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Sample records for vl mi 12-14

  1. 19 CFR 12.14 - Detention.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Detention. 12.14 Section 12.14 Customs Duties U.S... OF MERCHANDISE Plants and Plant Products § 12.14 Detention. (a) Port directors shall refuse release... prohibited shipment immediately, the port director shall report the facts to the U.S. Department...

  2. Congenital Cataract in Gpr161vl/vl Mice Is Modified by Proximal Chromosome 15

    Science.gov (United States)

    Li, Bo I.; Ababon, Myka R.; Matteson, Paul G.; Lin, Yong; Nanda, Vikas; Millonig, James H.

    2017-01-01

    The morphology and severity of human congenital cataract varies even among individuals with the same mutation, suggesting that genetic background modifies phenotypic penetrance. The spontaneous mouse mutant, vacuolated lens (vl), arose on the C3H/HeSnJ background. The mutation disrupts secondary lens fiber development by E16.5, leading to full penetrance of congenital cataract. The vl locus was mapped to a frameshift deletion in the orphan G protein-coupled receptor, Gpr161, which is expressed in differentiating lens fiber cells. When Gpr161vl/vl C3H mice are crossed to MOLF/EiJ mice an unexpected rescue of cataract is observed, suggesting that MOLF modifiers affect cataract penetrance. Subsequent QTL analysis mapped three modifiers (Modvl3-5: Modifier of vl) and in this study we characterized Modvl4 (Chr15; LOD = 4.4). A Modvl4MOLF congenic was generated and is sufficient to rescue congenital cataract and the lens fiber defect at E16.5. Additional phenotypic analysis on three subcongenic lines narrowed down the interval from 55 to 15Mb. In total only 18 protein-coding genes and 2 micro-RNAs are in this region. Fifteen of the 20 genes show detectable expression in the E16.5 eye. Subsequent expression studies in Gpr161vl/vl and subcongenic E16.5 eyes, bioinformatics analysis of C3H/MOLF polymorphisms, and the biological relevancy of the genes in the interval identified three genes (Cdh6, Ank and Trio) that likely contribute to the rescue of the lens phenotype. These studies demonstrate that modification of the Gpr161vl/vl cataract phenotype is likely due to genetic variants in at least one of three closely linked candidate genes on proximal Chr15. PMID:28135291

  3. Improved prediction of antibody VL-VH orientation.

    Science.gov (United States)

    Marze, Nicholas A; Lyskov, Sergey; Gray, Jeffrey J

    2016-10-01

    Antibodies are important immune molecules with high commercial value and therapeutic interest because of their ability to bind diverse antigens. Computational prediction of antibody structure can quickly reveal valuable information about the nature of these antigen-binding interactions, but only if the models are of sufficient quality. To achieve high model quality during complementarity-determining region (CDR) structural prediction, one must account for the VL-VH orientation. We developed a novel four-metric VL-VH orientation coordinate frame. Additionally, we extended the CDR grafting protocol in RosettaAntibody with a new method that diversifies VL-VH orientation by using 10 VL-VH orientation templates rather than a single one. We tested the multiple-template grafting protocol on two datasets of known antibody crystal structures. During the template-grafting phase, the new protocol improved the fraction of accurate VL-VH orientation predictions from only 26% (12/46) to 72% (33/46) of targets. After the full RosettaAntibody protocol, including CDR H3 remodeling and VL-VH re-orientation, the new protocol produced more candidate structures with accurate VL-VH orientation than the standard protocol in 43/46 targets (93%). The improved ability to predict VL-VH orientation will bolster predictions of other parts of the paratope, including the conformation of CDR H3, a grand challenge of antibody homology modeling.

  4. Admission Control of VL in AFDX Under HRT Constraints

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qiang; QU Zhenliang; LIN Hengqing

    2011-01-01

    Avionics full duplex switched ethernet (AFDX) is a switched interconnection technology developed to provide reliable data exchange with strong data transmission time guarantees in internal communication of the spacecraft or aircraft. Virtual link (VL) is an important concept of AFDX to meet quality of service (QoS) requirements in terms of end-to-end message deadlines. A VL admission control algorithm in AFDX network under hard real-time (HRT) constraints is studied. Based on the scheduling principle of AFDX protocol, a packet scheduling scheme under HRT constraints is proposed, and after that an efficient VL admission control algorithm is presented. Analytical proof that the algorithm can effectively determine whether VL should be admitted is given. Finally simulative examples are presented to promote the conclusion.

  5. ABangle: characterising the VH-VL orientation in antibodies.

    Science.gov (United States)

    Dunbar, J; Fuchs, A; Shi, J; Deane, C M

    2013-10-01

    The binding site of an antibody is formed between the two variable domains, VH and VL, of its antigen binding fragment (Fab). Understanding how VH and VL orientate with respect to one another is important both for studying the mechanisms of antigen specificity and affinity and improving antibody modelling, docking and engineering. Different VH-VL orientations are commonly described using relative measures such as root-mean-square deviation. Recently, the orientation has also been characterised using the absolute measure of a VH-VL packing angle. However, a single angle cannot fully describe all modes of orientation. Here, we present a method which fully characterises VH-VL orientation in a consistent and absolute sense using five angles (HL, HC1, LC1, HC2 and LC2) and a distance (dc). Additionally, we provide a computational tool, ABangle, to allow the VH-VL orientation for any antibody to be automatically calculated and compared with all other known structures. We compare previous studies and show how the modes of orientation being identified relate to movements of different angles. Thus, we are able to explain why different studies identify different structural clusters and different residues as important. Given this result, we then identify those positions and their residue identities which influence each of the angular measures of orientation. Finally, by analysing VH-VL orientation in bound and unbound forms, we find that antibodies specific for protein antigens are significantly more flexible in their unbound form than antibodies specific for hapten antigens. ABangle is freely available at http://opig.stats.ox.ac.uk/webapps/abangle.

  6. 44 CFR 12.14 - Annual comprehensive review.

    Science.gov (United States)

    2010-10-01

    ... formation recommendations in: program planning, decision making, more effective achievement of program... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Annual comprehensive review. 12.14 Section 12.14 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT...

  7. THE DYNAMICS AND TRACTION ENERGY METRICS LOCOMOTIVE VL40

    Directory of Open Access Journals (Sweden)

    S. V. Pylypenko

    2008-03-01

    Full Text Available In the article the results of dynamic running and traction-energy tests of the electric locomotive VL40U are presented. In accordance with the test results a conclusion about the suitability of electric locomotive of such a type for operation with trains containing up to 15 passenger coaches inclusive is made.

  8. Analysis and prediction of VH/VL packing in antibodies.

    Science.gov (United States)

    Abhinandan, K R; Martin, Andrew C R

    2010-09-01

    The packing of V(H) and V(L) domains in antibodies can vary, influencing the topography of the antigen-combining site. However, until recently, this has largely been ignored in modelling antibody structure. We present an analysis of the degree of variability observed in known structures together with a machine-learning approach to predict the packing angle. A neural network was trained on sets of interface residues and a genetic algorithm designed to perform 'feature selection' to define which sets of interface residues could be used most successfully to perform the prediction. While this training procedure was very computationally intensive, prediction is performed in a matter of seconds. Thus, not only do we provide a rapid method for predicting the packing angle, but also we define a set of residues that may be important in antibody humanization in order to obtain the correct binding site topography.

  9. Prediction of VH-VL domain orientation for antibody variable domain modeling.

    Science.gov (United States)

    Bujotzek, Alexander; Dunbar, James; Lipsmeier, Florian; Schäfer, Wolfgang; Antes, Iris; Deane, Charlotte M; Georges, Guy

    2015-04-01

    The antigen-binding site of antibodies forms at the interface of their two variable domains, VH and VL, making VH-VL domain orientation a factor that codetermines antibody specificity and affinity. Preserving VH-VL domain orientation in the process of antibody engineering is important in order to retain the original antibody properties, and predicting the correct VH-VL orientation has also been recognized as an important factor in antibody homology modeling. In this article, we present a fast sequence-based predictor that predicts VH-VL domain orientation with Q(2) values ranging from 0.54 to 0.73 on the evaluation set. We describe VH-VL orientation in terms of the six absolute ABangle parameters that have recently been proposed as a means to separate the different degrees of freedom of VH-VL domain orientation. In order to assess the impact of adjusting VH-VL orientation according to our predictions, we use the set of antibody structures of the recently published Antibody Modeling Assessment (AMA) II study. In comparison to the original AMAII homology models, we find an improvement in the accuracy of VH-VL orientation modeling, which also translates into an improvement in the average root-mean-square deviation with regard to the crystal structures.

  10. Forecasting the 12-14 March 1993 superstorm

    Energy Technology Data Exchange (ETDEWEB)

    Uccellini, L.W.; Kocin, P.J.; Schneider, R.S.; Stokols, P.M.; Dorr, R.A. [National Weather Service, Camp Springs, MD (United States)]|[National Weather Service, Bohemia, NY (United States)

    1995-02-01

    This paper describes the decision-making process used by the forecasters in the National Meteorological Center`s (NMC`s) Meterolological Operations Division and in Weather Forecast Offices of the National Weather Service to provide the successful forecasts of the superstorm of 12-14 March 1993. This review illustrates (1) the difficult decisions forecasters faced when using sometimes conflicting model guidance, (2) the forecasters` success in recognizing the mesoscale aspects of the storm as it began to develop and move along the Gulf and East Coasts of the United States, and (3) their ability to produce one of the most successful heavy snow and blizzard forecasts ever for a major winter storm that affected the eastern third of the United States. The successful aspects of the forecasts include the following. (1) Cyclogenesis was predicted up to 5 days prior to its onset. (2) The unusual intensity of the storm was predicted three days in advance, allowing forecasters, government officials, and the media ample time to prepare the public, marine, and aviation interests to take precautions for the protection of life and property. (3) The excessive amounts and areal distribution of snowfall were prediceted two days in advance of its onset. (4) An extensive number of blizzard watches and warnings were issued throughout the eastern United States with unprecedented lead times. (5) The coordination of forecasts within the National Weather Service and between the National Weather Service, private forecasters, and media meteorologists was perhaps the most extensive in recent history.

  11. Data of evolutionary structure change: 1VL8A-2UVDD [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1VL8A-2UVDD 1VL8 2UVD A D FDLRGRVALVTGGSRGLGFGIAQGLAEAGCSVVVASRN-...ne>ALA CA 330 SER CA 279 2UVD D 2UVDD VNYAGNEQKAN EEE H...0431976318 2.622323989868164 1 2UV...D D 2UVDD EIKKL-GSDA

  12. Data of evolutionary structure change: 1VL8B-2UVDB [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1VL8B-2UVDB 1VL8 2UVD B B VFDLRGRVALVTGGSRGLGFGIAQGLAEAGCSVVVASRN...>GLU CA 241 ALA CA 324 SER CA 282 2UV...D B 2UVDB VNYAGNEQKAN 2.647510051727295 1 2UV...D B 2UVDB EIKKL-GSDAI

  13. Antibody VH and VL recombination using phage and ribosome display technologies reveals distinct structural routes to affinity improvements with VH-VL interface residues providing important structural diversity.

    Science.gov (United States)

    Groves, Maria A T; Amanuel, Lily; Campbell, Jamie I; Rees, D Gareth; Sridharan, Sudharsan; Finch, Donna K; Lowe, David C; Vaughan, Tristan J

    2014-01-01

    In vitro selection technologies are an important means of affinity maturing antibodies to generate the optimal therapeutic profile for a particular disease target. Here, we describe the isolation of a parent antibody, KENB061 using phage display and solution phase selections with soluble biotinylated human IL-1R1. KENB061 was affinity matured using phage display and targeted mutagenesis of VH and VL CDR3 using NNS randomization. Affinity matured VHCDR3 and VLCDR3 library blocks were recombined and selected using phage and ribosome display protocol. A direct comparison of the phage and ribosome display antibodies generated was made to determine their functional characteristics.In our analyses, we observed distinct differences in the pattern of beneficial mutations in antibodies derived from phage and ribosome display selections, and discovered the lead antibody Jedi067 had a ~3700-fold improvement in KD over the parent KENB061. We constructed a homology model of the Fv region of Jedi067 to map the specific positions where mutations occurred in the CDR3 loops. For VL CDR3, positions 94 to 97 carry greater diversity in the ribosome display variants compared with the phage display. The positions 95a, 95b and 96 of VLCDR3 form part of the interface with VH in this model. The model shows that positions 96, 98, 100e, 100f, 100 g, 100h, 100i and 101 of the VHCDR3 include residues at the VH and VL interface. Importantly, Leu96 and Tyr98 are conserved at the interface positions in both phage and ribosome display indicating their importance in maintaining the VH-VL interface. For antibodies derived from ribosome display, there is significant diversity at residues 100a to 100f of the VH CDR3 compared with phage display. A unique deletion of isoleucine at position 102 of the lead candidate, Jedi067, also occurs in the VHCDR3.As anticipated, recombining the mutations via ribosome display led to a greater structural diversity, particularly in the heavy chain CDR3, which in turn

  14. Vlček Seminars” About the System Approaches at CTU in Prague

    Directory of Open Access Journals (Sweden)

    Veronika Vlčková

    2016-12-01

    Full Text Available In the academic year 2015-2016 at CTU in Prague, Faculty of Transportation Sciences carried out in a more traditional "Vlček seminars", which take place intermittently since 1999. The purpose of the seminars is to look for new, innovative impulses, systems approach to problem solving, organize knowledges and insights on systems engineering tools and objectives and possible areas of their application. The methodological basis is constructive theory of systems, presented by prof. Jaroslav Vlček.

  15. Abstracts of the 4th International MELODI Workshop 12 -14 September 2012, Helsinki, Finland

    Energy Technology Data Exchange (ETDEWEB)

    Sulonen, N. (ed.)

    2012-08-15

    The Fourth International MELODI Workshop is organized by STUK - Radiation and Nuclear Safety Authority in Helsinki, Finland, on 12-14 September 2012. The workshop offers an update of recent low-dose research issues, and an opportunity to participate in the MELODI Low Dose Research Platform, a major step in the long term goals that the European Low-Dose Risk research intends to achieve. The main goal of MELODI is to develop and maintain a Strategic Research Agenda (SRA) in the field of low-dose radiation research, and to actively promote its implementation. DoReMi Network of Excellence funded by the European Commission is supporting the setting up of the Platform and addressing some of its research needs. In line with one of the main SRA goals, a major aim of the workshop was to set all topics in an interdisciplinary context. The Workshop abstracts cover plenary lectures as well as poster presentations related to topical discussions in breakout sessions. The theme of the first day 'Low dose risk research - state of the art' provides an introduction to the MELODI activities and the SRA and an update on recent epidemiological studies and dosimetric aspects of low dose studies. Potential implications of cardiovascular disease risk for radiation protection are also addressed. Discussion on the state-of-the art of MELODI SRA took place in three break-out groups addressing epidemiological approaches, cancer mechanisms and models and infrastructures and knowledge management. The second day 'Emerging scientific challenges' features the development of science and novel technologies, covering topics such as epigenetics, systems biology, stem cells as well as biomarkers that could be potentially used in molecular epidemiological studies. The associated breakout sessions explore the roadmap for future research, covering themes on biomarkers and biobanks, non-cancer effects, as well as low dose dosimetry and dose concept. The third day 'Integrating the

  16. Responses to Deficiencies and Suggestions, AIHA Site Assessment July 12-14, 2016

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, Jack T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Harding, Ruth N. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-08-11

    These are the responses to the deficiencies and suggestions found during the American Industrial Hygiene Association external site assessment carried out July 12-14, 2016 in the Analytical Services and Instrumentation Division Analytical Laboratory.

  17. Isolated T Wave Inversion in Lead aVL: An ECG Survey and a Case Report

    Directory of Open Access Journals (Sweden)

    Getaw Worku Hassen

    2015-01-01

    Full Text Available Background. Computerized electrocardiogram (ECG analysis has been of tremendous help for noncardiologists, but can we rely on it? The importance of ST depression and T wave inversions in lead aVL has not been emphasized and not well recognized across all specialties. Objective. This study’s goal was to analyze if there is a discrepancy of interpretation by physicians from different specialties and a computer-generated ECG reading in regard to a TWI in lead aVL. Methods. In this multidisciplinary prospective study, a single ECG with isolated TWI in lead aVL that was interpreted by the computer as normal was given to all participants to interpret in writing. The readings by all physicians were compared by level of education and by specialty to one another and to the computer interpretation. Results. A total of 191 physicians participated in the study. Of the 191 physicians 48 (25.1% identified and 143 (74.9% did not identify the isolated TWI in lead aVL. Conclusion. Our study demonstrated that 74.9% did not recognize the abnormality. New and subtle ECG findings should be emphasized in their training so as not to miss significant findings that could cause morbidity and mortality.

  18. Estimation of under-reported visceral Leishmaniasis (Vl cases in Bihar: a Bayesian approach

    Directory of Open Access Journals (Sweden)

    A Ranjan

    2013-12-01

    Full Text Available Background: Visceral leishmaniasis (VL is a major health problem in the state of Bihar and adjoining areas in India. In absence of any active surveillance mechanism for the disease, there seems to be gross under-reporting of VL cases. Objective: The objective of this study was to estimate extent of under-reporting of VL cases in Bihar using pooled analysis of published papers. Method: We calculated the pooled common ratio (RRMH based on three studies and combined it with a prior distribution of ratio using inverse-variance weighting method. Bayesian method was used to estimate the posterior distribution of the “under-reporting factor” (ratio of unreported to reported cases. Results: The posterior distribution of ratio of unreported to reported cases yielded a mean of 3.558, with 95% posterior limits of 2.81 and 4.50. Conclusion: Bayesian approach gives evidence to the fact that the total number of VL cases in the state may be nearly more than three times that of currently reported figures. 

  19. VL51ES (Generation 6 Li-Ion Cell for Satellites

    Directory of Open Access Journals (Sweden)

    Defer M.

    2017-01-01

    Full Text Available This paper presents the design of Saft’s VL51ES (Generation 6 Li-Ion cell, the main challenges in the course of the development, the main BOL characteristics and performances achieved during the development program. Finally, it also describes how this cell fits in Saft’s battery range and the benefits of it.

  20. File list: ALL.Emb.05.AllAg.Mitotic_cycle_12-14 [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Oth.Emb.10.AllAg.Mitotic_cycle_12-14 [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  3. File list: InP.Emb.20.AllAg.Mitotic_cycle_12-14 [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  20. File list: ALL.Emb.10.AllAg.Mitotic_cycle_12-14 [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Unc.Emb.50.AllAg.Mitotic_cycle_12-14 [Chip-atlas[Archive

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  3. File list: NoD.Emb.05.AllAg.Mitotic_cycle_12-14 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Emb.05.AllAg.Mitotic_cycle_12-14 dm3 No description Embryo Mitotic cycle 12-14 ...http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/NoD.Emb.05.AllAg.Mitotic_cycle_12-14.bed ...

  4. Tau Leptonic Decay τ→lVlVτ in Littlest Higgs Model*

    Institute of Scientific and Technical Information of China (English)

    YUEChong-Xing; WANGWei

    2004-01-01

    We consider the T leptonic decay τ→lVlVτ in the framework of the littlest Higgs (LH) model and calculate the corrections of new particles to this decay. We find that the contributions of the charged scalars can be safely ignored and the LH model is in perfect agreement with the universality of the couplings of the SU gauge bosons to the leptonic charged currents. The corrections of the LH model to the T leptonic decay τ→lVlVτ are not sensitive to the parameter c, but depend strongly on the parameters f and x. The precision measured data about the T leptonic decay demand that the parameter f approximately equal 3.5 TeV and x > 0.1, while agree with the general expectation based on other phenomenological explorations.

  5. Effectiveness Study of Paromomycin IM Injection (PMIM for the Treatment of Visceral Leishmaniasis (VL in Bangladesh.

    Directory of Open Access Journals (Sweden)

    Kazi M Jamil

    Full Text Available This study was conducted in Bangladeshi patients in an outpatient setting to support registration of Paromomycin Intramuscular Injection (PMIM as a low-cost treatment option in Bangladesh.This Phase IIIb, open-label, multi-center, single-arm trial assessed the efficacy and safety of PMIM administered at 11 mg/kg (paromomycin base intramuscularly once daily for 21 consecutive days to children and adults with VL in a rural outpatient setting in Bangladesh. Patients ≥5 and ≤55 years were eligible if they had signs and symptoms of VL (intermittent fever, weight loss/decreased appetite, and enlarged spleen, positive rK39 test, and were living in VL-endemic areas. Compliance was the percentage of enrolled patients who received 21 daily injections over no more than 22 days. Efficacy was evaluated by initial clinical response, defined as resolution of fever and reduction of splenomegaly at end of treatment, and final clinical response, defined as the absence of new clinical signs and symptoms of VL 6 months after end of treatment. Safety was assessed by evaluation of adverse events.A total of 120 subjects (49% pediatric were enrolled. Treatment compliance was 98.3%. Initial clinical response in the Intent-to-Treat population was 98.3%, and final clinical response 6 months after end of treatment was 94.2%. Of the 119 subjects who received ≥1 dose of PMIM, 28.6% reported at least one adverse event. Injection site pain was the most commonly reported adverse event. Reversible renal impairment and/or hearing loss were reported in 2 subjects.PMIM was an effective and safe treatment for VL in Bangladesh. The short treatment duration and lower cost of PMIM compared with other treatment options may make this drug a preferred treatment to be investigated as part of a combination therapy regimen. This study supports the registration of PMIM for use in government health facilities in Bangladesh.ClinicalTrials.gov identifier: NCT01328457.

  6. The Conception of Risk in Minority Young Adolescents Aged 12-14 Years

    Science.gov (United States)

    Leblanc, Raymond; Drolet, Marie; Ducharme, Daphne; Arcand, Isabelle; Head, Robert; Alphonse, Jean R.

    2015-01-01

    This study examines the conceptualization of risk behavior held by 26 Franco-Ontarian young adolescents (12-14 years of age) who participated in Lions Quest, a program specially designed to promote physical and mental health and to prevent drug and alcohol use. More specifically, it seeks to better understand the participating adolescents'…

  7. 2007 Intertextile Pavilion will open on 12-14 July 2007

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    2007 Intertextile Pavilion at the 7th China (Shenzhen)International Brand Clothing & Accessories Fair at Shenzhen Convention & Exhibition Center,Shenzhen,China on 12-14 July 2007. Technology upgrades boost output for apparel makers in Shenzhen-creating great opportunities for textile manufacturers looking for buyers

  8. Die letterlike vertolking van metaforiese taal in Josua 10:12-14

    Directory of Open Access Journals (Sweden)

    A.P.B. Breytenbach

    2002-11-01

    Full Text Available The literal understanding of metaphoric language in Joshua 10:12-14In this article the well-known passage in Joshua 10:12-14 is critically investigated within the context of the pericope of Joshua 10. A literary critical investigation shows, inter alia, that the oldest version of the pericope probably was a heroic saga of Joshua’s campaign, with the miraculous intervention of YHWH having been “written into” the narrative at a later stage. During the latter process a poetic fragment, the original of which is lost to us, was interpreted literally, thus creating a miracle account. This miracle account serves the main focus of the pericope: YHWH alone makes possible the impossible for his people.

  9. Requirements Engineering and Analysis Workshop Proceedings Held in Pittsburgh, Pennsylvania on 12-14 March 1991

    Science.gov (United States)

    1991-12-01

    urally. 6.5 Summary of Current or Potential Approaches Many approaches to context analysis were discussed by the group, including: * Causal Trees * SWOT ...This could come in the form of a purchase at a shopping mall , buying lunch, or delivering a pizza. The estimated economic loss due to congestion has...Requirements Engineering and Analysis Work- shop in Pittsburgh, Pennsylvania, on March 12-14, 1991. The intention of the workshop was to focus (please turn

  10. DOE-NSF-NIH Workshop on Opportunities in THz Science, February 12-14, 2004

    Energy Technology Data Exchange (ETDEWEB)

    Sherwin, M.A.; Bucksbaum, P.H.; Schmuttenmaer, C. A.; Allen, J.; Biedron, S.; Carr, L.; Chamberlain, M.; Crowe, T.; DeLucia, F.; Hu, Q.; Jones, B.; Noordham, B.; Norris, T.; Orenstein, J.; Unterrainer, K.; Van der Meer, L.; Wilke, I.; Williams, G.; Zhang, X.-C.; Cheville, A.; Markelz, A.; Parks, B.; Plancken, P.; Shan, J.; Austin, B.; Basov, D.; Citrin, D.; Grundfest, W.; Heinz, T.; Kono, J.; Mittleman, D.; Siegel, P.; Taylor, T.; Jones, B.; Markelz, A.; Martin, M.; Nelson, K.; Smith, T.; Williams, G.; Allen, M.; Averitt, R.; Brunel, L.; Heilweil, T.; Heyman, J.; Jepsen, P.; Kaind, R.; Leemans, W.; Mihaly, L.; Rangan, C.; Tom, H.; Wallace, V.; Zimdars, D.

    2004-02-14

    This is the report of the Workshop on Opportunities in THz Science, held on February 12-14, 2004 in Arlington, VA. This workshop brought together researchers who use or produce THz radiation for physics, chemistry, biology, medicine, and materials science to discuss new research opportunities and common resource needs. The charge from the sponsors of the workshop was to focus on basic science questions within these disciplines that have and can be answered using THz radiation.

  11. Methodological Approaches to Pedagogical Control in Physical Education of Girls Aged 12-14

    Directory of Open Access Journals (Sweden)

    О. Іващенко

    2016-12-01

    Full Text Available The objective is to determine the methodological approaches to pedagogical control in physical education of girls aged 12-14. Materials and methods. The participants of the study were girls aged 12 (n = 31, aged 13 (n = 26, and aged 14 (n = 28. To achieve the tasks set, the study relied on the following methods: analysis of scientific literature, pedagogical testing and methods of mathematical statistics. To evaluate the functional and motor preparedness of the girls aged 12-14, we recorded the results of Stange and Genchi, Serkin and motor tests. Results. The standardized coefficients of the canonical discriminant function allow to determine the relation of the variables contribution to the function result. The first function explains the results variation by 86.8% (p < 0.001, the second — by 13.2% (p < 0.001. The above proves that pedagogical control is possible in physical education based on the classification of the age differences in girls aged 12-14, by the results of their functional, strength and coordination preparedness tested. The structural coefficients of the first canonical discriminant function indicate that a significant difference between the girls aged 12 and the girls aged 13-14 occurs in the level of development of their motor coordination, speed strength and the results of Stange’s test. The structural coefficients of the second canonical discriminant function indicate that a significant difference between the girls aged 13 and 14 occurs in the level of development of the static and relative strength of their arm muscles. Conclusions. The final pedagogical control of motor and functional preparedness of the girls aged 12-14 can rest on the first discriminant function with emphasis on the most informative variables.

  12. A Study on L-Asparaginase of Nocardia levis MK-VL_113

    Directory of Open Access Journals (Sweden)

    Alapati Kavitha

    2012-01-01

    Full Text Available An enzyme-based drug, L-asparaginase, was produced by Nocardia levis MK-VL_113 isolated from laterite soils of Guntur region. Cultural parameters affecting the production of L-asparaginase by the strain were optimized. Maximal yields of L-asparaginase were recorded from 3-day-old culture grown in modified asparagine-glycerol salts broth with initial pH 7.0 at temperature 30∘C. Glycerol (2% and yeast extract (1.5% served as good carbon and nitrogen sources for L-asparaginase production, respectively. Cell-disrupting agents like EDTA slightly enhanced the productivity of L-asparaginase. Ours is the first paper on the production of L-asparaginase by N. levis.

  13. Construction and characterization of VL-VH tail-parallel genetically engineered antibodies against staphylococcal enterotoxins.

    Science.gov (United States)

    He, Xianzhi; Zhang, Lei; Liu, Pengchong; Liu, Li; Deng, Hui; Huang, Jinhai

    2015-03-01

    Staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus have increasingly given rise to human health and food safety. Genetically engineered small molecular antibody is a useful tool in immuno-detection and treatment for clinical illness caused by SEs. In this study, we constructed the V(L)-V(H) tail-parallel genetically engineered antibody against SEs by using the repertoire of rearranged germ-line immunoglobulin variable region genes. Total RNA were extracted from six hybridoma cell lines that stably express anti-SEs antibodies. The variable region genes of light chain (V(L)) and heavy chain (V(H)) were cloned by reverse transcription PCR, and their classical murine antibody structure and functional V(D)J gene rearrangement were analyzed. To construct the eukaryotic V(H)-V(L) tail-parallel co-expression vectors based on the "5'-V(H)-ivs-IRES-V(L)-3'" mode, the ivs-IRES fragment and V(L) genes were spliced by two-step overlap extension PCR, and then, the recombined gene fragment and V(H) genes were inserted into the pcDNA3.1(+) expression vector sequentially. And then the constructed eukaryotic expression clones termed as p2C2HILO and p5C12HILO were transfected into baby hamster kidney 21 cell line, respectively. Two clonal cell lines stably expressing V(L)-V(H) tail-parallel antibodies against SEs were obtained, and the antibodies that expressed intracytoplasma were evaluated by enzyme-linked immunosorbent assay, immunofluorescence assay, and flow cytometry. SEs can stimulate the expression of some chemokines and chemokine receptors in porcine IPEC-J2 cells; mRNA transcription level of four chemokines and chemokine receptors can be blocked by the recombinant SE antibody prepared in this study. Our results showed that it is possible to get functional V(L)-V(H) tail-parallel genetically engineered antibodies in same vector using eukaryotic expression system.

  14. Investigation of physical performance parameters of children aged 12-14 years

    Directory of Open Access Journals (Sweden)

    Murat Özşaker

    2011-08-01

    Full Text Available This study aims to investigate the physical performance parameters and to determine the profiles of children aged 12-14 years and attending the secondary stage of public schools in Izmir province. The study included a total of 650 voluntary students (323 girls, and 327 boys attending the 6th, 7th and 8th classes. Physical parameters of students were evaluated with tests selected from Fitnessgram, American Alliance for Health, Physical Education, Recreation and Dance (AAHPERD and Eurofit Test Battery (Muscle Strength: hand grip strength, standing long jump; Muscle Resistance: pull-up; Flexibility: sit and reach test; Cardiovascular Endurance:1 mile running test (1609 m endurance running; Speed: 30 m sprint.Statistical analysis of data was made by Two-Way Variance Analysis in SPSS 15.0 packet software, and Further Bonferroni analysis was used for age.As a result of the study, performance parameters of children aged 12-14 years were determined to be lower than those reported by similar studies made on the same age group. Among the reasons, there are lack of physical activity, sedentary lifestyle, inadequate physical education and sport class and the reflections of education system.

  15. Investigation of physical performance parameters of children aged 12-14 years

    Directory of Open Access Journals (Sweden)

    Murat Özşaker

    2011-07-01

    Full Text Available This study aims to investigate the physical performance parameters and to determine the profiles of children aged 12-14 years and attending the secondary stage of public schools in Izmir province. The study included a total of 650 voluntary students (323 girls, and 327 boys attending the 6th, 7th and 8th classes. Physical parameters of students were evaluated with tests selected from Fitnessgram, American Alliance for Health, Physical Education, Recreation and Dance (AAHPERD and Eurofit Test Battery (Muscle Strength: hand grip strength, standing long jump; Muscle Resistance: pull-up; Flexibility: sit and reach test; Cardiovascular Endurance:1 mile running test (1609 m endurance running; Speed: 30 m sprint.Statistical analysis of data was made by Two-Way Variance Analysis in SPSS 15.0 packet software, and Further Bonferroni analysis was used for age. As a result of the study, performance parameters of children aged 12-14 years were determined to be lower than those reported by similar studies made on the same age group. Among the reasons, there are lack of physical activity, sedentary lifestyle, inadequate physical education and sport class and the reflections of education system.

  16. Oxidation of [1,12-14C]dodecanedioic acid by rat pancreatic islets.

    Science.gov (United States)

    Malaisse, W J; Greco, A V; Mingrone, G

    2000-10-01

    Several aliphatic dioic acids were recently reported to stimulate insulin release in isolated rat pancreatic islets incubated at close-to-physiological D-glucose concentrations. In order to gain insight into the mode of action of these acids in pancreatic islet B-cells, the oxidation of [1,12-14C]dodecanedioic acid (5.0 mM) was now measured in rat islets. Expressed as pmol of [1, 12-14C]dodecanedioic acid equivalent, the production of 14CO2 was close to 1.0 pmol/islet per 120 min, representing about 8% of that attributable to the oxidation of D-[U-14C]-glucose (8.3 mM). The dioic acid and the hexose failed to exert any significant reciprocal effect upon their respective oxidation rate. These findings support the view that the insulinotropic action of dodecanedioic acid, and presumably other aliphatic dioic acids, is causally linked to their capacity to act as nutrients in pancreatic islet cells.

  17. Prevalence of dental caries among 12-14 year old children in Qatar.

    Science.gov (United States)

    Al-Darwish, Mohammed; El Ansari, Walid; Bener, Abdulbari

    2014-07-01

    To ensure the oral health of a population, clinicians must deliver appropriate dental services, and local communities need to have access to dental care facilities. However, establishment of this infrastructure must be based on reliable information regarding disease prevalence and severity in the target population. The aims of this study were to measure the incidence of dental caries in school children aged 12-14 throughout Qatar, including the influence of socio-demographic factors. A cross-sectional study was conducted in Qatar from October 2011 to March 2012. A total of 2113 children aged 12-14 were randomly selected from 16 schools located in different geographic areas. Three calibrated examiners using World Health Organization (WHO) criteria to diagnose dental caries performed the clinical examinations. Data analyses were subsequently conducted. The mean decayed, missing, and filled teeth index values were respectively 4.62 (±3.2), 4.79 (±3.5), and 5.5 (±3.7), for 12, 13, and 14 year-old subjects. Caries prevalence was 85%. The mandibular incisors and canines were least affected by dental caries, while maxillary and mandibular molars exhibited the highest incidence of dental caries. Dental caries were affected by socio-demographic factors; significant differences were detected between female and male children, where more female children showed dental caries than male children. In addition, children residing in semi-urban areas showed more dental caries than in urban areas. Results indicated that dental caries prevalence among school children in Qatar has reached critical levels, and is influenced by socio-demographic factors. The mean decayed, missing, and filled teeth values obtained in this study were the second highest detected in the Eastern Mediterranean region.

  18. Hypocretin-2 saporin lesions of the ventrolateral periaquaductal gray (vlPAG increase REM sleep in hypocretin knockout mice.

    Directory of Open Access Journals (Sweden)

    Satvinder Kaur

    Full Text Available Ten years ago the sleep disorder narcolepsy was linked to the neuropeptide hypocretin (HCRT, also known as orexin. This disorder is characterized by excessive day time sleepiness, inappropriate triggering of rapid-eye movement (REM sleep and cataplexy, which is a sudden loss of muscle tone during waking. It is still not known how HCRT regulates REM sleep or muscle tone since HCRT neurons are localized only in the lateral hypothalamus while REM sleep and muscle atonia are generated from the brainstem. To identify a potential neuronal circuit, the neurotoxin hypocretin-2-saporin (HCRT2-SAP was used to lesion neurons in the ventral lateral periaquaductal gray (vlPAG. The first experiment utilized hypocretin knock-out (HCRT-ko mice with the expectation that deletion of both HCRT and its target neurons would exacerbate narcoleptic symptoms. Indeed, HCRT-ko mice (n = 8 given the neurotoxin HCRT2-SAP (16.5 ng/23nl/sec each side in the vlPAG had levels of REM sleep and sleep fragmentation that were considerably higher compared to HCRT-ko given saline (+39%; n = 7 or wildtype mice (+177%; n = 9. However, cataplexy attacks did not increase, nor were levels of wake or non-REM sleep changed. Experiment 2 determined the effects in mice where HCRT was present but the downstream target neurons in the vlPAG were deleted by the neurotoxin. This experiment utilized an FVB-transgenic strain of mice where eGFP identifies GABA neurons. We verified this and also determined that eGFP neurons were immunopositive for the HCRT-2 receptor. vlPAG lesions in these mice increased REM sleep (+79% versus saline controls and it was significantly correlated (r = 0.89 with loss of eGFP neurons. These results identify the vlPAG as one site that loses its inhibitory control over REM sleep, but does not cause cataplexy, as a result of hypocretin deficiency.

  19. Reconstruction of large maxillary defect with the use of vastus lateralis (VL free flap. Case report

    Directory of Open Access Journals (Sweden)

    Nikolaos Papadogeorgakis, Vlasios Oktseloglou, Eleni Pappa, Petros Spyriounis

    2010-08-01

    Full Text Available Large defects of the maxilla, following ablative surgery, significantly affect functions such as chewing, swallowing, speech and also the aesthetics. Reconstruction of soft tissues and bone defects can be achieved, either with the use of an obturator, or with free flaps. In the literature there is no sufficient evidence on the primacy of the one or the other method. The choice depends on the judgment, the experience and the ability of the surgical team. In recent years, the use of anterolateral thigh (ALTfree flap for reconstruction of large defects of the maxillary region, has gained a lot of popularity. The vastuslateralis free flap (VL is a variation of ALT. VL’s advantages include long pedicle, easier harvesting, and fewer anatomical variations. We present a case of a 75 year old male with recurrent squamous cell carcinoma of the medial canthal region, invading the maxillary bone, the medial wall and the floor of the orbit. The patient underwent a total maxillectomy, orbital exenteration, and reconstruction with vastus lateralis free flap.

  20. miRSeqNovel

    DEFF Research Database (Denmark)

    Qian, Kui; Auvinen, Eeva; Greco, Dario

    2012-01-01

    We present miRSeqNovel, an R based workflow for miRNA sequencing data analysis. miRSeqNovel can process both colorspace (SOLiD) and basespace (Illumina/Solexa) data by different mapping algorithms. It finds differentially expressed miRNAs and gives conservative prediction of novel miRNA candidates...... with customized parameters. miRSeqNovel is freely available at http://sourceforge.net/projects/mirseq/files....

  1. Method of estimation of technical preparedness level of baseballs aged 12-14 years

    Directory of Open Access Journals (Sweden)

    Agapov D.V.

    2013-02-01

    Full Text Available The method of estimation of level of technical preparedness is developed for young baseballs. The scale of estimation of level of technical preparedness of sportsmen is formed on the method of sigmantion rejections. In an experiment took part 100 boys in age 12-14 years. The test of the program «Aquafina MLB Pitch was utillized, Hit & Run». The maximally attained indexes are certain on separate baseball skills. The level of development of technical preparedness is exposed after an experiment on the program: a test of «pitch» is 450 marks, a test of «hit» is 402 marks, a test of «run» is a 361 mark, indexes of general marks are 1043 marks. The comparative analysis of level of technical preparedness of baseballs of control and experimental groups is conducted. Authenticity of distinctions is proved between control and experimental groups on the followings criteria of technical preparedness: throw, blow at run.

  2. Purification and biological evaluation of the metabolites produced by Streptomyces sp. TK-VL_333.

    Science.gov (United States)

    Kavitha, Alapati; Prabhakar, Peddikotla; Vijayalakshmi, Muvva; Venkateswarlu, Yenamandra

    2010-06-01

    An Actinobacterium strain isolated from laterite soils of the Guntur region was identified as Streptomyces sp. TK-VL_333 by 16S rRNA analysis. Cultural, morphological and physiological characteristics of the strain were recorded. The secondary metabolites produced by the strain cultured on galactose-tyrosine broth were extracted and concentrated followed by defatting of the crude extract with cyclohexane to afford polar and non-polar residues. Purification of the two residues by column chromatography led to isolation of five polar and one non-polar fraction. Bioactivity- guided fractions were rechromatographed on a silica gel column to obtain four compounds, namely 1H-indole-3-carboxylic acid, 2,3-dihydroxy-5-(hydroxymethyl) benzaldehyde, 4-(4-hydroxyphenoxy) butan-2-one and acetic acid-2-hydroxy-6-(3-oxo-butyl)-phenyl ester from three active polar fractions and 8-methyl decanoic acid from one non-polar fraction. The structure of the compounds was elucidated on the basis of FT-IR, mass and NMR spectroscopy. The antimicrobial activity of the bioactive compounds produced by the strain was tested against the bacteria and fungi and expressed in terms of minimum inhibitory concentration. Antifungal activity of indole-3-carboxylic acid was further evaluated under in vitro and in vivo conditions. This is the first report of 2,3-dihydroxy-5-(hydroxymethyl) benzaldehyde, 4-(4-hydroxyphenoxy) butan-2-one, acetic acid-2-hydroxy-6-(3-oxo-butyl)-phenyl ester and 8-methyl decanoic acid from the genus Streptomyces.

  3. miRMaid

    DEFF Research Database (Denmark)

    Jacobsen, Anders; Krogh, Anders; Kauppinen, Sakari;

    2010-01-01

    here as miRMaid, with the goal of integrating miRNA data resources in a uniform web service interface that can be accessed and queried by researchers and, most importantly, by computers. miRMaid is built around data from miRBase and is designed to follow the official miRBase data releases. It exposes...... application. The software framework is freely available under the LGPL open source license for academic and commercial use. CONCLUSION: miRMaid is an intuitive and modular software platform designed to unify miRBase and independent miRNA data resources. It enables miRNA researchers to computationally address...... complex questions involving the multitude of miRNA data resources. Furthermore, miRMaid constitutes a basic framework for further programming in which microRNA-interested bioinformaticians can readily develop their own tools and data sources....

  4. Generation and antitumor effects of an engineered and energized fusion protein VL-LDP-AE composed of single-domain antibody and lidamycin

    Institute of Scientific and Technical Information of China (English)

    MIAO QingFang; SHANG BoYang; OUYANG ZhiGang; LIU XiaoYun; ZHEN YongSu

    2007-01-01

    Type Ⅳ collagenase plays a pivotal role in invasion, metastasis and angiogenesis of tumor. Single domain antibodies are attractive as tumor-targeting vehicle because of their much smaller size compared with antibody molecules produced by conventional methods. Lidamycin (LDM) is a potent enediyne-containing antitumor antibiotic. In this study an engineered and energized fusion protein VL-LDP-AE composed of lidamycin and VL domain of mAb 3G11 directed against type Ⅳ collagenase was prepared using a novel two-step method. First a VL-LDP fusion protein was constructed by DNA recombination. Secondly VL-LDP-AE was obtained by molecular reconstitution. In MTT assay,VL-LDP-AE showed potent cytotoxicity to HT-1080 cells and KB cells with IC50 values of 8.55×10-12 and 1.70×10-11 mol/L, respectively. VL-LDP-AE showed antiangiogenic activity in chick chrorioallantoic membrane (CAM) assay and tube formation assay. In in vivo experiments, VL-LDP-AE was proved to be more effective than free LDM against the growth of subcutaneously transplanted hepatoma 22 in mice.Drugs were given intravenously on day 3 and 10 after tumor transplantation. Compared in terms of maximal tolerated doses, VL-LDP-AE at 0.25 mg/kg suppressed the tumor growth by 89.5%, LDM at 0.05mg/kg by 69.9%, and mitomycin at 1 mg/kg by 35%. Having a molecular weight of 25.2 kDa, VL-LDP-AE was much smaller than other reported antibody-based drugs. The results suggested that VL-LDP-AE would be a promising candidate for tumor targeting therapy. And the 2-step approach could serve as a new technology platform for making a series of highly potent engineered antibody-based drugs for a variety of cancers.

  5. Generation and antitumor effects of an engineered and energized fusion protein VL-LDP-AE composed of single-domain antibody and lidamycin

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Type IV collagenase plays a pivotal role in invasion, metastasis and angiogenesis of tumor. Single domain antibodies are attractive as tumor-targeting vehicle because of their much smaller size com-pared with antibody molecules produced by conventional methods. Lidamycin (LDM) is a potent enediyne-containing antitumor antibiotic. In this study an engineered and energized fusion protein VL-LDP-AE composed of lidamycin and VL domain of mAb 3G11 directed against type IV collagenase was prepared using a novel two-step method. First a VL-LDP fusion protein was constructed by DNA recombination. Secondly VL-LDP-AE was obtained by molecular reconstitution. In MTT assay, VL-LDP-AE showed potent cytotoxicity to HT-1080 cells and KB cells with IC50 values of 8.55×10-12 and 1.70×10-11 mol/L, respectively. VL-LDP-AE showed antiangiogenic activity in chick chrorioallantoic membrane (CAM) assay and tube formation assay. In in vivo experiments, VL-LDP-AE was proved to be more effective than free LDM against the growth of subcutaneously transplanted hepatoma 22 in mice. Drugs were given intravenously on day 3 and 10 after tumor transplantation. Compared in terms of maximal tolerated doses, VL-LDP-AE at 0.25 mg/kg suppressed the tumor growth by 89.5%, LDM at 0.05 mg/kg by 69.9%, and mitomycin at 1 mg/kg by 35%. Having a molecular weight of 25.2 kDa, VL-LDP-AE was much smaller than other reported antibody-based drugs. The results suggested that VL-LDP-AE would be a promising candidate for tumor targeting therapy. And the 2-step approach could serve as a new technology platform for making a series of highly potent engineered antibody-based drugs for a variety of cancers.

  6. Head impact exposure in youth football: middle school ages 12-14 years.

    Science.gov (United States)

    Daniel, Ray W; Rowson, Steven; Duma, Stefan M

    2014-09-01

    The head impact exposure experienced by football players at the college and high school levels has been well documented; however, there are limited data regarding youth football despite its dramatically larger population. The objective of this study was to investigate head impact exposure in middle school football. Impacts were monitored using a commercially available accelerometer array installed inside the helmets of 17 players aged 12-14 years. A total of 4678 impacts were measured, with an average (±standard deviation) of 275 ± 190 impacts per player. The average of impact distributions for each player had a median impact of 22 ± 2 g and 954 ± 122 rad/s², and a 95th percentile impact of 54 ± 9 g and 2525 ± 450 rad/s². Similar to the head impact exposure experienced by high school and collegiate players, these data show that middle school football players experience a greater number of head impacts during games than practices. There were no significant differences between median and 95th percentile head acceleration magnitudes experienced during games and practices; however, a larger number of impacts greater than 80 g occurred during games than during practices. Impacts to the front and back of the helmet were most common. Overall, these data are similar to high school and college data that have been collected using similar methods. These data have applications toward youth football helmet design, the development of strategies designed to limit head impact exposure, and child-specific brain injury criteria.

  7. Rac1 modification by an electrophilic 15-deoxy Δ12,14-prostaglandin J2 analog

    Directory of Open Access Journals (Sweden)

    S.B. Wall

    2015-04-01

    Full Text Available Vascular endothelial cells (ECs are important for maintaining vascular homeostasis. Dysfunction of ECs contributes to cardiovascular diseases, including atherosclerosis, and can impair the healing process during vascular injury. An important mediator of EC response to stress is the GTPase Rac1. Rac1 responds to extracellular signals and is involved in cytoskeletal rearrangement, reactive oxygen species generation and cell cycle progression. Rac1 interacts with effector proteins to elicit EC spreading and formation of cell-to-cell junctions. Rac1 activity has recently been shown to be modulated by glutathiolation or S-nitrosation via an active site cysteine residue. However, it is not known whether other redox signaling compounds can modulate Rac1 activity. An important redox signaling mediator is the electrophilic lipid, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2. This compound is a downstream product of cyclooxygenase and forms covalent adducts with specific cysteine residues, and induces cellular signaling in a pleiotropic manner. In this study, we demonstrate that a biotin-tagged analog of 15d-PGJ2 (bt-15d-PGJ2 forms an adduct with Rac1 in vitro at the C157 residue, and an additional adduct was detected on the tryptic peptide associated with C178. Rac1 modification in addition to modulation of Rac1 activity by bt-15d-PGJ2 was observed in cultured ECs. In addition, decreased EC migration and cell spreading were observed in response to the electrophile. These results demonstrate for the first time that Rac1 is a target for 15d-PGJ2 in ECs, and suggest that Rac1 modification by electrophiles such as 15d-PGJ2 may alter redox signaling and EC function.

  8. A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties.

    Science.gov (United States)

    Tiller, Thomas; Schuster, Ingrid; Deppe, Dorothée; Siegers, Katja; Strohner, Ralf; Herrmann, Tanja; Berenguer, Marion; Poujol, Dominique; Stehle, Jennifer; Stark, Yvonne; Heßling, Martin; Daubert, Daniela; Felderer, Karin; Kaden, Stefan; Kölln, Johanna; Enzelberger, Markus; Urlinger, Stefanie

    2013-01-01

    This report describes the design, generation and testing of Ylanthia, a fully synthetic human Fab antibody library with 1.3E+11 clones. Ylanthia comprises 36 fixed immunoglobulin (Ig) variable heavy (VH)/variable light (VL) chain pairs, which cover a broad range of canonical complementarity-determining region (CDR) structures. The variable Ig heavy and Ig light (VH/VL) chain pairs were selected for biophysical characteristics favorable to manufacturing and development. The selection process included multiple parameters, e.g., assessment of protein expression yield, thermal stability and aggregation propensity in fragment antigen binding (Fab) and IgG1 formats, and relative Fab display rate on phage. The framework regions are fixed and the diversified CDRs were designed based on a systematic analysis of a large set of rearranged human antibody sequences. Care was taken to minimize the occurrence of potential posttranslational modification sites within the CDRs. Phage selection was performed against various antigens and unique antibodies with excellent biophysical properties were isolated. Our results confirm that quality can be built into an antibody library by prudent selection of unmodified, fully human VH/VL pairs as scaffolds.

  9. Pharmaco-miR

    DEFF Research Database (Denmark)

    Rukov, Jakob Lewin; Wilentzik, Roni; Jaffe, Ishai;

    2014-01-01

    curated from the literature, can be searched and downloaded via Pharmaco-miR and informs on trends and generalities published in the field. Overall, we present examples of how Pharmaco-miR provides possible explanations for previously published observations, including how the cisplatin and 5-fluorouracil...... links miRNA expression and drug function by combining data on miRNA targeting and protein-drug interactions. miRNA targeting information derive from both experimental data and computational predictions, and protein-drug interactions are annotated by the Pharmacogenomics Knowledge base (Pharm...... resistance induced by miR-148a may be caused by miR-148a targeting of the gene KIT. The information is available at www.Pharmaco-miR.org....

  10. E12-14-009: Ratio of the electric form factor in the mirror nuclei 3He and 3H

    CERN Document Server

    Myers, L S; Arrington, J R

    2014-01-01

    E12-14-009: We propose to extract the ratio of the electric form factor (G_E) of 3He and 3H from the measured ratio of the elastic-scattering cross sections at E_beam = 1.1 GeV. Measurements at low Q^2 ( < 0.1 GeV^2) will allow accurate extraction of G_E with minimal contributions from the magnetic form factor (G_M) and Coulomb corrections. From this data we will extract the difference between the charge radii for 3He and 3H. This short experiment, 1.5 days, will utilize the left Hall A high resolution spectrometer and the one-time availability of a 1 kCi tritium target at Jefferson Lab which has been approved for the E12-10-103, E12-11-112 and E12-14-011 experiments.

  11. Searching Physical Fitness Norms by Eurofit Tests of Male Students in The Age Group of 12-14

    Directory of Open Access Journals (Sweden)

    Bilgehan BAYDİL

    2006-12-01

    Full Text Available The aim of this study is to make adetermination about the case, by searching Eurofit tests and physicalfitness norms of boy students in the age group of 12-14 at Kastamonu Region, and to make a contribution to literature. The investigation was mode on the age group of 12-14 years old, volunteered 63 boy students who are studying at Gazipaa Primary Education School and Merkez Primary Education School that were chosen at random, in Kastamonu. Height and weight, measure of subcutan fat flamingo balance test, test of touching to discs, flexibility, long jump by pausing, strenght shuttle test, 10x5 m runnig test, vertical jumping test by pausing and 20 m shuttle run test, were applied to these students.

  12. VH and VL Domains of Polyspecific IgM and Monospecific IgG Antibodies Contribute Differentially to Antigen Recognition and Virus Neutralization Functions.

    Science.gov (United States)

    Pasman, Y; Kaushik, A K

    2016-07-01

    We analysed contributions of variable heavy (FdVH ) and variable light (FdVL ) domains in comparison to scFv (FdVH +FdVL ) of naturally occurring polyspecific bovine IgM with an exceptionally long CDR3H and an induced monospecific bovine herpes virus-1 (BoHV-1) neutralizing IgG1 antibody in the context of to antigen-binding site and antibody function. Various recombinant FdVH , FdVL and scFv were constructed and expressed in Pichia pastoris from the bovine IgM and IgG1 antibody encoding cDNA. The scFv1H12 showed polyspecific antigen binding similar to parent IgM antibody, though subtle differences, for example, higher thyroglobulin recognition. Such differences reflect influence of the constant region on the antigen-binding site configuration. Unlike, variable light domain FdVL 1H12, the variable heavy domain FdVH 1H12 alone recognized multiple antigens that differed from the recognition pattern of scFv1H12 (FdVH +FdVL ) and the parent IgM antibody. Nonetheless, role of FdVL 1H12 in providing structural support to FdVH in antigen recognition is noted, apart from its intrinsic antigen recognition ability. Surface plasmon resonance analysis revealed low to moderate affinity of scFv1H12 to IgG antigen. By contrast, the individual FdVH 073 and FdVL 074, originating from induced BoHV-1 neutralizing IgG1 antibody, recognized target epitope on BoHV-1 weakly when compared to FdVH +FdVL (scFv3-18L). Interestingly, both the FdVH and FdVL domains of induced IgG antibody are required to achieve BoHV-1 neutralization. To conclude, there exist subtle functional differences in the contribution of FdVH and FdVL to antigen-binding site generation of polyspecific IgM and monospecific IgG antibodies relevant to antigen recognition and virus neutralization functions.

  13. Diagnostic Value of Electrocardiographic T Wave Inversion in Lead aVL in Diagnosing Coronary Artery Disease in Patients with Chronic Stable Angina

    Directory of Open Access Journals (Sweden)

    Hatem L. Farhan

    2010-04-01

    Full Text Available Objectives: The clinical value of T wave inversion in lead aVL in diagnosing coronary artery disease (CAD remains unclear. This study aims to investigate the correlation between aVL T wave inversion and CAD in patients with chronic stable angina.Methods: Electrocardiograms (ECGs of 257 consecutive patients undergoing coronary angiography were analyzed. All patients had chronic stable angina. All patients with secondary T wave inversion had been excluded (66 patients. The remaining 191 patients constituted the study population. Detailed ECG interpretation and coronary angiographic findings were conducted by experienced cardiologists.Results: T wave inversion in aVL was identified in 89 ECGs (46.8% with definite ischemic Q-ST-T changes in different leads in 97 ECGs (50.8%. Stand alone aVL T wave inversion was found in 27 ECGs (14.1% while ischemic changes in other leads with normal aVL were identified in 36 ECGs (18.8%. The incidence of CAD was 86.3%. Single, two- and multi-vessel CAD were found in 38.8%, 28.5% and 32.7% of cases respectively. The prevalence of left main, left anterior descending, left circumflex and right coronary arteries were 4.7%, 61.2%, 29.3% and 44.5%, respectively. T wave inversion in aVL was found to be the only ECG variable significantly predicting mid segment left anterior descending artery (LAD lesions (Odds Ratio 2.93, 95% Confidence Interval 1.59-5.37, p=0.001.Conclusion: This study provides new information relating to T wave inversion in lead aVL to mid segment LAD lesions. Implication of this simple finding may help in bedside diagnosis of CAD typically mid LAD lesions. However, further studies are needed to corroborate this finding.

  14. Differences among Tennis Players Aged 12, 14 And 16 Years in Certain Morphological Characteristics: A Croatian Prospective.

    Science.gov (United States)

    Novak, Dario; Milanović, Dragan; Barbaros-Tudor, Petar

    2015-09-01

    A sample of young tennis players aged 12, 14 and 16 in Croatia. Sixty (60) tennis players ranked on the scale of the Croatian Tennis Association were analyzed through differences in morphological characteristics, as identified by a standard laboratory diagnostic procedure in Sports-diagnostic Centre of the Faculty of Kinesiology at the University of Zagreb. Significant differences were obtained in most of the monitored measures for the assessment of the morphological characteristics but the most significant differences were reflected in the variables for assessment of longitudinal dimensionality of the skeleton and body mass and voluminosity of the body. The statistical significance was defined at ptennis players playing style.

  15. Phases of QCD: Summary of the Rutgers Long Range Plan Town Meeting, January 12-14, 2007

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Peter; Kharzeev, Dmitri; Muller, Berndt; Nagle, Jamie; Rajagopal, Krishna; Vigdor, Steve

    2007-05-14

    This White Paper summarizes the outcome of the Town Meeting on Phases of QCD that took place January 12-14, 2007 at Rutgers University, as part of the NSAC 2007 Long Range Planning process. The meeting was held in conjunction with the Town Meeting on Hadron Structure, including a full day of joint plenary sessions of the two meetings. Appendix A.1 contains the meeting agenda. This Executive Summary presents the prioritized recommendations that were determined at the meeting. Subsequent chapters present the essential background to the recommendations. While this White Paper is not a scholarly article and contains few references, it is intended to provide the non-expert reader

  16. Prevalence of proteinuria in school children (aged 12-14 years in Kashmir valley, India, using dipstick method

    Directory of Open Access Journals (Sweden)

    Hilal Ahmad Malla

    2016-01-01

    Full Text Available Screening for kidney diseases by urinalysis in school children is being conducted in many parts of the world with inexpensive tools such as urinary dipsticks. We conducted this study to know the prevalence of asymptomatic proteinuria in school children (age group 12-14 years in Kashmir valley as no previous study is available. After applying exclusion criteria, 2068 children were screened for proteinuria by dipstick method. Another test was performed in the children with abnormal findings in the first sample with dipstick of the same brand, after a period of one-month. These children were also assessed by timed urine collection (i.e., 24 h urinary protein. In the first dipstick test, the prevalence of proteinuria in the studied population was 6.2% which persisted in 2.17% after second dipstick examination. No child in the studied group was found to have glycosuria. In our study, no statistically significant association was found between proteinuria and gender, body mass index, or hypertension. In our study, the prevalence of persistent proteinuria in school children (age group 12-14 years in Kashmir valley was almost similar to the studies conducted in different parts of the world.

  17. Research of a level of morphofunctional state of young bicyclists at the age of 12-14 years specialized at BMX.

    Directory of Open Access Journals (Sweden)

    Prudnikova М.С.

    2011-03-01

    Full Text Available The morphological and functional state of young bicyclists is considered 12-14 years, engaging in the extreme type of the cycle racing (ВМХ. Research is conducted during two year cycles of the морфофункционального state of young bicyclists 12-14 years, specialized in bicycle мотокроссе. Physician-biology control which allowed educing the level of the functional state of young bicyclists 12-14 years on the type of build is shown.

  18. Restoration and Reexamination of Data from the Apollo 11, 12, 14, and 15 Dust, Thermal and Radiation Engineering Measurements Experiments

    Science.gov (United States)

    McBride, Marie J.; Williams, David R.; Kent, H.; Turner, Niescja

    2012-01-01

    As part of an effort by the Lunar Data Node (LDN) we are restoring data returned by the Apollo Dust, Thermal, and Radiation Engineering Measurements (DTREM) packages emplaced on the lunar surface by the crews of Apollo 11, 12, 14, and 15. Also commonly known as the Dust Detector experiments, the DTREM packages measured the outputs of exposed solar cells and thermistors over time. They operated on the surface for up to nearly 8 years, returning data every 54 seconds. The Apollo 11 DTREM was part of the Early Apollo Surface Experiments Package (EASEP), and operated for a few months as planned following emplacement in July 1969. The Apollo 12, 14, and 15 DTREMs were mounted on the central station as part of the Apollo Lunar Surface Experiments Package (ALSEP) and operated from deployment until ALSEP shutdown in September 1977. The objective of the DTREM experiments was to determine the effects of lunar and meteoric dust, thermal stresses, and radiation exposure on solar cells. The LDN, part of the Geosciences Node of the Planetary Data System (PDS), operates out of the National Space Science Data Center (NSSDC) at Goddard Space Flight Center. The goal of the LDN is to extract lunar data stored on older media and/or in obsolete formats, restore the data into a usable digital format, and archive the data with PDS and NSSDC. For the DTREM data we plan to recover the raw telemetry, translate the raw counts into appropriate output units, and then apply calibrations. The final archived data will include the raw, translated, and calibrated data and the associated conversion tables produced from the microfilm, as well as ancillary supporting data (metadata) packaged in PDS format.

  19. Type specimens of taxa of Artemisia L. (Asteraceae from Siberia and the Far East kept in the Herbarium of V.L. Komarov Botanical Insitute

    Directory of Open Access Journals (Sweden)

    A. A. Korobkov

    2015-04-01

    Full Text Available Typification of 97 Artemisia (Asteraceae taxa from Siberia and the Far East kept in the Herbarium of V.L. Komarov Botanical Institute was carried out. Holotypes for 39 taxa, lectotypes for 48 taxa, 28 syntypes and 4 isotypes are given.

  20. Increased oxidative stress and toxicity in ADH and CYP2E1 overexpressing human hepatoma VL-17A cells exposed to high glucose.

    Science.gov (United States)

    Chandrasekaran, Karthikeyan; Swaminathan, Kavitha; Kumar, S Mathan; Clemens, Dahn L; Dey, Aparajita

    2012-05-01

    High glucose mediated oxidative stress and cell death is a well documented phenomenon. Using VL-17A cells which are HepG2 cells over-expressing alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1) and control HepG2 cells, the association of ADH and CYP2E1 with high glucose mediated oxidative stress and toxicity in liver cells was investigated. Cell viability was measured and apoptosis or necrosis was determined through caspase-3 activity, Annexin V-propidium iodide staining and detecting decreases in mitochondrial membrane potential. Reactive oxygen species, lipid peroxidation and the formation of advanced glycated-end products were assessed. The levels of several antioxidants which included glutathione, glutathione peroxidase, catalase and superoxide dismutase were altered in high glucose treated VL-17A cells. Greater toxicity was observed in VL-17A cells exposed to high glucose when compared to HepG2 cells. Oxidative stress parameters were greatly increased in high glucose exposed VL-17A cells and apoptotic cell death was observed. Inhibition of CYP2E1 or caspase 3 or addition of the antioxidant trolox led to significant decreases in high glucose mediated oxidative stress and toxicity. Thus, the over-expression of ADH and CYP2E1 in liver cells is associated with increased high glucose mediated oxidative stress and toxicity.

  1. Topographic Lidar Survey of Dauphin Island, Alabama and Chandeleur, Stake, Grand Gosier and Breton Islands, Louisiana, July 12-14, 2013 -- Classified Point Data

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — A topographic lidar survey was conducted July 12-14, 2013 over Dauphin Island, Alabama and Chandeleur, Stake, Grand Gosier and Breton Islands, Louisiana. Lidar data...

  2. Topographic Lidar Survey of Dauphin Island, Alabama and Chandeleur, Stake, Grand Gosier and Breton Islands, Louisiana, July 12-14, 2013 -- Classified Point Data

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — A topographic lidar survey was conducted July 12-14, 2013 over Dauphin Island, Alabama and Chandeleur, Stake, Grand Gosier and Breton Islands, Louisiana. Lidar data...

  3. Topographic Lidar Survey of Dauphin Island, Alabama and Chandeleur, Stake, Grand Gosier and Breton Islands, Louisiana, July 12-14, 2013 -- Bare Earth Digital Elevation Models (DEMs)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — A topographic lidar survey was conducted on July 12-14, 2013 over Dauphin Island, Alabama and Chandeleur, Stake, Grand Gosier and Breton Islands, Louisiana. The data...

  4. Topographic Lidar Survey of Dauphin Island, Alabama and Chandeleur, Stake, Grand Gosier and Breton Islands, Louisiana, July 12-14, 2013 -- Bare Earth Digital Elevation Models (DEMs)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — A topographic lidar survey was conducted on July 12-14, 2013 over Dauphin Island, Alabama and Chandeleur, Stake, Grand Gosier and Breton Islands, Louisiana. The data...

  5. MiNube

    OpenAIRE

    Villanueva Hernández, Yarilo David

    2015-01-01

    [ES]MiNube es una solución de almacenamiento de datos online enfocada en la privacidad, seguridad y control del usuario final. A diferencia de otras plataformas de almacenamiento en la nube en el que se depende de agentes externos, MiNube cede el control de los datos al usuario, permitiéndole configurar su propio entorno y definiendo políticas de encriptación en las que el propio usuario es el único agente capaz de acceder a sus datos. MiNube se compone de tres partes: Un servidor web para s...

  6. DE TIAM MI ESTAS ESPERANTISTO

    Institute of Scientific and Technical Information of China (English)

    Verkis V.Setala

    1996-01-01

    En 1903, iufoje mi vojais de Bukareto alKonstantinpolo, kaj mi prenis sidlokon en larestoracia vagono. Apenaǚ mi sidiis, mividis ke iu eksterlandano penas komprenigi alkelnero kion li deziras. La kelnero uzas sian tu-tan lingvoscion: li parolas rumane, serbe,turke, bulgare kaj ruse, sed vane! La fremd-landano ne komprenas e unu vorton. Mi

  7. Effects of Temperature and Humidity Factors on the Pathogenicity of Verticillium lecanii VL17 to Trialeurodes vaporariorum Westwood%温湿度对蜡蚧轮枝菌VL17菌株侵染温室白粉虱的毒力影响

    Institute of Scientific and Technical Information of China (English)

    纪明山; 辛鑫; 王艳辉; 王瑞雪

    2010-01-01

    测定了蜡蚧轮枝菌VL17菌株在不同温湿度条件下对温室白粉虱的致病力.结果表明:在15~35℃的温度范围内,VL17菌株对温室白粉虱2龄若虫均有致病力,若虫死亡率随着温度升高而增加.在25℃温度条件下,采用1.8×107个/mL孢子悬浮液处理,温室白粉虱2龄若虫第7天死亡率达100%.湿度越大,蜡蚧轮枝菌VL17菌株对温室白粉虱的致病力越强.

  8. IUPAC-NIST Solubility Data Series. 85. Transition and 12-14 Main Group Metals, Lanthanide, Actinide, and Ammonium Halates

    Science.gov (United States)

    Miyamoto, Hiroshi

    2008-06-01

    This paper is the fourth and final volume in the halate solubility series. The solubility data for halates of transition metals, lanthanides, actinides, ammonium, and metallic elements of the main groups 12-14 are reviewed. Where appropriate, binary, ternary, and multicomponent systems are critically evaluated. Most of the solubility results were obtained in water or aqueous solutions of electrolytes. The solubility in organic solvents and aqueous-organic solvent mixtures is also collected in this volume. All these data were critically examined for their reliability. The best values were selected on the basis of critical evaluations and presented in tabular form. Fitting equations and graphical plots are also provided. When numerical data were not reported in an original publication, they were read out from figures and digitized by the compilers. The quantities, units, and symbols used in this volume are in accord with IUPAC recommendations. We always reported the original data and, if necessary, transferred them into the IUPAC recommended units and symbols. The literature on the solubility data was researched through 2002. The halates of these metals play a role in industrial processes. For example, some halates are essential as catalysts, heat stabilizers, and blanching reagents for manufacturing polymer products such as textiles and resins. Some iodates are used in pyrotechnic compounds for weather modification and colored smoke generation. The nonlinear halate crystals are important in construction of optical devices.

  9. Feedback Control of the Arachidonate Cascade in Osteoblastic Cells by 15-deoxy-Δ12,14-Prostaglandin J2

    Science.gov (United States)

    Ishino, Hidetaka; Kawahito, Yutaka; Tsubouchi, Yasunori; Kohno, Masataka; Wada, Makoto; Yamamoto, Aihiro; Hamaguchi, Masahide; Kadoya, Masatoshi; Tokunaga, Daisaku; Hojo, Tatsuya; Matsuyama, Masahide; Yoshimura, Rikio; Yoshikawa, Toshikazu

    2008-01-01

    15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-γ ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ2 can suppress interleukin (IL)-1β-induced prostaglandin E2 (PGE2) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE2 synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis. In this study, we investigated the feedback mechanism of the arachidonate cascade in mouse osteoblastic cells, MC3T3-E1 cells, which differentiate into mature osteoblasts. Treatment with 15d-PGJ2 led to a significant increase in IL-1α-induced COX-2 expression and PGE2 production in a dose dependent manner. The effect of 15d-PGJ2 was stronger than that of TRO. However, it did not affect the expression of COX-1. In addition, cell viability of MC3T3-E1 cells was not changed in the condition we established. This means that 15d-PGJ2 exerts a positive feedback regulation of the arachidonate cascade of PGE2 in osteoblastic cells. These results may provide important information about the pathogenesis and treatment of bone resorption in a variety of diseases such as RA and osteoporosis. PMID:18231633

  10. 15-deoxy-Δ12,14-PGJ2 induces synoviocyte apoptosis and suppresses adjuvant-induced arthritis in rats

    Science.gov (United States)

    Kawahito, Yutaka; Kondo, Motoharu; Tsubouchi, Yasunori; Hashiramoto, Akira; Bishop-Bailey, David; Inoue, Ken-ichiro; Kohno, Masataka; Yamada, Ryoji; Hla, Timothy; Sano, Hajime

    2000-01-01

    Peroxisome proliferator–activated receptors (PPARs) are members of the nuclear hormone receptor superfamily and have a dominant regulatory role in adipocyte and monocyte differentiation. PPAR-γ agonists are also negative regulators of macrophage activation and have modulatory effects on tumorigenesis. In this study we demonstrate that synovial tissue localized expression of PPAR-γ in patients with rheumatoid arthritis (RA). We detected markedly enhanced expression of PPAR-γ in macrophages, as well as modestly enhanced expression in the synovial lining layer, fibroblasts, and endothelial cells. Activation of the PPAR-γ by 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and the synthetic PPAR-γ ligand (troglitazone) induced RA synoviocyte apoptosis in vitro. Moreover, intraperitoneal administration of these PPAR-γ ligands ameliorated adjuvant-induced arthritis with suppression of pannus formation and mononuclear cell infiltration in female Lewis rats. Anti-inflammatory effects of 15d-PGJ2 were more potent than troglitazone. These findings suggest that PPAR-γ may be an important immunoinflammatory mediator and its ligands, especially 15d-PGJ2, may be useful in the treatment of RA. PMID:10903334

  11. Variability in New Shortening Estimates from Southern Peru (12-14S); Implications for Mass Balance of the Andean Plateau.

    Science.gov (United States)

    Gotberg, N.; McQuarrie, N.

    2008-12-01

    One of the fundamental questions of interest with regards to the Andean Plateau is the mass balance of material needed to create and sustain a 3-4 km high plateau. Is crustal shortening sufficient to support an isostatically compensated crust of 60-70km? We present new estimates of shortening across the northern margin of the Andean Plateau. The cross section extent, from the eastern edge of the volcanic arc to foreland basin, is approximately one half of the physiographic width of the Andean Plateau in Peru. Cross sectional shortening estimates in southern Peru (12-14°S) provide a best estimate of 123 km or 40% shortening with an absolute minimum estimate of 86 km or 30% and absolute maximum estimate of 275 km or 60%. We determined the maximum and minimum shortening estimates using the cross sectional area and possible variations in assumptions made about the amount of erosion, detachment dip, involvement of basement thrusts and displacement along faults. The best estimate of shortening is well short of the required 240-300km of shortening needed in order to account for a 60-70km thick crust under the entire plateau. This suggests that for an isostatically equilibrated crust either 1) there is a significant amount of shortening (~150km) in the western half of the plateau which, is hidden by the volcanic arc or 2) crustal material is being added to the Peruvian section of the Andean Plateau either through lower crustal flow or a process of magmatic underplating followed by differentiation and delamination.

  12. Mi Pueblo Food Center

    Directory of Open Access Journals (Sweden)

    Alexis A. Babb

    2016-04-01

    Full Text Available This case describes a current growth opportunity for Mi Pueblo Food Center, a Hispanic grocery chain with locations throughout the Bay Area, California. The CEO of Mi Pueblo is contemplating opening a new store location in East Palo Alto, CA, which has been without a local, full-service grocery store for over 20 years. Case objectives are for students to develop an understanding of how the grocery industry operates, the risks and opportunities associated with opening a new grocery store location, and the impact on social, environmental, and economic sustainability. The SWOT (Strengths, Weaknesses, Opportunities, Threats framework is used to analyze whether or not it is feasible for Mi Pueblo to open a new location in East Palo Alto. This case may be used with students in graduate and advanced undergraduate courses.

  13. MiDAS

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads

    2015-01-01

    The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties...... communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study...... of microbial ecology of the activated sludge process and related treatment processes. The online MiDAS field guide is a collaborative workspace intended to facilitate a better understanding of the ecology of activated sludge and related treatment processes—knowledge that will be an invaluable resource...

  14. A VL-linker-VH Orientation Dependent Single Chain Variable Antibody Fragment Against Rabies Virus G Protein with Enhanced Neutralizing Potency in vivo.

    Science.gov (United States)

    Cheng, Yue; Li, Zhuang; Xi, Hualong; Gu, Tiejun; Yuan, Ruosen; Chen, Xiaoxu; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2016-01-01

    Lethal rabies can be prevented effectively by post-exposure prophylactic (PEP) with rabies immunoglobulin (RIG). Single-chain variable fragment (scFv), which is composed of a variable heavy chain (VH) and variable light chain (VL) connected by a peptide linker, may be developed as alternative to RIG for neutralizing rabies virus (RV). However, our previously constructed scFv (FV57S) with the (NH2) VH-linker-VL (COOH) orientation showed a lower neutralizing potency than its parent RIG. This orientation may inhibit FV57S from refolding into an intact and correct conformation. Therefore, the RFV57S protein with a VL-linker-VH orientation was constructed based on FV57S. A HIS tag was incorporated to aid in purification and detection of RFV57S and FV57S. However, abilities of RFV57S and FV57S to bind with the anti-HIS tag mAb were different. Therefore, a novel direct ELISA was established by utilizing a biotin-labeled truncated glycoprotein of RV. Although with similar stability and in vitro neutralizing potency as FV57S, RFV57S showed enhanced binding ability, affinity and in vivo protective efficacy against lethal dose of RV. Our studies support the feasibility of developing a scFv with reversed orientation and provide a novel method for evaluating the binding ability, stability and affinity of engineered antibodies recognizing linear epitope.

  15. Treasury Offset Program (TOP) MI

    Data.gov (United States)

    Social Security Administration — The TOP MI helps OPSOS coordinate TOP case processing in the regions. The MI also helped communicate our progress and findings to BFQM and ORDP, as well as the ACOSS.

  16. Electronic Services Monthly MI Report

    Data.gov (United States)

    Social Security Administration — This electronic services monthly MI report contains monthly MI data for most public facing online online applications such as iClaim, electronic access, Mobile wage...

  17. Painter Liu Mi

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    LIU Mi graduated from the Department of Oil Painting at the Sichuan Academy of Fine Arts. In following years, she worked in stage and wardrobe design for the military song and dance ensemble. She later worked for the Chongqing Foreign Trade Company where her packaging design achievements won

  18. MI 4010 Thermoelectric Modules.

    Science.gov (United States)

    The report covers the design justification, physical specification and characterization of the MI 4010 module . The purpose of the contract was to...demonstrate the capability to fabricate pieceparts, process into assemblies, and test thermoelectric modules equivalent to the module used in the Hand...Held Thermal Viewer. The completed modules were also subjected to limited demonstration tests of reliability and useful life.

  19. MI 6040 Thermoelectric Modules.

    Science.gov (United States)

    The report covers the design justification, physical specification and characterization of the MI 6040 module . The purpose of the thermoelectric... modules is the cooling of infrared detector arrays to temperature of 170K or colder. The completed modules were also subjected to limited demonstration tests of reliability and useful life.

  20. 15-Deoxy-Δ12,14-prostaglandin J2 inhibits macrophage colonization by Salmonella enterica serovar Typhimurium.

    Science.gov (United States)

    Buckner, Michelle M C; Antunes, L Caetano M; Gill, Navkiran; Russell, Shannon L; Shames, Stephanie R; Finlay, B Brett

    2013-01-01

    15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2) is an anti-inflammatory downstream product of the cyclooxygenase enzymes. It has been implicated to play a protective role in a variety of inflammatory mediated diseases, including rheumatoid arthritis, neural damage, and myocardial infarctions. Here we show that 15d-PGJ2 also plays a role in Salmonella infection. Salmonella enterica Typhimurium is a Gram-negative facultative intracellular pathogen that is able to survive and replicate inside phagocytic immune cells, allowing for bacterial dissemination to systemic sites. Salmonella species cause a wide range of morbidity and mortality due to gastroenteritis and typhoid fever. Previously we have shown that in mouse models of typhoid fever, Salmonella infection causes a major perturbation in the prostaglandin pathway. Specifically, we saw that 15d-PGJ2 production was significantly increased in both liver and feces. In this work we show that 15d-PGJ2 production is also significantly increased in macrophages infected with Salmonella. Furthermore, we show that the addition of 15d-PGJ2 to Salmonella infected RAW264.7, J774, and bone marrow derived macrophages is sufficient to significantly reduce bacterial colonization. We also show evidence that 15d-PGJ2 is reducing bacterial uptake by macrophages. 15d-PGJ2 reduces the inflammatory response of these infected macrophages, as evidenced by a reduction in the production of cytokines and reactive nitrogen species. The inflammatory response of the macrophage is important for full Salmonella virulence, as it can give the bacteria cues for virulence. The reduction in bacterial colonization is independent of the expression of Salmonella virulence genes SPI1 and SPI2, and is independent of the 15d-PGJ2 ligand PPAR-γ. 15d-PGJ2 also causes an increase in ERK1/2 phosphorylation in infected macrophages. In conclusion, we show here that 15d-PGJ2 mediates the outcome of bacterial infection, a previously unidentified role for this

  1. 15-Deoxy-Δ12,14-prostaglandin J2 inhibits macrophage colonization by Salmonella enterica serovar Typhimurium.

    Directory of Open Access Journals (Sweden)

    Michelle M C Buckner

    Full Text Available 15-deoxy-Δ(12,14-prostaglandin J2 (15d-PGJ2 is an anti-inflammatory downstream product of the cyclooxygenase enzymes. It has been implicated to play a protective role in a variety of inflammatory mediated diseases, including rheumatoid arthritis, neural damage, and myocardial infarctions. Here we show that 15d-PGJ2 also plays a role in Salmonella infection. Salmonella enterica Typhimurium is a Gram-negative facultative intracellular pathogen that is able to survive and replicate inside phagocytic immune cells, allowing for bacterial dissemination to systemic sites. Salmonella species cause a wide range of morbidity and mortality due to gastroenteritis and typhoid fever. Previously we have shown that in mouse models of typhoid fever, Salmonella infection causes a major perturbation in the prostaglandin pathway. Specifically, we saw that 15d-PGJ2 production was significantly increased in both liver and feces. In this work we show that 15d-PGJ2 production is also significantly increased in macrophages infected with Salmonella. Furthermore, we show that the addition of 15d-PGJ2 to Salmonella infected RAW264.7, J774, and bone marrow derived macrophages is sufficient to significantly reduce bacterial colonization. We also show evidence that 15d-PGJ2 is reducing bacterial uptake by macrophages. 15d-PGJ2 reduces the inflammatory response of these infected macrophages, as evidenced by a reduction in the production of cytokines and reactive nitrogen species. The inflammatory response of the macrophage is important for full Salmonella virulence, as it can give the bacteria cues for virulence. The reduction in bacterial colonization is independent of the expression of Salmonella virulence genes SPI1 and SPI2, and is independent of the 15d-PGJ2 ligand PPAR-γ. 15d-PGJ2 also causes an increase in ERK1/2 phosphorylation in infected macrophages. In conclusion, we show here that 15d-PGJ2 mediates the outcome of bacterial infection, a previously unidentified

  2. 15-deoxy-△12,14-prostaglandin J2 ameliorates endotoxin-induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    Liu Dong; Geng Zhilong; Zhu Wankun; Wang Huiwen; Chen Ye; Liang Juan

    2014-01-01

    Background A proinflammatory milieu emerging in the lung due to neutrophil accumulation and activation is a key in the pathogenesis of acute lung injury (ALI).15-deoxy-△12,14-prostaglandin J2 (15d-PGJ2),one of the terminal products of the cyclooxygenase-2 pathway,is known to be the endogenous ligand of peroxisome proliferator-activated receptor y (PPAR-y) with multiple physiological properties.Growing evidence indicates that 15d-PGJ2 has anti-inflammatory,antiproliferative,cytoprotective and pro-resolving effects.We investigated whether 15d-PGJ2 has a protective effect against endotoxin-induced acute lung injury in rats.Methods Twenty-four male Wistar rats were randomly assigned into four groups (n=6 per group):sham+vehicle group,sham+15d-PGJ2 group,LPS+vehicle group,and LPS+15d-PGJ2 group.The rats were given either lipopolysaccharide (LPS,6 mg/kg intravenously) or saline,and pretreated with 15d-PGJ2 (0.3 mg/kg intravenously) or its vehicle (dimethyl sulphoxide) 30 minutes before LPS.Histological alterations,wet/dry weight (W/D) ratio and myeloperoxidase (MPO) activity as well as tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels were determined in lung tissues four hours after LPS injection.Immunohistochemical analysis for intercellular adhesion molecule-1 (ICAM-1) expression and Western blotting analysis for nuclear factor (NF)-κB p65 translocation and IκBα protein levels were also studied.Results 15d-PGJ2 pretreatment significantly attenuated LPS-induced lung injury,and reduced the increased W/D ratio,MPO activity,TNF-α,CINC-1 levels,and ICAM-1 expression in the lung.15d-PGJ2 also suppressed the nuclear NF-ΚB p65 translocation and increased cytosolic IKBα levels.Conclusions 15d-PGJ2 protects against endotoxin-induced acute lung injury,most likely through the reduction of proinflammatory protein levels during endotoxemia subsequent to the inhibition of NF-ΚB activation.

  3. Changes in excitatory and inhibitory circuits of the rat hippocampus 12-14 months after complete forebrain ischemia.

    Science.gov (United States)

    Arabadzisz, D; Freund, T F

    1999-01-01

    Changes in interneuron distribution and excitatory connectivity have been investigated in animals which had survived 12-14 months after complete forebrain ischemia, induced by four-vessel occlusion. Anterograde tracing with Phaseolus vulgaris leucoagglutinin revealed massive Schaffer collateral input even to those regions of the CA1 subfield where hardly any surviving pyramidal cells were found. Boutons of these Schaffer collaterals formed conventional synaptic contacts on dendritic spines and shafts, many of which likely belong to interneurons. Mossy fibres survived the ischemic challenge, however, large mossy terminals showed altered morphology, namely, the number of filopodiae on these terminals decreased significantly. The entorhinal input to the hippocampus did not show any morphological alterations. The distribution of interneurons was investigated by neurochemical markers known to label functionally distinct GABAergic cell populations. In the hilus, spiny interneurons showed a profound decrease in number. This phenomenon was not as obvious in CA3, but the spiny metabotropic glutamate receptor 1alpha-positive non-pyramidal cells, some of which contain calretinin or substance P receptor, disappeared from stratum lucidum of this area. In the CA1 region, somatostatin immunoreactivity disappeared from stratum oriens/lacunosum-moleculare-associated cells, while in metabotropic glutamate receptor 1alpha-stained sections these cells seemed unaffected in number. Other interneurons did not show an obvious decrease in number. In stratum radiatum of the CA1 subfield, some interneuron types had altered morphology: the substance P receptor-positive dendrites lost their characteristic radial orientation, and the metabotropic glutamate receptor 1alpha-expressing cells became extremely spiny. The loss of inhibitory interneurons at the first two stages of the trisynaptic loop coupled with a well-preserved excitatory connectivity among the subfields suggests that

  4. Proteomic identification of protein targets for 15-deoxy-Δ(12,14-prostaglandin J2 in neuronal plasma membrane.

    Directory of Open Access Journals (Sweden)

    Yasuhiro Yamamoto

    Full Text Available 15-deoxy-Δ(12,14-prostaglandin J(2 (15d-PGJ(2 is one of factors contributed to the neurotoxicity of amyloid β (Aβ, a causative protein of Alzheimer's disease. Type 2 receptor for prostaglandin D(2 (DP2 and peroxysome-proliferator activated receptorγ (PPARγ are identified as the membrane receptor and the nuclear receptor for 15d-PGJ(2, respectively. Previously, we reported that the cytotoxicity of 15d-PGJ(2 was independent of DP2 and PPARγ, and suggested that 15d-PGJ(2 induced apoptosis through the novel specific binding sites of 15d-PGJ(2 different from DP2 and PPARγ. To relate the cytotoxicity of 15d-PGJ(2 to amyloidoses, we performed binding assay [(3H]15d-PGJ(2 and specified targets for 15d-PGJ(2 associated with cytotoxicity. In the various cell lines, there was a close correlation between the susceptibilities to 15d-PGJ(2 and fibrillar Aβ. Specific binding sites of [(3H]15d-PGJ(2 were detected in rat cortical neurons and human bronchial smooth muscle cells. When the binding assay was performed in subcellular fractions of neurons, the specific binding sites of [(3H]15d-PGJ(2 were detected in plasma membrane, nuclear and cytosol, but not in microsome. A proteomic approach was used to identify protein targets for 15d-PGJ(2 in the plasma membrane. By using biotinylated 15d-PGJ(2, eleven proteins were identified as biotin-positive spots and classified into three different functional proteins: glycolytic enzymes (Enolase2, pyruvate kinase M1 (PKM1 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH, molecular chaperones (heat shock protein 8 and T-complex protein 1 subunit α, cytoskeletal proteins (Actin β, F-actin-capping protein, Tubulin β and Internexin α. GAPDH, PKM1 and Tubulin β are Aβ-interacting proteins. Thus, the present study suggested that 15d-PGJ(2 plays an important role in amyloidoses not only in the central nervous system but also in the peripheral tissues.

  5. Chemical, physical, and meteorological data collected on multiple cruises in the Indian and Pacific oceans from 12/14/1965 - 3/17/1977 (NODC Accession 0000080)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Cruise Dates: 12/14/1965 - 3/22/1966 12/21/1974 - 3/13/1975 1/10/1975 - 2/19/1975 1/10/1975 - 3/17/1975 1/16/1975 - 3/9/1975 5/2/1975 - 6/22/1975 5/15/1975 -...

  6. Investigating the Effect of Educating Philosophy in the Children on the Spiritual Development of Female Students with 12-14 Years Old in the City of Isfahan

    Science.gov (United States)

    Abaspour, Nafiseh; Nowrozi, Reza Ali; Latifi, Zohreh

    2015-01-01

    The goal of this study was to investigate the effect of educating philosophy curriculum in the children on the spiritual development of female students with 12-14 years old in the city of Isfahan. The present study is a semi-experiment research. The research design is pretest-posttest research with experiment and control group. In order to select…

  7. SeaBASS Bio-optical and pigment data collected from 1979-08-22 to 2011-12-14 (NCEI Accession 0086308)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This accession contains SeaWiFS Bio-optical Archive and Storage System (SeaBASS) bio-optical, pigment, and other data collected from 1979-08-22 to 2011-12-14....

  8. Albumin-Binding and Tumor Vasculature Determine the Antitumor Effect of 15-Deoxy-Delta(12,14)-Prostaglandin-J(2) In Vivo

    NARCIS (Netherlands)

    Prakash, Jai; Bansal, Ruchi; Post, Eduard; de Jager-Krikken, Alie; Lub-de Hooge, Marjolijn N.; Poelstra, Klaas

    2009-01-01

    15-Deoxy-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)), a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, induces cell death in tumor cells in vitro; however, no study showed its in vivo effect on tumors. Here, we report that 15d-PGJ(2) shows antitumor effects in vivo in mice.

  9. Report of the Interagency Optical Network Testbeds Workshop 2 September 12-14, 2006 NASA Ames Research Center

    Energy Technology Data Exchange (ETDEWEB)

    Joe Mambretti Richard desJardins

    2006-05-01

    A new generation of optical networking services and technologies is rapidly changing the world of communications. National and international networks are implementing optical services to supplement traditional packet routed services. On September 12-14, 2005, the Optical Network Testbeds Workshop 2 (ONT2), an invitation-only forum hosted by the NASA Research and Engineering Network (NREN) and co-sponsored by the Department of Energy (DOE), was held at NASA Ames Research Center in Mountain View, California. The aim of ONT2 was to help the Federal Large Scale Networking Coordination Group (LSN) and its Joint Engineering Team (JET) to coordinate testbed and network roadmaps describing agency and partner organization views and activities for moving toward next generation communication services based on leading edge optical networks in the 3-5 year time frame. ONT2 was conceived and organized as a sequel to the first Optical Network Testbeds Workshop (ONT1, August 2004, www.nren.nasa.gov/workshop7). ONT1 resulted in a series of recommendations to LSN. ONT2 was designed to move beyond recommendations to agree on a series of “actionable objectives” that would proactively help federal and partner optical network testbeds and advanced research and education (R&E) networks to begin incorporating technologies and services representing the next generation of advanced optical networks in the next 1-3 years. Participants in ONT2 included representatives from innovative prototype networks (Panel A), basic optical network research testbeds (Panel B), and production R&D networks (Panels C and D), including “JETnets,” selected regional optical networks (RONs), international R&D networks, commercial network technology and service providers (Panel F), and senior engineering and R&D managers from LSN agencies and partner organizations. The overall goal of ONT2 was to identify and coordinate short and medium term activities and milestones for researching, developing, identifying

  10. MiRTargetLink--miRNAs, Genes and Interaction Networks.

    Science.gov (United States)

    Hamberg, Maarten; Backes, Christina; Fehlmann, Tobias; Hart, Martin; Meder, Benjamin; Meese, Eckart; Keller, Andreas

    2016-04-14

    Information on miRNA targeting genes is growing rapidly. For high-throughput experiments, but also for targeted analyses of few genes or miRNAs, easy analysis with concise representation of results facilitates the work of life scientists. We developed miRTargetLink, a tool for automating respective analysis procedures that are frequently applied. Input of the web-based solution is either a single gene or single miRNA, but also sets of genes or miRNAs, can be entered. Validated and predicted targets are extracted from databases and an interaction network is presented. Users can select whether predicted targets, experimentally validated targets with strong or weak evidence, or combinations of those are considered. Central genes or miRNAs are highlighted and users can navigate through the network interactively. To discover the most relevant biochemical processes influenced by the target network, gene set analysis and miRNA set analysis are integrated. As a showcase for miRTargetLink, we analyze targets of five cardiac miRNAs. miRTargetLink is freely available without restrictions at www.ccb.uni-saarland.de/mirtargetlink.

  11. Mi-spillet

    DEFF Research Database (Denmark)

    Larsen, Lea Lund; Hejlesen, Stine

    2003-01-01

    MI-spillet er et undervisningsspil til folkeskolens mellemtrin og udskolingen. Spillet omformer Howard Gardners teori om de mange intelligenser til et praktisk og håndgribeligt værktøj til brug i folkeskolen. Spillet indeholder et undervisningsmateriale bestående af lærervejledning og kopimappe...... emnebaseret eller tværfagligt arbejde. Alt materialet ligger samlet på en cd-rom, hvorfra materialet printes. Skolen kan derfor ved køb af én cd-rom printe og producere et ubegrænset antal spil. Cd-rommen indeholder: 1. Lærervejledning 2. MI-spillet * Gulvpladerne * Spørgsmål til spillet * Bilag til...

  12. Mi-spillet

    DEFF Research Database (Denmark)

    Larsen, Lea Lund; Hejlesen, Stine

    2003-01-01

    emnebaseret eller tværfagligt arbejde. Alt materialet ligger samlet på en cd-rom, hvorfra materialet printes. Skolen kan derfor ved køb af én cd-rom printe og producere et ubegrænset antal spil. Cd-rommen indeholder: 1. Lærervejledning 2. MI-spillet * Gulvpladerne * Spørgsmål til spillet * Bilag til...

  13. Measurement of the direct <mi>CP> -violating parameter <mi>Ami><mi>CP> in the decay <mi>D>+<mi>Kmi>-<mimi>+<mi>π>+

    Energy Technology Data Exchange (ETDEWEB)

    Abazov, V. M.; Abbott, B.; Acharya, B. S.; Adams, M.; Adams, T.; Agnew, J. P.; Alexeev, G. D.; Alkhazov, G.; Alton, A.; Askew, A.; Atkins, S.; Augsten, K.; Avila, C.; Badaud, F.; Bagby, L.; Baldin, B.; Bandurin, D. V.; Banerjee, S.; Barberis, E.; Baringer, P.; Bartlett, J. F.; Bassler, U.; Bazterra, V.; Bean, A.; Begalli, M.; Bellantoni, L.; Beri, S. B.; Bernardi, G.; Bernhard, R.; Bertram, I.; Besançon, M.; Beuselinck, R.; Bhat, P. C.; Bhatia, S.; Bhatnagar, V.; Blazey, G.; Blessing, S.; Bloom, K.; Boehnlein, A.; Boline, D.; Boos, E. E.; Borissov, G.; Borysova, M.; Brandt, A.; Brandt, O.; Brock, R.; Bross, A.; Brown, D.; Bu, X. B.; Buehler, M.; Buescher, V.; Bunichev, V.; Burdin, S.; Buszello, C. P.; Camacho-Pérez, E.; Casey, B. C. K.; Castilla-Valdez, H.; Caughron, S.; Chakrabarti, S.; Chan, K. M.; Chandra, A.; Chapon, E.; Chen, G.; Cho, S. W.; Choi, S.; Choudhary, B.; Cihangir, S.; Claes, D.; Clutter, J.; Cooke, M.; Cooper, W. E.; Corcoran, M.; Couderc, F.; Cousinou, M. -C.; Cutts, D.; Das, A.; Davies, G.; de Jong, S. J.; De La Cruz-Burelo, E.; Déliot, F.; Demina, R.; Denisov, D.; Denisov, S. P.; Desai, S.; Deterre, C.; DeVaughan, K.; Diehl, H. T.; Diesburg, M.; Ding, P. F.; Dominguez, A.; Dubey, A.; Dudko, L. V.; Duperrin, A.; Dutt, S.; Eads, M.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Enari, Y.; Evans, H.; Evdokimov, V. N.; Fauré, A.; Feng, L.; Ferbel, T.; Fiedler, F.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Fortner, M.; Fox, H.; Fuess, S.; Garbincius, P. H.; Garcia-Bellido, A.; García-González, J. A.; Gavrilov, V.; Geng, W.; Gerber, C. E.; Gershtein, Y.; Ginther, G.; Gogota, O.; Golovanov, G.; Grannis, P. D.; Greder, S.; Greenlee, H.; Grenier, G.; Gris, Ph.; Grivaz, J. -F.; Grohsjean, A.; Grünendahl, S.; Grünewald, M. W.; Guillemin, T.; Gutierrez, G.; Gutierrez, P.; Haley, J.; Han, L.; Harder, K.; Harel, A.; Hauptman, J. M.; Hays, J.; Head, T.; Hebbeker, T.; Hedin, D.; Hegab, H.; Heinson, A. P.; Heintz, U.; Hensel, C.; Heredia-De La Cruz, I.; Herner, K.; Hesketh, G.; Hildreth, M. D.; Hirosky, R.; Hoang, T.; Hobbs, J. D.; Hoeneisen, B.; Hogan, J.; Hohlfeld, M.; Holzbauer, J. L.; Howley, I.; Hubacek, Z.; Hynek, V.; Iashvili, I.; Ilchenko, Y.; Illingworth, R.; Ito, A. S.; Jabeen, S.; Jaffré, M.; Jayasinghe, A.; Jeong, M. S.; Jesik, R.; Jiang, P.; Johns, K.; Johnson, E.; Johnson, M.; Jonckheere, A.; Jonsson, P.; Joshi, J.; Jung, A. W.; Juste, A.; Kajfasz, E.; Karmanov, D.; Katsanos, I.; Kaur, M.; Kehoe, R.; Kermiche, S.; Khalatyan, N.; Khanov, A.; Kharchilava, A.; Kharzheev, Y. N.; Kiselevich, I.; Kohli, J. M.; Kozelov, A. V.; Kraus, J.; Kumar, A.; Kupco, A.; Kurča, T.; Kuzmin, V. A.; Lammers, S.; Lebrun, P.; Lee, H. S.; Lee, S. W.; Lee, W. M.; Lei, X.; Lellouch, J.; Li, D.; Li, H.; Li, L.; Li, Q. Z.; Lim, J. K.; Lincoln, D.; Linnemann, J.; Lipaev, V. V.; Lipton, R.; Liu, H.; Liu, Y.; Lobodenko, A.; Lokajicek, M.; Lopes de Sa, R.; Luna-Garcia, R.; Lyon, A. L.; Maciel, A. K. A.; Madar, R.; Magaña-Villalba, R.; Malik, S.; Malyshev, V. L.; Mansour, J.; Martínez-Ortega, J.; McCarthy, R.; McGivern, C. L.; Meijer, M. M.; Melnitchouk, A.; Menezes, D.; Mercadante, P. G.; Merkin, M.; Meyer, A.; Meyer, J.; Miconi, F.; Mondal, N. K.; Mulhearn, M.; Nagy, E.; Narain, M.; Nayyar, R.; Neal, H. A.; Negret, J. P.; Neustroev, P.; Nguyen, H. T.; Nunnemann, T.; Orduna, J.; Osman, N.; Osta, J.; Pal, A.; Parashar, N.; Parihar, V.; Park, S. K.; Partridge, R.; Parua, N.; Patwa, A.; Penning, B.; Perfilov, M.; Peters, Y.; Petridis, K.; Petrillo, G.; Pétroff, P.; Pleier, M. -A.; Podstavkov, V. M.; Popov, A. V.; Prewitt, M.; Price, D.; Prokopenko, N.; Qian, J.; Quadt, A.; Quinn, B.; Ratoff, P. N.; Razumov, I.; Ripp-Baudot, I.; Rizatdinova, F.; Rominsky, M.; Ross, A.; Royon, C.; Rubinov, P.; Ruchti, R.; Sajot, G.; Sánchez-Hernández, A.; Sanders, M. P.; Santos, A. S.; Savage, G.; Savitskyi, M.; Sawyer, L.; Scanlon, T.; Schamberger, R. D.; Scheglov, Y.; Schellman, H.; Schwanenberger, C.; Schwienhorst, R.; Sekaric, J.; Severini, H.; Shabalina, E.; Shary, V.; Shaw, S.; Shchukin, A. A.; Simak, V.; Skubic, P.; Slattery, P.; Smirnov, D.; Snow, G. R.; Snow, J.; Snyder, S.; Söldner-Rembold, S.; Sonnenschein, L.; Soustruznik, K.; Stark, J.; Stoyanova, D. A.; Strauss, M.; Suter, L.; Svoisky, P.; Titov, M.; Tokmenin, V. V.; Tsai, Y. -T.; Tsybychev, D.; Tuchming, B.; Tully, C.; Uvarov, L.; Uvarov, S.; Uzunyan, S.; Van Kooten, R.; van Leeuwen, W. M.; Varelas, N.; Varnes, E. W.; Vasilyev, I. A.; Verkheev, A. Y.; Vertogradov, L. S.; Verzocchi, M.; Vesterinen, M.; Vilanova, D.; Vokac, P.; Wahl, H. D.; Wang, M. H. L. S.; Warchol, J.; Watts, G.; Wayne, M.; Weichert, J.; Welty-Rieger, L.; Williams, M. R. J.; Wilson, G. W.; Wobisch, M.; Wood, D. R.; Wyatt, T. R.; Xie, Y.; Yamada, R.; Yang, S.; Yasuda, T.; Yatsunenko, Y. A.; Ye, W.; Ye, Z.; Yin, H.; Yip, K.; Youn, S. W.; Yu, J. M.; Zennamo, J.; Zhao, T. G.; Zhou, B.; Zhu, J.; Zielinski, M.; Zieminska, D.; Zivkovic, L.

    2014-12-01

    We measure the direct mi>Cmi>mi>P>-violating parameter mi>Ami>mi>Cmi>mi>Pmi> for the decay of the charged charm meson, mi>Dmi>+mi>Kmi>-mi>πmi>+mi>πmi>+ (and charge conjugate), using the full 10.4 mi>fbmi>-1 sample of mi>p>mi>p>¯ collisions at mi>smi>=1.96 mi>TeVmi> collected by the D0 detector at the Fermilab Tevatron collider. We extract the raw reconstructed charge asymmetry by fitting the invariant mass distributions for the sum and difference of charge-specific samples. This quantity is then corrected for detector-related asymmetries using data-driven methods and for possible physics asymmetries (from mi>B>mi>D

  14. Oxidation of D-[U-(14)C] glucose and [1,12-(14)C] dodecanedioic acid by pancreatic islets from Goto-Kakizaki rats.

    Science.gov (United States)

    Malaisse, W J; Doherty, M; Ladrière, L; Greco, A V; Mingrone, G

    2001-08-01

    In pancreatic islets from hereditarily diabetic GK rats, [1,12 -(14)C] dodecanedioic acid (5.0 mM) was oxidized at a rate representing about 5 % of that of D-[U - (14)C] glucose (8.3 mM). Dioic acid and hexose failed to exert any significant reciprocal effects on their respective oxidation. The production of (14)CO(2) from [1,12 -(14)C] dodecanedioic acid was proportional to its concentration in the 0.2 - 5.0 mM range. These results were essentially comparable to those obtained in islets from control rats. They extend, therefore, to GK rats the knowledge that dodecanedioic acid acts as a nutrient in pancreatic islet cells.

  15. Prevalensi Trauma Gigi Permanen Anterior Anak Usia 12-14 Tahun pada Sekolah Menengah Pertama di kecamatan Medan Barat dan Medan Sunggal

    OpenAIRE

    2015-01-01

    Trauma gigi permanen anterior atau yang dikenal dengan Traumatic Dental Injury (TDI) adalah kerusakan yang mengenai jaringan keras dan atau periodontal gigi permanen anterior karena sebab mekanis. Penelitian ini dilakukan untuk mengetahui besar prevalensi trauma gigi permanen anterior pada siswa Sekolah Menengah Pertama di kecamatan Medan Barat dan kecamatan Medan Sunggal. Jenis penelitian ini adalah survei cross-sectional. Jumlah sampel sebanyak 290 anak usia 12-14 tahun berasal dari empa...

  16. Measurement of the direct <mi>CP> -violating parameter <mi>Ami><mi>CP> in the decay <mi>D>+<mi>Kmi>-<mimi>+<mi>π>+

    Energy Technology Data Exchange (ETDEWEB)

    Abazov, V. M.; Abbott, B.; Acharya, B. S.; Adams, M.; Adams, T.; Agnew, J. P.; Alexeev, G. D.; Alkhazov, G.; Alton, A.; Askew, A.; Atkins, S.; Augsten, K.; Avila, C.; Badaud, F.; Bagby, L.; Baldin, B.; Bandurin, D. V.; Banerjee, S.; Barberis, E.; Baringer, P.; Bartlett, J. F.; Bassler, U.; Bazterra, V.; Bean, A.; Begalli, M.; Bellantoni, L.; Beri, S. B.; Bernardi, G.; Bernhard, R.; Bertram, I.; Besançon, M.; Beuselinck, R.; Bhat, P. C.; Bhatia, S.; Bhatnagar, V.; Blazey, G.; Blessing, S.; Bloom, K.; Boehnlein, A.; Boline, D.; Boos, E. E.; Borissov, G.; Borysova, M.; Brandt, A.; Brandt, O.; Brock, R.; Bross, A.; Brown, D.; Bu, X. B.; Buehler, M.; Buescher, V.; Bunichev, V.; Burdin, S.; Buszello, C. P.; Camacho-Pérez, E.; Casey, B. C. K.; Castilla-Valdez, H.; Caughron, S.; Chakrabarti, S.; Chan, K. M.; Chandra, A.; Chapon, E.; Chen, G.; Cho, S. W.; Choi, S.; Choudhary, B.; Cihangir, S.; Claes, D.; Clutter, J.; Cooke, M.; Cooper, W. E.; Corcoran, M.; Couderc, F.; Cousinou, M. -C.; Cutts, D.; Das, A.; Davies, G.; de Jong, S. J.; De La Cruz-Burelo, E.; Déliot, F.; Demina, R.; Denisov, D.; Denisov, S. P.; Desai, S.; Deterre, C.; DeVaughan, K.; Diehl, H. T.; Diesburg, M.; Ding, P. F.; Dominguez, A.; Dubey, A.; Dudko, L. V.; Duperrin, A.; Dutt, S.; Eads, M.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Enari, Y.; Evans, H.; Evdokimov, V. N.; Fauré, A.; Feng, L.; Ferbel, T.; Fiedler, F.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Fortner, M.; Fox, H.; Fuess, S.; Garbincius, P. H.; Garcia-Bellido, A.; García-González, J. A.; Gavrilov, V.; Geng, W.; Gerber, C. E.; Gershtein, Y.; Ginther, G.; Gogota, O.; Golovanov, G.; Grannis, P. D.; Greder, S.; Greenlee, H.; Grenier, G.; Gris, Ph.; Grivaz, J. -F.; Grohsjean, A.; Grünendahl, S.; Grünewald, M. W.; Guillemin, T.; Gutierrez, G.; Gutierrez, P.; Haley, J.; Han, L.; Harder, K.; Harel, A.; Hauptman, J. M.; Hays, J.; Head, T.; Hebbeker, T.; Hedin, D.; Hegab, H.; Heinson, A. P.; Heintz, U.; Hensel, C.; Heredia-De La Cruz, I.; Herner, K.; Hesketh, G.; Hildreth, M. D.; Hirosky, R.; Hoang, T.; Hobbs, J. D.; Hoeneisen, B.; Hogan, J.; Hohlfeld, M.; Holzbauer, J. L.; Howley, I.; Hubacek, Z.; Hynek, V.; Iashvili, I.; Ilchenko, Y.; Illingworth, R.; Ito, A. S.; Jabeen, S.; Jaffré, M.; Jayasinghe, A.; Jeong, M. S.; Jesik, R.; Jiang, P.; Johns, K.; Johnson, E.; Johnson, M.; Jonckheere, A.; Jonsson, P.; Joshi, J.; Jung, A. W.; Juste, A.; Kajfasz, E.; Karmanov, D.; Katsanos, I.; Kaur, M.; Kehoe, R.; Kermiche, S.; Khalatyan, N.; Khanov, A.; Kharchilava, A.; Kharzheev, Y. N.; Kiselevich, I.; Kohli, J. M.; Kozelov, A. V.; Kraus, J.; Kumar, A.; Kupco, A.; Kurča, T.; Kuzmin, V. A.; Lammers, S.; Lebrun, P.; Lee, H. S.; Lee, S. W.; Lee, W. M.; Lei, X.; Lellouch, J.; Li, D.; Li, H.; Li, L.; Li, Q. Z.; Lim, J. K.; Lincoln, D.; Linnemann, J.; Lipaev, V. V.; Lipton, R.; Liu, H.; Liu, Y.; Lobodenko, A.; Lokajicek, M.; Lopes de Sa, R.; Luna-Garcia, R.; Lyon, A. L.; Maciel, A. K. A.; Madar, R.; Magaña-Villalba, R.; Malik, S.; Malyshev, V. L.; Mansour, J.; Martínez-Ortega, J.; McCarthy, R.; McGivern, C. L.; Meijer, M. M.; Melnitchouk, A.; Menezes, D.; Mercadante, P. G.; Merkin, M.; Meyer, A.; Meyer, J.; Miconi, F.; Mondal, N. K.; Mulhearn, M.; Nagy, E.; Narain, M.; Nayyar, R.; Neal, H. A.; Negret, J. P.; Neustroev, P.; Nguyen, H. T.; Nunnemann, T.; Orduna, J.; Osman, N.; Osta, J.; Pal, A.; Parashar, N.; Parihar, V.; Park, S. K.; Partridge, R.; Parua, N.; Patwa, A.; Penning, B.; Perfilov, M.; Peters, Y.; Petridis, K.; Petrillo, G.; Pétroff, P.; Pleier, M. -A.; Podstavkov, V. M.; Popov, A. V.; Prewitt, M.; Price, D.; Prokopenko, N.; Qian, J.; Quadt, A.; Quinn, B.; Ratoff, P. N.; Razumov, I.; Ripp-Baudot, I.; Rizatdinova, F.; Rominsky, M.; Ross, A.; Royon, C.; Rubinov, P.; Ruchti, R.; Sajot, G.; Sánchez-Hernández, A.; Sanders, M. P.; Santos, A. S.; Savage, G.; Savitskyi, M.; Sawyer, L.; Scanlon, T.; Schamberger, R. D.; Scheglov, Y.; Schellman, H.; Schwanenberger, C.; Schwienhorst, R.; Sekaric, J.; Severini, H.; Shabalina, E.; Shary, V.; Shaw, S.; Shchukin, A. A.; Simak, V.; Skubic, P.; Slattery, P.; Smirnov, D.; Snow, G. R.; Snow, J.; Snyder, S.; Söldner-Rembold, S.; Sonnenschein, L.; Soustruznik, K.; Stark, J.; Stoyanova, D. A.; Strauss, M.; Suter, L.; Svoisky, P.; Titov, M.; Tokmenin, V. V.; Tsai, Y. -T.; Tsybychev, D.; Tuchming, B.; Tully, C.; Uvarov, L.; Uvarov, S.; Uzunyan, S.; Van Kooten, R.; van Leeuwen, W. M.; Varelas, N.; Varnes, E. W.; Vasilyev, I. A.; Verkheev, A. Y.; Vertogradov, L. S.; Verzocchi, M.; Vesterinen, M.; Vilanova, D.; Vokac, P.; Wahl, H. D.; Wang, M. H. L. S.; Warchol, J.; Watts, G.; Wayne, M.; Weichert, J.; Welty-Rieger, L.; Williams, M. R. J.; Wilson, G. W.; Wobisch, M.; Wood, D. R.; Wyatt, T. R.; Xie, Y.; Yamada, R.; Yang, S.; Yasuda, T.; Yatsunenko, Y. A.; Ye, W.; Ye, Z.

    2014-12-01

    We measure the direct mi>Cmi>mi>P>-violating parameter mi>Ami>mi>Cmi>mi>Pmi> for the decay of the charged charm meson, mi>Dmi>+mi>Kmi>-mi>πmi>+mi>πmi>+ (and charge conjugate), using the full 10.4 mi>fbmi>-1 sample of mi>p>mi>p>¯ collisions at mi>smi>=1.96 mi>TeVmi> collected by the D0 detector at the Fermilab Tevatron collider. We extract the raw reconstructed charge asymmetry by fitting the invariant mass distributions for the sum and difference of charge-specific samples. This quantity is then corrected for detector-related asymmetries using data-driven methods and for possible physics asymmetries (from mi>B>mi>D

  17. MiDAS

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Kirkegaard, Rasmus Hansen; McIlroy, Bianca

    A deep understanding of the microbial communities and dynamics in wastewater treatment systems is a powerful tool for process optimization and design (Rittmann et al., 2006). With the advent of amplicon sequencing of the 16S rRNA gene, the diversity within the microbial communities can now...... web platform about the microbes in activated sludge and their associated ADs. The MiDAS taxonomy proposes putative names for each genus-level-taxon that can be used as a common vocabulary for all researchers in the field....

  18. Berpikir Pseudo Penalaran Kovariasi dalam Mengkonstruksi Grafik Fungsi Kejadian Dinamik: Sebuah Analisis Berdasarkan Kerangka Kerja VL2P dan Implikasinya pada Pembelajaran Matematika

    Directory of Open Access Journals (Sweden)

    Subanji Subanji

    2016-02-01

    Full Text Available This article discusses the thinking process of pseudo covariational reasoning in constructing graphs of dynamic events. The reasoning is examined using the VL2P framework (Vinner, Lithner, Leron, and Pape. The thinking process of one student taking Calculus II course was analysed, followed with interviews, revealing that at the low level, the pseudo covariational reasoning was close to Vinner’s pseudo analytic; that higher level of reasoning was equal to Lithner’s Establish Experience; that the reasoning was dominantly affected by the first process of Leron’s Dual Process Theory; and that it took place when direct translation was involved consistent with Pape’s Direct Translation Approach. These suggest that process view be emphasized in mathematics teaching and learning.

  19. Forced recombination of psi-modified murine leukaemia virus-based vectors with murine leukaemia-like and VL30 murine endogenous retroviruses

    DEFF Research Database (Denmark)

    Mikkelsen, J G; Lund, Anders Henrik; Duch, M;

    1999-01-01

    -impaired Akv-MLV-derived vectors, we here examine putative genetic interactions between vector RNAs and copackaged endogenous retroviral RNAs of the murine leukaemia virus (MLV) and VL30 retroelement families. We show (i) that MLV recombination is not blocked by nonhomology within the 5' untranslated region...... harbouring the supposed RNA dimer-forming cis -elements and (ii) that copackaged retroviral RNAs can recombine despite pronounced sequence dissimilarity at the cross-over site(s) and within parts of the genome involved in RNA dimerization, encapsidation and strand transferring during reverse transcription....... We note that recombination-based rescue of primer binding site knock-out retroviral vectors may constitute a sensitive assay to register putative genetic interactions involving endogenous retroviral RNAs present in cells of various species....

  20. Role of pri-miRNA tertiary structure in miR-17~92 miRNA biogenesis.

    Science.gov (United States)

    Chaulk, Steven G; Thede, Gina L; Kent, Oliver A; Xu, Zhizhong; Gesner, Emily M; Veldhoen, Richard A; Khanna, Suneil K; Goping, Ing Swie; MacMillan, Andrew M; Mendell, Joshua T; Young, Howard S; Fahlman, Richard P; Glover, J N Mark

    2011-01-01

    MicroRNAs (miRNAs) regulate gene expression in a variety of biological pathways such as development and tumourigenesis. miRNAs are initially expressed as long primary transcripts (pri-miRNAs) that undergo sequential processing by Drosha and then Dicer to yield mature miRNAs. miR-17~92 is a miRNA cluster that encodes 6 miRNAs and while it is essential for development it also has reported oncogenic activity. To date, the role of RNA structure in miRNA biogenesis has only been considered in terms of the secondary structural elements required for processing of pri-miRNAs by Drosha. Here we report that the miR-17~92 cluster has a compact globular tertiary structure where miRNAs internalized within the core of the folded structure are processed less efficiently than miRNAs on the surface of the structure. Increased miR-92 expression resulting from disruption of the compact miR-17~92 structure results in increased repression of integrin α5 mRNA, a known target of miR-92a. In summary, we describe the first example of pri-miRNA structure modulating differential expression of constituent miRNAs.

  1. Électrolytes-gels pour piles au lithium système PVdF-HFP/SiO2/VL-LiTFSI

    Science.gov (United States)

    Caillon-Caravanier, M.; Claude-Montigny, B.; Lemordant, D.; Bosser, G.

    2002-04-01

    Les électrolytes-gels étudiés sont constitués du copolymère poly (fluorure de vinylidène-hexafluoropropylène) (PVdF-HFP) contenant où non de la silice et ayant absorbé un électrolyte liquide obtenu par dissolution du (trifluorométhyl sulfone) imidure de lithium (LiTFSI) dans la gamma-valérolactone (VL) ou dans le mélange VL:EC (90:10 en moles) (EC:carbonate d'éthylène). L'influence du pourcentage en sel de lithium dans l'électrolyte liquide, de la proportion de silice dans le copolymère sec et de la température sur la capacité d'absorption est étudiée. L'évolution de la conductivité en fonction de la composition de l'électrolyte-gel et de la température ainsi que l'étude de la solvatation de l'ion Li^+ par spectroscopie RAMAN ont permis de proposer un modèle de conductivité ionique pour ces matériaux. Après avoir déterminé le domaine d'électroactivité des gels, l'évolution des spectres d'impédance à l'interface Li / gel est interprétée par le modèle “couche polymère solide" (SPL).

  2. Synthesis and characterization of Ni(II) complex with 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-7,14-dienium bromide

    Energy Technology Data Exchange (ETDEWEB)

    Yusoff, Latifah M.; Yusoff, Siti Fairus M.; Ismail, Wafiuddin; Yamin, Bohari M. [School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor (Malaysia)

    2014-09-03

    Nickel(II) complex have been synthesized by treating a 14-membered ring tetraaza macrocyclic compound, 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-7,14-dienium, bromide (Me{sub 6}N{sub 4}H{sub 4})Br{sub 2} with nickel acetate in metanol. The complex was characterized using elemental analysis, Fourier Transform Infrared (FTIR), Ultraviolet-Visible (UV-Vis), and single crystal diffraction (X-ray). The nickel atom coordinates through four nitrogen atoms in the ligand. Square planar geometry has been proposed for this complex.

  3. Synthesis and characterization of Ni(II) complex with 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-7,14-dienium bromide

    Science.gov (United States)

    Yusoff, Latifah M.; Yusoff, Siti Fairus M.; Ismail, Wafiuddin; Yamin, Bohari M.

    2014-09-01

    Nickel(II) complex have been synthesized by treating a 14-membered ring tetraaza macrocyclic compound, 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-7,14-dienium, bromide (Me6N4H4)Br2 with nickel acetate in metanol. The complex was characterized using elemental analysis, Fourier Transform Infrared (FTIR), Ultraviolet-Visible (UV-Vis), and single crystal diffraction (X-ray). The nickel atom coordinates through four nitrogen atoms in the ligand. Square planar geometry has been proposed for this complex.

  4. The Anti-inflammatory Prostaglandin 15-Deoxy-Δ12,14-PGJ2 Inhibits CRM1-dependent Nuclear Protein Export*

    OpenAIRE

    Hilliard, Mark; Frohnert, Cornelia; Spillner, Christiane; Marcone, Simone; Nath, Annegret; Lampe, Tina; Fitzgerald, Desmond J; Kehlenbach, Ralph H.

    2010-01-01

    The signaling molecule 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has been described as the “anti-inflammatory prostaglandin.” Here we show that substrates of the nuclear export receptor CRM1 accumulate in the nucleus in the presence of 15d-PGJ2, identifying this prostaglandin as a regulator of CRM1-dependent nuclear protein export that can be produced endogenously. Like leptomycin B (LMB), an established fungal CRM1-inhibitor, 15d-PGJ2 reacts with a conserved cysteine residue in the CRM1 se...

  5. Study of the <mi>Zc>+ channel using lattice QCD

    Energy Technology Data Exchange (ETDEWEB)

    Prelovsek, Sasa; Lang, C. B.; Leskovec, Luka; Mohler, Daniel

    2015-01-01

    Recently experimentalists have discovered several charged charmoniumlike hadrons mi>Zmi>mi>cmi>+ with unconventional quark content mi>c>¯mi>c>mi>d>¯mi>u>. We perform a search for mi>Zmi>mi>cmi>+ with mass below 4.2 GeV in the channel mi>Imi>mi>G>(mi>Jmi>mi>Pmi>mi>C>)=1+(1+-) using lattice QCD. The major challenge is presented by the two-meson states mi>Jmi>/mi>ψmi>π>, mi>ψ>2mi>Smi>mi>π>, mi>ψ>1mi>Dmi>

  6. On the mechanism of inhibition of p27 degradation by 15-deoxy-Delta12,14-prostaglandin J2 in lymphoblasts of Alzheimer's disease patients.

    Science.gov (United States)

    Muñoz, U; Bartolomé, F; Esteras, N; Bermejo-Pareja, F; Martín-Requero, A

    2008-11-01

    It has been proposed that neuroinflammation, among other factors, may trigger an aberrant neuronal cell cycle re-entry leading to neuronal death. Cell cycle disturbances are also detectable in peripheral cells from Alzheimer's disease (AD) patients. We previously reported that the anti-inflammatory 15- deoxy-Delta(12,14)-prostaglandin J (2) (15d-PGJ (2)) increased the cellular content of the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This work aimed at elucidating the mechanisms of 15d-PGJ (2)-induced p27 accumulation. Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein were altered by 15d-PGJ2 by mechanisms dependent on PI3K/Akt activity. 15d-PGJ (2) prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by blocking its binding to the 85-kDa regulatory subunit of PI3K. These effects of 15d-PGJ (2) were not mimicked by 9,10-dihydro-15-deoxy-Delta(12,14)- prostaglandin J (2), suggesting that 15d-PGJ (2) acts independently of peroxisome proliferator-activated receptor gamma activation and that the alpha,beta-unsaturated carbonyl group in the cyclopentenone ring of 15d-PGJ (2) is a requisite for the observed effects.

  7. 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

  8. Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients

    Directory of Open Access Journals (Sweden)

    Qiu Shuwei

    2013-01-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM is the most common and aggressive brain tumor with poor clinical outcome. Identification and development of new markers could be beneficial for the diagnosis and prognosis of GBM patients. Deregulation of microRNAs (miRNAs or miRs is involved in GBM. Therefore, we attempted to identify and develop specific miRNAs as prognostic and predictive markers for GBM patient survival. Methods Expression profiles of miRNAs and genes and the corresponding clinical information of 480 GBM samples from The Cancer Genome Atlas (TCGA dataset were downloaded and interested miRNAs were identified. Patients’ overall survival (OS and progression-free survival (PFS associated with interested miRNAs and miRNA-interactions were performed by Kaplan-Meier survival analysis. The impacts of miRNA expressions and miRNA-interactions on survival were evaluated by Cox proportional hazard regression model. Biological processes and network of putative and validated targets of miRNAs were analyzed by bioinformatics. Results In this study, 6 interested miRNAs were identified. Survival analysis showed that high levels of miR-326/miR-130a and low levels of miR-323/miR-329/miR-155/miR-210 were significantly associated with long OS of GBM patients, and also showed that high miR-326/miR-130a and low miR-155/miR-210 were related with extended PFS. Moreover, miRNA-323 and miRNA-329 were found to be increased in patients with no-recurrence or long time to progression (TTP. More notably, our analysis revealed miRNA-interactions were more specific and accurate to discriminate and predict OS and PFS. This interaction stratified OS and PFS related with different miRNA levels more detailed, and could obtain longer span of mean survival in comparison to that of one single miRNA. Moreover, miR-326, miR-130a, miR-155, miR-210 and 4 miRNA-interactions were confirmed for the first time as independent predictors for survival by Cox regression model

  9. Down-regulated miR-9 and miR-433 in human gastric carcinoma

    Directory of Open Access Journals (Sweden)

    Nie Na

    2009-06-01

    Full Text Available Abstract Background MircoRNAs(miRNAs are short, endogenously non-coding RNAs. The abnormal expression of miRNAs may be valuable for the diagnosis and treatment of tumors. Methods To screening the special miRNAs in gastric carcinoma, expression level of miRNAs in gastric carcinoma and normal gaster samples were detected by miRNA gene chip. Then, the expressions of miR-9 and miR-433 in gastric carcinoma tissue and SGC7901 cell line were validated by qRT-PCR. GRB2 and RAB34, targets of miR-433 and miR-9 respectively, were detected by Western blot. Results We found 19 miRNAs and 7 miRNAs were down-regulated and up-regulated respectively. Compared with normal gaster samples, our data showed that miR-9 and miR-433 were down-regulated in gastric carcinoma. Meanwhile, we also found that miR-433 and miR-9 regulated the expression levels of GRB2 and RAB34 respectively. Conclusion Our data show miR-9 and miR-433 was down-regulated in gastric carcinoma. The targets of miR-433 and miR-9 were tumor-associated proteins GRB2 and RAB34 respectively. This result provided the related information of miRNAs in gastric carcinoma.

  10. Review of miRNA Technology

    Institute of Scientific and Technical Information of China (English)

    Zhang Tangyao

    2015-01-01

    miRNAs are non-coding RNA molecules exist in eukaryotic with 22 nucleotides. The abnormal expression of miRNAs are also lead to somedisease. The monitoring of cancer related miRNAs, oncomiRs, will help diagnose caners. The main methods to analyzing the profile of miRNA expression fordiagnosing cancer are microarray test and real-time PCR. The the studies on miRomics will bring revolutionary breakthrough to medicine and carcinobiology.

  11. miRNAs Related to Skeletal Diseases.

    Science.gov (United States)

    Seeliger, Claudine; Balmayor, Elizabeth R; van Griensven, Martijn

    2016-09-01

    miRNAs as non-coding, short, double-stranded RNA segments are important for cellular biological functions, such as proliferation, differentiation, and apoptosis. miRNAs mainly contribute to the inhibition of important protein translations through their cleavage or direct repression of target messenger RNAs expressions. In the last decade, miRNAs got in the focus of interest with new publications on miRNAs in the context of different diseases. For many types of cancer or myocardial damage, typical signatures of local or systemically circulating miRNAs have already been described. However, little is known about miRNA expressions and their molecular effect in skeletal diseases. An overview of published studies reporting miRNAs detection linked with skeletal diseases was conducted. All regulated miRNAs were summarized and their molecular interactions were illustrated. This review summarizes the involvement and interaction of miRNAs in different skeletal diseases. Thereby, 59 miRNAs were described to be deregulated in tissue, cells, or in the circulation of osteoarthritis (OA), 23 miRNAs deregulated in osteoporosis, and 107 miRNAs deregulated in osteosarcoma (OS). The molecular influences of miRNAs regarding OA, osteoporosis, and OS were illustrated. Specific miRNA signatures for skeletal diseases are described in the literature. Some overlapped, but also unique ones for each disease exist. These miRNAs may present useful targets for the development of new therapeutic approaches and are candidates for diagnostic evaluations.

  12. The Effect o f Entertaining Fun Athletics Training Program R elated To the Self - Confidence Levels among Children Aged 12 - 14 Years

    Directory of Open Access Journals (Sweden)

    Erkan YARIMKAYA

    2014-12-01

    Full Text Available The aim of this study is to examine the effect of entertaining fun athletics training program on the self - conf i dence levels of children. The sample group of the study is occuring 160 students in 12 - 14 age group from Keçiören Hacı Sabancı Primary School loc ated in Keçiören district of Ankara. Both the experimental and the control group were applied Piers - Harris Self - Confidence test developed by Piers and Harr i s (1984 before and after 8 - week procedure. The SPSS statistical program (version 15.0 was used for data analysis.The research indicates a statistical difference (P<0,05 between the experimental and the control group in terms of post - test. In the compari son of pre - test and post - test results of the experimental group, there is a significant difference between pre - test and post - test results. ( P<0,05. In those comparisons, it was found that the post - test results are higher than pre - test results. As a resul t, in the survey made for inspecting the self - confidence of the children in 12 – 14 age group who are making e ntertaining fun athletics excersises, it is fixed that the entertaining fun athletics excersise applied to the test group effects the self - confide nce level of the kids significiantly. In this context, we can say that e ntertaining fun athletics excersise positively effect the self - confidence properties of the kids in 12 - 14 age group.

  13. Synthesis and Evaluation of the Novel Prostamide, 15-Deoxy, Δ(12,14)-Prostamide J2, as a Selective Antitumor Therapeutic.

    Science.gov (United States)

    Ladin, Daniel A; Soliman, Eman; Escobedo, Rene; Fitzgerald, Timothy L; Yang, Li V; Burns, Colin; Van Dross, Rukiyah

    2017-05-01

    15-deoxy, Δ(12,14)-prostaglandin J2-ethanolamide, also known as 15-deoxy, Δ(12,14)-prostamide J2 (15d-PMJ2) is a novel product of the metabolism of arachidonoyl ethanolamide (AEA) by COX-2. 15d-PMJ2 preferentially induced cell death and apoptosis in tumorigenic A431 keratinocytes and B16F10 melanoma cells compared with nontumorigenic HaCaT keratinocytes and Melan-A melanocytes. Activation of the ER stress execution proteins, PERK and CHOP10, was evaluated to determine whether this process was involved in 15d-PMJ2 cell death. 15d-PMJ2 increased the phosphorylation of PERK and expression of CHOP10 in tumorigenic but not nontumorigenic cells. The known ER stress inhibitors, salubrinal and 4-phenylbutaric acid, significantly inhibited 15d-PMJ2-mediated apoptosis, suggesting ER stress as a primary apoptotic mediator. Furthermore, the reactive double bond present within the cyclopentenone structure of 15d-PMJ2 was identified as a required moiety for the induction of ER stress apoptosis. The effect of 15d-PMJ2 on B16F10 melanoma growth was also evaluated by dosing C57BL/6 mice with 0.5 mg/kg 15d-PMJ2 Tumors of animals treated with 15d-PMJ2 exhibited significantly reduced growth and mean weights compared with vehicle and untreated animals. TUNEL and IHC analysis of tumor tissues showed significant cell death and ER stress in tumors of 15d-PMJ2-treated compared with control group animals. Taken together, these findings suggest that the novel prostamide, 15d-PMJ2, possesses potent antitumor activity in vitro and in vivoMol Cancer Ther; 16(5); 838-49. ©2017 AACR. ©2017 American Association for Cancer Research.

  14. Circulating microRNAs, miR-939, miR-595, miR-519d and miR-494, Identify Cirrhotic Patients with HCC.

    Directory of Open Access Journals (Sweden)

    Francesca Fornari

    Full Text Available The performance of circulating biomarkers for the diagnosis of hepatocellular carcinoma (HCC is sub-optimal. In this study we tested circulating microRNAs as biomarkers for HCC in cirrhotic patients by performing a two stage study: a discovery phase conducted by microarray and a validation phase performed by qRT-PCR in an independent series of 118 patients. Beside miRNAs emerged from the discovery phase, miR-21, miR-221, miR-519d were also tested in the validation setting on the basis of literary and tissue findings. Deregulated microRNAs were assayed in HCC-derived cells in the intracellular compartment, cell culture supernatant and exosomal fraction. Serum and tissue microRNA levels were compared in 14 patients surgically treated for HCC. From the discovery study, it emerged that seven circulating microRNAs were differentially expressed in cirrhotic patients with and without HCC. In the validation set, miR-939, miR-595 and miR-519d were shown to differentiate cirrhotic patients with and without HCC. MiR-939 and miR-595 are independent factors for HCC. ROC curves of miR-939, miR-595 and miR-519d displayed that AUC was higher than AFP. An exosomal secretion of miR-519d, miR-21, miR-221 and miR-1228 and a correlation between circulating and tissue levels of miR-519d, miR-494 and miR-21 were found in HCC patients. Therefore, we show that circulating microRNAs deserve attention as non-invasive biomarkers in the diagnostic setting of HCC and that exosomal secretion contributes to discharging a subset of microRNAs into the extracellular compartment.

  15. Circulating microRNAs, miR-939, miR-595, miR-519d and miR-494, Identify Cirrhotic Patients with HCC

    Science.gov (United States)

    Fornari, Francesca; Ferracin, Manuela; Trerè, Davide; Milazzo, Maddalena; Marinelli, Sara; Galassi, Marzia; Venerandi, Laura; Pollutri, Daniela; Patrizi, Clarissa; Borghi, Alberto; Foschi, Francesco G.; Stefanini, Giuseppe F.; Negrini, Massimo; Bolondi, Luigi; Gramantieri, Laura

    2015-01-01

    The performance of circulating biomarkers for the diagnosis of hepatocellular carcinoma (HCC) is sub-optimal. In this study we tested circulating microRNAs as biomarkers for HCC in cirrhotic patients by performing a two stage study: a discovery phase conducted by microarray and a validation phase performed by qRT-PCR in an independent series of 118 patients. Beside miRNAs emerged from the discovery phase, miR-21, miR-221, miR-519d were also tested in the validation setting on the basis of literary and tissue findings. Deregulated microRNAs were assayed in HCC-derived cells in the intracellular compartment, cell culture supernatant and exosomal fraction. Serum and tissue microRNA levels were compared in 14 patients surgically treated for HCC. From the discovery study, it emerged that seven circulating microRNAs were differentially expressed in cirrhotic patients with and without HCC. In the validation set, miR-939, miR-595 and miR-519d were shown to differentiate cirrhotic patients with and without HCC. MiR-939 and miR-595 are independent factors for HCC. ROC curves of miR-939, miR-595 and miR-519d displayed that AUC was higher than AFP. An exosomal secretion of miR-519d, miR-21, miR-221 and miR-1228 and a correlation between circulating and tissue levels of miR-519d, miR-494 and miR-21 were found in HCC patients. Therefore, we show that circulating microRNAs deserve attention as non-invasive biomarkers in the diagnostic setting of HCC and that exosomal secretion contributes to discharging a subset of microRNAs into the extracellular compartment. PMID:26509672

  16. miRConnect: identifying effector genes of miRNAs and miRNA families in cancer cells.

    Directory of Open Access Journals (Sweden)

    Youjia Hua

    Full Text Available micro(miRNAs 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 on the biological state of the cell and, hence, of the function of the expressed miRNAs. We have compared the large amount of available gene array data on the steady state system of the NCI60 cell lines to two different data sets containing information on the expression of 583 individual miRNAs. In addition, we 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. By focusing on the genes that correlate with the expression of miRNAs without necessarily being direct targets of miRNAs, we have clustered miRNAs into different functional groups. This has resulted in the identification of three novel miRNAs that are linked to the epithelial-to-mesenchymal transition (EMT in addition to the known EMT regulators of the miR-200 miRNA family. In addition, an analysis of gene signatures associated with EMT, c-MYC activity, and ribosomal protein gene expression allowed us to assign different activities to each of the functional clusters of miRNAs. All correlation data are available via a web interface that allows investigators to identify genes whose expression correlates with the expression of single miRNAs or entire miRNA families. miRConnect.org will aid in identifying pathways regulated by miRNAs without requiring specific knowledge of miRNA targets.

  17. miRConnect: identifying effector genes of miRNAs and miRNA families in cancer cells.

    Science.gov (United States)

    Hua, Youjia; Duan, Shiwei; Murmann, Andrea E; Larsen, Niels; Kjems, Jørgen; Lund, Anders H; Peter, Marcus E

    2011-01-01

    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 on the biological state of the cell and, hence, of the function of the expressed miRNAs. We have compared the large amount of available gene array data on the steady state system of the NCI60 cell lines to two different data sets containing information on the expression of 583 individual miRNAs. In addition, we 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. By focusing on the genes that correlate with the expression of miRNAs without necessarily being direct targets of miRNAs, we have clustered miRNAs into different functional groups. This has resulted in the identification of three novel miRNAs that are linked to the epithelial-to-mesenchymal transition (EMT) in addition to the known EMT regulators of the miR-200 miRNA family. In addition, an analysis of gene signatures associated with EMT, c-MYC activity, and ribosomal protein gene expression allowed us to assign different activities to each of the functional clusters of miRNAs. All correlation data are available via a web interface that allows investigators to identify genes whose expression correlates with the expression of single miRNAs or entire miRNA families. miRConnect.org will aid in identifying pathways regulated by miRNAs without requiring specific knowledge of miRNA targets.

  18. Tenkostěnný sendvičový systém z vysokohodnotného betonu vyztuženého čedičovými vlákny

    DEFF Research Database (Denmark)

    Hodicky, Kamil; Hulin, Thomas

    2013-01-01

    The paper presents a new thin-walled high performance concrete (HPC) sandwich panel system reinforced with basalt fiber-reinforced plastic (BFRP). System is characteristic with a high structural resistance, thermal resistance and environmental friendliness. The newly developed shear connecting...

  19. Reference miRNAs for miRNAome analysis of urothelial carcinomas.

    Directory of Open Access Journals (Sweden)

    Nadine Ratert

    Full Text Available BACKGROUND/OBJECTIVE: Reverse transcription quantitative real-time PCR (RT-qPCR is widely used in microRNA (miRNA expression studies on cancer. To compensate for the analytical variability produced by the multiple steps of the method, relative quantification of the measured miRNAs is required, which is based on normalization to endogenous reference genes. No study has been performed so far on reference miRNAs for normalization of miRNA expression in urothelial carcinoma. The aim of this study was to identify suitable reference miRNAs for miRNA expression studies by RT-qPCR in urothelial carcinoma. METHODS: Candidate reference miRNAs were selected from 24 urothelial carcinoma and normal bladder tissue samples by miRNA microarrays. The usefulness of these candidate reference miRNAs together with the commonly for normalization purposes used small nuclear RNAs RNU6B, RNU48, and Z30 were thereafter validated by RT-qPCR in 58 tissue samples and analyzed by the algorithms geNorm, NormFinder, and BestKeeper. PRINCIPAL FINDINGS: Based on the miRNA microarray data, a total of 16 miRNAs were identified as putative reference genes. After validation by RT-qPCR, miR-101, miR-125a-5p, miR-148b, miR-151-5p, miR-181a, miR-181b, miR-29c, miR-324-3p, miR-424, miR-874, RNU6B, RNU48, and Z30 were used for geNorm, NormFinder, and BestKeeper analyses that gave different combinations of recommended reference genes for normalization. CONCLUSIONS: The present study provided the first systematic analysis for identifying suitable reference miRNAs for miRNA expression studies of urothelial carcinoma by RT-qPCR. Different combinations of reference genes resulted in reliable expression data for both strongly and less strongly altered miRNAs. Notably, RNU6B, which is the most frequently used reference gene for miRNA studies, gave inaccurate normalization. The combination of four (miR-101, miR-125a-5p, miR-148b, and miR-151-5p or three (miR-148b, miR-181b, and miR-874

  20. Physical and underway data collected aboard the ATLANTIS during cruise AT15-58 in the North Pacific Ocean from 2009-12-14 to 2010-01-03 (NODC Accession 0103914)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC accession 0103914 includes physical and underway data collected aboard the ATLANTIS during cruise AT15-58 in the North Pacific Ocean from 2009-12-14 to...

  1. Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells.

    Science.gov (United States)

    Steinsbø, Øyvind; Henry Dunand, Carole J; Huang, Min; Mesin, Luka; Salgado-Ferrer, Marlene; Lundin, Knut E A; Jahnsen, Jørgen; Wilson, Patrick C; Sollid, Ludvig M

    2014-06-09

    Coeliac disease (CD), an enteropathy caused by cereal gluten ingestion, is characterized by CD4(+) T cells recognizing deamidated gluten and by antibodies reactive to gluten or the self-antigen transglutaminase 2 (TG2). TG2-specific immunoglobulin A (IgA) of plasma cells (PCs) from CD lesions have limited somatic hypermutation (SHM). Here we report that gluten-specific IgA of lesion-resident PCs share this feature. Monoclonal antibodies were expression cloned from single PCs of patients either isolated from cultures with reactivity to complex deamidated gluten antigen or by sorting with gluten peptide tetramers. Typically, the antibodies bind gluten peptides related to T-cell epitopes and many have higher reactivity to deamidated peptides. There is restricted VH and VL combination and usage among the antibodies. Limited SHM suggests that a common factor governs the mutation level in PCs producing TG2- and gluten-specific IgA. The antibodies have potential use for diagnosis of CD and for detection of gluten.

  2. The Tumor Cytosol miRNAs, Fluid miRNAs and Exosome miRNAs in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xin eQin

    2015-01-01

    Full Text Available The focus of this review is to provide an update on the progress of microRNAs (miRNAs as potential biomarkers for lung cancer. miRNAs are single-stranded, small noncoding RNAs that regulate gene expression and show tissue-specific signatures. Accumulating evidence indicates that miRNA expression patterns represent the in vivo status in physiology and disease. Moreover, miRNAs are stable in serum and other clinically convenient and available tissue sources, so they are being developed as biomarkers for cancer and other diseases. Cancer is currently the primary driver of the field, but miRNA biomarkers are being developed for many other diseases such as cardiovascular and central nervous system diseases. Here we examine the framework and scope of the miRNA landscape as it specifically relates to the translation of miRNA expression patterns/signatures into biomarkers for developing diagnostics for lung cancer. We focus on examining tumor cytosol miRNAs, fluid miRNAs, and exosome miRNAs in lung cancer, the connections among these miRNAs, and the potential of miRNA biomarkers for the development of diagnostics. In lung cancer, miRNAs have been studied in both cell populations and in the circulation. However, a major challenge is to develop biomarkers to monitor cancer development and to identify circulating miRNAs that are linked to cancer stage. Importantly, the fact that miRNAs can be successfully harvested from biological fluids allows for the development of biofluid biopsies, in which miRNAs as circulating biomarkers can be captured and analyzed ex vivo. Our hope is that these minimally invasive entities provide a window to the in vivo milieu of the patients without the need for costly, complex invasive procedures, rapidly moving miRNAs from research to the clinic.

  3. Mi ángel protector

    OpenAIRE

    Alvarado Calvache, Marian Seinef; Pontificia Universidad Javeriana, Cali

    2013-01-01

    Un día, una hora, un minuto o quizás un segundo. Cuando se trata de tomar decisiones, si no te das prisa puedes arrepentirte el resto de tu vida. ¿Una prueba de esto? Bueno, aquí está mi historia. Tengo vagos recuerdos de lo que pasó ese día. Pero el sentimiento que me invadió cuando desperté sola, en un hospital y con mi ropa ensangrentada, es difícil de olvidar aun cuando solo tenía ocho años. 22 de Abril de 2002, 7:00 p.m. – Chao mami, le dije, mientras me subía al carro junto con mi padre...

  4. Identification of miRNAs and miRNA-mediated regulatory pathways in Carica papaya.

    Science.gov (United States)

    Liang, Gang; Li, Yang; He, Hua; Wang, Fang; Yu, Diqiu

    2013-10-01

    Plant microRNAs (miRNAs) post-transcriptionally regulate target gene expression to modulate growth and development and biotic and abiotic stress responses. By analyzing small RNA deep sequencing data in combination with the genome sequence, we identified 75 conserved miRNAs and 11 novel miRNAs. Their target genes were also predicted. For most conserved miRNAs, the miRNA-target pairs were conserved across plant species. In addition to these conserved miRNA-target pairs, we also identified some papaya-specific miRNA-target regulatory pathways. Both miR168 and miR530 target the Argonaute 1 gene, indicating a second autoregulatory mechanism for miRNA regulation. A non-conserved miRNA was mapped within an intron of Dicer-like 1 (DCL1), suggesting a conserved homeostatic autoregulatory mechanism for DCL1 expression. A 21-nt miRNA triggers secondary siRNA production from its target genes, nucleotide-binding site leucine-rich repeat protein genes. Certain phased-miRNAs were processed from their conserved miRNA precursors, indicating a putative miRNA evolution mechanism. In addition, we identified a Carica papaya-specific miRNA that targets an ethylene receptor gene, implying its function in the ethylene signaling pathway. This work will also advance our understanding of miRNA functions and evolution in plants.

  5. New miRNAs cloned from neuroblastoma

    Directory of Open Access Journals (Sweden)

    Glatting Karl-Heinz

    2008-01-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are a novel class of gene expression regulators implicated in cancer biology. Neuroblastoma (NB is an embryonal tumour consisting of neural crest-derived undifferentiated cells and is characterised by variable clinical courses ranging from spontaneous regression to therapy-resistant progression. Recent advances identified a subset of miRNAs with putative function in NB biology. However, the full repertoire of miRNAs expressed in NBs is not available. Results We describe miRNA profiles of 13 NB specimens and 2 NB cell lines as determined by miRNA cloning. A total of 3153 sequences were sequenced and analysed by a miRNA prediction tool (miRpredict. Our library covered 27% miRNAs known to date. 39 reads corresponding to 25 individual sequences were classified as novel miRNAs, including miRNA* species of 10 known miRNAs. Expression of 5 new miRNA* forms and 8 individual sequences was supported by Northern blotting. Most of the novel miRNA genes are not related to each other and do not share homology with the annotated sequences in the public miRNA database, but they are conserved within mammals or have close homologues in primates genomes. Conclusion We provide evidence for 29 new miRNA and miRNA-like sequences (24 novel sequences and 5 miRNAs discovered initially in other species. Some of these newly identified sequences reside within frequently altered chromosomal regions in NB tumours and may play a role in NB biology.

  6. Fundamental characteristics of the expressed immunoglobulin VH and VL repertoire in different canine breeds in comparison with those of humans and mice.

    Science.gov (United States)

    Steiniger, Sebastian C J; Dunkle, William E; Bammert, Gary F; Wilson, Thomas L; Krishnan, Abhiram; Dunham, Steven A; Ippolito, Gregory C; Bainbridge, Graeme

    2014-05-01

    Complementarity determining regions (CDR) are responsible for binding antigen and provide substantial diversity to the antibody repertoire, with VH CDR3 of the immunoglobulin variable heavy (VH) domain playing a dominant role. In this study, we examined 1200 unique canine VH and 500 unique variable light (VL) sequences of large and small canine breeds derived from peripheral B cells. Unlike the human and murine repertoire, the canine repertoire is heavily dominated by the Canis lupus familiaris IGHV1 subgroup, evolutionarily closest to the human IGHV3 subgroup. Our studies clearly show that the productive canine repertoire of all analyzed breeds shows similarities to both human and mouse; however, there are distinct differences in terms of VH CDR3 length and amino acid paratope composition. In comparison with the human and murine antibody repertoire, canine VH CDR3 regions are shorter in length than the human counterparts, but longer than the murine VH CDR3. Similar to corresponding human and mouse VH CDR3, the amino acids at the base of the VH CDR3 loop are strictly conserved. For identical CDR positions, there were significant changes in chemical paratope composition. Similar to human and mouse repertoires, the neutral amino acids tyrosine, glycine and serine dominate the canine VH CDR3 interval (comprising 35%) although the interval is nonetheless relatively depleted of tyrosine when compared to human and mouse. Furthermore, canine VH CDR3 displays an overrepresentation of the neutral amino acid threonine and the negatively charged aspartic acid while proline content is similar to that in the human repertoire. In general, the canine repertoire shows a bias towards small, negatively charged amino acids. Overall, this analysis suggests that functional canine therapeutic antibodies can be obtained from human and mouse sequences by methods of speciation and affinity maturation.

  7. Fission product yield distribution in the 12, 14, and 16 MeV bremsstrahlung-induced fission of {sup 232}Th

    Energy Technology Data Exchange (ETDEWEB)

    Naik, H. [Bhabha Atomic Research Centre, Radiochemistry Division, Mumbai (India); Kyungpook National University, Department of Physics and Center for High Energy Physics, Daegu (Korea, Republic of); Kim, G.N.; Kim, K. [Kyungpook National University, Department of Physics and Center for High Energy Physics, Daegu (Korea, Republic of); Schwengner, R.; John, R.; Massarczyk, R.; Junghans, A.; Wagner, A. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Goswami, A. [Bhabha Atomic Research Centre, Radiochemistry Division, Mumbai (India)

    2015-11-15

    The absolute cumulative yields of various fission products in the 12, 14, and 16 MeV bremsstrahlung-induced fission of {sup 232}Th were determined using a recoil catcher and an off-line γ -ray spectrometric technique using the ELBE electron linac of Helmholtz-Zentrum Dresden-Rossendorf in Dresden, Germany. The mass chain yields were obtained from the absolute cumulative yields by correcting the charge distribution. The peak-to-valley ratio, average light mass (left angle A{sub L} right angle) and heavy mass (left angle A{sub H} right angle) values, and average number of neutrons (left angle n right angle {sub exp}) in the bremsstrahlung-induced fission of {sup 232}Th at different excitation energies were obtained from the mass chain yield data. The present study and existing literature data for the {sup 232}Th(γ, f) reaction are compared with similar data for the {sup 238}U(γ, f) reaction at various excitation energies, and surprisingly different behavior was found in the two fissioning systems. (orig.)

  8. The PPAR-γ Agonist 15-Deoxy-Δ12,14-Prostaglandin J2 Attenuates Microglial Production of IL-12 Family Cytokines: Potential Relevance to Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Jihong Xu

    2008-01-01

    Full Text Available Accumulation of amyloid-β peptide (Aβ appears to contribute to the pathogenesis of Alzheimer's disease (AD. Therapeutic hope for the prevention or removal of Aβ deposits has been placed in strategies involving immunization against the Aβ peptide. Initial Aβ immunization studies in animal models of AD showed great promise. However, when this strategy was attempted in human subjects with AD, an unacceptable degree of meningoencephalitis occurred. It is generally believed that this adverse outcome resulted from a T-cell response to Aβ. Specifically, CD4+ Th1 and Th17 cells may contribute to severe CNS inflammation and limit the utility of Aβ immunization in the treatment of AD. Interleukin (IL-12 and IL-23 play critical roles in the development of Th1 and Th17 cells, respectively. In the present study, Aβ1−42 synergistically elevated the expression of IL-12 and IL-23 triggered by inflammatory activation of microglia, and the peroxisome proliferator-activated receptor (PPAR-γ agonist 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2 effectively blocked the elevation of these proinflammatory cytokines. Furthermore, 15d-PGJ2 suppressed the Aβ-related synergistic induction of CD14, MyD88, and Toll-like receptor 2, molecules that play critical roles in neuroinflammatory conditions. Collectively, these studies suggest that PPAR-γ agonists may be effective in modulating the development of AD.

  9. A Euploid Line of Human Embryonic Stem Cells Derived from a 43,XX,dup(9q),+12,-14,-15,-18,-21 Embryo

    Science.gov (United States)

    Fonseca, Simone Aparecida Siqueira; Costas, Roberta Montero; Morato-Marques, Mariana; Costa, Silvia; Alegretti, Jose Roberto; Rosenberg, Carla; da Motta, Eduardo Leme Alves; Serafini, Paulo C.; Pereira, Lygia V.

    2015-01-01

    Aneuploid embryos diagnosed by FISH-based preimplantation genetic screening (PGS) have been shown to yield euploid lines of human embryonic stem cells (hESCs) with a relatively high frequency. Given that the diagnostic procedure is usually based on the analysis of 1–2 blastomeres of 5 to 10-cell cleavage-stage embryos, mosaicism has been a likely explanation for the phenomena. However, FISH-based PGS can have a significant rate of misdiagnosis, and therefore some of those lines may have been derived from euploid embryos misdiagnosed as aneuploid. More recently, coupling of trophectoderm (TE) biopsy at the blastocyst stage and array-CGH lead to a more informative form of PGS. Here we describe the establishment of a new line of hESCs from an embryo with a 43,XX,dup(9q),+12,-14,-15,-18,-21 chromosomal content based on array-CGH of TE biopsy. We show that, despite the complex chromosomal abnormality, the corresponding hESC line BR-6 is euploid (46,XX). Single nucleotide polymorphism analysis showed that the embryo´s missing chromosomes were not duplicated in BR-6, suggesting the existence of extensive mosaicism in the TE lineage. PMID:26540511

  10. Complex translocation t(1;12;14)(q42;q14;q32) and HMGA2 deletion in a fetus presenting growth delay and bilateral cataracts.

    Science.gov (United States)

    Raymond, Laure; Francou, Bruno; Petit, François; Tosca, Lucie; Briand-Suleau, Audrey; Metay, Corinne; Martinovic, Jelena; Cordier, Anne-Gaël; Benachi, Alexandra; Pineau, Dominique; Guiochon-Mantel, Anne; Goossens, Michel; Tachdjian, Gérard; Brisset, Sophie

    2015-11-01

    We report the prenatal detection of a de novo unbalanced complex chromosomal rearrangement (CCR), in a fetus with growth delay and bilateral cataracts. Standard karyotype and FISH analyses on amniotic fluid revealed a complex de novo translocation, resulting in a 46,XY,t(1;12;14)(q42;q14;q32) karyotype. CGH-array showed a significant deletion of 387  kb at 12q14.3, at a distance of only 200-700 kb from the breakpoint at 12q14, which encompassed the HMGA2 gene and occurred de novo. Although 12q14 microdeletions are associated with growth delay in several reports in the literature, we present here the smallest deletion prenatally detected, and we detail the clinical description of the fetus. The correlation between cataracts and this complex genotype is puzzling. Among the genes disrupted by the breakpoint in 12q14, GRIP1 has been associated with abnormal eye development in mice, including lens degeneration. Interestingly, HMGA2 is expressed in the mouse's developing lens, and its expression is decreased in lens of elderly humans, correlated with the severity of lens opacity. In this report, we refine the link between HMGA2 loss of function and growth delay during prenatal development. We also discuss the correlation between cataracts and genotype in this unbalanced CCR case of unexpected complexity.

  11. Sexual risk attitudes and intentions of youth aged 12-14 years: survey comparisons of parent-teen prevention and control groups.

    Science.gov (United States)

    Lederman, Regina P; Chan, Wenyaw; Roberts-Gray, Cynthia

    2004-01-01

    In this study, the authors compared differences in sexual risk attitudes and intentions for three groups of youth (experimental program, n = 90; attention control, n = 80; and nonparticipant control, n = 634) aged 12-14 years. Two student groups participated with their parents in programs focused on strengthening family interaction and prevention of sexual risks, HIV, and adolescent pregnancy. Surveys assessed students' attitudes and intentions regarding early sexual and other health-risk behaviors, family interactions, and perceived parental disapproval of risk behaviors. The authors used general linear modeling to compare results. The experimental prevention program differentiated the total scores of the 3 groups (p < .05). A similar result was obtained for student intentions to avoid sex (p < .01). Pairwise comparisons showed the experimental program group scored higher than the nonparticipant group on total scores (p < .01) and on students' intention to avoid sex (p < .01). The results suggest this novel educational program involving both parents and students offers a promising approach to HIV and teen pregnancy prevention.

  12. 15-Deoxy-Delta(12,14)-prostaglandin-J(2) reveals a new pVHL-independent, lysosomal-dependent mechanism of HIF-1alpha degradation.

    Science.gov (United States)

    Olmos, Gemma; Arenas, María I; Bienes, Raquel; Calzada, María Jose; Aragonés, Julián; Garcia-Bermejo, Maria Laura; Landazuri, Manuel O; Lucio-Cazaña, Javier

    2009-07-01

    Hypoxia-inducible factor-1alpha (HIF-1alpha) protein is degraded under normoxia by its association to von Hippel-Lindau protein (pVHL) and further proteasomal digestion. However, human renal cells HK-2 treated with 15-deoxy-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) accumulate HIF-1alpha in normoxic conditions. Thus, we aimed to investigate the mechanism involved in this accumulation. We found that 15d-PGJ(2) induced an over-accumulation of HIF-1alpha in RCC4 cells, which lack pVHL and in HK-2 cells treated with inhibitors of the pVHL-proteasome pathway. These results indicated that pVHL-proteasome-independent mechanisms are involved, and therefore we aimed to ascertain them. We have identified a new lysosomal-dependent mechanism of HIF-1alpha degradation as a target for 15d-PGJ(2) based on: (1) HIF-1alpha colocalized with the specific lysosomal marker Lamp-2a, (2) 15d-PGJ(2) inhibited the activity of cathepsin B, a lysosomal protease, and (3) inhibition of lysosomal activity did not result in over-accumulation of HIF-1alpha in 15d-PGJ(2)-treated cells. Therefore, expression of HIF-1alpha is also modulated by lysosomal degradation.

  13. 15-Deoxy-Delta12,14-prostaglandin J2 modifies components of the proteasome and inhibits inflammatory responses in human endothelial cells

    Directory of Open Access Journals (Sweden)

    Simone Marcone

    2016-10-01

    Full Text Available 15-Deoxy-delta12,14-prostaglandin J2 (15d-PGJ2 is an electrophilic lipid mediator derived from PGD2 with potent anti-inflammatory effects. These are likely to be due to the covalent modification of cellular proteins, via a reactive α,β-unsaturated carbonyl group in its cyclopentenone ring. This study was carried out to identify novel cellular target(s for covalent modification by 15d-PGJ2 and to investigate the anti-inflammatory effects of the prostaglandin on endothelial cells. The data presented here show that 15d-PGJ2 modifies and inhibits components of the proteasome and consequently inhibits the activation of the NF-kB pathway in response to TNF-a. This, in turn, inhibits the adhesion and migration of monocytes toward activated endothelial cells, by reducing the expression of adhesion molecules and chemokines in the endothelial cell. The effects are consistent with the covalent modification of 13 proteins in the 19S particle of the proteasome identified by mass spectrometry and the suppression of proteasome function, and were similar to the effects seen with a known proteasome inhibitor (MG132. The ubiquitin-proteasome system has been implicated in the regulation of several inflammatory processes and the observation that 15d-PGJ2 profoundly affects the proteasome functions in human endothelial cell suggests that 15d-PGJ2 may regulate the progression of inflammatory disorders such as atherosclerosis.

  14. Induction of heme oxygenase-1 in normal and malignant B lymphocytes by 15-deoxy-Δ12, 14-prostaglandin J2 requires Nrf2

    Science.gov (United States)

    Bancos, Simona; Baglole, Carolyn J.; Rahman, Irfan; Phipps, Richard P.

    2011-01-01

    Heme-oxygenase-1 (HO-1) is induced in response to oxidative stress and is believed to be a cytoprotective and anti-inflammatory enzyme. It is unknown whether normal or malignant human B lineage cells express HO-1. 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2) is an interesting electrophilic lipid mediator able to increase oxidative stress in B cells. Here, we tested normal and malignant human B lineage cells for their ability to express HO-1 in response to 15d-PGJ2, as well as the signaling pathways required for HO-1 expression. 15d-PGJ2 potently induced HO-1 protein expression in normal and malignant B cells. Malignant B cells exhibited a greater induction of HO-1 protein compared to normal B lymphocytes. Using siRNA directed against the transcription factor Nrf2 and B cells isolated from Nrf2-deficient mice, we show that HO-1 induction by 15d-PGJ2 is dependent on Nrf2. These results show that, compared to normal B lymphocytes, malignant B cells have a greater capacity to increase their HO-1 protein levels in response to 15d-PGJ2. We speculate that the ability to highly express HO-1 by malignant B cells could confer a survival advantage. PMID:20064636

  15. Induction of heme oxygenase-1 in normal and malignant B lymphocytes by 15-deoxy-Delta(12,14)-prostaglandin J(2) requires Nrf2.

    Science.gov (United States)

    Bancos, Simona; Baglole, Carolyn J; Rahman, Irfan; Phipps, Richard P

    2010-01-01

    Heme-oxygenase-1 (HO-1) is induced in response to oxidative stress and is believed to be a cytoprotective and anti-inflammatory enzyme. It is unknown whether normal or malignant human B-lineage cells express HO-1. 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is an interesting electrophilic lipid mediator able to increase oxidative stress in B cells. Here, we tested normal and malignant human B-lineage cells for their ability to express HO-1 in response to 15d-PGJ(2), as well as the signaling pathways required for HO-1 expression. 15d-PGJ(2) potently induced HO-1 protein expression in normal and malignant B cells. Malignant B cells exhibited a greater induction of HO-1 protein compared to normal B lymphocytes. Using siRNA directed against the transcription factor Nrf2 and B cells isolated from Nrf2-deficient mice, we show that HO-1 induction by 15d-PGJ(2) is dependent on Nrf2. These results show that, compared to normal B lymphocytes, malignant B cells have a greater capacity to increase their HO-1 protein levels in response to 15d-PGJ(2). We speculate that the ability to highly express HO-1 by malignant B cells could confer a survival advantage.

  16. Synthesis and Crystal Structure of Dicyanamide(5,7,7,12,14,14-Hexamethyl-1,4,8,11-tetraazacyclotetradecane) Copper(II) Percholatehydrate

    Institute of Scientific and Technical Information of China (English)

    李宝宗; 王寿武; 李宝龙; 张勇

    2004-01-01

    The copper(II) complex [Cu(teta)N(CN)2](ClO4)·H2O (teta = 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane) has been synthesized and the crystal structure was determined by single-crystal X-ray diffraction.Crystal data: C18H38ClCuN7O5,monoclinic,space group P21/n,a = 8.796(3),b = 11.885(4),c = 23.054(9)(A),β = 97.540(4)o,V = 2389.3(15)(A)3,Mr = 531.54,Z = 4,Dc = 1.478 g/cm3,F(000) = 1124,μ = 1.070 mm-1,the final R = 0.0566 and Wr = 0.1162 for 4749 observed reflections (I > 2б(I)).The center copper ion is coordinated by five nitrogen atoms in a square pyramidal geometry,with four from the macrocyclic ligand teta and the other one from a nitrile nitrogen atom of dicyanamide which is coordinated to the metal atoms as uni-dentate manner via nitrile nitrogen atom.

  17. Protonated 14-membered 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetrazacyclotetradeca-7,14-diene Salts and Their Biological Activity

    Directory of Open Access Journals (Sweden)

    Siti Fairus M. Yusoff

    2013-01-01

    Full Text Available The 14-membered heterocyclic 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetrazacyclotetradeca-7,14-diene, [(Me6[14]N4diene], salts with structural formula of [(Me6[14]N4diene]Br2(H2O2, [(Me6[14]N4dieneCl2](H2O3, Me6[14]N4diene.(ClO42, Me6[14]N4diene.(PF62¬  and   Me6[14]N4diene.(NO32   have been  synthesized without the necessity of a template. The salts were characterized by FTIR, and NMR spectroscopic techniques. X-ray study showed that the macrocyclic cation consists of a pair of protonated amines and azomethine nitrogen atoms located diagonally and opposite to each other. Only the macrocylic bromide and perchlorate salts showed activity against gram-positive E. faecalis and gram-negative E. Coli.

  18. The eicosapentaenoic acid metabolite 15-deoxy-δ(12,14-prostaglandin J3 increases adiponectin secretion by adipocytes partly via a PPARγ-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Jennifer Lefils-Lacourtablaise

    Full Text Available The intake of ω-3 polyunsaturated fatty acids (PUFAs, which are abundant in marine fish meat and oil, has been shown to exert many beneficial effects. The mechanisms behind those effects are numerous, including interference with the arachidonic acid cascade that produces pro-inflammatory eicosanoids, formation of novel bioactive lipid mediators, and change in the pattern of secreted adipocytokines. In our study, we show that eicosapentaenoic acid (EPA increases secreted adiponectin from 3T3-L1 adipocytes and in plasma of mice as early as 4 days after initiation of an EPA-rich diet. Using 3T3-L1 adipocytes, we report for the first time that 15-deoxy-δ(12,14-PGJ3 (15d-PGJ3, a product of EPA, also increases the secretion of adiponectin. We demonstrate that the increased adiponectin secretion induced by 15d-PGJ3 is partially peroxisome proliferator-activated receptor-gamma (PPAR-γ-mediated. Finally, we show that 3T3-L1 adipocytes can synthesize 15d-PGJ3 from EPA. 15d-PGJ3 was also detected in adipose tissue from EPA-fed mice. Thus, these studies provide a novel mechanism(s for the therapeutic benefits of ω-3 polyunsaturated fatty acids dietary supplementation.

  19. Challenges in the miRNA research

    DEFF Research Database (Denmark)

    Singh, Tiratha Raj; Gupta, Arun; Suravajhala, Prashanth

    2013-01-01

    While it is known that the human genes are regulated by microRNAs (miRNAs), recent links with cancer and other diseases have widely caught interest. With several bioinformatics platforms and approaches on rise that has led to discovery of human miRNAs, validation and need for understanding miRNAs...

  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. Stability engineering of anti-EGFR scFv antibodies by rational design of a lambda-to-kappa swap of the VL framework using a structure-guided approach.

    Science.gov (United States)

    Lehmann, Andreas; Wixted, Josephine H F; Shapovalov, Maxim V; Roder, Heinrich; Dunbrack, Roland L; Robinson, Matthew K

    2015-01-01

    Phage-display technology facilitates rapid selection of antigen-specific single-chain variable fragment (scFv) antibodies from large recombinant libraries. ScFv antibodies, composed of a VH and VL domain, are readily engineered into multimeric formats for the development of diagnostics and targeted therapies. However, the recombinant nature of the selection strategy can result in VH and VL domains with sub-optimal biophysical properties, such as reduced thermodynamic stability and enhanced aggregation propensity, which lead to poor production and limited application. We found that the C10 anti-epidermal growth factor receptor (EGFR) scFv, and its affinity mutant, P2224, exhibit weak production from E. coli. Interestingly, these scFv contain a fusion of lambda3 and lambda1 V-region (LV3 and LV1) genes, most likely the result of a PCR aberration during library construction. To enhance the biophysical properties of these scFvs, we utilized a structure-based approach to replace and redesign the pre-existing framework of the VL domain to one that best pairs with the existing VH. We describe a method to exchange lambda sequences with a more stable kappa3 framework (KV3) within the VL domain that incorporates the original lambda DE-loop. The resulting scFvs, C10KV3_LV1DE and P2224KV3_LV1DE, are more thermodynamically stable and easier to produce from bacterial culture. Additionally, C10KV3_LV1DE and P2224KV3_LV1DE retain binding affinity to EGFR, suggesting that such a dramatic framework swap does not significantly affect scFv binding. We provide here a novel strategy for redesigning the light chain of problematic scFvs to enhance their stability and therapeutic applicability.

  2. Challenges in the miRNA research

    DEFF Research Database (Denmark)

    Singh, Tiratha Raj; Gupta, Arun; Suravajhala, Prashanth

    2013-01-01

    RNAs from their progenitor messenger RNAs (mRNAs) have arisen. Furthermore, the miRNAs are known to have synergism involving regulation of their condition-specific target genes (mRNAs). In this review, we provide a bioinformatics approach of the miRNAs and their challenges with respect to annotation......While it is known that the human genes are regulated by microRNAs (miRNAs), recent links with cancer and other diseases have widely caught interest. With several bioinformatics platforms and approaches on rise that has led to discovery of human miRNAs, validation and need for understanding mi...

  3. Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors.

    Science.gov (United States)

    Thokala, Radhika; Olivares, Simon; Mi, Tiejuan; Maiti, Sourindra; Deniger, Drew; Huls, Helen; Torikai, Hiroki; Singh, Harjeet; Champlin, Richard E; Laskowski, Tamara; McNamara, George; Cooper, Laurence J N

    2016-01-01

    Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using VH and VL chains derived from different CD123-specific mAbs to generate a panel of CAR+ T cells. While all CARs exhibited specificity to CD123, one VH and VL combination had reduced lysis of normal hematopoietic stem cells. This CAR's in vivo anti-tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR+ T cells. These data help support the use of CD123-specific CARs for treatment of CD123+ hematologic malignancies.

  4. Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors

    Science.gov (United States)

    Olivares, Simon; Mi, Tiejuan; Maiti, Sourindra; Deniger, Drew; Huls, Helen; Torikai, Hiroki; Singh, Harjeet; Champlin, Richard E.; Laskowski, Tamara; McNamara, George; Cooper, Laurence J. N.

    2016-01-01

    Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using VH and VL chains derived from different CD123-specific mAbs to generate a panel of CAR+ T cells. While all CARs exhibited specificity to CD123, one VH and VL combination had reduced lysis of normal hematopoietic stem cells. This CAR’s in vivo anti-tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR+ T cells. These data help support the use of CD123-specific CARs for treatment of CD123+ hematologic malignancies. PMID:27548616

  5. Cyclopentenone prostaglandin, 15-deoxy-Delta12,14-PGJ2, is metabolized by HepG2 cells via conjugation with glutathione.

    Science.gov (United States)

    Brunoldi, Enrico M; Zanoni, Giuseppe; Vidari, Giovanni; Sasi, Soumya; Freeman, Michael L; Milne, Ginger L; Morrow, Jason D

    2007-10-01

    15-deoxy-Delta12,14-prostaglandin J2 (15-d-PGJ2) is a dehydration product of PGD2. This compound possesses a highly reactive polyunsaturated carbonyl moiety that is a substrate for Michael addition with thiol-containing biomolecules such as glutathione and cysteine residues on proteins. By reacting with glutathione and proteins, 15-d-PGJ2 is believed to exert potent biological activity. Despite the large number of publications that have ascribed bioactivity to this molecule, it is not known to what extent 15-d-PGJ2 is formed in vivo. Levels of free 15-d-PGJ2 measured in human biological fluids such as urine are low, and the biological importance of this compound has thus been questioned. Because of its reactivity, we hypothesized that 15-d-PGJ2 is present in vivo primarily as a Michael conjugate. Therefore, we undertook a detailed study of the metabolism of this compound in HepG2 cells that are known to metabolize other cyclopentenone eicosanoids. We report that HepG2 cells primarily convert 15-d-PGJ2 to a glutathione conjugate in which the carbonyl at C-11 is reduced to a hydroxyl. Subsequently, the glutathione portion of the molecule is hydrolyzed with loss of glutamic acid and glycine resulting in a cysteine conjugate. These findings confirm a general route for the metabolism of cyclopentenone eicosanoids in HepG2 cells and may pave the way for new insights regarding the formation of 15-d-PGJ2 in vivo.

  6. Inhibition of IkappaB kinase and IkappaB phosphorylation by 15-deoxy-Delta(12,14)-prostaglandin J(2) in activated murine macrophages.

    Science.gov (United States)

    Castrillo, A; Díaz-Guerra, M J; Hortelano, S; Martín-Sanz, P; Boscá, L

    2000-03-01

    Activation of the macrophage cell line RAW 264.7 with lipopolysaccharide (LPS) and gamma interferon (IFN-gamma) induces the expression of gene products involved in host defense, among them type 2 nitric oxide synthase. Treatment of cells with 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2)) inhibited the LPS- and IFN-gamma-dependent synthesis of NO, a process that was not antagonized by similar concentrations of prostaglandin J(2), prostaglandin E(2), or rosiglitazone, a peroxisomal proliferator-activated receptor gamma ligand. Incubation of activated macrophages with 15dPGJ(2) inhibited the degradation of IkappaBalpha and IkappaBbeta and increased their levels in the nuclei. NF-kappaB activity, as well as the transcription of NF-kappaB-dependent genes, such as those encoding type 2 nitric oxide synthase and cyclooxygenase 2, was impaired under these conditions. Analysis of the steps leading to IkappaB phosphorylation showed an inhibition of IkappaB kinase by 15dPGJ(2) in cells treated with LPS and IFN-gamma, resulting in an impaired phosphorylation of IkappaBalpha, at least in the serine 32 residue required for targeting and degradation of this protein. Incubation of partially purified activated IkappaB kinase with 2 microM 15dPGJ(2) reduced by 83% the phosphorylation in serine 32 of IkappaBalpha, suggesting that this prostaglandin exerts direct inhibitory effects on the activity of the IkappaB kinase complex. These results show rapid actions of 15dPGJ(2), independent of peroxisomal proliferator receptor gamma activation, in macrophages challenged with low doses of LPS and IFN-gamma.

  7. 15-Deoxy-Δ{sup 12,14}-prostaglandin J{sub 2} inhibits IL-13 production in T cells via an NF-κB-dependent mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, Marie-Christine; Tremblay, Sarah [Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke (QC), Canada J1K 2R1 (Canada); Dumais, Nancy, E-mail: nancy.dumais@usherbrooke.ca [Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke (QC), Canada J1K 2R1 (Canada)

    2013-02-15

    Highlights: ► 15d-PGJ{sub 2} decreased IL-13 mRNA transcription and secretion in activated T cells. ► IL-13 inhibition by 15d-PGJ{sub 2} is independent of PPAR-γ. ► The nuclear factor-κB mediates the 15d-PGJ{sub 2}-dependent down regulation of IL-13. -- Abstract: Interleukin (IL)-13 is a cytokine produced by activated CD4{sup +} T cells that plays a critical role in promoting allergic responses and tumor cell growth. The 15-deoxy-Δ{sup 12,14}-prostaglandin J{sub 2} (15d-PGJ{sub 2}) is a natural ligand for the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ), a known regulator of anti-inflammatory activities. We determined the effects of 15d-PGJ{sub 2} on IL-13 expression in the Jurkat E6.1 T-cell line and in peripheral blood mononuclear cells. Semi-quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay revealed that treatment of activated T cells with 15d-PGJ{sub 2} significantly decreased IL-13 mRNA transcription and secretion, respectively. This inhibition by 15d-PGJ{sub 2} was independent of PPAR-γ since treatment with GW9662, an irreversible antagonist of the nuclear receptor, produced no effect. Our data also revealed the involvement of nuclear factor-κB in mediating 15d-PGJ{sub 2}-dependent down regulation of IL-13 expression. Collectively, these results demonstrate the potential of 15d-PGJ{sub 2} in attenuating expression and production of IL-13 in activated T cells.

  8. Peroxisome proliferator-activated receptor-gamma ligand, 15-deoxy-Delta12,14-prostaglandin J2, reduces neutrophil migration via a nitric oxide pathway.

    Science.gov (United States)

    Napimoga, Marcelo H; Vieira, Silvio M; Dal-Secco, Daniela; Freitas, Andressa; Souto, Fabrício O; Mestriner, Fabiola L; Alves-Filho, José C; Grespan, Renata; Kawai, Toshihisa; Ferreira, Sérgio H; Cunha, Fernando Q

    2008-01-01

    Ligands for peroxisome proliferator-activated receptor gamma (PPAR-gamma), such as 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) have been implicated as a new class of anti-inflammatory compounds with possible clinical applications. Based on this concept, this investigation was designed to determine the effect of 15d-PGJ2-mediated activation of PPAR-gamma ligand on neutrophil migration after an inflammatory stimulus and clarify the underlying molecular mechanisms using a mouse model of peritonitis. Our results demonstrated that 15d-PGJ2 administration decreases leukocyte rolling and adhesion to the inflamed mesenteric tissues by a mechanism dependent on NO. Specifically, pharmacological inhibitors of NO synthase remarkably abrogated the 15d-PGJ2-mediated suppression of neutrophil migration to the inflammatory site. Moreover, inducible NOS-/- mice were not susceptible to 15d-PGJ2-mediated suppression of neutrophil migration to the inflammatory sites when compared with their wild type. In addition, 15d-PGJ2-mediated suppression of neutrophil migration appeared to be independent of the production of cytokines and chemokines, since their production were not significantly affected in the carrageenan-injected peritoneal cavities. Finally, up-regulation of carrageenan-triggered ICAM-1 expression in the mesenteric microcirculation vessels was abrogated by pretreatment of wild-type mice with 15d-PGJ2, whereas 15d-PGJ2 inhibited F-actin rearrangement process in neutrophils. Taken together these findings demonstrated that 15d-PGJ2 suppresses inflammation-initiated neutrophil migration in a mechanism dependent on NO production in mesenteric tissues.

  9. 15-Deoxy-Delta-12,14-Prostaglandin J2 Inhibits Lung Inflammation and Remodeling in Distinct Murine Models of Asthma

    Directory of Open Access Journals (Sweden)

    Diego S. Coutinho

    2017-06-01

    Full Text Available 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2 has been described as an anti-inflammatory lipid mediator in several in vitro and in vivo studies, but its effect on allergic pulmonary inflammation remains elusive. The aim of this study was to investigate the therapeutic potential of 15d-PGJ2 based on distinct murine models of allergic asthma triggered by either ovalbumin (OVA or house dust mite extract (HDM. Characteristics of lung inflammation, airway hyper-reactivity (AHR, mucus exacerbation, and lung remodeling in sensitized A/J mice treated or not with 15d-PGJ2 were assessed. 15d-PGJ2 treatments were carried out systemically or topically given via subcutaneous injection or intranasal instillation, respectively. Analyses were carried out 24 h after the last allergen provocation. Irrespective of the route of administration, 15d-PGJ2 significantly inhibited the peribronchial accumulation of eosinophils and neutrophils, subepithelial fibrosis and also mucus exacerbation caused by either OVA or HDM challenge. The protective effect of 15d-PGJ2 occurred in parallel with inhibition of allergen-induced AHR and lung tissue production of pro-inflammatory cytokines, such as interleukin (IL-5, IL-13, IL-17, and TNF-α. Finally, 15d-PGJ2 was found effective in inhibiting NF-κB phosphorylation upon HDM challenge as measured by Western blotting. In conclusion, our findings suggest that 15d-PGJ2 can reduce crucial features of asthma, including AHR, lung inflammation, and remodeling in distinct murine models of the disease. These effects are associated with a decrease in lung tissue generation of pro-inflammatory cytokines by a mechanism related to downregulation of NF-κB phosphorylation.

  10. Miscarriage after a normal scan at 12-14 gestational weeks in women at low risk of carrying a fetus with chromosomal anomaly according to nuchal translucency screening.

    Science.gov (United States)

    Westin, M; Källén, K; Saltvedt, S; Almström, H; Grunewald, C; Valentin, L

    2007-10-01

    To estimate the risk of second-trimester miscarriage in women with low risk of carrying a fetus with chromosomal abnormality, according to nuchal translucency (NT) screening, and to determine whether NT thickness or other factors affect the risk. The study population comprised 14 278 singleton pregnancies with a risk of Down syndrome < 1:250 at NT scan, and where no fetal karyotyping was performed < 25 weeks. Risk factors for miscarriage were investigated by logistic regression. The median risk of Down syndrome was 1 : 3138 (range 1 : 9651-1 : 251) and median NT was 1.7 (range 0.4-3.0) mm. The miscarriage rate was 0.5% (77/14 278; 95% CI 0.4-0.6). After having controlled for maternal age, we found the number of previous deliveries and miscarriages to independently predict miscarriage: odds ratio (OR) for each previous delivery 1.48, 95% CI 1.22-1.94, P < 0.0001; OR for each previous miscarriage 1.34, 95% CI 1.07-1.68, P = 0.01. Excluding women with any previous miscarriage and adjusting for parity, we found a U-shaped relationship between maternal age and miscarriage (P = 0.04). In singleton pregnancies with estimated risk of Down syndrome < 1:250 according to NT screening at 12-14 weeks, the spontaneous fetal loss rate before 25 weeks is likely to be around 0.5%. NT thickness up to 3 mm does not seem to affect the risk of miscarriage in such pregnancies. Instead, the risk seems to increase with number of previous miscarriages and deliveries, and possibly the risk is highest in the youngest and oldest women. Copyright (c) 2007 ISUOG

  11. 15-Deoxy-Δ(12,14)-prostaglandin J2 exerts pro- and anti-inflammatory effects in mesangial cells in a concentration-dependent manner.

    Science.gov (United States)

    Martínez, Alma E; Sánchez-Gómez, Francisco J; Díez-Dacal, Beatriz; Oeste, Clara L; Pérez-Sala, Dolores

    2012-02-01

    Cyclopentenone prostaglandins play a modulatory role in inflammation, in part through their ability to covalently modify key proinflammatory proteins. Using mesangial cells as a cellular model of inflammation we have observed that 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) exerts a biphasic effect on cell activation by cytokines, with nanomolar concentrations eliciting an amplification of nitric oxide (NO) production and iNOS and COX-2 levels, and concentrations of 5 μM and higher inhibiting proinflammatory gene expression. An analog of 15d-PGJ(2) lacking the cyclopentenone structure (9,10-dihydro-15d-PGJ(2)) showed reduced ability to elicit both types of effects, suggesting that the electrophilic nature of 15d-PGJ(2) is important for its biphasic action. Interestingly, the switch from stimulatory to inhibitory actions occurred within a narrow concentration range and correlated with the ability of 15d-PGJ(2) to induce heme oxygenase 1 and γ-GCSm expression. These events are highly dependent on the triggering of the antioxidant response, which is considered as a sensor of thiol group modification. Indeed, the levels of the master regulator of the antioxidant response Nrf2 increased upon treatment with concentrations of 15d-PGJ(2) above 5 μM, an effect that could not be mimicked by 9,10-dihydro-15d-PGJ(2). Thus, an interplay of redox and electrophilic signalling mechanisms can be envisaged by which 15d-PGJ(2), as several other redox mediators, could contribute both to the onset and to the resolution of inflammation in a context or concentration-dependent manner.

  12. Synergistic effects of 15-deoxy Δ12,14-prostaglandin J2 on the anti-tumor activity of doxorubicin in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yasuhiro Yamamoto

    2017-03-01

    Full Text Available An endogenous anticancer agent, 15-deoxy -Δ12,14-prostaglandin J2 (15d-PGJ2 induces apoptosis in the chemoresistant renal cell carcinoma (RCC. Peroxisome proliferator-activated receptor-γ (PPARγ is a nuclear receptor for 15d-PGJ2, and mediates the cytotoxicity of 15d-PGJ2 in many cancerous cells. However, 15d-PGJ2 induces apoptosis independently of PPARγ in human RCC cell line such as Caki-2. In the present study, we found that 15d-PGJ2 ameliorated the chemoresistance to one of anthracycline antibiotics, doxorubicin, in Caki-2 cells. Doxorubicin alone exhibited weak cytotoxicity at the concentrations effective for other cancer cells such as Hela cells. In addition, it did not activate caspase 3. However, the cytotoxicity of doxorubicin was increased remarkably and accompanied with the caspase- 3 activation in the presence of 15d-PGJ2. Doxorubicin alone damaged plasma membrane, and the combined application of 15d-PGJ2 with doxorubicin increased the membrane permeability slightly. PPARγ was involved in neither the anti-tumor activity nor the synergistic effect of 15d-PGJ2. 15d-PGJ2 induces apoptosis in Caki-2 cells via suppressing the phosphoinositide 3-kinase (PI3K-Akt pathway. The effect of PI3K inhibitor on the cytotoxicity of doxorubicin was additive, but not synergistic. Although the PI3K inhibitor mimicked the cytotoxicity of 15d-PGJ2, it might not be involved in the synergism between 15d-PGJ2 and doxorubicin. In conclusion, 15d-PGJ2 enhanced the chemosensitivity of doxorubicin via the pathway independent of PPARγ and PI3K.

  13. Albumin-Binding and Tumor Vasculature Determine the Antitumor Effect of 15-Deoxy-Δ12,14-Prostaglandin-J2in vivo

    Directory of Open Access Journals (Sweden)

    Jai Prakash

    2009-12-01

    Full Text Available 15-Deoxy-Δ12,14-prostaglandin-J2 (15d-PGJ2, a peroxisome proliferator-activated receptor γ (PPARγ agonist, induces cell death in tumor cells in vitro; however, no study showed its in vivo effect on tumors. Here, we report that 15d-PGJ2 shows antitumor effects in vivo in mice. However, its effects correlate with tumor uptake of albumin, to which it reversibly binds. 15d-PGJ2 induces cell death in B16F10 melanoma and C26 colon carcinoma cells in vitro. These effects were not elicited through PPARγ-dependent pathways because an irreversible PPARγ antagonist GW9662 did not inhibit these effects. Caspase- and nuclear factor κB- (NF-κB dependent pathways were found to be involved as determined with caspase-3/7 fluorescent assay and NF-κB containing plasmid transfection assay, respectively. Noticeably, 15d-PGJ2 had significantly stronger effects in C26 cells compared with B16 cells in all assays. However, in vivo, there was no effect on C26 tumors, yet it significantly inhibited the B16 tumor growth in mice by 75%. We found that 15d-PGJ2 rapidly bound to albumin and in vivo albumin greatly distributed to B16 tumors compared with C26 tumors, shown with γ-camera imaging and immunohistochemical staining. Albumin accumulation can be attributed to the large blood vessel diameter in B16 tumors and an enhanced permeability and retention effect. These findings suggest that 15d-PGJ2 can be an effective therapeutic agent for cancer, although its effects seem to be limited to the tumors allowing albumin penetration.

  14. Measurement of target and double-spin asymmetries for the <mi>e><mi>pmi><mi>emi><mimi>+(<mi>n>) reaction in the nucleon resonance region at low <mi>Q>2

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, X.; Adhikari, K. P.; Bosted, P.; Deur, A.; Drozdov, V.; El Fassi, L.; Kang, Hyekoo; Kovacs, K.; Kuhn, S.; Long, E.; Phillips, S. K.; Ripani, M.; Slifer, K.; Smith, L. C.; Adikaram, D.; Akbar, Z.; Amaryan, M. J.; Anefalos Pereira, S.; Asryan, G.; Avakian, H.; Badui, R. A.; Ball, J.; Baltzell, N. A.; Battaglieri, M.; Batourine, V.; Bedlinskiy, I.; Biselli, A. S.; Briscoe, W. J.; Bültmann, S.; Burkert, V. D.; Carman, D. S.; Celentano, A.; Chandavar, S.; Charles, G.; Chen, J. -P.; Chetry, T.; Choi, Seonho; Ciullo, G.; Clark, L.; Colaneri, L.; Cole, P. L.; Compton, N.; Contalbrigo, M.; Crede, V.; D' Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Djalali, C.; Dodge, G. E.; Dupre, R.; Egiyan, H.; El Alaoui, A.; Elouadrhiri, L.; Eugenio, P.; Fanchini, E.; Fedotov, G.; Fersch, R.; Filippi, A.; Fleming, J. A.; Gevorgyan, N.; Ghandilyan, Y.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Gleason, C.; Golovach, E.; Gothe, R. W.; Griffioen, K. A.; Guidal, M.; Guler, N.; Guo, L.; Hanretty, C.; Harrison, N.; Hattawy, M.; Hicks, K.; Holtrop, M.; Hughes, S. M.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jenkins, D.; Jiang, H.; Jo, H. S.; Joosten, S.; Keller, D.; Khachatryan, G.; Khandaker, M.; Kim, A.; Kim, W.; Klein, F. J.; Kubarovsky, V.; Lanza, L.; Lenisa, P.; Livingston, K.; MacGregor, I. J. D.; Markov, N.; McKinnon, B.; Mirazita, M.; Mokeev, V.; Movsisyan, A.; Munevar, E.; Munoz Camacho, C.; Murdoch, G.; Nadel-Turonski, P.; Net, L. A.; Ni, A.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Ostrovidov, A. I.; Paolone, M.; Paremuzyan, R.; Park, K.; Pasyuk, E.; Peng, P.; Pisano, S.; Pogorelko, O.; Price, J. W.; Puckett, A. J. R.; Raue, B. A.; Rizzo, A.; Rosner, G.; Rossi, P.; Roy, P.; Sabatié, F.; Salgado, C.; Schumacher, R. A.; Sharabian, Y. G.; Skorodumina, Iu.; Smith, G. D.; Sokhan, D.; Sparveris, N.; Stankovic, I.; Strakovsky, I. I.; Strauch, S.; Taiuti, M.; Tian, Ye; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Watts, D. P.; Wei, X.; Weinstein, L. B.; Wood, M. H.; Zachariou, N.; Zhang, J.; Zonta, I.

    2016-10-01

    We report measurements of target- and double-spin asymmetries for the exclusive channel <mi>e><mi>pmi><mi>emi><mimi>+(<mi>n>) in the nucleon resonance region at Jefferson Lab using the CEBAF Large Acceptance Spectrometer (CLAS). These asymmetries were extracted from data obtained using a longitudinally polarized NH3 target and a longitudinally polarized electron beam with energies 1.1, 1.3, 2.0, 2.3, and 3.0 GeV. The new results are consistent with previous CLAS publications but are extended to a low Q2 range from 0.0065 to 0.35 (GeV/c)2. The Q2 access was made possible by a custom-built Cherenkov detector that allowed the detection of electrons for scattering angles as low as 6 degrees. These results are compared with the unitary isobar models JANR and MAID, the partial-wave analysis prediction from SAID, and the dynamic model DMT. In many kinematic regions our results, in particular results on the target asymmetry, help to constrain the polarization-dependent components of these models.

  15. The regulatory epicenter of miRNAs

    Indian Academy of Sciences (India)

    Ashwani Jha; Mrigaya Mehra; Ravi Shankar

    2011-09-01

    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 around the genomic sequences of precursor miRNAs and RNA-binding protein (RBP) sites in miRNA precursor sequences, analysed and tested in comprehensive manner. Here, we report that miRNA precursor regions are positionally enriched for binding of transcription factors as well as RBPs around the 3′ end of mature miRNA region in 5′ arm. The pattern and distribution of such regulatory sites appears to be a characteristic of precursor miRNA sequences when compared with non-miRNA sequences as negative dataset and tested statistically. When compared with 1 kb upstreamregions, a sudden sharp peak for binding sites arises in the enriched zone near the mature miRNA region. An expression-data-based correlation analysis was performed between such miRNAs and their corresponding transcription factors and RBPs for this region. Some specific groups of binding factors and associated miRNAs were identified. We also identified some of the overrepresented transcription factors and associated miRNAs with high expression correlation values which could be useful in cancer-related studies. The highly correlated groups were found to host experimentally validated composite regulatory modules, in which Lmo2-GATA1 appeared as the predominant one. For many of RBP–miRNAs associations, co-expression similarity was also evident among the associated miRNA common to given RBPs, supporting the Regulon model, suggesting a common role and common control of these miRNAs by the associated RBPs. 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

  16. 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

    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 on the biolog......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...... 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...

  17. 15-deoxy-δ12,14-prostaglandin j2 inhibits osteolytic breast cancer bone metastasis and estrogen deficiency-induced bone loss.

    Directory of Open Access Journals (Sweden)

    Ki Rim Kim

    Full Text Available Breast cancer is the major cause of cancer death in women worldwide. The most common site of metastasis is bone. Bone metastases obstruct the normal bone remodeling process and aberrantly enhance osteoclast-mediated bone resorption, which results in osteolytic lesions. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2 is an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPARγ that has anti-inflammatory and antitumor activity at micromolar concentrations through PPARγ-dependent and/or PPARγ-independent pathways. We investigated the inhibitory activity of 15d-PGJ2 on the bone loss that is associated with breast cancer bone metastasis and estrogen deficiency caused by cancer treatment. 15d-PGJ2 dose-dependently inhibited viability, migration, invasion, and parathyroid hormone-related protein (PTHrP production in MDA-MB-231 breast cancer cells. 15d-PGJ2 suppressed receptor activator of nuclear factor kappa-B ligand (RANKL mRNA levels and normalized osteoprotegerin (OPG mRNA levels in hFOB1.19 osteoblastic cells treated with culture medium from MDA-MB-231 cells or PTHrP, which decreased the RANKL/OPG ratio. 15d-PGJ2 blocked RANKL-induced osteoclastogenesis and inhibited the formation of resorption pits by decreasing the activities of cathepsin K and matrix metalloproteinases, which are secreted by mature osteoclasts. 15d-PGJ2 exerted its effects on breast cancer and bone cells via PPARγ-independent pathways. In Balb/c nu/nu mice that received an intracardiac injection of MDA-MB-231 cells, subcutaneously injected 15d-PGJ2 substantially decreased metastatic progression, cancer cell-mediated bone destruction in femora, tibiae, and mandibles, and serum PTHrP levels. 15d-PGJ2 prevented the destruction of femoral trabecular structures in estrogen-deprived ICR mice as measured by bone morphometric parameters and serum biochemical data. Therefore, 15d-PGJ2 may be beneficial for the prevention and treatment of breast cancer

  18. Interleukin-6 synthesis in human chondrocytes is regulated via the antagonistic actions of prostaglandin (PGE2 and 15-deoxy-Δ(12,14-PGJ2.

    Directory of Open Access Journals (Sweden)

    Pu Wang

    Full Text Available BACKGROUND: Elevated levels of interleukin-6 (IL-6, prostaglandin (PGE(2, PGD(2 and its dehydration end product 15-deoxy-Δ(12,14-PGJ(2 (15d-PGJ(2 have been detected in joint synovial fluids from patients with rheumatoid arthritis (RA. PGE(2 directly stimulates IL-6 production in human articular chondrocytes. However, the effects of PGD(2 and 15d-PGJ(2 in the absence or presence of PGE(2 on IL-6 synthesis in human chondrocytes have yet to be determined. It is believed that dysregulated overproduction of IL-6 is responsible for the systemic inflammatory manifestations and abnormal laboratory findings in RA patients. METHODOLOGY/PRINCIPAL FINDINGS: Using the T/C-28a2 chondrocyte cell line as a model system, we report that exogenous PGE(2 and PGD(2/15d-PGJ(2 exert antagonistic effects on IL-6 synthesis in human T/C-28a2 chondrocytes. Using a synthesis of sophisticated molecular biology techniques, we determined that PGE(2 stimulates Toll-like receptor 4 (TLR4 synthesis, which is in turn responsible for the activation of the ERK1/2, PI3K/Akt and PKA/CREB pathways that phosphorylate the NF-κB p65 subunit leading to NF-κB activation. Binding of the activated NF-κB p65 subunit to IL-6 promoter induces IL-6 synthesis in human T/C28a2 chondrocytes. PGD(2 or 15d-PGJ(2 concurrently downregulates TLR4 and upregulates caveolin-1, which in turn inhibit the PGE(2-dependent ERK1/2, PI3-K and PKA activation, and ultimately with NF-κB-dependent IL-6 synthesis in chondrocytes. CONCLUSIONS/SIGNIFICANCE: We have delineated the signaling cascade by which PGE(2 and PGD(2/15d-PGJ(2 exert opposing effects on IL-6 synthesis in human chondrocytes. Elucidation of the molecular pathway of IL-6 synthesis and secretion by chondrocytes will provide insights for developing strategies to reduce inflammation and pain in RA patients.

  19. miRNA-based drought regulation in wheat.

    Science.gov (United States)

    Akdogan, Guray; Tufekci, Ebru Derelli; Uranbey, Serkan; Unver, Turgay

    2016-05-01

    MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs that regulate gene expression by guiding target mRNA cleavage or translational inhibition. Drought is a common environmental stress influencing crop growth and development. To date, it has been reported that a number of plant miRNA are involved in drought stress response. In this study, we comparatively investigated drought stress-responsive miRNAs in the root and leaf of bread wheat (Triticum aestivum cv. Sivas 111/33) by miRNA microarray screening. miRNA microarray analysis showed that 285 miRNAs (207 upregulated and 78 downregulated) and 244 miRNAs (115 upregulated and 129 downregulated) were differentially expressed in leaf and root tissues, respectively. Among the differentially expressed miRNAs, 23 miRNAs were only expressed in the leaf and 26 miRNAs were only expressed in the root of wheat growth under drought stress. Upon drought treatment, expression of miR159, miR160, miR166, miR169, miR172, miR395, miR396, miR408, miR472, miR477, miR482, miR1858, miR2118, and miR5049 were found to be significantly differentiated in bread wheat. The regulatory network analysis showed that miR395 has connections with a number of target transcripts, and miR159 and miR319 share a number of target genes. Drought-tolerant and drought-sensitive wheat cultivars showed altered expression pattern upon drought stress in terms of investigated miRNA and their target transcript expression level.

  20. Cardio-miRNAs and onco-miRNAs: circulating miRNA-based diagnostics for non-cancerous and cancerous diseases

    Directory of Open Access Journals (Sweden)

    Masaru eKatoh

    2014-10-01

    Full Text Available Cardiovascular diseases and cancers are the leading causes of morbidity and mortality in the world. MicroRNAs (miRNAs are short non-coding RNAs that primarily repress target mRNAs. Here, miR-24, miR-125b, miR-195 and miR-214 were selected as representative cardio-miRs that are upregulated in human heart failure. To bridge the gap between miRNA studies in cardiology and oncology, the targets and functions of these miRNAs in cardiovascular diseases and cancers will be reviewed. ACVR1B, BCL2, BIM, eNOS, FGFR3, JPH2, MEN1, MYC, p16 and ST7L are miR-24 targets that have been experimentally validated in human cells. ARID3B, BAK1, BCL2, BMPR1B, ERBB2, FGFR2, IL6R, MUC1, SITR7, Smoothened, STAT3, TET2 and TP53 are representative miR-125b targets. ACVR2A, BCL2, CCND1, E2F3, GLUT3, MYB, RAF1, VEGF, WEE1 and WNT7A are representative miR-195 targets. BCL2L2, ß-catenin, BIM, CADM1, EZH2, FGFR1, NRAS, PTEN, TP53 and TWIST1 are representative miR-214 targets. miR-125b is a good cardio-miR that protects cardiomyocytes; miR-195 is a bad cardio-miR that elicits cardiomyopathy and heart failure; miR-24 and miR-214 are bi-functional cardio-miRs. By contrast, miR-24, miR-125b, miR-195 and miR-214 function as oncogenic or tumor suppressor miRNAs in a cancer (subtype-dependent manner. Circulating miR-24 is elevated in diabetes, breast cancer and lung cancer. Circulating miR-195 is elevated in acute myocardial infarction, breast cancer, prostate cancer and colorectal adenoma. Circulating miR-125b and miR-214 are elevated in some cancers. Cardio-miRs and onco-miRs bear some similarities in functions and circulation profiles. Because circulating miRNA profiles are modulated by genetic and environmental factors and are dysregulated by genetic and epigenetic alterations in somatic cells, circulating miRNA association studies (CMASs within several thousands of cases each for common non-cancerous diseases and major cancers are necessary for miRNA-based diagnostics.

  1. Tertiary structure mapping of the pri-miRNA miR-17~92.

    Science.gov (United States)

    Chaulk, Steven G; Fahlman, Richard P

    2014-01-01

    The understanding of RNA in regulating gene expression has exploded over the past 15 years. MicroRNAs (miRNAs) have vastly expanded the role of RNA in gene regulation beyond spliceosomal, ribosomal, and messenger RNAs. Approximately one half of miRNAs are polycistronic, where two or more miRNAs are encoded on a single pri-miRNA transcript, termed a miRNA cluster. The six miRNAs of the miR-17~92 cluster are contained within a ~800 nucleotide region within intron 3 of the cl13orf25 ~7 kb pri-miRNA transcript. We recently reported on the tertiary structured domain of miR-17~92 and its role in modulating miRNA biogenesis. The key finding was that the cluster structure explained the differential processing of the miRNA hairpins by Drosha. This work demonstrated the need to consider pri-miRNA tertiary structure in miRNA biogenesis. Since biochemical structure probing is typically performed on relatively short RNAs (≤200 nucleotides), we had to adapt these methodologies for application on large RNAs (~800 nucleotide miR-17~92 pri-miRNA). We present here our adaptation of a protection footprinting method using ribonucleases to probe the structure of the ~800 nucleotide miR-17~92 pri-miRNA. We outline the technical difficulties involved in probing large RNAs and data visualization using denaturing polyacrylamide gel electrophoresis and how we adapted the existing approaches to probe large RNAs. The methodology outlined here is generally applicable to large RNAs including long noncoding RNAs (lncRNA).

  2. Labda-8(17),12,14-trien-19-oic acid contained in fruits of Cupressus sempervirens suppresses benign prostatic hyperplasia in rat and in vitro human models through inhibition of androgen and STAT-3 signaling.

    Science.gov (United States)

    Verma, Vikas; Sharma, Vikas; Singh, Vishal; Kumar, Rajeev; Khan, Mohammad F; Singh, Anil K; Sharma, Rolee; Arya, Kamal R; Maikhuri, J P; Dalela, Diwakar; Maurya, Rakesh; Gupta, Gopal

    2014-08-01

    Fruit extract of Cupressus sempervirens (CS), which is used traditionally to treat Benign Prostatic Hyperplasia (BPH)-like urinary symptoms in patients, was scientifically validated for anti-BPH activity. The ethanolic fruit extract of CS inhibited proliferation of human BPH-stromal cells and the activity was localized to its chloroform-soluble, diterpene-rich fraction. Eight major diterpenes isolated from this fraction exhibited moderate to potent activity and the most active diterpene (labda-8(17),12,14-trien-19-oic acid) exhibited an IC50 of 37.5 μM (antiproliferative activity against human BPH-stromal cells). It significantly inhibited activation (phosphorylation) of Stat-3 in BPH-stromal cells and prevented transactivation of androgen sensitive KLK3/PSA and TMPRSS2 genes in LNCaP cells. Labda-8(17),12,14-trien-19-oic acid-rich CS fraction prevented prostatic hyperplasia in rat model and caused TUNEL labeling of stromal cells with lower expressions of IGF-I, TGF-ß and PCNA, and bcl-2/bax ratio. Human BPH tissues exhibited precise lowering of stromal component after incubation in labda-8(17),12,14-trien-19-oic acid, ex vivo. We conclude that labda-8(17),12,14-trien-19-oic acid contained in CS exhibits anti-BPH activity through inhibition of stromal proliferation and suppression of androgen action in the prostate, presenting a unique lead structure for further optimization of anti-BPH activity.

  3. Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant pleural mesothelioma

    DEFF Research Database (Denmark)

    Andersen, Morten; Grauslund, Morten; Ravn, Jesper;

    2014-01-01

    RNAs in formalin-fixed, paraffin-embedded, preoperative diagnostic biopsy samples, surgically resected MPM specimens previously treated with chemotherapy, and corresponding non-neoplastic pleura (NNP), from five patients. miR-126, miR-143, miR-145, and miR-652 were significantly down-regulated (≥twofold.......88-1.00). The level of miR-126 in MPM was inversely correlated with that of the known target, the large neutral amino acid transporter, small subunit 1 (r = -0.38; 95% CI, -0.63 to -0.06). Overall, these results indicate that these four miRNAs may be suitable biomarkers for distinguishing MPM from RMPs....

  4. The miRNome of bipolar disorder.

    Science.gov (United States)

    Fries, Gabriel R; Carvalho, Andre F; Quevedo, Joao

    2017-09-23

    Epigenetic mechanisms have been suggested to play a key role in the pathophysiology of bipolar disorder (BD), among which microRNAs (miRNAs) may be of particular significance according to recent studies. We aimed to summarize miRNA studies in BD to identify consistent findings, limitations, and future directions of this emerging field. We performed a comprehensive search on PUBMED and Medline for studies investigating an association between BD and miRNAs. The included studies report miRNA alterations in postmortem brain tissues and in the periphery, cell culture and preclinical findings, genetic associations, and the effects of medications. Several studies report changes in miRNA expression levels in postmortem brain and in the periphery of patients, although most of the results so far have not been replicated and are not concordant between different populations. Genetic studies also suggest that miRNA genes are located within susceptibility loci of BD, and also a putative role of miRNAs in modulating genes previously shown to confer risk of BD. We did not perform a systematic review of the literature, and miRNAs represent only one facet of the plethora of epigenetic mechanisms that might be involved in BD's pathophysiology. miRNA findings in BD significantly vary between studies, but are consistent to suggest a key role for these molecules in BD's pathophysiology and treatment, particularly miR-34a and miR-137. Accordingly, miRNA might represent important biomarkers of illness to be used in the clinical settings, and potentially also for the development of novel therapeutics for BD in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Circulating miRNA and cancer diagnosis

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    miRNAs are a class of small RNA molecules with regulatory function, and play an important role in tumor development and progression. It has been demonstrated that tumor-derived miRNAs exist in the circulating nucleic acids of cancer patients. This phenomenon implies that detection of the circulating miRNA may be an effective method for non-invasive diagnosis of cancer. In this review, we summarize the applications of the circulating miRNA as biomarkers in cancer diagnosis, as well as the latest research progress in this area.

  6. 米非司酮及米索前列醇用于妊娠12-14周孕妇流产57例临床观察%12-14 weeks of pregnancy miscarriage mifepristone and misoprostol used in the clinical observation of 57cases

    Institute of Scientific and Technical Information of China (English)

    李艳

    2012-01-01

    Objective: To explore the application of mifepristone and misoprostol clinical value in the medium-term pregnancy 12 to 14 weeks of pregnancy abortion. Methods: In our hospital from April 2009 to April 2010 Obstetrics and Gynecology require induction of labor 12 to 14 weeks of pregnancy of 140 cases, the blind patients were randomly divided into two groups, the observation group of pregnant women in the forefront of mifepristone and misoprostol alcohol for medical abortion, pregnant women in the control group to facilitate where Noel medical abortion. Results: The pregnant women abortion effective 54 cases, the proportion of 95.71%, which complete abortion in 38cases (71.43%), incomplete abortion in 13 cases (24.29); pregnant women in the control group effective abortion 36 cases, the proportion of 67.14%complete abortion in 24 cases (41.43%), 12 cases (25.71) Maternity incomplete. The observation group miscarriage efficient, complete abortion rate compared to the control group was significantly increased (P0.05). Discussion: mifepristone and misoprostol in 12 to 14 weeks of gestation trimester abortion in effect is more significant, and fewer adverse reaction, has a higher value in clinical applications.%目的探讨中期妊娠12-14周孕妇流产中应用米非司酮与米索前列醇的临床价值.方法在我院2009年4月-2010年4月妇产科要求引产的12-14周妊娠孕妇90例,将患者随机盲分为两组,观察组孕妇以米非司酮与米索前列醇进行药物流产,对照组孕妇以利凡诺尔进行药物流产.结果观察组孕妇有效流产54例,所占比例为95.71%,其中完全流产38例(71.43%),不完全流产13例(24.29);对照组孕妇有效流产36例,所占比例为67.14%,其中完全流产24例(41.43%),不完全流产12例(25.71).观察组流产有效率、完全流产率相比对照组显著提高(P0.05).讨论米非司酮与米索前列醇在妊娠12-14周的中期流产中效果较为显著,且不良反

  7. miRTex: A Text Mining System for miRNA-Gene Relation Extraction.

    Science.gov (United States)

    Li, Gang; Ross, Karen E; Arighi, Cecilia N; Peng, Yifan; Wu, Cathy H; Vijay-Shanker, K

    2015-01-01

    MicroRNAs (miRNAs) regulate a wide range of cellular and developmental processes through gene expression suppression or mRNA degradation. Experimentally validated miRNA gene targets are often reported in the literature. In this paper, we describe miRTex, a text mining system that extracts miRNA-target relations, as well as miRNA-gene and gene-miRNA regulation relations. The system achieves good precision and recall when evaluated on a literature corpus of 150 abstracts with F-scores close to 0.90 on the three different types of relations. We conducted full-scale text mining using miRTex to process all the Medline abstracts and all the full-length articles in the PubMed Central Open Access Subset. The results for all the Medline abstracts are stored in a database for interactive query and file download via the website at http://proteininformationresource.org/mirtex. Using miRTex, we identified genes potentially regulated by miRNAs in Triple Negative Breast Cancer, as well as miRNA-gene relations that, in conjunction with kinase-substrate relations, regulate the response to abiotic stress in Arabidopsis thaliana. These two use cases demonstrate the usefulness of miRTex text mining in the analysis of miRNA-regulated biological processes.

  8. Evolutionary and Expression Analysis of miR-#-5p and miR-#-3p at the miRNAs/isomiRs Levels

    Directory of Open Access Journals (Sweden)

    Li Guo

    2015-01-01

    Full Text Available We mainly discussed miR-#-5p and miR-#-3p under three aspects: (1 primary evolutionary analysis of human miRNAs; (2 evolutionary analysis of miRNAs from different arms across the typical 10 vertebrates; (3 expression pattern analysis of miRNAs at the miRNA/isomiR levels using public small RNA sequencing datasets. We found that no bias can be detected between the numbers of 5p-miRNA and 3p-miRNA, while miRNAs from miR-#-5p and miR-#-3p show variable nucleotide compositions. IsomiR expression profiles from the two arms are always stable, but isomiR expressions in diseased samples are prone to show larger degree of dispersion. miR-#-5p and miR-#-3p have relative independent evolution/expression patterns and datasets of target mRNAs, which might also contribute to the phenomena of arm selection and/or arm switching. Simultaneously, miRNA/isomiR expression profiles may be regulated via arm selection and/or arm switching, and the dynamic miRNAome and isomiRome will adapt to functional and/or evolutionary pressures. A comprehensive analysis and further experimental study at the miRNA/isomiR levels are quite necessary for miRNA study.

  9. 基于LabVlEW的FSAE赛车动态性能测试系统%Design of FSAE Race Dynamic Performance Test System Based on LabVIEW

    Institute of Scientific and Technical Information of China (English)

    董瑞佳; 汪国民

    2011-01-01

    介绍了基于图形语言LabVlEW和无线传输的FSAE赛车动态性能测试系统,重点讲解电气和程序控制部分的开发和设计.该系统利用了无线传输系统和计算机串口,可实现FSAE赛车75米直线加速和绕8字等动态性能测试与实时监控,该系统具有较高的测试精度与可靠性.

  10. miRNA-mediated deregulation in leukemia

    Directory of Open Access Journals (Sweden)

    Carmela eDell'Aversana

    2012-11-01

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs 18 to 22 nucleotides (nt long able to fine-tune post-transcriptional gene expression. Extensive investigation intobiogenesis, mechanism of action and functions of miRNAs has clearly revealed their prompt control in developmental timing, differentiation, proliferation, cell death and metabolism. Deregulationof miRNA-mediated pathways may contribute to pathological conditions such as tumors, including hematological cancer, thus suggesting that miRNAs act both as tumor-suppressor genes (TSG and oncogenes (OG.Here, we provide an overview of the current understanding of the aberration of miRNA biogenesis, activity and post-transcriptional control in leukemogenesis.

  11. MiRNA Biogenesis and Intersecting Pathways

    DEFF Research Database (Denmark)

    Ben Chaabane, Samir

    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...... 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...

  12. miRNA deregulation in multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    BI Chong Lei; CHNG Wee Joo

    2011-01-01

    Multiple myeloma (MM) is an incurable plasma cell malignancy and is the second most common hematological cancer. It is characterized by complex, recurrent genetic and epigenetic abnormalities. Recent publications have linked miRNAs, a novel class of gene regulators to cancer including MM. miRNAs are about 20 nucleotide, single strand, non-coding RNAs that repress gene expression by mRNA degradation or translational repression. Aberrant miRNA expression profiles have been described in MM, and their functional roles in MM pathogenesis are being increasingly recognized. This review summarizes the current literature on the role of miRNAs in MM and offers perspectives on future research and utilization of miRNAs in MM management.

  13. Mi oíslo

    Directory of Open Access Journals (Sweden)

    Mitja Skubic

    2006-12-01

    Full Text Available Hablando Sancho en su primer encuentro con don Quijote de su mujer Juana Gutiérrez, llamada en seguida Teresa Panza o simplemente Teresa, la nombra mi oíslo y repite lo mismo otras dos veces. Conviene tener presente que de su mujer Sancho habla siempre respetuosamente y con mucho cariño, con excepción de una conversación que llega a ser un litigio, II, 5. Allí, Sancho expresa su idea de cómo y con quién casar a la hija Sanchica y por fin impone su voluntad. Teresa se le opone vigorosamente y esto induce a Sancho, sobreexcitado, a formular una gradación sorprendente: mujer mía; mirad, Teresa; mujer; calla, boba; bestia y mujer de Barrabás; animalia; mentecata e ignorante.

  14. Vasopressin-regulated miRNAs and AQP2-targeting miRNAs in kidney collecting duct cells.

    Science.gov (United States)

    Kim, Jae-Eun; Jung, Hyun Jun; Lee, Yu-Jung; Kwon, Tae-Hwan

    2015-04-01

    Mature microRNA (miRNA) acts as an important posttranscriptional regulator. We aimed to profile vasopressin-responsive miRNAs in kidney inner medullary collecting duct cells and to identify aquaporin-2 (AQP2)-targeting miRNAs. Microarray chip assay was carried out in inner medullary collecting duct tubule suspensions from rat kidneys in the absence or presence of desmopressin (dDAVP) stimulation (10(-9) M, 2 h). The results demonstrated 19 miRNAs, including both precursor and mature miRNAs, as potential candidates that showed significant changes in expression after dDAVP stimulation (P 1.3-fold changes in expression on the microarray (miR-127, miR-1, miR-873, miR-16, miR-206, miR-678, miR-496, miR-298, and miR-463) were further examined by quantitative real-time PCR, and target genes of the selected miRNAs were predicted. Next, to identify AQP2-targeting miRNAs, in silico analysis was performed. Four miRNAs (miR-32, miR-137, miR-216a, and miR-216b) target the 3'-untranslated region of rat AQP2 mRNA. Target seed regions of miR-32 and miR-137 were also conserved in the 3'-untranslated region of mouse AQP2 mRNA. Quantitative real-time PCR and immunoblot analysis demonstrated that dDAVP-induced AQP2 expression was significantly attenuated in mpkCCDc14 cells when cells were transfected with miRNA mimics of miR-32 or miR-137. Moreover, luciferase reporter assay demonstrated a significant decrease of AQP2 translation in mpkCCDc14 cells transfected with miRNA mimics of miR-32 or miR-137. The present study provides novel insights into the regulation of AQP2 by RNA interference; however, vasopressin-regulated miRNAs did not include miR-32 or miR-137, indicating that the interaction of miRNAs with the AQP2 regulatory pathway requires further analysis. Copyright © 2015 the American Physiological Society.

  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; Di Gennaro, Gianfranco; Finotti, Alessia; Ghimenton, Claudio; Eccher, Albino; Dechecchi, Maria; Scarpa, Aldo; Hirshman, Brian; Chen, Clark; Ferracin, Manuela; Negrini, Massimo; Gambari, Roberto; Cabrini, Giulio

    2016-05-10

    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.

  16. Expression of serum microRNAs( miR-222,miR-181,miR-216 ) in human hepatocellular carcinoma and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    占美晓

    2013-01-01

    Objective To investigate the abnormal expression of microRNAs (miR-216,miR-222,miR-181) in the serum of patients with hepatocellular carcinoma (HCC) and its clinical significance.Methods Serum miRNAs expression was investigated in 49 patients with HCC and 25healthy normal controls by using real-time PCR technique,and then correlations between miRNAs expression

  17. FOREWORD: Proceedings of the Second Workshop on Theory meets Industry (Erwin-Schrödinger-Institute (ESI), Vienna, Austria, 12 14 June 2007)

    Science.gov (United States)

    Hafner, Jürgen

    2008-02-01

    their application to key areas of condensed matter physics. Researchers from industry mainly focused on challenges arising from applied industrial research; contributions describing successful applications of DFT techniques to industrial problems were more scarce. Progress during the last decade has been very fast. The ESF research program has been renewed under the much bolder title 'Towards Computational Materials Design' and is now approaching the end of this second funding period. Due to the development of accurate, efficient and stable software packages for ab initio simulations, DFT-based techniques are now routinely used in many industrial laboratories worldwide. It was therefore considered timely to organize a second 'Theory meets Industry' workshop. The meeting took place between 12-14 June 2007 at the Erwin-Schrödinger-Institute (ESI) for Mathematical Physics in Vienna (Austria). It was sponsored by the Universität Wien through the VASP (Vienna Ab-initio Simulation Program) project, the Center for Computational Materials Science Vienna, the Erwin-Schrödinger-Institute and the ESF Program 'Towards Computational Materials Design'. The program of the workshop was decided by an international advisory board consisting of Ryoji Asahi (Toyota Central Research and Development Laboratory), Risto Nieminen (Helsinki University of Technology), Herve Toulhoat (Institut Français du Pétrole), Erich Wimmer (Materials Design Inc.), Chris Wolverton (Ford Motor Co. and Northwestern University) and Jürgen Hafner (Universität Wien). The 35 invited talks presented at the meeting were divided equally between researchers from academia and from industry. The contributions from academia concentrated on a wide range of new developments in DFT and post-DFT simulations (with contributions from the developers of leading software packages for ab initio simulations), as well as on applications in front-line materials research. In contrast to the first workshop nine years ago, all

  18. Proceedings of the Second Workshop on Theory meets Industry (Erwin-Schrödinger-Institute (ESI), Vienna, Austria, 12-14 June 2007).

    Science.gov (United States)

    Hafner, Jürgen

    2008-02-13

    and their application to key areas of condensed matter physics. Researchers from industry mainly focused on challenges arising from applied industrial research; contributions describing successful applications of DFT techniques to industrial problems were more scarce. Progress during the last decade has been very fast. The ESF research program has been renewed under the much bolder title 'Towards Computational Materials Design' and is now approaching the end of this second funding period. Due to the development of accurate, efficient and stable software packages for ab initio simulations, DFT-based techniques are now routinely used in many industrial laboratories worldwide. It was therefore considered timely to organize a second 'Theory meets Industry' workshop. The meeting took place between 12-14 June 2007 at the Erwin-Schrödinger-Institute (ESI) for Mathematical Physics in Vienna (Austria). It was sponsored by the Universität Wien through the VASP (Vienna Ab-initio Simulation Program) project, the Center for Computational Materials Science Vienna, the Erwin-Schrödinger-Institute and the ESF Program 'Towards Computational Materials Design'. The program of the workshop was decided by an international advisory board consisting of Ryoji Asahi (Toyota Central Research and Development Laboratory), Risto Nieminen (Helsinki University of Technology), Herve Toulhoat (Institut Français du Pétrole), Erich Wimmer (Materials Design Inc.), Chris Wolverton (Ford Motor Co. and Northwestern University) and Jürgen Hafner (Universität Wien). The 35 invited talks presented at the meeting were divided equally between researchers from academia and from industry. The contributions from academia concentrated on a wide range of new developments in DFT and post-DFT simulations (with contributions from the developers of leading software packages for ab initio simulations), as well as on applications in front-line materials research. In contrast to the first workshop nine years ago

  19. 15-脱氧-△12,14-前列腺素J2在兔肾近曲小管钠和碳酸氢根转运作用及机制%Effects and Mechanisms of 15-deoxy-△12,14-prostaglandin J2 on Na+/HCO3-Transport in Rabbit Renal Proximal Tubular

    Institute of Scientific and Technical Information of China (English)

    李月红; 王茹; 王梅

    2011-01-01

    Objective To examine the effects of 15-deoxy- Δ12,14-prostaglandin J2 (15d-PGJ2), the selective ligand of PPAR-γ, on Na+/HCO3- transport in rabbit proximal tubular and the underlying mechanisms. Methods The responses Na+/HCO3-cotransporter induced by different 15d-PGJ2 concentrations were compared in isolated rabbit renal proximal tubules, with or without MAPKK/MEK inhibitor PD98059 or PPAR-γ antagonist GW9662. The phospholipase of ERK was examined by Western blotting. Results 15d-PGJ2 stimulated the activity of Na+/HCO3- cotransporter with the concentration increase (0.1 μmol/L, 0.3 μmol/L, 1 μmol/L and 10 μmol/L). The stimulation of NBC activity induced by 0.3 μmol/1 of 15d-PGJ2 was inhibited by a MAPKK/MEK inhibitor PD98059 as well as by a PPAR-γ antagonist GW9662. In rabbit renal tubular, 0.3 μmol/L dPGJ2 and 0.3 μmol/L pioglitazone both induced the ERK phosphorylation but it was inhibited by PPAR-γ antagonist. Conclusion The PPAR-γ-dependent ERK activation was involved in PPAR-γ ligand (15-dPGJ2)-induced Na+/HCO3- cotransport stimulation in rabbit renal proximal tubular.%目的 探讨过氧化物酶体增生物活化受体-y(PPAR-y)的选择性配体15-脱氧-△12,14-前列腺素J2(15dPGJ2)在兔肾近曲小管钠和碳酸氢根的转运作用及其传导通路.方法 在15d-PGJ2(0.1、0.3、1.0、10.0 μmol/L)及PPAR-y拮抗剂(5 μmol/L GW9662)或MAPKK/ MEK抑制剂(10 μmol/L PD98059)作用下,观察兔肾近曲小管钠和碳酸氢根转运活动度的变化,Western blotting法测定细胞外信号调节激酶(extracellular signal regulated kinase,ERK)的磷酸化.结果 15d-PGJ2刺激兔肾近曲小管钠和碳酸氢根的转运,随浓度增加刺激作用增强.0.3μmol/L 15d-PGJ2引起的刺激作用被MAPKK/MEK抑制剂及PPAR-y拮抗剂阻止.PPAR-y的两种选择性配体0.3 μmol/L 15d-PGJ2和0.3 μmol/L吡格列酮刺激ERK磷酸化,并被PPAR-y拮抗剂阻滞.结论 通过PPAR-y依赖的ERK磷酸化介导15d-PGJ2在兔肾近曲小管钠和碳酸氢根的转运.

  20. A novel panel of serum miR-21/miR-155/miR-365 as a potential diagnostic biomarker for breast cancer

    Science.gov (United States)

    Han, Ji-Guang; Jiang, Yong-Dong; Zhang, Chun-Hui; Yang, Yan-Mei; Pang, Da; Song, Yan-Ni

    2017-01-01

    Purpose Insufficient sensitivity and specificity prevent the use of most existing biomarkers for early detection of breast cancer. Recently, it was reported that serum microRNAs (miRNAs) may be potential biomarkers in many cancer diseases. In this study, we investigated whether serum levels of 5 miRNAs including miR-21, miR-125b, miR-145, miR-155, and miR-365 could discriminate breast cancer patients and healthy controls. Methods Serum levels of miRNAs were measured by using quantitative real-time polymerase chain reaction in 99 breast cancer patients and 21 healthy controls. The abundance change of serum miRNAs were also evaluated following surgical resection in 20 breast cancer patients. Receiver operating characteristic (ROC) curve analysis was performed to assess the sensitivity and specificity of miRNAs as diagnostic biomarkers. Results Serum levels of miR-21 and miR-155 was significantly higher, while miR-365 was significantly lower in breast cancer as compared with healthy controls. The serum levels of miR-21 and miR-155 significantly decreased following surgical resection. Additionally, the serum level of miR-155 at stages I and II was significantly higher compared to stage III. The serum miR-145 level was remarkably higher in progesterone receptor (PR)-positive patients than PR-negative. The positivity of miR-21, miR-155, and miR-365 was high compared to CA 153 and CEA in breast cancer. ROC curve analyses of a combination of miR-21, miR-155, and miR-365 yielded much higher area under curve and enhanced sensitivity and specificity in comparison to each miRNA alone. Conclusion The combination of serum miR-21/miR-155/miR-365 may potentially serve as a sensitive and specific biomarker that enables differentiation of breast cancer from healthy controls. PMID:28203552

  1. 强直性脊柱炎患者外周血中 miR-17、miR-181、miR-106、miR-30和miR-495表达的分析%miR-17,miR-181,miR-106,miR-30 and miR-495 level differences in peripheral blood of patients with ankylosing spondylitis

    Institute of Scientific and Technical Information of China (English)

    刘鑫; 魏军; 杨芝红; 周林林; 郑锡铭; 徐广贤

    2014-01-01

    目的:为了探讨microRNA在强直性脊柱炎患者发病过程中的作用,我们通过检测强直性脊柱炎患者外周血液中miR-17、miR-181、miR-106、miR-30和miR-495的表达情况,从而为研究microRNA在强直性脊柱炎发病机制中的调控作用和临床诊断价值提供新的思路。方法:收集强直性脊柱炎患者及正常人的外周血液,对外周血液中单个核细胞进行分离,并提取PBMC small RNA,用特异性茎环引物反转录成cDNA,并构建成熟的miR-17、miR-181、miR-106、miR-30和miR-495的T载体,制作标准曲线,利用stem-loop法通过Real-time PCR技术,检测miR-17、miR-181、miR-106、miR-30和miR-495的表达量。结果:本实验共收集临床样本92例,其中AS患者61例,正常人31例。通过Real-time PCR检测发现,与正常人相比,在强直性脊柱炎患者外周血中表达上调的有miR-106(P>0.05)与miR-30(P>0.05);表达下调的有miR-181(P<0.05)、 miR-495(P<0.05)和miR-17(P>0.05),其中miR-181和miR-495有统计学意义。结论:与正常人相比在强直性脊柱炎患者外周血中miR-181和miR-495的表达量存在差异,它们可以靶向调控TLR-4,HLA-B,DVL和GSK/3β等基因,这一发现可能为强直性脊柱炎发病机制的研究提供新的思路,成为临床诊断中新的标志物。%Objective:In order to investigate the role of microRNA in the pathogenesis of ankylosing spondylitis patients,we detected the peripheral blood of patients with ankylosing spondylitis in miR-17,miR-181,miR-106,miR-30 and miR-495 expression, thereby to study the role of microRNA regulation of clinical and diagnostic value in the pathogenesis of ankylosing spondylitis provide new ideas.Methods:Collection of patients with ankylosing spondylitis and normal peripheral blood,peripheral blood mononuclear cells were isolated and extracted PBMC small RNA,using primers specific stem-loop reverse transcribed into c

  2. miRNA signature identification of retinoblastoma and the correlations between differentially expressed miRNAs during retinoblastoma progression.

    Science.gov (United States)

    Yang, Yang; Mei, Qi

    2015-01-01

    Retinoblastoma (RB) is a common pediatric cancer. The study aimed to uncover the mechanisms of RB progression and identify novel therapeutic biomarkers. The miRNA expression profile GSE7072, which includes three RB samples and three healthy retina samples, was used. After data normalization using the preprocessCore package, differentially expressed miRNAs (DE-miRs) were selected by the limma package. The targets of the DE-miRs were predicted based on two databases, followed by construction of the miRNA-target network. Pathway enrichment analysis was conducted for the targets of the DE-miRNAs using DAVID. The CTD database was used to predict RB-related genes, followed by clustering analysis using the pvclust package. The correlation network of DE-miRs was established. MiRNA expression was validated in another data set, GSE41321. In total, 24 DE-miRs were identified whose targets were correlated with the cell cycle pathway. Among them, hsa-miR-373, hsa-miR-125b, and hsa-miR-181a were highlighted in the miRNA-target regulatory network; 14 DE-miRs, including hsa-miR-373, hsa-miR-125b, hsa-miR-18a, hsa-miR-25, hsa-miR-20a, and hsa-let-7 (a, b, c), were shown to distinguish RB from healthy tissue. In addition, hsa-miR-25, hsa-miR-18a, and hsa-miR-20a shared the common target BCL2L11; hsa-let-7b and hsa-miR-125b targeted the genes CDC25A, CDK6, and LIN28A. Expression of three miRNAs in GSE41321 was consistent with that in GSE7072. Several critical miRNAs were identified in RB progression. Hsa-miR-373 might regulate RB invasion and metastasis, hsa-miR-181a might involve in the CDKN1B-mediated cell cycle pathway, and hsa-miR-125b and hsa-let-7b might serve as tumor suppressors by coregulating CDK6, CDC25A, and LIN28A. The miRNAs hsa-miR-25, hsa-miR-18a, and hsa-miR-20a might exert their function by coregulating BCL2L1.

  3. miR-200 family and its mechanism%miR-200及其作用机制

    Institute of Scientific and Technical Information of China (English)

    苏娟; 张庆瑜

    2011-01-01

    miR-200是一簇与上皮间质转化(EMT)密切相关的微RNA(miRNA)家族,其家族成员包括miR-200a、miR-200b、miR-200c、miR-141及miR-429.miR-200是EMT的主要调节分子并可维持细胞的上皮表型,在EMT的发生和肿瘤的进展过程中发挥重要的作用.%MiR-200 family is a cluster of miRNAs closely linked to EMT. The miR-200 family contains miR-200a, miR-200b, miR-200c, miR-141 and miR-429. Many studies have shown that miR-200 family are key regulators of EMT and determine the epithelial phenotype. They are important to both EMT development and tumor progression. This paper reviews the advancement in the research of miR-200 family and its mechanism.

  4. MiR-221 and miR-130a regulate lung airway and vascular development.

    Directory of Open Access Journals (Sweden)

    Sana Mujahid

    Full Text Available Epithelial-mesenchymal interactions play a crucial role in branching morphogenesis, but very little is known about how endothelial cells contribute to this process. Here, we examined how anti-angiogenic miR-221 and pro-angiogenic miR-130a affect airway and vascular development in the fetal lungs. Lung-specific effects of miR-130a and miR-221 were studied in mouse E14 whole lungs cultured for 48 hours with anti-miRs or mimics to miR-130a and miR-221. Anti-miR 221 treated lungs had more distal branch generations with increased Hoxb5 and VEGFR2 around airways. Conversely, mimic 221 treated lungs had reduced airway branching, dilated airway tips and decreased Hoxb5 and VEGFR2 in mesenchyme. Anti-miR 130a treatment led to reduced airway branching with increased Hoxa5 and decreased VEGFR2 in the mesenchyme. Conversely, mimic 130a treated lungs had numerous finely arborized branches extending into central lung regions with diffusely localized Hoxa5 and increased VEGFR2 in the mesenchyme. Vascular morphology was analyzed by GSL-B4 (endothelial cell-specific lectin immunofluorescence. Observed changes in airway morphology following miR-221 inhibition and miR-130a enhancement were mirrored by changes in vascular plexus formation around the terminal airways. Mouse fetal lung endothelial cells (MFLM-91U were used to study microvascular cell behavior. Mimic 221 treatment resulted in reduced tube formation and cell migration, where as the reverse was observed with mimic 130a treatment. From these data, we conclude that miR-221 and miR-130a have opposing effects on airway and vascular morphogenesis of the developing lung.

  5. Identification of novel targets for miR-29a using miRNA proteomics.

    Directory of Open Access Journals (Sweden)

    Rhishikesh Bargaje

    Full Text Available MicroRNAs (miRNAs are short regulatory RNA molecules that interfere with the expression of target mRNA by binding to complementary sequences. Currently, the most common method for identification of targets of miRNAs is computational prediction based on free energy change calculations, target site accessibility and conservation. Such algorithms predict hundreds of targets for each miRNA, necessitating tedious experimentation to identify the few functional targets. Here we explore the utility of miRNA-proteomics as an approach to identifying functional miRNA targets. We used Stable Isotope Labeling by amino acids in cell culture (SILAC based proteomics to detect differences in protein expression induced by the over-expression of miR-34a and miR-29a. Over-expression of miR-29a, a miRNA expressed in the brain and in cells of the blood lineage, resulted in the differential expression of a set of proteins. Gene Ontology based classification showed that a significant sub-set of these targets, including Voltage Dependent Anion Channel 1 and 2 (VDAC1 and VDAC2 and ATP synthetase, were mitochondrial proteins involved in apoptosis. Using reporter assays, we established that miR-29a targets the 3' Untranslated Regions (3' UTR of VDAC1 and VDAC2. However, due to the limited number of proteins identified using this approach and the inability to differentiate between primary and secondary effects we conclude that miRNA-proteomics is of limited utility as a high-throughput alternative for sensitive and unbiased miRNA target identification. However, this approach was valuable for rapid assessment of the impact of the miRNAs on the cellular proteome and its biological role in apoptosis.

  6. MiBoard: Multiplayer Interactive Board Game

    CERN Document Server

    Dempsey, Kyle B; Jackson, G Tanner; Boonthum, Chutima; Levinstein, Irwin B; McNamara, Danielle S

    2010-01-01

    Serious games have recently emerged as an avenue for curriculum delivery. Serious games incorporate motivation and entertainment while providing pointed curriculum for the user. This paper presents a serious game, called MiBoard, currently being developed from the iSTART Intelligent Tutoring System. MiBoard incorporates a multiplayer interaction that iSTART was previously unable to provide. This multiplayer interaction produces a wide variation across game trials, while also increasing the repeat playability for users. This paper presents a demonstration of the MiBoard system and the expectations for its application.

  7. Inference of Gene Regulation via miRNAs During ES Cell Differentiation Using MiRaGE Method

    Directory of Open Access Journals (Sweden)

    Jun Yasuda

    2011-12-01

    Full Text Available MicroRNA (miRNA is a critical regulator of cell growth, differentiation, and development. To identify important miRNAs in a biological process, many bioinformatical tools have been developed. We have developed MiRaGE (MiRNA Ranking by Gene Expression method to infer the regulation of gene expression by miRNAs from changes of gene expression profiles. The method does not require precedent array normalization. We applied the method to elucidate possibly important miRNAs during embryonic stem (ES cell differentiation to neuronal cells and we infer that certain miRNAs, including miR-200 family, miR-429, miR-302 family, and miR-17-92 cluster members may be important to the maintenance of undifferentiated status in ES cells.

  8. Using miRNA-Analyzer for the Analysis of miRNA Data

    Science.gov (United States)

    Guzzi, Pietro Hiram; Tradigo, Giuseppe; Veltri, Pierangelo

    2016-01-01

    MicroRNAs (miRNAs) are small biological molecules that play an important role during the mechanisms of protein formation. Recent findings have demonstrated that they act as both positive and negative regulators of protein formation. Thus, the investigation of miRNAs, i.e., the determination of their level of expression, has developed a huge interest in the scientific community. One of the leading technologies for extracting miRNA data from biological samples is the miRNA Affymetrix platform. It provides the quantification of the level of expression of the miRNA in a sample, thus enabling the accumulation of data and allowing the determination of relationships among miRNA, genes, and diseases. Unfortunately, there is a lack of a comprehensive platform able to provide all the functions needed for the extraction of information from miRNA data. We here present miRNA-Analyzer, a complete software tool providing primary functionalities for miRNA data analysis. The current version of miRNA-Analyzer wraps the Affymetrix QCTool for the preprocessing of binary data files, and then provides feature selection (the filtering by species and by the associated p-value of preprocessed files). Finally, preprocessed and filtered data are analyzed by the Multiple Experiment Viewer (T-MEV) and Short Time Series Expression Miner (STEM) tools, which are also wrapped into miRNA-Analyzer, thus providing a unique environment for miRNA data analysis. The tool offers a plug-in interface so it is easily extensible by adding other algorithms as plug-ins. Users may download the tool freely for academic use at https://sites.google.com/site/mirnaanalyserproject/d. PMID:27983673

  9. MicroRNAs, macrocontrol : Regulation of miRNA processing

    NARCIS (Netherlands)

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

    2010-01-01

    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

  10. 78 FR 15796 - Michigan Disaster #MI-00038.

    Science.gov (United States)

    2013-03-12

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Michigan Disaster MI-00038. AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... adversely affected by the disaster: Primary Counties: Mecosta. Contiguous Counties: Michigan:...

  11. Lo que mi abuelo me cuenta

    OpenAIRE

    Benavides Muhamad, Amal; Pontificia Universidad Javeriana Cali

    2014-01-01

    En el estado de Palestina, ubicado en oriente medio, hace más de 57 años en Kofor malek –un pequeño pueblo– vivía una familia muy numerosa. Era la familia de mi abuelo que estaba conformada por once personas incluyendo a sus padres. Como la describe el, su familia la integraban: “Mi madre, una mujer muy cariñosa, excelente cocinera y muy dedicada a su hogar; la madre típica de ese entonces que casi nunca salía del hogar. Su vida giraba en torno a mi padre y a nosotros, sus hijos. Mi padre un ...

  12. The NuMI Neutrino Beam

    CERN Document Server

    Adamson, P; Andrews, M; Andrews, R; Anghel, I; Augustine, D; Aurisano, A; Avvakumov, S; Ayres, D S; Baller, B; Barish, B; Barr, G; Barrett, W L; Bernstein, R H; Biggs, J; Bishai, M; Blake, A; Bocean, V; Bock, G J; Boehnlein, D J; Bogert, D; Bourkland, K; Cao, S V; Castromonte, C M; Childress, S; Choudhary, B C; Coelho, J A B; Cobb, J H; Corwin, L; Crane, D; Cravens, J P; Cronin-Hennessy, D; Ducar, R J; de Jong, J K; Devan, A V; Devenish, N E; Diwan, M V; Erwin, A R; Escobar, C O; Evans, J J; Falk, E; Feldman, G J; Fields, T H; Ford, R; Frohne, M V; Gallagher, H R; Garkusha, V; Gomes, R A; Goodman, M C; Gouffon, P; Graf, N; Gran, R; Grossman, N; Grzelak, K; Habig, A; Hahn, S R; Harding, D; Harris, D; Harris, P G; Hartnell, J; Hatcher, R; Hays, S; Heller, K; Holin, A; Huang, J; Hylen, J; Ibrahim, A; Indurthy, D; Irwin, G M; Isvan, Z; Jaffe, D E; James, C; Jensen, D; Johnstone, J; Kafka, T; Kasahara, S M S; Koizumi, G; Kopp, S; Kordosky, M; Kreymer, A; Lang, K; Laughton, C; Lefeuvre, G; Ling, J; Litchfield, P J; Loiacono, L; Lucas, P; Mann, W A; Marchionni, A; Marshak, M L; Mayer, N; McGivern, C; Medeiros, M M; Mehdiyev, R; Meier, J R; Messier, M D; Michael, D G; Milburn, R H; Miller, J L; Miller, W H; Mishra, S R; Sher, S Moed; Moore, C D; Morfin, J; Mualem, L; Mufson, S; Murgia, S; Murtagh, M; Musser, J; Naples, D; Nelson, J K; Newman, H B; Nichol, R J; Nowak, J A; Connor, J O; Oliver, W P; Olsen, M; Orchanian, M; Osprey, S; Pahlka, R B; Paley, J; Para, A; Patterson, R B; Patzak, T; Pavlovic, Z; Pawloski, G; Perch, A; Peterson, E A; Petyt, D A; Pfutzner, M; Phan-Budd, S; Plunkett, R K; Poonthottathil, N; Prieto, P; Pushka, D; Qiu, X; Radovic, A; Rameika, R A; Ratchford, J; Rebel, B; Reilly, R; Rosenfeld, C; Rubin, H A; Ruddick, K; Sanchez, M C; Saoulidou, N; Sauer, L; Schneps, J; Schoo, D; Schreckenberger, A; Schreiner, P; Shanahan, P; Sharma, R; Smart, W; Smith, C; Sousa, A; Stefanik, A; Tagg, N; Talaga, R L; Tassotto, G; Thomas, J; Thompson, J; Thomson, M A; Tian, X; Timmons, A; Tinsley, D; Tognini, S C; Toner, R; Torretta, D; Trostin, I; Tzanakos, G; Urheim, J; Vahle, P; Vaziri, K; Villegas, E; Viren, B; Vogel, G; Webber, R C; Weber, A; Webb, R C; Wehmann, A; White, C; Whitehead, L; Whitehead, L H; Wojcicki, S G; Wong-Squires, M L; Yang, T; Yumiceva, F X; Zarucheisky, V; Zwaska, R

    2015-01-01

    This paper describes the hardware and operations of the Neutrinos at the Main Injector (NuMI) beam at Fermilab. It elaborates on the design considerations for the beam as a whole and for individual elements. The most important design details of individual components are described. Beam monitoring systems and procedures, including the tuning and alignment of the beam and NuMI long-term performance, are also discussed.

  13. The NuMI neutrino beam

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, P.; Anderson, K.; Andrews, M.; Andrews, R. [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Anghel, I. [Department of Physics and Astronomy, Iowa State University, Ames, IA 50011 (United States); Argonne National Laboratory, Argonne, IL 60439 (United States); Augustine, D. [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Aurisano, A. [Department of Physics, University of Cincinnati, Cincinnati, OH 45221 (United States); Avvakumov, S. [Department of Physics, Stanford University, Stanford, CA 94305 (United States); Ayres, D.S. [Argonne National Laboratory, Argonne, IL 60439 (United States); Baller, B. [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Barish, B. [Lauritsen Laboratory, California Institute of Technology, Pasadena, CA 91125 (United States); Barr, G. [Subdepartment of Particle Physics, University of Oxford, Oxford OX1 3RH (United Kingdom); Barrett, W.L. [Physics Department, Western Washington University, Bellingham, WA 98225 (United States); Bernstein, R.H.; Biggs, J. [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Bishai, M. [Brookhaven National Laboratory, Upton, NY 11973 (United States); Blake, A. [Cavendish Laboratory, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Bocean, V.; Bock, G.J.; Boehnlein, D.J. [Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); and others

    2016-01-11

    This paper describes the hardware and operations of the Neutrinos at the Main Injector (NuMI) beam at Fermilab. It elaborates on the design considerations for the beam as a whole and for individual elements. The most important design details of individual components are described. Beam monitoring systems and procedures, including the tuning and alignment of the beam and NuMI long-term performance, are also discussed.

  14. Effect of 15-deoxy-△~(12,14)-prostagliandxin J2 on hypertrophic scar in rabbit ear%15-脱氧-△~(12,14)-前列腺素J2对兔耳增生性瘢痕的作用

    Institute of Scientific and Technical Information of China (English)

    潘姝; 李叶扬; 方力; 梁佩红; 戴丽冰; 李建平; 张琰; 李罡; 张涛

    2010-01-01

    目的 探讨r过氧化物酶体增殖物激活受体(peroxisome proliferator activated receptor-r,PPAR-r)的配体15-脱氧-△~(12,14)-前列腺素J2(15-deoxy-△~(12,14)-prostagliandxin J2,15d-PGJ2)对兔耳增生性瘢痕Ⅰ型胶原、结缔组织生长因子(connective tissue growth factor,CTGF)、a平滑肌肌动蛋白(a-smooth muscle actin,a-SMA)表达的影响,探讨15d-PGJ2防治增生性瘢痕的可能性.方法 选取新西兰大白兔18只,在兔耳腹侧面制作2 cm× 3 cm全层皮肤缺损创面,每耳2个,共计72个,建立兔耳增生性瘢痕动物模型,随机分为2组,一组为实验组,另一组为对照组,分别用15d-PGJ2和生理盐水行瘢痕内注射,1次/d,共7次.停药后第7、14、21天两组同时取材;每组每次切取12个组织块.应用免疫组织化学检测Ⅰ型胶原、CTGF和a-SMA的表达.结果 各组兔耳腹侧创面愈合后均不同程度出现类似人增生性瘢痕的组织块.与对照组相比,15d-PGJ2注射后瘢痕体积缩小,变软变平,色泽轻度变浅.在各个时间点15d-PGJ2组Ⅰ型胶原、CTGF和a-SMA的表达均较对照组低,且差异有统计学意义(P<0.05).结论 PPAR-r的配体15d-PGJ2可降低瘢痕内Ⅰ型胶原、CTGF和a-SMA的含量,引起瘢痕萎缩,有一定防治瘢痕的作用,可能为临床治疗增生性瘢痕提供一条新的途径.%Objective To investigate the effect of 15d-PGJ2 on the expression of collagen type,CTGF and a-SMA in the hypertrophic scar in the rabbit ear,and the possibility of hypertrophic scar treated by 15d-PGJ2.Methods 18 New Zealand white rabbits were used to establish a hypertrophic scar model on the rabbit ear.The wounds were established as follows:2 cm × 3 cm wounds with total skin loses on the ventral side,2 wounds for each ear,totally 72 wounds.The wounds were randomly divided into the 15d-PGJ2 treatment group and NS control group.20μl 15d-PGJ2 or NS was injected into the ear scar once a day for 7 days.At 7,14 and 21 days after the

  15. A conserved gene structure and expression regulation of miR-433 and miR-127 in mammals.

    Directory of Open Access Journals (Sweden)

    Guisheng Song

    Full Text Available MicroRNAs play essential roles in many cellular processes. However, limited information is available regarding the gene structure and transcriptional regulation of miRNAs. We explored the gene cluster encoding miR-433/127 in mammalian species using bioinformatics and in vitro "gene" expression approaches. Multiple sequence alignments (MSA showed that the precursors of miR-433 and of miR-127 exhibited 95% and 100% similarity, respectively, in human, chimpanzee, horse, dog, monkey, rat, cow, and mouse. MSA of the promoter sequences of miR-433 and of miR-127 revealed lower sequence similarity among these mammalian species. However, the distance between miR-433 and miR-127 was strikingly similar, which was between 986 and 1007 bp and the position of transcription factor (TF binding motifs, including estrogen related receptor response element (ERRE, was well conserved. Transient transfection assays showed that promoters of miR-433 and of miR-127 from human, rat, and dog were activated by estrogen related receptor gamma (ERRgamma and inhibited by small heterodimer partner (SHP. ChIP assays confirmed the physical association of ERRgamma with the endogenous promoters of miR-433 and miR-127. In vitro over-expression of the human, rat, or dog miR-433/127 loci in cells, using an expression vector containing miR-433/127 and their promoter regions, markedly induced a differential expression of both primary and mature miR-433 and miR-127, indicating that miR-433 and miR-127 were possessed from their independent promoters. Our studies for the first time demonstrate a conserved gene structure and transcriptional regulation of miR-433 and miR-127 in mammals. The data suggest that the miR-433/127 loci may have evolved from a common gene of origin.

  16. Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer

    DEFF Research Database (Denmark)

    Wiklund, Erik D; Bramsen, Jesper B; Hulf, Toby

    2011-01-01

    MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and miR-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting the t...

  17. Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer

    DEFF Research Database (Denmark)

    Wiklund, Erik D; Bramsen, Jesper B; Hulf, Toby

    2011-01-01

    MicroRNAs (miRNA) are small noncoding RNAs commonly deregulated in cancer. The miR-200 family (miR-200a, -200b, -200c, -141 and -429) and miR-205 are frequently silenced in advanced cancer and have been implicated in epithelial to mesenchymal transition (EMT) and tumor invasion by targeting...

  18. Role of miR-1 and miR-133a in myocardial ischemic postconditioning

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    Xie Bing

    2011-03-01

    Full Text Available Abstract Background Ischemic postconditioning (IPost has aroused much attention since 2003 when it was firstly reported. The role of microRNAs (miRNAs or miRs in IPost has rarely been reported. The present study was undertaken to investigate whether miRNAs were involved in the protective effect of IPost against myocardial ischemia-reperfusion (IR injury and the probable mechanisms involved. Methods Thirty SD rats weighing 250-300 g were equally randomized to three groups: Control group, where the rats were treated with thoracotomy only; IR group, where the rats were treated with ischemia for 60 min and reperfusion for 180 min; and IPost group, where the rats were treated with 3 cycles of transient IR just before reperfusion. The extent of myocardial infarction, LDH and CK activities were measured immediately after treatment. Myocardial apoptosis was detected by TUNEL assay. The myocardial tissue was collected after IR or IPost stimulation to evaluate the miRNAs expression level by miRNA-microarray and quantitative real-time RT-PCR. Real-time PCR was conducted to identify changes in mRNA expression of apoptosis-related genes such as Bcl-2, Bax and Caspase-9 (CASP9, and Western blot was used to compare the protein expression level of CASP9 in the three groups. The miRNA mimics and anti-miRNA oligonucleotides (AMO were transferred into the cultured neonatal cardiomyocytes and myocardium before they were treated with IR. The effect of miRNAs on apoptosis was determined by flow cytometry and TUNEL assay. CASP9, as one of the candidate target of miR-133a, was compared during IR after the miR-133a mimic or AMO-133a was transferred into the myocardium. Results IPost reduced the IR-induced infarct size of the left ventricle, and decreased CK and LDH levels. TUNEL assay showed that myocardial apoptosis was attenuated by IPost compared with IR. MiRNA-microarray and RT-PCR showed that myocardial-specific miR-1 and miR-133a were down-regulated by IR, and up

  19. MiRNATIP: a SOM-based miRNA-target interactions predictor.

    Science.gov (United States)

    Fiannaca, Antonino; Rosa, Massimo La; Paglia, Laura La; Rizzo, Riccardo; Urso, Alfonso

    2016-09-22

    MicroRNAs (miRNAs) are small non-coding RNA sequences with regulatory functions to post-transcriptional level for several biological processes, such as cell disease progression and metastasis. MiRNAs interact with target messenger RNA (mRNA) genes by base pairing. Experimental identification of miRNA target is one of the major challenges in cancer biology because miRNAs can act as tumour suppressors or oncogenes by targeting different type of targets. The use of machine learning methods for the prediction of the target genes is considered a valid support to investigate miRNA functions and to guide related wet-lab experiments. In this paper we propose the miRNA Target Interaction Predictor (miRNATIP) algorithm, a Self-Organizing Map (SOM) based method for the miRNA target prediction. SOM is trained with the seed region of the miRNA sequences and then the mRNA sequences are projected into the SOM lattice in order to find putative interactions with miRNAs. These interactions will be filtered considering the remaining part of the miRNA sequences and estimating the free-energy necessary for duplex stability. We tested the proposed method by predicting the miRNA target interactions of both the Homo sapiens and the Caenorhbditis elegans species; then, taking into account validated target (positive) and non-target (negative) interactions, we compared our results with other target predictors, namely miRanda, PITA, PicTar, mirSOM, TargetScan and DIANA-microT, in terms of the most used statistical measures. We demonstrate that our method produces the greatest number of predictions with respect to the other ones, exhibiting good results for both species, reaching the for example the highest percentage of sensitivity of 31 and 30.5 %, respectively for Homo sapiens and for C. elegans. All the predicted interaction are freely available at the following url: http://tblab.pa.icar.cnr.it/public/miRNATIP/ . Results state miRNATIP outperforms or is comparable to the other six state

  20. Analyzing miRNA co-expression networks to explore TF-miRNA regulation

    Directory of Open Access Journals (Sweden)

    Bhattacharyya Malay

    2009-05-01

    Full Text Available Abstract Background Current microRNA (miRNA research in progress has engendered rapid accumulation of expression data evolving from microarray experiments. Such experiments are generally performed over different tissues belonging to a specific species of metazoan. For disease diagnosis, microarray probes are also prepared with tissues taken from similar organs of different candidates of an organism. Expression data of miRNAs are frequently mapped to co-expression networks to study the functions of miRNAs, their regulation on genes and to explore the complex regulatory network that might exist between Transcription Factors (TFs, genes and miRNAs. These directions of research relating miRNAs are still not fully explored, and therefore, construction of reliable and compatible methods for mining miRNA co-expression networks has become an emerging area. This paper introduces a novel method for mining the miRNA co-expression networks in order to obtain co-expressed miRNAs under the hypothesis that these might be regulated by common TFs. Results Three co-expression networks, configured from one patient-specific, one tissue-specific and a stem cell-based miRNA expression data, are studied for analyzing the proposed methodology. A novel compactness measure is introduced. The results establish the statistical significance of the sets of miRNAs evolved and the efficacy of the self-pruning phase employed by the proposed method. All these datasets yield similar network patterns and produce coherent groups of miRNAs. The existence of common TFs, regulating these groups of miRNAs, is empirically tested. The results found are very promising. A novel visual validation method is also proposed that reflects the homogeneity as well as statistical properties of the grouped miRNAs. This visual validation method provides a promising and statistically significant graphical tool for expression analysis. Conclusion A heuristic mining methodology that resembles a

  1. Differential Expression and Clinical Significance of miR-328, miR-22 and miR-147 in Coronary Heart Disease Patients%miR-328、miR-147和miR-22在冠心病患者中的表达变化及临床意义

    Institute of Scientific and Technical Information of China (English)

    冯荣; 傅广; 黄树斌; 石顺华; 汤华; 王爱平

    2015-01-01

    目的 探讨冠心病患者血浆及外周血单个核细胞(PBMC) miR-328、miR-22、miR-147的表达变化及其临床意义.方法 筛选100例冠心病患者及相对健康对照组,采用实时荧光定量PCR技术检测各组血浆及PBMC中miR-328、miR-147、miR-22的表达水平.结果 冠心病患者血浆中miR-328、miR-22的表达较非冠心病患者明显升高,而miR-147的表达明显降低;在冠心病患者PBMC中,miR-328表达没有明显变化,miR-22表达略微增加,miR-147表达明显下降.在心肌梗死患者中,血浆中miR-328和miR-22表达水平明显增加,而miR-147表达明显下降;心肌梗死患者PBMC中miR-328表达略降低,miR-22表达增加,miR-147表达水平略有下降.结论 miR-328、miR-22及miR-147在冠心病患者中的差异表达,有望作为冠心病疾病中一种新的标记物或基因治疗靶点.

  2. 子宫内膜异位症中miR-143、miR-145和miR-126的差异表达%Differential expression of miR-143,miR-145 and miR-126 in endometriosis

    Institute of Scientific and Technical Information of China (English)

    郑冰冰; 徐超逸; 赵益萍; 韩灵芝; 虞楼超; 段萍

    2016-01-01

    目的 探索子宫内膜异位症(EMs)中miR-143、miR-145和miR-126的差异表达,以及不同月经周期的影响.方法 利用real time RT-PCR技术,比较miR-143、miR-145和miR-126在EMs患者在位内膜(EU,2例)、异位内膜(EC,14例)、配对EU+EC(14例),与非EMs患者内膜(EN,28例)中的表达差异;并分析EN和EC组不同月经周期对miR-143、miR-145和miR-126表达的影响.结果 不同月经周期的影响分析,发现仅EN标本中miR-143增生期表达量高于分泌期,差异有统计学意义(P<0.05).与EN相比,miR-143和miR-145在EU中均表达上调(P<0.05),miR-143、miR-145和miR-126在EC中均表达上调(P<0.01).配对EU-EC中,miR-143、miR-145和miR-126在EC中均表达上调(P<0.01).结论 miR-143、miR-145和miR-126在EMs中表达高于非EMs,在EC中表达高于EU.

  3. Synthesis and X-ray Crystal Structure of Meso-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane-1,8-di-(1-methylnaphthalene

    Directory of Open Access Journals (Sweden)

    Dean R. Hutchings

    2003-02-01

    Full Text Available The pendant-arm macrocycle, meso-5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane-1,8-di-(1-methylnaphthalene has been synthesized and its single crystal structure determined. The molecule crystallizes in a primitive monoclinic cell, with the space group P21/a (#14. The cell dimensions are a = 10.778(3Å, b = 13.809(3 Å, c = 11.420(2 Å, = 102.49(2°, volume = 1659.5(6 Å3.

  4. Haplotype distribution and evolutionary pattern of miR-17 and miR-124 families based on population analysis.

    Directory of Open Access Journals (Sweden)

    Li Guo

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are small, endogenously expressed non-coding RNAs that regulate mRNAs post-transcriptionally. Previous studies have explored miRNA evolutionary trend, but evolutionary history and pattern in the miRNA world are still not fully clear. In the paper, we intended to analyze miRNA haplotype distribution and evolutionary network by analyzing miRNA sequences of miR-17 and miR-124 families across animal species as special populations. PRINCIPAL FINDINGS: 31 haplotypes were detected in miR-17 family while only 9 haplotypes were defined in miR-124 family. The complex miR-17 family was mainly distributed in vertebrates, but miR-124 was shared by more animal species from Caenorhabditis to Homo and had a wide distribution spectrum. Some haplotypes of the two miRNA families appeared discontinuous distributions across animals. Compared with a simple phylogenetic network in miR-124 family, miR-17 family indicated a complex network with some median vectors that might be lost ancestral or potential miRNA haplotypes. By analyzing different miRNAs across 12 animal species, we found these small RNAs showed different haplotype diversities, haplotype distributions and phylogenetic networks. CONCLUSIONS: Different miRNAs had quite different haplotype distributions and evolutionary patterns. Discontinuous distributions of miRNAs and median vectors in phylogenetic networks implied more members in the miRNA world. miRNA may be an excellent phylogenetic marker to discover its evolutionary history and pattern across the animal kingdom.

  5. Analysis of miR-205 and miR-155 expression in the blood of breast cancer patients

    Institute of Scientific and Technical Information of China (English)

    Jingjing Liu; Qixin Mao; Yan Liu; Xiaomeng Hao; Sheng Zhang; Jin Zhang

    2013-01-01

    The purpose of this study was to identify and validate circulating microRNAs (miRNAs) in human plasma for use as breast cancer (BC) biomarkers and to analyze their relationship to clinicopathologic features and its preliminary biological function.Genome-wide expression profiling of miRNAs in BC was investigated by microarray analysis.nmiR-155 was up-regulated greater than two-fold in BC compared with Normal Adjacent Tissue (NAT),whereas let-7b,miR-381,miR-10b,miR-125a-Sp,miR-335,miR-205 and miR-145 were down-regulated greater than two-fold.Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of BC patients compared to controls.Using real-time PCR (RT-PCR),we analyzed miR-205 and miR-155 in archived serum from 30 participants,20 with breast cancer and 10 healthy people.miR-205 was down-regulated in BC patient serum while miR-155 was up-regulated.Furthermore,we analyzed the relationship between the expression levels of these two miRNAs and the clinicopathologic parameters of BC patients.High expression of miR155 was associated with clinical stage,molecular type,Ki-67 and p53 in BC patients (P<0.05).By contrast,we found no significant correlation between miR-205 and BC patient clinicopathologic parameters.Functional analysis showed that ectopic expression of miR-205 significantly inhibits cell proliferation and promotes apoptosis.miR-205 was down-regulated and miR-155 was up-regulated in BC patient serum.miR-155 was positive correlated with clinical stage and ki-67 and negatively correlated with p53 status.

  6. Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status

    DEFF Research Database (Denmark)

    Rask, Lene; Balslev, Eva; Søkilde, Rolf;

    2014-01-01

    PURPOSE: Therapeutic decisions in breast cancer are increasingly guided by prognostic and predictive biomarkers. Non-protein-coding microRNAs (miRNAs) have recently been found to be deregulated in breast cancers and, in addition, to be correlated with several clinico-pathological features. One...... of the most consistently up-regulated miRNAs is miR-21. Here, we specifically searched for differentially expressed miRNAs in high-risk breast cancer patients as compared to low-risk breast cancer patients. In the same patients, we also compared miR-21 expression with the expression of its presumed target...... PTEN. METHODS: Both microarray and RT-qPCR techniques were used to assess miRNA expression levels in lymph node-positive and -negative human invasive ductal carcinoma tissues. Simultaneously, PTEN protein expression levels were assessed using immunohistochemistry. RESULTS: miR-486-5p and miR-139-5p...

  7. miR-221和miR-222在胃癌中的表达及临床意义%Expression of miR-221 and miR-222 in Gastric Cancer and its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    金晶; 闫竞一; 薛向阳; 武文一; 黄颖鹏; 朱冠保; 沈贤

    2011-01-01

    [Purpose] To investigate the expression of miR-221 and miR-222 in gastric cancer and its relationship with clinicopathologic features. [ Method ] The expression of miR-221 and miR-222 in 32 cases of gastric cancer tissues and their matched non-tumor adjacent tissues was examined by stem-loop RT-PCR. And the correlation with clinicopathologic features was investigated. [ Resuits] The expression of miR-221 and miR-222 in gastric cancer tissues was significantly higher than those in adjacent tissues (P<0.05). The ratio of miR-221/miR-222 expression had significant difference (P=0.05). The expression of miR-222 was related to differentiation (P=0.046); the expression of miR-221 was related to lymph node metastasis(P=0.013). [Conclusion] The expressions of miR-221 and miR-222 in gastric cancer markedly up regulation,they are important markers for gastric cancer,and they may play different effect with different stages in gastric cancer.%[目的]探讨miR-221和miR-222在胃癌中的表达及与临床病理特征的关系.[方法]应用茎环RT-PCR方法检测32例胃癌及癌旁胃黏膜组织中miR-221和miR-222表达,分析miR-221和miR-222表达与胃癌临床病理指标的关系.[结果]胃癌组织miR-221和miR-222表达明显高于对应的正常胃黏膜组织(P<0.05),且胃癌与正常胃黏膜组织中miR-221和miR-222比值也有显著性差异(P=0.05).miR-222表达与胃癌分化程度相关(P=0.046);miR-221表达与淋巴结转移相关(P=0.013).[结论]miR-221和miR-222在胃癌中表达明显上调是胃癌的重要标志.但两者在胃癌发生发展的不同阶段,可能发挥不同的效应.

  8. Reprogramming of miRNA networks in cancer and leukemia

    Science.gov (United States)

    Volinia, Stefano; Galasso, Marco; Costinean, Stefan; Tagliavini, Luca; Gamberoni, Giacomo; Drusco, Alessandra; Marchesini, Jlenia; Mascellani, Nicoletta; Sana, Maria Elena; Abu Jarour, Ramzey; Desponts, Caroline; Teitell, Michael; Baffa, Raffaele; Aqeilan, Rami; Iorio, Marilena V.; Taccioli, Cristian; Garzon, Ramiro; Di Leva, Gianpiero; Fabbri, Muller; Catozzi, Marco; Previati, Maurizio; Ambs, Stefan; Palumbo, Tiziana; Garofalo, Michela; Veronese, Angelo; Bottoni, Arianna; Gasparini, Pierluigi; Harris, Curtis C.; Visone, Rosa; Pekarsky, Yuri; de la Chapelle, Albert; Bloomston, Mark; Dillhoff, Mary; Rassenti, Laura Z.; Kipps, Thomas J.; Huebner, Kay; Pichiorri, Flavia; Lenze, Dido; Cairo, Stefano; Buendia, Marie-Annick; Pineau, Pascal; Dejean, Anne; Zanesi, Nicola; Rossi, Simona; Calin, George A.; Liu, Chang-Gong; Palatini, Jeff; Negrini, Massimo; Vecchione, Andrea; Rosenberg, Anne; Croce, Carlo M.

    2010-01-01

    We studied miRNA profiles in 4419 human samples (3312 neoplastic, 1107 nonmalignant), corresponding to 50 normal tissues and 51 cancer types. The complexity of our database enabled us to perform a detailed analysis of microRNA (miRNA) activities. We inferred genetic networks from miRNA expression in normal tissues and cancer. We also built, for the first time, specialized miRNA networks for solid tumors and leukemias. Nonmalignant tissues and cancer networks displayed a change in hubs, the most connected miRNAs. hsa-miR-103/106 were downgraded in cancer, whereas hsa-miR-30 became most prominent. Cancer networks appeared as built from disjointed subnetworks, as opposed to normal tissues. A comparison of these nets allowed us to identify key miRNA cliques in cancer. We also investigated miRNA copy number alterations in 744 cancer samples, at a resolution of 150 kb. Members of miRNA families should be similarly deleted or amplified, since they repress the same cellular targets and are thus expected to have similar impacts on oncogenesis. We correctly identified hsa-miR-17/92 family as amplified and the hsa-miR-143/145 cluster as deleted. Other miRNAs, such as hsa-miR-30 and hsa-miR-204, were found to be physically altered at the DNA copy number level as well. By combining differential expression, genetic networks, and DNA copy number alterations, we confirmed, or discovered, miRNAs with comprehensive roles in cancer. Finally, we experimentally validated the miRNA network with acute lymphocytic leukemia originated in Mir155 transgenic mice. Most of miRNAs deregulated in these transgenic mice were located close to hsa-miR-155 in the cancer network. PMID:20439436

  9. Effects of polycystic ovary syndrome (PCOS), sex hormones, and obesity on circulating miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 expression.

    Science.gov (United States)

    Murri, Mora; Insenser, María; Fernández-Durán, Elena; San-Millán, José L; Escobar-Morreale, Héctor F

    2013-11-01

    MicroRNAs (miRNAs) are small, noncoding RNA sequences that negatively regulate gene expression at the post-transcriptional level. miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 have been associated with metabolic disorders such as obesity and diabetes, which are also associated with polycystic ovary syndrome (PCOS). We aimed to evaluate the effects of sex, sex hormones, and PCOS and their interactions with obesity on the expression in the circulation of these miRNAs. This was a case-control study. The setting was an academic hospital. We included 12 control women, 12 patients with PCOS, and 12 men selected as to have similar body mass index (BMI) and age. Six subjects per group had normal weight (BMI obese (BMI ≥ 30 kg/m(2)). Blood samples were collected early in the morning after a 12-hour fast. We measured whole blood expression of miRNA-21, miRNA-27b, miRNA-103, and miRNA-155. Obesity significantly reduced the expression of miRNA-21, miRNA-27b, and miRNA-103. However, there was a significant interaction between obesity and the group of subjects in the expression of miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 consisting of obesity reducing the expression of these miRNAs in control woman and men, but tending to increase their expression in women with PCOS. These differences paralleled those observed in serum T concentrations. The present results suggest that miRNAs that play an important role in metabolic and immune system processes are influenced by obesity and circulating androgen concentrations.

  10. miR-29b, miR-205 and miR-221 enhance chemosensitivity to gemcitabine in HuH28 human cholangiocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Kinya Okamoto

    Full Text Available BACKGROUND AND AIMS: Cholangiocarcinoma (CCA is highly resistant to chemotherapy, including gemcitabine (Gem treatment. MicroRNAs (miRNAs are endogenous, non-coding, short RNAs that can regulate multiple genes expression. Some miRNAs play important roles in the chemosensitivity of tumors. Here, we examined the relationship between miRNA expression and the sensitivity of CCA cells to Gem. METHODS: Microarray analysis was used to determine the miRNA expression profiles of two CCA cell lines, HuH28 and HuCCT1. To determine the effect of candidate miRNAs on Gem sensitivity, expression of each candidate miRNA was modified via either transfection of a miRNA mimic or transfection of an anti-oligonucleotide. Ontology-based programs were used to identify potential target genes of candidate miRNAs that were confirmed to affect the Gem sensitivity of CCA cells. RESULTS: HuCCT1 cells were more sensitive to Gem than were HuH28 cells, and 18 miRNAs were differentially expressed whose ratios over ± 2log2 between HuH28 and HuCCT1. Among these 18 miRNAs, ectopic overexpression of each of three downregulated miRNAs in HuH28 (miR-29b, miR-205, miR-221 restored Gem sensitivity to HuH28. Suppression of one upregulated miRNA in HuH28, miR-125a-5p, inhibited HuH28 cell proliferation independently to Gem treatment. Selective siRNA-mediated downregulation of either of two software-predicted targets, PIK3R1 (target of miR-29b and miR-221 or MMP-2 (target of miR-29b, also conferred Gem sensitivity to HuH28. CONCLUSIONS: miRNA expression profiling was used to identify key miRNAs that regulate Gem sensitivity in CCA cells, and software that predicts miRNA targets was used to identify promising target genes for anti-tumor therapies.

  11. miReader: Discovering Novel miRNAs in Species without Sequenced Genome.

    Directory of Open Access Journals (Sweden)

    Ashwani Jha

    Full Text Available Along with computational approaches, NGS led technologies have caused a major impact upon the discoveries made in the area of miRNA biology, including novel miRNAs identification. However, to this date all microRNA discovery tools compulsorily depend upon the availability of reference or genomic sequences. Here, for the first time a novel approach, miReader, has been introduced which could discover novel miRNAs without any dependence upon genomic/reference sequences. The approach used NGS read data to build highly accurate miRNA models, molded through a Multi-boosting algorithm with Best-First Tree as its base classifier. It was comprehensively tested over large amount of experimental data from wide range of species including human, plants, nematode, zebrafish and fruit fly, performing consistently with >90% accuracy. Using the same tool over Illumina read data for Miscanthus, a plant whose genome is not sequenced; the study reported 21 novel mature miRNA duplex candidates. Considering the fact that miRNA discovery requires handling of high throughput data, the entire approach has been implemented in a standalone parallel architecture. This work is expected to cause a positive impact over the area of miRNA discovery in majority of species, where genomic sequence availability would not be a compulsion any more.

  12. Oligoasthenoteratozoospermia and infertility in mice deficient for miR-34b/c and miR-449 loci.

    Directory of Open Access Journals (Sweden)

    Stefano Comazzetto

    2014-10-01

    Full Text Available Male fertility requires the continuous production of high quality motile spermatozoa in abundance. Alterations in all three metrics cause oligoasthenoteratozoospermia, the leading cause of human sub/infertility. Post-mitotic spermatogenesis inclusive of several meiotic stages and spermiogenesis (terminal spermatozoa differentiation are transcriptionally inert, indicating the potential importance for the post-transcriptional microRNA (miRNA gene-silencing pathway therein. We found the expression of miRNA generating enzyme Dicer within spermatogenesis peaks in meiosis with critical functions in spermatogenesis. In an expression screen we identified two miRNA loci of the miR-34 family (miR-34b/c and miR-449 that are specifically and highly expressed in post-mitotic male germ cells. A reduction in several miRNAs inclusive of miR-34b/c in spermatozoa has been causally associated with reduced fertility in humans. We found that deletion of both miR34b/c and miR-449 loci resulted in oligoasthenoteratozoospermia in mice. MiR-34bc/449-deficiency impairs both meiosis and the final stages of spermatozoa maturation. Analysis of miR-34bc-/-;449-/- pachytene spermatocytes revealed a small cohort of genes deregulated that were highly enriched for miR-34 family target genes. Our results identify the miR-34 family as the first functionally important miRNAs for spermatogenesis whose deregulation is causal to oligoasthenoteratozoospermia and infertility.

  13. Value of combined detection of serum miR-21,miR-195 and miR-222 in the diagnosis of early breast cancer

    Institute of Scientific and Technical Information of China (English)

    Wen-Zhao Zhang; Ying Li; De-Xiang Wu

    2016-01-01

    Objective:To study level of miRNA in the serum of early breast carcinoma patients and to evaluate the clinical diagnostic value of combined detection of early breast carcinoma. Methods:A total of 54 cases of early breast carcinoma, 58 cases of benign breast diseases and 70 cases of healthy physical examination women were selected as the research subjects, to analysis serum miR-21, miR-195 and miR-222 levels by fluorescence quantitative PCR method and to analyze the diagnostic value of single and combined detection in early breast cancer by receiver operating characteristic curve. Results:The relative expression levels of miR-21, miR-222 and miR-195 in early breast carcinoma patients were significantly higher than those in benign breast disease and healthy controls;there was no significant difference in the relative expression of miR-21, miR-222 and miR-195 in the benign breast disease group and healthy control group;receiver operating characteristic curve analysis showed that AUC of miR-21, miR-195 and miR-222 in the diagnosis of early breast carcinoma were 0.805, 0.86 and 0.848 respectively, the sensitivity were 63.3%, 70.0%and 70.0%, and the specificity were 86.7%, 93.3%and 90.0%;AUC, sensitivity and specificity of the combined detection were 0.974, 93.3%and 96.7%respectively. Conclusion:miR-21, miR-195 and miR-222 levels in serum of patients with early breast carcinoma rise, the combined detection of the 3 indicators have a high diagnostic value for early breast carcinoma, and contribute to early breast carcinoma screening and diagnosis.

  14. Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance

    Science.gov (United States)

    Danza, Katia; Silvestris, Nicola; Simone, Giovanni; Signorile, Michele; Saragoni, Luca; Brunetti, Oronzo; Monti, Manlio; Mazzotta, Annalisa; De Summa, Simona; Mangia, Anita; Tommasi, Stefania

    2016-01-01

    ABSTRACT Despite the search for new therapeutic strategies for gastric cancer (GC), there is much evidence of progression due to resistance to chemotherapy. Multidrug resistance (MDR) is the ability of cancer cells to survive after exposure to chemotherapeutic agents. The involvement of miRNAs in the development of MDR has been well described but miRNAs able to modulate the sensitivity to chemotherapy by regulating hypoxia signaling pathways have not yet been fully addressed in GC. Our aim was to analyze miR-20b, miR-27a and miR-181a expression with respect to (epirubicin/oxaliplatin/capecitabine (EOX)) chemotherapy regimen in a set of GC patients, in order to investigate whether miRNAs deregulation may influence GC MDR also via hypoxia signaling modulation. Cancer biopsy were obtained from 21 untreated HER2 negative advanced GC patients, retrospectively analyzed. All patients received a first-line chemotherapy (EOX) regimen. MirWalk database was used to identify miR-27a, miR-181a and miR-20b target genes. The expression of miRNAs and of HIPK2, HIF1A and MDR1 genes were detected by real-time PCR. HIPK2 localization was assessed by immunohistochemistry. Our data showed the down-regulation of miR-20b, miR-27a, miR-181a concomitantly to higher levels of MDR1, HIF1A and HIPK2 genes in GC patients with a progressive disease respect to those with a disease control rate. Moreover, immunohistochemistry assay highlighted a higher cytoplasmic HIPK2 staining, suggesting a different role for it. We showed that aberrant expression of miR-20b, miR27a and miR-181a was associated with chemotherapeutic response in GC through HIF1A, MDR1 and HIPK2 genes modulation, suggesting a possible novel therapeutic strategy. PMID:26793992

  15. Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance.

    Science.gov (United States)

    Danza, Katia; Silvestris, Nicola; Simone, Giovanni; Signorile, Michele; Saragoni, Luca; Brunetti, Oronzo; Monti, Manlio; Mazzotta, Annalisa; De Summa, Simona; Mangia, Anita; Tommasi, Stefania

    2016-04-02

    Despite the search for new therapeutic strategies for gastric cancer (GC), there is much evidence of progression due to resistance to chemotherapy. Multidrug resistance (MDR) is the ability of cancer cells to survive after exposure to chemotherapeutic agents. The involvement of miRNAs in the development of MDR has been well described but miRNAs able to modulate the sensitivity to chemotherapy by regulating hypoxia signaling pathways have not yet been fully addressed in GC. Our aim was to analyze miR-20b, miR-27a and miR-181a expression with respect to (epirubicin/oxaliplatin/capecitabine (EOX)) chemotherapy regimen in a set of GC patients, in order to investigate whether miRNAs deregulation may influence GC MDR also via hypoxia signaling modulation. Cancer biopsy were obtained from 21 untreated HER2 negative advanced GC patients, retrospectively analyzed. All patients received a first-line chemotherapy (EOX) regimen. MirWalk database was used to identify miR-27a, miR-181a and miR-20b target genes. The expression of miRNAs and of HIPK2, HIF1A and MDR1 genes were detected by real-time PCR. HIPK2 localization was assessed by immunohistochemistry. Our data showed the down-regulation of miR-20b, miR-27a, miR-181a concomitantly to higher levels of MDR1, HIF1A and HIPK2 genes in GC patients with a progressive disease respect to those with a disease control rate. Moreover, immunohistochemistry assay highlighted a higher cytoplasmic HIPK2 staining, suggesting a different role for it. We showed that aberrant expression of miR-20b, miR27a and miR-181a was associated with chemotherapeutic response in GC through HIF1A, MDR1 and HIPK2 genes modulation, suggesting a possible novel therapeutic strategy.

  16. Early Sámi visual artists - Western fine art meets Sámi culture

    Directory of Open Access Journals (Sweden)

    Tuija Hautala-Hirvioja

    2014-04-01

    Full Text Available Johan Turi (1854–1936, Nils Nilsson Skum (1872–1951 and John Savio (1902–1938 were among the first Sámi visual artists. The production of their art work occurred between the 1910s and the early 1950s. Sámi aesthetics had its basis in folklore, i.e., handicraft or duodji, which did not follow the principle of art for art’s sake but combined beauty and practicality. Art was part of community life. Not until the 1970s was the word daidda, which is Finnish in origin and which means “art”, adopted into the Sámi language. Turi and Skum became famous through their books. They drew and wrote in order to pass the traditional knowledge of their people on to succeeding generations. They also wanted to introduce Sámi life and culture to non-Sámi people. One typical feature of their work is that they depicted Sáminess in a realistic way and sought to strengthen and preserve the Sámi identity through their art. In Turi and Skum’s work, both the documentation of community life and their own personal expression were strongly present and equally important; for this reason their pictures and texts have both practical and aesthetic dimensions. They did not attend school and were self-taught artists. The third pioneer of Sámi visual arts was John Savio, who, unlike the other two, attended secondary school and studied visual arts both independently and under the guidance of a mentor. He expressively combined Western ways of depiction with Sámi subjects. My article examines what made these early Sámi artists change over from Sámi handicraft, duodji, to Western visual arts, how they used Western pictorial conventions in dealing with their Sámi subjects, and the significance of their art for Sámi identity and culture. They lived and worked under cross pressure: the first few decades of the 20th century were characterized by racial theories that denigrated Sámi people, and the period following World War II was marked by demands for

  17. Expression profiles of miRNAs and involvement of miR-100 and miR-34 in regulation of cell cycle arrest in Artemia.

    Science.gov (United States)

    Zhao, Ling-Ling; Jin, Feng; Ye, Xiang; Zhu, Lin; Yang, Jin-Shu; Yang, Wei-Jun

    2015-09-01

    Regulation of the cell cycle is complex but critical for proper development, reproduction and stress resistance. To survive unfavourable environmental conditions, the crustacean Artemia produces diapause embryos whose metabolism is maintained at extremely low levels. In the present study, the expression profiles of miRNAs during Artemia diapause entry and termination were characterized using high-throughput sequencing. A total of 13 unclassified miRNAs and 370 miRNAs belonging to 87 families were identified; among them, 107 were differentially expressed during diapause entry and termination. We focused on the roles of two of these miRNAs, miR-100 and miR-34, in regulating cell cycle progression; during the various stages of diapause entry, these miRNAs displayed opposing patterns of expression. A functional analysis revealed that miR-100 and miR-34 regulate the cell cycle during diapause entry by targeting polo-like kinase 1 (PLK1), leading to activation of the mitogen-activated protein kinase kinase-extracellular signal-regulated kinase-ribosomal S6 kinase 2 (MEK-ERK-RSK2) pathway and cyclin K, leading to suppression of RNA polymerase II (RNAP II) activity respectively. The findings presented in the present study provide insights into the functions of miR-100 and miR-34 and suggest that the expression profiles of miRNAs in Artemia can be used to characterize their functions in cell cycle regulation.

  18. Discovery of miRNAs and Their Corresponding miRNA Genes in Atlantic Cod (Gadus morhua: Use of Stable miRNAs as Reference Genes Reveals Subgroups of miRNAs That Are Highly Expressed in Particular Organs.

    Directory of Open Access Journals (Sweden)

    Rune Andreassen

    Full Text Available Atlantic cod (Gadus morhua is among the economically most important species in the northern Atlantic Ocean and a model species for studying development of the immune system in vertebrates. MicroRNAs (miRNAs are an abundant class of small RNA molecules that regulate fundamental biological processes at the post-transcriptional level. Detailed knowledge about a species miRNA repertoire is necessary to study how the miRNA transcriptome modulate gene expression. We have therefore discovered and characterized mature miRNAs and their corresponding miRNA genes in Atlantic cod. We have also performed a validation study to identify suitable reference genes for RT-qPCR analysis of miRNA expression in Atlantic cod. Finally, we utilized the newly characterized miRNA repertoire and the dedicated RT-qPCR method to reveal miRNAs that are highly expressed in certain organs.The discovery analysis revealed 490 mature miRNAs (401 unique sequences along with precursor sequences and genomic location of the miRNA genes. Twenty six of these were novel miRNA genes. Validation studies ranked gmo-miR-17-1-5p or the two-gene combination gmo-miR25-3p and gmo-miR210-5p as most suitable qPCR reference genes. Analysis by RT-qPCR revealed 45 miRNAs with significantly higher expression in tissues from one or a few organs. Comparisons to other vertebrates indicate that some of these miRNAs may regulate processes like growth, lipid metabolism, immune response to microbial infections and scar damage repair. Three teleost-specific and three novel Atlantic cod miRNAs were among the differentially expressed miRNAs.The number of known mature miRNAs was considerably increased by our identification of miRNAs and miRNA genes in Atlantic cod. This will benefit further functional studies of miRNA expression using deep sequencing methods. The validation study showed that stable miRNAs are suitable reference genes for RT-qPCR analysis of miRNA expression. Applying RT-qPCR we have identified

  19. MI Gap Clearing Kicker Magnet Design Review

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Chris; /Fermilab

    2008-10-01

    The kicker system requirements were originally conceived for the NOvA project. NOvA is a neutrino experiment located in Minnesota. To achieve the desired neutrino flux several upgrades are required to the accelerator complex. The Recycler will be used as a proton pre-injector for the Main Injector (MI). As the Recycler is the same size as the MI, it is possible to do a single turn fill ({approx}11 {micro}sec), minimizing the proton injection time in the MI cycle and maximizing the protons on target. The Recycler can then be filled with beam while the MI is ramping to extract beam to the target. To do this requires two new transfer lines. The existing Recycler injection line was designed for 10{pi} pbar beams, not the 20{pi} proton beams we anticipate from the Booster. The existing Recycler extraction line allows for proton injection through the MI, while we want direct injection from the Booster. These two lines will be decommissioned. The new injection line from the MI8 line into the Recycler will start at 848 and end with injection kickers at RR104. The new extraction line in the RR30 straight section will start with a new extraction kicker at RR232 and end with new MI injection kickers at MI308. Finally, to reduce beam loss activation in the enclosure, a new gap clearing kicker will be used to extract uncaptured beam created during the slip stack injection process down the existing dump line. It was suggested that the MI could benefit from this type of system immediately. This led to the early installation of the gap clearing system in the MI, followed by moving the system to Recycler during NOvA. The specifications also changed during this process. Initially the rise and fall time requirements were 38 ns and the field stability was {+-}1%. The 38 ns is based on having a gap of 2 RF buckets between injections. (There are 84 RF buckets that can be filled from the Booster for each injection, but 82 would be filled with beam. MI and Recycler contain 588 RF buckets

  20. Identification of ovarian cancer metastatic miRNAs.

    Directory of Open Access Journals (Sweden)

    Souriya Vang

    Full Text Available Serous epithelial ovarian cancer (EOC patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2-4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.

  1. MDRL lncRNA regulates the processing of miR-484 primary transcript by targeting miR-361.

    Directory of Open Access Journals (Sweden)

    Kun Wang

    2014-07-01

    Full Text Available Long noncoding RNAs (lncRNAs are emerging as new players in gene regulation, but whether lncRNAs operate in the processing of miRNA primary transcript is unclear. Also, whether lncRNAs are involved in the regulation of the mitochondrial network remains to be elucidated. Here, we report that a long noncoding RNA, named mitochondrial dynamic related lncRNA (MDRL, affects the processing of miR-484 primary transcript in nucleus and regulates the mitochondrial network by targeting miR-361 and miR-484. The results showed that miR-361 that predominantly located in nucleus can directly bind to primary transcript of miR-484 (pri-miR-484 and prevent its processing by Drosha into pre-miR-484. miR-361 is able to regulate mitochondrial fission and apoptosis by regulating miR-484 levels. In exploring the underlying molecular mechanism by which miR-361 is regulated, we identified MDRL and demonstrated that it could directly bind to miR-361 and downregulate its expression levels, which promotes the processing of pri-miR-484. MDRL inhibits mitochondrial fission and apoptosis by downregulating miR-361, which in turn relieves inhibition of miR-484 processing by miR-361. Our present study reveals a novel regulating model of mitochondrial fission program which is composed of MDRL, miR-361 and miR-484. Our work not only expands the function of the lncRNA pathway in gene regulation but also establishes a new mechanism for controlling miRNA expression.

  2. miR-10b, miR-26a, miR-146a And miR-153 Expression in Triple Negative Vs Non Triple Negative Breast Cancer: Potential Biomarkers.

    Science.gov (United States)

    Fkih M'hamed, Insaf; Privat, Maud; Trimeche, Mounir; Penault-Llorca, Frédérique; Bignon, Yves-Jean; Kenani, Abderraouf

    2017-01-18

    MicroRNAs (miRNAs) are small non-coding RNAs composed of 18-25 nucleotides that can post-transcriptionally regulate gene expression and have key regulatory roles in cancer, acting as both oncogenes and tumor suppressors. About 1000 genes in humans encode miRNAs, which account for approximately 3% of the human genome, and up to 30% of human protein coding genes may be regulated by miRNAs. The objective of this article is to evaluate the expression profile of four miRNAs previously implicated in triple negative breast cancer: miR-10b, miR-26a, miR-146a and miR-153, and to determine their possible interaction in triple negative and non triple negative breast cancer based on clinical outcome and the expression of BRCA1. 24 triple-negative and 13 non triple negative breast cancer cases, were studied by q-RT-PCR and immunohistochemistry to determine the expression of the four studied miRNAs and the BRCA1 protein, respectively. We observed that the BRCA1 protein was absent in 62.5% of the triple negative cases. Besides, the miR-146a and miR-26a were over expressed in triple negative breast cancer. These two miRNAs, miR-10b and miR-153 were significantly associated to lymph node metastases occurrence in triple negative breast carcinoma. All the analyzed microRNAs were not associated with the expression of BRCA1 in our conditions. Our work provides evidence that miR-146a, miR-26a, miR-10b and miR-153 could be defined as biomarkers in triple negative breast cancer to predict lymph node metastases (LNM).

  3. Differentially expressed miRNAs in trisomy 21 placentas.

    Science.gov (United States)

    Svobodová, Iveta; Korabečná, Marie; Calda, Pavel; Břešťák, Miroslav; Pazourková, Eva; Pospíšilová, Šárka; Krkavcová, Miroslava; Novotná, Michaela; Hořínek, Aleš

    2016-08-01

    Molecular pathogenesis of Down syndrome (DS) is still incompletely understood. Epigenetic mechanisms, including miRNAs gene expression regulation, belong to potential influencing factors. The aims of this study were to compare miRNAs expressions in placentas with normal and trisomic karyotype and to associate differentially expressed miRNAs with concrete biological pathways. A total of 80 CVS samples - 41 with trisomy 21 and 39 with normal karyotype - were included in our study. Results obtained in the pilot study using real-time PCR technology and TaqMan Human miRNA Array Cards were subsequently validated on different samples using individual TaqMan miRNA Assays. Seven miRNAs were verified as upregulated in DS placentas (miR-99a, miR-542-5p, miR-10b, miR-125b, miR-615, let-7c and miR-654); three of these miRNAs are located on chromosome 21 (miR-99a, miR-125b and let-7c). Many essential biological processes, transcriptional regulation or apoptosis, were identified as being potentially influenced by altered miRNA levels. Moreover, miRNAs overexpressed in DS placenta apparently regulate genes involved in placenta development (GJA1, CDH11, EGF, ERVW-1, ERVFRD-1, LEP or INHA). These findings suggest the possible participation of miRNAs in Down syndrome impaired placentation and connected pregnancy pathologies. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  4. The regulation roles of miR-125b, miR-221 and miR-27b in porcine Salmonella infection signalling pathway.

    Science.gov (United States)

    Yao, Min; Gao, Weihua; Yang, Jun; Liang, Xiongyan; Luo, Jingbo; Huang, Tinghua

    2016-08-01

    miRNAs are non-coding RNA molecules typically 18-22 nucleotides long that can suppress the expression of their target genes. Several laboratories have attempted to identify miRNAs from the pig that are involved in Salmonella infection. These bioinformatics strategies using the newly available genomic sequence are generally successful. Here, we report an in silico identification of miRNAs in pig focusing on the Salmonella infection pathway, and further investigated the differential expression of those miRNAs by quantitative real-time PCR during pre- and post-natal stage of Salmonella inoculation from the peripheral blood of commercially breed pigs. We identified 29 miRNAs that have predicted targets in the Salmonella infection pathway and nine of them were not yet described in pig. In addition, the expression of nine selected miRNAs was validated in the peripheral blood by northern blotting. Through expression analyses, differences were found between pre- and post-natal stages of Salmonella inoculation for miR-221, miR-125b and miR-27b-all of them were suppressed 2 days after Salmonella inoculation. The predicted targets of those three miRNAs were validated by luciferase reporter assays. We show that FOS is a direct target of miR-221, miR-125b can suppress MAPK14, and miR-27b can target IFNG. These findings will be helpful in understanding the function and processing of these miRNAs in Salmonella infection. The miRNA differentially expressed in the peripheral blood of commercial breed pigs suggest that it can be used as genetic markers for salmonella infection resistance in pigs.

  5. Identification of miR414 and expression analysis of conserved miRNAs from Stevia rebaudiana.

    Science.gov (United States)

    Guleria, Praveen; Yadav, Sudesh Kumar

    2011-12-01

    MicroRNAs (miRNAs) usually contain 19-24 nucleotides and have been identified as important eukaryotic gene regulators. Applications of various computational approaches have simplified the task by predicting miRNAs from available sequence data sources. In this study, we identified a conserved miR414 from a computational analysis of EST sequence data available from Stevia rebaudiana. In addition, we also identified six conserved miRNAs namely miR169, miR319, miR414, miR164, miR167 and miR398 using stem-loop RT-PCR analysis. Hence, miR414 was commonly identified using both methods. The expression analysis of these miRNAs documented their roles in growth and development of Stevia. Furthermore, the detected miRNAs were found to target genes involved in plant growth, development, metabolism and signal transduction. This is the first study reporting these conserved miRNAs and their expression in Stevia.

  6. Fluoxetine Increases the Expression of miR-572 and miR-663a in Human Neuroblastoma Cell Lines

    Science.gov (United States)

    Mundalil Vasu, Mahesh; Anitha, Ayyappan; Takahashi, Taro; Thanseem, Ismail; Iwata, Keiko; Asakawa, Tetsuya; Suzuki, Katsuaki

    2016-01-01

    Evidence suggests neuroprotective effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on the developed neurons in the adult brain. In contrast, the drug may be deleterious to immature or undifferentiated neural cells, although the mechanism is unclear. Recent investigations have suggested that microRNAs (miRNA) may be critical for effectiveness of psychotropic drugs including SSRI. We investigated whether fluoxetine could modulate expressions of neurologically relevant miRNAs in two neuroblastoma SK-N-SH and SH-SY5Y cell lines. Initial screening results revealed that three (miR-489, miR-572 and miR-663a) and four (miR-320a, miR-489, miR-572 and miR-663a) miRNAs were up-regulated in SK-N-SH cells and SH-SY5Y cells, respectively, after 24 hours treatment of fluoxetine (1–25 μM). Cell viability was reduced according to the dose of fluoxetine. The upregulation of miR-572 and miR-663a was consistent in both the SH-SY5Y and SK-N-SH cells, confirmed by a larger scale culture condition. Our data is the first in vitro evidence that fluoxetine could increase the expression of miRNAs in undifferentiated neural cells, and that putative target genes of those miRNAs have been shown to be involved in fundamental neurodevelopmental processes. PMID:27716787

  7. Use of Mature miRNA Strand Selection in miRNAs Families in Cervical Cancer Development

    Directory of Open Access Journals (Sweden)

    Angelica Judith Granados-López

    2017-02-01

    Full Text Available Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt chain sizes. In general, mature 5p strands are larger: two miRNAs of 24 nt, 24 miRNAs of 23 nt, 35 miRNAs of 22 nt and three miRNAs of 21 nt. On the other hand, the 3p strands lengths observed are: seven miRNAs of 23 nt, 50 miRNAs of 22 nt, six miRNAs of 21 nt and four miRNAs of 20 nt. Based on the analysis of the 20 miRNA families associated with cervical cancer, 67 3p strands and 65 5p strands are selected suggesting selectivity and specificity mechanisms regulating cell processes like proliferation, apoptosis, migration, invasion, metabolism and Warburg effect. The insight reviewed here could be used in the miRNA based therapy, diagnosis and prognosis approaches.

  8. Use of Mature miRNA Strand Selection in miRNAs Families in Cervical Cancer Development

    Science.gov (United States)

    Granados-López, Angelica Judith; Ruiz-Carrillo, José Luis; Servín-González, Luis Steven; Martínez-Rodríguez, José Luis; Reyes-Estrada, Claudia Araceli; Gutiérrez-Hernández, Rosalinda; López, Jesús Adrián

    2017-01-01

    Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt) chain sizes. In general, mature 5p strands are larger: two miRNAs of 24 nt, 24 miRNAs of 23 nt, 35 miRNAs of 22 nt and three miRNAs of 21 nt. On the other hand, the 3p strands lengths observed are: seven miRNAs of 23 nt, 50 miRNAs of 22 nt, six miRNAs of 21 nt and four miRNAs of 20 nt. Based on the analysis of the 20 miRNA families associated with cervical cancer, 67 3p strands and 65 5p strands are selected suggesting selectivity and specificity mechanisms regulating cell processes like proliferation, apoptosis, migration, invasion, metabolism and Warburg effect. The insight reviewed here could be used in the miRNA based therapy, diagnosis and prognosis approaches. PMID:28216603

  9. 15-脱氧-△12,14-前列腺素J2对兔耳增生性瘢痕Ⅰ型胶原表达的影响%Effects of 15-deoxy-△12,14-prostagliandxin J2 on the expression of type Ⅰ collagen in hypertrophic scar of rabbit ears

    Institute of Scientific and Technical Information of China (English)

    潘姝; 李罡; 李叶扬; 方力; 祁少海; 舒斌; 梁佩红; 戴丽冰; 李建平; 张琰

    2010-01-01

    Objective To investigate the effect of 15d-PGJ2 on the expression of type Ⅰ collagen in hypertrophic scar of rabbit ears, and the possibility of hypertrophic scar treated by 15d-PGJ2. Methods Eighteen New Zealand white rabbits were used to establish the hypertrophic scar models on the rabbit ears. The wounds were created as follows: 2 cm × 3 cm wounds with total skin loses on the ventral side, 2wounds for each ear, total 72 wounds. The wounds were randomly divided into the 15d-PGJ2 treatment group and NS control group. A total of 20 μl 15d-PGJ2 or NS was injected into the ear scar once a day for 7 days. At the 14th and 21st day after the injection, 18 scars in each group were harvested. The expression levels of type Ⅰ collagen was detected by immunohistochemistry, fluorescence quantitative polymerase chain reaction (PCR) and Western blotting. Results Compared with the NS control group, the 15d-PGJ2-treated scars appeared to be smaller, softer, flatter and lighter in color. The expression of type Ⅰcollagen was mainly distributed in matrix, fibroblast cytoplasma and the vascular wall. The mRNA and protein levels of type Ⅰ collagen were significantly decreased in the 15d-PGJ2-treated group as compared with those in the NS control group at different time points (P < 0. 05). Conclusion 15d-PGJ2, the ligand of PPAR-γ, can reduce the expression of type Ⅰ collagen in hypertrophic scar of rabbit ears and plays an important role in the prevention and treatment of hypertrophic scar. It offers a new way for treating the hypertrophic scar clinically.%目的 观察过氧化物酶体增殖物激活受体γ(PPARγ)的配体15-脱氧-△12,14-前列腺素J2(15d-PGJ2)对兔耳增生性瘢痕Ⅰ型胶原表达的影响,探讨15d-PGJ2防治增生性瘢痕的可行性.方法 选取新西兰大白兔18只,在兔耳腹侧面制作2 cm×3 cm全层皮肤缺损创面,每耳2个,共计72个,建立兔耳增生性瘢痕动物模型,随机分组,分别用15d-PGJ2及

  10. "Seed-Milarity" confers to hsa-miR-210 and hsa-miR-147b similar functional activity.

    Directory of Open Access Journals (Sweden)

    Thomas Bertero

    Full Text Available Specificity of interaction between a microRNA (miRNA and its targets crucially depends on the seed region located in its 5'-end. It is often implicitly considered that two miRNAs sharing the same biological activity should display similarity beyond the strict six nucleotide region that forms the seed, in order to form specific complexes with the same mRNA targets. We have found that expression of hsa-miR-147b and hsa-miR-210, though triggered by different stimuli (i.e. lipopolysaccharides and hypoxia, respectively, induce very similar cellular effects in term of proliferation, migration and apoptosis. Hsa-miR-147b only shares a "minimal" 6-nucleotides seed sequence with hsa-miR-210, but is identical with hsa-miR-147a over 20 nucleotides, except for one base located in the seed region. Phenotypic changes induced after heterologous expression of miR-147a strikingly differ from those induced by miR-147b or miR-210. In particular, miR-147a behaves as a potent inhibitor of cell proliferation and migration. These data fit well with the gene expression profiles observed for miR-147b and miR-210, which are very similar, and the gene expression profile of miR-147a, which is distinct from the two others. Bioinformatics analysis of all human miRNA sequences indicates multiple cases of miRNAs from distinct families exhibiting the same kind of similarity that would need to be further characterized in terms of putative functional redundancy. Besides, it implies that functional impact of some miRNAs can be masked by robust expression of miRNAs belonging to distinct families.

  11. A path-based measurement for human miRNA functional similarities using miRNA-disease associations

    Science.gov (United States)

    Ding, Pingjian; Luo, Jiawei; Xiao, Qiu; Chen, Xiangtao

    2016-09-01

    Compared with the sequence and expression similarity, miRNA functional similarity is so important for biology researches and many applications such as miRNA clustering, miRNA function prediction, miRNA synergism identification and disease miRNA prioritization. However, the existing methods always utilized the predicted miRNA target which has high false positive and false negative to calculate the miRNA functional similarity. Meanwhile, it is difficult to achieve high reliability of miRNA functional similarity with miRNA-disease associations. Therefore, it is increasingly needed to improve the measurement of miRNA functional similarity. In this study, we develop a novel path-based calculation method of miRNA functional similarity based on miRNA-disease associations, called MFSP. Compared with other methods, our method obtains higher average functional similarity of intra-family and intra-cluster selected groups. Meanwhile, the lower average functional similarity of inter-family and inter-cluster miRNA pair is obtained. In addition, the smaller p-value is achieved, while applying Wilcoxon rank-sum test and Kruskal-Wallis test to different miRNA groups. The relationship between miRNA functional similarity and other information sources is exhibited. Furthermore, the constructed miRNA functional network based on MFSP is a scale-free and small-world network. Moreover, the higher AUC for miRNA-disease prediction indicates the ability of MFSP uncovering miRNA functional similarity.

  12. Dynamic expression of miR-132, miR-212, and miR-146 in the brain of different hosts infected with Angiostrongylus cantonensis.

    Science.gov (United States)

    Yu, Liping; Liao, Qi; Chen, Xiaoguang; Xu, Lian; Zeng, Xin; Lv, Zhiyue; Sun, Xi; Zhen, Huanqin; Wu, Zhongdao

    2014-01-01

    Increasing evidence shows that microRNAs (miRNAs) are a family of regulatory molecules involved in many physiological processes, including the inflammation in central nervous system (CNS) and neurological disorders. Angiostrongylus cantonensis (A. cantonensis) is the major cause of human infectious eosinophilic meningitis and can induce CNS injury. In the present study, we investigated the expression of miRNAs involved in neuronal functions such as miR-132-3p/212-3p, and miR-146a-5p, inflammation-related miRNA, in the modulation of inflammation of CNS of mice and rats induced by A. cantonensis. The functions of differentially expressed miRNAs were analyzed through bioinformatics methods, and the expression of chosen target genes were investigated by quantitative reverse transcription polymerase chain reaction. The results showed that miR-146a-5p upregulated in the brain of rats after 21 days; A. cantonensis infection and the expression of miR-132-3p and miR-146a-5p upregulated in the brain of mice model infected by A. cantonensis. The expression of the target genes of mmu-miR-146a-5p such as Irak1 and Traf6 downregulated in 14 days and 21 days after A. cantonensis infection. Our results supply more information about the involvement of the miRNAs in the regulation of inflammation of CNS induced by A. cantonensis.

  13. EL CIRCO Y MI DILEMA

    Directory of Open Access Journals (Sweden)

    Martalucía Tamayo

    2015-03-01

    habilidades excepcionales, temo que lo que se esté buscando (¿o logrando? es un aplauso lleno de compasión o lástima por su condición de “seres diferentes”; o más bien agradados por haber presenciado “un fenómeno” digno de ser exhibido para la curiosidad morbosa de la gente. Ojalá no haya sido por eso. Tengo el mismo sentimiento de rechazo a los movimientos tipo “Teletón”, que suelen recoger ayuda económica mediante la explotación de un sentimiento de “compasión y lástima”. He luchado toda mi vida para que la sociedad no olvide el valor de la diferencia, el respeto a ella, el derecho a ser y vivir diferente; y hemos trabajado por muchos años para que esas personas “diferentes” sean (seamos “sujetos de derechos” igual que cualquier otro ser humano. Lo triste, y he ahí mi dilema, es que muchas personas del público comentan “pobrecitos, tan tiernos, al menos estos dos tienen empleo y viven de algo” y me digo que es verdad; son de los pocos que quizás logren sobrevivir económicamente bien en un mundo que está lejos de ser fácil para ellos. Pero ahí surge el dilema y el temor de que la sociedad aprenda a ver las cosas de manera equivocada. Y... ¿la dignidad? ¿Dónde queda la concientización o sensibilización de la sociedad? ¿Dónde queda el respeto a la diferencia? ¿A quién podría gustarle ser exhibido como fenómeno? ¿Alguien se ha preguntado el drama que vive el “ser diferente” en un mundo que no está diseñado para todo el mundo?...

  14. Dissection of miRNA pathways using arabidopsis mesophyll protoplasts.

    Science.gov (United States)

    Martinho, Cláudia; Confraria, Ana; Elias, Carlos Alexandre; Crozet, Pierre; Rubio-Somoza, Ignacio; Weigel, Detlef; Baena-González, Elena

    2015-02-01

    MicroRNAs (miRNAs) control gene expression mostly post-transcriptionally by guiding transcript cleavage and/or translational repression of complementary mRNA targets, thereby regulating developmental processes and stress responses. Despite the remarkable expansion of the field, the mechanisms underlying miRNA activity are not fully understood. In this article, we describe a transient expression system in Arabidopsis mesophyll protoplasts, which is highly amenable for the dissection of miRNA pathways. We show that by transiently overexpressing primary miRNAs and target mimics, we can manipulate miRNA levels and consequently impact on their targets. Furthermore, we developed a set of luciferase-based sensors for quantifying miRNA activity that respond specifically to both endogenous and overexpressed miRNAs and target mimics. We demonstrate that these miRNA sensors can be used to test the impact of putative components of the miRNA pathway on miRNA activity, as well as the impact of specific mutations, by either overexpression or the use of protoplasts from the corresponding mutants. We further show that our miRNA sensors can be used for investigating the effect of chemicals on miRNA activity. Our cell-based transient expression system is fast and easy to set up, and generates quantitative results, being a powerful tool for assaying miRNA activity in vivo.

  15. miEAA: microRNA enrichment analysis and annotation.

    Science.gov (United States)

    Backes, Christina; Khaleeq, Qurratulain T; Meese, Eckart; Keller, Andreas

    2016-07-08

    Similar to the development of gene set enrichment and gene regulatory network analysis tools over a decade ago, microRNA enrichment tools are currently gaining importance. Building on our experience with the gene set analysis toolkit GeneTrail, we implemented the miRNA Enrichment Analysis and Annotation tool (miEAA). MiEAA is a web-based application that offers a variety of commonly applied statistical tests such as over-representation analysis and miRNA set enrichment analysis, which is similar to Gene Set Enrichment Analysis. Besides the different statistical tests, miEAA also provides rich functionality in terms of miRNA categories. Altogether, over 14 000 miRNA sets have been added, including pathways, diseases, organs and target genes. Importantly, our tool can be applied for miRNA precursors as well as mature miRNAs. To make the tool as useful as possible we additionally implemented supporting tools such as converters between different miRBase versions and converters from miRNA names to precursor names. We evaluated the performance of miEAA on two sets of miRNAs that are affected in lung adenocarcinomas and have been detected by array analysis. The web-based application is freely accessible at: http://www.ccb.uni-saarland.de/mieaa_tool/.

  16. miRNA expression during prickly pear cactus fruit development.

    Science.gov (United States)

    Rosas-Cárdenas, Flor de Fátima; Caballero-Pérez, Juan; Gutiérrez-Ramos, Ximena; Marsch-Martínez, Nayelli; Cruz-Hernández, Andrés; de Folter, Stefan

    2015-02-01

    miRNAs are a class of small non-coding RNAs that regulate gene expression. They are involved in the control of many developmental processes, including fruit development. The increasing amount of information on miRNAs, on their expression, abundance, and conservation between various species, provides a new opportunity to study the role of miRNAs in non-model plant species. In this work, we used a combination of Northern blot and tissue print hybridization analysis to identify conserved miRNAs expressed during prickly pear cactus (Opuntia ficus indica) fruit development. Comparative profiling detected the expression of 34 miRNAs, which were clustered in three different groups that were associated with the different phases of fruit development. Variation in the level of miRNA expression was observed. Gradual expression increase of several miRNAs was observed during fruit development, including miR164. miR164 was selected for stem-loop RT-PCR and for a detailed spatial-temporal expression analysis. At early floral stages, miR164 was mainly localized in meristematic tissues, boundaries and fusion zones, while it was more homogenously expressed in fruit tissues. Our results provide the first evidence of miRNA expression in the prickly pear cactus and provide the basis for future research on miRNAs in Opuntia. Moreover, our analyses suggest that miR164 plays different roles during prickly pear cactus fruit development.

  17. Differential Expression of miR-21, miR-126, miR-143, miR-373 in Normal Cervical Tissue, Cervical Cancer Tissue and Hela Cell%miR-21、miR-126、miR-143和miR-373在正常宫颈组织、宫颈癌组织及Hela细胞中的表达差异

    Institute of Scientific and Technical Information of China (English)

    刘琳; 王月玲; 王江芬

    2012-01-01

    目的 研究miR-21、miR-126、miR-143和miR-373在正常宫颈组织、宫颈癌组织及Hela细胞中的表达差异,探讨microRNAs(miRNAs)对宫颈癌发生的调控作用.方法 荧光实时定量检测20例良性肿瘤患者的正常宫颈组织,20例宫颈癌组织及Hela细胞中miR-21、miR-126、miR-143和miR-373的表达.结果 m iR-21在宫颈癌组织及Hela细胞系中高表达,在正常宫颈标本中低表达,在宫颈癌组织中相对定量为正常宫颈组织的11.3196倍(P<0.05);miR-143、miR-373在宫颈癌组织及Hela细胞中均低表达,在正常宫颈标本中高表达,miR-143、miR-373在宫颈癌组织中相对定量分别为正常宫颈组织的0.1553倍和0.4907倍(P<0.05);miR-126的表达无明显变化.结论 miRNAs与宫颈癌的发生和调控密切相关.在宫颈癌组织和Hela细胞中,miR-21表达上调,可能在宫颈癌的发生过程中发挥癌基因的作用;miR-143、miR-373表达下调可能发挥抑癌基因的作用;miR-126表达无差异,与宫颈癌无明显关系.%Objective To investigate the differential expression of miR-21 ,miR-126 ,miR-143 and miR-373 in normal cervical tissue, cervical cancer tissue and Hela cell.Methods The expressions of miR-21, miR-126, miR-143 and miR-373 were detected by real-time PCR in cervical cancer tissue,cervical tissue of benign uterine tumor and Hela cell. Results High expression of miR-21 was observed in cervical cancer and Hela cell, while low expression was observed in normal cervical tissue. The relative quantification of miR-21 in cerveical cancer was 11.3196 times that of miR-21 in normal cervical tissue (P0. 05). Conclusion miRNAs are closely related to the occurrence and regulation of cervical cancer. The high expression of miR-21 in cervical cancer and Hela cell indicate that it may play a possible role of oncogenes, while miR-143 and miR-373 with low expression may play the role of tumor suppressor genes.

  18. 淋巴瘤患者血浆中miR-21、miR-155、miR-210的表达及临床意义%The expression and clinical significance of miR-21,miR-155,miR-210 of plasma lymphoma patients

    Institute of Scientific and Technical Information of China (English)

    曹慧琴; 韦玮

    2016-01-01

    目的:探讨 miR-21、miR-155、miR-210的临床表达意义及其与淋巴瘤病理特征的相关性。方法采用RT-PCR 技术及免疫组化法测定60例行淋巴瘤患者血清中 miR-21、miR-155、miR-210表达量及 BCL-6蛋白水平,并对其与淋巴瘤病理特征相关性进行分析。结果与正常对照组相比,淋巴瘤患者 miR-21、miR-155、miR-210表达量显著提高,差异有统计学意义(P <0.05)。经相关分析可知,miR-21、miR-155表达量与免疫分型、MYC 基因、BCL-6蛋白有关,而 miR-210表达量则与免疫分型、MYC 基因有关。结论miR-21、miR-155、miR-210可能与淋巴瘤发生及进展相关。通过测定 miR-21、miR-155、miR-210表达情况可有效预测淋巴瘤病情的进展,对临床淋巴瘤诊治具有重要的指导意义。%Objective To investigate the expression and clinical significance of miR-21,miR-155,miR-210 of plasma lymphoma patients.Methods The expression levels of miR-21,miR-155,miR-210 and BCL-6 protein of 60 cases of plasma lymphoma patients were measured with RT-PCR and immunohistochemical staining,the features associated with lymphoma were analyzed.Results The levels of miR-21,miR-155,miR-210 of plasma lymphoma patients were higher than control group(P <0.05).The expression of miR-21,miR-155 were relationship with immune typing,MYC gene, BCL-6 protein,whereas the expression of miR-210 were relationship with immune typing,MYC genes.Conclusion miR-21,miR-155,miR-210 may occur and progress associated with lymphoma.By measuring miR-21,miR-155,miR-210 expression can predict disease progression of lymphoma,has important significance for clinical diagnosis and treatment of lymphoma.

  19. Inhibition of 14q32 MicroRNAs miR-329, miR-487b, miR-494, and miR-495 Increases Neovascularization and Blood Flow Recovery After Ischemia

    DEFF Research Database (Denmark)

    Welten, S. M. J.; Bastiaansen, Ajnm; de Jong, R. C. M.;

    2014-01-01

    in mice after single femoral artery ligation. Methods and Results: Gene silencing oligonucleotides (GSOs) were used to inhibit 4 14q32 microRNAs, miR-329, miR-487b, miR-494, and miR-495, 1 day before double femoral artery ligation. Blood flow recovery was followed by laser Doppler perfusion imaging. All 4......, as well as to increased arterial myofibroblast proliferation. Conclusions: The 14q32 microRNA gene cluster is highly involved in neovascularization. Inhibition of 14q32 microRNAs miR-329, miR-487b, miR-494, and miR-495 provides a promising tool for future therapeutic neovascularization....

  20. Expression of miR-143 and miR-145 and their functional study in gastric carcinoma%miR-143和miR-145在胃癌中的表达及功能研究

    Institute of Scientific and Technical Information of China (English)

    邢晓芳; 李子禹

    2015-01-01

    Objective To investigate the expressions of miR-143 and miR-145 in gastric cancer tissues and their biological functions. Methods A set of gastric cancer metastasis-related miRNAs was screened by comparing the miRNA profiles between the primary gastric cancer and matched liver metastasis. Among these miRNAs, expressions of miR-143 and miR-145 were further validated. The influence on metastasis was analyzed by transwell assay. Results Expressions of miR-143 and miR-145 down-regulated significantly in gastric cancer tissues compared to adjacent normal tissues (miR-143, 0.028 ±0.005 vs. 0.052 ±0.014, P=0.058; miR-145, 0.922 ±0.135 vs. 1.722 ±0.285, P=0.007), and decreased significantly in the metastatic lesion compared with the primary lesion (miR-143, 0.059±0.025 vs. 0.182±0.045, P=0.021; miR-145, 0.164±0.076 vs. 0.594±0.283, P=0.042). Expressions of miR-143 and miR-145 were significantly correlated (r=0.400, P=0.000), and they synergistically inhibited gastric cancer cell migration. Conclusion miR-143 and miR-145 may take part in the progression of gastric cancer metastasis, and they may have synergetic effects.%目的:探讨miR-143和miR-145在胃癌组织中的表达情况,观察其生物学功能。方法通过高通量芯片检测比较11对胃癌原发灶及其配对肝转移灶的miRNA表达谱,采用Real-time PCR方法观察miR-145和miR-143在55例胃癌组织中的表达情况。同时使用Transwell方法观察其对细胞转移能力的影响。结果 miR-143和miR-145在胃癌组织中的表达明显低于癌旁正常组织(miR-143:0.028±0.005比0.052±0.014,P=0.058;miR-145:0.922±0.135比1.772±0.285,P=0.007),在转移灶中的表达明显低于原发灶(miR-143:0.059±0.025比0.182±0.045,P=0.021;miR-145:0.164±0.076比0.594±0.283,P=0.042),相关性分析显示,miR-143和miR-145表达具有显著相关性(r=0.400, P=0.000)。体外实验显

  1. Circular RNA and miR-7 in Cancer

    DEFF Research Database (Denmark)

    Hansen, Thomas Birkballe; Kjems, Jørgen; Damgaard, Christian Kroun

    2013-01-01

    MicroRNAs (miRNA) play important roles in fine-tuning gene expression and are often deregulated in cancer. The identification of competing endogenous RNA and circular RNA (circRNA) as important regulators of miRNA activity underscores the increasing complexity of ncRNA-mediated regulatory networks....... Particularly, the recently identified circular RNA, ciRS-7, which acts as a designated miR-7 inhibitor/sponge, has conceptually changed the mechanistic understanding of miRNA networks. As miR-7 modulates the expression of several oncogenes, disclosing the regulation of miR-7 activity will likely advance...... the understanding of various cancer etiologies. Here, we review the current knowledge about the ciRS-7/miR-7 axis in cancer-related pathways and discuss possible models explaining the relevance of coexpressing miR-7 along with a circRNA inhibitor....

  2. miR-24 and miR-205 expression is dependent on HPV onco-protein expression in keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, Declan J., E-mail: dj.mckenna@ulster.ac.uk [Biomedical Sciences Research Institute, University of Ulster, Coleraine, Co. Derry BT52 1SA (United Kingdom); Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen' s University Belfast, Belfast BT9 7BL (United Kingdom); Patel, Daksha, E-mail: d.patel@qub.ac.uk [Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen' s University Belfast, Belfast BT9 7BL (United Kingdom); McCance, Dennis J., E-mail: d.mccance@qub.ac.uk [Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen' s University Belfast, Belfast BT9 7BL (United Kingdom)

    2014-01-05

    A screen of microRNA (miRNA) expression following differentiation in human foreskin keratinocytes (HFKs) identified changes in several miRNAs, including miR-24 and miR-205. We investigated how expression of Human Papilloma Virus Type-16 (HPV16) onco-proteins E6 and E7 affected expression of miR-24 and miR-205 during proliferation and differentiation of HFKs. We show that the induction of both miR-24 and miR-205 observed during differentiation of HFKs is lost in HFKs expressing E6 and E7. We demonstrate that the effect on miR-205 is due to E7 activity, as miR-205 expression is dependent on pRb expression. Finally, we provide evidence that miR-24 effects in the cell may be due to targeting of cyclin dependent kinase inhibitor p27. In summary, these results indicate that expression of both miR-24 and miR-205 are impacted by E6 and/or E7 expression, which may be one mechanism by which HPV onco-proteins can disrupt the balance between proliferation and differentiation in keratinocytes. - Highlights: • miR-24 and miR-205 are induced during keratinocyte differentiation. • This induction is lost in keratinocytes expressing HPV onco-proteins E6 and E7. • miR-205 is dependent upon pRb expression. • miR-24 targets p27 in cycling keratinocytes.

  3. Overexpression of miR-484 and miR-744 in Vero cells alters Dengue virus replication

    Science.gov (United States)

    Castrillón-Betancur, Juan Camilo; Urcuqui-Inchima, Silvio

    2017-01-01

    BACKGROUND Dengue is considered one of the world’s most important mosquito-borne diseases. MicroRNAs (miRNAs) are small non-coding single-stranded RNAs that play an important role in the regulation of gene expression in eukaryotes. Although miRNAs possess antiviral activity against many mammalian-infecting viruses, their involvement in Dengue virus (DENV) replication remains poorly understood. OBJECTIVE To determine the role of miR-484 and miR-744 in DENV infection and to examine whether DENV infection alters the expression of both miRNAs. METHODS We used bioinformatics tools to explore the relationship between DENV and cellular miRNAs. We then overexpressed miR-484 or miR-744 in Vero cells to examine their role in DENV replication using flow cytometry, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), and western blotting. FINDINGS We found several cellular miRNAs that target a conserved region within the 3′ untranslated region (3′ UTR) of the genome of the four DENV serotypes and found that overexpression of miR-484 or miR-744 inhibits infection by DENV-1 to DENV-4. Furthermore, we observed that DENV RNA might be involved in the downregulation of endogenous miR-484 and miR-744. CONCLUSION Our study identifies miR-484 and miR-744 as two possible restriction host factors against DENV infection. However, further studies are needed to directly verify whether miR-484 and miR-744 both have an anti-DENV effect in vivo. PMID:28327787

  4. A miRNA-responsive cell-free translation system facilitates isolation of hepatitis C virus miRNP complexes

    Science.gov (United States)

    Bradrick, Shelton S.; Nagyal, Simardeep; Novatt, Hilary

    2013-01-01

    Micro(mi)RNAs are 21- to 23-nt RNAs that regulate multiple biological processes. In association with Argonaute (Ago) proteins and other factors that form the RNA-induced silencing complex (RISC), miRNAs typically bind mRNA 3′ untranslated regions (UTRs) and repress protein production through antagonizing translation and transcript stability. For a given mRNA–miRNA interaction, cis-acting RNA elements and trans-acting RNA-binding proteins (RBPs) may influence mRNA fate. This is particularly true of the hepatitis C virus (HCV) genome which interacts with miR-122, an abundant liver miRNA. miR-122 binding to HCV RNA considerably stimulates virus replication in cultured cells and primates, but the mechanism(s) and associated host factors required for enhancement of HCV replication have not been fully elucidated. We recapitulated miR-122–HCV RNA interactions in a cell-free translation system derived from cells that express miR-122. Specifically, lysates produced from HEK-293 cells that inducibly transcribe and process pri-miR-122 were characterized alongside those from isogenic cells lacking miR-122 expression. We observed a stimulatory effect of miR-122 on HCV reporter mRNAs in a manner that depended on expression of miR-122 and intact target sites within the HCV 5′ UTR. We took advantage of this system to affinity-purify miR-122-HCV RNP complexes. Similar to functional assays, we found that association of immobilized HCV internal ribosome entry site (IRES) RNA with endogenous Ago2 requires both miR-122 expression and intact miR-122 target sites in cis. This combined approach may be generalizable to affinity purification of miRNP complexes for selected target mRNAs, allowing identification of miRNP components and RBPs that may contribute to regulation. PMID:23793894

  5. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor.

    Science.gov (United States)

    Park, Jong-Kook; Henry, Jon C; Jiang, Jinmai; Esau, Christine; Gusev, Yuriy; Lerner, Megan R; Postier, Russell G; Brackett, Daniel J; Schmittgen, Thomas D

    2011-03-25

    Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over-expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target the retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G(2)/M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the β2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2- to 4-fold. We report that over-expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over-expression of these miRNAs is likely due to increased expression of several E2F target genes. The β2 adrenergic pathway may play an important role in this novel mechanism. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Real-time PCR in detection of plasmic miRNA in patients with esophageal cancer%实时荧光定量PCR检测食管癌循环miRNA的研究

    Institute of Scientific and Technical Information of China (English)

    彭学宏; 陈暖; 李克; 郑邦希

    2014-01-01

    Objective To investigate the differential expression of miR-424,miR-373,miR-34c,miR-129,miR-130b,miR-203,miR-9,miR-15b,miR-100,miR-145,miR-21 in serum of esophageal cancer.Methods The expression levels of miR-424,miR-373,miR-34c,miR-129,miR-130b,miR-203,miR-9,miR-15b,miR-100,miR-145,miR-21 were detected by real-time PCR in serum of 20 human esophageal cancer and 20 normal person.Results Over-expression of miR-424,miR-373,miR-34c,miR-203,miR-15b and low-expression of miR-100 were observed in serum of esophageal cancer.Conclusions miRNAs in the serum maybe a new biological indicator for diagnosis of human esophageal cancer.%目的 研究miR-424、miR-373、miR-34c、miR-129、miR-130b、miR-203、miR-9、miR-15b、miR-100、miR-145、miR-21在食管癌患者外周血的差异表达.方法 采用Real-time PCR定量检测方法分析比较20例食管癌患者血液与健康对照者血液之间miR-424、miR-373、miR-34c、miR-129、miR-130b、miR-203、miR-9、miR-15b、miR-100、miR-145、miR-21表达差异情况.结果 miR-424、miR-373、miR-34c、miR-203、miR-15b表达上调,miR-100表达下调.结论 外周血miRNA可能成为食管癌患者早期诊断新的生物学指标.

  7. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong-Kook [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States); Henry, Jon C. [Department of Surgery, Ohio State University, Columbus, OH 43210 (United States); Jiang, Jinmai [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States); Esau, Christine [Regulus Therapeutics, Carlsbad, CA (United States); Gusev, Yuriy [Lombardi Cancer Center, Georgetown University, Washington, DC (United States); Lerner, Megan R. [Veterans Affairs Medical Center, Oklahoma City, OK (United States); Postier, Russell G. [Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Brackett, Daniel J. [Veterans Affairs Medical Center, Oklahoma City, OK (United States); Schmittgen, Thomas D., E-mail: Schmittgen.2@osu.edu [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States)

    2011-03-25

    Research highlights: {yields} The expression of miR-132 and miR-212 are significantly increased in pancreatic cancer. {yields} miR-132 and miR-212 target the tumor suppressor pRb, resulting in enhanced proliferation. {yields} miR-132 and miR-212 expression is increased by a {beta}2 adrenergic receptor agonist, suggesting a novel mechanism for pancreatic cancer progression. -- Abstract: Numerous microRNAs (miRNAs) are reported as differentially expressed in cancer, however the consequence of miRNA deregulation in cancer is unknown for many miRNAs. We report that two miRNAs located on chromosome 17p13, miR-132 and miR-212, are over-expressed in pancreatic adenocarcinoma (PDAC) tissues. Both miRNAs are predicted to target the retinoblastoma tumor suppressor, Rb1. Validation of this interaction was confirmed by luciferase reporter assay and western blot in a pancreatic cancer cell line transfected with pre-miR-212 and pre-miR-132 oligos. Cell proliferation was enhanced in Panc-1 cells transfected with pre-miR-132/-212 oligos. Conversely, antisense oligos to miR-132/-212 reduced cell proliferation and caused a G{sub 2}/M cell cycle arrest. The mRNA of a number of E2F transcriptional targets were increased in cells over expressing miR-132/-212. Exposing Panc-1 cells to the {beta}2 adrenergic receptor agonist, terbutaline, increased the miR-132 and miR-212 expression by 2- to 4-fold. We report that over-expression of miR-132 and miR-212 result in reduced pRb protein in pancreatic cancer cells and that the increase in cell proliferation from over-expression of these miRNAs is likely due to increased expression of several E2F target genes. The {beta}2 adrenergic pathway may play an important role in this novel mechanism.

  8. Measurement of L X-ray fluorescence cross-sections for 74W at excitation energies 12, 14, 15 and 16.5 keV with synchrotron radiation

    Science.gov (United States)

    Kumar, R.; Rani, A.; Singh, R. M.; Tiwari, M. K.; Singh, A. K.

    2017-02-01

    Ll, Lα, Lβ and Lγ1 X-ray fluorescence cross-sections for 74W have been measured at excitation energies of 12, 14, 15 and 16.5 keV using synchrotron radiations. A Peltier cooled Vortex solid state detector (SII Nano Technology, USA) with an energy resolution of 138 eV at 5.96 keV X-rays was employed for analysis. The experimental results were compared with the theoretical estimates of Krause (1979), Campbell (2003) and Puri et al. (1993) and also compared with existing experimental results (Barrea and Bonzi, 2001b) of L XRF cross sections at the excitation energy of 12 and 14 keV. Present results were found to be closer to the Puri's data in comparison to existing experimental results. For the first time, to our knowledge, L XRF cross section for 74W at energies 15 and 16.5 keV are also being reported here.

  9. (2-Carboxybenzoato-κ2O1,O1′(5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane-κ4Nnickel(II perchlorate monohydrate

    Directory of Open Access Journals (Sweden)

    Guang-Chuan Ou

    2009-07-01

    Full Text Available The title compound, [Ni(C8H5O4(C16H36N4]ClO4·H2O, has the NiII atom in a distorted octahedral geometry, surrounded by coordination by four N atoms of the 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane ligand in a folded configuration, and two carboxylate O atoms of the 2-carboxybenzoate ligand in cis positions. The complex cation, the disordered perchlorate anion [occupancies 0.639 (8:0.361 (8] and uncoordinated water molecules engage in N—H...O and O—H...O hydrogen bonding, forming a layer structure parallel to (010.

  10. Exosomes as miRNA Carriers: Formation-Function-Future.

    Science.gov (United States)

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

    2016-12-02

    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.

  11. miRNAting control of DNA methylation

    Indian Academy of Sciences (India)

    Ashwani Jha; Ravi Shankar

    2014-06-01

    DNA methylation is a type of epigenetic modification where a methyl group is added to the cytosine or adenine residue of a given DNA sequence. It has been observed that DNA methylation is achieved by some collaborative agglomeration of certain proteins and non-coding RNAs. The assembly of IDN2 and its homologous proteins with siRNAs recruits the enzyme DRM2, which adds a methyl group at certain cytosine residues within the DNA sequence. In this study, it was found that de novo DNA methylation might be regulated by miRNAs through systematic targeting of the genes involved in DNA methylation. A comprehensive genome-wide and system-level study of miRNA targeting, transcription factors, DNA-methylation-causing genes and their target genes has provided a clear picture of an interconnected relationship of all these factors which regulate DNA methylation in Arabidopsis. The study has identified a DNA methylation system that is controlled by four different genes: IDN2, IDNl1, IDNl2 and DRM2. These four genes along with various critical transcription factors appear to be controlled by five different miRNAs. Altogether, DNA methylation appears to be a finely tuned process of opposite control systems of DNA-methylation-causing genes and certain miRNAs pitted against each other.

  12. Saginaw Bay, MI LiDAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TASK NAME:(NRCS) Saginaw Bay, MI LiDAR LiDAR Data Acquisition and Processing Production Task USGS Contract No. G10PC00057 Task Order No. G11PD01254 Woolpert Order...

  13. 78 FR 36631 - Michigan Disaster #MI-00039

    Science.gov (United States)

    2013-06-18

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Michigan Disaster MI-00039 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... INFORMATION CONTACT: A. Escobar, Office of Disaster Assistance, U.S. Small Business Administration, 409...

  14. Mini Networked Screens (MiNeS)

    NARCIS (Netherlands)

    Prins, C.A.; Maris, M.; Breen, P.C.; Versteeg, N.; Terwisga, P.F. van; Ort, C.M.; Blok, J.J.

    2005-01-01

    The forward areas for an LPD in littoral waters can be full of surprises. A novel concept is presented for a networked screen consisting of elements of increasing capability to provide a progressive response to the threat. This MiNeS concept substantially improves the capability of the LPD as an aut

  15. Altered Expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the Formation of Chronic Brucellosis

    Science.gov (United States)

    Budak, Ferah; Bal, Salih Haldun; Tezcan, Gulcin; Akalın, Halis; Goral, Guher

    2016-01-01

    Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10–30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-139-3p were decreased (p 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis. PMID:27722176

  16. Altered Expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the Formation of Chronic Brucellosis.

    Science.gov (United States)

    Budak, Ferah; Bal, Salih Haldun; Tezcan, Gulcin; Akalın, Halis; Goral, Guher; Oral, Haluk Barbaros

    2016-01-01

    Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10-30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-139-3p were decreased (p 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis.

  17. Inga Lindströmi edu saladus / Jaanus Noormets

    Index Scriptorium Estoniae

    Noormets, Jaanus

    2009-01-01

    2004. aastal alustas Saksamaa telekanal ZDF romantiliste telefilmide "Inga Lindströmi armastuslood" filmide näitamist. Inga Lindströmi pseudonüümi kasutab stsenarist Christiane Sadlo. Seriaal on teinud suure töö Rootsi reklaamimisel reisisihina

  18. Cortical Morphogenesis during Embryonic Development Is Regulated by miR-34c and miR-204

    Science.gov (United States)

    Venø, Morten T.; Venø, Susanne T.; Rehberg, Kati; van Asperen, Jessy V.; Clausen, Bettina H.; Holm, Ida E.; Pasterkamp, R. Jeroen; Finsen, Bente; Kjems, Jørgen

    2017-01-01

    The porcine brain closely resembles the human brain in aspects such as development and morphology. Temporal miRNA profiling in the developing embryonic porcine cortex revealed a distinct set of miRNAs, including miR-34c and miR-204, which exhibited a highly specific expression profile across the time of cortical folding. These miRNAs were found to target Doublecortin (DCX), known to be involved in neuron migration during cortical folding of gyrencephalic brains. In vivo modulation of miRNA expression in mouse embryos confirmed that miR-34c and miR-204 can control neuronal migration and cortical morphogenesis, presumably by posttranscriptional regulation of DCX. PMID:28232790

  19. 小鼠着床前胚胎miR-125a,miR-295和miR-181b的表达%Expression of miR-125a, miR-295 and miR-181b in mouse preimplantation embryos

    Institute of Scientific and Technical Information of China (English)

    张平; 杨艳红; 王晓红; 王珺; 姜峰; 罗亚宁; 姚元庆

    2008-01-01

    目的:研究小鼠着床前胚胎发育过程中miRNA表达水平的变化,探讨miRNA对着床前胚胎发育过程的作用. 方法:建立小鼠超排、交配系统,收集着床前胚胎,提取small RNA;采用miRNA特异RT引物进行反转录,采用SYBR Green实时定量PCR技术,研究miR-125a, miR-295和miR-181b在小鼠着床前胚胎发育过程中表达水平的变化. 结果:着床前胚胎发育的各阶段均表达miR-125a, miR-295和miR-181b;随着胚胎发育进程,miR-295的表达呈逐渐上升的趋势;miR-125a在卵母细胞到2细胞发育阶段呈下降趋势,以后随发育进程呈逐渐上升趋势. 结论:小鼠着床前胚胎中表达miRNA,着床前胚胎的发育和分化过程可能受到miRNA的调控.

  20. miR319, miR390, and miR393 Are Involved in Aluminum Response in Flax (Linum usitatissimum L.)

    Science.gov (United States)

    Zyablitsin, Alexander V.; Rozhmina, Tatiana A.; Speranskaya, Anna S.; Sadritdinova, Asiya F.

    2017-01-01

    Acid soils limit agricultural production worldwide. Major reason of crop losses in acid soils is the toxicity of aluminum (Al). In the present work, we investigated expression alterations of microRNAs in flax (Linum usitatissimum L.) plants under Al stress. Flax seedlings of resistant (TMP1919 and G1071/4_k) and sensitive (Lira and G1071/4_o) to Al cultivars and lines were exposed to AlCl3 solution for 4 and 24 hours. Twelve small RNA libraries were constructed and sequenced using Illumina platform. In total, 97 microRNAs from 18 conserved families were identified. miR319, miR390, and miR393 revealed expression alterations associated with Al treatment of flax plants. Moreover, for miR390 and miR393, the alterations were distinct in sensitive and resistant to Al genotypes. Expression level changes of miR319 and miR390 were confirmed using qPCR analysis. In flax, potential targets of miR319 are TCPs, miR390–TAS3 and GRF5, and miR393–AFB2-coding transcripts. TCPs, TAS3, GRF5, and AFB2 participate in regulation of plant growth and development. The involvement of miR319, miR390, and miR393 in response to Al stress in flax was shown here for the first time. We speculate that these microRNAs play an important role in Al response via regulation of growth processes in flax plants.

  1. Relationship between arterial atheromatous plaque morphology and platelet-associated miR-126 and miR-223 expressions

    Institute of Scientific and Technical Information of China (English)

    Heng-Song Tian; Qing-Guo Zhou; Fang Shao

    2015-01-01

    Objective: To study the expression of miR-126 and miR-223 in platelet of rabbit arterial plaque models, and explore its correlation with plaque morphology. Methods: Rabbit arterial plaque models were established, peripheral blood of models and control animals was collected. Plaque morphologies were divided into type Ⅰ, type Ⅱ and type Ⅲ based on angiography plaque morphology and Ambrose method. Platelet isolation kit was applied to isolate and purify peripheral blood platelets, CD45 immunomagnetic beads were used to remove the residual white blood cells. The miRNAs of platelets was extracted by miRNA Isolation Kit, and expressions of miR-126 and miR-223 of the platelets samples were detected by Real-time PCR. The correlation between plaque morphology and platelet-associated miR-126 and miR-223 expressions were analyzed. Expressions of target gene VCAM-1 and P2Y12 receptors of miR-126 and miR-223 in the atherosclerosis plaque of rabbit model were detected by Western blot. Results: Relative expression levels of miR-126 and miR-223 in the model group were 0.27±0.10 and 0.71±0.14, respectively. Plaque morphology was divided into types Ⅰ, Ⅱ and Ⅲ;and miR-126 and miR-223 expression levels were detected in each type. Expression levels of miR-126 in each type were 0.42±0.07, 0.17±0.11 and 0.22±0.15, respectively; and expression levels of miR-223 in each type are 0.68±0.02, 0.57±0.06 and 0.88±0.10, respectively. Relative to the control group, miR-126 and miR-223 known target genes in VCAM-1 and P2Y12 receptors increased platelets in rabbit atherosclerotic plaque models (P<0.05). Conclusions:Relative to normal control animals, miR-126 and miR-223 platelets were reduced in the rabbit atherosclerotic plaque model group (P<0.05). In the type Ⅱ plaque morphology group, miR-126 was greatly reduced; and there is no significant correlation between miR-223 and plaque morphology.

  2. Identification of novel miRNAs and miRNA dependent developmental shifts of gene expression in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Shuhua Zhan

    Full Text Available microRNAs (miRNAs are small, endogenous RNAs of 20 approximately 25 nucleotides, processed from stem-loop regions of longer RNA precursors. Plant miRNAs act as negative regulators of target mRNAs predominately by slicing target transcripts, and a number of miRNAs play important roles in development. We analyzed a number of published datasets from Arabidopsis thaliana to characterize novel miRNAs, novel miRNA targets, and miRNA-regulated developmental changes in gene expression. These data include microarray profiling data and small RNA (sRNA deep sequencing data derived from miRNA biogenesis/transport mutants, microarray profiling data of mRNAs in a developmental series, and computational predictions of conserved genomic stem-loop structures. Our conservative analyses identified five novel mature miRNAs and seven miRNA targets, including one novel target gene. Two complementary miRNAs that target distinct mRNAs were encoded by one gene. We found that genes targeted by known miRNAs, and genes up-regulated or down-regulated in miRNA mutant inflorescences, are highly expressed in the wild type inflorescence. In addition, transcripts upregulated within the mutant inflorescences were abundant in wild type leaves and shoot meristems and low in pollen and seed. Downregulated transcripts were abundant in wild type pollen and seed and low in shoot meristems, roots and leaves. Thus, disrupting miRNA function causes the inflorescence transcriptome to resemble the leaf and meristem and to differ from pollen and seed. Applications of our computational approach to other species and the use of more liberal criteria than reported here will further expand the number of identified miRNAs and miRNA targets. Our findings suggest that miRNAs have a global role in promoting vegetative to reproductive transitions in A. thaliana.

  3. Plasma levels of miR-10b, miR-122, miR-16 and miR-183 in patients with non-small-cell lung cancer and their relationships with the overall survival%非小细胞肺癌患者血浆miR-10b、miR-122、miR-16和miR-183水平及其与总生存期的关系

    Institute of Scientific and Technical Information of China (English)

    王富民; 张寰; 曲金力; 钱碧云

    2016-01-01

    Objective To observe the levels of miR-10b, miR-122, miR-16 and miR-183 in patients with non-small-cell lung cancer (NSCLC) and to explore their relationships with the overall survival .Methods According to recurrence, 40 NSCLC patients were divided into two groups:non-recurrence group (n=8) and recurrence group (n=32).The ex-pression levels of 4 miRNAs were detected by real time quantitative PCR .NSCLC patients were divided into the high miR-NA expression group and low expression group according to the mean value of miRNAs expression .Kaplan-Meier survival a-nalysis and Cox regression were performed to determine the associations between different levels of miRNAs expression and overall survival ( OS) .Results The expression of miR-183 was higher in the non-recurrence group as compared with that of the recurrence group (P0.05).Cox proportional hazard regression showed that miR-183 was the independent risk factor for the overall survival of NSCLC patients (HR=2.854, 95%CI=1.154-7.055, P0.05. miR-183低水平者OS高于高水平者(P0.05. Cox比例风险回归模型分析显示,miR-183是NSCLC患者OS的独立影响因素( HR=2.854,95%CI为1.154~7.055,P<0.05). 结论 miR-183可能是NSCLC患者OS的独立影响因素,而miR-10b、miR-122和miR-16与患者OS无关.

  4. miR-106b、miR-20a和miR-221在早期胃癌中表达的研究%A study on miR-106b, miR-20a and miR-221 expressions in early gastric cancer

    Institute of Scientific and Technical Information of China (English)

    蔡辉; 袁媛; 韦雪; 魏丽; 王晓鹏; 郝云飞; 张迎梅; 郭天康

    2014-01-01

    Objective To study the exprssion of miR-106b,miR-20a and miR-221 in early development of gastric cancer.Methods The plasma expression of 15 selected microRNAs (miR-1,miR-106a,miR-106b,miR-17-5p,miR-20a,miR-21,miR-221,miR-27a,miR-34,miR-376c,miR-378,miR-423-5p,miR-451,miR-486,miR-744) in 30 gastric cancer (GC) patients and 30 age-and gendermatched healthy controls were measured and then the differences of those micro-RNAs expressions in other 60 GC patients and 60 matched controls were evaluated by using quantitative reverse transcription polymerase chain reaction.The areas under the receiver operating characteristic (ROC) curves were used to test the sensitivity and specificity of GC diagnosis using these identified plasma microRNAs.Results Three plasma microRNAs miR-106b,miR-20a,and miR-221,were significantly elevated in GC patients than in healthy controls (P < 0.05).Furthermore,the areas under the ROC curves using miR-106b,miR-20a,and miR-221 for GC diagnosis were 0.773 (95% CI 0.776-0.841),0.859 (95% CI 0.805-0.914),and 0.796 (95% CI 0.726-0.866),respectively.These three microRNAs were on a statistically significant elevation in GC patients compared with healthy controls at each of the four stages.However,there were no significant differences in the plasma levels of the three microRNAs among the four TNM stages (P > 0.05).Conclusions Plasma miR-106b,miR-20a,and miR-221 may be used as biomarkers for the detection of early GC.%目的 探讨血浆微小RNA在早期胃癌中的表达情况,研究其在胃癌发生发展中的意义.方法 本研究首先对30例胃癌患者和30例健康对照人群血浆中的15种微小RNA(miR-1、miR-106a、miR-106b、miR-17-5p、miR-20a、miR-21、miR-221、miR-27a、miR-34、miR-376c、miR-378、miR-423-5p、miR-451、miR-486、miR-744)进行检测,然后通过定量逆转录聚合酶链反应来确定另外60例胃癌患者和60例健康对照人群的血浆微小RNA是否存在差异.通过受试者工作特征

  5. miRSeq: A User-Friendly Standalone Toolkit for Sequencing Quality Evaluation and miRNA Profiling

    Directory of Open Access Journals (Sweden)

    Cheng-Tsung Pan

    2014-01-01

    Full Text Available MicroRNAs (miRNAs present diverse regulatory functions in a wide range of biological activities. Studies on miRNA functions generally depend on determining miRNA expression profiles between libraries by using a next-generation sequencing (NGS platform. Currently, several online web services are developed to provide small RNA NGS data analysis. However, the submission of large amounts of NGS data, conversion of data format, and limited availability of species bring problems. In this study, we developed miRSeq to provide alternatives. To test the performance, we had small RNA NGS data from four species, including human, rat, fly, and nematode, analyzed with miRSeq. The alignments results indicate that miRSeq can precisely evaluate the sequencing quality of samples regarding percentage of self-ligation read, read length distribution, and read category. miRSeq is a user-friendly standalone toolkit featuring a graphical user interface (GUI. After a simple installation, users can easily operate miRSeq on a PC or laptop by using a mouse. Within minutes, miRSeq yields useful miRNA data, including miRNA expression profiles, 3′ end modification patterns, and isomiR forms. Moreover, miRSeq supports the analysis of up to 105 animal species, providing higher flexibility.

  6. miR-375 ameliorates sepsis by downregulating miR-21 level via inhibiting JAK2-STAT3 signaling.

    Science.gov (United States)

    Sheng, Bo; Zhao, Lei; Zang, Xuefeng; Zhen, Jie; Chen, Wei

    2017-02-01

    Accumulating evidences have confirmed that miRNAs have important roles in sepsis. Myeloid-derived suppressor cells (MDSCs) enhance late sepsis development through immunosuppression in mice. Here, the functions and mechanisms of miR-375 in sepsis were revealed. We found that miR-375 level was downregulated but miR-21 level was upregulated in sepsis patients and that their levels were correlated negatively. Importantly, ectopic expression of miR-375 could decrease the number of sepsis Gr1+CD11b+ MDSCs in mice. Mechanistically, miR-375 could target Janus kinase 2 (JAK2) and further impaired signal transducer and activator of transcription 3 (STAT3) in sepsis Gr1+CD11b+ MDSC. Gain and loss of function of experiments showed that upregulation or downregulation of miR-375 level could decrease or increase miR-21 level. Moreover, pretreatment of JAK2 overexpressing vector could abolish the effects of miR-375 on miR-21 level and the amount of sepsis Gr1+CD11b+ MDSCs. Therefore, our results demonstrate that miR-375 could block JAK2-STAT3 pathway and thus modulate miR-21 level, which is involved in regulation of late sepsis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Altering β-cell number through stable alteration of miR-21 and miR-34a expression

    DEFF Research Database (Denmark)

    Backe, Marie Balslev; Novotny, Guy Wayne; Christensen, Dan Ploug;

    2014-01-01

    RNAs, miR-21 and miR-34a, may be involved in mediating cytokine-induced β-cell dysfunction. Therefore, manipulation of miR-21 and miR-34a levels may potentially be beneficial to β cells. To study the effect of long-term alterations of miR-21 or miR-34a levels upon net β-cell number, we stably overexpressed...... miR-21 and knocked down miR-34a, and investigated essential cellular processes. Materials and Methods: miRNA expression was manipulated using Lentiviral transduction of the β-cell line INS-1. Stable cell lines were generated, and cell death, NO synthesis, proliferation, and total cell number were...... monitored in the absence or presence of cytokines. Results: Overexpression of miR-21 decreased net β-cell number in the absence of cytokines, and increased apoptosis and NO synthesis in the absence and presence of cytokines. Proliferation was increased upon miR-21 overexpression. Knockdown of miR-34a...

  8. SOCIO-DKMOGRAPHIC AND REPRODUC II VL ...

    African Journals Online (AJOL)

    2002-04-04

    Apr 4, 2002 ... Subjects were recruited after the study had been explained to them and ... date, or, if the patient had an ultrasound scan dating before the sixth week. .... schooling for the subjects with a history of induced-abortion was 8.9 ...

  9. DEPRElVl KlJVVı

    Directory of Open Access Journals (Sweden)

    Hüseyin KASAP

    2003-08-01

    Full Text Available B u ç a l ış nıada , dep rem yükleri al t ı ndaki 4,6, 8 ve 10 katlı perdeli-çerçeveli 3 ayrı tip binanınperde e nkesi t değişinlinin sisteınin kesıne kuvYetidağ ı lı ını na etkisi incelenntiştir.Döşeme kalı n lı ğ ı, döşeme ağırlığı, kiriş a ğ ı r l ığı ,perde a ğırlığ ı duvar a ğır lı ğı ve bunlara b ağlıolarak kolon boyutu ta yi n e dil ıni ş ti r .Kolonboyutlarına bağlı olarak kat ağıı4hkları t ay inedilnıiştir.Hesaplanan kat a ğ ır lı kl a rı ile ta b ankesme kuv,

  10. miRNA Isolation from FFPET Specimen: A Technical Comparison of miRNA and Total RNA Isolation Methods.

    Science.gov (United States)

    Nagy, Zsófia Brigitta; Wichmann, Barnabás; Kalmár, Alexandra; Barták, Barbara Kinga; Tulassay, Zsolt; Molnár, Béla

    2016-07-01

    MiRNA remain stable for detection and PCR-based amplification in FFPE tissue samples. Several miRNA extraction kits are available, however miRNA fraction, as part of total RNA can be isolated using total RNA purification methods, as well. Our primary aim was to compare four different miRNA and total RNA isolation methods from FFPE tissues. Further purposes were to evaluate quantitatively and qualitatively the yield of the isolated miRNA. MiRNAs were isolated from normal colorectal cancer FFPE specimens from the same patients. Two miRNA isolation kits (High Pure miRNA Isolation Kit, miRCURY™ RNA Isolation Kit) and two total RNA isolation kits were compared (High Pure RNA Paraffin Kit, MagNA Pure 96 Cellular RNA LV Kit). Quantity and quality were determined, expression analysis was performed by real-time PCR using qPCR Human Panel I + II (Exiqon) method detecting 742 human miRNAs in parallel. The yield of total RNA was found to be higher than miRNA purification protocols (in CRC: Ex: 0203 ± 0021 μg; HPm: 1,45 ± 0,8 μg; HPp: 21,36 ± 4,98 μg; MP: 8,6 ± 5,1 μg). MiRNAs were detected in lower relative quantity of total RNA compared to the miRNA kits. Higher number of miRNAs could be detected by the miRNA isolation kits in comparison to the total RNA isolation methods. (Ex: 497 ± 16; HPm: 542 ± 11; HPp: 332 ± 36; MP: 295 ± 74). Colon specific miRNAs (miR-21-5p;-34-5p) give satisfying results by miRNA isolation kits. Although miRNA can be detected also after total RNA isolation methods, for reliable and reproducible miRNA expression profiling the use of miRNA isolation kits are more suitable.

  11. Identification of miRNAs contributing to neuroblastoma chemoresistance

    Directory of Open Access Journals (Sweden)

    Duncan Ayers

    2015-01-01

    Conclusions: Based on the initial miRNA findings, this study elucidates the dys-regulation of four miRNAs in three separate NB chemoresistant cell line models, spanning two cell lines (SH-SY5Y and UKF-NB-3 and two chemotherapeutic agents (doxorubicin and etoposide. These miRNAs may thus be possibly linked to chemoresistance induction in NB. Such miRNAs are good candidates to be novel drug targets for future miRNA based therapies against aggressive tumours that are not responding to conventional chemotherapy.

  12. miR-10 in development and cancer

    DEFF Research Database (Denmark)

    Lund, Anders Henrik

    2010-01-01

    The microRNA (miRNA) miR-10 family has attracted attention because of its conservation and the position of the miR-10 genes within the Hox clusters of developmental regulators. In several species, miR-10 is coexpressed with a set of Hox genes and has been found to regulate the translation of Hox ...... function to the miRNA repertoire.Cell Death and Differentiation advance online publication, 22 May 2009; doi:10.1038/cdd.2009.58....

  13. 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....

  14. 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....

  15. miR-21, miR-221 and miR-222 expression and prostate cancer recurrence among obese and non-obese cases

    Institute of Scientific and Technical Information of China (English)

    Ernest K Amankwah; Evelyn Anegbe; Hyun Park; Julio Pow-Sang; Ardeshir Hakam; Jong Y Park

    2013-01-01

    Recent evidence shows that certain microRNAs (miRNAs) play a role in both obesity and prostate cancer recurrence,but the association between the expression of these miRNAs and obesity in prostate cancer recurrence is unknown.In this study,we examined the effect of the interaction between obesity and miR-21,miR-221 or miR-222 expression on prostate cancer recurrence among 28 recurrent and 37 non-recurrent prostate cancer cases,miRNA expression was determined using quantitative real-time polymerase chain reaction.Cox proportional hazard models adjusting for age at diagnosis,clinical stage and Gleason score were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for recurrence free survival.A significantly (P=0.014) higher proportion of recurrent cases (78.6%) than non-recurrent cases (48.6%) had a low expression of miR-21 and the difference was more prominent in obese than non-obese patients.Multivariate analysis showed that the expression of miR-21 was an independent risk factor for recurrence in obese (HR=6.15,95% CI=1.04-36.48,P=0.045),but not in non-obese (HR=1.28,95% CI=0.30-5.49,P=0.74) cases.A significant association with recurrence was not observed for the expression of miR-221 and miR-222.In summary,our findings show that miR-21 is associated with prostate cancer recurrence after radical prostatectomy and suggest that the differential expression of miR-21 is more prominent in obese than in non-obese cases.Future larger studies are warranted to confirm these initial findings and to elucidate the mechanisms involved.

  16. miRNA control of tissue repair and regeneration.

    Science.gov (United States)

    Sen, Chandan K; Ghatak, Subhadip

    2015-10-01

    Tissue repair and regeneration rely on the function of miRNA, molecular silencers that enact post-transcriptional gene silencing of coding genes. Disruption of miRNA homeostasis is developmentally lethal, indicating that fetal tissue development is tightly controlled by miRNAs. Multiple critical facets of adult tissue repair are subject to control by miRNAs, as well. Sources of cell pool for tissue repair and regeneration are diverse and provided by processes including cellular dedifferentiation, transdifferentiation, and reprogramming. Each of these processes is regulated by miRNAs. Furthermore, induced pluripotency may be achieved by miRNA-based strategies independent of transcription factor manipulation. The observation that miRNA does not integrate into the genome makes miRNA-based therapeutic strategies translationally valuable. Tools to manipulate cellular and tissue miRNA levels include mimics and inhibitors that may be specifically targeted to cells of interest at the injury site. Here, we discuss the extraordinary importance of miRNAs in tissue repair and regeneration based on emergent reports and rapid advances in miRNA-based therapeutics.

  17. Microprocessor activity controls differential miRNA biogenesis In Vivo.

    Science.gov (United States)

    Conrad, Thomas; Marsico, Annalisa; Gehre, Maja; Orom, Ulf Andersson

    2014-10-23

    In miRNA biogenesis, pri-miRNA transcripts are converted into pre-miRNA hairpins. The in vivo properties of this process remain enigmatic. Here, we determine in vivo transcriptome-wide pri-miRNA processing using next-generation sequencing of chromatin-associated pri-miRNAs. We identify a distinctive Microprocessor signature in the transcriptome profile from which efficiency of the endogenous processing event can be accurately quantified. This analysis reveals differential susceptibility to Microprocessor cleavage as a key regulatory step in miRNA biogenesis. Processing is highly variable among pri-miRNAs and a better predictor of miRNA abundance than primary transcription itself. Processing is also largely stable across three cell lines, suggesting a major contribution of sequence determinants. On the basis of differential processing efficiencies, we define functionality for short sequence features adjacent to the pre-miRNA hairpin. In conclusion, we identify Microprocessor as the main hub for diversified miRNA output and suggest a role for uncoupling miRNA biogenesis from host gene expression.

  18. Entropy-based model for miRNA isoform analysis.

    Directory of Open Access Journals (Sweden)

    Shengqin Wang

    Full Text Available MiRNAs have been widely studied due to their important post-transcriptional regulatory roles in gene expression. Many reports have demonstrated the evidence of miRNA isoform products (isomiRs in high-throughput small RNA sequencing data. However, the biological function involved in these molecules is still not well investigated. Here, we developed a Shannon entropy-based model to estimate isomiR expression profiles of high-throughput small RNA sequencing data extracted from miRBase webserver. By using the Kolmogorov-Smirnov statistical test (KS test, we demonstrated that the 5p and 3p miRNAs present more variants than the single arm miRNAs. We also found that the isomiR variant, except the 3' isomiR variant, is strongly correlated with Minimum Free Energy (MFE of pre-miRNA, suggesting the intrinsic feature of pre-miRNA should be one of the important factors for the miRNA regulation. The functional enrichment analysis showed that the miRNAs with high variation, particularly the 5' end variation, are enriched in a set of critical functions, supporting these molecules should not be randomly produced. Our results provide a probabilistic framework for miRNA isoforms analysis, and give functional insights into pre-miRNA processing.

  19. 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.

  20. Neuronal Activity Regulates Hippocampal miRNA Expression

    Science.gov (United States)

    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 relatively recently discovered player in the regulation of translation in the nervous system. We have conducted an in depth analysis of how neuronal activity regulates miRNA expression in the hippocampus. Using deep sequencing we exhaustively identify all miRNAs, including 15 novel miRNAs, expressed in hippocampus of the adult mouse. We identified 119 miRNAs documented in miRBase but less than half of these miRNA were expressed at a level greater than 0.1% of total miRNA. Expression profiling following induction of neuronal activity by electroconvulsive shock demonstrates that most miRNA show a biphasic pattern of expression: rapid induction of specific mature miRNA expression followed by a decline in expression. These results have important implications into how miRNAs influence activity-dependent translational control. PMID:21984899

  1. Neuronal activity regulates hippocampal miRNA expression.

    Directory of Open Access Journals (Sweden)

    Stephen M Eacker

    Full Text Available 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 relatively recently discovered player in the regulation of translation in the nervous system. We have conducted an in depth analysis of how neuronal activity regulates miRNA expression in the hippocampus. Using deep sequencing we exhaustively identify all miRNAs, including 15 novel miRNAs, expressed in hippocampus of the adult mouse. We identified 119 miRNAs documented in miRBase but less than half of these miRNA were expressed at a level greater than 0.1% of total miRNA. Expression profiling following induction of neuronal activity by electroconvulsive shock demonstrates that most miRNA show a biphasic pattern of expression: rapid induction of specific mature miRNA expression followed by a decline in expression. These results have important implications into how miRNAs influence activity-dependent translational control.

  2. Exosomal miRNAs as cancer biomarkers and therapeutic targets

    Directory of Open Access Journals (Sweden)

    Arron Thind

    2016-07-01

    Full Text Available Intercommunication between cancer cells and with their surrounding and distant environments is key to the survival, progression and metastasis of the tumour. Exosomes play a role in this communication process. MicroRNA (miRNA expression is frequently dysregulated in tumour cells and can be reflected by distinct exosomal miRNA (ex-miRNA profiles isolated from the bodily fluids of cancer patients. Here, the potential of ex-miRNA as a cancer biomarker and therapeutic target is critically analysed. Exosomes are a stable source of miRNA in bodily fluids but, despite a number of methods for exosome extraction and miRNA quantification, their suitability for diagnostics in a clinical setting is questionable. Furthermore, exosomally transferred miRNAs can alter the behaviour of recipient tumour and stromal cells to promote oncogenesis, highlighting a role in cell communication in cancer. However, our incomplete understanding of exosome biogenesis and miRNA loading mechanisms means that strategies to target exosomes or their transferred miRNAs are limited and not specific to tumour cells. Therefore, if ex-miRNA is to be employed in novel non-invasive diagnostic approaches and as a therapeutic target in cancer, two further advances are necessary: in methods to isolate and detect ex-miRNA, and a better understanding of their biogenesis and functions in tumour-cell communication.

  3. Oleic Acid Induces MiR-7 Processing through Remodeling of Pri-MiR-7/Protein Complex.

    Science.gov (United States)

    Kumar, Santosh; Downie Ruiz Velasco, Angela; Michlewski, Gracjan

    2017-06-02

    MicroRNAs (miRs) play a vital role in governing cell function, with their levels tightly controlled at transcriptional and post-transcriptional levels. Different sets of RNA-binding proteins interact with primary miRs (pri-miRs) and precursor-miR transcripts (pre-miRs), controlling their biogenesis post-transcriptionally. The Hu antigen R (HuR)-mediated binding of Musashi homolog2 (MSI2) to the conserved terminal loop of pri-miR-7 regulates the levels of brain-enriched miR-7 formation in a tissue-specific manner. Here, we show that oleic acid (OA) inhibits the binding of proteins containing RNA recognition motifs (RRM) to the conserved terminal loop of pri-miR-7. Using electrophoretic mobility shift assays in HeLa cell extracts, we show that OA treatment disrupts pre-miR/protein complexes. Furthermore, OA rescues in vitro processing of pri-miR-7, which is otherwise blocked by HuR and MSI2 proteins. On the contrary, pri-miR-16 shows reduced processing in the presence of OA. This indicates that OA may inhibit the binding of other RRM-containing protein/s necessary for miR-16 processing. Finally, we demonstrate that OA induces mature miR-7 production in HeLa cells. Together, our results demonstrate that OA can regulate the processing of pri-miRs by remodeling their protein complexes. This provides a new tool to study RNA processing and a potential lead for small molecules that target the miR-7 biogenesis pathway. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. 冠心病患者血清同型半胱氨酸、miR-1、miR-126和 miR-208的相关性分析%Correlation analysis of Hcy,miR-1,miR-126 and miR-208 in coronary heart disease patients

    Institute of Scientific and Technical Information of China (English)

    金洁; 王俊; 王磊; 蔡晓敏; 王立军; 宫剑滨

    2014-01-01

    Objective To study the correlation between miRNA (miR-1,miR-126,miR-208) and homocysteine (Hcy) con-bining on the severity of stenosis of coronary artery .Methods One hundred and two patients undergoing quantitative coronary angiogra -phy were involved in this study .Patients were categorized into control group and coronary artery disease ( CAD) group.The concentra-tion of Hcy and miRNA (miR-1,miR-126,miR-208) were measured.The severity scale of coronary artery stenosis was quantitatively assessed according to coronary angiography by Gensini score .The correlation analysis and linear regression were used to show the asso-ciation of Hcy,miRNA (miR-1,miR-126 and miR-208) and Gensini score.Results The concentration of Hcy and miRNA (miR-1, miR-126 and miR-208) were higher in CAD group than those in control group .In the correlation analysis ,Gensini score was positively associated with Hcy,miR-1 and miR-126 (r=0.575,0.649,and 0.499,P<0.01) and the positive correlation between them remained significant after revising partial correlation analysis (r'=0.693,0.621,and 0.532,P<0.05).Hcy was influenced by miR-1 and miR-126 both in the Spearson correlation analysis (r=0.513,0.56,P<0.01) and partial correlation analysis (r'=0.599,0.614,P<0.05),but not by miR-208.Conclusion Hcy,miRNA (miR-1,miR-126 and miR-208) are independent risk factor for coronary heart disease and are increased along with stenosis of coronary arteries .%目的:结合冠状动脉狭窄程度,探讨冠心病患者血清同型半胱氨酸( Hcy)与微小RNA( miR-1、miR-126及miR-208)之间的相互关系。方法选取行冠脉造影术的患者共102名,根据造影结果分为对照组和观察组,检测Hcy、miR-1、miR-126及miR-208水平,同时对冠脉造影结果进行评价并计算Gensini积分,应用相关及线性回归分析Hcy、miRNA( miR-1、miR-126、miR-208)以及Gensini积分的相互关系。结果观察组血清Hcy、miRNA(miR-1、miR-126、miR-208)水平均

  5. Prognostic significance of miR-205 in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Mihriban Karaayvaz

    Full Text Available PURPOSE: microRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues. EXPERIMENTAL DESIGN: Total RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0. RESULTS: The expression levels of miR-200c (P<0.0001 and miR-205 (P<0.0001 were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028. Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues. CONCLUSION: miR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

  6. Role of miRNA-9 in Brain Development

    Science.gov (United States)

    Radhakrishnan, Balachandar; Alwin Prem Anand, A.

    2016-01-01

    MicroRNAs (miRNAs) are a class of small regulatory RNAs involved in gene regulation. The regulation is effected by either translational inhibition or transcriptional silencing. In vertebrates, the importance of miRNA in development was discovered from mice and zebrafish dicer knockouts. The miRNA-9 (miR-9) is one of the most highly expressed miRNAs in the early and adult vertebrate brain. It has diverse functions within the developing vertebrate brain. In this article, the role of miR-9 in the developing forebrain (telencephalon and diencephalon), midbrain, hindbrain, and spinal cord of vertebrate species is highlighted. In the forebrain, miR-9 is necessary for the proper development of dorsoventral telencephalon by targeting marker genes expressed in the telencephalon. It regulates proliferation in telencephalon by regulating Foxg1, Pax6, Gsh2, and Meis2 genes. The feedback loop regulation between miR-9 and Nr2e1/Tlx helps in neuronal migration and differentiation. Targeting Foxp1 and Foxp2, and Map1b by miR-9 regulates the radial migration of neurons and axonal development. In the organizers, miR-9 is inversely regulated by hairy1 and Fgf8 to maintain zona limitans interthalamica and midbrain–hindbrain boundary (MHB). It maintains the MHB by inhibiting Fgf signaling genes and is involved in the neurogenesis of the midbrain–hindbrain by regulating Her genes. In the hindbrain, miR-9 modulates progenitor proliferation and differentiation by regulating Her genes and Elav3. In the spinal cord, miR-9 modulates the regulation of Foxp1 and Onecut1 for motor neuron development. In the forebrain, midbrain, and hindbrain, miR-9 is necessary for proper neuronal progenitor maintenance, neurogenesis, and differentiation. In vertebrate brain development, miR-9 is involved in regulating several region-specific genes in a spatiotemporal pattern. PMID:27721656

  7. Evolutionary relationships between miRNA genes and their activity.

    Science.gov (United States)

    Zhu, Yan; Skogerbø, Geir; Ning, Qianqian; Wang, Zhen; Li, Biqing; Yang, Shuang; Sun, Hong; Li, Yixue

    2012-12-22

    The emergence of vertebrates is characterized by a strong increase in miRNA families. MicroRNAs interact broadly with many transcripts, and the evolution of such a system is intriguing. However, evolutionary questions concerning the origin of miRNA genes and their subsequent evolution remain unexplained. In order to systematically understand the evolutionary relationship between miRNAs gene and their function, we classified human known miRNAs into eight groups based on their evolutionary ages estimated by maximum parsimony method. New miRNA genes with new functional sequences accumulated more dynamically in vertebrates than that observed in Drosophila. Different levels of evolutionary selection were observed over miRNA gene sequences with different time of origin. Most genic miRNAs differ from their host genes in time of origin, there is no particular relationship between the age of a miRNA and the age of its host genes, genic miRNAs are mostly younger than the corresponding host genes. MicroRNAs originated over different time-scales are often predicted/verified to target the same or overlapping sets of genes, opening the possibility of substantial functional redundancy among miRNAs of different ages. Higher degree of tissue specificity and lower expression level was found in young miRNAs. Our data showed that compared with protein coding genes, miRNA genes are more dynamic in terms of emergence and decay. Evolution patterns are quite different between miRNAs of different ages. MicroRNAs activity is under tight control with well-regulated expression increased and targeting decreased over time. Our work calls attention to the study of miRNA activity with a consideration of their origin time.

  8. 非小细胞肺癌血浆miR-223、miR-93和miR-218的表达及其临床意义%Expression and clinical value analysis of plasma miR-223, miR-93 and miR-218 in non-small lung cancer

    Institute of Scientific and Technical Information of China (English)

    蔡静清; 王宁; 张敏

    2014-01-01

    Objective To explore the levels of plasma miR⁃223, miR⁃93 and miR⁃218 in non⁃small lung cancer( NSCLC) and analysis the relationship between the 3 indicators and clinicopathological parameters of NSCLC. Methods Plasma samples from 85 NSCLC patients before treatment were collected as NSCLC group. The real⁃time quantitative RT⁃PCR( qRT⁃PCR) was used to detect the levels of miR⁃223, miR⁃93 and miR⁃218 and the clinicopathological parameters of NSCLC patients were collected. The clinicopatho⁃logical parameters of patients with different levels of miR⁃223, miR⁃93 and miR⁃218 were compared. The receiver operating characteris⁃tic curve( ROC) was employed to analysis the clinical value of plasma miR⁃223, miR⁃93 and miR⁃218 in the diagnosis of NSCLC. Meanwhile, the plasma samples from 90 healthy volunteers at the same time were selected as control( control group) . Results There were higher levels of miR⁃223 and miR⁃93 but lower miR⁃218 in NSCLC group compaired with control group with significant difference ( P<0�05) . The level of miR⁃223 was related with TNM stage and tumor size, and miR⁃93 was related with histological type and lymph node metastasis, and miR⁃218 was related with tumor size and degree of differentiation, showing with significant difference ( P all<0�05) . The plasma level of miR⁃223 was positively correlated with miR⁃93( r=0�411) , but miR⁃223 and miR⁃93 were negatively cor⁃related with miR⁃218(r=-0�361 and r=-0�451)with statistically significance(P<0�05). The AUC, sensitivity and specificity of plasma miR⁃223, miR⁃93 and miR⁃218 in the diagnosis of NSCLC were 0�926, 95�2% and 87�1%, 0�912, 88�4% and 92�5%, and 0�941, 92�7% and 84�4%, higher than 0�774, 75�1% and 66�2% of carcinoembryonic antigen( CEA) . The combined efficiency of miR⁃223, miR⁃93 and miR⁃218 in NSCLC was superior to that alone. Conclusion There are higher expression of miR⁃223 and

  9. miRSponge: a manually curated database for experimentally supported miRNA sponges and ceRNAs.

    Science.gov (United States)

    Wang, Peng; Zhi, Hui; Zhang, Yunpeng; Liu, Yue; Zhang, Jizhou; Gao, Yue; Guo, Maoni; Ning, Shangwei; Li, Xia

    2015-01-01

    In this study, we describe miRSponge, a manually curated database, which aims at providing an experimentally supported resource for microRNA (miRNA) sponges. Recent evidence suggests that miRNAs are themselves regulated by competing endogenous RNAs (ceRNAs) or 'miRNA sponges' that contain miRNA binding sites. These competitive molecules can sequester miRNAs to prevent them interacting with their natural targets to play critical roles in various biological and pathological processes. It has become increasingly important to develop a high quality database to record and store ceRNA data to support future studies. To this end, we have established the experimentally supported miRSponge database that contains data on 599 miRNA-sponge interactions and 463 ceRNA relationships from 11 species following manual curating from nearly 1200 published articles. Database classes include endogenously generated molecules including coding genes, pseudogenes, long non-coding RNAs and circular RNAs, along with exogenously introduced molecules including viral RNAs and artificial engineered sponges. Approximately 70% of the interactions were identified experimentally in disease states. miRSponge provides a user-friendly interface for convenient browsing, retrieval and downloading of dataset. A submission page is also included to allow researchers to submit newly validated miRNA sponge data. Database URL: http://www.bio-bigdata.net/miRSponge.

  10. Identification and analysis of miRNAs and their targets in ginger using bioinformatics approach.

    Science.gov (United States)

    Singh, Noopur; Srivastava, Swati; Sharma, Ashok

    2016-01-10

    MicroRNAs (miRNAs) are a large family of endogenous small RNAs derived from the non-protein coding genes. miRNA regulates the gene expression at the post-transcriptional level and plays an important role in plant development. Zingiber officinale is an important medicinal plant having numerous therapeutic properties. Its bioactive compound gingerol and essential oil posses important pharmacological and physiological activities. In this study, we used a homology search based computational approach for identifying miRNAs in Z. officinale. A total of 16 potential miRNA families (miR167, miR407, miR414, miR5015, miR5021, miR5644, miR5645, miR5656, miR5658, miR5664, miR827, miR838, miR847, miR854, miR862 and miR864) were predicted in ginger. Phylogenetic and conserved analyses were performed for predicted miRNAs. Thirteen miRNA families were found to regulate 300 target transcripts and play an important role in cell signaling, reproduction, metabolic process and stress. To understand the miRNA mediated gene regulatory control and to validate miRNA target predictions, a biological network was also constructed. Gene ontology and pathway analyses were also done. miR5015 was observed to regulate the biosynthesis of gingerol by inhibiting phenyl ammonia lyase (PAL), a precursor enzyme in the biosynthesis of gingerol. Our results revealed that most of the predicted miRNAs were involved in the regulation of rhizome development. miR5021, miR854 and miR838 were identified to regulate the rhizome development and the essential oil biosynthesis in ginger. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Study of miR-125b, miR-29a and miR-155-5p as biomarkers of tuberculous meningitis%miR-125b、miR-29a和miR-155-5p作为诊断结核性脑膜炎生物标志的研究

    Institute of Scientific and Technical Information of China (English)

    柴璐璐; 田宋新; 袁俐; 王宏

    2015-01-01

    Objective To investigate the expression levels of microRNA(miR)-125b, miR-29a and miR-155-5p in ce⁃rebrospinal fluid (CSF) and plasma from the patients with tuberculous meningitis and their clinic significance. Methods Cerebrospinal fluid and plasma samples were collected from 20 patients with tuberculous meningitis (tuberculous meningitis group) and 20 patients suffered from primary headache (control group). The total RNAs were extracted.The levels of miR-125b, miR-29a and miR-155-5p were determined by real-time quantitative PCR (q-PCR). Results Levels of miR-29a and miR-125b in both CSF and plasma of patients in tuberculous meningitis group were significantly higher than those in pa⁃tients from control group with statistical significance (P<0.01). Mean time, the level of miR-155-5p in plasma but not in CSF of patients in tuberculous meningitis group was higher than those in control group with statistical significance ( P<0.01). Conclusion Expression of miR-125b, miR-29a and miR-155-5p may participate in regulating the occurrence and development of tuberculous meningitis. And miR-125b and miR-29a may be used as potential biomarkers for diagnosing tu⁃berculous meningitis.%目的:探讨结核性脑膜炎患者脑脊液及血浆中microRNA (miR)-125b、miR-29a和miR-155-5p的表达水平及其临床意义。方法收集20例结核性脑膜炎患者(结脑组)和20例原发性头痛患者(对照组)的脑脊液和血浆,分别提取总RNA,使用实时定量PCR方法分别检测脑脊液和血浆中miR-125b、miR-29a及miR-155-5p的表达水平。结果与对照组相比,结脑组脑脊液、血浆中miR-29a、miR-125b表达水平明显上调,结脑组血浆中miR-155-5p表达水平明显上调,差异均有统计学意义(均P<0.01),而2组脑脊液中miR-155-5p表达水平比较差异无统计学意义。结论 miR-125b、miR-29a和miR-155-5p可能参与了调节结核性脑膜炎的发生、发展过程,miR-125b和miR-29a有可能

  12. MiR-578 and miR-573 as potential players in BRCA-related breast cancer angiogenesis.

    Science.gov (United States)

    Danza, Katia; De Summa, Simona; Pinto, Rosamaria; Pilato, Brunella; Palumbo, Orazio; Merla, Giuseppe; Simone, Gianni; Tommasi, Stefania

    2015-01-01

    The involvement of microRNA (miRNAs), a new class of small RNA molecules, in governing angiogenesis has been well described. Our aim was to investigate miRNA-mediated regulation of angiogenesis in a series of familial breast cancers stratified by BRCA1/2 mutational status in BRCA carriers and BRCA non-carriers (BRCAX). Affymetrix GeneChip miRNA Arrays were used to perform miRNA expression analysis on 43 formalin-fixed paraffin-embedded (FFPE) tumour tissue familial breast cancers (22 BRCA 1/2-related and 21 BRCAX). Pathway enrichment analysis was carried out with the DIANA miRPath v2.0 web-based computational tool, and the miRWalk database was used to identify target genes of deregulated miRNAs. An independent set of 8 BRCA 1/2-related and 11 BRCAX breast tumors was used for validation by Real-Time PCR. In vitro analysis on HEK293, MCF-7 and SUM149PT cells were performed to best-clarify miR-573 and miR-578 role. A set of 16 miRNAs differentially expressed between BRCA 1/2-related and BRCAX breast tumors emerged from the profile analysis. Among these, miR-578 and miR-573 were found to be down-regulated in BRCA 1/2-related breast cancer and associated to the Focal adhesion, Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-1 (HIF-1) signaling pathways. Our data highlight the role of miR-578 and miR-573 in controlling BRCA 1/2-related angiogenesis by targeting key regulators of Focal adhesion, VEGF and HIF-1 signaling pathways.

  13. A Biogenesis Step Upstream of Microprocessor Controls miR-17∼92 Expression.

    Science.gov (United States)

    Du, Peng; Wang, Longfei; Sliz, Piotr; Gregory, Richard I

    2015-08-13

    The precise control of miR-17∼92 microRNA (miRNA) is essential for normal development, and overexpression of certain miRNAs from this cluster is oncogenic. Here, we find that the relative expression of the six miRNAs processed from the primary (pri-miR-17∼92) transcript is dynamically regulated during embryonic stem cell (ESC) differentiation. Pri-miR-17∼92 is processed to a biogenesis intermediate, termed "progenitor-miRNA" (pro-miRNA). Pro-miRNA is an efficient substrate for Microprocessor and is required to selectively license production of pre-miR-17, pre-miR-18a, pre-miR-19a, pre-miR-20a, and pre-miR-19b from this cluster. Two complementary cis-regulatory repression domains within pri-miR-17∼92 are required for the blockade of miRNA processing through the formation of an autoinhibitory RNA conformation. The endonuclease CPSF3 (CPSF73) and the spliceosome-associated ISY1 are responsible for pro-miRNA biogenesis and expression of all miRNAs within the cluster except miR-92. Thus, developmentally regulated pro-miRNA processing is a key step controlling miRNA expression and explains the posttranscriptional control of miR-17∼92 expression in development.

  14. miRFam: an effective automatic miRNA classification method based on n-grams and a multiclass SVM

    Directory of Open Access Journals (Sweden)

    Zhou Shuigeng

    2011-05-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are ~22 nt long integral elements responsible for post-transcriptional control of gene expressions. After the identification of thousands of miRNAs, the challenge is now to explore their specific biological functions. To this end, it will be greatly helpful to construct a reasonable organization of these miRNAs according to their homologous relationships. Given an established miRNA family system (e.g. the miRBase family organization, this paper addresses the problem of automatically and accurately classifying newly found miRNAs to their corresponding families by supervised learning techniques. Concretely, we propose an effective method, miRFam, which uses only primary information of pre-miRNAs or mature miRNAs and a multiclass SVM, to automatically classify miRNA genes. Results An existing miRNA family system prepared by miRBase was downloaded online. We first employed n-grams to extract features from known precursor sequences, and then trained a multiclass SVM classifier to classify new miRNAs (i.e. their families are unknown. Comparing with miRBase's sequence alignment and manual modification, our study shows that the application of machine learning techniques to miRNA family classification is a general and more effective approach. When the testing dataset contains more than 300 families (each of which holds no less than 5 members, the classification accuracy is around 98%. Even with the entire miRBase15 (1056 families and more than 650 of them hold less than 5 samples, the accuracy surprisingly reaches 90%. Conclusions Based on experimental results, we argue that miRFam is suitable for application as an automated method of family classification, and it is an important supplementary tool to the existing alignment-based small non-coding RNA (sncRNA classification methods, since it only requires primary sequence information. Availability The source code of miRFam, written in C++, is freely and publicly

  15. Expression and clinical value analysis of plasma miR-205, miR-212 and miR-429 in ovarian cancer%卵巢癌患者血浆miR-205、miR-212及miR-429的水平分析及意义∗

    Institute of Scientific and Technical Information of China (English)

    穆鹏; 李联崑; 贾海清; 王晓彬

    2015-01-01

    Objective To explore the levels of plasma miR⁃205, miR⁃212 and miR⁃429 in ovarian cancer and analyze the re⁃lationship between the above indicators and clinical pathology parameters of ovarian cancer. Methods Plasma samples from 71 ovarian cancer patients before treatment were collected. The real⁃time quantitative RT⁃PCR ( qRT⁃PCR) was used to detect the levels of miR⁃205, miR⁃212 and miR⁃429, and the clinical pathology parameters of ovarian cancer ( age, clinical stage, degree of differentiation, histological type and lymph node metastasis) were collected. The clinical pathology parameters of patients with different levels of miR⁃205, miR⁃212 and miR⁃429 were compared. The receiver operating characteristic curve ( ROC) was employed to analyze the clinical value of plasma miR⁃205, miR⁃212 and miR⁃429 in the diagnosis of ovarian cancer. Meanwhile, the plasma samples from 68 healthy volunteers (healthy control group) and 66 patients with benign ovarian tumor (benign group) were collected as control. Results There were higher levels of miR⁃205 and but lower miR⁃212 and miR⁃429 in ovarian cancer group versus other two groups with signifi⁃cant difference ( P all<0�05) . In ovarian cancer, the level of miR⁃205 was related with age, clinical stage, degree of differentiation and lymph node metastasis, and miR⁃212 was related with clinical stage and degree of differentiation, and miR⁃429 was related with clinical stage and lymph node metastasis ( P all<0�05) . The plasma level of miR⁃205 was negatively correlated with miR⁃212 and miR⁃429 ( r=-0�572、-0�325) , and miR⁃212 was positively correlated with miR⁃429 with statistically significance ( r=0�473,P<0�05) . The AUC, sensitivity and specificity of plasma miR⁃205, miR⁃212 and miR⁃429 in the diagnosis of ovarian cancer were 0�915, 92�1%and 86�2%, 0�944,87�3% and 91�0%, and 0�905, 88�5% and 83�6%. Conclusion There was higher

  16. Analytical Study of Hexapod miRNAs using Phylogenetic Methods

    CERN Document Server

    Mishra, A K

    2012-01-01

    MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate gene expression. Identification of total number of miRNAs even in completely sequenced organisms is still an open problem. However, researchers have been using techniques that can predict limited number of miRNA in an organism. In this paper, we have used homology based approach for comparative analysis of miRNA of hexapoda group .We have used Apis mellifera, Bombyx mori, Anopholes gambiae and Drosophila melanogaster miRNA datasets from miRBase repository. We have done pair wise as well as multiple alignments for the available miRNAs in the repository to identify and analyse conserved regions among related species. Unfortunately, to the best of our knowledge, miRNA related literature does not provide in depth analysis of hexapods. We have made an attempt to derive the commonality among the miRNAs and to identify the conserved regions which are still not available in miRNA repositories. The results are good approximation with a small number of mis...

  17. Comparative analysis of known miRNAs across platyhelminths.

    Science.gov (United States)

    Jin, Xiaoliang; Lu, Lixia; Su, Hailong; Lou, Zhongzi; Wang, Fang; Zheng, Yadong; Xu, Guo-Tong

    2013-08-01

    MicroRNAs (miRNAs) are a subtype of small regulatory RNAs that are involved in numerous biological processes through small RNA-induced silencing networks. In an attempt to explore the phylogeny of miRNAs across five platyhelminths, we integrated annotated miRNAs and their full genomes. We identified conserved miRNA clusters and, in particular, miR-71/2 was conserved from planarian to parasitic flatworms and was expanded in free-living Schmidtea mediterranea. Analysis of 22 miRNA loci provided compelling evidence that most known miRNAs are conserved across platyhelminths. Meanwhile, we also observed alterations of known protein-coding genes flanking miRNA(s), such as transcriptional direction conversion and locus relocation, in around ~ 41% of 22 known miRNA loci. Compared with Echinococcus multilocularis, the majority of these events occurred in evolution-distant Hymenolepis microstoma, Schistosoma japonicum or/and S. mediterranea. These results imply rearrangement events occurred near the known miRNA loci.

  18. Characterization of miRNomes in Acute and Chronic Myeloid

    Directory of Open Access Journals (Sweden)

    Qian Xiong

    2014-04-01

    Full Text Available Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA (miRNA expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia (AML cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia (CML cell line, K562, via massively parallel signature sequencing. mRNA expression profiles of these cell lines that were established previously in our lab facilitated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis and target prediction suggested numerous miRNA signatures in AML and CML cell lines. Some miRNAs may act as either tumor suppressors or oncomiRs in AML and CML by targeting key genes in AML and CML pathways. Expression patterns of cell type-specific miRNAs could partially reflect the characteristics of K562, HL-60 and THP-1 cell lines, such as actin filament-based processes, responsiveness to stimulus and phagocytic activity. miRNAs may also regulate myeloid differentiation, since they usually suppress differentiation regulators. Our study provides a resource to further investigate the employment of miRNAs in human leukemia subtyping, leukemogenesis and myeloid development. In addition, the distinctive miRNA signatures may be potential candidates for the clinical diagnosis, prognosis and treatment of myeloid leukemias.

  19. miR-148 regulates Mitf in melanoma cells.

    Directory of Open Access Journals (Sweden)

    Benedikta S Haflidadóttir

    Full Text Available The Microphthalmia associated transcription factor (Mitf is an important regulator in melanocyte development and has been shown to be involved in melanoma progression. The current model for the role of Mitf in melanoma assumes that the total activity of the protein is tightly regulated in order to secure cell proliferation. Previous research has shown that regulation of Mitf is complex and involves regulation of expression, splicing, protein stability and post-translational modifications. Here we show that microRNAs (miRNAs are also involved in regulating Mitf in melanoma cells. Sequence analysis revealed conserved binding sites for several miRNAs in the Mitf 3'UTR sequence. Furthermore, miR-148 was shown to affect Mitf mRNA expression in melanoma cells through a conserved binding site in the 3'UTR sequence of mouse and human Mitf. In addition we confirm the previously reported effects of miR-137 on Mitf. Other miRNAs, miR-27a, miR-32 and miR-124 which all have conserved binding sites in the Mitf 3'UTR sequence did not have effects on Mitf. Our data show that miR-148 and miR-137 present an additional level of regulating Mitf expression in melanocytes and melanoma cells. Loss of this regulation, either by mutations or by shortening of the 3'UTR sequence, is therefore a likely factor in melanoma formation and/or progression.

  20. miR-375 and miR-30d in the Effect of Chromium-Containing Chinese Medicine Moderating Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    2014-01-01

    Full Text Available In China, TianMai Xiaoke tablet (TM is used to treat type 2 diabetes. However, the exact mechanism of TM is not clear. This study is to investigate the effect of TM on glucose metabolism in diabetic rats and to identify whether TM takes a direct action through microRNAs on islet. Rats were divided into control group, diabetic group, low dose of TM group (TML, and high dose of TM group (TMH. Pancreas samples were analyzed using microRNA array and Q-PCR. Eight-week treatment with TM significantly decreased fasting blood glucose. The blood glucose was significantly reduced in TM-treated groups before and after oral glucose administration. Fasting insulin and HOMA-IR were suppressed in TM-treated groups. miR-448, let-7b, miR-540, miR-296, miR-880, miR-200a, miR-500, miR-10b, miR-336, miR-30d, miR-208, let-7e, miR-142-5p, miR-874, miR-375, miR-879, miR-501, and miR-188 were upregulated, while miR-301b, miR-134, and miR-652 were downregulated in TMH group. Through target gene analysis and real-time PCR verification, we found that these miRNAs, especially miR-375 and miR-30d, can stimulate insulin secretion in islet. Our data suggest that TM can improve blood glucose in diabetic rats which involved increasing the expression of miR-375 and miR-30d to activate insulin synthesis in islet.

  1. Peroxisome proliferator-activated receptor-gamma-independent inhibition of macrophage activation by the non-thiazolidinedione agonist L-796,449. Comparison with the effects of 15-deoxy-delta(12,14)-prostaglandin J(2).

    Science.gov (United States)

    Castrillo, A; Mojena, M; Hortelano, S; Boscá, L

    2001-09-07

    The effects of L-796,449 (3-chloro-4-(3-(3-phenyl-7-propylbenzofuran-6-yloxy)propylthio)phenylacetic acid; referred to henceforth as compound G), a thiazolidinedione-unrelated peroxisome proliferator activated-receptor-gamma (PPAR-gamma) agonist, on early signaling in lipopolysaccharide-activated RAW 264.7 macrophages were analyzed and compared with those elicited by 15-deoxy-Delta(12,14)-prostaglandin J(2) and the thiazolidinedione rosiglitazone. Compound G inhibited the activation of nuclear factor kappa B through the impairment of the targeting and degradation of I kappa B proteins and promoted a redistribution of I kappa B alpha and I kappa B beta in the nucleus of activated cells. Compound G inhibited I kappa B kinase (IKK) activity both in vivo and in vitro, suggesting a direct mechanism of interaction between this molecule and the IKK complex. The effect of compound G on IKK activity was independent of PPAR-gamma engagement because RAW 264.7 cells expressed negligible levels of this nuclear receptor, and rosiglitazone failed to mimic these actions. Moreover, treatment of activated macrophages with compound G enhanced the synthesis of superoxide anion, which, in combination with the NO produced under activation conditions, triggered apoptosis through the intracellular synthesis of peroxynitrite. These results suggest that compound G might contribute to the resolution of inflammation by favoring the induction of apoptosis through mechanisms independent of PPAR-gamma engagement.

  2. Satellite Instrument Calibration for Measuring Global Climate Change. Report of a Workshop at the University of Maryland Inn and Conference Center, College Park, MD. , November 12-14, 2002

    Science.gov (United States)

    Ohring, G.; Wielicki, B.; Spencer, R.; Emery, B.; Datla, R.

    2004-01-01

    Measuring the small changes associated with long-term global climate change from space is a daunting task. To address these problems and recommend directions for improvements in satellite instrument calibration some 75 scientists, including researchers who develop and analyze long-term data sets from satellites, experts in the field of satellite instrument calibration, and physicists working on state of the art calibration sources and standards met November 12 - 14, 2002 and discussed the issues. The workshop defined the absolute accuracies and long-term stabilities of global climate data sets that are needed to detect expected trends, translated these data set accuracies and stabilities to required satellite instrument accuracies and stabilities, and evaluated the ability of current observing systems to meet these requirements. The workshop's recommendations include a set of basic axioms or overarching principles that must guide high quality climate observations in general, and a roadmap for improving satellite instrument characterization, calibration, inter-calibration, and associated activities to meet the challenge of measuring global climate change. It is also recommended that a follow-up workshop be conducted to discuss implementation of the roadmap developed at this workshop.

  3. Satellite Instrument Calibration for Measuring Global Climate Change. Report of a Workshop at the University of Maryland Inn and Conference Center, College Park, MD. , November 12-14, 2002

    Science.gov (United States)

    Ohring, G.; Wielicki, B.; Spencer, R.; Emery, B.; Datla, R.

    2004-01-01

    Measuring the small changes associated with long-term global climate change from space is a daunting task. To address these problems and recommend directions for improvements in satellite instrument calibration some 75 scientists, including researchers who develop and analyze long-term data sets from satellites, experts in the field of satellite instrument calibration, and physicists working on state of the art calibration sources and standards met November 12 - 14, 2002 and discussed the issues. The workshop defined the absolute accuracies and long-term stabilities of global climate data sets that are needed to detect expected trends, translated these data set accuracies and stabilities to required satellite instrument accuracies and stabilities, and evaluated the ability of current observing systems to meet these requirements. The workshop's recommendations include a set of basic axioms or overarching principles that must guide high quality climate observations in general, and a roadmap for improving satellite instrument characterization, calibration, inter-calibration, and associated activities to meet the challenge of measuring global climate change. It is also recommended that a follow-up workshop be conducted to discuss implementation of the roadmap developed at this workshop.

  4. 15-Deoxy-delta12,14-PGJ2, but not troglitazone, modulates IL-1beta effects in human chondrocytes by inhibiting NF-kappaB and AP-1 activation pathways.

    Science.gov (United States)

    Boyault, S; Simonin, M A; Bianchi, A; Compe, E; Liagre, B; Mainard, D; Bécuwe, P; Dauça, M; Netter, P; Terlain, B; Bordji, K

    2001-07-13

    The activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to inhibit the production and the effects of proinflammatory cytokines. Since interleukin-1beta (IL-1beta) directly mediates cartilage degradation in osteoarthritis, we investigated the capability of PPARgamma ligands to modulate IL-1beta effects on human chondrocytes. RT-PCR and Western blot analysis revealed that PPARgamma expression was decreased by IL-1beta. 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), in contrast to troglitazone, was highly potent to counteract IL-1beta-induced cyclooxygenase-2 and inductible nitric oxide synthase expression, NO production and the decrease in proteoglycan synthesis. Western blot and gel-shift analyses demonstrated that 15d-PGJ2 inhibited NF-kappaB activation, while troglitazone was ineffective. Although 15d-PGJ2 attenuated activator protein-1 binding on the DNA, it potentiated c-jun migration in the nucleus. The absence or the low effect of troglitazone suggests that 15d-PGJ2 action in human chondrocytes is mainly PPARgamma-independent.

  5. Heterogeneity of miRNA expression in localized prostate cancer with clinicopathological correlations

    DEFF Research Database (Denmark)

    Zedan, Ahmed Hussein; Blavnsfeldt, Søren Garm; Hansen, Torben Frøstrup

    2017-01-01

    curatively intended surgery for localized PCa, were investigated with a panel of 6 miRNAs (miRNA-21, miRNA-34a, miRNA-125b, miRNA-126, miRNA-143, and miRNA-145) using tissue micro-array (TMA) and in situ hybridization (ISH). Inter- and intra-patient variation was assessed using intra-class correlation (ICC...

  6. The Roles of miR-26, miR-29, and miR-203 in the Silencing of the Epigenetic Machinery during Melanocyte Transformation.

    Science.gov (United States)

    Gasque Schoof, Cláudia Regina; Izzotti, Alberto; Jasiulionis, Miriam Galvonas; Vasques, Luciana Dos Reis

    2015-01-01

    The epigenetic marks located throughout the genome exhibit great variation between normal and transformed cancer cells. While normal cells contain hypomethylated CpG islands near gene promoters and hypermethylated repetitive DNA, the opposite pattern is observed in cancer cells. Recently, it has been reported that alteration in the microenvironment of melanocyte cells, such as substrate adhesion blockade, results in the selection of anoikis-resistant cells, which have tumorigenic characteristics. Melanoma cells obtained through this model show an altered epigenetic pattern, which represents one of the first events during the melanocytes malignant transformation. Because microRNAs are involved in controlling components of the epigenetic machinery, the aim of this work was to evaluate the potential association between the expression of miR-203, miR-26, and miR-29 family members and the genes Dnmt3a, Dnmt3b, Mecp2, and Ezh2 during cells transformation. Our results show that microRNAs and their validated or predicted targets are inversely expressed, indicating that these molecules are involved in epigenetic reprogramming. We also show that miR-203 downregulates Dnmt3b in mouse melanocyte cells. In addition, treatment with 5-aza-CdR promotes the expression of miR-26 and miR-29 in a nonmetastatic melanoma cell line. Considering the occurrence of CpG islands near the miR-26 and miR-29 promoters, these data suggest that they might be epigenetically regulated in cancer.

  7. 慢性心力衰竭患者血浆miRNA表达谱分析%Profiling of plasma miRNA in chronic heart failure patients

    Institute of Scientific and Technical Information of China (English)

    李璐; 陈群蓉; 纪玲

    2016-01-01

    目的:对慢性心力衰竭(CHF)患者的血浆miRNA进行二代测序,探讨CHF患者血浆中miRNA的表达差异。方法收集2013年7月至2015年6月间在北京大学深圳医院治疗的40例CHF患者和10例健康对照个体,应用第二代高通量测序技术对其血浆miRNA进行测序,寻找差异表达的miRNA。另收集同期CHF患者和健康对照个体各96例,用逆转录-实时荧光定量聚合酶链反应对差异表达的miRNA进行验证。结果与健康对照者相比,高通量测序显示在CHF患者的血浆中miR-184、miR-651-5p、miR-130b-5p、miR-203a-3p、miR-548e-3p和miR-106a-5p的表达水平存在显著上调,miR-31-5p和miR-5091的表达水平存在下调,逆转录-实时荧光定量聚合酶链反应检测血浆miRNA的表达差异与高通量测序的结果相符。结论 CHF患者的血浆miRNA与健康个体的表达谱存在差异,差异表达的miR-184、miR-651-5p、miR-130b-5p、miR-203a-3p、miR-548e-3p、miR-106a-5p、miR-31-5p和miR-5091或许与CHF的发生有关。%Objective To search for differentially expressed plasma miRNAs between patients with chronic heart failure (CHF) and healthy controls by next-generation small RNA sequencing. Methods Forty CHF patients and 10 healthy volunteers were recruited to search for differentially expressed plasma miRNAs in next-generation small RNA sequencing study from Peking University Shenzhen Hospital between July 2013 and June 2015. miRNAs expres-sion were validated in another 96 patients and 96 controls by RT-PCR analysis during the same period. Results Com-paring to healthy group, miRNA sequencing showed that miR-184, miR-651-5p, miR-130b-5p, miR-203a-3p, miR-548e-3p, and miR-106a-5p were upregulated and miR-31-5p and miR-5091 were downregulated in CHF pa-tients. The levels of miRNA measured by RT-PCR were consistent with the results obtained from miRNA sequencing technology. Conclusion A differentially expressed miRNA profiling was seen between

  8. miR-181a and miR-630 regulate cisplatin-induced cancer cell death.

    Science.gov (United States)

    Galluzzi, Lorenzo; Morselli, Eugenia; Vitale, Ilio; Kepp, Oliver; Senovilla, Laura; Criollo, Alfredo; Servant, Nicolas; Paccard, Caroline; Hupé, Philippe; Robert, Thomas; Ripoche, Hugues; Lazar, Vladimir; Harel-Bellan, Annick; Dessen, Philippe; Barillot, Emmanuel; Kroemer, Guido

    2010-03-01

    MicroRNAs (miRNA) are noncoding RNAs that regulate multiple cellular processes, including proliferation and apoptosis. We used microarray technology to identify miRNAs that were upregulated by non-small cell lung cancer (NSCLC) A549 cells in response to cisplatin (CDDP). The corresponding synthetic miRNA precursors (pre-miRNAs) per se were not lethal when transfected into A549 cells yet affected cell death induction by CDDP, C2-ceramide, cadmium, etoposide, and mitoxantrone in an inducer-specific fashion. Whereas synthetic miRNA inhibitors (anti-miRNAs) targeting miR-181a and miR-630 failed to modulate the response of A549 to CDDP, pre-miR-181a and pre-miR-630 enhanced and reduced CDDP-triggered cell death, respectively. Pre-miR-181a and pre-miR-630 consistently modulated mitochondrial/postmitochondrial steps of the intrinsic pathway of apoptosis, including Bax oligomerization, mitochondrial transmembrane potential dissipation, and the proteolytic maturation of caspase-9 and caspase-3. In addition, pre-miR-630 blocked early manifestations of the DNA damage response, including the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and of two ATM substrates, histone H2AX and p53. Pharmacologic and genetic inhibition of p53 corroborated the hypothesis that pre-miR-630 (but not pre-miR-181a) blocks the upstream signaling pathways that are ignited by DNA damage and converge on p53 activation. Pre-miR-630 arrested A549 cells in the G0-G1 phase of the cell cycle, correlating with increased levels of the cell cycle inhibitor p27(Kip1) as well as with reduced proliferation rates and resulting in greatly diminished sensitivity of A549 cells to the late S-G2-M cell cycle arrest mediated by CDDP. Altogether, these results identify miR-181a and miR-630 as novel modulators of the CDDP response in NSCLC.

  9. MiPS (Mi Prostate Score Urine test) — EDRN Public Portal

    Science.gov (United States)

    The MiPS assay is a multiplex analysis of T2-ERG gene fusion, PCA3, and serum PSA (KLK3). It is commercially available through the University of Michigan MLabs. The MiPS assay tests for the presence of two prostate cancer biomarkers: a piece of RNA made from the PCA3 gene, found to be overactive in 95 percent of all prostate cancers, and another RNA marker that is found only when TMPRSS2 and ERG abnormally fuse. TMPRSS2:ERG, or T2-ERG, is a strong indicator of prostate cancer.

  10. Expression and clinical significance of miR-29c, miR-133b and miR-1 in ovarian cancer tissue%卵巢癌组织中miR-29c、miR-133b和miR-1的水平分析及临床意义

    Institute of Scientific and Technical Information of China (English)

    穆鹏; 张菁如

    2015-01-01

    Objective To explore the expressions of miR⁃29c, miR⁃133b and miR⁃1 in ovarian cancer tissue and analyze the relationship between the above indicators and clinical pathology parameters of ovarian cancer. Methods Cancer tissue from 65 patients with ovarian cancer were collected as cancer group. The real⁃time quantitative PCR ( qRT⁃PCR) was used to detect the expressions of miR⁃29c, miR⁃133b and miR⁃1 and the clinical pathology parameters of ovarian cancer ( age, clinical stage, degree of differentiation, histological type and lymph node metastasis) were collected. Meanwhile, 32 cases of normal ovarian epithelial tissues ( normal group) and 39 cases of benign ovarian cyst tissue ( benign group) were taken as control. The average level of three indices of normal group were chosen as boundary value, and then the patients were categorized into high⁃level group (>boundary value) and low⁃level group (≤boundary value) . The clinical pathology parameters of patients with different levels of miR⁃29c, miR⁃133b and miR⁃1 were com⁃pared. The relationships among miR⁃29c, miR⁃133b and miR⁃1 were investigated in cancer group. Results There were higher levels of miR⁃29c and but lower miR⁃133b and miR⁃1 in ovarian cancer group versus other two groups with significant difference ( P<0�05) . In ovarian cancer, the levels of three miRNAs were related with degree of differentiation, and miR⁃29c was related with clinical stage and lymph node metastasis, and miR⁃133b was related with lymph node metastasis (P<0�05). The level of miR⁃29c was negatively correlated with miR⁃133b and miR⁃1 ( r=-0�541, r=-0�361) , and miR⁃133b was positively correlated with miR⁃1 with statistically significance ( P<0�05) . Conclusion There were higher expression of miR⁃29c but lower expression of miR⁃133b and miR⁃1. The lev⁃els of the above miRNAs were related with clinical pathology parameters in ovarian cancer tissue, showing a certain

  11. Expression of miR-155 and miR-126 in situ in cutaneous T-cell lymphoma

    DEFF Research Database (Denmark)

    Kopp, Katharina L; Ralfkiaer, Ulrik; Nielsen, Boye S;

    2013-01-01

    Recently, miR-155 has been implicated in cutaneous T-cell lymphoma (CTCL). Thus, elevated levels of miR-155 were observed in skin lesions from CTCL patients as judged from qPCR and micro-array analysis and aberrant, high miR-155 expression was associated with severe disease. Moreover, miR-155...... promoted proliferation of malignant T cells in vitro. Little is, however, known about which cell types express miR-155 in vivo in CTCL skin lesions. Here, we study miR-155 expression using in situ hybridization (ISH) with a miR-155 probe, a negative control (scrambled), and a miR-126 probe as a positive...... control in nine patients with mycosis fungoides, the most frequent subtype of CTCL. We provide evidence that both malignant and non-malignant T cells stain weakly to moderately positive with the miR-155 probe, but generally negative with the miR-126 and negative control probes. Reversely, endothelial...

  12. miR-29 and human diseases%微RNA miR-29与人类疾病

    Institute of Scientific and Technical Information of China (English)

    黄昌发; 刘小珊

    2010-01-01

    人类微RNA miR-29包括miR-29a、miR-29b1、miR-29b2和miR-29c.miR-29在胚胎期组织不表达或低表达,而在生物体成熟组织细胞中广泛表达.实验证实的miR-29作用的靶点包括DNMT3A/3B、YY1、Mcl-1、BACE1以及HIV-1病毒等.miR-29与人类疾病密切相关,miR-29在多种肿瘤细胞、心肌梗塞与散发性阿尔茨海默病等病变组织细胞中表达受抑.本文就miR-29基因结构,基因表达与调控、生物学功能以及与疾病发生相关性作一综述.

  13. Quantitative proteomic analysis of gene regulation by miR-34a and miR-34c.

    Directory of Open Access Journals (Sweden)

    Olivia A Ebner

    Full Text Available microRNAs (miRNAs repress target genes by destabilizing mRNAs and/or by inhibiting translation. The best known factor for target recognition is the so called seed--a short continuous region of Watson-Crick base pairing between nucleotides 2-7 of the miRNA and complementary sequences in 3' untranslated regions of target mRNAs. The miR-34 family consists of three conserved members with important tumor suppressor functions linked to the p53 pathway. The family members share the same seed, raising the question if they also have the same targets. Here, we analyse the effect of miR-34a and miR-34c on protein synthesis by pSILAC. Despite significant overlap, we observe that the impact of both family members on protein synthesis differs. The ability to identify specific targets of a family member is complicated by the occurrence of * strand mediated repression. Transfection of miR-34 chimeras indicates that the 3'end of the miRNA might be responsible for differential regulation in case of targets without a perfect seed site. Pathway analysis of regulated proteins indicates overlapping functions related to cell cycle and the p53 pathway and preferential targeting of several anti-apoptotic proteins by miR-34a. We used luciferase assays to confirm that Vcl and Fkbp8, an important anti-apoptotic protein, are specifically repressed by miR-34a. In summary, we find that miR-34a and miR-34c down-regulate distinct subsets of targets which might mediate different cellular outcomes. Our data provides a rich resource of miR-34 targets that might be relevant for clinical trials that want to implement the miR-34 family in cancer therapy.

  14. MicroRNA Detection Using a Double Molecular Beacon Approach: Distinguishing Between miRNA and Pre-miRNA.

    Science.gov (United States)

    James, Amanda Marie; Baker, Meredith B; Bao, Gang; Searles, Charles D

    2017-01-01

    MicroRNAs (miRNAs) are small, noncoding RNAs that post-transcriptionally regulate gene expression and are recognized for their roles both as modulators of disease progression and as biomarkers of disease activity, including neurological diseases, cancer, and cardiovascular disease (CVD). Commonly, miRNA abundance is assessed using quantitative real-time PCR (qRT-PCR), however, qRT-PCR for miRNA can be labor intensive, time consuming, and may lack specificity for detection of mature versus precursor forms of miRNA. Here, we describe a novel double molecular beacon approach to miRNA assessment that can distinguish and quantify mature versus precursor forms of miRNA in a single assay, an essential feature for use of miRNAs as biomarkers for disease. Using this approach, we found that molecular beacons with DNA or combined locked nucleic acid (LNA)-DNA backbones can detect mature and precursor miRNAs (pre-miRNAs) of low (beacon assay was accurate in assessing miRNA abundance in a sample containing a mixed population of mature and precursor miRNAs. In contrast, qRT-PCR and the single molecular beacon assay overestimated miRNA abundance. Additionally, the double molecular beacon assay was less labor intensive than traditional qRT-PCR and had 10-25% increased specificity. Our data suggest that the double molecular beacon-based approach is more precise and specific than previous methods, and has the promise of being the standard for assessing miRNA levels in biological samples.

  15. miR-203 and miR-205 expression patterns identify subgroups of prognosis in cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Cañueto, J; Cardeñoso-Álvarez, E; García-Hernández, J L; Galindo-Villardón, P; Vicente-Galindo, P; Vicente-Villardón, J L; Alonso-López, D; De Las Rivas, J; Valero, J; Moyano-Sáez, E; Fernández-López, E; Mao, J H; Castellanos-Martín, A; Román-Curto, C; Pérez-Losada, J

    2016-12-11

    Cutaneous squamous cell carcinoma is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as poor-prognosis diseases, and therefore it is important to identify new markers to better predict its clinical evolution. Here, we identified the expression pattern of miRNAs at different stages of skin cancer progression in a panel of murine skin cancer cell lines. We determined that miR-203 and miR-205 are differentially expressed in this panel, and evaluated their potential use as biomarkers of prognosis in human tumours. MiR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. MiR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. MiR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features. This work highlights the utility of miRNA-205 and miRNA-203 as prognostic markers in cutaneous squamous cell carcinoma. This article is protected by copyright. All rights reserved.

  16. Identification of targets of miRNA-221 and miRNA-222 in fulvestrant-resistant breast cancer

    Science.gov (United States)

    Liu, Pengfei; Sun, Manna; Jiang, Wenhua; Zhao, Jinkun; Liang, Chunyong; Zhang, Huilai

    2016-01-01

    The present study aimed to identify the differentially expressed genes (DEGs) regulated by microRNA (miRNA)-221 and miRNA-222 that are associated with the resistance of breast cancer to fulvestrant. The GSE19777 transcription profile was downloaded from the Gene Expression Omnibus database, and includes data from three samples of antisense miRNA-221-transfected fulvestrant-resistant MCF7-FR breast cancer cells, three samples of antisense miRNA-222-transfected fulvestrant-resistant MCF7-FR cells and three samples of control inhibitor (green fluorescent protein)-treated fulvestrant-resistant MCF7-FR cells. The linear models for microarray data package in R/Bioconductor was employed to screen for DEGs in the miRNA-transfected cells, and the pheatmap package in R was used to perform two-way clustering. Pathway enrichment was conducted using the Gene Set Enrichment Analysis tool. Furthermore, a miRNA-messenger (m) RNA regulatory network depicting interactions between miRNA-targeted upregulated DEGs was constructed and visualized using Cytoscape. In total, 492 and 404 DEGs were identified for the antisense miRNA-221-transfected MCF7-FR cells and the antisense miRNA-222-transfected MCF7-FR cells, respectively. Genes of the pentose phosphate pathway (PPP) were significantly enriched in the antisense miRNA-221-transfected MCF7-FR cells. In addition, components of the Wnt signaling pathway and cell adhesion molecules (CAMs) were significantly enriched in the antisense miRNA-222-transfected MCF7-FR cells. In the miRNA-mRNA regulatory network, miRNA-222 was demonstrated to target protocadherin 10 (PCDH10). The results of the present study suggested that the PPP and Wnt signaling pathways, as well as CAMs and PCDH10, may be associated with the resistance of breast cancer to fulvestrant. PMID:27895744

  17. 先天性心脏病相关性肺动脉高压患者血miR-18a、miR-27b、miR-130a、miR-204水平研究%The changes of plasma miR-18a, miR-27b, miR-130a, miR-204 in patients with pulmonary arterial hypertension due to congenital heart disease

    Institute of Scientific and Technical Information of China (English)

    吕宁; 戴海龙; 尹小龙

    2014-01-01

    目的 探索先天性心性脏病相关性肺动脉高压(PAH)患者血清中miR-18a、miR-27b、miR-130a和miR-204的表达水平,以及与PAH的相关性.方法 收集昆明医科大学附属延安医院心血管内科2012年4~12月被确诊为先天性心脏病的患者78例,其中肺动脉压正常组37例,合并轻、中度肺动脉高压组25例,重度肺动脉高压组16例;另设正常对照组20例.应用实时荧光定量PCR (Taqman探针法)检测miR-18a、miR-27b、miR-130a、miR-204在血液中的表达水平,分析先天性心脏病相关性肺动脉高压与miR-NA表达水平之间的关系.结果 先天性心脏病相关肺动脉高压患者血miR-18a、miR-27b、miR-130a表达水平显著上调,miR-204表达水平显著下调.随着肺动脉压力的不断增高,血miR-18a、miR-27b、miR-130a表达量明显升高,miR-204表达量显著下调.直线相关分析显示,先天性心脏病继发性肺动脉高压患者血miR-18a、miR-27b、miR-130a表达水平与肺动脉压力存在高度正相关关系(r=0.927,r=0.927,r=0.933,P<0.01),miR-204表达水平与肺动脉压力存在高度负相关关系(r=-0.773,P<0.01).结论 血miR-18a、miR-27b、miR-130a、miR-204水平可作为判断先天性心脏病合并肺动脉高压较好的临床血清学指标,预判价值较高.

  18. 脑胶质瘤患者血清miR-21、miR-221、miR-222和miR-10b的相对表达量及临床意义%The Relative Expression of Serum miR-21 ,miR-221 ,miR-222 and miR-10b in Patients with Glioma and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    朱建军; 李春生

    2015-01-01

    目的 探讨血清中miR-21、miR-221、miR-222和miR-10b对脑胶质瘤恶性程度的鉴别价值.方法 采用Real-timePCR技术检测34例低级别脑胶质瘤患者和50例高级别脑胶质瘤患者miR-21、miR-221、miR-222和miR-10b的相对表达量,使用受试者工作特征曲线(receiver operating characteristic curve,ROC)评价其诊断价值.结果 与低级别脑胶质瘤组相比,高级别脑胶质瘤组血清miR-10b、miR-21和miR-221的相对表达量均显著升高,且差异具有统计学意义,miR-222相对表达量的差异无统计学意义.ROC曲线评价血清miR-10b、miR-21和miR-221对于脑胶质瘤恶性程度的诊断价值,miR-10b的曲线下面积(area under curve,AUC)值最大,为0.722(0.694,0.751),对于低级别脑胶质瘤的诊断敏感性和特异性分别为79.41%和78.00%.使用二元Logistic回归分析评价血清miR-10b、miR-21和miR-221联合检测对于脑胶质瘤恶性程度的诊断价值,其曲线下面积为0.915(0.855,0.977),对于低级别脑胶质瘤的诊断敏感性和特异性分别为85.29%和88.00%.与miR-10b、miR-21和miR-221单独检测的诊断价值相比,其曲线下面积均有显著提高(P=0.026、P=0.012、P=0.008).结论 miR-10b、miR-21和miR-221联合诊断可以为临床脑胶质瘤患者的鉴别诊断提供一种潜在的辅助诊断方法.

  19. Association between single nucleotide polymorphism in miR-499, miR-196a2, miR-146a and miR-149 and prostate cancer risk in a sample of Iranian population.

    Science.gov (United States)

    Hashemi, Mohammad; Moradi, Nazanin; Ziaee, Seyed Amir Mohsen; Narouie, Behzad; Soltani, Mohammad Hosein; Rezaei, Maryam; Shahkar, Ghazaleh; Taheri, Mohsen

    2016-05-01

    MicroRNAs (miRNAs) play an important role in regulating gene expression at the post-transcriptional level and are involved in numerous physiological processes. Accumulating evidence suggests that single-nucleotide polymorphisms (SNPs) in human miRNA genes may affect miRNA biogenesis pathway and influence the susceptibility to several diseases such as cancer. The present study aimed to evaluate the impact of miR-499 rs3746444, miR-196a2 rs11614913, miR-149 rs2292832, and miR-146a rs2910164 polymorphisms on prostate cancer (PCa) risk in a sample of Iranian population. This case-control study was done on 169 patients with pathologically confirmed PCa and 182 benign prostatic hyperplasia (BPH). The genotyping assays were done using T-ARMS-PCR or PCR-RFLP methods. The findings indicated that CC genotype of miR-499 rs3746444 polymorphism increased the risk of PCa (OR = 1.76, 95% CI = 1.12-2.79, P = 0.019) compared to TT genotype. No statistically significant association was found between miR-196a2 rs11614913, miR-149 rs2292832, and miR-146a rs2910164 polymorphisms and PCa risk. In summary, the findings indicated that miR-499 rs3746444 polymorphism increased the risk of PCa in an Iranian population. Further studies with larger sample sizes and different ethnicities are necessary to verify the findings of the present study.

  20. Association between single nucleotide polymorphism in miR-499, miR-196a2, miR-146a and miR-149 and prostate cancer risk in a sample of Iranian population

    Science.gov (United States)

    Hashemi, Mohammad; Moradi, Nazanin; Ziaee, Seyed Amir Mohsen; Narouie, Behzad; Soltani, Mohammad Hosein; Rezaei, Maryam; Shahkar, Ghazaleh; Taheri, Mohsen

    2016-01-01

    MicroRNAs (miRNAs) play an important role in regulating gene expression at the post-transcriptional level and are involved in numerous physiological processes. Accumulating evidence suggests that single-nucleotide polymorphisms (SNPs) in human miRNA genes may affect miRNA biogenesis pathway and influence the susceptibility to several diseases such as cancer. The present study aimed to evaluate the impact of miR-499 rs3746444, miR-196a2 rs11614913, miR-149 rs2292832, and miR-146a rs2910164 polymorphisms on prostate cancer (PCa) risk in a sample of Iranian population. This case-control study was done on 169 patients with pathologically confirmed PCa and 182 benign prostatic hyperplasia (BPH). The genotyping assays were done using T-ARMS-PCR or PCR-RFLP methods. The findings indicated that CC genotype of miR-499 rs3746444 polymorphism increased the risk of PCa (OR = 1.76, 95% CI = 1.12–2.79, P = 0.019) compared to TT genotype. No statistically significant association was found between miR-196a2 rs11614913, miR-149 rs2292832, and miR-146a rs2910164 polymorphisms and PCa risk. In summary, the findings indicated that miR-499 rs3746444 polymorphism increased the risk of PCa in an Iranian population. Further studies with larger sample sizes and different ethnicities are necessary to verify the findings of the present study. PMID:27222754

  1. miR-10b、miR-18b及miR-130b在肺癌中的表达研究%Expression of miR-10b、miR-18b and miR-130b in lung cancer

    Institute of Scientific and Technical Information of China (English)

    曾龙剑; 吴锡南; 杨凯云; 李苹; 徐俪烜; 姚树祥; 何越峰

    2014-01-01

    目的 探讨miR-10b、miR-18b及miR-130b在肺癌中的表达特征及其在肺癌发生发展过程中的作用.方法 收集47例肺癌住院患者的癌组织和癌旁组织,利用Trizol提取总RNA,实时荧光定量PCR检测基因相对表达量.结果 肺癌组织与癌旁组织中miR-10b(t=2.83,P<0.05)、miR-18b(t=2.88,P<0.05)及miR-130b(t =2.46,P<0.05)表达量均差异存在显著性.比较鳞癌、腺癌和癌旁组织中miR-10b(F =7.16,P<0.05)、miR-18b(F =4.11,P<0.05)及miR-130b(F =3.43,P<0.05)的表达量也有显著性.癌组织中miR-10b与pri-miR-10b表达量存在负相关关系(r=-0.50,P<0.05) . 癌组织与临床指标之间的关系中miR-18b、miR-130b与KI67呈正相关(P<0.05),pri-miR-10b与TOPOⅡ、pri-miR-130b与MRP呈负相关(P<0.05).结论 miR-10b、miR-18b及miR-130b在癌组织中表达量上调,可能具有促进肺癌发生发展的作用.

  2. Role of miR-383 and miR-146b in different propensities to obesity in male mice.

    Science.gov (United States)

    Xia, Shu-Fang; Duan, Xiao-Mei; Cheng, Xiang-Rong; Chen, Li-Mei; Kang, Yan-Jun; Wang, Peng; Tang, Xue; Shi, Yong-Hui; Le, Guo-Wei

    2017-08-01

    The study was designed to investigate the possible mechanisms of hepatic microRNAs (miRs) in regulating local thyroid hormone (TH) action and ultimately different propensities to high-fat diet (HFD)-induced obesity. When obesity-prone (OP) and obesity-resistant (OR) mice were fed HFD for 7 weeks, OP mice showed apparent hepatic steatosis, with significantly higher body weight and lower hepatic TH receptor b (TRb) expression and type 1 deiodinase (DIO1) activity than OR mice. Next-generation sequencing technology revealed that 13 miRs in liver were dysregulated between the two phenotypes, of which 8 miRs were predicted to target on Dio1 or TRb When mice were fed for 17 weeks, OR mice had mild hepatic steatosis and increased Dio1 and TRb expression than OP mice, with downregulation of T3 target genes (including Srebp1c, Acc1, Scd1 and Fasn) and upregulation of Cpt1α, Atp5c1, Cox7c and Cyp7a1 A stem-loop qRT-PCR analysis confirmed that the levels of miR-383, miR-34a and miR-146b were inversely correlated with those of DIO1 or TRb. Down-regulated expression of miR-383 or miR-146b by miR-383 inhibitor (anti-miR-383) or miR-146b inhibitor (anti-miR-146b) in free fatty acid-treated primary mouse hepatocytes led to increased DIO1 and TRb expressions, respectively, and subsequently decreased cellular lipid accumulation, while miR-34a inhibitor (anti-miR-34a) transfection had on effects on TRb expression. Luciferase reporter assay illustrated that miR-146b could directly target TRb 3'untranslated region (3'UTR). These findings suggested that miR-383 and miR-146b might play critical roles in different propensities to diet-induced obesity via targeting on Dio1 and TRb, respectively. © 2017 Society for Endocrinology.

  3. miRNA-124 in Immune System and Immune Disorders

    OpenAIRE

    2016-01-01

    In recent years, miR-124 has emerged as a critical modulator of immunity and inflammation. Here, we summarize studies on the function and mechanism of miR-124 in the immune system and immunity-related diseases. They indicated that miR-124 exerts a crucial role in the development of immune system, regulation of immune responses, and inflammatory disorders. It is evident that miR-124 may serve as an informative diagnostic biomarker and therapeutic target in the future.

  4. Principles of miRNA-Target Regulation in Metazoan Models

    Directory of Open Access Journals (Sweden)

    Epaminondas Doxakis

    2013-08-01

    Full Text Available MicroRNAs (miRs are key post-transcriptional regulators that silence gene expression by direct base pairing to target sites of RNAs. They have a wide variety of tissue expression patterns and are differentially expressed during development and disease. Their activity and abundance is subject to various levels of control ranging from transcription and biogenesis to miR response elements on RNAs, target cellular levels and miR turnover. This review summarizes and discusses current knowledge on the regulation of miR activity and concludes with novel non-canonical functions that have recently emerged.

  5. MicroRNA miR-125b causes leukemia.

    Science.gov (United States)

    Bousquet, Marina; Harris, Marian H; Zhou, Beiyan; Lodish, Harvey F

    2010-12-14

    MicroRNA miR-125b has been implicated in several kinds of leukemia. The chromosomal translocation t(2;11)(p21;q23) found in patients with myelodysplasia and acute myeloid leukemia leads to an overexpression of miR-125b of up to 90-fold normal. Moreover, miR-125b is also up-regulated in patients with B-cell acute lymphoblastic leukemia carrying the t(11;14)(q24;q32) translocation. To decipher the presumed oncogenic mechanism of miR-125b, we used transplantation experiments in mice. All mice transplanted with fetal liver cells ectopically expressing miR-125b showed an increase in white blood cell count, in particular in neutrophils and monocytes, associated with a macrocytic anemia. Among these mice, half died of B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia, or a myeloproliferative neoplasm, suggesting an important role for miR-125b in early hematopoiesis. Furthermore, coexpression of miR-125b and the BCR-ABL fusion gene in transplanted cells accelerated the development of leukemia in mice, compared with control mice expressing only BCR-ABL, suggesting that miR-125b confers a proliferative advantage to the leukemic cells. Thus, we show that overexpression of miR-125b is sufficient both to shorten the latency of BCR-ABL-induced leukemia and to independently induce leukemia in a mouse model.

  6. miR-1279, miR-548j, miR-548m, and miR-548d-5p binding sites in CDSs of paralogous and orthologous PTPN12, MSH6, and ZEB1 Genes.

    Science.gov (United States)

    Ivashchenko, Anatoliy T; Issabekova, Assel S; Berillo, Olga A

    2013-01-01

    Only PTPN12, MSH6, and ZEB1 have significant miR-1279 binding sites among paralogous genes of human tyrosine phosphatase family, DNA mismatch repair family, and zinc finger family, respectively. All miRNA binding sites are located within CDSs of studied mRNAs. Nucleotide sequences of hsa-miR-1279 binding sites with mRNAs of human PTPN12, MSH6, and ZEB1 genes encode TKEQYE, EGSSDE, and GEKPYE oligopeptides, respectively. The conservation of miRNA binding sites encoding oligopeptides has been revealed. MRNAs of many paralogs of zinc finger gene family have from 1 to 12 binding sites coding the same GEKPYE hexapeptide. MRNAs of PTPN12, MSH6, and ZEB1 orthologous genes from different animal species have binding sites for hsa-miR-1279 which consist of homologous oligonucleotides encoding similar human oligopeptides TKEQYE, EGSSDE, and GEKPYE. MiR-548j, miR-548m, and miR-548d-5p have homologous binding sites in the mRNA of PTPN12 orthologous genes which encode PRTRSC, TEATDI, and STASAT oligopeptides, respectively. All regions of miRNA are important for binding with the mRNA.

  7. miR-1279, miR-548j, miR-548m, and miR-548d-5p Binding Sites in CDSs of Paralogous and Orthologous PTPN12, MSH6, and ZEB1 Genes

    Directory of Open Access Journals (Sweden)

    Anatoliy T. Ivashchenko

    2013-01-01

    Full Text Available Only PTPN12, MSH6, and ZEB1 have significant miR-1279 binding sites among paralogous genes of human tyrosine phosphatase family, DNA mismatch repair family, and zinc finger family, respectively. All miRNA binding sites are located within CDSs of studied mRNAs. Nucleotide sequences of hsa-miR-1279 binding sites with mRNAs of human PTPN12, MSH6, and ZEB1 genes encode TKEQYE, EGSSDE, and GEKPYE oligopeptides, respectively. The conservation of miRNA binding sites encoding oligopeptides has been revealed. MRNAs of many paralogs of zinc finger gene family have from 1 to 12 binding sites coding the same GEKPYE hexapeptide. MRNAs of PTPN12, MSH6, and ZEB1 orthologous genes from different animal species have binding sites for hsa-miR-1279 which consist of homologous oligonucleotides encoding similar human oligopeptides TKEQYE, EGSSDE, and GEKPYE. MiR-548j, miR-548m, and miR-548d-5p have homologous binding sites in the mRNA of PTPN12 orthologous genes which encode PRTRSC, TEATDI, and STASAT oligopeptides, respectively. All regions of miRNA are important for binding with the mRNA.

  8. miR-1279, miR-548j, miR-548m, and miR-548d-5p Binding Sites in CDSs of Paralogous and Orthologous PTPN12, MSH6, and ZEB1 Genes

    OpenAIRE

    Ivashchenko, Anatoliy T.; Issabekova, Assel S.; Berillo, Olga A.

    2013-01-01

    Only PTPN12, MSH6, and ZEB1 have significant miR-1279 binding sites among paralogous genes of human tyrosine phosphatase family, DNA mismatch repair family, and zinc finger family, respectively. All miRNA binding sites are located within CDSs of studied mRNAs. Nucleotide sequences of hsa-miR-1279 binding sites with mRNAs of human PTPN12, MSH6, and ZEB1 genes encode TKEQYE, EGSSDE, and GEKPYE oligopeptides, respectively. The conservation of miRNA binding sites encoding oligopeptides has been r...

  9. miRNAs as biomarkers of atrial fibrillation.

    Science.gov (United States)

    Gomes da Silva, Ananília Medeiros; Silbiger, Vivian Nogueira

    2014-12-01

    Atrial fibrillation (AF) is a highly prevalent arrhythmia with pronounced morbidity and mortality. Genetics analysis has established electrophysiological substrates, which determine individual vulnerability to AF occurrence and maintenance. MicroRNAs (miRNAs) found in virtually all organisms function as negative regulators of protein-coding genes. Several studies have suggested a role for miRNAs in the regulation of cardiac excitability and arrhythmogenesis. This review is based on 18 studies conducted between 2009 and 2013 to investigate the association of miRNAs with AF. miRNAs are discussed here as candidate biomarkers for AF in blood and cardiac tissues and as potential targets for AF therapy.

  10. 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.

  11. 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.

  12. Progress in miRNA target prediction and identification

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Recently, the identification of miRNA targets has received much attention. The strategies to determine miRNA targets include bioinformatic prediction and experimental assays. The bioinformatic prediction methods are mainly based on the confirmed rules of interaction between miRNAs and their targets, and are carried out by programs, such as miRanda, TargetScan, TargetScanS, RNAhybrid, DIANA-microT, PicTar, RNA22 and FindTar, which follow well-known principles. The experimental assays to find miRNA targets employ immunoprecipitation of AGO proteins to identify interacting mRNAs, or the analysis of mRNA or protein levels to identify genes which can be regulated by miRNAs. The improvement of current bioinformatic and experimental assays and the development of novel assays will enable greater efficiency in the identification of miRNA targets and thus facilitate miRNA research. This paper describes progress in the prediction and identification of miRNA targets.

  13. Epidemiological investigation of dental caries on 12, 14 years old students in Pinghu City of Zhejiang Province%浙江省平湖市12、14岁学生龋病流行病学调查

    Institute of Scientific and Technical Information of China (English)

    吴玲英

    2014-01-01

    目的:了解平湖市城乡12、14岁年龄组学生恒牙龋齿状况及相关发病因素,为龋病预防提供科学依据。方法采取随机抽样调查方法,按照WHO口腔调查基本方法中的龋病诊断标准对平湖市城乡12岁1030名和14岁1012名学生进行口腔龋病及相关因素调查。结果1030名12岁学生患龋率为56.02%,龋均为1.30,显著性龋均指数3.06,充填率9.71%,残冠残根率10.98%,有80.10%儿童偏好甜食和饮料或二者同时兼食。14岁1012名学生患龋率为60.87%,龋均为1.71,显著性龋均指数3.98,充填率19.96%,残冠残根率17.89%,89.43%学生偏好甜食和饮料或二者同时兼食。两组女性患龋率均高于男性,差异有统计学(P0.05)。结论平湖市12、14岁学生患龋率高,残冠残根率较高,治疗率低,偏好甜食和饮料者多。%Objective To investigate the permanent dental caries status and related risk factors on 12, 14 years old stu-dents in Pinghu City, to provide the scientific evidence of caries disease prevention. Methods 1030 cases of 12 years old students and 1012 cases of 14 years old students were selected to investigate the permanent dental caries status and related risk factors according to random sampling method and WHO oral survey basic method in Pinghu City. Re-sults Dental caries rate of 12 years old students among 1030 cases was 56.02%, average caries was 1.30, significant caries index was 3.06, dental caries filling ratio was 9.71%, the residual crown and residual root rate was 10.98%, 80.10% children were enjoyed with sweet food and drinks or both of them. Dental caries rate of 14 years old students among 1012 cases was 60.87%, average caries was 1.71, significant caries index was 3.98, dental caries filling ratio was 19.96%, the residual crown and residual root rate was 17.89%, 89.43% children were enjoyed with sweet food and drinks or both of them. The dental caries rate in female was higher than that in male in both groups, the

  14. miRMaid: a unified programming interface for microRNA data resources

    DEFF Research Database (Denmark)

    Jacobsen, Anders; Krogh, Anders; Kauppinen, Sakari;

    2010-01-01

    miRBase data as inter-connected web services. Third-party miRNA data resources can be modularly integrated as miRMaid plugins or they can loosely couple with miRMaid as individual entities in the World Wide Web. miRMaid is available as a public web service but is also easily installed as a local...

  15. Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15-deoxy-Δ(12,14)-prostagandin J2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring.

    Science.gov (United States)

    Lu, Pei-Chen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Lin, Yu-Ju; Chen, Chih-Cheng; Tiao, Mao-Meng; Tsai, Ching-Chou; Huang, Li-Tung; Tain, You-Lin

    2016-07-01

    Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake.

  16. Changes in the Th1 : Th2 Cytokine Bias in Pregnancy and the Effects of the Anti-Inflammatory Cyclopentenone Prostaglandin 15-Deoxy-Δ12,14-Prostaglandin J2

    Directory of Open Access Journals (Sweden)

    Lynne Sykes

    2012-01-01

    Full Text Available Pregnancy is a complex immunological state in which a bias towards T helper 2 (Th2 protects the fetus. Evidence suggests that proinflammatory cytokines increase the risk of poor neonatal outcome, independently of the direct effect of preterm labour. The anti-inflammatory prostaglandin 15-deoxy-Δ12,14-Prostaglandin J2 (15dPGJ2 inhibits nuclear factor Kappa B (NF-κB in amniocytes and myocytes in vitro and is a ligand for the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2 receptor. Here we examine the Th1:Th2 cytokine bias in pregnancy and whether 15dPGJ2 could be used to inhibit the production of the proinflammatory cytokines through inhibition of NF-κB while simultaneously promoting Th2 interleukin 4 (IL-4 synthesis via CRTH2 in T helper cells. Peripheral blood mononuclear cells (PBMCs from women at 28 weeks, term pre-labour, term labour as well as non-pregnant female controls were cultured with 15dPGJ2 or vehicle control and stimulated with phorbol myristyl acetate (PMA/ionomycin. The percentage of CD4+ cells producing interferon gamma (IFN-γ and tumor necrosis factor alpha (TNF-α in response to PMA/ionomycin was significantly reduced in pregnancy. 15dPGJ2 reduced IFN-γ and TNF-α production in stimulated T helper cells, but did not alter IL-4 production in CRTH2+ve cells. 15dPGJ2 also reduced phospho-p65 in stimulated PBMCs. In summary, 15dPGJ2 suppresses the Th1 response of PBMCs during pregnancy and active labour whilst maintaining the Th2 response suggesting a therapeutic benefit in reducing neonatal morbidity in inflammation-induced PTL.

  17. Therapeutic Treatment of Arthritic Mice with 15-Deoxy Δ(12,14)-Prostaglandin J2 (15d-PGJ2) Ameliorates Disease through the Suppression of Th17 Cells and the Induction of CD4(+)CD25(-)FOXP3(+) Cells.

    Science.gov (United States)

    Carregaro, Vanessa; Napimoga, Marcelo H; Peres, Raphael S; Benevides, Luciana; Sacramento, Laís Amorim; Pinto, Larissa G; Grespan, Renata; Cunha, Thiago M; da Silva, João Santana; Cunha, Fernando Q

    2016-01-01

    The prostaglandin, 15-deoxy Δ(12,14)-prostaglandin J2 (15d-PGJ2), is a lipid mediator that plays an important role in the control of chronic inflammatory disease. However, the role of prostanoid in rheumatoid arthritis (RA) is not well determined. We demonstrated the therapeutic effect of 15d-PGJ2 in an experimental model of arthritis. Daily administration of 15d-PGJ2 attenuated the severity of CIA, reducing the clinical score, pain, and edema. 15d-PGJ2 treatment was associated with a marked reduction in joint levels of proinflammatory cytokines. Although the mRNA expression of ROR-γt was profoundly reduced, FOXP3 was enhanced in draining lymph node cells from 15d-PGJ2-treated arthritic mice. The specific and polyclonal CD4(+) Th17 cell responses were limited during the addition of prostaglandin to cell culture. Moreover, in vitro 15d-PGJ2 increased the expression of FOXP3, GITR, and CTLA-4 in the CD4(+)CD25(-) population, suggesting the induction of Tregs on conventional T cells. Prostanoid addition to CD4(+)CD25(-) cells selectively suppressed Th17 differentiation and promoted the enhancement of FOXP3 under polarization conditions. Thus, 15d-PGJ2 ameliorated symptoms of collagen-induced arthritis by regulating Th17 differentiation, concomitant with the induction of Tregs, and, consequently, protected mice from diseases aggravation. Altogether, these results indicate that 15d-PGJ2 may represent a potential therapeutic strategy in RA.

  18. 15-Deoxy-Δ12,14-Prostaglandin J2 Protects PC12 cells from LPS-Induced Cell Death Through Nrf2 pathway in PPAR-γ Dependent Manner

    Directory of Open Access Journals (Sweden)

    Fariba Khodagholi

    2012-02-01

    Full Text Available Introduction:The inflammatory response requires a coordinated integration of various signaling pathway including cyclooxygenase (COX.COX catalyzes the formation of prostaglandins from arachidonic acid. Among prostaglandins, 15-Deoxy-D12,14-prostaglandin J2 (15d-PGJ2,an endogenous ligand of Peroxisome proliferator-activated receptor-gamma (PPAR-γ,has been demonstrated to have anti-inflammatory actions.In this study,we investigated whether 15d-PGJ2 as a PPAR-γ ligand could exert neuroprotective effects in rat pheochromocytoma (PC12 cells in PPAR-γ dependent manner. Methods: In our experiment, using PC12 cells, the levels of NF-κB, Nrf2, γ-glutamylcysteine synthetase (γ-GCS, hemeoxygenase (HO-1 and apoptosis factors were determined using Western blot in different groups. Also cell viability was determined by the conventional MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide reduction assay and two staining involved Hoechst staining and Acridine Ordange/Ethidiume Bromide staining respectively. Results: Our results show that NS-398, a selective COX-2 inhibitor and 15d-PGJ2, a natural potent ligand of PPAR-γ, were neuroprotective through modulation of at least three different, but related pathways and molecules, including NF-κB and Nrf2 signaling pathway. Our data showed that 15d-PGJ2 and NS-398 induced Nrf2 signaling pathway and its downstream factors such as HO-1 and γ-GCS, while 15d-PGJ2 and NS-398 decreased NF-κB level. Interestingly, the observed protective effects were mediated through PPAR-γ-dependent mechanisms, as they reversed by GW9662, an irreversible antagonist of PPAR-γ receptor. Discussion: Thus we conclude that 15d-PGJ2 as well as NS-398 exert anti cell death effect in a PPAR-γ dependent mechanisms.

  19. 15-Deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} enhanced the anti-tumor activity of camptothecin against renal cell carcinoma independently of topoisomerase-II and PPAR{gamma} pathways

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Yasuhiro [Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, Kami-ohno 7-Chome, Himeji, Hyogo 670-8524 (Japan); Fujita, Megumi [Faculty of Pharmaceutical Sciences, Mukogawa Women' s University, 11-68 Koshien-kyuban-cho, Nishinomiya, Hyogo 663-8179 (Japan); Koma, Hiromi [Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, Kami-ohno 7-Chome, Himeji, Hyogo 670-8524 (Japan); Yamamori, Motohiro [Faculty of Pharmaceutical Sciences, Mukogawa Women' s University, 11-68 Koshien-kyuban-cho, Nishinomiya, Hyogo 663-8179 (Japan); Nakamura, Tsutomu [Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, Kami-ohno 7-Chome, Himeji, Hyogo 670-8524 (Japan); Okamura, Noboru [Faculty of Pharmaceutical Sciences, Mukogawa Women' s University, 11-68 Koshien-kyuban-cho, Nishinomiya, Hyogo 663-8179 (Japan); Yagami, Tatsurou, E-mail: yagami@himeji-du.ac.jp [Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, Kami-ohno 7-Chome, Himeji, Hyogo 670-8524 (Japan)

    2011-07-08

    Highlights: {yields} A topoisomerase-I inhibitor, camptothecin, exhibited synergistically toxicity with 15d-PGJ{sub 2}. {yields} The combination of 15d-PGJ{sub 2} and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. {yields} A PPAR{gamma} antagonist did not prevent Caki-2 from undergoing 15d-PGJ{sub 2}-induced cytotoxicity. {yields} The treatment of camptothecin combined with 15d-PGJ{sub 2} activated caspase-3 more than the separate treatment. -- Abstract: Renal cell carcinoma (RCC) is chemoresistant cancer. Although several clinical trials were conducted to explore effective medications, the chemoresistance of RCC has not yet been conquered. An endogenous ligand for peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}), 15-deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} (15d-PGJ{sub 2}), induces apoptosis in RCC. Here, we examined synergistic effects of several carcinostatics on the anti-tumor activity of 15d-PGJ{sub 2} in Caki-2 cell line by MTT assay. A topoisomerase-I inhibitor, camptothecin (CPT), exhibited synergistically toxicity with 15d-PGJ{sub 2}, but neither 5-fluorouracil nor cisplatin did. The combination of 15d-PGJ{sub 2} and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. The synergistic effect of topoisomerase-I and II inhibitors was not also detected. A PPAR{gamma} antagonist, GW9662, did not prevent Caki-2 from undergoing 15d-PGJ{sub 2}-induced cytotoxicity. The treatment of CPT combined with 15d-PGJ{sub 2} activated caspase-3 more than the separate treatment. These results suggest that 15d-PGJ{sub 2} exhibited the anti-tumor activity synergistically with CPT independent of topoisomerase-II and PPAR{gamma}.

  20. 15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity

    Directory of Open Access Journals (Sweden)

    Kan Chen

    2014-01-01

    Full Text Available Objective. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2 reduces inflammation and has been identified as an anti-inflammatory prostaglandin in numerous animal models. In this study, we investigated both effects of 15d-PGJ2 and its protection mechanism in concanavalin A- (ConA- induced autoimmune hepatitis in mice. Materials and Methods. In vivo, Balb/C mice were injected with ConA (25 mg/kg to induce acute autoimmune hepatitis, and 15d-PGJ2 (10 μg or 25 μg was administered 1 h before the ConA injection. The histological grade, proinflammatory cytokine levels, and NF-κB and PPARγ activity were determined 6, 12, and 24 h after the ConA injection. In vitro, LO2 cells and RAW264.7 cells were pretreated with 15d-PGJ2 (2 μM 1 h before the stimulation with ConA (30 μg/mL. The NF-κB and PPARγ activity were determined 30 min after the ConA administration. Results. Pretreatment with 15d-PGJ2 reduced the pathological effects of ConA-induced autoimmune hepatitis and significantly reduced the levels of cytokines after injection. 15d-PGJ2 activated PPARγ, blocked the degradation of IκBα, and inhibited the translocation of NF-κB into the nucleus. Conclusion. These results indicate that 15d-PGJ2 protects against ConA-induced autoimmune hepatitis by reducing proinflammatory cytokines. This reduction in inflammation may correlate with the activation of PPARγ and the reduction in NF-κB activity.

  1. 淋巴瘤患者血浆中miR-21、miR-155、miR-210的表达及临床意义%Expressions of miR-21, miR-155 and miR-210 in Plasma of Patients with Lymphoma and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    葛甜甜; 宋嘉; 王化泉; 邢莉民; 关晶; 李丽娟; 邵宗鸿; 梁勇; 付蓉; 王国锦; 阮二宝; 瞿文; 王晓明; 刘鸿; 吴玉红

    2012-01-01

    This study was purposed to investigate the expressions of miR-21, miR-155 and miR-210 in plasma of patients with lymphoma, and explore their role played in diagnosis, evaluation of chemotherapy effect and prognosis of lymphoma. The expressions of miR-21, miR-155 and miR-210 were assayed by RT-PCR in plasma of 54 cases of lymphoma, 10 cases of lymphonode inflammation and 27 cases of normal controls. The results indicated that the expressions of miR-21, miR-155 and miR-210 in plasma of lymphoma patients were higher than those of control group and lymphonode inflammation group(P 0.05). The expression of miR-21 in plasma of lymphoma patient group significantly correlated with their serum LDH level. The expressions of miR-21 and miR-210 in plasma of previously untreated lymphoma patient group were higher than those of the patients treated for 6 or more courses (P < 0.05). The diagnostic accuracy of miR-21, miR-155 and miR-210 used for lymphoma patients was 56% , 65% , 48% respectively, and reached to 83% when combined three of them. It is concluded that the expressions of miR-21 , miR-155 and miR-210 in plasma of lymphoma patients were significantly higher. Detection of these 3 miRNA in plasma of patients can contribute to the clinical diagnosis, treatment and prognosis evaluation of lymphoma.%本研究旨在检测淋巴瘤患者血浆中miR-21、miR-155、miR-210的表达,分析其与临床特征的相关性并探讨其在淋巴瘤诊断、评价疗效及预后方面的作用.运用RT-PCR方法检测淋巴瘤患者(55例)、淋巴结炎性肿大患者(10例)和正常对照(27名)血浆中miR-21、miR-155、miR-210的表达.结果表明,淋巴瘤患者血浆中miR-21、miR-155、miR-210的表达量均明显高于正常对照及淋巴结炎性肿大患者(P<0.05),淋巴结炎性肿大患者血浆中miR-21、miR-210的表达量与正常对照无显著差异.淋巴瘤患者血浆中miR-21的表达随血清乳酸脱氢酶水平增高而增高.初治淋巴瘤患者血浆中mi

  2. The miRNA plasma signature in response to acute aerobic exercise and endurance training.

    Directory of Open Access Journals (Sweden)

    Søren Nielsen

    Full Text Available MiRNAs are potent intracellular posttranscriptional regulators and are also selectively secreted into the circulation in a cell-specific fashion. Global changes in miRNA expression in skeletal muscle in response to endurance exercise training have been reported. Therefore, our aim was to establish the miRNA signature in human plasma in response to acute exercise and chronic endurance training by utilizing a novel methodological approach. RNA was isolated from human plasma collected from young healthy men before and after an acute endurance exercise bout and following 12 weeks of endurance training. Global miRNA (742 miRNAs measurements were performed as a screening to identify detectable miRNAs in plasma. Using customized qPCR panels we quantified the expression levels of miRNAs detected in the screening procedure (188 miRNAs. We demonstrate a dynamic regulation of circulating miRNA (ci-miRNA levels following 0 hour (miR-106a, miR-221, miR-30b, miR-151-5p, let-7i, miR-146, miR-652 and miR-151-3p, 1 hour (miR-338-3p, miR-330-3p, miR-223, miR-139-5p and miR-143 and 3 hours (miR-1 after an acute exercise bout (P<0.00032. Where ci-miRNAs were all downregulated immediately after an acute exercise bout (0 hour the 1 and 3 hour post exercise timepoints were followed by upregulations. In response to chronic training, we identified seven ci-miRNAs with decreased levels in plasma (miR-342-3p, let-7d, miR-766, miR-25, miR-148a, miR-185 and miR-21 and two miRNAs that were present at higher levels after the training period (miR-103 and miR-107 (P<0.00032. In conclusion, acute exercise and chronic endurance training, likely through specific mechanisms unique to each stimulus, robustly modify the miRNA signature of human plasma.

  3. miRNA-target chimeras reveal miRNA 3'-end pairing as a major determinant of Argonaute target specificity

    DEFF Research Database (Denmark)

    Moore, Michael J; Scheel, Troels K H; Luna, Joseph M

    2015-01-01

    microRNAs (miRNAs) act as sequence-specific guides for Argonaute (AGO) proteins, which mediate posttranscriptional silencing of target messenger RNAs. Despite their importance in many biological processes, rules governing AGO-miRNA targeting are only partially understood. Here we report a modified...... AGO HITS-CLIP strategy termed CLEAR (covalent ligation of endogenous Argonaute-bound RNAs)-CLIP, which enriches miRNAs ligated to their endogenous mRNA targets. CLEAR-CLIP mapped ∼130,000 endogenous miRNA-target interactions in mouse brain and ∼40,000 in human hepatoma cells. Motif and structural...

  4. Evaluation of Different Mi Situation Such As Emotional Stress, Physical Activity, Rest, … at Time of Mi Presentation

    Directory of Open Access Journals (Sweden)

    M Imami-Maibodi

    2004-10-01

    Full Text Available Introduction: Previous studies have shown that various factors such as emotional stress can trigger of MI in susceptible persons. More studies are needed to evaluate the characteristics of patients regarding to emotional stress, heavy work, routine activity, infection or rest before occurrence of MI. Methods: We studied 608 consecutive hospitalized in CCUs from May 2000 to October 2001. For patients, questionnaires including demographic, clinical and paraclinical characteristics were completed and data analyzed. Results: In this study rest (33.4% and ordinary activity (32.4% were more prevalent among the MI situations and infection had the lowest prevalence (0.7%. In patients higher than 45 years we had similar results, but in age group younger than 45 year ordinary activity (30.6% and after heavy work (20.8% had the highest prevalence before occurring of MI. In Diabetic patients, MI developed in sleep situation more frequently.(17.8%,(P=0.03 52.5% of MI mortality occurred in rest situation.(P=0.009 Conclusion: Rest had the highest prevalence of MI compared to other situations but in age group younger than 45 years MI after heavy work had the highest prevalence. Autonomic neuropathy may be one of the reason of higher prevalence of MI in sleep situation.

  5. The Associations of Single Nucleotide Polymorphisms in miR196a2, miR-499, and miR-608 With Breast Cancer Susceptibility

    Science.gov (United States)

    Dai, Zhi-Ming; Kang, Hua-Feng; Zhang, Wang-Gang; Li, Hong-Bao; Zhang, Shu-Qun; Ma, Xiao-Bin; Lin, Shuai; Wang, Meng; Feng, Yan-Jing; Liu, Kang; Liu, Xing-Han; Xu, Peng; Dai, Zhi-Jun

    2016-01-01

    Abstract MicroRNAs (miRNAs) play an important role as regulators of tumor suppressors and oncogenes in cancer-related processes. Single nucleotide polymorphisms (SNPs) in miRNAs have been shown to be relevant to various different cancers, including breast cancer (BC). The aim of this study was to estimate the associations between miRNA-related gene polymorphisms (miR-196a2, miR-499, and miR-608) and the risk of BC in a Chinese population. Gene polymorphisms were analyzed in 1143 subjects (controls = 583; BC = 560). The 3 SNPs were genotyped using the Sequenom Mass-ARRAY platform. The associations between the SNP frequencies and BC were assessed by computing odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as by applying Chi-square tests. The miR-196a2 (rs11614913) T allele was associated with a decreased risk of BC based on results from dominant (OR = 0.67, 95% CI = 0.52–0.86), recessive (OR = 0.65, 95% CI = 0.48–0.86), and allele models (OR = 0.73, 95% CI = 0.62–0.86). In contrast, the miR-499 (rs3746444) AG/GG genotypes were associated with an increased risk of BC (OR = 1.45, 95% CI = 1.10–1.91), and miR-608 (rs4919510) was not significantly associated with BC risk. Our study suggested that the polymorphisms of rs11614913 and rs3746444 may be associated with BC risk in Chinese individuals. PMID:26886638

  6. Circulating miR-22, miR-24 and miR-34a as novel predictive biomarkers to pemetrexed-based chemotherapy in advanced non-small cell lung cancer.

    Science.gov (United States)

    Franchina, Tindara; Amodeo, Valeria; Bronte, Giuseppe; Savio, Giuseppina; Ricciardi, Giuseppina R R; Picciotto, Maria; Russo, Antonio; Giordano, Antonio; Adamo, Vincenzo

    2014-01-01

    Pemetrexed has been widely used in patients with advanced non-small cell lung cancer (NSCLC). The clinical relevance of polymorphisms of folate pathway genes for pemetrexed metabolism have not been fully elucidated yet. The aim of this study was to evaluate the expression levels of circulating miR-22, miR-24, and miR-34a, possibly involved in folate pathway, in NSCLC patients treated with pemetrexed compared with healthy controls and to investigate their impact on patient clinical outcomes. A total of 22 consecutive patients with advanced NSCLC, treated with pemetrexed-based chemotherapy and 27 age and sex matched healthy controls were included in this preliminary analysis. miR-22, miR-24, and miR-34a targets were identified by TargetScan 6.2 algorithm, validating the involvement of these microRNAs in folate pathway. MicroRNAs were isolated from whole blood and extracted with miRNAeasy Mini Kit (Qiagen). miRNA profiling was performed using Real-Time PCR. SPSS 17 was used to data analysis. miR-22, miR-24, and miR-34a were found upregulated (P<0.05) in NSCLC patients versus healthy controls. Higher expression levels were recorded for miR-34a. Nevertheless, significantly higher miR-22 expression was observed in patients developing progressive disease (P=0.03). No significant associations with clinical outcome were recorded for miR-24 and miR-34a. Albeit preliminary, these data support the involvement of miR-22, miR-24, and miR-34a in advanced NSCLC. The correlation between high expression of miR-22 in whole blood and the lack of response in pemetrexed treated NSCLC patients indicates that miR-22 could represent a novel predictive biomarker for pemetrexed-based treatment.

  7. Measurement of the Single Top Quark Production Cross Section and |<mi>Vmi><mi>tb>| in Events with One Charged Lepton, Large Missing Transverse Energy, and Jets at CDF

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, T.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Appel, J. A.; Arisawa, T.; Artikov, A.; Asaadi, J.; Ashmanskas, W.; Auerbach, B.; Aurisano, A.; Azfar, F.; Badgett, W.; Bae, T.; Barbaro-Galtieri, A.; Barnes, V. E.; Barnett, B. A.; Barria, P.; Bartos, P.; Bauce, M.; Bedeschi, F.; Behari, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Beretvas, A.; Bhatti, A.; Bland, K. R.; Blumenfeld, B.; Bocci, A.; Bodek, A.; Bortoletto, D.; Boudreau, J.; Boveia, A.; Brigliadori, L.; Bromberg, C.; Brucken, E.; Budagov, J.; Budd, H. S.; Burkett, K.; Busetto, G.; Bussey, P.; Butti, P.; Buzatu, A.; Calamba, A.; Camarda, S.; Campanelli, M.; Canelli, F.; Carls, B.; Carlsmith, D.; Carosi, R.; Carrillo, S.; Casal, B.; Casarsa, M.; Castro, A.; Catastini, P.; Cauz, D.; Cavaliere, V.; Cerri, A.; Cerrito, L.; Chen, Y. C.; Chertok, M.; Chiarelli, G.; Chlachidze, G.; Cho, K.; Chokheli, D.; Clark, A.; Clarke, C.; Convery, M. E.; Conway, J.; Corbo, M.; Cordelli, M.; Cox, C. A.; Cox, D. J.; Cremonesi, M.; Cruz, D.; Cuevas, J.; Culbertson, R.; d’Ascenzo, N.; Datta, M.; de Barbaro, P.; Demortier, L.; Deninno, M.; D’Errico, M.; Devoto, F.; Di Canto, A.; Di Ruzza, B.; Dittmann, J. R.; Donati, S.; D’Onofrio, M.; Dorigo, M.; Driutti, A.; Ebina, K.; Edgar, R.; Elagin, A.; Erbacher, R.; Errede, S.; Esham, B.; Farrington, S.; Fernández Ramos, J. P.; Field, R.; Flanagan, G.; Forrest, R.; Franklin, M.; Freeman, J. C.; Frisch, H.; Funakoshi, Y.; Galloni, C.; Garfinkel, A. F.; Garosi, P.; Gerberich, H.; Gerchtein, E.; Giagu, S.; Giakoumopoulou, V.; Gibson, K.; Ginsburg, C. M.; Giokaris, N.; Giromini, P.; Glagolev, V.; Glenzinski, D.; Gold, M.; Goldin, D.; Golossanov, A.; Gomez, G.; Gomez-Ceballos, G.; Goncharov, M.; González López, O.; Gorelov, I.; Goshaw, A. T.; Goulianos, K.; Gramellini, E.; Grosso-Pilcher, C.; Group, R. C.; Guimaraes da Costa, J.; Hahn, S. R.; Han, J. Y.; Happacher, F.; Hara, K.; Hare, M.; Harr, R. F.; Harrington-Taber, T.; Hatakeyama, K.; Hays, C.; Heinrich, J.; Herndon, M.; Hirschbuehl, D.; Hocker, A.; Hong, Z.; Hopkins, W.; Hou, S.; Hughes, R. E.; Husemann, U.; Hussein, M.; Huston, J.; Introzzi, G.; Iori, M.; Ivanov, A.; James, E.; Jang, D.; Jayatilaka, B.; Jeon, E. J.; Jindariani, S.; Jones, M.; Joo, K. K.; Jun, S. Y.; Junk, T. R.; Kambeitz, M.; Kamon, T.; Karchin, P. E.; Kasmi, A.; Kato, Y.; Ketchum, W.; Keung, J.; Kilminster, B.; Kim, D. H.; Kim, H. S.; Kim, J. E.; Kim, M. J.; Kim, S. H.; Kim, S. B.; Kim, Y. J.; Kim, Y. K.; Kimura, N.; Kirby, M.; Knoepfel, K.; Kondo, K.; Kong, D. J.; Konigsberg, J.; Kotwal, A. V.; Kreps, M.; Kroll, J.; Kruse, M.; Kuhr, T.; Kurata, M.; Laasanen, A. T.; Lammel, S.; Lancaster, M.; Lannon, K.; Latino, G.; Lee, H. S.; Lee, J. S.; Leo, S.; Leone, S.; Lewis, J. D.; Limosani, A.; Lipeles, E.; Lister, A.; Liu, H.; Liu, Q.; Liu, T.; Lockwitz, S.; Loginov, A.; Lucchesi, D.; Lucà, A.; Lueck, J.; Lujan, P.; Lukens, P.; Lungu, G.; Lys, J.; Lysak, R.; Madrak, R.; Maestro, P.; Malik, S.; Manca, G.; Manousakis-Katsikakis, A.; Marchese, L.; Margaroli, F.; Marino, P.; Matera, K.; Mattson, M. E.; Mazzacane, A.; Mazzanti, P.; McNulty, R.; Mehta, A.; Mehtala, P.; Mesropian, C.; Miao, T.; Mietlicki, D.; Mitra, A.; Miyake, H.; Moed, S.; Moggi, N.; Moon, C. S.; Moore, R.; Morello, M. J.; Mukherjee, A.; Muller, Th.; Murat, P.; Mussini, M.; Nachtman, J.; Nagai, Y.; Naganoma, J.; Nakano, I.; Napier, A.; Nett, J.; Neu, C.; Nigmanov, T.; Nodulman, L.; Noh, S. Y.; Norniella, O.; Oakes, L.; Oh, S. H.; Oh, Y. D.; Oksuzian, I.; Okusawa, T.; Orava, R.; Ortolan, L.; Pagliarone, C.; Palencia, E.; Palni, P.; Papadimitriou, V.; Parker, W.; Pauletta, G.; Paulini, M.; Paus, C.; Phillips, T. J.; Pianori, E.; Pilot, J.; Pitts, K.; Plager, C.; Pondrom, L.; Poprocki, S.; Potamianos, K.; Pranko, A.; Prokoshin, F.; Ptohos, F.; Punzi, G.; Redondo Fernández, I.; Renton, P.; Rescigno, M.; Rimondi, F.; Ristori, L.; Robson, A.; Rodriguez, T.; Rolli, S.; Ronzani, M.; Roser, R.; Rosner, J. L.; Ruffini, F.; Ruiz, A.; Russ, J.; Rusu, V.; Sakumoto, W. K.; Sakurai, Y.; Santi, L.; Sato, K.; Saveliev, V.; Savoy-Navarro, A.; Schlabach, P.; Schmidt, E. E.; Schwarz, T.; Scodellaro, L.; Scuri, F.; Seidel, S.; Seiya, Y.; Semenov, A.; Sforza, F.; Shalhout, S. Z.; Shears, T.; Shepard, P. F.; Shimojima, M.; Shochet, M.; Shreyber-Tecker, I.; Simonenko, A.; Sliwa, K.; Smith, J. R.; Snider, F. D.; Song, H.; Sorin, V.; St. Denis, R.; Stancari, M.; Stentz, D.; Strologas, J.; Sudo, Y.; Sukhanov, A.; Suslov, I.; Takemasa, K.; Takeuchi, Y.; Tang, J.; Tecchio, M.; Teng, P. K.; Thom, J.; Thomson, E.; Thukral, V.; Toback, D.; Tokar, S.; Tollefson, K.; Tomura, T.; Tonelli, D.; Torre, S.; Torretta, D.; Totaro, P.; Trovato, M.; Ukegawa, F.; Uozumi, S.; Vázquez, F.; Velev, G.; Vellidis, C.; Vernieri, C.; Vidal, M.; Vilar, R.; Vizán, J.; Vogel, M.; Volpi, G.; Wagner, P.; Wallny, R.; Wang, S. M.; Waters, D.; Wester, W. C.; Whiteson, D.; Wicklund, A. B.; Wilbur, S.; Williams, H. H.; Wilson, J. S.; Wilson, P.; Winer, B. L.; Wittich, P.; Wolbers, S.; Wolfe, H.; Wright, T.; Wu, X.; Wu, Z.; Yamamoto, K.; Yamato, D.; Yang, T.; Yang, U. K.; Yang, Y. C.; Yao, W. -M.; Yeh, G. P.; Yi, K.; Yoh, J.; Yorita, K.; Yoshida, T.; Yu, G. B.; Yu, I.; Zanetti, A. M.; Zeng, Y.; Zhou, C.; Zucchelli, S.

    2014-12-31

    We report a measurement of single top quark production in proton-antiproton collisions at a center-of-mass energy of mi>smi>=1.96 mi>TeVmi> using a data set corresponding to 7.5 mi>fbmi>-1 of integrated luminosity collected by the Collider Detector at Fermilab. We select events consistent with the single top quark decay process mi>t>mi>Wmi>b>mi>νmi>b> by requiring the presence of an electron or muon, a large imbalance of transverse momentum indicating the presence of a neutrino, and two or three jets including at least one originating from a bottom quark. An artificial neural network is used to discriminate the signal from backgrounds. We measure a single top quark production cross section of 3.04-0.53+0.57 mi>pb> and set a lower limit on the magnitude of the coupling between the top quark and bottom quark |

  8. Distribution of miRNA expression across human tissues.

    Science.gov (United States)

    Ludwig, Nicole; Leidinger, Petra; Becker, Kurt; Backes, Christina; Fehlmann, Tobias; Pallasch, Christian; Rheinheimer, Steffi; Meder, Benjamin; Stähler, Cord; Meese, Eckart; Keller, Andreas

    2016-05-05

    We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10(-8)) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas). © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. miR-124 and miR-506 inhibit colorectal cancer progression by targeting DNMT3B and DNMT1.

    Science.gov (United States)

    Chen, Zhiheng; Liu, Shaojun; Tian, Li; Wu, Minghao; Ai, Feiyan; Tang, Wuliang; Zhao, Lian; Ding, Juan; Zhang, Liyang; Tang, Anliu

    2015-11-10

    miR-124 and miR-506 are reportedly down-regulated and associated with tumor progression in many cancers, but little is known about their intrinsic regulatory mechanisms in colorectal cancer (CRC). In this study, we found that the miR-124 and miR-506 levels were significantly lower in human CRC tissues than in controls, as indicated by qRT-PCR and in situ hybridization histochemistry. We also found that the overexpression of miR-124 or miR-506 inhibited tumor cell progression and increased sensitivity to chemotherapy in vitro. Increased miR-124 or miR-506 expression also inhibited tumor cell proliferation and invasion in vivo. Luciferase reporter assays and western blotting were used to determine the association between miR-124, miR-506 and their target genes, DNMTs. We further identified that miR-124 and miR-506 directly targeted DNMT3B and indirectly targeted DNMT1. The overexpression of miR-124 and miR-506 reduced global DNA methylation and restored the expression of E-cadherin, MGMT and P16. In conclusion, our data showed that miR-124 and miR-506 inhibit progression and increase sensitivity to chemotherapy by targeting DNMT3B and DNMT1 in CRC. These findings may provide novel avenues for the development of targeted therapies.

  10. Meta-analysis using a novel database, miRStress, reveals miRNAs that are frequently associated with the radiation and hypoxia stress-responses.

    Directory of Open Access Journals (Sweden)

    Laura Ann Jacobs

    Full Text Available Organisms are often exposed to environmental pressures that affect homeostasis, so it is important to understand the biological basis of stress-response. Various biological mechanisms have evolved to help cells cope with potentially cytotoxic changes in their environment. miRNAs are small non-coding RNAs which are able to regulate mRNA stability. It has been suggested that miRNAs may tip the balance between continued cytorepair and induction of apoptosis in response to stress. There is a wealth of data in the literature showing the effect of environmental stress on miRNAs, but it is scattered in a large number of disparate publications. Meta-analyses of this data would produce added insight into the molecular mechanisms of stress-response. To facilitate this we created and manually curated the miRStress database, which describes the changes in miRNA levels following an array of stress types in eukaryotic cells. Here we describe this database and validate the miRStress tool for analysing miRNAs that are regulated by stress. To validate the database we performed a cross-species analysis to identify miRNAs that respond to radiation. The analysis tool confirms miR-21 and miR-34a as frequently deregulated in response to radiation, but also identifies novel candidates as potentially important players in this stress response, including miR-15b, miR-19b, and miR-106a. Similarly, we used the miRStress tool to analyse hypoxia-responsive miRNAs. The most frequently deregulated miRNAs were miR-210 and miR-21, as expected. Several other miRNAs were also found to be associated with hypoxia, including miR-181b, miR-26a/b, miR-106a, miR-213 and miR-192. Therefore the miRStress tool has identified miRNAs with hitherto unknown or under-appreciated roles in the response to specific stress types. The miRStress tool, which can be used to uncover new insight into the biological roles of miRNAs, and also has the potential to unearth potential biomarkers for

  11. Mutual induction of transcription factor PPARγ and microRNAs miR-145 and miR-329.

    Science.gov (United States)

    Dharap, Ashutosh; Pokrzywa, Courtney; Murali, Shruthi; Kaimal, Balarama; Vemuganti, Raghu

    2015-10-01

    MicroRNAs (miRNAs) are small non-coding RNAs that are known to control mRNA translation. Most miRNAs are transcribed from specific genes with well-defined promoters located throughout the genome. The mechanisms that control miRNA expression under normal and pathological conditions are not yet understood clearly. Peroxisome proliferator-activated receptor (PPAR) γ is a ligand-activated transcription factor that is extensively distributed in the CNS. PPARγ activation induces neuroprotection by modulating genes that contain peroxisome proliferator response elements (PPREs) in their promoters. We presently evaluated if PPARγ modulates miRNA expression. When adult rats were treated with PPARγ agonist rosiglitazone, expression of 28 miRNAs altered significantly (12 up- and 16 down-regulated; 3-119 fold) in the cerebral cortex compared to vehicle-treated controls. In silico analysis showed 1-5 PPREs in the putative promoter regions (within 1 Kb upstream of the transcription start site) of these miRNA genes. Cotransfection with a PPARγ constitutively expressing vector significantly induced the miR-145 and miR-329 promoter vectors (each have four PPREs), which was curtailed by point mutations of PPREs in their promoters. Interestingly, the PPARγ promoter has binding sites for both these miRNAs and transfection with miR-329 mimic and miR-145 mimic induced the PPARγ expression. Thus, these studies show a cyclical induction of miRNAs and PPARγ, indicating that the pleiotropic beneficial effects of PPARγ agonists might be modulated in part by miRNAs and their down-stream mRNAs. We proposed that promoters of many microRNAs contain the binding sites for the transcription factor PPARγ. Activation of PPARγ modulates the expression of these microRNAs. Two such PPARγ-responsive microRNAs (miR-145 and miR-329) bind to PPARγ promoter to induce its expression. This indicates the presence of a feedback loop by which transcription factors and microRNAs can modulate each other.

  12. Evidence for a cytoplasmic microprocessor of pri-miRNAs.

    Science.gov (United States)

    Shapiro, Jillian S; Langlois, Ryan A; Pham, Alissa M; Tenoever, Benjamin R

    2012-07-01

    microRNAs (miRNAs) represent a class of noncoding RNAs that fine-tune gene expression through post-transcriptional silencing. While miRNA biogenesis occurs in a stepwise fashion, initiated by the nuclear microprocessor, rare noncanonical miRNAs have also been identified. Here we characterize the molecular components and unique attributes associated with the processing of virus-derived cytoplasmic primary miRNAs (c-pri-miRNAs). RNA in situ hybridization and inhibition of cellular division demonstrated a complete lack of nuclear involvement in c-pri-miRNA cleavage while genetic studies revealed that maturation still relied on the canonical nuclear RNase III enzyme, Drosha. The involvement of Drosha was mediated by a dramatic relocalization to the cytoplasm following virus infection. Deep sequencing analyses revealed that the cytoplasmic localization of Drosha does not impact the endogenous miRNA landscape during infection, despite allowing for robust synthesis of virus-derived miRNAs in the cytoplasm. Taken together, this research describes a unique function for Drosha in the processing of highly structured cytoplasmic RNAs in the context of virus infection.

  13. Miíase na topografia de saco lacrimal

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    Simone Haber Duellberg von Faber Bison

    2016-02-01

    Full Text Available RESUMO A miíase é a infestação dos tecidos humanos por larvas Diptera. O comprometimento ocular é raro. Os autores apresentam um caso de miíase na topografia do saco lacrimal e discutem as modalidades terapêuticas para o tratamento desta doença.

  14. Exosomal miRNAs as biomarkers for prostate cancer

    Directory of Open Access Journals (Sweden)

    Nina Pettersen Hessvik

    2013-03-01

    Full Text Available miRNAs are small non-coding RNAs that finely regulate gene expression in cells. Alterations in miRNA expression have been associated with development of cancer, and miRNAs are now being investigated as biomarkers for cancer as well as other diseases. Recently, miRNAs have been found outside cells in body fluids. Extracellular miRNAs exist in different forms - associated with Ago2 proteins, loaded into extracellular vesicles (exosomes, microvesicles or apoptotic bodies or into high density lipoprotein particles. These extracellular miRNAs are probably products of distinct cellular processes, and might therefore play different roles. However, their functions in vivo are currently unknown. In spite of this, they are considered as promising, noninvasive diagnostic and prognostic tools. Prostate cancer is the most common cancer in men in the Western world, but the currently used biomarker (prostate specific antigen has low specificity. Therefore, novel biomarkers are highly needed. In this review we will discuss possible biological functions of extracellular miRNAs, as well as the potential use of miRNAs from extracellular vesicles as biomarkers for prostate cancer.

  15. Base Composition Characteristics of Mammalian miRNAs

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    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.

  16. Miłosz’s Sojourns in Parallel (Translation Universes

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    Ewa Rajewska

    2012-01-01

    Full Text Available The well known interpretation of Miłosz’s work as an attempt to capture fulness, has been most fully formulated by Jan Błoński’s “Miłosz jak świat” [“Miłosz like a World”]. The author of the article provides a more detailed version of the interpretation, presenting Miłosz’s work as a multiplied universe: in translation and in self-translation. Miłosz’s universe has been multiplied through translation: undertaking translation of so many and so various poets, Miłosz, by extension, translated their poetic worlds. In doing so, he had to go beyond the borders of the world of his own idiom and imagination. Miłosz’s attempts at transgression beyond the borders of his own language and imagination, and into a poetic “parallel universe”, are conducted, according to the present author, in two ways: through similarity and through completion. Miłosz translates works which he which he selected on the principle of an exceptional poetic kinship (for example in his Excerpts from Useful Books. Other translations were an opportunity to test himself on an intriguing poetic material, which he himself would not be willing to create (for example in poetry by Anna Świrszczyńska.

  17. Regulation of turkey myogenic satellite cell migration by MicroRNAs miR-128 and miR-24.

    Science.gov (United States)

    Velleman, S G; Harding, R L

    2016-12-05

    Myogenic satellite cells are an adult stem cell responsible for all post-hatch muscle growth in poultry. As a stem cell population, satellite cells are highly heterogeneous, but the origin of this heterogeneity remains unclear. Heterogeneity is, in part, regulated by gene expression. One method of endogenous gene regulation that may contribute to heterogeneity is microRNAs (miRNAs). Two miRNAs previously shown to regulate poultry myogenic satellite cell proliferation and differentiation, miR-128 and miR-24, were studied to determine if they also affected satellite cell migration. Satellite cell migration is an essential step for both proliferation and differentiation. During proliferation, satellite cells will migrate and align to form new myofibers or donate their nuclei to existing myofibers leading to muscle fiber hypertrophy or regeneration. Transient transfection of miRNA specific mimics to each miRNA reduced migration of satellite cells following a cell culture scratch at 72 h of proliferation when the cultures were 90 to 100% confluent. However, only the migration in cells transfected with miR-24 mimics at 24 and 30 h following the scratch was significantly reduced (P ≤ 0.05) to around 70% of the distance migrated by controls. Alternately, transfection with inhibitors specific to miR-128 or miR-24 significantly (P ≤ 0.05) increased migration between 147 and 252% compared to their controls between 24 and 48 h following the scratch. These data demonstrate that miR-128 and miR-24 play a role in myogenic satellite cell migration, which will impact muscle development and growth.

  18. MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium

    Science.gov (United States)

    Cerutti, Camilla; Edwards, Laura J.; de Vries, Helga E.; Sharrack, Basil; Male, David K.; Romero, Ignacio A.

    2017-01-01

    Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Leukocyte adhesion is mediated mainly by selectins, cell adhesion molecules and chemokines induced by pro-inflammatory cytokines such as TNFα and IFNγ, but the regulation of this process is not fully clear. This study investigated the regulation of firm leukocyte adhesion to human brain endothelium by two different brain endothelial microRNAs (miRs), miR-126 and miR-126*, that are downregulated by TNFα and IFNγ in a human brain endothelial cell line, hCMEC/D3. Using a leukocyte adhesion in vitro assay under shear forces mimicking blood flow, we observed that reduction of endothelial miR-126 and miR-126* enhanced firm monocyte and T cell adhesion to hCMEC/D3 cells, whereas their increased expression partially prevented THP1, Jurkat and primary MS patient-derived PBMC firm adhesion. Furthermore, we observed that miR-126* and miR-126 downregulation increased E-selectin and VCAM1, respectively, while miR-126 overexpression reduced VCAM1 and CCL2 expression by hCMEC/D3 cells, suggesting that these miRs regulate leukocyte adhesion by modulating the expression of adhesion-associated endothelial mRNA targets. Hence, human brain endothelial miR-126 and miR-126* could be used as a therapeutic tool to reduce leukocyte adhesion and thus reduce neuroinflammation. PMID:28358058

  19. MiR-101 and miR-144 regulate the expression of the CFTR chloride channel in the lung.

    Science.gov (United States)

    Hassan, Fatemat; Nuovo, Gerard J; Crawford, Melissa; Boyaka, Prosper N; Kirkby, Stephen; Nana-Sinkam, Serge P; Cormet-Boyaka, Estelle

    2012-01-01

    The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that plays a critical role in the lung by maintaining fluid homeostasis. Absence or malfunction of CFTR leads to Cystic Fibrosis, a disease characterized by chronic infection and inflammation. We recently reported that air pollutants such as cigarette smoke and cadmium negatively regulate the expression of CFTR by affecting several steps in the biogenesis of CFTR protein. MicroRNAs (miRNAs) have recently received a great deal of attention as both biomarkers and therapeutics due to their ability to regulate multiple genes. Here, we show that cigarette smoke and cadmium up-regulate the expression of two miRNAs (miR-101 and miR-144) that are predicted to target CFTR in human bronchial epithelial cells. When premature miR-101 and miR-144 were transfected in human airway epithelial cells, they directly targeted the CFTR 3'UTR and suppressed the expression of the CFTR protein. Since miR-101 was highly up-regulated by cigarette smoke in vitro, we investigated whether such increase also occurred in vivo. Mice exposed to cigarette smoke for 4 weeks demonstrated an up-regulation of miR-101 and suppression of CFTR protein in their lungs. Finally, we show that miR-101 is highly expressed in lung samples from patients with severe chronic obstructive pulmonary disease (COPD) when compared to control patients. Taken together, these results suggest that chronic cigarette smoking up-regulates miR-101 and that this miRNA could contribute to suppression of CFTR in the lungs of COPD patients.

  20. miRNA and miRNA target genes in copy number variations occurring in individuals with intellectual disability.

    Science.gov (United States)

    Qiao, Ying; Badduke, Chansonette; Mercier, Eloi; Lewis, Suzanne M E; Pavlidis, Paul; Rajcan-Separovic, Evica

    2013-08-10

    MicroRNAs (miRNAs) are a family of short, non-coding RNAs modulating expression of human protein coding genes (miRNA target genes). Their dysfunction is associated with many human diseases, including neurodevelopmental disorders. It has been recently shown that genomic copy number variations (CNVs) can cause aberrant expression of integral miRNAs and their target genes, and contribute to intellectual disability (ID). To better understand the CNV-miRNA relationship in ID, we investigated the prevalence and function of miRNAs and miRNA target genes in five groups of CNVs. Three groups of CNVs were from 213 probands with ID (24 de novo CNVs, 46 familial and 216 common CNVs), one group of CNVs was from a cohort of 32 cognitively normal subjects (67 CNVs) and one group of CNVs represented 40 ID related syndromic regions listed in DECIPHER (30 CNVs) which served as positive controls for CNVs causing or predisposing to ID. Our results show that 1). The number of miRNAs is significantly higher in de novo or DECIPHER CNVs than in familial or common CNV subgroups (P genes are found in de novo, familial and DECIPHER CNVs than in the common CNV subgroup (P genes from de novo and DECIPHER CNV subgroups. Our findings reveal an increase in miRNA and miRNA target gene content in de novo versus common CNVs in subjects with ID. Their expression profile and participation in pathways support a possible role of miRNA copy number change in cognition and/or CNV-mediated developmental delay. Systematic analysis of expression/function of miRNAs in addition to coding genes integral to CNVs could uncover new causes of ID.

  1. Repertoire of bovine miRNA and miRNA-like small regulatory RNAs expressed upon viral infection.

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    Evgeny A Glazov

    Full Text Available MicroRNA (miRNA and other types of small regulatory RNAs play a crucial role in the regulation of gene expression in eukaryotes. Several distinct classes of small regulatory RNAs have been discovered in recent years. To extend the repertoire of small RNAs characterized in mammals and to examine relationship between host miRNA expression and viral infection we used Illumina's ultrahigh throughput sequencing approach. We sequenced three small RNA libraries prepared from cell line derived from the adult bovine kidney under normal conditions and upon infection of the cell line with Bovine herpesvirus 1. We used a bioinformatics approach to distinguish authentic mature miRNA sequences from other classes of small RNAs and short RNA fragments represented in the sequencing data. Using this approach we detected 219 out of 356 known bovine miRNAs and 115 respective miRNA* sequences. In addition we identified five new bovine orthologs of known mammalian miRNAs and discovered 268 new cow miRNAs many of which are not identifiable in other mammalian genomes and thus might be specific to the ruminant lineage. In addition we found seven new bovine mirtron candidates. We also discovered 10 small nucleolar RNA (snoRNA loci that give rise to small RNA with possible miRNA-like function. Results presented in this study extend our knowledge of the biology and evolution of small regulatory RNAs in mammals and illuminate mechanisms of small RNA biogenesis and function. New miRNA sequences and the original sequencing data have been submitted to miRNA repository (miRBase and NCBI GEO archive respectively. We envisage that these resources will facilitate functional annotation of the bovine genome and promote further functional and comparative genomics studies of small regulatory RNA in mammals.

  2. Water deficit down-regulates miR398 and miR408 in pea (Pisum sativum L.).

    Science.gov (United States)

    Jovanović, Živko; Stanisavljević, Nemanja; Mikić, Aleksandar; Radović, Svetlana; Maksimović, Vesna

    2014-10-01

    MicroRNAs (miRNAs), recently recognized as important regulator of gene expression at posttranscriptional level, have been found to be involved in plant stress responses. The observation that some miRNAs are up- or down regulated by stress implies that they could play vital roles in plant resistance to abiotic and biotic stress. We investigated the effect of water stress treatment during 10 days on expression of conserved miRNAs-miR398a/b and miR408 in pea plants. This time frame reflects the changes as close as possible to the changes where water stress causes visible effects under field condition. It was observed that dehydration strongly down regulates the expression of both miR398a/b and miR408 in pea roots and shoots. The down-regulation of miR398a/b and the up-regulation of potential target genes - copper superoxide dismutase, CSD1, highlight the involvement of this miRNA in pea stress response. To the contrary, the mRNA level of cytochrome c oxidase subunit 5 (COX5b) did not change in roots and shoots of water-stressed plants, compared to control (well) hydrated plants. This suggests that COX5b is not the target of miR398, or that its expression is regulated by some other mechanism. P1B-ATPase expression increased during water deficit only in the shoots of pea; in the roots there were no changes in expression. Our results help to understand the possible role of investigated miRNAs and their contribution to pea capacity to cope with water deficit.

  3. 15-deoxy-Delta12,14-prostaglandin J2 up-regulates death receptor 5 gene expression in HCT116 cells: involvement of reactive oxygen species and C/EBP homologous transcription factor gene transcription.

    Science.gov (United States)

    Su, Rong-Ying; Chi, Kwan-Hwa; Huang, Duen-Yi; Tai, Ming-Hui; Lin, Wan-Wan

    2008-10-01

    Although 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2)) was reported to up-regulate death receptor 5 (DR5) protein expression and sensitize TRAIL-induced cytotoxicity, its action mechanism remains unclear. Using HCT116 colon cancer cells, we found that sensitization of TRAIL-induced cytotoxicity by 15dPGJ(2) resulted from up-regulation of DR5 via gene transcription but was not associated with PPAR-gamma activation. Moreover, 15dPGJ(2) induced GRP78, XBP1, and C/EBP homologous transcription factor (CHOP) expression in HCT116 cells, confirming that 15dPGJ(2) is an endoplasmic reticulum stress inducer. Knockdown of the CHOP gene by siRNA attenuated DR5 up-regulation and the sensitized cytotoxicity in colon cancer HCT116 and SW480. With deletion plasmids of DR5 promoters, we found that the CHOP-binding site was involved in activating the DR5 gene by 15dPGJ(2). A mechanistic study showed the contributions of reactive oxygen species (ROS) and intracellular calcium in CHOP and DR5 gene up-regulation. 15dPGJ(2) was also found to induce DR5 in two prostate cancer cell lines, LNCaP and PC3. Although in LNCaP DR5 up-regulation was accompanied by CHOP expression by 15dPGJ(2), no significant increase in CHOP expression or DR5 promoter activity was observed in PC3 cells. Intriguingly, 15dPGJ(2) induced ROS and calcium production in PC3 cells. This inability to induce CHOP was not due to the p53-null in PC3 cells, as similar extents of increase in CHOP protein were found due to 15dPGJ(2) in both wild-type and p53-null HCT116 cells. In summary, the effect of up-regulation of DR5 by 15dPGJ(2) in colon cancer cells is independent of PPAR-gamma and p53 but relies on CHOP induction through gene transcription involving ROS and calcium.

  4. 米非司酮配伍米索前列醇在12~14周钳刮术中的心理护理%Psychological care of mifepristone and misoprostol at 12~14 weeks of curretage

    Institute of Scientific and Technical Information of China (English)

    欧雪琴

    2015-01-01

    目的:通过对妊娠12~14周药物流产中钳刮术者进行分期心里护理,以减轻或消除受术者术前、术中、术后的各种不良心理反应,提高手术质量,减少术后并发症。方法:通过术前宣教、交谈、咨询,术中安慰、鼓励、术后抚慰、支持等措施缓解、释放受术者心理压力,改善心理状态。结果:310例受术者全部不同程度地减轻了不良心理反应,释放了心理压力,提高了手术效果。结论:对药物流产配合钳刮术者针对性进行心理护理,可有效提高手术质量,减少术后并发症,保护受术者的身心健康。%Objective:Through psychological caring of mifepristone and misoprostol at 12~14 weeks of curettage,to reduce or eliminate the various adverse psychological reactions by preoperative,intraoperative and postoperative,improve the quality of surgery,reduce postoperative complications.Methods:Through the preoperative education,conversation,consultation,intraoperative, postoperative comfort comfort,encourage,support and other measures to alleviate the recipients,release psychological pressure, improve the psychological state.Results:310 patients are in varying degrees to reduce the adverse psychological reactions,release psychological pressure,improve the operation effect.Conclusion:For medical abortion with curettage patients using psychological care can effectively improve the quality of surgery,reduce postoperative complications,protect the patient's physical and mental health.

  5. A comparison between the impact of noise from aircraft, road traffic and trains on long-term recall and recognition of a text in children aged 12-14 years.

    Science.gov (United States)

    Hygge, S

    1993-01-01

    A total of 417 students in the seventh grade, 12-14 old, took part in three 15 min learning sessions in their ordinary class-rooms. Their task was to read a text, and they were tested one week later with difficult recall questions and less difficult recognition items on the text. The first session was a pretest for their learning abilities. This session was run in ambient noise conditions and all the students read the very same text. The scores from this session were employed to split the pupils along the median into two groups of learning ability. Sessions two and three were counterbalanced as a noise condition or an ambient noise condition. In these sessions two other texts were employed, and they appeared equally often under the noise and ambient conditions, as well as under the two different presentation orders. Three subgroups of the pupils were exposed to aircraft noise, train noise and road-traffic noise. The noise types were of the same equivalent level (66 dB(A) Leq) in all subgroups. The design of the study permitted two different analyses of long-term learning. First, in a within subject analysis, the difference scores between the noise and ambient noise conditions in session 2 and 3 were calculated, and crossed with learning ability (high and low) and type of noise. In a second between subject analysis, the difference scores in session 1 and 2 were crossed with the group factor whether they had noise or ambient conditions in session 2, and the ability and noise type factors. Both analyses yielded the same results. Noise impaired long-term recall of the difficult items. Degree of impairment on the recall items did not interact with noise source or learning ability. The average impairment due to aircraft and road traffic noise was around 23% of the scores. Train noise had no effect. For the easy recognition items there were no effects of noise exposure, nor of its interaction with noise source and learning ability. Since the number of pages read did not

  6. miR-200 Regulates Endometrial Development During Early Pregnancy.

    Science.gov (United States)

    Jimenez, Patricia T; Mainigi, Monica A; Word, R Ann; Kraus, W Lee; Mendelson, Carole R

    2016-09-01

    For successful embryo implantation, endometrial stromal cells must undergo functional and morphological changes, referred to as decidualization. However, the molecular mechanisms that regulate implantation and decidualization are not well defined. Here we demonstrate that the estradiol- and progesterone-regulated microRNA (miR)-200 family was markedly down-regulated in mouse endometrial stromal cells prior to implantation, whereas zinc finger E-box binding homeobox-1 and -2 and other known and predicted targets were up-regulated. Conversely, miR-200 was up-regulated during in vitro decidualization of human endometrial stromal cells. Knockdown of miR-200 negatively affected decidualization and prevented the mesenchymal-epithelial transition-like changes that accompanied decidual differentiation. Notably, superovulation of mice and humans altered miR-200 expression. Our findings suggest that hormonal alterations that accompany superovulation may negatively impact endometrial development and decidualization by causing aberrant miR-200 expression.

  7. Impact of tiny miRNAs on cancers

    Institute of Scientific and Technical Information of China (English)

    Wei Liu; Sheng-Yong Mao; Wei-Yun Zhu

    2007-01-01

    miRNAs are a class of small, ~22nt, non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. They play profound and pervasive roles in manipulating gene expression involved in cell development, proliferation and apoptosis in various eukaryotes, which, in theory, could provide an access to many human diseases in theory. Recent evidence demonstrates that aberrant miRNA expression is a hallmark of tumor development, revealing that miRNA genes could function as potential oncogenes and repressors in the human body. miRNAs can affect tumorigenesis mainly by interrupting the cell cycle at the cellular level and by interacting with signaling,oncogenes and with the response to environmental factors at the molecular level. The established miRNA expression signature could be a potent tool to diagnose and treat human cancers in the future.

  8. miR-345 in Metastatic Colorectal Cancer

    DEFF Research Database (Denmark)

    Schou, Jakob V; Rossi, Simona; Jensen, Benny V

    2014-01-01

    INTRODUCTION: MicroRNAs (miRNAs) have important regulatory functions in cellular processes and have shown promising potential as prognostic markers for disease outcome in patients with cancer. The aim of the present study was to find miRNA expression profiles in whole blood that were prognostic...... for overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan. METHODS: From 138 patients with mCRC in 3rd line therapy with cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs were isolated and profiled from whole blood...... to treatment with cetuximab and irinotecan. CONCLUSION: We identified miR-345 in whole blood as a potential biomarker for clinical outcome. MiR-345 was a single prognostic biomarker for both OS and PFS in all patients and also in the non-KRAS mutant population....

  9. Towards an understanding of miRNA regulation

    DEFF Research Database (Denmark)

    Jensen, Trine Ilsø

    report a new method to investigate and potentially characterize the pri-miRNA transcript. Overexpression of a transdominant Drosha mutant, which is unable to cleave its substrate, enables stabilization of the pri-miRNA transcript. Drosha mutant immunoprecipitation from the nuclear compartment......miRNAs are well-known regulators of gene expression. They function post-transcriptionally by binding to complementary sites within the 3´UTR of target mRNAs, which mediates translational repression and destabilization. However, miRNA expression itself is also subjected to regulation. Here, we...... is performed followed by high-throughput sequencing (nuclear Drosha Mt2 RIPseq). This method allows for the detection of global pri-miRNA signature and also provides a method to potentially identify new Drosha substrates. Furthermore, data on the identification of a novel endogenous circular RNA sponge (ciRS-7...

  10. The Roles of miR-26, miR-29, and miR-203 in the Silencing of the Epigenetic Machinery during Melanocyte Transformation

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    Cláudia Regina Gasque Schoof

    2015-01-01

    Full Text Available The epigenetic marks located throughout the genome exhibit great variation between normal and transformed cancer cells. While normal cells contain hypomethylated CpG islands near gene promoters and hypermethylated repetitive DNA, the opposite pattern is observed in cancer cells. Recently, it has been reported that alteration in the microenvironment of melanocyte cells, such as substrate adhesion blockade, results in the selection of anoikis-resistant cells, which have tumorigenic characteristics. Melanoma cells obtained through this model show an altered epigenetic pattern, which represents one of the first events during the melanocytes malignant transformation. Because microRNAs are involved in controlling components of the epigenetic machinery, the aim of this work was to evaluate the potential association between the expression of miR-203, miR-26, and miR-29 family members and the genes Dnmt3a, Dnmt3b, Mecp2, and Ezh2 during cells transformation. Our results show that microRNAs and their validated or predicted targets are inversely expressed, indicating that these molecules are involved in epigenetic reprogramming. We also show that miR-203 downregulates Dnmt3b in mouse melanocyte cells. In addition, treatment with 5-aza-CdR promotes the expression of miR-26 and miR-29 in a nonmetastatic melanoma cell line. Considering the occurrence of CpG islands near the miR-26 and miR-29 promoters, these data suggest that they might be epigenetically regulated in cancer.

  11. 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.

  12. Epigenetic regulation of miR-21 in colorectal cancer

    Science.gov (United States)

    Ferraro, Angelo; Kontos, Christos K; Boni, Themis; Bantounas, Ioannis; Siakouli, Dimitra; Kosmidou, Vivian; Vlassi, Margarita; Spyridakis, Yannis; Tsipras, Iraklis; Zografos, George; Pintzas, Alexander

    2014-01-01

    Previous studies have uncovered several transcription factors that determine biological alterations in tumor cells to execute the invasion-metastasis cascade, including the epithelial-mesenchymal transition (EMT). We sought to investigate the role of miR-21 in colorectal cancer regulation. For this purpose, miR-21 expression was quantified in a panel of colorectal cancer cell lines and clinical specimens. High expression was found in cell lines with EMT properties and in the vast majority of human tumor specimens. We demonstrate in a cell-specific manner the occupancy of MIR-21 gene promoter by AP-1 and ETS1 transcription factors and, for the first time, the pattern of histone posttranslational modifications necessary for miR-21 overexpression. We also show that Integrin-β4 (ITGβ4), exclusively expressed in polarized epithelial cells, is a novel miR-21 target gene and plays a role in the regulation of EMT, since it is remarkably de-repressed after transient miR-21 silencing and downregulated after miR-21 overexpression. miR-21-dependent change of ITGβ4 expression significantly affects cell migration properties of colon cancer cells. Finally, in a subgroup of tumor specimens, ROC curve analysis performed on quantitative PCR data sets for miR-21, ITGβ4, and PDCD4 shows that the combination of high miR-21 with low ITGβ4 and PDCD4 expression is able to predict presence of metastasis. In conclusion, miR-21 is a key player in oncogenic EMT, its overexpression is controlled by the cooperation of genetic and epigenetic alterations, and its levels, along with ITGβ4 and PDCD4 expression, could be exploited as a prognostic tool for CRC metastasis. PMID:24149370

  13. Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Vrba, Lukas; Jensen, Taylor J.; Garbe, James C.; Heimark, Ronald L.; Cress, Anne E.; Dickinson, Sally; Stampfer, Martha R.; Futscher, Bernard W.

    2009-12-23

    BACKGROUND: The microRNA-200 family participates in the maintenance of an epithelial phenotype and loss of its expression can result in epithelial to mesenchymal transition (EMT). Furthermore, the loss of expression of miR-200 family members is linked to an aggressive cancer phenotype. Regulation of the miR-200 family expression in normal and cancer cells is not fully understood. METHODOLOGY/ PRINCIPAL FINDINGS: Epigenetic mechanisms participate in the control of miR-200c and miR-141 expression in both normal and cancer cells. A CpG island near the predicted mir-200c/mir-141 transcription start site shows a striking correlation between miR-200c and miR-141 expression and DNA methylation in both normal and cancer cells, as determined by MassARRAY technology. The CpG island is unmethylated in human miR-200/miR-141 expressing epithelial cells and in miR-200c/miR-141 positive tumor cells. The CpG island is heavily methylated in human miR-200c/miR-141 negative fibroblasts and miR-200c/miR-141 negative tumor cells. Mouse cells show a similar inverse correlation between DNA methylation and miR-200c expression. Enrichment of permissive histone modifications, H3 acetylation and H3K4 trimethylation, is seen in normal miR-200c/miR-141-positive epithelial cells, as determined by chromatin immunoprecipitation coupled to real-time PCR. In contrast, repressive H3K9 dimethylation marks are present in normal miR-200c/miR-141-negative fibroblasts and miR-200c/miR-141 negative cancer cells and the permissive histone modifications are absent. The epigenetic modifier drug, 5-aza-2'-deoxycytidine, reactivates miR-200c/miR-141 expression showing that epigenetic mechanisms play a functional role in their transcriptional control. CONCLUSIONS/ SIGNIFICANCE: We report that DNA methylation plays a role in the normal cell type-specific expression of miR-200c and miR-141 and this role appears evolutionarily conserved, since similar results were obtained in mouse. Aberrant DNA methylation

  14. miRNA-mRNA integrated analysis reveals roles for miRNAs in primary breast tumors.

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    Espen Enerly

    Full Text Available INTRODUCTION: Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information. METHODS: We investigate the relationship between these molecular components, in terms of their correlation with each other and with clinical characteristics. We use a systems biology approach to examine the correlative relationship between miRNA and mRNAs using statistical enrichment methods. RESULTS: We identify statistical significant differential expression of miRNAs between molecular intrinsic subtypes, and between samples with different levels of proliferation. Specifically, we point to miRNAs significantly associated with TP53 and ER status. We also show that several cellular processes, such as proliferation, cell adhesion and immune response, are strongly associated with certain miRNAs. We validate the role of miRNAs in regulating proliferation using high-throughput lysate-microarrays on cell lines and point to potential drivers of this process. CONCLUSION: This study provides a comprehensive dataset as well as methods and system-level results that jointly form a basis for further work on understanding the role of miRNA in primary breast cancer.

  15. Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer

    DEFF Research Database (Denmark)

    Winther, Mette; Alsner, Jan; Tramm, Trine

    2015-01-01

    of miR-21 and miR-375 in primary esophageal squamous cell carcinomas (ESCC) and esophagogastric adenocarcinomas (EAC). MATERIAL AND METHODS: Pre-therapeutic tumor specimens from 195 patients with loco-regional esophageal cancer treated with neoadjuvant or definitive chemoradiotherapy or perioperative...

  16. 78 FR 13015 - Designation for the Sandusky, MI; Davenport, IA; Enid, OK; Keokuk, IA; Marshall, MI; and Omaha...

    Science.gov (United States)

    2013-02-26

    ... the September 13, 2012 Federal Register (77 FR 56608), GIPSA requested applications for designation to... Grain Inspection, Packers and Stockyards Administration Designation for the Sandusky, MI; Davenport, IA; Enid, OK; Keokuk, IA; Marshall, MI; and Omaha, NE Areas AGENCY: Grain Inspection, Packers...

  17. 75 FR 16067 - Designation for the Champaign, IL; Emmett, MI; Davenport, IA; Enid, OK; Keokuk, IA; Marshall, MI...

    Science.gov (United States)

    2010-03-31

    ... Register (74 FR 45803), GIPSA requested applications for designation to provide official services in the...; Davenport, IA; Enid, OK; Keokuk, IA; Marshall, MI; and Omaha, NE Areas AGENCY: Grain Inspection, Packers and.... Detroit Emmett, MI (810-395-2105) 4/1/2010 3/31/2013 Eastern Iowa Davenport, IA (563-322-7149). 4/1/2010...

  18. miR-137 and miR-491 Negatively Regulate Dopamine Transporter Expression and Function in Neural Cells.

    Science.gov (United States)

    Jia, Xiaojian; Wang, Feng; Han, Ying; Geng, Xuewen; Li, Minghua; Shi, Yu; Lu, Lin; Chen, Yun

    2016-12-01

    The dopamine transporter (DAT) is involved in the regulation of extracellular dopamine levels. A 40-bp variable-number tandem repeat (VNTR) polymorphism in the 3'-untranslated region (3'UTR) of the DAT has been reported to be associated with various phenotypes that are involved in the aberrant regulation of dopaminergic neurotransmission. In the present study, we found that miR-137 and miR-491 caused a marked reduction of DAT expression, thereby influencing neuronal dopamine transport. Moreover, the regulation of miR-137 and miR-491 on this transport disappeared after the DAT was silenced. The miR-491 seed region that is located on the VNTR sequence in the 3'UTR of the DAT and the regulatory effect of miR-491 on the DAT depended on the VNTR copy-number. These data indicate that miR-137 and miR-491 regulate DAT expression and dopamine transport at the post-transcriptional level, suggesting that microRNA may be targeted for the treatment of diseases associated with DAT dysfunction.

  19. MmPalateMiRNA, an R package compendium illustrating analysis of miRNA microarray data.

    Science.gov (United States)

    Brock, Guy N; Mukhopadhyay, Partha; Pihur, Vasyl; Webb, Cynthia; Greene, Robert M; Pisano, M Michele

    2013-01-08

    MicroRNAs (miRNAs) constitute the largest family of noncoding RNAs involved in gene silencing and represent critical regulators of cell and tissue differentiation. Microarray expression profiling of miRNAs is an effective means of acquiring genome-level information of miRNA activation and inhibition, as well as the potential regulatory role that these genes play within a biological system. As with mRNA expression profiling arrays, miRNA microarrays come in a variety of platforms from numerous manufacturers, and there are a multitude of techniques available for reducing and analyzing these data. In this paper, we present an analysis of a typical two-color miRNA microarray experiment using publicly available packages from R and Bioconductor, the open-source software project for the analysis of genomic data. Covered topics include visualization, normalization, quality checking, differential expression, cluster analysis, miRNA target identification, and gene set enrichment analysis. Many of these tools carry-over from the analysis of mRNA microarrays, but with some notable differences that require special attention. The paper is presented as a "compendium" which, along with the accompanying R package MmPalateMiRNA, contains all of the experimental data and source code to reproduce the analyses contained in the paper. The compendium presented in this paper will provide investigators with an access point for applying the methods available in R and Bioconductor for analysis of their own miRNA array data.

  20. The coordinated roles of miR-26a and miR-30c in regulating TGFβ1-induced epithelial-to-mesenchymal transition in diabetic nephropathy

    DEFF Research Database (Denmark)

    Zheng, Zongji; Guan, Meiping; Jia, Yijie

    2016-01-01

    MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy. Here, we compared the protective efficacies of miR-26a and miR-30c in renal tubular epithelial cells (NRK-52E) and determined whether they demonstrated additive effects in the attenuation of renal fibrosis. TGFβ1 supp....... Our study provides evidence for the cooperative roles of miR-26a and miR-30c in the pathogenesis of diabetic nephropathy, and the co-targeting of miR-26a and miR-30c could provide a new direction for diabetic nephropathy treatment.......MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy. Here, we compared the protective efficacies of miR-26a and miR-30c in renal tubular epithelial cells (NRK-52E) and determined whether they demonstrated additive effects in the attenuation of renal fibrosis. TGFβ1...... ameliorated TGFβ1-induced EMT in NRK-52E cells. Co-silencing of miR-26a and miR-30c exhibited the opposite effect. Moreover, miR-26a and miR-30c co-silenced CTGF to decrease ERK1/2 and p38 MAPK activation. Furthermore, miR-26a was up-regulated in urinary extracellular vesicles of diabetic nephropathy patients...

  1. Common miR-590 Variant rs6971711 Present Only in African Americans Reduces miR-590 Biogenesis.

    Directory of Open Access Journals (Sweden)

    Xiaoping Lin

    Full Text Available MicroRNAs (miRNAs are recognized as important regulators of cardiac development, hypertrophy and fibrosis. Recent studies have demonstrated that genetic variations which cause alterations in miRNA:target interactions can lead to disease. We hypothesized that genetic variations in miRNAs that regulate cardiac hypertrophy/fibrosis might be involved in generation of the cardiac phenotype in patients diagnosed with hypertrophic cardiomyopathy (HCM. To investigate this question, we Sanger sequenced 18 miRNA genes previously implicated in myocyte hypertrophy/fibrosis and apoptosis, using genomic DNA isolated from the leukocytes of 199 HCM patients. We identified a single nucleotide polymorphism (rs6971711, C57T SNP at the 17th position of mature miR-590-3p (= 57th position of pre-miR-590 that is common in individuals of African ancestry. SNP frequency was higher in African American HCM patients (n = 55 than ethnically-matched controls (n = 100, but the difference was not statistically significant (8.2% vs. 6.5%; p = 0.5. Using a cell culture system, we discovered that presence of this SNP resulted in markedly lower levels of mature miR-590-5p (39 ± 16%, p<0.003 and miR-590-3p (20 ± 2%, p<0.003, when compared with wild-type (WT miR-590, without affecting levels of pri-miR-590 and pre-miR-590. Consistent with this finding, the SNP resulted in reduced target suppression when compared to WT miR-590 (71% suppression by WT vs 60% suppression by SNP, p<0.03. Since miR-590 can regulate TGF-β, Activin A and Akt signaling, SNP-induced reduction in miR-590 biogenesis could influence cardiac phenotype by de-repression of these signaling pathways. Since the SNP is only present in African Americans, population studies in this patient population would be valuable to investigate effects of this SNP on myocyte function and cardiac physiology.

  2. Repression of human activation induced cytidine deaminase by miR-93 and miR-155

    Directory of Open Access Journals (Sweden)

    Holton Nathaniel W

    2011-08-01

    Full Text Available Abstract Background Activation Induced cytidine Deaminase (AID targets the immunoglobulin genes of activated B cells, where it converts cytidine to uracil to induce mutagenesis and recombination. While essential for immunoglobulin gene diversification, AID misregulation can result in genomic instability and oncogenic transformation. This is classically illustrated in Burkitt's lymphoma, which is characterized by AID-induced mutation and reciprocal translocation of the c-MYC oncogene with the IgH loci. Originally thought to be B cell-specific, AID now appears to be misexpressed in several epithelial cancers, raising the specter that AID may also participate in non-B cell carcinogenesis. Methods The mutagenic potential of AID argues for the existence of cellular regulators capable of repressing inappropriate AID expression. MicroRNAs (miRs have this capacity, and we have examined the publically available human AID EST dataset for miR complementarities to the human AID 3'UTR. In this work, we have evaluated the capacity of two candidate miRs to repress human AID expression in MCF-7 breast carcinoma cells. Results We have discovered moderate miR-155 and pronounced miR-93 complementary target sites encoded within the human AID mRNA. Luciferase reporter assays indicate that both miR-93 and miR-155 can interact with the 3'UTR of AID to block expression. In addition, over-expression of either miR in MCF-7 cells reduces endogenous AID protein, but not mRNA, levels. Similarly indicative of AID translational regulation, depletion of either miR in MCF-7 cells increases AID protein levels without concurrent increases in AID mRNA. Conclusions Together, our findings demonstrate that miR-93 and miR-155 constitutively suppress AID translation in MCF-7 cells, suggesting widespread roles for these miRs in preventing genome cytidine deaminations, mutagenesis, and oncogenic transformation. In addition, our characterization of an obscured miR-93 target site located

  3. BCG对小鼠RAW264.7巨噬细胞miR-203、miR-142-3p、miR-21表达的影响%Effect of BCG on expression of miR-203, miR-142-3p and miR-21 in mouse RAW264.7 macrophages

    Institute of Scientific and Technical Information of China (English)

    张兆波; 魏军; 汤建中; 赵志军; 张一琳; 张瑞芹; 徐广贤

    2013-01-01

    目的:检测卡介苗(Bacillus Calmette-Guerin,BCG)刺激巨噬细胞后miR-203、miR-142-3p、miR-21表达量的变化,为研究microRNA(miRNA)在巨噬细胞抗结核分枝杆菌免疫应答中的调控作用提供依据.方法:利用浓度为1.0 ×107ml-1的BCG刺激培养的小鼠RAW264.7细胞,分别在4、8、12、24小时提取细胞small RNA,并利用相应的茎环反转录引物,反转录成cDNA,同时构建成熟miR-203、miR-142-3p、miR-21的T载体,绘制标准曲线,利用Real-Time PCR检测miR-203、miR-142-3p、miR-21的表达量.结果:BCG作用RAW264.7细胞4、8、12、24小时后,miR-21表达显著性上调(10倍以上,P<0.05),miR-142-3p表达显著性下调(20倍以上,P<0.05),miR-203在4、8、12小时表达下调(3倍以上,P<0.05),24小时后表达上调(2倍以上,P<0.05).结论:BCG刺激RAW264.7巨噬细胞后,miR-203、miR-142-3p、miR-21的表达发生显著性变化,说明这些miRNA可能通过调控免疫相关基因在巨噬细胞抗结核分枝杆菌的免疫应答中发挥着重要的作用.%Objective: To detect the influence of Bacillus Calmette-Guerin (BCG) on the expression of miit-203, miR-142-3p and miR-21 in the macrophages and provide the basis to study the regulation of miRNA in the immune response of macrophages to My-cobacterium tuberculosis. Methods:Small RNA was extracted at different times after stimulated with a concentration of 1.0 × 107 ml"1 of BCG in cultured mouse RAW264. 7 cells. After using stem-loop reverse transcription primers to reverse transcribed into cDNA, the expression of miR-203, miR-142-3p and miR-21 was detected by Real-time PCR. At the same time, building the T vector of mature miR-203, miR-142-3p and miR- 21 to make the standard curve. Results:After RAW264.7 cells was treated by BCG for 4, 8, 12 and 24 h, miR-21 expression was up-regulated significantly (More than 10 times, P < 0. 05). However, miR-142-3 p was significantly down-regulated at the same time( More than 20 times, P <0. 05

  4. Expression and clinical significance of miR-181a, miR-200a, miR-200c in lung cancer tissues and cells%肺癌细胞及组织中miR-181a、miR-200a、miR-200c表达变化及意义

    Institute of Scientific and Technical Information of China (English)

    王勇; 李宇男; 于晓松

    2014-01-01

    Objective To observe the expression and significance of miR-181a, miR-200a, miR-200c in lung cancer tissues and cells.Methods RT-PCR method was used to detect the expression of miR-181a, miR-200a, miR-200c in lung cancer cell lines NCI-H1299, NCI-H358, H460, A549 and normal human bronchial epithelial cell line HBE , and in the lung cancer tissues and adjacent tissues .To analyze the relationship between the expression of miR-181a, miR-200a, miR-200c and clinicopathological parameters of lung cancer by means of Mann-Whitney.Results miR-181a expression in NCI-H1299, NCI-H358 and A549 were lower than that in HBE (all P0.05).miR-200c expression in lung cancer tissues was higher than that in cancer-adjacent tissues (P<0.01).miR-200a expression in the lung cancer patients with lymphatic metastasis was lower than that in lung cancer patients without lymphatic metastasis (P<0.01).Conclusions The expression of miR-181a, miR-200a were generally decreased , while miR-200c was generally increased in lung cancer cell lines and tissues , which maight be related to the occur of lung cancer .%目的:观察肺癌细胞及组织中 miR-181a、miR-200a、miR-200c 的表达变化,并探讨其临床意义。方法选择人肺癌细胞系NCI-H1299、NCI-H358、H460、A549及人正常支气管上皮细胞HBE,10例肺癌患者的癌组织及其相应癌旁组织。采用RT-PCR法检测各细胞系及组织中的miR-181a、miR-200a、miR-200c,并分析miRNA表达与临床参数的关系。结果 NCI-H1299、NCI-H358、A549细胞中miR-181a相对表达量均低于HBE细胞,NCI-H1299、NCI-H358、H460、A549细胞中miR-200a相对表达量均低于HBE细胞,NCI-H358、H460细胞中miR-200c相对表达量均高于HBE细胞,P均<0.05。肺癌及癌旁组织中miR-181a和miR-200a相对表达量比较,P均>0.05;肺癌组织中miR-200c相对表达量高于癌旁组织,P<0.01。有淋巴结转移的肺癌患者miR-200a相对表达量低

  5. Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer.

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    Wangyu Zhu

    Full Text Available BACKGROUND: Altered expression of miRNA expression contributes to human carcinogenesis. This study was designed to detect aberrant miRNA expressions as a potential biomarker for early detection and prognosis prediction of non-small cell lung cancer (NSCLC. METHODS: miRNA array was used to profile differentially expressed miRNAs and Taqman-based quantitative RT-PCR assays were used to analyze levels of miR-29c, miR-93, and miR-429 expression in NSCLC tissue samples, corresponding normal tissue samples, and serum samples from 70 NSCLC patients as well as in serum samples from 48 healthy controls. RESULTS: Levels of miR-29c and miR-93 expression were upregulated in NSCLC tissues, while serum levels of miR-29c were also upregulated, but levels of serum miR-429 were decreased in NSCLC. Moreover, the levels of miR-429 expression in NSCLC tissues were associated with those in serum samples. Receiver operating characteristic (ROC curve analysis showed that at the optimal cut-off point, the areas under the ROC curve for serum levels of miR-29c and miR-429 were 0.723 and 0.727, respectively, levels which are higher than that of carcinoma embryonic antigen (0.534 in diagnosis of stage I NSCLC. In addition, serum levels of miR-429 were associated with poor overall survival of NSCLC patients. Both univariate and multivariate analyses showed that serum miR-429 level was an independent prognostic predictor for NSCLC. CONCLUSIONS: The results of the current study suggest that detection of serum miR-29c and miR-429 expression should be further evaluated as a novel, non-invasive biomarker for early stage NSCLC.

  6. miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Auguet, Teresa; Aragonès, Gemma; Berlanga, Alba; Guiu-Jurado, Esther; Martí, Andreu; Martínez, Salomé; Sabench, Fàtima; Hernández, Mercé; Aguilar, Carmen; Sirvent, Joan Josep; del Castillo, Daniel; Richart, Cristóbal

    2016-01-01

    Specific miRNA expression profiles have been shown to be associated with nonalcoholic fatty liver disease (NAFLD). We examined the correlation between the circulating levels and hepatic expression of miR122 and miR33a/b*, the key lipid metabolism-related gene expression and the clinicopathological factors of obese women with NAFLD. We measured miR122 and miR33a/b* expression in liver samples from 62 morbidly obese (MO), 30 moderately obese (ModO), and eight normal-weight controls. MiR122 and miR33a/b* expression was analyzed by qRT-PCR. Additionally, miR122 and miR33b* circulating levels were analyzed in 122 women. Hepatic miR33b* expression was increased in MO compared to ModO and controls, whereas miR122 expression was decreased in the MO group compared to ModO. In obese cohorts, miR33b* expression was increased in nonalcoholic steatohepatitis (NASH). Regarding circulating levels, MO patients with NASH showed higher miR122 levels than MO with simple steatosis (SS). These circulating levels are good predictors of histological features associated with disease severity. MO is associated with altered hepatic miRNA expression. In obese women, higher miR33b* liver expression is associated with NASH. Moreover, multiple correlations between miRNAs and the expression of genes related to lipid metabolism were found, that would suggest a miRNA-host gene circuit. Finally, miR122 circulating levels could be included in a panel of different biomarkers to improve accuracy in the non-invasive diagnosis of NASH. PMID:27669236

  7. Binding Sites of miR-1273 Family on the mRNA of Target Genes

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    Anatoly Ivashchenko

    2014-01-01

    Full Text Available This study examined binding sites of 2,578 miRNAs in the mRNAs of 12,175 human genes using the MirTarget program. It found that the miRNAs of miR-1273 family have between 33 and 1,074 mRNA target genes, with a free hybridization energy of 90% or more of its maximum value. The miR-1273 family consists of miR-1273a, miR-1273c, miR-1273d, miR-1273e, miR-1273f, miR-1273g-3p, miR-1273g-5p, miR-1273h-3p, and miR-1273h-5p. Unique miRNAs (miR-1273e, miR-1273f, and miR-1273g-3p have more than 400 target genes. We established 99 mRNA nucleotide sequences that contain arranged binding sites for the miR-1273 family. High conservation of each miRNA binding site in the mRNA of the target genes was found. The arranged binding sites of the miR-1273 family are located in the 5′UTR, CDS, or 3′UTR of many mRNAs. Five repeating sites containing some of the miR-1273 family’s binding sites were found in the 3′UTR of several target genes. The oligonucleotide sequences of miR-1273 binding sites located in CDSs code for homologous amino acid sequences in the proteins of target genes. The biological role of unique miRNAs was also discussed.

  8. Association between ankylosing spondylitis and the miR-146a and miR-499 polymorphisms.

    Directory of Open Access Journals (Sweden)

    Hui Ying Xu

    Full Text Available miRNAs are small, non-coding RNAs that regulate the expression of multiple target genes at the post-transcriptional level. Single-nucleotide polymorphisms (SNPs in miRNA sequences may alter miRNA expression and have been implicated in the pathogenesis of multiple forms of arthritis, including rheumatoid arthritis (RA and osteoarthritis. The present study explored the association between ankylosing spondylitis (AS and two single nucleotide polymorphisms (SNPs, miR-146a rs2910164G>C and miR-499 rs3746444T>C, in a Han Chinese population. A case-control study consisting of 102 subjects with AS and 105 healthy controls was designed. The two miRNA SNPs were identified by direct sequencing. Subsequently, their gene and genotype frequencies were compared with healthy controls. A significant difference was observed in the miR-146a rs2910164G>C SNP. The frequency of the G allele was markedly higher in the AS patients than in the healthy controls (P = 0.005, Pc = 0.01, OR = 1.787, and the frequency of the GG genotype was higher in AS patients than in controls (P = 0.014, Pc = 0.042, OR = 2.516. However, no significant association was found between the miR-499 rs3746444T>C variant and susceptibility to AS. This is the first study to address the association between the miR-146a rs2910164G>C and miR-499 rs3746444T>C polymorphisms and AS, and it suggests a potential pathogenic factor for AS. Further studies are needed to validate our findings in a larger series, as well as in other ethnic backgrounds.

  9. Transcriptional, post-transcriptional and chromatin-associated regulation of pri-miRNAs, pre-miRNAs and moRNAs.

    Science.gov (United States)

    Nepal, Chirag; Coolen, Marion; Hadzhiev, Yavor; Cussigh, Delphine; Mydel, Piotr; Steen, Vidar M; Carninci, Piero; Andersen, Jesper B; Bally-Cuif, Laure; Müller, Ferenc; Lenhard, Boris

    2016-04-20

    MicroRNAs (miRNAs) play a major role in the post-transcriptional regulation of target genes, especially in development and differentiation. Our understanding about the transcriptional regulation of miRNA genes is limited by inadequate annotation of primary miRNA (pri-miRNA) transcripts. Here, we used CAGE-seq and RNA-seq to provide genome-wide identification of the pri-miRNA core promoter repertoire and its dynamic usage during zebrafish embryogenesis. We assigned pri-miRNA promoters to 152 precursor-miRNAs (pre-miRNAs), the majority of which were supported by promoter associated post-translational histone modifications (H3K4me3, H2A.Z) and RNA polymerase II (RNAPII) occupancy. We validated seven miR-9 pri-miRNAs by in situ hybridization and showed similar expression patterns as mature miR-9. In addition, processing of an alternative intronic promoter of miR-9-5 was validated by 5' RACE PCR. Developmental profiling revealed a subset of pri-miRNAs that are maternally inherited. Moreover, we show that promoter-associated H3K4me3, H2A.Z and RNAPII marks are not only present at pri-miRNA promoters but are also specifically enriched at pre-miRNAs, suggesting chromatin level regulation of pre-miRNAs. Furthermore, we demonstrated that CAGE-seq also detects 3'-end processing of pre-miRNAs on Drosha cleavage site that correlates with miRNA-offset RNAs (moRNAs) production and provides a new tool for detecting Drosha processing events and predicting pre-miRNA processing by a genome-wide assay.

  10. MicroRNAs (miRNAs) in neurodegenerative diseases.

    Science.gov (United States)

    Nelson, Peter T; Wang, Wang-Xia; Rajeev, Bernard W

    2008-01-01

    Aging-related neurodegenerative diseases (NDs) are the culmination of many different genetic and environmental influences. Prior studies have shown that RNAs are pathologically altered during the inexorable course of some NDs. Recent evidence suggests that microRNAs (miRNAs) may be a contributing factor in neurodegeneration. miRNAs are brain-enriched, small ( approximately 22 nucleotides) non-coding RNAs that participate in mRNA translational regulation. Although discovered in the framework of worm development, miRNAs are now appreciated to play a dynamic role in many mammalian brain-related biochemical pathways, including neuroplasticity and stress responses. Research about miRNAs in the context of neurodegeneration is accumulating rapidly, and the goal of this review is to provide perspective for these new data that may be helpful to specialists in either field. An overview is provided about the normal functions for miRNAs, including some of the newer concepts related to the human brain. Recently published studies pertaining to the roles of miRNAs in NDs--including Alzheimer's disease, Parkinson's disease and triplet repeat disorders-are described. Finally, a discussion is included with theoretical syntheses and possible future directions in exploring the nexus between miRNA and ND research.

  11. miRNA Expression Analyses in Prostate Cancer Clinical Tissues.

    Science.gov (United States)

    Bucay, Nathan; Shahryari, Varahram; Majid, Shahana; Yamamura, Soichiro; Mitsui, Yozo; Tabatabai, Z Laura; Greene, Kirsten; Deng, Guoren; Dahiya, Rajvir; Tanaka, Yuichiro; Saini, Sharanjot

    2015-09-08

    A critical challenge in prostate cancer (PCa) clinical management is posed by the inadequacy of currently used biomarkers for disease screening, diagnosis, prognosis and treatment. In recent years, microRNAs (miRNAs) have emerged as promising alternate biomarkers for prostate cancer diagnosis and prognosis. However, the development of miRNAs as effective biomarkers for prostate cancer heavily relies on their accurate detection in clinical tissues. miRNA analyses in prostate cancer clinical specimens is often challenging owing to tumor heterogeneity, sampling errors, stromal contamination etc. The goal of this article is to describe a simplified workflow for miRNA analyses in archived FFPE or fresh frozen prostate cancer clinical specimens using a combination of quantitative real-time PCR (RT-PCR) and in situ hybridization (ISH). Within this workflow, we optimize the existing methodologies for miRNA extraction from FFPE and frozen prostate tissues and expression analyses by Taqman-probe based miRNA RT-PCR. In addition, we describe an optimized method for ISH analyses formiRNA detection in prostate tissues using locked nucleic acid (LNA)- based probes. Our optimized miRNA ISH protocol can be applied to prostate cancer tissue slides or prostate cancer tissue microarrays (TMA).

  12. Tumour angiogenesis regulation by the miR-200 family

    Science.gov (United States)

    Pecot, Chad V.; Ivan, Cristina; Lu, Chunhua; Wu, Sherry; Han, Hee-Dong; Shah, Maitri Y.; Rodriguez-Aguayo, Cristian; Bottsford-Miller, Justin; Liu, Yuexin; Kim, Sang Bae; Unruh, Anna; Gonzalez-Villasana, Vianey; Huang, Li; Zand, Behrouz; Moreno-Smith, Myrthala; Mangala, Lingegowda S.; Taylor, Morgan; Dalton, Heather J.; Sehgal, Vasudha; Wen, Yunfei; Kang, Yu; Baggerly, Keith A.; Lee, Ju-Seog; Ram, Prahlad T.; Ravoori, Murali K.; Kundra, Vikas; Zhang, Xinna; Ali-Fehmi, Rouba; Gonzalez-Angulo, Ana-Maria; Massion, Pierre P.; Calin, George A.; Lopez-Berestein, Gabriel; Zhang, Wei; Sood, Anil K.

    2013-01-01

    The miR-200 family is well known to inhibit the epithelial–mesenchymal transition, suggesting it may therapeutically inhibit metastatic biology. However, conflicting reports regarding the role of miR-200 in suppressing or promoting metastasis in different cancer types have left unanswered questions. Here we demonstrate a difference in clinical outcome based on miR-200's role in blocking tumour angiogenesis. We demonstrate that miR-200 inhibits angiogenesis through direct and indirect mechanisms by targeting interleukin-8 and CXCL1 secreted by the tumour endothelial and cancer cells. Using several experimental models, we demonstrate the therapeutic potential of miR-200 delivery in ovarian, lung, renal and basal-like breast cancers by inhibiting angiogenesis. Delivery of miR-200 members into the tumour endothelium resulted in marked reductions in metastasis and angiogenesis, and induced vascular normalization. The role of miR-200 in blocking cancer angiogenesis in a cancer-dependent context defines its utility as a potential therapeutic agent. PMID:24018975

  13. miSolRNA: A tomato micro RNA relational database

    Directory of Open Access Journals (Sweden)

    Fernie Alisdair R

    2010-11-01

    Full Text Available Abstract Background The economic importance of Solanaceae plant species is well documented and tomato has become a model for functional genomics studies. In plants, important processes are regulated by microRNAs (miRNA. Description We describe here a data base integrating genetic map positions of miRNA-targeted genes, their expression profiles and their relations with quantitative fruit metabolic loci and yield associated traits. miSolRNA provides a metadata source to facilitate the construction of hypothesis aimed at defining physiological modes of action of regulatory process underlying the metabolism of the tomato fruit. Conclusions The MiSolRNA database allows the simple extraction of metadata for the proposal of new hypothesis concerning possible roles of miRNAs in the regulation of tomato fruit metabolism. It permits i to map miRNAs and their predicted target sites both on expressed (SGN-UNIGENES and newly annotated sequences (BAC sequences released, ii to co-locate any predicted miRNA-target interaction with metabolic QTL found in tomato fruits, iii to retrieve expression data of target genes in tomato fruit along their developmental period and iv to design further experiments for unresolved questions in complex trait biology based on the use of genetic materials that have been proven to be a useful tools for map-based cloning experiments in Solanaceae plant species.

  14. miR-21 Is Linked to Glioma Angiogenesis

    DEFF Research Database (Denmark)

    Hermansen, Simon Kjær; Nielsen, Boye Schnack; Aaberg-Jessen, Charlotte

    2016-01-01

    (Sox2) and CD133. We developed an image analysis-based co-localization approach allowing global alignment and quantitation of the individual markers, and measured the miR-21 in situ hybridization signal against the immunohistochemical staining of the six different markers. miR-21 significantly co......-positive tumor cells, we systematically stained consecutive serial sections from ten astrocytomas for miR-21, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), phosphatase and tensin homolog (PTEN), octamer-binding transcription factor 4 (Oct4), sex-determining region Y box 2......-localized with the hypoxia- and angiogenesis-associated markers HIF-1α (p=0.0020) and VEGF (p=0.0096), whereas the putative miR-21 target, PTEN, was expressed independently of miR-21. Expression of stem cell markers Oct4, Sox2 and CD133 was not associated with miR-21. In six glioblastoma cultures, miR-21 did not correlate...

  15. Targeting miR-155 to Treat Experimental Scleroderma.

    Science.gov (United States)

    Yan, Qingran; Chen, Jie; Li, Wei; Bao, Chunde; Fu, Qiong

    2016-02-01

    Scleroderma is a refractory autoimmune skin fibrotic disorder. Alterations of microRNAs in lesional skin could be a new approach to treating the disease. Here, we found that expression of miR-155 was up regulated in lesional skin tissue from patients with either systemic or localized scleroderma, and correlated with fibrosis area. Then we demonstrated the potential of miR-155 as a therapeutic target in pre-clinical scleroderma models. MiR-155(-/-) mice were resistant to bleomycin induced skin fibrosis. Moreover, topical antagomiR-155 could effectively treat mice primed with subcutaneous bleomycin. In primary skin fibroblast, miR-155 silencing could inhibit collagen synthesis function, as well as signaling intensity of two pro-fibrotic pathways, Wnt/β-catenin and Akt, simultaneously. We further showed that miR-155 could regulate the two pathways via directly targeting casein kinase 1α (CK1α) and Src homology 2-containing inositol phosphatase-1 (SHIP-1), as previous reports. Mice with miR-155 knockout or topical antagomir-155 treatment showed inhibited Wnt/β-catenin and Akt signaling in skin upon bleomycin challenge. Together, our data suggest the potential of miR-155 silencing as a promising treatment for dermal fibrosis, especially in topical applications.

  16. miRNA therapeutics in cardiovascular diseases: promises and problems

    Directory of Open Access Journals (Sweden)

    Nazila eNouraee

    2015-06-01

    Full Text Available miRNAs are a novel class of non-coding RNAs which found their way into the clinic due to their fundamental roles in cellular processes such as differentiation, proliferation and apoptosis. Recently, miRNAs have been known as micromodulators in cellular communications being involved in cell signaling and microenvironment remodeling. In this review, we will focus on the role of miRNAs in cardiovascular diseases (CVDs and their reliability as diagnostic and therapeutic biomarkers in these conditions. Cardiovascular diseases comprise a variety of blood vessels and heart disorders with a high rate of morbidity and mortality worldwide. This necessitates introduction of novel molecular biomarkers for early detection, prevention or treatment of these diseases. miRNAs, due to their stability, tissue-specific expression pattern and secretion to the corresponding body fluids, are attractive targets for cardiovascular-associated therapeutics. Explaining the challenges ahead of miRNA-based therapies, we will discuss the exosomes as delivery packages for miRNA drugs and promising novel strategies for the future of miRNA-based therapeutics. These approaches provide insights to the future of personalized medicine for the treatment of cardiovascular diseases.

  17. Exo-miRExplorer: A Comprehensive Resource for Exploring and Comparatively Analyzing Exogenous MicroRNAs.

    Science.gov (United States)

    Zheng, Ling-Ling; Deng, Kai-Wen; Deng, An-Cheng; Wu, Jie; Yang, Jian-Hua; Lun, Zhao-Rong; Qu, Liang-Hu

    2017-01-01

    MicroRNAs (miRNAs) are small regulatory RNAs that play important roles in animals, plants, and viruses. Deep-sequencing technology has been widely adopted in miRNA investigations. However, it is still a big mysterious why nearly all sequencing data contain miRNA sequences from exogenous species, called exo-miRNAs. In this study, we developed a novel platform, exo-miRExplorer, for mining and identifying exo-miRNAs from high-throughput small RNA sequencing experiments which originated from tissues and cell lines of multiple organisms. Thousands of exo-miRNAs are characterized with their expression abundance, the RNA families, original organisms and the sequencing platforms presented in exo-miRExplorer. Subsequently, we used exo-miRExplorer to perform further analysis. Comparative analysis of the exo-miRNAs between different sequencing datasets revealed significant correlation of exo-miRNAs between experiments in the same study. The plant-derived exo-miRNAs analysis provided robust evidence for non-diet source of exo-miRNAs. Virus-derived exo-miRNA analysis showed that pathogen RNAs could transfer to host cells and exist in deep-sequencing result at abundance level. In conclusion, exo-miRExplorer provides users with an integrative resource to facilitate detection and analysis of exo-miRNAs. exo-miRExplorer is available at the following URL: http://rna.sysu.edu.cn/exomiRDB/.

  18. miR-92a family and their target genes in tumorigenesis and metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Molin, E-mail: molin_li@hotmail.com [Department of Pathophysiology, Basic Medical Science of Dalian Medical University, Dalian 116044 (China); Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian 116044 (China); Guan, Xingfang; Sun, Yuqiang [Department of Pathophysiology, Basic Medical Science of Dalian Medical University, Dalian 116044 (China); Mi, Jun [Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian 116044 (China); Shu, Xiaohong [College of Pharmacy, Dalian Medical University Cancer Center, Dalian 116044 (China); Liu, Fang [Department of Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027 (China); Li, Chuangang, E-mail: li_chuangang@sina.com [Department of Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027 (China)

    2014-04-15

    The miR-92a family, including miR-25, miR-92a-1, miR-92a-2 and miR-363, arises from three different paralog clusters miR-17-92, miR-106a-363, and miR-106b-25 that are highly conservative in the process of evolution, and it was thought as a group of microRNAs (miRNAs) correlated with endothelial cells. Aberrant expression of miR-92a family was detected in multiple cancers, and the disturbance of miR-92a family was related with tumorigenesis and tumor development. In this review, the progress on the relationship between miR-92a family and their target genes and malignant tumors will be summarized. - Highlights: • Aberrant expression of miR-92a, miR-25 and miR-363 can be observed in many kinds of malignant tumors. • The expression of miR-92a family is regulated by LOH, epigenetic alteration, transcriptional factors such as SP1, MYC, E2F, wild-type p53 etc. • Roles of miR-92a family in tumorigenesis and development: promoting cell proliferation, invasion and metastasis, inhibiting cell apoptosis.

  19. 下调miR-18a和miR-328抑制肺腺癌A549细胞的侵袭和迁移%Downregulation of miR-18a or miR-328 inhibits the invasion and migration of lung adenocarcinoma A549 cells

    Institute of Scientific and Technical Information of China (English)

    杜传冲; 郑金旭; 陆小威; 汪毅

    2016-01-01

    目的 分析miR-18a和miR-328在肺腺癌A549细胞中的表达,并探讨下调miR-18a或miR-328的表达对其侵袭和迁移能力的影响.方法 用荧光定量PCR检测A549细胞中miR-18a和miR-328的表达;通过转染miR-18a抑制物(miR-18ainhibitor)或miR-328 inhibitor,下调miR-18a或miR-328的表达,采用TranswellTM侵袭、迁移实验分析A549细胞侵袭和迁移能力的变化.结果 A549细胞中miR-18a和miR-328均呈高表达;而转染相应抑制物后miR-18a、miR-328表达下降,A549细胞的侵袭、迁移能力均明显降低.结论 下调A549细胞miR-18a或miR-328水平可有效抑制肿瘤细胞的侵袭、迁移.

  20. Decreased miR-143 and increased miR-21 placental expression levels are associated with macrosomia.

    Science.gov (United States)

    Zhang, Ji-Tai; Cai, Qian-Ying; Ji, Si-Si; Zhang, Heng-Xin; Wang, Yu-Huan; Yan, Hong-Tao; Yang, Xin-Jun

    2016-04-01

    Macrosomia, a birth weight ≥ 4,000 g, is associated with maternal and infant health problems. The dysregulation of microRNAs (miRNAs) in the placenta is associated with adverse birth outcomes, yet whether aberrantly expressed placental miRNAs are associated with macrosomia remains unknown. The aim of the current study was to characterize the expression of three placental miRNAs (miR‑6, ‑21 and ‑143) and evaluate their association with macrosomia. The miRNA expression in placental tissues from 67 macrosomic pregnancies and 64 normal pregnancies were analyzed using reverse transcription‑quantitative polymerase chain reaction. The expression of miR‑21 was observed to be elevated in macrosomic placenta compared with control samples, while miR‑143 expression was significantly lower than in control placenta (Pmacrosomia increased with miR‑21 expression quartile: Q2, odds ratio (OR)=6.67 [95% confidence interval (CI), 1.39‑32.05]; Q3, OR=4.10 (95% CI, 0.88‑19.11); Q4, OR=16.19 (95% CI, 2.46‑106.68). Conversely, higher levels of miR‑143 expression were protective against macrosomia: Q2, OR=0.22 (95% CI, 0.049‑0.98); Q3, OR=0.11 (95% CI, 0.024‑0.55), and Q4, OR=0.16 (95% CI, 0.032‑0.79). Thus, statistical analysis demonstrated that high levels of miR‑21 expression and low levels of miR‑143 expression predict the risk for macrosomia, indicating an interaction between the two miRNAs. Bioinformatic analysis suggested that they are likely to function in the mitogen‑activated protein kinases signaling pathway to influence the risk of macrosomia. The results of the present study provide evidence that placental miR-21 and -143 are important in the formation of macrosomia.

  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. Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Honglei; Peng, Wujian; Shen, Xuemei; Huang, Yunhui; Ouyang, Xin; Dai, Yong [Clinical Medical Research Center, Second Clinical Medical College, Shenzhen People' s Hospital, Jinan University, Shenzhen, Guangdong (China)

    2012-10-19

    Circulating microRNAs (miRNAs) may represent a potential noninvasive molecular biomarker for various pathological conditions. Moreover, the detection of circulating miRNAs can provide important novel disease-related information. In particular, inflammation-associated miR-155 and endothelial-enriched miR-126 are reported to be associated with vascular homeostasis. Vascular damage is a common event described in end-stage renal disease (ESRD). We hypothesized that miR-155 and miR-126 may be detectable in the circulation and serve as potential biomarkers for risk stratification. In this study, we assessed miR-155 and miR-126 in the plasma of 30 ESRD patients and 20 healthy controls using real-time quantification RT-PCR. The circulating levels of miR-155 and miR-126 were significantly reduced in patients with ESRD compared to healthy controls. However, there was no significant difference of circulating miR-155 and miR-126 levels between prehemodialysis and posthemodialysis patients. Furthermore, both circulating miR-126 and miR-155 correlated positively with estimated glomerular filtration rate (miR-126: r = 0.383, P = 0.037; miR-155: r = 0.494, P = 0.006) and hemoglobin (miR-126: r = 0.515, P = 0.004; miR-155: r = 0.598, P < 0.001) and correlated inversely with phosphate level (miR-126: r = -0.675, P < 0.001; miR-155: r = -0.399, P = 0.029). Pearson's correlation was used to compare circulating levels of miRNAs with clinical parameters. These results suggested that circulating miR-155 and miR-126 might be involved in the development of ESRD. Further studies are needed to demonstrate the role of circulating miR-155 and miR-126 as candidate biomarkers for risk estimation.

  3. MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells.

    Science.gov (United States)

    Dong, Peixin; Xiong, Ying; Watari, Hidemichi; Hanley, Sharon J B; Konno, Yosuke; Ihira, Kei; Yamada, Takahiro; Kudo, Masataka; Yue, Junming; Sakuragi, Noriaki

    2016-09-05

    In ovarian cancer (OC) cells, Snail was reported to induce the epithelial-to-mesenchymal transition (EMT), which is a critical step in OC metastasis. At present little is known about controlling Snail expression in OC cells by using specific microRNAs (miRNAs). We first used a computational target prediction analysis to identify 6 candidate miRNAs that bind to the 3'-untranslated region (3'-UTR) region of the Snail mRNA. Among these miRNAs, two miRNAs (miR-137 and miR-34a) with a potential to regulate Snail were validated by quantitative real-time PCR, Western blot analysis, and Snail 3'-UTR reporter assays. We assessed the effects of miR-137 and miR-34a on EMT, invasion and sphere formation in OC cells. We also evaluated the expression of miR-137 and miR-34a in OC tissues and adjacent normal tissues and analyzed the relationship between their expression and patient survival. We report that OC tissues possess significantly decreased levels of miR-137 and miR-34a and increased expression of Snail when compared to their adjacent normal tissues, and lower miR-137 and miR-34a expression correlates with worse patient survival. Using luciferase constructs containing the 3'-UTR region of Snail mRNA combined with miRNA overexpression and mutagenesis, we identified miR-137 and miR-34a as direct suppressors of Snail in OC cells. The introduction of miR-137 and miR-34a resulted in the suppression of Snail at both the transcript and protein levels, and effectively suppressed the EMT phenotype and sphere formation of OC cells. However, the inhibition of miR-137 and miR-34a with antisense oligonucleotides promoted EMT and OC cell invasion. Moreover, ectopic expression of Snail significantly reversed the inhibitory effects of miR-137 and miR-34a on OC cell invasion and sphere formation. These findings suggest that both miR-137 and miR-34a act as Snail suppressors to negatively regulate EMT, invasive and sphere-forming properties of OC cells.

  4. miRMaid: a unified programming interface for microRNA data resources

    Directory of Open Access Journals (Sweden)

    Krogh Anders

    2010-01-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are endogenous small RNAs that play a key role in post-transcriptional regulation of gene expression in animals and plants. The number of known miRNAs has increased rapidly over the years. The current release (version 14.0 of miRBase, the central online repository for miRNA annotation, comprises over 10.000 miRNA precursors from 115 different species. Furthermore, a large number of decentralized online resources are now available, each contributing with important miRNA annotation and information. Results We have developed a software framework, designated here as miRMaid, with the goal of integrating miRNA data resources in a uniform web service interface that can be accessed and queried by researchers and, most importantly, by computers. miRMaid is built around data from miRBase and is designed to follow the official miRBase data releases. It exposes miRBase data as inter-connected web services. Third-party miRNA data resources can be modularly integrated as miRMaid plugins or they can loosely couple with miRMaid as individual entities in the World Wide Web. miRMaid is available as a public web service but is also easily installed as a local application. The software framework is freely available under the LGPL open source license for academic and commercial use. Conclusion miRMaid is an intuitive and modular software platform designed to unify miRBase and independent miRNA data resources. It enables miRNA researchers to computationally address complex questions involving the multitude of miRNA data resources. Furthermore, miRMaid constitutes a basic framework for further programming in which microRNA-interested bioinformaticians can readily develop their own tools and data sources.

  5. miR-200 family and gastrointestinal tumors%miR-200家族在消化系肿瘤中的研究进展

    Institute of Scientific and Technical Information of China (English)

    杜平; 张庆瑜

    2011-01-01

    The miR-200 family (including miR-200a, miR-200b, miR-200c, miR-141, and miR-429) play important roles in proliferation, invasion and metastasis of tumors of epithelial origin. Gastrointestinal tumors belong to a group of tumors of epithelial origin. This article reviews the latest advances in understanding the relationship between the miR-200 family and gastrointestinal tumors.%miR-200家族(miR-200a、miR-200b、miR-200c、miR-141、miR-429)是众多已被发现的mieroRNA中的一员,其在上皮来源肿瘤的增殖、侵袭、转移中的作用成为近年来的研究热点之一,本文对miR-200家族在同为上皮来源的消化系肿瘤中的研究进展进行了综述.

  6. Diagnostic and prognostic value of miR-1 and miR-29b on adverse ventricular remodeling after acute myocardial infarction - The SITAGRAMI-miR analysis.

    Science.gov (United States)

    Grabmaier, U; Clauss, S; Gross, L; Klier, I; Franz, W M; Steinbeck, G; Wakili, R; Theiss, H D; Brenner, C

    2017-10-01

    MicroRNAs (miRs) have shown to exert fibrotic and anti-fibrotic effects in preclinical models of acute myocardial infarction (AMI). The aim of this study was to evaluate miR-1, miR-21, miR-29b and miR-92a as circulating biomarkers for adverse ventricular remodeling (AVR) in post-AMI patients. Plasma levels of miR-1, miR-21, miR-29b and miR-92a were measured in 44 patients of the SITAGRAMI trial population at day 4, day 9 and 6month after AMI and in 18 matched controls (CTL). MiR expression patterns were correlated with magnetic resonance imaging (MRI) parameters for AVR (absolute change (Δ) in infarct volume (IV), left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume (LVEDV) between day 4 and 6months after AMI) and a combined cardiovascular endpoint. Expression of miR-1, miR-21 and miR-29b but not miR-92a was increased in AMI vs. CTL cohort showing highest miR levels at d9. However, only miR-1 and miR-29b levels significantly correlated with ΔIV and showed a trend for correlation with ΔLVEF. Only miR-29b levels at day 9 correlated with ΔLVEDV at 6-month follow-up. There was no correlation of miR levels with an adverse outcome. Mir-1 and miR-29b plasma levels post-AMI correlate with IV changes. In addition, miR-29b levels are associated with changes of LVEDV over time. These results provide insights into the role of miRs as diagnostic AVR surrogate markers. Further large scale clinical trials will be needed to evaluate the real prognostic relevance of these miRs with respect to a clinical implication in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Involvement of FOS-mediated miR-181b/miR-21 signalling in the progression of malignant gliomas.

    Science.gov (United States)

    Tao, Tao; Wang, Yingyi; Luo, Hui; Yao, Lei; Wang, Lin; Wang, Jiajia; Yan, Wei; Zhang, Junxia; Wang, Huibo; Shi, Yan; Yin, Yu; Jiang, Tao; Kang, Chunsheng; Liu, Ning; You, Yongping

    2013-09-01

    Recently, a group of microRNAs (miRNAs) were shown to be dysregulated in gliomas, and involved in glioma development. However, the effect of miRNA-miRNA functional networks on gliomas is poorly understood. In this study, we identified that FBJ murine osteosarcoma viral oncogene homolog (FOS)-mediated miR-181b/miR-21 signalling was critical for glioma progression. Using microarrays and quantitative RT-PCR (qRT-PCR), we found increased FOS in high grade gliomas. FOS depletion (via FOS-shRNA), inhibited invasion and promoted apoptosis in glioma cells. Using microarrays, combined with Pearson correlation analysis, we found FOS positively correlated with miR-21 expression. Reduction of FOS inhibited miR-21 expression by binding to the miR-21 promoter using luciferase reporter assays. Introduction of miR-21 abrogated FOS knockdown-induced cell invasion and apoptosis. Moreover, bioinformatics and luciferase reporter assays showed that miR-181b modulated FOS expression by directly targeting the binding site within the 3'UTR. Expression of FOS with a FOS cDNA lacking 3'UTR overrided miR-181b-induced miR-21 expression and cell function. Finally, immunohistochemistry (IHC) and in situ hybridisation (ISH) analysis revealed a significant correlation in miR-181b, FOS and miR-21 expression in nude mouse tumour xenograft and human glioma tissues. To our knowledge, it is the first time to demonstrate that miR-181b/FOS/miR-21 signalling plays a critical role in the progression of gliomas, providing important clues for understanding the key roles of transcription factor mediated miRNA-miRNA functional network in the regulation of gliomas.

  8. miR-31 and miR-17-5p levels change during transformation of follicular lymphoma.

    Science.gov (United States)

    Thompson, Mary Ann; Edmonds, Mick D; Liang, Shan; McClintock-Treep, Sara; Wang, Xuan; Li, Shaoying; Eischen, Christine M

    2016-04-01

    The 30% of patients whose indolent follicular lymphoma transforms to aggressive diffuse large B-cell lymphoma (DLBCL) have poor survival. Reliable predictors of follicular B-cell lymphoma transformation to DLBCL are lacking, and diagnosis of those that will progress is challenging. MicroRNA, which regulates gene expression, has critical functions in the growth and progression of many cancers and contributes to the pathogenesis of lymphoma. Using 5 paired samples from patients who presented with follicular lymphoma and progressed to DLBCL, we identified specific microRNA differentially expressed between the two. Specifically, miR-17-5p levels were low in follicular lymphoma and increased as the disease transformed. In contrast, miR-31 expression was high in follicular lymphoma and decreased as the lymphoma progressed. These results were confirmed in additional unpaired cases of low-grade follicular lymphoma (n = 13) and high-grade follicular lymphoma grade 3 or DLBCL (n = 17). Loss of miR-31 expression in DLBCL was not due to deletion of the locus. Changes in miR-17-5p and miR-31 were not correlated with immunophenotype, genetics, or status of the MYC oncogene. However, increased miR-17-5p expression did significantly correlate with increased expression of p53 protein, which is indicative of mutant TP53. Two pro-proliferative genes, E2F2 and PI3KC2A, were identified as direct messenger RNA targets of miR-31, suggesting that these may contribute to follicular lymphoma transformation. Our results indicate that changes in miR-31 and miR-17-5p reflect the transformation of follicular lymphoma to an aggressive large B-cell lymphoma and may, along with their targets, be viable markers for this process.

  9. miRNA调节心脏发育的信号网络%miRNA Regulatory Networks in Cardiac Development

    Institute of Scientific and Technical Information of China (English)

    刘怀钰

    2011-01-01

    心脏是整个生命过程中精确的功能调控器官.任何对心脏结构和功能的微弱干抚都会造成致命性的结果.最近研究表明在心血管的发育和疾病中,miRNAs控制了这一过程中的基因表达.进入心脏循环系统的miRNAs为基因提供了一个互动的监管系统,并控制心脏基因的表达图谱.miRNAs的调控网络的发现,有利于治疗心脏疾病保护心脏功能.主要讨论了miRNA在心脏成型和功能中发挥的调节作用.%The heart requires precise functionality on a second-to-second basis throughout the lifespan of the organism. Any weak disturbance to the structure and function of heart would lead to fatal result. Recent studies had revealed central roles for miRNAs as governors of gene expression during cardiovascular development and disease. The integration of miRNAs into the genetic circuitry of the heart provided a rich and robust array of regulatory interactions to control cardiac gene expression. miRNA regulatory networks also offered opportunities for therapeutically modulating cardiac function through the manipulation of pathogenic and protective miRNAs. The roles of miRNAs as regulators of cardiac form and function were discussed.

  10. Circulating miR-765 and miR-149: Potential Noninvasive Diagnostic Biomarkers for Geriatric Coronary Artery Disease Patients

    Directory of Open Access Journals (Sweden)

    Md Sayed Ali Sheikh

    2015-01-01

    Full Text Available The purpose of this study was to evaluate the diagnostic value of circulating miR-765 and miR-149 as noninvasive early biomarkers for geriatric coronary artery disease (CAD patients. A total of 69 angiographically documented CAD patients including 37 stable CAD (72.9 ± 4.2 years and 32 unstable CAD (72.03 ± 4.3 years and 20 healthy subjects (71.7 ± 5.2 years, matched for age, sex, smoking habit, hypertension, and diabetes, were enrolled in this study. Compared with healthy subjects, circulating miR-765 levels were increased by 2.9-fold in stable CAD and 5.8-fold in unstable CAD patients, respectively, while circulating miR-149 levels were downregulated by 3.5-fold in stable CAD and 4.2-fold in unstable CAD patients, respectively. Furthermore, plasma levels of miR-765 were found to be positively correlated with ages within control, stable, and unstable groups. The ROC curves of miR-765 and miR-149 represented significant diagnostic values with an area under curve (AUC of 0.959, 0.972 and 0.938, 0.977 in stable CAD patients and unstable CAD patients as compared with healthy subjects, respectively. Plasma levels of miR-765 and miR-149 might be used as noninvasive biomarkers for the diagnosis of CAD in geriatric people.

  11. Involvement of miR160/miR393 and their targets in cassava responses to anthracnose disease.

    Science.gov (United States)

    Pinweha, Nattaya; Asvarak, Thipa; Viboonjun, Unchera; Narangajavana, Jarunya

    2015-02-01

    Cassava is a starchy root crop for food and industrial applications in many countries around the world. Among the factors that affect cassava production, diseases remain the major cause of yield loss. Cassava anthracnose disease is caused by the fungus Colletotrichum gloeosporioides. Severe anthracnose attacks can cause tip die-backs and stem cankers, which can affect the availability of planting materials especially in large-scale production systems. Recent studies indicate that plants over- or under-express certain microRNAs (miRNAs) to cope with various stresses. Understanding how a disease-resistant plant protects itself from pathogens should help to uncover the role of miRNAs in the plant immune system. In this study, the disease severity assay revealed different response to C. gloeosporioides infection in two cassava cultivars. Quantitative RT-PCR analysis uncovered the differential expression of the two miRNAs and their target genes in the two cassava cultivars that were subjected to fungal infection. The more resistant cultivar revealed the up-regulation of miR160 and miR393, and consequently led to low transcript levels in their targets, ARF10 and TIR1, respectively. The more susceptible cultivar exhibited the opposite pattern. The cis-regulatory elements relevant to defense and stress responsiveness, fungal elicitor responsiveness and hormonal responses were the most prevalent present in the miRNAs gene promoter regions. The possible dual role of these specific miRNAs and their target genes associated with cassava responses to C. gloeosporioides is discussed. This is the first study to address the molecular events by which miRNAs which might play a role in fungal-infected cassava. A better understanding of the functions of miRNAs target genes should greatly increase our knowledge of the mechanism underlying susceptibility and lead to new strategies to enhance disease tolerance in this economically important crop.

  12. Circulating level of miR-378 predicts left ventricular hypertrophy in patients with aortic stenosis.

    Directory of Open Access Journals (Sweden)

    Zhongxiu Chen

    Full Text Available Excessively high left ventricle mass is an independent predictor of adverse prognosis. MicroRNAs (miRs play crucial roles in the regulation of left ventricle hypertrophy (LVH. However, few circulating miRs have been established as predictors of LVH in aortic stenosis (AS patients. In this study, we aimed to investigate whether circulating levels of miR-1, miR-133, and miR-378 predict LVH in patients with AS.One-hundred twelve patients with moderate to severe AS and 40 healthy controls were included in the study. Levels of miR-1, miR-133, and miR-378 in the plasma were measured by qPCR. Compared with healthy controls, AS patients had significantly lower circulating levels of miR-1, miR-133, and miR-378. AS patients with LVH had significantly lower miR-378 but not miR-1 and miR-133 compared with those without LVH. Linear regression analysis showed circulating miR-378 had strong correlation with left ventricular mass index (r = 0.283, p = 0.002 and logistic regression showed that lower miR-378 was an independent predictor for LVH in patients with AS (p = 0.037, OR 4.110, 95% CI 1.086 to 15.558.Circulating levels of miR-1, miR-133 and miR-378 were decreased in AS patients, and miR-378 predicts LVH independent of the pressure gradient. Further prospective investigations are needed to elucidate whether these circulating miRs affect clinical outcome.

  13. "Language Immersion Tepee" as a Facilitator of Sámi Language Learning

    Science.gov (United States)

    Keskitalo, Pigga; Määttä, Kaarina; Uusiautti, Satu

    2014-01-01

    Due to the history of assimilation, power relations, and their sociolinguistic situation, the Sámi languages are categorized as endangered. The position of the Sámi languages in Sámi education is reviewed, and language immersion as a teaching method and as a means of language maintenance is discussed. Sámi language learning is described through…

  14. miRNAs of two medically important mosquito species: Aedes aegypti and Anopheles stephensi

    Science.gov (United States)

    Hu, Wanqi; Crisione, Frank; Liang, Shaohui; Tu, Zhijian

    2014-01-01

    MicroRNAs (miRNAs) are endogenous, single-stranded small RNAs that have important regulatory functions at the post-transcriptional level. Here, we characterize miRNAs in two divergent mosquito species, Aedes aegypti and Anopheles stephensi, through deep sequencing of small RNAs spanning all developmental stages. We discovered eight novel miRNAs in Ae. aegypti and 20 novel miRNAs in An. stephensi, which enabled the first systematic analysis of miRNA evolution in mosquitos. We traced the phylogenetic history of all miRNAs in both species and report a rate of 0.055–0.13 miRNA net gain per million years. Most novel miRNAs originate de novo. Duplications that produced miRNA clusters and families are more common in Ae. aegypti than in An. stephensi. We also identified arm-switch as a source of new miRNAs. Expression profile analysis identified mosquito-specific miRNAs that showed strong stage-specific expression in one or both lineages. For example, the aae-miR-2941/2946 family represents the most abundant maternally-deposited and zygotically transcribed miRNAs in Ae. aegypti. miR-2943 is a highly expressed zygotic miRNA in both Ae. aegypti and An. stephensi. Such information provides the basis to study the function of these miRNAs in biology common to all mosquitos or unique to one particular lineage. PMID:25420875

  15. An ultraconserved lnc to miRNA processing.

    Science.gov (United States)

    Plosky, Brian S

    2014-07-03

    Very few specific functions have been assigned to ultraconserved regions. In this issue of Molecular Cell, Liz et al. (2014) describe how a lncRNA transcribed from an ultraconserved region can negatively regulate miRNA maturation.

  16. 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.

  17. Noored klassikas / Kristina Kõrver, Anastassia Mišenkina

    Index Scriptorium Estoniae

    Kõrver, Kristina, 1979-

    2009-01-01

    11. novembril Estonia kontserdisaalis ja 12. novembril Vanemuise kontserimajas toimunud Tallinna Muusikakeskkooli ja Georg Otsa nimelise Tallinna Muusikakooli ühiskontserdist jagavad muljeid TMKK muusikaajaloo õpetaja K. Kõrver ja Otsa kooli õpilane A. Mišenkina

  18. Cumulative Production Per Township - SaMiRa

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This dataset contains a selected township grid within the Sagebrush Mineral Resource Assessment project (SaMiRa) study area attributed with cumulative oil and gas...

  19. miRMOD: a tool for identification and analysis of 5′ and 3′ miRNA modifications in Next Generation Sequencing small RNA data

    Directory of Open Access Journals (Sweden)

    Abhinav Kaushik

    2015-10-01

    Full Text Available In the past decade, the microRNAs (miRNAs have emerged to be important regulators of gene expression across various species. Several studies have confirmed different types of post-transcriptional modifications at terminal ends of miRNAs. The reports indicate that miRNA modifications are conserved and functionally significant as it may affect miRNA stability and ability to bind mRNA targets, hence affecting target gene repression. Next Generation Sequencing (NGS of the small RNA (sRNA provides an efficient and reliable method to explore miRNA modifications. The need for dedicated software, especially for users with little knowledge of computers, to determine and analyze miRNA modifications in sRNA NGS data, motivated us to develop miRMOD. miRMOD is a user-friendly, Microsoft Windows and Graphical User Interface (GUI based tool for identification and analysis of 5′ and 3′ miRNA modifications (non-templated nucleotide additions and trimming in sRNA NGS data. In addition to identification of miRNA modifications, the tool also predicts and compares the targets of query and modified miRNAs. In order to compare binding affinities for the same target, miRMOD utilizes minimum free energies of the miRNA:target and modified-miRNA:target interactions. Comparisons of the binding energies may guide experimental exploration of miRNA post-transcriptional modifications. The tool is available as a stand-alone package to overcome large data transfer problems commonly faced in web-based high-throughput (HT sequencing data analysis tools. miRMOD package is freely available at http://bioinfo.icgeb.res.in/miRMOD.

  20. Distinct roles for miR-1 and miR-133a in the proliferation and differentiation of rhabdomyosarcoma cells.

    Science.gov (United States)

    Rao, Prakash K; Missiaglia, Edoardo; Shields, Lauren; Hyde, Greg; Yuan, Bingbing; Shepherd, Christopher J; Shipley, Janet; Lodish, Harvey F

    2010-09-01

    Rhabdomyosarcoma is the most common soft tissue sarcoma in the pediatric population. As this tumor has an undifferentiated myogenic phenotype, agents that promote differentiation hold particular promise as part of a novel therapeutic approach to combat this type of cancer. In this report, we focus on the contribution of two microRNAs (miRNAs) in rhabdomyosarcomas. Levels of miR-1 and miR-133a are drastically reduced in representative cell lines from each major rhabdomyosarcoma subtype (embryonal and alveolar). Introduction of miR-1 and miR-133a into an embryonal rhabdomyosarcoma-derived cell line is cytostatic, thereby suggesting a tumor suppressor-like role for these myogenic miRNAs. Transcriptional profiling of cells after miR-1 and miR-133a expression reveals that miR-1 (but not miR-133a) exerts a strong promyogenic influence on these poorly differentiated tumor cells. We identify mRNAs that are down-regulated by these miRNAs and propose roles for miR-1 and miR-133a in repressing isoforms of genes that are normally not expressed in muscle. Finally, we show that mRNA targets of miR-1 and miR-133a are up-regulated in rhabdomyosarcomas, suggesting a causative role for these miRNAs in the development of rhabdomyosarcomas. More important, these results point to the promise of enhancing rhabdomyosarcoma therapy using miRNAs as agents that mediate cytostasis and promote muscle differentiation.

  1. MiR-107 and MiR-185 can induce cell cycle arrest in human non small cell lung cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Yukari Takahashi

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are short single stranded noncoding RNAs that suppress gene expression through either translational repression or degradation of target mRNAs. The annealing between messenger RNAs and 5' seed region of miRNAs is believed to be essential for the specific suppression of target gene expression. One miRNA can have several hundred different targets in a cell. Rapidly accumulating evidence suggests that many miRNAs are involved in cell cycle regulation and consequentially play critical roles in carcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Introduction of synthetic miR-107 or miR-185 suppressed growth of the human non-small cell lung cancer cell lines. Flow cytometry analysis revealed these miRNAs induce a G1 cell cycle arrest in H1299 cells and the suppression of cell cycle progression is stronger than that by Let-7 miRNA. By the gene expression analyses with oligonucleotide microarrays, we find hundreds of genes are affected by transfection of these miRNAs. Using miRNA-target prediction analyses and the array data, we listed up a set of likely targets of miR-107 and miR-185 for G1 cell cycle arrest and validate a subset of them using real-time RT-PCR and immunoblotting for CDK6. CONCLUSIONS/SIGNIFICANCE: We identified new cell cycle regulating miRNAs, miR-107 and miR-185, localized in frequently altered chromosomal regions in human lung cancers. Especially for miR-107, a large number of down-regulated genes are annotated with the gene ontology term 'cell cycle'. Our results suggest that these miRNAs may contribute to regulate cell cycle in human malignant tumors.

  2. Association of Circulating Serum miR-34a and miR-122 with Dyslipidemia among Patients with Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Salvoza, Noel C; Klinzing, David C; Gopez-Cervantes, Juliet; Baclig, Michael O

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of diseases from simple steatosis to non-alcoholic steatohepatitis, with approximately 20% risk of progressing to fibrosis and cirrhosis. The aim of this study was to compare the relative expression levels of circulating miR-21, miR-34a, miR-122, miR-125b and miR-375 between healthy controls and NAFLD patients, and to assess the feasibility of microRNAs as potential biomarkers for NAFLD. A cross-sectional study was conducted to evaluate circulating serum miRNAs as potential diagnostic markers for NAFLD. Twenty-eight clinically diagnosed and histologically-confirmed NAFLD patients, as well as 36 healthy controls were enrolled in this study. The relative expression of serum microRNAs were calculated using the comparative cycle threshold with spiked-in C. elegans miR-39 as exogenous internal control. Serum levels of miR-34a and miR-122 were significantly higher in NAFLD patients than in healthy controls (P = NAFLD. Interestingly, receiver operating characteristic (ROC) curve analysis revealed that miR-34a and miR-122 are potential markers for discriminating NAFLD patients from healthy controls with an area under the curve (AUC) values of 0.781 and 0.858, respectively. Serum levels of miR-34a and miR-122 were found to be significantly higher among NAFLD patients, and were positively correlated with VLDL-C and triglyceride levels. Thus, circulating miR-34a and miR-122 can be used as potential biomarkers for discriminating NAFLD patients from healthy controls. Larger cohorts are required to validate the utility of miR-34a and miR-122 in monitoring liver injury.

  3. miR-107 and miR-25 simultaneously target LATS2 and regulate proliferation and invasion of gastric adenocarcinoma (GAC) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Mingjun; Wang, Xiaolei [Cancer Center, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601 (China); Li, Wanhu [MRI Room of Shandong Cancer Hospital & Institute, Jinan 250117 (China); Cui, Yongchun, E-mail: yongchuncui1@126.com [Drug Clinical Trial Institution of Shandong Cancer Hospital & Institute, #440, Jiyan Road, Jinan 250117 (China)

    2015-05-08

    Although a series of oncogenes and tumor suppressors were identified in the pathological development of gastric adenocarcinoma (GAC), the underlying molecule mechanism were still not fully understood. The current study explored the expression profile of miR-107 and miR-25 in GAC patients and their downstream regulative network. qRT-PCR analysis was performed to quantify the expression of these two miRNAs in serum samples from both patients and healthy controls. Dual luciferase assay was conducted to verify their putative bindings with LATS2. MTT assay, cell cycle assay and transwell assay were performed to explore how miR-107 and miR-25 regulate proliferation and invasion of gastric cancer cells. Findings of this study demonstrated that total miR-107 or miR-25 expression might be overexpressed in gastric cancer patients and they can simultaneously and synchronically regulate LATS2 expression, thereby affecting gastric cancer cell growth and invasion. Therefore, the miR-25/miR-107-LATS2 axis might play an important role in proliferation and invasion of the gastric cancer cells. - Highlights: • Total miR-107 and miR-25 expression is significantly increased in GAC patients. • Both miR-107 and miR-25 can promote proliferation and invasion of GAC cells. • Both miR-107 and miR-25 can target LATS2 and regulate its expression. • miR-107 and miR-25 regulate proliferation and invasion of GAC cells though LATS2.

  4. "Now the Work Begins": Gender Equality in Sámi Politics

    OpenAIRE

    2014-01-01

    This study examines gender equality in Sámi politics after 2005, the year the Sámi Parliament achieved balanced gender representation. The project seeks to answer the question: Within the context of Sámi politics, how is gender equality represented and addressed? To answer this question, the study is based on official documents by the Sámi Parliament and the women’s organization Sámi NissonForum, as well as six semi-structured interviews with Sámi politicians and Sámi women’s activists. Quali...

  5. Sobre mi traducción de "Ser y Tiempo"

    OpenAIRE

    2005-01-01

    Este escrito pretende dos cosas: primero, desarrollar brevemente mi propia idea de lo que es traducir, y, segundo, explicar la solución que di a ciertos problemas que surgieron en mi traducción de la obra "Ser y Tiempo" de Heidegger. (In this article the author develops his own idea of a translation and explains the solutions given to problems arisen in the translation of Heidegger’s Being and Time.)

  6. Sobre mi traducción de "Ser y Tiempo"

    Directory of Open Access Journals (Sweden)

    Jorge Eduardo Rivera

    2005-12-01

    Full Text Available Este escrito pretende dos cosas: primero, desarrollar brevemente mi propia idea de lo que es traducir, y, segundo, explicar la solución que di a ciertos problemas que surgieron en mi traducción de la obra "Ser y Tiempo" de Heidegger. (In this article the author develops his own idea of a translation and explains the solutions given to problems arisen in the translation of Heidegger’s Being and Time.

  7. The miR-10 microRNA precursor family

    DEFF Research Database (Denmark)

    Tehler, Disa; Høyland-Kroghsbo, Nina Molin; Lund, Anders H

    2011-01-01

    The miR-10 microRNA precursor family encodes a group of short non-coding RNAs involved in gene regulation. The miR-10 family is highly conserved and has sparked the interest of many research groups because of the genomic localization in the vicinity of, coexpression with and regulation of the Hox...... gene developmental regulators. Here, we review the current knowledge of the evolution, physiological function and involvement in cancer of this family of microRNAs....

  8. Regulation signature of miR-143 and miR-26 in porcine Salmonella infection identified by binding site enrichment analysis.

    Science.gov (United States)

    Yao, Min; Gao, Weihua; Tao, Hengxun; Yang, Jun; Liu, Guoping; Huang, Tinghua

    2016-04-01

    Salmonella infects many vertebrate species, and pigs colonized with Salmonella are typically Salmonella carriers. Transcriptomic analysis of the response to Salmonella infection in whole blood has been reported for the pig. The objective of this study is to identify the important miRNAs involved in Salmonella infection using binding site enrichment analysis. We predicted porcine microRNA (miRNA) binding sites in the 3' UTR of protein-coding genes for all miRNA families. Based on those predictions, we analyzed miRNA-binding sites for mRNAs expressed in peripheral blood to investigate the functional importance of miRNAs in Salmonella infection in pig. Enrichment analysis revealed that binding sites of five miRNAs (including miR-143, -9839, -26, -2483, and -4335) were significantly over represented for the differentially expressed gene sets. Real-time PCR results indicated that selected members of this miRNA group (miR-143, -26, and -4335) were differentially expressed in whole blood after Salmonella inoculation. The luciferase reporter assay showed that ATP6V1A and IL13RA1 were targets of miR-143 and that miR-26 regulates BINP3L and ARL6IP6. The results strongly suggest that miR-143 and miR-26 play important regulatory roles in the development of Salmonella infection in pig.

  9. Expression profilings of miRNA in mouse preimplantation embryos%miRNA在小鼠着床前胚胎的表达

    Institute of Scientific and Technical Information of China (English)

    张平; 王颖

    2009-01-01

    目的:研究小鼠发育过程中miRNA表达水平的变化,探讨miRNA对着床前胚胎发育过程的作用.方法:建立小鼠超排、交配系统,收集着床前胚胎提取低分子量 RNA;采用miRNA特异RT引物进行反转录,采用SYBR Green实时定量PCR技术,研究miR-125a、miR-295和miR-181b在小鼠着床前胚胎发育过程中表达水平的变化.结果:着床前胚胎发育的各阶段均表达miR-125a、miR-295和miR-181b;随着胚胎发育进程,miR-295的表达呈逐渐上升的趋势;miR-125a在卵母细胞到2细胞发育阶段呈下降趋势,以后随发育进程呈逐渐上升趋势.结论:小鼠着床前胚胎中表达miRNA,着床前胚胎的发育和分化过程可能受到miRNA的调控.

  10. TGF-β1 regulating miR-205/miR-195 expression affects the TGF-β signal pathway by respectively targeting SMAD2/SMAD7.

    Science.gov (United States)

    Duan, Yingjun; Chen, Qianxue

    2016-10-01

    Transforming growth factor-β (TGF-β) proteins are important cytokines in the occurrence and development of tumors. However, its neural functions in glioma are still not understood. In the present study, we evaluated the effects of TGF-β1 on glioma cell line U87. miR-205 and miR-195 were involved in TGF-β1 signaling pathway. Quantitative real-time PCR was used to detect miR-205 and miR-195 levels in human glioma tissue samples and U87 cells treated with different concentrations of TGF-β1. Enzyme-linked immunosorbent assay (ELISA) was performed to determine TGF-β1 in the glioma patients peripheral blood. In vitro, U87 cells were transfected with mimics or inhibitors of miR-205 and miR-195. SMAD proteins were assayed by western blotting. Luciferase assay and co-immunoprecipitation (Co-IP)were used to determine the relationships between miR-205 and SMAD2, miR-195 and SMAD7. Effects of miR-205 and miR-195 on glioma cell proliferation and invasion using colony forming and cell migration assays. It was shown that miR-205 was decreased in glioma tissue, but miR-195 and TGF-β1 was increased. In addition, TGF-β1 concentration was negatively correlated with miR-205 mRNA level, but positively correlated with miR-195 mRNA. In addition, miR-205 was downregulated and miR-195 was upregulated by TGF-β1 in a dose-dependent manner. miR-205 and miR-195 targeted and inhibited SMAD2 and SMAD7 expression, respectively, in U87. High expression of miR-205 but not miR-195 reduced SMAD2 and SMAD4 heteromer formation. In addition, it was also shown that miR-205 overexpression inhibited U87 proliferation and invasion efficiently. All the results suggested that miR-205 and miR-195 participated in the TGF-β1 signaling pathway and showed opposite effects in glioma. These findings contribute to the understanding of TGF-β1 function in glioma.

  11. Genetic versus Non-Genetic Regulation of miR-103, miR-143 and miR-483-3p Expression in Adipose Tissue and Their Metabolic Implications-A Twin Study

    DEFF Research Database (Denmark)

    Bork-Jensen, Jette; Thuesen, Anne Cathrine Baun; Bang-Bertelsen, Claus Heiner;

    2014-01-01

    Murine models suggest that the microRNAs miR-103 and miR-143 may play central roles in the regulation of subcutaneous adipose tissue (SAT) and development of type 2 diabetes (T2D). The microRNA miR-483-3p may reduce adipose tissue expandability and cause ectopic lipid accumulation, insulin resist...

  12. Investigation of miRNA Biology by Bioinformatic Tools and Impact of miRNAs in Colorectal Cancer: Regulatory Relationship of c-Myc and p53 with miRNAs

    Directory of Open Access Journals (Sweden)

    Yaguang Xi

    2007-01-01

    Full Text Available MicroRNAs (miRNAs are a class of small non-coding RNAs that mediate gene expression at the posttranscriptional and translational levels and have been demonstrated to be involved in diverse biological functions. Mounting evidence in recent years has shown that miRNAs play key roles in tumorigenesis due to abnormal expression of and mutations in miRNAs. High throughput miRNA expression profiling of several major tumor types has identified miRNAs associated with clinical diagnosis and prognosis of cancer treatment. Previously our group has discovered a novel regulatory relationship between tumor suppressor gene p53 with miRNAs expression and a number of miRNA promoters contain putative p53 binding sites. In addition, others have reported that c-myc can mediate a large number of miRNAs expression. In this review, we will emphasize algorithms to identify mRNA targets of miRNAs and the roles of miRNAs in colorectal cancer. In particular, we will discuss a novel regulatory relationship of miRNAs with tumor suppressor p53 and c-myc. miRNAs are becoming promising novel targets and biomarkers for future cancer therapeutic development and clinical molecular diagnosis.

  13. MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes.

    Directory of Open Access Journals (Sweden)

    Damon Polioudakis

    Full Text Available miRNAs play a central role in numerous pathologies including multiple cancer types. miR-191 has predominantly been studied as an oncogene, but the role of miR-191 in the proliferation of primary cells is not well characterized, and the miR-191 targetome has not been experimentally profiled. Here we utilized RNA induced silencing complex immunoprecipitations as well as gene expression profiling to construct a genome wide miR-191 target profile. We show that miR-191 represses proliferation in primary human fibroblasts, identify multiple proto-oncogenes as novel miR-191 targets, including CDK9, NOTCH2, and RPS6KA3, and present evidence that miR-191 extensively mediates target expression through coding sequence (CDS pairing. Our results provide a comprehensive genome wide miR-191 target profile, and demonstrate miR-191's regulation of primary human fibroblast proliferation.

  14. MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes.

    Science.gov (United States)

    Polioudakis, Damon; Abell, Nathan S; Iyer, Vishwanath R

    2015-01-01

    miRNAs play a central role in numerous pathologies including multiple cancer types. miR-191 has predominantly been studied as an oncogene, but the role of miR-191 in the proliferation of primary cells is not well characterized, and the miR-191 targetome has not been experimentally profiled. Here we utilized RNA induced silencing complex immunoprecipitations as well as gene expression profiling to construct a genome wide miR-191 target profile. We show that miR-191 represses proliferation in primary human fibroblasts, identify multiple proto-oncogenes as novel miR-191 targets, including CDK9, NOTCH2, and RPS6KA3, and present evidence that miR-191 extensively mediates target expression through coding sequence (CDS) pairing. Our results provide a comprehensive genome wide miR-191 target profile, and demonstrate miR-191's regulation of primary human fibroblast proliferation.

  15. miRNA-216 and miRNA-499 target cyb561d2 in zebrafish in response to fipronil exposure.

    Science.gov (United States)

    Zhou, Yongyong; Huang, Hannian; Zhang, Kai; Ding, Xianfeng; Jia, Longlue; Yu, Liang; Zhu, Guonian; Guo, Jiangfeng

    2016-07-01

    MicroRNA (miRNA) can regulate the expression of its target gene by mediating mRNA cleavage or by translational repression at a post-transcriptional level. Usually, one miRNA may regulate many genes as its targets, while one gene may also be targeted by many miRNAs. We previously demonstrated that cyb561d2, whose protein product is involved in cell defense, and chemical stress, is targeted by miR-155 in adult zebrafish (Danio rerio) when exposed to fipronil (5-amino-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl) sulphinyl]-1H-pyrazole-3-carbonitrile). Microcosm Targets prediction showed that the cyb561d2 gene is also highly possibly targeted by miR-194a, miR-216b, miR-429, and miR-499. These interactions need to be further validated experimentally. In this study, we evaluated the effects of fipronil on miR-194a, miR-216b, miR-429, miR-499 and cyb561d2 in zebrafish and investigated whether these four miRNAs could regulate the expression of cyb561d2 in both mRNA and protein levels. The expression of cyb561d2 was upregulated in both mRNA and protein level in a dose-dependent manner upon stimulation of fipronil, and miR-216b and miR-499 were downregulated concurrently, whereas there was no significant changes were observed in the expression level of miR-194a and miR-429. The dual luciferase report assay demonstrated that miR-216b and miR-499 interacted with cyb561d2 3'-untranslated regions (3'-UTR), miR-194a and miR-429 did not stimulate degradation of cyb561d2 mRNA. The expression of cyb561d2 was reduced in both mRNA and protein level when ZF4 cells were transfected with miR-499 mimic, whereas expression level of both mRNA and protein was increased when endogenous miR-499 was inhibited by transfection with miR-499 inhibitor. Likewise, the mRNA and protein level of cyb561d2 was affected by treatment with the mimics and the inhibitor of miR-216b. In contrast, when ZF4 cells were transfected with a mimic of miR-194a or miR-429, the expression of cyb561d2

  16. Evaluation of SNPs in miR-196-a2, miR-27a and miR-146a as risk factors of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Renata Hezova; Rostislav Vyzula,; Ondrej Slaby; Alena Kovarikova; Julie Bienertova-Vasku; Milana Sachlova; Martina Redova; Anna Vasku; Marek Svoboda; Lenka Radova; Igor Kiss,

    2012-01-01

    AIM:To investigate whether selected single nucleotide polymorphisms (SNPs) in miR-196a2,miR-27a and miR146a genes are associated with sporadic colorectal cancer (CRC).METHODS:In order to investigate the effect of these SNPs in CRC,we performed a case-control study of 197 cases of sporadic CRC and 212 cancer-free controls originating from the Central-European Caucasian population using TaqMan Real-Time polymerase chain reaction and allelic discrimination analysis.RESULTS:The genotype and allele frequencies of SNPs were compared between the cases and the controis.None of the performed analysis showed any statistically significant results.CONCLUSION:Our data suggest a lack of association between rs11614913,rs895819 and rs2910164 and colorectal cancer risk in the Central-European Caucasian population,a population with an extremely high incidence of sporadic colorectal cancer.

  17. Quantitative miR analysis in chronic lymphocytic leukaemia/small lymphocytic lymphoma - proliferation centres are characterized by high miR-92a and miR-155 and low miR-150 expression.

    Science.gov (United States)

    Szurián, Kinga; Csala, Irén; Piurkó, Violetta; Deák, Linda; Matolcsy, András; Reiniger, Lilla

    2017-07-01

    Proliferation centres (PCs) are histological hallmarks of lymph nodes in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). Chromosomal abnormalities have already been described to accumulate preferably in the PCs as opposed to the intervening small cell areas. To further characterize the pathogenic role of PCs, the expression levels of 17 selected miRs known to be involved in the development of CLL/SLL were compared in the PCs and the intervening small cell areas in lymph nodes of 15 patients with CLL/SLL. The miR expression levels were also compared to the cytogenetic alterations defined by FISH analysis. Our results show that two known oncomiRs, miR-155 and -92a were upregulated and the tumour suppressor miR-150 was downregulated in the PCs. Low expression of miR-150 was also associated with loss of 11q. In summary we found significantly higher expression of oncomiRs and lower expression of a tumour suppressor miR in PCs of CLL/SLL lymph nodes, which support the hypothesis that the PCs may drive the disease and play a role in progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. miR-223 reverses experimental pulmonary arterial hypertension.

    Science.gov (United States)

    Meloche, Jolyane; Le Guen, Marie; Potus, François; Vinck, Jérôme; Ranchoux, Benoit; Johnson, Ian; Antigny, Fabrice; Tremblay, Eve; Breuils-Bonnet, Sandra; Perros, Frederic; Provencher, Steeve; Bonnet, Sébastien

    2015-09-15

    Pulmonary arterial hypertension (PAH) is a devastating disease affecting lung vasculature. The pulmonary arteries become occluded due to increased proliferation and suppressed apoptosis of the pulmonary artery smooth muscle cells (PASMCs) within the vascular wall. It was recently shown that DNA damage could trigger this phenotype by upregulating poly(ADP-ribose)polymerase 1 (PARP-1) expression, although the exact mechanism remains unclear. In silico analyses and studies in cancer demonstrated that microRNA miR-223 targets PARP-1. We thus hypothesized that miR-223 downregulation triggers PARP-1 overexpression, as well as the proliferation/apoptosis imbalance observed in PAH. We provide evidence that miR-223 is downregulated in human PAH lungs, distal PAs, and isolated PASMCs. Furthermore, using a gain and loss of function approach, we showed that increased hypoxia-inducible factor 1α, which is observed in PAH, triggers this decrease in miR-223 expression and subsequent overexpression of PARP-1 allowing PAH-PASMC proliferation and resistance to apoptosis. Finally, we demonstrated that restoring the expression of miR-223 in lungs of rats with monocrotaline-induced PAH reversed established PAH and provided beneficial effects on vascular remodeling, pulmonary resistance, right ventricle hypertrophy, and survival. We provide evidence that miR-223 downregulation in PAH plays an important role in numerous pathways implicated in the disease and restoring its expression is able to reverse PAH.

  19. Cell-free Circulating miRNA Biomarkers in Cancer

    Directory of Open Access Journals (Sweden)

    Meng-Hsuan Mo, Liang Chen, Yebo Fu, Wendy Wang, Sidney W. Fu

    2012-01-01

    Full Text Available Considerable attention and an enormous amount of resources have been dedicated to cancer biomarker discovery and validation. However, there are still a limited number of useful biomarkers available for clinical use. An ideal biomarker should be easily assayed with minimally invasive medical procedures but possess high sensitivity and specificity. Commonly used circulating biomarkers are proteins in serum, most of which require labor-intensive analysis hindered by low sensitivity in early tumor detection. Since the deregulation of microRNA (miRNA is associated with cancer development and progression, profiling of circulating miRNAs has been used in a number of studies to identify novel minimally invasive miRNA biomarkers. In this review, we discuss the origin of the circulating cell-free miRNAs and their carriers in blood. We summarize the clinical use and function of potentially promising miRNA biomarkers in a variety of different cancers, along with their downstream target genes in tumor initiation and development. Additionally, we analyze some technical challenges in applying miRNA biomarkers to clinical practice.

  20. Lipid Nanoparticles to Deliver miRNA in Cancer.

    Science.gov (United States)

    Campani, Virginia; De Rosa, Giuseppe; Misso, Gabriella; Zarone, Mayra R; Grimaldi, Anna

    MicroRNAs (miRNAs) are a class of post-transcriptional gene expression modulators. In the past two decades, over 1500 human miRNAs were discovered. These small non-coding RNAs regulate various biological processes, including cell growth, proliferation, differentiation, and cell death. Thus, miRNAs have been proposed as new therapeutical agents in different multifactorial diseases such as cancer. Since miRNAs therapies represent a great promise, many research studies have been focused on the development of delivery strategies to overcome miRNAs biopharmaceutical issues. Lipid delivery systems are undoubtedly the non-viral carriers most largely investigated due to their biocompatibility, biodegradability, easy production, low toxicity and immunogenicity, possibility to easily modify the carriers for targeting strategies. In this mini-review we provide a rapid and updated overview on the lipid delivery system currently used to deliver miRNAs, pointing out the progresses achieved in the optimization of these nanovectors, which led up to the first clinical trial.

  1. Characterization of the Melanoma miRNAome by Deep Sequencing.

    Directory of Open Access Journals (Sweden)

    Mitchell S Stark

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are 18-23 nucleotide non-coding RNAs that regulate gene expression in a sequence specific manner. Little is known about the repertoire and function of miRNAs in melanoma or the melanocytic lineage. We therefore undertook a comprehensive analysis of the miRNAome in a diverse range of pigment cells including: melanoblasts, melanocytes, congenital nevocytes, acral, mucosal, cutaneous and uveal melanoma cells. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced 12 small RNA libraries using Illumina's Genome Analyzer II platform. This massively parallel sequencing approach of a diverse set of melanoma and pigmen