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Sample records for involving mirna deregulation

  1. MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation

    DEFF Research Database (Denmark)

    Leucci, E; Cocco, M; Onnis, A

    2008-01-01

    at the standardization of FISH procedures in lymphoma diagnosis, we found that five cases out of 35 classic endemic BLs were negative for MYC translocations by using a split-signal as well as a dual-fusion probe. Here we investigated the expression pattern of miRNAs predicted to target c-Myc, in BL cases, to clarify...... whether alternative pathogenetic mechanisms may be responsible for lymphomagenesis in cases lacking the MYC translocation. miRNAs are a class of small RNAs that are able to regulate gene expression at the post-transcriptional level. Several studies have reported their involvement in cancer...

  2. Chronic lymphocytic leukemia-associated chromosomal abnormalities and miRNA deregulation

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    Kiefer Y

    2012-03-01

    Full Text Available Yvonne Kiefer1, Christoph Schulte2, Markus Tiemann2, Joern Bullerdiek11Center for Human Genetics, University of Bremen, Bremen, Germany; 2Hematopathology Hamburg, Hamburg, GermanyAbstract: Chronic lymphocytic leukemia is the most common leukemia in adults. By cytogenetic investigations major subgroups of the disease can be identified that reflect different routes of tumor development. Of these chromosomal deviations, trisomy 12 and deletions of parts of either the long arm of chromosome 13, the long arm of chromosome 11, or the short arm of chromosome 17 are most commonly detected. In some of these aberrations the molecular target has been identified as eg, ataxia telangiectasia mutated (ATM in case of deletions of chromosomal region 11q22~23 and the genes encoding microRNAs miR-15a/16-1 as likely targets of deletions of chromosomal band 13q14.3. Of note, these aberrations do not characterize independent subgroups but often coexist within the metaphases of one tumor. Generally, complex aberrations are associated with a worse prognosis than simple karyotypic alterations. Due to smaller sizes of the missing segment the detection of recurrent deletions is not always possible by means of classical cytogenetics but requires more advanced techniques as in particular fluorescence in situ hybridization (FISH. Nevertheless, at this time it is not recommended to replace classical cytogenetics by FISH because this would miss additional information given by complex or secondary karyotypic alterations. However, the results of cytogenetic analyses allow the stratification of prognostic and predictive groups of the disease. Of these, the group characterized by deletions involving TP53 is clinically most relevant. In the future refined methods as eg, array-based comparative genomic hybridization will supplement the existing techniques to characterize CLL. Keywords: chronic lymphocytic leukemia, chromosomal abnormality, miRNA deregulation

  3. Comparative analysis of melanoma deregulated miRNAs in the medaka and Xiphophorus pigment cell cancer models.

    Science.gov (United States)

    Mishra, Rasmi R; Kneitz, Susanne; Schartl, Manfred

    2014-06-01

    Malignant melanoma is the most aggressive and deadly form of skin cancer, with an almost 100% development of resistance to current therapeutic approaches at progression stages. The incidence of melanoma is steadily increasing worldwide. Although many details leading to the development of malignant melanoma are known, the complex process of melanomagenesis is poorly understood. MicroRNAs (miRNAs) are a class of small noncoding-RNAs of ~22nt length that regulate gene expression at the post-transcriptional level. It is now well established that deregulated miRNA expression is seen in many cancers including melanoma. To further study the miRNA functions in melanoma formation and progression we use a transgenic melanoma model in Japanese ricefish (medaka; Oryzias latipes) and the natural Xiphophorus melanoma model. In these fishes, dependent on the genetic background various histo- and patho-types of tumors appear, comparable to human melanoma types. We have studied expression profiles of ten known human melanoma-associated miRNAs and their respective target gene expression in the fish melanoma models. We show that miRNAs of the miR-17-92 cluster (miR-20a2, miR-92a1, miR-17 and miR-18a), miR-126, miR-182, miR-210 and miR-214 are upregulated and their respective target genes (RUNX1, HIF1A, TGFBR2, THBS1 and JAK2) are down-regulated in melanoma. MicroRNA-125b is down-regulated and the target genes (ERBB3a and ERBB3b) are upregulated in fish melanomas. Results provide clear evidence that the fish melanoma-associated miRNAs and respective target genes are deregulated generally like in human melanoma. Our results confirm the value of fish; such as medaka and Xiphophorus as good model systems to identify and decipher molecular mechanisms associated with malignant melanoma. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Arterial remodeling and atherosclerosis: miRNAs involvement.

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    Quintavalle, Manuela; Condorelli, Gianluigi; Elia, Leonardo

    2011-10-01

    Cardiometabolic diseases (CMD) (such as atherosclerosis, diabetes, and hypertension) are the primary cause of death and disability in the Western world. Although lifestyle programs and therapeutic approaches have significantly reduced the socio-economic burden of CMD, a large number of events still cannot be avoided (the so called residual risk). Recent developments in genetics and genomics provide a platform for investigating further this area with the aim of deepening our understanding of the atherosclerotic phenomena underlying CMD, for instance by providing better information on the type of subjects who would benefit the most from therapeutic interventions, or by discovering new genetic and metabolic derangements that may be targeted for the development of new interventions. MicroRNAs (miRNA) are short, non-coding RNAs that negatively regulate the expression of proteins by binding to specific sequences on the 3' region of target mRNAs. Bioinformatics analysis predicts that each miRNA may regulate hundreds of targets, suggesting that miRNAs may play roles in almost every biological pathway and process, including those of the cardiovascular system. Studies are beginning to unravel their fundamental importance in vessel biology. Here, we review recent advance regarding the involvement of miRNAs in arterial remodeling and atherosclerosis. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Identification of miRNAs involved in fruit ripening in Cavendish bananas by deep sequencing.

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    Bi, Fangcheng; Meng, Xiangchun; Ma, Chao; Yi, Ganjun

    2015-10-13

    MicroRNAs (miRNAs) are a family of non-coding small RNAs that play an important regulatory role in various biological processes. Previous studies have reported that miRNAs are closely related to the ripening process in model plants. However, the miRNAs that are closely involved in the banana fruit ripening process remain unknown. Here, we investigated the miRNA populations from banana fruits in response to ethylene or 1-MCP treatment using a deep sequencing approach and bioinformatics analysis combined with quantitative RT-PCR validation. A total of 125 known miRNAs and 26 novel miRNAs were identified from three libraries. MiRNA profiling of bananas in response to ethylene treatment compared with 1-MCP treatment showed differential expression of 82 miRNAs. Furthermore, the differentially expressed miRNAs were predicted to target a total of 815 target genes. Interestingly, some targets were annotated as transcription factors and other functional proteins closely involved in the development and the ripening process in other plant species. Analysis by qRT-PCR validated the contrasting expression patterns between several miRNAs and their target genes. The miRNAome of the banana fruit in response to ethylene or 1-MCP treatment were identified by high-throughput sequencing. A total of 82 differentially expressed miRNAs were found to be closely associated with the ripening process. The miRNA target genes encode transcription factors and other functional proteins, including SPL, APETALA2, EIN3, E3 ubiquitin ligase, β-galactosidase, and β-glucosidase. These findings provide valuable information for further functional research of the miRNAs involved in banana fruit ripening.

  6. miRNA profiling of B-cell subsets : specific miRNA profile for germinal center B cells with variation between centroblasts and centrocytes

    NARCIS (Netherlands)

    Tan, Lu Ping; Wang, Miao; Robertus, Jan-Lukas; Schakel, Rikst Nynke; Gibcus, Johan H.; Diepstra, Arjan; Harms, Geert; Peh, Suat-Cheng; Reijmers, Rogier M.; Pals, Steven T.; Kroesen, Bart-Jan; Kluin, Philip M.; Poppema, Sibrand; van den Berg, Anke

    MicroRNAs ( miRNAs) are an important class of small RNAs that regulate gene expression at the post-transcriptional level. It has become evident that miRNAs are involved in hematopoiesis, and that deregulation of miRNAs may give rise to hematopoietic malignancies. The aim of our study was to

  7. miRNA profiling of B-cell subsets: specific miRNA profile for germinal center B cells with variation between centroblasts and centrocytes

    NARCIS (Netherlands)

    Tan, Lu Ping; Wang, Miao; Robertus, Jan-Lukas; Schakel, Rikst Nynke; Gibcus, Johan H.; Diepstra, Arjan; Harms, Geert; Peh, Suat-Cheng; Reijmers, Rogier M.; Pals, Steven T.; Kroesen, Bart-Jan; Kluin, Philip M.; Poppema, Sibrand; van den Berg, Anke

    2009-01-01

    MicroRNAs ( miRNAs) are an important class of small RNAs that regulate gene expression at the post-transcriptional level. It has become evident that miRNAs are involved in hematopoiesis, and that deregulation of miRNAs may give rise to hematopoietic malignancies. The aim of our study was to

  8. Genetic Subtraction Profiling Identifies Candidate miRNAs Involved in Rice Female Gametophyte Abortion

    Directory of Open Access Journals (Sweden)

    Liyu Yang

    2017-07-01

    Full Text Available The female gametophyte is an important participant in the sexual reproduction of plants. The molecular mechanism of its development has received much attention in recent years. As important regulators of gene expression, miRNAs have been certified to play a significant role in many biological processes of plants, including sexual reproduction. In this study, to investigate the potential regulatory effects of miRNAs on rice female gametophyte abortion, we used the high-throughput sequencing method to compare the miRNA transcriptome in ovules of a high frequency female-sterile line (fsv1 and a rice wild-type line (Gui 99 during ovule development. As a result, 522 known miRNAs and 295 novel miRNAs were expressed in the developing ovule of rice, while 100 known miRNAs were significantly differentially expressed between these two rice lines during ovule development. Combining with gene expression information, a total of 627 coherent target genes of these differential expressed known miRNAs between fsv1 and Gui 99 were identified. The functional analyses of these coherent target genes revealed that the coherent target genes of differential expressed known miRNAs between the two rice lines are involved in many biological pathways, such as protein degradation, auxin signal transduction, and transcription factor regulation. These results provide us with important clues to investigate the regulatory roles of miRNAs in rice female gametophyte abortion.

  9. Analysis of miRNAs Involved in Mouse Brain Damage upon Enterovirus 71 Infection.

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    Yang, Xiaoxia; Xie, Jing; Jia, Leili; Liu, Nan; Liang, Yuan; Wu, Fuli; Liang, Beibei; Li, Yongrui; Wang, Jinyan; Sheng, Chunyu; Li, Hao; Liu, Hongbo; Ma, Qiuxia; Yang, Chaojie; Du, Xinying; Qiu, Shaofu; Song, Hongbin

    2017-01-01

    Enterovirus 71 (EV71) infects the central nervous system (CNS) and causes brainstem encephalitis in children. MiRNAs have been found to play various functions in EV71 infection in human cell lines. To identify potential miRNAs involved in the inflammatory injury in CNS, our study, for the first time, performed a miRNA microarray assay in vivo using EV71 infected mice brains. Twenty differentially expressed miRNAs were identified (four up- and 16 down-regulated) and confirmed by qRT-PCR. The target genes of these miRNAs were analyzed using KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, revealing that the miRNAs were mainly involved in the regulation of inflammation and neural system function. MiR-150-5p, -3082-5p, -3473a, -468-3p, -669n, -721, -709, and -5107-5p that regulate MAPK and chemokine signaling were all down-regulated, which might result in increased cytokine production. In addition, miR-3473a could also regulate focal adhesion and leukocyte trans-endothelial migration, suggesting a role in virus-induced blood-brain barrier disruption. The miRNAs and pathways identified in this study could help to understand the intricate interactions between EV71 and the brain injury, offering new insight for the future research of the molecular mechanism of EV71 induced brainstem encephalitis.

  10. Cloning and Characterization of Maize miRNAs Involved in Responses to Nitrogen Deficiency

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    Zhao, Meng; Tai, Huanhuan; Sun, Suzhen; Zhang, Fusuo; Xu, Yunbi; Li, Wen-Xue

    2012-01-01

    Although recent studies indicated that miRNAs regulate plant adaptive responses to nutrient deprivation, the functional significance of miRNAs in adaptive responses to nitrogen (N) limitation remains to be explored. To elucidate the molecular biology underlying N sensing/signaling in maize, we constructed four small RNA libraries and one degradome from maize seedlings exposed to N deficiency. We discovered a total of 99 absolutely new loci belonging to 47 miRNA families by small RNA deep sequencing and degradome sequencing, as well as 9 new loci were the paralogs of previously reported miR169, miR171, and miR398, significantly expanding the reported 150 high confidence genes within 26 miRNA families in maize. Bioinformatic and subsequent small RNA northern blot analysis identified eight miRNA families (five conserved and three newly identified) differentially expressed under the N-deficient condition. Predicted and degradome-validated targets of the newly identified miRNAs suggest their involvement in a broad range of cellular responses and metabolic processes. Because maize is not only an important crop but is also a genetic model for basic biological research, our research contributes to the understanding of the regulatory roles of miRNAs in plant adaption to N-deficiency stress. PMID:22235323

  11. Involvement of miRNAs in Placental Alterations Mediated by Oxidative Stress

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    Alexander Rudov

    2014-01-01

    Full Text Available Oxidative stress (OS is known to be strongly involved in a large number of fetal, neonatal, and adult diseases, including placental disorders, leading to pregnancy loss and stillbirths. A growing body of research links OS to preeclampsia, gestational diabetes, obesity, spontaneous abortion, recurrent pregnancy, preterm labor, and intrauterine growth restriction. While a considerable number of miRNAs have been related to physiological functions and pathological conditions of the placenta, a direct link among these miRNAs, placental functions, and OS is still lacking. This review summarizes data describing the role of miRNAs in placental pathophysiological processes and their possible impact on OS damaging responses. As miRNAs can be found in circulation, improving our understanding on their role in the pathogenesis of pregnancy related disorders could have an important impact on the diagnosis and prognosis of these diseases.

  12. Study of miRNA Based Gene Regulation, Involved in Solid Cancer, by the Assistance of Argonaute Protein

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    Surya Narayan Rath

    2016-09-01

    Full Text Available Solid tumor is generally observed in tissues of epithelial or endothelial cells of lung, breast, prostate, pancreases, colorectal, stomach, and bladder, where several genes transcription is regulated by the microRNAs (miRNAs. Argonaute (AGO protein is a family of protein which assists in miRNAs to bind with mRNAs of the target genes. Hence, study of the binding mechanism between AGO protein and miRNAs, and also with miRNAs-mRNAs duplex is crucial for understanding the RNA silencing mechanism. In the current work, 64 genes and 23 miRNAs have been selected from literatures, whose deregulation is well established in seven types of solid cancer like lung, breast, prostate, pancreases, colorectal, stomach, and bladder cancer. In silico study reveals, miRNAs namely, miR-106a, miR-21, and miR-29b-2 have a strong binding affinity towards PTEN, TGFBR2, and VEGFA genes, respectively, suggested as important factors in RNA silencing mechanism. Furthermore, interaction between AGO protein (PDB ID-3F73, chain A with selected miRNAs and with miRNAs-mRNAs duplex were studied computationally to understand their binding at molecular level. The residual interaction and hydrogen bonding are inspected in Discovery Studio 3.5 suites. The current investigation throws light on understanding miRNAs based gene silencing mechanism in solid cancer.

  13. Possible involvement of miRNAs in tropism of Parvovirus B19.

    Science.gov (United States)

    Anbarlou, Azadeh; AkhavanRahnama, Mahshid; Atashi, Amir; Soleimani, Masoud; Arefian, Ehsan; Gallinella, Giorgio

    2016-03-01

    Human Parvovirus B19 (PVB19) is one of the most important pathogens that targets erythroid lineage. Many factors were mentioned for restriction to erythroid progenitor cells (EPCs). Previous studies showed that in non-permissive cells VP1 and VP2 (structural proteins) mRNAs were detected but could not translate to proteins. A bioinformatics study showed that this inhibition might be due to specific microRNAs (miRNAs) present in non-permissive cells but not in permissive EPCs. To confirm the hypothesis, we evaluated the effect of miRNAs on VP expression. CD34(+) HSCs were separated from cord blood. Then, CD34(+) cells were treated with differentiation medium to obtain CD36(+) EPCs. To evaluate the effect of miRNAs on VP expression in MCF7 and HEK-293 cell lines (non-permissive cells) and CD36(+) EPCs, dual luciferase assay was performed in presence of shRNAs against Dicer and Drosha to disrupt miRNA biogenesis. QRT-PCR was performed to check down-regulation of Dicer and Drosha after transfection. All measurements were done in triplicate. Data means were compared using one-way ANOVAs. MicroRNA prediction was done by the online microRNA prediction tools. No significant difference was shown in luciferase activity of CD36(+) EPCs after co-transfection with shRNAs, while it was significant in non-permissive cells. Our study revealed that miRNAs may be involved in inhibition of VP expression in non-permissive cells, although further studies are required to demonstrate which miRNAs exactly are involved in regulation of PVB19 replication.

  14. Identification of cisregulatory elements and bioinformatic prediction of transcriptional factors involved in regulation of miRNAs in plants

    International Nuclear Information System (INIS)

    Perez Quintero, Alvaro; Lopez, Camilo

    2013-01-01

    MicroRNAs (miRNAs) are a group of small non coding MAS involved in the control of gene expression through the degradation of miRNAs in a sequence specific manner, miRNAs expression is dependent on RNA polymerase ii as most of the coding protein genes. The regulation of miRNAs expression is under the coordinated and combinatorial control of transcription factors (TFS). A bioinformatics approach was carried out to identify transcription factor binding sites (TFBS) in the promoter of miRNAs genes in 17 different plant species and the possible involvement of TF in antibacterial response was analyzed. In nine of the plants studied significant differences in TFBS distribution in the promoter of miRNAs were observed when compare to the promoter of protein coding genes. TFBS as CCA1, T-box y SORLREP3 were present on the promoters of the cassava miRNAs induced in response to the infection by the bacteria Xanthomonas axonopodis pv. manihotis. These TFBS are also present in the promoter of genes coding for proteins involved in circadian rhythm and light responses, suggesting a crosstalk between these process and immune plant responses. Taken together, the results here described give insight about the transcriptional mechanisms involved in the expression of miRNAs.

  15. Small RNA profiles of the rice PTGMS line Wuxiang S reveal miRNAs involved in the fertility transition

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    Yi eDing

    2016-04-01

    Full Text Available MicroRNAs (miRNAs play key roles in the regulation of plant growth and developmental processes. In this study, the RNA-seq technique was employed to examine the expression profiles of miRNAs in a novel rice photo-thermo sensitive generic male sterile (PTGMS line Wuxiang S (WXS during the fertility transition. A total of 497 known miRNAs and 273 novel miRNAs were identified. By means of the differentially expression analysis, a total of 26 miRNAs were discovered to be significant difference expression between WXS (Sterility, S and WXS (Fertility, F. And some of these miRNAs were validated by quantitative real-time PCR. Among these miRNAs, eleven of which were decreased, and fifteen of which were increased in the expression levels of genes when WXS (S compared with WXS (F, respectively. Some of these miRNAs such as osa-miR156a-j, osa-miR164d and osa-miR528, were showed to be negatively correlated with their targets. These targets have previously been reported to be related with pollen development and male sterility, suggesting that these miRNAs might be involved in the regulation of pollen development in the rice PTGMS line WXS. Furthermore, the miRNAs editing events were also observed. A possible control model of miRNAs and signaling pathway was proposed in the process of fertility transition of rice PTGMS line WXS in this study. These findings contribute to our understanding of the roles of miRNAs during anther development of PTGMS occurrence in rice.

  16. Turmeric (Curcuma longa): miRNAs and their regulating targets are involved in development and secondary metabolite pathways.

    Science.gov (United States)

    Singh, Noopur; Sharma, Ashok

    Turmeric has been used as a therapeutic herb over centuries in traditional medicinal systems due to the presence of several secondary metabolite compounds. microRNAs are known to regulate gene expression at the post-transcriptional level by transcriptional cleavage or translation repression. miRNAs have been demonstrated to play an active role in secondary metabolism regulation. The present work was focused on the identification of the miRNAs involved in the regulation of secondary metabolite and development process of turmeric. Eighteen miRNA families were identified for turmeric. Sixteen miRNA families were observed to regulate 238 target transcripts. LncRNAs targets of the putative miRNA candidates were also predicted. Our results indicated their role in binding, reproduction, stress, and other developmental processes. Gene annotation and pathway analysis illustrated the biological function of the targets regulated by the putative miRNAs. The miRNA-mediated gene regulatory network also revealed co-regulated targets that were regulated by two or more miRNA families. miR156 and miR5015 were observed to be involved in rhizome development. miR5021 showed regulation for terpenoid backbone biosynthesis and isoquinoline alkaloid biosynthesis pathways. The flavonoid biosynthesis pathway was observed to be regulated by miR2919. The analysis revealed the probable involvement of three miRNAs (miR1168.2, miR156b and miR1858) in curcumin biosynthesis. Other miRNAs were found to be involved in the growth and developmental process of turmeric. Phylogenetic analysis of selective miRNAs was also performed. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  17. Small RNA Profiles of the Rice PTGMS Line Wuxiang S Reveal miRNAs Involved in Fertility Transition.

    Science.gov (United States)

    Zhang, Hongyuan; Hu, Jihong; Qian, Qian; Chen, Hao; Jin, Jing; Ding, Yi

    2016-01-01

    MicroRNAs (miRNAs) play key roles in the regulation of plant growth and developmental processes. In this study, RNA-seq was used to examine the expression profiles of miRNAs in a novel, photo-thermosensitive genic male sterile (PTGMS) rice line, Wuxiang S (WXS), during fertility transition. A total of 497 known miRNAs and 273 novel miRNAs were identified. In a differential expression analysis, 26 miRNAs exhibited significant differential expression between WXS (Sterile, S) and WXS (Fertile, F). Some of these miRNAs were validated by quantitative real-time PCR. Among these miRNAs, 11 showed decreased expression levels, and 15 showed increased expression levels in WXS (S) compared to WXS (F). Some of these miRNAs, such as osa-miR156a-j, osa-miR164d, and osa-miR528, were shown to be negatively correlated with their targets. These targets have previously been reported to be related to pollen development and male sterility, suggesting that these miRNAs may be involved in the regulation of pollen development in the rice PTGMS line WXS. Furthermore, miRNA-mediated editing events were also observed. In this study, a possible model for the control of signaling pathways during the process of fertility transition in the rice PTGMS line WXS by miRNAs was developed. These findings contribute to our understanding of the roles of miRNAs during anther development in PTGMS lines in rice.

  18. De-regulated microRNAs in pediatric cancer stem cells target pathways involved in cell proliferation, cell cycle and development.

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    Patricia C Sanchez-Diaz

    Full Text Available microRNAs (miRNAs have been implicated in the control of many biological processes and their deregulation has been associated with many cancers. In recent years, the cancer stem cell (CSC concept has been applied to many cancers including pediatric. We hypothesized that a common signature of deregulated miRNAs in the CSCs fraction may explain the disrupted signaling pathways in CSCs.Using a high throughput qPCR approach we identified 26 CSC associated differentially expressed miRNAs (DEmiRs. Using BCmicrO algorithm 865 potential CSC associated DEmiR targets were obtained. These potential targets were subjected to KEGG, Biocarta and Gene Ontology pathway and biological processes analysis. Four annotated pathways were enriched: cell cycle, cell proliferation, p53 and TGF-beta/BMP. Knocking down hsa-miR-21-5p, hsa-miR-181c-5p and hsa-miR-135b-5p using antisense oligonucleotides and small interfering RNA in cell lines led to the depletion of the CSC fraction and impairment of sphere formation (CSC surrogate assays.Our findings indicated that CSC associated DEmiRs and the putative pathways they regulate may have potential therapeutic applications in pediatric cancers.

  19. Next-generation sequencing identifies deregulation of microRNAs involved in both innate and adaptive immune response in ALK+ ALCL.

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    Julia Steinhilber

    Full Text Available Anaplastic large cell lymphoma (ALCL is divided into two systemic diseases according to the expression of the anaplastic lymphoma kinase (ALK. We investigated the differential expression of miRNAs between ALK+ ALCL, ALK- ALCL cells and normal T-cells using next generation sequencing (NGS. In addition, a C/EBPβ-dependent miRNA profile was generated. The data were validated in primary ALCL cases. NGS identified 106 miRNAs significantly differentially expressed between ALK+ and ALK- ALCL and 228 between ALK+ ALCL and normal T-cells. We identified a signature of 56 miRNAs distinguishing ALK+ ALCL, ALK- ALCL and T-cells. The top candidates significant differentially expressed between ALK+ and ALK- ALCL included 5 upregulated miRNAs: miR-340, miR-203, miR-135b, miR-182, miR-183; and 7 downregulated: miR-196b, miR-155, miR-146a, miR-424, miR-503, miR-424*, miR-542-3p. The miR-17-92 cluster was also upregulated in ALK+ cells. Additionally, we identified a signature of 3 miRNAs significantly regulated by the transcription factor C/EBPβ, which is specifically overexpressed in ALK+ ALCL, including the miR-181 family. Of interest, miR-181a, which regulates T-cell differentiation and modulates TCR signalling strength, was significantly downregulated in ALK+ ALCL cases. In summary, our data reveal a miRNA signature linking ALK+ ALCL to a deregulated immune response and may reflect the abnormal TCR antigen expression known in ALK+ ALCL.

  20. miRNA778 and SUVH6 are involved in phosphate homeostasis in Arabidopsis.

    Science.gov (United States)

    Wang, Lei; ZengJ, Hou Qing; Song, Jun; Feng, Sheng Jun; Yang, Zhi Min

    2015-09-01

    microRNAs (miRNAs) play an important role in plant adaptation to phosphate (Pi) starvation. Histone methylation can remodel chromatin structure and mediate gene expression. This study identified Arabidopsis miR778, a Pi-responsive miRNA, and its target gene Su(var) 3-9 homologs 6 (SUVH6) encoding a histone H3 lysine 9 (H3K9) methyltransferase. Overexpression of miR778 moderately enhanced primary and lateral root growth, free phosphate accumulation in shoots, and accumulation of anthocyanin under Pi deficient conditions. miR778 overexpression relieved the arrest of columella cell development under Pi starvation. Conversely, transgenic plants overexpressing a miR778-target mimic (35S::MIM778), that act as a sponge and sequesters miR778, showed opposite phenotypes of 35S::miR778 plants under Pi deficiency. Expression of several Pi deficiency-responsive genes such as miR399, Phosphate Transporter (PHT1;4), Low Phosphate-Resistant1 (LPR1) and Production of Anthocyanin Pigment 1 (PAP1) were elevated in the miR778 overexpressing plants, suggesting that both miR778 and SUVH6 are involved in phosphate homeostasis in plants. This study has provided a basis for further investigation on how SUVH6 regulates its downstream genes through chromatin remodeling and DNA methylation in plants stressed by Pi deficiency. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Small RNA profiling for identification of miRNAs involved in regulation of saponins biosynthesis in Chlorophytum borivilianum.

    Science.gov (United States)

    Kajal, Monika; Singh, Kashmir

    2017-12-28

    MicroRNAs act as molecular regulator of cell signaling, plant growth and development, and regulate various primary and secondary plant metabolic processes. In the present study, deep sequencing of small RNAs was carried out to identify known and novel miRNAs from pharmaceutically important plant, Chlorophytum borivilianum. Total 442 known miRNAs and 5 novel miRNAs were identified from young leaf small RNA library. Experimental validation with stem loop RT-PCR confirmed the in silico identification. Based on transcriptome data of root and leaf of C. borivilianum, Oryza sativa, and Arabidopsis thaliana target gene prediction was done using psRNAtarget and mirRanda. BLAST2GO helped in localization of predicted targets and KEGG (Kyoto Encyclopedia for Genes and Genomes) pathway analysis concluded that miR9662, miR894, miR172, and miR166 might be involved in regulating saponin biosynthetic pathway. The correlation between miRNA and its target gene was further validated by RT-qPCR analysis. This study provides first elaborated glimpse of miRNA pool of C. borivilianum, which can help to understand the miRNA dependent regulation of saponin biosynthesis and to design further metabolic engineering experiment to enhance their contents in the plant.

  2. Potential miRNA involvement in the anti-adipogenic effect of resveratrol and its metabolites.

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    Itziar Eseberri

    Full Text Available Scientific research is constantly striving to find molecules which are effective against excessive body fat and its associated complications. Taking into account the beneficial effects that resveratrol exerts on other pathologies through miRNA, the aim of the present work was to analyze the possible involvement of miRNAs in the regulation of adipogenic transcription factors peroxisome proliferator-activated receptor γ (pparγ, CCAAT enhancer-binding proteins α and β (cebpβ and cebpα induced by resveratrol and its metabolites.3T3-L1 maturing pre-adipocytes were treated during differentiation with 25 μM of trans-resveratrol (RSV, trans-resveratrol-3-O-sulfate (3S, trans-resveratrol-3'-O-glucuronide (3G and trans-resveratrol-4'-O-glucuronide (4G. After computational prediction and bibliographic search of miRNAs targeting pparγ, cebpβ and cebpα, the expression of microRNA-130b-3p (miR-130b-3p, microRNA-155-5p (miR-155-5p, microRNA-27b-3p (miR-27b-3p, microRNA-31-5p (miR-31-5p, microRNA-326-3p (miR-326-3p, microRNA-27a-3p (miR-27a-3p, microRNA-144-3p (miR-144-3p, microRNA-205-5p (miR-205-5p and microRNA-224-3p (miR-224-3p was analyzed. Moreover, other adipogenic mediators such as sterol regulatory element binding transcription factor 1 (srebf1, krüppel-like factor 5 (klf5, liver x receptor α (lxrα and cAMP responding element binding protein 1 (creb1, were measured by Real Time RT-PCR. As a confirmatory assay, cells treated with RSV were transfected with anti-miR-155 in order to measure cebpβ gene and protein expressions.Of the miRNAs analyzed only miR-155 was modified after resveratrol and glucuronide metabolite treatment. In transfected cells with anti-miR-155, RSV did not reduce cebpβ gene and protein expression. 3S decreased gene expression of creb1, klf5, srebf1 and lxrα.While RSV and glucuronide metabolites exert their inhibitory effect on adipogenesis through miR-155 up-regulation, the anti-adipogenic effect of 3S is not mediated

  3. miRNA-34b is directly involved in the aging of macrophages.

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    Liang, Wei; Gao, Sheng; Liang, Liu; Huang, Xianing; Hu, Nan; Lu, Xiaoling; Zhao, Yongxiang

    2017-08-01

    MicroRNAs (miRNAs) are a class of short noncoding RNA that play important regulatory roles in living organisms. These RNA molecules are implicated in the development and progression of malignant diseases such as cancer and are closely associated with cell aging. Findings demonstrating that microRNA is associated with aging in macrophages have nevertheless rarely been reported. This study's objective was to investigate if miRNA-34 is linked to aging process of macrophages. We built a cell aging model in mouse RAW264.7 macrophages using D-galactose and determined the expression levels of miRNA-34a, miRNA-34b, and miRNA-34c in aging and normal macrophages by fluorescence quantitative polymerase chain reaction (q-PCR). We predicted a target gene of miRNA-34 using biological information techniques and constructed the recombinant plasmid pGL3-E2f3 for the putative target gene E2f3. The expression level of miRNA-34b was 5.23 times higher in aging macrophages than in normal macrophages. The luciferase activity decreased by nearly 50 % in cells transfected with miRNA-34b mimics, while no significant decrease in luciferase activity was noted in cells transfected with the miRNA-34b inhibitor or unrelated sequences. Our findings provide the groundwork for further research into the molecular mechanisms whereby miRNA-34b regulates the aging of macrophages. miRNA-34b is associated with the aging of RAW264.7 macrophages, and E2f3 is a target gene of miRNA-34b.

  4. MYC translocation-negative classical Burkitt lymphoma cases: an alternative pathogenetic mechanism involving miRNA deregulation.

    NARCIS (Netherlands)

    Leucci, E.; Cocco, M.; Onnis, A.; Falco, G De; Cleef, P van; Bellan, C.; Rijk, A van; Nyagol, J.; Byakika, B.; Lazzi, S.; Tosi, P.; Krieken, H. van; Leoncini, L.

    2008-01-01

    The molecular feature of Burkitt lymphoma (BL) is the translocation that places c-Myc under the control of immunoglobulin gene regulatory elements. However, there is accumulating evidence that some cases may lack an identifiable MYC translocation. In addition, during the EUROFISH project, aiming at

  5. Deregulation of mTOR signaling is involved in thymic lymphoma development in Atm-/- mice

    Energy Technology Data Exchange (ETDEWEB)

    Kuang, Xianghong; Shen, Jianjun; Wong, Paul K.Y. [Department of Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Science Park-Research Division, Park Road 1C, Smithville, TX 78957 (United States); Yan, Mingshan, E-mail: mingyan@mdanderson.org [Department of Carcinogenesis, The University of Texas, MD Anderson Cancer Center, Science Park-Research Division, Park Road 1C, Smithville, TX 78957 (United States)

    2009-06-05

    Abnormal thymocyte development with thymic lymphomagenesis inevitably occurs in Atm-/- mice, indicating that ATM plays a pivotal role in regulating postnatal thymocyte development and preventing thymic lymphomagenesis. The mechanism for ATM controls these processes is unclear. We have shown previously that c-Myc, an oncoprotein regulated by the mammalian target of rapamycin (mTOR), is overexpressed in Atm-/- thymocytes. Here, we show that inhibition of mTOR signaling with its specific inhibitor, rapamycin, suppresses normal thymocyte DNA synthesis by downregulating 4EBP1, but not S6K, and that 4EBP1 phosphorylation and cyclin D1 expression are coordinately increased in Atm-/- thymocytes. Administration of rapamycin to Atm-/- mice attenuates elevated phospho-4EBP1, c-Myc and cyclin D1 in their thymocytes, and delays thymic lymphoma development. These results indicate that mTOR downstream effector 4EBP1 is essential for normal thymocyte proliferation, but deregulation of 4EBP1 in Atm deficiency is a major factor driving thymic lymphomagenesis in the animals.

  6. Deregulation of microRNA expression in thyroid neoplasias.

    Science.gov (United States)

    Pallante, Pierlorenzo; Battista, Sabrina; Pierantoni, Giovanna Maria; Fusco, Alfredo

    2014-02-01

    MicroRNAs (miRNAs) have emerged as a class of powerful gene expression regulators. Acting at the post-transcriptional level, miRNAs modulate the expression of at least one-third of the mRNAs that are encoded by the human genome. The expression of a single gene can be regulated by several miRNAs, and every miRNA has more than one target gene. Thus, the miRNA regulatory circuit, which affects essential cellular functions, is of enormous complexity. Moreover, a fundamental role for miRNAs has been determined in the onset and progression of human cancers. Here, we summarize the main alterations in miRNA expression that have been identified in thyroid neoplasias and examine the mechanisms through which miRNA deregulation might promote thyroid cell transformation. We also discuss how the emerging knowledge on miRNA deregulation could be harnessed for the diagnosis and treatment of thyroid neoplasias.

  7. In vitro combinatory effects of the Alternaria mycotoxins alternariol and altertoxin II and potentially involved miRNAs.

    Science.gov (United States)

    Vejdovszky, Katharina; Sack, Matej; Jarolim, Katharina; Aichinger, Georg; Somoza, Mark M; Marko, Doris

    2017-02-05

    Alternariol (AOH) and altertoxin II (ATX II) are mycotoxins formed by Alternaria spp. Since they are expected to co-occur in Alternaria-infested food and feed, we addressed the question of combinatory effects. In addition, potentially involved regulatory microRNAs were surveyed in an exploratory approach. Cytotoxicity measurements in constant ratio combinations of 1:10 or 1:1 (ATX II: AOH) mainly revealed additive effects in HepG2, HT29 and HCEC-1CT cells. Yet, in specific high doses antagonism was found. Microarray analysis of miRNA expression profiles in HepG2 cells indicated different patterns of miRNA regulation by AOH and ATX II, including several miRNA species for which no distinct functions are currently known. Among others, miR-4654, miR-4715_3p and miR-6720_3p were up-regulated by AOH and miR-5583_5p was down-regulated by ATX II. Additionally, miR-1323, involved in hindering DNA repair mechanisms, was decreased by ATX II. Digital droplet PCR (ddPCR) analysis of selected miRNAs indicated regulation of miR-29a by AOH, which might play a role in AOH-induced apoptosis. miR-192 and miR-224 regulation was associated with antagonistic cytotoxic effects of AOH and ATX II combinations. Our study represents the first evaluation on combinatory effects of AOH and ATX II. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Deregulated microRNAs in CD4+ T cells from individuals with latent tuberculosis versus active tuberculosis.

    Science.gov (United States)

    Fu, Yurong; Yi, Zhengjun; Li, Jianhua; Li, Ruifang

    2014-03-01

    The mechanisms of latent tuberculosis (TB) infection remain elusive. Roles of microRNA (miRNA) have been highlighted in pathogen-host interactions recently. To identify miRNAs involved in the immune response to TB, expression profiles of miRNAs in CD4(+) T cells from patients with latent TB, active TB and healthy controls were investigated by microarray assay and validated by RT-qPCR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyse the significant functions and involvement in signalling pathways of the differentially expressed miRNAs. To identify potential target genes for miR-29, interferon-γ (IFN-γ) mRNA expression was measured by RT-qPCR. Our results showed that 27 miRNAs were deregulated among the three groups. RT-qPCR results were generally consistent with the microarray data. We observed an inverse correlation between miR-29 level and IFN-γ mRNA expression in CD4(+) T cells. GO and KEGG pathway analysis showed that the possible target genes of deregulated miRNAs were significantly enriched in mitogen-activated protein kinase signalling pathway, focal adhesion and extracellular matrix receptor interaction, which might be involved in the transition from latent to active TB. In all, for the first time, our study revealed that some miRNAs in CD4(+) T cells were altered in latent and active TB. Function and pathway analysis highlighted the possible involvement of miRNA-deregulated mRNAs in TB. The study might help to improve understanding of the relationship between miRNAs in CD4(+) T cells and TB, and laid an important foundation for further identification of the underlying mechanisms of latent TB infection and its reactivation. © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  9. Spontaneous deregulation

    NARCIS (Netherlands)

    Edelman, Benjamin; Geradin, Damien

    Platform businesses such as Airbnb and Uber have risen to success partly by sidestepping laws and regulations that encumber their traditional competitors. Such rule flouting is what the authors call “spontaneous private deregulation,” and it’s happening in a growing number of industries. The authors

  10. Electrical deregulation

    International Nuclear Information System (INIS)

    Simpson, R.

    2001-01-01

    Deregulation in the electricity sector took effect on January 1, 2001 in Alberta. Business consumers discovered that their electricity rates had almost doubled in a one-month period. The government argued that it was the case of short term pain for long term gain. The intent of the deregulation is the lowering of prices through competition. This principle applies when the supply meets the demand, but when the demand exceeds the supply, prices increase. When initial plans were made for the deregulation of the sector, utilities did not invest huge amounts of capital to build new generation plants, as it was not known how they would fare in the deregulated environment. This situation was compounded by the fact that there was an economic boom around the same time in Alberta, adding to the demands made on the existing generation infrastructure (approximately 4 per cent per year over the past decade). At the moment, some resource developers such as Syncrude, Amoco, and Daishowa produce their own electricity and export their excess capacity to the provincial grid for general use. The rules of the deregulated market have been clarified and a number of utilities are planning new generation plants and facilities. TransAlta, EPCOR, and Enmax Corp. have announced plans to expand or build new coal-fired plants. Alberta has an estimated 35 billion tonnes of recoverable coal, and 25 million tonnes of coal were used in 1999 to produce 75 per cent of the electricity required in Alberta. Over the next ten years, 4,000 megawatts of new capacity is planned, representing a 50 per cent increase over current levels. AES Corporation, a Virginia power giant, has also announced plans to build a generator in Alberta

  11. High-Throughput Sequencing of Small RNA Transcriptomes in Maize Kernel Identifies miRNAs Involved in Embryo and Endosperm Development

    Directory of Open Access Journals (Sweden)

    Lijuan Xing

    2017-12-01

    Full Text Available Maize kernel development is a complex biological process that involves the temporal and spatial expression of many genes and fine gene regulation at a transcriptional and post-transcriptional level, and microRNAs (miRNAs play vital roles during this process. To gain insight into miRNA-mediated regulation of maize kernel development, a deep-sequencing technique was used to investigate the dynamic expression of miRNAs in the embryo and endosperm at three developmental stages in B73. By miRNA transcriptomic analysis, we characterized 132 known miRNAs and six novel miRNAs in developing maize kernel, among which, 15 and 14 miRNAs were commonly differentially expressed between the embryo and endosperm at 9 days after pollination (DAP, 15 DAP and 20 DAP respectively. Conserved miRNA families such as miR159, miR160, miR166, miR390, miR319, miR528 and miR529 were highly expressed in developing embryos; miR164, miR171, miR393 and miR2118 were highly expressed in developing endosperm. Genes targeted by those highly expressed miRNAs were found to be largely related to a regulation category, including the transcription, macromolecule biosynthetic and metabolic process in the embryo as well as the vitamin biosynthetic and metabolic process in the endosperm. Quantitative reverse transcription-PCR (qRT-PCR analysis showed that these miRNAs displayed a negative correlation with the levels of their corresponding target genes. Importantly, our findings revealed that members of the miR169 family were highly and dynamically expressed in the developing kernel, which will help to exploit new players functioning in maize kernel development.

  12. High-throughput sequencing of small RNAs from pollen and silk and characterization of miRNAs as candidate factors involved in pollen-silk interactions in maize.

    Directory of Open Access Journals (Sweden)

    Xiao Ming Li

    Full Text Available In angiosperms, successful pollen-pistil interactions are the prerequisite and guarantee of subsequent fertilization and seed production. Recent profile analyses have helped elucidate molecular mechanisms underlying these processes at both transcriptomic and proteomic levels, but the involvement of miRNAs in pollen-pistil interactions is still speculative. In this study, we sequenced four small RNA libraries derived from mature pollen, in vitro germinated pollen, mature silks, and pollinated silks of maize (Zea mays L.. We identified 161 known miRNAs belonging to 27 families and 82 novel miRNAs. Of these, 40 conserved and 16 novel miRNAs showed different expression levels between mature and germinated pollen, and 30 conserved and eight novel miRNAs were differentially expressed between mature and pollinated silks. As candidates for factors associated with pollen-silk (pistil interactions, expression patterns of the two sets of differentially expressed miRNAs were confirmed by stem-loop real-time RT-PCR. Transcript levels of 22 predicted target genes were also validated using real-time RT-PCR; most of these exhibited expression patterns contrasting with those of their corresponding miRNAs. In addition, GO analysis of target genes of differentially expressed miRNAs revealed that functional categories related to auxin signal transduction and gene expression regulation were overrepresented. These results suggest that miRNA-mediated auxin signal transduction and transcriptional regulation have roles in pollen-silk interactions. The results of our study provide novel information for understanding miRNA regulatory roles in pollen-pistil interactions.

  13. Telecommunications Deregulation

    OpenAIRE

    Jerry A. Hausman; William E. Taylor

    2012-01-01

    From Fred Kahn's writings and experiences as a telecommunications regulator and commenter, we draw the following conclusions: prices must be informed by costs; costs are actual incremental costs; costs and prices are an outcome of a Schumpeterian competitive process, not the starting point; excluding incumbents from markets is fundamentally anticompetitive; and a regulatory transition to deregulation entails propensities to micromanage the process to generate preferred outcomes, visible compe...

  14. miRNA expression patterns in normal breast tissue and invasive breast cancers of BRCA1 and BRCA2 germ-line mutation carriers

    NARCIS (Netherlands)

    Vos, Shoko; Vesuna, Farhad; Raman, Venu; van Diest, Paul J.; van der Groep, Petra

    2015-01-01

    miRNA deregulation has been found to promote carcinogenesis. Little is known about miRNA deregulation in hereditary breast tumors as no miRNA expression profiling studies have been performed in normal breast tissue of BRCA1 and BRCA2 mutation carriers. miRNA profiles of 17 BRCA1- and 9

  15. miRNA expression in control and FSHD fetal human muscle biopsies.

    Directory of Open Access Journals (Sweden)

    Débora Morueco Portilho

    Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is an autosomal-dominant disorder and is one of the most common forms of muscular dystrophy. We have recently shown that some hallmarks of FSHD are already expressed in fetal FSHD biopsies, thus opening a new field of investigation for mechanisms leading to FSHD. As microRNAs (miRNAs play an important role in myogenesis and muscle disorders, in this study we compared miRNAs expression levels during normal and FSHD muscle development.Muscle biopsies were obtained from quadriceps of both healthy control and FSHD1 fetuses with ages ranging from 14 to 33 weeks of development. miRNA expression profiles were analyzed using TaqMan Human MicroRNA Arrays.During human skeletal muscle development, in control muscle biopsies we observed changes for 4 miRNAs potentially involved in secondary muscle fiber formation and 5 miRNAs potentially involved in fiber maturation. When we compared the miRNA profiles obtained from control and FSHD biopsies, we did not observe any differences in the muscle specific miRNAs. However, we identified 8 miRNAs exclusively expressed in FSHD1 samples (miR-330, miR-331-5p, miR-34a, miR-380-3p, miR-516b, miR-582-5p, miR-517* and miR-625 which could represent new biomarkers for this disease. Their putative targets are mainly involved in muscle development and morphogenesis. Interestingly, these FSHD1 specific miRNAs do not target the genes previously described to be involved in FSHD.This work provides new candidate mechanisms potentially involved in the onset of FSHD pathology. Whether these FSHD specific miRNAs cause deregulations during fetal development, or protect against the appearance of the FSHD phenotype until the second decade of life still needs to be investigated.

  16. The Emerging Role of miRNAs in HTLV-1 Infection and ATLL Pathogenesis

    Directory of Open Access Journals (Sweden)

    Ramona Moles

    2015-07-01

    Full Text Available Human T-cell leukemia virus (HTLV-1 is a human retrovirus and the etiological agent of adult T-cell leukemia/lymphoma (ATLL, a fatal malignancy of CD4/CD25+ T lymphocytes. In recent years, cellular as well as virus-encoded microRNA (miRNA have been shown to deregulate signaling pathways to favor virus life cycle. HTLV-1 does not encode miRNA, but several studies have demonstrated that cellular miRNA expression is affected in infected cells. Distinct mechanisms such as transcriptional, epigenetic or interference with miRNA processing machinery have been involved. This article reviews the current knowledge of the role of cellular microRNAs in virus infection, replication, immune escape and pathogenesis of HTLV-1.

  17. Melatonin regulating the expression of miRNAs involved in hair follicle cycle of cashmere goats skin.

    Science.gov (United States)

    Fu, Shaoyin; Zhao, Hongli; Zheng, Zhuqing; Li, Jinquan; Zhang, Wenguang

    2014-12-01

    Melatonin and microRNAs (miRNAs) play important roles in regulating hair follicle development. However, the effect of melatonin on the expression pattern of miRNAs in skin and follicle of cashmere goats remain largely undefined. To explore the mechanism of melatonin affecting cashmere growth mediated by miRNAs, the effect of melatonin implants administered in Nei Mongol cashmere goats was assessed. In the experiment, five yearling does were implanted with melatonin, with the remaining other five females as control group. The expression of six candidate miRNAs was quantified by reverse transcription-real time polymerase chain reaction (RT-qPCR). The results indicated that melatonin significantly altered the expression pattern of miRNAs. Except for let-7a, the expression levels of miR-203, miR-205, miR-96, miR-183 and miR-199a occur three transitions during a cashmere cycle; melatonin changed the co-expression pattern of miRNAs. The correlation coefficient between miRNAs is 0.87-0.99 in control group(Pcashmere mediated by down-regulating the expression level of some miRNAs in June in melatonin implanted group.

  18. IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation.

    Science.gov (United States)

    Oktay, Yavuz; Ülgen, Ege; Can, Özge; Akyerli, Cemaliye B; Yüksel, Şirin; Erdemgil, Yiğit; Durası, I Melis; Henegariu, Octavian Ioan; Nanni, E Paolo; Selevsek, Nathalie; Grossmann, Jonas; Erson-Omay, E Zeynep; Bai, Hanwen; Gupta, Manu; Lee, William; Turcan, Şevin; Özpınar, Aysel; Huse, Jason T; Sav, M Aydın; Flanagan, Adrienne; Günel, Murat; Sezerman, O Uğur; Yakıcıer, M Cengiz; Pamir, M Necmettin; Özduman, Koray

    2016-06-10

    The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17-16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94-27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association.

  19. miRTrail - a comprehensive webserver for analyzing gene and miRNA patterns to enhance the understanding of regulatory mechanisms in diseases

    Directory of Open Access Journals (Sweden)

    Laczny Cedric

    2012-02-01

    Full Text Available Abstract Background Expression profiling provides new insights into regulatory and metabolic processes and in particular into pathogenic mechanisms associated with diseases. Besides genes, non-coding transcripts as microRNAs (miRNAs gained increasing relevance in the last decade. To understand the regulatory processes of miRNAs on genes, integrative computer-aided approaches are essential, especially in the light of complex human diseases as cancer. Results Here, we present miRTrail, an integrative tool that allows for performing comprehensive analyses of interactions of genes and miRNAs based on expression profiles. The integrated analysis of mRNA and miRNA data should generate more robust and reliable results on deregulated pathogenic processes and may also offer novel insights into the regulatory interactions between miRNAs and genes. Our web-server excels in carrying out gene sets analysis, analysis of miRNA sets as well as the combination of both in a systems biology approach. To this end, miRTrail integrates information on 20.000 genes, almost 1.000 miRNAs, and roughly 280.000 putative interactions, for Homo sapiens and accordingly for Mus musculus and Danio rerio. The well-established, classical Chi-squared test is one of the central techniques of our tool for the joint consideration of miRNAs and their targets. For interactively visualizing obtained results, it relies on the network analyzers and viewers BiNA or Cytoscape-web, also enabling direct access to relevant literature. We demonstrated the potential of miRTrail by applying our tool to mRNA and miRNA data of malignant melanoma. MiRTrail identified several deregulated miRNAs that target deregulated mRNAs including miRNAs hsa-miR-23b and hsa-miR-223, which target the highest numbers of deregulated mRNAs and regulate the pathway "basal cell carcinoma". In addition, both miRNAs target genes like PTCH1 and RASA1 that are involved in many oncogenic processes. Conclusions The application

  20. Exploring miRNAs involved in blue/UV-A light response in Brassica rapa reveals special regulatory mode during seedling development.

    Science.gov (United States)

    Zhou, Bo; Fan, Pengzhen; Li, Yuhua; Yan, Haifang; Xu, Qijiang

    2016-05-10

    Growth, development, and pigment synthesis in Brassica rapa subsp. rapa cv. Tsuda, a popular vegetable crop, are influenced by light. Although microRNAs (miRNAs) have vital roles in the metabolic processes and abiotic stress responses of plants, whether miRNAs play a role in anthocyanin biosynthesis and development of Tsuda seedlings exposed to light is unknown. Seventeen conserved and 226 novel miRNAs differed at least 2-fold in response to blue and UV-A light compared with levels after a dark treatment. Real time PCR showed that BrmiR159, BrmiRC0191, BrmiRC0460, BrmiRC0323, BrmiRC0418, BrmiRC0005 were blue light-induced and northern blot revealed that the transcription level of BrmiR167 did not differ significantly among seedlings treated with dark, blue or UV-light. BrmiR156 and BrmiR157 were present in the greatest amount (number of reads) and among their 8 putative targets in the SPL gene family, only SPL9 (Bra004674) and SPL15 (Bra003305) increased in expression after blue or UV-A exposure. In addition, miR157-guided cleavage of target SPL9 mRNAs (Bra004674, Bra016891) and SPL15 mRNAs (Bra003305, Bra014599) took place 10 or 11 bases from the 5' ends of the binding region in the miR157 sequence. A set of miRNAs and their targets involved in the regulation of the light-induced photomorphogenic phenotype in seedlings of Brassica rapa was identified, providing new insights into blue and UV-A light-responsive miRNAs in seedlings of Tsuda and evidence of multiple targets for the miRNAs and their diverse roles in plant development.

  1. miRNA signature and Dicer requirement during human endometrial stromal decidualization in vitro.

    Directory of Open Access Journals (Sweden)

    Carlos Estella

    Full Text Available Decidualization is a morphological and biochemical transformation of endometrial stromal fibroblast into differentiated decidual cells, which is critical for embryo implantation and pregnancy establishment. The complex regulatory networks have been elucidated at both the transcriptome and the proteome levels, however very little is known about the post-transcriptional regulation of this process. miRNAs regulate multiple physiological pathways and their de-regulation is associated with human disorders including gynaecological conditions such as endometriosis and preeclampsia. In this study we profile the miRNAs expression throughout human endometrial stromal (hESCs decidualization and analyze the requirement of the miRNA biogenesis enzyme Dicer during this process. A total of 26 miRNAs were upregulated and 17 miRNAs downregulated in decidualized hESCs compared to non-decidualized hESCs. Three miRNAs families, miR-181, miR-183 and miR-200, are down-regulated during the decidualization process. Using miRNAs target prediction algorithms we have identified the potential targets and pathways regulated by these miRNAs. The knockdown of Dicer has a minor effect on hESCs during in vitro decidualization. We have analyzed a battery of decidualization markers such as cell morphology, Prolactin, IGFBP-1, MPIF-1 and TIMP-3 secretion as well as HOXA10, COX2, SP1, C/EBPß and FOXO1 expression in decidualized hESCs with decreased Dicer function. We found decreased levels of HOXA10 and altered intracellular organization of actin filaments in Dicer knockdown decidualized hESCs compared to control. Our results provide the miRNA signature of hESC during the decidualization process in vitro. We also provide the first functional characterization of Dicer during human endometrial decidualization although surprisingly we found that Dicer plays a minor role regulating this process suggesting that alternative biogenesis miRNAs pathways must be involved in human

  2. Epigenetic architecture and miRNA: reciprocal regulators

    DEFF Research Database (Denmark)

    Wiklund, Erik Digman; Kjems, Jørgen; Clark, Susan

    2010-01-01

    Deregulation of epigenetic and microRNA (miRNA) pathways are emerging as key events in carcinogenesis. miRNA genes can be epigenetically regulated and miRNAs can themselves repress key enzymes that drive epigenetic remodeling. Epigenetic and miRNA functions are thus tightly interconnected......RNAs) are considered especially promising in clinical applications, and their biogenesis and function is a subject of active research. In this review, the current status of epigenetic miRNA regulation is summarized and future therapeutic prospects in the field are discussed with a focus on cancer....

  3. Profiling olfactory stem cells from living patients identifies miRNAs relevant for autism pathophysiology.

    Science.gov (United States)

    Nguyen, Lam Son; Lepleux, Marylin; Makhlouf, Mélanie; Martin, Christelle; Fregeac, Julien; Siquier-Pernet, Karine; Philippe, Anne; Feron, François; Gepner, Bruno; Rougeulle, Claire; Humeau, Yann; Colleaux, Laurence

    2016-01-01

    Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders caused by the interaction between genetic vulnerability and environmental factors. MicroRNAs (miRNAs) are key posttranscriptional regulators involved in multiple aspects of brain development and function. Previous studies have investigated miRNAs expression in ASD using non-neural cells like lymphoblastoid cell lines (LCL) or postmortem tissues. However, the relevance of LCLs is questionable in the context of a neurodevelopmental disorder, and the impact of the cause of death and/or post-death handling of tissue likely contributes to the variations observed between studies on brain samples. miRNA profiling using TLDA high-throughput real-time qPCR was performed on miRNAs extracted from olfactory mucosal stem cells (OMSCs) biopsied from eight patients and six controls. This tissue is considered as a closer tissue to neural stem cells that could be sampled in living patients and was never investigated for such a purpose before. Real-time PCR was used to validate a set of differentially expressed miRNAs, and bioinformatics analysis determined common pathways and gene targets. Luciferase assays and real-time PCR analysis were used to evaluate the effect of miRNAs misregulation on the expression and translation of several autism-related transcripts. Viral vector-mediated expression was used to evaluate the impact of miRNAs deregulation on neuronal or glial cells functions. We identified a signature of four miRNAs (miR-146a, miR-221, miR-654-5p, and miR-656) commonly deregulated in ASD. This signature is conserved in primary skin fibroblasts and may allow discriminating between ASD and intellectual disability samples. Putative target genes of the differentially expressed miRNAs were enriched for pathways previously associated to ASD, and altered levels of neuronal transcripts targeted by miR-146a, miR-221, and miR-656 were observed in patients' cells. In the mouse brain, miR-146a, and miR-221

  4. MiRNA-133a is involved in the regulation of postmenopausal osteoporosis through promoting osteoclast differentiation.

    Science.gov (United States)

    Li, Zhongqi; Zhang, Wenzhi; Huang, Yan

    2018-02-07

    The important role of miR-133a in the progress and development of postmenopausal osteoporosis has been reported, however, the underlying mechanism is not clear yet. In this study, qRT-PCR analysis was performed to assess miR-133 expression in serum isolated from postmenopausal osteoporosis patients (PMOP) and healthy controls. Bone mineral density (BMD) was measured at the lumbar spine by dual-energy X-ray absorptiometry (DXA). The results showed that miR-133a was significantly upregulated and negatively correlated with lumbar spine BMD in serum of postmenopausal osteoporotic women. The miR-133a mimic, miR-133a inhibitor, and the corresponding controls were transfected into RAW264.7 and THP-1 cells, respectively. TRAP-positive cells were counted and the protein expression of NFATc1, c-Fos and TRAP were detected by western blot analysis. We found that MiR-133a was upregulated during osteoclastogenesis, and overexpression of miR-133a promoted RANKL-induced differentiation of RAW264.7 and THP-1 cells into osteoclasts, whereas miR-133a knockdown showed the reversed results. In in vivo experiment, rats were bilaterally ovariectomized (OVX) and injected with antagomiR-133a or antagoNC, and were sacrificed for collecting serum and lumbar spine for ELISA, micro-computed Tomography (CT) and bone histomorphology analysis, respectively. It was found that, in OVX rats, miR-133a knockdown altered the levels of osteoclastogenesis-related factors in serum and increased lumbar spine BMD and changed bone histomorphology. Collectively, miRNA-133a is involved in the regulation of postmenopausal osteoporosis through promoting osteoclast differentiation. © The Author(s) 2018. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Viral miRNAs Alter Host Cell miRNA Profiles and Modulate Innate Immune Responses

    Directory of Open Access Journals (Sweden)

    Afsar R. Naqvi

    2018-03-01

    Full Text Available Prevalence of the members of herpesvirus family in oral inflammatory diseases is increasingly acknowledged suggesting their likely role as an etiological factor. However, the underlying mechanisms remain obscure. In our recent miRNA profiling of healthy and diseased human tooth pulps, elevated expression of human herpesvirus encoded viral microRNAs (v-miRs were identified. Based on the fold induction and significance values, we selected three v-miRs namely miR-K12-3-3p [Kaposi sarcoma-associated virus (KSHV], miR-H1 [herpes simplex virus 1 (HSV1], and miR-UL-70-3p [human cytomegalovirus (HCMV] to further examine their impact on host cellular functions. We examined their impact on cellular miRNA profiles of primary human oral keratinocytes (HOK. Our results show differential expression of several host miRNAs in v-miR-transfected HOK. High levels of v-miRs were detected in exosomes derived from v-miR transfected HOK as well as the KSHV-infected cell lines. We show that HOK-derived exosomes release their contents into macrophages (Mφ and alter expression of endogenous miRNAs. Concurrent expression analysis of precursor (pre-miRNA and mature miRNA suggest transcriptional or posttranscriptional impact of v-miRs on the cellular miRNAs. Employing bioinformatics, we predicted several pathways targeted by deregulated cellular miRNAs that include cytoskeletal organization, endocytosis, and cellular signaling. We validated three novel targets of miR-K12-3-3p and miR-H1 that are involved in endocytic and intracellular trafficking pathways. To evaluate the functional consequence of this regulation, we performed phagocytic uptake of labeled bacteria and noticed significant attenuation in miR-H1 and miR-K12-3-3p but not miR-UL70-3p transfected primary human Mφ. Multiple cytokine analysis of E. coli challenged Mφ revealed marked reduction of secreted cytokine levels with important roles in innate and adaptive immune responses suggesting a role of v-miRs in

  6. miRNA Regulation Network Analysis in Qianliening Capsule Treatment of Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Liya Liu

    2015-01-01

    Full Text Available Objective. The objective of this study was to evaluate the molecular mechanism by which Qianliening capsule (QC treats benign prostatic hyperplasia (BPH. Methods. Benign prostatic hyperplasia epithelial cell line BPH-1 was treated with 0, 1.25, 2.5, and 5 mg/mL QC for 48 h, respectively. Evaluation of cell viability and observation of morphologic changes of BPH-1 cell gene expression and miRNA expression profiles were analyzed. Real-time quantitative PCR was used to confirm changes in miRNA and gene expression. GO and KEGG pathway-based approaches were used to investigate biological functions and signaling pathways affected by differentially expressed mRNAs. Results. QC inhibited BPH-1 cell proliferation. Differential expression of 19 upregulated and 2 downregulated miRNAs was observed in QC-treated BPH-1 cells compared to untreated control cells. 107 upregulated and 71 downregulated genes were identified between the two groups. Significantly enriched signaling pathways based on deregulated mRNAs were mainly involved in regulation of cell proliferation, apoptosis, and so on. Additionally, miRNA-mRNA network analysis integrated these miRNAs and genes by outlining interactions of miRNA and related genes. Conclusion. The study was the first report of differentially expressed miRNA and mRNA in QC-treated BPH-1 cells.

  7. The thymic orchestration involving Aire, miRNAs and cell-cell interactions during the induction of central tolerance

    Directory of Open Access Journals (Sweden)

    Geraldo eAleixo Passos

    2015-07-01

    Full Text Available Developing thymocytes interact sequentially with two distinct structures within the thymus: the cortex and medulla. Surviving single-positive and double-positive thymocytes from the cortex migrate into the medulla, where they interact with medullary thymic epithelial cells (mTECs. These cells ectopically express a vast set of peripheral tissue antigens (PTAs, a property termed promiscuous gene expression that is associated with the presentation of PTAs by mTECs to thymocytes. Thymocyte clones that have a high affinity for PTAs are eliminated by apoptosis in a process termed negative selection, which is essential for tolerance induction. The Aire gene is an important factor that controls the expression of a large set of PTAs. In addition to PTAs, Aire also controls the expression of miRNAs in mTECs. These miRNAs are important in the organization of the thymic architecture and act as posttranscriptional controllers of PTAs. Herein, we discuss recent discoveries and highlight open questions regarding the migration and interaction of developing thymocytes with thymic stroma, the ectopic expression of PTAs by mTECs, the association between Aire and miRNAs and its effects on central tolerance.

  8. Comparative microRNA-seq Analysis Depicts Candidate miRNAs Involved in Skin Color Differentiation in Red Tilapia

    Directory of Open Access Journals (Sweden)

    Lanmei Wang

    2018-04-01

    Full Text Available Differentiation and variation in body color has been a growing limitation to the commercial value of red tilapia. Limited microRNA (miRNA information is available on skin color differentiation and variation in fish so far. In this study, a high-throughput Illumina sequencing of sRNAs was conducted on three color varieties of red tilapia and 81,394,491 raw reads were generated. A total of 158 differentially expressed miRNAs (|log2(fold change| ≥ 1 and q-value ≤ 0.001 were identified. Target prediction and functional analysis of color-related miRNAs showed that a variety of putative target genes—including slc7a11, mc1r and asip—played potential roles in pigmentation. Moreover; the miRNA-mRNA regulatory network was illustrated to elucidate the pigmentation differentiation, in which miR-138-5p and miR-722 were predicted to play important roles in regulating the pigmentation process. These results advance our understanding of the molecular mechanisms of skin pigmentation differentiation in red tilapia.

  9. Comparative microRNA-seq Analysis Depicts Candidate miRNAs Involved in Skin Color Differentiation in Red Tilapia.

    Science.gov (United States)

    Wang, Lanmei; Zhu, Wenbin; Dong, Zaijie; Song, Feibiao; Dong, Juanjuan; Fu, Jianjun

    2018-04-16

    Differentiation and variation in body color has been a growing limitation to the commercial value of red tilapia. Limited microRNA (miRNA) information is available on skin color differentiation and variation in fish so far. In this study, a high-throughput Illumina sequencing of sRNAs was conducted on three color varieties of red tilapia and 81,394,491 raw reads were generated. A total of 158 differentially expressed miRNAs (|log₂(fold change)| ≥ 1 and q -value ≤ 0.001) were identified. Target prediction and functional analysis of color-related miRNAs showed that a variety of putative target genes—including slc7a11 , mc1r and asip —played potential roles in pigmentation. Moreover; the miRNA-mRNA regulatory network was illustrated to elucidate the pigmentation differentiation, in which miR-138-5p and miR-722 were predicted to play important roles in regulating the pigmentation process. These results advance our understanding of the molecular mechanisms of skin pigmentation differentiation in red tilapia.

  10. Evaluating the involvement and interaction of abscisic acid and miRNA156 in the induction of anthocyanin biosynthesis in drought-stressed plants.

    Science.gov (United States)

    González-Villagra, Jorge; Kurepin, Leonid V; Reyes-Díaz, Marjorie M

    2017-08-01

    ABA is involved in anthocyanin synthesis through the regulation of microRNA156, augmenting the level of expression of anthocyanin synthesis-related genes and, therefore, increasing anthocyanin level. Drought stress is the main cause of agricultural crop loss in the world. However, plants have developed mechanisms that allow them to tolerate drought stress conditions. At cellular level, drought stress induces changes in metabolite accumulation, including increases in anthocyanin levels due to upregulation of the anthocyanin biosynthetic pathway. Recent studies suggest that the higher anthocyanin content observed under drought stress conditions could be a consequence of a rise in the abscisic acid (ABA) concentration. This plant hormone crosses the plasma membrane by specific transporters, and it is recognized at the cytosolic level by receptors known as pyrabactin resistance (PYR)/regulatory component of ABA receptors (PYR/RCARs) that regulate downstream components. In this review, we discuss the hypothesis regarding the involvement of ABA in the regulation of microRNA156 (miRNA156), which is upregulated as part of dehydration stress responsiveness in different species. The miRNA156 upregulation produces a greater level of anthocyanin gene expression, forming the multienzyme complex that will synthesize an increased level of anthocyanins at the cytosolic face of the rough endoplasmic reticulum (RER). After synthesis, anthocyanins are transported from the RER to the vacuole by two possible models of transport: (1) membrane vesicle-mediated transport, or (2) membrane transporter-mediated transport. Thus, the aim was to analyze the recent findings on synthesis, transport and the possible mechanism by which ABA could increase anthocyanin synthesis under drought stress conditions potentially throughout microRNA156 (miRNA156).

  11. Integrated analysis of miRNA and mRNA expression in childhood medulloblastoma compared with neural stem cells.

    Directory of Open Access Journals (Sweden)

    Laura A Genovesi

    Full Text Available Medulloblastoma (MB is the most common malignant brain tumor in children and a leading cause of cancer-related mortality and morbidity. Several molecular sub-types of MB have been identified, suggesting they may arise from distinct cells of origin. Data from animal models indicate that some MB sub-types arise from multipotent cerebellar neural stem cells (NSCs. Hence, microRNA (miRNA expression profiles of primary MB samples were compared to CD133+ NSCs, aiming to identify deregulated miRNAs involved in MB pathogenesis. Expression profiling of 662 miRNAs in primary MB specimens, MB cell lines, and human CD133+ NSCs and CD133- neural progenitor cells was performed by qRT-PCR. Clustering analysis identified two distinct sub-types of MB primary specimens, reminiscent of sub-types obtained from their mRNA profiles. 21 significantly up-regulated and 12 significantly down-regulated miRNAs were identified in MB primary specimens relative to CD133+ NSCs (p<0.01. The majority of up-regulated miRNAs mapped to chromosomal regions 14q32 and 17q. Integration of the predicted targets of deregulated miRNAs with mRNA expression data from the same specimens revealed enrichment of pathways regulating neuronal migration, nervous system development and cell proliferation. Transient over-expression of a down-regulated miRNA, miR-935, resulted in significant down-regulation of three of the seven predicted miR-935 target genes at the mRNA level in a MB cell line, confirming the validity of this approach. This study represents the first integrated analysis of MB miRNA and mRNA expression profiles and is the first to compare MB miRNA expression profiles to those of CD133+ NSCs. We identified several differentially expressed miRNAs that potentially target networks of genes and signaling pathways that may be involved in the transformation of normal NSCs to brain tumor stem cells. Based on this integrative approach, our data provide an important platform for future

  12. Identification in GRMD dog muscle of critical miRNAs involved in pathophysiology and effects associated with MuStem cell transplantation.

    Science.gov (United States)

    Robriquet, Florence; Babarit, Candice; Larcher, Thibaut; Dubreil, Laurence; Ledevin, Mireille; Goubin, Hélicia; Rouger, Karl; Guével, Laëtitia

    2016-05-11

    Duchenne muscular dystrophy (DMD) is an X-linked muscle disease that leads to fibre necrosis and progressive paralysis. At present, DMD remains a lethal disease without any effective treatment, requiring a better understanding of the pathophysiological processes and comprehensive assessment of the newly identified therapeutic strategies. MicroRNAs including members of the muscle-specific myomiR family have been identified as being deregulated in muscle of DMD patients and in mdx mice used as a model for DMD. In recent years, the Golden Retriever muscular dystrophy (GRMD) dog has appeared as the crucial animal model for objectively assessing the potential of new innovative approaches. Here, we first aim at establishing the muscle expression pattern of five selected miRNAs in this clinically relevant model to determine if they are similarly affected compared with other DMD contexts. Second, we attempt to show whether these miRNAs could be impacted by the systemic delivery of a promising stem cell candidate (referred to as MuStem cells) to implement our knowledge on its mode of action and/or identify markers associated with cell therapy efficacy. A comparative study of miRNAs expression levels and cellular localization was performed on 9-month-old healthy dogs, as well as on three sub-sets of GRMD dog (without immunosuppression or cell transplantation, with continuous immunosuppressive regimen and with MuStem cell transplantation under immunosuppression), using RT-qPCR and in situ hybridization. We find that miR-222 expression is markedly up-regulated in GRMD dog muscle compared to healthy dog, while miR-486 tends to be down-expressed. Intriguingly, the expression of miR-1, miR-133a and miR-206 does not change. In situ hybridization exploration reveals, for the first time, that miR-486 and miR-206 are mainly localized in newly regenerated fibres in GRMD dog muscle. In addition, we show that cyclosporine-based immunosuppression, classically used in allogeneic cell

  13. Analysis of Deregulated microRNAs and Their Target Genes in Gastric Cancer.

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    Simonas Juzėnas

    Full Text Available MicroRNAs (miRNAs are widely studied non-coding RNAs that modulate gene expression. MiRNAs are deregulated in different tumors including gastric cancer (GC and have potential diagnostic and prognostic implications. The aim of our study was to determine miRNA profile in GC tissues, followed by evaluation of deregulated miRNAs in plasma of GC patients. Using available databases and bioinformatics methods we also aimed to evaluate potential target genes of confirmed differentially expressed miRNA and validate these findings in GC tissues.The study included 51 GC patients and 51 controls. Initially, we screened miRNA expression profile in 13 tissue samples of GC and 12 normal gastric tissues with TaqMan low density array (TLDA. In the second stage, differentially expressed miRNAs were validated in a replication cohort using qRT-PCR in tissue and plasma samples. Subsequently, we analyzed potential target genes of deregulated miRNAs using bioinformatics approach, determined their expression in GC tissues and performed correlation analysis with targeting miRNAs.Profiling with TLDA revealed 15 deregulated miRNAs in GC tissues compared to normal gastric mucosa. Replication analysis confirmed that miR-148a-3p, miR-204-5p, miR-223-3p and miR-375 were consistently deregulated in GC tissues. Analysis of GC patients' plasma samples showed significant down-regulation of miR-148a-3p, miR-375 and up-regulation of miR-223-3p compared to healthy subjects. Further, using bioinformatic tools we identified targets of replicated miRNAs and performed disease-associated gene enrichment analysis. Ultimately, we evaluated potential target gene BCL2 and DNMT3B expression by qRT-PCR in GC tissue, which correlated with targeting miRNA expression.Our study revealed miRNA profile in GC tissues and showed that miR-148a-3p, miR-223-3p and miR-375 are deregulated in GC plasma samples, but these circulating miRNAs showed relatively weak diagnostic performance as sole biomarkers

  14. MiRNA Biogenesis and Intersecting Pathways

    DEFF Research Database (Denmark)

    Ben Chaabane, Samir

    (DCL1) protein complex. Mature miRNAs are loaded onto and guide an ARGONAUTE1 (AGO1) effector complex, leading to target mRNA silencing. The miRNA pathway is under tight temporal and spatial control and is regulated at multiple levels from transcription and precursor processing through miRNA mode...... questions need to be addressed to establish a valid link, we provide encouraging evidence of the involvement of chromatin remodeling factors FAS1 and FAS2 in miRNA biogenesis. Together, we have expanded our understanding of the intersections between miRNA biogenesis and other pathways....

  15. Salivary miRNA profiles identify children with autism spectrum disorder, correlate with adaptive behavior, and implicate ASD candidate genes involved in neurodevelopment.

    Science.gov (United States)

    Hicks, Steven D; Ignacio, Cherry; Gentile, Karen; Middleton, Frank A

    2016-04-22

    Autism spectrum disorder (ASD) is a common neurodevelopmental disorder that lacks adequate screening tools, often delaying diagnosis and therapeutic interventions. Despite a substantial genetic component, no single gene variant accounts for >1 % of ASD incidence. Epigenetic mechanisms that include microRNAs (miRNAs) may contribute to the ASD phenotype by altering networks of neurodevelopmental genes. The extracellular availability of miRNAs allows for painless, noninvasive collection from biofluids. In this study, we investigated the potential for saliva-based miRNAs to serve as diagnostic screening tools and evaluated their potential functional importance. Salivary miRNA was purified from 24 ASD subjects and 21 age- and gender-matched control subjects. The ASD group included individuals with mild ASD (DSM-5 criteria and Autism Diagnostic Observation Schedule) and no history of neurologic disorder, pre-term birth, or known chromosomal abnormality. All subjects completed a thorough neurodevelopmental assessment with the Vineland Adaptive Behavior Scales at the time of saliva collection. A total of 246 miRNAs were detected and quantified in at least half the samples by RNA-Seq and used to perform between-group comparisons with non-parametric testing, multivariate logistic regression and classification analyses, as well as Monte-Carlo Cross-Validation (MCCV). The top miRNAs were examined for correlations with measures of adaptive behavior. Functional enrichment analysis of the highest confidence mRNA targets of the top differentially expressed miRNAs was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), as well as the Simons Foundation Autism Database (AutDB) of ASD candidate genes. Fourteen miRNAs were differentially expressed in ASD subjects compared to controls (p adaptive behavior. These miRNAs have high specificity and cross-validated utility as a potential screening tool for ASD.

  16. miRNAs in lung cancer - Studying complex fingerprints in patient's blood cells by microarray experiments

    International Nuclear Information System (INIS)

    Keller, Andreas; Leidinger, Petra; Borries, Anne; Wendschlag, Anke; Wucherpfennig, Frank; Scheffler, Matthias; Huwer, Hanno; Lenhof, Hans-Peter; Meese, Eckart

    2009-01-01

    Deregulated miRNAs are found in cancer cells and recently in blood cells of cancer patients. Due to their inherent stability miRNAs may offer themselves for blood based tumor diagnosis. Here we addressed the question whether there is a sufficient number of miRNAs deregulated in blood cells of cancer patients to be able to distinguish between cancer patients and controls. We synthesized 866 human miRNAs and miRNA star sequences as annotated in the Sanger miRBase onto a microarray designed by febit biomed gmbh. Using the fully automated Geniom Real Time Analyzer platform, we analyzed the miRNA expression in 17 blood cell samples of patients with non-small cell lung carcinomas (NSCLC) and in 19 blood samples of healthy controls. Using t-test, we detected 27 miRNAs significantly deregulated in blood cells of lung cancer patients as compared to the controls. Some of these miRNAs were validated using qRT-PCR. To estimate the value of each deregulated miRNA, we grouped all miRNAs according to their diagnostic information that was measured by Mutual Information. Using a subset of 24 miRNAs, a radial basis function Support Vector Machine allowed for discriminating between blood cellsamples of tumor patients and controls with an accuracy of 95.4% [94.9%-95.9%], a specificity of 98.1% [97.3%-98.8%], and a sensitivity of 92.5% [91.8%-92.5%]. Our findings support the idea that neoplasia may lead to a deregulation of miRNA expression in blood cells of cancer patients compared to blood cells of healthy individuals. Furthermore, we provide evidence that miRNA patterns can be used to detect human cancers from blood cells

  17. Natural gas and deregulation

    International Nuclear Information System (INIS)

    Maisonnier, G.

    2001-01-01

    The gas market is progressively moving towards new organizations under the effect of the deregulation initiated in the United States, the United Kingdom and transposed to other countries, particularly in Europe, at least for the member countries of the European union. Within the framework provided by this overall trend, Cedigaz proposes this study in order to describe the main developments affecting these markets on account of deregulation. This report is structured on the basis of three main topics (market organization, marketing modes, pricing) which appear to be the most cogent in terms of deregulation. This grouping by major topics accordingly offers a relatively synthetic view of the main trends which could be observed on the European market, for example. Our analysis is largely based on the example of the American market and, to a lesser extent, on the British situation. Whenever possible, concrete examples are provided for a closer understanding of this complex subject. On the whole, deregulation is not a frozen process, but has to adapt permanently to developments in a market stage-managed by politics, the regulator and the industrial players. This obviously means a dynamic and constantly evolving process, making it a highly complex process. This report aims to shed some light on the subject. (author)

  18. Global Analysis of miRNA Gene Clusters and Gene Families Reveals Dynamic and Coordinated Expression

    Directory of Open Access Journals (Sweden)

    Li Guo

    2014-01-01

    Full Text Available To further understand the potential expression relationships of miRNAs in miRNA gene clusters and gene families, a global analysis was performed in 4 paired tumor (breast cancer and adjacent normal tissue samples using deep sequencing datasets. The compositions of miRNA gene clusters and families are not random, and clustered and homologous miRNAs may have close relationships with overlapped miRNA species. Members in the miRNA group always had various expression levels, and even some showed larger expression divergence. Despite the dynamic expression as well as individual difference, these miRNAs always indicated consistent or similar deregulation patterns. The consistent deregulation expression may contribute to dynamic and coordinated interaction between different miRNAs in regulatory network. Further, we found that those clustered or homologous miRNAs that were also identified as sense and antisense miRNAs showed larger expression divergence. miRNA gene clusters and families indicated important biological roles, and the specific distribution and expression further enrich and ensure the flexible and robust regulatory network.

  19. Identification of a set of endogenous reference genes for miRNA expression studies in Parkinson's disease blood samples.

    Science.gov (United States)

    Serafin, Alice; Foco, Luisa; Blankenburg, Hagen; Picard, Anne; Zanigni, Stefano; Zanon, Alessandra; Pramstaller, Peter P; Hicks, Andrew A; Schwienbacher, Christine

    2014-10-10

    Research on microRNAs (miRNAs) is becoming an increasingly attractive field, as these small RNA molecules are involved in several physiological functions and diseases. To date, only few studies have assessed the expression of blood miRNAs related to Parkinson's disease (PD) using microarray and quantitative real-time PCR (qRT-PCR). Measuring miRNA expression involves normalization of qRT-PCR data using endogenous reference genes for calibration, but their choice remains a delicate problem with serious impact on the resulting expression levels. The aim of the present study was to evaluate the suitability of a set of commonly used small RNAs as normalizers and to identify which of these miRNAs might be considered reliable reference genes in qRT-PCR expression analyses on PD blood samples. Commonly used reference genes snoRNA RNU24, snRNA RNU6B, snoRNA Z30 and miR-103a-3p were selected from the literature. We then analyzed the effect of using these genes as reference, alone or in any possible combination, on the measured expression levels of the target genes miR-30b-5p and miR-29a-3p, which have been previously reported to be deregulated in PD blood samples. We identified RNU24 and Z30 as a reliable and stable pair of reference genes in PD blood samples.

  20. Regulating deregulated energy markets

    International Nuclear Information System (INIS)

    Jackson, M.

    2002-01-01

    The North American gas and electricity markets are fast evolving, and regulators are currently faced with a host of issues such as market-based rates, unbundling, stranded costs, open access, and incentive regulation are surfacing as a result of deregulation. The regulatory environment in Ontario was reviewed by the author. Deregulated markets rule, from commodities to gas and electricity. Additionally, there is an evolution of traditional utility regulation. A look at deregulated markets revealed that there are regulations on boundary conditions on the deregulated market. Under the Ontario Energy Board (OEB), all generators, transmitters, distributors, and retailers of electricity must be licensed. The standard supply service (SSS) offered by electricity distributors and system gas which is still being sold by natural gas distributors continues to be regulated by OEB. One issue that was addressed was separation for revenues and costs of the utility's purchase and sale of gas business, at least for accounting purposes. The next issue discussed was cost of system gas and SSS, followed by timely signals and prudent incurred costs. Historical benefits were reviewed, such as historical commitments to low-cost electricity. Pooling transportation costs, transmission pricing continued, market-based rates, unbundling, stranded costs, open access, incentive regulation/ performance based regulation (PBR) were all discussed. Price cap on PBR, both partial and comprehensive were looked at. A requirement to review guidelines on cost of capital and an application to extend blanket approval provisions for gas storage were discussed, as they are amongst some of the challenges of the future. Other challenges include revised rules and practice and procedure; practice directions for cost awards, appeals, and other functions; confidentiality guidelines; and refinements to the role of and approaches to alternative dispute resolution. The future role of regulators was examined in light

  1. Lack of miRNA misregulation at early pathological stages in Drosophila neurodegenerative disease models

    Directory of Open Access Journals (Sweden)

    Anita eReinhardt

    2012-10-01

    Full Text Available Late onset neurodegenerative diseases represent a major public health concern as the population in many countries ages. Both frequent diseases such as Alzheimer disease (AD, 14% incidence for 80-84 year old Europeans or Parkinson disease (PD, 1.4% prevalence for > 55 years old share, with other low-incidence neurodegenerative pathologies such as spinocerebellar ataxias (SCAs, 0.01% prevalence and frontotemporal lobar degeneration (FTLD, 0.02% prevalence, a lack of efficient treatment in spite of important research efforts. Besides significant progress, studies with animal models have revealed unexpected complexities in the degenerative process, emphasizing a need to better understand the underlying pathological mechanisms. Recently, microRNAs, a class of small regulatory non-coding RNAs, have been implicated in some neurodegenerative diseases. The current data supporting a role of miRNAs in PD, tauopathies, dominant ataxias and FTLD will first be discussed to emphasize the different levels of the pathological processes which may be affected by miRNAs. To investigate a potential involvement of miRNA dysregulation in the early stages of these neurodegenerative diseases we have used Drosophila models for 7 diseases (PD, 3 FTLD, 3 dominant ataxias that recapitulate many features of the human diseases. We performed deep sequencing of head small RNAs after 3 days of pathological protein expression in the fly head neurons. We found no evidence for a statistically significant difference in miRNA expression in this early stage of the pathological process. In addition, we could not identify small non coding CAG repeat RNAs (sCAG in polyQ disease models. Thus our data suggest that transcriptional deregulation of miRNAs or sCAG is unlikely to play a significant role in the initial stages of neurodegenerative diseases.

  2. Lack of evidence for a liver or intestinal miRNA regulation involved in the hypertriglyceridemic effect of APOC3 3'UTR variant SstI.

    Science.gov (United States)

    Dancer, Marine; Caussy, Cyrielle; Di Filippo, Mathilde; Moulin, Philippe; Marçais, Christophe; Charrière, Sybil

    2016-12-01

    APOC3 is a major regulator of triglycerides metabolism. Several APOC3 variants are associated with hypertriglyceridemia (HTG). Our aim was to establish the potential regulation of APOC3 3'UTR variants associated with HTG by liver or intestinal miRNAs. We sequenced APOC3 3'UTR in 100 type 2 diabetic (TD2) patients with severe HTG (TG > 15 mmol/L) (HTG group) compared to 100 normotriglyceridemic patients (NTG group). We performed in silico studies to identify potential loss of miRNA binding induced by APOC3 3'UTR variants. We also performed in vitro studies to test the functionality of miRNA/APOC3 variants interactions: APOC3 3'UTR plasmids coupled with a firefly luciferase reporter were transfected in HepG2, HuH-7 and Caco-2 cells. We identified only two variants: SstI (rs5128) and BbvI (rs5225) in APOC3 3'UTR in the 2 groups of patients. Only the SstI-S2 rare allele was significantly associated with HTG (allele frequency 19,5% in HTG group vs. 9,5% in NTG group, p = 0.0045). In silico studies predicted a potential loss in the binding of 5 miRNAs induced by the S2 variant. These 5 miRNAs are all endogenously expressed in human liver and intestine, as well as in the cell models studied. However, in vitro, the S2 variant did not modulate APOC3 3'UTR reporter gene expression in HepG2, HuH-7 and Caco-2 cells. Our results do not confirm the hypothesis of a direct regulation of the APOC3 SstI variant by hepatic or intestinal miRNAs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. miRNAs in inflammatory skin diseases and their clinical implications

    DEFF Research Database (Denmark)

    Løvendorf, Marianne B; Skov, Lone

    2015-01-01

    miRNAs are a class of non-coding RNA molecules that modulate gene expression post-transcriptionally. They have a major impact on several physiological and pathological cellular processes including modulation of the innate and the adaptive immune system. The role of miRNAs in skin biology is still...... incomplete; however, it is known that miRNAs are implicated in various cellular processes of both normal and diseased skin. Some miRNAs appear to be consistently deregulated in several different inflammatory skin diseases, including psoriasis and atopic dermatitis, indicating a common role in fundamental...

  4. Detection of deregulated modules using deregulatory linked path.

    Directory of Open Access Journals (Sweden)

    Yuxuan Hu

    Full Text Available The identification of deregulated modules (such as induced by oncogenes is a crucial step for exploring the pathogenic process of complex diseases. Most of the existing methods focus on deregulation of genes rather than the links of the path among them. In this study, we emphasize on the detection of deregulated links, and develop a novel and effective regulatory path-based approach in finding deregulated modules. Observing that a regulatory pathway between two genes might involve in multiple rather than a single path, we identify condition-specific core regulatory path (CCRP to detect the significant deregulation of regulatory links. Using time-series gene expression, we define the regulatory strength within each gene pair based on statistical dependence analysis. The CCRPs in regulatory networks can then be identified using the shortest path algorithm. Finally, we derive the deregulated modules by integrating the differential edges (as deregulated links of the CCRPs between the case and the control group. To demonstrate the effectiveness of our approach, we apply the method to expression data associated with different states of Human Epidermal Growth Factor Receptor 2 (HER2. The experimental results show that the genes as well as the links in the deregulated modules are significantly enriched in multiple KEGG pathways and GO biological processes, most of which can be validated to suffer from impact of this oncogene based on previous studies. Additionally, we find the regulatory mechanism associated with the crucial gene SNAI1 significantly deregulated resulting from the activation of HER2. Hence, our method provides not only a strategy for detecting the deregulated links in regulatory networks, but also a way to identify concerning deregulated modules, thus contributing to the target selection of edgetic drugs.

  5. Gas deregulation in North America

    International Nuclear Information System (INIS)

    Gurney, Judith

    1998-04-01

    Contains Executive Summary and Chapters on: The North American gas industry; Upstream deregulation in the US and Canada; Retail regulation in the US and Canada; Customer choice in Pennsylvania and Ohio; Customer choice in Massachusetts; Deregulation legislation in Georgia; US pilot programme results; The Canadian experience; Market centres, hubs and storage; Marketers and trading companies; New roles for pipelines; Mergers and Joint ventures; Opportunities in Mexico; Conclusions - the pros and cons of deregulation. (Author)

  6. miRNA-197 and miRNA-184 are associated with brain metastasis in EGFR-mutant lung cancers.

    Science.gov (United States)

    Remon, J; Alvarez-Berdugo, D; Majem, M; Moran, T; Reguart, N; Lianes, P

    2016-02-01

    The prognostic value of EGFR mutation in lung cancer patients with brain metastases is uncertain and therapeutic efficacy with EGFR TKI is limited. Looking for biomarkers closely related with early tumor changes and brain metastases in non-small cell lung cancer is warranted. MicroRNAs (miRNAs) are frequently deregulated in lung cancer. The objective of this study was to investigate whether some miRNAs are related with brain metastasis risk in EGFR-mutant non-small cell lung cancer patients. miRNA quantification was retrospectively performed in formalin-fixed, extracranial paraffin-embedded adenocarcinoma tumor tissue available from 17 human samples of advanced non-small cell lung cancer patients. Samples were classified as brain metastasis group (5 EGFR-mutant patients with initial BM, EGFRm-BM+; and 6 EGFR wild-type patients with initial BM) and the control group (6 EGFR-mutant NSCLC patients without BM). The RNA obtained was preamplified and retro-transcribed, and the miRNA was quantified with the TaqMan OpenArray Human MiRNA Panel in the QuantStudio™ 12 K Flex Real-Time PCR system. miRNA-197 and miRNA-184 showed a significant higher expression in EGFRm-BM+ group than in the control group (p = 0.017 and p = 0.01, for miRNA-197 and miRNA-184, respectively), with a trend toward overexpression in BM group compared with the control group (p = 0.08 and p = 0.065, for miRNA-197 and miRNA-184, respectively), without differences in expression in BM group according to EGFR mutational status (EGFR wild type vs. EGFR-mutant: p = 0.175 and p = 0.117, for miRNA-197, miRNA-184 respectively). miRNA-197 and miRNA-184 are overexpressed in EGFR-mutant patients with BM and they might be a new biomarker for stratifying the risk of BM in this subpopulation.

  7. Endoplasmic reticulum stress in the regulation of liver diseases: Involvement of Regulated IRE1α and β-dependent decay and miRNA.

    Science.gov (United States)

    Rashid, Harun-Or; Kim, Hyun-Kyoung; Junjappa, Raghupatil; Kim, Hyung-Ryong; Chae, Han-Jung

    2017-05-01

    Compromised protein folding capacity in the endoplasmic reticulum (ER) leads to a protein traffic jam that produces a toxic environment called ER stress. However, the ER smartly handles such a critical situation by activating a cascade of proteins responsible for sensing and responding to the noxious stimuli of accumulated proteins. The ER protein load is higher in secretory cells, such as liver hepatocytes, which are thus prone to stress-mediated toxicity and various diseases, including alcohol-induced liver injury, fatty liver disease, and viral hepatitis. Therefore, we discuss the molecular cues that connect ER stress to hepatic diseases. Moreover, we review the literature on ER stress-regulated miRNA in the pathogenesis of liver diseases to give a comprehensive overview of mechanistic insights connecting ER stress and miRNA in the context of liver diseases. We also discuss currently discovered regulated IRE1 dependent decay in regulation of hepatic diseases. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  8. Targeting deregulated epigenetic control in cancer.

    Science.gov (United States)

    Zaidi, Sayyed K; Van Wijnen, Andre J; Lian, Jane B; Stein, Janet L; Stein, Gary S

    2013-11-01

    Cancer is a multifaceted disease that involves acquisition of genetic mutations, deletions, and amplifications as well as deregulation of epigenetic mechanisms that fine-tune gene regulation. Key epigenetic mechanisms that include histone modifications, DNA methylation, and non-coding RNA-mediated gene silencing are often deregulated in a variety of cancers. Subnuclear localization of key proteins in the interphase nucleus and bookmarking of genes by lineage commitment factors in mitosis-a new dimension to epigenetic control of fundamental biological processes-is also modified in cancer. In this review, we discuss the various aspects of epigenetic control that are operative in a variety of cancers and their potential for risk assessment, early detection, targeted therapy, and personalized medicine. Copyright © 2013 Wiley Periodicals, Inc.

  9. Viral miRNAs exploiting the endosomal-exosomal pathway for intercellular cross-talk and immune evasion.

    Science.gov (United States)

    Pegtel, D Michiel; van de Garde, Martijn D B; Middeldorp, Jaap M

    2011-01-01

    The class of persistent gamma-herpesviruses has developed a variety of strategies that exploit host-cell regulatory pathways to ensure a long-lasting, well-balanced infection of their host. However when these pathways are deregulated, an otherwise harmless infection can lead to disease including cancer. We recently demonstrated that the human herpes virus 4 (HHV4) also known as Epstein-Barr virus (EBV), encodes for small regulatory non-coding microRNAs (miRNAs) that can be transferred from an infected cell to uninfected neighboring cells. Upon arrival these miRNAs are functional in the recipient cell, in that they are able to down regulate specific target genes. These secreted miRNAs are transported to recipient cells via small nano-sized vesicles (known as exosomes) that are of endosomal origin, formed as intraluminal vesicles (ILV) inside multivesicular bodies (MVB). One question that needs to be addressed is how viral miRNAs are sorted into these exosomes. Mature miRNAs, including those of viral origin, are loaded into RNA-induced silencing complexes (RISC) for gene silencing via blocking mRNA translation and/or initiating mRNA decay. Recent insights indicate that cytoplasmic RNA granules rich in RISC complexes are closely associated with endosomes. In fact, selective components of RISC, including GW182 and Argonaut proteins, miRNAs and mRNAs are present in exosomes. Thus miRNA function, mRNA stability and exosome-mediated intercellular communication converge at the level of endosomes. Since endosomes can be considered as key intracellular cross-roads that regulate communication of cells with their exterior, including neighboring cells, it is perhaps not surprising that viruses have found means to exploit this pathway to their benefit. Little is known however, how and if (micro) RNA species are specifically sorted into ILVs and what (micro)RNA-binding proteins are involved. Here we discuss recent developments relating to intracellular trafficking and function of

  10. Utility deregulation and AMR technology

    International Nuclear Information System (INIS)

    Moore, G.

    1991-01-01

    This article reviews the effects of deregulation on other utilities and services and examines how the electric utilities can avoid the worst of these effects and capitalize of the best aspects of competition in achieving marketing excellence. The article presents deregulation as a customer service and underscores the need for utilities to learn to compete aggressively and intelligently and provide additional services available through technology such as automated meter reading

  11. Identification of novel miRNAs and miRNA expression profiling in wheat hybrid necrosis.

    Directory of Open Access Journals (Sweden)

    Jianping Zhou

    Full Text Available MicroRNAs (miRNAs play essential roles in a vast array of biological processes, including growth and development, defense against viral infection, and responses to environmental changes in plant. Wheat hybrid necrosis is an interesting genetic phenomenon observed frequency and it is lethal or semi lethal, resulting in gradual death or loss of productivity. However, the molecular basis and mechanisms associated with hybrid necrosis in wheat are still not well understood. Here, we report the population and expression profiles of miRNAs in wheat hybrid necrosis. We identified a total of 57 conserved miRNA families as well as 182 putative novel miRNAs. Expression profiling revealed that expression of 49 known miRNAs and 165 novel miRNAs was changed in hybrid necrosis. And the expression levels of some miRNAs and their predicated targets have been confirmed by qRT-PCR. These results indicate that these miRNAs, especially miR159, miR166, miR167 and miR5072 could be involved in the extensive regulation of gene expression in response to hybrid necrosis.

  12. Identification of novel miRNAs and miRNA expression profiling in wheat hybrid necrosis.

    Science.gov (United States)

    Zhou, Jianping; Cheng, Yan; Yin, Meiqi; Yang, Ennian; Gong, Wenping; Liu, Cheng; Zheng, Xuelian; Deng, Kejun; Ren, Zhenglong; Zhang, Yong

    2015-01-01

    MicroRNAs (miRNAs) play essential roles in a vast array of biological processes, including growth and development, defense against viral infection, and responses to environmental changes in plant. Wheat hybrid necrosis is an interesting genetic phenomenon observed frequency and it is lethal or semi lethal, resulting in gradual death or loss of productivity. However, the molecular basis and mechanisms associated with hybrid necrosis in wheat are still not well understood. Here, we report the population and expression profiles of miRNAs in wheat hybrid necrosis. We identified a total of 57 conserved miRNA families as well as 182 putative novel miRNAs. Expression profiling revealed that expression of 49 known miRNAs and 165 novel miRNAs was changed in hybrid necrosis. And the expression levels of some miRNAs and their predicated targets have been confirmed by qRT-PCR. These results indicate that these miRNAs, especially miR159, miR166, miR167 and miR5072 could be involved in the extensive regulation of gene expression in response to hybrid necrosis.

  13. Deregulation and the American Education Marketplace

    Science.gov (United States)

    Dorsey, Dana N. Thompson; Plucker, Jonathan A.

    2016-01-01

    The deregulation movement has impacted the social, political, and economic landscape in the United States and continues to do so. In this article, we briefly summarize the general history of deregulation in this country and the meaning of deregulation within the specific context of education policy and reform. We focus on deregulation efforts…

  14. Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling.

    Science.gov (United States)

    Arribas, Alberto J; Gómez-Abad, Cristina; Sánchez-Beato, Margarita; Martinez, Nerea; Dilisio, Lorena; Casado, Felipe; Cruz, Miguel A; Algara, Patrocinio; Piris, Miguel A; Mollejo, Manuela

    2013-07-01

    Splenic marginal zone lymphoma is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B-cell lymphomas is hampered by the lack of specific markers. We have analyzed the gene expression and miRNA profiles of 31 splenic marginal zone lymphoma cases. For comparison, 7 spleens with reactive lymphoid hyperplasia, 10 spleens infiltrated by chronic lymphocytic leukemia, 12 spleens with follicular lymphoma, 6 spleens infiltrated by mantle cell lymphoma and 15 lymph nodes infiltrated by nodal marginal zone lymphoma were included. The results were validated by qRT-PCR in an independent series including 77 paraffin-embedded splenic marginal zone lymphomas. The splenic marginal zone lymphoma miRNA signature had deregulated expression of 51 miRNAs. The most highly overexpressed miRNAs were miR-155, miR-21, miR-34a, miR-193b and miR-100, while the most repressed miRNAs were miR-377, miR-27b, miR-145, miR-376a and miR-424. MiRNAs located in 14q32-31 were underexpressed in splenic marginal zone lymphoma compared with reactive lymphoid tissues and other B-cell lymphomas. Finally, the gene expression data were integrated with the miRNA profile to identify functional relationships between genes and deregulated miRNAs. Our study reveals miRNAs that are deregulated in splenic marginal zone lymphoma and identifies new candidate diagnostic molecules for splenic marginal zone lymphoma.

  15. IFN-β antiproliferative effect and miRNA regulation in Human Papilloma Virus E6- and E7-transformed keratinocytes.

    Science.gov (United States)

    Chiantore, Maria Vincenza; Mangino, Giorgio; Iuliano, Marco; Zangrillo, Maria Simona; De Lillis, Ilaria; Vaccari, Gabriele; Accardi, Rosita; Tommasino, Massimo; Fiorucci, Gianna; Romeo, Giovanna

    2017-01-01

    Human Papilloma Viruses (HPVs) are the causative agents of cervical cancer although other types of cancers are associated with HPV infection. Type I Interferons can interfere with HPV E6- and/or E7-dependent transformation and can affect microRNA (miRNA) expression. Cancer cells show a specific pattern of miRNA expression and HPVs are able to modulate miRNAs expressed in infected cells. Keratinocytes transduced with E6 and E7 from mucosal HPV-16 or cutaneous HPV-38 (K16 and K38) were studied to analyze the involvement of HPV oncoproteins in the anti-proliferative activity of IFN-β. In view of our previous data showing senescence induction by the cytokine in K38 cells, we observe that IFN-β treatment leads to p53-indipendent apoptosis in K16 cells whereas induces senescence in K16 cells if E6 is silenced and p53 expression is restored. The levels of selected miRNAs, deregulated in K16 and K38 cells, can be modulated by IFN-β when E6 and E7 proteins of HPV-16, but not HPV-38, are expressed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. The undertow of deregulation : reregulation

    International Nuclear Information System (INIS)

    Bradford, J.A.

    2003-01-01

    Alberta, Ontario and New Brunswick each initiated measures to deregulate their electric power industries in order to remain competitive with lower electricity rates in some U.S. states where the industry was also moving towards deregulation. This paper considers how the original sweep of deregulation policy goals succumbed to electricity reregulation policies. The decision by British Columbia to re-examine its deregulation plans in light of the experience in Canada's 3 other province's was also examined. The paper describes the electric power industry from 1900 to 1960s, before the deregulation wave hit the industry. It then proceeds to the 1970s which was marked by the oil embargo. The 1980s saw a new era of policy shifts towards deregulation and privatization activity which was intended to introduce competition into regulated industries. Alberta was the first Canadian province to introduce competition to its electricity industry in an effort to remain competitive with neighbouring U.S. jurisdictions. By the 1990s Ontario's vertically integrated electricity industry was in trouble and recommendations were made to dissolve Ontario's Hydro One monopoly, particularly in power generation. In 1999, New Brunswick restructured its electricity industry to remain competitive with New England's electricity industry. The paper describes the gradual pull back from deregulation by all 3 provinces and the measures taken to impose price controls. Both industry and consumers paid a price for major policy changes. Complete competition in New Brunswick never materialized. It was suggested that controlled competition will likely move the electricity industry in the future. 40 refs

  17. Hepatitis C Virus-Induced Upregulation of MicroRNA miR-146a-5p in Hepatocytes Promotes Viral Infection and Deregulates Metabolic Pathways Associated with Liver Disease Pathogenesis

    Science.gov (United States)

    Bandiera, Simonetta; Pernot, Sophie; El Saghire, Hussein; Durand, Sarah C.; Thumann, Christine; Crouchet, Emilie; Ye, Tao; Fofana, Isabel; Oudot, Marine A.; Barths, Jochen; Schuster, Catherine; Pessaux, Patrick

    2016-01-01

    ABSTRACT Hepatitis C virus (HCV)-induced chronic liver disease is a leading cause of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HCC development following chronic HCV infection remain poorly understood. MicroRNAs (miRNAs) play an important role in homeostasis within the liver, and deregulation of miRNAs has been associated with liver disease, including HCC. While host miRNAs are essential for HCV replication, viral infection in turn appears to induce alterations of intrahepatic miRNA networks. Although the cross talk between HCV and liver cell miRNAs most likely contributes to liver disease pathogenesis, the functional involvement of miRNAs in HCV-driven hepatocyte injury and HCC remains elusive. Here we combined a hepatocyte-like cell-based model system, high-throughput small RNA sequencing, computational analysis, and functional studies to investigate HCV-miRNA interactions that may contribute to liver disease and HCC. Profiling analyses indicated that HCV infection differentially regulated the expression of 72 miRNAs by at least 2-fold, including miRNAs that were previously described to target genes associated with inflammation, fibrosis, and cancer development. Further investigation demonstrated that the miR-146a-5p level was consistently increased in HCV-infected hepatocyte-like cells and primary human hepatocytes, as well as in liver tissue from HCV-infected patients. Genome-wide microarray and computational analyses indicated that miR-146a-5p overexpression modulates pathways that are related to liver disease and HCC development. Furthermore, we showed that miR-146a-5p has a positive impact on late steps of the viral replication cycle, thereby increasing HCV infection. Collectively, our data indicate that the HCV-induced increase in miR-146a-5p expression both promotes viral infection and is relevant for pathogenesis of liver disease. IMPORTANCE HCV is a leading cause of chronic liver disease and cancer. However, how HCV

  18. MiRNA Biogenesis and Intersecting Pathways

    DEFF Research Database (Denmark)

    Ben Chaabane, Samir

    of action and turnover. During my PhD period we have shown that the STA1 protein, a factor for pre-mRNA splicing and mRNA stability, is specifically involved in the splicing of pri-miRNAs and in the modulation of DCL1 transcript levels. Also, we established a novel and essential regulatory network in which......MicroRNAs (miRNAs) are small non-coding RNAs that function as guide molecules in RNA silencing. Plant miRNAs are critical for plant growth, development and stress response, and are processed in Arabidopsis from primary miRNA transcripts (pri-miRNAs) by the endonuclease activity of the DICER-LIKE1...... (DCL1) protein complex. Mature miRNAs are loaded onto and guide an ARGONAUTE1 (AGO1) effector complex, leading to target mRNA silencing. The miRNA pathway is under tight temporal and spatial control and is regulated at multiple levels from transcription and precursor processing through miRNA mode...

  19. A 4-miRNA signature to predict survival in glioblastomas

    DEFF Research Database (Denmark)

    Hermansen, Simon K; Sørensen, Mia D; Hansen, Anker

    2017-01-01

    Glioblastomas are among the most lethal cancers; however, recent advances in survival have increased the need for better prognostic markers. microRNAs (miRNAs) hold great prognostic potential being deregulated in glioblastomas and highly stable in stored tissue specimens. Moreover, miRNAs control...... multiple genes representing an additional level of gene regulation possibly more prognostically powerful than a single gene. The aim of the study was to identify a novel miRNA signature with the ability to separate patients into prognostic subgroups. Samples from 40 glioblastoma patients were included...... that expression patterns of miRNAs; particularly the four miRNAs: hsa-miR-107_st, hsa-miR-548x_st, hsa-miR-3125_st and hsa-miR-331-3p_st could determine short- and long-term survival with a predicted accuracy of 78%. Heatmap dendrograms dichotomized glioblastomas into prognostic subgroups with a significant...

  20. MiRNA-155 and miRNA-132 as potential diagnostic biomarkers for pulmonary tuberculosis: A preliminary study.

    Science.gov (United States)

    Zheng, Meng-Li; Zhou, Nai-Kang; Luo, Cheng-Hua

    2016-11-01

    In our study, we aimed to profile a panel microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary tuberculosis (PTB) and to illuminate the molecular mechanisms in the development of PTB. Firstly, gene expression profile of E-GEOD-49951 was downloaded from ArrayExpress database, and quantile-adjusted conditional maximum likelihood method was utilized to identify statistical difference between miRNAs of Mycobacterium tuberculosis (MTB)-infected individuals and healthy subjects. Furthermore, in order to assess the performance of our methodology, random forest (RF) classification model was utilized to identify the top 10 miRNAs with better Area Under The Curve (AUC) using 10-fold cross-validation method. Additionally, Monte Carlo Cross-Validation was repeated 50 times to explore the best miRNAs. In order to learn more about the differentially-expressed miRNAs, the target genes of differentially-expressed miRNAs were retrieved from TargetScan database and Ingenuity Pathways Analysis (IPA) was used to screen out biological pathways where target genes were involved. After normalization, a total of 478 miRNAs with higher than 0.25-fold quantile average across all samples were required. Based on the differential expression analysis, 38 differentially expressed miRNAs were identified when the significance was set as false discovery rate (FDR) < 0.01. Among the top 10 differentially expressed miRNAs, miRNA-155 obtained a highest AUC value 0.976, showing a good performance between PTB and control groups. Similarly, miRNA-449a, miRNA-212 and miRNA-132 revealed also a good performance with AUC values 0.947, 0.931 and 0.930, respectively. Moreover, miRNA-155, miRNA-449a, miRNA-29b-1* and miRNA-132 appeared in 50, 49, 49 and 48 bootstraps. Thus, miRNA-155 and miRNA-132 might be important in the progression of PTB and thereby, might present potential signatures for diagnosis of PTB. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Involvement of epigenetics and EMT-related miRNA in arsenic-induced neoplastic transformation and their potential clinical use.

    Science.gov (United States)

    Michailidi, Christina; Hayashi, Masamichi; Datta, Sayantan; Sen, Tanusree; Zenner, Kaitlyn; Oladeru, Oluwadamilola; Brait, Mariana; Izumchenko, Evgeny; Baras, Alexander; VandenBussche, Christopher; Argos, Maria; Bivalacqua, Trinity J; Ahsan, Habibul; Hahn, Noah M; Netto, George J; Sidransky, David; Hoque, Mohammad Obaidul

    2015-03-01

    Exposure to toxicants leads to cumulative molecular changes that overtime increase a subject's risk of developing urothelial carcinoma. To assess the impact of arsenic exposure at a time progressive manner, we developed and characterized a cell culture model and tested a panel of miRNAs in urine samples from arsenic-exposed subjects, urothelial carcinoma patients, and controls. To prepare an in vitro model, we chronically exposed an immortalized normal human bladder cell line (HUC1) to arsenic. Growth of the HUC1 cells was increased in a time-dependent manner after arsenic treatment and cellular morphology was changed. In a soft agar assay, colonies were observed only in arsenic-treated cells, and the number of colonies gradually increased with longer periods of treatment. Similarly, invaded cells in an invasion assay were observed only in arsenic-treated cells. Withdrawal of arsenic treatment for 2.5 months did not reverse the tumorigenic properties of arsenic-treated cells. Western blot analysis demonstrated decreased PTEN and increased AKT and mTOR in arsenic-treated HUC1 cells. Levels of miR-200a, miR-200b, and miR-200c were downregulated in arsenic-exposed HUC1 cells by quantitative RT-PCR. Furthermore, in human urine, miR-200c and miR-205 were inversely associated with arsenic exposure (P = 0.005 and 0.009, respectively). Expression of miR-205 discriminated cancer cases from controls with high sensitivity and specificity (AUC = 0.845). Our study suggests that exposure to arsenic rapidly induces a multifaceted dedifferentiation program and miR-205 has potential to be used as a marker of arsenic exposure as well as a maker of early urothelial carcinoma detection. ©2015 American Association for Cancer Research.

  2. Computational identification of miRNAs and their targets in Phaseolus vulgaris.

    Science.gov (United States)

    Han, J; Xie, H; Kong, M L; Sun, Q P; Li, R Z; Pan, J B

    2014-01-21

    MicroRNAs (miRNAs) are a class of non-coding small RNAs that negatively regulate gene expression at the post-transcriptional level. Although thousands of miRNAs have been identified in plants, limited information is available about miRNAs in Phaseolus vulgaris, despite it being an important food legume worldwide. The high conservation of plant miRNAs enables the identification of new miRNAs in P. vulgaris by homology analysis. Here, 1804 known and unique plant miRNAs from 37 plant species were blast-searched against expressed sequence tag and genomic survey sequence databases to identify novel miRNAs in P. vulgaris. All candidate sequences were screened by a series of miRNA filtering criteria. Finally, we identified 27 conserved miRNAs, belonging to 24 miRNA families. When compared against known miRNAs in P. vulgaris, we found that 24 of the 27 miRNAs were newly discovered. Further, we identified 92 potential target genes with known functions for these novel miRNAs. Most of these target genes were predicted to be involved in plant development, signal transduction, metabolic pathways, disease resistance, and environmental stress response. The identification of the novel miRNAs in P. vulgaris is anticipated to provide baseline information for further research about the biological functions and evolution of miRNAs in P. vulgaris.

  3. Deregulation - a source of crisis?

    International Nuclear Information System (INIS)

    Haavardstein, Hilde; Sandsmark, Maria

    2003-01-01

    Since the beginning of the 1990s, deregulation has become widespread in many of the worlds power markets. When it is no longer the authorities, but the players in the market who are deciding on investments in new production capacity, on the basis of business economic estimates of profitability, it is important that the external conditions are worked out such that they provide incentives to investments of the right extent and to the right time. Examples from deregulated markets show that the formulation of such external frames has contributed to a tight power balance

  4. Association between the miRNA Signatures in Plasma and Bronchoalveolar Fluid in Respiratory Pathologies

    Directory of Open Access Journals (Sweden)

    Sonia Molina-Pinelo

    2012-01-01

    Full Text Available The identification of new less invasive biomarkers is necessary to improve the detection and prognostic outcome of respiratory pathological processes. The measurement of miRNA expression through less invasive techniques such as plasma and serum have been suggested to analysis of several lung malignancies including lung cancer. These studies are assuming a common deregulated miRNA expression both in blood and lung tissue. The present study aimed to obtain miRNA representative signatures both in plasma and bronchoalveolar cell fraction that could serve as biomarker in respiratory diseases. Ten patients were evaluated to assess the expression levels of 381 miRNAs. We found that around 50% miRNAs were no detected in both plasma and bronchoalveolar cell fraction and only 20% of miRNAs showed similar expression in both samples. These results show a lack of association of miRNA signatures between plasma and bronchoalveolar cytology in the same patient. The profiles are not comparable; however, there is a similarity in the relative expression in a very small subset of miRNAs (miR-17, miR-19b, miR-195 and miR-20b between both biological samples in all patients. This finding supports that the miRNAs profiles obtained from different biological samples have to be carefully validated to link with respiratory diseases.

  5. Energy deregulation: the Vattenfall experience

    International Nuclear Information System (INIS)

    Nyquist, C.E.

    1999-01-01

    In 1992, Sweden prepared itself for deregulation by transforming Vattenfall, the country's main supplier of energy, from a public utility into a limited liability company. Vattenfall was still 100% owned by the state, but began to operate as a commercial entity with a separate board of directors. On January 1, 1996, Sweden and Finland deregulated, and the three Nordic countries - Norway, Sweden and Denmark - became a completely open market. Beginning November 1, 1999, Sweden will introduce simplified metering, bringing competition directly to consumers, which represents the purest and most advanced form of electricity competition, forcing Vattenfall and its peers to fight for the loyalty of customers from the smallest retail household upwards. As a central participant in deregulation, Vattenfall was faced with some major challenges. In essence, Vattenfall had to evolve from a parochial Swedish public utility into a pan-European energy services company. The transition was successful and Vattenfall today represents about 20% of Scandinavia's generation capacity, with operations that are about 1/2 the size of those of Ontario Hydro. Vattenfall had to take a number of steps to get ready for a fully competitive retail market. First it established a market oriented group organization based on three units: Vattenfall Electricity Generation, Vattenfall Energy Market, and Vattenfall Electricity Networks and Services. Second it expanded its relationship with its customers. Third it adjusted to the fact that electricity deregulation led to an immediate generation surplus. The main lessons learned from the experience are summarized

  6. Deregulation of microRNA expression in purified T and B lymphocytes from patients with primary Sjögren’s syndrome

    Science.gov (United States)

    Wang-Renault, Shu-Fang; Boudaoud, Saida; Nocturne, Gaétane; Roche, Elodie; Sigrist, Nelly; Daviaud, Christian; Bugge Tinggaard, Andreas; Renault, Victor; Deleuze, Jean-François; Mariette, Xavier; Tost, Jörg

    2018-01-01

    Objective MicroRNAs (miRNAs) play an important role in the pathogenesis of autoimmune diseases such as primary Sjögren’s syndrome (pSS). This study is the first to investigate miRNA expression patterns in purified T and B lymphocytes from patients with pSS using a high-throughput quantitative PCR (qPCR) approach. Methods Two independent cohorts of both patients with pSS and controls, one for discovery and one for replication, were included in this study. CD4+ T cells and CD19+ B cells were isolated from peripheral blood mononuclear cells by magnetic microbeads and expression of miRNAs was profiled using the Exiqon Human miRNome panel I analysing 372 miRNAs. A selection of differentially expressed miRNAs was replicated in the second cohort using specific qPCR assays. Results A major difference in miRNA expression patterns was observed between the lymphocyte populations from patients with pSS and controls. In CD4 T lymphocytes, hsa-let-7d-3p, hsa-miR-155–5 p, hsa-miR-222–3 p, hsa-miR-30c-5p, hsa-miR-146a-5p, hsa-miR-378a-3p and hsa-miR-28–5 p were significantly differentially expressed in both the discovery and the replication cohort. In B lymphocytes, hsa-miR-378a-3p, hsa-miR-222–3 p, hsa-miR-26a-5p, hsa-miR-30b-5p and hsa-miR-19b-3p were significantly differentially expressed. Potential target mRNAs were enriched in disease relevant pathways. Expression of B-cell activating factor (BAFF) mRNA was inversely correlated with the expression of hsa-miR-30b-5p in B lymphocytes from patients with pSS and functional experiments showed increased expression of BAFF after inhibiting hsa-miR-30b-5p. Conclusions This study demonstrates major miRNAs deregulation in T and B cells from patients with pSS in two independent cohorts, which might target genes known to be involved in the pathogenesis of pSS. PMID:28916716

  7. Does duration of deregulated religious markets affect Church attendance? Evidence from twenty-six religious markets in Europe and North America between 1981 and 2006

    NARCIS (Netherlands)

    Aarts, Olav; Need, Ariana; Grotenhuis, Manfred Te; Graaf, Nan Dirk de

    2010-01-01

    This study tests the deregulation hypothesis of religious market theory in 26 European and Northern American countries by examining differences in religious involvement between and within countries. The deregulation hypothesis, which is assumed to be universally valid, predicts that religious

  8. Current perspectives in micrornas (mirna)

    CERN Document Server

    Ying, Shao-Yao

    2008-01-01

    In this book, many new perspectives of the miRNA research are reviewed and discussed. These new findings provide significant insight into the various mechanisms of miRNAs and offer a great opportunity in developing new therapeutic interventions.

  9. Isolation and Identification of miRNAs in Jatropha curcas

    Science.gov (United States)

    Wang, Chun Ming; Liu, Peng; Sun, Fei; Li, Lei; Liu, Peng; Ye, Jian; Yue, Gen Hua

    2012-01-01

    MicroRNAs (miRNAs) are small noncoding RNAs that play crucial regulatory roles by targeting mRNAs for silencing. To identify miRNAs in Jatropha curcas L, a bioenergy crop, cDNA clones from two small RNA libraries of leaves and seeds were sequenced and analyzed using bioinformatic tools. Fifty-two putative miRNAs were found from the two libraries, among them six were identical to known miRNAs and 46 were novel. Differential expression patterns of 15 miRNAs in root, stem, leave, fruit and seed were detected using quantitative real-time PCR. Ten miRNAs were highly expressed in fruit or seed, implying that they may be involved in seed development or fatty acids synthesis in seed. Moreover, 28 targets of the isolated miRNAs were predicted from a jatropha cDNA library database. The miRNA target genes were predicted to encode a broad range of proteins. Sixteen targets had clear BLASTX hits to the Uniprot database and were associated with genes belonging to the three major gene ontology categories of biological process, cellular component, and molecular function. Four targets were identified for JcumiR004. By silencing JcumiR004 primary miRNA, expressions of the four target genes were up-regulated and oil composition were modulated significantly, indicating diverse functions of JcumiR004. PMID:22419887

  10. Methylation of miRNA genes and oncogenesis.

    Science.gov (United States)

    Loginov, V I; Rykov, S V; Fridman, M V; Braga, E A

    2015-02-01

    Interaction between microRNA (miRNA) and messenger RNA of target genes at the posttranscriptional level provides fine-tuned dynamic regulation of cell signaling pathways. Each miRNA can be involved in regulating hundreds of protein-coding genes, and, conversely, a number of different miRNAs usually target a structural gene. Epigenetic gene inactivation associated with methylation of promoter CpG-islands is common to both protein-coding genes and miRNA genes. Here, data on functions of miRNAs in development of tumor-cell phenotype are reviewed. Genomic organization of promoter CpG-islands of the miRNA genes located in inter- and intragenic areas is discussed. The literature and our own results on frequency of CpG-island methylation in miRNA genes from tumors are summarized, and data regarding a link between such modification and changed activity of miRNA genes and, consequently, protein-coding target genes are presented. Moreover, the impact of miRNA gene methylation on key oncogenetic processes as well as affected signaling pathways is discussed.

  11. Viruses and miRNAs: More Friends than Foes.

    Science.gov (United States)

    Bruscella, Patrice; Bottini, Silvia; Baudesson, Camille; Pawlotsky, Jean-Michel; Feray, Cyrille; Trabucchi, Michele

    2017-01-01

    There is evidence that eukaryotic miRNAs (hereafter called host miRNAs) play a role in the replication and propagation of viruses. Expression or targeting of host miRNAs can be involved in cellular antiviral responses. Most times host miRNAs play a role in viral life-cycles and promote infection through complex regulatory pathways. miRNAs can also be encoded by a viral genome and be expressed in the host cell. Viral miRNAs can share common sequences with host miRNAs or have totally different sequences. They can regulate a variety of biological processes involved in viral infection, including apoptosis, evasion of the immune response, or modulation of viral life-cycle phases. Overall, virus/miRNA pathway interaction is defined by a plethora of complex mechanisms, though not yet fully understood. This article review summarizes recent advances and novel biological concepts related to the understanding of miRNA expression, control and function during viral infections. The article also discusses potential therapeutic applications of this particular host-pathogen interaction.

  12. Viruses and miRNAs: More Friends than Foes

    Directory of Open Access Journals (Sweden)

    Patrice Bruscella

    2017-05-01

    Full Text Available There is evidence that eukaryotic miRNAs (hereafter called host miRNAs play a role in the replication and propagation of viruses. Expression or targeting of host miRNAs can be involved in cellular antiviral responses. Most times host miRNAs play a role in viral life-cycles and promote infection through complex regulatory pathways. miRNAs can also be encoded by a viral genome and be expressed in the host cell. Viral miRNAs can share common sequences with host miRNAs or have totally different sequences. They can regulate a variety of biological processes involved in viral infection, including apoptosis, evasion of the immune response, or modulation of viral life-cycle phases. Overall, virus/miRNA pathway interaction is defined by a plethora of complex mechanisms, though not yet fully understood. This article review summarizes recent advances and novel biological concepts related to the understanding of miRNA expression, control and function during viral infections. The article also discusses potential therapeutic applications of this particular host–pathogen interaction.

  13. Deregulator: Judgment Day for microeconomics

    International Nuclear Information System (INIS)

    Keen, S.

    2004-01-01

    The economic theory that motivated the deregulation and privatization of the US electricity industry is seriously flawed in three crucial ways. First, the Marshallian theory of the firm is based on two mathematical errors which, when amended, reverse the accepted welfare rankings of competitive and monopoly industry structures: on the grounds of corrected neoclassical theory, monopoly should be preferred to competition. Second, while proponents of deregulation expected market-clearing equilibrium prices to apply, it is well known that the equilibrium of a system of spot market prices is unstable. This implies that imposing spot market pricing on as basic an industry as electricity is likely to lead to the kind of volatility observed under the deregulation. Third, extensive empirical research has established that on the order of 95% of firms do not produce under conditions of rising marginal cost. Requiring electricity firms to price at marginal cost was therefore likely to lead to bankruptcies, as indeed occurred. The economic preference for marginal cost spot market pricing is therefore theoretically unsound, and it is no wonder that the actual deregulatory experience was as bad as it was. (author)

  14. Deregulator: Judgment Day for microeconomics

    Energy Technology Data Exchange (ETDEWEB)

    Keen, S. [University of Western Sydney, Penrith (Australia). School of Economics and Finance

    2004-09-01

    The economic theory that motivated the deregulation and privatization of the US electricity industry is seriously flawed in three crucial ways. First, the Marshallian theory of the firm is based on two mathematical errors which, when amended, reverse the accepted welfare rankings of competitive and monopoly industry structures: on the grounds of corrected neoclassical theory, monopoly should be preferred to competition. Second, while proponents of deregulation expected market-clearing equilibrium prices to apply, it is well known that the equilibrium of a system of spot market prices is unstable. This implies that imposing spot market pricing on as basic an industry as electricity is likely to lead to the kind of volatility observed under the deregulation. Third, extensive empirical research has established that on the order of 95% of firms do not produce under conditions of rising marginal cost. Requiring electricity firms to price at marginal cost was therefore likely to lead to bankruptcies, as indeed occurred. The economic preference for marginal cost spot market pricing is therefore theoretically unsound, and it is no wonder that the actual deregulatory experience was as bad as it was. (author)

  15. The miRNA-200 family and miRNA-9 exhibit differential expression in primary versus corresponding metastatic tissue in breast cancer

    DEFF Research Database (Denmark)

    Gravgaard, Karina H; Lyng, Maria Bibi; Laenkholm, Anne-Vibeke

    2012-01-01

    Metastases are the major cause of cancer-related deaths, but the mechanisms of the metastatic process remain poorly understood. In recent years, the involvement of microRNAs (miRNAs) in cancer has become apparent, and the objective of this study was to identify miRNAs associated with breast cancer...... progression. Global miRNA expression profiling was performed on 47 tumor samples from 14 patients with paired samples from primary breast tumors and corresponding lymph node and distant metastases using LNA-enhanced miRNA microarrays. The identified miRNA expression alterations were validated by real-time PCR...

  16. Current trends in miRNAs and their relationship with oral squamous cell carcinoma.

    Science.gov (United States)

    Pérez-Sayáns, Mario; Pilar, Gayoso-Diz; Barros-Angueira, Francisco; Suárez-Peñaranda, José Manuel; Fernández, Alexia Conde; Gándara-Rey, José Manuel; García-García, Abel

    2012-07-01

    A micro RNA (miRNA) is a single-stranded endogenous, non-coding RNA, with length ranging between 18 and 24 nucleotides and the ability of regulating the expression of other genes on a post-transcriptional level by means of various processes, degradation or repression of target mRNA. miRNAs play a crucial role in regulating fundamental processes such as cell cycle, differentiation and apoptosis; thus, their deregulation can affect normal cell growth and development, and even participate in carcinogenesis. The goals of this paper are: to outline the formation and functions of miRNAs; to determine their role in oral squamous cell carcinoma; to analyze the different miRNAs described and their roles as oncogenes or tumor suppressor genes, depending on their overexpression or subexpression; to describe the different polymorphisms and epigenetic alterations identified; and to determine their role in multidrug resistance. © 2011 John Wiley & Sons A/S.

  17. Integrating miRNA and mRNA Expression Profiling Uncovers miRNAs Underlying Fat Deposition in Sheep

    Directory of Open Access Journals (Sweden)

    Guangxian Zhou

    2017-01-01

    Full Text Available MicroRNAs (miRNAs are endogenous, noncoding RNAs that regulate various biological processes including adipogenesis and fat metabolism. Here, we adopted a deep sequencing approach to determine the identity and abundance of miRNAs involved in fat deposition in adipose tissues from fat-tailed (Kazakhstan sheep, KS and thin-tailed (Tibetan sheep, TS sheep breeds. By comparing HiSeq data of these two breeds, 539 miRNAs were shared in both breeds, whereas 179 and 97 miRNAs were uniquely expressed in KS and TS, respectively. We also identified 35 miRNAs that are considered to be putative novel miRNAs. The integration of miRNA-mRNA analysis revealed that miRNA-associated targets were mainly involved in the gene ontology (GO biological processes concerning cellular process and metabolic process, and miRNAs play critical roles in fat deposition through their ability to regulate fundamental pathways. These pathways included the MAPK signaling pathway, FoxO and Wnt signaling pathway, and focal adhesion. Taken together, our results define miRNA expression signatures that may contribute to fat deposition and lipid metabolism in sheep.

  18. Epigenetic regulation of normal human mammary cell type-specific miRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Vrba, Lukas [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Inst. of Plant Molecular Biology, Ceske Budejovice (Czech Republic). Biology Centre ASCR; Garbe, James C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Stampfer, Martha R. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Futscher, Bernard W. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center and Dept. of Pharmacology & Toxicology

    2011-08-26

    Epigenetic mechanisms are important regulators of cell type–specific genes, including miRNAs. In order to identify cell type-specific miRNAs regulated by epigenetic mechanisms, we undertook a global analysis of miRNA expression and epigenetic states in three isogenic pairs of human mammary epithelial cells (HMEC) and human mammary fibroblasts (HMF), which represent two differentiated cell types typically present within a given organ, each with a distinct phenotype and a distinct epigenotype. While miRNA expression and epigenetic states showed strong interindividual concordance within a given cell type, almost 10% of the expressed miRNA showed a cell type–specific pattern of expression that was linked to the epigenetic state of their promoter. The tissue-specific miRNA genes were epigenetically repressed in nonexpressing cells by DNA methylation (38%) and H3K27me3 (58%), with only a small set of miRNAs (21%) showing a dual epigenetic repression where both DNA methylation and H3K27me3 were present at their promoters, such as MIR10A and MIR10B. Individual miRNA clusters of closely related miRNA gene families can each display cell type–specific repression by the same or complementary epigenetic mechanisms, such as the MIR200 family, and MIR205, where fibroblasts repress MIR200C/141 by DNA methylation, MIR200A/200B/429 by H3K27me3, and MIR205 by both DNA methylation and H3K27me3. Since deregulation of many of the epigenetically regulated miRNAs that we identified have been linked to disease processes such as cancer, it is predicted that compromise of the epigenetic control mechanisms is important for this process. Overall, these results highlight the importance of epigenetic regulation in the control of normal cell type–specific miRNA expression.

  19. Dynamics of miRNA biogenesis and nuclear transport

    Directory of Open Access Journals (Sweden)

    Kotipalli Aneesh

    2016-12-01

    Full Text Available MicroRNAs (miRNAs are short noncoding RNA sequences ~22 nucleotides in length that play an important role in gene regulation-transcription and translation. The processing of these miRNAs takes place in both the nucleus and the cytoplasm while the final maturation occurs in the cytoplasm. Some mature miRNAs with nuclear localisation signals (NLS are transported back to the nucleus and some remain in the cytoplasm. The functional roles of these miRNAs are seen in both the nucleus and the cytoplasm. In the nucleus, miRNAs regulate gene expression by binding to the targeted promoter sequences and affect either the transcriptional gene silencing (TGS or transcriptional gene activation (TGA. In the cytoplasm, targeted mRNAs are translationally repressed or cleaved based on the complementarity between the two sequences at the seed region of miRNA and mRNA. The selective transport of mature miRNAs to the nucleus follows the classical nuclear import mechanism. The classical nuclear import mechanism is a highly regulated process, involving exportins and importins. The nuclear pore complex (NPC regulates all these transport events like a gate keeper. The half-life of miRNAs is rather low, so within a short time miRNAs perform their function. Temporal studies of miRNA biogenesis are, therefore, useful. We have carried out simulation studies for important miRNA biogenesis steps and also classical nuclear import mechanism using ordinary differential equation (ODE solver in the Octave software.

  20. Dynamics of miRNA biogenesis and nuclear transport.

    Science.gov (United States)

    Kotipalli, Aneesh; Gutti, Ravikumar; Mitra, Chanchal K

    2016-12-22

    MicroRNAs (miRNAs) are short noncoding RNA sequences ~22 nucleotides in length that play an important role in gene regulation-transcription and translation. The processing of these miRNAs takes place in both the nucleus and the cytoplasm while the final maturation occurs in the cytoplasm. Some mature miRNAs with nuclear localisation signals (NLS) are transported back to the nucleus and some remain in the cytoplasm. The functional roles of these miRNAs are seen in both the nucleus and the cytoplasm. In the nucleus, miRNAs regulate gene expression by binding to the targeted promoter sequences and affect either the transcriptional gene silencing (TGS) or transcriptional gene activation (TGA). In the cytoplasm, targeted mRNAs are translationally repressed or cleaved based on the complementarity between the two sequences at the seed region of miRNA and mRNA. The selective transport of mature miRNAs to the nucleus follows the classical nuclear import mechanism. The classical nuclear import mechanism is a highly regulated process, involving exportins and importins. The nuclear pore complex (NPC) regulates all these transport events like a gate keeper. The half-life of miRNAs is rather low, so within a short time miRNAs perform their function. Temporal studies of miRNA biogenesis are, therefore, useful. We have carried out simulation studies for important miRNA biogenesis steps and also classical nuclear import mechanism using ordinary differential equation (ODE) solver in the Octave software.

  1. Novel Insights into miRNA in Lung and Heart Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Amit Kishore

    2014-01-01

    Full Text Available MicroRNAs (miRNAs are noncoding regulatory sequences that govern posttranscriptional inhibition of genes through binding mainly at regulatory regions. The regulatory mechanism of miRNAs are influenced by complex crosstalk among single nucleotide polymorphisms (SNPs within miRNA seed region and epigenetic modifications. Circulating miRNAs exhibit potential characteristics as stable biomarker. Functionally, miRNAs are involved in basic regulatory mechanisms of cells including inflammation. Thus, miRNA dysregulation, resulting in aberrant expression of a gene, is suggested to play an important role in disease susceptibility. This review focuses on the role of miRNA as diagnostic marker in pathogenesis of lung inflammatory diseases and in cardiac remodelling events during inflammation. From recent reports, In this context, the information about the models in which miRNAs expression were investigated including types of biological samples, as well as on the methods for miRNA validation and prediction/definition of their gene targets are emphasized in the review. Besides disease pathogenesis, promising role of miRNAs in early disease diagnosis and prognostication is also discussed. However, some miRNAs are also indicated with protective role. Thus, identifications and usage of such potential miRNAs as well as disruption of disease susceptible miRNAs using antagonists, antagomirs, are imperative and may provide a novel therapeutic approach towards combating the disease progression.

  2. miRNA array analysis determines miR-205 is overexpressed in head and neck squamous cell carcinoma and enhances cellular proliferation

    Directory of Open Access Journals (Sweden)

    Howard JD

    2013-08-01

    Full Text Available MicroRNAs (miRNAs play a critical role in cell cycle and pro-survival signal regulation. Consequently, their deregulation can enhance tumorigenesis and cancer progression. In the current investigation, we determined whether cancer- or human papillomavirus (HPV-specific miRNA deregulation could further elucidate signal transduction events unique to head and neck squamous cell carcinoma (HNSCC. Twenty-nine newly diagnosed HNSCC tumors (HPV-positive: 14, HPV-negative: 15 and four normal mucosa samples were analyzed for global miRNA expression. Differential miRNA expression analysis concluded HNSCC is characterized by a general upregulation of miRNAs compared to normal mucosa. Additionally, miR-449a and miR-129-3p were statistically significant miRNAs differentially expressed between HPV-positive and HPV-negative HNSCC. The upregulation of miR-449a was also validated within an independent dataset obtained from TCGA containing 279 HNSCCs and 39 normal adjacent mucosa samples. To gain a better understanding of miRNA-mediated cell cycle deregulation in HNSCC, we functionally evaluated miR-205, a transcript upregulated in our cancer-specific analysis and a putative regulator of E2F1. Modulation of miR-205 with a miRNA mimic and inhibitor revealed miR-205 is capable of regulating E2F1 expression in HNSCC and overexpression of this transcript enhances proliferation. This study demonstrates miRNA expression is highly deregulated in HNSCC and functional evaluations of these miRNAs may reveal novel HPV context dependent mechanisms in this disease.

  3. Propolis modulates miRNAs involved in TLR-4 pathway, NF-κB activation, cytokine production and in the bactericidal activity of human dendritic cells.

    Science.gov (United States)

    Conti, Bruno J; Santiago, Karina B; Cardoso, Eliza O; Freire, Paula P; Carvalho, Robson F; Golim, Marjorie A; Sforcin, José M

    2016-12-01

    Dendritic cells (DCs) are antigen-presenting cells, essential for recognition and presentation of pathogens to T cells. Propolis, a resinous material produced by bees from various plants, exhibits numerous biological properties, highlighting its immunomodulatory action. Here, we assayed the effects of propolis on the maturation and function of human DCs. DCs were generated from human monocytes and incubated with propolis and LPS. NF-κB and cytokines production were determined by ELISA. microRNA's expression was analysed by RT-qPCR and cell markers detection by flow cytometry. Colony-forming units were obtained to assess the bactericidal activity of propolis-treated DCs. Propolis activated DCs in the presence of LPS, inducing NF-kB, TNF-α, IL-6 and IL-10 production. The inhibition of hsa-miR-148a and hsa-miR-148b abolished the inhibitory effects on HLA-DR and pro-inflammatory cytokines. The increased expression of hsa-miR-155 may be correlated to the increase in TLR-4 and CD86 expression, maintaining LPS-induced expression of HLA-DR and CD40. Such parameters may be involved in the increased bactericidal activity of DCs against Streptococcus mutans. Propolis modulated the maturation and function of DCs and may be useful in the initial steps of the immune response, providing a novel approach to the development of DC-based strategies and for the discovery of new immunomodulators. © 2016 Royal Pharmaceutical Society.

  4. ACC oxidase and miRNA 159a, and their involvement in fresh fruit bunch yield (FFB) via sex ratio determination in oil palm.

    Science.gov (United States)

    Somyong, Suthasinee; Poopear, Supannee; Sunner, Supreet Kaur; Wanlayaporn, Kitti; Jomchai, Nukoon; Yoocha, Thippawan; Ukoskit, Kittipat; Tangphatsornruang, Sithichoke; Tragoonrung, Somvong

    2016-06-01

    Oil palm (Elaeis guineesis Jacq.) is the most productive oil-bearing crop, yielding more oil per area than any other oil-bearing crops. However, there are still efforts to improve oil palm yield, in order to serve consumer and manufacturer demand. Oil palm produces female and male inflorescences in an alternating cycle. So, high sex ratio (SR), the ratio of female inflorescences to the total inflorescences, is a favorable trait in term of increasing yields in oil palm. This study aims to understand the genetic control for SR related traits, such as fresh fruit bunch yield (FFB), by characterizing genes at FFB quantitative trait loci (QTLs) on linkage 10 (chromosome 6) and linkage 15 (chromosome 10). Published oil palm sequences at the FFB QTLs were used to develop gene-based and simple sequence repeat (SSR) markers. We used the multiple QTL analysis model (MQM) to characterize the relationship of new markers with the SR traits in the oil palm population. The RNA expression of the most linked QTL genes was also evaluated in various tissues of oil palm. We identified EgACCO1 (encoding aminocyclopropane carboxylate (ACC) oxidase) at chromosome 10 and EgmiR159a (microRNA 159a) at chromosome 6 to be the most linked QTL genes or determinants for FFB yield and/or female inflorescence number with a phenotype variance explained (PVE) from 10.4 to 15 % and suggest that these play the important roles in sex determination and differentiation in oil palm. The strongest expression of EgACCO1 and the predicted precursor of EgmiR159a was found in ovaries and, to a lesser extent, fruit development. In addition, highly normalized expression of EgmiR159a was found in female flowers. In summary, the QTL analysis and the RNA expression reveal that EgACCO1 and EgmiR159a are the potential genetic factors involved in female flower determination and hence would affect yield in oil palm. However, to clarify how these genetic factors regulate female flower determination, more investigation

  5. Deregulation, a challenge for regulators

    International Nuclear Information System (INIS)

    Alonso, Augustin

    2001-01-01

    Deregulation and competitiveness in the electricity market invites the plant owner/operator to reduce operating cost with a potential reduction in maintenance, degradation of investment in safety, reduction of operating staff and a downgrading in research and development. On the other side, deregulation and competitiveness brings the social and industrial benefit of reducing the electricity cost. Regulatory organisations have to watch that the safety level of the plant does not go beyond the established level, while recognising the benefits of the new situation; therefore they have the moral responsibility of regulating nuclear energy effectively and efficiently and in eliminating unnecessary regulatory burdens. Regulation has evolved with time and in accordance with the knowledge gained from research and the analysis of operating experience. The knowledge gained has made it possible to follow the path of other modern advanced technologies, where risk is quantified and the system approved when the risk becomes lower than an accepted level. The regulatory use of this advanced tool is being now developed by the most advanced regulatory organisations, under the name of risk informed regulation, where the reference level is the expected frequency of core damage. Deregulation and competitiveness will not change the basis of the already well established procedure to verify compliance. Nevertheless, the contents of Safety Analysis Reports and other regulatory documents, such as Technical Specifications for Operation, offer room for improvement in the sense of being more to the roots of the matter and becoming more efficient tools in the verification process. The contents of these documents have been evolving along the time and they have become unnecessary voluminous and rather burdensome. Much work has been done to improve the efficiency of regulatory inspections by concentrating on basic aspects. As a partial application of the already mentioned risk-informed regulation

  6. Inflation targeting and product market deregulation

    OpenAIRE

    Moretti, Laura

    2012-01-01

    I evaluate the effect of inflation targeting on inflation and how it interacts with product market deregulation during the disinflationary process in the 1990s. Using a sample of 21 OECD countries, I show that, after controlling for product market deregulation, the effect of inflation targeting is quantitatively important and statistically significant. Moreover, product market deregulation also matters in particular in countries that adopted an inflation targeting regime. I propose a New Keyn...

  7. The entire miR-200 seed family is strongly deregulated in clear cell renal cell cancer compared to the proximal tubular epithelial cells of the kidney

    NARCIS (Netherlands)

    Duns, Gerben; van den Berg, Anke; van Dijk, Marcory C. R. F.; van Duivenbode, Inge; Giezen, Cor; Kluiver, Joost; van Goor, Harry; Hofstra, Robert M. W.; van den Berg, Eva; Kok, Klaas

    Despite numerous studies reporting deregulated microRNA (miRNA) and gene expression patterns in clear cell renal cell carcinoma (ccRCC), no direct comparisons have been made to its presumed normal counterpart: the renal proximal tubular epithelial cells (PTECs). The aim of this study was to

  8. miRNA Repertoires of Demosponges Stylissa carteri and Xestospongia testudinaria

    KAUST Repository

    Liew, Yi Jin

    2016-02-12

    MicroRNAs (miRNAs) are small regulatory RNAs that are involved in many biological process in eukaryotes. They play a crucial role in modulating genetic expression of their targets, which makes them integral components of transcriptional regulatory networks. As sponges (phylum Porifera) are commonly considered the most basal metazoan, the in-depth capture of miRNAs from these organisms provides additional clues to the evolution of miRNA families in metazoans. Here, we identified the core proteins involved in the biogenesis of miRNAs, and obtained evidence for bona fide miRNA sequences for two marine sponges Stylissa carteri and Xestospongia testudinaria (11 and 19 respectively). Our analysis identified several miRNAs that are conserved amongst demosponges, and revealed that all of the novel miRNAs identified in these two species are specific to the class Demospongiae.

  9. miRNA Repertoires of Demosponges Stylissa carteri and Xestospongia testudinaria.

    Directory of Open Access Journals (Sweden)

    Yi Jin Liew

    Full Text Available MicroRNAs (miRNAs are small regulatory RNAs that are involved in many biological process in eukaryotes. They play a crucial role in modulating genetic expression of their targets, which makes them integral components of transcriptional regulatory networks. As sponges (phylum Porifera are commonly considered the most basal metazoan, the in-depth capture of miRNAs from these organisms provides additional clues to the evolution of miRNA families in metazoans. Here, we identified the core proteins involved in the biogenesis of miRNAs, and obtained evidence for bona fide miRNA sequences for two marine sponges Stylissa carteri and Xestospongia testudinaria (11 and 19 respectively. Our analysis identified several miRNAs that are conserved amongst demosponges, and revealed that all of the novel miRNAs identified in these two species are specific to the class Demospongiae.

  10. miRNA Repertoires of Demosponges Stylissa carteri and Xestospongia testudinaria.

    Science.gov (United States)

    Liew, Yi Jin; Ryu, Taewoo; Aranda, Manuel; Ravasi, Timothy

    2016-01-01

    MicroRNAs (miRNAs) are small regulatory RNAs that are involved in many biological process in eukaryotes. They play a crucial role in modulating genetic expression of their targets, which makes them integral components of transcriptional regulatory networks. As sponges (phylum Porifera) are commonly considered the most basal metazoan, the in-depth capture of miRNAs from these organisms provides additional clues to the evolution of miRNA families in metazoans. Here, we identified the core proteins involved in the biogenesis of miRNAs, and obtained evidence for bona fide miRNA sequences for two marine sponges Stylissa carteri and Xestospongia testudinaria (11 and 19 respectively). Our analysis identified several miRNAs that are conserved amongst demosponges, and revealed that all of the novel miRNAs identified in these two species are specific to the class Demospongiae.

  11. A bootstrap based analysis pipeline for efficient classification of phylogenetically related animal miRNAs

    Directory of Open Access Journals (Sweden)

    Gu Xun

    2007-03-01

    Full Text Available Abstract Background Phylogenetically related miRNAs (miRNA families convey important information of the function and evolution of miRNAs. Due to the special sequence features of miRNAs, pair-wise sequence identity between miRNA precursors alone is often inadequate for unequivocally judging the phylogenetic relationships between miRNAs. Most of the current methods for miRNA classification rely heavily on manual inspection and lack measurements of the reliability of the results. Results In this study, we designed an analysis pipeline (the Phylogeny-Bootstrap-Cluster (PBC pipeline to identify miRNA families based on branch stability in the bootstrap trees derived from overlapping genome-wide miRNA sequence sets. We tested the PBC analysis pipeline with the miRNAs from six animal species, H. sapiens, M. musculus, G. gallus, D. rerio, D. melanogaster, and C. elegans. The resulting classification was compared with the miRNA families defined in miRBase. The two classifications were largely consistent. Conclusion The PBC analysis pipeline is an efficient method for classifying large numbers of heterogeneous miRNA sequences. It requires minimum human involvement and provides measurements of the reliability of the classification results.

  12. Gas purchasing in the deregulated electricity industry

    International Nuclear Information System (INIS)

    Bachmann, G.C.

    1996-01-01

    The impact of electricity deregulation on the manner in which gas is purchased for consumption at power plants affected by deregulation, was discussed. An overview of deregulation in the electric power industry as it has occurred in Alberta, was provided, since Alberta has set the standard as the only operational power pool and deregulated marketplace for new power generation in North America. Ultimately, electricity deregulation will have a significant effect on many gas producers in Alberta. How the gas industry responds to the new challenges will determine what role gas will play in the electric marketplace. It can be safely predicted that the gas purchaser for a power producer will attempt to retain the least cost, most flexible gas supply available

  13. Differential Expression of Several miRNAs and the Host Genes AATK and DNM2 in Leukocytes of Sporadic ALS Patients.

    Science.gov (United States)

    Vrabec, Katarina; Boštjančič, Emanuela; Koritnik, Blaž; Leonardis, Lea; Dolenc Grošelj, Leja; Zidar, Janez; Rogelj, Boris; Glavač, Damjan; Ravnik-Glavač, Metka

    2018-01-01

    Genetic studies have managed to explain many cases of familial amyotrophic lateral sclerosis (ALS) through mutations in several genes. However, the cause of a majority of sporadic cases remains unknown. Recently, epigenetics, especially miRNA studies, show some promising aspects. We aimed to evaluate the differential expression of 10 miRNAs, including miR-9, miR-338, miR-638, miR-663a, miR-124a, miR-143, miR-451a, miR-132, miR-206, and let-7b, for which some connection to ALS was shown previously in ALS culture cells, animal models or patients, and in three miRNA host genes, including C1orf61 (miR-9), AATK (miR-338), and DNM2 (miR-638), in leukocyte samples of 84 patients with sporadic ALS. We observed significant aberrant dysregulation across our patient cohort for miR-124a, miR-206, miR-9, let-7b, and miR-638. Since we did not use neurological controls we cannot rule out that the revealed differences in expression of investigated miRNAs are specific for ALS. Nevertheless, the group of these five miRNAs is worth of additional research in leukocytes of larger cohorts from different populations in order to verify their potential association to ALS disease. We also detected a significant up-regulation of the AAKT gene and down-regulation of the DNM2 gene, and thus, for the first time, we connected these with sporadic ALS cases. These findings open up new research toward miRNAs as diagnostic biomarkers and epigenetic processes involved in ALS. The detected significant deregulation of AAKT and DNM2 in sporadic ALS also represents an interesting finding. The DNM2 gene was previously found to be mutated in Charcot-Marie-Tooth neuropathy-type CMT2M and centronuclear myopathy (CNM). In addition, as recent studies connected AATK and frontotemporal dementia (FTD) and DNM2 and hereditary spastic paraplegia (HSP), these two genes together with our results genetically connect, at least in part, five diseases, including FTD, HSP, Charcot-Marie-Tooth (type CMT2M), CNM, and ALS

  14. miRNA and cancer; computational and experimental approaches.

    Science.gov (United States)

    Tutar, Yusuf

    2014-01-01

    Human genome sequencing was started to solve four letter algorithm of the genome to understand the complex nature of human metabolism. However, after completion of Human Genome Project many scientists realized that sequence information alone was not sufficient to solve the biochemical mechanism of the organism through classical approaches. Non-coding parts of the genome produce small conserved ribonucleic acids, miRNAs to control cellular and physiological processes [1, 2]. This breakthrough discovery directed researches to examine role of miRNA in cancer since miRNAs are involved in the development, cell differentiation, and regulation of cell cycle [3]. The first paper of the special issue provides general information of miRNA in cancer research. This thematic issue presents two computational approaches for miRNA identification and their role in cancer. The first one comes from Dr. Wang and his presented work predicts cancer-related miRNAs by using expression profiles in tumor tissues. The work relies on R-squared method to investigate miRNA-mRNA regulatory relationship between miRNAs and mRNAs from different tissues and predicts miRNAs associated with colon, prostate, pancreatic, lung, breast, bladder, and kidney cancer. The second paper by Allmer et al. examines miRNA-gene regulatory networks and their implications in cancer. Their work provides complex network of expression regulation and miRNAs' role in personalized medicine. miRNAs regulate tumor progression and metastasis by interacting with target genes in the cells. Exosomal shuttle small RNAs mediate cell to cell communication and regulate cancer metastasis. The regulation via heterotypic signals in the microenvironment was explained by Dr. Liang and Dr. Yu groups. The rest of the issue highlights the roles of miRNAs on multiple myeloma, non-small cell lung cancer, urological malignancies, myeloid leukemia, and laryngeal squamous cell carcinoma. Proliferation of bone marrow of malignant plasma cells

  15. Profile of differentially expressed miRNAs in high-grade serous carcinoma and clear cell ovarian carcinoma, and the expression of miR-510 in ovarian carcinoma.

    Science.gov (United States)

    Zhang, Xinchen; Guo, Gordon; Wang, Guang; Zhao, Jinyao; Wang, Bo; Yu, Xiaotang; Ding, Yanfang

    2015-12-01

    Improved insight into the molecular and genetic profile of different types of epithelial ovarian cancer (EOC) is required for understanding the carcinogenesis of EOC and may potentially be exploited by future targeted therapies. The aim of the present study was to identify a unique microRNA (miRNA) patterns and key miRNAs, which may assist in predicting progression and prognosis in high‑grade serous carcinoma (HGSC) and clear cell carcinoma (CCC). To identify unique miRNA patterns associated with HGSC and CCC, a miRNA microarray was performed using Chinese tumor bank specimens of patients with HGSC or CCC in a retrospective analysis. The expression levels of four deregulated miRNAs were further validated using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) in an external cohort of 42 cases of HGSC and 36 cases of CCC. Kaplan‑Meier analysis was performed to analyze the correlation between the expression levels of the four miRNAs and patient prognosis. Among these validated miRNAs, miR‑510 was further examined in another cohort of normal ovarian tissues, as well as the HGSC, low‑grade serous carcinoma (LGSC) and CCC specimens using RT‑qPCR and in situ hybridization. The results revealed that, of the 768 miRNAs analyzed in the microarray, 33 and 50 miRNAs were significantly upregulated and downregulated, respectively, with at least a 2‑fold difference in HGSC, compared with CCC. The quantitative analysis demonstrated that miR‑510 and miR‑129‑3p were significantly downregulated, and that miR‑483‑5p and miR‑miR‑449a were significantly upregulated in CCC, compared with HGSC (Povarian tissues. The results of the present study suggested that different subtypes of EOC have specific miRNA signatures, and that miR‑510 may be involved differently in HGSC and CCC. Thus, miR‑510 and miR‑129‑3p may be considered as potential novel candidate clinical biomarkers for predicting the outcome of EOC.

  16. Maternal chromium restriction modulates miRNA profiles related to lipid metabolism disorder in mice offspring.

    Science.gov (United States)

    Zhang, Qian; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2017-08-01

    Increasing evidence shows that maternal nutrition status has a vital effect on offspring susceptibility to obesity. MicroRNAs are related to lipid metabolism processes. This study aimed to evaluate whether maternal chromium restriction could affect miRNA expression involved in lipid metabolism in offspring. Weaning C57BL/6J mice born from mothers fed with normal control diet or chromium-restricted diet were fed for 13 weeks. The adipose miRNA expression profile was analyzed by miRNA array analysis. At 16 weeks old, pups from dams fed with chromium-restricted diet exhibit higher body weight, fat weight, and serum TC, TG levels. Six miRNAs were identified as upregulated in the RC group compared with the CC group, whereas eight miRNAs were lower than the threshold level set in the RC group. In the validated target genes of these differentially expressed miRNA, the MAPK signaling pathway serves an important role in the influence of early life chromium-restricted diet on lipid metabolism through miRNA. Long-term programming on various specific miRNA and MAPK signaling pathway may be involved in maternal chromium restriction in the adipose of female offspring. Impact statement For the first time, our study demonstrates important miRNA differences in the effect of maternal chromium restriction in offspring. These miRNAs may serve as "bridges" between the mother and the offspring by affecting the MAPK pathway.

  17. Generation of miRNA sponge constructs

    NARCIS (Netherlands)

    Kluiver, Joost; Slezak-Prochazka, Izabella; Smigielska-Czepiel, Katarzyna; Halsema, Nancy; Kroesen, Bart-Jan; van den Berg, Anke

    2012-01-01

    MicroRNA (miRNA) sponges are RNA molecules with repeated miRNA antisense sequences that can sequester miRNAs from their endogenous targets and thus serve as a decoy. Stably expressed miRNA sponges are especially valuable for long-term loss-of-function studies and can be used in vitro and in vivo. We

  18. MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma.

    Directory of Open Access Journals (Sweden)

    Fabian Feiersinger

    Full Text Available Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases.We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR.All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01. MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01. No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01.In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases.

  19. miRNA profiles in plasma from patients with sleep disorders reveal dysregulation of miRNAs in narcolepsy and other central hypersomnias

    DEFF Research Database (Denmark)

    Holm, Anja; Bang-Berthelsen, Claus Heiner; Knudsen, Stine

    2014-01-01

    STUDY OBJECTIVES: MicroRNAs (miRNAs) have been implicated in the pathogenesis of human diseases including neurological disorders. The aim is to address the involvement of miRNAs in the pathophysiology of central hypersomnias including autoimmune narcolepsy with cataplexy and hypocretin deficiency...

  20. MYC Deregulation in Primary Human Cancers.

    Science.gov (United States)

    Kalkat, Manpreet; De Melo, Jason; Hickman, Katherine Ashley; Lourenco, Corey; Redel, Cornelia; Resetca, Diana; Tamachi, Aaliya; Tu, William B; Penn, Linda Z

    2017-05-25

    MYC regulates a complex biological program by transcriptionally activating and repressing its numerous target genes. As such, MYC is a master regulator of many processes, including cell cycle entry, ribosome biogenesis, and metabolism. In cancer, the activity of the MYC transcriptional network is frequently deregulated, contributing to the initiation and maintenance of disease. Deregulation often leads to constitutive overexpression of MYC, which can be achieved through gross genetic abnormalities, including copy number alterations, chromosomal translocations, increased enhancer activity, or through aberrant signal transduction leading to increased MYC transcription or increased MYC mRNA and protein stability. Herein, we summarize the frequency and modes of MYC deregulation and describe both well-established and more recent findings in a variety of cancer types. Notably, these studies have highlighted that with an increased appreciation for the basic mechanisms deregulating MYC in cancer, new therapeutic vulnerabilities can be discovered and potentially exploited for the inhibition of this potent oncogene in cancer.

  1. Power system deregulation and the Balkan countries

    International Nuclear Information System (INIS)

    Glamochanin, Vlastimir; Stojkovska, Biljana; Cherepnalkoski, Trajche

    2001-01-01

    The aim of the paper is to show the current state and planned activities of the Power System deregulation and privatization in the following Balkan countries: Macedonia, Romania, Bulgaria, Yugoslavia, Greece, Croatia, Slovenia and Turkey

  2. Banking deregulation and corporate tax avoidance

    Directory of Open Access Journals (Sweden)

    Bill B. Francis

    2017-06-01

    Full Text Available We investigate whether tax avoidance substitutes for external financing. We exploit interstate banking deregulation as a quasi-external shock to examine whether firms engage in less tax avoidance after banking deregulation, because of cheaper and easier access to credit from banks. We find no empirical evidence to support this substitutive relation, even for firms with higher financial constraints or firms with higher external financing dependence.

  3. Profiling circulating miRNAs in serum from pigs infected with the porcine whipworm, Trichuris suis

    DEFF Research Database (Denmark)

    Hansen, Eline Palm; Kringel, Helene; Thamsborg, Stig Milan

    2016-01-01

    microRNAs (miRNAs) are recently discovered as key regulators of gene translation and are becoming increasingly recognized for their involvement in various diseases. This study investigates the miRNA profile in pig serum during the course of an infection with the gastrointestinal parasite, Trichur...... for asthma and we hypothesize possible interactions between these host- and parasite-derived miRNAs and their immunomodulating roles....

  4. Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival.

    LENUS (Irish Health Repository)

    Bray, Isabella

    2009-01-01

    MiRNAs regulate gene expression at a post-transcriptional level and their dysregulation can play major roles in the pathogenesis of many different forms of cancer, including neuroblastoma, an often fatal paediatric cancer originating from precursor cells of the sympathetic nervous system. We have analyzed a set of neuroblastoma (n = 145) that is broadly representative of the genetic subtypes of this disease for miRNA expression (430 loci by stem-loop RT qPCR) and for DNA copy number alterations (array CGH) to assess miRNA involvement in disease pathogenesis. The tumors were stratified and then randomly split into a training set (n = 96) and a validation set (n = 49) for data analysis. Thirty-seven miRNAs were significantly over- or under-expressed in MYCN amplified tumors relative to MYCN single copy tumors, indicating a potential role for the MYCN transcription factor in either the direct or indirect dysregulation of these loci. In addition, we also determined that there was a highly significant correlation between miRNA expression levels and DNA copy number, indicating a role for large-scale genomic imbalances in the dysregulation of miRNA expression. In order to directly assess whether miRNA expression was predictive of clinical outcome, we used the Random Forest classifier to identify miRNAs that were most significantly associated with poor overall patient survival and developed a 15 miRNA signature that was predictive of overall survival with 72.7% sensitivity and 86.5% specificity in the validation set of tumors. We conclude that there is widespread dysregulation of miRNA expression in neuroblastoma tumors caused by both over-expression of the MYCN transcription factor and by large-scale chromosomal imbalances. MiRNA expression patterns are also predicative of clinical outcome, highlighting the potential for miRNA mediated diagnostics and therapeutics.

  5. Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival.

    Directory of Open Access Journals (Sweden)

    Isabella Bray

    Full Text Available MiRNAs regulate gene expression at a post-transcriptional level and their dysregulation can play major roles in the pathogenesis of many different forms of cancer, including neuroblastoma, an often fatal paediatric cancer originating from precursor cells of the sympathetic nervous system. We have analyzed a set of neuroblastoma (n = 145 that is broadly representative of the genetic subtypes of this disease for miRNA expression (430 loci by stem-loop RT qPCR and for DNA copy number alterations (array CGH to assess miRNA involvement in disease pathogenesis. The tumors were stratified and then randomly split into a training set (n = 96 and a validation set (n = 49 for data analysis. Thirty-seven miRNAs were significantly over- or under-expressed in MYCN amplified tumors relative to MYCN single copy tumors, indicating a potential role for the MYCN transcription factor in either the direct or indirect dysregulation of these loci. In addition, we also determined that there was a highly significant correlation between miRNA expression levels and DNA copy number, indicating a role for large-scale genomic imbalances in the dysregulation of miRNA expression. In order to directly assess whether miRNA expression was predictive of clinical outcome, we used the Random Forest classifier to identify miRNAs that were most significantly associated with poor overall patient survival and developed a 15 miRNA signature that was predictive of overall survival with 72.7% sensitivity and 86.5% specificity in the validation set of tumors. We conclude that there is widespread dysregulation of miRNA expression in neuroblastoma tumors caused by both over-expression of the MYCN transcription factor and by large-scale chromosomal imbalances. MiRNA expression patterns are also predicative of clinical outcome, highlighting the potential for miRNA mediated diagnostics and therapeutics.

  6. Genome-wide exploration of miRNA function in mammalian muscle cell differentiation.

    Science.gov (United States)

    Polesskaya, Anna; Degerny, Cindy; Pinna, Guillaume; Maury, Yves; Kratassiouk, Gueorgui; Mouly, Vincent; Morozova, Nadya; Kropp, Jeremie; Frandsen, Niels; Harel-Bellan, Annick

    2013-01-01

    MiRNAs impact on the control of cell fate by regulating gene expression at the post-transcriptional level. Here, using mammalian muscle differentiation as a model and a phenotypic loss-of-function screen, we explored the function of miRNAs at the genome-wide level. We found that the depletion of a high number of miRNAs (63) impacted on differentiation of human muscle precursors, underscoring the importance of this post-transcriptional mechanism of gene regulation. Interestingly, a comparison with miRNA expression profiles revealed that most of the hit miRNAs did not show any significant variations of expression during differentiation. These constitutively expressed miRNAs might be required for basic and/or essential cell function, or else might be regulated at the post-transcriptional level. MiRNA inhibition yielded a variety of phenotypes, reflecting the widespread miRNA involvement in differentiation. Using a functional screen (the STarS--Suppressor Target Screen--approach, i. e. concomitant knockdown of miRNAs and of candidate target proteins), we discovered miRNA protein targets that are previously uncharacterized controllers of muscle-cell terminal differentiation. Our results provide a strategy for functional annotation of the human miRnome.

  7. miRNA Profiling Reveals Dysregulation of RET and RET-Regulating Pathways in Hirschsprung's Disease.

    Directory of Open Access Journals (Sweden)

    Shuangshuang Li

    Full Text Available Hirschsprung's disease (HSCR, the most common congenital malformation of the gut, is regulated by multiple signal transduction pathways. Several components of these pathways are important targets for microRNAs (miRNAs. Multiple miRNAs have been associated with the pathophysiology of HSCR, and serum miRNAs profiles of HSCR patients have been reported, but miRNA expression in HSCR colon tissue is almost completely unexplored. Using microarray technology, we screened colon tissue to detect miRNAs whose expression profiles were altered in HSCR and identify targets of differentially expressed miRNAs. Following filtering of low-intensity signals, data normalization, and volcano plot filtering, we identified 168 differentially expressed miRNAs (104 up-regulated and 64 down-regulated. Fifty of these mRNAs represent major targets of dysegulated miRNAs and may thus important roles in the pathophysiology of HSCR. Pathway analysis revealed that 7 of the miRNA targets encode proteins involved in regulation of cell proliferation and migration via RET and related signaling pathways (MAPK and PI3K/AKT. Our results identify miRNAs that play key roles in the pathophysiology of the complex multi-factorial disease HSCR.

  8. Retail experience in the de-regulated market

    International Nuclear Information System (INIS)

    Cummings, R.

    2003-01-01

    This paper describes the experience gained to date in the de-regulated electricity market through an examination of the commercial market. In 2001, chaos provided opportunity, while in 2002 the emphasis was on operations. In 2003, the landscape reflected hyper-competition, selling second services, and a changing landscape. A discussion followed on the residential market with a look at market structure, economics, and uncertainty concerning the future. The following components were identified as working well: wholesale market, commercial market, market model/data, and innovation in offerings and green supply. Areas requiring further improvement were also identified. It was suggested that the residential de-regulated roadmap should be clarified and retail friendly transactions should be imposed. Other improvements involve education and operations/system capabilities. The author concluded that the deregulated electricity market is still an immature market, where progress is being made in the commercial market. The residential market is in a critical period, with a market model still evolving. figs

  9. Consequences of electricity deregulation on nuclear safety

    International Nuclear Information System (INIS)

    Podjavorsek, M.

    2007-01-01

    The evolution of deregulation of electricity market started a couple of years ago and has not been finished yet. Deregulation causes increased pressure to reduce the costs of electricity generation. This presents a new challenge to regulatory bodies. They have to assess the impact of these changes on the safety of nuclear power plants. Accordingly, it is important to identify the risks to the nuclear power industry resulting from the deregulation. Today's trend is that the number of electricity generating power companies will be reduced in Europe and also in Slovenia due to tough competition in the electricity market. The electricity price has decreased after the introduction of the deregulated market in most countries. This has been also the main reason for less investment to new generating capacities since the price has been lower than the generation costs. Investment problems are also present for the existing units, because of danger of inappropriate maintenance and reduction of the number of staff and their qualifications below the desired level that leads to loss of institutional memory. It is expected that only the biggest companies can stand the consequences of competition in electricity prices and consequential pressure to reduce the cost. In order to review the impact of deregulation of the electricity market some relevant points are discussed in this paper such as the need to cut costs of companies by reducing the number of their activities and increasing the efficiency in the remaining activities and /or outsourcing of activities, power station operating regime, safety culture, grid reliability, reliability and safety of operation, increased number of transients, ageing of components, outage duration, extended cycle and response of nuclear regulators. From a regulatory point of view the impact of deregulation on nuclear safety is an important issue. This paper also discusses analyses and evaluations of this impact and proposes some measures how to

  10. Evaluation of circulating miRNAs during late pregnancy in the mare.

    Directory of Open Access Journals (Sweden)

    Shavahn C Loux

    Full Text Available MicroRNAs (miRNAs are small, non-coding RNAs which are produced throughout the body. Individual tissues tend to have a specific expression profile and excrete many of these miRNAs into circulation. These circulating miRNAs may be diagnostically valuable biomarkers for assessing the presence of disease while minimizing invasive testing. In women, numerous circulating miRNAs have been identified which change significantly during pregnancy-related complications (e.g. chorioamnionitis, eclampsia, recurrent pregnancy loss; however, no prior work has been done in this area in the horse. To identify pregnancy-specific miRNAs, we collected serial whole blood samples in pregnant mares at 8, 9, 10 m of gestation and post-partum, as well as from non-pregnant (diestrous mares. In total, we evaluated a panel of 178 miRNAs using qPCR, eventually identifying five miRNAs of interest. One miRNA (miR-374b was differentially regulated through late gestation and four miRNAs (miR-454, miR-133b, miR-486-5p and miR-204b were differentially regulated between the pregnant and non-pregnant samples. We were able to identify putative targets for the differentially regulated miRNAs using two separate target prediction programs, miRDB and Ingenuity Pathway Analysis. The targets for the miRNAs differentially regulated during pregnancy were predicted to be involved in signaling pathways such as the STAT3 pathway and PI3/AKT signaling pathway, as well as more endocrine-based pathways, including the GnRH, prolactin and insulin signaling pathways. In summary, this study provides novel information about the changes occurring in circulating miRNAs during normal pregnancy, as well as attempting to predict the biological effects induced by these miRNAs.

  11. Epigenetic dysregulation in neuroblastoma: A tale of miRNAs and DNA methylation.

    Science.gov (United States)

    Parodi, Federica; Carosio, Roberta; Ragusa, Marco; Di Pietro, Cinzia; Maugeri, Marco; Barbagallo, Davide; Sallustio, Fabio; Allemanni, Giorgio; Pistillo, Maria Pia; Casciano, Ida; Forlani, Alessandra; Schena, Francesco P; Purrello, Michele; Romani, Massimo; Banelli, Barbara

    2016-12-01

    In neuroblastoma, the epigenetic landscape is more profoundly altered in aggressive compared to lower grade tumors and the concomitant hypermethylation of many genes, defined as "methylator phenotype", has been associated with poor outcome. DNA methylation can interfere with gene expression acting at distance through the methylation or demethylation of the regulatory regions of miRNAs. The multiplicity of miRNA targets may result in the simultaneous alteration of many biological pathways like cell proliferation, apoptosis, migration and differentiation. We have analyzed the methylation status of a set of miRNAs in a panel of neuroblastoma cell lines and identified a subset of hypermethylated and down-regulated miRNAs (miRNA 34b-3p, miRNA 34b-5p, miRNA34c-5p, and miRNA 124-2-3p) involved in the regulation of cell cycle, apoptosis and in the control of MYCN expression. These miRNAs share, in part, some of the targets whose expression is inversely correlated to the methylation and expression of the corresponding miRNA. To simulate the effect of the demethylation of miRNAs, we transfected the corresponding miRNA-mimics in the same cell lines and observed the down-regulation of a set of their target genes as well as the partial block of the cell cycle and the activation of the apoptotic pathway. The epigenetic alterations of miRNAs described in the present study were found also in a subset of patients at high risk of progression. Our data disclosed a complex network of interactions between epigenetically altered miRNAs and target genes, that could interfere at multiple levels in the control of cell homeostasis. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Differential expression of miRNAs and their relation to active tuberculosis.

    Science.gov (United States)

    Xu, Zhihong; Zhou, Aiping; Ni, Jinjing; Zhang, Qiufen; Wang, Ying; Lu, Jie; Wu, Wenjuan; Karakousis, Petros C; Lu, Shuihua; Yao, Yufeng

    2015-07-01

    The aim of this work was to screen miRNA signatures dysregulated in tuberculosis to improve our understanding of the biological role of miRNAs involved in the disease. Datasets deposited in publically available databases from microarray studies on infectious diseases and malignancies were retrieved, screened, and subjected to further analysis. Effect sizes were combined using the inverse-variance model and between-study heterogeneity was evaluated by the random effects model. 35 miRNAs were differentially expressed (12 up-regulated, 23 down-regulated; p tuberculosis and other infectious diseases. 15 miRNAs were found to be significantly differentially regulated (7 up-regulated, 8 down-regulated; p tuberculosis and malignancies. Most of the miRNA signatures identified in this study were found to be involved in immune responses and metabolism. Expression of these miRNA signatures in serum samples from TB subjects (n = 11) as well as healthy controls (n = 10) was examined by TaqMan miRNA array. Taken together, the results revealed differential expression of miRNAs in TB, but available datasets are limited and these miRNA signatures should be validated in future studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Conserved miRNAs and Their Response to Salt Stress in Wild Eggplant Solanum linnaeanum Roots

    Directory of Open Access Journals (Sweden)

    Yong Zhuang

    2014-01-01

    Full Text Available The Solanaceae family includes some important vegetable crops, and they often suffer from salinity stress. Some miRNAs have been identified to regulate gene expression in plant response to salt stress; however, little is known about the involvement of miRNAs in Solanaceae species. To identify salt-responsive miRNAs, high-throughput sequencing was used to sequence libraries constructed from roots of the salt tolerant species, Solanum linnaeanum, treated with and without NaCl. The sequencing identified 98 conserved miRNAs corresponding to 37 families, and some of these miRNAs and their expression were verified by quantitative real-time PCR. Under the salt stress, 11 of the miRNAs were down-regulated, and 3 of the miRNAs were up-regulated. Potential targets of the salt-responsive miRNAs were predicted to be involved in diverse cellular processes in plants. This investigation provides valuable information for functional characterization of miRNAs in S. linnaeanum, and would be useful for developing strategies for the genetic improvement of the Solanaceae crops.

  14. Deregulated power prices: comparison of diurnal patterns

    International Nuclear Information System (INIS)

    Li Ying; Flynn, Peter C.

    2004-01-01

    We examine electrical power price, and in particular its daily and average weekday vs. weekend pattern of change, for 14 deregulated markets. Power price in deregulated markets shows fundamentally different patterns. North American markets show a monotonic diurnal weekday price pattern, while all other markets studied show more than one price peak. Deregulated power markets differ in maximum vs. minimum daily average price and in average weekday to weekend price, in turn creating a different incentive for a consumer to time shift power consuming activities. Markets differ in the extent to which a small fraction of the days shapes the average diurnal pattern and value of price. Deregulated markets show a wide variation in the correlation between load and price. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent, and hence that can encourage a customer to shape consumption behaviors. Other markets, for example South Australia, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to escape risk through hedging mechanisms

  15. Deregulated power prices: comparison of diurnal patterns

    International Nuclear Information System (INIS)

    Ying Li; Flynn, P.C.

    2004-01-01

    We examine electrical power price, and in particular its daily and average weekday vs. weekend pattern of change, for 14 deregulated markets. Power price in deregulated markets shows fundamentally different patterns. North American markets show a monotonic diurnal weekday price pattern, while all other markets studied show more than one price peak. Deregulated power markets differ in maximum vs. minimum daily average price and in average weekday to weekend price, in turn creating a different incentive for a consumer to time shift power consuming activities. Markets differ in the extent to which a small fraction of the days shapes the average diurnal pattern and value of price. Deregulated markets show a wide variation in the correlation between load and price. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent, and hence that can encourage a customer to shape consumption behaviors. Other markets, for example South Australia, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to escape risk through hedging mechanisms. (Author)

  16. Laminin α2 chain-deficiency is associated with microRNA deregulation in skeletal muscle and plasma

    Directory of Open Access Journals (Sweden)

    Johan eHolmberg

    2014-07-01

    Full Text Available MicroRNAs (miRNAs are widespread regulators of gene expression, but little is known of their potential roles in congenital muscular dystrophy type 1A (MDC1A. MDC1A is a severe form of muscular dystrophy caused by mutations in the gene encoding laminin α2 chain. To gain insight into the pathophysiological roles of miRNAs associated with MDC1A pathology, laminin α2 chain-deficient mice were evaluated by quantitative PCR. We demonstrate that expression of muscle-specific miR-1, miR-133a, and miR-206 is deregulated in laminin α2 chain-deficient muscle. Furthermore, expression of miR-223 and miR-21, associated with immune cell infiltration and fibrosis, respectively, is altered. Finally, we show that plasma levels of muscle-specific miRNAs are markedly elevated in laminin α2 chain-deficient mice and partially normalized in response to proteasome inhibition therapy. Altogether, our data suggest important roles for miRNAs in MDC1A pathology and we propose plasma levels of muscle-specific miRNAs as promising biomarkers for the progression of MDC1A.

  17. miRNAs: Small but deadly | Bano | African Journal of Biotechnology

    African Journals Online (AJOL)

    microRNAs (miRNAs) are unique class of global gene regulators identified both in plants and animals. They can reduce protein levels of their target genes with a minor impact on the target genes mRNA. Levels of some miRNAs are found altered in cancers, so we might expect these regulatory molecules to be involved in ...

  18. Induction of microRNAome deregulation in rat liver by long-term tamoxifen exposure

    International Nuclear Information System (INIS)

    Pogribny, Igor P.; Tryndyak, Volodymyr P.; Boyko, Alex; Rodriguez-Juarez, Rocio; Beland, Frederick A.; Kovalchuk, Olga

    2007-01-01

    Micro RNAs (miRNAs) are small non-coding RNA molecules that function as negative regulators of gene expression. They play a crucial role in the regulation of genes involved in the control of development, cell proliferation, apoptosis, and stress response. Although miRNA levels are substantially altered in tumors, their role in carcinogenesis, specifically at the early pre-cancerous stages, has not been established. Here we report that exposure of Fisher 344 rats to tamoxifen, a potent hepatocarcinogen in rats, for 24 weeks leads to substantial changes in the expression of miRNA genes in the liver. We noted a significant up-regulation of known oncogenic miRNAs, such as the 17-92 cluster, miR-106a, and miR-34. Furthermore, we confirmed the corresponding changes in the expression of proteins targeted by these miRNAs, which include important cell cycle regulators, chromatin modifiers, and expression regulators implicated in carcinogenesis. All these miRNA changes correspond to previously reported alterations in full-fledged tumors, including hepatocellular carcinomas. Thus, our findings indicate that miRNA changes occur prior to tumor formation and are not merely a consequence of a transformed state

  19. Transmission planning in a deregulated environment

    DEFF Research Database (Denmark)

    Xu, Zhao

    2006-01-01

    and approaches toward transmission planning should be carefully designed to ensure system reliability as well as meeting the market requirements. A market-oriented approach for transmission planning in a deregulated environment is proposed. Case studies using the IEEE 14-bus system and the Australian national......The worldwide trend for the deregulation of the electricity generation and transmission industries has led to dramatic changes in system operation and planning procedures. The optimum approach to transmission-expansion planning in a deregulated environment is an open problem especially when...... the responsibilities of the organisations carrying out the planning work need to be addressed. To date there is a consensus that the system operator and network manager perform the expansion planning work in a centralised way. However, with an increasing input from the electricity market, the objectives, constraints...

  20. Analyzing Technique of Power Systems Under Deregulation

    Science.gov (United States)

    Miyauchi, Hajime; Kita, Hiroyuki; Ishigame, Atsushi

    Deregulation of the electric utilities has been progressing. Even under the deregulation, the reliability should be the most important problem of power systems. However, according to the deregulation, operation and scheduling of power systems are changing and new techniques to analyze power systems are introducing. To evaluate reliability of power systems, adequacy and security are well employed recently. This paper presents the new analyzing technique which will be realized in near future from the viewpoint of adequacy and security. First, simulation tool to evaluate adequacy is described. As an example of this tool, MARS and other methods are mentioned. Next, to evaluate the security, security constrained unit commitment (SCUC) and security constrained optimal power flow (SCOPF) are mentioned. Finally, some topics concerning ancillary service are described.

  1. 34A, miRNA-944, miRNA-101 and miRNA-218 in cervical cancer

    African Journals Online (AJOL)

    Expressions and clinic significance of miRNA-143, miRNA- ... cancer tissues. Our research on miRNAs is aimed to provide reference for the early clinical diagnosis of cervical cancer and provide novel therapeutic target for cervical cancer. .... Table 2: Baseline demographics and disease characteristics. Group. Height (cm).

  2. Classification of various muscular tissues using miRNA profiling.

    Science.gov (United States)

    Endo, Kosuke; Weng, Huachun; Naito, Yukiko; Sasaoka, Toshikuni; Takahashi, Akio; Fukushima, Yasue; Iwai, Naoharu

    2013-01-01

    MicroRNAs (miRNAs) are endogenous small RNAs of 18-23 nucleotides that regulate gene expression. Recently, plasma miRNAs have been investigated as biomarkers for various diseases. In the present study, we explored whether miRNA expression profiling of various muscle cells may be useful for the diagnosis of various diseases involving muscle necrosis. miRNA expression profiling was assessed by miRNA array and real-time reverse-transcriptase polymerase chain reaction by using a reverse primer of a stem loop structure. Profiling of various muscle cells of mouse, including cardiac muscles, skeletal muscles, and vascular and visceral smooth muscles, indicated that profiling of miR-1, miR-133a, miR-133b, miR-145, miR-206, miR-208a, miR-208b, and miR499 were adequate to discriminate muscle cells. miR-145 was remarkably highly expressed in smooth muscles. miR-208a and miR-499 were highly expressed in cardiomyocytes. miR-133a was highly expressed in fast-twitch skeletal muscles. miR-206 and miR-208b were expressed in the slow-twitch skeletal muscles, and they can likely discriminate fast- and slow-twitch types of skeletal muscle cells. We observed that brown fat adipose cells had an miRNA expression profile very similar to those of skeletal muscle cells in the mouse. Plasma concentrations of miR-133a and miR-145 were extremely useful in diagnosing skeletal muscle necrosis in a mouse model of Duchenne muscular dystrophy and colon smooth muscle necrosis in a rat ischemic colitis model, respectively. In the present study, we investigated the miRNA expression profiles of various muscular tissues. Our results suggest that expression profiling would be useful for the diagnosis of various diseases such as muscular necrosis.

  3. Deregulation of Interferon Signaling in Malignant Cells

    Directory of Open Access Journals (Sweden)

    Leonidas C. Platanias

    2010-02-01

    Full Text Available Interferons (IFNs are a family of cytokines with potent antiproliferative, antiviral, and immunomodulatory properties. Much has been learned about IFNs and IFN-activated signaling cascades over the last 50 years. Due to their potent antitumor effects in vitro and in vivo, recombinant IFNs have been used extensively over the years, alone or in combination with other drugs, for the treatment of various malignancies. This review summarizes the current knowledge on IFN signaling components and pathways that are deregulated in human malignancies. The relevance of deregulation of IFN signaling pathways in defective innate immune surveillance and tumorigenesis are discussed.

  4. Potential role of miRNAs in developmental haemostasis.

    Directory of Open Access Journals (Sweden)

    Raúl Teruel

    Full Text Available MicroRNAs (miRNAs are an abundant class of small non-coding RNAs that are negative regulators in a crescent number of physiological and pathological processes. However, their role in haemostasis, a complex physiological process involving multitude of effectors, is just beginning to be characterized. We evaluated the changes of expression of miRNAs in livers of neonates (day one after birth and adult mice by microarray and qRT-PCR trying to identify miRNAs that potentially may also be involved in the control of the dramatic change of hepatic haemostatic protein levels associated with this transition. Twenty one out of 41 miRNAs overexpressed in neonate mice have hepatic haemostatic mRNA as potential targets. Six of them identified by two in silico algorithms potentially bind the 3'UTR regions of F7, F9, F12, FXIIIB, PLG and SERPINC1 mRNA. Interestingly, miR-18a and miR-19b, overexpressed 5.4 and 8.2-fold respectively in neonates, have antithrombin, a key anti-coagulant with strong anti-angiogenic and anti-inflammatory roles, as a potential target. The levels of these two miRNAs inversely correlated with antithrombin mRNA levels during development (miR-19b: R = 0.81; p = 0.03; miR-18a: R = 0.91; p<0.001. These data suggest that miRNAs could be potential modulators of the haemostatic system involved in developmental haemostasis.

  5. Elsevier Trophoblast Research Award Lecture: origin, evolution and future of placenta miRNAs.

    Science.gov (United States)

    Morales-Prieto, D M; Ospina-Prieto, S; Schmidt, A; Chaiwangyen, W; Markert, U R

    2014-02-01

    MicroRNAs (miRNAs) regulate the expression of a large number of genes in plants and animals. Placental miRNAs appeared late in evolution and can be found only in mammals. Nevertheless, these miRNAs are constantly under evolutionary pressure. As a consequence, miRNA sequences and their mRNA targets may differ between species, and some miRNAs can only be found in humans. Their expression can be tissue- or cell-specific and can vary time-dependently. Human placenta tissue exhibits a specific miRNA expression pattern that dynamically changes during pregnancy and is reflected in the maternal plasma. Some placental miRNAs are involved in or associated with major pregnancy disorders, such as preeclampsia, intrauterine growth restriction or preterm delivery and, therefore, have a strong potential for usage as sensitive and specific biomarkers. In this review we summarize current knowledge on the origin of placental miRNAs, their expression in humans with special regard to trophoblast cells, interspecies differences, and their future as biomarkers. It can be concluded that animal models for human reproduction have a different panel of miRNAs and targets, and can only partly reflect or predict the situation in humans. Copyright © 2013. Published by Elsevier Ltd.

  6. MicroRNA profiling of tomato leaf curl new delhi virus (tolcndv infected tomato leaves indicates that deregulation of mir159/319 and mir172 might be linked with leaf curl disease

    Directory of Open Access Journals (Sweden)

    Haq Qazi MR

    2010-10-01

    Full Text Available Abstract Background Tomato leaf curl virus (ToLCV, a constituent of the genus Begomovirus, infects tomato and other plants with a hallmark disease symptom of upward leaf curling. Since microRNAs (miRs are known to control plants developmental processes, we evaluated the roles of miRNAs in Tomato leaf curl New Delhi virus (ToLCNDV induced leaf curling. Results Microarray analyses of miRNAs, isolated from the leaves of both healthy and ToLCNDV agroinfected tomato cv Pusa Ruby, revealed that ToLCNDV infection significantly deregulated various miRNAs representing ~13 different conserved families (e.g., miR319, miR172, etc.. The precursors of these miRNAs showed similar deregulated patterns, indicating that the transcription regulation of respective miRNA genes was perhaps the cause of deregulation. The expression levels of the miRNA-targeted genes were antagonistic with respect to the amount of corresponding miRNA. Such deregulation was tissue-specific in nature as no analogous misexpression was found in flowers. The accumulation of miR159/319 and miR172 was observed to increase with the days post inoculation (dpi of ToLCNDV agroinfection in tomato cv Pusa Ruby. Similarly, these miRs were also induced in ToLCNDV agroinfected tomato cv JK Asha and chilli plants, both exhibiting leaf curl symptoms. Our results indicate that miR159/319 and miR172 might be associated with leaf curl symptoms. This report raises the possibility of using miRNA(s as potential signature molecules for ToLCNDV infection. Conclusions The expression of several host miRNAs is affected in response to viral infection. The levels of the corresponding pre-miRs and the predicted targets were also deregulated. This change in miRNA expression levels was specific to leaf tissues and observed to be associated with disease progression. Thus, certain host miRs are likely indicator of viral infection and could be potentially employed to develop viral resistance strategies.

  7. Mutation of miRNA target sequences during human evolution

    DEFF Research Database (Denmark)

    Gardner, Paul P; Vinther, Jeppe

    2008-01-01

    It has long-been hypothesized that changes in non-protein-coding genes and the regulatory sequences controlling expression could undergo positive selection. Here we identify 402 putative microRNA (miRNA) target sequences that have been mutated specifically in the human lineage and show that genes...... containing such deletions are more highly expressed than their mouse orthologs. Our findings indicate that some miRNA target mutations are fixed by positive selection and might have been involved in the evolution of human-specific traits....

  8. A miRNA expression signature that separates between normal and malignant prostate tissues

    Directory of Open Access Journals (Sweden)

    Lubovac Zelmina

    2011-05-01

    Full Text Available Abstract Background MicroRNAs (miRNAs constitute a class of small non-coding RNAs that post-transcriptionally regulate genes involved in several key biological processes and thus are involved in various diseases, including cancer. In this study we aimed to identify a miRNA expression signature that could be used to separate between normal and malignant prostate tissues. Results Nine miRNAs were found to be differentially expressed (p Conclusions We found an expression signature based on nine differentially expressed miRNAs that with high accuracy (85% could classify the normal and malignant prostate tissues in patients from the Swedish Watchful Waiting cohort. The results show that there are significant differences in miRNA expression between normal and malignant prostate tissue, indicating that these small RNA molecules might be important in the biogenesis of prostate cancer and potentially useful for clinical diagnosis of the disease.

  9. Bioinformatic identification of cassava miRNAs differentially expressed in response to infection by Xanthomonas axonopodis pv. manihotis

    Science.gov (United States)

    2012-01-01

    Background microRNAs (miRNAs) are short RNA molecules that control gene expression by silencing complementary mRNA. They play a crucial role in stress response in plants, including biotic stress. Some miRNAs are known to respond to bacterial infection in Arabidopsis thaliana but it is currently unknown whether these responses are conserved in other plants and whether novel species-specific miRNAs could have a role in defense. Results This work addresses the role of miRNAs in the Manihot esculenta (cassava)-Xanthomonas axonopodis pv. manihotis (Xam) interaction. Next-generation sequencing was used for analyzing small RNA libraries from cassava tissue infected and non-infected with Xam. A full repertoire of cassava miRNAs was characterized, which included 56 conserved families and 12 novel cassava-specific families. Endogenous targets were predicted in the cassava genome for many miRNA families. Some miRNA families' expression was increased in response to bacterial infection, including miRNAs known to mediate defense by targeting auxin-responding factors as well as some cassava-specific miRNAs. Some bacteria-repressed miRNAs included families involved in copper regulation as well as families targeting disease resistance genes. Putative transcription factor binding sites (TFBS) were identified in the MIRNA genes promoter region and compared to promoter regions in miRNA target genes and protein coding genes, revealing differences between MIRNA gene transcriptional regulation and other genes. Conclusions Taken together these results suggest that miRNAs in cassava play a role in defense against Xam, and that the mechanism is similar to what's known in Arabidopsis and involves some of the same families. PMID:22361011

  10. Exchange Rate Deregulation and Industrial Performance: An ...

    African Journals Online (AJOL)

    The study found that a long-run relationship exists between the industrial productivity growth rate, ration of industrial production to gross domestic product, exchange rate, interest rate and terms of trade, and that exchange rate deregulation has significant impact on industrial performance. In order to determine the short term ...

  11. Deregulation-restructuring: Evidence for individual industries

    Energy Technology Data Exchange (ETDEWEB)

    Costello, K.W.; Graniere, R.J.

    1997-05-01

    Several studies have measured the effects of regulation on a particular industry. These studies range widely in sophistication, from simple observation (comparison) of pre-transformation and post-transformation actual industry performance to econometric analysis that attempt to separate the effects of deregulation from other factors in explaining changes in an industry`s performance. The major problem with observation studies is that they are unable to measure the effect of one particular event, such as deregulation, on an industry`s performance. For example, at the same time that the United Kingdom privatized its electric power industry, it also radically restructured the industry to encourage competition and instituted a price-cap mechanism to regulate the prices of transmission, distribution, and bundled retail services. Subsequent to these changes in 1991, real prices for most UK electricity customers have fallen. It is not certain however, which of these factors was most important or even contributed to the decline in price. In any event, one must be cautious in interpreting the results of studies that attempt to measure the effect of deregulation per se for a specific industry. This report highlights major outcomes for five industries undergoing deregulation or major regulatory and restructuring reforms. These include the natural gas, transportation, UK electric power, financial, and telecommunications industries. Particular attention was given to the historical development of events in the telecommunications industry.

  12. Deregulation of natural gas in Georgia

    International Nuclear Information System (INIS)

    Wise, S.

    2002-01-01

    The Natural Gas Competition and Deregulation Act of 1997 in Georgia is discussed. New legislation passed the Natural Gas Consumer Relief Act in 2002 legislative session to provide additional protection and increase competition. This Act and its impacts are discussed in detail. Additional commission responsibilities are summarized. (R.P.)

  13. Deregulation and Macroeconomic Drivers Of Foreign Direct ...

    African Journals Online (AJOL)

    Deregulation and Macroeconomic Drivers Of Foreign Direct Investment In Nigerian Agriculture (1970 -2009): An Econometric Analysis. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like more ...

  14. Exchange Rate Deregulation and Industrial Performance: An ...

    African Journals Online (AJOL)

    FIRST LADY

    Abstract. This paper investigated the impact of exchange rate deregulation on industrial performance in Nigeria. In this study, secondary data over the period 1975 – 2005 was used and the co-integration technique and chow breakpoint test were considered as analytical tools. The study found that a long-run relationship ...

  15. Regulatory concern about economic deregulation in Finland

    International Nuclear Information System (INIS)

    Virolainen, R.; Koutaniemi, P.

    2001-01-01

    The deregulation of the electricity market may cause an increased pressure to reduce the costs of electricity generation. This makes a new challenge to the regulatory body to assess the impact of these changes on the safety of nuclear power plants. Accordingly, it is important to identify the risks to the nuclear power industry resulting from the economic deregulation. This paper is to discuss the current situation in Finland with regard to the economic deregulation of the electricity market and the experiences so far. A common view today is that the number of electricity generating power companies will be reduced in Europe because of tough competition in the electricity market. It is expected that only the biggest companies can stand the consequences of tough competition in electricity prices and the consequential pressure to reduce costs. In order to review the impact of deregulation of the electricity market some relevant points have been discussed in this paper, such as change of ownership of power companies due to the economic pressure, the need to cut costs of the companies by reducing the number of their activities and increasing the efficiency in the remaining activities and/or outsourcing of activities. The need to pursue reduction or delay of planned investments in safety upgrades are discussed as well. (author)

  16. Deregulation, economic growth and growth acceleration

    Czech Academy of Sciences Publication Activity Database

    Stankov, Petar

    -, č. 424 (2010), s. 1-42 ISSN 1211-3298 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:MSM0021620846 Keywords : deregulation * economic growth * origins of institutional change Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp424.pdf

  17. Design of reactive power procurement in deregulated electricity market

    African Journals Online (AJOL)

    Reactive power management is different in the deregulated electricity market of various countries. In this paper, a novel reactive power procurement model is proposed, which ensure secure and reliable operation of deregulated electricity market. Various issues of reactive power management in the deregulated electricity ...

  18. Assessment of the impacts of deregulation on Nigeria's economic ...

    African Journals Online (AJOL)

    This paper examines the effect of economic deregulation in Nigerian economy. The study identified the different forms and policy instruments used by Nigerian government for effective deregulation. It highlighted the potential gains of deregulation and suggested ways of improving the Nigerian economy through guided ...

  19. Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia

    DEFF Research Database (Denmark)

    Moraes, Leonardo N; Fernandez, Geysson J; Vechetti-Júnior, Ivan J

    2017-01-01

    between miRNA and mRNA expression profiles of muscle wasting during CC. Global gene expression profiling identified 1,281 genes and 19 miRNAs differentially expressed in muscle wasting during CC. Several of these deregulated genes are known or putative targets of the altered miRNAs, including miR-29a-3p......, miR-29b-3p, miR-210-5p, miR-214, and miR-489. Gene ontology analysis on integrative mRNA/miRNA expression profiling data revealed miRNA interactions affecting genes that regulate extra-cellular matrix (ECM) organization, proteasome protein degradation, citric acid cycle and respiratory electron...

  20. miRNAs in brain development

    Energy Technology Data Exchange (ETDEWEB)

    Petri, Rebecca; Malmevik, Josephine; Fasching, Liana; Åkerblom, Malin; Jakobsson, Johan, E-mail: johan.jakobsson@med.lu.se

    2014-02-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs have been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function.

  1. miRNAs in brain development

    International Nuclear Information System (INIS)

    Petri, Rebecca; Malmevik, Josephine; Fasching, Liana; Åkerblom, Malin; Jakobsson, Johan

    2014-01-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs have been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function

  2. MicroRNAs 142-3p, miR-155 and miR-203 Are Deregulated in Gastric MALT Lymphomas Compared to Chronic Gastritis.

    Science.gov (United States)

    Fernández, Concepción; Bellosillo, Beatriz; Ferraro, Mariana; Seoane, Agustín; Sánchez-González, Blanca; Pairet, Silvia; Pons, Aina; Barranco, Luis; Vela, María Carmen; Gimeno, Eva; Colomo, Lluís; Besses, Carles; Navarro, Alfons; Salar, Antonio

    2017-01-02

    Over the last years, our knowledge on pathogenesis of gastric MALT lymphoma has greatly improved, but its morphological diagnosis is still hampered by overlapping histological features with advanced chronic gastritis. MicroRNAs are deregulated in lymphomas, but their role and usefulness in gastric MALT lymphoma has not been extensively investigated. We analyzed the expression of 384 miRNAs using TaqMan microRNA assay in a training series of 10 gastric MALT lymphomas, 3 chronic gastritis and 2 reactive lymph nodes. Then, significantly deregulated miRNAs were individually assessed by real-time PCR in a validation series of 16 gastric MALT lymphomas and 12 chronic gastritis. Gastric MALT lymphoma is characterized by a specific miRNA expression profile. Among the differentially expressed miRNAs, a significant overexpression of miR-142-3p and miR-155 and down-regulation of miR-203 was observed in gastric MALT lymphoma when compared to chronic gastritis. miR-142-3p, miR-155 and miR-203 expression levels might be helpful biomarkers for the differential diagnosis between gastric MALT lymphomas and chronic gastritis. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Pauline E Jullien

    2010-03-01

    Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

  4. Alu-directed transcriptional regulation of some novel miRNAs

    Directory of Open Access Journals (Sweden)

    Zhao Xi W

    2009-11-01

    Full Text Available Abstract Background Despite many studies on the biogenesis, molecular structure and biological functions of microRNAs, little is known about the transcriptional regulatory mechanisms controlling the spatiotemporal expression pattern of human miRNA gene loci. Several lines of experimental results have indicated that both polymerase II (Pol-II and polymerase III (Pol-III may be involved in transcribing miRNAs. Here, we assessed the genomic evidence for Alu-directed transcriptional regulation of some novel miRNA genes in humans. Our data demonstrate that the expression of these Alu-related miRNAs may be modulated by Pol-III. Results We present a comprehensive exploration of the Alu-directed transcriptional regulation of some new miRNAs. Using a new computational approach, a variety of Alu-related sequences from multiple sources were pooled and filtered to obtain a subset containing Alu elements and characterized miRNA genes for which there is clear evidence of full-length transcription (embedded in EST. We systematically demonstrated that 73 miRNAs including five known ones may be transcribed by Pol-III through Alu or MIR. Among the new miRNAs, 33 were determined by high-throughput Solexa sequencing. Real-time TaqMan PCR and Northern blotting verified that three newly identified miRNAs could be induced to co-express with their upstream Alu transcripts by heat shock or cycloheximide. Conclusion Through genomic analysis, Solexa sequencing and experimental validation, we have identified candidate sequences for Alu-related miRNAs, and have found that the transcription of these miRNAs could be governed by Pol-III. Thus, this study may elucidate the mechanisms by which the expression of a class of small RNAs may be regulated by their upstream repeat elements.

  5. MiRNA profiles of prostate carcinoma detected by multi-platform miRNA screening

    DEFF Research Database (Denmark)

    Wach, Sven; Nolte, Elke; Szczyrba, Jaroslaw

    2012-01-01

    MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. They play a vital role in tumorigenesis. To characterize the diagnostic potential of miRNAs in prostate cancer, a leading cause of cancer mortality, we performed...... screening of miRNA expression profiles. We used commercially available microarrays to establish miRNA expression profiles from a cohort of 20 cancer samples. The expression of selected miRNAs was analyzed by quantitative real-time PCR and the identity of miRNA expressing cells was determined by miRNA...... in situ hybridization. We identified 25 miRNAs that showed a significant differential expression in cancer samples. The comparison with previously published data generated by deep sequencing of cDNA libraries of small RNA molecules revealed a concordance rate of 47% among miRNAs identified with both...

  6. Infinity: An In-Silico Tool for Genome-Wide Prediction of Specific DNA Matrices in miRNA Genomic Loci.

    Directory of Open Access Journals (Sweden)

    Emmanuela Falcone

    Full Text Available miRNAs are potent regulators of gene expression and modulate multiple cellular processes in physiology and pathology. Deregulation of miRNAs expression has been found in various cancer types, thus, miRNAs may be potential targets for cancer therapy. However, the mechanisms through which miRNAs are regulated in cancer remain unclear. Therefore, the identification of transcriptional factor-miRNA crosstalk is one of the most update aspects of the study of miRNAs regulation.In the present study we describe the development of a fast and user-friendly software, named infinity, able to find the presence of DNA matrices, such as binding sequences for transcriptional factors, on ~65kb (kilobase of 939 human miRNA genomic sequences, simultaneously. Of note, the power of this software has been validated in vivo by performing chromatin immunoprecipitation assays on a subset of new in silico identified target sequences (CCAAT for the transcription factor NF-Y on colon cancer deregulated miRNA loci. Moreover, for the first time, we have demonstrated that NF-Y, through its CCAAT binding activity, regulates the expression of miRNA-181a, -181b, -21, -17, -130b, -301b in colon cancer cells.The infinity software that we have developed is a powerful tool to underscore new TF/miRNA regulatory networks.Infinity was implemented in pure Java using Eclipse framework, and runs on Linux and MS Windows machine, with MySQL database. The software is freely available on the web at https://github.com/bio-devel/infinity. The website is implemented in JavaScript, PHP and HTML with all major browsers supported.

  7. Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data

    Directory of Open Access Journals (Sweden)

    Biecek Przemysław

    2011-06-01

    Full Text Available Abstract Background Deregulation between two different cell populations manifests itself in changing gene expression patterns and changing regulatory interactions. Accumulating knowledge about biological networks creates an opportunity to study these changes in their cellular context. Results We analyze re-wiring of regulatory networks based on cell population-specific perturbation data and knowledge about signaling pathways and their target genes. We quantify deregulation by merging regulatory signal from the two cell populations into one score. This joint approach, called JODA, proves advantageous over separate analysis of the cell populations and analysis without incorporation of knowledge. JODA is implemented and freely available in a Bioconductor package 'joda'. Conclusions Using JODA, we show wide-spread re-wiring of gene regulatory networks upon neocarzinostatin-induced DNA damage in Human cells. We recover 645 deregulated genes in thirteen functional clusters performing the rich program of response to damage. We find that the clusters contain many previously characterized neocarzinostatin target genes. We investigate connectivity between those genes, explaining their cooperation in performing the common functions. We review genes with the most extreme deregulation scores, reporting their involvement in response to DNA damage. Finally, we investigate the indirect impact of the ATM pathway on the deregulated genes, and build a hypothetical hierarchy of direct regulation. These results prove that JODA is a step forward to a systems level, mechanistic understanding of changes in gene regulation between different cell populations.

  8. Diet and lifestyle factors associated with miRNA expression in colorectal tissue

    Directory of Open Access Journals (Sweden)

    Slattery ML

    2016-12-01

    Full Text Available Martha L Slattery,1 Jennifer S Herrick,1 Lila E Mullany,1 John R Stevens,2 Roger K Wolff1 1Department of Internal Medicine, The University of Utah, Salt Lake City, 2Department of Mathematics and Statistics, Utah State University, Logan, UT, USA Abstract: MicroRNAs (miRNAs are small non-protein-coding RNA molecules that regulate gene expression. Diet and lifestyle factors have been hypothesized to be involved in the regulation of miRNA expression. In this study it was hypothesized that diet and lifestyle factors are associated with miRNA expression. Data from 1,447 cases of colorectal cancer to evaluate 34 diet and lifestyle variables using miRNA expression in normal colorectal mucosa as well as for differential expression between paired carcinoma and normal tissue were used. miRNA data were obtained using an Agilent platform. Multiple comparisons were adjusted for using the false discovery rate q-value. There were 250 miRNAs differentially expressed between carcinoma and normal colonic tissue by level of carbohydrate intake and 198 miRNAs differentially expressed by the level of sucrose intake. Of these miRNAs, 166 miRNAs were differentially expressed for both carbohydrate intake and sucrose intake. Ninety-nine miRNAs were differentially expressed by the level of whole grain intake in normal colonic mucosa. Level of oxidative balance score was associated with 137 differentially expressed miRNAs between carcinoma and paired normal rectal mucosa. Additionally, 135 miRNAs were differentially expressed in colon tissue based on recent NSAID use. Other dietary factors, body mass index, waist and hip circumference, and long-term physical activity levels did not alter miRNA expression after adjustment for multiple comparisons. These results suggest that diet and lifestyle factors regulate miRNA level. They provide additional support for the influence of carbohydrate, sucrose, whole grains, NSAIDs, and oxidative balance score on colorectal cancer risk

  9. Utilities' ''obligation to serve'' under deregulation

    International Nuclear Information System (INIS)

    Alexander, C.B.

    1997-01-01

    The utility no longer has protected status, and the traditional franchise concept is under attack. Exclusive rights once conveyed to the utilities are being denied and not just in the area of gas sales. Exclusive rights once conveyed to utilities will be denied in more areas. State by state, the utilities' franchise is being examined to see which, if any, of its provisions are necessary in a deregulated environment. Can the free market provide everything that's been provided for many years under monopolistic arrangements? Some of the most critical and difficult of these provisions concern the obligation to serve, which utilities, in most states, have assumed as part of their franchise agreement. Regulators, courts, utilities, marketers and others are busy sorting through these issues, but resolution could take years. The paper discusses deregulation, universal service fee, representation without taxation, suppliers and marketer restrictions

  10. Transcriptional control of mitosis: deregulation and cancer

    Directory of Open Access Journals (Sweden)

    Somsubhra eNath

    2015-05-01

    Full Text Available Research over the past few decades has well established the molecular functioning of mitosis. Deregulation of these functions has also been attributed to the generation of aneuploidy in different tumor types. Numerous studies have given insight into the regulation of mitosis by cell cycle specific proteins. Optimum abundance of these proteins is pivotal to timely execution of mitosis. Aberrant expressions of these mitotic proteins have been reported in different cancer types. Several post-transcriptional mechanisms and their interplay have subsequently been identified that control the level of mitotic proteins. However, to date, infrequent incidences of cancer-associated mutations have been reported for the genes expressing these proteins. Therefore, altered expression of these mitotic regulators in tumor samples can largely be attributed to transcriptional deregulation. This review discusses the biology of transcriptional control for mitosis and evaluates its role in the generation of aneuploidy and tumorigenesis.

  11. Deregulation of Electricity Supply Industry in Oman

    Directory of Open Access Journals (Sweden)

    Hamed S. Al-Maghderi

    2002-06-01

    Full Text Available This paper examines the opportunities available and the conditions needed for the deregulation of the Electricity Supply Industry (ESI, with particular reference to the Sultanate of Oman. The paper highlights the general issues of regulation required to encourage competition in the ESI.  After that, the discussion focuses on regulation methods in the privatized ESI by describing the regulators control through price caps setting for regulatees, the conduct regulation process, the rate of return regulation setting, and the spot market (the pool contract. Finally, the prospects of restructuring and privatizing the ESI in the Sultanate of Oman are examined by reviewing the current structure of the industry and government objectives in deregulation of the electricity sector as well as the regulation framework.

  12. Gas directive. Which deregulation for France

    International Nuclear Information System (INIS)

    1999-09-01

    This study deals with the following aspects of natural gas market: deregulation of the French market; status and perspectives of the gas market: overview of the gas supplies in Europe at the 2010/2015 vista; situation of regulations: status of the gas directive at the European level and impact on member states market, transposition of the gas directive in France: present day legislation, main stakes and situation of the dialogue with the actors; consequences and actors' strategy: testimony of suppliers, past and future situation, development of new activities in the gas/power industry, possible contractual evolutions, position of the supplier; testimony of clients: new suppliers, new contracts, new risks; legal stakes for the clients: impact of deregulation on contracts, future contractual organization of the market, evolution of 'take or pay' contracts, impairment of contracts obligations, negotiation of supply contracts. (J.S.)

  13. Identification and functional demonstration of miRNAs in the fungus Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Nan Jiang

    Full Text Available microRNAs (miRNAs, endogenous posttranscriptional repressors by base-pairing of their cognate mRNAs in plants and animals, have mostly been thought lost in the kingdom of fungi. Here, we report the identification of miRNAs from the fungus Cryptococcus neoformans. With bioinformatics and Northern blotting approaches, we found that these miRNAs and their hairpin precursors were present in this fungus. The size of miR1 and miR2 is 22 nt and 18 nt, respectively. The precursors are about ∼70 nt in length that is close to mammalian pre-miRNAs. Characteristic features of miRNAs are also found in miR1/2. We demonstrated that the identified miRNAs, miR1 and miR2, caused transgene silencing via the canonical RNAi pathway. Bioinformantics analysis helps to reveal a number of identical sequences of the miR1/2 in transposable elements (TEs and pseudogenes, prompting us to think that fungal miRNAs might be involved in the regulation of the activity of transposons and the expression of pseudogenes. This study identified functional miRNAs in C. neoformans, and sheds light on the diversity and evolutionary origin of eukaryotic miRNAs.

  14. Dysregulated miRNAs and their pathogenic implications for the neurometabolic disease propionic acidemia.

    Science.gov (United States)

    Rivera-Barahona, Ana; Fulgencio-Covián, Alejandro; Pérez-Cerdá, Celia; Ramos, Ricardo; Barry, Michael A; Ugarte, Magdalena; Pérez, Belén; Richard, Eva; Desviat, Lourdes R

    2017-07-18

    miRNome expression profiling was performed in a mouse model of propionic acidemia (PA) and in patients' plasma samples to investigate the role of miRNAs in the pathophysiology of the disease and to identify novel biomarkers and therapeutic targets. PA is a potentially lethal neurometabolic disease with patients developing neurological deficits and cardiomyopathy in the long-term, among other complications. In the PA mouse liver we identified 14 significantly dysregulated miRNAs. Three selected miRNAs, miR-34a-5p, miR-338-3p and miR-350, were found upregulated in brain and heart tissues. Predicted targets involved in apoptosis, stress-signaling and mitochondrial function, were inversely found down-regulated. Functional analysis with miRNA mimics in cellular models confirmed these findings. miRNA profiling in plasma samples from neonatal PA patients and age-matched control individuals identified a set of differentially expressed miRNAs, several were coincident with those identified in the PA mouse, among them miR-34a-5p and miR-338-3p. These two miRNAs were also found dysregulated in childhood and adult PA patients' cohorts. Taken together, the results reveal miRNA signatures in PA useful to identify potential biomarkers, to refine the understanding of the molecular mechanisms of this rare disease and, eventually, to improve the management of patients.

  15. Expression analysis of miRNA and target mRNAs in esophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Meng, X.R. [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Lu, P. [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Mei, J.Z.; Liu, G.J. [Medical Oncology Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Fan, Q.X. [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)

    2014-08-01

    We aimed to investigate miRNAs and related mRNAs through a network-based approach in order to learn the crucial role that they play in the biological processes of esophageal cancer. Esophageal squamous-cell carcinoma (ESCC) and adenocarcinoma (EAC)-related miRNA and gene expression data were downloaded from the Gene Expression Omnibus database, and differentially expressed miRNAs and genes were selected. Target genes of differentially expressed miRNAs were predicted and their regulatory networks were constructed. Differentially expressed miRNA analysis selected four miRNAs associated with EAC and ESCC, among which hsa-miR-21 and hsa-miR-202 were shared by both diseases. hsa-miR-202 was reported for the first time to be associated with esophageal cancer in the present study. Differentially expressed miRNA target genes were mainly involved in cancer-related and signal-transduction pathways. Functional categories of these target genes were related to transcriptional regulation. The results may indicate potential target miRNAs and genes for future investigations of esophageal cancer.

  16. Multiple miRNAs jointly regulate the biosynthesis of ecdysteroid in the holometabolous insects, Chilo suppressalis.

    Science.gov (United States)

    He, Kang; Sun, Yang; Xiao, Huamei; Ge, Chang; Li, Fei; Han, Zhaojun

    2017-12-01

    The accurate rise and fall of active hormones is important for insect development. The ecdysteroids must be cleared in a timely manner. However, the mechanism of suppressing the ecdysteroid biosynthesis at the right time remains unclear. Here, we sequenced a small RNA library of Chilo suppressalis and identified 300 miRNAs in this notorious rice insect pest. Microarray analysis yielded 54 differentially expressed miRNAs during metamorphosis development. Target prediction and in vitro dual-luciferase assays confirmed that seven miRNAs (two conserved and five novel miRNAs) jointly targeted three Halloween genes in the ecdysteroid biosynthesis pathway. Overexpression of these seven miRNAs reduced the titer of 20-hydroxyecdysone (20E), induced mortality, and retarded development, which could be rescued by treatment with 20E. Comparative analysis indicated that the miRNA regulation of metamorphosis development is a conserved process but that the miRNAs involved are highly divergent. In all, we present evidence that both conserved and lineage-specific miRNAs have crucial roles in regulating development in insects by controlling ecdysteroid biosynthesis, which is important for ensuring developmental convergence and evolutionary diversity. © 2017 He et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  17. Mitochondrial miRNA (MitomiR): a new player in cardiovascular health.

    Science.gov (United States)

    Srinivasan, Hemalatha; Das, Samarjit

    2015-10-01

    Cardiovascular disease is one of the major causes of human morbidity and mortality in the world. MicroRNAs (miRNAs) are small RNAs that regulate gene expression and are known to be involved in the pathogenesis of heart diseases, but the translocation phenomenon and the mode of action in mitochondria are largely unknown. Recent mitochondrial proteome analysis unveiled at least 2000 proteins, of which only 13 are made by the mitochondrial genome. There are numerous studies demonstrating the translocation of proteins into the mitochondria and also translocation of ribosomal RNA (viz., 5S rRNA) into mitochondria. Recent studies have suggested that miRNAs contain sequence elements that affect their subcellular localization, particularly nuclear localization. If there are sequence elements that direct miRNAs to the nucleus, it is also possible that similar sequence elements exist to direct miRNAs to the mitochondria. In this review we have summarized most of the miRNAs that have been shown to play an important role in mitochondrial function, either by regulating mitochondrial genes or by regulating nuclear genes that are known to influence mitochondrial function. While the focus of this review is cardiovascular diseases, we also illustrate the role of mitochondrial miRNA (MitomiR) in the initiation and progression of various diseases, including cardiovascular diseases, metabolic diseases, and cancer. Our goal here is to summarize the miRNAs that are localized to the mitochondrial fraction of cells, and how these miRNAs modulate cardiovascular health.

  18. Transcriptional Control of Mitosis: Deregulation and Cancer

    OpenAIRE

    Nath, Somsubhra; Ghatak, Dishari; Das, Pijush; Roychoudhury, Susanta

    2015-01-01

    Research over the past few decades has well established the molecular functioning of mitosis. Deregulation of these functions has also been attributed to the generation of aneuploidy in different tumor types. Numerous studies have given insight into the regulation of mitosis by cell cycle specific proteins. Optimum abundance of these proteins is pivotal to timely execution of mitosis. Aberrant expressions of these mitotic proteins have been reported in different cancer types. Several post-tra...

  19. Network industries deregulation and energy industries reorganization

    International Nuclear Information System (INIS)

    Delaporte, P.; Chevalier, J.M.; Bourdaire, J.M.

    1999-01-01

    The electric power distribution systems deregulation is going to change the economical and institutional scenery. The empowerment term can be anything but a happy change for the customer by giving him the free choice. But this evolution calls the public power in question again. Meanwhile the government has to remain vigilant and watch over the safety in terms of cartel and environment risk. (A.L.B.)

  20. Clinico-Pathological Association of Delineated miRNAs in Uveal Melanoma with Monosomy 3/Disomy 3 Chromosomal Aberrations.

    Directory of Open Access Journals (Sweden)

    Nalini Venkatesan

    Full Text Available To correlate the differentially expressed miRNAs with clinico-pathological features in uveal melanoma (UM tumors harbouring chromosomal 3 aberrations among South Asian Indian cohort.Based on chromosomal 3 aberration, UM (n = 86 were grouped into monosomy 3 (M3; n = 51 and disomy 3 (D3; n = 35 by chromogenic in-situ hybridisation (CISH. The clinico-pathological features were recorded. miRNA profiling was performed in formalin fixed paraffin embedded (FFPE UM samples (n = 6 using Agilent, Human miRNA microarray, 8x15KV3 arrays. The association between miRNAs and clinico-pathological features were studied using univariate and multivariate analysis. miRNA-gene targets were predicted using Target-scan and MiRanda database. Significantly dys-regulated miRNAs were validated in FFPE UM (n = 86 and mRNAs were validated in frozen UM (n = 10 by qRT-PCR. Metastasis free-survival and miRNA expressions were analysed by Kaplen-Meier analysis in UM tissues (n = 52.Unsupervised analysis revealed 585 differentially expressed miRNAs while supervised analysis demonstrated 82 miRNAs (FDR; Q = 0.0. Differential expression of 8 miRNAs: miR-214, miR-149*, miR-143, miR-146b, miR-199a, let7b, miR-1238 and miR-134 were studied. Gene target prediction revealed SMAD4, WISP1, HIPK1, HDAC8 and C-KIT as the post-transcriptional regulators of miR-146b, miR-199a, miR-1238 and miR-134. Five miRNAs (miR-214, miR146b, miR-143, miR-199a and miR-134 were found to be differentially expressed in M3/ D3 UM tumors. In UM patients with liver metastasis, miR-149* and miR-134 expressions were strongly correlated.UM can be stratified using miRNAs from FFPE sections. miRNAs predicting liver metastasis and survival have been identified. Mechanistic linkage of de-regulated miRNA/mRNA expressions provide new insights on their role in UM progression and aggressiveness.

  1. Scenarios for a deregulated, restructured electric industry

    International Nuclear Information System (INIS)

    Ford, G.C.

    1998-01-01

    Deregulation is moving rapidly on some fronts, while opposition by some affected parties is growing. The restructured industry is emerging, in the growth of new businesses such as power marketing and energy services, and also in reorganization by utilities to prepare for the future under deregulation. The market levels and opportunities will depend not only on the decisions of individual state and Federal regulators, but also on those of utilities, power marketers, developers and others who can drive the direction and the outcome of the changes. Scenarios for deregulation and restructuring are examined, from a rapid pace toward full competition, to a process slowed or blocked by conflicting interests and opposition from parties bent on preserving existing positions. A key development already underway with expected major impact on the future of the industry will be major consolidations, including convergence of electric and gas supply, and emergence of very large and powerful players. The generation business and energy supply to customers, based on aggressive marketing will lead the way

  2. Deregulated power prices: comparison of volatility

    International Nuclear Information System (INIS)

    Li Ying; Flynn, P.C.

    2004-01-01

    We examine electrical power price variability for 14 deregulated markets. Power price volatility is measured by price velocity, the daily average of the absolute value of price change per hour. Deregulated markets show a wide variability in price velocity. Some price velocity is expected and arises from the daily diurnal price pattern, which differs significantly between markets. Even when the expected daily variability in price is removed, the residual unexpected variability differs between markets. Some deregulated markets, most notably Britain and Spain, show patterns that are predictable and consistent and have low values of unexpected price velocity. These markets create a climate conducive to consumers facing the market through real time pricing and shaping consumption behaviors in response to price changes. Other markets, for example, South Australia and Alberta, have patterns that are inconsistent and irregular, and hence are hard for a customer to interpret; a customer in such a market will have a higher incentive to avoid demand side management and escape risk through hedging mechanisms

  3. Gas and electricity 2000: energy deregulation

    International Nuclear Information System (INIS)

    Hulot, J.C.; Charbit, N.; Tuot, Th.

    2000-11-01

    This document brings together 17 testimonies of experts about the deregulation of the gas and electricity markets. Content: 1 - the new rules controlling the market: schedule and regulatory evolutions, the new legal framework, the new regulation, the missions and competences of the Commission of Electricity Regulation; 2 - the new commercial practices: the question of electricity transport and of the network independence, the development of trading, the stock exchanges and the forecasting of Paris market, the correlations with the environment (eco-taxes and climate change); 3 - the proposals of new actors: the contribution of a deregulated market like Spain, the comparison with a fully open market like Germany, an internal out-sourcing example to create an energy entity as a whole, the role of a bank in the risk management and the derived markets, the contribution of new technologies from service suppliers; 4 - the consumers attitude with respect to new offers: the historical gas and electricity utilities at the service of French and European clients, the new opportunities offered by the deregulation, the contribution of an independent supplier to consumers, the expectations of big companies and eligible consumers. (J.S.)

  4. An integrative genomic approach reveals coordinated expression of intronic miR-335, miR-342, and miR-561 with deregulated host genes in multiple myeloma.

    Science.gov (United States)

    Ronchetti, Domenica; Lionetti, Marta; Mosca, Laura; Agnelli, Luca; Andronache, Adrian; Fabris, Sonia; Deliliers, Giorgio Lambertenghi; Neri, Antonino

    2008-08-13

    The role of microRNAs (miRNAs) in multiple myeloma (MM) has yet to be fully elucidated. To identify miRNAs that are potentially deregulated in MM, we investigated those mapping within transcription units, based on evidence that intronic miRNAs are frequently coexpressed with their host genes. To this end, we monitored host transcript expression values in a panel of 20 human MM cell lines (HMCLs) and focused on transcripts whose expression varied significantly across the dataset. miRNA expression was quantified by Quantitative Real-Time PCR. Gene expression and genome profiling data were generated on Affymetrix oligonucleotide microarrays. Significant Analysis of Microarrays algorithm was used to investigate differentially expressed transcripts. Conventional statistics were used to test correlations for significance. Public libraries were queried to predict putative miRNA targets. We identified transcripts specific to six miRNA host genes (CCPG1, GULP1, EVL, TACSTD1, MEST, and TNIK) whose average changes in expression varied at least 2-fold from the mean of the examined dataset. We evaluated the expression levels of the corresponding intronic miRNAs and identified a significant correlation between the expression levels of MEST, EVL, and GULP1 and those of the corresponding miRNAs miR-335, miR-342-3p, and miR-561, respectively. Genome-wide profiling of the 20 HMCLs indicated that the increased expression of the three host genes and their corresponding intronic miRNAs was not correlated with local copy number variations. Notably, miRNAs and their host genes were overexpressed in a fraction of primary tumors with respect to normal plasma cells; however, this finding was not correlated with known molecular myeloma groups. The predicted putative miRNA targets and the transcriptional profiles associated with the primary tumors suggest that MEST/miR-335 and EVL/miR-342-3p may play a role in plasma cell homing and/or interactions with the bone marrow microenvironment. Our

  5. An integrative genomic approach reveals coordinated expression of intronic miR-335, miR-342, and miR-561 with deregulated host genes in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Agnelli Luca

    2008-08-01

    Full Text Available Abstract Background The role of microRNAs (miRNAs in multiple myeloma (MM has yet to be fully elucidated. To identify miRNAs that are potentially deregulated in MM, we investigated those mapping within transcription units, based on evidence that intronic miRNAs are frequently coexpressed with their host genes. To this end, we monitored host transcript expression values in a panel of 20 human MM cell lines (HMCLs and focused on transcripts whose expression varied significantly across the dataset. Methods miRNA expression was quantified by Quantitative Real-Time PCR. Gene expression and genome profiling data were generated on Affymetrix oligonucleotide microarrays. Significant Analysis of Microarrays algorithm was used to investigate differentially expressed transcripts. Conventional statistics were used to test correlations for significance. Public libraries were queried to predict putative miRNA targets. Results We identified transcripts specific to six miRNA host genes (CCPG1, GULP1, EVL, TACSTD1, MEST, and TNIK whose average changes in expression varied at least 2-fold from the mean of the examined dataset. We evaluated the expression levels of the corresponding intronic miRNAs and identified a significant correlation between the expression levels of MEST, EVL, and GULP1 and those of the corresponding miRNAs miR-335, miR-342-3p, and miR-561, respectively. Genome-wide profiling of the 20 HMCLs indicated that the increased expression of the three host genes and their corresponding intronic miRNAs was not correlated with local copy number variations. Notably, miRNAs and their host genes were overexpressed in a fraction of primary tumors with respect to normal plasma cells; however, this finding was not correlated with known molecular myeloma groups. The predicted putative miRNA targets and the transcriptional profiles associated with the primary tumors suggest that MEST/miR-335 and EVL/miR-342-3p may play a role in plasma cell homing and

  6. Therapeutic modulation of miRNA for the treatment of proinflammatory lung diseases.

    LENUS (Irish Health Repository)

    Hassan, Tidi

    2012-03-01

    miRNAs are short, nonprotein coding RNAs that regulate target gene expression principally by causing translational repression and\\/or mRNA degradation. miRNAs are involved in most mammalian biological processes and have pivotal roles in controlling the expression of factors involved in basal and stimulus-induced signaling pathways. Considering their central role in the regulation of gene expression, miRNAs represent therapeutic drug targets. Here we describe how miRNAs are involved in the regulation of aspects of innate immunity and inflammation, what happens when this goes awry, such as in the chronic inflammatory lung diseases cystic fibrosis and asthma, and discuss the current state-of-the-art miRNA-targeted therapeutics.

  7. Computational prediction of miRNAs and their targets in Phaseolus vulgaris using simple sequence repeat signatures.

    Science.gov (United States)

    Nithin, Chandran; Patwa, Nisha; Thomas, Amal; Bahadur, Ranjit Prasad; Basak, Jolly

    2015-06-12

    MicroRNAs (miRNAs) are endogenous, noncoding, short RNAs directly involved in regulating gene expression at the post-transcriptional level. In spite of immense importance, limited information of P. vulgaris miRNAs and their expression patterns prompted us to identify new miRNAs in P. vulgaris by computational methods. Besides conventional approaches, we have used the simple sequence repeat (SSR) signatures as one of the prediction parameter. Moreover, for all other parameters including normalized Shannon entropy, normalized base pairing index and normalized base-pair distance, instead of taking a fixed cut-off value, we have used 99% probability range derived from the available data. We have identified 208 mature miRNAs in P. vulgaris belonging to 118 families, of which 201 are novel. 97 of the predicted miRNAs in P. vulgaris were validated with the sequencing data obtained from the small RNA sequencing of P. vulgaris. Randomly selected predicted miRNAs were also validated using qRT-PCR. A total of 1305 target sequences were identified for 130 predicted miRNAs. Using 80% sequence identity cut-off, proteins coded by 563 targets were identified. The computational method developed in this study was also validated by predicting 229 miRNAs of A. thaliana and 462 miRNAs of G. max, of which 213 for A. thaliana and 397 for G. max are existing in miRBase 20. There is no universal SSR that is conserved among all precursors of Viridiplantae, but conserved SSR exists within a miRNA family and is used as a signature in our prediction method. Prediction of known miRNAs of A. thaliana and G. max validates the accuracy of our method. Our findings will contribute to the present knowledge of miRNAs and their targets in P. vulgaris. This computational method can be applied to any species of Viridiplantae for the successful prediction of miRNAs and their targets.

  8. Role of miRNAs in Epicardial Adipose Tissue in CAD Patients with T2DM.

    Science.gov (United States)

    Liu, Yang; Fu, Wenbo; Lu, Mu; Huai, Shitao; Song, Yaqin; Wei, Yutao

    2016-01-01

    Background. Epicardial adipose tissue (EAT) is identified as an atypical fat depot surrounding the heart with a putative role in the involvement of metabolic disorders, including obesity, type-2 diabetes mellitus, and atherosclerosis. We profiled miRNAs in EAT of metabolic patients with coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) versus metabolically healthy patients by microarray. Compared to metabolically healthy patients, we identified forty-two miRNAs that are differentially expressed in patients with CAD and T2DM from Xinjiang, China. Eleven miRNAs were selected as potential novel miRNAs according to P value and fold change. Then the potential novel miRNAs targeted genes were predicted via TargetScan, PicTar, and miRTarbase, and the function of the target genes was predicted via Gene Ontology (GO) analysis while the enriched KEGG pathway analyses of the miRNAs targeted genes were performed by bioinformatics software DAVID. Then protein-protein interaction networks of the targeted gene were conducted by online software STRING. Finally, using microarray, bioinformatics approaches revealed the possible molecular mechanisms pathogenesis of CAD and T2DM. A total of 11 differentially expressed miRNAs were identified and among them, hsa-miR-4687-3p drew specific attention. Bioinformatics analysis revealed that insulin signaling pathway is the central way involved in the progression of metabolic disorders. Conclusions. The current findings support the fact that miRNAs are involved in the pathogenesis of metabolic disorders in EAT of CAD patients with T2DM, and validation of the results of these miRNAs by independent and prospective study is certainly warranted.

  9. Role of miRNAs in Epicardial Adipose Tissue in CAD Patients with T2DM

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2016-01-01

    Full Text Available Background. Epicardial adipose tissue (EAT is identified as an atypical fat depot surrounding the heart with a putative role in the involvement of metabolic disorders, including obesity, type-2 diabetes mellitus, and atherosclerosis. We profiled miRNAs in EAT of metabolic patients with coronary artery disease (CAD and type-2 diabetes mellitus (T2DM versus metabolically healthy patients by microarray. Compared to metabolically healthy patients, we identified forty-two miRNAs that are differentially expressed in patients with CAD and T2DM from Xinjiang, China. Eleven miRNAs were selected as potential novel miRNAs according to P value and fold change. Then the potential novel miRNAs targeted genes were predicted via TargetScan, PicTar, and miRTarbase, and the function of the target genes was predicted via Gene Ontology (GO analysis while the enriched KEGG pathway analyses of the miRNAs targeted genes were performed by bioinformatics software DAVID. Then protein-protein interaction networks of the targeted gene were conducted by online software STRING. Finally, using microarray, bioinformatics approaches revealed the possible molecular mechanisms pathogenesis of CAD and T2DM. A total of 11 differentially expressed miRNAs were identified and among them, hsa-miR-4687-3p drew specific attention. Bioinformatics analysis revealed that insulin signaling pathway is the central way involved in the progression of metabolic disorders. Conclusions. The current findings support the fact that miRNAs are involved in the pathogenesis of metabolic disorders in EAT of CAD patients with T2DM, and validation of the results of these miRNAs by independent and prospective study is certainly warranted.

  10. miRNA regulation of LDL-cholesterol metabolism.

    Science.gov (United States)

    Goedeke, Leigh; Wagschal, Alexandre; Fernández-Hernando, Carlos; Näär, Anders M

    2016-12-01

    In the past decade, microRNAs (miRNAs) have emerged as key regulators of circulating levels of lipoproteins. Specifically, recent work has uncovered the role of miRNAs in controlling the levels of atherogenic low-density lipoprotein LDL (LDL)-cholesterol by post-transcriptionally regulating genes involved in very low-density lipoprotein (VLDL) secretion, cholesterol biosynthesis, and hepatic LDL receptor (LDLR) expression. Interestingly, several of these miRNAs are located in genomic loci associated with abnormal levels of circulating lipids in humans. These findings reinforce the interest of targeting this subset of non-coding RNAs as potential therapeutic avenues for regulating plasma cholesterol and triglyceride (TAG) levels. In this review, we will discuss how these new miRNAs represent potential pre-disposition factors for cardiovascular disease (CVD), and putative therapeutic targets in patients with cardiometabolic disorders. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernández-Hernando and Yajaira Suárez. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. miRNA Long-Term Response to Early Metabolic Environmental Challenge in Hypothalamic Arcuate Nucleus

    Directory of Open Access Journals (Sweden)

    Charlotte Benoit

    2018-03-01

    Full Text Available Epidemiological reports and studies using rodent models indicate that early exposure to nutrient and/or hormonal challenges can reprogram metabolism at adulthood. Hypothalamic arcuate nucleus (ARC integrates peripheral and central signals to adequately regulate energy homeostasis. microRNAs (miRNAs participate in the control of gene expression of large regulatory networks including many signaling pathways involved in epigenetics regulations. Here, we have characterized and compared the miRNA population of ARC of adult male rats continuously exposed to a balanced metabolic environment to the one of adult male rats exposed to an unbalanced high-fat/high-carbohydrate/moderate-protein metabolic environment during the perinatal period and/or at adulthood that consequently displayed hyperinsulinemia and/or hyperleptinemia. We identified more than 400 miRNA species in ARC of adult male rats. By comparing the miRNA content of six biological replicates in each of the four perinatal/adult environments/rat groups, we identified the 10 miRNAs specified by clusters miR-96/182/183, miR-141/200c, and miR-200a/200b/429 as miRNAs of systematic and uncommonly high variation of expression. This uncommon variation of expression may underlie high individual differences in aging disease susceptibilities. By comparing the miRNA content of the adult ARC between the rat groups, we showed that the miRNA population was not affected by the unbalanced adult environment while, in contrast, the expression of 11 miRNAs was repeatedly impacted by the perinatal unbalanced environment. Our data revealed a miRNA response of adult ARC to early metabolic environmental challenge.

  12. Characterization of miRNAs associated with Botrytis cinerea infection of tomato leaves.

    Science.gov (United States)

    Jin, Weibo; Wu, Fangli

    2015-01-16

    Botrytis cinerea Pers. Fr. is an important pathogen causing stem rot in tomatoes grown indoors for extended periods. MicroRNAs (miRNAs) have been reported as gene expression regulators related to several stress responses and B. cinerea infection in tomato. However, the function of miRNAs in the resistance to B. cinerea remains unclear. The miRNA expression patterns in tomato in response to B. cinerea stress were investigated by high-throughput sequencing. In total, 143 known miRNAs and seven novel miRNAs were identified and their corresponding expression was detected in mock- and B. cinerea-inoculated leaves. Among those, one novel and 57 known miRNAs were differentially expressed in B. cinerea-infected leaves, and 8 of these were further confirmed by quantitative reverse-transcription PCR (qRT-PCR). Moreover, five of these eight differentially expressed miRNAs could hit 10 coding sequences (CDSs) via CleaveLand pipeline and psRNAtarget program. In addition, qRT-PCR revealed that four targets were negatively correlated with their corresponding miRNAs (miR319, miR394, and miRn1). Results of sRNA high-throughput sequencing revealed that the upregulation of miRNAs may be implicated in the mechanism by which tomato respond to B. cinerea stress. Analysis of the expression profiles of B. cinerea-responsive miRNAs and their targets strongly suggested that miR319, miR394, and miRn1 may be involved in the tomato leaves' response to B. cinerea infection.

  13. miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease.

    Science.gov (United States)

    Schulte, Christian; Molz, Simon; Appelbaum, Sebastian; Karakas, Mahir; Ojeda, Francisco; Lau, Denise M; Hartmann, Tim; Lackner, Karl J; Westermann, Dirk; Schnabel, Renate B; Blankenberg, Stefan; Zeller, Tanja

    2015-01-01

    Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction. The aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD. Levels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR). The median follow-up period was 4 years (IQR 2.78-5.04). The median age of all patients was 64 years (IQR 57-69) with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS), 61.1% were diagnosed with stable angina pectoris (SAP). Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR) 1.77 per one standard deviation (SD) increase (95% confidence interval (CI) 1.20; 2.60), p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14), p = 0.011, C-index 0.80). In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01), p = 0.006, C-index 0.89); miRA-223: HR 4.94 per one SD increase (1.42; 17.20), p = 0.012, C-index 0.89). Serum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers with prognostic value with respect to future

  14. Autophagy regulated by miRNAs in colorectal cancer progression and resistance

    Directory of Open Access Journals (Sweden)

    Andrew Fesler

    2017-01-01

    Full Text Available The catabolic process of autophagy is an essential cellular function that allows for the breakdown and recycling of cellular macromolecules. In recent years, the impact of epigenetic regulation of autophagy by noncoding miRNAs has been recognized in human cancer. In colorectal cancer, autophagy plays critical roles in cancer progression as well as resistance to chemotherapy, and recent evidence demonstrates that miRNAs are directly involved in mediating these functions. In this review, we focus on the recent advancements in the field of miRNA regulation of autophagy in colorectal cancer.

  15. Deregulated gas in 1985 seen costly

    Energy Technology Data Exchange (ETDEWEB)

    Schaffer, P.

    1980-05-05

    Deregulation of natural gas wellhead prices will mean higher prices for nonboiler industrial users, according to an Energy and Environmental Analysis Inc. (EEA) study. The price increases of high-sulfur residual fuel oil will exceed inflation rates, but low-sulfur residual oil and distillate oil will have smaller increases because of upgraded refineries. Te economc imact analysis is broken down by region and includes estimates of gas, high-sulfur coal, and low-sulfur coal prices thrugh 1995. Free copies of the report are available from the Federal Energy Regulatory Commission's Office of Public Information. (DCK)

  16. Immunological Deregulation in Classic Hodgkin Lymphoma

    Science.gov (United States)

    Romano, Alessandra; Vetro, Calogero; Caocci, Giovanni; Greco, Marianna; Parrinello, Nunziatina Laura; Di Raimondo, Francesco; La Nasa, Giorgio

    2014-01-01

    Classic Hodgkin Lymphoma (cHL) has a unique histology since only a few neoplastic cells are surrounded by inflammatory accessory cells that in the last years have emerged as crucial players in sustaining the course of disease. In addition, recent studies suggest that the abnormal activity of these inflammatory cells (such as deregulation in regulatory T cells signaling, expansion of myeloid derived suppressor cells, HLA-G signaling and natural killer cells dysfunction) may have prognostic significance. This review is focused on summarizing recent advanced in immunological defects in cHL with translational implications. PMID:24959336

  17. Inflation targeting and product market deregulation : [Version Januar 2012

    OpenAIRE

    Moretti, Laura

    2012-01-01

    I evaluate the effect of inflation targeting on inflation and how it interacts with product market deregulation during the disinflationary process in the 1990s. Using a sample of 21 OECD countries, I show that, after controlling for product market deregulation, the effect of inflation targeting is quantitatively important and statistically significant. Moreover, product market deregulation also matters in particular in countries that adopted an inflation targeting regime. I propose a New Keyn...

  18. Deregulation and common carriage in the Nordic Power System

    Energy Technology Data Exchange (ETDEWEB)

    Bjorvatn, K.; Tjotta, S. [Foundation for Research in Economics and Business Administration, Bergen-Sandviken (Norway)

    1993-12-31

    In this paper we analyze deregulation and integration of the Nordic markets for electric power. Nordic trade in electricity is controlled by national monopolies and is confined to occasional power. No transit is allowed. Due to its central location, Sweden plays a crucial role in the Nordic electricity market. For Sweden, common carriage without some form of compensation is not likely to be an acceptable form of integration. The Shapley values reveal that compensatory demands are likely to be quite large - a fact which might complicate negotiations on the introduction of common carriage. An alternative to common carriage would be for Sweden to exert market power through monopolistic pricing of its transmission services. Government involvement may be necessary to secure a successful integration of international electricity markets. 25 refs., 2 figs., 2 tabs.

  19. Impact of electricity market deregulation on information systems

    International Nuclear Information System (INIS)

    Pharabod, E.; Berrier, M.

    2005-01-01

    Electricity market deregulation is based on un-bundling of activities between generation, transmission and distribution. In a very short time, mechanisms were put in place in order to allow the new market participants to buy and sell electricity. The market operation requires to exchange information at various time horizon, from yearly to real time exchanges, between various actors geographically distributed. The recent market opening to professional customers has also increased the amount of data involved. The information system developed by RTE to manage these data is organised around referential data base, internal and external exchange tools. It must be operated respecting confidentiality of commercial data and being non discriminatory with actors. The security of this information system is now a key issue for the electricity market operation. (authors)

  20. The regulatory epicenter of miRNAs

    Indian Academy of Sciences (India)

    miRNAs are small non-coding RNAs with average length of ∼21 bp. miRNA formation seems to be dependent upon multiple factors besides Drosha and Dicer, in a tissue/stage-specific manner, with interplay of several specific binding factors. In the present study, we have investigated transcription factor binding sites in and ...

  1. Global population-specific variation in miRNA associated with cancer risk and clinical biomarkers.

    Science.gov (United States)

    Rawlings-Goss, Renata A; Campbell, Michael C; Tishkoff, Sarah A

    2014-08-28

    MiRNA expression profiling is being actively investigated as a clinical biomarker and diagnostic tool to detect multiple cancer types and stages as well as other complex diseases. Initial investigations, however, have not comprehensively taken into account genetic variability affecting miRNA expression and/or function in populations of different ethnic backgrounds. Therefore, more complete surveys of miRNA genetic variability are needed to assess global patterns of miRNA variation within and between diverse human populations and their effect on clinically relevant miRNA genes. Genetic variation in 1524 miRNA genes was examined using whole genome sequencing (60x coverage) in a panel of 69 unrelated individuals from 14 global populations, including European, Asian and African populations. We identified 33 previously undescribed miRNA variants, and 31 miRNA containing variants that are globally population-differentiated in frequency between African and non-African populations (PD-miRNA). The top 1% of PD-miRNA were significantly enriched for regulation of genes involved in glucose/insulin metabolism and cell division (p < 10(-7)), most significantly the mitosis pathway, which is strongly linked to cancer onset. Overall, we identify 7 PD-miRNAs that are currently implicated as cancer biomarkers or diagnostics: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908. Notably, hsa-mir-202, a potential breast cancer biomarker, was found to show significantly high allele frequency differentiation at SNP rs12355840, which is known to affect miRNA expression levels in vivo and subsequently breast cancer mortality. MiRNA expression profiles represent a promising new category of disease biomarkers. However, population specific genetic variation can affect the prevalence and baseline expression of these miRNAs in diverse populations. Consequently, miRNA genetic and expression level variation among ethnic groups may be contributing in

  2. miRNAtools: Advanced Training Using the miRNA Web of Knowledge

    Directory of Open Access Journals (Sweden)

    Ewa Ł. Stępień

    2018-02-01

    Full Text Available Micro-RNAs (miRNAs are small non-coding RNAs that act as negative regulators of the genomic output. Their intrinsic importance within cell biology and human disease is well known. Their mechanism of action based on the base pairing binding to their cognate targets have helped the development not only of many computer applications for the prediction of miRNA target recognition but also of specific applications for functional assessment and analysis. Learning about miRNA function requires practical training in the use of specific computer and web-based applications that are complementary to wet-lab studies. In order to guide the learning process about miRNAs, we have created miRNAtools (http://mirnatools.eu, a web repository of miRNA tools and tutorials. This article compiles tools with which miRNAs and their regulatory action can be analyzed and that function to collect and organize information dispersed on the web. The miRNAtools website contains a collection of tutorials that can be used by students and tutors engaged in advanced training courses. The tutorials engage in analyses of the functions of selected miRNAs, starting with their nomenclature and genomic localization and finishing with their involvement in specific cellular functions.

  3. Selling power : marketing energy under deregulation

    International Nuclear Information System (INIS)

    Drummond, J.; Hanna, F.

    2001-01-01

    This book discussed the marketing of energy in a deregulated environment. Experience from long distance telephone service providers has shown that historical dominance is not a guarantee for future success. As new brands are introduced and as consumer choice increases, so does the ability to change from one provider to another. Price is only one of the factors prompting that change. Old rules and practices do not bind new competitors who must face the challenge of open competition and must be aware of the ever-changing face of business. It was recommended that the strategic solution would be to build a brand and to develop significant market shares and create effective customer retention programs. This book focused on the elements that energy marketing professionals must use to maintain and increase share without product differentiation. It also explained how energy providers can effectively attract and retain customers over the long term while keeping marketing and service delivery costs down. It was suggested that small players can compete with the growing strength of regional providers by creating new alliances between larger energy conglomerates. The chapters of the book were entitled: (1) Introduction, (2) The Goals of Deregulation, (3) Strategic Marketing Choices, (4) Relationship Marketing, (5) The Role of Customer Service, (6) The Question of Outsourcing, and (7) Final Thoughts and Observations. 24 refs., 3 figs

  4. Energy service unbundling: where deregulation is heading

    International Nuclear Information System (INIS)

    Croft, M.

    2002-01-01

    The workings of the natural gas market is provided by the speaker at the beginning of the presentation, and covers pre-regulation, early regulation and deregulation. The pre-regulation era provided no customer choice, and the early regulation period saw industrial customers with some degree of choice (mid-1980s). The advent of deregulation created core market customer choice (around 1996). At Coral Energy, there is choice of energy supplier, choice of price structure, and choice of transportation and distribution. A forecast of North American gas demand is provided, along with the natural gas supply and the North American gas supply basins. For the period January 1996 to May 2000, a comparison of annualized volatility is discussed. The author discusses the strategies for purchasing gas: 1) to know yourself and your risk tolerance, flexibility, and load profile; 2) switching gas supply provider. It is important to choose a three year term, combination pricing, and storage position. The risk management options are reviewed: limit exposure to price volatility, mitigate price/volume volatility, and enhance bottom line by capturing market opportunities. figs

  5. Competing in a fully deregulated market

    International Nuclear Information System (INIS)

    Bengtsson, A.; Schoen, G.; Johansson, B.

    1999-01-01

    Vattenfall, Sweden's largest utility, has provided competitively priced nuclear electricity to a price-conscious market for several decades. As Sweden is an exporting country, the cost of products must be kept as low as possible to meet tough European competition. Since Sweden relies almost exclusively on electricity for energy, electric prices must be low to keep Swedish products competitive. Because of the available hydropower in Sweden and Norway, nuclear power plants have been forced to operate with high availability and low cost. From the first years after nuclear plants began operation, there has been a continuous development of organization, management, and work practices to sustain low-cost production. Now, the European electricity market is undergoing deregulation and open competition. This is taking place in a situation where the increase in demand is relatively weak and where the availability of generation capacity is good. Sweden is at the forefront of the competition. According to the well-known law of supply and demand, this entails the risk of squeezed prices, but the situation also offers many opportunities for those making the right decisions. The availability of electricity at competitive prices has great significance for the competitiveness of the industry in general and for the electricity-intensive industry in particular. If the customer then, in a deregulated market is free to choose the supplier, the focus definitely is on the customer

  6. Zap... Alberta is jolted by electric deregulation

    International Nuclear Information System (INIS)

    Howe, M.E.

    2001-01-01

    Of all Canadian provinces, Alberta has travelled the furthest along the electric deregulation road. On January 1, 2001, full retail competition came into effect. Wholesale electricity prices are set by the province through an auction process. The bids from purchasers are made through the Power Pool of Alberta against supply offers. Power prices increased from being amongst the lowest in the world to being amongst the highest in North America as a result of deregulation. Changes to the Electric Utilities Act were made recently by the Alberta government to try to mitigate the factors affecting power price increases. RBC Dominion Securities is of the opinion that the changes will not significantly impact the Alberta Pool Price. It is expected that the trend for power price increases to continue, despite some relief from relatively low-cost electricity being felt by other Canadian provinces as a result of the energy crisis in North America. Based on the Electric Competition Unfolds in Alberta report dated June 2, 2001 prepared by RBC Dominion Securities, this document examines the factors at play in electric price increases, assess the sustainability of current power prices in Alberta, and identify Canadian companies believed to be best positioned in the pipeline and gas and electric sectors to benefit from the high power prices in Alberta. Those companies were ATCO, Canadian Utilities, Westcoast Energy and TransCanada PipeLines, and TransAlta. 5 tabs., 5 figs

  7. Expression profiles of miRNAs from bovine mammary glands in response to Streptococcus agalactiae-induced mastitis.

    Science.gov (United States)

    Pu, Junhua; Li, Rui; Zhang, Chenglong; Chen, Dan; Liao, Xiangxiang; Zhu, Yihui; Geng, Xiaohan; Ji, Dejun; Mao, Yongjiang; Gong, Yunchen; Yang, Zhangping

    2017-08-01

    This study aimed to describe the expression profiles of microRNAs (miRNAs) from mammary gland tissues collected from dairy cows with Streptococcus agalactiae-induced mastitis and to identify differentially expressed miRNAs related to mastitis. The mammary glands of Chinese Holstein cows were challenged with Streptococcus agalactiae to induce mastitis. Small RNAs were isolated from the mammary tissues of the test and control groups and then sequenced using the Solexa sequencing technology to construct two small RNA libraries. Potential target genes of these differentially expressed miRNAs were predicted using the RNAhybrid software, and KEGG pathways associated with these genes were analysed. A total of 18 555 913 and 20 847 000 effective reads were obtained from the test and control groups, respectively. In total, 373 known and 399 novel miRNAs were detected in the test group, and 358 known and 232 novel miRNAs were uncovered in the control group. A total of 35 differentially expressed miRNAs were identified in the test group compared to the control group, including 10 up-regulated miRNAs and 25 down-regulated miRNAs. Of these miRNAs, miR-223 exhibited the highest degree of up-regulation with an approximately 3-fold increase in expression, whereas miR-26a exhibited the most decreased expression level (more than 2-fold). The RNAhybrid software predicted 18 801 genes as potential targets of these 35 miRNAs. Furthermore, several immune response and signal transduction pathways, including the RIG-I-like receptor signalling pathway, cytosolic DNA sensing pathway and Notch signal pathway, were enriched in these predicted targets. In summary, this study provided experimental evidence for the mechanism underlying the regulation of bovine mastitis by miRNAs and showed that miRNAs might be involved in signal pathways during S. agalactiae-induced mastitis.

  8. Dehydration-responsive miRNAs in foxtail millet: genome-wide identification, characterization and expression profiling.

    Science.gov (United States)

    Yadav, Amita; Khan, Yusuf; Prasad, Manoj

    2016-03-01

    A set of novel and known dehydration-responsive miRNAs have been identified in foxtail millet. These findings provide new insights into understanding the functional role of miRNAs and their respective targets in regulating plant response to dehydration stress. MicroRNAs perform significant regulatory roles in growth, development and stress response of plants. Though the miRNA-mediated gene regulatory networks under dehydration stress remain largely unexplored in plant including foxtail millet (Setaria italica), which is a natural abiotic stress tolerant crop. To find out the dehydration-responsive miRNAs at the global level, four small RNA libraries were constructed from control and dehydration stress treated seedlings of two foxtail millet cultivars showing contrasting tolerance behavior towards dehydration stress. Using Illumina sequencing technology, 55 known and 136 novel miRNAs were identified, representing 22 and 48 miRNA families, respectively. Eighteen known and 33 novel miRNAs were differentially expressed during dehydration stress. After the stress treatment, 32 dehydration-responsive miRNAs were up-regulated in tolerant cultivar and 22 miRNAs were down-regulated in sensitive cultivar, suggesting that miRNA-mediated molecular regulation might play important roles in providing contrasting characteristics to these cultivars. Predicted targets of identified miRNAs were found to encode various transcription factors and functional enzymes, indicating their involvement in broad spectrum regulatory functions and biological processes. Further, differential expression patterns of seven known miRNAs were validated by northern blot and expression of ten novel dehydration-responsive miRNAs were confirmed by SL-qRT PCR. Differential expression behavior of five miRNA-target genes was verified under dehydration stress treatment and two of them also validated by RLM RACE. Overall, the present study highlights the importance of dehydration stress-associated post

  9. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology.

    Directory of Open Access Journals (Sweden)

    Kasandra Burgos

    Full Text Available The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility of the diseased tissue--such as the inability to biopsy or test tissue from the central nervous system directly. RNAs originating from hard to access tissues, such as neurons within the brain and spinal cord, have the potential to get to the periphery where they can be detected non-invasively. The formation and extracellular release of microvesicles and RNA binding proteins have been found to carry RNA from cells of the central nervous system to the periphery and protect the RNA from degradation. Extracellular miRNAs detectable in peripheral circulation can provide information about cellular changes associated with human health and disease. In order to associate miRNA signals present in cell-free peripheral biofluids with neurodegenerative disease status of patients with Alzheimer's and Parkinson's diseases, we assessed the miRNA content in cerebrospinal fluid and serum from postmortem subjects with full neuropathology evaluations. We profiled the miRNA content from 69 patients with Alzheimer's disease, 67 with Parkinson's disease and 78 neurologically normal controls using next generation small RNA sequencing (NGS. We report the average abundance of each detected miRNA in cerebrospinal fluid and in serum and describe 13 novel miRNAs that were identified. We correlated changes in miRNA expression with aspects of disease severity such as Braak stage, dementia status, plaque and tangle densities, and the presence and severity of Lewy body pathology. Many of the differentially expressed miRNAs detected in peripheral cell-free cerebrospinal fluid and serum were previously reported in the literature to be deregulated in brain tissue from patients with neurodegenerative disease. These data indicate that extracellular miRNAs detectable in the cerebrospinal fluid and serum are reflective of cell-based changes in pathology and can

  10. Dysregulation of Placental miRNA in Maternal Obesity Is Associated With Pre- and Postnatal Growth.

    Science.gov (United States)

    Carreras-Badosa, Gemma; Bonmatí, Alexandra; Ortega, Francisco-Jose; Mercader, Josep-Maria; Guindo-Martínez, Marta; Torrents, David; Prats-Puig, Anna; Martinez-Calcerrada, Jose-Maria; de Zegher, Francis; Ibáñez, Lourdes; Fernandez-Real, Jose-Manuel; Lopez-Bermejo, Abel; Bassols, Judit

    2017-07-01

    Human placenta exhibits a specific microRNA (miRNA) expression pattern. Some of these miRNAs are dysregulated in pregnancy disorders such as preeclampsia and intrauterine growth restriction and are potential biomarkers for these pathologies. To study the placental miRNA profile in pregnant women with pregestational overweight/obesity (preOB) or gestational obesity (gestOB) and explore the associations between placental miRNAs dysregulated in maternal obesity and prenatal and postnatal growth. TaqMan Low Density Arrays and real-time polymerase chain reaction were used to profile the placental miRNAs in 70 pregnant women (20 preOB, 25 gestOB, and 25 control). Placentas and newborns were weighed at delivery, and infants were weighed at 1, 4, and 12 months of age. Eight miRNAs were decreased in placentas from preOB or gestOB (miR-100, miR-1269, miR-1285, miR-181, miR-185, miR-214, miR-296, and miR-487) (all P 30%) and increased postnatal weight gain (all P 20%). In silico analysis showed that these miRNAs were related to cell proliferation and insulin signaling pathways. miR-296 was also present in plasma samples and associated with placental expression and prenatal and postnatal growth parameters (all P < 0.05). We identified a specific placental miRNA profile in maternal obesity. Placental miRNAs dysregulated in maternal obesity may be involved in mediation of growth-promoting effects of maternal obesity on offspring and could be used as early markers of prenatal and postnatal growth. Copyright © 2017 Endocrine Society

  11. Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics.

    Science.gov (United States)

    Gatto, Francesco; Schulze, Almut; Nielsen, Jens

    2016-07-19

    Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Combinatorial epigenetic deregulation by Helicobacter pylori and Epstein-Barr virus infections in gastric tumourigenesis.

    Science.gov (United States)

    Wu, William Kk; Yu, Jun; Chan, Matthew Tv; To, Ka F; Cheng, Alfred Sl

    2016-07-01

    Epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodelling and microRNAs, convert environmental signals to transcriptional outputs but are commonly hijacked by pathogenic microorganisms. Recent advances in cancer epigenomics have shed new light on the importance of epigenetic deregulation in Helicobacter pylori- and Epstein-Barr virus (EBV)-driven gastric tumourigenesis. Moreover, it is becoming apparent that epigenetic mechanisms interact through crosstalk and feedback loops, which modify global gene expression patterns. The SWI/SNF remodelling complexes are commonly involved in gastric cancers associated with H. pylori or EBV through different mechanisms, including microRNA-mediated deregulation and genetic mutations. While H. pylori causes epigenetic silencing of tumour-suppressor genes to deregulate cellular pathways, EBV-positive tumours exhibit a widespread and distinctive DNA hypermethylation profile. Given the early successes of epigenetic drugs in haematological malignancies, further studies are mandated to enrich and translate our understanding of combinatorial epigenetic deregulation in gastric cancers into interventional strategies in the clinic. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. Progress risk assessment of oral premalignant lesions with saliva miRNA analysis

    International Nuclear Information System (INIS)

    Yang, Ya; Li, Yue-xiu; Yang, Xi; Jiang, Long; Zhou, Zuo-jun; Zhu, Ya-qin

    2013-01-01

    Oral cancer develops through multi-stages: from normal to mild (low grade) dysplasia (LGD), moderate dysplasia, and severe (high grade) dysplasia (HGD), to carcinoma in situ (CIS) and finally invasive oral squamous cell carcinomas (OSCC). Clinical and histological assessments are not reliable in predicting which precursor lesions will progress. The aim of this study was to assess the potential of a noninvasive approach to assess progress risk of oral precancerous lesions. We first used microRNA microarray to profile progressing LGD oral premaligant lesions (OPLs) from non-progressing LGD OPLs in order to explore the possible microRNAs deregulated in low grade OPLs which later progressed to HGD or OSCC. We then used RT-qPCR to detect miRNA targets from the microarray results in saliva samples of these patients. We identified a specific miRNA signature that is aberrantly expressed in progressing oral LGD leukoplakias. Similar expression patterns were detected in saliva samples from these patients. These results show promise for using saliva miRNA signature for monitoring of cancer precursor lesions and early detection of disease progression

  14. miRNA expression profiling of formalin-fixed paraffin-embedded (FFPE hereditary breast tumors

    Directory of Open Access Journals (Sweden)

    Miljana Tanić

    2015-03-01

    Full Text Available Hereditary breast cancer constitutes only 5–10% of all breast cancer cases and is characterized by strong family history of breast and/or other associated cancer types. Only ~25% of hereditary breast cancer cases carry a mutation in BRCA1 or BRCA2 gene, while mutations in other rare high and moderate-risk genes and common low penetrance variants may account for additional 20% of the cases. Thus the majority of cases are still unaccounted for and designated as BRCAX tumors. MicroRNAs are small non-coding RNAs that play important roles as regulators of gene expression and are deregulated in cancer. To characterize hereditary breast tumors based on their miRNA expression profiles we performed global microarray miRNA expression profiling on a retrospective cohort of 80 FFPE breast tissues, including 66 hereditary breast tumors (13 BRCA1, 10 BRCA2 and 43 BRCAX, 10 sporadic breast carcinomas and 4 normal breast tissues, using Exiqon miRCURY LNA™ microRNA Array v.11.0. Here we describe in detail the miRNA microarray expression data and tumor samples used for the study of BRCAX tumor heterogeneity (Tanic et al., 2013 and biomarkers associated with positive BRCA1/2 mutation status (Tanic et al., 2014. Additionally, we provide the R code for data preprocessing and quality control.

  15. A comprehensive genome-wide study on tissue-specific and abiotic stress-specific miRNAs in Triticum aestivum.

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    Ritu Pandey

    Full Text Available Productivity of wheat crop is largely dependent on its growth and development that, in turn, is mainly regulated by environmental conditions, including abiotic stress factors. miRNAs are key regulators of gene expression networks involved in diverse aspects of development and stress responses in plants. Using high-throughput sequencing of eight small RNA libraries prepared from diverse abiotic stresses and tissues, we identified 47 known miRNAs belonging to 20 families, 49 true novel and 1030 candidate novel miRNAs. Digital gene expression analysis revealed that 257 miRNAs exhibited tissue-specific expression and 74 were associated with abiotic stresses. Putative target genes were predicted for miRNAs identified in this study and their grouping into functional categories indicated that the putative targets were involved in diverse biological processes. RLM-RACE of predicted targets of three known miRNAs (miR156, miR160 and miR164 confirmed their mRNA cleavage, thus indicating their regulation at post-transcriptional level by the corresponding miRNAs. Mapping of the sequenced data onto the wheat progenitors and closely related monocots revealed a large number of evolutionary conserved miRNAs. Additional expression profiling of some of these miRNAs in other abiotic stresses underline their involvement in multiple stresses. Our findings provide valuable resource for an improved understanding of the role of miRNAs in stress tolerance as well as plant development.

  16. Low genetic diversity and functional constraint of miRNA genes participating pollen-pistil interaction in rice.

    Science.gov (United States)

    Wang, Kun; Wang, Xin; Li, Ming; Shi, Tao; Yang, Pingfang

    2017-09-01

    In this study, we sequenced and analyzed the expression and evolution of rice miRNA genes participating pollen-pistil interaction that is crucial to rice yield. Pollen-pistil interaction is an essential reproductive process for all flowering plants. While microRNAs (miRNAs) are important noncoding small RNAs that regulate mRNA levels in eukaryotic cells, there is little knowledge about which miRNAs involved in the early stages of pollen-pistil interaction in rice and how they evolve under this conserved process. In this study, we sequenced the small RNAs in rice from unpollinated pistil (R0), pistil from 5 min and 15 min after pollination, respectively, to identify known and novel miRNAs that are involved in this process. By comparing the corresponding mRNA-seq dataset, we identified a group of miRNAs with strong negative expression pattern with their target genes. Further investigation of all miRNA loci (MIRNAs) across 1083 public rice accessions revealed significantly reduced genetic diversity in MIRNAs with strong negative expression of their targets when comparing to those with little or no impact on targets during pollen-pistil interaction. Annotation of targets suggested that those MIRNAs with strong impact on targets were pronounced in cell wall related processes such as xylan metabolism. Additionally, plant conserved miRNAs, such as those with functions in gibberellic acid, auxin and nitrate signaling, were also with strong negative expression of their targets. Overall, our analyses identified key miRNAs participating pollen-pistil interaction and their evolutionary patterns in rice, which can facilitate the understanding of molecular mechanisms associated with seed setting.

  17. Ras-mediated deregulation of the circadian clock in cancer.

    Directory of Open Access Journals (Sweden)

    Angela Relógio

    Full Text Available Circadian rhythms are essential to the temporal regulation of molecular processes in living systems and as such to life itself. Deregulation of these rhythms leads to failures in biological processes and eventually to the manifestation of pathological phenotypes including cancer. To address the questions as to what are the elicitors of a disrupted clock in cancer, we applied a systems biology approach to correlate experimental, bioinformatics and modelling data from several cell line models for colorectal and skin cancer. We found strong and weak circadian oscillators within the same type of cancer and identified a set of genes, which allows the discrimination between the two oscillator-types. Among those genes are IFNGR2, PITX2, RFWD2, PPARγ, LOXL2, Rab6 and SPARC, all involved in cancer-related pathways. Using a bioinformatics approach, we extended the core-clock network and present its interconnection to the discriminative set of genes. Interestingly, such gene signatures link the clock to oncogenic pathways like the RAS/MAPK pathway. To investigate the potential impact of the RAS/MAPK pathway - a major driver of colorectal carcinogenesis - on the circadian clock, we used a computational model which predicted that perturbation of BMAL1-mediated transcription can generate the circadian phenotypes similar to those observed in metastatic cell lines. Using an inducible RAS expression system, we show that overexpression of RAS disrupts the circadian clock and leads to an increase of the circadian period while RAS inhibition causes a shortening of period length, as predicted by our mathematical simulations. Together, our data demonstrate that perturbations induced by a single oncogene are sufficient to deregulate the mammalian circadian clock.

  18. Ras-Mediated Deregulation of the Circadian Clock in Cancer

    Science.gov (United States)

    Relógio, Angela; Thomas, Philippe; Medina-Pérez, Paula; Reischl, Silke; Bervoets, Sander; Gloc, Ewa; Riemer, Pamela; Mang-Fatehi, Shila; Maier, Bert; Schäfer, Reinhold; Leser, Ulf; Herzel, Hanspeter; Kramer, Achim; Sers, Christine

    2014-01-01

    Circadian rhythms are essential to the temporal regulation of molecular processes in living systems and as such to life itself. Deregulation of these rhythms leads to failures in biological processes and eventually to the manifestation of pathological phenotypes including cancer. To address the questions as to what are the elicitors of a disrupted clock in cancer, we applied a systems biology approach to correlate experimental, bioinformatics and modelling data from several cell line models for colorectal and skin cancer. We found strong and weak circadian oscillators within the same type of cancer and identified a set of genes, which allows the discrimination between the two oscillator-types. Among those genes are IFNGR2, PITX2, RFWD2, PPARγ, LOXL2, Rab6 and SPARC, all involved in cancer-related pathways. Using a bioinformatics approach, we extended the core-clock network and present its interconnection to the discriminative set of genes. Interestingly, such gene signatures link the clock to oncogenic pathways like the RAS/MAPK pathway. To investigate the potential impact of the RAS/MAPK pathway - a major driver of colorectal carcinogenesis - on the circadian clock, we used a computational model which predicted that perturbation of BMAL1-mediated transcription can generate the circadian phenotypes similar to those observed in metastatic cell lines. Using an inducible RAS expression system, we show that overexpression of RAS disrupts the circadian clock and leads to an increase of the circadian period while RAS inhibition causes a shortening of period length, as predicted by our mathematical simulations. Together, our data demonstrate that perturbations induced by a single oncogene are sufficient to deregulate the mammalian circadian clock. PMID:24875049

  19. The economics of energy storage in 14 deregulated power markets

    International Nuclear Information System (INIS)

    Figueiredo, F.C.; Flynn, P.C.; Cabral, E.A.

    2006-01-01

    In regulated power markets, electricity is stored to better utilize existing generation and to defer costly investment in generation. The justification is a reduction in the overall regulated price of power compared to the alternative investment in new primary generation. However, any storage of electrical power also involves a capital investment and incurs the cost of inefficiency. In deregulated energy markets, the sale of electricity or ancillary services from pumped storage can be evaluated based on each individual project. The economic basis for power storage is that power is purchased during periods of low price and resold during periods of high price. This study used historical power price data from 14 deregulated markets around the world to evaluate the economic incentive to use pumped storage for electrical energy. Each market was shown to have a unique average diurnal power price profile that results in a unique price spread for pumped storage. The diurnal price pattern and efficiency of storage was used to assess the net income potential from energy sales from pumped storage for each market. The markets were ranked in terms of the incentive to invest in pumped energy storage as well as on available revenue, and on potential return on investment. An optimal operating profile was illustrated in detail based on historical price patterns for one of the markets. The net income potential was then combined with the capital and operating cost of pumped storage. The adequacy of return on investment for pumped storage was analyzed by two different methods. The differences between markets stem from different diurnal power price patterns that reflect the generation mix, market design and participant behaviours. 17 refs., 7 tabs., 7 figs., 1 appendix

  20. On the causes and consequences of US power retail deregulation

    Science.gov (United States)

    Mercado, Jorge E.

    As relevant research in power retail deregulation had identified, the point of departure to consider power markets reforms had been the comparison of state retail prices to those at the average national level as well as the behavior of natural gas prices as an indication of potential entrance of more efficient generation. As a way to have a final answer on the real causes and consequences of retail deregulation, I propose to use a structural model of price and effects of deregulation to show that the causes of deregulation go further than the difference with respect to average national prices and that competitive market reforms by themselves may not be the main reason behind price reduction in states that decided to deregulate their power retail. In particular, the sign on the price difference variable, contrary to what has been argued in the literature, strongly suggest that those states with lower prices tend to favor deregulation, hence obtaining even better electricity prices through reform. Results also suggest that a more complex process of decision to deregulate the power retail has occurred at the state level, since not only price differences mattered as has been the argument so far, but also income per capita, the ratio of small to big businesses, and the party composition of legislatures had played a determinant role on explaining decisions to deregulate as well as price behavior.

  1. Next-generation sequencing analysis of miRNA expression in control and FSHD myogenesis.

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    Veronica Colangelo

    Full Text Available Emerging evidence has demonstrated that miRNA sequences can regulate skeletal myogenesis by controlling the process of myoblast proliferation and differentiation. However, at present a deep analysis of miRNA expression in control and FSHD myoblasts during differentiation has not yet been derived. To close this gap, we used a next-generation sequencing (NGS approach applied to in vitro myogenesis. Furthermore, to minimize sample genetic heterogeneity and muscle-type specific patterns of gene expression, miRNA profiling from NGS data was filtered with FC ≥ 4 (log(2FC ≥ 2 and p-value<0.05, and its validation was derived by qRT-PCR on myoblasts from seven muscle districts. In particular, control myogenesis showed the modulation of 38 miRNAs, the majority of which (34 out 38 were up-regulated, including myomiRs (miR-1, -133a, -133b and -206. Approximately one third of the modulated miRNAs were not previously reported to be involved in muscle differentiation, and interestingly some of these (i.e. miR-874, -1290, -95 and -146a were previously shown to regulate cell proliferation and differentiation. FSHD myogenesis evidenced a reduced number of modulated miRNAs than healthy muscle cells. The two processes shared nine miRNAs, including myomiRs, although with FC values lower in FSHD than in control cells. In addition, FSHD cells showed the modulation of six miRNAs (miR-1268, -1268b, -1908, 4258, -4508- and -4516 not evidenced in control cells and that therefore could be considered FSHD-specific, likewise three novel miRNAs that seem to be specifically expressed in FSHD myotubes. These data further clarify the impact of miRNA regulation during control myogenesis and strongly suggest that a complex dysregulation of miRNA expression characterizes FSHD, impairing two important features of myogenesis: cell cycle and muscle development. The derived miRNA profiling could represent a novel molecular signature for FSHD that includes diagnostic biomarkers and

  2. Regulatory trends : deregulation, where in the world is it working?

    International Nuclear Information System (INIS)

    Sofield, J.

    2001-01-01

    The issue of electricity deregulation was the focus of this Power-Point presentation, which discussed what deregulation entails, what it is meant to achieve and whether there is only one right answer. Different approaches and performance results were presented with reference to international experiences in the United Kingdom, Australia, New Zealand, and California. The main objective of deregulation is introduce competition to give customers a choice between suppliers and products, to allow market forces to set prices with the hope that they will be lower, and to encourage industry efficiency, reduce costs, improve productivity, and ensure that the right investments are made. The underlying agenda is to raise billions of dollars to reduce government debt and to transfer the risks and investment requirements to the investors and away from the government/taxpayers and ratepayers. Deregulation entails restructuring, privatization and unbundling of monopolies. It also entails a set of market rules and new systems processes to enable retail competition. The author emphasized that there are different characteristics to deregulation in each jurisdiction and that the state of the pre-deregulation industry plays a significant role in the eventual success of deregulation. The lessons learned from international experience is that open, non-discriminatory access is essential for both transmission and distribution and that political will for restructuring is essential. It was also determined that partial deregulation will not work, since wholesale and retail markets are connected. It was concluded that deregulation can work to different degrees under different designs. Progress so far has been slow and customers have yet to see the full benefits of deregulation. tabs

  3. Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways.

    Science.gov (United States)

    Wilfred, Bernard R; Wang, Wang-Xia; Nelson, Peter T

    2007-07-01

    MicroRNAs (miRNAs) are powerful regulators of gene expression. Although first discovered in worm larvae, miRNAs play fundamental biological roles-including in humans-well beyond development. MiRNAs participate in the regulation of metabolism (including lipid metabolism) for all animal species studied. A review of the fascinating and fast-growing literature on miRNA regulation of metabolism can be parsed into three main categories: (1) adipocyte biochemistry and cell fate determination; (2) regulation of metabolic biochemistry in invertebrates; and (3) regulation of metabolic biochemistry in mammals. Most research into the 'function' of a given miRNA in metabolic pathways has concentrated on a given miRNA acting upon a particular 'target' mRNA. Whereas in some biological contexts the effects of a given miRNA:mRNA pair may predominate, this might not be the case generally. In order to provide an example of how a single miRNA could regulate multiple 'target' mRNAs or even entire human metabolic pathways, we include a discussion of metabolic pathways that are predicted to be regulated by the miRNA paralogs, miR-103 and miR-107. These miRNAs, which exist in vertebrate genomes within introns of the pantothenate kinase (PANK) genes, are predicted by bioinformatics to affect multiple mRNA targets in pathways that involve cellular Acetyl-CoA and lipid levels. Significantly, PANK enzymes also affect these pathways, so the miRNA and 'host' gene may act synergistically. These predictions require experimental verification. In conclusion, a review of the literature on miRNA regulation of metabolism leads us believe that the future will provide researchers with many additional energizing revelations.

  4. Identification of novel target genes specifically activated by deregulated E2F in human normal fibroblasts.

    Science.gov (United States)

    Kitamura, Hodaka; Ozono, Eiko; Iwanaga, Ritsuko; Bradford, Andrew P; Okuno, Junko; Shimizu, Emi; Kurayoshi, Kenta; Kugawa, Kazuyuki; Toh, Hiroyuki; Ohtani, Kiyoshi

    2015-09-01

    The transcription factor E2F is the principal target of the tumor suppressor pRB. E2F plays crucial roles not only in cell proliferation by activating growth-related genes but also in tumor suppression by activating pro-apoptotic and growth-suppressive genes. We previously reported that, in human normal fibroblasts, the tumor suppressor genes ARF, p27(Kip1) and TAp73 are activated by deregulated E2F activity induced by forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation. In contrast, growth-related E2F targets are activated by both E2F activities, underscoring the roles of deregulated E2F in tumor suppression in the context of dysfunctional pRB. In this study, to further understand the roles of deregulated E2F, we explored new targets that are specifically activated by deregulated E2F using DNA microarray. The analysis identified nine novel targets (BIM, RASSF1, PPP1R13B, JMY, MOAP1, RBM38, ABTB1, RBBP4 and RBBP7), many of which are involved in the p53 and RB tumor suppressor pathways. Among these genes, the BIM gene was shown to be activated via atypical E2F-responsive promoter elements and to contribute to E2F1-mediated apoptosis. Our results underscore crucial roles of deregulated E2F in growth suppression to counteract loss of pRB function. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  5. MicroRNAs, macrocontrol : Regulation of miRNA processing

    NARCIS (Netherlands)

    Slezak-Prochazka, Izabella; Durmus, Selvi; Kroesen, Bart-Jan; van den Berg, Anke

    MicroRNAs (miRNAs) are a set of small, non-protein-coding RNAs that regulate gene expression at the post-transcriptional level. Maturation of miRNAs comprises several regulated steps resulting in similar to 22-nucleotide single-stranded mature miRNAs. Regulation of miRNA expression can occur both at

  6. Altered expression of miRNAs in the uterus from a letrozole-induced rat PCOS model.

    Science.gov (United States)

    Li, Chunjin; Chen, Lu; Zhao, Yun; Chen, Shuxiong; Fu, Lulu; Jiang, Yanwen; Gao, Shan; Liu, Zhuo; Wang, Fengge; Zhu, Xiaoling; Rao, Jiahui; Zhang, Jing; Zhou, Xu

    2017-01-20

    Polycystic ovary syndrome (PCOS) causes female subfertility with ovarian disorders and may be associated with increased rate of early-pregnancy failure. Rat PCOS models were established using letrozole to understand the uterine pathogenesis of PCOS. The differential expression of microRNAs (miRNAs) was observed in rat uterus with PCOS. After estrous cycles were disrupted, significantly abnormal ovarian morphology and hormone level were observed in rats with PCOS. A total of 148 miRNAs differentially expressed were identified in the uterus from the letrozole-induced rat model compared with the control. These miRNAs included 111 upregulated miRNAs and 37 downregulated miRNAs. The differential expression of miR-484, miR-375-3p, miR-324-5p, and miR-223-3p was further confirmed by quantitative reverse transcription polymerase chain reaction. Bioinformatic analysis showed that these four miRNAs were predicted to regulate a large number of genes with different functions. Pathway analysis supported that target genes of miRNAs were involved in insulin secretion and signaling pathways, such as wnt, AMPK, PI3K-Akt, and Ras. These data indicated that miRNAs differentially expressed in rat uterus with PCOS may be associated with PCOS pathogenesis in the uterus. Our findings can help clarify the mechanism of uterine defects in PCOS. Copyright © 2016. Published by Elsevier B.V.

  7. Growth promotion-related miRNAs in Oncidium orchid roots colonized by the endophytic fungus Piriformospora indica.

    Directory of Open Access Journals (Sweden)

    Wei Ye

    Full Text Available Piriformospora indica, an endophytic fungus of Sebacinales, colonizes the roots of a wide range of host plants and establishes various benefits for the plants. In this work, we describe miRNAs which are upregulated in Oncidium orchid roots after colonization by the fungus. Growth promotion and vigorous root development were observed in Oncidium hybrid orchid, while seedlings were colonized by P. indica. We performed a genome-wide expression profiling of small RNAs in Oncidium orchid roots either colonized or not-colonized by P. indica. After sequencing, 24,570,250 and 24744,141 clean reads were obtained from two libraries. 13,736 from 17,036,953 unique sequences showed homology to either 86 miRNA families described in 41 plant species, or to 46 potential novel miRNAs, or to 51 corresponding miRNA precursors. The predicted target genes of these miRNAs are mainly involved in auxin signal perception and transduction, transcription, development and plant defense. The expression analysis of miRNAs and target genes demonstrated the regulatory functions they may participate in. This study revealed that growth stimulation of the Oncidium orchid after colonization by P. indica includes an intricate network of miRNAs and their targets. The symbiotic function of P. indica on Oncidium orchid resembles previous findings on Chinese cabbage. This is the first study on growth regulation and development of Oncidium orchid by miRNAs induced by the symbiotic fungus P. indica.

  8. Electric utility deregulation - A nuclear opportunity

    International Nuclear Information System (INIS)

    DeMella, J.R.

    2002-01-01

    The implications of electric deregulation are and will continue to be pervasive and significant. Not only will the fundamental monopoly regulatory concepts of managing electric utilities change but deregulation will have a profound and dramatic impact on the way electric generating plants are managed and operated. In the past, under the various approaches to financial regulation, the economic benefits normally attributed to competition or that would have otherwise been derived from competitive or open market forces, were assumed to be embodied in and inherent to the various processes, methods and principles of financial oversight of utility companies by regional, state and municipal regulatory authorities. Traditionally, under the various forms of regulated monopolies, a utility company, in exchange for an exclusive franchise to produce and sell electricity in a particular region, was obligated to provide an adequate supply to all consumers wanting it, at a price that was 'just and reasonable'. The determination of adequate supply and reasonable price was a matter of interpretation by utility companies and their regulators. In essence, the ultimate economic benefits, normally attributed to price equilibrium, in balance with supply, demand and other market forces, were expected to be achieved through a complex, political process of financial regulatory oversight, in which utility companies were usually reimbursed for all annual expenses or their 'cost of service' and additionally allowed to earn a 'reasonable' rate of return on plant investments. The result was often escalating electric prices, over supplies of electric capacity, by justifying unnecessarily high reserve margins based on long planning horizons (typically 20 years or greater) with extrapolated demand requirements that were generally in excess of what actually occurred over time. Although the regulatory process varied from country or country and region-to-region, the fundamental principles, which

  9. miRNAs associated with immune response in teleost fish.

    Science.gov (United States)

    Andreassen, Rune; Høyheim, Bjørn

    2017-10-01

    MicroRNAs (miRNAs) have been identified as important post transcriptional regulators of gene expression. In higher vertebrates, a subset of miRNAs has been identified as important regulators of a number of key genes in immune system gene networks, and this paper review recent studies on miRNAs associated with immune response in teleost fish. Challenge studies conducted in several species have identified differently expressed miRNAs associated with viral or bacterial infection. The results from these studies point out several miRNAs that are likely to have evolutionary conserved functions that are related to immune response in teleost fish. Changed expression levels of mature miRNAs from the five miRNA genes miRNA-462, miRNA-731, miRNA-146, miRNA-181 and miRNA-223 are observed following viral as well as bacterial infection in several teleost fish. Furthermore, significant changes in expression of mature miRNAs from the five genes miRNA-21, miRNA-155, miRNA-1388, miRNA-99 and miRNA-100 are observed in multiple studies of virus infected fish while changes in expression of mature miRNA from the three genes miRNA-122, miRNA-192 and miRNA-451 are observed in several studies of fish with bacterial infections. Interestingly, some of these genes are not present in higher vertebrates. The function of the evolutionary conserved miRNAs responding to infection depends on the target gene(s) they regulate. A few target genes have been identified while a large number of target genes have been predicted by in silico analysis. The results suggest that many of the targets are genes from the host's immune response gene networks. We propose a model with expected temporal changes in miRNA expression if they target immune response activators/effector genes or immune response inhibitors, respectively. The best way to understand the function of a miRNA is to identify its target gene(s), but as the amount of genome resources for teleost fish is limited, with less well characterized genomes

  10. IL-4 Up-Regulates MiR-21 and the MiRNAs Hosted in the CLCN5 Gene in Chronic Lymphocytic Leukemia.

    Directory of Open Access Journals (Sweden)

    Natalia Ruiz-Lafuente

    Full Text Available Interleukin 4 (IL-4 induces B-cell differentiation and survival of chronic lymphocytic leukemia (CLL cells. MicroRNAs (miRNAs regulate mRNA and protein expression, and several miRNAs, deregulated in CLL, might play roles as oncogenes or tumor suppressors. We have studied the miRNA profile of CLL, and its response to IL-4, by oligonucleotide microarrays, resulting in the detection of a set of 129 mature miRNAs consistently expressed in CLL, which included 41 differentially expressed compared to normal B cells (NBC, and 6 significantly underexpressed in ZAP-70 positive patients. IL-4 stimulation brought about up-regulation of the 5p and 3p mature variants of the miR-21 gene, which maps immediately downstream to the VMP1 gene, and of the mature forms generated from the miR-362 (3p and 5p, miR-500a (3p, miR-502 (3p, and miR-532 (3p and 5p genes, which map within the third intron of the CLCN5 gene. Both genes are in turn regulated by IL-4, suggesting that these miRNAs were regulated by IL-4 as passengers from their carrier genes. Their levels of up-regulation by IL-4 significantly correlated with cytoprotection. MiR-21 has been reported to be leukemogenic, associated to bad prognosis in CLL, and the miRNA more frequently overexpressed in human cancer. Up-regulation by IL-4 of miR-21 and the miRNAs hosted in the CLCN5 locus may contribute to evasion of apoptosis of CLL cells. These findings indicate that the IL-4 pathway and the miRNAs induced by IL-4 are promising targets for the development of novel therapies in CLL.

  11. Integrated miRNA and mRNA Expression Profiling in Inflamed Colon of Patients with Ulcerative Colitis

    Science.gov (United States)

    Van der Goten, Jan; Vanhove, Wiebe; Lemaire, Katleen; Van Lommel, Leentje; Machiels, Kathleen; Wollants, Willem-Jan; De Preter, Vicky; De Hertogh, Gert; Ferrante, Marc; Van Assche, Gert; Rutgeerts, Paul; Schuit, Frans; Vermeire, Séverine; Arijs, Ingrid

    2014-01-01

    Background Ulcerative colitis (UC) is associated with differential colonic expression of genes involved in immune response (e.g. IL8) and barrier integrity (e.g. cadherins). MicroRNAs (miRNAs) are regulators of gene expression and are involved in various immune-related diseases. In this study, we investigated (1) if miRNA expression in UC mucosa is altered and (2) if any of these changes correlate with mucosal mRNA expression. Integration of mRNA and miRNA expression profiling may allow the identification of functional links between dysregulated miRNAs and their target mRNA. Methodology Colonic mucosal biopsies were obtained from 17 UC (10 active and 7 inactive) patients and 10 normal controls. Total RNA was used to analyze miRNA and mRNA expression via Affymetrix miRNA 2.0 and Affymetrix Human Gene 1.0ST arrays, respectively. Both miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their corresponding predicted target mRNA. Microarray data were validated with qRT-PCR. Regulation of IL8 and CDH11 expression by hsa-miR-200c-3p was determined by luciferase reporter assays. Results When comparing active UC patients vs. controls, 51 miRNAs and 1543 gene probe sets gave significantly different signals. In contrast, in inactive UC vs. controls, no significant miRNA expression differences were found while 155 gene probe sets had significantly different signals. We then identified potential target genes of the significantly dysregulated miRNAs and genes in active UC vs. controls and found a highly significant inverse correlation between hsa-miR-200c-3p and IL8, an inflammatory marker, and between hsa-miR-200c-3p and CDH11, a gene related to intestinal epithelial barrier function. We could demonstrate that hsa-miR-200c-3p directly regulates IL8 and CDH11 expression. Conclusion Differential expression of immune- and barrier-related genes in inflamed UC mucosa may be influenced by altered expression of miRNAs

  12. Detection of miRNA regulatory effect on triple negative breast cancer transcriptome.

    Science.gov (United States)

    Martignetti, Loredana; Tesson, Bruno; Almeida, Anna; Zinovyev, Andrei; Tucker, Gordon C; Dubois, Thierry; Barillot, Emmanuel

    2015-01-01

    Identifying key microRNAs (miRNAs) contributing to the genesis and development of a particular disease is a focus of many recent studies. We introduce here a rank-based algorithm to detect miRNA regulatory activity in cancer-derived tissue samples which combines measurements of gene and miRNA expression levels and sequence-based target predictions. The method is designed to detect modest but coordinated changes in the expression of sequence-based predicted target genes. We applied our algorithm to a cohort of 129 tumour and healthy breast tissues and showed its effectiveness in identifying functional miRNAs possibly involved in the disease. These observations have been validated using an independent publicly available breast cancer dataset from The Cancer Genome Atlas. We focused on the triple negative breast cancer subtype to highlight potentially relevant miRNAs in this tumour subtype. For those miRNAs identified as potential regulators, we characterize the function of affected target genes by enrichment analysis. In the two independent datasets, the affected targets are not necessarily the same, but display similar enriched categories, including breast cancer related processes like cell substrate adherens junction, regulation of cell migration, nuclear pore complex and integrin pathway. The R script implementing our method together with the datasets used in the study can be downloaded here (http://bioinfo-out.curie.fr/projects/targetrunningsum).

  13. Expression Variations of miRNAs and mRNAs in Rice (Oryza sativa).

    Science.gov (United States)

    Wen, Ming; Xie, Munan; He, Lian; Wang, Yushuai; Shi, Suhua; Tang, Tian

    2016-12-31

    Differences in expression levels are an important source of phenotypic variation within and between populations. MicroRNAs (miRNAs) are key players in post-transcriptional gene regulation that are important for plant development and stress responses. We surveyed expression variation of miRNAs and mRNAs of six accessions from two rice subspecies Oryza sativa L. ssp. indica and Oryza sativa L. ssp. japonica using deep sequencing. While more than half (53.7%) of the mature miRNAs exhibit differential expression between grains and seedlings of rice, only 11.0% show expression differences between subspecies, with an additional 2.2% differentiated for the development-by-subspecies interaction. Expression variation is greater for lowly conserved miRNAs than highly conserved miRNAs, whereas the latter show stronger negative correlation with their targets in expression changes between subspecies. Using a permutation test, we identified 51 miRNA-mRNA pairs that correlate negatively or positively in expression level among cultivated rice. Genes involved in various metabolic processes and stress responses are enriched in the differentially expressed genes between rice indica and japonica subspecies. Our results indicate that stabilizing selection is the major force governing miRNA expression in cultivated rice, albeit positive selection may be responsible for much of the between-subspecies expression divergence. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  14. Nuclear communications and deregulated energy market

    International Nuclear Information System (INIS)

    Ruuskanen, Antti

    1998-01-01

    The electricity market a over the world is facing the most profound change ever. The market is to be deregulated, competition will be increased and companies privatised. The boom started from the UK but today the Nordic market is the most liberalised in the world. Nordic market consists of annual power sales around 350 TWh and only a modest growth potential of 12 percent per year. All fuels and all technologies meet in the marketplace. Nuclear has its good one fourth share of the production there. Nuclear is clearly for base-load with low marginal costs next to hydro electric power. There are four major players in the Nordic market. Swedish Vattenfall, IVO Group and Swedish Sydkraft are the three biggest in that order, and all of them have nuclear assets. The market is characterised by lowest power prices in Europe, two electricity exchanges and continuous power trade across the borders. The described market change from national and less open utility driven sector has clear impacts to companies strategies and consequently also to communications. All these circumstances demand, New target groups from corporate communications' point of view; new communications language to change to more business-like; new insider rules and new information practices; new business orientated journalists against a new reference group. This all opens new challenges and possibilities to re-build nuclear image. Market economy in electricity will also ease governmental nationally oriented energy policies and let market forces to decide whether investments are viable or not. This is positive for nuclear - again if and only if the power plants are managed in an economically viable way. Deregulation may open the market from political deadlock to new nuclear investments in case the above mentioned requirements are correct. All in all, market change comes sooner or later to regions not yet liberalised. It will challenge nuclear companies and their communications. The change always creates

  15. Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma.

    Science.gov (United States)

    Gai, Chiara; Camussi, Francesco; Broccoletti, Roberto; Gambino, Alessio; Cabras, Marco; Molinaro, Luca; Carossa, Stefano; Camussi, Giovanni; Arduino, Paolo G

    2018-04-18

    Several studies in the past have investigated the expression of micro RNAs (miRNAs) in saliva as potential biomarkers. Since miRNAs associated with extracellular vesicles (EVs) are known to be protected from enzymatic degradation, we evaluated whether salivary EVs from patients with oral squamous cell carcinoma (OSCC) were enriched with specific subsets of miRNAs. OSCC patients and controls were matched with regards to age, gender and risk factors. Total RNA was extracted from salivary EVs and the differential expression of miRNAs was evaluated by qRT-PCR array and qRT-PCR. The discrimination power of up-regulated miRNAs as biomarkers in OSCC patients versus controls was evaluated by the Receiver Operating Characteristic (ROC) curves. A preliminary qRT-PCR array was performed on samples from 5 OSCC patients and 5 healthy controls whereby a subset of miRNAs were identified that were differentially expressed. On the basis of these results, a cohort of additional 16 patients and 6 controls were analyzed to further confirm the miRNAs that were up-regulated or selectively expressed in the previous pilot study. The following miRNAs: miR-302b-3p and miR-517b-3p were expressed only in EVs from OSCC patients and miR-512-3p and miR-412-3p were up-regulated in salivary EVs from OSCC patients compared to controls with the ROC curve showing a good discrimination power for OSCC diagnosis. The Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis suggested the possible involvement of the miRNAs identified in pathways activated in OSCC. In this work, we suggest that salivary EVs isolated by a simple charge-based precipitation technique can be exploited as a non-invasive source of miRNAs for OSCC diagnosis. Moreover, we have identified a subset of miRNAs selectively enriched in EVs of OSCC patients that could be potential biomarkers.

  16. Genome-wide miRNA screening reveals miR-310 family members negatively regulate the immune response in Drosophila melanogaster via co-targeting Drosomycin.

    Science.gov (United States)

    Li, Yao; Li, Shengjie; Li, Ruimin; Xu, Jiao; Jin, Ping; Chen, Liming; Ma, Fei

    2017-03-01

    Although innate immunity mediated by Toll signaling has been extensively studied in Drosophila melanogaster, the role of miRNAs in regulating the Toll-mediated immune response remains largely unknown. In this study, following Gram-positive bacterial challenge, we identified 93 differentially expressed miRNAs via genome-wide miRNA screening. These miRNAs were regarded as immune response related (IRR). Eight miRNAs were confirmed to be involved in the Toll-mediated immune response upon Gram-positive bacterial infection through genetic screening of 41 UAS-miRNA lines covering 60 miRNAs of the 93 IRR miRNAs. Interestingly, four out of these eight miRNAs, miR-310, miR-311, miR-312 and miR-313, are clustered miRNAs and belong to the miR-310 family. These miR-310 family members were shown to target and regulate the expression of Drosomycin, an antimicrobial peptide produced by Toll signaling. Taken together, our study implies important regulatory roles of miRNAs in the Toll-mediated innate immune response of Drosophila upon Gram-positive bacterial infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Computational analysis of drought stress-associated miRNAs and miRNA co-regulation network in Physcomitrella patens.

    Science.gov (United States)

    Wan, Ping; Wu, Jun; Zhou, Yuan; Xiao, Junshu; Feng, Jie; Zhao, Weizhong; Xiang, Shen; Jiang, Guanglong; Chen, Jake Y

    2011-04-01

    miRNAs are non-coding small RNAs that involve diverse biological processes. Until now, little is known about their roles in plant drought resistance. Physcomitrella patens is highly tolerant to drought; however, it is not clear about the basic biology of the traits that contribute P. patens this important character. In this work, we discovered 16 drought stress-associated miRNA (DsAmR) families in P. patens through computational analysis. Due to the possible discrepancy of expression periods and tissue distributions between potential DsAmRs and their targeting genes, and the existence of false positive results in computational identification, the prediction results should be examined with further experimental validation. We also constructed an miRNA co-regulation network, and identified two network hubs, miR902a-5p and miR414, which may play important roles in regulating drought-resistance traits. We distributed our results through an online database named ppt-miRBase, which can be accessed at http://bioinfor.cnu.edu.cn/ppt_miRBase/index.php. Our methods in finding DsAmR and miRNA co-regulation network showed a new direction for identifying miRNA functions. Copyright © 2011 Beijing Genomics Institute. Published by Elsevier Ltd. All rights reserved.

  18. Bidding Strategy for Deregulated Power Markets

    Directory of Open Access Journals (Sweden)

    Preeti

    2016-07-01

    Full Text Available Load and Price forecasting play a vital role in enhancing the energy-efficient and reliable operation of electricity companies. This paper proposes a bidding strategy based on Short-Term Load Forecasting and Short-Term Price Forecasting technique used in the deregulated electricity market. The main aim of the proposed approach is to forecast load and price so as to enhance the efficiency of the power system. The input variables which are taken into account include the past load, weather and calendar data and price bidding on an hourly basis. A comparison of the accuracy of fuzzy, artificial neural network and state estimation technique is performed on the two datasets of the electricity markets of IEEE Reliability Test System and Haryana State Load Dispatch Centre. The forecasted load and price aids in increasing the profits by judiciously utilizing the generators with less cost in periods of high demand. Price forecasts are used to determine the cost of electric power and hence, plan the budget according to the consumption of power over the scheduled interval.

  19. Deregulation and Nuclear Training: Cost Effective Alternatives

    International Nuclear Information System (INIS)

    Richard P. Coe; Patricia A. Lake

    2000-01-01

    Training is crucial to the success of any organization. It is also expensive, with some estimates exceeding $50 billion annually spent on training by U.S. corporations. Nuclear training, like that of many other highly technical organizations, is both crucial and costly. It is unlikely that the amount of training can be significantly reduced. If anything, current trends indicate that training needs will probably increase as the industry and workforce ages and changes. With the advent of energy deregulation in the United States, greater pressures will surface to make the costs of energy more cost-competitive. This in turn will drive businesses to more closely examine existing costs and find ways to do things in a more cost-effective way. The commercial nuclear industry will be no exception, and nuclear training will be equally affected. It is time for nuclear training and indeed the entire nuclear industry to begin using more aggressive techniques to reduce costs. This includes the need for nuclear training to find alternatives to traditional methods for the delivery of cost-effective high-quality training that meets regulatory requirements and produces well-qualified personnel capable of working in an efficient and safe manner. Computer-based and/or Web-based training are leading emerging technologies

  20. Coal marketability: Effects of deregulation and regulation

    International Nuclear Information System (INIS)

    Attanasi, E.

    2000-01-01

    Electrical utility deregulation will force power plants to compete for sales because they will not longer have captive markets. Market uncertainty and uncertainty about future environmental regulations have encouraged power plants to shift to low sulfur coal and/or to use emissions allowances to comply with Phase 2 of the 1990 Clean Air Act Amendments. Mines in Northern and Central Appalachia and the Illinois Basin shipped 240 million tons of non-compliance coal to power plants without scrubbers in 1997. Under Phase 2, this coal will be replaced by low sulfur coal and/or be used with emission permits. It is possible that Powder River Basin coal production will have to increase by over 200 million tons/year to meet new demand. The prices of emissions permits will impose penalties on non-compliance coal that will probably drive out marginal coal producers. For example, if the cost of an emission permit is $200, coal from the Pittsburgh bed could bear a sulfur penalty of $6.55 per ton and similarly, coal from the Herrinbed could bear a penalty of $8.64 per ton

  1. Selective release of miRNAs via extracellular vesicles is associated with house-dust mite allergen-induced airway inflammation.

    Science.gov (United States)

    Gon, Y; Maruoka, S; Inoue, T; Kuroda, K; Yamagishi, K; Kozu, Y; Shikano, S; Soda, K; Lötvall, J; Hashimoto, S

    2017-12-01

    MicroRNAs (miRNAs) may facilitate cell-to-cell communication via extracellular vesicles (EVs). The biological roles of miRNAs in EVs on allergic airway inflammation are unclear. Airway-secreted EVs (AEVs) were isolated from bronchoalveolar lavage fluid (BALF) of control and house-dust mite (HDM) allergen-exposed HDM-sensitized mice. The expression of miRNAs in AEVs or miRNAs and mRNAs in lung tissue was analysed using miRNA microarray. The amount of AEV increased 8.9-fold in BALF from HDM-exposed mice compared with that from sham-control mice. HDM exposure resulted in significant changes in the expression of 139 miRNAs in EVs and 175 miRNAs in lung tissues, with 54 miRNAs being common in both samples. Expression changes of these 54 miRNAs between miRNAs in AEVs and lung tissues after HDM exposure were inversely correlated. Computational analysis revealed that 31 genes, including IL-13 and IL-5Ra, are putative targets of the miRNAs up-regulated in AEVs but down-regulated in lung tissues after HDM exposure. The amount of AEV in BALF after HDM exposure was diminished by treatment with the sphingomyelinase inhibitor GW4869. The treatment with GW4869 also decreased Th2 cytokines and eosinophil counts in BALFs and reduced eosinophil accumulation in airway walls and mucosa. These results indicate that selective sorting of miRNA including Th2 inhibitory miRNAs into AEVs and increase release to the airway after HDM exposure would be involved in the pathogenesis of allergic airway inflammation. © 2017 John Wiley & Sons Ltd.

  2. DNA methyltransferase 1-targeting miRNA-148aof dairymilk: apotential bioactive modifier of thehumanepigenome

    Directory of Open Access Journals (Sweden)

    Bodo C. Melnik

    2017-09-01

    Full Text Available Background: The perception of milk has changed from a “simple food” to a more sophisticated bioactive functional signaling system that promotes mTORC1-driven postnatal anabolism, growth, and development of the newborn infant. Accumulating evidence supports the view that milk´s miRNAs significantly contribute to these processes. The most abundant miRNA of milk found in milk fat and milk exosomes is miRNA-148a, which targets DNA methyltransferase 1 (DNMT1, a pivotal epigenetic regulator that suppresses transcription. Furthermore, milk-derived miRNA-125b, miRNA-30d, and miRNA-25 target TP53, the guardian of the genome that interacts with DNMT1 and regulates metabolism, cell kinetics, and apoptosis. Thus, the question arose whether cow´s milk-derived miRNAs may modify epigenetic regulation of the human milk consumer. Methods: To understand the potential impact of dairy milk consumption on human epigenetics, we have analyzed all relevant research-based bioinformatics data related to milk, milk miRNAs, epigenetic regulation, and lactation performance with special attention to bovine miRNAs that modify gene expression of DNA methyltransferase 1 (DNMT1 and p53 (TP53, the two guardians of the mammalian genome. By means of translational research and comparative functional genomics, we investigated the potential impact of cow´s milk miRNAs on epigenetic regulation of human DNMT1, TP53, FOXP3, and FTO, which are critically involved in immunologic and metabolic programming respectively. miRNA sequences have been obtained from mirbase.org. miRNA-target site prediction has been performed using TargetScan release 7.0. Results: The most abundant miRNA of cow´s milk is miRNA-148a, which represents more than 10% of all miRNAs of cow´s milk, survives pasteurization and refrigerated storage. The seed sequence of human and bovine miRNA-148a-3p is identical. Furthermore, human and bovine DNMT1 mRNA share 88% identity. The miRNA-148a 7mer seed is conserved in

  3. Deregulation of the electric utility industry - implications for nuclear power

    International Nuclear Information System (INIS)

    Fern, A.Rose

    2000-01-01

    The deregulation movement sweeping the international electric utility community represents a dramatic shift om the traditional business model of utilities. This paper will focus on deregulation in thc United States and the new challenges for nuclear power plant operators. An overview of the new operating models being implemented in the US will lead into a discussion on new economic and operating concerns for nuclear power plant operators. (author)

  4. Deregulation of the electric utility industry - implications for nuclear power

    International Nuclear Information System (INIS)

    Fern, A.R.

    2001-01-01

    The deregulation movement sweeping the international electric utility community represents a dramatic shift from the traditional utility business model. This paper will focus on deregulation in the United States and the new challenges for nuclear power plant operators. An overview of the new operating models being implemented in the US will lead into a discussion on new economic and operating concerns for nuclear power plant operators. (author)

  5. Oxidative Stress Alters miRNA and Gene Expression Profiles in Villous First Trimester Trophoblasts

    Directory of Open Access Journals (Sweden)

    Courtney E. Cross

    2015-01-01

    Full Text Available The relationship between oxidative stress and miRNA changes in placenta as a potential mechanism involved in preeclampsia (PE is not fully elucidated. We investigated the impact of oxidative stress on miRNAs and mRNA expression profiles of genes associated with PE in villous 3A first trimester trophoblast cells exposed to H2O2 at 12 different concentrations (0-1 mM for 0.5, 4, 24, and 48 h. Cytotoxicity, determined using the SRB assay, was used to calculate the IC50 of H2O2. RNA was extracted after 4 h exposure to H2O2 for miRNA and gene expression profiling. H2O2 exerted a concentration- and time-dependent cytotoxicity on 3A trophoblast cells. Short-term exposure of 3A cells to low concentration of H2O2 (5% of IC50 significantly altered miRNA profile as evidenced by significant changes in 195 out of 595 evaluable miRNAs. Tool for annotations of microRNAs (TAM analysis indicated that these altered miRNAs fall into 43 clusters and 34 families, with 41 functions identified. Exposure to H2O2 altered mRNA expression of 22 out of 84 key genes involved in dysregulation of placental development. In conclusion, short-term exposure of villous first trimester trophoblasts to low concentrations of H2O2 significantly alters miRNA profile and expression of genes implicated in placental development.

  6. Identification and comparative analysis of cadmium tolerance-associated miRNAs and their targets in two soybean genotypes.

    Directory of Open Access Journals (Sweden)

    Xiaolong Fang

    Full Text Available MicroRNAs (miRNAs play crucial roles in regulating the expression of various stress responses genes in plants. To investigate soybean (Glycine max miRNAs involved in the response to cadmium (Cd, microarrays containing 953 unique miRNA probes were employed to identify differences in the expression patterns of the miRNAs between different genotypes, Huaxia3 (HX3, Cd-tolerant and Zhonghuang24 (ZH24, Cd-sensitive. Twenty six Cd-responsive miRNAs were identified in total. Among them, nine were detected in both cultivars, while five were expressed only in HX3 and 12 were only in ZH24. The expression of 16 miRNAs was tested by qRT-PCR and most of the identified miRNAs were found to have similar expression patterns with microarray. Three hundred and seventy six target genes were identified for 204 miRNAs from a mixture degradome library, which was constructed from the root of HX3 and ZH24 with or without Cd treatment. Fifty five genes were identified to be cleaved by 14 Cd-responsive miRNAs. Gene ontology (GO annotations showed that these target transcripts are implicated in a broad range of biological processes. In addition, the expression patterns of ten target genes were validated by qRT-PCR. The characterization of the miRNAs and the associated target genes in response to Cd exposure provides a framework for understanding the molecular mechanism of heavy metal tolerance in plants.

  7. Global approaches to the role of miRNAs in drug-induced changes in gene expression

    Directory of Open Access Journals (Sweden)

    Jodi E Eipper-Mains

    2012-06-01

    Full Text Available Neurons modulate gene expression with subcellular precision through excitation-coupled local protein synthesis, a process that is regulated in part through the involvement of microRNAs (miRNAs, a class of small noncoding RNAs. The biosynthesis of miRNAs is reviewed, with special emphasis on miRNA families, the subcellular localization of specific miRNAs in neurons, and their potential roles in the response to drugs of abuse. For over a decade, DNA microarrays have dominated genome-wide gene expression studies, revealing widespread effects of drug exposure on neuronal gene expression. We review a number of recent studies that explore the emerging role of miRNAs in the biochemical and behavioral responses to cocaine. The more powerful next-generation sequencing technology offers certain advantages and is supplanting microarrays for the analysis of complex transcriptomes. RNA-Seq is unparalleled in its ability to identify and quantify low-abundance transcripts without prior sequence knowledge, facilitating the accurate detection and quantification of miRNAs expressed in total tissue and miRNAs localized to postsynaptic densities (PSDs. We previously identified cocaine-responsive miRNAs, synaptically-enriched and depleted miRNA families, and confirmed cocaine-induced changes in protein expression for several bioinformatically predicted target genes. The miR-8 family was found to be highly enriched and cocaine-regulated at the PSD, where its members may modulate expression of cell adhesion molecules. An integrative approach that combines mRNA, miRNA, and protein expression profiling in combination with focused single gene studies and innovative behavioral paradigms should facilitate the development of more effective therapeutic approaches to treat addiction.

  8. Cold-responsive miRNAs and their target genes in the wild eggplant species Solanum aculeatissimum.

    Science.gov (United States)

    Yang, Xu; Liu, Fei; Zhang, Yu; Wang, Lu; Cheng, Yu-Fu

    2017-12-29

    Low temperature is an important abiotic stress in plant growth and development, especially for thermophilic plants. Eggplants are thermophilic vegetables, although the molecular mechanism of their response to cold stress remains to be elucidated. MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that play an essential role during plant development and stress responses. Although the role of many plant miRNAs in facilitating chilling tolerance has been verified, little is known about the mechanisms of eggplant chilling tolerance. Here, we used high-throughput sequencing to extract the miRNA and target genes expression profiles of Solanum aculeatissimum (S. aculeatissimum) under low temperature stress at different time periods(0 h, 2 h, 6 h, 12 h, 24 h). Differentially regulated miRNAs and their target genes were analyzed by comparing the small RNA (sRNA) and miRBase 20.0 databases using BLAST or BOWTIE, respectively. Fifty-six down-regulated miRNAs and 28 up-regulated miRNAs corresponding to 220 up-regulated mRNAs and 94 down-regulated mRNAs, respectively, were identified in S. aculeatissimum. Nine significant differentially expressed miRNAs and twelve mRNAs were identified by quantitative Real-time PCR and association analysis, and analyzed for their GO function enrichment and KEGG pathway association. In summary, numerous conserved and novel miRNAs involved in the chilling response were identified using high-throughput sequencing, which provides a theoretical basis for the further study of low temperature stress-related miRNAs and the regulation of cold-tolerance mechanisms of eggplant at the miRNA level.

  9. Discovering miRNA regulatory networks in Holt-Oram Syndrome using a Zebrafish model

    Directory of Open Access Journals (Sweden)

    Romina D'Aurizio

    2016-07-01

    Full Text Available microRNAs (miRNAs are small non-coding RNAs that play an important role in the post- transcriptional regulation of gene expression. miRNAs are involved in the regulation of many biological processes such as differentiation, apoptosis and cell proliferation. miRNAs are expressed in embryonic, postnatal, and adult hearts and they have a key role in the regulation of gene expression during cardiovascular development and disease. Aberrant expression of miRNAs is associated with abnormal cardiac cell differentiation and dysfunction. Tbx5 is a member of the T-box gene family which acts as transcription factor involved in the vertebrate heart development. Alteration of Tbx5 level affects the expression of hundreds of genes. Haploinsufficiency and gene duplication of Tbx5 are at the basis of the cardiac abnormalities associated with Holt-Oram syndrome (HOS. Recent data indicate that miRNAs might be an important part of the regulatory circuit through which Tbx5 controls heart development. Using high-throughput technology we characterized genome-widely the miRNA and mRNA expression profiles in WT and Tbx5 depleted zebrafish embryos at two developmental time points, 24 and 48 hours post fertilization (hpf. We found that several miRNAs which are potential effectors of Tbx5 are differentially expressed, some of them are already known to be involved in cardiac development and functions, such as miR-30, miR-34, miR-190, miR-21. We performed an integrated analysis of miRNA expression data with gene expression profiles to refine computational target prediction approaches by means of the inversely correlation of miRNA-mRNA expressions. Interestingly these targets have roles in cardiac contractility, cardiomyocyte proliferation/apoptosis and valve formation which are crucial functions regulated by Tbx5. This approach allowed to discover complex regulatory circuits involving novel miRNAs and protein coding genes not considered before in the HOS such as miR-34a and

  10. Comparative Analysis of Fruit Ripening-Related miRNAs and Their Targets in Blueberry Using Small RNA and Degradome Sequencing.

    Science.gov (United States)

    Hou, Yanming; Zhai, Lulu; Li, Xuyan; Xue, Yu; Wang, Jingjing; Yang, Pengjie; Cao, Chunmei; Li, Hongxue; Cui, Yuhai; Bian, Shaomin

    2017-12-19

    MicroRNAs (miRNAs) play vital roles in the regulation of fruit development and ripening. Blueberry is an important small berry fruit crop with economical and nutritional value. However, nothing is known about the miRNAs and their targets involved in blueberry fruit ripening. In this study, using high-throughput sequencing of small RNAs, 84 known miRNAs belonging to 28 families and 16 novel miRNAs were identified in white fruit (WF) and blue fruit (BF) libraries, which represent fruit ripening onset and in progress, respectively. Among them, 41 miRNAs were shown to be differentially expressed during fruit maturation, and 16 miRNAs representing 16 families were further chosen to validate the sRNA sequencing data by stem-loop qRT-PCR. Meanwhile, 178 targets were identified for 41 known and 7 novel miRNAs in WF and BF libraries using degradome sequencing, and targets of miR160 were validated using RLM-RACE (RNA Ligase-Mediated (RLM)-Rapid Amplification of cDNA Ends) approach. Moreover, the expression patterns of 6 miRNAs and their targets were examined during fruit development and ripening. Finally, integrative analysis of miRNAs and their targets revealed a complex miRNA-mRNA regulatory network involving a wide variety of biological processes. The findings will facilitate future investigations of the miRNA-mediated mechanisms that regulate fruit development and ripening in blueberry.

  11. Decision modelling tools for utilities in the deregulated energy market

    Energy Technology Data Exchange (ETDEWEB)

    Makkonen, S. [Process Vision Oy, Helsinki (Finland)

    2005-07-01

    This thesis examines the impact of the deregulation of the energy market on decision making and optimisation in utilities and demonstrates how decision support applications can solve specific encountered tasks in this context. The themes of the thesis are presented in different frameworks in order to clarify the complex decision making and optimisation environment where new sources of uncertainties arise due to the convergence of energy markets, globalisation of energy business and increasing competition. This thesis reflects the changes in the decision making and planning environment of European energy companies during the period from 1995 to 2004. It also follows the development of computational performance and evolution of energy information systems during the same period. Specifically, this thesis consists of studies at several levels of the decision making hierarchy ranging from top-level strategic decision problems to specific optimisation algorithms. On the other hand, the studies also follow the progress of the liberalised energy market from the monopolistic era to the fully competitive market with new trading instruments and issues like emissions trading. This thesis suggests that there is an increasing need for optimisation and multiple criteria decision making methods, and that new approaches based on the use of operations research are welcome as the deregulation proceeds and uncertainties increase. Technically, the optimisation applications presented are based on Lagrangian relaxation techniques and the dedicated Power Simplex algorithm supplemented with stochastic scenario analysis for decision support, a heuristic method to allocate common benefits and potential losses of coalitions of power companies, and an advanced Branch- and-Bound algorithm to solve efficiently nonconvex optimisation problems. The optimisation problems are part of the operational and tactical decision making process that has become very complex in the recent years. Similarly

  12. Stochastic optimization of electric power generation in a deregulated market

    Science.gov (United States)

    Valenzuela, Jorge Fernando

    The electric power industry is in the process of undergoing deregulation. In the new unregulated environment, decision making will become much harder because of the uncertainties involved in the marketplace. The wholesale price of electricity will no longer be predetermined but set by free competition. In this dissertation, a new formulation of the unit commitment problem that takes into account the effects of deregulation is proposed. The unit commitment problem is here expressed as a stochastic optimization problem in which the objective is to maximize expected profits and the decision actions are required to meet the standard operating constraints. The formulation includes the option of trading with a power pool at market-clearing prices. It is shown that when the spot market of electricity is brought into the formulation, the optimization problem can be separated by individual units. There is no need to iterate on the values of the Lagrange multipliers because they become equivalent to the market-clearing prices of electricity. An algorithm written in C is developed to solve the optimization problem via probabilistic dynamic programming. The solution procedure requires the evaluation of the joint probability distribution of the market-clearing price at two different hours. The hourly market-clearing price is modeled based on the underlying stochastic process of the marginal unit, which depends on two sources of uncertainty, the aggregate load and the generating unit availabilities. The exact computation of the distribution is prohibitive for systems with more than eight units. Three approximation methods are proposed and evaluated for larger systems. The results show that the large deviation approximation is very accurate for computing tail probabilities, and accurate solutions are therefore obtained using this method in solving the stochastic optimization problem. However, the computational time for a market of 150 units becomes prohibitive. The Edgeworth and

  13. Decision modelling tools for utilities in the deregulated energy market

    International Nuclear Information System (INIS)

    Makkonen, S.

    2005-01-01

    This thesis examines the impact of the deregulation of the energy market on decision making and optimisation in utilities and demonstrates how decision support applications can solve specific encountered tasks in this context. The themes of the thesis are presented in different frameworks in order to clarify the complex decision making and optimisation environment where new sources of uncertainties arise due to the convergence of energy markets, globalisation of energy business and increasing competition. This thesis reflects the changes in the decision making and planning environment of European energy companies during the period from 1995 to 2004. It also follows the development of computational performance and evolution of energy information systems during the same period. Specifically, this thesis consists of studies at several levels of the decision making hierarchy ranging from top-level strategic decision problems to specific optimisation algorithms. On the other hand, the studies also follow the progress of the liberalised energy market from the monopolistic era to the fully competitive market with new trading instruments and issues like emissions trading. This thesis suggests that there is an increasing need for optimisation and multiple criteria decision making methods, and that new approaches based on the use of operations research are welcome as the deregulation proceeds and uncertainties increase. Technically, the optimisation applications presented are based on Lagrangian relaxation techniques and the dedicated Power Simplex algorithm supplemented with stochastic scenario analysis for decision support, a heuristic method to allocate common benefits and potential losses of coalitions of power companies, and an advanced Branch- and-Bound algorithm to solve efficiently nonconvex optimisation problems. The optimisation problems are part of the operational and tactical decision making process that has become very complex in the recent years. Similarly

  14. miRNA Involved in Six1-Induced Breast Cancer

    Science.gov (United States)

    2013-05-01

    First author review based on TGF-β biology: Smith AL, Robin TP, & Ford HL. Molecular Pathways: Targeting the TGF-β pathway for Cancer Therapy ...this pathway a difficult target in cancer therapy . Additionally, our data shows that the presence of Six1 in cells will implement the switch of TGFβ...was calculated by log-rank analysis. A full colour version of this figure is available at the Oncogene journal online. The miR-106b-25 cluster

  15. AmiRNA Designer - new method of artificial miRNA design.

    Science.gov (United States)

    Mickiewicz, Agnieszka; Rybarczyk, Agnieszka; Sarzynska, Joanna; Figlerowicz, Marek; Blazewicz, Jacek

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that have been found in most of the eukaryotic organisms. They are involved in the regulation of gene expression at the post-transcriptional level in a sequence specific manner. MiRNAs are produced from their precursors by Dicer-dependent small RNA biogenesis pathway. Involvement of miRNAs in a wide range of biological processes makes them excellent candidates for studying gene function or for therapeutic applications. For this purpose, different RNA-based gene silencing techniques have been developed. Artificially transformed miRNAs (amiRNAs) targeting one or several genes of interest represent one of such techniques being a potential tool in functional genomics. Here, we present a new approach to amiRNA*design, implemented as AmiRNA Designer software. Our method is based on the thermodynamic analysis of the native miRNA/miRNA* and miRNA/target duplexes. In contrast to the available automated tools, our program allows the user to perform analysis of natural miRNAs for the organism of interest and to create customized constraints for the design stage. It also provides filtering of the amiRNA candidates for the potential off-targets. AmiRNA Designer is freely available at http://www.cs.put.poznan.pl/arybarczyk/AmiRNA/.

  16. Roles of miRNAs in microcystin-LR-induced Sertoli cell toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yuan [Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); Wang, Hui [The Centre for Individualized Medication, Linköping University Hospital, Linköping University, Linköping SE-58185 (Sweden); Wang, Cong [Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); Qiu, Xuefeng [Department of Urology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008 (China); Benson, Mikael [The Centre for Individualized Medication, Linköping University Hospital, Linköping University, Linköping SE-58185 (Sweden); Yin, Xiaoqin [Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); Xiang, Zou [Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Institute of Biomedicine, University of Gothenburg, Gothenburg (Sweden); Li, Dongmei, E-mail: lidm@nju.edu.cn [Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); and others

    2015-08-15

    Microcystin (MC)-LR, a cyclic heptapeptide, is a potent reproductive system toxin. To understand the molecular mechanisms of MC-induced reproductive system cytotoxicity, we evaluated global changes of miRNA and mRNA expression in mouse Sertoli cells following MC-LR treatment. Our results revealed that the exposure to MC-LR resulted in an altered miRNA expression profile that might be responsible for the modulation of mRNA expression. Bio-functional analysis indicated that the altered genes were involved in specific cellular processes, including cell death and proliferation. Target gene analysis suggested that junction injury in Sertoli cells exposed to MC-LR might be mediated by miRNAs through the regulation of the Sertoli cell-Sertoli cell pathway. Collectively, these findings may enhance our understanding on the modes of action of MC-LR on mouse Sertoli cells as well as the molecular mechanisms underlying the toxicity of MC-LR on the male reproductive system. - Highlights: • miRNAs were altered in Sertoli cells exposed to MC-LR. • Alerted genes were involved in different cell functions including the cell morphology. • MC-LR adversely affected Sertoli cell junction formation through the regulating miRNAs.

  17. Role of human GRP75 in miRNA mediated regulation of dengue virus replication.

    Science.gov (United States)

    Kakumani, Pavan Kumar; Medigeshi, Guruprasad R; Kaur, Inderjeet; Malhotra, Pawan; Mukherjee, Sunil K; Bhatnagar, Raj K

    2016-07-15

    In recent times, RNAi has emerged as an important defence system that regulates replication of pathogens in host cells. Many RNAi related host factors especially the host miRNAs play important roles in all intrinsic cellular functions, including viral infection. We have been working on identification of mammalian host factors involved in Dengue virus infection. In the present study, we identified Glucose Regulated Protein 75kDa (GRP75), as a host factor that is associated with dicer complex, in particular with HADHA (trifunctional enzyme subunit alpha, mitochondrial), an auxiliary component of dicer complex. Knockdown of GRP75 by respective siRNAs in Huh-7 cells resulted in the accumulation of dengue viral genomic RNA suggesting a role of GRP75 in regulating dengue virus replication in human cell lines. To elucidate the mode of action of GRP75, we over expressed the protein in Huh-7 cells and analysed the host miRNAs processing. The results revealed that, GRP75 is involved in processing of host miRNA, hsa-mir-126, that down regulates dengue virus replication. These findings suggest a regulatory role of human miRNA pathway especially GRP75 protein and hsa-mir-126 in dengue virus replication. These results thus provide insights into the role of miRNAs and RNAi machinery in dengue life cycle. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Alteration of the miRNA expression profile in male porcine anterior pituitary cells in response to GHRH and CST and analysis of the potential roles for miRNAs in regulating GH.

    Science.gov (United States)

    Qi, Qi-En; Xi, Qian-Yun; Ye, Rui-Song; Chen, Ting; Cheng, Xiao; Li, Chao-Yun; Zhu, Xiao-Tong; Shu, Gang; Wang, Li-Na; Jiang, Qing-Yan; Zhang, Yong-Liang

    2015-04-01

    Growth hormone releasing hormone (GHRH) is a major positive regulator of growth hormone (GH) in the anterior pituitary gland, while cortistatin's (CST) role is negative. miRNAs (microRNAs or miRs) are small RNA molecules modulating gene expression at the post-transcriptional level. However, little is known about the function of miRNAs in the regulation of GH synthesis and/or secretion. This study investigated potential functional miRNAs involved in GH secretion in the normal porcine pituitary. Primary porcine anterior pituitary cells were cultivated and then treated with 10 nmol/L GHRH and 100 nmol/L CST, respectively. The effects of GHRH and CST on GH secretion were determined using RIA. miRNA microarrays were employed to analyze miRNA expression after treatment and then differentially expressed miRNAs were screened. Bioinformatics analysis was used to analyze the potential targets in growth hormone regulation of altered miRNAs. Furthermore, functional experiments were conducted to study the function of ssc-let-7c. GHRH significantly promoted GH secretion, while CST suppressed GH secretion. 19 and 35 differentially expressed miRNAs were identified in response to GHRH and CST treatments respectively. Verification of 5 randomly selected miRNAs by quantitative real-time PCR (qRT-PCR) showed similar changes with microarray analysis. Target analysis showed that some miRNAs may be involved in GH secretion-related pathways. Importantly, ssc-let-7c was predicted to target GH1 and GHRHR mRNA 3'untranslated regions (3'UTRs), which was supported by luciferase reporter assay. Furthermore, functional experimental results showed that ssc-let-7c was involved in GH secretion regulation, and overexpression of ssc-let-7c inhibited GH secretion in porcine anterior pituitary cells. GHRH and CST modulated porcine pituitary cell miRNA expression. Bioinformatics analysis revealed a complicated network among differentially expressed miRNAs, GH regulation-related genes and hormones. More

  19. The undertow of de-regulation : re-regulation

    International Nuclear Information System (INIS)

    Bradford, J.A.

    2003-01-01

    Alberta, Ontario and New Brunswick each initiated steps to deregulate their electric power industries in order to remain competitive with lower electricity rates in certain American states where the industry was also moving towards deregulation. This paper considers how the original sweep of deregulation policy goals succumbed to electricity re regulation policies. The decision by British Columbia to re-examine its deregulation plans in light of the experience in Canada's 3 other province's was also examined. The paper describes the electric power industry from 1900 to 1960s, before the deregulation wave hit the industry and then proceeds to the 1970s which was marked by the oil embargo. The 1980s saw a new era of policy shifts towards deregulation and privatization activity which was intended to introduce competition into regulated industries. Technological advances were taking place in the electricity sector, improving the viability of small gas turbines and making cogeneration possible. In the 1990s, Alberta was the first Canadian province to introduce competition to its electricity industry in an effort to remain competitive with neighbouring U.S. jurisdictions. By the 1990s Ontario's vertically integrated electricity industry was in trouble and recommendations were made to dissolve Ontario's Hydro One monopoly, particularly in power generation. In 1999, New Brunswick restructured its electricity industry to remain competitive with New England's electricity industry. The paper describes the gradual pull back from deregulation by all three provinces and the measures taken to impose price controls. Both industry and consumers paid a price for major policy changes. Complete competition in New Brunswick never materialized. It was suggested that controlled competition will likely move the electricity industry in the future. 40 refs

  20. MirPlex: a tool for identifying miRNAs in high-throughput sRNA datasets without a genome.

    Science.gov (United States)

    Mapleson, Daniel; Moxon, Simon; Dalmay, Tamas; Moulton, Vincent

    2013-01-01

    MicroRNAs (miRNAs) are a class of small non-coding RNA (sRNA) involved in gene regulation through mRNA decay and translational repression. In animals, miRNAs have crucial regulatory functions during embryonic development and they have also been implicated in several diseases such as cancer, cardiovascular and neurodegenerative disorders. As such, it is of importance to successfully characterize new miRNAs in order to further study their function. Recent advances in sequencing technologies have made it possible to capture a high-resolution snapshot of the complete sRNA content of an organism or tissue. A common approach to miRNA detection involves searching such data for telltale miRNA signatures. However, current miRNA prediction tools usually require a sequenced genome to analyse regions flanking aligned sRNA reads in order to identify characteristic miRNA hairpin secondary structures. Since only a handful of published genomes are available, there is a need for novel methods to identify miRNAs in sRNA datasets from high-throughput sequencing devices without requiring a reference genome. This paper presents miRPlex, a tool for miRNA prediction that requires only sRNA datasets as input. Mature miRNAs are predicted from such datasets through a multi-stage process, involving filtering, miRNA:miRNA* duplex generation and duplex classification using a support vector machine. Tests on sRNA datasets from model animals demonstrate that the tool is effective at predicting genuine miRNA duplexes, and, for some sets, achieves a high degree of precision when considering only the mature sequence. Copyright © 2012 Wiley Periodicals, Inc.

  1. Current perspectives in microRNAs (miRNA)

    CERN Document Server

    Ying, Shao-Yao

    2008-01-01

    In this book, many new perspectives of the miRNA research are reviewed and discussed. These new findings provide significant insight into the various mechanisms of miRNAs and offer a great opportunity in developing new therapeutic interventions.

  2. German energy policy in deregulated Europe

    International Nuclear Information System (INIS)

    Kuhnt, D.

    2000-01-01

    The author argues in favor of a more fact-oriented German energy policy: Firstly, German energy policy must accept the new European framework of a market economy. This means that German utilities must no longer be burdened with the implementation of political objectives. The German power industry needs a level playing field for competition on a European scale. Consequently, also the European partner countries should not limit themselves to the minimum conditions of the Single Market Directive in opening their markets. Secondly, German energy policy must develop new forms of cooperation with the power industry so as to maintain domestic employment and the addition of value despite considerably stronger competitive pressure. Also the conflicting targets of sustainability, continuity of supply, and economic viability must not only be discussed, but must be turned into productive approaches. Thirdly, this means that there must be no inadmissible solution in matters nuclear. If the German power industry is to remain strong, in the interest of domestic jobs and opportunities for the future, it must not lose any more domestic market share to other European companies. Fourthly, we need a new energy policy which takes cognizance of the results of market development in a more rational, less emotional way. In this respect, it should be limited henceforth to supporting renewable energies and technologies so as to enhance energy efficiency in line with market requirements. Fifthly, German energy policy must not commit the mistake of enforcing deregulation and, at the same time, exempting large segments of the market from competition. Thus, the planned expansion of renewable energies, and the increase in cogeneration to more than thirty percent of the German electricty generation, by way of quotas and revenues for electricity from these sources fed into the public grid, are incompatible with competition in Europe. The electricity tax within the framework of the eco tax, the

  3. Role of Viral miRNAs and Epigenetic Modifications in Epstein-Barr Virus-Associated Gastric Carcinogenesis.

    Science.gov (United States)

    Giudice, Aldo; D'Arena, Giovanni; Crispo, Anna; Tecce, Mario Felice; Nocerino, Flavia; Grimaldi, Maria; Rotondo, Emanuela; D'Ursi, Anna Maria; Scrima, Mario; Galdiero, Massimiliano; Ciliberto, Gennaro; Capunzo, Mario; Franci, Gianluigi; Barbieri, Antonio; Bimonte, Sabrina; Montella, Maurizio

    2016-01-01

    MicroRNAs are short (21-23 nucleotides), noncoding RNAs that typically silence posttranscriptional gene expression through interaction with target messenger RNAs. Currently, miRNAs have been identified in almost all studied multicellular eukaryotes in the plant and animal kingdoms. Additionally, recent studies reported that miRNAs can also be encoded by certain single-cell eukaryotes and by viruses. The vast majority of viral miRNAs are encoded by the herpesviruses family. These DNA viruses including Epstein-Barr virus encode their own miRNAs and/or manipulate the expression of cellular miRNAs to facilitate respective infection cycles. Modulation of the control pathways of miRNAs expression is often involved in the promotion of tumorigenesis through a specific cascade of transduction signals. Notably, latent infection with Epstein-Barr virus is considered liable of causing several types of malignancies, including the majority of gastric carcinoma cases detected worldwide. In this review, we describe the role of the Epstein-Barr virus in gastric carcinogenesis, summarizing the functions of the Epstein-Barr virus-encoded viral proteins and related epigenetic alterations as well as the roles of Epstein-Barr virus-encoded and virally modulated cellular miRNAs.

  4. In silico identification and characterization of conserved miRNAs and their target genes in sweet potato (Ipomoea batatas L.) expressed sequence tags (ESTs).

    Science.gov (United States)

    Dehury, Budheswar; Panda, Debashis; Sahu, Jagajjit; Sahu, Mousumi; Sarma, Kishore; Barooah, Madhumita; Sen, Priyabrata; Modi, Mahendra

    2013-01-01

    The endogenous small non-coding micro RNAs (miRNAs), which are typically ~21-24 nt nucleotides, play a crucial role in regulating the intrinsic normal growth of cells and development of the plants as well as in maintaining the integrity of genomes. These small non-coding RNAs function as the universal specificity factors in post-transcriptional gene silencing. Discovering miRNAs, identifying their targets, and further inferring miRNA functions is a routine process to understand normal biological processes of miRNAs and their roles in the development of plants. Comparative genomics based approach using expressed sequence tags (EST) and genome survey sequences (GSS) offer a cost-effective platform for identification and characterization of miRNAs and their target genes in plants. Despite the fact that sweet potato (Ipomoea batatas L.) is an important staple food source for poor small farmers throughout the world, the role of miRNA in various developmental processes remains largely unknown. In this paper, we report the computational identification of miRNAs and their target genes in sweet potato from their ESTs. Using comparative genomics-based approach, 8 potential miRNA candidates belonging to miR168, miR2911, and miR156 families were identified from 23 406 ESTs in sweet potato. A total of 42 target genes were predicted and their probable functions were illustrated. Most of the newly identified miRNAs target transcription factors as well as genes involved in plant growth and development, signal transduction, metabolism, defense, and stress response. The identification of miRNAs and their targets is expected to accelerate the pace of miRNA discovery, leading to an improved understanding of the role of miRNA in development and physiology of sweet potato, as well as stress response.

  5. Genome-wide analyses of radioresistance-associated miRNA expression profile in nasopharyngeal carcinoma using next generation deep sequencing.

    Directory of Open Access Journals (Sweden)

    Guo Li

    Full Text Available BACKGROUND: Rapidly growing evidence suggests that microRNAs (miRNAs are involved in a wide range of cancer malignant behaviours including radioresistance. Therefore, the present study was designed to investigate miRNA expression patterns associated with radioresistance in NPC. METHODS: The differential expression profiles of miRNAs and mRNAs associated with NPC radioresistance were constructed. The predicted target mRNAs of miRNAs and their enriched signaling pathways were analyzed via biological informatical algorithms. Finally, partial miRNAs and pathways-correlated target mRNAs were validated in two NPC radioreisitant cell models. RESULTS: 50 known and 9 novel miRNAs with significant difference were identified, and their target mRNAs were narrowed down to 53 nasopharyngeal-/NPC-specific mRNAs. Subsequent KEGG analyses demonstrated that the 53 mRNAs were enriched in 37 signaling pathways. Further qRT-PCR assays confirmed 3 down-regulated miRNAs (miR-324-3p, miR-93-3p and miR-4501, 3 up-regulated miRNAs (miR-371a-5p, miR-34c-5p and miR-1323 and 2 novel miRNAs. Additionally, corresponding alterations of pathways-correlated target mRNAs were observed including 5 up-regulated mRNAs (ICAM1, WNT2B, MYC, HLA-F and TGF-β1 and 3 down-regulated mRNAs (CDH1, PTENP1 and HSP90AA1. CONCLUSIONS: Our study provides an overview of miRNA expression profile and the interactions between miRNA and their target mRNAs, which will deepen our understanding of the important roles of miRNAs in NPC radioresistance.

  6. In silico identification and characterization of conserved miRNAs and their target genes in sweet potato (Ipomoea batatas L.) Expressed Sequence Tags (ESTs)

    Science.gov (United States)

    Dehury, Budheswar; Panda, Debashis; Sahu, Jagajjit; Sahu, Mousumi; Sarma, Kishore; Barooah, Madhumita; Sen, Priyabrata; Modi, Mahendra Kumar

    2013-01-01

    The endogenous small non-coding micro RNAs (miRNAs), which are typically ~21–24 nt nucleotides, play a crucial role in regulating the intrinsic normal growth of cells and development of the plants as well as in maintaining the integrity of genomes. These small non-coding RNAs function as the universal specificity factors in post-transcriptional gene silencing. Discovering miRNAs, identifying their targets, and further inferring miRNA functions is a routine process to understand normal biological processes of miRNAs and their roles in the development of plants. Comparative genomics based approach using expressed sequence tags (EST) and genome survey sequences (GSS) offer a cost-effective platform for identification and characterization of miRNAs and their target genes in plants. Despite the fact that sweet potato (Ipomoea batatas L.) is an important staple food source for poor small farmers throughout the world, the role of miRNA in various developmental processes remains largely unknown. In this paper, we report the computational identification of miRNAs and their target genes in sweet potato from their ESTs. Using comparative genomics-based approach, 8 potential miRNA candidates belonging to miR168, miR2911, and miR156 families were identified from 23 406 ESTs in sweet potato. A total of 42 target genes were predicted and their probable functions were illustrated. Most of the newly identified miRNAs target transcription factors as well as genes involved in plant growth and development, signal transduction, metabolism, defense, and stress response. The identification of miRNAs and their targets is expected to accelerate the pace of miRNA discovery, leading to an improved understanding of the role of miRNA in development and physiology of sweet potato, as well as stress response. PMID:24067297

  7. [Preliminary study on aberrant expression of miRNAs related to the formation of the distinction between pediatric and adult types of brainstem gliomas].

    Science.gov (United States)

    Wang, Xuan; Zhang, Hong-wei; Zhang, An-ling; Han, Lei; Wang, Kun; Pu, Pei-yu; Shen, Chang-hong; Kang, Chun-sheng; Yu, Chun-jiang

    2012-11-01

    To study the different expression of miRNA between pediatric and adult types of brainstem gliomas, and to provide the target miRNAs for explore the mechanism and miRNA interference of the malignant progression of pediatric BSG. miRNA expression profiles in orthotopic models which could simulate the BSG heterogeneity were examined by microarray and analyzed to obtain the aberrantly expressed miRNAs. The two types of human BSG tissue were utilized to verify the microarray data by qRT-PCR and in situ hybridization for the putative causative miRNAs. There were 216 miRNAs detected in both the pediatric BSG group and the adult BSG group, 39 miRNAs to be differential expressed in the pediatric BSG group versus adult group, including 10 up-regulated and 29 down-regulated. qRT-PCR and in situ hybridization indicated good consistency with that of the microarray method. Aberrantly expressed miRNA may serve as putative causative involvement of malignant progression of pediatric BSG, thereby might be potentially novel targets for therapy.

  8. Search for signatures in miRNAs associated with cancer

    Science.gov (United States)

    Kothandan, Ram; Biswas, Sumit

    2013-01-01

    Since the first discovery in the early 1990's, the predicted and validated population of microRNAs (miRNAs or miRs) has grown significantly. These small (~22 nucleotides long) regulators of gene expression have been implicated and associated with several genes in the cancer pathway as well. Globally, the identification and verification of microRNAs as biomarkers for cancer cell types has been the area of thrust for most miRNA biologists. However, there has been a noticeable vacuum when it comes to identifying a common signature or trademark that could be used to demarcate a miR to be associated with the development or suppression of cancer. To answer these queries, we report an in silico study involving the identification of global signatures in experimentally validated microRNAs which have been associated with cancer. This study has thrown light on the presence of significant common signatures, viz., - sequential and hybridization, which may distinguish a miR to be associated with cancer. Based on our analysis, we suggest the utility of such signatures in the design and development of algorithms for prediction of miRs involved in the cancer pathway. PMID:23861569

  9. The regulatory epicenter of miRNAs

    Indian Academy of Sciences (India)

    21 bp. miRNA formation seems to be dependent upon multiple factors besides Drosha and Dicer, in a tissue/stage-specific manner, with interplay of several specific binding factors. In the present study, we have investigated transcription factor ...

  10. The regulatory epicenter of miRNAs

    Indian Academy of Sciences (India)

    Based on our findings, we propose that the observed characteristic distribution of regulatory sites in precursor miRNA sequence regions could be critical inmiRNA transcription, processing, stability and formation and are important for therapeutic studies. Our findings also support the recently proposed theory of self-sufficient ...

  11. Viral miRNAs and immune evasion.

    Science.gov (United States)

    Boss, Isaac W; Renne, Rolf

    2011-01-01

    Viral miRNAs, ~22nt RNA molecules which post-transcriptionally regulate gene expression, are emerging as important tools in immune evasion. Viral infection is a complex process that requires immune evasion in order to establish persistent life-long infection of the host. During this process viruses express both protein-coding and non-coding genes, which help to modulate the cellular environment making it more favorable for infection. In the last decade, it was uncovered that DNA viruses express a diverse and abundant pool of small non-coding RNA molecules, called microRNAs (miRNAs). These virally encoded miRNAs are non-immunogenic and therefore are important tools used to evade both innate and adaptive immune responses. This review aims to summarize our current knowledge of herpesvirus- and polyomavirus-encoded miRNAs, and how they contribute to immune evasion by targeting viral and/or host cellular genes. This article is part of a Special Issue entitled: MicroRNAs in viral gene regulation. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Plasma and White Blood Cells Show Different miRNA Expression Profiles in Parkinson's Disease.

    Science.gov (United States)

    Schwienbacher, Christine; Foco, Luisa; Picard, Anne; Corradi, Eloina; Serafin, Alice; Panzer, Jörg; Zanigni, Stefano; Blankenburg, Hagen; Facheris, Maurizio F; Giannini, Giulia; Falla, Marika; Cortelli, Pietro; Pramstaller, Peter P; Hicks, Andrew A

    2017-06-01

    Parkinson's disease (PD) diagnosis is based on the assessment of motor symptoms, which manifest when more than 50% of dopaminergic neurons are degenerated. To date, no validated biomarkers are available for the diagnosis of PD. The aims of the present study are to evaluate whether plasma and white blood cells (WBCs) are interchangeable biomarker sources and to identify circulating plasma-based microRNA (miRNA) biomarkers for an early detection of PD. We profiled plasma miRNA levels in 99 L-dopa-treated PD patients from two independent data collections, in ten drug-naïve PD patients, and in unaffected controls matched by sex and age. We evaluated expression levels by reverse transcription and quantitative real-time PCR (RT-qPCR) and combined the results from treated PD patients using a fixed effect inverse-variance weighted meta-analysis. We revealed different expression profiles comparing plasma and WBCs and drug-naïve and L-dopa-treated PD patients. We observed an upregulation trend for miR-30a-5p in L-dopa-treated PD patients and investigated candidate target genes by integrated in silico analyses. We could not analyse miR-29b-3p, normally expressed in WBCs, due to the very low expression in plasma. We observed different expression profiles in WBCs and plasma, suggesting that they are both suitable but not interchangeable peripheral sources for biomarkers. We revealed miR-30a-5p as a potential biomarker for PD in plasma. In silico analyses suggest that miR-30a-5p might have a regulatory role in mitochondrial dynamics and autophagy. Further investigations are needed to confirm miR-30a-5p deregulation and targets and to investigate the influence of L-dopa treatment on miRNA expression levels.

  13. Modified least-variant set normalization for miRNA microarray

    Science.gov (United States)

    Suo, Chen; Salim, Agus; Chia, Kee-Seng; Pawitan, Yudi; Calza, Stefano

    2010-01-01

    MicroRNAs (miRNAs) are short noncoding RNAs that are involved in post-transcriptional regulation of mRNAs. Microarrays have been employed to measure global miRNA expressions; however, because the number of miRNAs is much smaller than the number of mRNAs, it is not clear whether traditional normalization methods developed for mRNA arrays are suitable for miRNA. This is an important question, since normalization affects downstream analyses of the data. In this paper we develop a least-variant set (LVS) normalization method, which was previously shown to outperform other methods in mRNA analysis when standard assumptions are violated. The selection of the LVS miRNAs is based on a robust linear model fit of the probe-level data that takes into account the considerable differences in variances between probes. In a spike-in study, we show that the LVS has similar operating characteristics, in terms of sensitivity and specificity, compared with the ideal normalization, and it is better than no normalization, 75th percentile-shift, quantile, global median, VSN, and lowess normalization methods. We evaluate four expression-summary measures using a tissue data set; summarization from the robust model performs as well as the others. Finally, comparisons using expression data from two dissimilar tissues and two similar ones show that LVS normalization has better operating characteristics than other normalizations. PMID:20980676

  14. Chemoresistance, Cancer Stem Cells, and miRNA Influences: The Case for Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Alfred Buhagiar

    2015-01-01

    Full Text Available Neuroblastoma is a type of cancer that develops most often in infants and children under the age of five years. Neuroblastoma originates within the peripheral sympathetic ganglia, with 30% of the cases developing within the adrenal medulla, although it can also occur within other regions of the body such as nerve tissue in the spinal cord, neck, chest, abdomen, and pelvis. MicroRNAs (miRNAs regulate cellular pathways, differentiation, apoptosis, and stem cell maintenance. Such miRNAs regulate genes involved in cellular processes. Consequently, they are implicated in the regulation of a spectrum of signaling pathways within the cell. In essence, the role of miRNAs in the development of cancer is of utmost importance for the understanding of dysfunctional cellular pathways that lead to the conversion of normal cells into cancer cells. This review focuses on highlighting the recent, important implications of miRNAs within the context of neuroblastoma basic research efforts, particularly concerning miRNA influences on cancer stem cell pathology and chemoresistance pathology for this condition, together with development of translational medicine approaches for novel diagnostic tools and therapies for this neuroblastoma.

  15. Study of bantam miRNA expression in brain tumour resulted due to ...

    Indian Academy of Sciences (India)

    ANIMESH BANERJEE

    2017-06-19

    Jun 19, 2017 ... Abstract. Disturbance of delicate concordance between stem cell proliferation, specification and differentiation during brain development leads to several neural disorders including tumours. Accumulating evidences have demonstrated involvement of short noncoding microRNAs (miRNAs) in governing ...

  16. Identification of miRNAs and their targets in maize in response to Sugarcane mosaic virus infection.

    Science.gov (United States)

    Xia, Zihao; Zhao, Zhenxing; Li, Mingjun; Chen, Ling; Jiao, Zhiyuan; Wu, Yuanhua; Zhou, Tao; Yu, Weichang; Fan, Zaifeng

    2018-04-01

    MicroRNAs (miRNAs) are endogenous non-coding small RNAs that play essential regulatory roles in plant development and environmental stress responses. Maize (Zea mays L.) is a global economically important food and forage crop. To date, a number of maize miRNAs have been identified as being involved in plant development and stress responses. However, the miRNA-mediated gene regulatory networks responsive to virus infections in maize remain largely unknown. In this study, the profiles of small RNAs in buffer- and Sugarcane mosaic virus (SCMV)-inoculated maize plants were obtained by high-throughput sequencing, respectively. A total of 154 known miRNAs and 213 novel miRNAs were profiled and most of the miRNAs identified were differentially expressed after SCMV infection. In addition, 70 targets of 13 known miRNAs and 3 targets of a novel miRNA were identified by degradome analysis. The results of Northern blotting and quantitative real-time PCR showed that the expression levels of the selected miRNAs and their targets were mostly influenced by SCMV infection at 12 days post inoculation, including up-regulation of miR168 and miR528, and down-regulation of miR159, miR397 and miR827. These results provide new insights into the regulatory networks of miRNAs and their targets in maize plants responsive to SCMV infection. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. Characterization of miRNAs in response to short-term waterlogging in three inbred lines of Zea mays.

    Directory of Open Access Journals (Sweden)

    Zhijie Liu

    Full Text Available Waterlogging of plants leads to low oxygen levels (hypoxia in the roots and causes a metabolic switch from aerobic respiration to anaerobic fermentation that results in rapid changes in gene transcription and protein synthesis. Our research seeks to characterize the microRNA-mediated gene regulatory networks associated with short-term waterlogging. MicroRNAs (miRNAs are small non-coding RNAs that regulate many genes involved in growth, development and various biotic and abiotic stress responses. To characterize the involvement of miRNAs and their targets in response to short-term hypoxia conditions, a quantitative real time PCR (qRT-PCR assay was used to quantify the expression of the 24 candidate mature miRNA signatures (22 known and 2 novel mature miRNAs, representing 66 miRNA loci and their 92 predicted targets in three inbred Zea mays lines (waterlogging tolerant Hz32, mid-tolerant B73, and sensitive Mo17. Based on our studies, miR159, miR164, miR167, miR393, miR408 and miR528, which are mainly involved in root development and stress responses, were found to be key regulators in the post-transcriptional regulatory mechanisms under short-term waterlogging conditions in three inbred lines. Further, computational approaches were used to predict the stress and development related cis-regulatory elements on the promoters of these miRNAs; and a probable miRNA-mediated gene regulatory network in response to short-term waterlogging stress was constructed. The differential expression patterns of miRNAs and their targets in these three inbred lines suggest that the miRNAs are active participants in the signal transduction at the early stage of hypoxia conditions via a gene regulatory network; and crosstalk occurs between different biochemical pathways.

  18. Walking the interactome to identify human miRNA-disease associations through the functional link between miRNA targets and disease genes

    Science.gov (United States)

    2013-01-01

    Background MicroRNAs (miRNAs) are important post-transcriptional regulators that have been demonstrated to play an important role in human diseases. Elucidating the associations between miRNAs and diseases at the systematic level will deepen our understanding of the molecular mechanisms of diseases. However, miRNA-disease associations identified by previous computational methods are far from completeness and more effort is needed. Results We developed a computational framework to identify miRNA-disease associations by performing random walk analysis, and focused on the functional link between miRNA targets and disease genes in protein-protein interaction (PPI) networks. Furthermore, a bipartite miRNA-disease network was constructed, from which several miRNA-disease co-regulated modules were identified by hierarchical clustering analysis. Our approach achieved satisfactory performance in identifying known cancer-related miRNAs for nine human cancers with an area under the ROC curve (AUC) ranging from 71.3% to 91.3%. By systematically analyzing the global properties of the miRNA-disease network, we found that only a small number of miRNAs regulated genes involved in various diseases, genes associated with neurological diseases were preferentially regulated by miRNAs and some immunological diseases were associated with several specific miRNAs. We also observed that most diseases in the same co-regulated module tended to belong to the same disease category, indicating that these diseases might share similar miRNA regulatory mechanisms. Conclusions In this study, we present a computational framework to identify miRNA-disease associations, and further construct a bipartite miRNA-disease network for systematically analyzing the global properties of miRNA regulation of disease genes. Our findings provide a broad perspective on the relationships between miRNAs and diseases and could potentially aid future research efforts concerning miRNA involvement in disease pathogenesis

  19. Natural gas deregulation: the need for further reform

    Energy Technology Data Exchange (ETDEWEB)

    Broadman, H.G.

    As with attempts at achieving effective regulation of economic activity where it is warranted, deregulation can entail hidden complexities and produce unintended outcomes. The principle that deregulation begets second order effects that may necessitate further regulator reform is epitomized in the case of natural gas. The author shows how the partial deregulation of natural gas wellhead markets under the Natural Gas Policy Act of 1978 caused a variety of distortions to emerge in other segments of the industry. Because the distortions are mutually reinforcing, no single policy, such as immediate decontrol of old gas or subjecting pipeline companies to common carrier obligations, will solve all of them; rather an integrated program of regulatory reform is required. The author concludes by outlining such a program and commenting on how its implementation through administrative and legislative actions should be carried out in order to reduce the need for further reform in the future.

  20. Turnover of Mature miRNAs and siRNAs in Plants and Algae.

    Science.gov (United States)

    Cerutti, Heriberto; Ibrahim, Fadia

    2011-01-01

    microRNAs (miRNAs) and small interfering RNAs (siRNAs) play important roles in gene regulation and defense responses against transposons and viruses in eukaryotes. These small RNAs generally trigger the silencing of cognate sequences through a variety of mechanisms, including RNA degradation, translational inhibition and transcriptional repression. In the past few years, the synthesis and the mode of action of miRNAs and siRNAs have attracted great attention. However, relatively little is known about mechanisms of quality control during small RNA biogenesis as well as those that regulate mature small RNA stability. Recent studies in Arabidopsis thaliana and Caenorhabditis elegans have implicated 3'-to-5' (SDNs) and 5'-to-3' (XRN-2) exoribonucleases in mature miRNA turnover and the modulation of small RNA levels and activity. In the green alga Chlamydomonas reinhardtii, a nucleotidyltransferase (MUT68) and an exosome subunit (RRP6) are involved in the 3' untemplated uridylation and the degradation of miRNAs and siRNAs. The latter enzymes appear to function as a quality control mechanism to eliminate putative dysfunctional or damaged small RNA molecules. Several post-transcriptional modifications of miRNAs and siRNAs such as 3' terminal methylation and untemplated nucleotide additions have also been reported to affect small RNA stability. These collective findings are beginning to uncover a new layer of regulatory control in the pathways involving small RNAs. We anticipate that understanding the mechanisms of mature miRNA and siRNA turnover will have direct implications for fundamental biology as well as for applications of RNA interference technology.

  1. MicroRNA-7: A miRNA with expanding roles in development and disease.

    Science.gov (United States)

    Horsham, Jessica L; Ganda, Clarissa; Kalinowski, Felicity C; Brown, Rikki A M; Epis, Michael R; Leedman, Peter J

    2015-12-01

    MicroRNAs (miRNAs) are a family of short, non-coding RNA molecules (∼22nt) involved in post-transcriptional control of gene expression. They act via base-pairing with mRNA transcripts that harbour target sequences, resulting in accelerated mRNA decay and/or translational attenuation. Given miRNAs mediate the expression of molecules involved in many aspects of normal cell development and functioning, it is not surprising that aberrant miRNA expression is closely associated with many human diseases. Their pivotal role in driving a range of normal cellular physiology as well as pathological processes has established miRNAs as potential therapeutics, as well as potential diagnostic and prognostic tools in human health. MicroRNA-7 (miR-7) is a highly conserved miRNA which displays restricted spatiotemporal expression during development and in maturity. In humans and mice, mature miR-7 is generated from three different genes, illustrating unexpected redundancy and also the importance of this miRNA in regulating key cellular processes. In this review we examine the expanding role of miR-7 in the context of health, with emphasis on organ differentiation and development, as well as in various mammalian diseases, particularly of the brain, heart, endocrine pancreas and skin, as well as in cancer. The more we learn about miR-7, the more we realise the complexity of its regulation and potential functional application both from a biomarker and therapeutic perspective. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Natural gas and deregulation in the European Market

    International Nuclear Information System (INIS)

    Anon.

    2000-01-01

    The gas market is progressively moving towards new organizations under the effect of deregulation initiated in the United States, the United Kingdom and transposed to other countries, particularly in Europe, at least for the member countries of the European Union. Within the framework provided by this overall trend, Cedigaz proposes a study titled 'Natural Gas and Deregulation' in order to describe the main developments affecting these markets on account of deregulation. This report is structured on the basis of three main topics (market organization, marketing modes, pricing) which appears to be the most cogent in terms of deregulation. This grouping by major topics accordingly offers a relatively synthetic view of the main trends which could be observed in the European market, for example. The analysis is largely based on the example of the American market and, to a lesser extent, on the British situation. Incidentally, it has adapted the terms 'regulated market' to define conventional markets and 'deregulated market' to define markets which have incorporated the principle of Third Party Access (TPA). This is obviously a mere convention, since in both cases, the gas market, a network market, is regulated either by the State or by an independent agency. Also noteworthy is the diversity of the regulation methods for the network markets. While an underlying principle prevails throughout, particularly the introduction of TPA, political and energy considerations alike are liable to condition strongly the final structure of a given market. The apparently comparable British and American experience thus display substantial differences. In other words, one should not imagine a sudden transposition of either case to the European market. The different States preserve considerable leeway to guide market developments in one direction or another. On the whole, deregulation is not a frozen process, but has to adapt permanently to developments in a market stage-managed by

  3. Deep sequencing of Brachypodium small RNAs at the global genome level identifies microRNAs involved in cold stress response

    Directory of Open Access Journals (Sweden)

    Chong Kang

    2009-09-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are endogenous small RNAs having large-scale regulatory effects on plant development and stress responses. Extensive studies of miRNAs have only been performed in a few model plants. Although miRNAs are proved to be involved in plant cold stress responses, little is known for winter-habit monocots. Brachypodium distachyon, with close evolutionary relationship to cool-season cereals, has recently emerged as a novel model plant. There are few reports of Brachypodium miRNAs. Results High-throughput sequencing and whole-genome-wide data mining led to the identification of 27 conserved miRNAs, as well as 129 predicted miRNAs in Brachypodium. For multiple-member conserved miRNA families, their sizes in Brachypodium were much smaller than those in rice and Populus. The genome organization of miR395 family in Brachypodium was quite different from that in rice. The expression of 3 conserved miRNAs and 25 predicted miRNAs showed significant changes in response to cold stress. Among these miRNAs, some were cold-induced and some were cold-suppressed, but all the conserved miRNAs were up-regulated under cold stress condition. Conclusion Our results suggest that Brachypodium miRNAs are composed of a set of conserved miRNAs and a large proportion of non-conserved miRNAs with low expression levels. Both kinds of miRNAs were involved in cold stress response, but all the conserved miRNAs were up-regulated, implying an important role for cold-induced miRNAs. The different size and genome organization of miRNA families in Brachypodium and rice suggest that the frequency of duplication events or the selection pressure on duplicated miRNAs are different between these two closely related plant species.

  4. Deregulation of purine pathway in Bacillus subtilis and its use in riboflavin biosynthesis

    Science.gov (United States)

    2014-01-01

    Background Purine nucleotides are essential metabolites for living organisms because they are involved in many important processes, such as nucleic acid synthesis, energy supply, and biosynthesis of several amino acids and riboflavin. Owing to the pivotal roles of purines in cell physiology, the pool of intracellular purine nucleotides must be maintained under strict control, and hence the de novo purine biosynthetic pathway is tightly regulated by transcription repression and inhibition mechanism. Deregulation of purine pathway is essential for this pathway engineering in Bacillus subtilis. Results Deregulation of purine pathway was attempted to improve purine nucleotides supply, based on a riboflavin producer B. subtilis strain with modification of its rib operon. To eliminate transcription repression, the pur operon repressor PurR and the 5’-UTR of pur operon containing a guanine-sensing riboswitch were disrupted. Quantitative RT-PCR analysis revealed that the relative transcription levels of purine genes were up-regulated about 380 times. Furthermore, site-directed mutagenesis was successfully introduced into PRPP amidotransferase (encoded by purF) to remove feedback inhibition by homologous alignment and analysis. Overexpression of the novel mutant PurF (D293V, K316Q and S400W) significantly increased PRPP amidotransferase activity and triggered a strong refractory effect on purine nucleotides mediated inhibition. Intracellular metabolite target analysis indicated that the purine nucleotides supply in engineered strains was facilitated by a stepwise gene-targeted deregulation. With these genetic manipulations, we managed to enhance the metabolic flow through purine pathway and consequently increased riboflavin production 3-fold (826.52 mg/L) in the purF-VQW mutant strain. Conclusions A sequential optimization strategy was applied to deregulate the rib operon and purine pathway of B. subtilis to create genetic diversities and to improve riboflavin production

  5. Buying and selling green: deregulation and green power marketing

    International Nuclear Information System (INIS)

    Evans, Andrew

    2000-01-01

    This article discusses the increasing trend towards deregulation of electricity markets, and the driving forces for liberalisation in the EU and North America. The use of green tariffs offered by utilities to differentiate themselves from competitors and to gain and keep customers is reported, and the situation with regard to green energy within the deregulated electricity markets in Australia, the EU, Denmark, Finland, Germany, the Netherlands, Portugal, Sweden, the UK, Canada and the USA is outlined. Customers switching as a result of green tariffs, the growing role of renewables, and opportunities for the promotion of green tariffs are discussed. (UK)

  6. MicroRNAs and their predicted target messenger RNAs are deregulated by exposure to a carcinogenic dose of comfrey in rat liver.

    Science.gov (United States)

    Li, Zhiguang; Fuscoe, James C; Chen, Tao

    2011-07-01

    MicroRNAs (MiRNAs) are small noncoding RNAs that function as regulators of gene expression to control cell growth and differentiation. In this study, we analyzed miRNA and mRNA expression in the livers of rats treated with a carcinogenic dose of comfrey (Symphytum officinale) for 12 weeks. Groups of six rats were fed a normal diet or a diet containing 8% comfrey root. The animals were sacrificed 1 day after the last treatment and the livers were isolated for miRNA expression analysis using LC Sciences miRNA microarrays and for mRNA expression analysis using Affymetrix rat genome microarrays. MiRNA expression levels were significantly changed by comfrey treatment. The treated samples were separated clearly from the control samples in both principal component analysis (PCA) and hierarchical clustering analysis (HCA). Quantitative measurements of seven miRNAs using TaqMan real-time PCR were consistent with the microarray results in terms of fold-change and the direction of the change in expression. Forty-five miRNAs (P comfrey treatment. Using a target prediction algorithm, 434 differentially expressed genes (DEGs) were predicted to be targeted by the differentially expressed miRNAs (DEMs). The DEM-targeted DEGs were more likely to be involved in carcinogenesis than the DEGs that were not targeted by the DEMs. The nontargeted DEGs were enriched in noncancer-related biological processes. Our data suggest that comfrey may exert its carcinogenic effects by disturbing miRNA expression resulting in altered mRNA levels of the DEM-targeted genes that are functionally associated with carcinogenesis. Copyright © 2011 Wiley-Liss, Inc.

  7. Deregulation and the Alberta experience : the implications for Ontario

    International Nuclear Information System (INIS)

    Spearman, C.

    2002-01-01

    The government of Alberta deregulated its electric power industry to introduce industry structure and regulatory reforms that would promote competitive electricity prices. The objective was to ensure fairness for customers and generating facilities. A graph depicting power pool prices shows the reality of soaring prices at the onset of deregulation in Alberta. Today, there remains uncertainty in the development of retail choice, additional rate riders, new generation, transmission expansion, other jurisdictions and future prices. Consumers are still poorly equipped to make decisions and farmers have no means of protection from fluctuating electricity prices. They see deregulation as a complete failure because costs are up and benefits are nowhere to be seen. Ontario can learn from the Alberta experience by adopting the recommendations to set financial penalties for incompetence, financial compensation to customers for errors, and to be fully ready with systems tested ahead of deregulation. Anticipated customer benefits should be clearly identified in advance. The future electric power industry in Ontario needs vision, stability, a cohesive plan, and leadership devoid of complacency. 1 fig

  8. The European gaseous market deregulation and its consequences for Russia

    International Nuclear Information System (INIS)

    Finon, D.; Locatelli, C.

    2002-07-01

    Russia, the first world producer of gas in 2001 is also the main producer in the european gas market. In this framework the evolution of its gas exportations market is a major stake for the russian gas industry and for the country economy. The consequences of this gas market deregulation are analyzed in this document. (A.L.B.)

  9. Understanding electricity market reforms and the case of Philippine deregulation

    Energy Technology Data Exchange (ETDEWEB)

    Santiago, Andrea; Roxas, Fernando

    2010-03-15

    The experience of the Philippines offers lessons that should be relevant to any country seeking to deregulate its power industry. Regardless of structure, consumers must face the real price of electricity production and delivery that is closer to marginal cost. Politically motivated prices merely shift the burden from ratepayers to taxpayers. And any reform should work within a reasonable timetable. (author)

  10. Deregulation of the Nigerian economy: The theoretical milieu

    Directory of Open Access Journals (Sweden)

    Nureni Opeyemi Akintoye

    2014-01-01

    Full Text Available The deregulation of Nigerian economy was the main thrust of the Structural Adjustment Programme (SAP introduced in the country in 1986 under the leadership of General Ibrahim Babandiga (1958-1993. Prior to that period the Nigerian economy was almost a command one with wide range of government control. Indeed, the introduction of SAP was said to be a final solution to the economic crisis faced by the Country. Unfortunately, SAP was introduced yet, the economy became more crunched. During the General Abach's regime (1993­1998, SAP was suspended out rightly. When General Abdulsalami Abubakar (1998-1999 took over, he continued pursuing the privatization programme which is a synonym of deregulation of the economy with the promulgation of another privatization decree. The civilian government led by President Obasanjo which took over from 1999 made deregulation the core with vigour. It is basked on this development that this paper intends to unravel the theoretical paradigm under which the deregulation of Nigerian economy could be explained. This includes capitalism, imperialism, colonialism particularly the incorporation of Nigerian into international capitalist system.

  11. Electricity pricing model in thermal generating stations under deregulation

    International Nuclear Information System (INIS)

    Reji, P.; Ashok, S.; Moideenkutty, K.M.

    2007-01-01

    In regulated public utilities with competitive power markets, deregulation has replaced the monopoly. Under the deregulated power market, the electricity price primarily depends on market mechanism and power demand. In this market, generators generally follow marginal pricing. Each generator fixes the electricity price based on their pricing strategy and it leads to more price volatility. This paper proposed a model to determine the electricity price considering all operational constraints of the plant and economic variables that influenced the price, for a thermal generating station under deregulation. The purpose of the model was to assist existing stations, investors in the power sector, regulatory authorities, transmission utilities, and new power generators in decision-making. The model could accommodate price volatility in the market and was based on performance incentive/penalty considering plant load factor, availability of the plant and peak/ off peak demand. The model was applied as a case study to a typical thermal utility in India to determine the electricity price. It was concluded that the case study of a thermal generating station in a deregulated environment showed that the electricity price mainly depended on the gross calorific value (GCV) of fuel, mode of operation, price of the fuel, and operating charges. 11 refs., 2 tabs., 1 fig

  12. Design of reactive power procurement in deregulated electricity market

    African Journals Online (AJOL)

    user

    The IEEE 24-bus RTS test system is used to illustrate the proposed reactive power procurement. The offers of generation have been considered by minimization of reactive generation cost followed by maximization of Societal Advantage Function. Keywords: Reactive Bids, Deregulation, Societal Advantage Function, ...

  13. Electrical Energy Service Options: Deregulation Presents New Opportunities.

    Science.gov (United States)

    Matterson, Gary C.

    1995-01-01

    It is noted that federal deregulation of the electrical utility industry will allow colleges and universities to buy electrical services from suppliers who provide the best reliability and cost combination. Considerations are examined for the following options: purchasing an existing electrical substation, building a new substation, using on-site…

  14. miRNA signatures and transcriptional regulation of their target genes in vitiligo.

    Science.gov (United States)

    Mansuri, Mohmmad Shoab; Singh, Mala; Begum, Rasheedunnisa

    2016-10-01

    miRNAs are small non-coding RNA molecules that post-transcriptionally regulate gene expression. We have earlier reported the skin miRNA expression profiling in patients with non-segmental vitiligo. In the present study, we show the expression of previously identified skin miRNAs signatures in blood and their target genes in whole blood and PBMCs as well as skin micro-environment of vitiligo patients and controls. miRNA expression profiling in whole blood was performed using customized TaqMan ® Low Density Array. We predicted the potential targets of differentially expressed miRNAs and investigated their expression levels in skin, whole blood and PBMCs from patients and controls using Real-time PCR. Our results showed miR-1, miR-184, miR-328, miR-383 and miR-577 hold similar pattern of expression as of skin, suggesting their potent eminence for being putative markers for vitiligo. In silico target prediction revealed miR-1 targets EDN1, G6PD, HSP60, HSP70, SERP1, SIRT1 & TYR; miR-184 targets EZR & LAMP1; miR-328 targets IL1B, POLH & TRPM1; miR-383 targets EDN1 & TYRP1; and miR-577 targets PTPN22 & TYRP1 which were corroborated by our validation study. In conclusion, the present study for the first time provides new insights into the crucial role of miRNA regulated gene network involved in oxidative stress, autoimmunity and ER stress mediated pathogenesis of vitiligo. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. A possible new mechanism for the control of miRNA expression in neurons.

    Science.gov (United States)

    Kinjo, Erika Reime; Higa, Guilherme Shigueto Vilar; de Sousa, Erica; Casado, Otávio Augusto Nocera; Damico, Marcio Vinicius; Britto, Luiz Roberto G; Kihara, Alexandre Hiroaki

    2013-10-01

    The control of gene expression by miRNAs has been widely investigated in different species and cell types. Following a probabilistic rather than a deterministic regimen, the action of these short nucleotide sequences on specific genes depends on intracellular concentration, which in turn reflects the balance between biosynthesis and degradation. Recent studies have described the involvement of XRN2, an exoribonuclease, in miRNA degradation and PAPD4, an atypical poly(A) polymerase, in miRNA stability. Herein, we examined the expression of XRN2 and PAPD4 in developing and adult rat hippocampi. Combining bioinformatics and real-time PCR, we demonstrated that XRN2 and PAPD4 expression is regulated by the uncorrelated action of transcription factors, resulting in distinct gene expression profiles during development. Analyses of nuclei position and nestin labeling revealed that both proteins progressively accumulated during neuronal differentiation, and that they are weakly expressed in immature neurons and absent in glial and endothelial cells. Despite the differences in subcellular localization, both genes were concurrently identified within identical neuronal subpopulations, including specific inhibitory interneurons. Thus, we cope with a singular circumstance in biology: an almost complete intersected expression of functional-opposed genes, reinforcing that their antagonistically driven actions on miRNAs "make sense" if simultaneously present at the same cells. Considering that the transcriptome in the nervous system is finely tuned to physiological processes, it was remarkable that miRNA stability-related genes were concurrently identified in neurons that play essential roles in cognitive functions such as memory and learning. In summary, this study reveals a possible new mechanism for the control of miRNA expression. © 2013 Elsevier Inc. All rights reserved.

  16. Apple miRNAs and tasiRNAs with novel regulatory networks.

    Science.gov (United States)

    Xia, Rui; Zhu, Hong; An, Yong-Qiang; Beers, Eric P; Liu, Zongrang

    2012-06-15

    MicroRNAs (miRNAs) and their regulatory functions have been extensively characterized in model species but whether apple has evolved similar or unique regulatory features remains unknown. We performed deep small RNA-seq and identified 23 conserved, 10 less-conserved and 42 apple-specific miRNAs or families with distinct expression patterns. The identified miRNAs target 118 genes representing a wide range of enzymatic and regulatory activities. Apple also conserves two TAS gene families with similar but unique trans-acting small interfering RNA (tasiRNA) biogenesis profiles and target specificities. Importantly, we found that miR159, miR828 and miR858 can collectively target up to 81 MYB genes potentially involved in diverse aspects of plant growth and development. These miRNA target sites are differentially conserved among MYBs, which is largely influenced by the location and conservation of the encoded amino acid residues in MYB factors. Finally, we found that 10 of the 19 miR828-targeted MYBs undergo small interfering RNA (siRNA) biogenesis at the 3' cleaved, highly divergent transcript regions, generating over 100 sequence-distinct siRNAs that potentially target over 70 diverse genes as confirmed by degradome analysis. Our work identified and characterized apple miRNAs, their expression patterns, targets and regulatory functions. We also discovered that three miRNAs and the ensuing siRNAs exploit both conserved and divergent sequence features of MYB genes to initiate distinct regulatory networks targeting a multitude of genes inside and outside the MYB family.

  17. Altered expression of miRNAs and methylation of their promoters are correlated in neuroblastoma.

    Science.gov (United States)

    Maugeri, Marco; Barbagallo, Davide; Barbagallo, Cristina; Banelli, Barbara; Di Mauro, Stefania; Purrello, Francesco; Magro, Gaetano; Ragusa, Marco; Di Pietro, Cinzia; Romani, Massimo; Purrello, Michele

    2016-12-13

    Neuroblastoma is the most common human extracranial solid tumor during infancy. Involvement of several miRNAs in its pathogenesis has been ascertained. Interestingly, most of their encoding genes reside in hypermethylated genomic regions: thus, their tumor suppressor function is normally disallowed in these tumors. To date, the therapeutic role of the demethylating agent 5'-Aza-2 deoxycytidine (5'-AZA) and its effects on miRNAome modulation in neuroblastoma have not been satisfactorily explored. Starting from a high-throughput expression profiling of 754 miRNAs and based on a proper selection, we focused on miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p as candidate miRNAs for our analysis. They resulted downregulated in four neuroblastoma cell lines with respect to normal adrenal gland. MiRNAs 29a-3p and 34b-3p also resulted downregulated in vivo in a murine neuroblastoma progression model. Unlike the amount of methylation of their encoding gene promoters, all these miRNAs were significantly overexpressed following treatment with 5'-AZA. Transfection with candidate miRNAs mimics significantly decreased neuroblastoma cells proliferation rate. A lower expression of miR-181c was significantly associated to a worse overall survival in a public dataset of 498 neuroblastoma samples (http://r2.amc.nl). Our data strongly suggest that CDK6, DNMT3A, DNMT3B are targets of miR-29a-3p, while CCNE2 and E2F3 are targets of miR-34b-3p. Based on all these data, we propose that miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p are disallowed tumor suppressor genes in neuroblastoma and suggest them as new therapeutic targets in neuroblastoma.

  18. 75 FR 68321 - Forage Genetics International; Supplemental Request for Partial Deregulation of Roundup Ready...

    Science.gov (United States)

    2010-11-05

    ...] Forage Genetics International; Supplemental Request for Partial Deregulation of Roundup Ready Alfalfa... Inspection Service has received a supplemental request for ``partial deregulation'' from Forage Genetics... affected persons of the availability of the documents submitted to the Agency from Forage Genetics...

  19. Deregulation of obesity-relevant genes is associated with progression in BMI and the amount of adipose tissue in pigs

    DEFF Research Database (Denmark)

    Mentzel, Caroline M. Junker; Cardoso, Tainã Figueiredo; Pipper, Christian Bressen

    2018-01-01

    The aim of this study was to elucidate the relative impact of three phenotypes often used to characterize obesity on perturbation of molecular pathways involved in obesity. The three obesity-related phenotypes are (1) body mass index (BMI), (2) amount of subcutaneous adipose tissue (SATa), and (3...... in the three tissues in association with changes in the three obesity-relevant phenotypes (BMI, SATa and RPATa). The deregulated pathways are involved in biosynthesis and transcript regulation in adipocytes, in lipid transport, lipolysis and metabolism, and in inflammatory responses. Deregulation seemed more...... by demonstrating that increasing amount of RPATa has a higher impact on perturbation of cellular pathways influencing obesity and obesity-related metabolic traits compared to increase in BMI and amount of SATa....

  20. Differential Effects of Chronic and Chronic-Intermittent Ethanol Treatment and Its Withdrawal on the Expression of miRNAs

    Directory of Open Access Journals (Sweden)

    Joanne M. Lewohl

    2013-05-01

    Full Text Available Chronic and excessive alcohol misuse results in changes in the expression of selected miRNAs and their mRNA targets in specific regions of the human brain. These expression changes likely underlie the cellular adaptations to long term alcohol misuse. In order to delineate the mechanism by which these expression changes occur, we have measured the expression of six miRNAs including miR-7, miR-153, miR-152, miR-15B, miR-203 and miR-144 in HEK293T, SH SY5Y and 1321 N1 cells following exposure to ethanol. These miRNAs are predicted to target key genes involved in the pathophysiology of alcoholism. Chronic and chronic-intermittent exposure to ethanol, and its removal, resulted in specific changes in miRNA expression in each cell line suggesting that different expression patterns can be elicited with different exposure paradigms and that the mechanism of ethanol’s effects is dependent on cell type. Specifically, chronic exposure to ethanol for five days followed by a five day withdrawal period resulted in up-regulation of several miRNAs in each of these cell lines similar to expression changes identified in post mortem human brain. Thus, this model can be used to elucidate the role of miRNAs in regulating gene expression changes that occur in response to ethanol exposure.

  1. In silico evaluation of miRNA binding site in mutated 3'UTR mRNA of G6PD

    Science.gov (United States)

    Azmi, Syarifah Anis Wafa Binti Syed Mohd; Noorden, Mohd Shihabudin; Yusof, Nurul Yuziana Mohd; Ismail, Endom

    2015-09-01

    MicroRNAs (miRNAs) are small non coding RNA sized 21-25 nucleotide. It has the ability to bind to the 3'- untranslated regions (3'UTR) of their target genes. Consequently, the binding of miRNA in the 3'UTR of targeted mRNA will regulate the expression of this gene. Thus, changes in 3'UTR may affect miRNA binding to mRNA of their target gene, leading to aberrations in mRNA regulations or expression and likely contribute to the various phenotypic changes or clinical risk for certain diseases in man. Therefore, the aim of this study is to evaluate candidate miRNAs species involved during the regulation of glucose-6-phosphate dehydrogenase (G6PD) mRNA with and without a specific 3'UTR nucleotide change that was previously shown to be responsible for G6PD deficiency in a Negrito sub-group of the Malaysian Orang Asli. We have conducted in silico analysis using TargetScan, PITA, RegRNA 2.0 and miRanda platform. Our results indicate that three potential miRNAs may have a functional role towards the regulated expression of those bearing the 3'UTR mutation. The role of these eleven miRNA can be investigated in future in vitro expression studies in order to verify its miRNA:mRNA relationship.

  2. Why Shops Close Again : An Evolutionary Perspective on the Deregulation of Shopping Hours

    NARCIS (Netherlands)

    Kosfeld, M.

    1999-01-01

    This paper introduces a new perspective on the deregulation of shopping hours based on ideas from evolutionary game theory. We study a retail economy where shopping hours have been deregulated recently. It is argued that first, the deregulation leads to a coordination problem between store owners

  3. Clinical and pathological implications of miRNA in bladder cancer

    Directory of Open Access Journals (Sweden)

    Braicu C

    2015-01-01

    Full Text Available Cornelia Braicu,1 Roxana Cojocneanu-Petric,1,2 Sergiu Chira,1 Anamaria Truta,1,3 Alexandru Floares,4 Bogdan Petrut,5,6 Patriciu Achimas-Cadariu,7,8,* Ioana Berindan-Neagoe1,9–11,*1Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania; 3Department of Medical Genetics, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4Solutions of Artificial Intelligence Applications, Cluj-Napoca, Romania; 5Department of Urology, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 6Department of Urology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 7Department of Surgery, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 8Department of Surgical Oncology and Gynaecological Oncology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 9Department of Immunology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 10Department of Functional Genomics and Experimental Pathology, The Oncology Institute “ Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 11Department of Experimental Therapeutics M.D. Anderson Cancer Center Houston, TX, USAAbstract: MicroRNAs (miRNAs are small, noncoding RNA species with a length of 20–22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with

  4. Embryonic miRNA Profiles of Normal and Ectopic Pregnancies

    OpenAIRE

    Dominguez, Francisco; Moreno-Moya, Juan Manuel; Lozoya, Teresa; Romero, Ainhoa; Martínez, Sebastian; Monterde, Mercedes; Gurrea, Marta; Ferri, Blanca; Núñez, Maria Jose; Simón, Carlos; Pellicer, Antonio

    2014-01-01

    Our objective was to investigate the miRNA profile of embryonic tissues in ectopic pregnancies (EPs) and controlled abortions (voluntary termination of pregnancy; VTOP). Twenty-three patients suffering from tubal EP and twenty-nine patients with a normal ongoing pregnancy scheduled for a VTOP were recruited. Embryonic tissue samples were analyzed by miRNA microarray and further validated by real time PCR. Microarray studies showed that four miRNAs were differentially downregulated (hsa-mir-19...

  5. Sexual dimorphism of miRNA expression: a new perspective in understanding the sex bias of autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Dai R

    2014-03-01

    Full Text Available Rujuan Dai, S Ansar Ahmed Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA Abstract: Autoimmune diseases encompass a diverse group of diseases which emanate from a dysregulated immune system that launches a damaging attack on its own tissues. Autoimmune attacks on self tissues can occur in any organ or body system. A notable feature of autoimmune disease is that a majority of these disorders occur predominantly in females. The precise basis of sex bias in autoimmune diseases is complex and potentially involves sex chromosomes, sex hormones, and sex-specific gene regulation in response to internal and external stimuli. Epigenetic regulation of genes, especially by microRNAs (miRNAs, is now attracting significant attention. miRNAs are small, non-protein-coding RNAs that are predicted to regulate a majority of human genes, including those involved in immune regulation. Therefore, it is not surprising that dysregulated miRNAs are evident in many diseases, including autoimmune diseases. Because there are marked sex differences in the incidence of autoimmune diseases, this review focuses on the role of sex factors on miRNA expression in the context of autoimmune diseases, an aspect not addressed thus far. Here, we initially review miRNA biogenesis and miRNA regulation of immunity and autoimmunity. We then summarize the recent findings of sexual dimorphism of miRNA expression in diverse tissues, which imply a critical role of miRNA in sex differentiation and in sex-specific regulation of tissue development and/or function. We also discuss the important contribution of the X chromosome and sex hormones to the sexual dimorphism of miRNA expression. Understanding sexually dimorphic miRNA expression in sex-biased autoimmune diseases not only offers us new insight into the mechanism of sex bias of the disease but will also aid us in developing new sex

  6. Genome-wide identification of alternate bearing-associated microRNAs (miRNAs in olive (Olea europaea L.

    Directory of Open Access Journals (Sweden)

    Yanik Huriye

    2013-01-01

    Full Text Available Abstract Background Alternate bearing is a widespread phenomenon among crop plants, defined as the tendency of certain fruit trees to produce a high-yield crop one year ("on-year", followed by a low-yield or even no crop the following year ("off-year". Several factors may affect the balance between such developmental phase-transition processes. Among them are the microRNA (miRNA, being gene-expression regulators that have been found to be involved as key determinants in several physiological processes. Results Six olive (Olea europaea L. cv. Ayvalik variety small RNA libraries were constructed from fruits (ripe and unripe and leaves (”on year” and ”off year” leaves in July and in November, respectively and sequenced by high-throughput Illumina sequencing. The RNA was retrotranscribed and sequenced using the high-throughput Illumina platform. Bioinformatics analyses of 93,526,915 reads identified 135 conserved miRNA, belonging to 22 miRNA families in the olive. In addition, 38 putative novel miRNAs were discovered in the datasets. Expression of olive tree miRNAs varied greatly among the six libraries, indicating the contribution of diverse miRNA in balancing between reproductive and vegetative phases. Predicted targets of miRNA were categorized into 108 process ontology groups with significance abundance. Among those, potential alternate bearing-associated processes were found, such as development, hormone-mediated signaling and organ morphogenesis. The KEGG analyses revealed that the miRNA-targeted genes are involved in seven main pathways, belonging to carbohydrate metabolism and hormone signal-transduction pathways. Conclusion A comprehensive study on olive miRNA related to alternate bearing was performed. Regulation of miRNA under different developmental phases and tissues indicated that control of nutrition and hormone, together with flowering processes had a noteworthy impact on the olive tree alternate bearing. Our results also

  7. Genome-wide identification of alternate bearing-associated microRNAs (miRNAs) in olive (Olea europaea L.).

    Science.gov (United States)

    Yanik, Huriye; Turktas, Mine; Dundar, Ekrem; Hernandez, Pilar; Dorado, Gabriel; Unver, Turgay

    2013-01-15

    Alternate bearing is a widespread phenomenon among crop plants, defined as the tendency of certain fruit trees to produce a high-yield crop one year ("on-year"), followed by a low-yield or even no crop the following year ("off-year"). Several factors may affect the balance between such developmental phase-transition processes. Among them are the microRNA (miRNA), being gene-expression regulators that have been found to be involved as key determinants in several physiological processes. Six olive (Olea europaea L. cv. Ayvalik variety) small RNA libraries were constructed from fruits (ripe and unripe) and leaves ("on year" and "off year" leaves in July and in November, respectively) and sequenced by high-throughput Illumina sequencing. The RNA was retrotranscribed and sequenced using the high-throughput Illumina platform. Bioinformatics analyses of 93,526,915 reads identified 135 conserved miRNA, belonging to 22 miRNA families in the olive. In addition, 38 putative novel miRNAs were discovered in the datasets. Expression of olive tree miRNAs varied greatly among the six libraries, indicating the contribution of diverse miRNA in balancing between reproductive and vegetative phases. Predicted targets of miRNA were categorized into 108 process ontology groups with significance abundance. Among those, potential alternate bearing-associated processes were found, such as development, hormone-mediated signaling and organ morphogenesis. The KEGG analyses revealed that the miRNA-targeted genes are involved in seven main pathways, belonging to carbohydrate metabolism and hormone signal-transduction pathways. A comprehensive study on olive miRNA related to alternate bearing was performed. Regulation of miRNA under different developmental phases and tissues indicated that control of nutrition and hormone, together with flowering processes had a noteworthy impact on the olive tree alternate bearing. Our results also provide significant data on the miRNA-fruit development

  8. Analysis of physiological and miRNA responses to Pi deficiency in alfalfa (Medicago sativa L.).

    Science.gov (United States)

    Li, Zhenyi; Xu, Hongyu; Li, Yue; Wan, Xiufu; Ma, Zhao; Cao, Jing; Li, Zhensong; He, Feng; Wang, Yufei; Wan, Liqiang; Tong, Zongyong; Li, Xianglin

    2018-03-01

    The induction of miR399 and miR398 and the inhibition of miR156, miR159, miR160, miR171, miR2111, and miR2643 were observed under Pi deficiency in alfalfa. The miRNA-mediated genes involved in basic metabolic process, root and shoot development, stress response and Pi uptake. Inorganic phosphate (Pi) deficiency is known to be a limiting factor in plant development and growth. However, the underlying miRNAs associated with the Pi deficiency-responsive mechanism in alfalfa are unclear. To elucidate the molecular mechanism at the miRNA level, we constructed four small RNA (sRNA) libraries from the roots and shoots of alfalfa grown under normal or Pi-deficient conditions. In the present study, alfalfa plants showed reductions in biomass, photosynthesis, and Pi content and increases in their root-to-shoot ratio and citric, malic, and succinic acid contents under Pi limitation. Sequencing results identified 47 and 44 differentially expressed miRNAs in the roots and shoots, respectively. Furthermore, 909 potential target genes were predicted, and some targets were validated by RLM-RACE assays. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed prominent enrichment in signal transducer activity, binding and basic metabolic pathways for carbohydrates, fatty acids and amino acids; cellular response to hormone stimulus and response to auxin pathways were also enriched. qPCR results verified that the differentially expressed miRNA profile was consistent with sequencing results, and putative target genes exhibited opposite expression patterns. In this study, the miRNAs associated with the response to Pi limitation in alfalfa were identified. In addition, there was an enrichment of miRNA-targeted genes involved in biological regulatory processes such as basic metabolic pathways, root and shoot development, stress response, Pi transportation and citric acid secretion.

  9. Computational Identification of Putative miRNAs from

    Directory of Open Access Journals (Sweden)

    Ganesh Sathyamurthy

    2010-01-01

    Full Text Available microRNAs represent a class of noncoding small RNAs of approximately 20–23 nt length, which are evolutionarily conserved and play a vital role in various biological processes by either degrading or repressing mRNA translation. The Felis catus (cat genome sequence has been published, and just revealed the number of miRNAs in the genome–-without mention of any further details on these miRNAs. This paper discusses an in silico comparative approach using all known sequences of vertebrate pre-miRNA as query sequence, and report 405 putative miRNAs from cat genome. We determine the identity values of pre-miRNAs and mature miRNAs besides statistical sequence characteristics. Interestingly, among 405 miRNAs–-90, 53 and 50 showed 100% identity to cattle, human and dog, respectively. Further, we have validated 6 miRNAs, whose identity are <85% with the query sequence and validated them using MiPred algorithm. We also identify 25 miRNA clusters in cat based on their homologs in other vertebrates. Most importantly, based on identities among pre-miRNA, mature miRNA, miRNA families and clusters, we observe that miRNAs from cat are more identical to cattle, than humans. Our results, therefore may add a new dimension to the studies related to the evolution of cat.

  10. Dynamics of miRNA biogenesis and nuclear transport

    OpenAIRE

    Kotipalli, Aneesh; Gutti, Ravikumar; Mitra, Chanchal K.

    2016-01-01

    MicroRNAs (miRNAs) are short noncoding RNA sequences ~22 nucleotides in length that play an important role in gene regulation-transcription and translation. The processing of these miRNAs takes place in both the nucleus and the cytoplasm while the final maturation occurs in the cytoplasm. Some mature miRNAs with nuclear localisation signals (NLS) are transported back to the nucleus and some remain in the cytoplasm. The functional roles of these miRNAs are seen in both the nucleus and the cyto...

  11. Exosomes as miRNA Carriers: Formation–Function–Future

    Science.gov (United States)

    Yu, Xiaojie; Odenthal, Margarete; Fries, Jochen W. U.

    2016-01-01

    Exosomes, which are one of the smallest extracellular vesicles released from cells, have been shown to carry different nucleic acids, including microRNAs (miRNAs). miRNAs significantly regulate cell growth and metabolism by posttranscriptional inhibition of gene expression. The rapidly changing understanding of exosomes’ formation and function in delivering miRNAs from cell to cell has prompted us to review current knowledge in exosomal miRNA secretion mechanisms as well as possible therapeutic applications for personalized medicine. PMID:27918449

  12. Exosomes as miRNA Carriers: Formation–Function–Future

    Directory of Open Access Journals (Sweden)

    Xiaojie Yu

    2016-12-01

    Full Text Available Exosomes, which are one of the smallest extracellular vesicles released from cells, have been shown to carry different nucleic acids, including microRNAs (miRNAs. miRNAs significantly regulate cell growth and metabolism by posttranscriptional inhibition of gene expression. The rapidly changing understanding of exosomes’ formation and function in delivering miRNAs from cell to cell has prompted us to review current knowledge in exosomal miRNA secretion mechanisms as well as possible therapeutic applications for personalized medicine.

  13. Exploration of miRNA families for hypotheses generation.

    KAUST Repository

    Kamanu, T.K.

    2013-10-15

    Technological improvements have resulted in increased discovery of new microRNAs (miRNAs) and refinement and enrichment of existing miRNA families. miRNA families are important because they suggest a common sequence or structure configuration in sets of genes that hint to a shared function. Exploratory tools to enhance investigation of characteristics of miRNA families and the functions of family-specific miRNA genes are lacking. We have developed, miRNAVISA, a user-friendly web-based tool that allows customized interrogation and comparisons of miRNA families for hypotheses generation, and comparison of per-species chromosomal distribution of miRNA genes in different families. This study illustrates hypothesis generation using miRNAVISA in seven species. Our results unveil a subclass of miRNAs that may be regulated by genomic imprinting, and also suggest that some miRNA families may be species-specific, as well as chromosome- and/or strand-specific.

  14. Viral miRNAs and immune evasion

    OpenAIRE

    Boss, Isaac W.; Renne, Rolf

    2011-01-01

    Viral miRNAs, ∼22nt RNA molecules which post-transcriptionally regulate gene expression, are emerging as important tools in immune evasion. Viral infection is a complex process that requires immune evasion in order to establish persistent life-long infection of the host. During this process viruses express both protein-coding and non-coding genes, which help to modulate the cellular environment making it more favorable for infection. In the last decade, it was uncovered that DNA viruses expre...

  15. Deregulation of brain insulin signaling in Alzheimer's disease.

    Science.gov (United States)

    Chen, Yanxing; Deng, Yanqiu; Zhang, Baorong; Gong, Cheng-Xin

    2014-04-01

    Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer's disease (AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid β precursor protein, and tau phosphorylation. We further discuss deficiencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders.

  16. Deregulation, privatisation and marketisation of Nordic comprehensive education

    DEFF Research Database (Denmark)

    Kosunen, Sonja; Kauko, Jaakko; Magnúsdóttir, Berglind

    2018-01-01

    economy. The aim of this article is to examine education in the five Nordic countries utilising three dimensions of political change: deregulation, marketisation and privatisation. We also analyse the parallel changes in relation to segregation and differentiation in education. The analysis shows...... that the themes related to deregulation seem to show fairly similar patterns and structures in all contexts. The emerging differences were discovered mainly in the themes of marketisation and privatisation. Institutional segregation emerges in all Nordic countries to different extents along the lines...... of these three processes, and we observe a simultaneous social segregation and differentiation with an ambiguous connection to them. Based on these findings, the question of what is left of the “Nordic model” could be raised....

  17. Revenue opportunities for gas plants arising from electricity deregulation

    International Nuclear Information System (INIS)

    Bachmann, G.C.

    1999-01-01

    A brief overview of deregulation in the electric power industry and an explanation of how these changes can be used to increase revenues of gas processing plants is provided. Deregulation in the electric power industry provides the potential to significantly reduce energy costs for the gas plant and allows technology to be applied to make a better use of a valuable commodity. Owners and operators of gas processing plants increase their operating income by taking advantage of co-generation systems which provide heat and electrical energy to the gas plant. Such an application has three revenue streams, the main one being the power sales to the gas plant, the second one heat sales, and the third increased revenues from the gas plant through a reduction of overall costs, not to mention significantly reduced downtime. Further savings are possible through diversion of excess energy produced to other facilities owned by the gas plant owner

  18. Customer choice: Purchasing energy in a deregulated market

    International Nuclear Information System (INIS)

    Thumann, A.

    1999-01-01

    This book presents the detailed guidance on how to effectively purchase deregulated energy, based on first-hand reports from many of the nation's most knowledgeable experts. It is designed to provide the kind of practical advice needed by professionals who are responsible for making energy purchasing decisions. The book gives a ten-step program to guide building owners in purchasing decision making, a state-by-state retail competition update, and guidelines for buying electricity and natural gas over the worldwide web. Other topics include contract renegotiation strategies, an assessment of power pools, the role of aggregators in the energy market, real time pricing issues, where cogeneration fits within today's marketplace, and lessons learned from deregulation experiences in Scandinavia and England

  19. SNHG16 is regulated by the Wnt pathway in colorectal cancer and affects genes involved in lipid metabolism.

    Science.gov (United States)

    Christensen, Lise Lotte; True, Kirsten; Hamilton, Mark P; Nielsen, Morten M; Damas, Nkerorema D; Damgaard, Christian K; Ongen, Halit; Dermitzakis, Emmanouil; Bramsen, Jesper B; Pedersen, Jakob S; Lund, Anders H; Vang, Søren; Stribolt, Katrine; Madsen, Mogens R; Laurberg, Søren; McGuire, Sean E; Ørntoft, Torben F; Andersen, Claus L

    2016-10-01

    It is well established that lncRNAs are aberrantly expressed in cancer where they have been shown to act as oncogenes or tumor suppressors. RNA profiling of 314 colorectal adenomas/adenocarcinomas and 292 adjacent normal colon mucosa samples using RNA-sequencing demonstrated that the snoRNA host gene 16 (SNHG16) is significantly up-regulated in adenomas and all stages of CRC. SNHG16 expression was positively correlated to the expression of Wnt-regulated transcription factors, including ASCL2, ETS2, and c-Myc. In vitro abrogation of Wnt signaling in CRC cells reduced the expression of SNHG16 indicating that SNHG16 is regulated by the Wnt pathway. Silencing of SNHG16 resulted in reduced viability, increased apoptotic cell death and impaired cell migration. The SNHG16 silencing particularly affected expression of genes involved in lipid metabolism. A connection between SNHG16 and genes involved in lipid metabolism was also observed in clinical tumors. Argonaute CrossLinking and ImmunoPrecipitation (AGO-CLIP) demonstrated that SNHG16 heavily binds AGO and has 27 AGO/miRNA target sites along its length, indicating that SNHG16 may act as a competing endogenous RNA (ceRNA) "sponging" miRNAs off their cognate targets. Most interestingly, half of the miRNA families with high confidence targets on SNHG16 also target the 3'UTR of Stearoyl-CoA Desaturase (SCD). SCD is involved in lipid metabolism and is down-regulated upon SNHG16 silencing. In conclusion, up-regulation of SNHG16 is a frequent event in CRC, likely caused by deregulated Wnt signaling. In vitro analyses demonstrate that SNHG16 may play an oncogenic role in CRC and that it affects genes involved in lipid metabolism, possible through ceRNA related mechanisms. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  20. Managing an evolution: Deregulation of the electric utility industry

    Energy Technology Data Exchange (ETDEWEB)

    Skinner, S.K.

    1994-12-31

    The author discusses the emerging competitive situation in the electric power industry as deregulation of electric utilities looms on the horizon. The paper supports this change, and the competition it will bring, but urges caution as changes are instituted, and the regulatory bodies decide how and how much to free, and at what rates. The reason for his urge for caution comes from historical experience of other industries, which were smaller and had less direct impact on every American.

  1. What has happened to airline operating expenses Since deregulation?

    OpenAIRE

    Jordan, William A.

    2007-01-01

    When airline deregulation was adopted in October 1978, the performance of the regulated trunk, local service and Alaskan/Hawaiian airlines (the original carriers) differed substantially from that of the four intrastate carriers whose operations solely within California, Florida or Texas had not been subject to the regulation of interstate air transportation by the Civil Aeronautics Board. One of these differences was the substantially lower total operating expenses per revenue ton-mile (RTM) ...

  2. Impact of deregulation on the task of commission control

    International Nuclear Information System (INIS)

    Haar, B.W.

    2004-01-01

    This paper offers perspective on the effects of a decade of deregulation in the telephone, electric and natural gas industries in the US. The paper focuses on the effects of policies implemented over the last 10 years and on their particular implications, policy as well as practical, for state utility regulatory commissions. Four critical trends are identified and provide the basis for the discussion. The paper is presented from the perspective of a practitioner. (author)

  3. Generation capacity expansion planning in deregulated electricity markets

    Science.gov (United States)

    Sharma, Deepak

    With increasing demand of electric power in the context of deregulated electricity markets, a good strategic planning for the growth of the power system is critical for our tomorrow. There is a need to build new resources in the form of generation plants and transmission lines while considering the effects of these new resources on power system operations, market economics and the long-term dynamics of the economy. In deregulation, the exercise of generation planning has undergone a paradigm shift. The first stage of generation planning is now undertaken by the individual investors. These investors see investments in generation capacity as an increasing business opportunity because of the increasing market prices. Therefore, the main objective of such a planning exercise, carried out by individual investors, is typically that of long-term profit maximization. This thesis presents some modeling frameworks for generation capacity expansion planning applicable to independent investor firms in the context of power industry deregulation. These modeling frameworks include various technical and financing issues within the process of power system planning. The proposed modeling frameworks consider the long-term decision making process of investor firms, the discrete nature of generation capacity addition and incorporates transmission network modeling. Studies have been carried out to examine the impact of the optimal investment plans on transmission network loadings in the long-run by integrating the generation capacity expansion planning framework within a modified IEEE 30-bus transmission system network. The work assesses the importance of arriving at an optimal IRR at which the firm's profit maximization objective attains an extremum value. The mathematical model is further improved to incorporate binary variables while considering discrete unit sizes, and subsequently to include the detailed transmission network representation. The proposed models are novel in the

  4. Competitive nuclear production on the nordic deregulated electricity market

    International Nuclear Information System (INIS)

    Bohl, T.

    2000-01-01

    The Nordic electricity market has been partly deregulated since 1994. Today only Denmark follows the timetable recommended by the European Union, while Sweden, Norway and Finland are completely deregulated. As in most countries, the production of electricity is deregulated while the distribution is still a monopoly. This deregulation of the electricity market has created a new situation for plant life management. In order to be competitive on the market it is important to cut cost down a level when the nuclear power companies earn money again. All means to cut cost have to be used while still maintaining safety and the possibilities for operation over at least 40+ years. The possibilities to invest in modernization are limited to the absolutely necessary modifications. All investments must be very thoroughly questioned and the money can only be spent where most benefit is gained. This means new prerequisites for the absolute necessary long-strategic planning. New safety requirements from the authorities have to be discussed between the industry and the authority. The requirement cost must be compared to the benefit to safety. The authority is today requested to carry out such analyses and do so in most cases. Since the electricity market is international the requirements of the authorities must be harmonized on the whole market. The political threat against nuclear power is serious in many countries and it is important to continue working with public acceptance and lobbying. Especially in Sweden a lot of effort is spent on trying to change the taxation of nuclear power. In the near future increasing electricity demand will make the prices go up to a level when nuclear power companies earn money again. The very serious worries about climate change will also strengthen the competitiveness of nuclear power. (author)

  5. Post-transcriptional generation of miRNA variants by multiple nucleotidyl transferases contributes to miRNA transcriptome complexity

    OpenAIRE

    Wyman, Stacia K.; Knouf, Emily C.; Parkin, Rachael K.; Fritz, Brian R.; Lin, Daniel W.; Dennis, Lucas M.; Krouse, Michael A.; Webster, Philippa J.; Tewari, Muneesh

    2011-01-01

    Modification of microRNA sequences by the 3′ addition of nucleotides to generate so-called “isomiRs” adds to the complexity of miRNA function, with recent reports showing that 3′ modifications can influence miRNA stability and efficiency of target repression. Here, we show that the 3′ modification of miRNAs is a physiological and common post-transcriptional event that shows selectivity for specific miRNAs and is observed across species ranging from C. elegans to human. The modifications resul...

  6. Hepatitis C Virus-Induced Changes in MicroRNA 107 (miRNA-107) and miRNA-449a Modulate CCL2 by Targeting the Interleukin-6 Receptor Complex in Hepatitis

    Science.gov (United States)

    Sarma, Nayan J.; Tiriveedhi, Venkataswarup; Crippin, Jeffrey S.; Chapman, William C.

    2014-01-01

    ABSTRACT Hepatitis C virus (HCV)-mediated liver diseases are one of the major health issues in the United States and worldwide. HCV infection has been reported to modulate microRNAs (miRNAs) that control various cell surface receptors and gene-regulatory complexes involved in hepatic inflammation and liver diseases. We report here that specific downregulation of miRNA-107 and miRNA-449a following HCV infection in patients with HCV-mediated liver diseases modulates expression of CCL2, an inflammatory chemokine upregulated in patients with chronic liver diseases, by targeting components of the interleukin-6 receptor (IL-6R) complex. Computational analysis for DNA-bound transcription factors in the CCL2 promoter identified adjacent binding sites for CCAAT/CEBPα, spleen focus-forming virus, proviral integration oncogene (SPI1/PU.1), and STAT3. We demonstrate that CEBPα, PU.1, and STAT3 interacted with each other physically to cooperatively bind to the promoter and activate CCL2 expression. Analysis of IL-6R and JAK1 expression in HCV patients by quantitative PCR showed significant upregulation when there was impaired miRNA-107 and miRNA-449a expression, along with upregulation of PU.1 and STAT3, but not CEBPα. miRNA-449a and miRNA-107 target expression of IL-6R and JAK1, respectively, in vitro and also inhibit IL-6 signaling and impair STAT3 activation in human hepatocytes. Taken together, our results demonstrate a novel gene-regulatory mechanism in which HCV-induced changes in miRNAs (miRNA-449a and miRNA-107) regulate CCL2 expression by activation of the IL-6-mediated signaling cascade, which we propose will result in HCV-mediated induction of inflammatory responses and fibrosis. IMPORTANCE Hepatitis C virus (HCV)-induced hepatitis is a major health concern worldwide. HCV infection results in modulation of noncoding microRNAs affecting major cellular pathways, including inflammatory responses. In this study, we have identified a microRNA-regulated pathway for the

  7. Inflow shortages in deregulated power markets - Reasons for concern?

    International Nuclear Information System (INIS)

    Bye, Torstein; Bruvoll, Annegrete; Aune, Finn Roar

    2008-01-01

    In many countries hydropower constitutes a large share of the electricity producing capacity. In the earlier regulated electricity markets, production capacities exceeded demand due to security of supply concerns. The present deregulated markets base investments upon profitability alone, and security of supply issues are claimed to be less important. Market operators trust the pricing mechanism in competitive markets to clear. Then low inflow constitutes a less problem. Several markets, both under regulated and deregulated regimes, have faced serious droughts. Some of them have experienced problems with market clearance (Chile, Brazil, California) while other markets functioned well (The Nordic market). Important features to the market response are the flexibility of demand, the pattern of inflow shortage, the storage capacities, the possibility of trade between regions with different production technologies, and the market design and concentration. We apply an empirical based market model to simulate the effects under two inflow shortage scenarios in an international market with combined hydro and thermal capacities and restricted transmission capacities. We compare the scenarios with actual events and show that the model and the real market outcome are comparable. The simulations do not reveal any problems with the functioning of the market, which should calm down the anxiousness about security of supply in deregulated markets with stochastic energy supply

  8. Multiobjective Optimization Methods for Congestion Management in Deregulated Power Systems

    Directory of Open Access Journals (Sweden)

    K. Vijayakumar

    2012-01-01

    Full Text Available Congestion management is one of the important functions performed by system operator in deregulated electricity market to ensure secure operation of transmission system. This paper proposes two effective methods for transmission congestion alleviation in deregulated power system. Congestion or overload in transmission networks is alleviated by rescheduling of generators and/or load shedding. The two objectives conflicting in nature (1 transmission line over load and (2 congestion cost are optimized in this paper. The multiobjective fuzzy evolutionary programming (FEP and nondominated sorting genetic algorithm II methods are used to solve this problem. FEP uses the combined advantages of fuzzy and evolutionary programming (EP techniques and gives better unique solution satisfying both objectives, whereas nondominated sorting genetic algorithm (NSGA II gives a set of Pareto-optimal solutions. The methods propose an efficient and reliable algorithm for line overload alleviation due to critical line outages in a deregulated power markets. The quality and usefulness of the algorithm is tested on IEEE 30 bus system.

  9. Cycles in deregulated electricity markets: Empirical evidence from two decades

    International Nuclear Information System (INIS)

    Arango, Santiago; Larsen, Erik

    2011-01-01

    In this article, we discuss the 'cycle hypothesis' in electricity generation, which states that the introduction of deregulation in an electricity system might lead to sustained fluctuations of over- and under-capacity. The occurrence of cycles is one of the major threats for electricity markets as it affects the security of supply, and creates uncertainty in both the profitability of electricity companies and in consumer prices. We discuss the background for these cycles using analogies with other capital-intensive industries, along with evidence from the analysis of behavioral simulation models as well as from experimental electricity markets. Using data from the oldest deregulated markets we find support for the hypothesis in the case of the English and Chilean markets, based on an autocorrelation analysis. Evidence from the Nordpool market is more ambiguous, although we might be observing the first half of a cycle in generation capacity. Comparing a simulation of the English market performed in 1992 with the actual performance we can observe that the qualitative behavior of the model is consistent with the actual evolution. Finally, we discuss possible mechanisms for damping cycles in electricity generation, such as mothballing, capacity payments, and reliability markets. - Research highlights: → We explore the emergence of cycles in the electricity generation capacity after deregulation. → We discuss the reason for cycles in generation capacity and compare different theories. → Analysis of England and Chile data show strong indications that cycles have emerged.

  10. Accounting for gas in a de-regulated environment

    International Nuclear Information System (INIS)

    Zawalykut, P.M.

    1992-01-01

    Since the natural gas industry was deregulated, the method of buying, selling and moving gas has changed significantly. Post-deregulation, the pipeline company moves the gas but does not acquire ownership. The full impact of deregulation is seen in opening up the market for buying and selling gas. Tracking of gas has become critical. The service customer is now buying and moving gas. The end-use customer nominates to the distribution company a quantity of gas to be transported. Responsibility is placed on the customer to estimate loads as accurately as possible to avoid possible charges. The distribution company passes the end-user nomination to the upstream transmission company, which in turn passes it along, a process that is repeated until the nomination reaches the production company. Authorizations for gas follow a similar path. The major difference between sales and service gas is the accounting and tracking. As the customer will not consume the exact amount nominated, there will be an imblance between what was nominated and metered. There will also be imbalances between what the producer places into the pipeline and what was nominated. These processes can cause administrative problems, and many customers are moving from sales to service

  11. Cycles in deregulated electricity markets: Empirical evidence from two decades

    Energy Technology Data Exchange (ETDEWEB)

    Arango, Santiago, E-mail: saarango@unal.edu.c [Institute of Management, University of Lugano, Via Buffi 13, CH-6904 Lugano (Switzerland); Complexity Center CeiBa, Universidad Nacional de Colombia (Colombia); Larsen, Erik, E-mail: saarango@unal.edu.c [Institute of Management, University of Lugano, Via Buffi 13, CH-6904 Lugano (Switzerland)

    2011-05-15

    In this article, we discuss the 'cycle hypothesis' in electricity generation, which states that the introduction of deregulation in an electricity system might lead to sustained fluctuations of over- and under-capacity. The occurrence of cycles is one of the major threats for electricity markets as it affects the security of supply, and creates uncertainty in both the profitability of electricity companies and in consumer prices. We discuss the background for these cycles using analogies with other capital-intensive industries, along with evidence from the analysis of behavioral simulation models as well as from experimental electricity markets. Using data from the oldest deregulated markets we find support for the hypothesis in the case of the English and Chilean markets, based on an autocorrelation analysis. Evidence from the Nordpool market is more ambiguous, although we might be observing the first half of a cycle in generation capacity. Comparing a simulation of the English market performed in 1992 with the actual performance we can observe that the qualitative behavior of the model is consistent with the actual evolution. Finally, we discuss possible mechanisms for damping cycles in electricity generation, such as mothballing, capacity payments, and reliability markets. - Research highlights: {yields} We explore the emergence of cycles in the electricity generation capacity after deregulation. {yields} We discuss the reason for cycles in generation capacity and compare different theories. {yields} Analysis of England and Chile data show strong indications that cycles have emerged.

  12. The First Report of miRNAs from a Thysanopteran Insect, Thrips palmi Karny Using High-Throughput Sequencing.

    Directory of Open Access Journals (Sweden)

    K B Rebijith

    Full Text Available Thrips palmi Karny (Thysanoptera: Thripidae is the sole vector of Watermelon bud necrosis tospovirus, where the crop loss has been estimated to be around USD 50 million annually. Chemical insecticides are of limited use in the management of T. palmi due to the thigmokinetic behaviour and development of high levels of resistance to insecticides. There is an urgent need to find out an effective futuristic management strategy, where the small RNAs especially microRNAs hold great promise as a key player in the growth and development. miRNAs are a class of short non-coding RNAs involved in regulation of gene expression either by mRNA cleavage or by translational repression. We identified and characterized a total of 77 miRNAs from T. palmi using high-throughput deep sequencing. Functional classifications of the targets for these miRNAs revealed that majority of them are involved in the regulation of transcription and translation, nucleotide binding and signal transduction. We have also validated few of these miRNAs employing stem-loop RT-PCR, qRT-PCR and Northern blot. The present study not only provides an in-depth understanding of the biological and physiological roles of miRNAs in governing gene expression but may also lead as an invaluable tool for the management of thysanopteran insects in the future.

  13. miRNA-205 affects infiltration and metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhouquan [Department of Chest Surgery, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061 (China); Department of Tumor, SenGong Hospital of Shaanxi, Xi’an 710300 (China); Liao, Hehe; Deng, Zhiping; Yang, Po; Du, Ning; Zhanng, Yunfeng [Department of Chest Surgery, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061 (China); Ren, Hong, E-mail: renhongs2000@yahoo.com.cn [Department of Chest Surgery, The First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061 (China)

    2013-11-08

    Highlights: •We detected expression of miR-205 in breast cancer cell lines and tissue samples. •We suggest miR-205 is downregulated in human breast cancer tissues and MCF7 cells. •We suggest the lower expression of miR-205 play a role in breast cancer onset. •These data suggest that miR-205 directly targets HER3 in human breast cancer. -- Abstract: Background: An increasing number of studies have shown that miRNAs are commonly deregulated in human malignancies, but little is known about the function of miRNA-205 (miR-205) in human breast cancer. The present study investigated the influence of miR-205 on breast cancer malignancy. Methods: The expression level of miR-205 in the MCF7 breast cancer cell line was determined by quantitative (q)RT-PCR. We then analyzed the expression of miR-205 in breast cancer and paired non-tumor tissues. Finally, the roles of miR-205 in regulating tumor proliferation, apoptosis, migration, and target gene expression were studied by MTT assay, flow cytometry, qRT-PCR, Western blotting and luciferase assay. Results: miR-205 was downregulated in breast cancer cells or tissues compared with normal breast cell lines or non-tumor tissues. Overexpression of miR-205 reduced the growth and colony-formation capacity of MCF7 cells by inducing apoptosis. Overexpression of miR-205 inhibited MCF7 cell migration and invasiveness. By bioinformation analysis, miR-205 was predicted to bind to the 3′ untranslated regions of human epidermal growth factor receptor (HER)3 mRNA, and upregulation of miR-205 reduced HER3 protein expression. Conclusion: miR-205 is a tumor suppressor in human breast cancer by post-transcriptional inhibition of HER3 expression.

  14. miRNA Signatures of Insulin Resistance in Obesity.

    Science.gov (United States)

    Jones, Angela; Danielson, Kirsty M; Benton, Miles C; Ziegler, Olivia; Shah, Ravi; Stubbs, Richard S; Das, Saumya; Macartney-Coxson, Donia

    2017-10-01

    Extracellular microRNAs (miRNAs) represent functional biomarkers for obesity and related disorders; this study investigated plasma miRNAs in insulin resistance phenotypes in obesity. One hundred seventy-five miRNAs were analyzed in females with obesity (insulin sensitivity, n = 11; insulin resistance, n = 19; type 2 diabetes, n = 15) and without obesity (n = 12). Correlations between miRNA level and clinical parameters and levels of 15 miRNAs in a murine obesity model were investigated. One hundred six miRNAs were significantly (adjusted P ≤ 0.05) different between controls and at least one obesity phenotype, including miRNAs with the following attributes: previously reported roles in obesity and altered circulating levels (e.g., miR-122, miR-192); known roles in obesity but no reported changes in circulating levels (e.g., miR-378a); and no current reported role in, or association with, obesity (e.g., miR-28-5p, miR-374b, miR-32). The miRNAs in the latter group were found to be associated with extracellular vesicles. Forty-eight miRNAs showed significant correlations with clinical parameters; stepwise regression retained let-7b, miR-144-5p, miR-34a, and miR-532-5p in a model predictive of insulin resistance (R 2  = 0.57, P = 7.5 × 10 -8 ). Both miR-378a and miR-122 were perturbed in metabolically relevant tissues in a murine model of obesity. This study expands on the role of extracellular miRNAs in insulin-resistant phenotypes of obesity and identifies candidate miRNAs not previously associated with obesity. © 2017 The Obesity Society.

  15. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    International Nuclear Information System (INIS)

    Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.

    2010-01-01

    Research highlights: → Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. → We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. → Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. → Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient-related hormones such as leptin

  16. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); and others

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  17. MiRNA Profiles in Lymphoblastoid Cell Lines of Finnish Prostate Cancer Families.

    Directory of Open Access Journals (Sweden)

    Daniel Fischer

    Full Text Available Heritable factors are evidently involved in prostate cancer (PrCa carcinogenesis, but currently, genetic markers are not routinely used in screening or diagnostics of the disease. More precise information is needed for making treatment decisions to distinguish aggressive cases from indolent disease, for which heritable factors could be a useful tool. The genetic makeup of PrCa has only recently begun to be unravelled through large-scale genome-wide association studies (GWAS. The thus far identified Single Nucleotide Polymorphisms (SNPs explain, however, only a fraction of familial clustering. Moreover, the known risk SNPs are not associated with the clinical outcome of the disease, such as aggressive or metastasised disease, and therefore cannot be used to predict the prognosis. Annotating the SNPs with deep clinical data together with miRNA expression profiles can improve the understanding of the underlying mechanisms of different phenotypes of prostate cancer.In this study microRNA (miRNA profiles were studied as potential biomarkers to predict the disease outcome. The study subjects were from Finnish high risk prostate cancer families. To identify potential biomarkers we combined a novel non-parametrical test with an importance measure provided from a Random Forest classifier. This combination delivered a set of nine miRNAs that was able to separate cases from controls. The detected miRNA expression profiles could predict the development of the disease years before the actual PrCa diagnosis or detect the existence of other cancers in the studied individuals. Furthermore, using an expression Quantitative Trait Loci (eQTL analysis, regulatory SNPs for miRNA miR-483-3p that were also directly associated with PrCa were found.Based on our findings, we suggest that blood-based miRNA expression profiling can be used in the diagnosis and maybe even prognosis of the disease. In the future, miRNA profiling could possibly be used in targeted screening

  18. Deregulation strategies for local governments and the role/opportunities for energy efficiency services in the utility industry deregulation

    International Nuclear Information System (INIS)

    Tseng, P.C.

    1998-01-01

    As the future shape of the electric utility industry continues to unfold and as retail competition becomes a reality, local governments are faced with balancing the need for: (1) economic development; (2) and to avoid the potential impact of cost-shifting among residents and businesses, while ensuring reliable and universal energy services. Furthermore, local governments need to find ways to recoup potential loss of franchise and tax revenues, to ensure fair and adequate energy-efficiency programs, and to continue other social programs for low income families. This paper will address two important issues every local government in the US are facing: (1) the development of viable deregulation strategies before, during and after the promulgation of utility deregulation; (2) opportunities for energy efficiency services in the competitive markets to serve local governments, which typically constitutes the largest market segment in utility's service territory. This paper presents issues and challenges common to all local governments. It documents strategies that several local governments are utilizing to embrace the coming electric utility restructuring and competition challenge to the benefits of their respective communities. This paper presents the results on deregulation work by the City of Portland, Oregon, Barnstable County, Massachusetts, and Montgomery County, Maryland. The research by these local governments was sponsored by the Urban Consortium Energy Task Force and Public Technology, Inc

  19. A study on the deregulation of the Finnish electricity markets

    International Nuclear Information System (INIS)

    Kopsakangas-Savolainen, M.

    2002-01-01

    Governments have regarded the electricity industry as a leading industrial sector throughout the history. Because of its strategic importance to industrial development, its impacts on the social and environmental issues and its natural monopoly characteristics, it has been seen necessary to regulate electricity industry effectively. However, in the mid 1980s it was realised that even though transmission and distribution networks are natural monopolies, the scale economies in electricity production at the generating unit level had exhausted at a unit size of about 500 MW. This meant that supply and generation had become potentially competitive activities. In Finland the new Electricity Market Act (EMA) came into force in 1.11.1995. According to it the production and supply of electricity became deregulated and competition was introduced to the industry. The main aim of the law was to improve efficiency. This dissertation analyses, both theoretically and empirically, the impacts of deregulation to the Finnish electricity markets. In chapter two we discuss on the grounds and incentives of the deregulation processes that have been carried out in different countries. We also determine the crucial factors in order succeed in the deregulation process. According to our view the success depend on the number of active players in the wholesale market, the rules of the bidding procedure, the organisation of the demand side operation, the neutrality of transmission grid, the structure of production technologies and the ownership structure of the industry. In chapter three we theoretically model the profit maximising behaviour of the Finnish electricity companies based on different stages of vertical integration and on different stage of competition. According to our results the profit maximising pricing rules of distribution units is dependent on the stage of integration and on the stage of competition. The separated distribution company maximises profits by setting the

  20. Computational analysis of human miRNAs phylogenetics | Bano ...

    African Journals Online (AJOL)

    MicroRNAs (miRNAs) are evolutionary conserved across broad phylogenetic distances and have gained considerable attention about evolution, genetic and phylogenetic analysis. Comparing sequences of miRNA precursors within a species and between closely related species should thus help to determine patterns of ...

  1. Base Composition Characteristics of Mammalian miRNAs

    Directory of Open Access Journals (Sweden)

    Bin Wang

    2013-01-01

    Full Text Available MicroRNAs (miRNAs are short RNA sequences that repress protein synthesis by either inhibiting the translation of messenger RNA (mRNA or increasing mRNA degradation. Endogenous miRNAs have been found in various organisms, including animals, plants, and viruses. Mammalian miRNAs are evolutionarily conserved, are scattered throughout chromosomes, and play an important role in the immune response and the onset of cancer. For this study, the author explored the base composition characteristics of miRNA genes from the six mammalian species that contain the largest number of known miRNAs. It was found that mammalian miRNAs are evolutionarily conserved and GU-rich. Interestingly, in the miRNA sequences investigated, A residues are clearly the most frequent occupants of positions 2 and 3 of the 5′ end of miRNAs. Unlike G and U residues that may pair with C/U and A/G, respectively, A residues can only pair with U residues of target mRNAs, which may augment the recognition specificity of the 5′ seed region.

  2. Viral miRNAs: tools for immune evasion.

    Science.gov (United States)

    Boss, Isaac W; Renne, Rolf

    2010-08-01

    MicroRNAs (miRNAs) are noncoding RNA molecules approximately 22 nucleotides in length that post-transcriptionally regulate gene expression by complementary binding to target mRNAs. MiRNAs have been identified in a diverse range of both metazoan and plant species. Functionally, miRNAs modulate multiple cellular processes including development, hematopoiesis, immunity, and oncogenesis. More recently, DNA viruses were found to encode and express miRNAs during host infection. Although the functions of most viral miRNAs are not well understood, early analysis of target genes pointed to immune modulation suggesting that viral miRNAs are a component of the immune evasion repertoire, which facilitates viral persistence. In addition to directly targeting immune functions, viral encoded miRNAs contribute to immune evasion by targeting proapoptotic genes, and in the case of herpesviruses, by controlling viral latency. Here we summarize the recently discovered targets of viral miRNAs and discuss the complex nature of this novel emerging regulatory mechanism. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. High mobility group A2 is a target for miRNA-98 in head and neck squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Nikitakis Nikolaos

    2007-01-01

    Full Text Available Abstract Background HMGA2 expression has been shown to be associated with enhanced selective chemosensitivity towards the topoisomerase (topo II inhibitor, doxorubicin, in cancer cells. Although the roles of signaling cascades and proteins as regulatory factors in development, neoplasia and adaptation to the environment are becoming well established, evidence for the involvement of regulatory small RNA molecules, such as microRNAs (miRNAs as important regulators of both transcriptional and posttranscriptional gene silencing is presently mounting. Results Here we report that HMGA2 expression in head and neck squamous cell carcinoma (HNSCC cells is regulated in part by miRNA-98 (miR-98. Albeit HMGA2 is associated with enhanced selective chemosensitivity towards topoisomerase (topo II inhibitor, doxorubicin in HNSCC, the expression of HMGA2 is thwarted by hypoxia. This is accompanied by enhanced expression of miRNA-98 and other miRNAs, which predictably target HMGA2. Moreover, we show that transfection of pre-miR-98™ during normoxia diminishes HMGA2 and potentiates resistance to doxorubicin and cisplatin. These findings implicate the role of a miRNA as a key element in modulating tumors in variable microenvironments. Conclusion These studies validate the observation that HMGA2 plays a prominent role in governing genotoxic responses. However, this may only represent cells growing under normal oxygen tensions. The demonstration that miRNA profiles are altered during hypoxia and repress a genotoxic response indicates that changes in microenvironment in eukaryotes mimic those of lower species and plants, where, for example, abiotic stresses regulate the expression of thousands of genes in plants at both transcriptional and posttranscriptional levels through a number of miRNAs and other small regulatory RNAs.

  4. The miRNA and mRNA Signatures of Peripheral Blood Cells in Humans Infected with Trypanosoma brucei gambiense.

    Directory of Open Access Journals (Sweden)

    Smiths Lueong

    Full Text Available Simple, reliable tools for diagnosis of human African Trypanosomiases could ease field surveillance and enhance patient care. In particular, current methods to distinguish patients with (stage II and without (stage I brain involvement require samples of cerebrospinal fluid. We describe here an exploratory study to find out whether miRNAs from peripheral blood leukocytes might be useful in diagnosis of human trypanosomiasis, or for determining the stage of the disease. Using microarrays, we measured miRNAs in samples from Trypanosoma brucei gambiense-infected patients (9 stage I, 10 stage II, 8 seronegative parasite-negative controls and 12 seropositive, but parasite-negative subjects. 8 miRNAs (out of 1205 tested showed significantly lower expression in patients than in seronegative, parasite-negative controls, and 1 showed increased expression. There were no clear differences in miRNAs between patients in different disease stages. The miRNA profiles could not distinguish seropositive, but parasitologically negative samples from controls and results within this group did not correlate with those from the trypanolysis test. Some of the regulated miRNAs, or their predicted mRNA targets, were previously reported changed during other infectious diseases or cancer. We conclude that the changes in miRNA profiles of peripheral blood lymphocytes in human African trypanosomiasis are related to immune activation or inflammation, are probably disease-non-specific, and cannot be used to determine the disease stage. The approach has little promise for diagnostics but might yield information about disease pathology.

  5. Decreased neutrophil-associated miRNA and increased B-cell associated miRNA expression during tuberculosis.

    Science.gov (United States)

    van Rensburg, I C; du Toit, L; Walzl, G; du Plessis, N; Loxton, A G

    2018-05-20

    MicroRNAs are short non-coding RNAs that regulate gene expression by binding to, and suppressing the expression of genes. Research show that microRNAs have potential to be used as biomarkers for diagnosis, treatment response and can be used for therapeutic interventions. Furthermore, microRNA expression has effects on immune cell functions, which may lead to disease. Considering the important protective role of neutrophils and B-cells during M.tb infection, we evaluated the expression of microRNAs, known to alter function of these cells, in the context of human TB. We utilised real-time PCR to evaluate the levels of microRNA transcripts in the peripheral blood of TB cases and healthy controls. We found that neutrophil-associated miR-197-3p, miR-99b-5p and miR-191-5p transcript levels were significantly lower in TB cases. Additionally, B-cell-associated miR-320a, miR-204-5p, miR331-3p and other transcript levels were higher in TB cases. The miRNAs differentially expressed in neutrophils are predominantly implicated in signalling pathways leading to cytokine productions. Here, the decreased expression in TB cases may imply a lack of suppression on signalling pathways, which may lead to increased production of pro-inflammatory cytokines such as interferon-gamma. Furthermore, the miRNAs differentially expressed in B-cells are mostly involved in the induction/suppression of apoptosis. Further functional studies are however required to elucidate the significance and functional effects of changes in the expression of these microRNAs. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. miRNAs in Normal and Malignant Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Ryutaro Kotaki

    2017-07-01

    Full Text Available Lineage specification is primarily regulated at the transcriptional level and lineage-specific transcription factors determine cell fates. MicroRNAs (miRNAs are 18–24 nucleotide-long non-coding RNAs that post-transcriptionally decrease the translation of target mRNAs and are essential for many cellular functions. miRNAs also regulate lineage specification during hematopoiesis. This review highlights the roles of miRNAs in B-cell development and malignancies, and discusses how miRNA expression profiles correlate with disease prognoses and phenotypes. We also discuss the potential for miRNAs as therapeutic targets and diagnostic tools for B-cell malignancies.

  7. Identification and characterization of miRNAs in two closely related C4 and C3 species of Cleome by high-throughput sequencing

    Science.gov (United States)

    Gao, Shuangcheng; Zhao, Wei; Li, Xiang; You, Qingbo; Shen, Xinjie; Guo, Wei; Wang, Shihua; Shi, Guoan; Liu, Zheng; Jiao, Yongqing

    2017-04-01

    Cleome gynandra and Cleome hassleriana, which are C4 and C3 plants, respectively, are two species of Cleome. The close genetic relationship between C. gynandra and C. hassleriana provides advantages for discovering the differences in leaf development and physiological processes between C3 and C4 plants. MicroRNAs (miRNAs) are a class of important regulators of various biological processes. In this study, we investigate the differences in the characteristics of miRNAs between C. gynandra and C. hassleriana using high-throughput sequencing technology. In total, 94 and 102 known miRNAs were identified in C. gynandra and C. hassleriana, respectively, of which 3 were specific for C. gynandra and 10 were specific for C. hassleriana. Ninety-one common miRNAs were identified in both species. In addition, 4 novel miRNAs were detected, including three in C. gynandra and three in C. hassleriana. Of these miRNAs, 67 were significantly differentially expressed between these two species and were involved in extensive biological processes, such as glycol-metabolism and photosynthesis. Our study not only provided resources for C. gynandra and C. hassleriana research but also provided useful clues for the understanding of the roles of miRNAs in the alterations of biological processes in leaf tissues during the evolution of the C4 pathway.

  8. Comparison of miRNAs and Their Targets in Seed Development between Two Maize Inbred Lines by High-Throughput Sequencing and Degradome Analysis.

    Directory of Open Access Journals (Sweden)

    Feng-Yao Wu

    Full Text Available MicroRNAs (miRNAs play an important role in plant growth, development, and response to environment. For identifying and comparing miRNAs and their targets in seed development between two maize inbred lines (i.e. PH6WC and PH4CV, two sRNAs and two degradome libraries were constructed. Through high-throughput sequencing and miRNA identification, 55 conserved and 24 novel unique miRNA sequences were identified in two sRNA libraries; moreover, through degradome sequencing and analysis, 137 target transcripts corresponding to 38 unique miRNA sequences were identified in two degradome libraries. Subsequently, 16 significantly differentially expressed miRNA sequences were verified by qRT-PCR, in which 9 verified sequences obviously target 30 transcripts mainly involved with regulation in flowering and development in embryo. Therefore, the results suggested that some miRNAs (e.g. miR156, miR171, miR396 and miR444 related reproductive development might differentially express in seed development between the PH6WC and PH4CV maize inbred lines in this present study.

  9. Deregulated Cardiac Specific MicroRNAs in Postnatal Heart Growth

    Directory of Open Access Journals (Sweden)

    Pujiao Yu

    2016-01-01

    Full Text Available The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs, as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs—miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p—were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.

  10. [Changes of miRNA-17-5p, miRNA-21 and miRNA-106a level during rat kidney ischemia-reperfusion injury].

    Science.gov (United States)

    Ma, Long; Wu, Kun; Liu, Kun; Gu, Shuo; Wang, Yi; Xu, Zongyuan; Yu, Xiangyou; Meng, Junsong

    2015-05-19

    Ischemia-reperfusion (I/R) is a main cause of acute kidney injury (AKI). The renal expression profiles of microRNA (miRNA) and time course of their changes after renal I/R were explored to screen acute AKI prognostic-related microRNAs and biomarkers. The expression profile of miRNA was analyzed for detecting miRNAs in kidney after renal I/R injury. Real-time polymerase chain reaction (PCR) was performed to validate the results of microarray. And the relationship was examined between kidney injury and time course of changes in selected miRNAs. Twenty-one miRNAs were differentially expressed in kidney of rats with renal I/R injury. And 5 miRNAs had prominent differences. miR-17-5p, miR-21 and miR-106a were selected for further confirmation by quantitative real-time-PCR. And the results were consistent with those of microarry. During early stage (4 h) after I/R, the expression level of miR-17-5p significantly increased (P reperfusion (P injury. And miR-17-5p is more sensitive than BUN and NGAL so that it is a more ideal biomarker for AKI.

  11. PML-RARA-associated cooperating mutations belong to a transcriptional network that is deregulated in myeloid leukemias.

    Science.gov (United States)

    Ronchini, C; Brozzi, A; Riva, L; Luzi, L; Gruszka, A M; Melloni, G E M; Scanziani, E; Dharmalingam, G; Mutarelli, M; Belcastro, V; Lavorgna, S; Rossi, V; Spinelli, O; Biondi, A; Rambaldi, A; Lo-Coco, F; di Bernardo, D; Pelicci, P G

    2017-09-01

    It has been shown that individual acute myeloid leukemia (AML) patients are characterized by one of few initiating DNA mutations and 5-10 cooperating mutations not yet defined among hundreds identified by massive sequencing of AML genomes. We report an in vivo insertional-mutagenesis screen for genes cooperating with one AML initiating mutations (PML-RARA, oncogene of acute promyelocytic leukemia, APL), which allowed identification of hundreds of genetic cooperators. The cooperators are mutated at low frequency in APL or AML patients but are always abnormally expressed in a cohort of 182 APLs and AMLs analyzed. These deregulations appear non-randomly distributed and present in all samples, regardless of their associated genomic mutations. Reverse-engineering approaches showed that these cooperators belong to a single transcriptional gene network, enriched in genes mutated in AMLs, where perturbation of single genes modifies expression of others. Their gene-ontology analysis showed enrichment of genes directly involved in cell proliferation control. Therefore, the pool of PML-RARA cooperating mutations appears large and heterogeneous, but functionally equivalent and deregulated in the majority of APLs and AMLs. Our data suggest that the high heterogeneity of DNA mutations in APLs and AMLs can be reduced to patterns of gene expression deregulation of a single 'mutated' gene network.

  12. Identification of miRNAs and their targets through high-throughput sequencing and degradome analysis in male and female Asparagus officinalis.

    Science.gov (United States)

    Chen, Jingli; Zheng, Yi; Qin, Li; Wang, Yan; Chen, Lifei; He, Yanjun; Fei, Zhangjun; Lu, Gang

    2016-04-12

    MicroRNAs (miRNAs), a class of non-coding small RNAs (sRNAs), regulate various biological processes. Although miRNAs have been identified and characterized in several plant species, miRNAs in Asparagus officinalis have not been reported. As a dioecious plant with homomorphic sex chromosomes, asparagus is regarded as an important model system for studying mechanisms of plant sex determination. Two independent sRNA libraries from male and female asparagus plants were sequenced with Illumina sequencing, thereby generating 4.13 and 5.88 million final clean reads, respectively. Both libraries predominantly contained 24-nt sRNAs, followed by 21-nt sRNAs. Further analysis identified 154 conserved miRNAs, which belong to 26 families, and 39 novel miRNA candidates seemed to be specific to asparagus. Comparative profiling revealed that 63 miRNAs exhibited significant differential expression between male and female plants, which was confirmed by real-time quantitative PCR analysis. Among them, 37 miRNAs were significantly up-regulated in the female library, whereas the others were preferentially expressed in the male library. Furthermore, 40 target mRNAs representing 44 conserved and seven novel miRNAs were identified in asparagus through high-throughput degradome sequencing. Functional annotation showed that these target mRNAs were involved in a wide range of developmental and metabolic processes. We identified a large set of conserved and specific miRNAs and compared their expression levels between male and female asparagus plants. Several asparagus miRNAs, which belong to the miR159, miR167, and miR172 families involved in reproductive organ development, were differentially expressed between male and female plants, as well as during flower development. Consistently, several predicted targets of asparagus miRNAs were associated with floral organ development. These findings suggest the potential roles of miRNAs in sex determination and reproductive developmental processes in

  13. miRNAs in human subcutaneous adipose tissue: Effects of weight loss induced by hypocaloric diet and exercise

    DEFF Research Database (Denmark)

    Kristensen, Malene M; Davidsen, Peter K; Vigelsø Hansen, Andreas

    2017-01-01

    tissue from 19 individuals with severe obesity (10 women and 9 men) before and after a 15-week weight loss intervention was studied using genome-wide microarray analysis. The microarray results were validated with RT-qPCR, and pathway enrichment analysis of in silico predicted targets was performed......RNA-target relationships correlated negatively, indicating possible miRNA regulation, including miR-29a-3p and lipoprotein lipase mRNA levels. Proteins involved in lipolysis were not affected by the intervention. Conclusions Weight loss influenced several miRNAs, some of which were negatively correlated with predicted...

  14. Comparative analysis reveals dynamic changes in miRNAs and their targets and expression during somatic embryogenesis in longan (Dimocarpus longan Lour..

    Directory of Open Access Journals (Sweden)

    Yuling Lin

    Full Text Available Somatic embryogenesis (SE, which resembles zygotic embryogenesis, is an essential component of the process of plant cell differentiation and embryo development. Although microRNAs (miRNAs are important regulators of many plant develop- mental processes, their roles in SE have not been thoroughly investigated. In this study, we used deep-sequencing, computational, and qPCR methods to identify, profile, and describe conserved and novel miRNAs involved in longan (Dimocarpus longan SE. A total of 643 conserved and 29 novel miRNAs (including star strands from more than 169 miRNA families were identified in longan embryogenic tissue using Solexa sequencing. By combining computational and degradome sequencing approaches, we were able to predict 2063 targets of 272 miRNAs and verify 862 targets of 181 miRNAs. Target annotation revealed that the putative targets were involved in a broad variety of biological processes, including plant metabolism, signal transduction, and stimulus response. Analysis of stage- and tissue-specific expressions of 20 conserved and 4 novel miRNAs indicated their possible roles in longan SE. These miRNAs were dlo-miR156 family members and dlo-miR166c* associated with early embryonic culture developmental stages; dlo-miR26, dlo-miR160a, and families dlo-miR159, dlo-miR390, and dlo-miR398b related to heart-shaped and torpedo- shaped embryo formation; dlo-miR4a, dlo-miR24, dlo-miR167a, dlo-miR168a*, dlo-miR397a, dlo-miR398b.1, dlo-miR398b.2, dlo-miR808 and dlo-miR5077 involved in cotyledonary embryonic development; and dlo-miR17 and dlo-miR2089*-1 that have regulatory roles during longan SE. In addition, dlo-miR167a, dlo-miR808, and dlo-miR5077 may be required for mature embryo formation. This study is the first reported investigation of longan SE involving large-scale cloning, characterization, and expression profiling of miRNAs and their targets. The reported results contribute to our knowledge of somatic embryo miRNAs and

  15. miRNA array screening reveals cooperative MGMT-regulation between miR-181d-5p and miR-409-3p in glioblastoma

    Science.gov (United States)

    Khalil, Susanna; Fabbri, Enrica; Santangelo, Alessandra; Bezzerri, Valentino; Cantù, Cinzia; Gennaro, Gianfranco Di; Finotti, Alessia; Ghimenton, Claudio; Eccher, Albino; Dechecchi, Maria; Scarpa, Aldo; Hirshman, Brian; Chen, Clark; Ferracin, Manuela; Negrini, Massimo; Gambari, Roberto; Cabrini, Giulio

    2016-01-01

    The levels of expression of O6-methylguanine-DNA methyltransferase (MGMT) are relevant in predicting the response to the alkylating chemotherapy in patients affected by glioblastoma. MGMT promoter methylation and the published MGMT regulating microRNAs (miRNAs) do not completely explain the expression pattern of MGMT in clinical glioblastoma specimens. Here we used a genome-wide microarray-based approach to identify MGMT regulating miRNAs. Our screen unveiled three novel MGMT regulating miRNAs, miR-127-3p, miR-409-3p, and miR-124-3p, in addition to the previously identified miR-181d-5p. Transfection of these three novel miRNAs into the T98G glioblastoma cell line suppressed MGMT mRNA and protein expression. However, their MGMT- suppressive effects are 30–50% relative that seen with miR-181d-5p transfection. In silico analyses of The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) revealed that miR-181d-5p is the only miRNA that consistently exhibited inverse correlation with MGMT mRNA expression. However, statistical models incorporating both miR-181d-5p and miR-409-3p expression better predict MGMT expression relative to models involving either miRNA alone. Our results confirmed miR-181d-5p as the key MGMT-regulating miRNA. Other MGMT regulating miRNAs, including the miR-409-3p identified in this report, modify the effect of miR-181d-5p on MGMT expression. MGMT expression is, thus, regulated by cooperative interaction between key MGMT-regulating miRNAs. PMID:27057640

  16. Post-transcriptional generation of miRNA variants by multiple nucleotidyl transferases contributes to miRNA transcriptome complexity.

    Science.gov (United States)

    Wyman, Stacia K; Knouf, Emily C; Parkin, Rachael K; Fritz, Brian R; Lin, Daniel W; Dennis, Lucas M; Krouse, Michael A; Webster, Philippa J; Tewari, Muneesh

    2011-09-01

    Modification of microRNA sequences by the 3' addition of nucleotides to generate so-called "isomiRs" adds to the complexity of miRNA function, with recent reports showing that 3' modifications can influence miRNA stability and efficiency of target repression. Here, we show that the 3' modification of miRNAs is a physiological and common post-transcriptional event that shows selectivity for specific miRNAs and is observed across species ranging from C. elegans to human. The modifications result predominantly from adenylation and uridylation and are seen across tissue types, disease states, and developmental stages. To quantitatively profile 3' nucleotide additions, we developed and validated a novel assay based on NanoString Technologies' nCounter platform. For certain miRNAs, the frequency of modification was altered by processes such as cell differentiation, indicating that 3' modification is a biologically regulated process. To investigate the mechanism of 3' nucleotide additions, we used RNA interference to screen a panel of eight candidate miRNA nucleotidyl transferases for 3' miRNA modification activity in human cells. Multiple enzymes, including MTPAP, PAPD4, PAPD5, ZCCHC6, ZCCHC11, and TUT1, were found to govern 3' nucleotide addition to miRNAs in a miRNA-specific manner. Three of these enzymes-MTPAP, ZCCHC6, and TUT1-have not previously been known to modify miRNAs. Collectively, our results indicate that 3' modification observed in next-generation small RNA sequencing data is a biologically relevant process, and identify enzymatic mechanisms that may lead to new approaches for modulating miRNA activity in vivo.

  17. Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation.

    Science.gov (United States)

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Yan, Yu-Hui; Li, Shao-Heng; Wang, Yue; Meng, Ya-Kun; Yang, Jing-Xian; Kang, Ting-Guo

    2016-09-01

    Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-κB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT-PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-α and IL-6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKα and IKKβ) expression and inhibit NF-κB signaling pathway activity; moreover, the increased miRNA-199a suppresses

  18. Deregulation of natural gas: focus on contract carriage

    Energy Technology Data Exchange (ETDEWEB)

    Montgomery, W.D.; Broadman, H.G.

    Deregulation under the Natural Gas Policy Act of 1978 introduced new concerns without solving the gas market problems. The external forces of warm weather, recession, and lower oil prices - which reduced demand at a time when wellhead prices were rising - have allowed prices to exceed market-clearing levels and prompted fuel switching among industrial users. Contracting and regulatory practices in the natural gas industry interfere with the supply and demand balance of a free market, creating inefficient production and regional price differentials. Corrective steps would be to change pipeline status from private to common carrier and to remove take-or-pay and other contract constraints. (DCK)

  19. Deregulation of the non-coding genome in leukemia.

    Science.gov (United States)

    Teppo, Susanna; Heinäniemi, Merja; Lohi, Olli

    2017-07-03

    Methodological advances that allow deeper characterization of non-coding elements in the genome have started to reveal the full spectrum of deregulation in cancer. We generated an inducible cell model to track transcriptional changes after induction of a well-known leukemia-inducing fusion gene, ETV6-RUNX1. Our data revealed widespread transcriptional alterations outside coding elements in the genome. This adds to the growing list of various alterations in the non-coding genome in cancer and pinpoints their role in diseased cellular state.

  20. Power systems locational marginal pricing in deregulated markets

    Science.gov (United States)

    Wang, Hui-Fung Francis

    Since the beginning of the 1990s, the electricity business is transforming from a vertical integrating business to a competitive market operations. The generation, transmission, distribution subsystem of an electricity utility are operated independently as Genco (generation subsystem), Transco (transmission subsystem), and Distco (distribution subsystem). This trend promotes more economical inter- and intra regional transactions to be made by the participating companies and the users of electricity to achieve the intended objectives of deregulation. There are various types of electricity markets that are implemented in the North America in the past few years. However, transmission congestion management becomes a key issue in the electricity market design as more bilateral transactions are traded across long distances competing for scarce transmission resources. It directly alters the traditional concept of energy pricing and impacts the bottom line, revenue and cost of electricity, of both suppliers and buyers. In this research, transmission congestion problem in a deregulated market environment is elucidated by implementing by the Locational Marginal Pricing (LMP) method. With a comprehensive understanding of the LMP method, new mathematical tools will aid electric utilities in exploring new business opportunities are developed and presented in this dissertation. The dissertation focuses on the development of concept of (LMP) forecasting and its implication to the market participants in deregulated market. Specifically, we explore methods of developing fast LMP calculation techniques that are differ from existing LMPs. We also explore and document the usefulness of the proposed LMP in determining electricity pricing of a large scale power system. The developed mathematical tools use of well-known optimization techniques such as linear programming that are support by several flow charts. The fast and practical security constrained unit commitment methods are the

  1. Deregulation and restructuring of the power industry in the United States

    International Nuclear Information System (INIS)

    Bernardini, O.

    2001-01-01

    The article addresses the causal relations between deregulation and restructuring of the power sector in the United States during the last two decades. To better appreciate the issues involved in this country, the analysis starts with an account of the origins of the regulatory process at the local, state and federal levels of government. The article proceeds with a discussion of the factors which determined the partial liberalisation of electricity generation from the end of the 1970s and the subsequent extensive liberalisation during the course of the 1990s, resulting in the functional separation between generation, transmission and ancillary services. It concludes with a description of the radical changes currently underway in the power sector [it

  2. Rough hypercuboid based supervised clustering of miRNAs.

    Science.gov (United States)

    Paul, Sushmita; Vera, Julio

    2015-07-01

    The microRNAs are small, endogenous non-coding RNAs found in plants, animals, and some viruses, which function in RNA silencing and post-transcriptional regulation of gene expression. It is suggested by various genome-wide studies that a substantial fraction of miRNA genes is likely to form clusters. The coherent expression of the miRNA clusters can then be used to classify samples according to the clinical outcome. In this regard, a new clustering algorithm, termed as rough hypercuboid based supervised attribute clustering (RH-SAC), is proposed to find such groups of miRNAs. The proposed algorithm is based on the theory of rough set, which directly incorporates the information of sample categories into the miRNA clustering process, generating a supervised clustering algorithm for miRNAs. The effectiveness of the new approach is demonstrated on several publicly available miRNA expression data sets using support vector machine. The so-called B.632+ bootstrap error estimate is used to minimize the variability and biasedness of the derived results. The association of the miRNA clusters to various biological pathways is also shown by doing pathway enrichment analysis.

  3. Identification of Appropriate Reference Genes for Normalization of miRNA Expression in Grafted Watermelon Plants under Different Nutrient Stresses.

    Science.gov (United States)

    Wu, Weifang; Deng, Qin; Shi, Pibiao; Yang, Jinghua; Hu, Zhongyuan; Zhang, Mingfang

    2016-01-01

    Watermelon (Citrullus lanatus) is a globally important crop belonging to the family Cucurbitaceae. The grafting technique is commonly used to improve its tolerance to stress, as well as to enhance its nutrient uptake and utilization. It is believed that miRNA is most likely involved in its nutrient-starvation response as a graft-transportable signal. The quantitative real-time reverse transcriptase polymerase chain reaction is the preferred method for miRNA functional analysis, in which reliable reference genes for normalization are crucial to ensure the accuracy. The purpose of this study was to select appropriate reference genes in scion (watermelon) and rootstocks (squash and bottle gourd) of grafted watermelon plants under normal growth conditions and nutrient stresses (nitrogen and phosphorus starvation). Under nutrient starvation, geNorm identified miR167c and miR167f as two most stable genes in both watermelon leaves and squash roots. miR166b was recommended by both geNorm and NormFinder as the best reference in bottle gourd roots under nutrient limitation. Expression of a new Cucurbitaceae miRNA, miR85, was used to validate the reliability of candidate reference genes under nutrient starvation. Moreover, by comparing several target genes expression in qRT-PCR analysis with those in RNA-seq data, miR166b and miR167c were proved to be the most suitable reference genes to normalize miRNA expression under normal growth condition in scion and rootstock tissues, respectively. This study represents the first comprehensive survey of the stability of miRNA reference genes in Cucurbitaceae and provides valuable information for investigating more accurate miRNA expression involving grafted watermelon plants.

  4. MicroRNA Expression Profiling in Clear Cell Renal Cell Carcinoma: Identification and Functional Validation of Key miRNAs.

    Directory of Open Access Journals (Sweden)

    Haowei He

    Full Text Available This study aims to profile dysregulated microRNA (miRNA expression in clear cell renal cell carcinoma (ccRCC and to identify key regulatory miRNAs in ccRCC.miRNA expression profiles in nine pairs of ccRCC tumor samples at three different stages and the adjacent, non-tumorous tissues were investigated using miRNA arrays. Eleven miRNAs were identified to be commonly dysregulated, including three up-regulated (miR-487a, miR-491-3p and miR-452 and eight down-regulated (miR-125b, miR-142-3p, miR-199a-5p, miR-22, miR-299-3p, miR-29a, miR-429, and miR-532-5p in tumor tissues as compared with adjacent normal tissues. The 11 miRNAs and their predicted target genes were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enrichment analysis, and three key miRNAs (miR-199a-5p, miR-22 and miR-429 were identified by microRNA-gene network analysis. Dysregulation of the three key miRNAs were further validated in another cohort of 15 ccRCC samples, and the human kidney carcinoma cell line 786-O, as compared with five normal kidney samples. Further investigation showed that over-expression of miR-199a-5p significantly inhibited the invasion ability of 786-O cells. Luciferase reporter assays indicated that miR-199a-5p regulated expression of TGFBR1 and JunB by directly interacting with their 3' untranslated regions. Transfection of miR-199a-5p successfully suppressed expression of TGFBR1 and JunB in the human embryonic kidney 293T cells, further confirming the direct regulation of miR-199a-5p on these two genes.This study identified 11 commonly dysregulated miRNAs in ccRCC, three of which (miR-199a-5p, miR-22 and miR-429 may represent key miRNAs involved in the pathogenesis of ccRCC. Further studies suggested that miR-199a-5p plays an important role in inhibition of cell invasion of ccRCC cells by suppressing expression of TGFBR1 and JunB.

  5. Comparative profiling of miRNAs and target gene identification in distant-grafting between tomato and Lycium (goji berry

    Directory of Open Access Journals (Sweden)

    A B M Khaldun

    2016-10-01

    Full Text Available Local translocation of small RNAs between cells is proved. Long distance translocation between rootstock and scion is also well documented in the homo-grafting system, but the process in distant-grafting is widely unexplored where rootstock and scion belonging to different genera. Micro RNAs are a class of small, endogenous, noncoding, gene silencing RNAs that regulate target genes of a wide range of important biological pathways in plants. In this study, tomato was grafted onto goji (Lycium chinense Mill. to reveal the insight of miRNAs regulation and expression patterns within a distant-grafting system. Goji is an important traditional Chinese medicinal plant with enriched phytochemicals. Illumina sequencing technology has identified 68 evolutionary known miRNAs of 37 miRNA families. Moreover, 168 putative novel miRNAs were also identified. Compared with control tomato, 43 (11 known and 32 novels and 163 (33 known and 130 novels miRNAs were expressed significantly different in shoot and fruit of grafted tomato, respectively. The fruiting stage was identified as the most responsive in the distant-grafting approach and 123 miRNAs were found as up-regulating in the grafted fruit which is remarkably higher compare to the grafted shoot tip (28. Potential targets of differentially expressed miRNAs were found to be involved in diverse metabolic and regulatory pathways. ADP binding activities, molybdopterin synthase complex and RNA helicase activity were found as enriched terms in GO (Gene Ontology analysis. Additionally, ‘metabolic pathways’ was revealed as the most significant pathway in KEGG (Kyoto Encyclopedia of Genes and Genomes analysis. The information of the small RNA transcriptomes that are obtained from this study might be the first miRNAs elucidation for a distant-grafting system, particularly between goji and tomato. The results from this study will provide the insights into the molecular aspects of miRNA-mediated regulation in the

  6. MicroRNA transfection and AGO-bound CLIP-seq data sets reveal distinct determinants of miRNA action

    DEFF Research Database (Denmark)

    Wen, Jiayu; Parker, Brian J; Jacobsen, Anders

    2011-01-01

    the predictive effect of target flanking features. We observe distinct target determinants between expression-based and CLIP-based data. Target flanking features such as flanking region conservation are an important AGO-binding determinant-we hypothesize that CLIP experiments have a preference for strongly bound......Microarray expression analyses following miRNA transfection/inhibition and, more recently, Argonaute cross-linked immunoprecipitation (CLIP)-seq assays have been used to detect miRNA target sites. CLIP and expression approaches measure differing stages of miRNA functioning-initial binding of the mi...... miRNP-target interactions involving adjacent RNA-binding proteins that increase the strength of cross-linking. In contrast, seed-related features are major determinants in expression-based studies, but less so for CLIP-seq studies, and increased miRNA concentrations typical of transfection studies...

  7. Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

    Energy Technology Data Exchange (ETDEWEB)

    Fukunaga, Satoki [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Kakehashi, Anna [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Sumida, Kayo; Kushida, Masahiko; Asano, Hiroyuki [Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558 (Japan); Gi, Min [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2015-08-01

    To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective of initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis.

  8. The RNA-binding protein HOS5 and serine/arginine-rich proteins RS40 and RS41 participate in miRNA biogenesis in Arabidopsis

    KAUST Repository

    Chen, Tao

    2015-07-30

    MicroRNAs are a class of small regulatory RNAs that are generated from primary miRNA (pri-miRNA) transcripts with a stem-loop structure. Accuracy of the processing of pri-miRNA into mature miRNA in plants can be enhanced by SERRATE (SE) and HYPONASTIC LEAVES 1 (HYL1). HYL1 activity is regulated by the FIERY2 (FRY2)/RNA polymerase II C-terminal domain phosphatase-like 1 (CPL1). Here, we discover that HIGH OSMOTIC STRESS GENE EXPRESSION 5 (HOS5) and two serine/arginine-rich splicing factors RS40 and RS41, previously shown to be involved in pre-mRNA splicing, affect the biogenesis of a subset of miRNA. These proteins are required for correct miRNA strand selection and the maintenance of miRNA levels. FRY2 dephosphorylates HOS5 whose phosphorylation status affects its subnuclear localization. HOS5 and the RS proteins bind both intronless and intron-containing pri-miRNAs. Importantly, all of these splicing-related factors directly interact with both HYL1 and SE in nuclear splicing speckles. Our results indicate that these splicing factors are directly involved in the biogenesis of a group of miRNA.

  9. Today or not today: Deregulating the Russian gas sector

    International Nuclear Information System (INIS)

    Grigoryev, Yuli

    2007-01-01

    Although Russia is the world's biggest producer of natural gas, its ability to maintain timely and reliable supply to meet the growing global demand has come under question in recent months. The gas war with Ukraine notwithstanding, concern has been raised by a number of observers that underinvestment in the gas sector will lead to a systemic failure of the state monopolist OAO Gazprom to increase or even maintain current levels of production. Yet with a quarter of European gas coming from Russia, and with increasing presence of Gazprom in European downstream operations (such as Germany, Hungary, and other CIS states) as well as seemingly closer ties with Algeria, another major supplier of gas to Europe, there has been a strong reaction from Europe's policy-makers to decrease dependence on Russian gas. Deregulating and liberalising the gas sector would see the lifting of restrictions to foreign or independent investors wishing to gain access to Russian reserves, as well as the unhindered access to the pipeline infrastructure and export markets. It would also signal the unbundling of Gazprom and an end to the artificially low price of gas to the domestic consumer. This paper discusses whether deregulation is the optimal way to raise capital, attract investment and increase supply security for Russia's Western neighbours. In doing so, the paper identifies the objectives of the EU as the importer whilst trying to align them with the objectives of the Russian Federation as the exporter, in the current political context

  10. Competition and deregulation in electricity : the national and continental dimension

    International Nuclear Information System (INIS)

    Garant, D.

    2000-01-01

    Some of the recent developments with Hydro-Quebec in terms of moving towards a deregulated competitive market were presented. In June 2000, the Quebec National Assembly passed legislation allowing for power generation and wholesale supply of electricity within Quebec will to be a deregulated business based on the gradual introduction of a competitive, contested market at the wholesale level. This legislation mitigates Hydro-Quebec's market power by legislating a long term fixed price supply contract between Hydro-Quebec's generation and distribution groups, operating as a functionally separate division within corporate Hydro-Quebec. Hydro-Quebec's market power in generation is 36,000 MW, the bulk of which will be committed to the Quebec distribution market at a fixed price of about 2.8 cents per kWh. Hydro-Quebec will maintain the rights to develop large scale hydro in Quebec if the development meets conditions of economic viability, environmental soundness and is locally acceptable. Hydro-Quebec is also expanding into new areas of generation such as wind power. The electric utility also believes it can play a role in Atlantic Canada by trading and moving off-peak and on-peak energy by using the storage capacity of their large hydro reservoirs

  11. Deregulation and internationalisation - impact on the Swedish nuclear industry

    International Nuclear Information System (INIS)

    Haukeland, Sverre R.

    2010-01-01

    The deregulation of the Swedish electricity market in 1996 was well known in advance, and the nuclear power plants in Sweden, as well as their main suppliers, made early preparations for a this new situation. In a study - performed by the author at Malardalen University in Sweden - it is concluded that the electricity industry, including the nuclear power plants, was fundamentally transformed in conjunction with market liberalisation. Two large foreign companies, E-on and Fortum, entered the Swedish market and became part-owners of the nuclear plants. After deregulation, the electricity market in Sweden is dominated by these two companies and the large national company Vattenfall. Similarly, Vattenfall has recently grown into an international energy company, acquiring generation capacity in Northern Europe outside of Sweden, including nuclear power plants in Germany. Restructuring of the nuclear industry on the supplier side started in the 1980's, when the Swedish company ASEA and BBC of Switzerland merged to become ABB. Several years later the Swedish nuclear plant supplier ABB-Atom became part of Westinghouse Electric Company, today owned by Toshiba. The Swedish experience thus confirms an international trend of mergers and consolidation in the nuclear industry. (authors)

  12. Effect of demand management on regulated and deregulated electricity sectors

    International Nuclear Information System (INIS)

    Fahrioglu, Murat

    2016-01-01

    Our society derives a quantifiable benefit from electric power. In particular, forced outages or blackouts have enormous consequences on society, one of which is loss of economic surplus. The society relies on having a continuous supply of electrical energy. Some customers may willingly risk this continuous supply and participate in demand management programs for electrical power. If the power system grid is in trouble, electric utilities need to have demand relief. Customers willing to reduce their demand to help the system can receive an incentive fee for helping the utilities. Demand relief can be system wide or location specific. Sometimes it can be more effective to fix the electrical demand vs. supply imbalance from the demand side. The value of demand management contracts is greatly affected by customer location. Inclusion of locational attributes into the contract design procedure increases the effectiveness of the contracts by helping a utility get more value from its demand management programs. Independent System Operators and regulators, among others, can also benefit from effective demand management. This paper will investigate how this type of demand management contracts can help the electricity sector both in regulated and deregulated environments. - Highlights: • Demand management can help prevent forced electricity outages. • Both electric utilities and ISOs can use demand management. • Regulated and deregulated electricity sectors can benefit from demand management. • Demand management contracts can be effectively used in power system grids.

  13. Deregulation and the Alberta experience : the implications for Ontario

    International Nuclear Information System (INIS)

    Desrochers, J.P.

    2002-01-01

    An overview of the first year of electric power industry deregulation in Alberta was presented. The way in which electricity is bought and sold in Ontario and throughout North America is changing. Costs are no longer fixed and regulated. Electricity is becoming a commodity with high levels of price volatility. The paper presented hedging options for Alberta consumers, contracting lessons, market issues and lessons for Ontario. A comparison of Alberta's deregulation schedule with that of Ontario's was included. One year after market opening in Alberta, power prices have dropped significantly. There is a greater than expected demand side response, increased development in power generation, and a decrease in natural gas prices. Issues that still need to be addressed in Alberta include billing and load settlement issues, invoicing/billing standards, the lack of competition at the retail level, and future balancing of pool charges. Energy Advantage Inc. (EA) does not foresee the same drastic increase in price as seen in Alberta market opening, but suggests that uncertainty and volatility will exist in Ontario. In Alberta, customers who did nothing and stayed on default were the ones who benefited, but took a great risk. EA suggests that customers must understand how and when they use electricity, how much is used during on- and off-peak hours, and in the summer versus the winter. When electricity is priced hourly, it is important to know consumption patterns. 7 figs

  14. Electricity deregulation, spot price patterns and demand-side management

    International Nuclear Information System (INIS)

    Li, Y.; Flynn, P.C.

    2006-01-01

    This paper examines extensive hourly or half-hourly power price data from 14 deregulated power markets. It analyzes average diurnal patterns, relationship to system load, volatility, and consistency over time. Diurnal patterns indicate the average price spread between off-peak and on-peak and weekend vs. weekday power consumption. Volatility is measured by price velocity: the average normalized hourly change in power price, calculated daily. The calculated price velocity is broken down into an expected component that arises from the diurnal pattern and an unexpected component that arises from unknown factors. The analysis reveals significant differences among markets, suggesting that demand-side management (DSM) of power consumption is far more difficult in some markets than in others. At one extreme, Spain, Britain and Scandinavia show consistent diurnal price patterns, a stable relationship between price and system load, and a low unexplained component of price volatility. A power consumer in these markets could form a reasonable expectation of a reward for DSM of elective power consumption. At the other extreme, two markets in Australia show erratic diurnal price patterns from year to year, low correlation between price and system load, and a high amount of unexpected price velocity. A power consumer in these markets would have far greater difficulty in realizing a benefit from DSM. Markets that experienced one period of very high prices without a clear external cause, such as California and Alberta, appear to have a significant longer-term erosion of public support for deregulation. (author)

  15. Generation capacity adequacy in deregulated markets : options for Alberta

    International Nuclear Information System (INIS)

    Ayres, M.

    2004-01-01

    The Canadian Energy Research Institute (CERI) is a Calgary-based non-profit organization that conducts studies on energy and related environmental issues to help Canadian business and government organizations. This paper summarized the information in a two volume CERI study report which assessed generation capacity issues in deregulated electricity markets in Canada. The study observed the restructuring experience in several jurisdictions and described how, or if, energy-only markets are succeeding in ensuring capacity additions. Supply-side and demand-side mechanisms have been proposed as solutions to address these problems. Theoretical and practical issues of adequacy that are most relevant from a Canadian perspective were presented. In fully developed energy markets, the price of energy reflects scarcity. When generating resources are abundant prices are low. Since investment decisions are based on price expectations, it is unlikely that deregulated markets in their current state can offer adequate generation for the long term. It was concluded that long-term investment will occur with competitive markets and by adding a capacity mechanism to the market design. tabs., figs

  16. A novel approach for modeling deregulated electricity markets

    International Nuclear Information System (INIS)

    Rubin, Ofir D.; Babcock, Bruce A.

    2011-01-01

    The theoretical framework developed in this study allows development of a model of deregulated electricity markets that explains two familiar empirical findings; the existence of forward premiums and price-cost markups in the spot market. This is a significant contribution because electricity forward premiums have been previously explained exclusively by the assumptions of perfect competition and risk-averse behavior while spot markups are generally the outcome of a body of literature assuming oligopolistic competition. Our theoretical framework indicates that a certain premium for forward contracting is required for efficient allocation of generation capacity. However, due to the uniqueness of electricity and the design of deregulated electricity markets this premium might be substantially higher than its optimal level. - Research highlights: → The state of knowledge regarding modeling electricity markets is incomplete. → Electricity forward premiums are not necessarily driven by risk aversion. → Efficiency in production requires a certain premium for forward contracting. → It is likely that market premiums are substantially higher than their optimal level. → Policy regulation should not seek to eliminate forward premium entirely.

  17. Artificial intelligence methods in deregulated power systems operations

    Science.gov (United States)

    Ilic, Jovan

    With the introduction of the power systems deregulation, many classical power transmission and distribution optimization tools became inadequate. Optimal Power Flow and Unit Commitment are common computer programs used in the regulated power industry. This work is addressing the Optimal Power Flow and Unit Commitment in the new deregulated environment. Optimal Power Flow is a high dimensional, non-linear, and non-convex optimization problem. As such, it is even now, after forty years since its introduction, a research topic without a widely accepted solution able to encompass all areas of interest. Unit Commitment is a high dimensional, combinatorial problem which should ideally include the Optimal Power Flow in its solution. The dimensionality of a typical Unit Commitment problem is so great that even the enumeration of all the combinations would take too much time for any practical purposes. This dissertation attacks the Optimal Power Flow problem using non-traditional tools from the Artificial Intelligence arena. Artificial Intelligence optimization methods are based on stochastic principles. Usually, stochastic optimization methods are successful where all other classical approaches fail. We will use Genetic Programming optimization for both Optimal Power Flow and Unit Commitment. Long processing times will also be addressed through supervised machine learning.

  18. Deregulation and internationalisation - impact on the Swedish nuclear industry

    Energy Technology Data Exchange (ETDEWEB)

    Haukeland, Sverre R. [Swedish Nuclear Society, Vattenfall Research and Development, 162 89 Stockholm (Sweden)

    2010-07-01

    The deregulation of the Swedish electricity market in 1996 was well known in advance, and the nuclear power plants in Sweden, as well as their main suppliers, made early preparations for a this new situation. In a study - performed by the author at Malardalen University in Sweden - it is concluded that the electricity industry, including the nuclear power plants, was fundamentally transformed in conjunction with market liberalisation. Two large foreign companies, E-on and Fortum, entered the Swedish market and became part-owners of the nuclear plants. After deregulation, the electricity market in Sweden is dominated by these two companies and the large national company Vattenfall. Similarly, Vattenfall has recently grown into an international energy company, acquiring generation capacity in Northern Europe outside of Sweden, including nuclear power plants in Germany. Restructuring of the nuclear industry on the supplier side started in the 1980's, when the Swedish company ASEA and BBC of Switzerland merged to become ABB. Several years later the Swedish nuclear plant supplier ABB-Atom became part of Westinghouse Electric Company, today owned by Toshiba. The Swedish experience thus confirms an international trend of mergers and consolidation in the nuclear industry. (authors)

  19. The impact of deregulation on the US nuclear industry

    International Nuclear Information System (INIS)

    Baratta, A.J.

    2001-01-01

    In the United States, the electric utility industry is undergoing a dramatic shift away from a tightly regulated monopoly to a free market system. The impact on the nuclear utility industry of deregulation coupled with recent changes in the nuclear regulatory environment has had a dramatic impact on the future of nuclear power in the United States. Utilities have been broken up into separate generation, transmission, and distribution companies and are now allowed to sell electricity outside of their former service areas. As economic deregulation has occurred, the U.S. Nuclear Regulatory Commission has also adopted a new approach to regulation -- risk informed regulation. The implementation of risk-informed regulation has resulted in the adoption of a new regulatory format that attempts to highlight those areas having greatest risk significance. This paper explores these and other changes that have resulted because of the changing economic and regulatory environment for nuclear energy and examines their impact on the future of nuclear energy in the United States. (author)

  20. Productivity growth and deregulation of Japanese electricity distribution

    International Nuclear Information System (INIS)

    Goto, Mika; Sueyoshi, Toshiyuki

    2009-01-01

    Deregulation of Japanese electric power industry began in 1995. After the amendment of Electricity Utility Industry Law in 1995, competition was partially introduced in a generation sector and retail competition started from 2000. Eligibility to choose suppliers was gradually extended from larger to smaller customers. As of 2008, almost all customers except households can choose their electricity suppliers. Based upon both previous implementation result of competition policy and review on their achievement, Japanese government will begin new policy debate in 2013 to assess further retail competition which includes household customers. To prepare for policy suggestion on the future electric power industry, this study examines the cost structure of Japanese electricity distribution. For the purpose, we estimate a multi-product translog cost function of Japanese electricity distribution from 1983 to 2003. Using the estimated cost function, we calculate several economic measures such as productivity growth, technical change and economies of scale and scope. The empirical results of this study indicate the improvement in productivity growth after deregulation.

  1. Maintenance cost models in deregulated power systems under opportunity costs

    International Nuclear Information System (INIS)

    Al-Arfaj, K.; Dahal, K.; Azaiez, M.N.

    2007-01-01

    In a centralized power system, the operator is responsible for scheduling maintenance. There are different types of maintenance, including corrective maintenance; predictive maintenance; preventive maintenance; and reliability-centred maintenance. The main cause of power failures is poor maintenance. As such, maintenance costs play a significant role in deregulated power systems. They include direct costs associated with material and labor costs as well as indirect costs associated with spare parts inventory, shipment, test equipment, indirect labor, opportunity costs and cost of failure. In maintenance scheduling and planning, the cost function is the only component of the objective function. This paper presented the results of a study in which different components of maintenance costs were modeled. The maintenance models were formulated as an optimization problem with single and multiple objectives and a set of constraints. The maintenance costs models could be used to schedule the maintenance activities of power generators more accurately and to identify the best maintenance strategies over a period of time as they consider failure and opportunity costs in a deregulated environment. 32 refs., 4 tabs., 4 figs

  2. MicroRNAs, Regulatory Networks, and Comorbidities

    DEFF Research Database (Denmark)

    Russo, Francesco; Belling, Kirstine; Jensen, Anders Boeck

    2017-01-01

    MicroRNAs (miRNAs) are small noncoding RNAs involved in the posttranscriptional regulation of messenger RNAs (mRNAs). Each miRNA targets a specific set of mRNAs. Upon binding the miRNA inhibits mRNA translation or facilitate mRNA degradation. miRNAs are frequently deregulated in several pathologi...

  3. Transient Gene and miRNA Expression Profile Changes of Confluent Human Fibroblast Cells in Space

    Science.gov (United States)

    Zhang, Ye; Lu, Tao; Wong, Michael; Feiveson, Alan; Stodieck, Louis; Karouia, Fathi; Wang, Xiaoyu; Wu, Honglu

    2015-01-01

    Microgravity or an altered gravity environment from the static 1 gravitational constant has been shown to influence global gene expression patterns and protein levels in cultured cells. However, most of the reported studies conducted in space or using simulated microgravity on the ground have focused on the growth or differentiation of the cells. Whether non-dividing cultured cells will sense the presence of microgravity in space has not been specifically addressed. In an experiment conducted on the International Space Station, confluent human fibroblast cells were fixed after being cultured in space for 3 and 14 days for investigations of gene and miRNA (microRNA) expression profile changes in these cells. A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for tissues, and plays a critical role in wound healing and other functions. Results of the experiment showed that on Day 3, both the flown and ground cells were still proliferating slowly even though they were confluent, as measured by the expression of the protein Ki-67 positive cells, and the cells in space grew slightly faster. Gene and miRNA expression data indicated activation of NF(sub kappa)B (nuclear factor kappa-light-chain-enhancer of activated B cells) and other growth related pathways involving HGF and VEGF in the flown cells. On Day 14 when the cells were mostly non-dividing, the gene and miRNA expression profiles between the flight and ground samples were indistinguishable. Comparison of gene and miRNA expressions in the Day 3 samples in respect to Day 14 revealed that most of the changes observed on Day 3 were related to cell growth for both the flown and ground cells. Analysis of cytoskeleton changes by immunohistochemistry staining of the cells with antibodies for alpha-tubulin showed no difference between the flight and ground samples. Results of our study suggest that in true non-dividing human fibroblast cells, microgravity in

  4. miRConnect:Identifying effector genes of miRNAs and miRNA families in cancer cells

    DEFF Research Database (Denmark)

    Hua, Youjia; Duan, Shiwei; Murmann, Andrea E

    2011-01-01

    have generated custom data sets containing expression information of 54 miRNA families sharing the same seed match. We have developed a novel strategy for correlating miRNAs with individual genes based on a summed Pearson Correlation Coefficient (sPCC) that mimics an in silico titration experiment......micro(mi)RNAs are small non-coding RNAs that negatively regulate expression of most mRNAs. They are powerful regulators of various differentiation stages, and the expression of genes that either negatively or positively correlate with expressed miRNAs is expected to hold information...

  5. Identification of miRNA from Porphyra yezoensis by high-throughput sequencing and bioinformatics analysis.

    Science.gov (United States)

    Liang, Chengwei; Zhang, Xiaowen; Zou, Jian; Xu, Dong; Su, Feng; Ye, Naihao

    2010-05-19

    miRNAs are a class of non-coding, small RNAs that are approximately 22 nucleotides long and play important roles in the translational level regulation of gene expression by either directly binding or cleaving target mRNAs. The red alga, Porphyra yezoensis is one of the most important marine economic crops worldwide. To date, only a few miRNAs have been identified in green unicellar alga and there is no report about Porphyra miRNAs. To identify miRNAs in Porphyra yezoensis, a small RNA library was constructed. Solexa technology was used to perform high throughput sequencing of the library and subsequent bioinformatics analysis to identify novel miRNAs. Specifically, 180,557,942 reads produced 13,324 unique miRNAs representing 224 conserved miRNA families that have been identified in other plants species. In addition, seven novel putative miRNAs were predicted from a limited number of ESTs. The potential targets of these putative miRNAs were also predicted based on sequence homology search. This study provides a first large scale cloning and characterization of Porphyra miRNAs and their potential targets. These miRNAs belong to 224 conserved miRNA families and 7 miRNAs are novel in Porphyra. These miRNAs add to the growing database of new miRNA and lay the foundation for further understanding of miRNA function in the regulation of Porphyra yezoensis development.

  6. Can nanotechnology improve cancer diagnosis through miRNA detection?

    Science.gov (United States)

    Fiammengo, Roberto

    2017-01-01

    miRNAs are key regulators of gene expression, and alterations in their expression levels correlate with the onset and progression of cancer. Although miRNAs have been proposed as biomarkers for cancer diagnosis, their application in routine clinical praxis is yet to come. Current quantification strategies have limitation, and there is a great interest in developing innovative ones. Since a few years, nanotechnology-based approaches for miRNA quantification are emerging at fast pace but there is urgent need to go beyond the proof-of-concept stage. Nanotechnology will have a strong impact on cancer diagnosis through miRNA detection only if it is demonstrated that the newly developed approaches are indeed working on 'real-world' samples under standardized conditions.

  7. miRNA delivery for skin wound healing.

    Science.gov (United States)

    Meng, Zhao; Zhou, Dezhong; Gao, Yongsheng; Zeng, Ming; Wang, Wenxin

    2017-12-19

    The wound healing has remained a worldwide challenge as one of significant public health problems. Pathological scars and chronic wounds caused by injury, aging or diabetes lead to impaired tissue repair and regeneration. Due to the unique biological wound environment, the wound healing is a highly complicated process, efficient and targeted treatments are still lacking. Hence, research-driven to discover more efficient therapeutics is a highly urgent demand. Recently, the research results have revealed that microRNA (miRNA) is a promising tool in therapeutic and diagnostic fields because miRNA is an essential regulator in cellular physiology and pathology. Therefore, new technologies for wound healing based on miRNA have been developed and miRNA delivery has become a significant research topic in the field of gene delivery. Copyright © 2017. Published by Elsevier B.V.

  8. Circulating miRNAs as biomarkers for endocrine disorders.

    Science.gov (United States)

    Butz, H; Kinga, N; Racz, K; Patocs, A

    2016-01-01

    Specific, sensitive and non-invasive biomarkers are always needed in endocrine disorders. miRNAs are short, non-coding RNA molecules with well-known role in gene expression regulation. They are frequently dysregulated in metabolic and endocrine diseases. Recently it has been shown that they are secreted into biofluids by nearly all kind of cell types. As they can be taken up by other cells they may have a role in a new kind of paracrine, cell-to-cell communication. Circulating miRNAs are protected by RNA-binding proteins or microvesicles hence they can be attractive candidates as diagnostic or prognostic biomarkers. In this review, we summarize the characteristics of extracellular miRNA's and our knowledge about their origin and potential roles in endocrine and metabolic diseases. Discussions about the technical challenges occurring during identification and measurement of extracellular miRNAs and future perspectives about their roles are also highlighted.

  9. Maternal Plasma miRNAs Expression in Preeclamptic Pregnancies

    Directory of Open Access Journals (Sweden)

    Hailing Li

    2013-01-01

    Full Text Available Objective. Preeclampsia (PE is a pregnancy-specific syndrome and one of the leading causes of maternal and fetal morbidity and mortality. The pathophysiological mechanisms of PE remain poorly known. Recently, circulating miRNAs are considered as potential useful noninvasive biomarkers. The aim of this study was to identify differentially expressed plasma miRNAs in preeclamptic pregnancies compared with normal pregnancies. Methods. Maternal plasma miRNA expression profiles were detected by SOLiD sequencing. Differential expressions between mPE/sPE and control group were found. Next, four differentially expressed plasma miRNAs were chosen to validate their expression in other large scale samples by real-time PCR. Results. In terms of sequencing results, we identified that 51 miRNAs were differentially expressed. Four differentially expressed plasma miRNAs (miR-141, miR-144, miR-221, and miR-29a were selected to validate the sequencing results. RT-PCR data confirmed the reliability of sequencing results. The further statistical analysis showed that maternal plasma miR-141 and miR-29a are significantly overexpressed in mPE (P<0.05. Maternal plasma miR-144 is significantly underexpressed in mPE and sPE (P<0.05. Conclusions. Results showed that there were differentially expressed maternal plasma miRNAs in patients with preeclampsia. These plasma miRNAs might be used as notable biomarkers for diagnosis of preeclampsia.

  10. Identification of miRNAs Responsive to Botrytis cinerea in Herbaceous Peony (Paeonia lactiflora Pall. by High-Throughput Sequencing

    Directory of Open Access Journals (Sweden)

    Daqiu Zhao

    2015-09-01

    Full Text Available Herbaceous peony (Paeonia lactiflora Pall., one of the world’s most important ornamental plants, is highly susceptible to Botrytis cinerea, and improving resistance to this pathogenic fungus is a problem yet to be solved. MicroRNAs (miRNAs play an essential role in resistance to B. cinerea, but until now, no studies have been reported concerning miRNAs induction in P. lactiflora. Here, we constructed and sequenced two small RNA (sRNA libraries from two B. cinerea-infected P. lactiflora cultivars (“Zifengyu” and “Dafugui” with significantly different levels of resistance to B. cinerea, using the Illumina HiSeq 2000 platform. From the raw reads generated, 4,592,881 and 5,809,796 sRNAs were obtained, and 280 and 306 miRNAs were identified from “Zifengyu” and “Dafugui”, respectively. A total of 237 conserved and 7 novel sequences of miRNAs were differentially expressed between the two cultivars, and we predicted and annotated their potential target genes. Subsequently, 7 differentially expressed candidate miRNAs were screened according to their target genes annotated in KEGG pathways, and the expression patterns of miRNAs and corresponding target genes were elucidated. We found that miR5254, miR165a-3p, miR3897-3p and miR6450a might be involved in the P. lactiflora response to B. cinerea infection. These results provide insight into the molecular mechanisms responsible for resistance to B. cinerea in P. lactiflora.

  11. Circulating Serum miRNAs as Diagnostic Markers for Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Abdel-Rahman N Zekri

    Full Text Available The study was designed to assess the possibility of using circulating miRNAs (serum miRNAs as diagnostic biomarkers in colorectal cancer (CRC and to identify their possibility as candidates for targeted therapy.The study involved two sample sets: 1- a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD, 18 with colonic polyps (CP and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group and 2- a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR- 135b and miR- 92a using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis.Data analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016, whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018. On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.017 and 0.016; respectively in CRC patients. However, the validation set showed that only miR-223 was significantly up-regulated in CRC patients (fold change = 4.06, p-value = 0.04.Aberrant miRNA expressions are highly involved in the cascade of colorectal carcinogenesis. We have found that (miR-17, miR-19a, miR-20a and miR-223 could be used as diagnostic biomarkers for CRC. On the other hand, miR-19b and miR-18a could be used as diagnostic biomarkers for

  12. MiRNA expression patterns predict survival in glioblastoma.

    Science.gov (United States)

    Niyazi, Maximilian; Zehentmayr, Franz; Niemöller, Olivier M; Eigenbrod, Sabina; Kretzschmar, Hans; Schulze-Osthoff, Klaus; Tonn, Jörg-Christian; Atkinson, Mike; Mörtl, Simone; Belka, Claus

    2011-11-10

    In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs) from paraffin tissues followed by a bio-mathematical analysis was performed. 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemo)therapy were included in this retrospective analysis. For microarray analysis the febit biochip "Geniom® Biochip MPEA homo-sapiens" was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days) (p = 0.01). The pattern and the prognostic power were both independent of the MGMT status. At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required.

  13. MiRNA expression patterns predict survival in glioblastoma

    Directory of Open Access Journals (Sweden)

    Niyazi Maximilian

    2011-11-01

    Full Text Available Abstract Background In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs from paraffin tissues followed by a bio-mathematical analysis was performed. Methods 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemotherapy were included in this retrospective analysis. For microarray analysis the febit biochip "Geniom® Biochip MPEA homo-sapiens" was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. Results It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days (p = 0.01. The pattern and the prognostic power were both independent of the MGMT status. Conclusions At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required.

  14. MiRNA expression patterns predict survival in glioblastoma

    International Nuclear Information System (INIS)

    Niyazi, Maximilian; Belka, Claus; Zehentmayr, Franz; Niemöller, Olivier M; Eigenbrod, Sabina; Kretzschmar, Hans; Osthoff, Klaus-Schulze; Tonn, Jörg-Christian; Atkinson, Mike; Mörtl, Simone

    2011-01-01

    In order to define new prognostic subgroups in patients with glioblastoma a miRNA screen (> 1000 miRNAs) from paraffin tissues followed by a bio-mathematical analysis was performed. 35 glioblastoma patients treated between 7/2005 - 8/2008 at a single institution with surgery and postoperative radio(chemo)therapy were included in this retrospective analysis. For microarray analysis the febit biochip 'Geniom ® Biochip MPEA homo-sapiens' was used. Total RNA was isolated from FFPE tissue sections and 1100 different miRNAs were analyzed. It was possible to define a distinct miRNA expression pattern allowing for a separation of distinct prognostic subgroups. The defined miRNA pattern was significantly associated with early death versus long-term survival (split at 450 days) (p = 0.01). The pattern and the prognostic power were both independent of the MGMT status. At present, this is the first dataset defining a prognostic role of miRNA expression patterns in patients with glioblastoma. Having defined such a pattern, a prospective validation of this observation is required

  15. Systems solutions for new market situations in the deregulated energy market

    International Nuclear Information System (INIS)

    Vouets, W.

    2001-01-01

    This extensive article presents a comprehensive overview of the various functions that are necessary for the efficient and secure operation of the electricity supply system in Switzerland within the framework of a deregulated electricity market. Both the physical and financial markets involved in the restructuring of the electricity market are examined in detail. The challenges placed on the parties involved in this process and the basic principles involved are discussed, including the generation, distribution and consumption of electricity and the control of production and demand. The mechanisms involved in this complex system are illustrated graphically and the requirements placed on an 'energy exchange' and its 'stockbrokers' are discussed from both the physical and financial points of view. Practical solutions are discussed and questions on topics in this area that are still to be answered are listed, including the availability of industrial solutions, support provided by information technology and grid-protection systems. Finally, the role of utilities that provide services both in the energy area (e.g. the supply of electricity, gas and water) as well as in the financial area (e.g. cost-calculation, wholesale and customer tariff aspects, profit optimisation and customer relations management) is discussed. The article is concluded with a summary of the situation and a look at the future of the energy market in Switzerland

  16. Core designs for the de-regulated market

    International Nuclear Information System (INIS)

    Almberger, J.; Bernro, R.; Pettersson, H.

    1999-01-01

    Complete text of publication follows: The electricity market deregulation in the Nordic countries encourages innovations and cost reductions for power production in the Vattenfall reactors. The competition on the electricity market is strong, electricity price reductions dramatic and uncertainties about the future power demand is large. In the fuel area this situation has given increased attention to traditional areas like flexibility in power production, improved core designs, need for margins (improved fuel designs), improved surveillance, decreased lead times. At Vattenfall new fuel designs are already being implemented following the last fuel purchase, for which flexibility and margins, were given high values in the evaluations with the multipurpose task of eliminating fuel related problems and meeting the future market situation. This strategy has given Vattenfall a flying start to meeting the demands of the de-regulated market. What has been added are broad studies undertaken to investigate the various route into the future with respect to finding the most effective strategies for fuel and core design and optimization. In the present paper the Vattenfall priorities for fuel designs and margins are presented in a schematic manner summarizing the results of the last fuel purchase and also presenting the current program for LFAs. Technical limitations, licensing and R and D aspects, with respect to improving the fuel utilization will be mentioned. The main focus in the paper is on the broad study carried out in the PWR core design area. Driven by the relatively low power demand various possibilities for higher production flexibility have been investigated specifically extended coast-down, coast-up and yearly load follow. Further to reduce the costs for fuel consumption improvements in core designs have been studied: improved low leakage loading patterns, low enriched end zones, improved Gd designs etc. Main results and conclusions of the core design studies will

  17. Air pollution effects due to deregulation of the electric industry

    Science.gov (United States)

    Davoodi, Khojasteh Riaz

    The Energy Policy Act of 1992 introduced the concept of open-access into the electric utility industry which allows privately-owned utilities to transmit power produced by non-utility generators and independent power producers (IPPs). In April 1996, the Federal Energy Regulatory Commission (FERC) laid down the final rules (Orders No. 888 & No. 889), which required utilities to open their transmission lines to any power producer and charge them no more than what they pay for the use of their own lines. These rules set the stage for the retail sale of electricity to industrial, commercial and residential utility customers; non-utility generators (Nugs); and power marketers. These statutory, regulatory and administrative changes create for the electric utility industry two different forces that contradict each other. The first is the concept of competition among utility companies; this places a greater emphasis on electric power generation cost control and affects generation/fuel mix selection and demand side management (DSM) activities. The second force, which is converse to the first, is that utilities are major contributors to the air pollution burden in the United States and environmental concerns are forcing them to reduce emissions of air pollutants by using more environmentally friendly fuels and implementing energy saving programs. This study evaluates the impact of deregulation within the investor owned electric utilities and how this deregulation effects air quality by investigating the trend in demand side management programs and generation/fuel mix. A survey was conducted of investor owned utilities and independent power producers. The results of the survey were analyzed by analysis of variance and regression analysis to determine the impact to Air Pollution. An air Quality Impact model was also developed in this study. This model consists of six modules: (1) demand side management and (2) consumption of coal, (3) gas, (4) renewable, (5) oil and (6

  18. Combination of Supervised and Unsupervised Approaches for miRNA Target Prediction.

    Science.gov (United States)

    Sedaghat, Nafiseh; Fathy, Mahmood; Modarressi, Mohammad Hossein; Shojaie, Ali

    2017-07-13

    MicroRNAs (miRNAs) are short non-coding RNAs which target mRNAs by binding to them and regulating their expression. Involvement of miRNAs has been discovered in many diseases, so it is fruitful to investigate the miRNAs and their targets to develop new therapeutic ways by designing anti-miRNA oligonucleotides. There are various computational methods to predict the target genes, however, their precisions are not good enough. In this paper, we apply a two-step approach to refine the results of sequence-based prediction algorithms. The first step is based on consensus learning according to our previous research, then the second step includes utilizing Support Vector Machine (SVM) classifier in unary and binary modes to identify validated interactions based on binding features as well as network features of genes in constructed gene regulatory network. Experimental results on two real data sets from TCGA database show the binary SVM classification significantly increases the precision of finding validated interactions.

  19. Serum miRNA disregulation during transport-related stress in turkey (Meleagris gallopavo

    Directory of Open Access Journals (Sweden)

    Andreia Tomás Marques

    2015-07-01

    Full Text Available MicroRNAs (miRNAs are small 21-25 nucleotide regulatory non-coding RNAs that modulate gene expression in eukaryotic organisms. miRNAs are complementary to the 3′-untranslated regions of mRNA and act as post-transcriptional regulators of gene expression, exhibiting remarkable stability in extracellular fluids such as blood. Turkey (Meleagris gallopavo farming is a species economically relevant but the lack of efficient protocols for the evaluation of commercial turkeys prevents to measure the impact of industry practices on birds productivity and welfare. In order to identify potential molecular biomarkers for monitoring stress in turkey’s handling, we investigated by TaqMan qPCR the abundance of five circulating miRNA, namely miR-22, miR-155, miR-181a, miR-204 and miR-365, previously demonstrated to be involved in stress in chicken due to feed deprivation. Road transportation related procedures were selected as stressful model for this study. The serum of twenty healthy animals was collected before and after 2h transportation. Our results demonstrated that miR-22, miR-155 and miR-365 are statistically more expressed after road transportation. Receiver-operator characteristics (ROC analysis was used to estimate the diagnostic value of these miRNAs to evaluate the stress in animals. The serum level of miR-22, miR-155 and miR-365 can discriminate stressed from non-stressed animals with an AUC=0.763, 0.710 and 0.704, respectively, and the average expression of their combination has the same specificity (AUC=0.745. miR-22, miR-155 and miR-365 are stress-specific markers and can be considered as suitable biomarkers to identify turkeys stressed by road transportation.

  20. Look who's talking: deregulated signaling in colorectal cancer.

    Science.gov (United States)

    Abba, Mohammed; Laufs, Stephanie; Aghajany, Monireh; Korn, Bernhard; Benner, Axel; Allgayer, Heike

    2012-01-01

    The phenotypic expression of any given heterogeneous tissue type is the composite of interactions between individual cell types governed principally by inherent, cell-specific molecular mechanisms. Using a combination of laser-capture microdissection, oligonucleotide microarrays, bioinformatic and statistical tools, we analyzed colorectal cancer tissues in order to spot the significant pathways that were differentially deregulated between the epithelial and stromal compartments and compared these alongside the ones of whole tissue dissection. The stromal pathway profiles were very similar to the ones of whole tissue, in contrast to the epithelial input, with stroma emerging as the major determinant of the cancer phenotype. Differentially expressed genes in the epithelial compartment correlated significantly with the carbohydrate antigen 19-9 tumor marker. The accurate interpretation of data arising from the analysis of heterogeneous tissue structures lends itself to inherent biases of its constitutive components with each component presenting explorable analytical advantages.

  1. Natural gas deregulation: have the handcuffs really been removed?

    International Nuclear Information System (INIS)

    Kelley, T.D.

    1995-01-01

    The natural gas market in New York State was reviewed and characterized as being very competitive. A brief description of the New York State Electric and Gas Corp. (NYSEG) was given. As regards recent developments, in October 1993, the New York Public Service Commission (NYPSC) instituted a proceeding (93-G-0932) on the restructuring of the gas market. Several guidelines for market restructuring were established as a result. The guidelines were in respect to service to consumers, safety of distribution, environmental implications, consumer concerns, gas rates, regulation, and access for core customers. The speaker noted that these guidelines did not promote deregulation. Competitive issues faced by local gas distributors were enumerated. Among these were (1)service to core and non-core customers (2)transition costs, (3)streaming, (4)unbundling and repackaged services, (5)price differentiation, and (6)small customer aggregation. It was expected that marketers would oppose the Public Service Commission giving local gas distributors additional pricing flexibility

  2. Market Model Considering Bilateral Transactions in the Deregulated Electricity Market

    Science.gov (United States)

    Ruiz Monroy, José Joaquín; Kita, Hiroyuki; Tanaka, Eiichi; Hasegawa, Jun

    This paper proposes an algorithm to simulate the transactions that take place in a free market of electricity. The algorithm presented is used for Bilateral Transaction Matrix (BTM) creation assuming that a day ahead load forecast is previously known. Bids can be made by both the generation side and the demand side to determine transaction prices, then the algorithm allocates the transactions according to market rules until the demand is satisfied. This creates feasible BTMs that can be used to study system security and to find future methods to regulate bilateral transactions through market mechanisms like the application of penalties to the transactions that affect the system’s security. Results show that the proposed algorithm is a good option for electricity market analysis. The proposed algorithm provides system planners with a practical tool for data creation to further study the effects of bilateral transactions in a deregulated electricity market.

  3. Power plant operation and management in a deregulated market

    International Nuclear Information System (INIS)

    Carraretto, Cristian

    2006-01-01

    This paper analyzes the influence of electricity deregulation on the design, operation and management of the power plants owned by strategic and non-strategic producers. After a sensitivity analysis aimed at finding market conditions of profitable operation for thermal and hydroelectric power plants, a Nash-equilibrium market model is used to determine producers' optimum strategies, depending on their relative market power and overall production characteristics. Attention is then focused on the operation of single thermal power plants. Their short-term management plans and consequent effects on emission levels and residual life are described. The available reserve for primary and secondary control deriving from producers' market strategies is discussed. Some design options to improve combined cycles contribution to reserve service are finally described. The paper discusses these problems with a general approach, and uses many cases and examples derived from the current Italian scenario. (author)

  4. Deregulation and the Alberta experience : the implications for Ontario

    International Nuclear Information System (INIS)

    Charach, L.

    2002-01-01

    This paper provides a 15 month assessment of Alberta's new competitive electricity market. It also presents lessons that Ontario customers could learn from Alberta's experience. The goal for restructuring is to achieve lower electricity prices, competitive retail markets, increased flexibility of contracts, and to remove investment risks from consumers. Alberta's restructured market includes power generation, high voltage transmission, low voltage transmission and retail sales. Economists agree that deregulation has brought lower prices and other consumer benefits despite some imperfections. After one year, prices in Alberta have gone down from $130/MWh to $30/MWh. Power supply has increased along with demand response, market competitiveness, liquidity, and thermal and economic efficiency. In 2001, Alberta was a net exporter of electricity. In 2001, it was ranked by the Center for Advancement of Energy Markets (CAEM) which ranks states and provinces by 22 attributes for how they are restructuring their power markets. Alberta ranked first overall in North America. Ontario ranked sixteenth. 4 tabs., 5 figs

  5. Single-Step Incubation Determination of miRNAs in Cancer Cells Using an Amperometric Biosensor Based on Competitive Hybridization onto Magnetic Beads

    Directory of Open Access Journals (Sweden)

    Eva Vargas

    2018-03-01

    Full Text Available This work reports an amperometric biosensor for the determination of miRNA-21, a relevant oncogene. The methodology involves a competitive DNA-target miRNA hybridization assay performed on the surface of magnetic microbeads (MBs and amperometric transduction at screen-printed carbon electrodes (SPCEs. The target miRNA competes with a synthetic fluorescein isothiocyanate (FITC-modified miRNA with an identical sequence for hybridization with a biotinylated and complementary DNA probe (b-Cp immobilized on the surface of streptavidin-modified MBs (b-Cp-MBs. Upon labeling, the FITC-modified miRNA attached to the MBs with horseradish peroxidase (HRP-conjugated anti-FITC Fab fragments and magnetic capturing of the MBs onto the working electrode surface of SPCEs. The cathodic current measured at −0.20 V (versus the Ag pseudo-reference electrode was demonstrated to be inversely proportional to the concentration of the target miRNA. This convenient biosensing method provided a linear range between 0.7 and 10.0 nM and a limit of detection (LOD of 0.2 nM (5 fmol in 25 μL of sample for the synthetic target miRNA without any amplification step. An acceptable selectivity towards single-base mismatched oligonucleotides, a high storage stability of the b-Cp-MBs, and usefulness for the accurate determination of miRNA-21 in raw total RNA (RNAt extracted from breast cancer cells (MCF-7 were demonstrated.

  6. BDI position on energy policy and energy market deregulation

    International Nuclear Information System (INIS)

    Kreklau, C.

    2003-01-01

    Secure energy supplies are indispensable for our modern way of life and our economy. Energy policy is a part of economic policy and must be shaped within the magic triangle of objectives, i.e. security, competitiveness, environmental compatibility. As a result of their outstanding role, electricity and natural gas, with respective shares of 70% in industrial energy use and 85% in energy costs, are in the focus of energy policy interest of the Federation of German Industries (BDI). One important development over the past few years has been the deregulation of the markets for electricity and gas. However, the markedly lower electricity rates to be paid by industry, commercial tariff consumers, and private customers are being offset by new burdens arising from government intervention and taxes. Other dirigistic interventions into the energy market by the red-green federal government since 1998, referred to as 'turning point of energy policy', are invalidating what market opening had been achieved. With a view to a sustainable energy policy for the future, BDI pleads in favor of a broad energy mix. In a mix neutral with respect to competition, this includes the classical energy sources, the renewables, and low-cost, environmentally friendly nuclear power. In principle, it is the forces of the market, coupled with responsible action, which are to steer further developments. On a European level, speedy implementation of the opening of the electricity and gas markets, as decided, should be urged. It is important that the leeway won as a result of deregulation not be constrained again by new regulations. More market, less regulation, and more direct responsibility must provide room for a powerful energy supply system under the premises of the triangle of objectives referred to above. (orig.) [de

  7. Economic use of a nuclear park in a deregulated market

    International Nuclear Information System (INIS)

    Eliasson, L.

    2000-01-01

    The deregulation of the electricity market has created a new situation for plant life management. In order to be competitive it is important to cut costs. All means to cut costs have to be used while still maintaining safety and production capacity. The possibilities to invest in modernization are limited to the absolute necessary modifications. All investments must be very thoroughly questioned and the money can only be spent where most benefit is gained. This means new prerequisites for the absolute necessary long strategic planning. New safety requirements from the regulatory body have to be discussed between the industry and the regulator. The cost of new requirements must be compared to the benefit for the safety. The regulator is today requested to carry out such analyses and do so in most cases. Still the electricity market is international and the requirements of the regulator must be harmonized on the whole market. The political threat against nuclear power is serious in many countries and it is important to continue working with public and political understanding and acceptance. Especially in Sweden a lot of effort is spent on trying to get harmonized taxes and environmental fees. Nuclear power is paying for all its costs and the external costs are already internalized. Still, at the deregulated market, nuclear power is competitive, creating positive cash flow, a good object for investments and environmentally favourable. Threats have to be removed to get prerequisites for long term strategic planning and investments. Steps in that direction will be increasing electricity demand, in the near future, which will make the prices to raise creating an improved economic situation. Also the very serious worries about climate change will strengthen the competitiveness of nuclear power. (author)

  8. Investments into plant replacements in a deregulated electricity market

    International Nuclear Information System (INIS)

    Elsaesser, R.F.

    2004-01-01

    The amendment to the Power Energy Act in April 1998 marked the complete deregulation of the electricity market in Germany. The debate is now beginning about ways and means to ensure new capital investments safeguarding the continuity of supply. The present power plant park has been characterized by a broad mix of primary energy sources and, admittedly, by some overcapacity as well. However, any further reduction of generating capacity will be at the expense of the continuity of supply. Although electricity prices in Germany are on the rise again after a clear drop, they have not yet reached a level sufficient for new investments. Only subsidized power plants are recovering their full costs. The question is for how long our economy is going to sustain this state of affairs. The balance among the energy policy goals of continuity of supply, environmental performance, and economic efficiency has been upset. In the period up until 2020, Germany alone will require approx. 37,000 MW of new generating capacity. Renewable and decentralized technologies alone do not constitute a sufficient and reliable alternative. However, there is the matter also of the practical feasibility of building the new power plants required. No experience is as yet available with re-investment cycles in the deregulated electricity market. Options are needed for a diversified structure of primary energy sources. There must be neither political definition of generating technologies nor exaggerated goals of environmental protection and climate protection. We advocate the free system of market prices and free access to the market. Major players able to guarantee sufficient security of investments are needed to cope with the challenges ahead. New investments with a life of thirty to forty years require a modicum of stability and realism in political framework conditions. (orig.)

  9. MR-02A GENOME-WIDE miRNA SCREEN REVEALED MIR-603 AS A MGMT-REGULATING miRNA IN GLIOBLASTOMAS

    OpenAIRE

    Kushwaha, Deepa; Ramakrishnan, Valya; Ng, Kimberly; Steed, Tyler; Nguyen, Thien; Futalan, Diahnn; Akers, Johnny; Tao, Jiang; Chowdhury, Dipanjan; Carter, Bob; Chen, Clark

    2014-01-01

    MGMT expression is a critical determinant for therapeutic resistance to DNA alkylating agents. We previously demonstrated that MGMT expression is post-transcriptionally regulated by miR-181d and other miRNAs. Here, we performed a genome-wide screen to identify MGMT regulating miRNAs. Candidate miRNAs were further tested for inverse correlation with MGMT expression in clinical specimens. We identified 15 candidate miRNAs. Comparison of these candidates to those predicted computational algorith...

  10. Novel miRNA-31 and miRNA-200a-Mediated Regulation of Retinoblastoma Proliferation

    Science.gov (United States)

    Montoya, Vanessa; Fan, Hanli; Bryar, Paul J.; Weinstein, Joanna L.; Mets, Marilyn B.; Feng, Gang; Martin, Joshua; Martin, Alissa; Jiang, Hongmei; Laurie, Nikia A.

    2015-01-01

    Retinoblastoma is the most common intraocular tumor in children. Current management includes broad-based treatments such as chemotherapy, enucleation, laser therapy, or cryotherapy. However, therapies that target specific pathways important for retinoblastoma progression could provide valuable alternatives for treatment. MicroRNAs are short, noncoding RNA transcripts that can regulate the expression of target genes, and their aberrant expression often facilitates disease. The identification of post-transcriptional events that occur after the initiating genetic lesions could further define the rapidly aggressive growth displayed by retinoblastoma tumors. In this study, we used two phenotypically different retinoblastoma cell lines to elucidate the roles of miRNA-31 and miRNA-200a in tumor proliferation. Our approach confirmed that miRNAs-31 and -200a expression is significantly reduced in human retinoblastomas. Moreover, overexpression of these two miRNAs restricts the expansion of a highly proliferative cell line (Y79), but does not restrict the growth rate of a less aggressive cell line (Weri1). Gene expression profiling of miRNA-31 and/or miRNA-200a-overexpressing cells identified differentially expressed mRNAs associated with the divergent response of the two cell lines. This work has the potential to enhance the development of targeted therapeutic approaches for retinoblastoma and improve the efficacy of treatment. PMID:26379276

  11. The neuroprotective effect of miRNA-132 against amyloid β-protein-induced neuronal damage via upregulation of brain-derived neurotrophic factor

    Directory of Open Access Journals (Sweden)

    Lei XIANG

    2016-08-01

    Full Text Available Background Brain-derived neurotrophic factor (BDNF plays a crucial role in the pathogenesis of Alzheimer's disease (AD. MicroRNA (miRNA-132, which is widely expressed in neurons, is involved in BDNF-mediated neural development by regulating the expression of target gene. This study aims to investigate the effect of miRNA-132 on BDNF and its neuroprotective effect.  Methods The hippocampal neurons were transfected by miRNA-132 after 72 h in vitro, then exposed to amyloid β-protein (Aβ on the 7th day to build AD models. The difference of miRNA-132 expression between AD group and control group was detected by real-time fluorescent quantitative polymerase chain reaction (PCR. The alterations of BDNF mRNA were observed in the neurons of different groups. Finally, the cell viability was observed by methyl thiazolyl tetrazolium (MTT assay in AD neurons transfected with miRNA-132 or incubated with BDNF. Results 1 MiRNA-132 was significantly decreased (t = 13.888, P = 0.000, and the expression of BDNF mRNA was also reduced in AD group (t = -12.274, P = 0.000. 2 Green fluorescence was clearly visible by inverted phase-contrast fluorescence microscopy after transfected with miRNA-132. BDNF mRNA was upregulated when miRNA-132 overexpression both in control group (t = 16.135, P = 0.000 and AD group (t = 8.656, P = 0.000. 3 Cell viability was obviously decreased in neurons exposed to Aβ (t = -6.023, P = 0.000, which was improved when transfected with miRNA-132 (t = 3.385, P = 0.007 or incubated with BDNF (t = 3.672, P = 0.004.  Conclusions The expression of miRNA-132 and BDNF was reduced in neuronal AD model. MiRNA-132 played an important role on neuroprotection against A β-induced neuronal damage via upregulation of BDNF. It could be expected to provide new perspective for the diagnosis and treatment of AD. DOI: 10.3969/j.issn.1672-6731.2016.07.009

  12. Analysis of miRNA and mRNA expression profiles highlights alterations in ionizing radiation response of human lymphocytes under modeled microgravity.

    Directory of Open Access Journals (Sweden)

    Cristina Girardi

    Full Text Available Ionizing radiation (IR can be extremely harmful for human cells since an improper DNA-damage response (DDR to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs small noncoding RNA that act as post-transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure.We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL incubated for 4 and 24 h in normal gravity (1 g and in modeled microgravity (MMG during the repair time after irradiation with 0.2 and 2Gy of γ-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiation and MMG. Integrated analyses of miRNA and mRNA expression profiles, carried out on PBL of the same donors, identified significant miRNA-mRNA anti-correlations of DDR pathway. Gene Ontology analysis reports that the biological category of "Response to DNA damage" is enriched when PBL are incubated in 1 g but not in MMG. Moreover, some anti-correlated genes of p53-pathway show a different expression level between 1 g and MMG. Functional validation assays using luciferase reporter constructs confirmed miRNA-mRNA interactions derived from target prediction analyses.On the whole, by integrating the transcriptome and microRNome, we provide evidence that modeled microgravity can affects the DNA-damage response to IR in human PBL.

  13. Small sample sizes in high-throughput miRNA screens: A common pitfall for the identification of miRNA biomarkers

    NARCIS (Netherlands)

    Kok, M. G. M.; de Ronde, M. W. J.; Moerland, P. D.; Ruijter, J. M.; Creemers, E. E.; Pinto-Sietsma, S. J.

    2018-01-01

    Since the discovery of microRNAs (miRNAs), circulating miRNAs have been proposed as biomarkers for disease. Consequently, many groups have tried to identify circulating miRNA biomarkers for various types of diseases including cardiovascular disease and cancer. However, the replicability of these

  14. B cell differentiation in EBV-positive Burkitt Lymphoma is impaired at post-transcriptional level by miRNA altered expression

    DEFF Research Database (Denmark)

    Leucci, E; Onnis, A; Cocco, M

    2009-01-01

    investigated the expression of specific miRNAs predicted to be involved in B cell differentiation and we found that hsa-miR-127 is differentially expressed between EBV-positive and EBV-negative BLs. In particular, it was strongly up-regulated only in EBV-positive BL samples, whereas EBV-negative cases showed...... levels of expression similar to normal controls, including microdissected GC cells.In addition, we found evidence that hsa-miR-127 is involved in B cell differentiation process through post transcriptional regulation of BLIMP1 and XBP1. The over-expression of this miRNA may thus represent a key event...

  15. Computational identification and characterization of conserved miRNAs and their target genes in beet (Beta vulgaris).

    Science.gov (United States)

    Li, J L; Cui, J; Cheng, D Y

    2015-08-07

    Highly conserved endogenous non-coding microRNAs (miRNAs) play important roles in plants and animals by silencing genes via destruction or blocking of translation of homologous mRNA. Sugar beet, Beta vulgaris, is one of the most important sugar crops in China, with properties that include wide adaptability and strong tolerance to salinity and impoverished soils. Seedlings of B. vulgaris can grow in soils containing up to 0.6% salt; it is important to understand the molecular mechanisms of salt tolerance to enrich genetic resources for breeding salt-tolerant sugar beets. Here, we report 13 mature miRNAs from 12 families, predicted using an in silico approach from 29,857 expressed sequence tags and 279,223 genome survey sequences. The psRNATarget server predicted 25 target genes for the 13 miRNAs. Most of the target genes appeared to encode transcription factors or were involved in metabolism, signal transduction, stress response, growth, and development. These results improve our understanding of the molecular mechanisms of miRNA in beet and may aid in the development of novel and precise techniques for understanding post-transcriptional gene-silencing mechanisms in response to stress tolerance.

  16. The miRNA biogenesis in marine bivalves

    Directory of Open Access Journals (Sweden)

    Umberto Rosani

    2016-03-01

    Full Text Available Small non-coding RNAs include powerful regulators of gene expression, transposon mobility and virus activity. Among the various categories, mature microRNAs (miRNAs guide the translational repression and decay of several targeted mRNAs. The biogenesis of miRNAs depends on few gene products, essentially conserved from basal to higher metazoans, whose protein domains allow specific interactions with dsRNA. Here, we report the identification of key genes responsible of the miRNA biogenesis in 32 bivalves, with particular attention to the aquaculture species Mytilus galloprovincialis and Crassostrea gigas. In detail, we have identified and phylogenetically compared eight evolutionary conserved proteins: DROSHA, DGCR8, EXP5, RAN, DICER TARBP2, AGO and PIWI. In mussels, we recognized several other proteins participating in the miRNA biogenesis or in the subsequent RNA silencing. According to digital expression analysis, these genes display low and not inducible expression levels in adult mussels and oysters whereas they are considerably expressed during development. As miRNAs play an important role also in the antiviral responses, knowledge on their production and regulative effects can shed light on essential molecular processes and provide new hints for disease prevention in bivalves.

  17. Overview of the developments in the domestic airline industry in South Africa since market deregulation

    Directory of Open Access Journals (Sweden)

    Rose Luke

    2013-05-01

    Full Text Available Deregulation or liberalisation of air transport has had major global impacts on the domestic air transport markets, with effects ranging from stimulation to changes in the structure and functioning of these markets. In South Africa, deregulation has had wide-reaching effects on the domestic market. The purpose of this article was to investigate the current domestic air transport market. A literature review was performed to examine the effects of deregulation in other domestic air transport markets around the world. This was followed by a review of the South African domestic air transport market prior to deregulation in order to determine the changes that were made following deregulation. The ten-year period immediately following deregulation was also examined; this period was characterised by relatively large numbers of market entries and exits. A database was obtained from the Airports Company South Africa; air traffic movements, passenger numbers and load factors were evaluated. The study showed that the market is still characterised by regular market entries and exits. Also that the entry of the low-cost carriers has stimulated the market, resulting in increased air traffic movements, higher passenger numbers, higher load factors in general and the opening of a secondary airport in Gauteng, Lanseria International. Deregulation and, more specifically, the entry of the low-cost carriers has resulted in structural changes in the market and more choice for passengers.

  18. Overview of the developments in the domestic airline industry in South Africa since market deregulation

    Directory of Open Access Journals (Sweden)

    Rose Luke

    2013-11-01

    Full Text Available Deregulation or liberalisation of air transport has had major global impacts on the domestic air transport markets, with effects ranging from stimulation to changes in the structure and functioning of these markets. In South Africa, deregulation has had wide-reaching effects on the domestic market. The purpose of this article was to investigate the current domestic air transport market. A literature review was performed to examine the effects of deregulation in other domestic air transport markets around the world. This was followed by a review of the South African domestic air transport market prior to deregulation in order to determine the changes that were made following deregulation. The ten-year period immediately following deregulation was also examined; this period was characterised by relatively large numbers of market entries and exits. A database was obtained from the Airports Company South Africa; air traffic movements, passenger numbers and load factors were evaluated. The study showed that the market is still characterised by regular market entries and exits. Also that the entry of the low-cost carriers has stimulated the market, resulting in increased air traffic movements, higher passenger numbers, higher load factors in general and the opening of a secondary airport in Gauteng, Lanseria International. Deregulation and, more specifically, the entry of the low-cost carriers has resulted in structural changes in the market and more choice for passengers.

  19. microRNAs and Their Targets in Apple (Malus domestica cv. “Fuji”) Involved in Response to Infection of Pathogen Valsa mali

    OpenAIRE

    Feng, Hao; Xu, Ming; Zheng, Xiang; Zhu, Tongyi; Gao, Xiaoning; Huang, Lili

    2017-01-01

    miRNAs are important regulators involving in plant-pathogen interactions. However, their roles in apple tree response to Valsa canker pathogen (Valsa mali, Vm) infection were poorly understood. In this study, we constructed two miRNA libraries using the twig bark tissues of apple tree (Malus domestica Borkh. cv. “Fuji”) inoculated with Vm (IVm) and PDA medium (control, BMd). Among all detected miRNAs, 23 miRNAs were specifically isolated from BMd and 39 miRNAs were specifically isolated from ...

  20. Neural network based load and price forecasting and confidence interval estimation in deregulated power markets

    Science.gov (United States)

    Zhang, Li

    With the deregulation of the electric power market in New England, an independent system operator (ISO) has been separated from the New England Power Pool (NEPOOL). The ISO provides a regional spot market, with bids on various electricity-related products and services submitted by utilities and independent power producers. A utility can bid on the spot market and buy or sell electricity via bilateral transactions. Good estimation of market clearing prices (MCP) will help utilities and independent power producers determine bidding and transaction strategies with low risks, and this is crucial for utilities to compete in the deregulated environment. MCP prediction, however, is difficult since bidding strategies used by participants are complicated and MCP is a non-stationary process. The main objective of this research is to provide efficient short-term load and MCP forecasting and corresponding confidence interval estimation methodologies. In this research, the complexity of load and MCP with other factors is investigated, and neural networks are used to model the complex relationship between input and output. With improved learning algorithm and on-line update features for load forecasting, a neural network based load forecaster was developed, and has been in daily industry use since summer 1998 with good performance. MCP is volatile because of the complexity of market behaviors. In practice, neural network based MCP predictors usually have a cascaded structure, as several key input factors need to be estimated first. In this research, the uncertainties involved in a cascaded neural network structure for MCP prediction are analyzed, and prediction distribution under the Bayesian framework is developed. A fast algorithm to evaluate the confidence intervals by using the memoryless Quasi-Newton method is also developed. The traditional back-propagation algorithm for neural network learning needs to be improved since MCP is a non-stationary process. The extended Kalman

  1. Embryonic miRNA profiles of normal and ectopic pregnancies.

    Directory of Open Access Journals (Sweden)

    Francisco Dominguez

    Full Text Available Our objective was to investigate the miRNA profile of embryonic tissues in ectopic pregnancies (EPs and controlled abortions (voluntary termination of pregnancy; VTOP. Twenty-three patients suffering from tubal EP and twenty-nine patients with a normal ongoing pregnancy scheduled for a VTOP were recruited. Embryonic tissue samples were analyzed by miRNA microarray and further validated by real time PCR. Microarray studies showed that four miRNAs were differentially downregulated (hsa-mir-196b, hsa-mir-30a, hsa-mir-873, and hsa-mir-337-3p and three upregulated (hsa-mir-1288, hsa-mir-451, and hsa-mir-223 in EP compared to control tissue samples. Hsa-miR-196, hsa-miR-223, and hsa-miR-451 were further validated by real time PCR in a wider population of EP and control samples. We also performed a computational analysis to identify the gene targets and pathways which might be modulated by these three differentially expressed miRNAs. The most significant pathways found were the mucin type O-glycan biosynthesis and the ECM-receptor-interaction pathways. We also checked that the dysregulation of these three miRNAs was able to alter the expression of the gene targets in the embryonic tissues included in these pathways such as GALNT13 and ITGA2 genes. In conclusion, analysis of miRNAs in ectopic and eutopic embryonic tissues shows different expression patterns that could modify pathways which are critical for correct implantation, providing new insights into the understanding of ectopic implantation in humans.

  2. Embryonic miRNA Profiles of Normal and Ectopic Pregnancies

    Science.gov (United States)

    Dominguez, Francisco; Moreno-Moya, Juan Manuel; Lozoya, Teresa; Romero, Ainhoa; Martínez, Sebastian; Monterde, Mercedes; Gurrea, Marta; Ferri, Blanca; Núñez, Maria Jose; Simón, Carlos; Pellicer, Antonio

    2014-01-01

    Our objective was to investigate the miRNA profile of embryonic tissues in ectopic pregnancies (EPs) and controlled abortions (voluntary termination of pregnancy; VTOP). Twenty-three patients suffering from tubal EP and twenty-nine patients with a normal ongoing pregnancy scheduled for a VTOP were recruited. Embryonic tissue samples were analyzed by miRNA microarray and further validated by real time PCR. Microarray studies showed that four miRNAs were differentially downregulated (hsa-mir-196b, hsa-mir-30a, hsa-mir-873, and hsa-mir-337-3p) and three upregulated (hsa-mir-1288, hsa-mir-451, and hsa-mir-223) in EP compared to control tissue samples. Hsa-miR-196, hsa-miR-223, and hsa-miR-451 were further validated by real time PCR in a wider population of EP and control samples. We also performed a computational analysis to identify the gene targets and pathways which might be modulated by these three differentially expressed miRNAs. The most significant pathways found were the mucin type O-glycan biosynthesis and the ECM-receptor-interaction pathways. We also checked that the dysregulation of these three miRNAs was able to alter the expression of the gene targets in the embryonic tissues included in these pathways such as GALNT13 and ITGA2 genes. In conclusion, analysis of miRNAs in ectopic and eutopic embryonic tissues shows different expression patterns that could modify pathways which are critical for correct implantation, providing new insights into the understanding of ectopic implantation in humans. PMID:25013942

  3. Identification of miRNAs and their target genes in developing soybean seeds by deep sequencing

    Directory of Open Access Journals (Sweden)

    Chen Shou-Yi

    2011-01-01

    Full Text Available Abstract Background MicroRNAs (miRNAs regulate gene expression by mediating gene silencing at transcriptional and post-transcriptional levels in higher plants. miRNAs and related target genes have been widely studied in model plants such as Arabidopsis and rice; however, the number of identified miRNAs in soybean (Glycine max is limited, and global identification of the related miRNA targets has not been reported in previous research. Results In our study, a small RNA library and a degradome library were constructed from developing soybean seeds for deep sequencing. We identified 26 new miRNAs in soybean by bioinformatic analysis and further confirmed their expression by stem-loop RT-PCR. The miRNA star sequences of 38 known miRNAs and 8 new miRNAs were also discovered, providing additional evidence for the existence of miRNAs. Through degradome sequencing, 145 and 25 genes were identified as targets of annotated miRNAs and new miRNAs, respectively. GO analysis indicated that many of the identified miRNA targets may function in soybean seed development. Additionally, a soybean homolog of Arabidopsis SUPPRESSOR OF GENE SLIENCING 3 (AtSGS3 was detected as a target of the newly identified miRNA Soy_25, suggesting the presence of feedback control of miRNA biogenesis. Conclusions We have identified large numbers of miRNAs and their related target genes through deep sequencing of a small RNA library and a degradome library. Our study provides more information about the regulatory network of miRNAs in soybean and advances our understanding of miRNA functions during seed development.

  4. Impacts of Whole-Genome Triplication on MIRNA Evolution in Brassica rapa.

    Science.gov (United States)

    Sun, Chao; Wu, Jian; Liang, Jianli; Schnable, James C; Yang, Wencai; Cheng, Feng; Wang, Xiaowu

    2015-11-01

    MicroRNAs (miRNAs) are a class of short non-coding, endogenous RNAs that play essential roles in eukaryotes. Although the influence of whole-genome triplication (WGT) on protein-coding genes has been well documented in Brassica rapa, little is known about its impacts on MIRNAs. In this study, through generating a comprehensive annotation of 680 MIRNAs for B. rapa, we analyzed the evolutionary characteristics of these MIRNAs from different aspects in B. rapa. First, while MIRNAs and genes show similar patterns of biased distribution among subgenomes of B. rapa, we found that MIRNAs are much more overretained than genes following fractionation after WGT. Second, multiple-copy MIRNAs show significant sequence conservation than that of single-copy MIRNAs, which is opposite to that of genes. This indicates that increased purifying selection is acting upon these highly retained multiple-copy MIRNAs and their functional importance over singleton MIRNAs. Furthermore, we found the extensive divergence between pairs of miRNAs and their target genes following the WGT in B. rapa. In summary, our study provides a valuable resource for exploring MIRNA in B. rapa and highlights the impacts of WGT on the evolution of MIRNA. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  5. Monitoring the Spatiotemporal Activities of miRNAs in Small Animal Models Using Molecular Imaging Modalities

    Directory of Open Access Journals (Sweden)

    Patrick Baril

    2015-03-01

    Full Text Available MicroRNAs (miRNAs are a class of small non-coding RNAs that regulate gene expression by binding mRNA targets via sequence complementary inducing translational repression and/or mRNA degradation. A current challenge in the field of miRNA biology is to understand the functionality of miRNAs under physiopathological conditions. Recent evidence indicates that miRNA expression is more complex than simple regulation at the transcriptional level. MiRNAs undergo complex post-transcriptional regulations such miRNA processing, editing, accumulation and re-cycling within P-bodies. They are dynamically regulated and have a well-orchestrated spatiotemporal localization pattern. Real-time and spatio-temporal analyses of miRNA expression are difficult to evaluate and often underestimated. Therefore, important information connecting miRNA expression and function can be lost. Conventional miRNA profiling methods such as Northern blot, real-time PCR, microarray, in situ hybridization and deep sequencing continue to contribute to our knowledge of miRNA biology. However, these methods can seldom shed light on the spatiotemporal organization and function of miRNAs in real-time. Non-invasive molecular imaging methods have the potential to address these issues and are thus attracting increasing attention. This paper reviews the state-of-the-art of methods used to detect miRNAs and discusses their contribution in the emerging field of miRNA biology and therapy.

  6. Deregulation and restructuring of the electric utility industry

    Energy Technology Data Exchange (ETDEWEB)

    Nixon, Hal [Utility Workers Union of America (UWUA), AFL-CIO, (United States)

    1997-12-31

    Federal and state policy makers are currently faced with the rapidly evolving issue of the restructuring and potential deregulation of the electric utility industry, a sector of the economy of huge importance through its sheer size and its impact on the daily life and livelihood of everyone. This paper describes eleven principles that must be adhered to in any restructuring of the electric industry. Adherence to the principle and positions outlined can help assure that the transition in this industry benefits all, not just a few, and that the general health and welfare of the people is protected and enhanced [Espanol] Los legisladores estatales y federales se estan enfrentando con el rapido y envolvente aspecto de la reestructuracion y desregulacion potencial de la industria electrica, un sector de la economia de enorme importancia por su tamano y su impacto en la vida diaria y los medios de vida. En esta ponencia se describen once principios y posiciones que deben ser considerados en cualquier reestructuracion de la industria electrica. El apego a los principios y posiciones comentados puede ayudar a asegurar que la transicion en esta industria deneficie a todos, no solo a unos cuantos, y que la salud general y bienestar de la gente sea protegida y mejorada

  7. Commercial banking in the conditions of deregulation vs. reregulation

    Directory of Open Access Journals (Sweden)

    Zaklan Damir

    2014-01-01

    Full Text Available This paper examines contemporary trends in commercial banking, confronting the stages of deregulation and reregulation in this field triggered by the global mortgage crisis. Under deregulatory conditions the competitive position of banks has toughened, and they reacted to it by intensifying: marketization, i.e. globalization, concentration, securitization and conglomeration, and by turning to the profit-oriented risk management of their activity. The contraction of their interest margin was thus neutralized by the reduction of operational costs and loss provisions, and by an increase in non-interest revenues, thereby maintaining banking profitability. The recent crisis has pinpointed the necessity of firmer regulation or reregulation of the banking sector, aimed at reducing its systemic risk, the most important aspect of which being the stricter international banking capital and liquidity standards, along with the requirement to adequately treat systemically important banks. Reregulation should strengthen capitalization and liquidity; mitigate the volume, concentration, internationalization and business dispersion, hence improving the supervision of the banking sector, implying its lower, yet more stable profitability. Such an impact of the adopted section of targeted regulatory measures has been indicated by higher liquidity, lower globalization, slower concentration and securitization, and stabilization-oriented risk management activities of today's banks. Their growth and profitability have shrunk.

  8. Equity effects of natural gas wellhead price deregulation

    Energy Technology Data Exchange (ETDEWEB)

    Stockfish, J.A.

    1982-01-01

    The author argues that the consumer burden doctrine is false because it incorrectly assumes that only two groups are affected by a natural gas price increase: direct consumers asnd producers. In a complex social economy, it is impossible for only a single price to change. No case can be made that a natural gas price increase would have a regressive effect on either direct (household users) or indirect (those who consume natural gas through the purchase of goods or as a production ingredient) consumers. No clear case can be made that the impact on income earners or resource owners will be regressive, although the effects of higher prices on the distribution of resource earnings is somewhat ambiguous. The report concludes that deregulation of wellhead prices will be mildly progressive for indirect consumers, but may be somewhat regressive in the long run for direct consumers. The elimination of production inefficiencies and the improvement of the terms of foreign trade will have a positive effect on both consumers and investors. 28 references, 16 tables.

  9. Reliability evaluation of deregulated electric power systems for planning applications

    International Nuclear Information System (INIS)

    Ehsani, A.; Ranjbar, A.M.; Jafari, A.; Fotuhi-Firuzabad, M.

    2008-01-01

    In a deregulated electric power utility industry in which a competitive electricity market can influence system reliability, market risks cannot be ignored. This paper (1) proposes an analytical probabilistic model for reliability evaluation of competitive electricity markets and (2) develops a methodology for incorporating the market reliability problem into HLII reliability studies. A Markov state space diagram is employed to evaluate the market reliability. Since the market is a continuously operated system, the concept of absorbing states is applied to it in order to evaluate the reliability. The market states are identified by using market performance indices and the transition rates are calculated by using historical data. The key point in the proposed method is the concept that the reliability level of a restructured electric power system can be calculated using the availability of the composite power system (HLII) and the reliability of the electricity market. Two case studies are carried out over Roy Billinton Test System (RBTS) to illustrate interesting features of the proposed methodology

  10. Natural gas market assessment ten years after deregulation

    International Nuclear Information System (INIS)

    1996-11-01

    Changes which have taken place in the Canadian natural gas market in the ten years since the gas market was de-regulated, were reviewed. A 1985 agreement created conditions for a competitive natural gas market. However, the National Energy Board ensured that the pipeline transmission sector of the gas industry would continue to be regulated because of its natural monopoly characteristics. Open non-discriminatory access was to be provided to all shippers on inter-provincial gas pipelines. One objective of this report was to provide the Board with the means of assuring itself that the market was operating in such a way that Canadian requirements for natural gas were being met at fair market prices. The report also provided a review of the major changes in the gas producing and transmission sector, and reviewed developments in gas markets and sales practices. The overall assessment was that the natural gas industry was efficient and responsive to the demands of the marketplace. 5 tabs., 30 figs

  11. Investment and deregulation in the electricity generation industry

    International Nuclear Information System (INIS)

    Peluchon, B.

    2007-12-01

    This work addresses the issue of investment in the electricity generation industry. As the analysis of many crisis which have affected electricity markets shows, there is a systematic under-investment in peak capacity. Electricity prices are not high enough to cover fixed costs of such generators, a phenomenon that has been dubbed 'missing money' in some recent papers (Stoft). The investment decisions of a duo-poly facing random demand are then compared to those of a public monopoly. The results are that no prices may be high enough to solve the 'missing money' problem, since the duo-poly is able to exercise market power in order to maximize his profit. This results systematically in fewer peak capacity in the duo-poly case than in the public monopoly case. This remains true in the case of a n-oligopoly. The necessity of designing a mechanism remunerating capacity is thus demonstrated. Capacity markets are then analysed in the light of those results. What appears is that operating reserves are a public good and, as such, prevents capacity markets to solve the 'missing money' problem. This casts a shadow on the pursuit of deregulation in the electricity industry. (author)

  12. Opportunities for privatization and alliances in a deregulated marketplace

    Energy Technology Data Exchange (ETDEWEB)

    Erling, J.M. [KPMG, Toronto, ON (Canada)

    1998-09-01

    The main implications for municipal electric utilities (MEUs) and businesses in a deregulated, open access energy market include a range of possible alternative business structures, constraints on choices, increased risks, the need to understand objectives, capabilities and capacity for bearing risks. The issue of what business MEUs are in, what services they provide and how those services should be delivered, was hotly debated. It was suggested that with increasing competition, the range of possible business structures and arrangements will widen significantly. The different public-private options available to MEUs are (1) the conventional tender process, (2) contracting out, (3) joint ventures with a private company, (4) franchising, (5) outsourcing of specific functions, (6) operating agreements, (7) lease arrangements, (8) build-operate-transfer options (BOTs), and (9) the full privatization scenario. It was noted that some forms of public-private partnerships are more suited to some businesses than others. Also, different partnership structures can be used in different parts of any business. Objectives for any partnership should include maximizing profitability, minimizing risk and promoting economic development but under competition. The ability to choose objectives will change significantly and the achievement of any of the objectives will be determined by the marketplace. Some guidelines on measuring success and on maximizing market value were offered. Global trends towards more unbundling and price transparency, more outsourcing to the private sector, more competition, less government, regulatory reform and blurring of the boundaries between utility sectors were predicted.

  13. Price-elastic demand in deregulated electricity markets

    Energy Technology Data Exchange (ETDEWEB)

    Siddiqui, Afzal S.

    2003-05-01

    The degree to which any deregulated market functions efficiently often depends on the ability of market agents to respond quickly to fluctuating conditions. Many restructured electricity markets, however, experience high prices caused by supply shortages and little demand-side response. We examine the implications for market operations when a risk-averse retailer's end-use consumers are allowed to perceive real-time variations in the electricity spot price. Using a market-equilibrium model, we find that price elasticity both increases the retailers revenue risk exposure and decreases the spot price. Since the latter induces the retailer to reduce forward electricity purchases, while the former has the opposite effect, the overall impact of price responsive demand on the relative magnitudes of its risk exposure and end-user price elasticity. Nevertheless, price elasticity decreases cumulative electricity consumption. By extending the analysis to allow for early settlement of demand, we find that forward stage end-user price responsiveness decreases the electricity forward price relative to the case with price-elastic demand only in real time. Moreover, we find that only if forward stage end-user demand is price elastic will the equilibrium electricity forward price be reduced.

  14. Deregulation and competitive power markets -- Its impact on developing economies

    International Nuclear Information System (INIS)

    Saran, K.

    1998-01-01

    The aim of privatization in developed countries is to encourage competition in generation and supply of power whereas the focus of developing economies is to bridge the demand supply gap by addition of capacity. However, there needs to be a reconciliation between these two apparently having conflicting objectives even in case of developing economies. In competitive power markets it is necessary that rules of the game are identified in advance and followed uniformly by all players. Existence of a ''referee'' would be necessary to regulate the game so as to ensure fair play. The regulatory institution would serve this purpose and work as a stimulator to development of privatization and competitive power markets in developing economies. Consumer interests should be of upper-most priority in the mind while establishing power markets and regulatory institutions, particularly as market forces are unfavorable to consumer interests in power shortage conditions. As competition fosters, gradually market forces take over and the ''harsh'' regulator would convert itself to a ''silent vigil referee'' so as to ensure genuine competition. The debate of deregulation vs. regulation will continue but the show must go on for building of an increasingly sound, competitive and vibrant power sector in the interest of end use consumers. The planned and phased restructuring though a delayed process is a preferred process and India is fully determined to achieve this

  15. Global implications of U.S. power deregulation

    International Nuclear Information System (INIS)

    Maschoff, D.C.

    1996-01-01

    With U.S. power deregulation remaining a topic that is dominating the entire North American energy marketplace, this paper provides an update of events occurring in U.S. electric power markets, offering some observations about changes due to increasing competition in electric power markets, and discusses some reasons why the events in U.S. electric power markets will soon transform global energy markets. How quickly is the move from local service territory to global markets proceeding? More than fifty U.S. utility companies with revenues of over $1 billion (U.S.) will soon be actively seeking and participating in global business opportunities. Using the same logic that led them to pursue utility initiatives nationally, U.S. utilities will use their core capabilities to compete in global energy services markets. In connection with these global initiatives, U.S. utilities will bring the same fuel-neutral, gas-electric perspective to international electric power and natural gas markets. (Author)

  16. Deregulation - precondition for distributed energy in the economies in transition

    International Nuclear Information System (INIS)

    Brendow, K.

    2001-01-01

    This paper holds that deregulation, i.e. restructuring, competition and privatisation, is the main precondition for a more pronounced development of distributed power (DP) in the economies in transition in central and eastern Europe. This, then, raises the question how far the electricity, gas, steam and heat generating industries have presently moved on their way towards more market-oriented frameworks, competition and private ownership. A good benchmark for measuring progress is the existence (or lack thereof), and nature, of regulatory regimes enabling fair competition among large centralised and small decentralised power, and between wholesale generators and distributors on the one hand and customers or ''autoproducers'' or power merchants on the other. The paper describes the regulatory models applied or contemplated in the winter 2000/2001 in the various countries of central and eastern Europe and identifies fifteen general issues that require attention and solution. With regard to DP, it concludes that a major upswing is unlikely to occur before 2005-2008. While technological options abound, the institutional frameworks for customer-owned competitive DP systems are only being contemplated at present and only rarely put in place.(author)

  17. Targeting Deregulated Epigenetic Control in Cancer: Cancer Epigenomics as a Platform for Risk Assessment, Early Detection, Targeted Therapy and Potential for Relapse

    Science.gov (United States)

    Zaidi, Sayyed K.; van Wijnen, Andre J.; Lian, Jane B.; Stein, Janet L.; Stein, Gary S.

    2013-01-01

    Summary Cancer is a multifaceted disease that involves acquisition of genetic mutations, deletions, and amplifications as well as deregulation of epigenetic mechanisms that fine-tune gene regulation. Key epigenetic mechanisms that include histone modifications, DNA methylation, and non-coding RNA-mediated gene silencing are often deregulated in a variety of cancers. Subnuclear localization of key proteins in the interphase nucleus and bookmarking of genes by lineage commitment factors in mitosis – a new dimension to epigenetic control of fundamental biological processes – is also modified in cancer. In this review, we discuss the various aspects of epigenetic control that are operative in a variety of cancers and their potential for risk assessment, early detection, targeted therapy and personalized medicine. PMID:23589100

  18. Genome-wide identification and functional annotation of miRNAs in anti-inflammatory plant and their cross-kingdom regulation in Homo sapiens.

    Science.gov (United States)

    Sharma, Ankita; Sahu, Sarika; Kumari, Pooja; Gopi, Soundhara Rajan; Malhotra, Rajesh; Biswas, Sagarika

    2017-05-01

    MicroRNAs (miRNAs) are newly discovered non-coding small (~17-24 nucleotide) RNAs that regulate gene expression of its target mRNA at the post-transcriptional levels. In this study, total 12,593 ESTs of Curcuma longa were taken from database of expressed sequence tags (dbEST) and clustered into 2821 contigs using EGassembler web server. Precursor miRNAs (pre-miRNAs) were predicted from these contigs that folded into stem-loop structure using MFold server. Thirty-four mature C. longa miRNAs (clo-miRNAs) were identified from pre-miRNAs having targets involved in various important functions of plant such as self-defence, growth and development, alkaloid metabolic pathway and ethylene signalling process. Sequence analysis of identified clo-miRNAs indicated that 56% miRNAs belong to ORF and 44% belong to non-ORF region. clo-mir-5 and clo-mir-6 were established as the conserved miRNAs, whereas clo-mir-20 was predicted to be the most stable miRNA. Phylogenetic analysis carried out by molecular evolutionary genetics analysis (MEGA) software indicated close evolutionary relationship of clo-mir-5075 with osa-MIR5075. Further, identified clo-miRNAs were checked for their cross-kingdom regulatory potential. clo-mir-14 was found to regulate various gene transcripts in humans that has been further investigated for its biostability in foetal bovine serum (FBS). The results indicated higher degree of stability of clo-mir-14 (48 h) in FBS. Thus, contribution of this miRNA to the cellular immune response during the inflamed condition of rheumatoid arthritis and adequate stability may make it a good choice for the therapeutic agent in near future.

  19. NF-kappaB p65-dependent transactivation of miRNA genes following Cryptosporidium parvum infection stimulates epithelial cell immune responses.

    Directory of Open Access Journals (Sweden)

    Rui Zhou

    2009-12-01

    Full Text Available Cryptosporidium parvum is a protozoan parasite that infects the gastrointestinal epithelium and causes diarrheal disease worldwide. Innate epithelial immune responses are key mediators of the host's defense to C. parvum. MicroRNAs (miRNAs regulate gene expression at the posttranscriptional level and are involved in regulation of both innate and adaptive immune responses. Using an in vitro model of human cryptosporidiosis, we analyzed C. parvum-induced miRNA expression in biliary epithelial cells (i.e., cholangiocytes. Our results demonstrated differential alterations in the mature miRNA expression profile in cholangiocytes following C. parvum infection or lipopolysaccharide stimulation. Database analysis of C. parvum-upregulated miRNAs revealed potential NF-kappaB binding sites in the promoter elements of a subset of miRNA genes. We demonstrated that mir-125b-1, mir-21, mir-30b, and mir-23b-27b-24-1 cluster genes were transactivated through promoter binding of the NF-kappaB p65 subunit following C. parvum infection. In contrast, C. parvum transactivated mir-30c and mir-16 genes in cholangiocytes in a p65-independent manner. Importantly, functional inhibition of selected p65-dependent miRNAs in cholangiocytes increased C. parvum burden. Thus, we have identified a panel of miRNAs regulated through promoter binding of the NF-kappaB p65 subunit in human cholangiocytes in response to C. parvum infection, a process that may be relevant to the regulation of epithelial anti-microbial defense in general.

  20. Regulatory Assessment of the Effects of Economic Deregulation of the Nuclear Industry

    International Nuclear Information System (INIS)

    2002-11-01

    The European Commission Nuclear Regulators Working Group (NRWG) appointed a Task Force (TF) to develop a common view among European regulators on the assessment of typical safety consequences resulting from economic pressure on operators as a result of deregulation of electricity markets. Although the report seems to imply that there are only negative aspects of deregulation, this is not the case. As the focus of the TF has been potential safety consequences we have not dealt with potential positive effects of deregulation. To provide a general background to the analyses of the safety consequences, the TF undertook a survey of the current situation within the EU and candidate countries on aspects of economic deregulation of the countries nuclear industry and the experiences so far of regulating these issues. Answers were submitted in of July 2001. 13 NRWG members with nuclear power plants took part in the survey. (author)

  1. Comparative Analysis of miRNAs and Their Target Transcripts between a Spontaneous Late-Ripening Sweet Orange Mutant and Its Wild-Type Using Small RNA and Degradome Sequencing.

    Science.gov (United States)

    Wu, Juxun; Zheng, Saisai; Feng, Guizhi; Yi, Hualin

    2016-01-01

    Fruit ripening in citrus is not well-understood at the molecular level. Knowledge of the regulatory mechanism of citrus fruit ripening at the post-transcriptional level in particular is lacking. Here, we comparatively analyzed the miRNAs and their target genes in a spontaneous late-ripening mutant, "Fengwan" sweet orange (MT) ( Citrus sinensis L. Osbeck), and its wild-type counterpart ("Fengjie 72-1," WT). Using high-throughput sequencing of small RNAs and RNA degradome tags, we identified 107 known and 21 novel miRNAs, as well as 225 target genes. A total of 24 miRNAs (16 known miRNAs and 8 novel miRNAs) were shown to be differentially expressed between MT and WT. The expression pattern of several key miRNAs and their target genes during citrus fruit development and ripening stages was examined. Csi-miR156k, csi-miR159, and csi-miR166d suppressed specific transcription factors ( GAMYBs, SPLs , and ATHBs ) that are supposed to be important regulators involved in citrus fruit development and ripening. In the present study, miRNA-mediated silencing of target genes was found under complicated and sensitive regulation in citrus fruit. The identification of miRNAs and their target genes provide new clues for future investigation of mechanisms that regulate citrus fruit ripening.

  2. The Central Conserved Region (CCR) of Respiratory Syncytial Virus (RSV) G Protein Modulates Host miRNA Expression and Alters the Cellular Response to Infection.

    Science.gov (United States)

    Bakre, Abhijeet A; Harcourt, Jennifer L; Haynes, Lia M; Anderson, Larry J; Tripp, Ralph A

    2017-07-03

    Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182-186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting.

  3. The Role of miRNA in Papillary Thyroid Cancer in the Context of miRNA Let-7 Family

    Directory of Open Access Journals (Sweden)

    Ewelina Perdas

    2016-06-01

    Full Text Available Papillary thyroid carcinoma (PTC is the most common endocrine malignancy. RET/PTC rearrangement is the most common genetic modification identified in this category of cancer, increasing proliferation and dedifferentiation by the activation of the RET/PTC-RAS-BRAF-MAPK-ERK signaling pathway. Recently, let-7 miRNA was found to reduce RAS levels, acting as a tumor suppressor gene. Circulating miRNA profiles of the let-7 family may be used as novel noninvasive diagnostic, prognostic, treatment and surveillance markers for PTC.

  4. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Motoo, Yoshiharu, E-mail: motoo@kanazawa-med.ac.jp [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Shimasaki, Takeo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan); Ishigaki, Yasuhito [Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Nakajima, Hideo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Kawakami, Kazuyuki; Minamoto, Toshinari [Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan)

    2011-01-24

    Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.

  5. Age-specific differences in oncogenic pathway deregulation seen in human breast tumors.

    Directory of Open Access Journals (Sweden)

    Carey K Anders

    Full Text Available PURPOSE: To define the biology driving the aggressive nature of breast cancer arising in young women. EXPERIMENTAL DESIGN: Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young or=65 years, 411 eligible patients (n = 200or=65 years with clinically-annotated Affymetrix microarray data were identified. GSEA, signatures of oncogenic pathway deregulation and predictors of chemotherapy sensitivity were evaluated within the two age-defined cohorts. RESULTS: In comparing deregulation of oncogenic pathways between age groups, a higher probability of PI3K (p = 0.006 and Myc (p = 0.03 pathway deregulation was observed in breast tumors arising in younger women. When evaluating unique patterns of pathway deregulation, a low probability of Src and E2F deregulation in tumors of younger women, concurrent with a higher probability of PI3K, Myc, and beta-catenin, conferred a worse prognosis (HR = 4.15. In contrast, a higher probability of Src and E2F pathway activation in tumors of older women, with concurrent low probability of PI3K, Myc and beta-catenin deregulation, was associated with poorer outcome (HR = 2.7. In multivariate analyses, genomic clusters of pathway deregulation illustrate prognostic value. CONCLUSION: Results demonstrate that breast cancer arising in young women represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathways that are prognostic, independent of currently available clinico-pathologic variables. These results should enable refinement of targeted treatment strategies in this clinically challenging situation.

  6. Impacts of Contingency Reserve on Nodal Price and Nodal Reliability Risk in Deregulated Power Systems

    DEFF Research Database (Denmark)

    Zhao, Qian; Wang, Peng; Goel, Lalit

    2013-01-01

    The deregulation of power systems allows customers to participate in power market operation. In deregulated power systems, nodal price and nodal reliability are adopted to represent locational operation cost and reliability performance. Since contingency reserve (CR) plays an important role...... and CR allocation. Customers' nodal unit commitment risk and nodal energy interruption have been evaluated through contingency analysis. Customers' reliability cost including reserve service cost and energy interruption cost have also been evaluated....

  7. Comprehensive analysis of differential genes and miRNA profiles for discovery of topping-responsive genes in flue-cured tobacco roots.

    Science.gov (United States)

    Qi, Yuancheng; Guo, Hongxiang; Li, Ke; Liu, Weiqun

    2012-03-01

    Decapitation/topping is an important cultivating measure for flue-cured tobacco, and diverse biology processes are changed to respond to the topping, such as hormonal balance, root development, source-sink relationship, ability of nicotine synthesis and stress tolerance. The purpose of this study was to clarify the molecular mechanism involved in the response of flue-cured tobacco to topping. The differentially expressed genes and micro RNAs (miRNAs) before and after topping were screened with a combination of suppression subtractive hybridization (SSH) and miRNA deep sequencing. In all, 560 differently expressed clones were sequenced by SSH, and then 129 high quality expressed sequence tags were acquired. These expressed sequence tags were mainly involved in secondary metabolism (13.5%), hormone metabolism (4%), signaling/transcription (17.5%), stress/defense (20%), protein metabolism (13%), carbon metabolism (7%), other metabolism (12%) and unknown function (13%). The results contribute new data to the list of possible candidate genes involved in the response of flue-cured tobacco to topping. NAC transcription factor, a differential gene identified by SSH, had been proved to have a role in the regulation of nicotine biosynthesis. High-throughput sequencing of two small RNA libraries in combination with SSH screening revealed 15 differential miRNAs whose target genes were identical to some differential genes identified in SSH, suggesting that miRNAs play a critical role in post-transcriptional gene regulation in the response of flue-cured tobacco to decapitation. Based on the role of these miRNAs and differential genes identified from SSH in response to topping, an miRNA mediated model for flue-cured tobacco in response to topping is proposed. © 2012 The Authors Journal compilation © 2012 FEBS.

  8. Identification of miRNA from Porphyra yezoensis by high-throughput sequencing and bioinformatics analysis.

    Directory of Open Access Journals (Sweden)

    Chengwei Liang

    Full Text Available BACKGROUND: miRNAs are a class of non-coding, small RNAs that are approximately 22 nucleotides long and play important roles in the translational level regulation of gene expression by either directly binding or cleaving target mRNAs. The red alga, Porphyra yezoensis is one of the most important marine economic crops worldwide. To date, only a few miRNAs have been identified in green unicellar alga and there is no report about Porphyra miRNAs. METHODOLOGY/PRINCIPAL FINDINGS: To identify miRNAs in Porphyra yezoensis, a small RNA library was constructed. Solexa technology was used to perform high throughput sequencing of the library and subsequent bioinformatics analysis to identify novel miRNAs. Specifically, 180,557,942 reads produced 13,324 unique miRNAs representing 224 conserved miRNA families that have been identified in other plants species. In addition, seven novel putative miRNAs were predicted from a limited number of ESTs. The potential targets of these putative miRNAs were also predicted based on sequence homology search. CONCLUSIONS/SIGNIFICANCE: This study provides a first large scale cloning and characterization of Porphyra miRNAs and their potential targets. These miRNAs belong to 224 conserved miRNA families and 7 miRNAs are novel in Porphyra. These miRNAs add to the growing database of new miRNA and lay the foundation for further understanding of miRNA function in the regulation of Porphyra yezoensis development.

  9. Characterization of miRNA Expression in Human Degenerative Lumbar Disks

    DEFF Research Database (Denmark)

    Ohrt-Nissen, Søren; Døssing, Kristina B V; Rossing, Maria

    2013-01-01

    microRNAs (miRNAs) are short ∼22 nucleotide RNA sequences that regulate messengerRNA translation. miRNAs have shown to play a role in synthesis of inflammatory mediators. Since inflammation play a role in intervertebral disk (IVD) degeneration, the objective was to isolate miRNA from human lumbar...... intervertebral disks and subsequently characterize the difference in miRNA expression between the annulus fibrosus (AF) and nucleus pulposus (NP)....

  10. Marked reduction of AKT1 expression and deregulation of AKT1-associated pathways in peripheral blood mononuclear cells of schizophrenia patients.

    Directory of Open Access Journals (Sweden)

    Nico J M van Beveren

    Full Text Available BACKGROUND: Recent studies have suggested that deregulated AKT1 signaling is associated with schizophrenia. We hypothesized that if this is indeed the case, we should observe both decreased AKT1 expression as well as deregulation of AKT1 regulated pathways in Peripheral Blood Mononuclear Cells (PBMCs of schizophrenia patients. OBJECTIVES: To examine PBMC expression levels of AKT1 in schizophrenia patients versus controls, and to examine whether functional biological processes in which AKT1 plays an important role are deregulated in schizophrenia patients. METHODS/RESULTS: A case-control study, investigating whole-genome PBMC gene expression in male, recent onset (<5 years schizophrenia patients (N = 41 as compared to controls (N = 29. Genes, differentially expressed between patients and controls were identified using ANOVA with Benjamini-Hochberg correction (false discovery rate (FDR = 0.05. Functional aspects of the deregulated set of genes were investigated with the Ingenuity Pathway Analysis (IPA Software Tool. We found significantly decreased PBMC expression of AKT1 (p<0.001, t = -4.25 in the patients. AKT1 expression was decreased in antipsychotic-free or -naive patients (N = 11, in florid psychotic (N = 20 and in remitted (N = 21 patients. A total of 1224 genes were differentially expressed between patients and controls (FDR = 0.05. Functional analysis of the entire deregulated gene set indicated deregulated canonical pathways involved in a large number of cellular processes: immune system, cell adhesion and neuronal guidance, neurotrophins and (neural growth factors, oxidative stress and glucose metabolism, and apoptosis and cell-cycle regulation. Many of these processes are associated with AKT1. CONCLUSIONS: We show significantly decreased PBMC gene expression of AKT1 in male, recent-onset schizophrenia patients. Our observations suggest that decreased PBMC AKT1 expression is a stable trait in recent onset

  11. Neuronal activity regulates hippocampal miRNA expression

    NARCIS (Netherlands)

    Eacker, S.M.; Keuss, M.J.; Berezikov, E.; Dawson, V.L.; Dawson, T.

    2011-01-01

    Neuronal activity regulates a broad range of processes in the hippocampus, including the precise regulation of translation. Disruptions in proper translational control in the nervous system are associated with a variety of disorders that fall in the autistic spectrum. MicroRNA (miRNA) represent a

  12. Neuronal Activity Regulates Hippocampal miRNA Expression

    NARCIS (Netherlands)

    Eacker, Stephen M.; Keuss, Matthew J.; Berezikov, Eugene; Dawson, Valina L.; Dawson, Ted M.

    2011-01-01

    Neuronal activity regulates a broad range of processes in the hippocampus, including the precise regulation of translation. Disruptions in proper translational control in the nervous system are associated with a variety of disorders that fall in the autistic spectrum. MicroRNA (miRNA) represent a

  13. Adverse Intrauterine Environment and Cardiac miRNA Expression

    Directory of Open Access Journals (Sweden)

    Mitchell C. Lock

    2017-12-01

    Full Text Available Placental insufficiency, high altitude pregnancies, maternal obesity/diabetes, maternal undernutrition and stress can result in a poor setting for growth of the developing fetus. These adverse intrauterine environments result in physiological changes to the developing heart that impact how the heart will function in postnatal life. The intrauterine environment plays a key role in the complex interplay between genes and the epigenetic mechanisms that regulate their expression. In this review we describe how an adverse intrauterine environment can influence the expression of miRNAs (a sub-set of non-coding RNAs and how these changes may impact heart development. Potential consequences of altered miRNA expression in the fetal heart include; Hypoxia inducible factor (HIF activation, dysregulation of angiogenesis, mitochondrial abnormalities and altered glucose and fatty acid transport/metabolism. It is important to understand how miRNAs are altered in these adverse environments to identify key pathways that can be targeted using miRNA mimics or inhibitors to condition an improved developmental response.

  14. Epigenetic architecture and miRNA: reciprocal regulators

    DEFF Research Database (Denmark)

    Wiklund, Erik D; Kjems, Jørgen; Clark, Susan J

    2010-01-01

    and crucial for maintaining correct local and global genomic architecture and gene expression patterns, yet the underlying molecular mechanisms and their widespread effects remain poorly understood. Due to the tissue specificity, versatility and relative stability of miRNAs, these small non-coding RNAs (nc...

  15. Recessive genetic deregulation abrogates c-myc suppression by interferon and is implicated in oncogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kimchi, A.; Resnitzky, D.; Ber, R.; Gat, G.

    1988-07-01

    Previously the authors demonstrated that many hematopoietic tumor cells are resistant to the inhibitory effects that interferon exerts on c-myc mRNA expression without losing other receptor-mediated intracellular responses. They report here that this partial resistance was overridden in two independent stable somatic cell hybrids prepared by fusion between sensitive and resistant cells. The c-myc mRNA transcribed from the active allele of the resistant parent cell was reduced by interferon within the context of the cell hybrid. It was therefore concluded that changes in the cis-acting sequences of c-myc were not involved in this type of relaxed regulation and that resistance resulted rather from inactivation or loss of postreceptor elements which operate in trans. The growth-stimulating effect that this genetic deregulation might have on cells was tested in experimental systems of cell differentiation in which an autocrine interferon is produced. For that purpose the authors isolated variant clones of M1 myeloid cells which were partially resistant to alpha and beta interferons and tested their growth behaviour during in vitro-induced differentiation. The resistant clones displayed higher proliferative activity on days 2 and 3 of differentiation than did the sensitive clones, which stopped proliferating. The loss of c-myc responses to the self-produced interferon disrupted the normal cessation of growth during differentiation and therefore might lead cells along the pathway of neoplasia.

  16. Novel insights into the pathways regulating the canine hair cycle and their deregulation in alopecia X.

    Science.gov (United States)

    Brunner, Magdalena A T; Jagannathan, Vidhya; Waluk, Dominik P; Roosje, Petra; Linek, Monika; Panakova, Lucia; Leeb, Tosso; Wiener, Dominique J; Welle, Monika M

    2017-01-01

    Alopecia X is a hair cycle arrest disorder in Pomeranians. Histologically, kenogen and telogen hair follicles predominate, whereas anagen follicles are sparse. The induction of anagen relies on the activation of hair follicle stem cells and their subsequent proliferation and differentiation. Stem cell function depends on finely tuned interactions of signaling molecules and transcription factors, which are not well defined in dogs. We performed transcriptome profiling on skin biopsies to analyze altered molecular pathways in alopecia X. Biopsies from five affected and four non-affected Pomeranians were investigated. Differential gene expression revealed a downregulation of key regulator genes of the Wnt (CTNNB1, LEF1, TCF3, WNT10B) and Shh (SHH, GLI1, SMO, PTCH2) pathways. In mice it has been shown that Wnt and Shh signaling results in stem cell activation and differentiation Thus our findings are in line with the lack of anagen hair follicles in dogs with Alopecia X. We also observed a significant downregulation of the stem cell markers SOX9, LHX2, LGR5, TCF7L1 and GLI1 whereas NFATc1, a quiescence marker, was upregulated in alopecia X. Moreover, genes coding for enzymes directly involved in the sex hormone metabolism (CYP1A1, CYP1B1, HSD17B14) were differentially regulated in alopecia X. These findings are in agreement with the so far proposed but not yet proven deregulation of the sex hormone metabolism in this disease.

  17. Image is all: Deregulation, restructuring and reputation in the natural gas industry

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    Does image affect how one views his local utility company--or energy supplier? Does one value his utility companies more if one sees a lot of image advertising and public relations stories about community involvement, environmental action and charitable work? Or does one view utilities as faceless and anonymous entities that provide necessary services one thinks little about until there's a problem? And, more important, what is the role of utility image in an era of deregulation, as companies begin a new scramble for customers? To find an answer to these questions, American Gas and Christopher Bonner Consultants conducted a survey of A.G.A. member companies to learn what, if anything, utility companies are doing in the areas of image assessment and change. The survey was sent to more than 200 A.G.A. member companies; written responses were received from 35. In addition, 13 follow-up telephone interviews were conducted, including four with companies that had not responded in writing. The picture that emerges if of an industry that is starting to pay greater and greater attention to image. And, as utilities reorganize and redefine themselves, they are also reexamining the ways they communicate with key audiences, including employees, customers, legislators, the financial community and the news media

  18. Fuel, environmental, and transmission pricing considerations in a deregulated environment

    Science.gov (United States)

    Obessis, Emmanouil Vlassios

    The 1992 National Energy Policy Act drastically changed the traditional structure of the vertically integrated utility. To facilitate increased competition in the power utility sector, all markets related to power generation have been opened to free competition and trading. To survive in the new competitive environment, power producers need to reduce costs and increase efficiency. Fuel marketing strategies are thus, getting more aggressive and fuel markets are becoming more competitive, offering more options regarding fuel supplies and contracts. At the same time, the 1990 Clean Air Act Amendments are taking effect. Although tightening the emission standards, this legislation offers utilities a wider flexibility in choosing compliance strategies. It also set maximum annual allowable levels replacing the traditional uniform maximum emission rates. The bill also introduced the concept of marketable emission allowances and provided for the establishment of nationwide markets where allowances may be traded, sold, or purchased. Several fuel- and emission-constrained algorithms have been historically presented, but those two classes of constraints, in general, were handled independently. The multiobjective optimization model developed in this research work, concurrently satisfies sets of detailed fuel and emission limits, modeling in a more accurate way the fuel supply and environmental limitations and their complexities in the new deregulated operational environment. Development of the implementation software is an integral part of this research project. This software may be useful for both daily scheduling activities and short-term operational planning. A Lagrangian multipliers-based variant is used to solve the problem. Single line searches are used to update the multipliers, thus offering attractive execution times. This work also investigates the applicability of cooperative games to the problem of transmission cost allocation. Interest in game theory as a powerful

  19. The deregulation connection : utility competition creates new niche company

    International Nuclear Information System (INIS)

    Roy, C.

    1999-01-01

    Deregulation in Ontario's utility market has created incentives for local utilities to add new services to attract and keep customers, knowing that in a competitive energy market, only those utilities which offer the best services will survive. London Hydro, which provides power to southwestern Ontario launched a private enterprise called LondonConnect Inc. The new enterprise offers high-speed digital services to area businesses. London Hydro made this unique move to take advantage of the fact that 20 per cent of businesses communicate electronically. London Hydro believes that in the next five years, that number will increase to 80 per cent. The Metropolitan Area Network (MAN) gives businesses greater connectivity to the Internet and web services. One of the network's capabilities is realtime video conferencing between hydro locations. MAN can also be used to create a secure and private virtual community-wide area network of computers and office machines. The advantages are numerous. For example, hospitals will be able to exchange information between remote sites at incredible speeds. MAN is made up of fiber-optic cables and electronic routers. LondonConnect is expecting to provide access throughout London by the fall of 1999. A dozen clients have already signed up for the service. Installation of the system will cost $1,000 with fixed monthly rates. The cost will vary depending on the level of service. The network will cost London Hydro $3 million, but it is expected to generate $2.5 million annually in its first two years. 3 figs

  20. The deregulation connection : utility competition creates new niche company

    Energy Technology Data Exchange (ETDEWEB)

    Roy, C

    1999-08-01

    Deregulation in Ontario's utility market has created incentives for local utilities to add new services to attract and keep customers, knowing that in a competitive energy market, only those utilities which offer the best services will survive. London Hydro, which provides power to southwestern Ontario launched a private enterprise called LondonConnect Inc. The new enterprise offers high-speed digital services to area businesses. London Hydro made this unique move to take advantage of the fact that 20 per cent of businesses communicate electronically. London Hydro believes that in the next five years, that number will increase to 80 per cent. The Metropolitan Area Network (MAN) gives businesses greater connectivity to the Internet and web services. One of the network's capabilities is realtime video conferencing between hydro locations. MAN can also be used to create a secure and private virtual community-wide area network of computers and office machines. The advantages are numerous. For example, hospitals will be able to exchange information between remote sites at incredible speeds. MAN is made up of fiber-optic cables and electronic routers. LondonConnect is expecting to provide access throughout London by the fall of 1999. A dozen clients have already signed up for the service. Installation of the system will cost $1,000 with fixed monthly rates. The cost will vary depending on the level of service. The network will cost London Hydro $3 million, but it is expected to generate $2.5 million annually in its first two years. 3 figs.

  1. Deregulation led to record-breaking profit for SPP

    International Nuclear Information System (INIS)

    Janoska, J.

    2004-01-01

    The state collected close to 15 bn Sk of SPP's last year profits. The income tax represents about 5,2 bn Sk and the dividends paid to state as owner of 51 percent of the stock of Slovensky plynarensky priemysel, a.s., Bratislava (SPP) amount up to 9,5 billion Sk. Investors Ruhrgas and Gaz de France will split 9 billion Sk. This was possible thank to a record-breaking net profit of 20.5 billion Sk made by the company due to deregulation of the distorted gas prices for consumers that lead to an average price increase by over 30 percent. A positive impact on the company's economy had also the dissolving of provisions and reserves but on the other hand the sales went down by close to 5 percent due to higher temperatures. Another factor that had a positive impact on the company revenues was the increase of gas volumes transported through the SPP network to Western Europe. Expenditures related to purchase of gas increased last year and not even the decrease USD exchange rates could eliminate the impact of increasing gas prices. The decrease of sales on the domestic market was one of the major factors that allowed the total cost to decrease on year-to-year basis by ten percent. A restructuring of SPP should bring along further savings but the company has not calculated the total effect of a restructuring yet. The strong positive impact the restructuring may have on the company should show in 2004 and later. Last year the company concentrated on savings in area of maintenance and repairs and this year it should be the procurement expenditures that should be decreased. The future economic result of the company would depend on several factors like exchange rates, sale volumes and price of natural gas. Oils prices have reached their new maximums and the gas prices, in general, follow the oil price

  2. Exploring cross-species-related miRNAs based on sequence and secondary structure.

    Science.gov (United States)

    Chen, Feng; Chen, Yi-Ping Phoebe

    2010-07-01

    MicroRNA (miRNA) plays an important role as a regulator of mRNA. But how miRNAs relate with each other in gene regulation network is still remaining. Understanding the reactions between miRNAs can be very significant for exploring miRNA target, gene regulation mechanism, and gene conservation in evolution process. We explore cross-species-related miRNAs to find out how miRNAs regulate each other by using joint entropy and mutual information, respectively. Our contribution includes the following: 1) our algorithms are based on the combination of sequence and secondary structure analysis because miRNAs are conserved much better in the secondary structure; and 2) when we consider if two miRNAs A and B are related, we consider the relationship between A (B) and other miRNAs in their own species too. If A (B) has a very close relationship with other miRNAs in its own species and the relationship of A and B is close too, then the relationship between A and B is more important. Therefore, this related miRNA pair is more significant. So, our algorithms confirm to the reality that genes regulate each other as a network. Through experiments on miRNAMap 2.0, it has been proven that we can not only find out the known related miRNA pairs but also predict some novel ones.

  3. miRNA profiles in cerebrospinal fluid from patients with central hypersomnias

    DEFF Research Database (Denmark)

    Holm, Anja; Bang-Berthelsen, Claus Heiner; Knudsen, Stine

    2014-01-01

    addressed whether miRNA levels are altered in the cerebrospinal fluid (CSF) of patients with central hypersomnias. We conducted high-throughput analyses of miRNAs in CSF from patients using quantitative real-time polymerase chain reaction panels. We identified 13, 9, and 11 miRNAs with a more than two...

  4. Identification of miRNA targets with stable isotope labeling by amino acids in cell culture

    DEFF Research Database (Denmark)

    Vinther, Jeppe; Hedegaard, Mads Marquardt; Gardner, Paul Phillip

    2006-01-01

    miRNAs are small noncoding RNAs that regulate gene expression. We have used stable isotope labeling by amino acids in cell culture (SILAC) to investigate the effect of miRNA-1 on the HeLa cell proteome. Expression of 12 out of 504 investigated proteins was repressed by miRNA-1 transfection...

  5. In silico miRNA prediction in metazoan genomes: balancing between sensitivity and specificity

    NARCIS (Netherlands)

    Burgt, van der A.; Fiers, M.W.E.J.; Nap, J.P.H.; Ham, van R.C.H.J.

    2009-01-01

    Background - MicroRNAs (miRNAs), short ~21-nucleotide RNA molecules, play an important role in post-transcriptional regulation of gene expression. The number of known miRNA hairpins registered in the miRBase database is rapidly increasing, but recent reports suggest that many miRNAs with restricted

  6. Practical data handling pipeline improves performance of qPCR-based circulating miRNA measurements

    NARCIS (Netherlands)

    de Ronde, Maurice W. J.; Ruijter, Jan M.; Lanfear, David; Bayes-Genis, Antoni; Kok, Maayke G. M.; Creemers, Esther E.; Pinto, Yigal M.; Pinto-Sietsma, Sara-Joan

    2017-01-01

    Since numerous miRNAs have been shown to be present in circulation, these so-called circulating miRNAs have emerged as potential biomarkers for disease. However, results of qPCR studies on circulating miRNA biomarkers vary greatly and many experiments cannot be reproduced. Missing data in qPCR

  7. Regulating BMI1 expression via miRNAs promote Mesenchymal to Epithelial Transition (MET and sensitizes breast cancer cell to chemotherapeutic drug.

    Directory of Open Access Journals (Sweden)

    Nibedita Patel

    Full Text Available Polycomb group (PcG proteinB lymphoma Mo-MLV insertion region 1 homolog (BMI1 is a transcriptional repressor that plays an important role in human carcinogenesis. MicroRNAs (miRNAs are endogenous small non-coding RNAsthat implicate a negative regulation on gene expression. Deregulation of the expression of miRNAs has been implicated in tumorigenesis. Here, we have shown that knock-down ofBMI1increases theexpression of tumor-suppressivemiRNAs. Elevated levels of expression of miR-200a, miR-200b, miR-15a, miR-429, miR-203were observed upon knock-down of BMI1. Up-regulation of these miRNAsleads to down-regulation ofPRC1 group of proteins i.e. BMI1, RING1A, RING1B and Ub-H2A. Interestingly, overexpression of miR-200a, miR-200b and miR-15aalso produced decreased BMI1 and Ub-H2A protein expression in the CD44+ Cancer Stem Cellpopulation of MDAMB-231cells. Also,elevating the levels of BMI1 regulated miRNAspromoted Mesenchymal to Epithelial transition by regulating the expression of N-Cadherin, Vimentin, β-Catenin, Zeb, Snail thereby resulting in decreased invasion, migration and proliferation. Here, we also report that miR-200a, miR-200b, miR-203 accretes the sensitivity of MDAMB-231 cells to the histone deacetylase inhibitor (HDACi SAHA and miR-15a sensitized breast cancer cells to the chemotherapeutic drug cisplatin leading to apoptosis. These findings suggest that modulatingspecific miRNAs may serve as a therapeutic approach for the treatment of breast cancer.

  8. Connecting rules from paired miRNA and mRNA expression data sets of HCV patients to detect both inverse and positive regulatory relationships

    OpenAIRE

    Song, Renhua; Liu, Qian; Liu, Tao; Li, Jinyan

    2015-01-01

    Background Intensive research based on the inverse expression relationship has been undertaken to discover the miRNA-mRNA regulatory modules involved in the infection of Hepatitis C virus (HCV), the leading cause of chronic liver diseases. However, biological studies in other fields have found that inverse expression relationship is not the only regulatory relationship between miRNAs and their targets, and some miRNAs can positively regulate a mRNA by binding at the 5' UTR of the mRNA. Result...