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  1. Fulltext Piper betle L. Modulates Senescence-Associated Genes Expression in Replicative Senescent Human Diploid Fibroblasts
    Durani LW, Khor SC, Tan JK, Chua KH, Mohd Yusof YA, Makpol S
    Biomed Res Int, 2017;2017:6894026.
    PMID: 28596968 DOI: 10.1155/2017/6894026
    Piper betle
    (PB) is a traditional medicine that is widely used to treat different diseases around Asian region. The leaf extracts contain various bioactive compounds, which were reported to have antidiabetic, antibacterial, anti-inflammatory, antioxidant, and anticancer effects. In this study, the effect of PB aqueous extracts on replicative senescent human diploid fibroblasts (HDFs) was investigated by determining the expressions of senescence-associated genes using quantitative PCR. Our results showed that PB extracts at 0.4 mg/ml can improve cell proliferation of young (143%), presenescent (127.3%), and senescent (157.3%) HDFs. Increased expressions ofPRDX6,TP53,CDKN2A,PAK2, andMAPK14were observed in senescent HDFs compared to young and/or presenescent HDFs. Treatment with PB extracts modulates the transcriptional profile changes in senescent HDFs. By contrast, expressions ofSOD1increased, whereasGPX1,PRDX6,TP53,CDKN2A,PAK2, andMAPK14were decreased in PB-treated senescent HDFs compared to untreated senescent HDFs. In conclusion, this study indicates the modulation of PB extracts on senescence-associated genes expression of replicative senescent HDFs. Further studies warrant determining the mechanism of PB in modulating replicative senescence of HDFs through these signaling pathways.
    Matched MeSH terms: Gene Expression Regulation/drug effects*
  2. Fulltext 'Movers and shakers' in the regulation of fruit ripening: a cross-dissection of climacteric versus non-climacteric fruit
    Cherian S, Figueroa CR, Nair H
    J Exp Bot, 2014 Sep;65(17):4705-22.
    PMID: 24994760 DOI: 10.1093/jxb/eru280
    Fruit ripening is a complex and highly coordinated developmental process involving the expression of many ripening-related genes under the control of a network of signalling pathways. The hormonal control of climacteric fruit ripening, especially ethylene perception and signalling transduction in tomato has been well characterized. Additionally, great strides have been made in understanding some of the major regulatory switches (transcription factors such as RIPENING-INHIBITOR and other transcriptional regulators such as COLOURLESS NON-RIPENING, TOMATO AGAMOUS-LIKE1 and ETHYLENE RESPONSE FACTORs), that are involved in tomato fruit ripening. In contrast, the regulatory network related to non-climacteric fruit ripening remains poorly understood. However, some of the most recent breakthrough research data have provided several lines of evidences for abscisic acid- and sucrose-mediated ripening of strawberry, a non-climacteric fruit model. In this review, we discuss the most recent research findings concerning the hormonal regulation of fleshy fruit ripening and their cross-talk and the future challenges taking tomato as a climacteric fruit model and strawberry as a non-climacteric fruit model. We also highlight the possible contribution of epigenetic changes including the role of plant microRNAs, which is opening new avenues and great possibilities in the fields of fruit-ripening research and postharvest biology.
    Matched MeSH terms: Gene Expression Regulation, Plant*; Gene Expression Regulation, Developmental
  3. 1'S-1'-acetoxyeugenol acetate: a novel phenylpropanoid from Alpinia conchigera enhances the apoptotic effects of paclitaxel in MCF-7 cells through NF-κB inactivation
    In LL, Azmi MN, Ibrahim H, Awang K, Nagoor NH
    Anticancer Drugs, 2011 Jun;22(5):424-34.
    PMID: 21346553 DOI: 10.1097/CAD.0b013e328343cbe6
    In this study, the apoptotic mechanism and combinatorial chemotherapeutic effects of the cytotoxic phenylpropanoid compound 1'S-1'-acetoxyeugenol acetate (AEA), extracted from rhizomes of the Malaysian ethnomedicinal plant Alpinia conchigera Griff. (Zingiberaceae), on MCF-7 human breast cancer cells were investigated for the first time. Data from cytotoxic and apoptotic assays such as live and dead and poly-(ADP-ribose) polymerase cleavage assays indicated that AEA was able to induce apoptosis in MCF-7 cells, but not in normal human mammary epithelial cells. A microarray global gene expression analysis of MCF-7 cells, treated with AEA, suggested that the induction of tumor cell death through apoptosis was modulated through dysregulation of the nuclear factor-kappaB (NF-κB) pathway, as shown by the reduced expression of various κB-regulated gene targets. Consequent to this, western blot analysis of proteins corresponding to the NF-κB pathway indicated that AEA inhibited phosphorylation levels of the inhibitor of κB-kinase complex, resulting in the elimination of apoptotic resistance originating from NF-κB activation. This AEA-based apoptotic modulation was elucidated for the first time in this study, and gave rise to the proposal of an NF-κB model termed the 'Switching/Alternating Model.' In addition to this, AEA was also found to synergistically enhance the proapoptotic effects of paclitaxel, when used in combination with MCF-7 cells, presumably by a chemosensitizing role. Therefore, it was concluded that AEA isolated from the Malaysian tropical ginger (A. conchigera) served as a very promising candidate for further in-vivo development in animal models and in subsequent clinical trials involving patients with breast-related malignancies.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic/drug effects; Gene Expression Profiling/methods
  4. 2-dodecanol (decyl methyl carbinol) inhibits hyphal formation and SIR2 expression in C. albicans
    Lim CS, Wong WF, Rosli R, Ng KP, Seow HF, Chong PP
    J Basic Microbiol, 2009 Dec;49(6):579-83.
    PMID: 19810039 DOI: 10.1002/jobm.200900035
    Candida albicans is capable of undergoing yeast-hypha transition to attain pathogenicity in humans. In this study, we investigated the differential expression of CaSIR2 via quantitative real-time PCR (qPCR), during yeast-hypha transition with and without the presence of 2-dodecanol. SIR2 transcript levels were found to be significantly enhanced after hyphal induction as compared to the yeast form. This study found that 2-dodecanol is able to inhibit hyphal development and block SIR2 up-regulation, even in hyphal-inducing growth conditions. We suggest that SIR2 may be involved in Candida albicans quorum-sensing and serum-induced yeast-hyphae transition via the Ras1-cAMP-Efg1 signalling cascade.
    Matched MeSH terms: Gene Expression Regulation, Fungal
  5. Fulltext 5-Azacytidine is insufficient for cardiogenesis in human adipose-derived stem cells
    Wan Safwani WK, Makpol S, Sathapan S, Chua KH
    J Negat Results Biomed, 2012;11:3.
    PMID: 22221649 DOI: 10.1186/1477-5751-11-3
    Adipose tissue is a source of multipotent adult stem cells and it has the ability to differentiate into several types of cell lineages such as neuron cells, osteogenic cells and adipogenic cells. Several reports have shown adipose-derived stem cells (ASCs) have the ability to undergo cardiomyogenesis. Studies have shown 5-azacytidine can successfully drive stem cells such as bone marrow derived stem cells to differentiate into cardiomyogenic cells. Therefore, in this study, we investigated the effect 5-azacytidine on the cardiogenic ability of ASCs.
    Matched MeSH terms: Gene Expression Regulation/drug effects
  6. 6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor γ (PPARγ)
    Tan BS, Kang O, Mai CW, Tiong KH, Khoo AS, Pichika MR, et al.
    Cancer Lett, 2013 Aug 9;336(1):127-39.
    PMID: 23612072 DOI: 10.1016/j.canlet.2013.04.014
    6-Shogaol has been shown to possess many antitumor properties including inhibition of cancer cell growth, inhibition of cancer metastasis, induction of apoptosis in cancer cells and induction of cancer cell differentiation. Despite its prominent antitumor effects, the direct molecular target of 6-shogaol has remained elusive. To identify the direct targets of 6-shogaol, a comprehensive antitumor profile of 6-shogaol (NSC752389) was tested in the NCI-60 cell line in an in vitro screen. The results show that 6-shogaol is COMPARE negative suggesting that it functions via a mechanism of action distinct from existing classes of therapeutic agents. Further analysis using microarray gene profiling and Connectivity Map analysis showed that MCF-7 cells treated with 6-shogaol display gene expression signatures characteristic of peroxisome proliferator activated receptor γ (PPARγ) agonists, suggesting that 6-shogaol may activate the PPARγ signaling pathway for its antitumor effects. Indeed, treatment of MCF-7 and HT29 cells with 6-shogaol induced PPARγ transcriptional activity, suppressed NFκB activity, and induced apoptosis in breast and colon cancer cells in a PPARγ-dependent manner. Furthermore, 6-shogaol is capable of binding to PPARγ with a binding affinity comparable to 15-delta prostaglandin J2, a natural ligand for PPARγ. Together, our findings suggest that the antitumor effects of 6-shogaol are mediated through activation of PPARγ and imply that activation of PPARγ might be beneficial for breast and colon cancer treatment.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic*
  7. A B-myb--DREAM complex is not critical to regulate the G2/M genes in HPV-transformed cell lines
    Rashid NN, Yusof R, Watson RJ
    Anticancer Res, 2014 Nov;34(11):6557-63.
    PMID: 25368258
    It is well-established that HPV E7 proteins, encoded by human papillomavirus (HPV) genes, frequently associated with cervical cancers bind avidly to the retinoblastoma (RB) family of pocket proteins and disrupt their association with members of the E2F transcription factor family. Our previous study showed that the repressive p130-dimerization partner, RB-like, E2F and multi-vulval class (DREAM) complex was disrupted by HPV16 E7 proteins in order to maintain the viral replication in CaSki cells. However, we would like to address whether the activator B-myb-DREAM complex is critical in regulating the replication and mitosis phase since our previous study showed increased B-myb-DREAM expression in HPV-transformed cell lines when compared to control cells.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  8. A Comprehensive Gene Inventory for Glucosinolate Biosynthetic Pathway in Arabidopsis thaliana
    Harun S, Abdullah-Zawawi MR, Goh HH, Mohamed-Hussein ZA
    J Agric Food Chem, 2020 Jul 15;68(28):7281-7297.
    PMID: 32551569 DOI: 10.1021/acs.jafc.0c01916
    Glucosinolates (GSLs) are plant secondary metabolites comprising sulfur and nitrogen mainly found in plants from the order of Brassicales, such as broccoli, cabbage, and Arabidopsis thaliana. The activated forms of GSL play important roles in fighting against pathogens and have health benefits to humans. The increasing amount of data on A. thaliana generated from various omics technologies can be investigated more deeply in search of new genes or compounds involved in GSL biosynthesis and metabolism. This review describes a comprehensive inventory of A. thaliana GSLs identified from published literature and databases such as KNApSAcK, KEGG, and AraCyc. A total of 113 GSL genes encoding for 23 transcription components, 85 enzymes, and five protein transporters were experimentally characterized in the past two decades. Continuous efforts are still on going to identify all molecules related to the production of GSLs. A manually curated database known as SuCCombase (http://plant-scc.org) was developed to serve as a comprehensive GSL inventory. Realizing lack of information on the regulation of GSL biosynthesis and degradation mechanisms, this review also includes relevant information and their connections with crosstalk among various factors, such as light, sulfur metabolism, and nitrogen metabolism, not only in A. thaliana but also in other crucifers.
    Matched MeSH terms: Gene Expression Regulation, Plant
  9. A Comprehensive Review of the Cosmeceutical Benefits of Vanda Species (Orchidaceae)
    Hadi H, Razali SN, Awadh AI
    Nat Prod Commun, 2015 Aug;10(8):1483-8.
    PMID: 26434147
    Orchidaceae is the largest family of flowering plants with over 35,000 species and 850 genera. About 3300 species of orchids are found in Malaysia and the diversity is highest in the Main, Keledang, Bintang and Tahan Ranges. Apart from being prized for their beauty, orchids have long been used by humans for medicinal purposes. Today the uses of orchids have been expanded to the food and cosmetics industries. Many cosmeceutical companies use orchid extracts as an active ingredient in their products. Previous studies provide riveting insights into the potential uses of orchid extracts as an active agent in cosmetics. This paper describes the cosmeceutical potential of orchids as an anti-aging, and skin moisturizing agent. Orchid extracts from Vanda coerulea and V. teres delay aging caused by reactive oxygen species (ROS) following LV irradiation through their antioxidant and anti-inflammatory activity. These extracts also show anti-aging properties by stimulating cytochrome c oxidase (complex IV), which is part of the electron transport chain in mitochondria. Stimulation of cytochrome c oxidase improves the respiratory function of mitochondria in keratinocytes. The presence of mucilage in orchids enables them to maintain skin hydration. Mucilage functions as a moisturizer and emollient due to its high water binding capacity. Additionally, orchid extracts provide skin hydration by stimulating aquaporin 3 (AQP3) and LEKTI protein expression. The presence of AQP3 leads to a five-fold increase in water permeability, which subsequently increases stratum corneum hydration. Increased LEKTI protein expression mediated by orchid extracts reduces the degradation of desmoglein-1 and enhances the structural function of desmosomes, which play important roles in preventing water evaporation.
    Matched MeSH terms: Gene Expression/drug effects
  10. A High-throughput Quantitative Expression Analysis of Cancer-related Genes in Human HepG2 Cells in Response to Limonene, a Potential Anticancer Agent
    Hafidh RR, Hussein SZ, MalAllah MQ, Abdulamir AS, Abu Bakar F
    Curr Cancer Drug Targets, 2018;18(8):807-815.
    PMID: 29141549 DOI: 10.2174/1568009617666171114144236
    BACKGROUND: Citrus bioactive compounds, as active anticancer agents, have been under focus by several studies worldwide. However, the underlying genes responsible for the anticancer potential have not been sufficiently highlighted.

    OBJECTIVES: The current study investigated the gene expression profile of hepatocellular carcinoma, HepG2, cells after treatment with Limonene.

    METHODS: The concentration that killed 50% of HepG2 cells was used to elucidate the genetic mechanisms of limonene anticancer activity. The apoptotic induction was detected by flow cytometry and confocal fluorescence microscope. Two of the pro-apoptotic events, caspase-3 activation and phosphatidylserine translocation were manifested by confocal fluorescence microscopy. Highthroughput real-time PCR was used to profile 1023 cancer-related genes in 16 different gene families related to the cancer development.

    RESULTS: In comparison to untreated cells, limonene increased the percentage of apoptotic cells up to 89.61%, by flow cytometry, and 48.2% by fluorescence microscopy. There was a significant limonene- driven differential gene expression of HepG2 cells in 15 different gene families. Limonene was shown to significantly (>2log) up-regulate and down-regulate 14 and 59 genes, respectively. The affected gene families, from the most to the least affected, were apoptosis induction, signal transduction, cancer genes augmentation, alteration in kinases expression, inflammation, DNA damage repair, and cell cycle proteins.

    CONCLUSION: The current study reveals that limonene could be a promising, cheap, and effective anticancer compound. The broad spectrum of limonene anticancer activity is interesting for anticancer drug development. Further research is needed to confirm the current findings and to examine the anticancer potential of limonene along with underlying mechanisms on different cell lines.

    Matched MeSH terms: Gene Expression Regulation, Neoplastic
  11. Fulltext A Hybrid One-Way ANOVA Approach for the Robust and Efficient Estimation of Differential Gene Expression with Multiple Patterns
    Mollah MM, Jamal R, Mokhtar NM, Harun R, Mollah MN
    PLoS One, 2015;10(9):e0138810.
    PMID: 26413858 DOI: 10.1371/journal.pone.0138810
    Identifying genes that are differentially expressed (DE) between two or more conditions with multiple patterns of expression is one of the primary objectives of gene expression data analysis. Several statistical approaches, including one-way analysis of variance (ANOVA), are used to identify DE genes. However, most of these methods provide misleading results for two or more conditions with multiple patterns of expression in the presence of outlying genes. In this paper, an attempt is made to develop a hybrid one-way ANOVA approach that unifies the robustness and efficiency of estimation using the minimum β-divergence method to overcome some problems that arise in the existing robust methods for both small- and large-sample cases with multiple patterns of expression.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic; Gene Expression Profiling/methods*
  12. Fulltext A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma
    Syafruddin SE, Rodrigues P, Vojtasova E, Patel SA, Zaini MN, Burge J, et al.
    Nat Commun, 2019 03 11;10(1):1152.
    PMID: 30858363 DOI: 10.1038/s41467-019-09116-x
    Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of the zinc finger family, regulates lipid homeostasis in clear cell renal cell carcinoma (ccRCC). We show that KLF6 supports the expression of lipid metabolism genes and promotes the expression of PDGFB, which activates mTOR signalling and the downstream lipid metabolism regulators SREBF1 and SREBF2. KLF6 expression is driven by a robust super enhancer that integrates signals from multiple pathways, including the ccRCC-initiating VHL-HIF2A pathway. These results suggest an underlying mechanism for high mTOR activity in ccRCC cells. More generally, the link between super enhancer-driven transcriptional networks and essential metabolic pathways may provide clues to the mechanisms that maintain the stability of cell identity-defining transcriptional programmes in cancer.
    Matched MeSH terms: Gene Expression Regulation, Neoplastic; Gene Expression Profiling
  13. A New Plant Expression System for Producing Pharmaceutical Proteins
    Abd-Aziz N, Tan BC, Rejab NA, Othman RY, Khalid N
    Mol Biotechnol, 2020 Apr;62(4):240-251.
    PMID: 32108286 DOI: 10.1007/s12033-020-00242-2
    In the past decade, interest in the production of recombinant pharmaceutical proteins in plants has tremendously progressed because plants do not harbor mammalian viruses, are economically competitive, easily scalable, and capable of carrying out complex post-translational modifications required for recombinant pharmaceutical proteins. Mucuna bracteata is an essential perennial cover crop species widely planted as an underground cover in oil palm and rubber plantations. As a legume, they have high biomass, thrive in its habitat, and can fix nitrogen. Thus, M. bracteata is a cost-efficient crop that shows ideal characteristics as a platform for mass production of recombinant protein. In this study, we established a new platform for the transient production of a recombinant protein in M. bracteata via vacuum-assisted agro-infiltration. Five-week-old M. bracteata plants were vacuum infiltrated with Agrobacterium tumefaciens harboring a plasmid that encodes for an anti-toxoplasma immunoglobulin (IgG) under different parameters, including trifoliate leaf positional effects, days to harvest post-infiltration, and the Agrobacterium strain used. Our results showed that vacuum infiltration of M. bracteata plant with A. tumefaciens strain GV3101 produced the highest concentration of heterologous protein in its bottom trifoliate leaf at 2 days post-infiltration. The purified anti-toxoplasma IgG was then analyzed using Western blot and ELISA. It was demonstrated that, while structural heterogeneity existed in the purified anti-toxoplasma IgG from M. bracteata, its transient expression level was two-fold higher than the model platform, Nicotiana benthamiana. This study has laid the foundation towards establishing M. bracteata as a potential platform for the production of recombinant pharmaceutical protein.
    Matched MeSH terms: Gene Expression
  14. Fulltext A P. falciparum NF54 Reporter Line Expressing mCherry-Luciferase in Gametocytes, Sporozoites, and Liver-Stages
    Marin-Mogollon C, Salman AM, Koolen KMJ, Bolscher JM, van Pul FJA, Miyazaki S, et al.
    Front Cell Infect Microbiol, 2019;9:96.
    PMID: 31058097 DOI: 10.3389/fcimb.2019.00096
    Transgenic malaria parasites expressing fluorescent and bioluminescent proteins are valuable tools to interrogate malaria-parasite biology and to evaluate drugs and vaccines. Using CRISPR/Cas9 methodology a transgenic Plasmodium falciparum (Pf) NF54 line was generated that expresses a fusion of mCherry and luciferase genes under the control of the Pf etramp10.3 gene promoter (line mCherry-luc@etramp10.3). Pf etramp10.3 is related to rodent Plasmodium uis4 and the uis4 promoter has been used to drive high transgene expression in rodent parasite sporozoites and liver-stages. We examined transgene expression throughout the complete life cycle and compared this expression to transgenic lines expressing mCherry-luciferase and GFP-luciferase under control of the constitutive gapdh and eef1a promoters. The mCherry-luc@etramp10.3 parasites express mCherry in gametocytes, sporozoites, and liver-stages. While no mCherry signal was detected in asexual blood-stage parasites above background levels, luciferase expression was detected in asexual blood-stages, as well as in gametocytes, sporozoites and liver-stages, with the highest levels of reporter expression detected in stage III-V gametocytes and in sporozoites. The expression of mCherry and luciferase in gametocytes and sporozoites makes this transgenic parasite line suitable to use in in vitro assays that examine the effect of transmission blocking inhibitors and to analyse gametocyte and sporozoite biology.
    Matched MeSH terms: Gene Expression Profiling
  15. A Perspective on Stem Cells as Biological Systems that Produce Differentiated Osteoblasts and Odontoblasts
    Ariffin SH, Manogaran T, Abidin IZ, Wahab RM, Senafi S
    Curr Stem Cell Res Ther, 2017;12(3):247-259.
    PMID: 27784228 DOI: 10.2174/1574888X11666161026145149
    Stem cells (SCs) are capable of self-renewal and multilineage differentiation. Human mesenchymal stem cells (MSCs) and haematopoietic stem cells (HSCs) which can be obtained from multiple sources, are suitable for application in regenerative medicine and transplant therapy. The aim of this review is to evaluate the potential of genomic and proteomic profiling analysis to identify the differentiation of MSCs and HSCs towards osteoblast and odontoblast lineages. In vitro differentiation towards both of these lineages can be induced using similar differentiation factors. Gene profiling cannot be utilised to confirm the lineages of these two types of differentiated cells. Differentiated cells of both lineages express most of the same markers. Most researchers have detected the expression of genes such as ALP, OCN, OPN, BMP2 and RUNX2 in osteoblasts and the expression of the DSPP gene in odontoblasts. Based on their cell-type specific protein profiles, various proteins are differentially expressed by osteoblasts and odontoblasts, except for vimentin and heterogeneous nuclear ribonucleoprotein C, which are expressed in both cell types, and LOXL2 protein, which is expressed only in odontoblasts.
    Matched MeSH terms: Gene Expression Profiling
  16. Fulltext A Pilot Study on Anti-Obesity Mechanisms of KappaphycusAlvarezii: The Role of Native κ-Carrageenan and the Leftover Sans-Carrageenan Fraction
    Chin YX, Mi Y, Cao WX, Lim PE, Xue CH, Tang QJ
    Nutrients, 2019 May 21;11(5).
    PMID: 31117266 DOI: 10.3390/nu11051133
    Kappaphycus is a commercially important edible red alga widely cultivated for carrageenan production. Here, we aimed to investigate the anti-obesity mechanism of Kappaphycusalvarezii by comparing the effects of whole seaweed (T), extracted native κ-carrageenan (CGN), and the leftover fraction sans-carrageenan (SCGN) supplementations (5%, w/w) on diet-induced obese C57BL/6J mice. A high-fat diet induced both a raised body fat percentage and serum cholesterol level, increased adipocytes size, abnormal levels of adipocytokines, and promoted gut dysbiosis. Our results showed that, overall, both CGN and SCGN were more effective in reversing obesity and related metabolic syndromes to normal levels than T. Furthermore, these findings suggested that CGN- and SCGN-modulated gut dysbiosis induced by a high-fat diet, which may play an influencing role in adiponectin dysregulation. Our data also showed some evidence that CGN and SCGN have distinct effects on selected genes involved in lipid metabolism. In conclusion, both κ-carrageenan and SCGN have novel anti-obesity potential with possible different mechanisms of action.
    Matched MeSH terms: Gene Expression Regulation/drug effects
  17. A Rhythmic Gene Entrained to Midnight May Regulate Photoperiod-Controlled Flowering in Arabidopsis
    Yeang HY
    Yale J Biol Med, 2019 06;92(2):213-223.
    PMID: 31249482
    The widely held explanation for photoperiod-controlled flowering in long-day plants is largely embodied in the External Coincidence Hypothesis which posits that flowering is induced when activity of a rhythmic gene that regulates it (a putative "flowering gene") occurs in the presence of light. Nevertheless, re-examination of the Arabidopsis flowering data from non 24-hour cycles of Roden et al. suggests that External Coincidence is not tenable if the circadian rhythm of the "flowering gene" were entrained to sunrise as commonly accepted. On the other hand, the hypothesis is supported if circadian cycling of the gene conforms to a solar rhythm, and its entrainment is to midnight on the solar clock. Data available point to flowering being induced by the gene which peaks in its expression between 16 to 19 h after midnight. In the normal 24 h cycle, that would be between 4 p.m. and 7 p.m., regardless of the photoperiod. Such timing of the "flowering gene" expression allows for variable coincidence between gene activity and light, depending on the photoperiod and cycle period. A correlation is found between earliness of flowering and the degree of coincidence of "flowering gene" expression with light (r = 0.88, p<0.01).
    Matched MeSH terms: Gene Expression Regulation, Plant/radiation effects
  18. A TRIZ-inspired bat algorithm for gene selection in cancer classification
    Al-Betar MA, Alomari OA, Abu-Romman SM
    Genomics, 2019 Oct 29.
    PMID: 31676302 DOI: 10.1016/j.ygeno.2019.09.015
    Gene expression data are expected to make a great contribution in the producing of efficient cancer diagnosis and prognosis. Gene expression data are coded by large measured genes, and only of a few number of them carry precious information for different classes of samples. Recently, several researchers proposed gene selection methods based on metaheuristic algorithms for analysing and interpreting gene expression data. However, due to large number of selected genes with limited number of patient's samples and complex interaction between genes, many gene selection methods experienced challenges in order to approach the most relevant and reliable genes. Hence, in this paper, a hybrid filter/wrapper, called rMRMR-MBA is proposed for gene selection problem. In this method, robust Minimum Redundancy Maximum Relevancy (rMRMR) as filter to select the most promising genes and an modified bat algorithm (MBA) as search engine in wrapper approach is proposed to identify a small set of informative genes. The performance of the proposed method has been evaluated using ten gene expression datasets. For performance evaluation, MBA is evaluated by studying the convergence behaviour of MBA with and without TRIZ optimisation operators. For comparative evaluation, the results of the proposed rMRMR-MBA were compared against ten state-of-arts methods using the same datasets. The comparative study demonstrates that the proposed method produced better results in terms of classification accuracy and number of selected genes in two out of ten datasets and competitive results on the remaining datasets. In a nutshell, the proposed method is able to produce very promising results with high classification accuracy which can be considered a promising contribution for gene selection domain.
    Matched MeSH terms: Gene Expression
  19. Fulltext A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk
    Lu Y, Beeghly-Fadiel A, Wu L, Guo X, Li B, Schildkraut JM, et al.
    Cancer Res, 2018 Sep 15;78(18):5419-5430.
    PMID: 30054336 DOI: 10.1158/0008-5472.CAN-18-0951
    Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10-6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10-7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10-3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419-30. ©2018 AACR.
    Matched MeSH terms: Gene Expression Profiling
  20. Fulltext A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer
    Zhong J, Jermusyk A, Wu L, Hoskins JW, Collins I, Mocci E, et al.
    J Natl Cancer Inst, 2020 Oct 01;112(10):1003-1012.
    PMID: 31917448 DOI: 10.1093/jnci/djz246
    BACKGROUND: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown.

    METHODS: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples).

    RESULTS: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction.

    CONCLUSIONS: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.

    Matched MeSH terms: Gene Expression
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