Rev, 2019 Apr;35(1):1-25.
    PMID: 30514178 DOI: 10.1080/02648725.2018.1551594
    DNA methylation and histone modifications are vital in maintaining genomic stability and modulating cellular functions in mammalian cells. These two epigenetic modifications are the most common gene regulatory systems known to spatially control gene expression. Transgene silencing by these two mechanisms is a major challenge to achieving effective gene therapy for many genetic conditions. The implications of transgene silencing caused by epigenetic modifications have been extensively studied and reported in numerous gene delivery studies. This review highlights instances of transgene silencing by DNA methylation and histone modification with specific focus on the role of these two epigenetic effects on the repression of transgene expression in mammalian cells from integrative and non-integrative based gene delivery systems in the context of gene therapy. It also discusses the prospects of achieving an effective and sustained transgene expression for future gene therapy applications.
    Matched MeSH terms: Epigenesis, Genetic
  20. Goh TX, Tan SL, Roebuck MM, Teo SH, Kamarul T
    Tissue Eng Part C Methods, 2022 10;28(10):511-528.
    PMID: 35959742 DOI: 10.1089/ten.TEC.2022.0092
    The state of host cells is reflected in the cargo carried by their extracellular vesicles (EVs). This makes EV a potential source of biomarkers for human diseases. Piwi-interacting RNA (piRNA) regulates gene expression through epigenetic regulation and post-transcriptional gene silencing. Thus, piRNA profiling in EVs derived from human clinical samples could identify markers that characterize disease stages and unveil their roles in disease pathology. This review aimed to report the expression profiles of EV-derived piRNA (EV-piRNA) in various human samples, as well as their role in each pathology. A systematic review was conducted to collate the findings of human EV-piRNA from original research articles published in indexed scientific journals up to February 16, 2022. Article searches were performed in PubMed, Web of Science, and Scopus databases, using a combination of keywords, including "EV" and "piRNA." A total of 775 nonredundant original articles were identified. After subjecting articles to inclusion and exclusion criteria, 34 articles were accepted for this review. The piRNA expression levels among the small RNA profiles of human-derived EVs range from 0.09% to 43.84%, with the lowest expression level reported in urine-derived EVs and the highest percentage in plasma-derived EVs. Differentially expressed EV-piRNAs have been identified in patients with specific disease conditions compared to their counterparts (healthy control), suggesting an association between piRNA and progression in various diseases. Seven articles identified piRNA putative target genes and/or the pathway enrichment of piRNA target genes, and one study demonstrated a direct role of piRNA candidates in disease pathology. In conclusion, EV-piRNA has been isolated successfully from various human body fluids. EV-piRNA is a new research niche in human disease pathology. The expression profiles of EV-piRNA in various tissue types and disease conditions remain largely unexplored. Furthermore, there is currently a lack of guidelines on piRNA bioinformatics analysis, which could lead to inconsistent results and thus hinder the progression of piRNA discoveries. Finally, the lack of published scientific evidence on the role of EV-piRNA supports the need for future research to focus on the functional analysis of EV-piRNA as part of the route in piRNA discoveries.
    Matched MeSH terms: Epigenesis, Genetic
Filters
Contact Us

Please provide feedback to Administrator ([email protected])

External Links