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Sample records for absolute methylation levels

  1. Estimating absolute methylation levels at single-CpG resolution from methylation enrichment and restriction enzyme sequencing methods

    PubMed Central

    Stevens, Michael; Cheng, Jeffrey B.; Li, Daofeng; Xie, Mingchao; Hong, Chibo; Maire, Cécile L.; Ligon, Keith L.; Hirst, Martin; Marra, Marco A.; Costello, Joseph F.; Wang, Ting

    2013-01-01

    Recent advancements in sequencing-based DNA methylation profiling methods provide an unprecedented opportunity to map complete DNA methylomes. These include whole-genome bisulfite sequencing (WGBS, MethylC-seq, or BS-seq), reduced-representation bisulfite sequencing (RRBS), and enrichment-based methods such as MeDIP-seq, MBD-seq, and MRE-seq. These methods yield largely comparable results but differ significantly in extent of genomic CpG coverage, resolution, quantitative accuracy, and cost, at least while using current algorithms to interrogate the data. None of these existing methods provides single-CpG resolution, comprehensive genome-wide coverage, and cost feasibility for a typical laboratory. We introduce methylCRF, a novel conditional random fields–based algorithm that integrates methylated DNA immunoprecipitation (MeDIP-seq) and methylation-sensitive restriction enzyme (MRE-seq) sequencing data to predict DNA methylation levels at single-CpG resolution. Our method is a combined computational and experimental strategy to produce DNA methylomes of all 28 million CpGs in the human genome for a fraction (<10%) of the cost of whole-genome bisulfite sequencing methods. methylCRF was benchmarked for accuracy against Infinium arrays, RRBS, WGBS sequencing, and locus-specific bisulfite sequencing performed on the same human embryonic stem cell line. methylCRF transformation of MeDIP-seq/MRE-seq was equivalent to a biological replicate of WGBS in quantification, coverage, and resolution. We used conventional bisulfite conversion, PCR, cloning, and sequencing to validate loci where our predictions do not agree with whole-genome bisulfite data, and in 11 out of 12 cases, methylCRF predictions of methylation level agree better with validated results than does whole-genome bisulfite sequencing. Therefore, methylCRF transformation of MeDIP-seq/MRE-seq data provides an accurate, inexpensive, and widely accessible strategy to create full DNA methylomes. PMID:23804401

  2. Estimating absolute methylation levels at single-CpG resolution from methylation enrichment and restriction enzyme sequencing methods.

    PubMed

    Stevens, Michael; Cheng, Jeffrey B; Li, Daofeng; Xie, Mingchao; Hong, Chibo; Maire, Cécile L; Ligon, Keith L; Hirst, Martin; Marra, Marco A; Costello, Joseph F; Wang, Ting

    2013-09-01

    Recent advancements in sequencing-based DNA methylation profiling methods provide an unprecedented opportunity to map complete DNA methylomes. These include whole-genome bisulfite sequencing (WGBS, MethylC-seq, or BS-seq), reduced-representation bisulfite sequencing (RRBS), and enrichment-based methods such as MeDIP-seq, MBD-seq, and MRE-seq. These methods yield largely comparable results but differ significantly in extent of genomic CpG coverage, resolution, quantitative accuracy, and cost, at least while using current algorithms to interrogate the data. None of these existing methods provides single-CpG resolution, comprehensive genome-wide coverage, and cost feasibility for a typical laboratory. We introduce methylCRF, a novel conditional random fields-based algorithm that integrates methylated DNA immunoprecipitation (MeDIP-seq) and methylation-sensitive restriction enzyme (MRE-seq) sequencing data to predict DNA methylation levels at single-CpG resolution. Our method is a combined computational and experimental strategy to produce DNA methylomes of all 28 million CpGs in the human genome for a fraction (<10%) of the cost of whole-genome bisulfite sequencing methods. methylCRF was benchmarked for accuracy against Infinium arrays, RRBS, WGBS sequencing, and locus-specific bisulfite sequencing performed on the same human embryonic stem cell line. methylCRF transformation of MeDIP-seq/MRE-seq was equivalent to a biological replicate of WGBS in quantification, coverage, and resolution. We used conventional bisulfite conversion, PCR, cloning, and sequencing to validate loci where our predictions do not agree with whole-genome bisulfite data, and in 11 out of 12 cases, methylCRF predictions of methylation level agree better with validated results than does whole-genome bisulfite sequencing. Therefore, methylCRF transformation of MeDIP-seq/MRE-seq data provides an accurate, inexpensive, and widely accessible strategy to create full DNA methylomes. PMID:23804401

  3. Absolute photoionization cross-section of the methyl radical.

    SciTech Connect

    Taatjes, C. A.; Osborn, D. L.; Selby, T.; Meloni, G.; Fan, H.; Pratt, S. T.; Chemical Sciences and Engineering Division; SNL

    2008-01-01

    The absolute photoionization cross-section of the methyl radical has been measured using two completely independent methods. The CH{sub 3} photoionization cross-section was determined relative to that of acetone and methyl vinyl ketone at photon energies of 10.2 and 11.0 eV by using a pulsed laser-photolysis/time-resolved synchrotron photoionization mass spectrometry method. The time-resolved depletion of the acetone or methyl vinyl ketone precursor and the production of methyl radicals following 193 nm photolysis are monitored simultaneously by using time-resolved synchrotron photoionization mass spectrometry. Comparison of the initial methyl signal with the decrease in precursor signal, in combination with previously measured absolute photoionization cross-sections of the precursors, yields the absolute photoionization cross-section of the methyl radical; {sigma}{sub CH}(10.2 eV) = (5.7 {+-} 0.9) x 10{sup -18} cm{sup 2} and {sigma}{sub CH{sub 3}}(11.0 eV) = (6.0 {+-} 2.0) x 10{sup -18} cm{sup 2}. The photoionization cross-section for vinyl radical determined by photolysis of methyl vinyl ketone is in good agreement with previous measurements. The methyl radical photoionization cross-section was also independently measured relative to that of the iodine atom by comparison of ionization signals from CH{sub 3} and I fragments following 266 nm photolysis of methyl iodide in a molecular-beam ion-imaging apparatus. These measurements gave a cross-section of (5.4 {+-} 2.0) x 10{sup -18} cm{sup 2} at 10.460 eV, (5.5 {+-} 2.0) x 10{sup -18} cm{sup 2} at 10.466 eV, and (4.9 {+-} 2.0) x 10{sup -18} cm{sup 2} at 10.471 eV. The measurements allow relative photoionization efficiency spectra of methyl radical to be placed on an absolute scale and will facilitate quantitative measurements of methyl concentrations by photoionization mass spectrometry.

  4. Isolation and determination of absolute configurations of insect-produced methyl-branched hydrocarbons.

    PubMed

    Bello, Jan E; McElfresh, J Steven; Millar, Jocelyn G

    2015-01-27

    Although the effects of stereochemistry have been studied extensively for volatile insect pheromones, little is known about the effects of chirality in the nonvolatile methyl-branched hydrocarbons (MBCHs) used by many insects as contact pheromones. MBCHs generally contain one or more chiral centers and so two or more stereoisomeric forms are possible for each structure. However, it is not known whether insects biosynthesize these molecules in high stereoisomeric purity, nor is it known whether insects can distinguish the different stereoisomeric forms of MBCHs. This knowledge gap is due in part to the lack of methods for isolating individual MBCHs from the complex cuticular hydrocarbon (CHC) blends of insects, as well as the difficulty in determining the absolute configurations of the isolated MBCHs. To address these deficiencies, we report a straightforward method for the isolation of individual cuticular hydrocarbons from the complex CHC blend. The method was used to isolate 36 pure MBCHs from 20 species in nine insect orders. The absolute stereochemistries of the purified MBCHs then were determined by digital polarimetry. The absolute configurations of all of the isolated MBCHs were determined to be (R) by comparison with a library of synthesized, enantiomerically pure standards, suggesting that the biosynthetic pathways used to construct MBCHs are highly conserved within the Insecta. The development of a straightforward method for isolation of specific CHCs will enable determination of their functional roles by providing pure compounds for bioassays. PMID:25583471

  5. Isolation and determination of absolute configurations of insect-produced methyl-branched hydrocarbons

    PubMed Central

    Bello, Jan E.; McElfresh, J. Steven; Millar, Jocelyn G.

    2015-01-01

    Although the effects of stereochemistry have been studied extensively for volatile insect pheromones, little is known about the effects of chirality in the nonvolatile methyl-branched hydrocarbons (MBCHs) used by many insects as contact pheromones. MBCHs generally contain one or more chiral centers and so two or more stereoisomeric forms are possible for each structure. However, it is not known whether insects biosynthesize these molecules in high stereoisomeric purity, nor is it known whether insects can distinguish the different stereoisomeric forms of MBCHs. This knowledge gap is due in part to the lack of methods for isolating individual MBCHs from the complex cuticular hydrocarbon (CHC) blends of insects, as well as the difficulty in determining the absolute configurations of the isolated MBCHs. To address these deficiencies, we report a straightforward method for the isolation of individual cuticular hydrocarbons from the complex CHC blend. The method was used to isolate 36 pure MBCHs from 20 species in nine insect orders. The absolute stereochemistries of the purified MBCHs then were determined by digital polarimetry. The absolute configurations of all of the isolated MBCHs were determined to be (R) by comparison with a library of synthesized, enantiomerically pure standards, suggesting that the biosynthetic pathways used to construct MBCHs are highly conserved within the Insecta. The development of a straightforward method for isolation of specific CHCs will enable determination of their functional roles by providing pure compounds for bioassays. PMID:25583471

  6. The Relation between the Absolute Level of Parenting and Differential Parental Treatment with Adolescent Siblings' Adjustment

    ERIC Educational Resources Information Center

    Tamrouti-Makkink, Ilse D.; Dubas, Judith Semon; Gerris, Jan R. M.; van Aken, Marcel A. G.

    2004-01-01

    Background: The present study extends existing studies on the role of differential parental treatment in explaining individual differences in adolescent problem behaviors above the absolute level of parenting and clarifies the function of gender of the child, birth rank and gender constellation of the sibling dyads. Method: The absolute level of…

  7. A Feature Selection Algorithm to Compute Gene Centric Methylation from Probe Level Methylation Data

    PubMed Central

    Baur, Brittany; Bozdag, Serdar

    2016-01-01

    DNA methylation is an important epigenetic event that effects gene expression during development and various diseases such as cancer. Understanding the mechanism of action of DNA methylation is important for downstream analysis. In the Illumina Infinium HumanMethylation 450K array, there are tens of probes associated with each gene. Given methylation intensities of all these probes, it is necessary to compute which of these probes are most representative of the gene centric methylation level. In this study, we developed a feature selection algorithm based on sequential forward selection that utilized different classification methods to compute gene centric DNA methylation using probe level DNA methylation data. We compared our algorithm to other feature selection algorithms such as support vector machines with recursive feature elimination, genetic algorithms and ReliefF. We evaluated all methods based on the predictive power of selected probes on their mRNA expression levels and found that a K-Nearest Neighbors classification using the sequential forward selection algorithm performed better than other algorithms based on all metrics. We also observed that transcriptional activities of certain genes were more sensitive to DNA methylation changes than transcriptional activities of other genes. Our algorithm was able to predict the expression of those genes with high accuracy using only DNA methylation data. Our results also showed that those DNA methylation-sensitive genes were enriched in Gene Ontology terms related to the regulation of various biological processes. PMID:26872146

  8. Predicting DNA methylation level across human tissues

    PubMed Central

    Ma, Baoshan; Wilker, Elissa H.; Willis-Owen, Saffron A. G.; Byun, Hyang-Min; Wong, Kenny C. C.; Motta, Valeria; Baccarelli, Andrea A.; Schwartz, Joel; Cookson, William O. C. M.; Khabbaz, Kamal; Mittleman, Murray A.; Moffatt, Miriam F.; Liang, Liming

    2014-01-01

    Differences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R2 increases from 0.38 (original R2 between tissues) to 0.89 for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles. PMID:24445802

  9. Predicting DNA methylation level across human tissues.

    PubMed

    Ma, Baoshan; Wilker, Elissa H; Willis-Owen, Saffron A G; Byun, Hyang-Min; Wong, Kenny C C; Motta, Valeria; Baccarelli, Andrea A; Schwartz, Joel; Cookson, William O C M; Khabbaz, Kamal; Mittleman, Murray A; Moffatt, Miriam F; Liang, Liming

    2014-04-01

    Differences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R(2) increases from 0.38 (original R(2) between tissues) to 0.89 for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles. PMID:24445802

  10. Usage tests of oak moss absolutes containing high and low levels of atranol and chloroatranol.

    PubMed

    Mowitz, Martin; Svedman, Cecilia; Zimerson, Erik; Bruze, Magnus

    2014-07-01

    Atranol and chloroatranol are strong contact allergens in oak moss absolute, a lichen extract used in perfumery. Fifteen subjects with contact allergy to oak moss absolute underwent a repeated open application test (ROAT) using solutions of an untreated oak moss absolute (sample A) and an oak moss absolute with reduced content of atranol and chloroatranol (sample B). All subjects were in addition patch-tested with serial dilutions of samples A and B. Statistically significantly more subjects reacted to sample A than to sample B in the patch tests. No corresponding difference was observed in the ROAT, though there was a significant difference in the time required to elicit a positive reaction. Still, the ROAT indicates that the use of a cosmetic product containing oak moss absolute with reduced levels of atranol and chloroatranol is capable of eliciting an allergic reaction in previously sensitised individuals. PMID:24287679

  11. Statistical Quantification of Methylation Levels by Next-Generation Sequencing

    PubMed Central

    Wu, Guodong; Yi, Nengjun; Absher, Devin; Zhi, Degui

    2011-01-01

    Background/Aims Recently, next-generation sequencing-based technologies have enabled DNA methylation profiling at high resolution and low cost. Methyl-Seq and Reduced Representation Bisulfite Sequencing (RRBS) are two such technologies that interrogate methylation levels at CpG sites throughout the entire human genome. With rapid reduction of sequencing costs, these technologies will enable epigenotyping of large cohorts for phenotypic association studies. Existing quantification methods for sequencing-based methylation profiling are simplistic and do not deal with the noise due to the random sampling nature of sequencing and various experimental artifacts. Therefore, there is a need to investigate the statistical issues related to the quantification of methylation levels for these emerging technologies, with the goal of developing an accurate quantification method. Methods In this paper, we propose two methods for Methyl-Seq quantification. The first method, the Maximum Likelihood estimate, is both conceptually intuitive and computationally simple. However, this estimate is biased at extreme methylation levels and does not provide variance estimation. The second method, based on Bayesian hierarchical model, allows variance estimation of methylation levels, and provides a flexible framework to adjust technical bias in the sequencing process. Results We compare the previously proposed binary method, the Maximum Likelihood (ML) method, and the Bayesian method. In both simulation and real data analysis of Methyl-Seq data, the Bayesian method offers the most accurate quantification. The ML method is slightly less accurate than the Bayesian method. But both our proposed methods outperform the original binary method in Methyl-Seq. In addition, we applied these quantification methods to simulation data and show that, with sequencing depth above 40–300 (which varies with different tissue samples) per cleavage site, Methyl-Seq offers a comparable quantification

  12. Salt stress alters DNA methylation levels in alfalfa (Medicago spp).

    PubMed

    Al-Lawati, A; Al-Bahry, S; Victor, R; Al-Lawati, A H; Yaish, M W

    2016-01-01

    Modification of DNA methylation status is one of the mechanisms used by plants to adjust gene expression at both the transcriptional and posttranscriptional levels when plants are exposed to suboptimal conditions. Under abiotic stress, different cultivars often show heritable phenotypic variation accompanied by epigenetic polymorphisms at the DNA methylation level. This variation may provide the raw materials for plant breeding programs that aim to enhance abiotic stress tolerance, including salt tolerance. In this study, methylation-sensitive amplified polymorphism (MSAP) analysis was used to assess cytosine methylation levels in alfalfa (Medicago spp) roots exposed to increasing NaCl concentrations (0.0, 8.0, 12.0, and 20.0 dS/m). Eleven indigenous landraces were analyzed, in addition to a salt-tolerant cultivar that was used as a control. There was a slight increase in DNA methylation upon exposure to high levels of soil salinity. Phylogenetic analysis using MSAP showed epigenetic variation within and between the alfalfa landraces when exposed to saline conditions. Based on MSAP and enzyme-linked immunosorbent assay results, we found that salinity increased global DNA methylation status, particularly in plants exposed to the highest level of salinity (20 dS/m). Quantitative reverse transcription-polymerase chain reaction indicated that this might be mediated by the overexpression of methyltransferase homolog genes after exposure to saline conditions. DNA demethylation using 5-azacytidine reduced seedling lengths and dry and fresh weights, indicating a possible decrease in salinity tolerance. These results suggest that salinity affects DNA methylation flexibility. PMID:26985924

  13. Relative and absolute level populations in beam-foil-excited neutral helium

    NASA Technical Reports Server (NTRS)

    Davidson, J.

    1975-01-01

    Relative and absolute populations of 19 levels in beam-foil-excited neutral helium at 0.275 MeV have been measured. The singlet angular-momentum sequences show dependences on principal quantum number consistent with n to the -3rd power, but the triplet sequences do not. Singlet and triplet angular-momentum sequences show similar dependences on level excitation energy. Excitation functions for six representative levels were measured in the range from 0.160 to 0.500 MeV. The absolute level populations increase with energy, whereas the neutral fraction of the beam decreases with energy. Further, the P angular-momentum levels are found to be overpopulated with respect to the S and D levels. The overpopulation decreases with increasing principal quantum number.

  14. Simultaneous estimation of lithospheric uplift rates and absolute sea level change in southwest Scandinavia from inversion of sea level data

    NASA Astrophysics Data System (ADS)

    Nielsen, Lars; Hansen, Jens Morten; Hede, Mikkel Ulfeldt; Clemmensen, Lars B.; Pejrup, Morten; Noe-Nygaard, Nanna

    2014-11-01

    Relative sea level curves contain coupled information about absolute sea level change and vertical lithospheric movement. Such curves may be constructed based on, for example tide gauge data for the most recent times and different types of geological data for ancient times. Correct account for vertical lithospheric movement is essential for estimation of reliable values of absolute sea level change from relative sea level data and vise versa. For modern times, estimates of vertical lithospheric movement may be constrained by data (e.g. GPS-based measurements), which are independent from the relative sea level data. Similar independent data do not exist for ancient times. The purpose of this study is to test two simple inversion approaches for simultaneous estimation of lithospheric uplift rates and absolute sea level change rates for ancient times in areas where a dense coverage of relative sea level data exists and well-constrained average lithospheric movement values are known from, for example glacial isostatic adjustment (GIA) models. The inversion approaches are tested and used for simultaneous estimation of lithospheric uplift rates and absolute sea level change rates in southwest Scandinavia from modern relative sea level data series that cover the period from 1900 to 2000. In both approaches, a priori information is required to solve the inverse problem. A priori information about the average vertical lithospheric movement in the area of interest is critical for the quality of the obtained results. The two tested inversion schemes result in estimated absolute sea level rise of ˜1.2/1.3 mm yr-1 and vertical uplift rates ranging from approximately -1.4/-1.2 mm yr-1 (subsidence) to about 5.0/5.2 mm yr-1 if an a priori value of 1 mm yr-1 is used for the vertical lithospheric movement throughout the study area. In case the studied time interval is broken into two time intervals (before and after 1970), absolute sea level rise values of ˜0.8/1.2 mm yr-1 (before

  15. Multiphase permittivity imaging using absolute value electrical capacitance tomography data and a level set algorithm.

    PubMed

    Al Hosani, E; Soleimani, M

    2016-06-28

    Multiphase flow imaging is a very challenging and critical topic in industrial process tomography. In this article, simulation and experimental results of reconstructing the permittivity profile of multiphase material from data collected in electrical capacitance tomography (ECT) are presented. A multiphase narrowband level set algorithm is developed to reconstruct the interfaces between three- or four-phase permittivity values. The level set algorithm is capable of imaging multiphase permittivity by using one set of ECT measurement data, so-called absolute value ECT reconstruction, and this is tested with high-contrast and low-contrast multiphase data. Simulation and experimental results showed the superiority of this algorithm over classical pixel-based image reconstruction methods. The multiphase level set algorithm and absolute ECT reconstruction are presented for the first time, to the best of our knowledge, in this paper and critically evaluated. This article is part of the themed issue 'Supersensing through industrial process tomography'. PMID:27185966

  16. Absolute frequency measurement at 10-16 level based on the international atomic time

    NASA Astrophysics Data System (ADS)

    Hachisu, H.; Fujieda, M.; Kumagai, M.; Ido, T.

    2016-06-01

    Referring to International Atomic Time (TAI), we measured the absolute frequency of the 87Sr lattice clock with its uncertainty of 1.1 x 10-15. Unless an optical clock is continuously operated for the five days of the TAI grid, it is required to evaluate dead time uncertainty in order to use the available five-day average of the local frequency reference. We homogeneously distributed intermittent measurements over the five-day grid of TAI, by which the dead time uncertainty was reduced to low 10-16 level. Three campaigns of the five (or four)-day consecutive measurements have resulted in the absolute frequency of the 87Sr clock transition of 429 228 004 229 872.85 (47) Hz, where the systematic uncertainty of the 87Sr optical frequency standard amounts to 8.6 x 10-17.

  17. Modelling and measurement of the absolute level of power radiated by antenna integrated THz UTC photodiodes.

    PubMed

    Natrella, Michele; Liu, Chin-Pang; Graham, Chris; van Dijk, Frederic; Liu, Huiyun; Renaud, Cyril C; Seeds, Alwyn J

    2016-05-30

    We determine the output impedance of uni-travelling carrier (UTC) photodiodes at frequencies up to 400 GHz by performing, for the first time, 3D full-wave modelling of detailed UTC photodiode structures. In addition, we demonstrate the importance of the UTC impedance evaluation, by using it in the prediction of the absolute power radiated by an antenna integrated UTC, over a broad frequency range and confirming the predictions by experimental measurements up to 185 GHz. This is done by means of 3D full-wave modelling and is only possible since the source (UTC) to antenna impedance match is properly taken into account. We also show that, when the UTC-to-antenna coupling efficiency is modelled using the classical junction-capacitance/series-resistance concept, calculated and measured levels of absolute radiated power are in substantial disagreement, and the maximum radiated power is overestimated by a factor of almost 7 dB. The ability to calculate the absolute emitted power correctly enables the radiated power to be maximised through optimisation of the UTC-to-antenna impedance match. PMID:27410104

  18. A novel electrochemical approach for prolonged measurement of absolute levels of extracellular dopamine in brain slices.

    PubMed

    Burrell, Mark H; Atcherley, Christopher W; Heien, Michael L; Lipski, Janusz

    2015-11-18

    Tonic dopamine (DA) levels influence the activity of dopaminergic neurons and the dynamics of fast dopaminergic transmission. Although carbon fiber microelectrodes and fast-scan cyclic voltammetry (FSCV) have been extensively used to quantify stimulus-induced release and uptake of DA in vivo and in vitro, this technique relies on background subtraction and thus cannot provide information about absolute extracellular concentrations. It is also generally not suitable for prolonged (>90 s) recordings due to drift of the background current. A recently reported, modified FSCV approach called fast-scan controlled-adsorption voltammetry (FSCAV) has been used to assess tonic DA levels in solution and in the anesthetized mouse brain. Here we describe a novel extension of FSCAV to investigate pharmacologically induced, slowly occurring changes in tonic (background) extracellular DA concentration, and phasic (stimulated) DA release in brain slices. FSCAV was used to measure adsorption dynamics and changes in DA concentration (for up to 1.5 h, sampling interval 30 s, detection threshold < 10 nM) evoked by drugs affecting DA release and uptake (amphetamine, l-DOPA, pargyline, cocaine, Ro4-1284) in submerged striatal slices obtained from rats. We also show that combined FSCAV-FSCV recordings can be used for concurrent study of stimulated release and changes in tonic DA concentration. Our results demonstrate that FSCAV can be effectively used in brain slices to measure prolonged changes in extracellular level of endogenous DA expressed as absolute values, complementing studies conducted in vivo with microdialysis. PMID:26322962

  19. Oxidative stability and ignition quality of algae derived methyl esters containing varying levels of methyl eicosapentaenoate and methyl docosahexaenoate

    NASA Astrophysics Data System (ADS)

    Bucy, Harrison

    Microalgae is currently receiving strong consideration as a potential biofuel feedstock to help meet the advanced biofuels mandate of the 2007 Energy Independence and Security Act because of its theoretically high yield (gallons/acre/year) in comparison to current terrestrial feedstocks. Additionally, microalgae also do not compete with food and can be cultivated with wastewater on non-arable land. Microalgae lipids can be converted into a variety of biofuels including fatty acid methyl esters (e.g. FAME biodiesel), renewable diesel, renewable gasoline, or jet fuel. For microalgae derived FAME, the fuel properties will be directly related to the fatty acid composition of the lipids produced by the given microalgae strain. Several microalgae species under consideration for wide scale cultivation, such as Nannochloropsis, produce lipids with fatty acid compositions containing substantially higher quantities of long chainpolyunsaturated fatty acids (LC-PUFA) in comparison to terrestrial feedstocks. It is expected that increased levels of LC-PUFA will be problematic in terms of meeting all of the current ASTM specifications for biodiesel. For example, it is known that oxidative stability and cetane number decrease with increasing levels of LC-PUFA. However, these same LC-PUFA fatty acids, such as eicosapentaenoic acid (EPA: C20:5) and docosahexaenoic acid (DHA: C22:6) are known to have high nutritional value thereby making separation of these compounds economically attractive. Given the uncertainty in the future value of these LC-PUFA compounds and the economic viability of the separation process, the goal of this study was to examine the oxidative stability and ignition quality of algae-based FAME with varying levels of EPA and DHA removal. Oxidative stability tests were conducted at a temperature of 110°C and airflow of 10 L/h using a Metrohm 743 Rancimat with automatic induction period determination following the EN 14112 Method from the ASTM D6751 and EN 14214

  20. Pretreatment long interspersed element (LINE)-1 methylation levels, not early hypomethylation under treatment, predict hematological response to azacitidine in elderly patients with acute myeloid leukemia

    PubMed Central

    Cross, Michael; Bach, Enrica; Tran, Thao; Krahl, Rainer; Jaekel, Nadja; Niederwieser, Dietger; Junghanss, Christian; Maschmeyer, Georg; Al-Ali, Haifa Kathrin

    2013-01-01

    Background Epigenetic modulations, including changes in DNA cytosine methylation, are implicated in the pathogenesis and progression of acute myeloid leukemia (AML). Azacitidine is a hypomethylating agent that is incorporated into RNA as well as DNA. Thus, there is a rationale to its use in patients with AML. We determined whether baseline and/or early changes in the methylation of long interspersed element (LINE)-1 or CDH13 correlate with bone marrow blast clearance, hematological response, or survival in patients with AML treated with azacitidine. Methods An open label, phase I/II trial was performed in 40 AML patients (median bone marrow blast count was 42%) unfit for intensive chemotherapy treated with azacitidine 75 mg/m2/day subcutaneously for 5 days every 4 weeks. Bone marrow mononuclear cell samples were taken on day 0 (pretreatment) and day 15 during the first treatment cycle; LINE-1 and CDH13 methylation levels were quantified by methylation-specific, semiquantitative, real-time polymerase chain reaction. Results Treatment with azacitidine significantly reduced LINE-1 but not CDH13 methylation levels over the first cycle (P < 0.0001). Absolute LINE-1 methylation levels tended to be lower on day 0 (P = 0.06) and day 15 of cycle 1 (P = 0.03) in patients who went on to achieve subsequent complete remission, partial remission or hematological improvement versus patients with stable disease. However, the decrease in LINE-1 methylation over the first treatment cycle did not correlate with subsequent response (P = 0.31). Baseline methylation levels of LINE-1 or CDH13 did not correlate with disease-related prognostic factors, including cytogenetic risk, relapsed/refractory AML, or presence of NPM1 or FLT3 mutations. No correlation was observed between LINE-1 or CDH13 methylation levels and overall survival. Conclusion Analysis of baseline LINE-1 methylation levels may help identify elderly AML patients who are most likely to respond to azacitidine therapy. PMID

  1. Comparison of the absolute level of epigenetic marks 5-methylcytosine, 5-hydroxymethylcytosine, and 5-hydroxymethyluracil between human leukocytes and sperm.

    PubMed

    Guz, Jolanta; Gackowski, Daniel; Foksinski, Marek; Rozalski, Rafal; Olinski, Ryszard

    2014-09-01

    5-Methylcytosine is one of the most important epigenetic modifications and has a profound impact on embryonic development. After gamete fusion, there is a widespread and rapid active demethylation process of sperm DNA, which suggests that the paternal epigenome has an important role during embryonic development. To better understand the epigenome of sperm DNA and its possible involvement in a developing embryo, we determined epigenetic marks in human sperm DNA and in surrogate somatic tissue leukocytes; the analyzed epigenetic modifications included 5-methyl-2'-deoxycytidine, 5-hydroxymethyl-2'-deoxycytidine, and 5-hydroxymethyl-2'-deoxyuridine. For absolute determination of the modification, we used liquid chromatography with UV detection and tandem mass spectrometry techniques with isotopically labeled internal standards. Our analyses demonstrated, for the first time to date, that absolute global values of 5-methyl-2'-deoxycytidine, 5-hydroxymethyl-2'-deoxycytidine, and 5-hydroxymethyl-2'-deoxyuridine in sperm are highly statistically different from those observed for leukocyte DNA, with respective mean values of 3.815% versus 4.307%, 0.797 versus 2.945 per 10⁴ deoxynucleosides, and 5.209 versus 0.492 per 10⁶ deoxynucleosides. We hypothesize that an exceptionally high value of 5-hydroxymethyluracil in sperm (>10-fold higher than in leukocytes) may play a not yet recognized regulatory role in the paternal genome. PMID:25061097

  2. Validation of Mean Absolute Sea Level of the North Atlantic obtained from Drifter, Altimetry and Wind Data

    NASA Technical Reports Server (NTRS)

    Maximenko, Nikolai A.

    2003-01-01

    Mean absolute sea level reflects the deviation of the Ocean surface from geoid due to the ocean currents and is an important characteristic of the dynamical state of the ocean. Values of its spatial variations (order of 1 m) are generally much smaller than deviations of the geoid shape from ellipsoid (order of 100 m) that makes the derivation of the absolute mean sea level a difficult task for gravity and satellite altimetry observations. Technique used by Niiler et al. for computation of the absolute mean sea level in the Kuroshio Extension was then developed into more general method and applied by Niiler et al. (2003b) to the global Ocean. The method is based on the consideration of balance of horizontal momentum.

  3. Easy Absolute Values? Absolutely

    ERIC Educational Resources Information Center

    Taylor, Sharon E.; Mittag, Kathleen Cage

    2015-01-01

    The authors teach a problem-solving course for preservice middle-grades education majors that includes concepts dealing with absolute-value computations, equations, and inequalities. Many of these students like mathematics and plan to teach it, so they are adept at symbolic manipulations. Getting them to think differently about a concept that they…

  4. Genetic and environmental impacts on DNA methylation levels in twins.

    PubMed

    Yet, Idil; Tsai, Pei-Chien; Castillo-Fernandez, Juan E; Carnero-Montoro, Elena; Bell, Jordana T

    2016-01-01

    Epigenetics describes the study of cellular modifications that can modify the expression of genes without changing the DNA sequence. DNA methylation is one of the most stable and prevalent epigenetic mechanisms. Twin studies have been a valuable model for unraveling the genetic and epigenetic epidemiology of complex traits, and now offer a potential to dissect the factors that impact DNA methylation variability and its biomedical significance. The twin design specifically allows for the study of genetic, environmental and lifestyle factors, and their potential interactions, on epigenetic profiles. Furthermore, genetically identical twins offer a unique opportunity to assess nongenetic impacts on epigenetic profiles. Here, we summarize recent findings from twin studies of DNA methylation profiles across tissues, to define current knowledge regarding the genetic and nongenetic factors that influence epigenetic variation. PMID:26678685

  5. Clinical implications of the LINE-1 methylation levels in patients with gastrointestinal cancer.

    PubMed

    Baba, Yoshifumi; Murata, Asuka; Watanabe, Masayuki; Baba, Hideo

    2014-10-01

    Epigenetic alterations, such as DNA methylation, histone modification and the loss of genome imprinting, are important indicators of human carcinogenesis. DNA methylation is a fundamental epigenetic process that modulates the gene expression levels. In cancer cells, DNA methylation may be altered in two principle ways: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Long interspersed element-1 (LINE-1 or L1) is a repetitive DNA retrotransposon that duplicates via a copy-and-paste genetic mechanism. Since LINE-1 constitutes a substantial portion (approximately 17 %) of the human genome, the extent of LINE-1 methylation is regarded to be a surrogate marker of global DNA methylation. Measuring the level of LINE-1 methylation using pyrosequencing technology has emerged as a cost-effective and high-throughput method for assessing the global DNA methylation status. In some types of gastrointestinal (GI) cancers, LINE-1 hypomethylation is strongly associated with a poor prognosis, supporting its potential role as a prognostic marker. In addition, the LINE-1 methylation level may prove to be a useful clinical biomarker for assessing the risk of cancer or predicting the chemotherapeutic efficacy of treatment in patients with GI cancers. In this article, we summarize current knowledge regarding LINE-1 methylation and its clinical implications in GI cancers, including colorectal cancer, gastric cancer and esophageal cancer. PMID:24150097

  6. Exploring the saturation levels of stimulated Raman scattering in the absolute regime.

    PubMed

    Michel, D T; Depierreux, S; Stenz, C; Tassin, V; Labaune, C

    2010-06-25

    This Letter reports new experimental results that evidence the transition between the absolute and convective growth of stimulated Raman scattering (SRS). Significant reflectivities were observed only when the instability grows in the absolute regime. In this case, saturation processes efficiently limit the SRS reflectivity that is shown to scale linearly with the laser intensity, and the electron density and temperature. Such a scaling agrees with the one established by T. Kolber et al. [Phys. Fluids B 5, 138 (1993)10.1063/1.860861] and B Bezzerides et al. [Phys. Rev. Lett. 70, 2569 (1993)10.1103/PhysRevLett.70.2569], from numerical simulations where the Raman saturation is due to the coupling of electron plasma waves with ion waves dynamics. PMID:20867387

  7. Supplementary absolute differential cross sections for the excitation of atomic hydrogen's n=3 and 4 levels by electron impact

    SciTech Connect

    Sweeney, Christopher J.; Shyn, Tong W.; Grafe, Alan

    2004-05-01

    We have conducted measurements of absolute differential cross sections for the excitation of hydrogen atoms to their n=3(3S+3P+3D) and 4(4S+4P+4D+4F) levels. A modulated, crossed-beam method was employed, and the impact energies were 40 and 60 eV. Comparison of our results with those of others is quite favorable.

  8. Sperm global DNA methylation level: association with semen parameters and genome integrity.

    PubMed

    Montjean, D; Zini, A; Ravel, C; Belloc, S; Dalleac, A; Copin, H; Boyer, P; McElreavey, K; Benkhalifa, M

    2015-03-01

    Sperm DNA methylation abnormalities have been detected in oligozoospermic men. However, the association between sperm DNA methylation defects, sperm parameters and sperm DNA, and chromatin integrity remains poorly understood. This study was designed to clarify this issue. We recruited a cohort of 92 men (62 normozoospermic and 30 oligoasthenozoospermic) presenting for infertility evaluation during a 1-year period. Sperm global DNA methylation was evaluated by an ELISA-like method, DNA fragmentation was evaluated by flow cytometry-based terminal transferase dUTP nick end-labeling (TUNEL) assay (reported as DNA fragmentation index or DFI), and sperm denaturation was evaluated by aniline blue staining (reported as sperm denaturation index or SDI, a marker of chromatin compaction). We found a significant positive association between sperm global DNA methylation level and conventional sperm parameters (sperm concentration and motility), supported by the results of methylation analysis on H19-DMR. We also identified significant inverse relationships between sperm global DNA methylation, and, both DFI and SDI. However, sperm global DNA methylation level was not related to sperm vitality or morphology. Our findings suggest that global sperm DNA methylation levels are related to conventional sperm parameters, as well as, sperm chromatin and DNA integrity. PMID:25755112

  9. Synchronous absolute EIT in three thoracic planes at different gravity levels

    NASA Astrophysics Data System (ADS)

    Hahn, G.; Just, A.; Dittmar, J.; Fromm, K. H.; Quintel, M.

    2013-04-01

    The validity of absolute Electrical Impedance Tomography (a-EIT) for assessment of local lung volume has been investigated far less than the well evaluated ventilation monitoring by functional EIT (f-EIT). To achieve progress in a-EIT we investigated 10 healthy volunteers in an upright sitting position by using a-EIT at normal gravity (1 g), weightlessness (0 g) and approx. double gravity (1.8 g) during parabolic flight manoeuvres. Lung resistivity in three thoracic planes was determined by a-EIT using a multiple-plane synchronised Goe-MF II EIT system. Tomograms of resistivity at end-expiration in normal spontaneous breathing were reconstructed by a modified SIRT algorithm. Local lung resistivity was determined separately for both lungs. The respective resistivity values at 1 g and 1.8 g before and after weightlessness show an almost reversible behaviour along the sequence of gravity changes with a tendency to be lower after occurrence of weightlessness. The results reveal not only the expected varying resistivity of lung tissue in cranio-caudal direction but also a clear difference in these cranio-caudal stratifications of local lung volume between the left and right lung. The resolution and stability of absolute EIT seem to be valid and expressive for future investigations of unilateral lung volume under different physiological and pathological conditions.

  10. DNA methylation levels of α-synuclein intron 1 in the aging brain.

    PubMed

    de Boni, Laura; Riedel, Linda; Schmitt, Ina; Kraus, Theo F J; Kaut, Oliver; Piston, Dominik; Akbarian, Schahram; Wüllner, Ullrich

    2015-12-01

    DNA methylation patterns change with age, and aging itself is a major confounding risk factor for Parkinson's disease (PD). Duplication and triplication, that is, increased expression of the α-synuclein (SNCA) gene, cause familial PD, and demethylation of SNCA intron 1 has been shown to result in increased expression of SNCA. We thus hypothesized that age-related alterations of SNCA methylation might underly the increased susceptibility toward PD in later life. The present study sought to determine (1) whether alterations of SNCA intron 1 methylation occurred during aging, (2) whether the methylation pattern differed between men and women, and (3) whether purified neurons compared with non-neuronal cells exhibited different methylation patterns. The analysis of DNA from brain tissue and fluorescence activated cell sorting-sorted purified neurons of 41 individuals revealed only a minor increase of SNCA intron 1 DNA methylation levels in presumably healthy individuals during aging but no significant difference between men and women. Interestingly enough, methylation of SNCA intron 1 was higher in neurons compared with non-neuronal cells, although non-neuronal cells express lower levels of SNCA. Therefore, the normal pattern of SNCA methylation during aging should not result in increased expression of α-synuclein protein. It is thus likely that additional, yet not identified, mechanisms contribute to the tissue specificity of SNCA expression and the presumed dysregulation in PD. PMID:26422361

  11. Highly sensitive detection of DNA methylation levels by using a quantum dot-based FRET method.

    PubMed

    Ma, Yunfei; Zhang, Honglian; Liu, Fangming; Wu, Zhenhua; Lu, Shaohua; Jin, Qinghui; Zhao, Jianlong; Zhong, Xinhua; Mao, Hongju

    2015-11-01

    DNA methylation is the most frequently studied epigenetic modification that is strongly involved in genomic stability and cellular plasticity. Aberrant changes in DNA methylation status are ubiquitous in human cancer and the detection of these changes can be informative for cancer diagnosis. Herein, we reported a facile quantum dot-based (QD-based) fluorescence resonance energy transfer (FRET) technique for the detection of DNA methylation. The method relies on methylation-sensitive restriction enzymes for the differential digestion of genomic DNA based on its methylation status. Digested DNA is then subjected to PCR amplification for the incorporation of Alexa Fluor-647 (A647) fluorophores. DNA methylation levels can be detected qualitatively through gel analysis and quantitatively by the signal amplification from QDs to A647 during FRET. Furthermore, the methylation levels of three tumor suppressor genes, PCDHGB6, HOXA9 and RASSF1A, in 20 lung adenocarcinoma and 20 corresponding adjacent nontumorous tissue (NT) samples were measured to verify the feasibility of the QD-based FRET method and a high sensitivity for cancer detection (up to 90%) was achieved. Our QD-based FRET method is a convenient, continuous and high-throughput method, and is expected to be an alternative for detecting DNA methylation as a biomarker for certain human cancers. PMID:26446775

  12. Absolute Zero

    NASA Astrophysics Data System (ADS)

    Donnelly, Russell J.; Sheibley, D.; Belloni, M.; Stamper-Kurn, D.; Vinen, W. F.

    2006-12-01

    Absolute Zero is a two hour PBS special attempting to bring to the general public some of the advances made in 400 years of thermodynamics. It is based on the book “Absolute Zero and the Conquest of Cold” by Tom Shachtman. Absolute Zero will call long-overdue attention to the remarkable strides that have been made in low-temperature physics, a field that has produced 27 Nobel Prizes. It will explore the ongoing interplay between science and technology through historical examples including refrigerators, ice machines, frozen foods, liquid oxygen and nitrogen as well as much colder fluids such as liquid hydrogen and liquid helium. A website has been established to promote the series: www.absolutezerocampaign.org. It contains information on the series, aimed primarily at students at the middle school level. There is a wealth of material here and we hope interested teachers will draw their student’s attention to this website and its substantial contents, which have been carefully vetted for accuracy.

  13. Global DNA Methylation Level among Ciprofloxacin-Resistant Clinical Isolates of Escherichia coli

    PubMed Central

    Yugendran, Thiyagarajan

    2016-01-01

    Introduction Fluoroquinolone resistant clinical isolates belonging to the family Enterobacteriaceae is a major public health concern in India. Data analysis in JIPMER hospital revealed 10% rise in fluoroquinolone resistance within a span of three years suggestive of the possible involvement of mechanism/s other than QRDR capable of imparting fluoroquinolone resistance. DNA methylation regulates gene expression. Moreover, methylated cytosine is a mutational hotspot. Thus, DNA methylation can alter bacterial gene expression profile as well as facilitate the bacteria in accumulating mutations possibly leading to increased antimicrobial resistance. Therefore, the present study was carried out to identify the potential involvement of DNA methylation in ciprofloxacin resistance. Aim To elucidate and compare the methylation level of genomic and plasmid DNA among clinical isolates of E. coli sensitive and resistant to ciprofloxacin. Materials and Methods The study included 40 clinical E. coli isolates of which, 30 were ciprofloxacin-resistant and 10 were sensitive to ciprofloxacin. Genomic DNA (gDNA) and plasmid DNA were extracted and quantified. Methylation levels were elucidated using 5-mC DNA ELISA kit (Zymoresearch, California, USA) as per kit protocol and guidelines. Statistical Analysis Spearman correlation 2-tailed test. A p-value <0.05 was considered significant. Results The MIC values of sensitive and resistant strains against ciprofloxacin ranged from 0.125 μg/mL – 0.75 μg/mL and 8 μg/mL - >256 μg/mL respectively. No difference was found in plasmid DNA methylation level but, the gDNA methylation level of the resistant strains significantly differed from that of the sensitive strains. Based on Spearman correlation test gDNA methylation level of bacteria was found to be inversely proportional to its MIC against ciprofloxacin with p= -0.956 (p-value < 0.0001). Conclusion The influence of DNA methylation over plasmid-mediated quinolone resistance needs to be

  14. Different Levels of DNA Methylation Detected in Human Sperms after Morphological Selection Using High Magnification Microscopy

    PubMed Central

    Cassuto, Nino Guy; Montjean, Debbie; Siffroi, Jean-Pierre; Bouret, Dominique; Marzouk, Flora; Copin, Henri; Benkhalifa, Moncef

    2016-01-01

    Objective. To analyze DNA methylation levels between two groups of spermatozoa taken from the same sample, following morphological selection by high magnification (HM) at 6100x microscopy. A prospective study was conducted and studied 876 spermatozoa from 10 randomly selected men. Sperm morphology was characterized at HM according to criteria previously established. High-scoring Score 6 and low-scoring Score 0 sperm were selected. Sperm DNA methylation level was assessed using an immunoassay method targeting 5-methylcytosine residues by fluorescence microscopy with imaging analysis system to detect DNA methylation in single spermatozoon. Results. In total, 448 S6 spermatozoa and 428 S0 spermatozoa were analyzed. A strong relationship was found between sperm DNA methylation levels and sperm morphology observed at HM. Sperm DNA methylation level in the S6 group was significantly lower compared with that in the S0 group (p < 10−6), OR = 2.4; and p < 0.001, as determined using the Wilcoxon test. Conclusion. Differences in DNA methylation levels are associated with sperm morphology variations as observed at HM, which allows spermatozoa with abnormal levels to be discarded and ultimately decrease birth defects, malformations, and epigenetic diseases that may be transmitted from sperm to offspring in ICSI. PMID:27148551

  15. Different Levels of DNA Methylation Detected in Human Sperms after Morphological Selection Using High Magnification Microscopy.

    PubMed

    Cassuto, Nino Guy; Montjean, Debbie; Siffroi, Jean-Pierre; Bouret, Dominique; Marzouk, Flora; Copin, Henri; Benkhalifa, Moncef

    2016-01-01

    Objective. To analyze DNA methylation levels between two groups of spermatozoa taken from the same sample, following morphological selection by high magnification (HM) at 6100x microscopy. A prospective study was conducted and studied 876 spermatozoa from 10 randomly selected men. Sperm morphology was characterized at HM according to criteria previously established. High-scoring Score 6 and low-scoring Score 0 sperm were selected. Sperm DNA methylation level was assessed using an immunoassay method targeting 5-methylcytosine residues by fluorescence microscopy with imaging analysis system to detect DNA methylation in single spermatozoon. Results. In total, 448 S6 spermatozoa and 428 S0 spermatozoa were analyzed. A strong relationship was found between sperm DNA methylation levels and sperm morphology observed at HM. Sperm DNA methylation level in the S6 group was significantly lower compared with that in the S0 group (p < 10(-6)), OR = 2.4; and p < 0.001, as determined using the Wilcoxon test. Conclusion. Differences in DNA methylation levels are associated with sperm morphology variations as observed at HM, which allows spermatozoa with abnormal levels to be discarded and ultimately decrease birth defects, malformations, and epigenetic diseases that may be transmitted from sperm to offspring in ICSI. PMID:27148551

  16. Higher Alu Methylation Levels in Catch-Up Growth in Twenty-Year-Old Offsprings

    PubMed Central

    Rerkasem, Kittipan; Rattanatanyong, Prakasit; Rerkasem, Amaraporn; Wongthanee, Antika; Rungruengthanakit, Kittipong; Mangklabruks, Ampica; Mutirangura, Apiwat

    2015-01-01

    Alu elements and long interspersed element-1 (LINE-1 or L1) are two major human intersperse repetitive sequences. Lower Alu methylation, but not LINE-1, has been observed in blood cells of people in old age, and in menopausal women having lower bone mass and osteoporosis. Nevertheless, Alu methylation levels also vary among young individuals. Here, we explored phenotypes at birth that are associated with Alu methylation levels in young people. In 2010, 249 twenty-years-old volunteers whose mothers had participated in a study association between birth weight (BW) and nutrition during pregnancy in 1990, were invited to take part in our present study. In this study, the LINE-1 and Alu methylation levels and patterns were measured in peripheral mononuclear cells and correlated with various nutritional parameters during intrauterine and postnatal period of offspring. This included the amount of maternal intake during pregnancy, the mother’s weight gain during pregnancy, birth weight, birth length, and the rate of weight gain in the first year of life. Catch-up growth (CUG) was defined when weight during the first year was >0.67 of the standard score, according to WHO data. No association with LINE-1 methylation was identified. The mean level of Alu methylation in the CUG group was significantly higher than those non-CUG (39.61% and 33.66 % respectively, P < 0.0001). The positive correlation between the history of CUG in the first year and higher Alu methylation indicates the role of Alu methylation, not only in aging cells, but also in the human growth process. Moreover, here is the first study that demonstrated the association between a phenotype during the newborn period and intersperse repetitive sequences methylation during young adulthood. PMID:25807557

  17. Highly sensitive detection of DNA methylation levels by using a quantum dot-based FRET method

    NASA Astrophysics Data System (ADS)

    Ma, Yunfei; Zhang, Honglian; Liu, Fangming; Wu, Zhenhua; Lu, Shaohua; Jin, Qinghui; Zhao, Jianlong; Zhong, Xinhua; Mao, Hongju

    2015-10-01

    DNA methylation is the most frequently studied epigenetic modification that is strongly involved in genomic stability and cellular plasticity. Aberrant changes in DNA methylation status are ubiquitous in human cancer and the detection of these changes can be informative for cancer diagnosis. Herein, we reported a facile quantum dot-based (QD-based) fluorescence resonance energy transfer (FRET) technique for the detection of DNA methylation. The method relies on methylation-sensitive restriction enzymes for the differential digestion of genomic DNA based on its methylation status. Digested DNA is then subjected to PCR amplification for the incorporation of Alexa Fluor-647 (A647) fluorophores. DNA methylation levels can be detected qualitatively through gel analysis and quantitatively by the signal amplification from QDs to A647 during FRET. Furthermore, the methylation levels of three tumor suppressor genes, PCDHGB6, HOXA9 and RASSF1A, in 20 lung adenocarcinoma and 20 corresponding adjacent nontumorous tissue (NT) samples were measured to verify the feasibility of the QD-based FRET method and a high sensitivity for cancer detection (up to 90%) was achieved. Our QD-based FRET method is a convenient, continuous and high-throughput method, and is expected to be an alternative for detecting DNA methylation as a biomarker for certain human cancers.DNA methylation is the most frequently studied epigenetic modification that is strongly involved in genomic stability and cellular plasticity. Aberrant changes in DNA methylation status are ubiquitous in human cancer and the detection of these changes can be informative for cancer diagnosis. Herein, we reported a facile quantum dot-based (QD-based) fluorescence resonance energy transfer (FRET) technique for the detection of DNA methylation. The method relies on methylation-sensitive restriction enzymes for the differential digestion of genomic DNA based on its methylation status. Digested DNA is then subjected to PCR

  18. Infrared mapping of ultrasound fields generated by medical transducers: Feasibility of determining absolute intensity levels

    PubMed Central

    Khokhlova, Vera A.; Shmeleva, Svetlana M.; Gavrilov, Leonid R.; Martin, Eleanor; Sadhoo, Neelaksh; Shaw, Adam

    2013-01-01

    Considerable progress has been achieved in the use of infrared (IR) techniques for qualitative mapping of acoustic fields of high intensity focused ultrasound (HIFU) transducers. The authors have previously developed and demonstrated a method based on IR camera measurement of the temperature rise induced in an absorber less than 2 mm thick by ultrasonic bursts of less than 1 s duration. The goal of this paper was to make the method more quantitative and estimate the absolute intensity distributions by determining an overall calibration factor for the absorber and camera system. The implemented approach involved correlating the temperature rise measured in an absorber using an IR camera with the pressure distribution measured in water using a hydrophone. The measurements were conducted for two HIFU transducers and a flat physiotherapy transducer of 1 MHz frequency. Corresponding correction factors between the free field intensity and temperature were obtained and allowed the conversion of temperature images to intensity distributions. The system described here was able to map in good detail focused and unfocused ultrasound fields with sub-millimeter structure and with local time average intensity from below 0.1 W/cm2 to at least 50 W/cm2. Significantly higher intensities could be measured simply by reducing the duty cycle. PMID:23927199

  19. Infrared mapping of ultrasound fields generated by medical transducers: feasibility of determining absolute intensity levels.

    PubMed

    Khokhlova, Vera A; Shmeleva, Svetlana M; Gavrilov, Leonid R; Martin, Eleanor; Sadhoo, Neelaksh; Shaw, Adam

    2013-08-01

    Considerable progress has been achieved in the use of infrared (IR) techniques for qualitative mapping of acoustic fields of high intensity focused ultrasound (HIFU) transducers. The authors have previously developed and demonstrated a method based on IR camera measurement of the temperature rise induced in an absorber less than 2 mm thick by ultrasonic bursts of less than 1 s duration. The goal of this paper was to make the method more quantitative and estimate the absolute intensity distributions by determining an overall calibration factor for the absorber and camera system. The implemented approach involved correlating the temperature rise measured in an absorber using an IR camera with the pressure distribution measured in water using a hydrophone. The measurements were conducted for two HIFU transducers and a flat physiotherapy transducer of 1 MHz frequency. Corresponding correction factors between the free field intensity and temperature were obtained and allowed the conversion of temperature images to intensity distributions. The system described here was able to map in good detail focused and unfocused ultrasound fields with sub-millimeter structure and with local time average intensity from below 0.1 W/cm(2) to at least 50 W/cm(2). Significantly higher intensities could be measured simply by reducing the duty cycle. PMID:23927199

  20. Genomewide analysis indicates that queen larvae have lower methylation levels in the honey bee ( Apis mellifera)

    NASA Astrophysics Data System (ADS)

    Shi, Yuan Yuan; Yan, Wei Yu; Huang, Zachary Y.; Wang, Zi Long; Wu, Xiao Bo; Zeng, Zhi Jiang

    2013-02-01

    The honey bee is a social insect characterized by caste differentiation, by which a young larva can develop into either a queen or a worker. Despite possessing the same genome, queen and workers display marked differences in reproductive capacity, physiology, and behavior. Recent studies have shown that DNA methylation plays important roles in caste differentiation. To further explore the roles of DNA methylation in this process, we analyzed DNA methylome profiles of both queen larvae (QL) and worker larvae (WL) of different ages (2, 4, and 6 day old), by using methylated DNA immunoprecipitation-sequencing (meDIP-seq) technique. The global DNA methylation levels varied between the larvae of two castes. DNA methylation increased from 2-day- to 4-day-old QL and then decreased in 6-day-old larvae. In WL, methylation levels increased with age. The methylcytosines in both larvae were enriched in introns, followed by coding sequence (CDS) regions, CpG islands, 2 kbp downstream and upstream of genes, and 5' and 3' untranslated regions (UTRs). The number of differentially methylated genes (DMGs) in 2-, 4-, and 6-day-old QL and WL was 725, 3,013, and 5,049, respectively. Compared to 4- and 6-day-old WL, a large number of genes in QL were downmethylated, which were involved in many processes including development, reproduction, and metabolic regulation. In addition, some DMGs were concerned with caste differentiation.

  1. Genomewide analysis indicates that queen larvae have lower methylation levels in the honey bee (Apis mellifera).

    PubMed

    Shi, Yuan Yuan; Yan, Wei Yu; Huang, Zachary Y; Wang, Zi Long; Wu, Xiao Bo; Zeng, Zhi Jiang

    2013-02-01

    The honey bee is a social insect characterized by caste differentiation, by which a young larva can develop into either a queen or a worker. Despite possessing the same genome, queen and workers display marked differences in reproductive capacity, physiology, and behavior. Recent studies have shown that DNA methylation plays important roles in caste differentiation. To further explore the roles of DNA methylation in this process, we analyzed DNA methylome profiles of both queen larvae (QL) and worker larvae (WL) of different ages (2, 4, and 6 day old), by using methylated DNA immunoprecipitation-sequencing (meDIP-seq) technique. The global DNA methylation levels varied between the larvae of two castes. DNA methylation increased from 2-day- to 4-day-old QL and then decreased in 6-day-old larvae. In WL, methylation levels increased with age. The methylcytosines in both larvae were enriched in introns, followed by coding sequence (CDS) regions, CpG islands, 2 kbp downstream and upstream of genes, and 5' and 3' untranslated regions (UTRs). The number of differentially methylated genes (DMGs) in 2-, 4-, and 6-day-old QL and WL was 725, 3,013, and 5,049, respectively. Compared to 4- and 6-day-old WL, a large number of genes in QL were downmethylated, which were involved in many processes including development, reproduction, and metabolic regulation. In addition, some DMGs were concerned with caste differentiation. PMID:23238637

  2. DNA methylation levels analysis in four tissues of sea cucumber Apostichopus japonicus based on fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP) during aestivation.

    PubMed

    Zhao, Ye; Chen, Muyan; Storey, Kenneth B; Sun, Lina; Yang, Hongsheng

    2015-03-01

    DNA methylation plays an important role in regulating transcriptional change in response to environmental stimuli. In the present study, DNA methylation levels of tissues of the sea cucumber Apostichopus japonicus were analyzed by the fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP) technique over three stages of the aestivation cycle. Overall, a total of 26,963 fragments were amplified including 9112 methylated fragments among four sea cucumber tissues using 18 pairs of selective primers. Results indicated an average DNA methylation level of 33.79% for A. japonicus. The incidence of DNA methylation was different across tissue types in the non-aestivation stage: intestine (30.16%), respiratory tree (27.61%), muscle (27.94%) and body wall (56.25%). Our results show that hypermethylation accompanied deep-aestivation in A. japonicus, which suggests that DNA methylation may have an important role in regulating global transcriptional suppression during aestivation. Further analysis indicated that the main DNA modification sites were focused on intestine and respiratory tree tissues and that full-methylation but not hemi-methylation levels exhibited significant increases in the deep-aestivation stage. PMID:25461675

  3. Aircraft noise-induced awakenings are more reasonably predicted from relative than from absolute sound exposure levels.

    PubMed

    Fidell, Sanford; Tabachnick, Barbara; Mestre, Vincent; Fidell, Linda

    2013-11-01

    Assessment of aircraft noise-induced sleep disturbance is problematic for several reasons. Current assessment methods are based on sparse evidence and limited understandings; predictions of awakening prevalence rates based on indoor absolute sound exposure levels (SELs) fail to account for appreciable amounts of variance in dosage-response relationships and are not freely generalizable from airport to airport; and predicted awakening rates do not differ significantly from zero over a wide range of SELs. Even in conjunction with additional predictors, such as time of night and assumed individual differences in "sensitivity to awakening," nominally SEL-based predictions of awakening rates remain of limited utility and are easily misapplied and misinterpreted. Probabilities of awakening are more closely related to SELs scaled in units of standard deviates of local distributions of aircraft SELs, than to absolute sound levels. Self-selection of residential populations for tolerance of nighttime noise and habituation to airport noise environments offer more parsimonious and useful explanations for differences in awakening rates at disparate airports than assumed individual differences in sensitivity to awakening. PMID:24180775

  4. Placental adiponectin gene DNA methylation levels are associated with mothers' blood glucose concentration.

    PubMed

    Bouchard, Luigi; Hivert, Marie-France; Guay, Simon-Pierre; St-Pierre, Julie; Perron, Patrice; Brisson, Diane

    2012-05-01

    Growing evidence suggests that epigenetic profile changes occurring during fetal development in response to in utero environment variations could be one of the mechanisms involved in the early determinants of adult chronic diseases. In this study, we tested whether maternal glycemic status is associated with the adiponectin gene (ADIPOQ) DNA methylation profile in placenta tissue, in maternal circulating blood cells, and in cord blood cells. We found that lower DNA methylation levels in the promoter of ADIPOQ on the fetal side of the placenta were correlated with higher maternal glucose levels during the second trimester of pregnancy (2-h glucose after the oral glucose tolerance test; r(s) ≤ -0.21, P < 0.05). Lower DNA methylation levels on the maternal side of the placenta were associated with higher insulin resistance index (homeostasis model assessment of insulin resistance) during the second and third trimesters of pregnancy (r(s) ≤ -0.27, P < 0.05). Finally, lower DNA methylation levels were associated with higher maternal circulating adiponectin levels throughout pregnancy (r(s) ≤ -0.26, P < 0.05). In conclusion, the ADIPOQ DNA methylation profile was associated with maternal glucose status and with maternal circulating adiponectin concentration. Because adiponectin is suspected to have insulin-sensitizing proprieties, these epigenetic adaptations have the potential to induce sustained glucose metabolism changes in the mother and offspring later in life. PMID:22396200

  5. DNA Methylation Analysis of the Macrosatellite Repeat Associated with FSHD Muscular Dystrophy at Single Nucleotide Level

    PubMed Central

    Huichalaf, Claudia; Micheloni, Stefano; Ferri, Giulia; Caccia, Roberta; Gabellini, Davide

    2014-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited diseases of the skeletal muscle. It is characterized by asymmetric muscle weakness and variable penetrance. FSHD is linked to a reduction in copy number of the D4Z4 3.3 kb macrosatellite repeat, located in 4q35. This causes the epigenetic de-repression of FSHD candidate genes leading to disease. Nevertheless, the molecular mechanism responsible for silencing of FSHD candidate genes in healthy subjects is not fully understood. While a role for DNA methylation has been suggested, so far there is limited information regarding the methylation status of the 325 CpGs contained in each D4Z4 unit. Using a human/rodent monochromosomal hybrid cell line containing a single human chromosome 4, we performed an in depth analysis of DNA methylation for the majority of the CpGs inside D4Z4 at single nucleotide level. We found that D4Z4 is not uniformly methylated and that the level of DNA methylation does not correlate with the density of CpG dinucleotides. Moreover, in several D4Z4 regions characterized by near complete methylation, we found specific unmethylated CpGs. These elements are enriched in transcription factor binding sites that could be involved in muscle-specific D4Z4 activity. Our approach also detected differential methylation among different D4Z4 units, suggesting that the D4Z4 array is a mosaic of euchromatic and heterochromatic domains. Finally, we found that DNA methylation and histone de-acetylation are required to maintain FSHD candidate genes repressed. Taken together, our data underscore new players involved in the epigenetic regulation of the FSHD locus that could be targeted for therapeutic purposes. PMID:25545674

  6. Absolute vertical uplift rates in western Washington inferred from historical leveling and tide gauge data

    NASA Astrophysics Data System (ADS)

    Alba, S.; Weldon, R.; Livelybrooks, D.; Schmidt, D. A.

    2009-12-01

    We present a new uplift rate map for western Washington based on reanalysis of water levels from the 12 major NOAA tide gauges, three new water level series that combine NOAA’s historical records and our temporarily deployed gauges (at Cape Disappointment, Olympia, and Point Grenville), and reinterpretation of repeated 1st and 2nd order NGS leveling lines. As previous studies have concluded, EW gradients in the vertical deformation field are consistent with strain accumulation across the Cascadia subduction zone interface; however, uplift rates are highly variable along the outer Washington coast, ranging from approximately +4 to -2 mm/yr, suggesting significant changes in the depth of locking along strike. Improved measure of uplift rates from water level changes are accomplished by aggressively editing available hourly data and applying a transfer function approach to better remove tides, ocean and atmospheric “noise”. The analysis allows uplift to be determined from shorter and less complete records and in some cases permits the identification of transients like slow earthquakes. As we found in a similar study in Oregon (Burgette et al, JGR, 2009), releveled lines need to be anchored to as many tide gauges as possible to remove systematic error, and repeated releveling (especially of tidal benchmarks) is required to identify the few stable benchmarks that link water levels at the tidal stations to each other through time and to the regional NGS leveling lines. A portion of the westernmost Washington coast, from an approximate latitude of 47.4 to 47.9 N, is subsiding, and tilts suggest that the peak in uplift rate is well onshore, indicating that the locked zone extends onshore, in contrast to most previous studies. To the north, the peak in uplift approximately passes through Neah Bay (the NW corner of the Olympic Peninsula, lat. 48.3 N), and to the south the peak is offshore from Grays Harbor (lat. 47 N) to the Columbia River (lat. 46.2 N). A north

  7. Variation in cytosine methylation patterns during ploidy level conversions in Eragrostis curvula.

    PubMed

    Ochogavía, Ana C; Cervigni, Gerardo; Selva, Juan P; Echenique, Viviana C; Pessino, Silvina C

    2009-05-01

    In many species polyploidization involves rearrangements of the progenitor genomes, at both genetic and epigenetic levels. We analyzed the cytosine methylation status in a 'tetraploid-diploid-tetraploid' series of Eragrostis curvula with a common genetic background by using the MSAP (Methylation-sensitive Amplified Polymorphism) technique. Considerable levels of polymorphisms were detected during ploidy conversions. The total level of methylation observed was lower in the diploid genotype compared to the tetraploid ones. A significant proportion of the epigenetic modifications occurring during the tetraploid-diploid conversion reverted during the diploid-tetraploid one. Genetic and expression data from previous work were used to analyze correlation with methylation variation. All genetic, epigenetic and gene expression variation data correlated significantly when compared by pairs in simple Mantel tests. Dendrograms reflecting genetic, epigenetic and expression distances as well as principal coordinate analysis suggested that plants of identical ploidy levels present similar sets of data. Twelve (12) different genomic fragments displaying different methylation behavior during the ploidy conversions were isolated, sequenced and characterized. PMID:19160057

  8. Comparing the role of absolute sea-level rise and vertical tectonic motions in coastal flooding, Torres Islands (Vanuatu)

    NASA Astrophysics Data System (ADS)

    Ballu, Valérie; Bouin, Marie-Noëlle; Siméoni, Patricia; Crawford, Wayne C.; Calmant, Stephane; Boré, Jean-Michel; Kanas, Tony; Pelletier, Bernard

    2011-08-01

    Since the late 1990s, rising sea levels around the Torres Islands (north Vanuatu, southwest Pacific) have caused strong local and international concern. In 2002-2004, a village was displaced due to increasing sea incursions, and in 2005 a United Nations Environment Programme press release referred to the displaced village as perhaps the world's first climate change "refugees." We show here that vertical motions of the Torres Islands themselves dominate the apparent sea-level rise observed on the islands. From 1997 to 2009, the absolute sea level rose by 150 + /-20 mm. But GPS data reveal that the islands subsided by 117 + /-30 mm over the same time period, almost doubling the apparent gradual sea-level rise. Moreover, large earthquakes that occurred just before and after this period caused several hundreds of mm of sudden vertical motion, generating larger apparent sea-level changes than those observed during the entire intervening period. Our results show that vertical ground motions must be accounted for when evaluating sea-level change hazards in active tectonic regions. These data are needed to help communities and governments understand environmental changes and make the best decisions for their future.

  9. Comparing the role of absolute sea-level rise and vertical tectonic motions in coastal flooding, Torres Islands (Vanuatu)

    PubMed Central

    Ballu, Valérie; Bouin, Marie-Noëlle; Siméoni, Patricia; Crawford, Wayne C.; Calmant, Stephane; Boré, Jean-Michel; Kanas, Tony; Pelletier, Bernard

    2011-01-01

    Since the late 1990s, rising sea levels around the Torres Islands (north Vanuatu, southwest Pacific) have caused strong local and international concern. In 2002–2004, a village was displaced due to increasing sea incursions, and in 2005 a United Nations Environment Programme press release referred to the displaced village as perhaps the world’s first climate change “refugees.” We show here that vertical motions of the Torres Islands themselves dominate the apparent sea-level rise observed on the islands. From 1997 to 2009, the absolute sea level rose by 150 + /-20 mm. But GPS data reveal that the islands subsided by 117 + /-30 mm over the same time period, almost doubling the apparent gradual sea-level rise. Moreover, large earthquakes that occurred just before and after this period caused several hundreds of mm of sudden vertical motion, generating larger apparent sea-level changes than those observed during the entire intervening period. Our results show that vertical ground motions must be accounted for when evaluating sea-level change hazards in active tectonic regions. These data are needed to help communities and governments understand environmental changes and make the best decisions for their future. PMID:21795605

  10. DNA Methylation of Lipid-Related Genes Affects Blood Lipid Levels

    PubMed Central

    Pfeiffer, Liliane; Wahl, Simone; Pilling, Luke C.; Reischl, Eva; Sandling, Johanna K.; Kunze, Sonja; Holdt, Lesca M.; Kretschmer, Anja; Schramm, Katharina; Adamski, Jerzy; Klopp, Norman; Illig, Thomas; Hedman, Åsa K.; Roden, Michael; Hernandez, Dena G.; Singleton, Andrew B.; Thasler, Wolfgang E.; Grallert, Harald; Gieger, Christian; Herder, Christian; Teupser, Daniel; Meisinger, Christa; Spector, Timothy D.; Kronenberg, Florian; Prokisch, Holger; Melzer, David; Peters, Annette; Deloukas, Panos; Ferrucci, Luigi; Waldenberger, Melanie

    2016-01-01

    Background Epigenetic mechanisms might be involved in the regulation of interindividual lipid level variability and thus may contribute to the cardiovascular risk profile. The aim of this study was to investigate the association between genome-wide DNA methylation and blood lipid levels high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. Observed DNA methylation changes were also further analyzed to examine their relationship with previous hospitalized myocardial infarction. Methods and Results Genome-wide DNA methylation patterns were determined in whole blood samples of 1776 subjects of the Cooperative Health Research in the Region of Augsburg F4 cohort using the Infinium HumanMethylation450 BeadChip (Illumina). Ten novel lipid-related CpG sites annotated to various genes including ABCG1, MIR33B/SREBF1, and TNIP1 were identified. CpG cg06500161, located in ABCG1, was associated in opposite directions with both high-density lipoprotein cholesterol (β coefficient=−0.049; P=8.26E-17) and triglyceride levels (β=0.070; P=1.21E-27). Eight associations were confirmed by replication in the Cooperative Health Research in the Region of Augsburg F3 study (n=499) and in the Invecchiare in Chianti, Aging in the Chianti Area study (n=472). Associations between triglyceride levels and SREBF1 and ABCG1 were also found in adipose tissue of the Multiple Tissue Human Expression Resource cohort (n=634). Expression analysis revealed an association between ABCG1 methylation and lipid levels that might be partly mediated by ABCG1 expression. DNA methylation of ABCG1 might also play a role in previous hospitalized myocardial infarction (odds ratio, 1.15; 95% confidence interval=1.06–1.25). Conclusions Epigenetic modifications of the newly identified loci might regulate disturbed blood lipid levels and thus contribute to the development of complex lipid-related diseases. PMID:25583993

  11. Is an absolute level of cortical beta suppression required for proper movement? Magnetoencephalographic evidence from healthy aging.

    PubMed

    Heinrichs-Graham, Elizabeth; Wilson, Tony W

    2016-07-01

    Previous research has connected a specific pattern of beta oscillatory activity to proper motor execution, but no study to date has directly examined how resting beta levels affect motor-related beta oscillatory activity in the motor cortex. Understanding this relationship is imperative to determining the basic mechanisms of motor control, as well as the impact of pathological beta oscillations on movement execution. In the current study, we used magnetoencephalography (MEG) and a complex movement paradigm to quantify resting beta activity and movement-related beta oscillations in the context of healthy aging. We chose healthy aging as a model because preliminary evidence suggests that beta activity is elevated in older adults, and thus by examining older and younger adults we were able to naturally vary resting beta levels. To this end, healthy younger and older participants were recorded during motor performance and at rest. Using beamforming, we imaged the peri-movement beta event-related desynchronization (ERD) and extracted virtual sensors from the peak voxels, which enabled absolute and relative beta power to be assessed. Interestingly, absolute beta power during the pre-movement baseline was much stronger in older relative to younger adults, and older adults also exhibited proportionally large beta desynchronization (ERD) responses during motor planning and execution compared to younger adults. Crucially, we found a significant relationship between spontaneous (resting) beta power and beta ERD magnitude in both primary motor cortices, above and beyond the effects of age. A similar link was found between beta ERD magnitude and movement duration. These findings suggest a direct linkage between beta reduction during movement and spontaneous activity in the motor cortex, such that as spontaneous beta power increases, a greater reduction in beta activity is required to execute movement. We propose that, on an individual level, the primary motor cortices have an

  12. Absolute Sea Level Monitoring and Altimeter Calibration At Gavdos, Crete, Greece

    NASA Astrophysics Data System (ADS)

    Pavlis, E. C.; Gavdos Team

    We present the mean sea level (MSL) monitoring aspect of the altimeter calibration fa- cility under deployment on western Crete and the isle of Gavdos. The Eastern Mediter- ranean area is one of great interest for its intense tectonic activity as well as for its regional oceanography. Recent observations have convincingly demonstrated the im- portance of that area for the regional meteorological and climatological changes. Tide- gauge monitoring with GPS has gained importance lately since tectonics contaminate the inferred sea level variations, and a global network of tide-gauges with long his- torical records can be used as satellite altimeter calibration sites for current and fu- ture missions (e.g. TOPEX/POSEIDON, GFO, JASON-1, ENVISAT, etc.). This is at present a common IOC-GLOSS-IGS effort, already underway (TIGA). Crete hosts two of the oldest tide-gauges in the regional network and our project will further ex- pand it to the south of the island with a new site on the isle of Gavdos, the southernmost European parcel of land. One component of our "GAVDOS" project is the repeated occupation of two already in existence tide-gauge sites at Souda Bay and Heraklion, and their tie to the new facility. We show here initial results from positioning of these sites and some of the available tidal records. Gavdos is situated under a ground-track crossing point of the present T/P and JASON-1 orbits. It is an ideal calibration site if the tectonic motions are monitored precisely and continuously. Our plans include the deployment of additional instrumentation at this site: GPS and DORIS beacons for positioning, transponders for direct calibration, water vapor radiometers, GPS-loaded buoys, airborne surveys with gravimeters and laser profiling lidars, etc., to ensure the best possible and most reliable results.

  13. Lipase-catalyzed resolution of (2R*,3S*)- and (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol at low temperatures and determination of the absolute configurations of the four stereoisomers.

    PubMed

    Sakai, Takashi; Liu, Yu; Ohta, Hiroshi; Korenaga, Toshinobu; Ema, Tadashi

    2005-02-18

    [reaction: see text] Lipase-catalyzed resolution of (2R*,3S*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-2, at low temperatures gave synthetically useful (2R,3S)-2 and its acetate (2S,3R)-2a with (2S)-selectivity (E = 55 at -40 degrees C), while a similar reaction of (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-3, gave (2S,3S)-3 and its acetate (2R,3R)-3a with (2R)-selectivity (E = 73 at -20 degrees C). Compound (+/-)-2 was prepared conveniently via diastereoselective addition of MeMgBr to tert-butyl 3-phenyl-2H-azirine-2-carboxylate, (+/-)-1a, which was successfully prepared by the Neber reaction of oxime tosylate of tert-butyl benzoyl acetate 7a. The tert-butyl ester was requisite to promote this reaction. For determination of the absolute configuration of (2S,3R)-2a, enantiopure (2S,3R)-2 was independently prepared in three steps involving diastereoselective methylation of 3-phenyl-2H-azirine-2-methanol, (S)-10, with MeMgBr. The absolute configuration of (2S,3S)-3 was determined by X-ray analysis of the corresponding N-(S)-2-(6-methoxy-2-naphthyl)propanoyl derivative (S,S,S)-13. PMID:15704972

  14. COMPARISON OF VENTED AND ABSOLUTE PRESSURE TRANSDUCERS FOR WATER-LEVEL MONITORING IN HANFORD SITE CENTRAL PLATEAU WELLS

    SciTech Connect

    MCDONALD JP

    2011-09-08

    Automated water-level data collected using vented pressure transducers deployed in Hanford Site Central Plateau wells commonly display more variability than manual tape measurements in response to barometric pressure fluctuations. To explain this difference, it was hypothesized that vented pressure transducers installed in some wells are subject to barometric pressure effects that reduce water-level measurement accuracy. Vented pressure transducers use a vent tube, which is open to the atmosphere at land surface, to supply air pressure to the transducer housing for barometric compensation so the transducer measurements will represent only the water pressure. When using vented transducers, the assumption is made that the air pressure between land surface and the well bore is in equilibrium. By comparison, absolute pressure transducers directly measure the air pressure within the wellbore. Barometric compensation is achieved by subtracting the well bore air pressure measurement from the total pressure measured by a second transducer submerged in the water. Thus, no assumption of air pressure equilibrium is needed. In this study, water-level measurements were collected from the same Central Plateau wells using both vented and absolute pressure transducers to evaluate the different methods of barometric compensation. Manual tape measurements were also collected to evaluate the transducers. Measurements collected during this study demonstrated that the vented pressure transducers over-responded to barometric pressure fluctuations due to a pressure disequilibrium between the air within the wellbores and the atmosphere at land surface. The disequilibrium is thought to be caused by the relatively long time required for barometric pressure changes to equilibrate between land surface and the deep vadose zone and may be exacerbated by the restriction of air flow between the well bore and the atmosphere due to the presence of sample pump landing plates and well caps. The

  15. Resource base influences genome-wide DNA methylation levels in wild baboons (Papio cynocephalus).

    PubMed

    Lea, Amanda J; Altmann, Jeanne; Alberts, Susan C; Tung, Jenny

    2016-04-01

    Variation in resource availability commonly exerts strong effects on fitness-related traits in wild animals. However, we know little about the molecular mechanisms that mediate these effects, or about their persistence over time. To address these questions, we profiled genome-wide whole-blood DNA methylation levels in two sets of wild baboons: (i) 'wild-feeding' baboons that foraged naturally in a savanna environment and (ii) 'Lodge' baboons that had ready access to spatially concentrated human food scraps, resulting in high feeding efficiency and low daily travel distances. We identified 1014 sites (0.20% of sites tested) that were differentially methylated between wild-feeding and Lodge baboons, providing the first evidence that resource availability shapes the epigenome in a wild mammal. Differentially methylated sites tended to occur in contiguous stretches (i.e., in differentially methylated regions or DMRs), in promoters and enhancers, and near metabolism-related genes, supporting their functional importance in gene regulation. In agreement, reporter assay experiments confirmed that methylation at the largest identified DMR, located in the promoter of a key glycolysis-related gene, was sufficient to causally drive changes in gene expression. Intriguingly, all dispersing males carried a consistent epigenetic signature of their membership in a wild-feeding group, regardless of whether males dispersed into or out of this group as adults. Together, our findings support a role for DNA methylation in mediating ecological effects on phenotypic traits in the wild and emphasize the dynamic environmental sensitivity of DNA methylation levels across the life course. PMID:26508127

  16. Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome

    PubMed Central

    Pedersen, Jakob Skou; Valen, Eivind; Velazquez, Amhed M. Vargas; Parker, Brian J.; Rasmussen, Morten; Lindgreen, Stinus; Lilje, Berit; Tobin, Desmond J.; Kelly, Theresa K.; Vang, Søren; Andersson, Robin; Jones, Peter A.; Hoover, Cindi A.; Tikhonov, Alexei; Prokhortchouk, Egor; Rubin, Edward M.; Sandelin, Albin; Gilbert, M. Thomas P.; Krogh, Anders; Willerslev, Eske; Orlando, Ludovic

    2014-01-01

    Epigenetic information is available from contemporary organisms, but is difficult to track back in evolutionary time. Here, we show that genome-wide epigenetic information can be gathered directly from next-generation sequence reads of DNA isolated from ancient remains. Using the genome sequence data generated from hair shafts of a 4000-yr-old Paleo-Eskimo belonging to the Saqqaq culture, we generate the first ancient nucleosome map coupled with a genome-wide survey of cytosine methylation levels. The validity of both nucleosome map and methylation levels were confirmed by the recovery of the expected signals at promoter regions, exon/intron boundaries, and CTCF sites. The top-scoring nucleosome calls revealed distinct DNA positioning biases, attesting to nucleotide-level accuracy. The ancient methylation levels exhibited high conservation over time, clustering closely with modern hair tissues. Using ancient methylation information, we estimated the age at death of the Saqqaq individual and illustrate how epigenetic information can be used to infer ancient gene expression. Similar epigenetic signatures were found in other fossil material, such as 110,000- to 130,000-yr-old bones, supporting the contention that ancient epigenomic information can be reconstructed from a deep past. Our findings lay the foundation for extracting epigenomic information from ancient samples, allowing shifts in epialleles to be tracked through evolutionary time, as well as providing an original window into modern epigenomics. PMID:24299735

  17. Obesity and ischemic stroke modulate the methylation levels of KCNQ1 in white blood cells.

    PubMed

    Gómez-Úriz, Ana M; Milagro, Fermín I; Mansego, María L; Cordero, Paúl; Abete, Itziar; De Arce, Ana; Goyenechea, Estíbaliz; Blázquez, Vanessa; Martínez-Zabaleta, Maite; Martínez, José Alfredo; López De Munain, Adolfo; Campión, Javier

    2015-03-01

    Obesity and stroke are multifactorial diseases in which genetic, epigenetic and lifestyle factors are involved. The research aims were, first, the description of genes with differential epigenetic regulation obtained by an 'omics' approach in patients with ischemic stroke and, second, to determine the importance of some regions of these selected genes in biological processes depending on the body mass index. A case-control study using two populations was designed. The first population consisted of 24 volunteers according to stroke/non-stroke and normal weight/obesity conditions. The second population included 60 stroke patients and 55 controls classified by adiposity. DNA from the first population was analyzed with a methylation microarray, showing 80 cytosine-guanine dinucleotides (CpG) sites differentially methylated in stroke and 96 CpGs in obesity, whereas 59 CpGs showed interaction. After validating these data by MassArray Epityper, the promoter region of peptidase M20 domain containing 1 (PM20D1) gene was significantly hypermethylated in stroke patients. One CpG site at Caldesmon 1 (CALD1) gene showed an interaction between stroke and obesity. Two CpGs located in the genes Wilms' tumor 1 (WT1) and potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) were significantly hypermethylated in obese patients. In the second population, KCNQ1 was also hypermethylated in the obese subjects. Two CpGs of this gene were subsequently validated by methylation-sensitive high-resolution melting. Moreover, KCNQ1 methylation levels were associated with plasma KCNQ1 protein concentrations. In conclusion, obesity induced changes in the KCNQ1 methylation pattern which were also dependent on stroke. Furthermore, the epigenetic marks differentially methylated in the stroke patients were dependent on the previous obese state. These DNA methylation patterns could be used as future potential stroke biomarkers. PMID:25429063

  18. Application of the LUminometric Methylation Assay to ecological species: tissue quality requirements and a survey of DNA methylation levels in animals.

    PubMed

    Head, Jessica A; Mittal, Krittika; Basu, Niladri

    2014-09-01

    The LUminometric Methylation Assay (LUMA) measures global DNA methylation. LUMA depends on digestion of DNA with methyl-sensitive and methyl-insensitive restriction enzymes, followed by pyrosequencing. Until recently, LUMA has been principally used for biomedical research. Here, we use chickens as a model to investigate sample quality issues relating to LUMA and then apply the method to ecological species. First, we assessed the effect of tissue storage conditions on DNA methylation values. This is an important consideration for ecological species because samples are not always ideally preserved and LUMA is sensitive to poor DNA quality. We found that good quality LUMA data could be obtained from chicken liver and brain tissues stored at 21 °C for at least 2 and 12 h, respectively. Longer storage times introduced nonspecific peaks to pyrograms which were associated with reduced DNA methylation. Repeatedly, freezing and thawing the tissues did not affect LUMA data. Second, we measured DNA methylation in 12 species representing five animal classes: amphibians (African and Western clawed frog), reptiles (green anole lizard), fish (yellow perch, goldfish, lake trout), mammals (American mink, polar bear, short-beaked common dolphin, Atlantic white-sided dolphin) and birds (chicken, Japanese quail). We saw a pattern of high DNA methylation in fish (84-87%), and intermediate levels in mammals (68-72%) and birds (52-71%). This pattern corresponds well with previous measures of DNA methylation generated by HPLC. Our data represent the first CpG methylation values to be reported in several species and provide a basis for studying patterns of epigenetic inheritance in an ecological context. PMID:24576185

  19. PAQR3 gene expression and its methylation level in colorectal cancer tissues

    PubMed Central

    Li, Ri-Heng; Zhang, Ai-Min; Li, Shuang; Li, Tian-Yang; Wang, Lian-Jing; Zhang, Hao-Ran; Shi, Jian-Wei; Liu, Xiao-Rui; Chen, Yuan; Chen, Ya-Chao; Wei, Teng-Yao; Gao, Ying; Li, Wei; Tang, Hong-Ying; Tang, Mei-Yu

    2016-01-01

    The aim of the present study was to investigate the PAQR3 gene expression and its methylation level in colorectal cancer tissues, as well as the association with colorectal cancer clinical data. In total, 54 cases of colorectal cancer tissue samples and normal adjacent tissue samples were collected between June, 2013 and July, 2014. RT-PCR and western blot analysis were used to detect the mRNA and protein levels of PAQR3 in colorectal samples, respectively. MSP was used to detect the methylation level of PAQR3 gene in colorectal samples, which was compared with colorectal data. The results showed that a decreased expression level of PAQR3 mRNA in colorectal cancer tissues and the expression reduction rate was 57.4% (31/54). Similarly, the expression level of PAQR3 protein was reduced in cancer tissues, and the reduction rate was 46.3% (25/54), while the protein expression reduction rate in cancer adjacent tissue was 5.6% (3/54), and the difference was statistically significant (P<0.05). Furthermore, the methylation rates of PAQR3 in cancer tissues and cancer adjacent tissues were 33.3% (18/54) and 5.6% (3/54), respectively. In addition, PAQR3 mRNA and protein levels in colorectal cancer tissues were associated with the differentiation degree, lymphatic metastasis and tumor infiltration depth. The methylation level of PAQR3 was associated with age, differentiated degree, lymphatic metastasis and tumor infiltration depth. In conclusion, the expression of PAQR3 mRNA and protein in colorectal cancer was reduced and methylation of PAQR3 occurred. Although the PAQR3 mRNA and protein levels were not associated with gender, age or the location of tumor, there was an association with differentiation degree, lymphatic metastasis and tumor infiltration depth. In addition, the methylation level of PAQR3 was not correlated with gender or tumor location, but was correlated with age, differentiation degree, lymphatic metastasis and tumor infiltration depth. PMID:27588124

  20. Probing the Crystal Structure, Composition-Dependent Absolute Energy Levels, and Electrocatalytic Properties of Silver Indium Sulfide Nanostructures.

    PubMed

    Saji, Pintu; Ganguli, Ashok K; Bhat, Mohsin A; Ingole, Pravin P

    2016-04-18

    The absolute electronic energy levels in silver indium sulfide (AIS) nanocrystals (NCs) with varying compositions and crystallographic phases have been determined by using cyclic voltammetry. Different crystallographic phases, that is, metastable cubic, orthorhombic, monoclinic, and a mixture of cubic and orthorhombic AIS NCs, were studied. The band gap values estimated from the cyclic voltammetry measurements match well with the band gap values calculated from the diffuse reflectance spectra measurements. The AIS nanostructures were found to show good electrocatalytic activity towards the hydrogen evolution reaction (HER). Our results clearly establish that the electronic and electrocatalytic properties of AIS NCs are strongly sensitive to the composition and crystal structure of AIS NCs. Monoclinic AIS was found to be the most active HER electrocatalyst, with electrocatalytic activity that is almost comparable to the MoS2 -based nanostructures reported in the literature, whereas cubic AIS was observed to be the least active of the studied crystallographic phases and compositions. In view of the HER activity and electronic band structure parameters observed herein, we hypothesize that the Fermi energy level of AIS NCs is an important factor that decides the electrocatalytic efficiency of these nanocomposites. The work presented herein, in addition to being the first of its kind regarding the composition and phase-dependence of electrochemical aspects of AIS NCs, also presents a simple solvothermal method for the synthesis of different crystallographic phases with various Ag/In molar ratios. PMID:26812447

  1. PrEMeR-CG: inferring nucleotide level DNA methylation values from MethylCap-seq data

    PubMed Central

    Park, Jincheol; Zoller, Mike W.; Ganbat, Javkhlan-Ochir; Curfman, John; Byrd, John C.; Lin, Shili; Marcucci, Guido; Yan, Pearlly; Bundschuh, Ralf

    2014-01-01

    Motivation: DNA methylation is an epigenetic change occurring in genomic CpG sequences that contribute to the regulation of gene transcription both in normal and malignant cells. Next-generation sequencing has been used to characterize DNA methylation status at the genome scale, but suffers from high sequencing cost in the case of whole-genome bisulfite sequencing, or from reduced resolution (inability to precisely define which of the CpGs are methylated) with capture-based techniques. Results: Here we present a computational method that computes nucleotide-resolution methylation values from capture-based data by incorporating fragment length profiles into a model of methylation analysis. We demonstrate that it compares favorably with nucleotide-resolution bisulfite sequencing and has better predictive power with respect to a reference than window-based methods, often used for enrichment data. The described method was used to produce the methylation data used in tandem with gene expression to produce a novel and clinically significant gene signature in acute myeloid leukemia. In addition, we introduce a complementary statistical method that uses this nucleotide-resolution methylation data for detection of differentially methylated features. Availability: Software in the form of Python and R scripts is available at http://bioserv.mps.ohio-state.edu/premer and is free for non-commercial use. Contact: pearlly.yan@osumc.edu; bundschuh@mps.ohio-state.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25178460

  2. Oxidative stress levels are correlated with P15 and P16 gene promoter methylation in myelodysplastic syndrome patients.

    PubMed

    Gonçalves, Ana Cristina; Cortesão, Emília; Oliveiros, Barbara; Alves, Vera; Espadana, Ana Isabel; Rito, Luís; Magalhães, Emília; Pereira, Sónia; Pereira, Amélia; Costa, José Manuel Nascimento; Mota-Vieira, Luisa; Sarmento-Ribeiro, Ana Bela

    2016-08-01

    Oxidative stress and abnormal DNA methylation have been implicated in some types of cancer, namely in myelodysplastic syndromes (MDS). Since both mechanisms are observed in MDS patients, we analyzed the correlation of intracellular levels of peroxides, superoxide anion, and glutathione (GSH), as well as ratios of peroxides/GSH and superoxide/GSH, with the methylation status of P15 and P16 gene promoters in bone marrow leukocytes from MDS patients. Compared to controls, these patients had lower GSH content, higher peroxide levels, peroxides/GSH and superoxide/GSH ratios, as well as higher methylation frequency of P15 and P16 gene promoters. Moreover, patients with methylated P15 gene had higher oxidative stress levels than patients without methylation (peroxides: 460 ± 42 MIF vs 229 ± 25 MIF, p = 0.001; superoxide: 383 ± 48 MIF vs 243 ± 17 MIF, p = 0.022; peroxides/GSH: 2.50 ± 0.08 vs 1.04 ± 0.34, p < 0.001; superoxide/GSH: 1.76 ± 0.21 vs 1.31 ± 0.10, p = 0.007). Patients with methylated P16 and at least one methylated gene had higher peroxide levels as well as peroxides/GSH ratio than patients without methylation. Interestingly, oxidative stress levels allow the discrimination of patients without methylation from ones with methylated P15, methylated P16, or at least one methylated (P15 or P16) promoter. Taken together, these findings support the hypothesis that oxidative stress is correlated with P15 and P16 hypermethylation. PMID:25982567

  3. Absolute level-to-level rate constants for inelastic collisions and exchange reactions in lithium + gaseous lithium(v,j) going to gaseous lithium(v',j') + lithium

    NASA Astrophysics Data System (ADS)

    Coppage, Steven Danforth

    We report 644 absolute level-to-level inelastic and reactive constants for the L7i*2 A1S+u (nui, ji) + 7Li → L7i*2 A1S+u (nu', j') + 7Li system with initial molecular quantum numbers nui = 2 and ji = 3, 11, and 19. We collected 87 rate constants for rotationally inelastic and vibrationally elastic collisions, 281 rate constants for vibrationally inelastic collisions, and 276 constants for exchange reactions with final vibrational levels from nu f = 0 to nuf = 3. Inelastic collisions are characterized by even changes in rotational quantum number, j , and exchange reactions are identified by odd Deltaj. Level-to-level rate constants for even Deltaj inelastic collisions show distributions similar to those in rare gas collisions with the excited Li2 molecule. The ECS (energy corrected sudden) scaling law of DePristo, et al., fit the vibrationally elastic data well. Reactive rate constant results are characterized by a statistical distribution for Deltanu of 0, -1, and -2 at a substantially reduced effective temperature consistent with a kinematic model proposed by Picconatto et al. Fitting quasiclassical trajectory studies to the data using a modified LEPS potential surface provide first insights into the parameters of the excited-state Li3* three-body potential.

  4. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    PubMed

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

  5. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels

    PubMed Central

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F.; Eszes, Marika; Faull, Richard L.M.; Curtis, Maurice A.; Waldvogel, Henry J.; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V.; Coppola, Giovanni; Yang, X. William

    2016-01-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=−0.41, p=5.5×10−8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

  6. Optimization of an HPLC Method for Determining the Genomic Methylation Levels of Taxus Cells.

    PubMed

    Li, Xiao-li; Yuan, Jie; Dong, Yan-shan; Fu, Chun-hua; Li, Mao-Teng; Yu, Long-jiang

    2016-02-01

    An HPLC method for quantifying total DNA methylation in Taxus chinensis cells is described. Optimal conditions for the method were established as follows: DNA was hydrolyzed with DNA degradase at 37°C for 3 h. The mobile phase was a mixture of Solvent A [50 mM potassium dihydrogen phosphate/triethylamine (100:0.2, v/v)] and Solvent B (methanol); the gradient was 10% (v/v) solvent B. The calibration curves for deoxycytidine monophosphate (dCMP) and methylated dCMP were linear within 1.0-160.0 µg mL(-1), with correlation coefficients of 0.9996 and 0.9998. The limits of detection for dCMP and 5-mdCMP were 0.482 and 0.301 ng mL(-1), respectively, and the limits of quantification were 1.6 and 1.0 ng mL(-1), respectively. The method has been validated according to the current International Conference Harmonization guidelines. The method was able to quantify the content of dCMP and methylated dCMP specifically, accurately and precisely. The global DNA methylation level in different Taxus cells was measured using as little as 3 µg of DNA according to the optimized procedure. In addition, degradation of 5-methylcytosine was prevented. PMID:26341490

  7. Association between serum organochlorines and global methylation level of leukocyte DNA among Japanese women: a cross-sectional study.

    PubMed

    Itoh, Hiroaki; Iwasaki, Motoki; Kasuga, Yoshio; Yokoyama, Shiro; Onuma, Hiroshi; Nishimura, Hideki; Kusama, Ritsu; Yoshida, Teruhiko; Yokoyama, Kazuhito; Tsugane, Shoichiro

    2014-08-15

    While the global methylation level of leukocyte DNA may be a suitable biomarker for cancer risk, the level may be influenced by multiple factors, both environmental and host-related, one of which is exposure to environmental pollutants. To date, three epidemiologic studies have examined associations between serum organochlorine levels and global DNA methylation level, but their findings are not fully consistent, and the associations thus require confirmation in other well-characterized populations. We tested the association between organochlorine exposure and the global DNA methylation level of leukocytes in Japanese women. We conducted a cross-sectional study using the control group of a breast cancer case-control study in Japan. Subjects were 403 Japanese women who provided blood samples. Serum polychlorinated biphenyls (PCBs) and nine pesticide-related organochlorines were measured by gas chromatography isotope-dilution high-resolution mass spectrometry. Further, global methylation level of peripheral leukocyte DNA among 399 women was measured by luminometric methylation assay. Linear trends in the association between methylation and quartile levels of organochlorines were evaluated by regression coefficients in a multivariable linear regression model. We found significant inverse associations between the global methylation level in leukocyte DNA and many of the organochlorine levels measured. Global methylation level was significantly decreased by 0.33-0.83% per quartile category for serum o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT), p,p'-DDT, p,p'-dichlorodiphenyldichloroethylene, trans-nonachlor, oxychlordane, hexachlorobenzene, β-hexachlorocyclohexane, PCB17, PCB52/69, PCB74, PCB114, and PCB183. Serum organochlorine levels were inversely associated with the global methylation level of leukocyte DNA in a relatively large sample of Japanese women. PMID:24880549

  8. LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk

    PubMed Central

    Karami, Sara; Andreotti, Gabriella; Liao, Linda M; Pfeiffer, Ruth M; Weinstein, Stephanie J; Purdue, Mark P; Hofmann, Jonathan N; Albanes, Demetrius; Mannisto, Satu; Moore, Lee E

    2015-01-01

    Abstract Higher levels of LINE1 methylation in blood DNA have been associated with increased kidney cancer risk using post-diagnostically collected samples; however, this association has never been examined using pre-diagnostic samples. We examined the association between LINE1 %5mC and renal cell carcinoma (RCC) risk using pre-diagnostic blood DNA from the United States-based, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (215 cases/436 controls), and the Alpha-tocopherol, Beta-carotene Cancer Prevention Study (ATBC) of Finnish male smokers (191 cases/575 controls). Logistic regression adjusted for age at blood draw, study center, pack-years of smoking, body mass index, hypertension, dietary alcohol intake, family history of cancer, and sex was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) using cohort and sex-specific methylation categories. In PLCO, higher, although non-significant, RCC risk was observed for participants at or above median methylation level (M2) compared to those below the median (M1) (OR: 1.37, 95% CI: 0.96–1.95). The association was stronger in males (M2 vs. M1, OR: 1.54, 95% CI: 1.00–2.39) and statistically significant among male smokers (M2 vs. M1, OR: 2.60, 95% CI: 1.46–4.63). A significant interaction for smoking was also detected (P-interaction: 0.01). No association was found among females or female smokers. Findings for male smokers were replicated in ATBC (M2 vs. M1, OR: 1.31, 95% CI: 1.07–1.60). In a pooled analysis of PLCO and ATBC male smokers (281cases/755controls), the OR among subjects at or above median methylation level (M2) compared to those below the median (M1) was 1.89 (95% CI: 1.34–2.67, P-value: 3 x 10–4); a trend was also observed by methylation quartile (P-trend: 0.002). These findings suggest that higher LINE1 methylation levels measured prior to cancer diagnosis may be a biomarker of future RCC risk among male smokers. PMID:25647181

  9. Cyclosporin A does not affect the absolute rate of cortical bone resorption at the organ level in the growing rat.

    PubMed

    Klein, L; Lemel, M S; Wolfe, M S; Shaffer, J

    1994-10-01

    The weanling rat, an animal model of rapid bone turnover, was used to evaluate the effects of various doses of cyclosporin A (CsA) on various bones during different time periods. Sprague-Dawley male rats were extensively prelabeled with 3H-tetracycline during 1-3 weeks of age. At 4 weeks of age, four groups of rats were given daily subcutaneous injections: vehicle or CsA--low dose (10 mg/kg), intermediary dose (20 mg/kg), or high dose (30 mg/kg) for 7, 14, or 28 days. Three different whole bones--the femur (low turnover), scapula (moderate turnover), and lumbar-6 vertebra (high turnover) were harvested intact at 4, 5, 6, and 8 weeks of age. The whole bones were assayed weekly for total dry defatted weight, calcium mass (formation), and loss of 3H-tetracycline (bone resorption) following treatment with CsA. Serum CsA levels, calcium creatinine, and alkaline phosphatase were measured weekly. Significant decreases in serum calcium and alkaline phosphatase were observed at 1 and 2 weeks, and were normalized by 4 weeks of treatment. No significant changes in serum creatinine were noted. For all three doses of CsA, no effect was observed on the absolute rate of cortical bone resorption of three different, whole bones over three time periods. Body weight and bone formation in treated animals was significantly smaller in a dose- and time-related fashion compared with control animals at sacrifice. However, compared with the initial control animals, body weights and bone masses of the final treated animals were much larger, suggesting that the smaller bone masses were due to insufficient growth and slow gain in bone mass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7820781

  10. DNA methylation modifies urine biomarker levels in 1,6-hexamethylene diisocyanate exposed workers: a pilot study.

    PubMed

    Nylander-French, Leena A; Wu, Michael C; French, John E; Boyer, Jayne C; Smeester, Lisa; Sanders, Alison P; Fry, Rebecca C

    2014-12-01

    DNA methylation may mediate inter-individual responses to chemical exposure and, thus, modify biomarker levels of exposure and effects. We analyzed inter-individual differences in inhalation and skin exposure to 1,6-hexamethylene diisocyanate (HDI) and urine biomarker 1,6-hexamethylene diamine (HDA) levels in 20 automotive spray-painters. Genome-wide 5-methyl cytosine (CpG) DNA methylation was assessed in each individual's peripheral blood mononuclear cells (PBMC) DNA using the Illumina 450K CpG array. Mediation analysis using linear regression models adjusted for age, ethnicity, and smoking was conducted to identify and assess the association between HDI exposure, CpG methylation, and urine HDA biomarker levels. We did not identify any CpGs common to HDI exposure and biomarker level suggesting that CpG methylation is a mediator that only partially explains the phenotype. Functional significance of genic- and intergenic-CpG methylation status was tested using protein-protein or protein-DNA interactions and gene-ontology enrichment to infer networks. Combined, the results suggest that methylation has the potential to affect HDI mass transport, permeation, and HDI metabolism. We demonstrate the potential use of PBMC methylation along with quantitative exposure and biomarker data to guide further investigation into the mediators of occupational exposure and biomarkers and its role in risk assessment. PMID:25445006

  11. P64QUANTITATIVE MGMT METHYLATION ANALYSIS BY PYROSEQUENCING REVEALS A STRONG CORRELATION BETWEEN 1P/19Q CO-DELETION AND HIGH LEVEL METHYLATION IN HIGH GRADE GLIOMAS

    PubMed Central

    Laxton, R.; Doey, L.; Aizpurua, M.; Bodi, I.; King, A.; Chandler, C.; Bhangoo, R.; Beaney, R.; Brazil, L.; Ashkan, K.; Al-Sarraj, S.

    2014-01-01

    INTRODUCTION: Pyrosequencing is a method that allows MGMT methylation to be measured in a quantitative manner. MGMT methylation, along with 1p/19q co-deletion and IDH1 mutation, is an important biomarker in high grade gliomas. MGMT methylation indicates an improved response to temozolomide chemotherapy; patients with 1p/19q co-deleted anaplastic oligodendrogliomas benefit from the addition of chemotherapy to radiotherapy. Aim: To compare the average MGMT promoter methylation level of high grade gliomas and correlate it with other clinical parameters and markers including IDH1&2 mutation and 1p/19q co-deletion. METHOD: For 171 high grade gliomas MGMT methylation analysis was performed by pyrosequencing, mutations to IDH1 and IDH2 genes were also detected by pyrosequencing, or immunohistochemistry (n = 166). Screening for 1p/19q deletion was by fluorescence in situ hybridisation (n = 46). Statistical analysis was performed using R-Stats v2.15.2. RESULTS: The results show that higher methylation was correlated with lower grade and mutation to either IDH1 or IDH2 (27.0% vs. 16.6% p = 0.008; and 27.5 vs. 16.1 p = 0.002 respectively). Interestingly 1p/19q co-deletion versus non co-deletion was associated with a particularly high level of methylation (42.2% vs. 17.7% p = 0.001). No significant differences were seen for age or gender. CONCLUSION: The results offer a potential explanation for the improved prognosis seen in glioma patients with 1p/19q co-deletion and when combined with IDH mutation status may provide an extra control to confirm true 1p/19q co-deletion.

  12. Use of implantable pellets to administer low levels of methyl mercury to fish

    USGS Publications Warehouse

    Arnold, B.S.; Jagoe, C.H.; Gross, T.S.

    1999-01-01

    Implantable pellets of methyl mercury chloride were tested in Nile Tilapia (Oreochromis niloticus) to appraise the effectiveness of the method for chronic studies of mercury. Two dosing regimes of 15 and 1.5 grams/CH3HgCl pellet (test 1) and 1 and 0.1 grams/pellet (test 2-3) of methyl mercury chloride were used in three tests. Additional pellets containing only matrix were used as controls. The pellets were inserted into the peritoneal cavity along with a microchip for identification. Three methods of incision closure: sutures and two types of surgical glue, were tested. Pellets used in test one released the dose too fast, resulting in premature death of the fish. Results from test 2 and 3 show blood mercury concentrations over time and tissue levels at necropsy consistent with dose suggesting that this is a viable method of dosing fish.

  13. Correlation of DNA methylation levels in blood and saliva DNA in young girls of the LEGACY Girls study

    PubMed Central

    Wu, Hui-Chen; Wang, Qiao; Chung, Wendy K; Andrulis, Irene L; Daly, Mary B; John, Esther M; Keegan, Theresa HM; Knight, Julia; Bradbury, Angela R; Kappil, Maya A; Gurvich, Irina; Santella, Regina M; Terry, Mary Beth

    2014-01-01

    Many epidemiologic studies of environmental exposures and disease susceptibility measure DNA methylation in white blood cells (WBC). Some studies are also starting to use saliva DNA as it is usually more readily available in large epidemiologic studies. However, little is known about the correlation of methylation between WBC and saliva DNA. We examined DNA methylation in three repetitive elements, Sat2, Alu, and LINE-1, and in four CpG sites, including AHRR (cg23576855, cg05575921), cg05951221 at 2q37.1, and cg11924019 at CYP1A1, in 57 girls aged 6–15 years with blood and saliva collected on the same day. We measured all DNA methylation markers by bisulfite-pyrosequencing, except for Sat2 and Alu, which were measured by the MethyLight assay. Methylation levels measured in saliva DNA were lower than those in WBC DNA, with differences ranging from 2.8% for Alu to 14.1% for cg05575921. Methylation levels for the three repetitive elements measured in saliva DNA were all positively correlated with those in WBC DNA. However, there was a wide range in the Spearman correlations, with the smallest correlation found for Alu (0.24) and the strongest correlation found for LINE-1 (0.73). Spearman correlations for cg05575921, cg05951221, and cg11924019 were 0.33, 0.42, and 0.79, respectively. If these findings are replicated in larger studies, they suggest that, for selected methylation markers (e.g., LINE-1), methylation levels may be highly correlated between blood and saliva, while for others methylation markers, the levels may be more tissue specific. Thus, in studies that differ by DNA source, each interrogated site should be separately examined in order to evaluate the correlation in DNA methylation levels across DNA sources. PMID:24756002

  14. Correlation of DNA methylation levels in blood and saliva DNA in young girls of the LEGACY Girls study.

    PubMed

    Wu, Hui-Chen; Wang, Qiao; Chung, Wendy K; Andrulis, Irene L; Daly, Mary B; John, Esther M; Keegan, Theresa H M; Knight, Julia; Bradbury, Angela R; Kappil, Maya A; Gurvich, Irina; Santella, Regina M; Terry, Mary Beth

    2014-07-01

    Many epidemiologic studies of environmental exposures and disease susceptibility measure DNA methylation in white blood cells (WBC). Some studies are also starting to use saliva DNA as it is usually more readily available in large epidemiologic studies. However, little is known about the correlation of methylation between WBC and saliva DNA. We examined DNA methylation in three repetitive elements, Sat2, Alu, and LINE-1, and in four CpG sites, including AHRR (cg23576855, cg05575921), cg05951221 at 2q37.1, and cg11924019 at CYP1A1, in 57 girls aged 6-15 years with blood and saliva collected on the same day. We measured all DNA methylation markers by bisulfite-pyrosequencing, except for Sat2 and Alu, which were measured by the MethyLight assay. Methylation levels measured in saliva DNA were lower than those in WBC DNA, with differences ranging from 2.8% for Alu to 14.1% for cg05575921. Methylation levels for the three repetitive elements measured in saliva DNA were all positively correlated with those in WBC DNA. However, there was a wide range in the Spearman correlations, with the smallest correlation found for Alu (0.24) and the strongest correlation found for LINE-1 (0.73). Spearman correlations for cg05575921, cg05951221, and cg11924019 were 0.33, 0.42, and 0.79, respectively. If these findings are replicated in larger studies, they suggest that, for selected methylation markers (e.g., LINE-1), methylation levels may be highly correlated between blood and saliva, while for others methylation markers, the levels may be more tissue specific. Thus, in studies that differ by DNA source, each interrogated site should be separately examined in order to evaluate the correlation in DNA methylation levels across DNA sources. PMID:24756002

  15. Effects of pH and Repellent Tactic Stimuli on Protein Methylation Levels in Escherichia coli

    PubMed Central

    Slonczewski, Joan L.; Macnab, Robert M.; Alger, Jeffry R.; Castle, Anna M.

    1982-01-01

    Intracellular pH (pHint) and extracellular pH (pHext) of Escherichia coli were measured at 12-s time resolution by 31P-nuclear magnetic resonance: a sudden neutral-to-acid shift in pHext (e.g., from 7.0 to 5.6) caused a transient failure of homeostasis, with pHint decreasing by about 0.4 unit in ca. 30 s and then returning to its original value (ca. 7.5) over a period of several minutes. Membrane proton conductance was estimated to be 20 pmol s−1 cm−2 pH unit−1. Addition of the membrane-permeant weak acid benzoate at constant pHext also caused a lowering of pHint; at high concentrations it generated an inverted transmembrane pH gradient (ΔpH). The buffering capacity of the cells was estimated by such experiments to be ca. 50 mM per pH unit. Effects of pH-related stimuli on the methyl-accepting chemotaxis proteins (MCPs) were examined: the steady-state methylation of MCP I was found to decrease when pHint was lowered by weak acid addition or when pHext was lowered. The extent of demethylation in the latter case was too great to be explained by imperfect steady-state homeostasis; a small but reproducible undershoot in methylation level correlated with the observed short-term homeostatic failure. MCP II underwent smaller and more complex changes than MCP I, in response to pH-related stimuli. The methylation level of MCP I could not, by any condition tested, be driven below a limit of ca. 15% of the control level (unstimulated cells at pHext 7.0). The weak-acid concentration needed to reach that limit was dependent on pHext, as would be expected on the basis of ΔpH-driven concentrative effects. The potency ranking of weak acids was the same with respect to lowering pHint, demethylating MCP I, and causing repellent behavioral responses. The data are consistent with a model whereby MCP I and hence tactic behavior are sensitive to both pHint and pHext. Evidence is presented that pHint may also have a direct (non-MCP-related) effect on motor function. Comparison of

  16. Epigenetics and cortical spreading depression: changes of DNA methylation level at retrotransposon sequences.

    PubMed

    Drongitis, Denise; Rainone, Sara; Piscopo, Marina; Viggiano, Emanuela; Viggiano, Alessandro; De Luca, Bruno; Fucci, Laura; Donizetti, Aldo

    2016-08-01

    Cortical spreading depression (CSD) is an evolutionarily conserved phenomenon that involves a slow and self-propagating depolarization wave associated with spontaneous depression of electrical neuronal activity. CSD plays a central role in the pathophysiology of several brain diseases and is considered to be able to promote "Preconditioning". This phenomenon consists of the brain protecting itself against future injury by adaptation. Understanding of the molecular mechanisms underlying Preconditioning has significant clinical implications. We have already proposed that the long-lasting effects of CSD could be related to silencing of retrotransposon sequences by histone methylation. We analyzed DNA methylation of two retrotransposon sequences, LINE1 and L1, and their corresponding expression pattern after CSD induction. Based on immunoprecipitation assay of the methylated DNA (meDIP), we demonstrated hypermethylation of both sequences in preconditioned rat brain cortex compared with a control 24 h after CSD induction. Using quantitative PCR, we also showed that CSD induction caused a decrease of the transcript level of both retrotransposon sequences. Our data are consistent with the hypothesis of epigenetic modifications in Preconditioning-dependent neuroprotection by increasing genome stability via the silencing of retrotransposon sequences. PMID:27169424

  17. Association of dietary and genetic factors related to one-carbon metabolism with global methylation level of leukocyte DNA.

    PubMed

    Ono, Hiroe; Iwasaki, Motoki; Kuchiba, Aya; Kasuga, Yoshio; Yokoyama, Shiro; Onuma, Hiroshi; Nishimura, Hideki; Kusama, Ritsu; Ohnami, Sumiko; Sakamoto, Hiromi; Yoshida, Teruhiko; Tsugane, Shoichiro

    2012-12-01

    Global hypomethylation of leukocyte DNA has been associated with an increased risk of cancer. As dietary and genetic factors related to one-carbon metabolism may influence both the methylation and synthesis of DNA, we investigated associations between these factors and the global methylation level of peripheral blood leukocyte DNA based on a cross-sectional study of 384 Japanese women. Dietary intake of folate and vitamins B2, B6, and B12 was assessed with a validated semiquantitative food frequency questionnaire. Five polymorphisms in methylenetetrahydrofolate reductase (MTHFR) (rs1801133 and rs1801131), methionine synthase (MTR) (rs1805087), and methionine synthase reductase (MTRR) (rs10380 and rs162049) were genotyped. Global DNA methylation of leukocyte DNA was quantified using Luminometric Methylation Assay. A linear trend of association between methylation and dietary and genetic factors was evaluated by regression coefficients in a multivariable linear regression model. Mean global methylation level (standard deviation) was 70.2% (3.4) and range was from 59.0% to 81.2%. Global methylation level significantly decreased by 0.36% (95% confidence interval, 0.03-0.69) per quartile category for folate level. Subgroup analysis suggested that alcohol drinking modified the association between folate intake and global methylation level (P(interaction)  = 0.01). However, no statistically significant association was observed for intake of vitamins B2, B6, and B12, alcohol consumption, or five single nucleotide polymorphisms of MTHFR, MTR, and MTRR. We found that higher folate intake was significantly associated with a lower level of global methylation of leukocyte DNA in a group of healthy Japanese females. PMID:22957669

  18. Quantification of global mitochondrial DNA methylation levels and inverse correlation with age at two CpG sites

    PubMed Central

    Mawlood, Shakhawan K.; Dennany, Lynn; Watson, Nigel; Dempster, John; Pickard, Benjamin S.

    2016-01-01

    Mammalian ageing features biological attrition evident at cellular, genetic and epigenetic levels. Mutation of mitochondrial DNA, and nuclear DNA methylation changes are well established correlates of ageing. The methylation of mitochondrial DNA (mtDNA) is a new and incompletely described phenomenon with unknown biological control and significance. Here we describe the bisulphite sequencing of mtDNA from 82 individuals aged 18‐91 years. We detected low and variable levels of mtDNA methylation at 54 of 133 CpG sites interrogated. Regression analysis of methylation levels at two CpG sites (M1215 and M1313) located within the 12S ribosomal RNA gene showed an inverse correlation with subject age suggesting their utility as epigenetic markers of ageing. PMID:26887692

  19. Absolute configuration of (1S,2S)-3-methyl-2-phenyl-2,3-dihydro­thia­zolo[2,3-b]quinazolin-5-one

    PubMed Central

    Ghorab, Mostafa. M.; Al-Said, Mansour. S.; Abdel-Kader, Maged. S.; Hemamalini, Madhukar; Fun, Hoong-Kun

    2012-01-01

    The absolute structure of the molecule in the crystal of the title compound, C17H14N2OS, was determined by the refinement of the Flack parameter to 0.0 (2) based on 1011 Friedel pairs. The quinazoline ring is essentially planar, with a maximum deviation of 0.037 (2) Å. The thia­zole ring is distorted from planarity [maximum deviation = 0.168 (2) Å] and adopts a slightly twisted envelope conformation, with the C atom as the flap atom. The central thia­zole ring makes dihedral angles of 7.01 (8) and 76.80 (10)° with the quinazoline and phenyl rings, respectively. The corresponding angle between the quinazoline and phenyl rings is 3.74 (9)°. In the crystal, there are no classical hydrogen bonds but stabilization is provided by weak C—H⋯π inter­actions, involving the centroids of the phenyl rings. PMID:22589992

  20. Association of interleukin-6 methylation in leukocyte DNA with serum level and the risk of ischemic heart disease.

    PubMed

    Yang, Qinghui; Zhao, Yushi; Zhang, Zhijie; Chen, Jianxin

    2016-07-01

    Background Interleukin-6 (IL-6), a multifunctional cytokine, plays an important role in the development of ischemic heart disease (IHD), and DNA hypomethylation of 2 CpGs, located downstream in the proximity of the IL-6 gene promoter, has been associated with risk factor for IHD. This study was to examine the association of blood leukocyte DNA methylation of the 2 CpGs in IL-6 with the risk of IHD and the serum IL-6 level. Methods IL-6 methylation levels of 582 cases and 673 controls were measured using the bisulfite pyrosequencing technology. Serum level of IL-6 was measured using enzyme-linked immunosorbent assay. Results The IL-6 methylation was significantly lower in IHD cases than in the controls, irrespective of CpG site. After multivariate adjustment, lower (< median) average IL-6 methylation was associated with an increased risk of IHD (OR 1.57, 95% CI 1.22-2.02, p < 0.001). Average IL-6 methylation level was inversely associated with serum IL-6 level (β = -1.02 pg/mL per increase in IL-6 methylation, p = 0.002) among IHD cases. This significant relationship was not observed among controls. Conclusions DNA hypomethylation of IL-6 gene measured in blood leukocytes was associated with increased risk of IHD. IL-6 demethylation may upregulate its expression, whereby exerting its risk effect on the development of IHD. PMID:26986049

  1. Absolute Summ

    NASA Astrophysics Data System (ADS)

    Phillips, Alfred, Jr.

    Summ means the entirety of the multiverse. It seems clear, from the inflation theories of A. Guth and others, that the creation of many universes is plausible. We argue that Absolute cosmological ideas, not unlike those of I. Newton, may be consistent with dynamic multiverse creations. As suggested in W. Heisenberg's uncertainty principle, and with the Anthropic Principle defended by S. Hawking, et al., human consciousness, buttressed by findings of neuroscience, may have to be considered in our models. Predictability, as A. Einstein realized with Invariants and General Relativity, may be required for new ideas to be part of physics. We present here a two postulate model geared to an Absolute Summ. The seedbed of this work is part of Akhnaton's philosophy (see S. Freud, Moses and Monotheism). Most important, however, is that the structure of human consciousness, manifest in Kenya's Rift Valley 200,000 years ago as Homo sapiens, who were the culmination of the six million year co-creation process of Hominins and Nature in Africa, allows us to do the physics that we do. .

  2. Melittin-Induced Lipid Extraction Modulated by the Methylation Level of Phosphatidylcholine Headgroups.

    PubMed

    Therrien, Alexandre; Lafleur, Michel

    2016-01-19

    Protein- and peptide-induced lipid extraction from membranes is a critical process for many biological events, including reverse cholesterol transport and sperm capacitation. In this work, we examine whether such processes could display specificity for some lipid species. Melittin, the main component of dry bee venom, was used as a model amphipathic α-helical peptide. We specifically determined the modulation of melittin-induced lipid extraction from membranes by the change of the methylation level of phospholipid headgroups. Phosphatidylcholine (PC) bilayers were demethylated either by substitution with phosphatidylethanolamine (PE) or chemically by using mono- and dimethylated PE. It is shown that demethylation reduces the association of melittin with membranes, likely because of the resulting tighter chain packing of the phospholipids, which reduces the capacity of the membranes to accommodate inserted melittin. This reduced binding of the peptide is accompanied by an inhibition of the lipid extraction caused by melittin. We demonstrate that melittin selectively extracts PC from PC/PE membranes. This selectivity is proposed to be a consequence of a PE depletion in the surroundings of bound melittin to minimize disruption of the interphospholipid interactions. The resulting PC-enriched vicinity of melittin would be responsible for the observed formation of PC-enriched lipid/peptide particles resulting from the lipid efflux. These findings reveal that modulating the methylation level of phospholipid headgroups is a simple way to control the specificity of lipid extraction from membranes by peptides/proteins and thereby modulate the lipid composition of the membranes. PMID:26789763

  3. Placental lipoprotein lipase DNA methylation levels are associated with gestational diabetes mellitus and maternal and cord blood lipid profiles.

    PubMed

    Houde, A A; St-Pierre, J; Hivert, M F; Baillargeon, J P; Perron, P; Gaudet, D; Brisson, D; Bouchard, L

    2014-04-01

    Placental lipoprotein lipase (LPL) is crucial for placental lipid transfer. Impaired LPL gene expression and activity were reported in pregnancies complicated by gestational diabetes mellitus (GDM) and intra-uterine growth restriction. We hypothesized that placental LPL DNA methylation is altered by maternal metabolic status and could contribute to fetal programming. The objective of this study was thus to assess whether placental LPL DNA methylation is associated with GDM and both maternal and newborn lipid profiles. Placenta biopsies were sampled at delivery from 126 women including 27 women with GDM diagnosed following a post 75 g-oral glucose tolerance test (OGTT) between weeks 24 and 28 of gestation. Placental LPL DNA methylation and expression levels were determined using bisulfite pyrosequencing and quantitative real-time PCR, respectively. DNA methylation levels within LPL proximal promoter region (CpG1) and intron 1 CpG island (CpGs 2 and 3) were lower in placenta of women with GDM. DNA methylation levels at LPL-CpG1 and CpG3 were also negatively correlated with maternal glucose (2-h post OGTT; r=-0.22; P=0.02) and HDL-cholesterol levels (third trimester of pregnancy; r=-0.20; p=0.03), respectively. Moreover, we report correlation between LPL-CpG2 DNA methylation and cord blood lipid profile. DNA methylation levels within intron 1 CpG island explained up to 26% (r⩽-0.51; P<0.001) of placental LPL mRNA expression variance. Overall, we showed that maternal metabolic profile is associated with placental LPL DNA methylation dysregulation. Our results suggest that site-specific LPL epipolymorphisms in the placenta are possibly functional and could potentially be involved in determining the future metabolic health of the newborn. PMID:24847699

  4. DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study

    PubMed Central

    Salas, Lucas A; Bustamante, Mariona; Gonzalez, Juan R; Gracia-Lavedan, Esther; Moreno, Victor; Kogevinas, Manolis; Villanueva, Cristina M

    2015-01-01

    Trihalomethanes (THM) are undesired disinfection byproducts (DBPs) formed during water treatment. Mice exposed to DBPs showed global DNA hypomethylation and c-myc and c-jun gene-specific hypomethylation, while evidence of epigenetic effects in humans is scarce. We explored the association between lifetime THM exposure and DNA methylation through an epigenome-wide association study. We selected 138 population-based controls from a case-control study of colorectal cancer conducted in Barcelona, Spain, exposed to average lifetime THM levels ≤85 μg/L vs. >85 μg/L (N = 68 and N = 70, respectively). Mean age of participants was 70 years, and 54% were male. Average lifetime THM level in the exposure groups was 64 and 130 µg/L, respectively. DNA was extracted from whole blood and was bisulphite converted to measure DNA methylation levels using the Illumina HumanMethylation450 BeadChip. Data preprocessing was performed using RnBeads. Methylation was compared between exposure groups using empirical Bayes moderated linear regression for CpG sites and Gaussian kernel for CpG regions. ConsensusPathDB was used for gene set enrichment. Statistically significant differences in methylation between exposure groups was found in 140 CpG sites and 30 gene-related regions, after false discovery rate <0.05 and adjustment for age, sex, methylation first principal component, and blood cell proportion. The annotated genes were localized to several cancer pathways. Among them, 29 CpGs had methylation levels associated with THM levels (|Δβ|≥0.05) located in 11 genes associated with cancer in other studies. Our results suggest that THM exposure may affect DNA methylation in genes related to tumors, including colorectal and bladder cancers. Future confirmation studies are required. PMID:26039576

  5. Fatty acid synthase methylation levels in adipose tissue: effects of an obesogenic diet and phenolic compounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA methylation is an epigenetic mechanism that can inhibit gene transcription. The aim of this study was to assess changes induced by an obesogenic diet in the methylation profile of genes involved in adipose tissue triacylglycerol metabolism, and to determine whether this methylation pattern can b...

  6. Harnessing immunomagnetic separation and quantum dot-based quantification capacities for the enumeration of absolute levels of biomarker

    NASA Astrophysics Data System (ADS)

    Park, Hoyoung; Hwang, Mintai P.; Lee, Jong-Wook; Choi, Jonghoon; Hyi Lee, Kwan

    2013-07-01

    The field of biomarker quantification has experienced a growth parallel to the discovery of new materials. In this paper, we propose an innovative system for the separation and quantification of biomarkers using a simple magnetic bead (MB)-quantum dot (QD) sandwich assay. The basis of the system lies in the interaction between histidine residues on protein G and Ni ions on QDs, and the use of imidazole to selectively detach QDs bound to target biomarkers, in effect enumerating the absolute number of biomarker units. We used C-reactive protein (CRP) as a proof-of-concept and demonstrated a detection sensitivity of 82.5 fmoles in 50 μl of sample volume, a commonly used analytical volume (e.g. ELISA). Although CRP was used as a model to conduct this study, the sensitivity and simplicity of this detachable system make it a viable approach in the quantification of other target analytes.

  7. Alterations of Cyclooxygenase-2 Methylation Levels Before and After Intervention Trial to Prevent Gastric Cancer in a Chinese Population.

    PubMed

    Zhang, Yang; Zeng, Hong-Mei; Nie, Xiao-Rui; Zhang, Lian; Ma, Jun-Ling; Li, Ji-You; Pan, Kai-Feng; You, Wei-Cheng

    2016-06-01

    To explore the epigenetic mechanisms underlying the effects of anti-Helicobacter pylori (H. pylori) alone and combined with COX-2 inhibitor (celecoxib), we dynamically evaluated the associations between COX-2 methylation alterations and gastric lesion evolution during the process of interventions. In a total of 809 trial participants COX-2 methylation levels were quantitatively detected before and after treatment. The self-comparison at the same stomach site for each subject showed significant methylation alteration differences among intervention groups (P < 0.001). With placebo group as reference, COX-2 methylation levels were decreased in anti-H. pylori [OR, 3.30; 95% confidence interval (CI), 2.16-5.02], celecoxib (OR, 2.04; 95% CI, 1.36-3.07), and anti-H. pylori followed by celecoxib (OR, 2.10; 95% CI, 1.38-3.17) groups. When stratified by baseline histology, the three active arms significantly decreased COX-2 methylation levels in indefinite dysplasia/dysplasia subjects, and ORs were 3.65 (95% CI, 1.96-6.80) for anti-H. pylori, 2.43 (95% CI 1.34-4.39) for celecoxib, and 2.80 (95% CI, 1.52-5.15) for anti-H. pylori followed by celecoxib, respectively. No additive effect on COX-2 methylation was found for anti-H. pylori followed by celecoxib than two treatments alone. Compared with subjects without methylation reduction, higher opportunity for gastric lesion regression was found in subjects with decreased COX-2 methylation levels, especially for indefinite dysplasia/dysplasia subjects (OR, 1.92; 95% CI, 1.03-3.60). These findings suggest that anti-H. pylori or celecoxib treatment alone could decrease COX-2 methylation levels in gastric mucosa. COX-2 methylation alteration was associated with the regression of indefinite dysplasia/dysplasia, which might serve as a potential biomarker for chemoprevention efficacy. Cancer Prev Res; 9(6); 484-90. ©2016 AACR. PMID:27020655

  8. Integrated analysis of PALSAR/Radarsat-1 InSAR and ENVISAT altimeter data for mapping of absolute water level changes in Louisiana wetlands

    USGS Publications Warehouse

    Kim, J.-W.; Lu, Zhiming; Lee, H.; Shum, C.K.; Swarzenski, C.M.; Doyle, T.W.; Baek, S.-H.

    2009-01-01

    Interferometric Synthetic Aperture Radar (InSAR) has been used to detect relative water level changes in wetlands. We developed an innovative method to integrate InSAR and satellite radar altimetry for measuring absolute or geocentric water level changes and applied the methodology to remote areas of swamp forest in coastal Louisiana. Coherence analysis of InSAR pairs suggested that the HH polarization is preferred for this type of observation, and polarimetric analysis can help to identify double-bounce backscattering areas in the wetland. ENVISAT radar altimeter-measured 18-Hz (along-track sampling of 417 m) water level data processed with regional stackfile method have been used to provide vertical references for water bodies separated by levees. The high-resolution (~ 40 m) relative water changes measured from ALOS PALSAR L-band and Radarsat-1 C-band InSAR are then integrated with ENVISAT radar altimetry to obtain absolute water level. The resulting water level time series were validated with in situ gauge observations within the swamp forest. We anticipate that this new technique will allow retrospective reconstruction and concurrent monitoring of water conditions and flow dynamics in wetlands, especially those lacking gauge networks. ?? 2009 Elsevier Inc.

  9. Changes in Biliary Levels of Arginine and its Methylated Derivatives after Hepatic Ischaemia/Reperfusion.

    PubMed

    Ferrigno, Andrea; Di Pasqua, Laura Giuseppina; Berardo, Clarissa; Rizzo, Vittoria; Richelmi, Plinio; Vairetti, Mariapia

    2016-07-01

    Arginine (Arg) can be methylated to form symmetrical dimethylarginine (SDMA) and asymmetrical dimethylarginine (ADMA), the latter an endogenous inhibitor of nitric oxide synthase (NOS). SDMA is excreted in the urine, while ADMA is mainly subjected to degradation in the liver. Arg competes with ADMA and SDMA for cellular transport across cationic amino-acid transporters (CATs). We evaluated the changes in serum, tissue and biliary levels of Arg, citrulline (Cit), ADMA and SDMA and the modifications in CATs after ischaemia-reperfusion (I/R). Male Wistar rats were subjected to 30-min. partial-hepatic ischaemia or sham-operated. After 60-min. reperfusion, the concentrations of ADMA, SDMA, Arg and Cit in serum, tissue and bile were measured. Serum levels of AST, ALT and alkaline phosphatase (AP) levels were determined. mRNA of cationic transporter 2A (CAT-2A) and 2B (CAT-2B) were also quantified. An increase in ADMA and a decrease in SDMA were observed in bile at the end of reperfusion. On the contrary, lower tissue ADMA levels and higher SDMA levels were quantified. No serum changes in ADMA and SDMA were found. A decrease in Arg and an increase of Cit were detected in serum, bile and tissue after I/R. A marked increase in AST, ALT and AP levels in serum confirmed I/R injury. A decrease in mRNA transporter CAT-2A but not in CAT-2B was detected. This study supported a biliary CAT-2B-dependent transport of ADMA and demonstrated, for the first time, that the liver is also responsible for the biliary excretion of SDMA into the bile. PMID:26663642

  10. The Promoter Methylation Status and mRNA Expression Levels of CTCF and SIRT6 in Sporadic Breast Cancer

    PubMed Central

    Wang, Da; Zhang, Xuemei

    2014-01-01

    Promoter hypermethylation causes gene silencing and is thought to be an early event in carcinogenesis. This study was to detect promoter methylation status and mRNA expression levels of CCCTC-binding factor (CTCF) and sirtuin 6 (SIRT6), and to explore the relationship between methylation and mRNA expression in breast cancer patient samples. Promoter methylation analysis and expression profile analysis of two genes were performed by methylation-specific PCR, bisulfite sequencing PCR, and quantitative real-time PCR in cancer lesions and matched normal tissues. The promoter region of CTCF has not been hypermethylated in all patient samples. In contrast, methylation of SIRT6 gene was present in invasive cancers (93.5%) and matched normal tissues (96.8%) from 62 patients. Promoter hypermethylation of SIRT6 was also observed in ductal carcinoma in situ (three of three) and matched normal tissues (two of three). mRNA expression of CTCF and SIRT6 in invasive tumors showed a lower level than that in paired normal tissues (p=0.008 and p=0.030, respectively). The fold change values of CTCF expression were significantly lower in invasive ductal cancer lesions with Ki-67-positive status (p=0.042). In conclusion, our data showed that the methylation status of CTCF and SIRT6 promoter regions was not statistically different in cancer lesions compared with matched normal tissues. No significant association between promoter methylation status and expression profiles of CTCF and SIRT6 was found in invasive breast cancers. PMID:24842653

  11. Modulation of DNA methylation levels sensitizes doxorubicin-resistant breast adenocarcinoma cells to radiation-induced apoptosis

    SciTech Connect

    Luzhna, Lidia; Kovalchuk, Olga

    2010-02-05

    Chemoresistant tumors often fail to respond to other cytotoxic treatments such as radiation therapy. The mechanisms of chemo- and radiotherapy cross resistance are not fully understood and are believed to be epigenetic in nature. We hypothesize that MCF-7 cells and their doxorubicin-resistant variant MCF-7/DOX cells may exhibit different responses to ionizing radiation due to their dissimilar epigenetic status. Similar to previous studies, we found that MCF-7/DOX cells harbor much lower levels of global DNA methylation than MCF-7 cells. Furthermore, we found that MCF-7/DOX cells had lower background apoptosis levels and were less responsive to radiation than MCF-7 cells. Decreased radiation responsiveness correlated to significant global DNA hypomethylation in MCF-7/DOX cells. Here, for the first time, we show that the radiation resistance of MCF-7/DOX cells can be reversed by an epigenetic treatment - the application of methyl-donor SAM. SAM-mediated reversal of DNA methylation led to elevated radiation sensitivity in MCF-7/DOX cells. Contrarily, application of SAM on the radiation sensitive and higher methylated MCF-7 cells resulted in a decrease in their radiation responsiveness. This data suggests that a fine balance of DNA methylation is needed to insure proper radiation and drug responsiveness.

  12. Methylation by NSun2 Represses the Levels and Function of MicroRNA 125b

    PubMed Central

    Yuan, Shuai; Tang, Hao; Xing, Junyue; Fan, Xiuqin; Cai, Xiaoyu; Li, Qiu; Han, Pei; Luo, Yuhong; Zhang, Zhuojun; Jiang, Bin; Dou, Yali; Gorospe, Myriam

    2014-01-01

    Methylation is a prevalent posttranscriptional modification of RNAs. However, whether mammalian microRNAs are methylated is unknown. Here, we show that the tRNA methyltransferase NSun2 methylates primary (pri-miR-125b), precursor (pre-miR-125b), and mature microRNA 125b (miR-125b) in vitro and in vivo. Methylation by NSun2 inhibits the processing of pri-miR-125b2 into pre-miR-125b2, decreases the cleavage of pre-miR-125b2 into miR-125, and attenuates the recruitment of RISC by miR-125, thereby repressing the function of miR-125b in silencing gene expression. Our results highlight the impact of miR-125b function via methylation by NSun2. PMID:25047833

  13. Correlation of MLH1 and MGMT methylation levels between peripheral blood leukocytes and colorectal tissue DNA samples in colorectal cancer patients

    PubMed Central

    LI, XIA; WANG, YIBAINA; ZHANG, ZUOMING; YAO, XIAOPING; GE, JIE; ZHAO, YASHUANG

    2013-01-01

    CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 (MLH1) and DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present study analyzed and compared the levels of MGMT and MLH1 gene methylation in the leukocytes of peripheral blood and colorectal tissues obtained from patients with colorectal cancer (CRC). The methylation levels of MGMT and MLH1 were examined using methylation-sensitive high-resolution melting (MS-HRM) analysis. A total of 44 patients with CRC were selected based on the MLH1 and MGMT gene methylation levels in the leukocytes of the peripheral blood. Corresponding colorectal tumor and normal tissues were obtained from each patient and the DNA methylation levels were determined. The correlation coefficients were evaluated using Spearman’s rank test. Agreement was determined by generalized κ-statistics. Spearman’s rank correlation coefficients (r) for the methylation levels of the MGMT and MLH1 genes in the leukocytes of the peripheral blood and normal colorectal tissue were 0.475 and 0.362, respectively (P=0.001 and 0.016, respectively). The agreement of the MGMT and MLH1 gene methylation levels in the leukocytes of the peripheral blood and normal colorectal tissue were graded as fair and poor (κ=0.299 and 0.126, respectively). The methylation levels of MGMT and MLH1 were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively. Blood-derived DNA methylation measurements may not always represent the levels of normal colorectal tissue methylation. PMID:24179526

  14. DNA Methylation Levels of CYP2R1 and CYP24A1 Predict Vitamin D Response Variation1, 2

    PubMed Central

    Zhou, Yu; Zhao, Lan-Juan; Xu, Xiaojing; Ye, An; Travers-Gustafson, Dianne; Zhou, Boting; Wang, Hong-Wei; Zhang, Weidong; Hamm, L. Lee; Deng, Hong-Wen; Recker, Robert R.; Lappe, Joan M.

    2013-01-01

    Factors contributing to the variability of serum 25-hydroxyvitamin D [25(OH)D] in response to a given dose of vitamin D supplementation are largely unknown. We examined whether DNA methylation levels of Cytochrome P450 (CYP) enzymes (CYP2R1, CYP24A1, CYP27A1, and CYP27B1) are potential biomarkers predicting vitamin D response variation. We randomized 446 white postmenopausal women to a calcium and vitamin D (1100 IU/day) intervention for at least 12 months. From these subjects, 18 with the highest 12-month increase in serum 25(OH)D were selected as “responders.” Another 18 with the lowest 12-month increase in serum 25(OH)D were selected as “non-responders.” DNA methylation levels between the groups were compared. To validate findings in the first study, association between DNA methylation levels and vitamin D response variation was studied in another 145 extended independent white postmenopausal women. In the first study, compared to non-responders, responders had significantly lower baseline DNA methylation levels in the promoter region of CYP2R1 (8% in the responders vs 30% in the non-responders, P=0.004), and CYP24A1 (13% in the responders vs 32% in the non-responders, P=0.001). In the validation study, for CYP2R1, baseline DNA methylation levels at eight CpG sites were negatively associated with 12-month increases in serum 25(OH)D (P<0.05). For CYP24A1, baseline DNA methylation levels at two CpG sites were also negatively associated with vitamin D response variation (r=−0.151, P=0.011; r=−0.131, P=0.025). These negative associations were consistent with the first study’s results. Our findings indicate that baseline DNA methylation levels of CYP2R1 and CYP24A1 may predict vitamin D response variation. PMID:24128439

  15. Across-Platform Imputation of DNA Methylation Levels Incorporating Nonlocal Information Using Penalized Functional Regression

    PubMed Central

    Zhang, Guosheng; Huang, Kuan-Chieh; Xu, Zheng; Tzeng, Jung-Ying; Conneely, Karen N.; Guan, Weihua; Kang, Jian; Li, Yun

    2016-01-01

    DNA methylation is a key epigenetic mark involved in both normal development and disease progression. Recent advances in high-throughput technologies have enabled genome-wide profiling of DNA methylation. However, DNA methylation profiling often employs different designs and platforms with varying resolution, which hinders joint analysis of methylation data from multiple platforms. In this study, we propose a penalized functional regression model to impute missing methylation data. By incorporating functional predictors, our model utilizes information from nonlocal probes to improve imputation quality. Here, we compared the performance of our functional model to linear regression and the best single probe surrogate in real data and via simulations. Specifically, we applied different imputation approaches to an acute myeloid leukemia dataset consisting of 194 samples and our method showed higher imputation accuracy, manifested, for example, by a 94% relative increase in information content and up to 86% more CpG sites passing post-imputation filtering. Our simulated association study further demonstrated that our method substantially improves the statistical power to identify trait-associated methylation loci. These findings indicate that the penalized functional regression model is a convenient and valuable imputation tool for methylation data, and it can boost statistical power in downstream epigenome-wide association study (EWAS). PMID:27061717

  16. Across-Platform Imputation of DNA Methylation Levels Incorporating Nonlocal Information Using Penalized Functional Regression.

    PubMed

    Zhang, Guosheng; Huang, Kuan-Chieh; Xu, Zheng; Tzeng, Jung-Ying; Conneely, Karen N; Guan, Weihua; Kang, Jian; Li, Yun

    2016-05-01

    DNA methylation is a key epigenetic mark involved in both normal development and disease progression. Recent advances in high-throughput technologies have enabled genome-wide profiling of DNA methylation. However, DNA methylation profiling often employs different designs and platforms with varying resolution, which hinders joint analysis of methylation data from multiple platforms. In this study, we propose a penalized functional regression model to impute missing methylation data. By incorporating functional predictors, our model utilizes information from nonlocal probes to improve imputation quality. Here, we compared the performance of our functional model to linear regression and the best single probe surrogate in real data and via simulations. Specifically, we applied different imputation approaches to an acute myeloid leukemia dataset consisting of 194 samples and our method showed higher imputation accuracy, manifested, for example, by a 94% relative increase in information content and up to 86% more CpG sites passing post-imputation filtering. Our simulated association study further demonstrated that our method substantially improves the statistical power to identify trait-associated methylation loci. These findings indicate that the penalized functional regression model is a convenient and valuable imputation tool for methylation data, and it can boost statistical power in downstream epigenome-wide association study (EWAS). PMID:27061717

  17. High-level production of extracellular lipase by Yarrowia lipolytica mutants from methyl oleate.

    PubMed

    Darvishi, Farshad; Destain, Jacqueline; Nahvi, Iraj; Thonart, Philippe; Zarkesh-Esfahani, Hamid

    2011-10-01

    The yeast Yarrowia lipolytica degrades efficiently low-cost hydrophobic substrates for the production of various added-value products such as lipases. To obtain yeast strains producing high levels of extracellular lipase, Y. lipolytica DSM3286 was subjected to mutation using ethyl methanesulfonate (EMS) and ultraviolet (UV) light. Twenty mutants were selected out of 1600 mutants of Y. lipolytica treated with EMS and UV based on lipase production ability on selective medium. A new industrial medium containing methyl oleate was optimized for lipase production. In the 20 L bioreactor containing new industrial medium, one UV mutant (U6) produced 356 U/mL of lipase after 24h, which is about 10.5-fold higher than that produced by the wild type strain. The properties of the mutant lipase were the same as those of the wild type: molecular weight 38 kDa, optimum temperature 37°C and optimum pH 7. Furthermore, the nucleotide sequences of extracellular lipase gene (LIP2) in wild type and mutant strains were determined. Only two silent substitutions at 362 and 385 positions were observed in the ORF region of LIP2. Two single substitutions and two duplications of the T nucleotide were also detected in the promoter region. LIP2 sequence comparison of the Y. lipolytica DSM3286 and U6 strains shows good targets to effective DNA recombinant for extracellular lipase of Y. lipolytica. PMID:21324386

  18. Highly active ppm level organic copper catalyzed photo-induced ICAR ATRP of methyl methacrylate.

    PubMed

    Jiang, Xiaowu; Wu, Jian; Zhang, Lifen; Cheng, Zhenping; Zhu, Xiulin

    2014-11-01

    A novel photo-induced homogeneous atom transfer radical polymerization (ATRP) system is constructed using an organic copper salt (Cu(SC(S)N(C2 H5 )2 )2 ) as a photo-induced catalyst at 30 °C. Herein, N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDETA) is used as a ligand, ethyl 2-bromophenylacetate (EBPA) as an ATRP initiator, and (2,4,6-trimethylbenzoyl) diphenylphosphine oxide (TPO) as a photo-induced radical initiator to establish an ICAR (initiators for continuous activator regeneration) ATRP using methyl methacrylate (MMA) as a modal monomer. The effect of the concentration of the organic copper on the polymerization is investigated in detail. It is found that well-controlled polymerization can be obtained even with the amount of (Cu(SC(S)N(C2 H5 )2 )2 decreasing to a 1.56 ppm level, with the molecular weight of the resultant polymers increasing linearly with monomer conversion while maintaining a narrow molecular weight distribution (M¯w/M¯n < 1.3). PMID:25250767

  19. DNA methylation levels at chromosome 8q24 in peripheral blood are associated with 8q24 cancer susceptibility loci.

    PubMed

    Barry, Kathryn Hughes; Moore, Lee E; Sampson, Joshua; Yan, Liying; Meyer, Ann; Oler, Andrew J; Chung, Charles C; Wang, Zhaoming; Yeager, Meredith; Amundadottir, Laufey; Berndt, Sonja I

    2014-12-01

    Chromosome 8q24 has emerged as an important region for genetic susceptibility to various cancers, but little is known about the contribution of DNA methylation at 8q24. To evaluate variability in DNA methylation levels at 8q24 and the relationship with cancer susceptibility single nucleotide polymorphisms (SNPs) in this region, we quantified DNA methylation levels in peripheral blood at 145 CpG sites nearby 8q24 cancer susceptibility SNPs or MYC using pyrosequencing among 80 Caucasian men in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. For the 60 CpG sites meeting quality control, which also demonstrated temporal stability over a 5-year period, we calculated pairwise Spearman correlations for DNA methylation levels at each CpG site with 42 8q24 cancer susceptibility SNPs. To account for multiple testing, we adjusted P values into q values reflecting the false discovery rate (FDR). In contrast to the MYC CpG sites, most sites nearby the SNPs demonstrated good reproducibility, high methylation levels, and moderate-high between-individual variation. We observed 10 statistically significant (FDR < 0.05) CpG site-SNP correlations. These included correlations between an intergenic CpG site at Chr8:128393157 and the prostate cancer SNP rs16902094 (ρ = -0.54; P = 9.7 × 10(-7); q = 0.002), a PRNCR1 CpG site at Chr8:128167809 and the prostate cancer SNP rs1456315 (ρ = 0.52; P = 1.4 × 10(-6); q = 0.002), and two POU5F1B CpG sites and several prostate/colorectal cancer SNPs (for Chr8:128498051 and rs6983267, ρ = 0.46; P = 2.0 × 10(-5); q = 0.01). This is the first report of correlations between blood DNA methylation levels and cancer susceptibility SNPs at 8q24, suggesting that DNA methylation at this important susceptibility locus may contribute to cancer risk. PMID:25315430

  20. Dietary Patterns Are Associated with Levels of Global Genomic DNA Methylation in a Cancer-Free Population12

    PubMed Central

    Zhang, Fang Fang; Morabia, Alfredo; Carroll, Joan; Gonzalez, Karina; Fulda, Kimberly; Kaur, Manleen; Vishwanatha, Jamboor K.; Santella, Regina M.; Cardarelli, Roberto

    2011-01-01

    Animal studies have provided direct evidence that dietary factors induce changes in DNA methylation patterns. In humans, studies on diet and DNA methylation have yielded inconsistent findings. Because humans tend to consume foods and nutrients that are highly interrelated, study of dietary patterns may have improved the power of detecting the effect of diet on DNA methylation. Using data collected from 149 participants aged 45–75 y in the North Texas Healthy Heart Study, we examined the relationship between dietary patterns and levels of genomic DNA methylation in peripheral blood leukocytes. Dietary data were collected from study participants using the Block FFQ. Genomic DNA methylation was measured using bisulfite conversion of DNA and real-time PCR (MethyLight) for LINE-1. Two dietary patterns were identified using factor analysis: a “prudent” dietary pattern characterized by a high intake of vegetables and fruits, and a “Western” dietary pattern characterized by a high intake of meats, grains, dairy, oils, and potatoes. The prudent dietary pattern was associated with a lower prevalence of DNA hypomethylation (Q4 vs. Q1; OR = 0.33, 95% CI: 0.12–0.92) and the association was dose dependent (P-trend = 0.04). There was no apparent association between the Western dietary pattern and global leukocyte DNA methylation (Q4 vs. Q1; OR = 1.28, 95% CI: 0.47–3.47; P-trend = 0.55). Thus, a dietary pattern characterized by a high intake of vegetables and fruits may protect against global DNA hypomethylation. Future studies with a larger sample size need to confirm that this association holds longitudinally. PMID:21525250

  1. Association of gastric cancer risk factors with DNA methylation levels in gastric mucosa of healthy Japanese: a cross-sectional study.

    PubMed

    Shimazu, Taichi; Asada, Kiyoshi; Charvat, Hadrien; Kusano, Chika; Otake, Yosuke; Kakugawa, Yasuo; Watanabe, Hidenobu; Gotoda, Takuji; Ushijima, Toshikazu; Tsugane, Shoichiro

    2015-11-01

    Helicobacter pylori infection induces aberrant DNA methylation, and methylation levels of several specific marker genes in gastric mucosa are associated with gastric cancer risk. However, it is unclear whether gastric cancer risk factors are associated with methylation levels of marker genes in healthy individuals. We conducted a cross-sectional study of 281 Japanese cancer screenees aged 40-69 years with no history of H.pylori eradication therapy who responded to a validated food frequency questionnaire. DNA methylation levels of marker genes (miR-124a-3, EMX1 and NKX6-1) in gastric mucosa were quantified by real-time methylation-specific polymerase chain reaction. A multivariate beta regression model was used to investigate the association of pack-years of smoking and intakes of green/yellow vegetables, fruit and salt with methylation levels of marker genes. All analyses were stratified by H.pylori status. We found 2.5 to 34.1 times higher mean methylation levels among those with current H.pylori infection (n = 117) compared to those without (n = 164). After adjustment for potential confounders, we found increased levels of miR-124a-3 methylation according to pack-years of smoking and decreased levels of methylation according to green/yellow vegetable intake. We did not detect these associations among those without H.pylori infection. In conclusion, smoking habits and green/yellow vegetable intake were associated with DNA methylation levels in gastric mucosae of healthy individuals with current H.pylori infection. Our study suggests that these risk factors may modify the effect of H.pylori on methylation induction and maintenance in gastric mucosa. PMID:26354778

  2. Elevations in Circulating Methylated and Unmethylated Preproinsulin DNA in New-Onset Type 1 Diabetes.

    PubMed

    Fisher, Marisa M; Watkins, Renecia A; Blum, Janice; Evans-Molina, Carmella; Chalasani, Naga; DiMeglio, Linda A; Mather, Kieren J; Tersey, Sarah A; Mirmira, Raghavendra G

    2015-11-01

    Elevated ratios of circulating unmethylated to methylated preproinsulin (INS) DNA have been suggested to reflect β-cell death in type 1 diabetes (T1D). We tested the hypothesis that absolute levels (rather than ratios) of unmethylated and methylated INS DNA differ between subjects with new-onset T1D and control subjects and assessed longitudinal changes in these parameters. We used droplet digital PCR to measure levels of unmethylated and methylated INS DNA in serum from subjects at T1D onset and at 8 weeks and 1 year post-onset. Compared with control subjects, levels of both unmethylated and methylated INS DNA were elevated at T1D onset. At 8 weeks post-onset, methylated INS DNA remained elevated, but unmethylated INS DNA fell. At 1 year postonset, both unmethylated and methylated INS DNA returned to control levels. Subjects with obesity, type 2 diabetes, and autoimmune hepatitis exhibited lower levels of unmethylated and methylated INS compared with subjects with T1D at onset and no differences compared with control subjects. Our study shows that elevations in both unmethylated and methylated INS DNA occurs in new-onset T1D and that levels of these DNA species change during T1D evolution. Our work emphasizes the need to consider absolute levels of differentially methylated DNA species as potential biomarkers of disease. PMID:26216854

  3. Altered Methylation in Tandem Repeat Element and Elemental Component Levels in Inhalable Air Particles

    PubMed Central

    Hou, Lifang; Zhang, Xiao; Zheng, Yinan; Wang, Sheng; Dou, Chang; Guo, Liqiong; Byun, Hyang-Min; Motta, Valeria; McCracken, John; Díaz, Anaité; Kang, Choong-Min; Koutrakis, Petros; Bertazzi, Pier Alberto; Li, Jingyun; Schwartz, Joel; Baccarelli, Andrea A.

    2014-01-01

    Exposure to particulate matter (PM) has been associated with lung cancer risk in epidemiology investigations. Elemental components of PM have been suggested to have critical roles in PM toxicity, but the molecular mechanisms underlying their association with cancer risks remain poorly understood. DNA methylation has emerged as a promising biomarker for environmental-related diseases, including lung cancer. In this study, we evaluated the effects of PM elemental components on methylation of three tandem repeats in a highly-exposed population in Beijing, China. The Beijing Truck Driver Air Pollution Study was conducted shortly before the 2008 Beijing Olympic Games (June 15-July 27, 2008) and included 60 truck drivers and 60 office workers. On two days separated by 1-2 weeks, we measured blood DNA methylation of SATα, NBL2, D4Z4, and personal exposure to eight elemental components in PM2.5, including aluminum (Al), silicon (Si), sulfur (S), potassium (K), calcium (Ca) titanium (Ti), iron (Fe), and zinc (Zn). We estimated the associations of individual elemental component with each tandem repeat methylation in generalized estimating equations (GEE) models adjusted for PM2.5 mass and other covariates. Out of the eight examined elements, NBL2 methylation was positively associated with concentrations of Si (0.121, 95%CI: 0.030; 0.212, FDR=0.047) and Ca (0.065, 95%CI: 0.014; 0.115, FDR=0.047) in truck drivers. In office workers, SATα methylation was positively associated with concentrations of S (0.115, 95%CI: 0.034; 0.196, FDR=0.042). PM-associated differences in blood tandem-repeat methylation may help detect biological effects of the exposure and identify individuals who may eventually experience higher lung cancer risk. PMID:24273195

  4. N-methyl-D-aspartate receptors strongly regulate postsynaptic activity levels during optic nerve regeneration.

    PubMed

    Kolls, Brad J; Meyer, Ronald L

    2013-10-01

    During development, neuronal activity is used as a cue to guide synaptic rearrangements to refine connections. Many studies, especially in the visual system, have shown that the N-methyl-D-aspartate receptor (NMDAr) plays a key role in mediating activity-dependent refinement through long-term potentiation (LTP)-like processes. Adult goldfish can regenerate their optic nerve and utilize neuronal activity to generate precise topography in their projection onto tectum. Although the NMDAr has been implicated in this process, its precise role in regeneration has not been extensively studied. In examining NMDAr function during regeneration, we found salient differences compared with development. By using field excitatory postsynaptic potential (fEPSP) recordings, the contribution of the NMDAr at the primary optic synapse was measured. In contrast to development, no increase in NMDAr function was detectable during synaptic refinement. Unlike development, LTP could not be reliably elicited during regeneration. Unexpectedly, we found that NMDAr exerted a major effect on regulating ongoing tectal (postsynaptic) activity levels during regeneration. Blocking NMDAr strongly suppressed spontaneous activity during regeneration but had no significant effect in the normal projection. This difference could be attributed to an occlusion effect of strong optic drive in the normal projection, which dominated ongoing tectal activity. During regeneration, this optic drive is largely absent. Optic nerve stimulation further indicated that the NMDAr had little effect on the ability of optic fibers to evoke early postsynaptic impulse activity but was important for late network activity. These results indicate that, during regeneration, the NMDAr may play a critical role in the homeostatic regulation of ongoing activity and network excitability. PMID:23873725

  5. [Correlation of fat content and dioxins, total mercury and methyl mercury levels in tuna].

    PubMed

    Kawakami, Hiroyuki; Amakura, Yoshiaki; Tsutsumi, Tomoaki; Sasaki, Kumiko; Iketsu, Ayumi; Inasaki, Mizue; Kubota, Emi; Toyoda, Masatake

    2010-01-01

    In this study, we analyzed the concentrations of mercury and dioxins in tuna with various fat contents (akami; the leaner meat, Chutoro; the belly area of the tuna along the side of the fish between the akami and the otoro. Otoro; the fattiest portion of the tuna) in wild and farmed bluefin tuna and farmed southern bluefin tuna. In the three kinds of tuna, average dioxins concentrations in Akami, chutoro and otoro were 1.7, 4.7 and 9.6 pg TEQ/g, respectively. The dioxins concentration in all three regions of tuna was in direct proportion to the fat content. In the farmed bluefin tuna, the dioxins concentration was almost the same as that of the wild tuna, but differed from that of the farmed southern bluefin tuna. Average total mercury concentration based on wet weight in akami was 0.42 µg/g, being higher than the values of 0.36 µg/g of chutoro and 0.31 µg/g of otoro, and in inverse proportion to the fat content. In all three regions, the total mercury concentration of the wild bluefin tuna was equal to that of the farmed tuna. The total mercury concentration in the latter was two to three times higher than that of the farmed southern bluefin tuna. If the Japanese intake is one fin of tuna (80 g) a day, the daily intake levels of dioxins and methyl mercury can be estimated as 0.48-37 pg TEQ/kg bw and 0.21-0.90 µg/kg bw, respectively. PMID:21071911

  6. Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans

    PubMed Central

    Houtepen, Lotte C.; Vinkers, Christiaan H.; Carrillo-Roa, Tania; Hiemstra, Marieke; van Lier, Pol A.; Meeus, Wim; Branje, Susan; Heim, Christine M.; Nemeroff, Charles B.; Mill, Jonathan; Schalkwyk, Leonard C.; Creyghton, Menno P.; Kahn, René S.; Joëls, Marian; Binder, Elisabeth B.; Boks, Marco P. M.

    2016-01-01

    DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene (KITLG; cg27512205) showed the strongest association with cortisol stress reactivity (P=5.8 × 10−6). Replication was obtained in two independent samples using either blood (N=45, P=0.001) or buccal cells (N=255, P=0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability. PMID:26997371

  7. Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans.

    PubMed

    Houtepen, Lotte C; Vinkers, Christiaan H; Carrillo-Roa, Tania; Hiemstra, Marieke; van Lier, Pol A; Meeus, Wim; Branje, Susan; Heim, Christine M; Nemeroff, Charles B; Mill, Jonathan; Schalkwyk, Leonard C; Creyghton, Menno P; Kahn, René S; Joëls, Marian; Binder, Elisabeth B; Boks, Marco P M

    2016-01-01

    DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene (KITLG; cg27512205) showed the strongest association with cortisol stress reactivity (P=5.8 × 10(-6)). Replication was obtained in two independent samples using either blood (N=45, P=0.001) or buccal cells (N=255, P=0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability. PMID:26997371

  8. High levels of glucose induce "metabolic memory" in cardiomyocyte via epigenetic histone H3 lysine 9 methylation.

    PubMed

    Yu, Xi-Yong; Geng, Yong-Jian; Liang, Jia-Liang; Zhang, Saidan; Lei, He-Ping; Zhong, Shi-Long; Lin, Qiu-Xiong; Shan, Zhi-Xin; Lin, Shu-Guang; Li, Yangxin

    2012-09-01

    Diabetic patients continue to develop inflammation and cardiovascular complication even after achieving glycemic control, suggesting a "metabolic memory". Metabolic memory is a major challenge in the treatment of diabetic complication, and the mechanisms underlying metabolic memory are not clear. Recent studies suggest a link between chromatin histone methylation and metabolic memory. In this study, we tested whether histone 3 lysine-9 tri-methylation (H3K9me3), a key epigenetic chromatin marker, was involved in high glucose (HG)-induced inflammation and metabolic memory. Incubating cardiomyocyte cells in HG resulted in increased levels of inflammatory cytokine IL-6 mRNA when compared with myocytes incubated in normal culture media, whereas mannitol (osmotic control) has no effect. Chromatin immunoprecipitation (ChIP) assays showed that H3K9me3 levels were significantly decreased at the promoters of IL-6. Immunoblotting demonstrated that protein levels of the H3K9me3 methyltransferase, Suv39h1, were also reduced after HG treatment. HG-induced apoptosis, mitochondrial dysfunction and cytochrome-c release were reversible. However, the effects of HG on the expression of IL-6 and the levels of H3K9me3 were irreversible after the removal of HG from the culture. These results suggest that HG-induced sustained inflammatory phenotype and epigenetic histone modification, rather than HG-induced mitochondrial dysfunction and apoptosis, are main mechanisms responsible for metabolic memory. In conclusion, our data demonstrate that HG increases expression of inflammatory cytokine and decreases the levels of histone-3 methylation at the cytokine promoter, and suggest that modulating histone 3 methylation and inflammatory cytokine expression may be a useful strategy to prevent metabolic memory and cardiomyopathy in diabetic patients. PMID:22707199

  9. Methyl chloroform

    SciTech Connect

    Wray, T.K.

    1994-04-01

    Methyl chloroform is identified as a Class 1 ozone-depleting substance under Title VI of the CAA Amendments. On Nov. 30, 1993, EPA ordered the phaseout of Class 1 ozone-depleting substances -- chlorofluorocarbons (CFCs), halons, carbon tetrachloride and methyl chloroform -- by Jan. 1, 1996. Methyl chloroform and other Class 1 substances may be used after the dead-line if sources can be found through recycling or existing inventories. Methyl chloroform is listed as a hazardous air pollutant under CAA. It also is a SARA Title III, Sec. 313 compound with a reportable quantity of 1,000 pounds. OSHA and the American Conference of Government Industrial Hygienists have set 350 ppm as the time-weighted average airborne exposure level for methyl chloroform. NIOSH lists its immediately dangerous to life or health'' concentration as 1,000 parts per million. DOT identifies the substance as a hazardous material, Class 6.1 (poison).

  10. Jasminum flexile flower absolute from India--a detailed comparison with three other jasmine absolutes.

    PubMed

    Braun, Norbert A; Kohlenberg, Birgit; Sim, Sherina; Meier, Manfred; Hammerschmidt, Franz-Josef

    2009-09-01

    Jasminum flexile flower absolute from the south of India and the corresponding vacuum headspace (VHS) sample of the absolute were analyzed using GC and GC-MS. Three other commercially available Indian jasmine absolutes from the species: J. sambac, J. officinale subsp. grandiflorum, and J. auriculatum and the respective VHS samples were used for comparison purposes. One hundred and twenty-one compounds were characterized in J. flexile flower absolute, with methyl linolate, benzyl salicylate, benzyl benzoate, (2E,6E)-farnesol, and benzyl acetate as the main constituents. A detailed olfactory evaluation was also performed. PMID:19831037

  11. Teaching Absolute Value Meaningfully

    ERIC Educational Resources Information Center

    Wade, Angela

    2012-01-01

    What is the meaning of absolute value? And why do teachers teach students how to solve absolute value equations? Absolute value is a concept introduced in first-year algebra and then reinforced in later courses. Various authors have suggested instructional methods for teaching absolute value to high school students (Wei 2005; Stallings-Roberts…

  12. An energy decomposition analysis for intermolecular interactions from an absolutely localized molecular orbital reference at the coupled-cluster singles and doubles level

    SciTech Connect

    Azar, R. Julian; Head-Gordon, Martin

    2012-01-14

    We propose a wave function-based method for the decomposition of intermolecular interaction energies into chemically-intuitive components, isolating both mean-field- and explicit correlation-level contributions. We begin by solving the locally-projected self-consistent field for molecular interactions equations for a molecular complex, obtaining an intramolecularly polarized reference of self-consistently optimized, absolutely-localized molecular orbitals (ALMOs), determined with the constraint that each fragment MO be composed only of atomic basis functions belonging to its own fragment. As explicit inter-electronic correlation is integral to an accurate description of weak forces underlying intermolecular interaction potentials, namely, coordinated fluctuations in weakly interacting electronic densities, we add dynamical correlation to the ALMO polarized reference at the coupled-cluster singles and doubles level, accounting for explicit dispersion and charge-transfer effects, which map naturally onto the cluster operator. We demonstrate the stability of energy components with basis set extension, follow the hydrogen bond-breaking coordinate in the C{sub s}-symmetry water dimer, decompose the interaction energies of dispersion-bound rare gas dimers and other van der Waals complexes, and examine charge transfer-dominated donor-acceptor interactions in borane adducts. We compare our results with high-level calculations and experiment when possible.

  13. Altered Levels of Zinc and N-methyl-D-aspartic Acid Receptor Underlying Multiple Organ Dysfunctions After Severe Trauma

    PubMed Central

    Wang, Guanghuan; Yu, Xiaojun; Wang, Dian; Xu, Xiaohu; Chen, Guang; Jiang, Xuewu

    2015-01-01

    Background Severe trauma can cause secondary multiple organ dysfunction syndrome (MODS) and death. Oxidative stress and/or excitatory neurotoxicity are considered as the final common pathway in nerve cell injuries. Zinc is the cofactor of the redox enzyme, and the effect of the excitatory neurotoxicity is related to N-methyl-D-aspartic acid receptor (NMDAR). Material/Methods We investigated the levels of zinc and brainstem NMDAR in a rabbit model of severe trauma. Zinc and serum biochemical profiles were determined. Immunohistochemistry was used to detect brainstem N-methyl-D-aspartic acid receptor 1 (NR1), N-methyl-D-aspartic acid receptor 2A (NR2A), and N-methyl-D-aspartic acid receptor 2B (NR2B) expression. Results Brain and brainstem Zn levels increased at 12 h, but serum Zn decreased dramatically after the trauma. NR1 in the brainstem dorsal regions increased at 6 h after injury and then decreased. NR2A in the dorsal regions decreased to a plateau at 12 h after trauma. The levels of NR2B were lowest in the death group in the brainstem. Serum zinc was positively correlated with NR2A and 2B and negatively correlated with zinc in the brain. Correlations were also found between the brainstem NR2A and that of the dorsal brainstem, as well as between brainstem NR2A and changes in NR2B. There was a negative correlation between zinc and NR2A. Conclusions Severe trauma led to an acute reduction of zinc enhancing oxidative stress and the changes of NMDAR causing the neurotoxicity of the nerve cells. This may be a mechanism for the occurrence of MODS or death after trauma. PMID:26335029

  14. Alterations in methylation and expression levels of imprinted genes H19 and Igf2 in the fetuses of diabetic mice.

    PubMed

    Shao, Wei-Juan; Tao, Ling-Yun; Gao, Cheng; Xie, Jian-Yun; Zhao, Ru-Qian

    2008-08-01

    The study aimed to reveal alterations in expression and methylation levels of the growth-related imprinted genes H19 and Igf2 in fetuses of diabetic mice. Diabetes was induced in female mice by intraperitoneal injection of streptozotocin. DNA and total RNA were extracted from fetuses obtained from diabetic and control dams on embryonic day (E) 14. Real-time RT-PCR analysis revealed that the mRNA expression of Igf2 in fetuses from diabetic mice was 0.65-fold of the control counterparts. Bisulfite genomic sequencing demonstrated that the methylation level of the H19-Igf2 imprint control region was 19.1% higher in diabetic fetuses than in those of control dams. In addition, the body weight of pups born to diabetic dams was 26.5% lower than that of the control group. The results indicate that maternal diabetes can affect fetal development by means of altered expression of imprinted genes. The modified genomic DNA methylation status of imprinting genes may account for the change in gene expression. PMID:18724775

  15. Total and methyl mercury levels in wild mammals from the PreCambrian Shield area of south central Ontario, Canada

    SciTech Connect

    Wren, C.; MacCrimmon, H.; Frank, R.; Suda, P.

    1980-07-01

    It has been established that elevated mercury levels in fish occur in areas remote from recognized point sources of mercury contamination. It may be expected, therefore, that mercury levels may also be accumulated through natural processes in wild mammals inhabiting those areas. A process for demethylating organic mercury to less toxic inorganic mercury has been suggested in some marine mammals exposed to high mercury levls. It is possible that similar demethylating process exists in terrestial mammals which are exposed to elevated levels of mercury in their diet. Natural mercury levels in fish have been reported in the PreCambrian Shield of the Muskoka District. The present paper compares total and methyl mercury levels occurring in various organs of wilder beaver, raccoon and otter representing herbivorous, omnivorous and carnivorous life styles, collected from the same general area where substantial mercury levels are known to occur in fish.

  16. Methylation and mRNA expression levels of P15, death-associated protein kinase, and suppressor of cytokine signaling-1 genes in multiple myeloma

    PubMed Central

    Liu, Lin; Tan, Lin; He, Zhenxin

    2016-01-01

    Objective(s): The aim of this study was to investigate the methylation status and mRNA expression levels of P15, death-associated protein kinase (DAPK), and suppressor of cytokine signaling-1 (SOCS1) genes in multiple myeloma (MM). Materials and Methods: The bone marrow samples of 54 MM patients were collected and the methylation status of the P15, DAPK, and SOCS1 gene promoter regions was determined by methylation-specific polymerase chain reaction. Automated sequencing technology was used to sequence the amplified products in order to analyze the base methylation sites. mRNA expression levels were determined using real-time fluorescent quantitative polymerase chain reaction. Results: Among the 54 MM patients, the positive methylation rates of the P15, DAPK, and SOCS1 genes were 27.78%, 18.52%, and 16.67%, respectively. The methylation results were confirmed by sequencing. The positive methylation rates of the P15, DAPK, and SOCS1 genes showed no correlation with patient gender, age, typing, staging, and grouping (P>0.05). There was no significant difference in the mRNA expression levels of the P15, DAPK, and SOCS1 genes between the MM patient group and the control group (P>0.05). Conclusions: Aberrant methylation of the P15, DAPK, and SOCS1 genes exists in MM, and these genes may play certain roles in pathogenesis of MM. There was no significant difference in mRNA expression levels between the methylated group and the non-methylated group, suggesting that these genes are regulated by other mechanisms during their transcription.

  17. Risk of childhood asthma is associated with CpG-site polymorphisms, regional DNA methylation and mRNA levels at the GSDMB/ORMDL3 locus

    PubMed Central

    Acevedo, Nathalie; Reinius, Lovisa E.; Greco, Dario; Gref, Anna; Orsmark-Pietras, Christina; Persson, Helena; Pershagen, Göran; Hedlin, Gunilla; Melén, Erik; Scheynius, Annika; Kere, Juha; Söderhäll, Cilla

    2015-01-01

    Single-nucleotide polymorphisms (SNPs) in GSDMB (Gasdermin B) and ORMDL3 (ORMDL sphingolipid biosynthesis regulator 3) are strongly associated with childhood asthma, but the molecular alterations contributing to disease remain unknown. We investigated the effects of asthma-associated SNPs on DNA methylation and mRNA levels of GSDMB and ORMDL3. Genetic association between GSDMB/ORMDL3 and physician-diagnosed childhood asthma was confirmed in the Swedish birth-cohort BAMSE. CpG-site SNPs (rs7216389 and rs4065275) showed differences in DNA methylation depending on carrier status of the risk alleles, and were significantly associated with methylation levels in two CpG sites in the 5′ UTR (untranslated region) of ORMDL3. In the Swedish Search study, we found significant differences in DNA methylation between asthmatics and controls in five CpG sites; after adjusting for lymphocyte and neutrophil cell counts, three remained significant: one in IKZF3 [IKAROS family zinc finger 3 (Aiolos); cg16293631] and two in the CpG island (CGI) of ORMDL3 (cg02305874 and cg16638648). Also, cg16293631 and cg02305874 correlated with mRNA levels of ORMDL3. The association between methylation and asthma was independent of the genotype in rs7216389, rs4065275 and rs12603332. Both SNPs and CpG sites showed significant associations with ORMDL3 mRNA levels. SNPs influenced expression independently of methylation, and the residual association between methylation and expression was not mediated by these SNPs. We found a differentially methylated region in the CGI shore of ORMDL3 with six CpG sites less methylated in CD8+ T-cells. In summary, this study supports that there are differences in DNA methylation at this locus between asthmatics and controls; and both SNPs and CpG sites are independently associated with ORMDL3 expression. PMID:25256354

  18. Eosinophil count - absolute

    MedlinePlus

    Eosinophils; Absolute eosinophil count ... the white blood cell count to give the absolute eosinophil count. ... than 500 cells per microliter (cells/mcL). Normal value ranges may vary slightly among different laboratories. Talk ...

  19. Expression level and DNA methylation status of Glutathione-S-transferase genes in normal murine prostate and TRAMP tumors

    PubMed Central

    Mavis, Cory K.; Kinney, Shannon R. Morey; Foster, Barbara A.; Karpf, Adam R.

    2010-01-01

    BACKGROUND Glutathione-S-transferase (Gst) genes are down-regulated in human prostate cancer, and GSTP1 silencing is mediated by promoter DNA hypermethylation in this malignancy. We examined Gst gene expression and Gst promoter DNA methylation in normal murine prostates and Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) tumors. METHODS Primary and metastatic tumors were obtained from TRAMP mice, and normal prostates were obtained from strain-matched WT mice (n=15/group). Quantitative real-time RT-PCR was used to measure GstA4, GstK1, GstM1, GstO1, and GstP1 mRNA expression, and Western blotting and immunohistochemical staining was used to measure GstM1 and GstP1 protein expression. MassARRAY Quantitative Methylation Analysis was used to measure DNA methylation of the 5’ CpG islands of GstA4, GstK1, GstM1, GstO1, and GstP1. TRAMP-C2 cells were treated with the epigenetic remodeling drugs decitabine and trichostatin A (TSA) alone and in combination, and Gst gene expression was measured. RESULTS Of the genes analyzed, GstM1 and GstP1 were expressed at highest levels in normal prostate. All five Gst genes showed greatly reduced expression in primary tumors compared to normal prostate, but not in tumor metastases. Gst promoter methylation was unchanged in TRAMP tumors compared to normal prostate. Combined decitabine + TSA treatment significantly enhanced the expression of 4/5 Gst genes in TRAMP-C2 cells. CONCLUSIONS Gst genes are extensively downregulated in primary but not metastatic TRAMP tumors. Promoter DNA hypermethylation does not appear to drive Gst gene repression in TRAMP primary tumors; however, pharmacological studies using TRAMP cells suggest the involvement of epigenetic mechanisms in Gst gene repression. PMID:19444856

  20. Electrochemiluminescence signal amplification combined with a conformation-switched hairpin DNA probe for determining the methylation level and position in the Hsp53 tumor suppressor gene.

    PubMed

    Zhang, Hui; Li, Meixing; Fan, Mengxing; Gu, Jinxing; Wu, Ping; Cai, Chenxin

    2014-03-18

    We report a new strategy for detection of the methylation level and position in the Hsp53 tumor suppressor gene based on the electrochemiluminescence signal amplification combined with a conformation-switched hairpin DNA probe for improving selectivity. PMID:24501739

  1. Electronic Absolute Cartesian Autocollimator

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B.

    2006-01-01

    An electronic absolute Cartesian autocollimator performs the same basic optical function as does a conventional all-optical or a conventional electronic autocollimator but differs in the nature of its optical target and the manner in which the position of the image of the target is measured. The term absolute in the name of this apparatus reflects the nature of the position measurement, which, unlike in a conventional electronic autocollimator, is based absolutely on the position of the image rather than on an assumed proportionality between the position and the levels of processed analog electronic signals. The term Cartesian in the name of this apparatus reflects the nature of its optical target. Figure 1 depicts the electronic functional blocks of an electronic absolute Cartesian autocollimator along with its basic optical layout, which is the same as that of a conventional autocollimator. Referring first to the optical layout and functions only, this or any autocollimator is used to measure the compound angular deviation of a flat datum mirror with respect to the optical axis of the autocollimator itself. The optical components include an illuminated target, a beam splitter, an objective or collimating lens, and a viewer or detector (described in more detail below) at a viewing plane. The target and the viewing planes are focal planes of the lens. Target light reflected by the datum mirror is imaged on the viewing plane at unit magnification by the collimating lens. If the normal to the datum mirror is parallel to the optical axis of the autocollimator, then the target image is centered on the viewing plane. Any angular deviation of the normal from the optical axis manifests itself as a lateral displacement of the target image from the center. The magnitude of the displacement is proportional to the focal length and to the magnitude (assumed to be small) of the angular deviation. The direction of the displacement is perpendicular to the axis about which the

  2. Degradation of kresoxim-methyl in soil: impact of varying moisture, organic matter, soil sterilization, soil type, light and atmospheric CO2 level.

    PubMed

    Khandelwal, Ashish; Gupta, Suman; Gajbhiye, Vijay T; Varghese, Eldho

    2014-09-01

    In the present investigation, persistence of kresoxim-methyl (a broad spectrum strobilurin fungicide) was studied in two different soil types of India namely Inceptisol and Ultisol. Results revealed that kresoxim-methyl readily form acid metabolite in soil. Therefore, residues of kresoxim-methyl were quantified on the basis of parent molecule alone and sum total of kresoxim-methyl and its acid metabolite. Among the two soil types, kresoxim-methyl and total residues dissipated at a faster rate in Inceptisol (T1/2 0.9 and 33.8d) than in Ultisol (T1/2 1.5 and 43.6d). Faster dissipation of kresoxim-methyl and total residues was observed in submerged soil conditions (T1/2 0.5 and 5.2d) followed by field capacity (T1/2 0.9 and 33.8d) and air dry (T1/2 2.3 and 51.0d) conditions. Residues also dissipated faster in 5% sludge amended soil (T1/2 0.7 and 21.1d) and on Xenon-light exposure (T1/2 0.5 and 8.0d). Total residues of kresoxim-methyl dissipated at a faster rate under elevated CO2 condition (∼550μLL(-)(1)) than ambient condition (∼385μLL(-)(1)). The study suggests that kresoxim-methyl alone has low persistence in soil. Because of the slow dissipation of acid metabolite, the total residues (kresoxim-methyl+acid metabolite) persist for a longer period in soil. Statistical analysis using SAS 9.3 software and Duncan's Multiple Range Test (DMRT) revealed the significant effect of moisture regime, organic matter, microbial population, soil type, light exposure and atmospheric CO2 level on the dissipation of kresoxim-methyl from soil (at 95% confidence level p<0.0001). PMID:24997920

  3. Twitching motility and cAMP levels: signal transduction through a single methyl-accepting chemotaxis protein.

    PubMed

    Jansari, Vibhuti H; Potharla, Vishwakanth Y; Riddell, Geoff T; Bardy, Sonia L

    2016-06-01

    The Pseudomonas aeruginosa Chp chemosensory system regulates twitching motility, intracellular adenosine 3('') 5(')-cyclic monophosphate (cAMP) levels and is postulated to be involved in directional twitching towards phosphatidylethanolamine (PE). Because PilJ is the only methyl-accepting chemotaxis protein (MCP) identified in the Chp system, we determined the role of PilJ in mediating signal transduction for the distinct outputs of this system. Mutants that lack the periplasmic domain of PilJ (pilJΔ74-273) showed lower levels of cAMP but retained directional twitching towards PE. While initial studies revealed reduced twitching motility by PilJΔ74-273, this was due to decreased cAMP levels. Our data illustrate the importance of the periplasmic domain of PilJ in regulating cAMP. This is the first time a defined domain within PilJ has been identified as having a distinct role in signal transduction. PMID:27190147

  4. A sensitive mass-spectrometry method for simultaneous quantification of DNA methylation and hydroxymethylation levels in biological samples

    PubMed Central

    Le, Thuc; Kim, Kee-Pyo; Fan, Guoping; Faull, Kym F.

    2011-01-01

    The recent discovery of 5-hydroxymethyl-cytosine (5hmC) in embryonic stem cells and post-mitotic neurons has triggered the need for quantitative measurements of both 5-methyl-cytosine (5mC) and 5hmC in the same sample. We have developed a method using liquid chromatography electrospray ionization tandem mass spectrometry with multiple reaction monitoring (LC-ESI-MS/MS-MRM) to simultaneously measure levels of 5mC and 5hmC in digested genomic DNA. This method is fast, robust and accurate, and is more sensitive than the current 5hmC quantitation methods such as end-labeling with thin-layer chromatography and radio-labeling by glycosylation [1; 2]. Only 50 ng of digested genomic DNA is required to measure the presence of 0.1% 5hmC in DNA from mouse embryonic stem cells. Using this procedure we show that human induced pluripotent stem cells exhibit a dramatic increase in 5mC and 5hmC levels compared to parental fibroblast cells, suggesting a dynamic regulation of DNA methylation and hydroxymethylation during cellular reprogramming. PMID:21272560

  5. Lower levels of transgene silencing in roots is associated with reduced DNA methylation levels at non-symmetrical sites but not at symmetrical sites.

    PubMed

    Andika, Ida Bagus; Kondo, Hideki; Rahim, Muhammad Danial; Tamada, Tetsuo

    2006-02-01

    Transgene transcripts were recently shown to accumulate at higher levels in roots, relative to leaves, of silenced-transgenic Nicotiana benthamiana plants and to be inversely related with the accumulation of small interfering RNAs (siRNAs), suggesting that RNA silencing is less active in roots than in leaves (Andika et al., 2005. Mol. Plant-Microbe Interact. 18: 194). Here we show that the lower transgene RNA silencing activity in roots was associated with lower transgene methylation levels at non-symmetrical CpNpN context but not at symmetrical CpG or CpNpG context in three sets of transformant plants with different exogenous genes. In contrast, such a difference between roots and leaves was not observed for the Tnt1 retrotransposon: no Tnt1 transcript was detected in roots or in leaves of N. benthamiana, while equal levels of Tnt1-derived siRNA accumulation and Tnt1 methylation were found. From our data and previously reported information, we suggest that roots have less of an activity that acts at the step of generation of siRNAs. PMID:16514564

  6. SERPINE1, PAI-1 protein coding gene, methylation levels and epigenetic relationships with adiposity changes in obese subjects with metabolic syndrome features under dietary restriction

    PubMed Central

    Lopez-Legarrea, Patricia; Mansego, Maria Luisa; Zulet, Marian Angeles; Martinez, Jose Alfredo

    2013-01-01

    Plasminogen activator inhibitor 1 (PAI-1) has been associated with metabolic disorders, through different mechanisms, which could involve changes in DNA methylation. This work aimed to assess the potential relationships of the cytosine methylation levels within SERPINE1 gene transcriptional regulatory region, which codes for PAI-1, in peripheral white blood cells with anthropometrical, metabolic and inflammatory features. Forty-six obese subjects with metabolic syndrome features followed Control or Metabolic Syndrome Reduction in Navarra (RESMENA) energy-restricted (−30%E) diets for 8 weeks. SERPINE1 transcriptional regulatory region methylation at baseline was analyzed by a microarray technical. Both dietary strategies reduced anthropometric and biochemical parameters. The Control group significantly reduced plasma PAI-1 concentrations but not the RESMENA group. Participants from both nutritional interventions with higher SERPINE1 methylation levels at baseline showed significantly major reductions in body weight, total fat mass, android fat mass, total cholesterol and triglycerides, as compared with those with lower initial SERPINE1 methylation levels. In conclusion, the DNA methylation levels of SERPINE1 transcriptional regulatory region were associated with some metabolic and anthropometric changes in obese subjects with metabolic syndrome under energy restriction, suggesting a complex epigenetic network in the regulation of this recognized pro-inflammatory marker. (www.clinicaltrials.gov; NCT01087086) PMID:24249967

  7. Umbrella motion of the methyl cation, radical, and anion molecules. I. Potentials, energy levels and partition functions

    NASA Astrophysics Data System (ADS)

    Ragni, Mirco; Bitencourt, Ana Carla P.; Prudente, Frederico V.; Barreto, Patricia R. P.; Posati, Tamara

    2016-03-01

    A study of the umbrella motion of the methyl cation, radical, and anion molecules is presented. This is the floppiest mode of vibration of all three species and its characterization is of fundamental importance for understanding their reactivity. Minimum Energy Paths of the umbrella motions according to the hyperspherical treatment were obtained, by single point calculations, at the CCSD(T)/aug-cc-pVQT level of theory in the Born-Oppenheimer approximation. These energy profiles permit us to calculate the vibrational levels through the Hyperquantization algorithm, which is shown appropriated for the description of the umbrella motion of these three molecules. The adiabatic electron affinity and ionization potentials were estimated to good accuracy. Partition functions are also calculated in order to obtain information on the reaction rates involving these groups.

  8. Absolute Income, Relative Income, and Happiness

    ERIC Educational Resources Information Center

    Ball, Richard; Chernova, Kateryna

    2008-01-01

    This paper uses data from the World Values Survey to investigate how an individual's self-reported happiness is related to (i) the level of her income in absolute terms, and (ii) the level of her income relative to other people in her country. The main findings are that (i) both absolute and relative income are positively and significantly…

  9. Absolute nuclear material assay

    DOEpatents

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2012-05-15

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  10. Absolute nuclear material assay

    DOEpatents

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2010-07-13

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  11. Effects of different levels of gum arabic, low methylated pectin and xylan on in vitro digestibility of beta-lactoglobulin.

    PubMed

    Mouécoucou, J; Sanchez, C; Villaume, C; Marrion, O; Frémont, S; Laurent, F; Méjean, L

    2003-12-01

    Plant hydrocolloids used in the food industry to improve texture and stability of food, such as dairy products, can reduce protein digestibility and, consequently, modify the bioavailability of amino acids. We studied the in vitro hydrolysis at 37 degrees C of beta-lactoglobulin (beta-lg) in mixed dispersions containing either gum arabic or low-methylated pectin or xylan at levels of 0, 1, 10, 20, 30, and 50% weight. Proteolysis used either pepsin alone by progressive reduction of pH during proteolysis or pepsin followed by trypsin and chymotrypsin in two different dialysis bags with a molecular weight (MW) cutoff of 1000 or 8000 Da. Results showed that beta-lg was almost resistant to pepsin digestion and that the three plant hydrocolloids inhibited significantly beta-lg digestibility as determined using dialysis bag with a 1000-Da MW cutoff. Among the three polysaccharides used, xylan showed a digestibility decrease greater than that obtained with gum arabic and low-methylated pectin. On the other hand, no significant effect of polysaccharides on the in vitro beta-lg digestibility was detected using the dialysis bag with an 8000 Da MW cutoff. This mainly suggests that peptides with MW in the range 1000 to 8000 Da may interact with polysaccharides more than peptides and proteins with a greater molecular weight to decrease the protein digestibility, and that the nature of the polysaccharides plays a role in the interaction. PMID:14740820

  12. Sub-parts-per-billion level detection of dimethyl methyl phosphonate (DMMP) by quantum cascade laser photoacoustic spectroscopy.

    PubMed

    Mukherjee, Anadi; Dunayevskiy, Ilya; Prasanna, Manu; Go, Rowel; Tsekoun, Alexei; Wang, Xiaojun; Fan, Jenyu; Patel, C Kumar N

    2008-04-01

    The need for the detection of chemical warfare agents (CWAs) is no longer confined to battlefield environments because of at least one confirmed terrorist attack, the Tokyo Subway [Emerg. Infect. Dis. 5, 513 (1999)] in 1995, and a suspected, i.e., a false-alarm of a CWA in the Russell Senate Office Building [Washington Post, 9 February 2006, p. B01]. Therefore, detection of CWAs with high sensitivity and low false-alarm rates is considered an important priority for ensuring public safety. We report a minimum detection level for a CWA simulant, dimethyl methyl phosphonate (DMMP), of <0.5 ppb (parts in 10(9)) by use of a widely tunable external grating cavity quantum cascade laser and photoacoustic spectroscopy. With interferents present in Santa Monica, California street air, we demonstrate a false-alarm rate of 1:10(6) at a detection threshold of 1.6 ppb. PMID:18382583

  13. Anharmonic Resonances among Low-Lying Vibrational Levels of Methyl Iso-Cyanide (H_3CNC)

    NASA Astrophysics Data System (ADS)

    Pracna, P.; Urban, J.; Urban, V. S.; Varga, J.; Horneman, V.-M.

    2010-06-01

    Vibrational levels up to 1000 wn of H_3C-N≡C are currently studied in FTIR spectra together with rotational transitions within these levels. This investigation comprises the low-lying excited vibrational levels of the CNC doubly degenerate bending vibration v8=1^± 1 (267.3 wn), v8=20,± 2 (524.6 wn (A), 545.3 wn (E)), and v8=3^± 1,± 3 (792.5 wn (A1+A2), 833.9 wn (E)), respectively, and the next higher fundamental level of the C-N valence vibration v4=1 (945 wn). All these vibrational levels exhibit cubic and quartic anharmonic resonances localized to moderate values of the rotational quantum number K≤10. Therefore the system of rovibrational levels has to be treated as a global polyad in order to describe all the available data quantitatively. The ground state constants have been improved considerably by extending the assignments to higher J/K rotational states both in the purely rotational spectra recorded in the ground vibrational level and in the ground state combination differences generated from the wavenumbers assigned in the fundamental ν_4 band. Similarities and differences with respect to isoelectronic molecules CH_3CN and CH_3CCH are discussed.

  14. Association of DNA Methylation Levels with Tissue-specific Expression of Adipogenic and Lipogenic Genes in Longissimus dorsi Muscle of Korean Cattle

    PubMed Central

    Baik, M.; Vu, T. T. T.; Piao, M. Y.; Kang, H. J.

    2014-01-01

    Epigenetic factors, such as DNA methylation status, may regulate adipogenesis and lipogenesis, thus affecting intramuscular fat (IMF) deposition in longissimus dorsi muscle (LM) of beef cattle. In Korean cattle steers, the LM consists mainly of muscle tissue. However, the LM tissue also contains IMF. We compared the gene expression levels between the IMF and muscle portions of the LM after tissue separation. Real-time polymerase chain reaction analysis showed that the mRNA levels of both adipogenic peroxisome proliferator-activated receptor gamma isoform 1 (PPARG1) and lipogenic fatty acid binding protein 4 (FABP4) were higher (p<0.01) in the IMF than in the muscle portion of the LM. We determined DNA methylation levels of regulatory regions of the PPARG1 and FABP4 genes by pyrosequencing of genomic DNA. DNA methylation levels of two of three CpG sites in the PPARG1 gene promoter region were lower (p<0.05) in the IMF than in the muscle portion of the LM. DNA methylation levels of all five CpG sites from the FABP4 gene promoter region were also lower (p<0.001) in the IMF than in the muscle portion. Thus, mRNA levels of both PPARG1 and FABP4 genes were inversely correlated with DNA methylation levels in regulatory regions of CpG sites of the corresponding gene. Our findings suggest that DNA methylation status regulates tissue-specific expression of adipogenic and lipogenic genes in the IMF and muscle portions of LM tissue in Korean cattle. PMID:25178302

  15. Methylation on the Circadian Gene BMAL1 Is Associated with the Effects of a Weight Loss Intervention on Serum Lipid Levels.

    PubMed

    Samblas, Mirian; Milagro, Fermin I; Gómez-Abellán, Purificación; Martínez, J Alfredo; Garaulet, Marta

    2016-06-01

    The circadian clock system has been linked to the onset and development of obesity and some accompanying comorbidities. Epigenetic mechanisms, such as DNA methylation, are putatively involved in the regulation of the circadian clock system. The aim of this study was to investigate the influence of a weight loss intervention based on an energy-controlled Mediterranean dietary pattern in the methylation levels of 3 clock genes, BMAL1, CLOCK, and NR1D1, and the association between the methylation levels and changes induced in the serum lipid profile with the weight loss treatment. The study sample enrolled 61 women (body mass index = 28.6 ± 3.4 kg/m(2); age: 42.2 ± 11.4 years), who followed a nutritional program based on a Mediterranean dietary pattern. DNA was isolated from whole blood obtained at the beginning and end point. Methylation levels at different CpG sites of BMAL1, CLOCK, and NR1D1 were analyzed by Sequenom's MassArray. The energy-restricted intervention modified the methylation levels of different CpG sites in BMAL1 (CpGs 5, 6, 7, 9, 11, and 18) and NR1D1 (CpGs 1, 10, 17, 18, 19, and 22). Changes in cytosine methylation in the CpG 5 to 9 region of BMAL1 with the intervention positively correlated with the eveningness profile (p = 0.019). The baseline methylation of the CpG 5 to 9 region in BMAL1 positively correlated with energy (p = 0.047) and carbohydrate (p = 0.017) intake and negatively correlated with the effect of the weight loss intervention on total cholesterol (p = 0.032) and low-density lipoprotein cholesterol (p = 0.005). Similar significant and positive correlations were found between changes in methylation levels in the CpG 5 to 9 region of BMAL1 due to the intervention and changes in serum lipids (p < 0.05). This research describes apparently for the first time an association between changes in the methylation of the BMAL1 gene with the intervention and the effects of a weight loss intervention on blood lipids levels. PMID:26873744

  16. Associations between the polymorphisms of GSTT1, GSTM1 and methylation of arsenic in the residents exposed to low-level arsenic in drinking water in China.

    PubMed

    Yang, Jinyou; Yan, Li; Zhang, Min; Wang, Yijun; Wang, Chun; Xiang, Quanyong

    2015-07-01

    We carry out a study to analyze the relation between polymorphisms of GSTT1, GSTM1 and the capacity of arsenic methylation in a human population exposed to arsenic in drinking water. 230 randomly chose subjects were divided into four subgroups based on the arsenic levels, and then the associations between the polymorphisms of GSTT1, GSTM1 and methylation of arsenic were investigated. The levels of inorganic arsenic (iAs), monomethylated arsenic (MMA), dimethylated arsenic (DMA) and total arsenic (TAs) in urine were higher in males than that in females. Moreover, the levels of iAs and TAs in urine in the subjects with genotype of GSTM1(+) were significantly higher than those with GSTM1(-); the level of DMA in the subjects with GSTT1(+) and GSTM1(+) were higher than those with GSTT1(-) and GSTM1(-), although it is not statistically significant. Secondary methylation index (SMI) was significantly higher in the subjects with genotype of GSTT1(+) than those with GSTT1(-). The levels of TAs in urine, together with the genotypes of GSTT1/GSTM1 were associated with the levels of MMA and DMA. Our results suggested that the polymorphisms of GSTT1 and GSTM1 were associated with the methylation of arsenic, especially the levels of DMA and SMI. PMID:25876999

  17. Expression level and methylation status of three tumor suppressor genes, DLEC1, ITGA9 and MLH1, in non-small cell lung cancer.

    PubMed

    Pastuszak-Lewandoska, Dorota; Kordiak, Jacek; Antczak, Adam; Migdalska-Sęk, Monika; Czarnecka, Karolina H; Górski, Paweł; Nawrot, Ewa; Kiszałkiewicz, Justyna M; Domańska-Senderowska, Daria; Brzeziańska-Lasota, Ewa

    2016-07-01

    Despite therapeutic advances, lung cancer remains one of the most common causes of cancer-related death in the world. There is a need to develop biomarkers of diagnostic and/or prognostic value and to translate findings in basic science research to clinical application. Tumor suppressor genes (TSGs) represent potential useful markers for disease detection, progression and treatment target. We tried to elucidate the role of three 3p21.3 TSGs: DLEC1, ITGA9 and MLH1, in non-small cell lung cancer (NSCLC). We assessed their expression pattern by qPCR in 59 NSCLC tissues and in the matched macroscopically unchanged lung tissues. Additionally, we analyzed gene promoter methylation status by methylation-specific PCR in NSCLC samples. We did not find significant correlations between gene expression and methylation. In case of DLEC1 and ITGA9, expression levels were decreased in 71-78 % of tumor samples and significantly different between tumor and normal tissues (P = 0.0001). It could point to their diagnostic value. ITGA9 could also be regarded as a diagnostic marker differentiating NSCLC subtypes, as its expression level was significantly lower in squamous cell carcinoma (P = 0.001). The simultaneous down-regulation of DLEC1 and ITGA9 was observed in 52.5 % of NSCLCs. MSPs revealed high frequencies of gene promoter methylation in NSCLCs: 84 % for DLEC1 and MLH1 and 57 % for ITGA9. Methylation indexes reflected moderate gene methylation levels: 34 % for ITGA9, 27 % for MLH1 and 26 % for DLEC1. However, frequent simultaneous methylation of the studied genes in more than 50 % of NSCLCs suggests the possibility of consider them as a panel of epigenetic markers. PMID:27287342

  18. Association of weight regain with specific methylation levels in the NPY and POMC promoters in leukocytes of obese men: a translational study.

    PubMed

    Crujeiras, Ana B; Campion, Javier; Díaz-Lagares, Angel; Milagro, Fermin I; Goyenechea, Estíbaliz; Abete, Itziar; Casanueva, Felipe F; Martínez, J Alfredo

    2013-09-10

    Specific methylation of appetite-related genes in leukocytes could serve as a useful biomarker to predict weight regain after an energy restriction program. We aimed to evaluate whether the pre-intervention DNA methylation patterns involved in the epigenetic control of appetite-regulatory genes in leukocytes are associated with the weight regain process. Eighteen men who lost ≥5% of body weight after an 8-week nutritional intervention were categorized as "regainers" (≥10% weight regain) and "non-regainers" (<10% weight regain) 32weeks after stopping dieting. At baseline, leukocytes were isolated and DNA was analyzed for epigenetic methylation patterns of appetite-related gene promoters by MALDI-TOF mass spectrometry. Regainers showed higher methylation levels than non-regainers in proopiomelanocortin (POMC) CpG sites +136bp and +138bp (fold change from non-regainers=26%; p=0.020) and lower methylation of the whole analyzed region of neuropeptide Y (NPY; fold change from non-regainers=-22%; p=0.033), as well as of several individual NPY-promoter CpG sites. Importantly, total baseline NPY methylation was associated with weight-loss regain (r=-0.76; p<0.001), baseline plasma ghrelin levels (r=0.60; p=0.011) and leptin/ghrelin ratio (r=-0.52; p=0.046). Lower methylation levels of POMC CpG sites +136bp and +138bp were associated with success in weight-loss maintenance (odds ratio=0.042 [95% CI 0.01-0.57]; p=0.018), whereas lower total methylation levels in NPY promoter were associated with higher risk of weight regain (odds ratio=14.0 [95% CI 1.13-172]; p=0.039). Therefore, the study of leukocyte methylation levels reflects a putative epigenetic regulation of NPY and POMC, which might be implicated in the weight regain process and be used as biomarkers for predicting weight regain after dieting. PMID:23831408

  19. Methylation levels of P16 and TP53 that are involved in DNA strand breakage of 16HBE cells treated by hexavalent chromium.

    PubMed

    Hu, Guiping; Li, Ping; Li, Yang; Wang, Tiancheng; Gao, Xin; Zhang, Wenxiao; Jia, Guang

    2016-05-13

    The correlations between methylation levels of p16 and TP53 with DNA strand breakage treated by hexavalent chromium [Cr(VI)] remain unknown. In this research, Human bronchial epithelial cells (16HBE cells) in vitro and bioinformatics analysis were used to analyze the epigenetic role in DNA damage and potential biomarkers. CCK-8 and single cell gel electrophoresis assay were chosen to detect the cellular biological damage. MALDI-TOF-MS was used to detect the methylation levels of p16 and TP53. qRT-PCR was used to measure their expression levels in different Cr(VI) treatment groups. The transcription factors with target sequences of p16 and TP53 were predicted using various bioinformatics software. The findings showed that the cellular toxicity and DNA strand damage were Cr(VI) concentration dependent. The hypermethylation of CpG1, CpG31 and CpG32 of p16 was observed in Cr(VI) treated groups. There was significant positive correlation between the CpG1 methylation level of p16 and cell damage. In Cr(VI) treated groups, the expression level of p16 was lower than that in control group. The expression level of TP53 increased when the Cr(VI)concentration above 5μM. About p16, there was significant negative correlation between the CpG1 methylation levels with its expression level. A lot of binding sites for transcription factors existed in our focused CpG islands of p16. All the results suggested that the CpG1 methylation level of p16 could be used as a biomarker of epigenetic effect caused by Cr(VI) treatment, which can enhance cell damage by regulating its expression or affecting some transcription factors to combine with their DNA strand sites. PMID:27005777

  20. Effects of low dietary levels of methyl mercury on mallard reproduction

    USGS Publications Warehouse

    Heinz, G.

    1974-01-01

    Mallard ducks were fed a control diet or a diet containing 0.5 ppm or 3 ppm mercury (as methylmercury dicyandiamide). Health of adults and reproductive success were studied. The dietary level of 3 ppm mercury had harmful effects on reproduction, although it did not appear to affect the health of the adults during the 12 months of dosage. Ducks that were fed the diet containing 0.5 ppm mercury reproduced as well as controls, and ducklings from parents fed 0.5 ppm mercury grew faster in the first week of life than did controls....The greatest harm to reproduction associated with the diet containing 3 ppm mercury was an increase in duckling mortality, but reduced egg laying and increased embryonic mortality also occurred....During the peak of egg laying, eggs laid by controls tended to be heavier than eggs laid by ducks fed either level of mercury; however, there seemed to be no eggshell thinning associated with mercury treatment. Levels of mercury reached about 1 ppm in eggs from ducks fed a dietary dosage of 0.5 ppm mercury and between 6 and 9 ppm in the eggs from ducks fed 3 ppm mercury.

  1. Absolute biological needs.

    PubMed

    McLeod, Stephen

    2014-07-01

    Absolute needs (as against instrumental needs) are independent of the ends, goals and purposes of personal agents. Against the view that the only needs are instrumental needs, David Wiggins and Garrett Thomson have defended absolute needs on the grounds that the verb 'need' has instrumental and absolute senses. While remaining neutral about it, this article does not adopt that approach. Instead, it suggests that there are absolute biological needs. The absolute nature of these needs is defended by appeal to: their objectivity (as against mind-dependence); the universality of the phenomenon of needing across the plant and animal kingdoms; the impossibility that biological needs depend wholly upon the exercise of the abilities characteristic of personal agency; the contention that the possession of biological needs is prior to the possession of the abilities characteristic of personal agency. Finally, three philosophical usages of 'normative' are distinguished. On two of these, to describe a phenomenon or claim as 'normative' is to describe it as value-dependent. A description of a phenomenon or claim as 'normative' in the third sense does not entail such value-dependency, though it leaves open the possibility that value depends upon the phenomenon or upon the truth of the claim. It is argued that while survival needs (or claims about them) may well be normative in this third sense, they are normative in neither of the first two. Thus, the idea of absolute need is not inherently normative in either of the first two senses. PMID:23586876

  2. The levels of H11/HspB8 DNA methylation in human melanoma tissues and xenografts are a critical molecular marker for 5'-Aza-2-deoxycytidine therapy

    PubMed Central

    Smith, Cynthia C.; Li, Baiquan; Liu, Juan; Lee, Kie-Sok; Aurelian, Laure

    2011-01-01

    H11/HspB8 is a functionally distinct small heat shock protein. It causes growth arrest in melanocytes, associated with inhibition of cyclin E/cdk2 and β~-catenin phosphorylation at the transcriptional activity site Ser552 and is silenced through DNA methylation in 27/35 (77%) melanoma tissues/early cultures. 5'-Aza-2-deoxycytidine (Aza-C) induces melanoma cell death correlated with the levels of H11/HspB8 DNA methylation (p<0.001). In lines with low/moderate H11/HspB8 methylation, PI3-K inhibition increases Aza-C-induced cell death. Aza-C Inhibits growth of melanoma xenografts related to the levels of H11/HspB8 methylation, and a non-methylated/non-TAK1 binding H11/HspB8 mutant confers Aza-C resistance. H11/HspB8 is a potential molecular marker for demethylation therapies. PMID:21649464

  3. Uric acid or 1-methyl uric acid in the urinary bladder increases serum glucose, insulin, true triglyceride, and total cholesterol levels in Wistar rats.

    PubMed

    Balasubramanian, T

    2003-10-01

    In animals deprived of food for a long period, a drop in the fat mass below 5% of the total body mass results in an increase in blood glucocorticoids and uric acid levels, followed by foraging activity. Since the glucocorticoids increase the uric acid excretion, an increase in the level of uric acid in the bladder urine could be the signal for this feeding behaviour and subsequent fat storage. Accumulation of fat is associated with hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and hypercholesterolaemia as seen in the metabolic syndrome or hibernation. It is hypothesized that uric acid or its structurally related compound, 1-methyl uric acid (one of the metabolites of the methyl xanthines namely caffeine, theophylline, and theobromine present in coffee, tea, cocoa, and some drugs), can act on the urinary bladder mucosa and increases the blood glucose, insulin, triglyceride, and cholesterol levels. In rats, perfusion of the urinary bladder with saturated aqueous solution of uric acid or 1-methyl uric acid results in a significant increase in the serum levels of glucose, insulin, true triglyceride, and total cholesterol in comparison with perfusion of the bladder with distilled water at 20, 40, and 80 min. The uric acid or the 1-methyl uric acid acts on the urinary bladder mucosa and increases the serum glucose, insulin, true triglyceride, and total cholesterol levels. PMID:15241498

  4. DNA methylation levels at individual age-associated CpG sites can be indicative for life expectancy

    PubMed Central

    Lin, Qiong; Weidner, Carola I.; Costa, Ivan G.; Marioni, Riccardo E.; Ferreira, Marcelo R. P.; Deary, Ian J.; Wagner, Wolfgang

    2016-01-01

    DNA-methylation (DNAm) levels at age-associated CpG sites can be combined into epigenetic aging signatures to estimate donor age. It has been demonstrated that the difference between such epigenetic age-predictions and chronological age is indicative for of all-cause mortality in later life. In this study, we tested alternative epigenetic signatures and followed the hypothesis that even individual age-associated CpG sites might be indicative for life-expectancy. Using a 99-CpG aging model, a five-year higher age-prediction was associated with 11% greater mortality risk in DNAm profiles of the Lothian Birth Cohort 1921 study. However, models based on three CpGs, or even individual CpGs, generally revealed very high offsets in age-predictions if applied to independent microarray datasets. On the other hand, we demonstrate that DNAm levels at several individual age-associated CpGs seem to be associated with life expectancy – e.g., at CpGs associated with the genes PDE4C and CLCN6. Our results support the notion that small aging signatures should rather be analysed by more quantitative methods, such as site-specific pyrosequencing, as the precision of age-predictions is rather low on independent microarray datasets. Nevertheless, the results hold the perspective that simple epigenetic biomarkers, based on few or individual age-associated CpGs, could assist the estimation of biological age. PMID:26928272

  5. Gene-Specific DNA Methylation Association with Serum Levels of C-Reactive Protein in African Americans

    PubMed Central

    Sun, Yan V.; Lazarus, Alicia; Smith, Jennifer A.; Chuang, Yu-Hsuan; Zhao, Wei; Turner, Stephen T.; Kardia, Sharon L. R.

    2013-01-01

    A more thorough understanding of the differences in DNA methylation (DNAm) profiles in populations may hold promise for identifying molecular mechanisms through which genetic and environmental factors jointly contribute to human diseases. Inflammation is a key molecular mechanism underlying several chronic diseases including cardiovascular disease, and it affects DNAm profile on both global and locus-specific levels. To understand the impact of inflammation on the DNAm of the human genome, we investigated DNAm profiles of peripheral blood leukocytes from 966 African American participants in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. By testing the association of DNAm sites on CpG islands of over 14,000 genes with C-reactive protein (CRP), an inflammatory biomarker of cardiovascular disease, we identified 257 DNAm sites in 240 genes significantly associated with serum levels of CRP adjusted for age, sex, body mass index and smoking status, and corrected for multiple testing. Of the significantly associated DNAm sites, 80.5% were hypomethylated with higher CRP levels. The most significant Gene Ontology terms enriched in the genes associated with the CRP levels were immune system process, immune response, defense response, response to stimulus, and response to stress, which are all linked to the functions of leukocytes. While the CRP-associated DNAm may be cell-type specific, understanding the DNAm association with CRP in peripheral blood leukocytes of multi-ethnic populations can assist in unveiling the molecular mechanism of how the process of inflammation affects the risks of developing common disease through epigenetic modifications. PMID:23977389

  6. HIGH LEVELS OF MONOAROMATIC COMPOUNDS LIMIT THE USE OF SOLID-PHASE MICROEXTRACTION OF METHYL TERTIARY BUTYL ETHER AND TERTIARY BUTYL ALCOHOL

    EPA Science Inventory

    Recently, two papers reported the use of solid-phase microextraction (SPME) with polydimethylsiloxane(PDMS)/Carboxen fibers to determine trace levels of methyl tertiary butyl ether (MTBE) and tertiary butyl alcohol (tBA) in water. Attempts were made to apply this technique to th...

  7. Relationship between blood levels of methyl donor and folate and mild cognitive impairment in Chinese patients with type 2 diabetes: a case-control study

    PubMed Central

    Zheng, Miaoyan; Zhang, Meilin; Yang, Juhong; Zhao, Shijing; Qin, Shanchun; Chen, Hui; Gao, Yuxia; Huang, Guowei

    2014-01-01

    Type 2 diabetes is a risk factor for Alzheimer’s disease and mild cognitive impairment. Folate insufficiency fosters a decline in the sole methyl donor, S-adenosylmethionine, and decreases methylation potential, which is associated with Alzheimer’s disease in non-diabetic patients. However, little is known in diabetic patients. We analyzed plasma levels of S-adenosylmethionine, S-adenosylhomocysteine and serum level of folate in 100 elderly type 2 diabetic patients with and without mild cognitive impairment. S-adenosylmethionine/S-adenosylhomocysteine ratio was used to reflect the methylation potential. Patients with mild cognitive impairment had significantly lower levels of S-adenosylmethionine, folate and S-adenosylmethionine/S-adenosylhomocysteineratios. Furthermore, logistic regression analysis indicated the plasma S-adenosylmethionine, S-adenosylmethionine/S-adenosylhomocysteine ratio and serum folate (OR, 0.96, 0.698, 0.72, respectively; p<0.05) were negatively associated with risk of mild cognitive impairment, even after adjusting for related covariates. In addition, folate level was positively correlated with S-adenosylmethionine and the S-adenosylmethionine/S-adenosylhomocysteine ratio (r = 0.38, 0.46, respectively; p<0.05) among patients within the middle tertile of folate levels (6.3–9.1 µg/L). These findings indicate mild cognitive impairment is associated with lower levels of S-adenosylmethionine, folate and weakened methylation potential; plasma S-adenosylmethionine and methylation potential may be predicted by serum folate within a suitable range of folate concentrations in diabetic patients. PMID:24688222

  8. Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface.

    PubMed

    Novakovic, Boris; Sibson, Mandy; Ng, Hong Kiat; Manuelpillai, Ursula; Rakyan, Vardhman; Down, Thomas; Beck, Stephan; Fournier, Thierry; Evain-Brion, Danielle; Dimitriadis, Eva; Craig, Jeffrey M; Morley, Ruth; Saffery, Richard

    2009-05-29

    Plasma concentrations of biologically active vitamin D (1,25-(OH)(2)D) are tightly controlled via feedback regulation of renal 1alpha-hydroxylase (CYP27B1; positive) and 24-hydroxylase (CYP24A1; catabolic) enzymes. In pregnancy, this regulation is uncoupled, and 1,25-(OH)(2)D levels are significantly elevated, suggesting a role in pregnancy progression. Epigenetic regulation of CYP27B1 and CYP24A1 has previously been described in cell and animal models, and despite emerging evidence for a critical role of epigenetics in placentation generally, little is known about the regulation of enzymes modulating vitamin D homeostasis at the fetomaternal interface. In this study, we investigated the methylation status of genes regulating vitamin D bioavailability and activity in the placenta. No methylation of the VDR (vitamin D receptor) and CYP27B1 genes was found in any placental tissues. In contrast, the CYP24A1 gene is methylated in human placenta, purified cytotrophoblasts, and primary and cultured chorionic villus sampling tissue. No methylation was detected in any somatic human tissue tested. Methylation was also evident in marmoset and mouse placental tissue. All three genes were hypermethylated in choriocarcinoma cell lines, highlighting the role of vitamin D deregulation in this cancer. Gene expression analysis confirmed a reduced capacity for CYP24A1 induction with promoter methylation in primary cells and in vitro reporter analysis demonstrated that promoter methylation directly down-regulates basal promoter activity and abolishes vitamin D-mediated feedback activation. This study strongly suggests that epigenetic decoupling of vitamin D feedback catabolism plays an important role in maximizing active vitamin D bioavailability at the fetomaternal interface. PMID:19237542

  9. The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter

    PubMed Central

    Ma, Yiyi; Smith, Caren E.; Lai, Chao-Qiang; Irvin, Marguerite R.; Parnell, Laurence D.; Lee, Yu-Chi; Pham, Lucia D.; Aslibekyan, Stella; Claas, Steven A.; Tsai, Michael Y.; Borecki, Ingrid B.; Kabagambe, Edmond K.; Ordovás, José M.; Absher, Devin M.; Arnett, Donna K.

    2016-01-01

    Scope Omega-3 PUFAs (n-3 PUFAs) reduce IL-6 gene expression, but their effects on transcription regulatory mechanisms are unknown. We aimed to conduct an integrated analysis with both population and in vitro studies to systematically explore the relationships among n-3 PUFA, DNA methylation, single nucleotide polymorphisms (SNPs), gene expression, and protein concentration of IL6. Methods and results Using data in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study and the Encyclopedia of DNA Elements (ENCODE) consortium, we found that higher methylation of IL6 promoter cg01770232 was associated with higher IL-6 plasma concentration (p = 0.03) and greater IL6 gene expression (p = 0.0005). Higher circulating total n-3 PUFA was associated with lower cg01770232 methylation (p = 0.007) and lower IL-6 concentration (p = 0.02). Moreover, an allele of IL6 rs2961298 was associated with higher cg01770232 methylation (p = 2.55 × 10−7). The association between n-3 PUFA and cg01770232 methylation was dependent on rs2961298 genotype (p = 0.02), but higher total n-3 PUFA was associated with lower cg01770232 methylation in the heterozygotes (p = 0.04) not in the homozygotes. Conclusion Higher n-3 PUFA is associated with lower methylation at IL6 promoter, which may be modified by IL6 SNPs. PMID:26518637

  10. Examining the ground and first excited states of methyl peroxy radical with high-level coupled-cluster theory

    NASA Astrophysics Data System (ADS)

    Copan, Andreas V.; Schaefer, Henry F., III; Agarwal, Jay

    2015-10-01

    Peroxy radicals (RO2) are intermediates in fuel combustion, where they engage in efficiency-limiting autoignition reactions. They also participate in atmospheric chemistry leading to the formation of unwanted tropospheric ozone. Advances in spectroscopic techniques have allowed for the possibility of employing the lowest (?) electronic transition of RO2 as a tool to selectively monitor these species, enabling accurate kinetic values to be obtained. Herein, high-level ab initio methods are employed to systematically refine spectroscopic predictions for the methyl peroxy radical (CH3O2), one of the most abundant peroxy radicals in the atmosphere. In particular, vibrationally corrected geometries and anharmonic vibrational frequencies for both the ground (?) and first excited (?) state are predicted using coupled-cluster theory with up to perturbative triples [CCSD(T)] and large atomic natural orbital basis sets. Equation-of-motion coupled-cluster theory is utilised to compute vertical ? transition properties; a radiative lifetime of 4.7 ms is suggested for the excited state. Finally, we predict the adiabatic excitation energy (T0) via systematic extrapolation to the complete basis limit of coupled-cluster with up to full quadruples (CCSDTQ). After accounting for several approximations, and including an anharmonic zero-point vibrational energy correction, we match experiment for this transition to within 9 cm-1. Dedicated to Professor Sourav Pal.

  11. Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas.

    PubMed

    Schroeder, Diane I; Jayashankar, Kartika; Douglas, Kory C; Thirkill, Twanda L; York, Daniel; Dickinson, Pete J; Williams, Lawrence E; Samollow, Paul B; Ross, Pablo J; Bannasch, Danika L; Douglas, Gordon C; LaSalle, Janine M

    2015-08-01

    Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs) and highly methylated domains (HMDs) with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq) analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo. PMID:26241857

  12. Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas

    PubMed Central

    Schroeder, Diane I.; Jayashankar, Kartika; Douglas, Kory C.; Thirkill, Twanda L.; York, Daniel; Dickinson, Pete J.; Williams, Lawrence E.; Samollow, Paul B.; Ross, Pablo J.; Bannasch, Danika L.; Douglas, Gordon C.; LaSalle, Janine M.

    2015-01-01

    Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs) and highly methylated domains (HMDs) with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq) analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo. PMID:26241857

  13. Importance of Multiple Methylation Sites in Escherichia coli Chemotaxis

    PubMed Central

    Sourjik, Victor

    2015-01-01

    Bacteria navigate within inhomogeneous environments by temporally comparing concentrations of chemoeffectors over the course of a few seconds and biasing their rate of reorientations accordingly, thereby drifting towards more favorable conditions. This navigation requires a short-term memory achieved through the sequential methylations and demethylations of several specific glutamate residues on the chemotaxis receptors, which progressively adjusts the receptors’ activity to track the levels of stimulation encountered by the cell with a delay. Such adaptation also tunes the receptors’ sensitivity according to the background ligand concentration, enabling the cells to respond to fractional rather than absolute concentration changes, i.e. to perform logarithmic sensing. Despite the adaptation system being principally well understood, the need for a specific number of methylation sites remains relatively unclear. Here we systematically substituted the four glutamate residues of the Tar receptor of Escherichia coli by non-methylated alanine, creating a set of 16 modified receptors with a varying number of available methylation sites and explored the effect of these substitutions on the performance of the chemotaxis system. Alanine substitutions were found to desensitize the receptors, similarly but to a lesser extent than glutamate methylation, and to affect the methylation and demethylation rates of the remaining sites in a site-specific manner. Each substitution reduces the dynamic range of chemotaxis, by one order of magnitude on average. The substitution of up to two sites could be partly compensated by the adaptation system, but the full set of methylation sites was necessary to achieve efficient logarithmic sensing. PMID:26683829

  14. The absolute path command

    2012-05-11

    The ap command traveres all symlinks in a given file, directory, or executable name to identify the final absolute path. It can print just the final path, each intermediate link along with the symlink chan, and the permissions and ownership of each directory component in the final path. It has functionality similar to "which", except that it shows the final path instead of the first path. It is also similar to "pwd", but it canmore » provide the absolute path to a relative directory from the current working directory.« less

  15. The absolute path command

    SciTech Connect

    Moody, A.

    2012-05-11

    The ap command traveres all symlinks in a given file, directory, or executable name to identify the final absolute path. It can print just the final path, each intermediate link along with the symlink chan, and the permissions and ownership of each directory component in the final path. It has functionality similar to "which", except that it shows the final path instead of the first path. It is also similar to "pwd", but it can provide the absolute path to a relative directory from the current working directory.

  16. Lsh Is Essential for Maintaining Global DNA Methylation Levels in Amphibia and Fish and Interacts Directly with Dnmt1

    PubMed Central

    Dunican, Donncha S.; Pennings, Sari; Meehan, Richard R.

    2015-01-01

    Eukaryotic genomes are methylated at cytosine bases in the context of CpG dinucleotides, a pattern which is maintained through cell division by the DNA methyltransferase Dnmt1. Dramatic methylation losses are observed in plant and mouse cells lacking Lsh (lymphoid specific helicase), predominantly at repetitive sequences and gene promoters. However, the mechanism by which Lsh contributes to the maintenance of DNA methylation is unknown. Here we show that DNA methylation is lost in Lsh depleted frog and fish embryos, both of which exhibit developmental delay. Additionally, we show that both Lsh and Dnmt1 are associated with chromatin and that Lsh knockdown leads to a decreased Dnmt1-chromatin association. Coimmunoprecipitation experiments reveal that Lsh and Dnmt1 are found in the same protein complex, and pulldowns show this interaction is direct. Our data indicate that Lsh is usually diffuse in the nucleus but can be recruited to heterochromatin in a HP1α-dependent manner. These data together (a) show that the role of Lsh in DNA methylation is conserved in plants, amphibian, fish, and mice and (b) support a model in which Lsh contributes to Dnmt1 binding to chromatin, explaining how its loss can potentially lead to perturbations in DNA methylation maintenance. PMID:26491684

  17. C(m)CGG methylation-independent parent-of-origin effects on genome-wide transcript levels in isogenic reciprocal F1 triploid plants.

    PubMed

    Donoghue, Mark T A; Fort, Antoine; Clifton, Rachel; Zhang, Xu; McKeown, Peter C; Voigt-Zielinksi, M L; Borevitz, Justin O; Spillane, Charles

    2014-01-01

    Triploid F1 hybrids generated via reciprocal interploidy crosses between genetically distinct parental plants can display parent-of-origin effects on gene expression or phenotypes. Reciprocal triploid F1 isogenic plants generated from interploidy crosses in the same genetic background allow investigation on parent-of-origin-specific (parental) genome-dosage effects without confounding effects of hybridity involving heterozygous mutations. Whole-genome transcriptome profiling was conducted on reciprocal F1 isogenic triploid (3x) seedlings of A. thaliana. The genetically identical reciprocal 3x genotypes had either an excess of maternally inherited 3x(m) or paternally inherited 3x(p) genomes. We identify a major parent-of-origin-dependent genome-dosage effect on transcript levels, whereby 602 genes exhibit differential expression between the reciprocal F1 triploids. In addition, using methylation-sensitive DNA tiling arrays, constitutive and polymorphic CG DNA methylation patterns at CCGG sites were analysed, which revealed that paternal-excess F1 triploid seedling C(m)CGG sites are overall hypermethylated. However, no correlation exists between C(m)CGG methylation polymorphisms and transcriptome dysregulation between the isogenic reciprocal F1 triploids. Overall, our study indicates that parental genome-dosage effects on the transcriptome levels occur in paternal-excess triploids, which are independent of C(m)CGG methylation polymorphisms. Such findings have implications for understanding parental effects and genome-dosage effects on gene expression and phenotypes in polyploid plants. PMID:24212467

  18. Placental DNA methylation of peroxisome-proliferator-activated receptor-γ co-activator-1α promoter is associated with maternal gestational glucose level.

    PubMed

    Xie, Xuemei; Gao, Hongjie; Zeng, Wanjiang; Chen, Suhua; Feng, Ling; Deng, Dongrui; Qiao, Fu-yuan; Liao, Lihong; McCormick, Kenneth; Ning, Qin; Luo, Xiaoping

    2015-08-01

    Intrauterine exposure to hyperglycaemia may increase the risk of later-life metabolic disorders. Although the underlying mechanism is not fully understood, epigenetic dysregulation in fetal programming has been implicated. With regard to energy homoeostasis, PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α, encoded by the PPARGC1A gene) plays a regulatory role in several biochemical processes. We hypothesized that maternal gestational glucose levels would positively correlate with DNA methylation of the PPARGC1A promoter in placental tissue. We undertook a cross-sectional study of 58 mothers who underwent uncomplicated Caesarean delivery in a university hospital. Maternal gestational glucose concentration was determined after a 75-g OGTT (oral glucose tolerance test) at 24-28 weeks of gestation. Placenta tissue and cord blood were collected immediately after delivery. Genomic DNA was extracted and thereafter bisulfite conversion was performed. After PCR amplification, the DNA methylation of the PPARGC1A promoter was quantified using a pyrosequencing technique. The protein level of PGC-1α was evaluated by Western blotting. For all participants as a whole, including the GDM (gestational diabetes mellitus) and normoglycaemia groups, the maternal gestational glucose level was positively correlated with placental DNA methylation, and negatively correlated with cord blood DNA methylation of the PPARGC1A promoter in a CpG site-specific manner. In the GDM group alone, the placental CpG site-specific methylation of the PPARGC1A promoter strongly correlated with gestational 2-h post-OGTT glycaemia. Epigenetic alteration of the PPAGRC1A promoter may be one of the potential mechanisms underlying the metabolic programming in offspring exposed to intrauterine hyperglycaemia. PMID:25875376

  19. Absolute optical instruments without spherical symmetry

    NASA Astrophysics Data System (ADS)

    Tyc, Tomáš; Dao, H. L.; Danner, Aaron J.

    2015-11-01

    Until now, the known set of absolute optical instruments has been limited to those containing high levels of symmetry. Here, we demonstrate a method of mathematically constructing refractive index profiles that result in asymmetric absolute optical instruments. The method is based on the analogy between geometrical optics and classical mechanics and employs Lagrangians that separate in Cartesian coordinates. In addition, our method can be used to construct the index profiles of most previously known absolute optical instruments, as well as infinitely many different ones.

  20. Consumption of Tropospheric Levels of Methyl Bromide by C1 Compound-Utilizing Bacteria and Comparison to Saturation Kinetics

    USGS Publications Warehouse

    Goodwin, K.D.; Varner, R.K.; Crill, P.M.; Oremland, R.S.

    2001-01-01

    Pure cultures of methylotrophs and methanotrophs are known to oxidize methyl bromide (MeBr); however, their ability to oxidize tropospheric concentrations (parts per trillion by volume [pptv]) has not been tested. Methylotrophs and methanotrophs were able to consume MeBr provided at levels that mimicked the tropospheric mixing ratio of MeBr (12 pptv) at equilibrium with surface waters (???2 pM). Kinetic investigations using picomolar concentrations of MeBr in a continuously stirred tank reactor (CSTR) were performed using strain IMB-1 and Leisingeria methylohalidivorans strain MB2T - terrestrial and marine methylotrophs capable of halorespiration. First-order uptake of MeBr with no indication of threshold was observed for both strains. Strain MB2T displayed saturation kinetics in batch experiments using micromolar MeBr concentrations, with an apparent Ks of 2.4 ??M MeBr and a Vmax of 1.6 nmol h-1 (106 cells)-1. Apparent first-order degradation rate constants measured with the CSTR were consistent with kinetic parameters determined in batch experiments, which used 35- to 1 ?? 107-fold-higher MeBr concentrations. Ruegeria algicola (a phylogenetic relative of strain MB2T), the common heterotrophs Escherichia coli and Bacillus pumilus, and a toluene oxidizer, Pseudomonas mendocina KR1, were also tested. These bacteria showed no significant consumption of 12 pptv MeBr; thus, the ability to consume ambient mixing ratios of MeBr was limited to C1 compound-oxidizing bacteria in this study. Aerobic C1 bacteria may provide model organisms for the biological oxidation of tropospheric MeBr in soils and waters.

  1. Consumption of Tropospheric Levels of Methyl Bromide by C1 Compound-Utilizing Bacteria and Comparison to Saturation Kinetics

    PubMed Central

    Goodwin, Kelly D.; Varner, Ruth K.; Crill, Patrick M.; Oremland, Ronald S.

    2001-01-01

    Pure cultures of methylotrophs and methanotrophs are known to oxidize methyl bromide (MeBr); however, their ability to oxidize tropospheric concentrations (parts per trillion by volume [pptv]) has not been tested. Methylotrophs and methanotrophs were able to consume MeBr provided at levels that mimicked the tropospheric mixing ratio of MeBr (12 pptv) at equilibrium with surface waters (≈2 pM). Kinetic investigations using picomolar concentrations of MeBr in a continuously stirred tank reactor (CSTR) were performed using strain IMB-1 and Leisingeria methylohalidivorans strain MB2T — terrestrial and marine methylotrophs capable of halorespiration. First-order uptake of MeBr with no indication of threshold was observed for both strains. Strain MB2T displayed saturation kinetics in batch experiments using micromolar MeBr concentrations, with an apparent Ks of 2.4 μM MeBr and a Vmax of 1.6 nmol h−1 (106 cells)−1. Apparent first-order degradation rate constants measured with the CSTR were consistent with kinetic parameters determined in batch experiments, which used 35- to 1 × 107-fold-higher MeBr concentrations. Ruegeria algicola (a phylogenetic relative of strain MB2T), the common heterotrophs Escherichia coli and Bacillus pumilus, and a toluene oxidizer, Pseudomonas mendocina KR1, were also tested. These bacteria showed no significant consumption of 12 pptv MeBr; thus, the ability to consume ambient mixing ratios of MeBr was limited to C1 compound-oxidizing bacteria in this study. Aerobic C1 bacteria may provide model organisms for the biological oxidation of tropospheric MeBr in soils and waters. PMID:11722890

  2. Genome-wide identification of differential methylation between primary and recurrent hepatocellular carcinomas.

    PubMed

    Cui, Chenghua; Lu, Zheming; Yang, Liu; Gao, Yanhong; Liu, Wei; Gu, Liankun; Yang, Chen; Wilson, James; Zhang, Zhiqian; Xing, Baocai; Deng, Dajun; Sun, Zhong Sheng

    2016-07-01

    A biomarker capable of clinically predicting hepatocellular carcinoma (HCC) recurrence has not previously been established. Here genome-wide differential methylation between primary and recurrent HCC cell lines (Hep-11 and Hep-12) from the same patient was characterized. The HCC samples from two independent cohorts, complete with follow-up data, were used to validate the feasibility of the selected methylation biomarkers in predicting HCC prognosis. A methylation array assay identified 30 candidate genes or intergenic-fragments with an absolute methylation fold-change >2.0 between these cell lines; 22 candidates were hypomethylated in Hep-12 cells relative to Hep-11 cells. Bisulfite sequencing confirmed these results. Most importantly, classification of tumors by LINE-2 methylation level was significantly associated with HCC recurrence in both cohorts (P < 0.02). Similarly, MAD1L1 and LINC00682 methylation levels also correlated with HCC recurrence. Survival analysis showed that a combined baseline LINE-2, MAD1L1, and LINC00682 methylation signature was significantly associated with short recurrence-free survival in patients from both cohorts. A synergic effect was observed between these markers on both recurrence-free survival (P < 0.010) and overall survival (P < 0.040). In conclusion, low levels of LINE-2, MAD1L1, and LINC00682 methylation were associated with recurrence and decreased overall survival in HCC patients. © 2015 Wiley Periodicals, Inc. PMID:26138747

  3. Absolute spectrum and charge ratio of cosmic ray muons in the energy region from 0.2 GeV to 100 GeV at 600 m above sea level

    NASA Technical Reports Server (NTRS)

    De Pascale, M. P.; Morselli, A.; Picozza, P.; Golden, R. L.; Grimani, C.; Kimbell, B. L.; Stephens, S. A.; Stochaj, S. J.; Webber, W. R.; Basini, G.

    1993-01-01

    We have determined the momentum spectrum and charge ratio of muons in the region from 250 MeV/c to 100 GeV/c using a superconducting magnetic spectrometer. The absolute differential spectrum of muons obtained in this experiment at 600 m above sea level is in good agreement with the previous measurements at sea level. The differential spectrum can be represented by a power law with a varying index, which is consistent with zero below 450 MeV/c and steepens to a value of -2.7 +/- 0.1 between 20 and 100 GeV/c. The integral f1ux of muons measured in this experiment span a very large range of momentum and is in excellent agreement with the earlier results. The positive to negative muon ratio appears to be constant in the entire momentum range covered in this experiment within the errors and the mean value is 1.220 +/- 0.044. The absolute momentum spectrum and the charge ratio measured in this experiment are also consistent with the theoretical expectations. This is the only experiment which covers a wide range of nearly three decades in momentum from a very low momentum.

  4. Down-regulation of promoter methylation level of CD4 gene after MDV infection in MD-susceptible chicken line

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease virus (MDV) is an oncovirus that induces lymphoid tumors in susceptible chickens, and may affect the epigenetic stability of the CD4 gene. The purpose of this study was to find how the effect of MDV infection on DNA methylation status of the CD4 gene differed between MD-resistant (L6...

  5. Canopy Level Emissions of 2-methyl-3-buten-2-ol, monoterpenes, and sesquiterpenes from a Pinus taeda Experimental Plantation

    EPA Science Inventory

    Emissions of biogenic volatile organic compounds (BVOC) observed during 2007 from a Pinus taeda experimental plantation in Central North Carolina are compared with model estimates from MEGAN 2.1. Relaxed Eddy Accumulation (REA) estimates of 2-methyl-3-buten-2-ol (MBO) fluxes are ...

  6. RATE OF SOIL REDUCTION AS AFFECTED BY LEVELS OF METHYL PARATHION AND 2, 4,-D (JOURNAL VERSION)

    EPA Science Inventory

    A simple technique was demonstrated for determining the potential for synthetic organics to stress microbial populations. Oxidized Crowly and Cecil soil materials were amended with varying concentrations of 2,4-D and methyl parathion, flooded, and then analyzed for changes in pH,...

  7. Bisulfite oligonucleotide-capture sequencing for targeted base- and strand-specific absolute 5-methylcytosine quantitation.

    PubMed

    Masser, Dustin R; Stanford, David R; Hadad, Niran; Giles, Cory B; Wren, Jonathan D; Sonntag, William E; Richardson, Arlan; Freeman, Willard M

    2016-06-01

    Epigenetic regulation through DNA methylation (5mC) plays an important role in development, aging, and a variety of diseases. Genome-wide studies of base- and strand-specific 5mC are limited by the extensive sequencing required. Targeting bisulfite sequencing to specific genomic regions through sequence capture with complimentary oligonucleotide probes retains the advantages of bisulfite sequencing while focusing sequencing reads on regions of interest, enables analysis of more samples by decreasing the amount of sequence required per sample, and provides base- and strand-specific absolute quantitation of CG and non-CG methylation levels. As an example, an oligonucleotide capture set to interrogate 5mC levels in all rat RefSeq gene promoter regions (18,814) and CG islands, shores, and shelves (18,411) was generated. Validation using whole-genome methylation standards and biological samples demonstrates enrichment of the targeted regions and accurate base-specific quantitation of CG and non-CG methylation for both forward and reverse genomic strands. A total of 170 Mb of the rat genome is covered including 6.6 million CGs and over 67 million non-CG sites, while reducing the amount of sequencing required by ~85 % as compared to existing whole-genome sequencing methods. This oligonucleotide capture targeting approach and quantitative validation workflow can also be applied to any genome of interest. PMID:27091453

  8. Low folate levels are associated with methylation-mediated transcriptional repression of miR-203 and miR-375 during cervical carcinogenesis

    PubMed Central

    HAO, MIN; ZHAO, WEIHONG; ZHANG, LILI; WANG, HONGHONG; YANG, XIN

    2016-01-01

    The aim of the present study was to investigate the correlation between a lack of folic acid and the abnormal expression of microRNA (miR)-203 and miR-375 in cervical cancer. In total, 60 tissue samples of cervical intraepithelial neoplasia (CIN) or stage IA-IIA cervical cancer (study group), and 30 samples without soluble interleukin or malignancy (control group) were examined. The expression of miR-203 and miR-375 was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the difference in expression levels was quantified using the 2−ΔΔCq method. In addition, CaSki cervical cancer cells were cultured in vitro and treated with various concentrations of folic acid. The DNA methylation states of miR-203 and miR-375 were subsequently detected by methylation-specific PCR, and the expression levels were evaluated using RT-PCR. miR-203 and miR-375 were significantly downregulated in CIN and cervical cancer tissues, compared with the control group. There was a marked difference in terms of the expression levels of miR-375 between the two groups (P<0.05). In CaSki cells, as the concentration of folic acid increased, the positive rate of DNA methylation of miR-203 and miR-375 decreased, while the expression levels of miR-203 and miR-375 demonstrated a gradual increase, which indicated that the latter two parameters were negatively correlated (P<0.05). Compared with normal cervical tissue, the expression levels of miR-203 and miR-375 were downregulated in CIN and cervical cancer. Methylation of these two miRs was apparent in CaSki cells, and was associated with a lack of folic acid. Therefore, reduced levels of folic acid, leading to increased methylation of miR-203 and miR-375, may be significant events during cervical carcinogenesis. PMID:27313708

  9. DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants

    PubMed Central

    Kwon, Eun Jin; Lee, Hye Ah; You, Young-Ah; Park, Hyesook; Cho, Su Jin; Ha, Eun Hee; Kim, Young Ju

    2016-01-01

    Abstract The association of preterm birth with obesity and metabolic syndrome later in life is well established. Although the biological mechanism for this association is poorly understood, epigenetic alterations of metabolic-related genes in early life may have important roles in metabolic dysfunction. Thus, we investigated the associations of DNA methylations of melanocortin 4 receptor (MC4R) and hepatocyte nuclear factor 4 alpha (HNF4α) with metabolic profiles in cord blood of term and preterm infants. We measured metabolic profiles in cord blood samples of 85 term and 85 preterm infants. DNA methylation and mRNA expression levels of MC4R and HNF4α in cord blood cells were quantified using pyrosequencing and real-time PCR. Triglyceride (TG) levels were grouped by percentile as low (<10th percentile), mid (11th–89th percentiles), and high (>90th percentile). A multiple linear regression model was used to assess the differential effects of DNA methylation on metabolic indices in cord blood between term and preterm infants. The beta-coefficients for associations between TG levels and methylation statuses of MC4R-CpG3 and HNF4α-CpG2 in the P1 promoter differed significantly between term and preterm infants (P = 0.04 and P = 0.003, respectively). DNA methylation statuses of MC4R-CpG3 and HNF4α–CpG2 in the P1 promoter were significantly lower in preterm infants in the high-TG group compared with those in the mid- and low-TG groups (P = 0.01). Notably, preterm infants in the high-TG group had higher TG levels in cord blood than term infants in the high-TG group (60.49 vs 54.57 mg/dL). In addition, MC4R and HNF4α expression levels were higher in preterm infants than in term infants (P < 0.05). Epigenetic alterations of the newly identified genes MC4R and HNF4α in early life might contribute to metabolic profile changes, especially increased TG levels, in the cord blood of preterm infants. PMID:27583872

  10. DNA methylations of MC4R and HNF4α are associated with increased triglyceride levels in cord blood of preterm infants.

    PubMed

    Kwon, Eun Jin; Lee, Hye Ah; You, Young-Ah; Park, Hyesook; Cho, Su Jin; Ha, Eun Hee; Kim, Young Ju

    2016-08-01

    The association of preterm birth with obesity and metabolic syndrome later in life is well established. Although the biological mechanism for this association is poorly understood, epigenetic alterations of metabolic-related genes in early life may have important roles in metabolic dysfunction. Thus, we investigated the associations of DNA methylations of melanocortin 4 receptor (MC4R) and hepatocyte nuclear factor 4 alpha (HNF4α) with metabolic profiles in cord blood of term and preterm infants.We measured metabolic profiles in cord blood samples of 85 term and 85 preterm infants. DNA methylation and mRNA expression levels of MC4R and HNF4α in cord blood cells were quantified using pyrosequencing and real-time PCR. Triglyceride (TG) levels were grouped by percentile as low (<10th percentile), mid (11th-89th percentiles), and high (>90th percentile). A multiple linear regression model was used to assess the differential effects of DNA methylation on metabolic indices in cord blood between term and preterm infants.The beta-coefficients for associations between TG levels and methylation statuses of MC4R-CpG3 and HNF4α-CpG2 in the P1 promoter differed significantly between term and preterm infants (P = 0.04 and P = 0.003, respectively). DNA methylation statuses of MC4R-CpG3 and HNF4α-CpG2 in the P1 promoter were significantly lower in preterm infants in the high-TG group compared with those in the mid- and low-TG groups (P = 0.01). Notably, preterm infants in the high-TG group had higher TG levels in cord blood than term infants in the high-TG group (60.49 vs 54.57 mg/dL). In addition, MC4R and HNF4α expression levels were higher in preterm infants than in term infants (P < 0.05).Epigenetic alterations of the newly identified genes MC4R and HNF4α in early life might contribute to metabolic profile changes, especially increased TG levels, in the cord blood of preterm infants. PMID:27583872

  11. Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation.

    PubMed

    Tsaprouni, Loukia G; Yang, Tsun-Po; Bell, Jordana; Dick, Katherine J; Kanoni, Stavroula; Nisbet, James; Viñuela, Ana; Grundberg, Elin; Nelson, Christopher P; Meduri, Eshwar; Buil, Alfonso; Cambien, Francois; Hengstenberg, Christian; Erdmann, Jeanette; Schunkert, Heribert; Goodall, Alison H; Ouwehand, Willem H; Dermitzakis, Emmanouil; Spector, Tim D; Samani, Nilesh J; Deloukas, Panos

    2014-10-01

    Smoking is a major risk factor in many diseases. Genome wide association studies have linked genes for nicotine dependence and smoking behavior to increased risk of cardiovascular, pulmonary, and malignant diseases. We conducted an epigenome wide association study in peripheral-blood DNA in 464 individuals (22 current smokers and 263 ex-smokers), using the Human Methylation 450 K array. Upon replication in an independent sample of 356 twins (41 current and 104 ex-smokers), we identified 30 probes in 15 distinct loci, all of which reached genome-wide significance in the combined analysis P < 5 × 10(-8). All but one probe (cg17024919) remained significant after adjusting for blood cell counts. We replicated all 9 known loci and found an independent signal at CPOX near GPR15. In addition, we found 6 new loci at PRSS23, AVPR1B, PSEN2, LINC00299, RPS6KA2, and KIAA0087. Most of the lead probes (13 out of 15) associated with cigarette smoking, overlapped regions of open chromatin (FAIRE and DNaseI hypersensitive sites) or/and H3K27Ac peaks (ENCODE data set), which mark regulatory elements. The effect of smoking on DNA methylation was partially reversible upon smoking cessation for longer than 3 months. We report the first statistically significant interaction between a SNP (rs2697768) and cigarette smoking on DNA methylation (cg03329539). We provide evidence that the metSNP for cg03329539 regulates expression of the CHRND gene located circa 95 Kb downstream of the methylation site. Our findings suggest the existence of dynamic, reversible site-specific methylation changes in response to cigarette smoking , which may contribute to the extended health risks associated with cigarette smoking. PMID:25424692

  12. RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients

    PubMed Central

    Araújo, Oscar C.; Rosa, Agatha S.; Fernandes, Arlete; Niel, Christian; Villela-Nogueira, Cristiane A.; Pannain, Vera; Araujo, Natalia M.

    2016-01-01

    Hepatocellular carcinoma (HCC) is the second most common cause of cancer mortality worldwide. Most cases of HCC are associated with cirrhosis related to chronic hepatitis B virus or hepatitis C virus infections. Hypermethylation of promoter regions is the main epigenetic mechanism of gene silencing and has been involved in HCC development. The aim of this study was to determine whether aberrant methylation of RASSF1A and DOK1 gene promoters is associated with the progression of liver disease in Brazilian patients. Methylation levels were measured by pyrosequencing in 41 (20 HCC, 9 cirrhotic, and 12 non-cirrhotic) liver tissue samples. Mean rates of methylation in RASSF1A and DOK1 were 16.2% and 12.0% in non-cirrhotic, 26.1% and 19.6% in cirrhotic, and 59.1% and 56.0% in HCC tissues, respectively, showing a gradual increase according to the progression of the disease, with significantly higher levels in tumor tissues. In addition, hypermethylation of RASSF1A and DOK1 was found in the vast majority (88%) of the HCC cases. Interestingly, DOK1 methylation levels in HCC samples were significantly higher in the group of younger (<40 years) patients, and higher in moderately differentiated than in poorly differentiated tumors (p < 0.05). Our results reinforce the hypothesis that hypermethylation of RASSF1A and DOK1 contributes to hepatocarcinogenesis and is associated to clinicopathological characteristics. RASSF1A and DOK1 promoter hypermethylation may be a valuable biomarker for early diagnosis of HCC and a potential molecular target for epigenetic-based therapy. PMID:27078152

  13. ABSOLUTE POLARIMETRY AT RHIC.

    SciTech Connect

    OKADA; BRAVAR, A.; BUNCE, G.; GILL, R.; HUANG, H.; MAKDISI, Y.; NASS, A.; WOOD, J.; ZELENSKI, Z.; ET AL.

    2007-09-10

    Precise and absolute beam polarization measurements are critical for the RHIC spin physics program. Because all experimental spin-dependent results are normalized by beam polarization, the normalization uncertainty contributes directly to final physics uncertainties. We aimed to perform the beam polarization measurement to an accuracy Of {Delta}P{sub beam}/P{sub beam} < 5%. The absolute polarimeter consists of Polarized Atomic Hydrogen Gas Jet Target and left-right pairs of silicon strip detectors and was installed in the RHIC-ring in 2004. This system features proton-proton elastic scattering in the Coulomb nuclear interference (CNI) region. Precise measurements of the analyzing power A{sub N} of this process has allowed us to achieve {Delta}P{sub beam}/P{sub beam} = 4.2% in 2005 for the first long spin-physics run. In this report, we describe the entire set up and performance of the system. The procedure of beam polarization measurement and analysis results from 2004-2005 are described. Physics topics of AN in the CNI region (four-momentum transfer squared 0.001 < -t < 0.032 (GeV/c){sup 2}) are also discussed. We point out the current issues and expected optimum accuracy in 2006 and the future.

  14. Construction and Characterization of Normalized cDNA Libraries by 454 Pyrosequencing and Estimation of DNA Methylation Levels in Three Distantly Related Termite Species

    PubMed Central

    Hayashi, Yoshinobu; Shigenobu, Shuji; Watanabe, Dai; Toga, Kouhei; Saiki, Ryota; Shimada, Keisuke; Bourguignon, Thomas; Lo, Nathan; Hojo, Masaru; Maekawa, Kiyoto; Miura, Toru

    2013-01-01

    In termites, division of labor among castes, categories of individuals that perform specialized tasks, increases colony-level productivity and is the key to their ecological success. Although molecular studies on caste polymorphism have been performed in termites, we are far from a comprehensive understanding of the molecular basis of this phenomenon. To facilitate future molecular studies, we aimed to construct expressed sequence tag (EST) libraries covering wide ranges of gene repertoires in three representative termite species, Hodotermopsissjostedti, Reticulitermessperatus and Nasutitermestakasagoensis. We generated normalized cDNA libraries from whole bodies, except for guts containing microbes, of almost all castes, sexes and developmental stages and sequenced them with the 454 GS FLX titanium system. We obtained >1.2 million quality-filtered reads yielding >400 million bases for each of the three species. Isotigs, which are analogous to individual transcripts, and singletons were produced by assembling the reads and annotated using public databases. Genes related to juvenile hormone, which plays crucial roles in caste differentiation of termites, were identified from the EST libraries by BLAST search. To explore the potential for DNA methylation, which plays an important role in caste differentiation of honeybees, tBLASTn searches for DNA methyltransferases (dnmt1, dnmt2 and dnmt3) and methyl-CpG binding domain (mbd) were performed against the EST libraries. All four of these genes were found in the H. sjostedti library, while all except dnmt3 were found in R. speratus and N. takasagoensis. The ratio of the observed to the expected CpG content (CpG O/E), which is a proxy for DNA methylation level, was calculated for the coding sequences predicted from the isotigs and singletons. In all of the three species, the majority of coding sequences showed depletion of CpG O/E (less than 1), and the distributions of CpG O/E were bimodal, suggesting the presence of DNA

  15. Construction and characterization of normalized cDNA libraries by 454 pyrosequencing and estimation of DNA methylation levels in three distantly related termite species.

    PubMed

    Hayashi, Yoshinobu; Shigenobu, Shuji; Watanabe, Dai; Toga, Kouhei; Saiki, Ryota; Shimada, Keisuke; Bourguignon, Thomas; Lo, Nathan; Hojo, Masaru; Maekawa, Kiyoto; Miura, Toru

    2013-01-01

    In termites, division of labor among castes, categories of individuals that perform specialized tasks, increases colony-level productivity and is the key to their ecological success. Although molecular studies on caste polymorphism have been performed in termites, we are far from a comprehensive understanding of the molecular basis of this phenomenon. To facilitate future molecular studies, we aimed to construct expressed sequence tag (EST) libraries covering wide ranges of gene repertoires in three representative termite species, Hodotermopsis sjostedti, Reticulitermes speratus and Nasutitermes takasagoensis. We generated normalized cDNA libraries from whole bodies, except for guts containing microbes, of almost all castes, sexes and developmental stages and sequenced them with the 454 GS FLX titanium system. We obtained >1.2 million quality-filtered reads yielding >400 million bases for each of the three species. Isotigs, which are analogous to individual transcripts, and singletons were produced by assembling the reads and annotated using public databases. Genes related to juvenile hormone, which plays crucial roles in caste differentiation of termites, were identified from the EST libraries by BLAST search. To explore the potential for DNA methylation, which plays an important role in caste differentiation of honeybees, tBLASTn searches for DNA methyltransferases (dnmt1, dnmt2 and dnmt3) and methyl-CpG binding domain (mbd) were performed against the EST libraries. All four of these genes were found in the H. sjostedti library, while all except dnmt3 were found in R. speratus and N. takasagoensis. The ratio of the observed to the expected CpG content (CpG O/E), which is a proxy for DNA methylation level, was calculated for the coding sequences predicted from the isotigs and singletons. In all of the three species, the majority of coding sequences showed depletion of CpG O/E (less than 1), and the distributions of CpG O/E were bimodal, suggesting the presence of

  16. Tissue specificity of methylation of cytosines in regulatory regions of four genes located in the locus FXYD5-COX7A1 of human chromosome 19: correlation with their expression level.

    PubMed

    Chalaya, T V; Akopov, S B; Nikolaev, L G; Sverdlov, E D

    2006-03-01

    In this study, we compared degree of methylation of selected CpG sites in CCGG sequences located in promoter regions of four human genes with expression level of these genes in several human cell lines and tissues. These genes were subdivided into two groups according to the dependence of their expression on CpG methylation in the 5 -regions. The first group, characterized by clear correlation of methylation with the transcription level, includes housekeeping gene COX6B (the absence of methylation unambiguously correlates with expression) and urothelium-specific uroplakin gene (the methylation coincides with absence of expression). The second group includes genes that are expressed in many, but not all tissues and cells. For these genes (LEAP-1 and ATP4A), there was no correlation between methylation and expression. It is possible that methylation provides some basal level of gene repression, which is overcome by binding of tissue-specific transcription factors, whereas lack of methylation gives the opportunity for gene expression in various cells and tissues. PMID:16545066

  17. Implants as absolute anchorage.

    PubMed

    Rungcharassaeng, Kitichai; Kan, Joseph Y K; Caruso, Joseph M

    2005-11-01

    Anchorage control is essential for successful orthodontic treatment. Each tooth has its own anchorage potential as well as propensity to move when force is applied. When teeth are used as anchorage, the untoward movements of the anchoring units may result in the prolonged treatment time, and unpredictable or less-than-ideal outcome. To maximize tooth-related anchorage, techniques such as differential torque, placing roots into the cortex of the bone, the use of various intraoral devices and/or extraoral appliances have been implemented. Implants, as they are in direct contact with bone, do not possess a periodontal ligament. As a result, they do not move when orthodontic/orthopedic force is applied, and therefore can be used as "absolute anchorage." This article describes different types of implants that have been used as orthodontic anchorage. Their clinical applications and limitations are also discussed. PMID:16463910

  18. Absolute Equilibrium Entropy

    NASA Technical Reports Server (NTRS)

    Shebalin, John V.

    1997-01-01

    The entropy associated with absolute equilibrium ensemble theories of ideal, homogeneous, fluid and magneto-fluid turbulence is discussed and the three-dimensional fluid case is examined in detail. A sigma-function is defined, whose minimum value with respect to global parameters is the entropy. A comparison is made between the use of global functions sigma and phase functions H (associated with the development of various H-theorems of ideal turbulence). It is shown that the two approaches are complimentary though conceptually different: H-theorems show that an isolated system tends to equilibrium while sigma-functions allow the demonstration that entropy never decreases when two previously isolated systems are combined. This provides a more complete picture of entropy in the statistical mechanics of ideal fluids.

  19. Associations between Serum Perfluoroalkyl Acids and LINE-1 DNA Methylation

    PubMed Central

    Watkins, Deborah J.; Wellenius, Gregory A.; Butler, Rondi A.; Bartell, Scott M.; Fletcher, Tony; Kelsey, Karl T.

    2014-01-01

    Perfluoroalkyl acids (PFAAs) are persistent, synthetic compounds that are used in a number of consumer products. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been associated with cardiovascular risk factors, and changes in gene expression and DNA methylation in animals and cellular systems. However, whether PFAA exposure is associated with LINE-1 DNA methylation, a potential marker of cardiovascular risk, in humans remains unknown. We sought to evaluate the cross-sectional associations between serum PFAAs and LINE-1 DNA methylation in a population highly exposed to PFOA. We measured serum PFAAs twice four to five years apart in 685 adult participants (47% male, mean age ± SD=42 ± 11 years). We measured percent LINE-1 DNA methylation in peripheral blood leukocytes at the second time point (follow-up), and estimated absolute differences in LINE-1 methylation associated with an interquartile (IQR) shift in mean PFAA serum levels. IQR increases in mean serum PFOA, PFOS, perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were associated with differences of −0.04 (p=0.16), 0.20 (p=0.001), 0.06 (p=0.19), and 0.02 (p=0.57), respectively, in % LINE-1 methylation at follow-up after adjustment for potential confounders. We observed a monotonic increase in LINE-1 DNA methylation across tertiles of PFOS and PFNA (ptrend=0.02 for both associations), but not across tertiles of PFOA or PFHxS (ptrend=0.71 and 0.44, respectively). In summary, serum PFOS was associated with LINE-1 methylation, while serum PFOA, PFHxS, and PFNA were not. Additional research is needed to more precisely determine whether these compounds are epigenetically active. PMID:24263140

  20. Human adipocytes from the subcutaneous superficial layer have greater adipogenic potential and lower PPAR-γ DNA methylation levels than deep layer adipocytes.

    PubMed

    Kosaka, Kentaro; Kubota, Yoshitaka; Adachi, Naoki; Akita, Shinsuke; Sasahara, Yoshitaro; Kira, Tomoe; Kuroda, Masayuki; Mitsukawa, Nobuyuki; Bujo, Hideaki; Satoh, Kaneshige

    2016-08-01

    Human subcutaneous fat tissue consists of two layers, superficial adipose tissue (SAT) and deep adipose tissue (DAT). Some recent reports suggest that a disproportionate accumulation of DAT is related to obesity-associated metabolic complications. However, the differences in adipocyte function between SAT and DAT are unclear. To clarify the differences in human adipocyte characteristics between SAT and DAT, human ceiling culture-derived proliferative adipocytes (ccdPAs) were primary cultured from SAT and DAT of three lean female patients. Differences in adipogenic differentiation potential and sensitivity to exogenous adipogenic factors were examined. Epigenetic modification of the CpG island DNA methylation levels of genes related to adipogenesis was measured. In histological analyses, the mean adipocyte size in SAT was significantly larger than that in DAT (8,741 ± 416 vs. 7,732 ± 213 μm(2), P < 0.05). Primary cultured adipocytes from SAT showed significantly greater adipogenesis than did those of DAT. Sensitivity to partial adipogenic stimulation was significantly different between ccdPAs of SAT and DAT. Peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expression and leptin protein secretion from ccdPAs were significantly higher in SAT than DAT. DNA methylation levels of PPAR-γ were significantly lower in ccdPAs of SAT than DAT. Adipocyte size was larger in SAT than DAT in vivo. This is consistent with the findings of an in vitro study that, compared with ccdPAs in DAT, ccdPAs in SAT have higher adipogenic potential and lower DNA methylation levels of PPAR-γ. PMID:27251439

  1. Levels of DNA Methylation Vary at CpG Sites across the BRCA1 Promoter, and Differ According to Triple Negative and “BRCA-Like” Status, in Both Blood and Tumour DNA

    PubMed Central

    Burghel, George J.; Chambers, Philip; Al-Baba, Shadi; Connley, Daniel D.; Brock, Ian W.; Cramp, Helen E.; Dotsenko, Olena; Wilks, Octavia; Wyld, Lynda; Cross, Simon S.; Cox, Angela

    2016-01-01

    Triple negative breast cancer is typically an aggressive and difficult to treat subtype. It is often associated with loss of function of the BRCA1 gene, either through mutation, loss of heterozygosity or methylation. This study aimed to measure methylation of the BRCA1 gene promoter at individual CpG sites in blood, tumour and normal breast tissue, to assess whether levels were correlated between different tissues, and with triple negative receptor status, histopathological scoring for BRCA-like features and BRCA1 protein expression. Blood DNA methylation levels were significantly correlated with tumour methylation at 9 of 11 CpG sites examined (p<0.0007). The levels of tumour DNA methylation were significantly higher in triple negative tumours, and in tumours with high BRCA-like histopathological scores (10 of 11 CpG sites; p<0.01 and p<0.007 respectively). Similar results were observed in blood DNA (6 of 11 CpG sites; p<0.03 and 7 of 11 CpG sites; p<0.02 respectively). This study provides insight into the pattern of CpG methylation across the BRCA1 promoter, and supports previous studies suggesting that tumours with BRCA1 promoter methylation have similar features to those with BRCA1 mutations, and therefore may be suitable for the same targeted therapies. PMID:27463681

  2. Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.

    PubMed

    Rönn, Tina; Volkov, Petr; Gillberg, Linn; Kokosar, Milana; Perfilyev, Alexander; Jacobsen, Anna Louisa; Jørgensen, Sine W; Brøns, Charlotte; Jansson, Per-Anders; Eriksson, Karl-Fredrik; Pedersen, Oluf; Hansen, Torben; Groop, Leif; Stener-Victorin, Elisabet; Vaag, Allan; Nilsson, Emma; Ling, Charlotte

    2015-07-01

    Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96 males and 94 females and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic biomarkers of aging in blood, including ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between adipose tissue DNA methylation and age in our study. The most significant association between age and adipose tissue DNA methylation was found upstream of ELOVL2. We identified 2825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1) where both DNA methylation and expression correlated with BMI. Methylation at previously reported HIF3A sites correlated significantly with BMI in females only. HbA1c (range 28-46 mmol/mol) correlated significantly with the methylation of 711 sites, annotated to, for example, RAB37, TICAM1 and HLA-DPB1. Pathway analyses demonstrated that methylation levels associated with age and BMI are overrepresented among genes involved in cancer, type 2 diabetes and cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on epigenetic variation of candidate genes for obesity, type 2 diabetes and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue. PMID:25861810

  3. Reduced 3-O-methyl-dopa levels in OCD patients and their unaffected parents is associated with the low activity M158 COMT allele

    PubMed Central

    Delorme, Richard; Betancur, Catalina; Chaste, Pauline; Kernéis, Solen; Stopin, Astrid; Mouren, Marie-Christine; Collet, Corinne; Bourgeron, Thomas; Leboyer, Marion; Launay, Jean-Marie

    2010-01-01

    Background The catechol-O-methyltransferase (COMT) gene is considered as a candidate gene in obsessive-compulsive disorder (OCD). Specifically, the COMT low-activity M158 allele has been suggested to be associated with OCD. However, there is no study reporting that COMT activity is decreased in OCD patients and that the decrease is mediated by the V158M polymorphism. Therefore, the purpose of our study was to assess COMT activity in OCD by measuring plasma levels of 3-O-methyl-dopa (3-OMD), which result from the methylation of levodopa by COMT, and to investigate the relationship between 3-OMD levels and the V158M polymorphism. We also examined whether 3-OMD levels represented an endophenotype, associated with the genetic liability to OCD, by assessing unaffected relatives of OCD patients. Method We assessed plasma 3-OMD levels in a sample of drug-free OCD probands (n = 34) and their unaffected parents (n = 63), and compared them with controls (n = 85). The COMT V158M polymorphism was genotyped in all participants. Results Lower plasma 3-OMD levels were found in OCD probands and their unaffected parents compared to controls. The COMT M158 allele was associated with reduced plasma 3-OMD levels in a co-dominant manner, both in OCD probands and their relatives, but not in controls. Conclusion Our results suggest that COMT activity could act as a limiting factor for the production of 3-OMD in OCD patients and in their relatives. These findings further support a role of COMT in the susceptibility to OCD and provide evidence that 3-OMD levels could represent an endophenotype in OCD. PMID:19676096

  4. Absolute neutrino mass measurements

    NASA Astrophysics Data System (ADS)

    Wolf, Joachim

    2011-10-01

    The neutrino mass plays an important role in particle physics, astrophysics and cosmology. In recent years the detection of neutrino flavour oscillations proved that neutrinos carry mass. However, oscillation experiments are only sensitive to the mass-squared difference of the mass eigenvalues. In contrast to cosmological observations and neutrino-less double beta decay (0v2β) searches, single β-decay experiments provide a direct, model-independent way to determine the absolute neutrino mass by measuring the energy spectrum of decay electrons at the endpoint region with high accuracy. Currently the best kinematic upper limits on the neutrino mass of 2.2eV have been set by two experiments in Mainz and Troitsk, using tritium as beta emitter. The next generation tritium β-experiment KATRIN is currently under construction in Karlsruhe/Germany by an international collaboration. KATRIN intends to improve the sensitivity by one order of magnitude to 0.2eV. The investigation of a second isotope (137Rh) is being pursued by the international MARE collaboration using micro-calorimeters to measure the beta spectrum. The technology needed to reach 0.2eV sensitivity is still in the R&D phase. This paper reviews the present status of neutrino-mass measurements with cosmological data, 0v2β decay and single β-decay.

  5. Absolute neutrino mass measurements

    SciTech Connect

    Wolf, Joachim

    2011-10-06

    The neutrino mass plays an important role in particle physics, astrophysics and cosmology. In recent years the detection of neutrino flavour oscillations proved that neutrinos carry mass. However, oscillation experiments are only sensitive to the mass-squared difference of the mass eigenvalues. In contrast to cosmological observations and neutrino-less double beta decay (0v2{beta}) searches, single {beta}-decay experiments provide a direct, model-independent way to determine the absolute neutrino mass by measuring the energy spectrum of decay electrons at the endpoint region with high accuracy.Currently the best kinematic upper limits on the neutrino mass of 2.2eV have been set by two experiments in Mainz and Troitsk, using tritium as beta emitter. The next generation tritium {beta}-experiment KATRIN is currently under construction in Karlsruhe/Germany by an international collaboration. KATRIN intends to improve the sensitivity by one order of magnitude to 0.2eV. The investigation of a second isotope ({sup 137}Rh) is being pursued by the international MARE collaboration using micro-calorimeters to measure the beta spectrum. The technology needed to reach 0.2eV sensitivity is still in the R and D phase. This paper reviews the present status of neutrino-mass measurements with cosmological data, 0v2{beta} decay and single {beta}-decay.

  6. Precise Measurement of the Absolute Fluorescence Yield

    NASA Astrophysics Data System (ADS)

    Ave, M.; Bohacova, M.; Daumiller, K.; Di Carlo, P.; di Giulio, C.; San Luis, P. Facal; Gonzales, D.; Hojvat, C.; Hörandel, J. R.; Hrabovsky, M.; Iarlori, M.; Keilhauer, B.; Klages, H.; Kleifges, M.; Kuehn, F.; Monasor, M.; Nozka, L.; Palatka, M.; Petrera, S.; Privitera, P.; Ridky, J.; Rizi, V.; D'Orfeuil, B. Rouille; Salamida, F.; Schovanek, P.; Smida, R.; Spinka, H.; Ulrich, A.; Verzi, V.; Williams, C.

    2011-09-01

    We present preliminary results of the absolute yield of fluorescence emission in atmospheric gases. Measurements were performed at the Fermilab Test Beam Facility with a variety of beam particles and gases. Absolute calibration of the fluorescence yield to 5% level was achieved by comparison with two known light sources--the Cherenkov light emitted by the beam particles, and a calibrated nitrogen laser. The uncertainty of the energy scale of current Ultra-High Energy Cosmic Rays experiments will be significantly improved by the AIRFLY measurement.

  7. Active coping toward predatory stress is associated with lower corticosterone and progesterone plasma levels and decreased methylation in the medial amygdala vasopressin system.

    PubMed

    Bowen, Michael T; Dass, Shantala A Hari; Booth, Jessica; Suraev, Anastasia; Vyas, Ajai; McGregor, Iain S

    2014-08-01

    An active coping style displayed under stress - which involves proactive investigatory responses toward environmental threats - has been associated with reduced vulnerability to psychiatric illness. However, the neurobiological determinants of coping styles are not well understood. When rats are exposed to a naturalistic stressor (cat fur) in a group, some individuals in the group show robust active investigation of the stimulus while others show a passive response involving retreat, immobility and close aggregation with conspecifics. Here we explored endocrine and epigenetic correlates of these contrasting coping styles. Male Wistar rats (n=48) were exposed to cat fur in groups of 4 and the passive and active responders were identified and assessed for endocrine and epigenetic differences. Three days after the final cat fur exposure, active responders had substantially lower plasma levels of corticosterone and progesterone than passive responders. Plasma and testicular testosterone levels did not differ between active and passive responders. Active responders had markedly less methylation of the AVP CGCG promoter region located at base 4970 in the posterodorsal region of the medial amygdala but did not differ in the methylation status of the CCGG sequence located at base 2243. This is in agreement with prior research suggesting that AVP and progesterone act in opposition within the medial amygdala to modulate stress-related behaviors. The present study reports striking endocrine and epigenetic differences between active and passive responders, providing insight into potential systems involved in the manifestation of differing coping styles. PMID:25127982

  8. Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus

    PubMed Central

    Wilson, Gareth A.; Rakyan, Vardhman K.; Teschendorff, Andrew E.; Akan, Pelin; Stupka, Elia; Down, Thomas A.; Prokopenko, Inga; Morison, Ian M.; Mill, Jonathan; Pidsley, Ruth; Deloukas, Panos; Frayling, Timothy M.; Hattersley, Andrew T.; McCarthy, Mark I.; Beck, Stephan; Hitman, Graham A.

    2010-01-01

    Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D), focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip) and absolute methylation values were estimated using a Bayesian algorithm (BATMAN). Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.40×10−4, permutation p = 1.0×10−3). Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p = 1.13×10−7). Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM), encapsulates a Highly Conserved Non-Coding Element (HCNE) that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA) SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases. PMID:21124985

  9. Absolute Identification by Relative Judgment

    ERIC Educational Resources Information Center

    Stewart, Neil; Brown, Gordon D. A.; Chater, Nick

    2005-01-01

    In unidimensional absolute identification tasks, participants identify stimuli that vary along a single dimension. Performance is surprisingly poor compared with discrimination of the same stimuli. Existing models assume that identification is achieved using long-term representations of absolute magnitudes. The authors propose an alternative…

  10. Be Resolute about Absolute Value

    ERIC Educational Resources Information Center

    Kidd, Margaret L.

    2007-01-01

    This article explores how conceptualization of absolute value can start long before it is introduced. The manner in which absolute value is introduced to students in middle school has far-reaching consequences for their future mathematical understanding. It begins to lay the foundation for students' understanding of algebra, which can change…

  11. Methyl Iodide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methyl iodide (MeI, iodomethane, CH3I) was reported as a potential alternative to the stratospheric ozone-depleting fumigant methyl bromide (MeBr) in the mid-1990s (Sims et al., 1995; Ohr et al., 1996). It has since received significant research attention to determine its environmental fate and tran...

  12. Effect on the H19 gene methylation of sperm and organs of offspring after chlorpyrifos-methyl exposure during organogenesis period.

    PubMed

    Shin, Hyo-Sook; Seo, Jong-Hun; Jeong, Sang-Hee; Park, Sung-Won; Park, Young-Il; Son, Seong-Wan; Kang, Hwan-Goo; Kim, Jin Suk

    2015-12-01

    To elucidate the effect on the H19 gene methylation of sperm and organs in offspring by chlorpyrifos-methyl (CPM) exposure during organogenesis period, CPM was administered at doses of 4 (CPM4), 20 (CPM20), and 100 (CPM100) mg/kg bw/day from 7 days post coitum (d.p.c.) to 17 d.p.c. after mating CAST/Ei (♂) and B6 (♀). Anogenital distance (AGD) was measured at postnatal day (PND) 21. Clinical signs, body weights, feed and water consumption, organs weights, serum hormone values, and H19 methylation level of organ and sperm were measured at PND63. Body weights were significantly lower than control until PND6. AGD was significantly decreased in the CPM100 group in males and increased in the CPM20 group in females. The absolute weights of the thymus and epididymis were significantly increased for males in all of CPM treatment groups. In the CPM20 group, absolute weights of liver, kidney, heart, lung, spleen, prostate gland, and testes were significantly increased. Testosterone concentrations in serum were significantly increased by CPM treatment in males. H19 methylation level of liver and thymus showed decreased pattern in a dose-dependent manner in males. The levels of H19 methylation in sperm were 73.76 ± 7.16% (Control), 57.84 ± 12.94% (CPM4), 64.24 ± 3.79% (CPM20), and 64.24 ± 3.79% (CPM100). Conclusively, CPM exposure during organogenesis period can disrupt H19 methylation in sperm, liver, and thymus and disturb the early development of offspring. PMID:25782373

  13. The relationship between lysine 4 on histone H3 methylation levels of alcohol tolerance genes and changes of ethanol tolerance in Saccharomyces cerevisiae

    PubMed Central

    Wang, Hang; Ji, Binfeng; Ren, Hongzhen; Meng, Chun

    2014-01-01

    We evaluated whether epigenetic changes contributed to improve ethanol tolerance in mutant populations of Saccharomyces cerevisiae (S. cerevisiae). Two ethanol-tolerant variants of S. cerevisiae were used to evaluate the genetic stability in the process of stress-free passage cultures. We found that acquired ethanol tolerance was lost and transcription level of some genes (HSP104, PRO1, TPS1, and SOD1) closely related to ethanol tolerance decreased significantly after the 10th passage in ethanol-free medium. Tri-methylation of lysine 4 on histone H3 (H3K4) enhanced at the promoter of HSP104, PRO1, TPS1 and SOD1 in ethanol-tolerant variants of S. cerevisiae was also diminished after tenth passage in stress-free cultures. The ethanol tolerance was reacquired when exogenous SOD1 transferred in some tolerance-lost strains. This showed that H3K4 methylation is involved in phenotypic variation with regard to ethanol tolerance with respect to classic breeding methods used in yeast. PMID:24779776

  14. Canopy level emissions of 2-methyl-3-buten-2-ol, monoterpenes, and sesquiterpenes from an experimental Pinus taeda plantation.

    PubMed

    Geron, Christopher D; Daly, Ryan W; Arnts, Robert R; Guenther, Alex B; Mowry, Fred L

    2016-09-15

    Emissions of Biogenic Volatile Organic Compounds (BVOCs) observed during 2007 from an experimental Pinus taeda plantation in Central North Carolina are compared with model estimates from the Model of Emissions of Gases and Aerosols from Nature (MEGAN) version 2.1. Relaxed eddy accumulation (REA) estimates of 2-methyl-3-buten-2-ol (MBO) fluxes are a factor of 3-4 higher than MEGAN estimates. MEGAN monoterpene emission estimates were a factor of approximately two higher than REA flux measurements. MEGAN β-caryophyllene emission estimates were within 60% of growing season REA flux estimates but were several times higher than REA fluxes during cooler, dormant season periods. The sum of other sesquiterpene emissions estimated by MEGAN was several times higher than REA estimates throughout the year. Model components are examined to understand these discrepancies. Measured summertime leaf area index (LAI) (and therefore foliar biomass) is a factor of two higher than assumed in MEGAN for the P. taeda default. Increasing the canopy mean MBO emission factor from 0.35 to 1.0mgm(-2)h(-1) also reduces MEGAN vs. REA flux differences. This increase is within current MBO emission factor uncertainties. The algorithm within MEGAN which adjusts isoprene emission estimates as a function of the temperature and light of the previous 24h seems also to improve the seasonal MEGAN MBO correlation with REA fluxes. Including the effects of the previous 240h, however, seems to degrade temporal model correlation with fluxes. Monoterpene and sesquiterpene composition data from the REA are compared with MEGAN2.1 estimates and also branch enclosure and needle extract data collected at this site. To our knowledge, the flux data presented here are the first reported for MBO and sesquiterpenes from a P. taeda ecosystem. PMID:27232720

  15. Gestational stress and fluoxetine treatment differentially affect plasticity, methylation and serotonin levels in the PFC and hippocampus of rat dams.

    PubMed

    Gemmel, Mary; Rayen, Ine; van Donkelaar, Eva; Loftus, Tiffany; Steinbusch, Harry W; Kokras, Nikolaos; Dalla, Christina; Pawluski, Jodi L

    2016-07-01

    Women are more likely to develop depression during childbearing years with up to 20% of women suffering from depression during pregnancy and in the postpartum period. Increased prevalence of depression during the perinatal period has resulted in frequent selective serotonin reuptake inhibitor (SSRI) antidepressant treatment; however the effects of such medications on the maternal brain remain limited. Therefore, the aim of the present study is to investigate the effects of the SSRI medication, fluoxetine, on neurobiological differences in the maternal brain. To model aspects of maternal depression, gestational stress was used. Sprague-Dawley rat dams were exposed to either gestational stress and/or fluoxetine (5mg/kg/day) to form the following four groups: 1. Control+Vehicle, 2. Stress+Vehicle, 3. Control+Fluoxetine, and 4. Stress+Fluoxetine. At weaning maternal brains were collected. Main findings show that gestational stress alone increased synaptophysin and serotonin metabolism in the cingulate cortex2 region of the cortex while fluoxetine treatment after stress normalized these effects. In the hippocampus, fluoxetine treatment, regardless of gestational stress exposure, decreased both global measures of methylation in the dentate gyrus, as measured by Dnmt3a immunoreactivity, as well as serotonin metabolism. No further changes in synaptophysin, PSD-95, or Dnmt3a immunoreactivity were seen in the cortical or hippocampal areas investigated. These findings show that gestational stress and SSRI medication affect the neurobiology of the maternal brain in a region-specific manner. This work adds to a much needed area of research aimed at understanding neurobiological changes associated with maternal depression and the role of SSRI treatment in altering these changes in the female brain. PMID:27060483

  16. Improving HST Pointing & Absolute Astrometry

    NASA Astrophysics Data System (ADS)

    Lallo, Matthew; Nelan, E.; Kimmer, E.; Cox, C.; Casertano, S.

    2007-05-01

    Accurate absolute astrometry is becoming increasingly important in an era of multi-mission archives and virtual observatories. Hubble Space Telescope's (HST's) Guidestar Catalog II (GSC2) has reduced coordinate error to around 0.25 arcsecond, a factor 2 or more compared with GSC1. With this reduced catalog error, special attention must be given to calibrate and maintain the Fine Guidance Sensors (FGSs) and Science Instruments (SIs) alignments in HST to a level well below this in order to ensure that the accuracy of science product's astrometry keywords and target positioning are limited only by the catalog errors. After HST Servicing Mission 4, such calibrations' improvement in "blind" pointing accuracy will allow for more efficient COS acquisitions. Multiple SIs and FGSs each have their own footprints in the spatially shared HST focal plane. It is the small changes over time in primarily the whole-body positions & orientations of these instruments & guiders relative to one another that is addressed by this work. We describe the HST Cycle 15 program CAL/OTA 11021 which, along with future variants of it, determines and maintains positions and orientations of the SIs and FGSs to better than 50 milli- arcseconds and 0.04 to 0.004 degrees of roll, putting errors associated with the alignment sufficiently below GSC2 errors. We present recent alignment results and assess their errors, illustrate trends, and describe where and how the observer sees benefit from these calibrations when using HST.

  17. Methylation similarities of two CpG sites within exon 5 of human H19 between normal tissues and testicular germ cell tumours of adolescents and adults, without correlation with allelic and total level of expression.

    PubMed Central

    Gillis, A. J.; Verkerk, A. J.; Dekker, M. C.; van Gurp, R. J.; Oosterhuis, J. W.; Looijenga, L. H.

    1997-01-01

    Testicular germ cell tumours (TGCTs) of adolescents and adults morphologically mimic different stages of embryogenesis. Established cell lines of these cancers are used as informative models to study early development. We found that, in contrast to normal development, TGCTs show a consistent biallelic expression of imprinted genes, including H19, irrespective of histology. Methylation of particular cytosine residues of H19 correlates with inhibition of expression, which has not been studied in TGCTs thus far. We investigated the methylation status of two CpG sites within the 3' region of H19 (exon 5: positions 3321 and 3324) both in normal tissues as well as in TGCTs. To obtain quantitative data of these specific sites, the ligation-mediated polymerase chain reaction technique, instead of Southern blot analysis, was applied. The results were compared with the allelic status and the total level of expression of this gene. Additionally, the undifferentiated cells and differentiated derivatives of the TGCT-derived cell line NT2-D1 were analysed. While peripheral blood showed no H19 expression and complete methylation, a heterogeneous but consistent pattern of methylation and level of expression was found in the other normal tissues, without a correlation between the two. The separate histological entities of TGCTs resembled the pattern of their nonmalignant tissues. While the CpG sites remained completely methylated in NT2-D1, H19 expression was induced upon differentiation. These data indicate that methylation of the CpG sites within exon 5 of H19 is tissue dependent, without regulating allelic status and/or total level of expression. Of special note is the finding that, also regarding methylation of these particular sites of H19, TGCTs mimic their non-malignant counterparts, in spite of their consistent biallelic expression. Images Figure 1 Figure 3 Figure 4 PMID:9310237

  18. LINE1 methylation levels associated with increased bladder cancer risk in pre-diagnostic blood DNA among US (PLCO) and European (ATBC) cohort study participants.

    PubMed

    Andreotti, Gabriella; Karami, Sara; Pfeiffer, Ruth M; Hurwitz, Lauren; Liao, Linda M; Weinstein, Stephanie J; Albanes, Demetrius; Virtamo, Jarmo; Silverman, Debra T; Rothman, Nathaniel; Moore, Lee E

    2014-03-01

    Global methylation in blood DNA has been associated with bladder cancer risk in case-control studies, but has not been examined prospectively. We examined the association between LINE1 total percent 5-methylcytosine and bladder cancer risk using pre-diagnostic blood DNA from the United States-based, Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) (299 cases/676 controls), and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) cohort of Finnish male smokers (391 cases/778 controls). Logistic regression adjusted for age at blood draw, study center, pack-years of smoking, and sex was used to estimate odd ratios (ORs) and 95% confidence intervals (CIs) using study- and sex-specific methylation quartiles. In PLCO, higher, although non-significant, bladder cancer risks were observed for participants in the highest three quartiles (Q2-Q4) compared with the lowest quartile (Q1) (OR = 1.36, 95% CI: 0.96 -1.92). The association was stronger in males (Q2-Q4 vs. Q1 OR = 1.48, 95% CI: 1.00-2.20) and statistically significant among male smokers (Q2-Q4 vs. Q1 OR = 1.83, 95% CI: 1.14-2.95). No association was found among females or female smokers. Findings for male smokers were validated in ATBC (Q2-Q4 vs. Q1: OR = 2.31, 95% CI: 1.62-3.30) and a highly significant trend was observed (P = 8.7 × 10(-7)). After determining that study data could be combined, pooled analysis of PLCO and ATBC male smokers (580 cases/1119 controls), ORs were significantly higher in Q2-Q4 compared with Q1 (OR = 2.03, 95% CI: 1.52-2.72), and a trend across quartiles was observed (P = 0.0001). These findings suggest that higher global methylation levels prior to diagnosis may increase bladder cancer risk, particularly among male smokers. PMID:24316677

  19. Expression Levels of Some Detoxification Genes in Liver and Testis of Rats Exposed to a Single Dose of Methyl-Tertiary Butyl Ether

    PubMed Central

    Badr, Ahmad Ali; Saadat, Mostafa

    2016-01-01

    AIM: Methyl-tertiary-butyl ether (MTBE), a well-known gasoline oxygenate compound, is still used in several countries. Several studies investigated the effects of MTBE on the activity of phase II metabolism enzymes. There is no published data on the effect(s) of short-term exposure to MTBE on mRNA levels of antioxidant genes. Therefore, the present study was carried out. METHODS: A total of 15 adults male Wistar rats were randomly divided into five equal experimental groups. They received a single dose of 0, 400, 800 and 1600 mg/Kg MTBE in peanut oil by gavages. The final group received no MTBE and peanut oil. After 24 hr animals were slaughtered then livers and testis were removed to extract the total RNA. Real-time PCR was done to detect the gene expressions of glutathione S-transferase family (Gstt1, Gstm1, and Gstp1). RESULTS: The mRNAs levels of the examined genes neither in liver nor in testis showed a significant difference between the exposed groups and control rats. CONCLUSIONS: The present data revealed that exposure to a single dose of MTBE has no significant effect on the mRNA levels of the Gstt1, Gstm1, and Gstp1 genes. PMID:27335592

  20. Red Wine Consumption is inversely associated with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA Adduct Levels in Prostate

    PubMed Central

    Rybicki, Benjamin A.; Neslund-Dudas, Christine; Bock, Cathryn H.; Nock, Nora L.; Rundle, Andrew; Jankowski, Michelle; Levin, Albert M.; Beebe-Dimmer, Jennifer; Savera, Adnan T.; Takahashi, Satoru; Shirai, Tomoyuki; Tang, Deliang

    2011-01-01

    In humans, genetic variation and dietary factors may alter the biologic effects of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the major heterocyclic amines generated from cooking meats at high temperatures that has carcinogenic potential through the formation of DNA adducts. Previously, we reported grilled red meat consumption associated with PhIP-DNA adduct levels in human prostate. In the present study, we expanded our investigation to estimate the associations between beverage consumption and PhIP-DNA adduct levels in prostate for 391 prostate cancer cases. Of the 15 beverages analyzed, red wine consumption had the strongest association with PhIP-DNA adduct levels showing an inverse correlation in both tumor (p=0.006) and non-tumor (p=0.002) prostate cells. Red wine consumption differed significantly between African-American and white cases, but PhIP-DNA adduct levels in prostate did not vary by race. In African Americans compared with whites, however, associations between red wine consumption and PhIP-DNA adduct levels were not as strong as associations with specific (e.g., SULT1A1 and UGT1A10 genotypes) and non-specific (e.g., African ancestry) genetic variation. In a multivariable model, the covariate for red wine consumption explained a comparable percentage (13-16%) of the variation in PhIP-DNA adduct levels in prostate across the two racial groups, but the aforementioned genetic factors explained 33% of the PhIP-DNA adduct variation in African-American cases, while only 19% of the PhIPDNA adduct variation in whites. We conclude that red wine consumption may counteract biologic effects of PhIP exposure in human prostate, but genetic factors may play an even larger role, particularly in African Americans. PMID:21846795

  1. Absolute Humidity and the Seasonality of Influenza (Invited)

    NASA Astrophysics Data System (ADS)

    Shaman, J. L.; Pitzer, V.; Viboud, C.; Grenfell, B.; Goldstein, E.; Lipsitch, M.

    2010-12-01

    Much of the observed wintertime increase of mortality in temperate regions is attributed to seasonal influenza. A recent re-analysis of laboratory experiments indicates that absolute humidity strongly modulates the airborne survival and transmission of the influenza virus. Here we show that the onset of increased wintertime influenza-related mortality in the United States is associated with anomalously low absolute humidity levels during the prior weeks. We then use an epidemiological model, in which observed absolute humidity conditions temper influenza transmission rates, to successfully simulate the seasonal cycle of observed influenza-related mortality. The model results indicate that direct modulation of influenza transmissibility by absolute humidity alone is sufficient to produce this observed seasonality. These findings provide epidemiological support for the hypothesis that absolute humidity drives seasonal variations of influenza transmission in temperate regions. In addition, we show that variations of the basic and effective reproductive numbers for influenza, caused by seasonal changes in absolute humidity, are consistent with the general timing of pandemic influenza outbreaks observed for 2009 A/H1N1 in temperate regions. Indeed, absolute humidity conditions correctly identify the region of the United States vulnerable to a third, wintertime wave of pandemic influenza. These findings suggest that the timing of pandemic influenza outbreaks is controlled by a combination of absolute humidity conditions, levels of susceptibility and changes in population mixing and contact rates.

  2. DNA Methylation

    PubMed Central

    Marinus, M.G.; Løbner-Olesen, A.

    2014-01-01

    The DNA of E. coli contains 19,120 6-methyladenines and 12,045 5-methylcytosines in addition to the four regular bases and these are formed by the postreplicative action of three DNA methyltransferases. The majority of the methylated bases are formed by the Dam and Dcm methyltransferases encoded by the dam (DNA adenine methyltransferase) and dcm (DNA cytosine methyltransferase) genes. Although not essential, Dam methylation is important for strand discrimination during repair of replication errors, controlling the frequency of initiation of chromosome replication at oriC, and regulation of transcription initiation at promoters containing GATC sequences. In contrast, there is no known function for Dcm methylation although Dcm recognition sites constitute sequence motifs for Very Short Patch repair of T/G base mismatches. In certain bacteria (e.g., Vibrio cholerae, Caulobacter crescentus) adenine methylation is essential and in C. crescentus, it is important for temporal gene expression which, in turn, is required for coordinating chromosome initiation, replication and division. In practical terms, Dam and Dcm methylation can inhibit restriction enzyme cleavage; decrease transformation frequency in certain bacteria; decrease the stability of short direct repeats; are necessary for site-directed mutagenesis; and to probe eukaryotic structure and function. PMID:26442938

  3. Absolute radiometry and the solar constant

    NASA Technical Reports Server (NTRS)

    Willson, R. C.

    1974-01-01

    A series of active cavity radiometers (ACRs) are described which have been developed as standard detectors for the accurate measurement of irradiance in absolute units. It is noted that the ACR is an electrical substitution calorimeter, is designed for automatic remote operation in any environment, and can make irradiance measurements in the range from low-level IR fluxes up to 30 solar constants with small absolute uncertainty. The instrument operates in a differential mode by chopping the radiant flux to be measured at a slow rate, and irradiance is determined from two electrical power measurements together with the instrumental constant. Results are reported for measurements of the solar constant with two types of ACRs. The more accurate measurement yielded a value of 136.6 plus or minus 0.7 mW/sq cm (1.958 plus or minus 0.010 cal/sq cm per min).

  4. Absolute calibration of TFTR helium proportional counters

    SciTech Connect

    Strachan, J.D.; Diesso, M.; Jassby, D.; Johnson, L.; McCauley, S.; Munsat, T.; Roquemore, A.L.; Barnes, C.W. |; Loughlin, M. |

    1995-06-01

    The TFTR helium proportional counters are located in the central five (5) channels of the TFTR multichannel neutron collimator. These detectors were absolutely calibrated using a 14 MeV neutron generator positioned at the horizontal midplane of the TFTR vacuum vessel. The neutron generator position was scanned in centimeter steps to determine the collimator aperture width to 14 MeV neutrons and the absolute sensitivity of each channel. Neutron profiles were measured for TFTR plasmas with time resolution between 5 msec and 50 msec depending upon count rates. The He detectors were used to measure the burnup of 1 MeV tritons in deuterium plasmas, the transport of tritium in trace tritium experiments, and the residual tritium levels in plasmas following 50:50 DT experiments.

  5. Mechanistic Insights into the Decomposition of Fructose to Hydroxy Methyl Furfural in Neutral and Acidic Environments Using High-Level Quantum Chemical Methods

    SciTech Connect

    Assary, Rajeev S.; Redfern, Paul C.; Greeley, Jeffrey P.; Curtiss, Larry A.

    2011-04-21

    Efficient catalytic chemical transformation of fructose to hydroxy methyl furfural (HMF) is one of the key steps for attaining industrial level conversion of biomass to useful chemicals. We report an investigation of the reaction mechanisms for the decomposition of fructose to HMF in both neutral and acidic environments at the Gaussian-4 level of theory including calculation of enthalpies, free energies, and effective solvation interactions. In neutral water solvent, the transformation of fructose to HMF involves a four step reaction sequence with four transition states. The effective activation energy relative to fructose in neutral water at 298 K is very large, about 74 kcal/mol, so that transformation in neutral media around this temperature is unlikely. In contrast, the computed potential energy surface is much more favorable for the transformation in acidic media at 498 K, as the effective activation barrier is about 39 kcal/mol. The transformation in acidic media is a much more complex mechanism involving dehydration and hydrogen transfer steps, which are more favorable when protonated intermediates are involved.

  6. Mechanistic Insights into the Decomposition of Fructose to Hydroxy Methyl Furfural in Neutral and Acidic Environments Using High-Level Quantum Chemical Methods

    SciTech Connect

    Assary, Rajeev S.; Redfern, Paul C.; Greeley, Jeffrey; Curtiss, Larry A.

    2011-03-28

    Efficient catalytic chemical transformation of fructose to hydroxy methyl furfural (HMF) is one of the key steps for attaining industrial level conversion of biomass to useful chemicals. We report an investigation of the reaction mechanisms for the decomposition of fructose to HMF in both neutral and acidic environments at the Gaussian-4 level of theory including calculation of enthalpies, free energies, and effective solvation interactions. In neutral water solvent, the transformation of fructose to HMF involves a four step reaction sequence with four transition states. The effective activation energy relative to fructose in neutral water at 298 K is very large, about 74 kcal/mol, so that transformation in neutral media around this temperature is unlikely. In contrast, the computed potential energy surface is much more favorable for the transformation in acidic media at 498 K, as the effective activation barrier is about 39 kcal/mol. The transformation in acidic media is a much more complex mechanism involving dehydration and hydrogen transfer steps, which are more favorable when protonated intermediates are involved.

  7. Mechanistic insights into the decomposition of fructose to hydroxy methyl furfural in neutral and acidic environments using high-level quantum chemical methods.

    PubMed

    Assary, Rajeev S; Redfern, Paul C; Greeley, Jeffrey; Curtiss, Larry A

    2011-04-21

    Efficient catalytic chemical transformation of fructose to hydroxy methyl furfural (HMF) is one of the key steps for attaining industrial level conversion of biomass to useful chemicals. We report an investigation of the reaction mechanisms for the decomposition of fructose to HMF in both neutral and acidic environments at the Gaussian-4 level of theory including calculation of enthalpies, free energies, and effective solvation interactions. In neutral water solvent, the transformation of fructose to HMF involves a four step reaction sequence with four transition states. The effective activation energy relative to fructose in neutral water at 298 K is very large, about 74 kcal/mol, so that transformation in neutral media around this temperature is unlikely. In contrast, the computed potential energy surface is much more favorable for the transformation in acidic media at 498 K, as the effective activation barrier is about 39 kcal/mol. The transformation in acidic media is a much more complex mechanism involving dehydration and hydrogen transfer steps, which are more favorable when protonated intermediates are involved. PMID:21443225

  8. Mechanistic insights into the decomposition of fructose to hydroxy methyl furfural in neutral and acidic environments using high-level quantum chemical methods.

    SciTech Connect

    Assary, R. S.; Redfern, P. C.; Greeley, J.; Curtiss, L. A.

    2011-03-28

    Efficient catalytic chemical transformation of fructose to hydroxy methyl furfural (HMF) is one of the key steps for attaining industrial level conversion of biomass to useful chemicals. We report an investigation of the reaction mechanisms for the decomposition of fructose to HMF in both neutral and acidic environments at the Gaussian-4 level of theory including calculation of enthalpies, free energies, and effective solvation interactions. In neutral water solvent, the transformation of fructose to HMF involves a four step reaction sequence with four transition states. The effective activation energy relative to fructose in neutral water at 298 K is very large, about 74 kcal/mol, so that transformation in neutral media around this temperature is unlikely. In contrast, the computed potential energy surface is much more favorable for the transformation in acidic media at 498 K, as the effective activation barrier is about 39 kcal/mol. The transformation in acidic media is a much more complex mechanism involving dehydration and hydrogen transfer steps, which are more favorable when protonated intermediates are involved.

  9. Absolute radiometric calibration of advanced remote sensing systems

    NASA Technical Reports Server (NTRS)

    Slater, P. N.

    1982-01-01

    The distinction between the uses of relative and absolute spectroradiometric calibration of remote sensing systems is discussed. The advantages of detector-based absolute calibration are described, and the categories of relative and absolute system calibrations are listed. The limitations and problems associated with three common methods used for the absolute calibration of remote sensing systems are addressed. Two methods are proposed for the in-flight absolute calibration of advanced multispectral linear array systems. One makes use of a sun-illuminated panel in front of the sensor, the radiance of which is monitored by a spectrally flat pyroelectric radiometer. The other uses a large, uniform, high-radiance reference ground surface. The ground and atmospheric measurements required as input to a radiative transfer program to predict the radiance level at the entrance pupil of the orbital sensor are discussed, and the ground instrumentation is described.

  10. Testing the quasi-absolute method in photon activation analysis

    SciTech Connect

    Sun, Z. J.; Wells, D.; Starovoitova, V.; Segebade, C.

    2013-04-19

    In photon activation analysis (PAA), relative methods are widely used because of their accuracy and precision. Absolute methods, which are conducted without any assistance from calibration materials, are seldom applied for the difficulty in obtaining photon flux in measurements. This research is an attempt to perform a new absolute approach in PAA - quasi-absolute method - by retrieving photon flux in the sample through Monte Carlo simulation. With simulated photon flux and database of experimental cross sections, it is possible to calculate the concentration of target elements in the sample directly. The QA/QC procedures to solidify the research are discussed in detail. Our results show that the accuracy of the method for certain elements is close to a useful level in practice. Furthermore, the future results from the quasi-absolute method can also serve as a validation technique for experimental data on cross sections. The quasi-absolute method looks promising.

  11. Methyl Bromide Poisoning

    PubMed Central

    Rathus, E. M.; Landy, P. J.

    1961-01-01

    Seven cases of methyl bromide poisoning which occurred amongst workers engaged on a fumigation project are described. The methods adopted for investigation of the environmental situation are discussed and the measurement of blood bromide levels on random samples of workers is suggested as an index of the effectiveness of equipment and working methods. PMID:13739738

  12. The evolution of invertebrate gene body methylation.

    PubMed

    Sarda, Shrutii; Zeng, Jia; Hunt, Brendan G; Yi, Soojin V

    2012-08-01

    DNA methylation of transcription units (gene bodies) occurs in the genomes of many animal and plant species. Phylogenetic persistence of gene body methylation implies biological significance; yet, the functional roles of gene body methylation remain elusive. In this study, we analyzed methylation levels of orthologs from four distantly related invertebrate species, including the honeybee, silkworm, sea squirt, and sea anemone. We demonstrate that in all four species, gene bodies distinctively cluster to two groups, which correspond to high and low methylation levels. This pattern resembles that of sequence composition arising from the mutagenetic effect of DNA methylation. In spite of this effect, our results show that protein sequences of genes targeted by high levels of methylation are conserved relative to genes lacking methylation. Our investigation identified many genes that either gained or lost methylation during the course of invertebrate evolution. Most of these genes appear to have lost methylation in the insect lineages we investigated, particularly in the honeybee. We found that genes that are methylated in all four invertebrate taxa are enriched for housekeeping functions related to transcription and translation, whereas the loss of DNA methylation occurred in genes whose functions include cellular signaling and reproductive processes. Overall, our study helps to illuminate the functional significance of gene body methylation and its impacts on genome evolution in diverse invertebrate taxa. PMID:22328716

  13. Absolute calibration of sniffer probes on Wendelstein 7-X.

    PubMed

    Moseev, D; Laqua, H P; Marsen, S; Stange, T; Braune, H; Erckmann, V; Gellert, F; Oosterbeek, J W

    2016-08-01

    Here we report the first measurements of the power levels of stray radiation in the vacuum vessel of Wendelstein 7-X using absolutely calibrated sniffer probes. The absolute calibration is achieved by using calibrated sources of stray radiation and the implicit measurement of the quality factor of the Wendelstein 7-X empty vacuum vessel. Normalized absolute calibration coefficients agree with the cross-calibration coefficients that are obtained by the direct measurements, indicating that the measured absolute calibration coefficients and stray radiation levels in the vessel are valid. Close to the launcher, the stray radiation in the empty vessel reaches power levels up to 340 kW/m(2) per MW injected beam power. Furthest away from the launcher, i.e., half a toroidal turn, still 90 kW/m(2) per MW injected beam power is measured. PMID:27587121

  14. Absolute calibration of sniffer probes on Wendelstein 7-X

    NASA Astrophysics Data System (ADS)

    Moseev, D.; Laqua, H. P.; Marsen, S.; Stange, T.; Braune, H.; Erckmann, V.; Gellert, F.; Oosterbeek, J. W.

    2016-08-01

    Here we report the first measurements of the power levels of stray radiation in the vacuum vessel of Wendelstein 7-X using absolutely calibrated sniffer probes. The absolute calibration is achieved by using calibrated sources of stray radiation and the implicit measurement of the quality factor of the Wendelstein 7-X empty vacuum vessel. Normalized absolute calibration coefficients agree with the cross-calibration coefficients that are obtained by the direct measurements, indicating that the measured absolute calibration coefficients and stray radiation levels in the vessel are valid. Close to the launcher, the stray radiation in the empty vessel reaches power levels up to 340 kW/m2 per MW injected beam power. Furthest away from the launcher, i.e., half a toroidal turn, still 90 kW/m2 per MW injected beam power is measured.

  15. Methyl chloride

    Integrated Risk Information System (IRIS)

    Methyl chloride ; CASRN 74 - 87 - 3 ( 07 / 17 / 2001 ) Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for

  16. Methyl acrylate

    Integrated Risk Information System (IRIS)

    Methyl acrylate ; CASRN 96 - 33 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Ef

  17. Methyl isocyanate

    Integrated Risk Information System (IRIS)

    Methyl isocyanate ; CASRN 624 - 83 - 9 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  18. Methyl iodide

    Integrated Risk Information System (IRIS)

    Methyl iodide ; CASRN 74 - 88 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effe

  19. Methyl parathion

    Integrated Risk Information System (IRIS)

    Methyl parathion ; CASRN 298 - 00 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  20. Methyl chlorocarbonate

    Integrated Risk Information System (IRIS)

    Methyl chlorocarbonate ; CASRN 79 - 22 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinog

  1. Methyl methacrylate

    Integrated Risk Information System (IRIS)

    Methyl methacrylate ; CASRN 80 - 62 - 6 ( 03 / 02 / 98 ) Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments f

  2. Absolute transition probabilities of phosphorus.

    NASA Technical Reports Server (NTRS)

    Miller, M. H.; Roig, R. A.; Bengtson, R. D.

    1971-01-01

    Use of a gas-driven shock tube to measure the absolute strengths of 21 P I lines and 126 P II lines (from 3300 to 6900 A). Accuracy for prominent, isolated neutral and ionic lines is estimated to be 28 to 40% and 18 to 30%, respectively. The data and the corresponding theoretical predictions are examined for conformity with the sum rules.-

  3. Increasing levels of the endocannabinoid 2-AG is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

    PubMed Central

    Mounsey, Ross B.; Mustafa, Sarah; Robinson, Lianne; Ross, Ruth A.; Riedel, Gernot; Pertwee, Roger G.; Teismann, Peter

    2015-01-01

    Parkinson's disease (PD) is a common chronic neurodegenerative disorder, usually of idiopathic origin. Symptoms including tremor, bradykinesia, rigidity and postural instability are caused by the progressive loss of dopaminergic neurons in the nigrostriatal region of the brain. Symptomatic therapies are available but no treatment slows or prevents the loss of neurons. Neuroinflammation has been implicated in its pathogenesis. To this end, the present study utilises the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to reproduce the pattern of cell death evident in PD patients. Herein, the role of a potential regulator of an immune response, the endocannabinoid system (ECS), is investigated. The most prevalent endocannabinoid, 2-arachidonoylglycerol (2-AG) (3 and 5 mg/kg), was added exogenously and its enzymatic degradation inhibited to provide protection against MPTP-induced cell death. Furthermore, the addition of DFU (25 mg/kg), a selective inhibitor of inflammatory mediator cyclooxygenase-2 (COX-2), potentiated these effects. Levels of 2-AG were shown to be upregulated in a time- and region-specific manner following MPTP administration, indicating that the ECS represents a natural defence mechanism against inflammation, potentiation of which could provide therapeutic benefits. The results expand the current understanding of the role that this signalling system has and its potential influence in PD. PMID:26244281

  4. Expression of the survival of motor neuron (SMN) gene in primary neurons and increase in SMN levels by activation of the N-methyl-D-aspartate glutamate receptor.

    PubMed

    Andreassi, Catia; Patrizi, Anna Letizia; Monani, Umrao R; Burghes, A H M; Brahe, Christina; Eboli, Maria Luisa

    2002-03-01

    Spinal muscular atrophy (SMA) is a common motor neuron degenerative disease caused by mutations of the survival of motor neuron (SMN) gene. The SMN protein is expressed ubiquitously as part of a 300-kilodalton multi-protein complex, incorporating several proteins critically required in pre-mRNA splicing. Although SMN mutations render SMN defective in this role, the specific alpha-motor neuron degenerative phenotype seen in the disease remains unexplained. During the differentiation process of spinal motor neurons and cerebellar granule cells, the acquisition of mature electrophysiological and molecular properties is linked to the activation of the glutamate receptors of N-methyl-D-aspartate (NMDA) subtype. We have used primary cultures of rat cerebellar granules to study SMN expression during neuronal differentiation in vitro and in response to the activation of the NMDA receptor. We report that the expression of gems, the nuclear structures where SMN concentrates, is developmentally regulated. The highest expression is associated with the cell clustering phase and expression of NMDA receptors. Stimulation of the NMDA receptor induces an increase in gem number and in SMN transcription, through activation of its promoter. These results demonstrate that SMN levels are dependent on synaptic activity, implying that SMN may have important neuron-specific functions downstream of synaptic activation. PMID:12030329

  5. Low Temperature Chlorine-Initiated Oxidation of Small-Chain Methyl Esters: Quantification of Chain-Terminating HO2-Elimination Channels.

    PubMed

    Muller, Giel; Scheer, Adam; Osborn, David L; Taatjes, Craig A; Meloni, Giovanni

    2016-03-17

    Cl-initiated oxidation reactions of three small-chain methyl esters, methyl propanoate (CH3CH2COOCH3; MP), methyl butanoate (CH3CH2CH2COOCH3; MB), and methyl valerate (CH3CH2CH2CH2COOCH3; MV), are studied at 1 or 8 Torr and 550 and 650 K. Products are monitored as a function of mass, time, and photoionization energy using multiplexed photoionization mass spectrometry coupled to tunable synchrotron photoionization radiation. Pulsed photolysis of molecular chlorine is the source of Cl radicals, which remove an H atom from the ester, forming a free radical. In each case, after addition of O2 to the initial radicals, chain-terminating HO2-elimination reactions are observed to be important. Branching ratios among competing HO2-elimination channels are determined via absolute photoionization spectra of the unsaturated methyl ester coproducts. At 550 K, HO2-elimination is observed to be selective, resulting in nearly exclusive production of the conjugated methyl ester coproducts, methyl propenoate, methyl-2-butenoate, and methyl-2-pentenoate, respectively. However, in MV, upon raising the temperature to 650 K, other HO2-elimination pathways are observed that yield methyl-3-pentenoate and methyl-4-pentenoate. In each methyl ester oxidation reaction, a peak is observed at a mass consistent with cyclic ether formation, indicating chain-propagating OH loss/ring formation pathways via QOOH intermediates. Evidence is observed for the participation of resonance-stabilized QOOH in the most prominent cyclic ether pathways. Stationary point energies for HO2-elimination pathways and select cyclic ether formation channels are calculated at the CBS-QB3 level of theory and assist in the assignment of reaction pathways and final products. PMID:26910881

  6. Whole-Genome Saliva and Blood DNA Methylation Profiling in Individuals with a Respiratory Allergy

    PubMed Central

    Declerck, Ken; Traen, Sophie; Koppen, Gudrun; Van Camp, Guy; Schoeters, Greet; Vanden Berghe, Wim; De Boever, Patrick

    2016-01-01

    The etiology of respiratory allergies (RA) can be partly explained by DNA methylation changes caused by adverse environmental and lifestyle factors experienced early in life. Longitudinal, prospective studies can aid in the unravelment of the epigenetic mechanisms involved in the disease development. High compliance rates can be expected in these studies when data is collected using non-invasive and convenient procedures. Saliva is an attractive biofluid to analyze changes in DNA methylation patterns. We investigated in a pilot study the differential methylation in saliva of RA (n = 5) compared to healthy controls (n = 5) using the Illumina Methylation 450K BeadChip platform. We evaluated the results against the results obtained in mononuclear blood cells from the same individuals. Differences in methylation patterns from saliva and mononuclear blood cells were clearly distinguishable (PAdj<0.001 and |Δβ|>0.2), though the methylation status of about 96% of the cg-sites was comparable between peripheral blood mononuclear cells and saliva. When comparing RA cases with healthy controls, the number of differentially methylated sites (DMS) in saliva and blood were 485 and 437 (P<0.05 and |Δβ|>0.1), respectively, of which 216 were in common. The methylation levels of these sites were significantly correlated between blood and saliva. The absolute levels of methylation in blood and saliva were confirmed for 3 selected DMS in the PM20D1, STK32C, and FGFR2 genes using pyrosequencing analysis. The differential methylation could only be confirmed for DMS in PM20D1 and STK32C genes in saliva. We show that saliva can be used for genome-wide methylation analysis and that it is possible to identify DMS when comparing RA cases and healthy controls. The results were replicated in blood cells of the same individuals and confirmed by pyrosequencing analysis. This study provides proof-of-concept for the applicability of saliva-based whole-genome methylation analysis in the field

  7. Optomechanics for absolute rotation detection

    NASA Astrophysics Data System (ADS)

    Davuluri, Sankar

    2016-07-01

    In this article, we present an application of optomechanical cavity for the absolute rotation detection. The optomechanical cavity is arranged in a Michelson interferometer in such a way that the classical centrifugal force due to rotation changes the length of the optomechanical cavity. The change in the cavity length induces a shift in the frequency of the cavity mode. The phase shift corresponding to the frequency shift in the cavity mode is measured at the interferometer output to estimate the angular velocity of absolute rotation. We derived an analytic expression to estimate the minimum detectable rotation rate in our scheme for a given optomechanical cavity. Temperature dependence of the rotation detection sensitivity is studied.

  8. The Absolute Spectrum Polarimeter (ASP)

    NASA Technical Reports Server (NTRS)

    Kogut, A. J.

    2010-01-01

    The Absolute Spectrum Polarimeter (ASP) is an Explorer-class mission to map the absolute intensity and linear polarization of the cosmic microwave background and diffuse astrophysical foregrounds over the full sky from 30 GHz to 5 THz. The principal science goal is the detection and characterization of linear polarization from an inflationary epoch in the early universe, with tensor-to-scalar ratio r much greater than 1O(raised to the power of { -3}) and Compton distortion y < 10 (raised to the power of{-6}). We describe the ASP instrument and mission architecture needed to detect the signature of an inflationary epoch in the early universe using only 4 semiconductor bolometers.

  9. Absolute calibration of optical flats

    DOEpatents

    Sommargren, Gary E.

    2005-04-05

    The invention uses the phase shifting diffraction interferometer (PSDI) to provide a true point-by-point measurement of absolute flatness over the surface of optical flats. Beams exiting the fiber optics in a PSDI have perfect spherical wavefronts. The measurement beam is reflected from the optical flat and passed through an auxiliary optic to then be combined with the reference beam on a CCD. The combined beams include phase errors due to both the optic under test and the auxiliary optic. Standard phase extraction algorithms are used to calculate this combined phase error. The optical flat is then removed from the system and the measurement fiber is moved to recombine the two beams. The newly combined beams include only the phase errors due to the auxiliary optic. When the second phase measurement is subtracted from the first phase measurement, the absolute phase error of the optical flat is obtained.

  10. Absolute Antenna Calibration at the US National Geodetic Survey

    NASA Astrophysics Data System (ADS)

    Mader, G. L.; Bilich, A. L.

    2012-12-01

    Geodetic GNSS applications routinely demand millimeter precision and extremely high levels of accuracy. To achieve these accuracies, measurement and instrument biases at the centimeter to millimeter level must be understood. One of these biases is the antenna phase center, the apparent point of signal reception for a GNSS antenna. It has been well established that phase center patterns differ between antenna models and manufacturers; additional research suggests that the addition of a radome or the choice of antenna mount can significantly alter those a priori phase center patterns. For the more demanding GNSS positioning applications and especially in cases of mixed-antenna networks, it is all the more important to know antenna phase center variations as a function of both elevation and azimuth in the antenna reference frame and incorporate these models into analysis software. Determination of antenna phase center behavior is known as "antenna calibration". Since 1994, NGS has computed relative antenna calibrations for more than 350 antennas. In recent years, the geodetic community has moved to absolute calibrations - the IGS adopted absolute antenna phase center calibrations in 2006 for use in their orbit and clock products, and NGS's CORS group began using absolute antenna calibration upon the release of the new CORS coordinates in IGS08 epoch 2005.00 and NAD 83(2011,MA11,PA11) epoch 2010.00. Although NGS relative calibrations can be and have been converted to absolute, it is considered best practice to independently measure phase center characteristics in an absolute sense. Consequently, NGS has developed and operates an absolute calibration system. These absolute antenna calibrations accommodate the demand for greater accuracy and for 2-dimensional (elevation and azimuth) parameterization. NGS will continue to provide calibration values via the NGS web site www.ngs.noaa.gov/ANTCAL, and will publish calibrations in the ANTEX format as well as the legacy ANTINFO

  11. Methyl gallate.

    PubMed

    Bebout, Deborah; Pagola, Silvina

    2009-01-01

    THE CRYSTAL STRUCTURE OF THE TITLE COMPOUND (SYSTEMATIC NAME: methyl 3,4,5-trihydroxy-benzoate), C(8)H(8)O(5), is composed of essentially planar mol-ecules [maximum departures from the mean carbon and oxygen skeleton plane of 0.0348 (10) Å]. The H atoms of the three hydroxyl groups, which function as hydrogen-bond donors and acceptors simultaneously, are oriented in the same direction around the aromatic ring. In addition to two intra-molecular hydrogen bonds, each mol-ecule is hydrogen bonded to six others, creating a three-dimensional hydrogen-bonded network. PMID:21581923

  12. Methyl gallate

    PubMed Central

    Bebout, Deborah; Pagola, Silvina

    2009-01-01

    The crystal structure of the title compound (systematic name: methyl 3,4,5-trihydroxy­benzoate), C8H8O5, is composed of essentially planar mol­ecules [maximum departures from the mean carbon and oxygen skeleton plane of 0.0348 (10) Å]. The H atoms of the three hydroxyl groups, which function as hydrogen-bond donors and acceptors simultaneously, are oriented in the same direction around the aromatic ring. In addition to two intra­molecular hydrogen bonds, each mol­ecule is hydrogen bonded to six others, creating a three-dimensional hydrogen-bonded network. PMID:21581923

  13. The AFGL absolute gravity program

    NASA Technical Reports Server (NTRS)

    Hammond, J. A.; Iliff, R. L.

    1978-01-01

    A brief discussion of the AFGL's (Air Force Geophysics Laboratory) program in absolute gravity is presented. Support of outside work and in-house studies relating to gravity instrumentation are discussed. A description of the current transportable system is included and the latest results are presented. These results show good agreement with measurements at the AFGL site by an Italian system. The accuracy obtained by the transportable apparatus is better than 0.1 microns sq sec 10 microgal and agreement with previous measurements is within the combined uncertainties of the measurements.

  14. The EpiTect Methyl qPCR Assay as novel age estimation method in forensic biology.

    PubMed

    Mawlood, Shakhawan K; Dennany, Lynn; Watson, Nigel; Pickard, Benjamin S

    2016-07-01

    Human aging is associated with epigenetic modification of the genome. DNA methylation at cytosines appears currently as the best characterised modification that occurs during the mammalian lifetime. Such methylation changes at regulatory region can provide insights to track contributor age for criminal investigation. The EpiTect Methyl II PCR system (QIAGEN) was used to compare methylation levels of CpG islands in the promoter regions of a number of age related genes, of which four successfully showed changes across the lifespan (NPTX2, KCNQ1DN, GRIA2 and TRIM58). This technique is based on the detection of remaining input genome after digestion with a methylation-sensitive restriction enzyme. This study examined DNA specimens from 80 female subjects of various ages (18-91 years) obtained from blood, using primers designed to flank the studied gene loci. The data obtained from DNA methylation quantification showed successful discrimination among volunteered ages. Overall, the difference between predicted and real age was about 11 years and absolute mean differences (AMD) was only 7.2 years error. We suggest the EpiTect system can be used as fast and simple innovative tool in future forensic age estimation. PMID:27108355

  15. Absolute calibration of ultraviolet filter photometry

    NASA Technical Reports Server (NTRS)

    Bless, R. C.; Fairchild, T.; Code, A. D.

    1972-01-01

    The essential features of the calibration procedure can be divided into three parts. First, the shape of the bandpass of each photometer was determined by measuring the transmissions of the individual optical components and also by measuring the response of the photometer as a whole. Secondly, each photometer was placed in the essentially-collimated synchrotron radiation bundle maintained at a constant intensity level, and the output signal was determined from about 100 points on the objective. Finally, two or three points on the objective were illuminated by synchrotron radiation at several different intensity levels covering the dynamic range of the photometers. The output signals were placed on an absolute basis by the electron counting technique described earlier.

  16. Tumor Mismatch Repair Immunohistochemistry and DNA MLH1 Methylation Testing of Patients With Endometrial Cancer Diagnosed at Age Younger Than 60 Years Optimizes Triage for Population-Level Germline Mismatch Repair Gene Mutation Testing

    PubMed Central

    Buchanan, Daniel D.; Tan, Yen Y.; Walsh, Michael D.; Clendenning, Mark; Metcalf, Alexander M.; Ferguson, Kaltin; Arnold, Sven T.; Thompson, Bryony A.; Lose, Felicity A.; Parsons, Michael T.; Walters, Rhiannon J.; Pearson, Sally-Ann; Cummings, Margaret; Oehler, Martin K.; Blomfield, Penelope B.; Quinn, Michael A.; Kirk, Judy A.; Stewart, Colin J.; Obermair, Andreas; Young, Joanne P.; Webb, Penelope M.; Spurdle, Amanda B.

    2014-01-01

    Purpose Clinicopathologic data from a population-based endometrial cancer cohort, unselected for age or family history, were analyzed to determine the optimal scheme for identification of patients with germline mismatch repair (MMR) gene mutations. Patients and Methods Endometrial cancers from 702 patients recruited into the Australian National Endometrial Cancer Study (ANECS) were tested for MMR protein expression using immunohistochemistry (IHC) and for MLH1 gene promoter methylation in MLH1-deficient cases. MMR mutation testing was performed on germline DNA of patients with MMR-protein deficient tumors. Prediction of germline mutation status was compared for combinations of tumor characteristics, age at diagnosis, and various clinical criteria (Amsterdam, Bethesda, Society of Gynecologic Oncology, ANECS). Results Tumor MMR-protein deficiency was detected in 170 (24%) of 702 cases. Germline testing of 158 MMR-deficient cases identified 22 truncating mutations (3% of all cases) and four unclassified variants. Tumor MLH1 methylation was detected in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative. A combination of MMR IHC plus MLH1 methylation testing in women younger than 60 years of age at diagnosis provided the highest positive predictive value for the identification of mutation carriers at 46% versus ≤ 41% for any other criteria considered. Conclusion Population-level identification of patients with MMR mutation-positive endometrial cancer is optimized by stepwise testing for tumor MMR IHC loss in patients younger than 60 years, tumor MLH1 methylation in individuals with MLH1 IHC loss, and germline mutations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation. PMID:24323032

  17. Increased DNA methylation in the suicide brain.

    PubMed

    Haghighi, Fatemeh; Xin, Yurong; Chanrion, Benjamin; O'Donnell, Anne H; Ge, Yongchao; Dwork, Andrew J; Arango, Victoria; Mann, J John

    2014-09-01

    Clinical studies find that childhood adversity and stressful life events in adulthood increase the risk for major depression and for suicide. The predispositions to either major depression or suicide are thought to depend on genetic risk factors or epigenetic effects. We investigated DNA methylation signatures postmortem in brains of suicides with diagnosis of major depressive disorder. DNA methylation levels were determined at single C-phosphate-G (CpG) resolution sites within ventral prefrontal cortex of 53 suicides and nonpsychiatric controls, aged 16 to 89 years. We found that DNA methylation increases throughout the lifespan. Suicides showed an 8-fold greater number of methylated CpG sites relative to controls (P < 2.2 x 10(-16)), with greater DNA methylation changes over and above the increased methylation observed in normal aging. This increased DNA methylation may be a significant contributor to the neuropathology and psychopathology underlying the risk of suicide in depression. PMID:25364291

  18. Cosmology with negative absolute temperatures

    NASA Astrophysics Data System (ADS)

    Vieira, J. P. P.; Byrnes, Christian T.; Lewis, Antony

    2016-08-01

    Negative absolute temperatures (NAT) are an exotic thermodynamical consequence of quantum physics which has been known since the 1950's (having been achieved in the lab on a number of occasions). Recently, the work of Braun et al. [1] has rekindled interest in negative temperatures and hinted at a possibility of using NAT systems in the lab as dark energy analogues. This paper goes one step further, looking into the cosmological consequences of the existence of a NAT component in the Universe. NAT-dominated expanding Universes experience a borderline phantom expansion (w < ‑1) with no Big Rip, and their contracting counterparts are forced to bounce after the energy density becomes sufficiently large. Both scenarios might be used to solve horizon and flatness problems analogously to standard inflation and bouncing cosmologies. We discuss the difficulties in obtaining and ending a NAT-dominated epoch, and possible ways of obtaining density perturbations with an acceptable spectrum.

  19. Methylation interactions in Arabidopsis hybrids require RNA-directed DNA methylation and are influenced by genetic variation.

    PubMed

    Zhang, Qingzhu; Wang, Dong; Lang, Zhaobo; He, Li; Yang, Lan; Zeng, Liang; Li, Yanqiang; Zhao, Cheng; Huang, Huan; Zhang, Heng; Zhang, Huiming; Zhu, Jian-Kang

    2016-07-19

    DNA methylation is a conserved epigenetic mark in plants and many animals. How parental alleles interact in progeny to influence the epigenome is poorly understood. We analyzed the DNA methylomes of Arabidopsis Col and C24 ecotypes, and their hybrid progeny. Hybrids displayed nonadditive DNA methylation levels, termed methylation interactions, throughout the genome. Approximately 2,500 methylation interactions occurred at regions where parental DNA methylation levels are similar, whereas almost 1,000 were at differentially methylated regions in parents. Methylation interactions were characterized by an abundance of 24-nt small interfering RNAs. Furthermore, dysfunction of the RNA-directed DNA methylation pathway abolished methylation interactions but did not affect the increased biomass observed in hybrid progeny. Methylation interactions correlated with altered genetic variation within the genome, suggesting that they may play a role in genome evolution. PMID:27382183

  20. Absolute photoionization cross-section of the propargyl radical

    SciTech Connect

    Savee, John D.; Welz, Oliver; Taatjes, Craig A.; Osborn, David L.; Soorkia, Satchin; Selby, Talitha M.

    2012-04-07

    Using synchrotron-generated vacuum-ultraviolet radiation and multiplexed time-resolved photoionization mass spectrometry we have measured the absolute photoionization cross-section for the propargyl (C{sub 3}H{sub 3}) radical, {sigma}{sub propargyl}{sup ion}(E), relative to the known absolute cross-section of the methyl (CH{sub 3}) radical. We generated a stoichiometric 1:1 ratio of C{sub 3}H{sub 3} : CH{sub 3} from 193 nm photolysis of two different C{sub 4}H{sub 6} isomers (1-butyne and 1,3-butadiene). Photolysis of 1-butyne yielded values of {sigma}{sub propargyl}{sup ion}(10.213 eV)=(26.1{+-}4.2) Mb and {sigma}{sub propargyl}{sup ion}(10.413 eV)=(23.4{+-}3.2) Mb, whereas photolysis of 1,3-butadiene yielded values of {sigma}{sub propargyl}{sup ion}(10.213 eV)=(23.6{+-}3.6) Mb and {sigma}{sub propargyl}{sup ion}(10.413 eV)=(25.1{+-}3.5) Mb. These measurements place our relative photoionization cross-section spectrum for propargyl on an absolute scale between 8.6 and 10.5 eV. The cross-section derived from our results is approximately a factor of three larger than previous determinations.

  1. Development of a methylation marker set for forensic age estimation using analysis of public methylation data and the Agena Bioscience EpiTYPER system.

    PubMed

    Freire-Aradas, A; Phillips, C; Mosquera-Miguel, A; Girón-Santamaría, L; Gómez-Tato, A; Casares de Cal, M; Álvarez-Dios, J; Ansede-Bermejo, J; Torres-Español, M; Schneider, P M; Pośpiech, E; Branicki, W; Carracedo, Á; Lareu, M V

    2016-09-01

    Individual age estimation has the potential to provide key information that could enhance and extend DNA intelligence tools. Following predictive tests for externally visible characteristics developed in recent years, prediction of age could guide police investigations and improve the assessment of age-related phenotype expression patterns such as hair colour changes and early onset of male pattern baldness. DNA methylation at CpG positions has emerged as the most promising DNA tests to ascertain the individual age of the donor of a biological contact trace. Although different methodologies are available to detect DNA methylation, EpiTYPER technology (Agena Bioscience, formerly Sequenom) provides useful characteristics that can be applied as a discovery tool in localized regions of the genome. In our study, a total of twenty-two candidate genomic regions, selected from the assessment of publically available data from the Illumina HumanMethylation 450 BeadChip, had a total of 177 CpG sites with informative methylation patterns that were subsequently investigated in detail. From the methylation analyses made, a novel age prediction model based on a multivariate quantile regression analysis was built using the seven highest age-correlated loci of ELOVL2, ASPA, PDE4C, FHL2, CCDC102B, C1orf132 and chr16:85395429. The detected methylation levels in these loci provide a median absolute age prediction error of ±3.07years and a percentage of prediction error relative to the age of 6.3%. We report the predictive performance of the developed model using cross validation of a carefully age-graded training set of 725 European individuals and a test set of 52 monozygotic twin pairs. The multivariate quantile regression age predictor, using the CpG sites selected in this study, has been placed in the open-access Snipper forensic classification website. PMID:27337627

  2. Swarm's Absolute Scalar Magnetometer metrological performances

    NASA Astrophysics Data System (ADS)

    Leger, J.; Fratter, I.; Bertrand, F.; Jager, T.; Morales, S.

    2012-12-01

    The Absolute Scalar Magnetometer (ASM) has been developed for the ESA Earth Observation Swarm mission, planned for launch in November 2012. As its Overhauser magnetometers forerunners flown on Oersted and Champ satellites, it will deliver high resolution scalar measurements for the in-flight calibration of the Vector Field Magnetometer manufactured by the Danish Technical University. Latest results of the ground tests carried out to fully characterize all parameters that may affect its accuracy, both at instrument and satellite level, will be presented. In addition to its baseline function, the ASM can be operated either at a much higher sampling rate (burst mode at 250 Hz) or in a dual mode where it also delivers vector field measurements as a by-product. The calibration procedure and the relevant vector performances will be discussed.

  3. DNA methylation level of cyp19a1a and Foxl2 gene related to their expression patterns and reproduction traits during ovary development stages of Japanese flounder (Paralichthys olivaceus).

    PubMed

    Si, Yufeng; Ding, Yuxia; He, Feng; Wen, Haishen; Li, Jifang; Zhao, Junli; Huang, Zhengju

    2016-01-10

    Foxl2 and cyp19a1a genes are crucial for the ovarian development, and Foxl2 could play a direct regulatory role on cyp19a1a transcription. In this study, we aimed to study DNA methylation status and mRNA expression patterns of Foxl2 and cyp19a1a genes during ovarian development of female Japanese flounder. The relative expression level of cyp19a1a and Foxl2 gene during the gonadal development stages was measured by quantitative PCR. Moreover, DNA methylation status in the promoter and coding regions of the two genes was detected by bisulfite sequencing. The estradiol-17β (E2) was measured by radioimmunoassay. The results showed low expression levels of cyp19a1a and Foxl2 genes in stages II and V, while the highest expression levels were detected in stage IV. The variation trend of the methylation level of all CpG sites in promoter and exon 1 of cyp19a1a gene and three CpG rich regions in coding region of Foxl2 gene was negatively associated with their expression levels during the ovarian development. In addition, two CpG sites in promoter and seven CpG sites in exon 1 of cyp19a1a were on the putative transcription factors binding sequence. Further studies showed that the forkhead domain, which is important for Foxl2 binding to cyp19a1a was located in the F1 and F2 region. These results provide a powerful theoretical basis for the regulatory mechanism on Foxl2 regulating cyp19a1a and promoting gonadal differentiation towards the female pathway, and further reveal that Foxl2 and cyp19a1a play a vital role in the female Japanese flounder gonad development. PMID:26343797

  4. A study protocol for quantitative targeted absolute proteomics (QTAP) by LC-MS/MS: application for inter-strain differences in protein expression levels of transporters, receptors, claudin-5, and marker proteins at the blood–brain barrier in ddY, FVB, and C57BL/6J mice

    PubMed Central

    2013-01-01

    Proteomics has opened a new horizon in biological sciences. Global proteomic analysis is a promising technology for the discovery of thousands of proteins, post-translational modifications, polymorphisms, and molecular interactions in a variety of biological systems. The activities and roles of the identified proteins must also be elucidated, but this is complicated by the inability of conventional proteomic methods to yield quantitative information for protein expression. Thus, a variety of biological systems remain “black boxes”. Quantitative targeted absolute proteomics (QTAP) enables the determination of absolute expression levels (mol) of any target protein, including low-abundance functional proteins, such as transporters and receptors. Therefore, QTAP will be useful for understanding the activities and roles of individual proteins and their differences, including normal/disease, human/animal, or in vitro/in vivo. Here, we describe the study protocols and precautions for QTAP experiments including in silico target peptide selection, determination of peptide concentration by amino acid analysis, setup of selected/multiple reaction monitoring (SRM/MRM) analysis in liquid chromatography–tandem mass spectrometry, preparation of protein samples (brain capillaries and plasma membrane fractions) followed by the preparation of peptide samples, simultaneous absolute quantification of target proteins by SRM/MRM analysis, data analysis, and troubleshooting. An application of QTAP in biological sciences was introduced that utilizes data from inter-strain differences in the protein expression levels of transporters, receptors, tight junction proteins and marker proteins at the blood–brain barrier in ddY, FVB, and C57BL/6J mice. Among 18 molecules, 13 (abcb1a/mdr1a/P-gp, abcc4/mrp4, abcg2/bcrp, slc2a1/glut1, slc7a5/lat1, slc16a1/mct1, slc22a8/oat3, insr, lrp1, tfr1, claudin-5, Na+/K+-ATPase, and γ-gtp) were detected in the isolated brain capillaries, and their

  5. Absolute oral bioavailability of ciprofloxacin.

    PubMed

    Drusano, G L; Standiford, H C; Plaisance, K; Forrest, A; Leslie, J; Caldwell, J

    1986-09-01

    We evaluated the absolute bioavailability of ciprofloxacin, a new quinoline carboxylic acid, in 12 healthy male volunteers. Doses of 200 mg were given to each of the volunteers in a randomized, crossover manner 1 week apart orally and as a 10-min intravenous infusion. Half-lives (mean +/- standard deviation) for the intravenous and oral administration arms were 4.2 +/- 0.77 and 4.11 +/- 0.74 h, respectively. The serum clearance rate averaged 28.5 +/- 4.7 liters/h per 1.73 m2 for the intravenous administration arm. The renal clearance rate accounted for approximately 60% of the corresponding serum clearance rate and was 16.9 +/- 3.0 liters/h per 1.73 m2 for the intravenous arm and 17.0 +/- 2.86 liters/h per 1.73 m2 for the oral administration arm. Absorption was rapid, with peak concentrations in serum occurring at 0.71 +/- 0.15 h. Bioavailability, defined as the ratio of the area under the curve from 0 h to infinity for the oral to the intravenous dose, was 69 +/- 7%. We conclude that ciprofloxacin is rapidly absorbed and reliably bioavailable in these healthy volunteers. Further studies with ciprofloxacin should be undertaken in target patient populations under actual clinical circumstances. PMID:3777908

  6. Absolute Instability in Coupled-Cavity TWTs

    NASA Astrophysics Data System (ADS)

    Hung, D. M. H.; Rittersdorf, I. M.; Zhang, Peng; Lau, Y. Y.; Simon, D. H.; Gilgenbach, R. M.; Chernin, D.; Antonsen, T. M., Jr.

    2014-10-01

    This paper will present results of our analysis of absolute instability in a coupled-cavity traveling wave tube (TWT). The structure mode at the lower and upper band edges are respectively approximated by a hyperbola in the (omega, k) plane. When the Briggs-Bers criterion is applied, a threshold current for onset of absolute instability is observed at the upper band edge, but not the lower band edge. The nonexistence of absolute instability at the lower band edge is mathematically similar to the nonexistence of absolute instability that we recently demonstrated for a dielectric TWT. The existence of absolute instability at the upper band edge is mathematically similar to the existence of absolute instability in a gyroton traveling wave amplifier. These interesting observations will be discussed, and the practical implications will be explored. This work was supported by AFOSR, ONR, and L-3 Communications Electron Devices.

  7. DNA Methylation Perturbations in Genes Involved in Polyunsaturated Fatty Acid Biosynthesis Associated with Depression and Suicide Risk

    PubMed Central

    Haghighi, Fatemeh; Galfalvy, Hanga; Chen, Sean; Huang, Yung-yu; Cooper, Thomas B.; Burke, Ainsley K.; Oquendo, Maria A.; Mann, J. John; Sublette, M. Elizabeth

    2015-01-01

    Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched healthy volunteers (n = 59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long-chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention. PMID:25972837

  8. DNA methylation perturbations in genes involved in polyunsaturated Fatty Acid biosynthesis associated with depression and suicide risk.

    PubMed

    Haghighi, Fatemeh; Galfalvy, Hanga; Chen, Sean; Huang, Yung-Yu; Cooper, Thomas B; Burke, Ainsley K; Oquendo, Maria A; Mann, J John; Sublette, M Elizabeth

    2015-01-01

    Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched healthy volunteers (n = 59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long-chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention. PMID:25972837

  9. Seasonality Modifies Methylation Profiles in Healthy People

    PubMed Central

    Ricceri, Fulvio; Trevisan, Morena; Fiano, Valentina; Grasso, Chiara; Fasanelli, Francesca; Scoccianti, Chiara; De Marco, Laura; Tos, Anna Gillio; Vineis, Paolo; Sacerdote, Carlotta

    2014-01-01

    DNA methylation is a well-characterized epigenetic modification that plays an important role in the regulation of gene expression. There is growing evidence on the involvement of epigenetic mechanisms in disease onset, including cancer. Environmental factors seem to induce changes in DNA methylation affecting human health. However, little is known about basal methylation levels in healthy people and about the correlation between environmental factors and different methylation profiles. We investigated the effect of seasonality on basal methylation by testing methylation levels in the long interspersed nucleotide element-1 (LINE-1) and in two cancer-related genes (RASSF1A and MGMT) of 88 healthy male heavy smokers involved in an Italian randomized study; at enrolment the subjects donated a blood sample collected in different months. Methylation analyses were performed by pyrosequencing. Mean methylation percentage was higher in spring and summer for the LINE1, RASSF1A and MGMT genes (68.26%, 2.35%, and 9.52% respectively) compared with autumn and winter (67.43%, 2.17%, and 8.60% respectively). In particular, LINE-1 was significantly hypomethylated (p = 0.04 or 0.05 depending on the CpG island involved) in autumn and winter compared with spring and summer. Seasonality seems to be a modifier of methylation levels and this observation should be taken into account in future analyses. PMID:25210735

  10. Absolute negative mobility of interacting Brownian particles

    NASA Astrophysics Data System (ADS)

    Ou, Ya-li; Hu, Cai-tian; Wu, Jian-chun; Ai, Bao-quan

    2015-12-01

    Transport of interacting Brownian particles in a periodic potential is investigated in the presence of an ac force and a dc force. From Brownian dynamic simulations, we find that both the interaction between particles and the thermal fluctuations play key roles in the absolute negative mobility (the particle noisily moves backwards against a small constant bias). When no the interaction acts, there is only one region where the absolute negative mobility occurs. In the presence of the interaction, the absolute negative mobility may appear in multiple regions. The weak interaction can be helpful for the absolute negative mobility, while the strong interaction has a destructive impact on it.

  11. Measurements of the reactor neutron power in absolute units

    NASA Astrophysics Data System (ADS)

    Lebedev, G. V.

    2015-12-01

    The neutron power of the reactor of the Yenisei space nuclear power plant is measured in absolute units using the modernized method of correlation analysis during the ground-based tests of the Yenisei prototypes. Results of the experiments are given. The desired result is obtained in a series of experiments carried out at the stage of the plant preparation for tests. The acceptability of experimental data is confirmed by the results of measuring the reactor neutron power in absolute units at the nominal level by the thermal balance during the life cycle tests of the ground prototypes.

  12. In-flight absolute radiometric calibration of the thematic mapper

    NASA Technical Reports Server (NTRS)

    Castle, K. R.; Holm, R. G.; Kastner, C. J.; Palmer, J. M.; Slater, P. N.; Dinguirard, M.; Ezra, C. E.; Jackson, R. D.; Savage, R. K.

    1983-01-01

    The TM multispectral scanner system was calibrated in an absolute manner before launch. To determine the temporal changes of the absolute radiometric calibration of the entire system, spectroradiometric measurements of the ground and the atmosphere were made simultaneously with TM collections over White Sands, New Mexico. By entering the measured values in an atmospheric radiative transfer program, the radiance levels of the in four of the spectral bands of the TM were determined. Tables show values for the reflectance of snow at White Sands measured by a modular 8 channel radiometer, and values for exoatmospheric irradiance within the TM passbands, calculated for the Earth-Sun distance using a solar radiometer.

  13. Measurements of the reactor neutron power in absolute units

    SciTech Connect

    Lebedev, G. V.

    2015-12-15

    The neutron power of the reactor of the Yenisei space nuclear power plant is measured in absolute units using the modernized method of correlation analysis during the ground-based tests of the Yenisei prototypes. Results of the experiments are given. The desired result is obtained in a series of experiments carried out at the stage of the plant preparation for tests. The acceptability of experimental data is confirmed by the results of measuring the reactor neutron power in absolute units at the nominal level by the thermal balance during the life cycle tests of the ground prototypes.

  14. Simultaneous Determination of Salicylic Acid, Jasmonic Acid, Methyl Salicylate, and Methyl Jasmonate from Ulmus pumila Leaves by GC-MS

    PubMed Central

    Huang, Zhi-hong; Wang, Zhi-li; Shi, Bao-lin; Wei, Dong; Chen, Jian-xin; Wang, Su-li; Gao, Bao-jia

    2015-01-01

    Salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate are important phytohormones and defensive signaling compounds, so it is of great importance to determine their levels rapidly and accurately. The study uses Ulmus pumila leaves infected by Tetraneura akinire Sasaki at different stages as materials; after extraction with 80% methanol and ethyl acetate and purification with primary secondary amine (PSA) and graphitized carbon blacks (GCB), the contents of signal compounds salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate were determined by GC-MS. The results showed that the level of salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate increased remarkably in U. pumila once infected by T. akinire Sasaki, but the maximums of these four compounds occurred at different times. Salicylic acid level reached the highest at the early stage, and jasmonic acid level went to the maximum in the middle stage; by contrast, change of content of methyl salicylate and methyl jasmonate was the quite opposite. PMID:26457083

  15. Simultaneous Determination of Salicylic Acid, Jasmonic Acid, Methyl Salicylate, and Methyl Jasmonate from Ulmus pumila Leaves by GC-MS.

    PubMed

    Huang, Zhi-Hong; Wang, Zhi-Li; Shi, Bao-Lin; Wei, Dong; Chen, Jian-Xin; Wang, Su-Li; Gao, Bao-Jia

    2015-01-01

    Salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate are important phytohormones and defensive signaling compounds, so it is of great importance to determine their levels rapidly and accurately. The study uses Ulmus pumila leaves infected by Tetraneura akinire Sasaki at different stages as materials; after extraction with 80% methanol and ethyl acetate and purification with primary secondary amine (PSA) and graphitized carbon blacks (GCB), the contents of signal compounds salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate were determined by GC-MS. The results showed that the level of salicylic acid, jasmonic acid, methyl salicylate, and methyl jasmonate increased remarkably in U. pumila once infected by T. akinire Sasaki, but the maximums of these four compounds occurred at different times. Salicylic acid level reached the highest at the early stage, and jasmonic acid level went to the maximum in the middle stage; by contrast, change of content of methyl salicylate and methyl jasmonate was the quite opposite. PMID:26457083

  16. DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins

    PubMed Central

    Sailani, M. Reza; Santoni, Federico A.; Letourneau, Audrey; Borel, Christelle; Makrythanasis, Periklis; Hibaoui, Youssef; Popadin, Konstantin; Bonilla, Ximena; Guipponi, Michel; Gehrig, Corinne; Vannier, Anne; Carre-Pigeon, Frederique; Feki, Anis; Nizetic, Dean; Antonarakis, Stylianos E.

    2015-01-01

    DNA methylation is essential in mammalian development. We have hypothesized that methylation differences induced by trisomy 21 (T21) contribute to the phenotypic characteristics and heterogeneity in Down syndrome (DS). In order to determine the methylation differences in T21 without interference of the interindividual genomic variation, we have used fetal skin fibroblasts from monozygotic (MZ) twins discordant for T21. We also used skin fibroblasts from MZ twins concordant for T21, normal MZ twins without T21, and unrelated normal and T21 individuals. Reduced Representation Bisulfite Sequencing (RRBS) revealed 35 differentially methylated promoter regions (DMRs) (Absolute methylation differences = 25%, FDR < 0.001) in MZ twins discordant for T21 that have also been observed in comparison between unrelated normal and T21 individuals. The identified DMRs are enriched for genes involved in embryonic organ morphogenesis (FDR = 1.60 e -03) and include genes of the HOXB and HOXD clusters. These DMRs are maintained in iPS cells generated from this twin pair and are correlated with the gene expression changes. We have also observed an increase in DNA methylation level in the T21 methylome compared to the normal euploid methylome. This observation is concordant with the up regulation of DNA methyltransferase enzymes (DNMT3B and DNMT3L) and down regulation of DNA demethylation enzymes (TET2 and TET3) observed in the iPSC of the T21 versus normal twin. Altogether, the results of this study highlight the epigenetic effects of the extra chromosome 21 in T21 on loci outside of this chromosome that are relevant to DS associated phenotypes. PMID:26317209

  17. DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins.

    PubMed

    Sailani, M Reza; Santoni, Federico A; Letourneau, Audrey; Borel, Christelle; Makrythanasis, Periklis; Hibaoui, Youssef; Popadin, Konstantin; Bonilla, Ximena; Guipponi, Michel; Gehrig, Corinne; Vannier, Anne; Carre-Pigeon, Frederique; Feki, Anis; Nizetic, Dean; Antonarakis, Stylianos E

    2015-01-01

    DNA methylation is essential in mammalian development. We have hypothesized that methylation differences induced by trisomy 21 (T21) contribute to the phenotypic characteristics and heterogeneity in Down syndrome (DS). In order to determine the methylation differences in T21 without interference of the interindividual genomic variation, we have used fetal skin fibroblasts from monozygotic (MZ) twins discordant for T21. We also used skin fibroblasts from MZ twins concordant for T21, normal MZ twins without T21, and unrelated normal and T21 individuals. Reduced Representation Bisulfite Sequencing (RRBS) revealed 35 differentially methylated promoter regions (DMRs) (Absolute methylation differences = 25%, FDR < 0.001) in MZ twins discordant for T21 that have also been observed in comparison between unrelated normal and T21 individuals. The identified DMRs are enriched for genes involved in embryonic organ morphogenesis (FDR = 1.60 e -03) and include genes of the HOXB and HOXD clusters. These DMRs are maintained in iPS cells generated from this twin pair and are correlated with the gene expression changes. We have also observed an increase in DNA methylation level in the T21 methylome compared to the normal euploid methylome. This observation is concordant with the up regulation of DNA methyltransferase enzymes (DNMT3B and DNMT3L) and down regulation of DNA demethylation enzymes (TET2 and TET3) observed in the iPSC of the T21 versus normal twin. Altogether, the results of this study highlight the epigenetic effects of the extra chromosome 21 in T21 on loci outside of this chromosome that are relevant to DS associated phenotypes. PMID:26317209

  18. An integrated workflow for DNA methylation analysis.

    PubMed

    Li, Pingchuan; Demirci, Feray; Mahalingam, Gayathri; Demirci, Caghan; Nakano, Mayumi; Meyers, Blake C

    2013-05-20

    The analysis of cytosine methylation provides a new way to assess and describe epigenetic regulation at a whole-genome level in many eukaryotes. DNA methylation has a demonstrated role in the genome stability and protection, regulation of gene expression and many other aspects of genome function and maintenance. BS-seq is a relatively unbiased method for profiling the DNA methylation, with a resolution capable of measuring methylation at individual cytosines. Here we describe, as an example, a workflow to handle DNA methylation analysis, from BS-seq library preparation to the data visualization. We describe some applications for the analysis and interpretation of these data. Our laboratory provides public access to plant DNA methylation data via visualization tools available at our "Next-Gen Sequence" websites (http://mpss.udel.edu), along with small RNA, RNA-seq and other data types. PMID:23706300

  19. Genome-wide analysis of DNA methylation in hepatoblastoma tissues

    PubMed Central

    Cui, Ximao; Liu, Baihui; Zheng, Shan; Dong, Kuiran; Dong, Rui

    2016-01-01

    DNA methylation has a crucial role in cancer biology. In the present study, a genome-wide analysis of DNA methylation in hepatoblastoma (HB) tissues was performed to verify differential methylation levels between HB and normal tissues. As alpha-fetoprotein (AFP) has a critical role in HB, AFP methylation levels were also detected using pyrosequencing. Normal and HB liver tissue samples (frozen tissue) were obtained from patients with HB. Genome-wide analysis of DNA methylation in these tissues was performed using an Infinium HumanMethylation450 BeadChip, and the results were confirmed with reverse transcription-quantitative polymerase chain reaction. The Infinium HumanMethylation450 BeadChip demonstrated distinctively less methylation in HB tissues than in non-tumor tissues. In addition, methylation enrichment was observed in positions near the transcription start site of AFP, which exhibited lower methylation levels in HB tissues than in non-tumor liver tissues. Lastly, a significant negative correlation was observed between AFP messenger RNA expression and DNA methylation percentage, using linear Pearson's R correlation coefficients. The present results demonstrate differential methylation levels between HB and normal tissues, and imply that aberrant methylation of AFP in HB could reflect HB development. Expansion of these findings could provide useful insight into HB biology. PMID:27446465

  20. PCMdb: Pancreatic Cancer Methylation Database

    NASA Astrophysics Data System (ADS)

    Nagpal, Gandharva; Sharma, Minakshi; Kumar, Shailesh; Chaudhary, Kumardeep; Gupta, Sudheer; Gautam, Ankur; Raghava, Gajendra P. S.

    2014-02-01

    Pancreatic cancer is the fifth most aggressive malignancy and urgently requires new biomarkers to facilitate early detection. For providing impetus to the biomarker discovery, we have developed Pancreatic Cancer Methylation Database (PCMDB, http://crdd.osdd.net/raghava/pcmdb/), a comprehensive resource dedicated to methylation of genes in pancreatic cancer. Data was collected and compiled manually from published literature. PCMdb has 65907 entries for methylation status of 4342 unique genes. In PCMdb, data was compiled for both cancer cell lines (53565 entries for 88 cell lines) and cancer tissues (12342 entries for 3078 tissue samples). Among these entries, 47.22% entries reported a high level of methylation for the corresponding genes while 10.87% entries reported low level of methylation. PCMdb covers five major subtypes of pancreatic cancer; however, most of the entries were compiled for adenocarcinomas (88.38%) and mucinous neoplasms (5.76%). A user-friendly interface has been developed for data browsing, searching and analysis. We anticipate that PCMdb will be helpful for pancreatic cancer biomarker discovery.

  1. Inequalities, Absolute Value, and Logical Connectives.

    ERIC Educational Resources Information Center

    Parish, Charles R.

    1992-01-01

    Presents an approach to the concept of absolute value that alleviates students' problems with the traditional definition and the use of logical connectives in solving related problems. Uses a model that maps numbers from a horizontal number line to a vertical ray originating from the origin. Provides examples solving absolute value equations and…

  2. Absolute optical metrology : nanometers to kilometers

    NASA Technical Reports Server (NTRS)

    Dubovitsky, Serge; Lay, O. P.; Peters, R. D.; Liebe, C. C.

    2005-01-01

    We provide and overview of the developments in the field of high-accuracy absolute optical metrology with emphasis on space-based applications. Specific work on the Modulation Sideband Technology for Absolute Ranging (MSTAR) sensor is described along with novel applications of the sensor.

  3. Monolithically integrated absolute frequency comb laser system

    DOEpatents

    Wanke, Michael C.

    2016-07-12

    Rather than down-convert optical frequencies, a QCL laser system directly generates a THz frequency comb in a compact monolithically integrated chip that can be locked to an absolute frequency without the need of a frequency-comb synthesizer. The monolithic, absolute frequency comb can provide a THz frequency reference and tool for high-resolution broad band spectroscopy.

  4. Introducing the Mean Absolute Deviation "Effect" Size

    ERIC Educational Resources Information Center

    Gorard, Stephen

    2015-01-01

    This paper revisits the use of effect sizes in the analysis of experimental and similar results, and reminds readers of the relative advantages of the mean absolute deviation as a measure of variation, as opposed to the more complex standard deviation. The mean absolute deviation is easier to use and understand, and more tolerant of extreme…

  5. Investigating Absolute Value: A Real World Application

    ERIC Educational Resources Information Center

    Kidd, Margaret; Pagni, David

    2009-01-01

    Making connections between various representations is important in mathematics. In this article, the authors discuss the numeric, algebraic, and graphical representations of sums of absolute values of linear functions. The initial explanations are accessible to all students who have experience graphing and who understand that absolute value simply…

  6. Absolute instability of the Gaussian wake profile

    NASA Technical Reports Server (NTRS)

    Hultgren, Lennart S.; Aggarwal, Arun K.

    1987-01-01

    Linear parallel-flow stability theory has been used to investigate the effect of viscosity on the local absolute instability of a family of wake profiles with a Gaussian velocity distribution. The type of local instability, i.e., convective or absolute, is determined by the location of a branch-point singularity with zero group velocity of the complex dispersion relation for the instability waves. The effects of viscosity were found to be weak for values of the wake Reynolds number, based on the center-line velocity defect and the wake half-width, larger than about 400. Absolute instability occurs only for sufficiently large values of the center-line wake defect. The critical value of this parameter increases with decreasing wake Reynolds number, thereby indicating a shrinking region of absolute instability with decreasing wake Reynolds number. If backflow is not allowed, absolute instability does not occur for wake Reynolds numbers smaller than about 38.

  7. Maternal Methyl-Group Donor Intake and Global DNA (Hydroxy)Methylation before and during Pregnancy

    PubMed Central

    Pauwels, Sara; Duca, Radu Corneliu; Devlieger, Roland; Freson, Kathleen; Straetmans, Dany; Van Herck, Erik; Huybrechts, Inge; Koppen, Gurdun; Godderis, Lode

    2016-01-01

    It is still unclear to which extent methyl-group intake during pregnancy can affect maternal global DNA (hydroxyl)methylation. Pregnancy methylation profiling and its link with methyl-group intake in a healthy population could enhance our understanding of the development of pregnancy related disorders. One hundred forty-eight women were enrolled in the MANOE (MAternal Nutrition and Offspring’s Epigenome) study. Thiry-four women were enrolled before pregnancy and 116 during the first trimester of pregnancy. Global DNA (hydroxy)methylation in blood using LC-MS/MS and dietary methyl-group intake (methionine, folate, betaine, and choline) using a food-frequency questionnaire were estimated pre-pregnancy, during each trimester, and at delivery. Global DNA (hydroxy)methylation levels were highest pre-pregnancy and at weeks 18–22 of pregnancy. We observed a positive relation between folic acid and global DNA methylation (p = 0.04) and hydroxymethylation (p = 0.04). A high intake of methionine pre-pregnancy and in the first trimester showed lower (hydroxy)methylation percentage in weeks 11–13 and weeks 18–22, respectively. Choline and betaine intake in the first weeks was negatively associated with hydroxymethylation. Women with a high intake of these three methyl groups in the second and third trimester showed higher hyrdoxymethylation/methylation levels in the third trimester. To conclude, a time trend in DNA (hydroxy)methylation was found and women with higher methyl-group intake showed higher methylation in the third trimester, and not in earlier phases of pregnancy. PMID:27509522

  8. Maternal Methyl-Group Donor Intake and Global DNA (Hydroxy)Methylation before and during Pregnancy.

    PubMed

    Pauwels, Sara; Duca, Radu Corneliu; Devlieger, Roland; Freson, Kathleen; Straetmans, Dany; Van Herck, Erik; Huybrechts, Inge; Koppen, Gurdun; Godderis, Lode

    2016-01-01

    It is still unclear to which extent methyl-group intake during pregnancy can affect maternal global DNA (hydroxyl)methylation. Pregnancy methylation profiling and its link with methyl-group intake in a healthy population could enhance our understanding of the development of pregnancy related disorders. One hundred forty-eight women were enrolled in the MANOE (MAternal Nutrition and Offspring's Epigenome) study. Thiry-four women were enrolled before pregnancy and 116 during the first trimester of pregnancy. Global DNA (hydroxy)methylation in blood using LC-MS/MS and dietary methyl-group intake (methionine, folate, betaine, and choline) using a food-frequency questionnaire were estimated pre-pregnancy, during each trimester, and at delivery. Global DNA (hydroxy)methylation levels were highest pre-pregnancy and at weeks 18-22 of pregnancy. We observed a positive relation between folic acid and global DNA methylation (p = 0.04) and hydroxymethylation (p = 0.04). A high intake of methionine pre-pregnancy and in the first trimester showed lower (hydroxy)methylation percentage in weeks 11-13 and weeks 18-22, respectively. Choline and betaine intake in the first weeks was negatively associated with hydroxymethylation. Women with a high intake of these three methyl groups in the second and third trimester showed higher hyrdoxymethylation/methylation levels in the third trimester. To conclude, a time trend in DNA (hydroxy)methylation was found and women with higher methyl-group intake showed higher methylation in the third trimester, and not in earlier phases of pregnancy. PMID:27509522

  9. Undetectable levels of N6-methyl adenine in mouse DNA: Cloning and analysis of PRED28, a gene coding for a putative mammalian DNA adenine methyltransferase.

    PubMed

    Ratel, David; Ravanat, Jean-Luc; Charles, Marie-Pierre; Platet, Nadine; Breuillaud, Lionel; Lunardi, Joël; Berger, François; Wion, Didier

    2006-05-29

    Three methylated bases, 5-methylcytosine, N4-methylcytosine and N6-methyladenine (m6A), can be found in DNA. However, to date, only 5-methylcytosine has been detected in mammalian genomes. To reinvestigate the presence of m6A in mammalian DNA, we used a highly sensitive method capable of detecting one N6-methyldeoxyadenosine per million nucleosides. Our results suggest that the total mouse genome contains, if any, less than 10(3) m6A. Experiments were next performed on PRED28, a putative mammalian N6-DNA methyltransferase. The murine PRED28 encodes two alternatively spliced RNA. However, although recombinant PRED28 proteins are found in the nucleus, no evidence for an adenine-methyltransferase activity was detected. PMID:16684535

  10. Developmental differences in posttranslational calmodulin methylation in pea plants

    SciTech Connect

    Oh, Sukheung; Roberts, D.M. )

    1990-05-01

    A calmodulin-N-methyltransferase was used to analyze the degree of lysine-115 methylation of pea calmodulin. Calmodulin was isolated from segments of developing roots of young etiolated and green pea plants and was tested for its ability to be methylated by the calmodulin methyltransferase in the presence of {sup 3}H-methyl-S-adenosylmethionine. Calmodulin methylation levels were lower in apical root segments and in the young lateral roots compared with the mature, differentiated root tissues. The methylation of these calmodulin samples occurs specifically at lysine 115 since site-directed mutants of calmodulin with substitutions at this position were not methylated and competitively inhibited methylation. The present findings, combined with previous data showing differences in NAD kinase activation by methylated and unmethylated calmodulins, raise the possibility that posttranslational methylation could affect calmodulin action.

  11. Methyl chloroform and the atmosphere

    SciTech Connect

    Ravishankara, A.R.; Albritton, D.L.

    1995-07-14

    The atmospheric abundance of methyl chloroform, CH{sub 3}CCl{sub 3}, a compound of only anthropogenic origin, is actually decreasing because of emission reductions in compliance with the United Nations Montreal Protocol and its subsequent amendments. This observation, reported by Prinn and co-workers elsewhere in this issue, is based on data from surface-level monitoring stations. The observed trends in methyl chloroform abundance have a few straightforward scientific consequences and substantial policy relevance as discussed in this article. 6 refs., 1 fig.

  12. Methyl salicylate overdose

    MedlinePlus

    Methyl salicylate (oil of wintergreen) is a chemical that smells like wintergreen. It is used in many over- ... muscle ache creams. It is related to aspirin. Methyl salicylate overdose occurs when someone swallows a dangerous amount ...

  13. DNA methylation and cognitive aging

    PubMed Central

    Xu, Xiangru

    2015-01-01

    With ever-increasing elder population, the high incidence of age-related diseases such as neurodegenerative disorders has turned out to be a huge public concern. Especially the elders and their families dreadfully suffer from the learning, behavioral and cognitive impairments. The lack of effective therapies for such a horrible symptom makes a great demanding for biological mechanism study for cognitive aging. Epigenetics is an emerging field that broadens the dimensions of mammalian genome blueprint. It is, unlike genetics, not only inheritable but also reversible. Recent studies suggest that DNA methylation, one of major epigenetic mechanisms, plays a pivotal role in the pathogenesis of age-related neurodegenerations and cognitive defects. In this review, the evolving knowledge of age-related cognitive functions and the potential DNA methylation mechanism of cognitive aging are discussed. That indicates the impairment of DNA methylation may be a crucial but reversible mechanism of behavioral and cognitive related neurodegeneration. The methods to examine the dynamics of DNA methylation patterns at tissue and single cell level and at the representative scale as well as the whole genome single base resolution are also briefly discussed. Importantly, the challenges of DNA methylation mechanism of cognitive aging research are brought up, and the possible solutions to tackle these difficulties are put forward. PMID:26015403

  14. Consequences of dietary methyl donor supplements: Is more always better?

    PubMed

    Shorter, Kimberly R; Felder, Michael R; Vrana, Paul B

    2015-07-01

    Epigenetic mechanisms are now recognized to play roles in disease etiology. Several diseases increasing in frequency are associated with altered DNA methylation. DNA methylation is accomplished through metabolism of methyl donors such as folate, vitamin B12, methionine, betaine (trimethylglycine), and choline. Increased intake of these compounds correlates with decreased neural tube defects, although this mechanism is not well understood. Consumption of these methyl donor pathway components has increased in recent years due to fortification of grains and high supplemental levels of these compounds (e.g. vitamins, energy drinks). Additionally, people with mutations in one of the enzymes that assists in the methyl donor pathway (5-MTHFR) are directed to consume higher amounts of methyl donors to compensate. Recent evidence suggests that high levels of methyl donor intake may also have detrimental effects. Individualized medicine may be necessary to determine the appropriate amounts of methyl donors to be consumed, particularly in women of child bearing age. PMID:25841986

  15. Initial results in the development of a reporter cell line for toxicology studies at gene expression level: activation of the electrophile-responsive element by copper and methyl parathion.

    PubMed

    Almeida, Daniela Volcan; Trindade, Gilma Santos; Geracitano, Laura A; Barros, Daniela Martí; Monserrat, José Maria; Marins, Luis Fernando

    2008-07-01

    Induction of many genes encoding detoxifying enzymes and antioxidant proteins is mediated through a common mechanism, which is controlled by electrophile-responsive elements (EpRE) within the regulatory region of those genes. Copper and methyl parathion are environmental pollutants known to induce the expression of EpRE-mediated genes. In order to evaluate the molecular response triggered by these pollutants, a stable cell line was produced, which carries a transgene comprised of the green fluorescent protein (GFP) reporter gene under transcriptional control of the mouse glutathione-S-transferase (gst1) electrophile-responsive element fused to the mouse metallothionein (mt1) minimal promoter. The rat HTC hepatoma cells were transfected with the EpREmt-GFP construct and successfully selected with G418 antibiotic. EpREmt-GFP HTC cells were treated with 0.002 mg L(-1), 0.02 mg L(-1), 0.2 mg L(-1) and 2 mg L(-1) copper sulfate and 0.001 mg L(-1), 0.01 mg L(-1), 0.1 mg L(-1) and 1 mg L(-1) methyl parathion for 48 h. GFP expression was directly quantified in living cells using a microplate fluorimeter. GFP expression was significantly increased in higher concentrations of both pollutants, showing a 1.80- and 2.58-fold induction of GFP at 2mg copper L(-1) and 1mg methyl parathion L(-1), respectively (p<0.01). The results obtained in the present study demonstrate that the EpREmt-GFP HTC cell line can be an interesting model for further development for the study of the cellular response to aquatic pollutants as well as a new tool for environmental monitoring at the molecular level. PMID:18533248

  16. GNSS Absolute Antenna Calibration at the National Geodetic Survey

    NASA Astrophysics Data System (ADS)

    Mader, G. L.; Bilich, A. L.; Geoghegan, C.

    2011-12-01

    Geodetic GNSS applications routinely demand millimeter precision and extremely high levels of accuracy. To achieve these accuracies, measurement and instrument biases at the centimeter to millimeter level must be understood. One of these biases is the antenna phase center, the apparent point of signal reception for a GNSS antenna. It has been well established that phase center patterns differ between antenna models and manufacturers; additional research suggests that the addition of a radome or the choice of antenna mount can significantly alter those a priori phase center patterns. For the more demanding GNSS positioning applications and especially in cases of mixed-antenna networks, it is all the more important to know antenna phase center variations as a function of both elevation and azimuth in the antenna reference frame and incorporate these models into analysis software. To help meet the needs of the high-precision GNSS community, the National Geodetic Survey (NGS) now operates an absolute antenna calibration facility. Located in Corbin, Virginia, this facility uses field measurements and actual GNSS satellite signals to quantitatively determine the carrier phase advance/delay introduced by the antenna element. The NGS facility was built to serve traditional NGS constituents such as the surveying and geodesy communities, however calibration services are open and available to all GNSS users as the calibration schedule permits. All phase center patterns computed by this facility will be publicly available and disseminated in both the ANTEX and NGS formats. We describe the NGS calibration facility, and discuss the observation models and strategy currently used to generate NGS absolute calibrations. We demonstrate that NGS absolute phase center variation (PCV) patterns are consistent with published values determined by other absolute antenna calibration facilities, and compare absolute calibrations to the traditional NGS relative calibrations.

  17. Absolute magnitudes of trans-neptunian objects

    NASA Astrophysics Data System (ADS)

    Duffard, R.; Alvarez-candal, A.; Pinilla-Alonso, N.; Ortiz, J. L.; Morales, N.; Santos-Sanz, P.; Thirouin, A.

    2015-10-01

    Accurate measurements of diameters of trans- Neptunian objects are extremely complicated to obtain. Radiomatric techniques applied to thermal measurements can provide good results, but precise absolute magnitudes are needed to constrain diameters and albedos. Our objective is to measure accurate absolute magnitudes for a sample of trans- Neptunian objects, many of which have been observed, and modelled, by the "TNOs are cool" team, one of Herschel Space Observatory key projects grantes with ~ 400 hours of observing time. We observed 56 objects in filters V and R, if possible. These data, along with data available in the literature, was used to obtain phase curves and to measure absolute magnitudes by assuming a linear trend of the phase curves and considering magnitude variability due to rotational light-curve. In total we obtained 234 new magnitudes for the 56 objects, 6 of them with no reported previous measurements. Including the data from the literature we report a total of 109 absolute magnitudes.

  18. A New Gimmick for Assigning Absolute Configuration.

    ERIC Educational Resources Information Center

    Ayorinde, F. O.

    1983-01-01

    A five-step procedure is provided to help students in making the assignment absolute configuration less bothersome. Examples for both single (2-butanol) and multi-chiral carbon (3-chloro-2-butanol) molecules are included. (JN)

  19. Determination of absolute configuration using ab initio calculation of optical rotation.

    PubMed

    Stephens, P J; Devlin, F J; Cheeseman, J R; Frisch, M J; Bortolini, O; Besse, P

    2003-01-01

    Ab initio Density Functional Theory (DFT) calculations of transparent spectral region, discrete frequency specific rotations were used to assign the absolute configurations (ACs) of: 1, 2H-naphtho[1,8-bc]thiophene 1-oxide; 2, m-F-phenyl glycidic acid methyl ester; 3, o-Br-phenyl glycidic acid methyl ester; 4, p-CH(3)-phenyl glycidic acid methyl ester; 5, 2-(1-hydroxyethyl)-chromen-4-one; and 6, 6-Br-2-(1-hydroxyethyl)-chromen-4-one. The ACs of 5 and 6 were previously determined via X-ray crystallography to be: 5, R(-)/S(+); 6, R(+)/S(-). The ACs obtained using [alpha](D) are the same for both 5 and 6: R(+)/S(-). We conclude that the previously reported AC of 5 is incorrect. PMID:12884375

  20. Population-based absolute risk estimation with survey data.

    PubMed

    Kovalchik, Stephanie A; Pfeiffer, Ruth M

    2014-04-01

    Absolute risk is the probability that a cause-specific event occurs in a given time interval in the presence of competing events. We present methods to estimate population-based absolute risk from a complex survey cohort that can accommodate multiple exposure-specific competing risks. The hazard function for each event type consists of an individualized relative risk multiplied by a baseline hazard function, which is modeled nonparametrically or parametrically with a piecewise exponential model. An influence method is used to derive a Taylor-linearized variance estimate for the absolute risk estimates. We introduce novel measures of the cause-specific influences that can guide modeling choices for the competing event components of the model. To illustrate our methodology, we build and validate cause-specific absolute risk models for cardiovascular and cancer deaths using data from the National Health and Nutrition Examination Survey. Our applications demonstrate the usefulness of survey-based risk prediction models for predicting health outcomes and quantifying the potential impact of disease prevention programs at the population level. PMID:23686614

  1. Human age estimation from blood using mRNA, DNA methylation, DNA rearrangement, and telomere length.

    PubMed

    Zubakov, Dmitry; Liu, Fan; Kokmeijer, Iris; Choi, Ying; van Meurs, Joyce B J; van IJcken, Wilfred F J; Uitterlinden, André G; Hofman, Albert; Broer, Linda; van Duijn, Cornelia M; Lewin, Jörn; Kayser, Manfred

    2016-09-01

    Establishing the age of unknown persons, or persons with unknown age, can provide important leads in police investigations, disaster victim identification, fraud cases, and in other legal affairs. Previous methods mostly relied on morphological features available from teeth or skeletal parts. The development of molecular methods for age estimation allowing to use human specimens that possess no morphological age information, such as bloodstains, is extremely valuable as this type of samples is commonly found at crime scenes. Recently, we introduced a DNA-based approach for human age estimation from blood based on the quantification of T-cell specific DNA rearrangements (sjTRECs), which achieves accurate assignment of blood DNA samples to one of four 20-year-interval age categories. Aiming at improving the accuracy of molecular age estimation from blood, we investigated different types of biomarkers. We started out by systematic genome-wide surveys for new age-informative mRNA and DNA methylation markers in blood from the same young and old individuals using microarray technologies. The obtained candidate markers were validated in independent samples covering a wide age range using alternative technologies together with previously proposed DNA methylation, sjTREC, and telomere length markers. Cross-validated multiple regression analysis was applied for estimating and validating the age predictive power of various sets of biomarkers within and across different marker types. We found that DNA methylation markers outperformed mRNA, sjTREC, and telomere length in age predictive power. The best performing model included 8 DNA methylation markers derived from 3 CpG islands reaching a high level of accuracy (cross-validated R(2)=0.88, SE±6.97 years, mean absolute deviation 5.07 years). However, our data also suggest that mRNA markers can provide independent age information: a model using a combined set of 5 DNA methylation markers and one mRNA marker could provide

  2. Techniques in protein methylation.

    PubMed

    Lee, Jaeho; Cheng, Donghang; Bedford, Mark T

    2004-01-01

    Proteins can be methylated on the side-chain nitrogens of arginine and lysine residues or on carboxy-termini. Protein methylation is a way of subtly changing the primary sequence of a peptide so that it can encode more information. This common posttranslational modification is implicated in the regulation of a variety of processes including protein trafficking, transcription and protein-protein interactions. In this chapter, we will use the arginine methyltransferases to illustrate different approaches that have been developed to assess protein methylation. Both in vivo and in vitro methylation techniques are described, and the use of small molecule inhibitors of protein methylation will be demonstrated. PMID:15173617

  3. KEY COMPARISON: Final report on international key comparison CCQM-K65: Gas standards containing methyl and ethyl mercaptans (at the level of 20-30 µmol/mol) in methane

    NASA Astrophysics Data System (ADS)

    Konopelko, L. A.; Kustikov, Y. A.; Vishnyakov, I. M.; Pavlov, M. V.; Efremova, O. V.; Woo, Jin-Chun; Kim, Yong-Doo; Wessel, Rob M.; Ziel, Paul R.; Milton, Martin J. T.; Vargha, G.; Brown, A.; Uprichard, Ian

    2010-01-01

    The key comparison CCQM-K65 was intended to compare the capabilities for the preparation and value assignment of gas standards for methyl and ethyl mercaptans in methane, maintained at the participating national metrological institutes: VNIIM (Russia), KRISS (Korea), VSL (Netherlands) and NPL (United Kingdom). The range of the nominal amount of substance fractions of the comparison gas mixtures was 20 µmol/mol to 30 µmol/mol, which is close to regulatory level (in several countries including Russia) for mercaptans in odorated natural gas. This comparison was proposed at the 12th GAWG meeting in October 2004 and was conducted in 2008. Conclusions are as follows: The results of all laboratories are consistent with the reference values. The observed differences between the reference and reported values are within +/-0.9% for methyl mercaptan and +/-0.75% for ethyl mercaptan relative to the gravimetric values, and do not exceed the appropriate assigned expanded uncertainties. The prepared mixtures were found to be stable during about a year within the uncertainty of the measurements. The gravimetric values were successfully validated with a dynamic method. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  4. In-flight Absolute Radiometric Calibration of the Thematic Mapper

    NASA Technical Reports Server (NTRS)

    Castle, K. R.; Holm, R. G.; Kastner, C. J.; Palmer, J. M.; Slater, P. N.; Dinguirard, M.; Ezra, C. E.; Jackson, D.; Savage, R. K.

    1984-01-01

    The Thematic Mapper (TM) multispectral scanner system was placed into Earth orbit on July 16, 1982, as part of NASA's LANDSAT 4 payload. To determine temporal changes of the absolute radiometric calibration of the entire system in flight, spectroradiometric measurements of the ground and the atmosphere are made simultaneously with TM image acquisitions over the White Sands, New Mexico area. By entering the measured values into an atmospheric radiative transfer program, the radiance levels at the entrance pupil of the TM in four of the TM spectral bands are determined. These levels are compared to the output digital counts from the detectors that sampled the radiometrically measured ground area, thus providing an absolute radiometric calibration of the entire TM system utilizing those detectors. By reference to an adjacent, larger uniform area, the calibration is extended to all 16 detectors in each of the three bands.

  5. In-flight absolute radiometric calibration of the thematic mapper

    NASA Technical Reports Server (NTRS)

    Castle, K. R.; Holm, R. G.; Kastner, C. J.; Palmer, J. M.; Slater, P. N.; Dinguirard, M.; Ezra, C. E.; Jackson, R. D.; Savage, R. K.

    1984-01-01

    In order to determine temporal changes of the absolute radiometric calibration of the entire TM system in flight spectroradiometric measurements of the ground and the atmosphere were made simultaneously with TM image collections over the White Sands, New Mexico area. By entering the measured values in an atmospheric radiative transfer program, the radiance levels in four of the spectral bands of the TM were determined, band 1:0.45 to 0.52 micrometers, band 2:0.53 to 0.61 micrometers band 3:0.62 to 0.70 micrometers and 4:0.78 to 0.91 micrometers. These levels were compared to the output digital counts from the detectors that sampled the radiometrically measured ground area, thus providing an absolute radiometric calibration of the entire TM system utilizing those detectors.

  6. In-flight absolute radiometric calibration of the Thematic Mapper

    NASA Technical Reports Server (NTRS)

    Castle, K. R.; Holm, R. G.; Kastner, C. J.; Palmer, J. M.; Slater, P. N.; Dinguirard, M.; Ezra, C. E.; Jackson, R. D.; Savage, R. K.

    1984-01-01

    In order to determine temporal changes of the absolute radiometric calibration of the entire TM system in flight spectroradiometric measurements of the ground and the atmosphere were made simultaneously with TM image collections over the White Sands, NM area. By entering the measured values in an atmospheric radiative transfer program, the radiance levels in four of the spectral bands of the TM were determined, band 1: 0.45 to 0.52 micrometers, band 2: 0.53 to 0.61 micrometers, band 3: 0.62 to 0.70 micrometers, and 4: 0.78 to 0.91 micrometers. These levels were compared to the output digital counts from the detectors that sampled the radiometrically measured ground area, thus providing an absolute radiometric calibration of the entire TM system utilizing those detectors. Previously announced in STAR as N84-15633

  7. Engine performance and the determination of absolute ceiling

    NASA Technical Reports Server (NTRS)

    Diehl, Walter S

    1924-01-01

    This report contains a brief study of the variation of engine power with temperature and pressure. The variation of propeller efficiency in standard atmosphere is obtained from the general efficiency curve which is developed in NACA report no. 168. The variation of both power available and power required are then determined and curves plotted, so that the absolute ceiling may be read directly from any known sea-level value of the ratio of power available to power required.

  8. Subchronic treatment with phencyclidine in adolescence leads to impaired exploratory behavior in adult rats without altering social interaction or N-methyl-D-aspartate receptor binding levels.

    PubMed

    Metaxas, A; Willems, R; Kooijman, E J M; Renjaän, V A; Klein, P J; Windhorst, A D; Donck, L Ver; Leysen, J E; Berckel, B N M van

    2014-11-01

    Although both the onset of schizophrenia and human phencyclidine (PCP) abuse typically present within the interval from adolescence to early adulthood, the majority of preclinical research employing the PCP model of schizophrenia has been conducted on neonatal or adult animals. The present study was designed to evaluate the behavioral and neurochemical sequelae of subchronic exposure to PCP in adolescence. Male 35-42-day-old Sprague Dawley rats were subcutaneously administered either saline (10 ml · kg(-1) ) or PCP hydrochloride (10 mg · kg(-1) ) once daily for a period of 14 days (n = 6/group). The animals were allowed to withdraw from treatment for 2 weeks, and their social and exploratory behaviors were subsequently assessed in adulthood by using the social interaction test. To examine the effects of adolescent PCP administration on the regulation of N-methyl-D-aspartate receptors (NMDARs), quantitative autoradiography was performed on brain sections of adult, control and PCP-withdrawn rats by using 20 nM (3) H-MK-801. Prior subchronic exposure to PCP in adolescence had no enduring effects on the reciprocal contact and noncontact social behavior of adult rats. Spontaneous rearing in response to the novel testing arena and time spent investigating its walls and floor were reduced in PCP-withdrawn animals compared with control. The long-term behavioral effects of PCP occurred in the absence of persistent deficits in spontaneous locomotion or self-grooming activity and were not mediated by altered NMDAR density. Our results document differential effects of adolescent PCP administration on the social and exploratory behaviors of adult rats, suggesting that distinct neurobiological mechanisms are involved in mediating these behaviors. PMID:24953757

  9. Leaf-Level Controls Over Emissions of Methanol and 2-Methyl-3-buten-2-ol, Oxygenated VOC With Different Production Mechanisms and Solubilities.

    NASA Astrophysics Data System (ADS)

    Harley, P. C.; Greenberg, J. P.; Guenther, A. B.

    2002-12-01

    Oxygenated VOC fluxes were investigated in leaves of deciduous trees and grasses, and needles of conifers, using a temperature-controlled leaf cuvette and a proton transfer reaction mass spectrometer. Two alcohols, 2-methyl-3-buten-2-ol (MBO) and methanol, emitted by these plants, illustrate two contrasting patterns of oxygenated VOC emissions. MBO is restricted to a small section of the genus Pinus, and is maximal in mature needles. Methanol production appears to be ubiquitous among higher plants, associated with demethylation of pectin during cell wall maturation, and emissions are therefore maximal during rapid leaf growth, decreasing in mature leaves. Although emissions of both compounds respond to variation in leaf temperature and incident light, the nature of the control is quite different. Production and emission of MBO are tightly coupled, and leaf pools are small. Light and temperature affect emissions directly through their effect on production which ceases rapidly in the dark. Effects of light and temperature on production of methanol are unknown, although emissions, and presumably production, continue through the night at reduced rates. Effects of light and temperature on methanol emission are indirect, through their effects on stomatal conductance and evapotranspiration. Data will be presented to justify a conceptual model in which methanol released in the demethylation of pectin partitions into the gas and liquid phase according to Henry's Law. Gas phase methanol is then emitted through the stomata. However, methanol emissions correlate more strongly with rates of evapotranspiration than with stomatal conductance, suggesting that much of the methanol is released from the dissolved pool along with the transpiration stream. At night, when stomatal conductance is low, and assuming constant production, gas phase concentrations increase, and the size of the aqueous pool increases in response. This aqueous pool then empties rapidly upon stomatal opening

  10. DMEAS: DNA methylation entropy analysis software

    PubMed Central

    He, Jianlin; Sun, Xinxi; Shao, Xiaojian; Liang, Liji; Xie, Hehuang

    2013-01-01

    Summary: DMEAS is the first user-friendly tool dedicated to analyze the distribution of DNA methylation patterns for the quantification of epigenetic heterogeneity. It supports the analysis of both locus-specific and genome-wide bisulfite sequencing data. DMEAS progressively scans the mapping results of bisulfite sequencing reads to extract DNA methylation patterns for contiguous CpG dinucleotides. It determines the DNA methylation level and calculates methylation entropy for genomic segments to enable the quantitative assessment of DNA methylation variations observed in cell populations. Availability and implementation: DMEAS program, user guide and all the testing data are freely available from http://sourceforge.net/projects/dmeas/files/ Contact: davidxie@vt.edu Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:23749987

  11. Four Years of Absolute Gravity in the Taiwan Orogen (AGTO)

    NASA Astrophysics Data System (ADS)

    Mouyen, M.; Masson, F.; Hwang, C.; Cheng, C.; Le Moigne, N.; Lee, C.; Kao, R.; Hsieh, N.

    2009-12-01

    AGTO is a scientific project between Taiwanese and French institutes which aim is to improve tectonic knowledge of Taiwan primarily using absolute gravity measurements and permanent GPS stations. Both tools are indeed useful to study vertical movements and mass transfers involved in mountain building, a major process in Taiwan located at the convergent margin between Philippine Sea plate and Eurasian plate. This convergence results in two subductions north and south of Taiwan (Ryukyu and Manilla trenches, respectively), while the center is experiencing collision. These processes make Taiwan very active tectonically, as illustrated by numerous large earthquakes and rapid uplift of the Central Range. High slopes of Taiwan mountains and heavy rains brought by typhoons together lead to high landslides and mudflows risks. Practically, absolute gravity measurements have been yearly repeated since 2006 along a transect across south Taiwan, from Penghu to Lutao island, using FG5 absolute gravimeters. This transect contains ten sites for absolute measurements and has been densified in 2008 by incorporating 45 sites for relative gravity measurements with CG5 gravimeters. At the end of 2009, the relative gravity network will be densified again in its eastern part, i.e. in the Longitudinal Valley and the Central Range. A fourth set of absolute gravity measurements will also be performed at the same period. Most of the absolute sites have been measured with a good accuracy, about 1 or 2 μGal. Only the site located in Tainan University has higher standard deviation, due to the city noise. The stronger change in gravity reaches -7 μGal a -1 west of the Longitudinal Valley and might be explained by tectonic movement along a fault. A large decrease of -5 μGal a-1 is also measured in Tainan city and could be correlated with uplift of this region, also denoted by InSAR, leveling and GPS. Changes occurring in the Central Range are more difficult to interpret due to the small

  12. DNA methylation contributes to natural human variation

    PubMed Central

    Heyn, Holger; Moran, Sebastian; Hernando-Herraez, Irene; Sayols, Sergi; Gomez, Antonio; Sandoval, Juan; Monk, Dave; Hata, Kenichiro; Marques-Bonet, Tomas; Wang, Liewei; Esteller, Manel

    2013-01-01

    DNA methylation patterns are important for establishing cell, tissue, and organism phenotypes, but little is known about their contribution to natural human variation. To determine their contribution to variability, we have generated genome-scale DNA methylation profiles of three human populations (Caucasian-American, African-American, and Han Chinese-American) and examined the differentially methylated CpG sites. The distinctly methylated genes identified suggest an influence of DNA methylation on phenotype differences, such as susceptibility to certain diseases and pathogens, and response to drugs and environmental agents. DNA methylation differences can be partially traced back to genetic variation, suggesting that differentially methylated CpG sites serve as evolutionarily established mediators between the genetic code and phenotypic variability. Notably, one-third of the DNA methylation differences were not associated with any genetic variation, suggesting that variation in population-specific sites takes place at the genetic and epigenetic levels, highlighting the contribution of epigenetic modification to natural human variation. PMID:23908385

  13. Conformation-selective methylation of geminivirus DNA.

    PubMed

    Paprotka, T; Deuschle, K; Metzler, V; Jeske, H

    2011-11-01

    Geminiviruses with small circular single-stranded DNA genomes replicate in plant cell nuclei by using various double-stranded DNA (dsDNA) intermediates: distinct open circular and covalently closed circular as well as heterogeneous linear DNA. Their DNA may be methylated partially at cytosine residues, as detected previously by bisulfite sequencing and subsequent PCR. In order to determine the methylation patterns of the circular molecules, the DNAs of tomato yellow leaf curl Sardinia virus (TYLCSV) and Abutilon mosaic virus were investigated utilizing bisulfite treatment followed by rolling circle amplification. Shotgun sequencing of the products yielded a randomly distributed 50% rate of C maintenance after the bisulfite reaction for both viruses. However, controls with unmethylated single-stranded bacteriophage DNA resulted in the same level of C maintenance. Only one short DNA stretch within the C2/C3 promoter of TYLCSV showed hyperprotection of C, with the protection rate exceeding the threshold of the mean value plus 1 standard deviation. Similarly, the use of methylation-sensitive restriction enzymes suggested that geminiviruses escape silencing by methylation very efficiently, by either a rolling circle or recombination-dependent replication mode. In contrast, attempts to detect methylated bases positively by using methylcytosine-specific antibodies detected methylated DNA only in heterogeneous linear dsDNA, and methylation-dependent restriction enzymes revealed that the viral heterogeneous linear dsDNA was methylated preferentially. PMID:21835804

  14. Epigenetic DNA Methylation Linked to Social Dominance

    PubMed Central

    Lenkov, Kapa; Lee, Mi H.; Lenkov, Olga D.; Swafford, Andrew; Fernald, Russell D.

    2015-01-01

    Social status hierarchies are ubiquitous in vertebrate social systems, including humans. It is well known that social rank can influence quality of life dramatically among members of social groups. For example, high-ranking individuals have greater access to resources, including food and mating prerogatives that, in turn, have a positive impact on their reproductive success and health. In contrast low ranking individuals typically have limited reproductive success and may experience lasting social and physiological costs. Ultimately, social rank and behavior are regulated by changes in gene expression. However, little is known about mechanisms that transduce social cues into transcriptional changes. Since social behavior is a dynamic process, we hypothesized that a molecular mechanism such as DNA methylation might play a role these changes. To test this hypothesis, we used an African cichlid fish, Astatotilapia burtoni, in which social rank dictates reproductive access. We show that manipulating global DNA methylation state strongly biases the outcomes of social encounters. Injecting DNA methylating and de-methylating agents in low status animals competing for status, we found that animals with chemically increased methylation states were statistically highly likely to ascend in rank. In contrast, those with inhibited methylation processes and thus lower methylation levels were statistically highly unlikely to ascend in rank. This suggests that among its many roles, DNA methylation may be linked to social status and more generally to social behavior. PMID:26717574

  15. From trans-methylation to cytosine methylation: evolution of the methylation hypothesis of schizophrenia.

    PubMed

    Grayson, Dennis R; Chen, Ying; Dong, Erbo; Kundakovic, Marija; Guidotti, Alessandro

    2009-04-01

    The role of methylation in the history of psychiatry has traversed a storied path. The original trans-methylation hypothesis was proposed at a time when chlorpromazine had been synthesized but not yet marketed as an antipsychotic (Thorazine). The premise was that abnormal metabolism led to the methylation of biogenic amines in the brains of schizophrenia patients and that these hallucinogenic compounds produced positive symptoms of the disease. At the time, some psychiatrists were interested in drugs such as mescaline and lysergic acid diethylamide that replicated clinical symptoms. They understood that these compounds might provide a biological basis for psychosis. The amino acid methionine (MET) was given to patients in the hopes of confiriming the transmethylation hypothesis. However with time, many realized that the hunt for an endogenous psychotropic compound would remain elusive. We now believe that the MET studies may have produced a toxic reaction in susceptible patients by disrupting epigenetic regulation in the brain. The focus of the current review is on the coordinate regulation of multiple promoters expressed in neurons that may be modulated through methylation. While certainly the identification of genes and promoters regulated epigenetically has been steadily increasing over the years, there have been few studies that examine methylation changes as a consequence of increased levels of a dietary amino acid such as methionine (MET). We suggest that the MET mouse model may provide information regarding the identification of genes that are regulated by epigenetic perturbations. In addition to our studies with the reelin and GAD67 promoters, we also have evidence that additional promoters expressed in select neurons of the brain are similarly affected by MET administration. We suggest that to expand our knowledge of epigenetically-responsive promoters using MET might allow for a better appreciation of global methylation changes occurring in selected brain

  16. Universal Cosmic Absolute and Modern Science

    NASA Astrophysics Data System (ADS)

    Kostro, Ludwik

    The official Sciences, especially all natural sciences, respect in their researches the principle of methodic naturalism i.e. they consider all phenomena as entirely natural and therefore in their scientific explanations they do never adduce or cite supernatural entities and forces. The purpose of this paper is to show that Modern Science has its own self-existent, self-acting, and self-sufficient Natural All-in Being or Omni-Being i.e. the entire Nature as a Whole that justifies the scientific methodic naturalism. Since this Natural All-in Being is one and only It should be considered as the own scientifically justified Natural Absolute of Science and should be called, in my opinion, the Universal Cosmic Absolute of Modern Science. It will be also shown that the Universal Cosmic Absolute is ontologically enormously stratified and is in its ultimate i.e. in its most fundamental stratum trans-reistic and trans-personal. It means that in its basic stratum. It is neither a Thing or a Person although It contains in Itself all things and persons with all other sentient and conscious individuals as well, On the turn of the 20th century the Science has begun to look for a theory of everything, for a final theory, for a master theory. In my opinion the natural Universal Cosmic Absolute will constitute in such a theory the radical all penetrating Ultimate Basic Reality and will substitute step by step the traditional supernatural personal Absolute.

  17. Reading the unique DNA methylation landscape of the brain: Non-CpG methylation, hydroxymethylation, and MeCP2

    PubMed Central

    Kinde, Benyam; Gabel, Harrison W.; Gilbert, Caitlin S.; Griffith, Eric C.; Greenberg, Michael E.

    2015-01-01

    DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system. PMID:25739960

  18. Karst Water System Investigated by Absolute Gravimetry

    NASA Astrophysics Data System (ADS)

    Quinif, Y.; Meus, P.; van Camp, M.; Kaufmann, O.; van Ruymbeke, M.; Vandiepenbeeck, M.; Camelbeeck, T.

    2006-12-01

    The highly anisotropic and heterogeneous hydrogeological characteristics of karst aquifers are difficult to characterize and present challenges for modeling of storage capacities. Little is known about the surface and groundwater interconnection, about the connection between the porous formations and the draining cave and conduits, and about the variability of groundwater volume within the system. Usually, an aquifer is considered as a black box, where water fluxes are monitored as input and output. However, water inflow and outflow are highly variable and cannot be measured directly. A recent project, begun in 2006 sought to constrain the water budget in a Belgian karst aquifer and to assess the porosity and water dynamics, combining absolute gravity (AG) measurements and piezometric levels around the Rochefort cave. The advantage of gravity measurements is that they integrate all the subsystems in the karst system. This is not the case with traditional geophysical tools like boring or monitoring wells, which are soundings affected by their near environment and its heterogeneity. The investigated cave results from the meander cutoff system of the Lomme River. The main inputs are swallow holes of the river crossing the limestone massif. The river is canalized and the karst system is partly disconnected from the hydraulic system. In February and March 2006, when the river spilled over its dyke and sank into the most important swallow hole, this resulted in dramatic and nearly instantaneous increases in the piezometric levels in the cave, reaching up to 13 meters. Meanwhile, gravity increased by 50 and 90 nms-2 in February and March, respectively. A first conclusion is that during these sudden floods, the pores and fine fissures were poorly connected with the enlarged fractures, cave, and conduits. With a rise of 13 meters in the water level and a 5% porosity, a gravity change of 250 nms-2 should have been expected. This moderate gravity variation suggests either a

  19. Methyl protodioscin increases ABCA1 expression and cholesterol efflux while inhibiting gene expressions for synthesis of cholesterol and triglycerides by suppressing SREBP transcription and microRNA 33a/b levels.

    PubMed

    Ma, Weilie; Ding, Hang; Gong, Xiaohua; Liu, Zhen; Lin, Yalin; Zhang, Zhizhen; Lin, Guorong

    2015-04-01

    Sterol regulatory element-binding proteins (SREBPs) regulate homeostasis of LDL, HDL and triglycerides. This study was aimed to determine if inhibition of SREBPs by methyl protodioscin (MPD) regulates downstream gene and protein expressions of lipid metabolisms. In THP-1 macrophages, MPD increases levels of ABCA1 mRNA and protein in dose- and time-dependent manners, and apoA-1-mediated cholesterol efflux. The underlying mechanisms for the effects is that MPD inhibits the transcription of SREBP1c and SREBP2, and decreases levels of microRNA 33a/b hosted in the introns of SREBPs, which leads to reciprocally increase ABCA1 levels. In HepG2 cells, MPD shows the same effects as these observed in THP-1 macrophages. MPD also decreases the gene expressions of HMGCR, FAS and ACC for cholesterol and fatty acid synthesis. MPD further promotes LDL receptor through reducing the PCSK9 level. Collectively, the study demonstrates that MPD potentially increase HDL cholesterol while reducing LDL cholesterol and triglycerides. PMID:25733328

  20. Information Thermodynamics of Cytosine DNA Methylation.

    PubMed

    Sanchez, Robersy; Mackenzie, Sally A

    2016-01-01

    Cytosine DNA methylation (CDM) is a stable epigenetic modification to the genome and a widespread regulatory process in living organisms that involves multicomponent molecular machines. Genome-wide cytosine methylation patterning participates in the epigenetic reprogramming of a cell, suggesting that the biological information contained within methylation positions may be amenable to decoding. Adaptation to a new cellular or organismal environment also implies the potential for genome-wide redistribution of CDM changes that will ensure the stability of DNA molecules. This raises the question of whether or not we would be able to sort out the regulatory methylation signals from the CDM background ("noise") induced by thermal fluctuations. Here, we propose a novel statistical and information thermodynamic description of the CDM changes to address the last question. The physical basis of our statistical mechanical model was evaluated in two respects: 1) the adherence to Landauer's principle, according to which molecular machines must dissipate a minimum energy ε = kBT ln2 at each logic operation, where kB is the Boltzmann constant, and T is the absolute temperature and 2) whether or not the binary stretch of methylation marks on the DNA molecule comprise a language of sorts, properly constrained by thermodynamic principles. The study was performed for genome-wide methylation data from 152 ecotypes and 40 trans-generational variations of Arabidopsis thaliana and 93 human tissues. The DNA persistence length, a basic mechanical property altered by CDM, was estimated with values from 39 to 66.9 nm. Classical methylome analysis can be retrieved by applying information thermodynamic modelling, which is able to discriminate signal from noise. Our finding suggests that the CDM signal comprises a language scheme properly constrained by molecular thermodynamic principles, which is part of an epigenomic communication system that obeys the same thermodynamic rules as do current

  1. Information Thermodynamics of Cytosine DNA Methylation

    PubMed Central

    Sanchez, Robersy; Mackenzie, Sally A.

    2016-01-01

    Cytosine DNA methylation (CDM) is a stable epigenetic modification to the genome and a widespread regulatory process in living organisms that involves multicomponent molecular machines. Genome-wide cytosine methylation patterning participates in the epigenetic reprogramming of a cell, suggesting that the biological information contained within methylation positions may be amenable to decoding. Adaptation to a new cellular or organismal environment also implies the potential for genome-wide redistribution of CDM changes that will ensure the stability of DNA molecules. This raises the question of whether or not we would be able to sort out the regulatory methylation signals from the CDM background (“noise”) induced by thermal fluctuations. Here, we propose a novel statistical and information thermodynamic description of the CDM changes to address the last question. The physical basis of our statistical mechanical model was evaluated in two respects: 1) the adherence to Landauer’s principle, according to which molecular machines must dissipate a minimum energy ε = kBT ln2 at each logic operation, where kB is the Boltzmann constant, and T is the absolute temperature and 2) whether or not the binary stretch of methylation marks on the DNA molecule comprise a language of sorts, properly constrained by thermodynamic principles. The study was performed for genome-wide methylation data from 152 ecotypes and 40 trans-generational variations of Arabidopsis thaliana and 93 human tissues. The DNA persistence length, a basic mechanical property altered by CDM, was estimated with values from 39 to 66.9 nm. Classical methylome analysis can be retrieved by applying information thermodynamic modelling, which is able to discriminate signal from noise. Our finding suggests that the CDM signal comprises a language scheme properly constrained by molecular thermodynamic principles, which is part of an epigenomic communication system that obeys the same thermodynamic rules as do

  2. Genome-wide identification of mononuclear cell DNA methylation sites potentially affected by fish oil supplementation in young infants: A pilot study.

    PubMed

    Lind, M V; Martino, D; Harsløf, L B S; Kyjovska, Z O; Kristensen, M; Lauritzen, L

    2015-10-01

    Recent evidence suggests that the effects of n-3LCPUFA might be mediated through epigenetic mechanisms, especially DNA-methylation, during pregnancy and early life. A randomized trial was conducted in 133 9-mo-old, infants who received 3.8g/day of fish oil (FO) or sunflower oil (SO) for 9 mo. In a subset of 12 children, buffy-coat DNA was extracted before and after intervention and analyzed on Illumina-Human-Methylation 450-arrays to explore genome-wide differences between the FO and SO groups. Genome-wide-methylation analysis did not reveal significant differences between groups after adjustment for multiple testing. However, analysis of the top-ranked CpG-sites revealed 43 CpG׳s that appear modified with an absolute difference in methylation of ≥10%. Methylation levels at these sites were associated with phenotypic changes mainly in blood pressure. In conclusion, our analyses suggest potential epigenome effects that might be associated with functional outcomes, yet the effect sizes were small and should be verified by additional investigation. PMID:26254087

  3. Absolute isotopic abundances of TI in meteorites

    NASA Astrophysics Data System (ADS)

    Niederer, F. R.; Papanastassiou, D. A.; Wasserburg, G. J.

    1985-03-01

    The absolute isotope abundance of Ti has been determined in Ca-Al-rich inclusions from the Allende and Leoville meteorites and in samples of whole meteorites. The absolute Ti isotope abundances differ by a significant mass dependent isotope fractionation transformation from the previously reported abundances, which were normalized for fractionation using 46Ti/48Ti. Therefore, the absolute compositions define distinct nucleosynthetic components from those previously identified or reflect the existence of significant mass dependent isotope fractionation in nature. The authors provide a general formalism for determining the possible isotope compositions of the exotic Ti from the measured composition, for different values of isotope fractionation in nature and for different mixing ratios of the exotic and normal components.

  4. Molecular iodine absolute frequencies. Final report

    SciTech Connect

    Sansonetti, C.J.

    1990-06-25

    Fifty specified lines of {sup 127}I{sub 2} were studied by Doppler-free frequency modulation spectroscopy. For each line the classification of the molecular transition was determined, hyperfine components were identified, and one well-resolved component was selected for precise determination of its absolute frequency. In 3 cases, a nearby alternate line was selected for measurement because no well-resolved component was found for the specified line. Absolute frequency determinations were made with an estimated uncertainty of 1.1 MHz by locking a dye laser to the selected hyperfine component and measuring its wave number with a high-precision Fabry-Perot wavemeter. For each line results of the absolute measurement, the line classification, and a Doppler-free spectrum are given.

  5. Stimulus probability effects in absolute identification.

    PubMed

    Kent, Christopher; Lamberts, Koen

    2016-05-01

    This study investigated the effect of stimulus presentation probability on accuracy and response times in an absolute identification task. Three schedules of presentation were used to investigate the interaction between presentation probability and stimulus position within the set. Data from individual participants indicated strong effects of presentation probability on both proportion correct and response times. The effects were moderated by the ubiquitous stimulus position effect. The accuracy and response time data were predicted by an exemplar-based model of perceptual cognition (Kent & Lamberts, 2005). The bow in discriminability was also attenuated when presentation probability for middle items was relatively high, an effect that will constrain future model development. The study provides evidence for item-specific learning in absolute identification. Implications for other theories of absolute identification are discussed. (PsycINFO Database Record PMID:26478959

  6. Absolute calibration in vivo measurement systems

    SciTech Connect

    Kruchten, D.A.; Hickman, D.P.

    1991-02-01

    Lawrence Livermore National Laboratory (LLNL) is currently investigating a new method for obtaining absolute calibration factors for radiation measurement systems used to measure internally deposited radionuclides in vivo. Absolute calibration of in vivo measurement systems will eliminate the need to generate a series of human surrogate structures (i.e., phantoms) for calibrating in vivo measurement systems. The absolute calibration of in vivo measurement systems utilizes magnetic resonance imaging (MRI) to define physiological structure, size, and composition. The MRI image provides a digitized representation of the physiological structure, which allows for any mathematical distribution of radionuclides within the body. Using Monte Carlo transport codes, the emission spectrum from the body is predicted. The in vivo measurement equipment is calibrated using the Monte Carlo code and adjusting for the intrinsic properties of the detection system. The calibration factors are verified using measurements of existing phantoms and previously obtained measurements of human volunteers. 8 refs.

  7. Proposal for an absolute, atomic definition of mass

    NASA Astrophysics Data System (ADS)

    Wignall, J. W. G.

    1991-11-01

    It is proposed that the mass of a particle be defined absolutely as its de Broglie frequency, measured as the mean de Broglie wavelength of the particle when it has a mean speed (v) and Lorentz factor (gamma); the masses of systems too large to have a measurable de Broglie wavelength mean are then to be derived by specifying the usual inertial and additive properties of mass. This definition avoids the use of an arbitrary macroscopic standard such as the prototype kilogram, and, if present theory is correct, does not even require the choice of a specific particle as a mass standard. Suggestions are made as to how this absolute mass can be realized and measured at the macroscopic level and, finally, some comments are made on the effect of the new definition on the form of the equations of physics.

  8. Absolutely relative or relatively absolute: violations of value invariance in human decision making.

    PubMed

    Teodorescu, Andrei R; Moran, Rani; Usher, Marius

    2016-02-01

    Making decisions based on relative rather than absolute information processing is tied to choice optimality via the accumulation of evidence differences and to canonical neural processing via accumulation of evidence ratios. These theoretical frameworks predict invariance of decision latencies to absolute intensities that maintain differences and ratios, respectively. While information about the absolute values of the choice alternatives is not necessary for choosing the best alternative, it may nevertheless hold valuable information about the context of the decision. To test the sensitivity of human decision making to absolute values, we manipulated the intensities of brightness stimuli pairs while preserving either their differences or their ratios. Although asked to choose the brighter alternative relative to the other, participants responded faster to higher absolute values. Thus, our results provide empirical evidence for human sensitivity to task irrelevant absolute values indicating a hard-wired mechanism that precedes executive control. Computational investigations of several modelling architectures reveal two alternative accounts for this phenomenon, which combine absolute and relative processing. One account involves accumulation of differences with activation dependent processing noise and the other emerges from accumulation of absolute values subject to the temporal dynamics of lateral inhibition. The potential adaptive role of such choice mechanisms is discussed. PMID:26022836

  9. Sunflower oil methyl ester as diesel fuel

    SciTech Connect

    Hassett, D.J.; Hasan, R.A.

    1982-01-01

    Methyl ester formation represents one approach to overcome the problems associated with the relatively high viscosity of sunflower oil when used as a diesel fuel replacement. Sunflower oil methyl ester is being prepared at the University of North Dakota Engieering Experiment Station. Physical and chemical properties of this material at varying levels of refinement and purity will be used to define fuel properties. Engine testing is being carried out to determine if the fouling characteristics of methyl ester are significantly less than those of sunflower oil. 1 figure, 1 table.

  10. Absolute GNSS Antenna Calibration at the National Geodetic Survey

    NASA Astrophysics Data System (ADS)

    Mader, G.; Bilich, A.; Geoghegan, C.

    2012-04-01

    Geodetic GNSS applications routinely demand millimeter precision and extremely high levels of accuracy. To achieve these accuracies, measurement and instrument biases at the centimeter to millimeter level must be understood. One of these biases is the antenna phase center, the apparent point of signal reception for a GNSS antenna. It has been well established that phase center patterns differ between antenna models and manufacturers; additional research suggests that the addition of a radome or the choice of antenna mount can significantly alter those a priori phase center patterns. For the more demanding GNSS positioning applications and especially in cases of mixed-antenna networks, it is all the more important to know antenna phase center variations as a function of both elevation and azimuth in the antenna reference frame and incorporate these models into analysis software. To help meet the needs of the high-precision GNSS community, the National Geodetic Survey (NGS) now operates an absolute antenna calibration facility. Located in Corbin, Virginia, this facility uses field measurements and actual GNSS satellite signals to quantitatively determine the carrier phase advance/delay introduced by the antenna element. The NGS facility was built to serve traditional NGS constituents such as the surveying and geodesy communities, however calibration services are open and available to all GNSS users as the calibration schedule permits. All phase center patterns computed by this facility will be publicly available and disseminated in both the ANTEX and NGS formats. We describe the NGS calibration facility, and discuss the observation models and strategy currently used to generate NGS absolute calibrations. We demonstrate that NGS absolute phase center variation (PCV) patterns are consistent with published values determined by other absolute antenna calibration facilities, and outline future planned refinements to the system.

  11. Is the Fungus Magnaporthe Losing DNA Methylation?

    PubMed Central

    Ikeda, Ken-ichi; Van Vu, Ba; Kadotani, Naoki; Tanaka, Masaki; Murata, Toshiki; Shiina, Kohta; Chuma, Izumi; Tosa, Yukio; Nakayashiki, Hitoshi

    2013-01-01

    The long terminal repeat retrotransposon, Magnaporthe gypsy-like element (MAGGY), has been shown to be targeted for cytosine methylation in a subset of Magnaporthe oryzae field isolates. Analysis of the F1 progeny from a genetic cross between methylation-proficient (Br48) and methylation-deficient (GFSI1-7-2) isolates revealed that methylation of the MAGGY element was governed by a single dominant gene. Positional cloning followed by gene disruption and complementation experiments revealed that the responsible gene was the DNA methyltransferase, MoDMT1, an ortholog of Neurospora crassa Dim-2. A survey of MAGGY methylation in 60 Magnaporthe field isolates revealed that 42 isolates from rice, common millet, wheat, finger millet, and buffelgrass were methylation proficient while 18 isolates from foxtail millet, green bristlegrass, Japanese panicgrass, torpedo grass, Guinea grass, and crabgrass were methylation deficient. Phenotypic analyses showed that MoDMT1 plays no major role in development and pathogenicity of the fungus. Quantitative polymerase chain reaction analysis showed that the average copy number of genomic MAGGY elements was not significantly different between methylation-deficient and -proficient field isolates even though the levels of MAGGY transcript were generally higher in the former group. MoDMT1 gene sequences in the methylation-deficient isolates suggested that at least three independent mutations were responsible for the loss of MoDMT1 function. Overall, our data suggest that MoDMT1 is not essential for the natural life cycle of the fungus and raise the possibility that the genus Magnaporthe may be losing the mechanism of DNA methylation on the evolutionary time scale. PMID:23979580

  12. Age-Related Changes in D-Aspartate Oxidase Promoter Methylation Control Extracellular D-Aspartate Levels and Prevent Precocious Cell Death during Brain Aging.

    PubMed

    Punzo, Daniela; Errico, Francesco; Cristino, Luigia; Sacchi, Silvia; Keller, Simona; Belardo, Carmela; Luongo, Livio; Nuzzo, Tommaso; Imperatore, Roberta; Florio, Ermanno; De Novellis, Vito; Affinito, Ornella; Migliarini, Sara; Maddaloni, Giacomo; Sisalli, Maria Josè; Pasqualetti, Massimo; Pollegioni, Loredano; Maione, Sabatino; Chiariotti, Lorenzo; Usiello, Alessandro

    2016-03-01

    The endogenous NMDA receptor (NMDAR) agonist D-aspartate occurs transiently in the mammalian brain because it is abundant during embryonic and perinatal phases before drastically decreasing during adulthood. It is well established that postnatal reduction of cerebral D-aspartate levels is due to the concomitant onset of D-aspartate oxidase (DDO) activity, a flavoenzyme that selectively degrades bicarboxylic D-amino acids. In the present work, we show that d-aspartate content in the mouse brain drastically decreases after birth, whereas Ddo mRNA levels concomitantly increase. Interestingly, postnatal Ddo gene expression is paralleled by progressive demethylation within its putative promoter region. Consistent with an epigenetic control on Ddo expression, treatment with the DNA-demethylating agent, azacitidine, causes increased mRNA levels in embryonic cortical neurons. To indirectly evaluate the effect of a putative persistent Ddo gene hypermethylation in the brain, we used Ddo knock-out mice (Ddo(-/-)), which show constitutively suppressed Ddo expression. In these mice, we found for the first time substantially increased extracellular content of d-aspartate in the brain. In line with detrimental effects produced by NMDAR overstimulation, persistent elevation of D-aspartate levels in Ddo(-/-) brains is associated with appearance of dystrophic microglia, precocious caspase-3 activation, and cell death in cortical pyramidal neurons and dopaminergic neurons of the substantia nigra pars compacta. This evidence, along with the early accumulation of lipufuscin granules in Ddo(-/-) brains, highlights an unexpected importance of Ddo demethylation in preventing neurodegenerative processes produced by nonphysiological extracellular levels of free D-aspartate. PMID:26961959

  13. Phosphatase Rtr1 Regulates Global Levels of Serine 5 RNA Polymerase II C-Terminal Domain Phosphorylation and Cotranscriptional Histone Methylation.

    PubMed

    Hunter, Gerald O; Fox, Melanie J; Smith-Kinnaman, Whitney R; Gogol, Madelaine; Fleharty, Brian; Mosley, Amber L

    2016-09-01

    In eukaryotes, the C-terminal domain (CTD) of Rpb1 contains a heptapeptide repeat sequence of (Y1S2P3T4S5P6S7)n that undergoes reversible phosphorylation through the opposing action of kinases and phosphatases. Rtr1 is a conserved protein that colocalizes with RNA polymerase II (RNAPII) and has been shown to be important for the transition from elongation to termination during transcription by removing RNAPII CTD serine 5 phosphorylation (Ser5-P) at a selection of target genes. In this study, we show that Rtr1 is a global regulator of the CTD code with deletion of RTR1 causing genome-wide changes in Ser5-P CTD phosphorylation and cotranscriptional histone H3 lysine 36 trimethylation (H3K36me3). Using chromatin immunoprecipitation and high-resolution microarrays, we show that RTR1 deletion results in global changes in RNAPII Ser5-P levels on genes with different lengths and transcription rates consistent with its role as a CTD phosphatase. Although Ser5-P levels increase, the overall occupancy of RNAPII either decreases or stays the same in the absence of RTR1 Additionally, the loss of Rtr1 in vivo leads to increases in H3K36me3 levels genome-wide, while total histone H3 levels remain relatively constant within coding regions. Overall, these findings suggest that Rtr1 regulates H3K36me3 levels through changes in the number of binding sites for the histone methyltransferase Set2, thereby influencing both the CTD and histone codes. PMID:27247267

  14. Improved age determination of blood and teeth samples using a selected set of DNA methylation markers

    PubMed Central

    Kamalandua, Aubeline

    2015-01-01

    Age estimation from DNA methylation markers has seen an exponential growth of interest, not in the least from forensic scientists. The current published assays, however, can still be improved by lowering the number of markers in the assay and by providing more accurate models to predict chronological age. From the published literature we selected 4 age-associated genes (ASPA, PDE4C, ELOVL2, and EDARADD) and determined CpG methylation levels from 206 blood samples of both deceased and living individuals (age range: 0–91 years). This data was subsequently used to compare prediction accuracy with both linear and non-linear regression models. A quadratic regression model in which the methylation levels of ELOVL2 were squared showed the highest accuracy with a Mean Absolute Deviation (MAD) between chronological age and predicted age of 3.75 years and an adjusted R2 of 0.95. No difference in accuracy was observed for samples obtained either from living and deceased individuals or between the 2 genders. In addition, 29 teeth from different individuals (age range: 19–70 years) were analyzed using the same set of markers resulting in a MAD of 4.86 years and an adjusted R2 of 0.74. Cross validation of the results obtained from blood samples demonstrated the robustness and reproducibility of the assay. In conclusion, the set of 4 CpG DNA methylation markers is capable of producing highly accurate age predictions for blood samples from deceased and living individuals PMID:26280308

  15. Screening of High-Level 4-Hydroxy-2 (or 5)-Ethyl-5 (or 2)-Methyl-3(2H)-Furanone-Producing Strains from a Collection of Gene Deletion Mutants of Saccharomyces cerevisiae

    PubMed Central

    Watanabe, Jun; Akao, Takeshi; Watanabe, Daisuke; Mogi, Yoshinobu; Shimoi, Hitoshi

    2014-01-01

    4-Hydroxy-2 (or 5)-ethyl-5 (or 2)-methyl-3(2H)-furanone (HEMF) is an important flavor compound that contributes to the sensory properties of many natural products, particularly soy sauce and soybean paste. The compound exhibits a caramel-like aroma and several important physiological activities, such as strong antioxidant activity. HEMF is produced by yeast species in soy sauce manufacturing; however, the enzymes involved in HEMF production remain unknown, hindering efforts to breed yeasts with high-level HEMF production. In this study, we identified high-level HEMF-producing mutants among a Saccharomyces cerevisiae gene deletion mutant collection. Fourteen deletion mutants were screened as high-level HEMF-producing mutants, and the ADH1 gene deletion mutant (adh1Δ) exhibited the maximum HEMF production capacity. Further investigations of the adh1Δ mutant implied that acetaldehyde accumulation contributes to HEMF production, agreeing with previous findings. Therefore, acetaldehyde might be a precursor for HEMF. The ADH1 gene deletion mutant of Zygosaccharomyces rouxii, which is the dominant strain of yeast found during soy sauce fermentation, also produces HEMF effectively, suggesting that acetaldehyde accumulation might be a benchmark for breeding industrial yeasts with excellent HEMF production abilities. PMID:25362059

  16. Screening of high-level 4-hydroxy-2 (or 5)-ethyl-5 (or 2)-methyl-3(2H)-furanone-producing strains from a collection of gene deletion mutants of Saccharomyces cerevisiae.

    PubMed

    Uehara, Kenji; Watanabe, Jun; Akao, Takeshi; Watanabe, Daisuke; Mogi, Yoshinobu; Shimoi, Hitoshi

    2015-01-01

    4-Hydroxy-2 (or 5)-ethyl-5 (or 2)-methyl-3(2H)-furanone (HEMF) is an important flavor compound that contributes to the sensory properties of many natural products, particularly soy sauce and soybean paste. The compound exhibits a caramel-like aroma and several important physiological activities, such as strong antioxidant activity. HEMF is produced by yeast species in soy sauce manufacturing; however, the enzymes involved in HEMF production remain unknown, hindering efforts to breed yeasts with high-level HEMF production. In this study, we identified high-level HEMF-producing mutants among a Saccharomyces cerevisiae gene deletion mutant collection. Fourteen deletion mutants were screened as high-level HEMF-producing mutants, and the ADH1 gene deletion mutant (adh1Δ) exhibited the maximum HEMF production capacity. Further investigations of the adh1Δ mutant implied that acetaldehyde accumulation contributes to HEMF production, agreeing with previous findings. Therefore, acetaldehyde might be a precursor for HEMF. The ADH1 gene deletion mutant of Zygosaccharomyces rouxii, which is the dominant strain of yeast found during soy sauce fermentation, also produces HEMF effectively, suggesting that acetaldehyde accumulation might be a benchmark for breeding industrial yeasts with excellent HEMF production abilities. PMID:25362059

  17. Absolute partial photoionization cross sections of ozone.

    SciTech Connect

    Berkowitz, J.; Chemistry

    2008-04-01

    Despite the current concerns about ozone, absolute partial photoionization cross sections for this molecule in the vacuum ultraviolet (valence) region have been unavailable. By eclectic re-evaluation of old/new data and plausible assumptions, such cross sections have been assembled to fill this void.

  18. Solving Absolute Value Equations Algebraically and Geometrically

    ERIC Educational Resources Information Center

    Shiyuan, Wei

    2005-01-01

    The way in which students can improve their comprehension by understanding the geometrical meaning of algebraic equations or solving algebraic equation geometrically is described. Students can experiment with the conditions of the absolute value equation presented, for an interesting way to form an overall understanding of the concept.

  19. Teaching Absolute Value Inequalities to Mature Students

    ERIC Educational Resources Information Center

    Sierpinska, Anna; Bobos, Georgeana; Pruncut, Andreea

    2011-01-01

    This paper gives an account of a teaching experiment on absolute value inequalities, whose aim was to identify characteristics of an approach that would realize the potential of the topic to develop theoretical thinking in students enrolled in prerequisite mathematics courses at a large, urban North American university. The potential is…

  20. Increasing Capacity: Practice Effects in Absolute Identification

    ERIC Educational Resources Information Center

    Dodds, Pennie; Donkin, Christopher; Brown, Scott D.; Heathcote, Andrew

    2011-01-01

    In most of the long history of the study of absolute identification--since Miller's (1956) seminal article--a severe limit on performance has been observed, and this limit has resisted improvement even by extensive practice. In a startling result, Rouder, Morey, Cowan, and Pfaltz (2004) found substantially improved performance with practice in the…

  1. On Relative and Absolute Conviction in Mathematics

    ERIC Educational Resources Information Center

    Weber, Keith; Mejia-Ramos, Juan Pablo

    2015-01-01

    Conviction is a central construct in mathematics education research on justification and proof. In this paper, we claim that it is important to distinguish between absolute conviction and relative conviction. We argue that researchers in mathematics education frequently have not done so and this has lead to researchers making unwarranted claims…

  2. Absolute Points for Multiple Assignment Problems

    ERIC Educational Resources Information Center

    Adlakha, V.; Kowalski, K.

    2006-01-01

    An algorithm is presented to solve multiple assignment problems in which a cost is incurred only when an assignment is made at a given cell. The proposed method recursively searches for single/group absolute points to identify cells that must be loaded in any optimal solution. Unlike other methods, the first solution is the optimal solution. The…

  3. Nonequilibrium equalities in absolutely irreversible processes

    NASA Astrophysics Data System (ADS)

    Murashita, Yuto; Funo, Ken; Ueda, Masahito

    2015-03-01

    Nonequilibrium equalities have attracted considerable attention in the context of statistical mechanics and information thermodynamics. Integral nonequilibrium equalities reveal an ensemble property of the entropy production σ as = 1 . Although nonequilibrium equalities apply to rather general nonequilibrium situations, they break down in absolutely irreversible processes, where the forward-path probability vanishes and the entropy production diverges. We identify the mathematical origins of this inapplicability as the singularity of probability measure. As a result, we generalize conventional integral nonequilibrium equalities to absolutely irreversible processes as = 1 -λS , where λS is the probability of the singular part defined based on Lebesgue's decomposition theorem. The acquired equality contains two physical quantities related to irreversibility: σ characterizing ordinary irreversibility and λS describing absolute irreversibility. An inequality derived from the obtained equality demonstrates the absolute irreversibility leads to the fundamental lower bound on the entropy production. We demonstrate the validity of the obtained equality for a simple model.

  4. Stimulus Probability Effects in Absolute Identification

    ERIC Educational Resources Information Center

    Kent, Christopher; Lamberts, Koen

    2016-01-01

    This study investigated the effect of stimulus presentation probability on accuracy and response times in an absolute identification task. Three schedules of presentation were used to investigate the interaction between presentation probability and stimulus position within the set. Data from individual participants indicated strong effects of…

  5. Precision absolute positional measurement of laser beams.

    PubMed

    Fitzsimons, Ewan D; Bogenstahl, Johanna; Hough, James; Killow, Christian J; Perreur-Lloyd, Michael; Robertson, David I; Ward, Henry

    2013-04-20

    We describe an instrument which, coupled with a suitable coordinate measuring machine, facilitates the absolute measurement within the machine frame of the propagation direction of a millimeter-scale laser beam to an accuracy of around ±4 μm in position and ±20 μrad in angle. PMID:23669658

  6. DNA Methylation Variation Trends during the Embryonic Development of Chicken

    PubMed Central

    Li, Shizhao; Zhu, Yufei; Zhi, Lihui; Han, Xiaoying; Shen, Jing; Liu, Yanli; Yao, Junhu; Yang, Xiaojun

    2016-01-01

    The embryogenesis period is critical for epigenetic reprogramming and is thus of great significance in the research field of poultry epigenetics for elucidation of the trends in DNA methylation variations during the embryonic development of birds, particularly due to differences in embryogenesis between birds and mammals. Here, we first examined the variations in genomic DNA methylation during chicken embryogenesis through high-performance liquid chromatography using broilers as the model organism. We then identified the degree of DNA methylation of the promoters and gene bodies involved in two specific genes (IGF2 and TNF-α) using the bisulfite sequencing polymerase chain reaction method. In addition, we measured the expression levels of IGF2, TNF-α and DNA methyltransferase (DNMT) 1, 3a and 3b. Our results showed that the genomic DNA methylation levels in the liver, heart and muscle increased during embryonic development and that the methylation level of the liver was significantly higher in mid-anaphase. In both the muscle and liver, the promoter methylation levels of TNF-α first increased and then decreased, whereas the gene body methylation levels remained lower at embryonic ages E8, 11 and 14 before increasing notably at E17. The promoter methylation level of IGF2 decreased persistently, whereas the methylation levels in the gene body showed a continuous increase. No differences in the expression of TNF-α were found among E8, 11 and 14, whereas a significant increase was observed at E17. IGF2 showed increasing expression level during the examined embryonic stages. In addition, the mRNA and protein levels of DNMTs increased with increasing embryonic ages. These results suggest that chicken shows increasing genomic DNA methylation patterns during the embryonic period. Furthermore, the genomic DNA methylation levels in tissues are closely related to the genes expression levels, and gene expression may be simultaneously regulated by promoter hypomethylation

  7. [Accidental methyl alcohol poisoning].

    PubMed

    Xiao, J H

    1990-05-01

    An accidental poisoning due to drinking methyl alcohol in Chaoyang county is reported, analysing the accident. The poison came from the "retail white spirit" which was contaminated with methyl alcohol. Twenty-nine persons drank the wine, fourteen of them died, two of them became blind. After drinking this "retail white spirit" the drinkers showed symptoms of vertigo, headache, weakness, vomiting, night sweat, dyspnea and blurring of vision etc. within 6-120 hours. On examining the remaining spirit, we found the content of methyl alcohol to be between 16.6 and 40.69 g/100 ml. Some of the patients' urine and blood also contained methyl alcohol. We reckoned that each one of the twenty patients had taken more than 27 g of methyl alcohol and each of the ten dead drank more than 40 ml of the alcohol. PMID:2253526

  8. Imaging Histone Methylations in Living Animals.

    PubMed

    Sekar, Thillai V; Paulmurugan, Ramasamy

    2016-01-01

    Histone modifications (methylation, acetylation, phosphorylation, sumoylation, etc.,) are at the heart of cellular regulatory mechanisms, which control expression of genes in an orderly fashion and control the entire cellular regulatory networks. Histone lysine methylation has been identified as one of the several posttranslational histone modifications that plays crucial role in regulating gene expressions in facultative heterochromatic DNA regions while maintaining structural integrity in constitutive heterochromatic DNA regions. Since histone methylation is dysregulated in various cellular diseases, it has been considered a potential therapeutic target for drug development. Currently there is no simple method available to screen and preclinically evaluate drugs modulating this cellular process, we recently developed two different methods by adopting reporter gene technology to screen drugs and to preclinically evaluate them in living animals. Method detects and quantitatively monitors the level of histone methylations in intact cells, is of a prerequisite to screen small molecules that modulate histone lysine methylation. Here, we describe two independent optical imaging sensors developed to image histone methylations in cells and in living animals. Since we used standard PCR-based cloning strategies to construct different plasmid vectors shown in this chapter, we are not providing any details regarding the construction methods, instead, we focus on detailing various methods used for measuring histone methylation-assisted luciferase quantitation in cells and imaging in living animals. PMID:27424907

  9. DNA methylation-mediated down-regulation of DNA methyltransferase-1 (DNMT1) is coincident with, but not essential for, global hypomethylation in human placenta.

    PubMed

    Novakovic, Boris; Wong, Nick C; Sibson, Mandy; Ng, Hong-Kiat; Morley, Ruth; Manuelpillai, Ursula; Down, Thomas; Rakyan, Vardhman K; Beck, Stephan; Hiendleder, Stefan; Roberts, Claire T; Craig, Jeffrey M; Saffery, Richard

    2010-03-26

    The genome of extraembryonic tissue, such as the placenta, is hypomethylated relative to that in somatic tissues. However, the origin and role of this hypomethylation remains unclear. The DNA methyltransferases DNMT1, -3A, and -3B are the primary mediators of the establishment and maintenance of DNA methylation in mammals. In this study, we investigated promoter methylation-mediated epigenetic down-regulation of DNMT genes as a potential regulator of global methylation levels in placental tissue. Although DNMT3A and -3B promoters lack methylation in all somatic and extraembryonic tissues tested, we found specific hypermethylation of the maintenance DNA methyltransferase (DNMT1) gene and found hypomethylation of the DNMT3L gene in full term and first trimester placental tissues. Bisulfite DNA sequencing revealed monoallelic methylation of DNMT1, with no evidence of imprinting (parent of origin effect). In vitro reporter experiments confirmed that DNMT1 promoter methylation attenuates transcriptional activity in trophoblast cells. However, global hypomethylation in the absence of DNMT1 down-regulation is apparent in non-primate placentas and in vitro derived human cytotrophoblast stem cells, suggesting that DNMT1 down-regulation is not an absolute requirement for genomic hypomethylation in all instances. These data represent the first demonstration of methylation-mediated regulation of the DNMT1 gene in any system and demonstrate that the unique epigenome of the human placenta includes down-regulation of DNMT1 with concomitant hypomethylation of the DNMT3L gene. This strongly implicates epigenetic regulation of the DNMT gene family in the establishment of the unique epigenetic profile of extraembryonic tissue in humans. PMID:20071334

  10. Combined Use of Absolute and Differential Seismic Arrival Time Data to Improve Absolute Event Location

    NASA Astrophysics Data System (ADS)

    Myers, S.; Johannesson, G.

    2012-12-01

    Arrival time measurements based on waveform cross correlation are becoming more common as advanced signal processing methods are applied to seismic data archives and real-time data streams. Waveform correlation can precisely measure the time difference between the arrival of two phases, and differential time data can be used to constrain relative location of events. Absolute locations are needed for many applications, which generally requires the use of absolute time data. Current methods for measuring absolute time data are approximately two orders of magnitude less precise than differential time measurements. To exploit the strengths of both absolute and differential time data, we extend our multiple-event location method Bayesloc, which previously used absolute time data only, to include the use of differential time measurements that are based on waveform cross correlation. Fundamentally, Bayesloc is a formulation of the joint probability over all parameters comprising the multiple event location system. The Markov-Chain Monte Carlo method is used to sample from the joint probability distribution given arrival data sets. The differential time component of Bayesloc includes scaling a stochastic estimate of differential time measurement precision based the waveform correlation coefficient for each datum. For a regional-distance synthetic data set with absolute and differential time measurement error of 0.25 seconds and 0.01 second, respectively, epicenter location accuracy is improved from and average of 1.05 km when solely absolute time data are used to 0.28 km when absolute and differential time data are used jointly (73% improvement). The improvement in absolute location accuracy is the result of conditionally limiting absolute location probability regions based on the precise relative position with respect to neighboring events. Bayesloc estimates of data precision are found to be accurate for the synthetic test, with absolute and differential time measurement

  11. The new Absolute Quantum Gravimeter (AQG): first results and perspectives

    NASA Astrophysics Data System (ADS)

    Bonvalot, Sylvain; Le Moigne, Nicolas; Merlet, Sebastien; Desruelle, Bruno; Lautier-Gaud, Jean; Menoret, Vincent; Vermeulen, Pierre

    2016-04-01

    Cold atom gravimetry represents one of the most innovative evolution in gravity instrumentation since the last 20 years. The concept of measuring the gravitational acceleration by dropping atoms and the development of the first instrumental devices during this last decade quickly revealed the promising perspectives of this new generation of gravity meters enabling accurate and absolute measurements of the Earth's gravity field for a wide range of applications (geophysics, geodesy, metrology, etc.). The Absolute Quantum Gravimeter (AQG) gravity meter, developed by MUQUANS (Talence, France - http://www.muquans.com/) with the support of RESIF, the French Seismologic and Geodetic Network (http://www.resif.fr/) belongs to this new generation of instruments. It also represents the first commercial device based on the utilization of advanced matter-wave interferometry techniques, which allow to characterize precisely the vertical acceleration experienced by a cloud of cold atoms. Recently, the first operational unit (AQG01) has been achieved as a compact transportable gravimeter with the aim of satisfying absolute gravity measurements in laboratory conditions under the following specifications: measurements the μGal level at a few Hz cycling frequency, sensitivity of 50μGal/√Hz, immunity to ground vibrations, easy and quickness of operation, automated continuous data acquisition for several months, etc. In order to evaluate the current performances of the AQG01, several experiments are carried out in collaboration between RESIF user's teams and the MUQUANS manufacturer on different reference gravity sites and laboratories in France. These measurements performed in indoor conditions including simultaneous observations with classical reference gravity instruments (corner-cube absolute gravity meters, relative superconducting meters) as well with the Cold Atom Gravity meter (CAG) developed by LNE-SYRTE, lead to a first objective characterization of the performances of

  12. Methods in DNA methylation profiling

    PubMed Central

    Zuo, Tao; Tycko, Benjamin; Liu, Ta-Ming; Lin, Huey-Jen L; Huang, Tim H-M

    2010-01-01

    Metastable and somatically heritable patterns of DNA methylation provide an important level of genomic regulation. In this article, we review methods for analyzing these genome-wide epigenetic patterns and offer a perspective on the ever-expanding literature, which we hope will be useful for investigators who are new to this area. The historical aspects that we cover will be helpful in interpreting this literature and we hope that our discussion of the newest analytical methods will stimulate future progress. We emphasize that no single approach can provide a complete view of the overall methylome, and that combinations of several modalities applied to the same sample set will give the clearest picture. Given the unexpected epigenomic patterns and new biological principles, as well as new disease markers, that have been uncovered in recent studies, it is likely that important discoveries will continue to be made using genome-wide DNA methylation profiling. PMID:20526417

  13. Methyl-CpG-binding domain sequencing reveals a prognostic methylation signature in neuroblastoma

    PubMed Central

    Decock, Anneleen; Ongenaert, Maté; Cannoodt, Robrecht; Verniers, Kimberly; De Wilde, Bram; Laureys, Geneviève; Van Roy, Nadine; Berbegall, Ana P.; Bienertova-Vasku, Julie; Bown, Nick; Clément, Nathalie; Combaret, Valérie; Haber, Michelle; Hoyoux, Claire; Murray, Jayne; Noguera, Rosa; Pierron, Gaelle; Schleiermacher, Gudrun; Schulte, Johannes H.; Stallings, Ray L.; Tweddle, Deborah A.; De Preter, Katleen; Speleman, Frank; Vandesompele, Jo

    2016-01-01

    Accurate assessment of neuroblastoma outcome prediction remains challenging. Therefore, this study aims at establishing novel prognostic tumor DNA methylation biomarkers. In total, 396 low- and high-risk primary tumors were analyzed, of which 87 were profiled using methyl-CpG-binding domain (MBD) sequencing for differential methylation analysis between prognostic patient groups. Subsequently, methylation-specific PCR (MSP) assays were developed for 78 top-ranking differentially methylated regions and tested on two independent cohorts of 132 and 177 samples, respectively. Further, a new statistical framework was used to identify a robust set of MSP assays of which the methylation score (i.e. the percentage of methylated assays) allows accurate outcome prediction. Survival analyses were performed on the individual target level, as well as on the combined multimarker signature. As a result of the differential DNA methylation assessment by MBD sequencing, 58 of the 78 MSP assays were designed in regions previously unexplored in neuroblastoma, and 36 are located in non-promoter or non-coding regions. In total, 5 individual MSP assays (located in CCDC177, NXPH1, lnc-MRPL3-2, lnc-TREX1-1 and one on a region from chromosome 8 with no further annotation) predict event-free survival and 4 additional assays (located in SPRED3, TNFAIP2, NPM2 and CYYR1) also predict overall survival. Furthermore, a robust 58-marker methylation signature predicting overall and event-free survival was established. In conclusion, this study encompasses the largest DNA methylation biomarker study in neuroblastoma so far. We identified and independently validated several novel prognostic biomarkers, as well as a prognostic 58-marker methylation signature. PMID:26646589

  14. Methyl-CpG-binding domain sequencing reveals a prognostic methylation signature in neuroblastoma.

    PubMed

    Decock, Anneleen; Ongenaert, Maté; Cannoodt, Robrecht; Verniers, Kimberly; De Wilde, Bram; Laureys, Geneviève; Van Roy, Nadine; Berbegall, Ana P; Bienertova-Vasku, Julie; Bown, Nick; Clément, Nathalie; Combaret, Valérie; Haber, Michelle; Hoyoux, Claire; Murray, Jayne; Noguera, Rosa; Pierron, Gaelle; Schleiermacher, Gudrun; Schulte, Johannes H; Stallings, Ray L; Tweddle, Deborah A; De Preter, Katleen; Speleman, Frank; Vandesompele, Jo

    2016-01-12

    Accurate assessment of neuroblastoma outcome prediction remains challenging. Therefore, this study aims at establishing novel prognostic tumor DNA methylation biomarkers. In total, 396 low- and high-risk primary tumors were analyzed, of which 87 were profiled using methyl-CpG-binding domain (MBD) sequencing for differential methylation analysis between prognostic patient groups. Subsequently, methylation-specific PCR (MSP) assays were developed for 78 top-ranking differentially methylated regions and tested on two independent cohorts of 132 and 177 samples, respectively. Further, a new statistical framework was used to identify a robust set of MSP assays of which the methylation score (i.e. the percentage of methylated assays) allows accurate outcome prediction. Survival analyses were performed on the individual target level, as well as on the combined multimarker signature. As a result of the differential DNA methylation assessment by MBD sequencing, 58 of the 78 MSP assays were designed in regions previously unexplored in neuroblastoma, and 36 are located in non-promoter or non-coding regions. In total, 5 individual MSP assays (located in CCDC177, NXPH1, lnc-MRPL3-2, lnc-TREX1-1 and one on a region from chromosome 8 with no further annotation) predict event-free survival and 4 additional assays (located in SPRED3, TNFAIP2, NPM2 and CYYR1) also predict overall survival. Furthermore, a robust 58-marker methylation signature predicting overall and event-free survival was established. In conclusion, this study encompasses the largest DNA methylation biomarker study in neuroblastoma so far. We identified and independently validated several novel prognostic biomarkers, as well as a prognostic 58-marker methylation signature. PMID:26646589

  15. DNA methylation in plants.

    PubMed

    Vanyushin, B F

    2006-01-01

    DNA in plants is highly methylated, containing 5-methylcytosine (m5C) and N6-methyladenine (m6A); m5C is located mainly in symmetrical CG and CNG sequences but it may occur also in other non-symmetrical contexts. m6A but not m5C was found in plant mitochondrial DNA. DNA methylation in plants is species-, tissue-, organelle- and age-specific. It is controlled by phytohormones and changes on seed germination, flowering and under the influence of various pathogens (viral, bacterial, fungal). DNA methylation controls plant growth and development, with particular involvement in regulation of gene expression and DNA replication. DNA replication is accompanied by the appearance of under-methylated, newly formed DNA strands including Okazaki fragments; asymmetry of strand DNA methylation disappears until the end of the cell cycle. A model for regulation of DNA replication by methylation is suggested. Cytosine DNA methylation in plants is more rich and diverse compared with animals. It is carried out by the families of specific enzymes that belong to at least three classes of DNA methyltransferases. Open reading frames (ORF) for adenine DNA methyltransferases are found in plant and animal genomes, and a first eukaryotic (plant) adenine DNA methyltransferase (wadmtase) is described; the enzyme seems to be involved in regulation of the mitochondria replication. Like in animals, DNA methylation in plants is closely associated with histone modifications and it affects binding of specific proteins to DNA and formation of respective transcription complexes in chromatin. The same gene (DRM2) in Arabidopsis thaliana is methylated both at cytosine and adenine residues; thus, at least two different, and probably interdependent, systems of DNA modification are present in plants. Plants seem to have a restriction-modification (R-M) system. RNA-directed DNA methylation has been observed in plants; it involves de novo methylation of almost all cytosine residues in a region of si

  16. Brain-specific Phgdh deletion reveals a pivotal role for L-serine biosynthesis in controlling the level of D-serine, an N-methyl-D-aspartate receptor co-agonist, in adult brain.

    PubMed

    Yang, Jung Hoon; Wada, Akira; Yoshida, Kazuyuki; Miyoshi, Yurika; Sayano, Tomoko; Esaki, Kayoko; Kinoshita, Masami O; Tomonaga, Shozo; Azuma, Norihiro; Watanabe, Masahiko; Hamase, Kenji; Zaitsu, Kiyoshi; Machida, Takeo; Messing, Albee; Itohara, Shigeyoshi; Hirabayashi, Yoshio; Furuya, Shigeki

    2010-12-31

    In mammalian brain, D-serine is synthesized from L-serine by serine racemase, and it functions as an obligatory co-agonist at the glycine modulatory site of N-methyl-D-aspartate (NMDA)-selective glutamate receptors. Although diminution in D-serine level has been implicated in NMDA receptor hypofunction, which is thought to occur in schizophrenia, the source of the precursor L-serine and its role in D-serine metabolism in adult brain have yet to be determined. We investigated whether L-serine synthesized in brain via the phosphorylated pathway is essential for D-serine synthesis by generating mice with a conditional deletion of D-3-phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95). This enzyme catalyzes the first step in L-serine synthesis via the phosphorylated pathway. HPLC analysis of serine enantiomers demonstrated that both L- and D-serine levels were markedly decreased in the cerebral cortex and hippocampus of conditional knock-out mice, whereas the serine deficiency did not alter protein expression levels of serine racemase and NMDA receptor subunits in these regions. The present study provides definitive proof that L-serine-synthesized endogenously via the phosphorylated pathway is a key rate-limiting factor for maintaining steady-state levels of D-serine in adult brain. Furthermore, NMDA-evoked transcription of Arc, an immediate early gene, was diminished in the hippocampus of conditional knock-out mice. Thus, this study demonstrates that in mature neuronal circuits L-serine availability determines the rate of D-serine synthesis in the forebrain and controls NMDA receptor function at least in the hippocampus. PMID:20966073

  17. Dietary and lifestyle factors of DNA methylation.

    PubMed

    Lim, Unhee; Song, Min-Ae

    2012-01-01

    Lifestyle factors, such as diet, smoking, physical activity, and body weight management, are known to constitute the majority of cancer causes. Epigenetics has been widely proposed as a main mechanism that mediates the reversible effects of dietary and lifestyle factors on carcinogenesis. This chapter reviews human studies on potential dietary and lifestyle determinants of DNA methylation. Apart from a few prospective investigations and interventions of limited size and duration, evidence mostly comes from cross-sectional observational studies and supports some associations. Studies to date suggest that certain dietary components may alter genomic and gene-specific DNA methylation levels in systemic and target tissues, affecting genomic stability and transcription of tumor suppressors and oncogenes. Most data and supportive evidence exist for folate, a key nutritional factor in one-carbon metabolism that supplies the methyl units for DNA methylation. Other candidate bioactive food components include alcohol and other key nutritional factors of one-carbon metabolism, polyphenols and flavonoids in green tea, phytoestrogen, and lycopene. Some data also support a link of DNA methylation with physical activity and energy balance. Effects of dietary and lifestyle exposures on DNA methylation may be additionally modified by common genetic variants, environmental carcinogens, and infectious agents, an aspect that remains largely unexplored. In addition, growing literature supports that the environmental conditions during critical developmental stages may influence later risk of metabolic disorders in part through persistent programming of DNA methylation. Further research of these modifiable determinants of DNA methylation will improve our understanding of cancer etiology and may present certain DNA methylation markers as attractive surrogate endpoints for prevention research. Considering the plasticity of epigenetic marks and correlated nature of lifestyle factors, more

  18. A genetic sensor for strong methylating compounds

    PubMed Central

    Moser, Felix; Horwitz, Andrew; Chen, Jacinto; Lim, Wendell A.; Voigt, Christopher A.

    2013-01-01

    Methylating chemicals are common in industry and agriculture and are often toxic, partly due to their propensity to methylate DNA. The Escherichia coli Ada protein detects methylating compounds by sensing aberrant methyl adducts on the phosphoester backbone of DNA. We characterize this system as a genetic sensor and engineer it to lower the detection threshold. By overexpressing Ada from a plasmid, we improve the sensor’s dynamic range to 350-fold induction and lower its detection threshold to 40 µM for methyl iodide. In eukaryotes, there is no known sensor of methyl adducts on the phosphoester backbone of DNA. By fusing the N-terminal domain of Ada to the Gal4 transcriptional activation domain, we built a functional sensor for methyl phosphotriester adducts in Saccharomyces cerevisiae. This sensor can be tuned to variable specifications by altering the expression level of the chimeric sensor and changing the number of Ada operators upstream of the Gal4-sensitive reporter promoter. These changes result in a detection threshold of 28 µM and 5.2-fold induction in response to methyl iodide. When the yeast sensor is exposed to different SN1 and SN2 alkylating compounds, its response profile is similar to that observed for the native Ada protein in E. coli, indicating that its native function is retained in yeast. Finally, we demonstrate that the specifications achieved for the yeast sensor are suitable for detecting methylating compounds at relevant concentrations in environmental samples. This work demonstrates the movement of a sensor from a prokaryotic to eukaryotic system and its rational tuning to achieve desired specifications. PMID:24032656

  19. Evolutionary patterns of genic DNA methylation vary across land plants.

    PubMed

    Takuno, Shohei; Ran, Jin-Hua; Gaut, Brandon S

    2016-01-01

    Little is known about patterns of genic DNA methylation across the plant kingdom or about the evolutionary processes that shape them. To characterize gene-body methylation (gbM) within exons, we have gathered single-base resolution methylome data that span the phylogenetic breadth of land plants. We find that a basal land plant, Marchantia polymorpha, lacks any evident signal of gbM within exons, but conifers have high levels of both CG and CHG (where H is A, C or T) methylation in expressed genes. To begin to understand the evolutionary forces that shape gbM, we first tested for correlations in methylation levels across orthologues(1,2). Genic CG methylation levels, but not CHG or CHH levels, are correlated across orthologues for species as distantly related as ferns and angiosperms. Hence, relative levels of CG methylation are a consistent property across genes, even for species that diverged ∼400 million years ago(3,4). In contrast, genic CHG methylation correlates with genome size, suggesting that the host epigenetic response to transposable elements also affects genes. Altogether, our data indicate that the evolutionary forces acting on DNA methylation vary substantially across species, genes and methylation contexts. PMID:27249194

  20. Quantitative DNA methylation analysis of candidate genes in cervical cancer.

    PubMed

    Siegel, Erin M; Riggs, Bridget M; Delmas, Amber L; Koch, Abby; Hakam, Ardeshir; Brown, Kevin D

    2015-01-01

    Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens. Bisulfite-modified genomic DNA was amplified and quantitative pyrosequencing completed for 10 genes (APC, CCNA, CDH1, CDH13, WIF1, TIMP3, DAPK1, RARB, FHIT, and SLIT2). A Methylation Index was calculated as the mean percent methylation across all CpG sites analyzed per gene (~4-9 CpG site) per sequence. A binary cut-point was defined at >15% methylation. Sensitivity, specificity and area under ROC curve (AUC) of methylation in individual genes or a panel was examined. The median methylation index was significantly higher in cases compared to controls in 8 genes, whereas there was no difference in median methylation for 2 genes. Compared to HPV and age, the combination of DNA methylation level of DAPK1, SLIT2, WIF1 and RARB with HPV and age significantly improved the AUC from 0.79 to 0.99 (95% CI: 0.97-1.00, p-value = 0.003). Pyrosequencing analysis confirmed that several genes are common targets for aberrant methylation in cervical cancer and DNA methylation level of four genes appears to increase specificity to identify cancer compared to HPV detection alone. Alterations in DNA methylation of specific genes in cervical cancers, such as DAPK1, RARB, WIF1, and SLIT2, may also occur early in cervical carcinogenesis and should be evaluated. PMID:25826459

  1. Quantitative DNA Methylation Analysis of Candidate Genes in Cervical Cancer

    PubMed Central

    Siegel, Erin M.; Riggs, Bridget M.; Delmas, Amber L.; Koch, Abby; Hakam, Ardeshir; Brown, Kevin D.

    2015-01-01

    Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens. Bisulfite-modified genomic DNA was amplified and quantitative pyrosequencing completed for 10 genes (APC, CCNA, CDH1, CDH13, WIF1, TIMP3, DAPK1, RARB, FHIT, and SLIT2). A Methylation Index was calculated as the mean percent methylation across all CpG sites analyzed per gene (~4-9 CpG site) per sequence. A binary cut-point was defined at >15% methylation. Sensitivity, specificity and area under ROC curve (AUC) of methylation in individual genes or a panel was examined. The median methylation index was significantly higher in cases compared to controls in 8 genes, whereas there was no difference in median methylation for 2 genes. Compared to HPV and age, the combination of DNA methylation level of DAPK1, SLIT2, WIF1 and RARB with HPV and age significantly improved the AUC from 0.79 to 0.99 (95% CI: 0.97–1.00, p-value = 0.003). Pyrosequencing analysis confirmed that several genes are common targets for aberrant methylation in cervical cancer and DNA methylation level of four genes appears to increase specificity to identify cancer compared to HPV detection alone. Alterations in DNA methylation of specific genes in cervical cancers, such as DAPK1, RARB, WIF1, and SLIT2, may also occur early in cervical carcinogenesis and should be evaluated. PMID:25826459

  2. Methylation plotter: a web tool for dynamic visualization of DNA methylation data

    PubMed Central

    2014-01-01

    Methylation plotter is a Web tool that allows the visualization of methylation data in a user-friendly manner and with publication-ready quality. The user is asked to introduce a file containing the methylation status of a genomic region. This file can contain up to 100 samples and 100 CpGs. Optionally, the user can assign a group for each sample (i.e. whether a sample is a tumoral or normal tissue). After the data upload, the tool produces different graphical representations of the results following the most commonly used styles to display this type of data. They include an interactive plot that summarizes the status of every CpG site and for every sample in lollipop or grid styles. Methylation values ranging from 0 (unmethylated) to 1 (fully methylated) are represented using a gray color gradient. A practical feature of the tool allows the user to choose from different types of arrangement of the samples in the display: for instance, sorting by overall methylation level, by group, by unsupervised clustering or just following the order in which data were entered. In addition to the detailed plot, Methylation plotter produces a methylation profile plot that summarizes the status of the scrutinized region, a boxplot that sums up the differences between groups (if any) and a dendrogram that classifies the data by unsupervised clustering. Coupled with this analysis, descriptive statistics and testing for differences at both CpG and group levels are provided. The implementation is based in R/shiny, providing a highly dynamic user interface that generates quality graphics without the need of writing R code. Methylation plotter is freely available at http://gattaca.imppc.org:3838/methylation_plotter/. PMID:25260021

  3. Methylation plotter: a web tool for dynamic visualization of DNA methylation data.

    PubMed

    Mallona, Izaskun; Díez-Villanueva, Anna; Peinado, Miguel A

    2014-01-01

    Methylation plotter is a Web tool that allows the visualization of methylation data in a user-friendly manner and with publication-ready quality. The user is asked to introduce a file containing the methylation status of a genomic region. This file can contain up to 100 samples and 100 CpGs. Optionally, the user can assign a group for each sample (i.e. whether a sample is a tumoral or normal tissue). After the data upload, the tool produces different graphical representations of the results following the most commonly used styles to display this type of data. They include an interactive plot that summarizes the status of every CpG site and for every sample in lollipop or grid styles. Methylation values ranging from 0 (unmethylated) to 1 (fully methylated) are represented using a gray color gradient. A practical feature of the tool allows the user to choose from different types of arrangement of the samples in the display: for instance, sorting by overall methylation level, by group, by unsupervised clustering or just following the order in which data were entered. In addition to the detailed plot, Methylation plotter produces a methylation profile plot that summarizes the status of the scrutinized region, a boxplot that sums up the differences between groups (if any) and a dendrogram that classifies the data by unsupervised clustering. Coupled with this analysis, descriptive statistics and testing for differences at both CpG and group levels are provided. The implementation is based in R/shiny, providing a highly dynamic user interface that generates quality graphics without the need of writing R code. Methylation plotter is freely available at http://gattaca.imppc.org:3838/methylation_plotter/. PMID:25260021

  4. MethylAction: detecting differentially methylated regions that distinguish biological subtypes

    PubMed Central

    Bhasin, Jeffrey M.; Hu, Bo; Ting, Angela H.

    2016-01-01

    DNA methylation differences capture substantial information about the molecular and gene-regulatory states among biological subtypes. Enrichment-based next generation sequencing methods such as MBD-isolated genome sequencing (MiGS) and MeDIP-seq are appealing for studying DNA methylation genome-wide in order to distinguish between biological subtypes. However, current analytic tools do not provide optimal features for analyzing three-group or larger study designs. MethylAction addresses this need by detecting all possible patterns of statistically significant hyper- and hypo- methylation in comparisons involving any number of groups. Crucially, significance is established at the level of differentially methylated regions (DMRs), and bootstrapping determines false discovery rates (FDRs) associated with each pattern. We demonstrate this functionality in a four-group comparison among benign prostate and three clinical subtypes of prostate cancer and show that the bootstrap FDRs are highly useful in selecting the most robust patterns of DMRs. Compared to existing tools that are limited to two-group comparisons, MethylAction detects more DMRs with strong differential methylation measurements confirmed by whole genome bisulfite sequencing and offers a better balance between precision and recall in cross-cohort comparisons. MethylAction is available as an R package at http://jeffbhasin.github.io/methylaction. PMID:26673711

  5. MethylAction: detecting differentially methylated regions that distinguish biological subtypes.

    PubMed

    Bhasin, Jeffrey M; Hu, Bo; Ting, Angela H

    2016-01-01

    DNA methylation differences capture substantial information about the molecular and gene-regulatory states among biological subtypes. Enrichment-based next generation sequencing methods such as MBD-isolated genome sequencing (MiGS) and MeDIP-seq are appealing for studying DNA methylation genome-wide in order to distinguish between biological subtypes. However, current analytic tools do not provide optimal features for analyzing three-group or larger study designs. MethylAction addresses this need by detecting all possible patterns of statistically significant hyper- and hypo- methylation in comparisons involving any number of groups. Crucially, significance is established at the level of differentially methylated regions (DMRs), and bootstrapping determines false discovery rates (FDRs) associated with each pattern. We demonstrate this functionality in a four-group comparison among benign prostate and three clinical subtypes of prostate cancer and show that the bootstrap FDRs are highly useful in selecting the most robust patterns of DMRs. Compared to existing tools that are limited to two-group comparisons, MethylAction detects more DMRs with strong differential methylation measurements confirmed by whole genome bisulfite sequencing and offers a better balance between precision and recall in cross-cohort comparisons. MethylAction is available as an R package at http://jeffbhasin.github.io/methylaction. PMID:26673711

  6. Absolute and relative dosimetry for ELIMED

    SciTech Connect

    Cirrone, G. A. P.; Schillaci, F.; Scuderi, V.; Cuttone, G.; Candiano, G.; Musumarra, A.; Pisciotta, P.; Romano, F.; Carpinelli, M.; Presti, D. Lo; Raffaele, L.; Tramontana, A.; Cirio, R.; Sacchi, R.; Monaco, V.; Marchetto, F.; Giordanengo, S.

    2013-07-26

    The definition of detectors, methods and procedures for the absolute and relative dosimetry of laser-driven proton beams is a crucial step toward the clinical use of this new kind of beams. Hence, one of the ELIMED task, will be the definition of procedures aiming to obtain an absolute dose measure at the end of the transport beamline with an accuracy as close as possible to the one required for clinical applications (i.e. of the order of 5% or less). Relative dosimetry procedures must be established, as well: they are necessary in order to determine and verify the beam dose distributions and to monitor the beam fluence and the energetic spectra during irradiations. Radiochromic films, CR39, Faraday Cup, Secondary Emission Monitor (SEM) and transmission ionization chamber will be considered, designed and studied in order to perform a fully dosimetric characterization of the ELIMED proton beam.

  7. Probing absolute spin polarization at the nanoscale.

    PubMed

    Eltschka, Matthias; Jäck, Berthold; Assig, Maximilian; Kondrashov, Oleg V; Skvortsov, Mikhail A; Etzkorn, Markus; Ast, Christian R; Kern, Klaus

    2014-12-10

    Probing absolute values of spin polarization at the nanoscale offers insight into the fundamental mechanisms of spin-dependent transport. Employing the Zeeman splitting in superconducting tips (Meservey-Tedrow-Fulde effect), we introduce a novel spin-polarized scanning tunneling microscopy that combines the probing capability of the absolute values of spin polarization with precise control at the atomic scale. We utilize our novel approach to measure the locally resolved spin polarization of magnetic Co nanoislands on Cu(111). We find that the spin polarization is enhanced by 65% when increasing the width of the tunnel barrier by only 2.3 Å due to the different decay of the electron orbitals into vacuum. PMID:25423049

  8. Absolute-magnitude distributions of supernovae

    SciTech Connect

    Richardson, Dean; Wright, John; Jenkins III, Robert L.; Maddox, Larry

    2014-05-01

    The absolute-magnitude distributions of seven supernova (SN) types are presented. The data used here were primarily taken from the Asiago Supernova Catalogue, but were supplemented with additional data. We accounted for both foreground and host-galaxy extinction. A bootstrap method is used to correct the samples for Malmquist bias. Separately, we generate volume-limited samples, restricted to events within 100 Mpc. We find that the superluminous events (M{sub B} < –21) make up only about 0.1% of all SNe in the bias-corrected sample. The subluminous events (M{sub B} > –15) make up about 3%. The normal Ia distribution was the brightest with a mean absolute blue magnitude of –19.25. The IIP distribution was the dimmest at –16.75.

  9. Asteroid absolute magnitudes and slope parameters

    NASA Technical Reports Server (NTRS)

    Tedesco, Edward F.

    1991-01-01

    A new listing of absolute magnitudes (H) and slope parameters (G) has been created and published in the Minor Planet Circulars; this same listing will appear in the 1992 Ephemerides of Minor Planets. Unlike previous listings, the values of the current list were derived from fits of data at the V band. All observations were reduced in the same fashion using, where appropriate, a single basis default value of 0.15 for the slope parameter. Distances and phase angles were computed for each observation. The data for 113 asteroids was of sufficiently high quality to permit derivation of their H and G. These improved absolute magnitudes and slope parameters will be used to deduce the most reliable bias-corrected asteroid size-frequency distribution yet made.

  10. Absolute enantioselective separation: optical activity ex machina.

    PubMed

    Bielski, Roman; Tencer, Michal

    2005-11-01

    The paper describes methodology of using three independent macroscopic factors affecting molecular orientation to accomplish separation of a racemic mixture without the presence of any other chiral compounds, i. e., absolute enantioselective separation (AES) which is an extension of a concept of applying these factors to absolute asymmetric synthesis. The three factors may be applied simultaneously or, if their effects can be retained, consecutively. The resulting three mutually orthogonal or near orthogonal directors constitute a true chiral influence and their scalar triple product is the measure of the chirality of the system. AES can be executed in a chromatography-like microfluidic process in the presence of an electric field. It may be carried out on a chemically modified flat surface, a monolithic polymer column made of a mesoporous material, each having imparted directional properties. Separation parameters were estimated for these media and possible implications for the natural homochirality are discussed. PMID:16342798

  11. An absolute measure for a key currency

    NASA Astrophysics Data System (ADS)

    Oya, Shunsuke; Aihara, Kazuyuki; Hirata, Yoshito

    It is generally considered that the US dollar and the euro are the key currencies in the world and in Europe, respectively. However, there is no absolute general measure for a key currency. Here, we investigate the 24-hour periodicity of foreign exchange markets using a recurrence plot, and define an absolute measure for a key currency based on the strength of the periodicity. Moreover, we analyze the time evolution of this measure. The results show that the credibility of the US dollar has not decreased significantly since the Lehman shock, when the Lehman Brothers bankrupted and influenced the economic markets, and has increased even relatively better than that of the euro and that of the Japanese yen.

  12. From Hubble's NGSL to Absolute Fluxes

    NASA Technical Reports Server (NTRS)

    Heap, Sara R.; Lindler, Don

    2012-01-01

    Hubble's Next Generation Spectral Library (NGSL) consists of R-l000 spectra of 374 stars of assorted temperature, gravity, and metallicity. Each spectrum covers the wavelength range, 0.18-1.00 microns. The library can be viewed and/or downloaded from the website, http://archive.stsci.edu/prepds/stisngsll. Stars in the NGSL are now being used as absolute flux standards at ground-based observatories. However, the uncertainty in the absolute flux is about 2%, which does not meet the requirements of dark-energy surveys. We are therefore developing an observing procedure that should yield fluxes with uncertainties less than 1 % and will take part in an HST proposal to observe up to 15 stars using this new procedure.

  13. Metallic Magnetic Calorimeters for Absolute Activity Measurement

    NASA Astrophysics Data System (ADS)

    Loidl, M.; Leblanc, E.; Rodrigues, M.; Bouchard, J.; Censier, B.; Branger, T.; Lacour, D.

    2008-05-01

    We present a prototype of metallic magnetic calorimeters that we are developing for absolute activity measurements of low energy emitting radionuclides. We give a detailed description of the realization of the prototype, containing an 55Fe source inside the detector absorber. We present the analysis of first data taken with this detector and compare the result of activity measurement with liquid scintillation counting. We also propose some ways for reducing the uncertainty on the activity determination with this new technique.

  14. Absolute photoionization cross sections of atomic oxygen

    NASA Technical Reports Server (NTRS)

    Samson, J. A. R.; Pareek, P. N.

    1985-01-01

    The absolute values of photoionization cross sections of atomic oxygen were measured from the ionization threshold to 120 A. An auto-ionizing resonance belonging to the 2S2P4(4P)3P(3Do, 3So) transition was observed at 479.43 A and another line at 389.97 A. The experimental data is in excellent agreement with rigorous close-coupling calculations that include electron correlations in both the initial and final states.

  15. Absolute photoionization cross sections of atomic oxygen

    NASA Technical Reports Server (NTRS)

    Samson, J. A. R.; Pareek, P. N.

    1982-01-01

    The absolute values of photoionization cross sections of atomic oxygen were measured from the ionization threshold to 120 A. An auto-ionizing resonance belonging to the 2S2P4(4P)3P(3Do, 3So) transition was observed at 479.43 A and another line at 389.97 A. The experimental data is in excellent agreement with rigorous close-coupling calculations that include electron correlations in both the initial and final states.

  16. Silicon Absolute X-Ray Detectors

    SciTech Connect

    Seely, John F.; Korde, Raj; Sprunck, Jacob; Medjoubi, Kadda; Hustache, Stephanie

    2010-06-23

    The responsivity of silicon photodiodes having no loss in the entrance window, measured using synchrotron radiation in the 1.75 to 60 keV range, was compared to the responsivity calculated using the silicon thickness measured using near-infrared light. The measured and calculated responsivities agree with an average difference of 1.3%. This enables their use as absolute x-ray detectors.

  17. Blood pressure targets and absolute cardiovascular risk.

    PubMed

    Odutayo, Ayodele; Rahimi, Kazem; Hsiao, Allan J; Emdin, Connor A

    2015-08-01

    In the Eighth Joint National Committee guideline on hypertension, the threshold for the initiation of blood pressure-lowering treatment for elderly adults (≥60 years) without chronic kidney disease or diabetes mellitus was raised from 140/90 mm Hg to 150/90 mm Hg. However, the committee was not unanimous in this decision, particularly because a large proportion of adults ≥60 years may be at high cardiovascular risk. On the basis of Eighth Joint National Committee guideline, we sought to determine the absolute 10-year risk of cardiovascular disease among these adults through analyzing the National Health and Nutrition Examination Survey (2005-2012). The primary outcome measure was the proportion of adults who were at ≥20% predicted absolute cardiovascular risk and above goals for the Seventh Joint National Committee guideline but reclassified as at target under the Eighth Joint National Committee guideline (reclassified). The Framingham General Cardiovascular Disease Risk Score was used. From 2005 to 2012, the surveys included 12 963 adults aged 30 to 74 years with blood pressure measurements, of which 914 were reclassified based on the guideline. Among individuals reclassified as not in need of additional treatment, the proportion of adults 60 to 74 years without chronic kidney disease or diabetes mellitus at ≥20% absolute risk was 44.8%. This corresponds to 0.8 million adults. The proportion at high cardiovascular risk remained sizable among adults who were not receiving blood pressure-lowering treatment. Taken together, a sizable proportion of reclassified adults 60 to 74 years without chronic kidney disease or diabetes mellitus was at ≥20% absolute cardiovascular risk. PMID:26056340

  18. Relative errors can cue absolute visuomotor mappings.

    PubMed

    van Dam, Loes C J; Ernst, Marc O

    2015-12-01

    When repeatedly switching between two visuomotor mappings, e.g. in a reaching or pointing task, adaptation tends to speed up over time. That is, when the error in the feedback corresponds to a mapping switch, fast adaptation occurs. Yet, what is learned, the relative error or the absolute mappings? When switching between mappings, errors with a size corresponding to the relative difference between the mappings will occur more often than other large errors. Thus, we could learn to correct more for errors with this familiar size (Error Learning). On the other hand, it has been shown that the human visuomotor system can store several absolute visuomotor mappings (Mapping Learning) and can use associated contextual cues to retrieve them. Thus, when contextual information is present, no error feedback is needed to switch between mappings. Using a rapid pointing task, we investigated how these two types of learning may each contribute when repeatedly switching between mappings in the absence of task-irrelevant contextual cues. After training, we examined how participants changed their behaviour when a single error probe indicated either the often-experienced error (Error Learning) or one of the previously experienced absolute mappings (Mapping Learning). Results were consistent with Mapping Learning despite the relative nature of the error information in the feedback. This shows that errors in the feedback can have a double role in visuomotor behaviour: they drive the general adaptation process by making corrections possible on subsequent movements, as well as serve as contextual cues that can signal a learned absolute mapping. PMID:26280315

  19. Absolute distance measurements by variable wavelength interferometry

    NASA Astrophysics Data System (ADS)

    Bien, F.; Camac, M.; Caulfield, H. J.; Ezekiel, S.

    1981-02-01

    This paper describes a laser interferometer which provides absolute distance measurements using tunable lasers. An active feedback loop system, in which the laser frequency is locked to the optical path length difference of the interferometer, is used to tune the laser wavelengths. If the two wavelengths are very close, electronic frequency counters can be used to measure the beat frequency between the two laser frequencies and thus to determine the optical path difference between the two legs of the interferometer.

  20. Absolute dosimetry for extreme-ultraviolet lithography

    NASA Astrophysics Data System (ADS)

    Berger, Kurt W.; Campiotti, Richard H.

    2000-06-01

    The accurate measurement of an exposure dose reaching the wafer on an extreme ultraviolet (EUV) lithographic system has been a technical challenge directly applicable to the evaluation of candidate EUV resist materials and calculating lithography system throughputs. We have developed a dose monitoring sensor system that can directly measure EUV intensities at the wafer plane of a prototype EUV lithographic system. This sensor system, located on the wafer stage adjacent to the electrostatic chuck used to grip wafers, operates by translating the sensor into the aerial image, typically illuminating an 'open' (unpatterned) area on the reticle. The absolute signal strength can be related to energy density at the wafer, and thus used to determine resist sensitivity, and the signal as a function of position can be used to determine illumination uniformity at the wafer plane. Spectral filtering to enhance the detection of 13.4 nm radiation was incorporated into the sensor. Other critical design parameters include the packaging and amplification technologies required to place this device into the space and vacuum constraints of a EUV lithography environment. We describe two approaches used to determine the absolute calibration of this sensor. The first conventional approach requires separate characterization of each element of the sensor. A second novel approach uses x-ray emission from a mildly radioactive iron source to calibrate the absolute response of the entire sensor system (detector and electronics) in a single measurement.

  1. Folate deficiency affects histone methylation.

    PubMed

    Garcia, Benjamin A; Luka, Zigmund; Loukachevitch, Lioudmila V; Bhanu, Natarajan V; Wagner, Conrad

    2016-03-01

    that the bound THF serves to protect the FAD class of histone demethylases from the destructive effects of formaldehyde generation by formation of 5,10-methylene-THF. We present pilot data showing that decreased folate in livers as a result of dietary folate deficiency is associated with increased levels of methylated lysine 4 of histone 3. This can be a result of decreased LSD1 activity resulting from the decreased folate available to scavenge the formaldehyde produced at the active site caused by the folate deficiency. Because LSD1 can regulate gene expression this suggests that folate may play a more important role than simply serving as a carrier of one-carbon units and be a factor in other diseases associated with low folate. PMID:26880641

  2. 40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... substituted methyl styrene, methyl methacrylate, and substituted silane. 721.6920 Section 721.6920 Protection... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

  3. 40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... substituted methyl styrene, methyl methacrylate, and substituted silane. 721.6920 Section 721.6920 Protection... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

  4. 40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... substituted methyl styrene, methyl methacrylate, and substituted silane. 721.6920 Section 721.6920 Protection... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

  5. The effects of cytosine methylation on general transcription factors

    PubMed Central

    Jin, Jianshi; Lian, Tengfei; Gu, Chan; Yu, Kai; Gao, Yi Qin; Su, Xiao-Dong

    2016-01-01

    DNA methylation on CpG sites is the most common epigenetic modification. Recently, methylation in a non-CpG context was found to occur widely on genomic DNA. Moreover, methylation of non-CpG sites is a highly controlled process, and its level may vary during cellular development. To study non-CpG methylation effects on DNA/protein interactions, we have chosen three human transcription factors (TFs): glucocorticoid receptor (GR), brain and muscle ARNT-like 1 (BMAL1) - circadian locomotor output cycles kaput (CLOCK) and estrogen receptor (ER) with methylated or unmethylated DNA binding sequences, using single-molecule and isothermal titration calorimetry assays. The results demonstrated that these TFs interact with methylated DNA with different effects compared with their cognate DNA sequences. The effects of non-CpG methylation on transcriptional regulation were validated by cell-based luciferase assay at protein level. The mechanisms of non-CpG methylation influencing DNA-protein interactions were investigated by crystallographic analyses and molecular dynamics simulation. With BisChIP-seq assays in HEK-293T cells, we found that GR can recognize highly methylated sites within chromatin in cells. Therefore, we conclude that non-CpG methylation of DNA can provide a mechanism for regulating gene expression through directly affecting the binding of TFs. PMID:27385050

  6. The effects of cytosine methylation on general transcription factors.

    PubMed

    Jin, Jianshi; Lian, Tengfei; Gu, Chan; Yu, Kai; Gao, Yi Qin; Su, Xiao-Dong

    2016-01-01

    DNA methylation on CpG sites is the most common epigenetic modification. Recently, methylation in a non-CpG context was found to occur widely on genomic DNA. Moreover, methylation of non-CpG sites is a highly controlled process, and its level may vary during cellular development. To study non-CpG methylation effects on DNA/protein interactions, we have chosen three human transcription factors (TFs): glucocorticoid receptor (GR), brain and muscle ARNT-like 1 (BMAL1) - circadian locomotor output cycles kaput (CLOCK) and estrogen receptor (ER) with methylated or unmethylated DNA binding sequences, using single-molecule and isothermal titration calorimetry assays. The results demonstrated that these TFs interact with methylated DNA with different effects compared with their cognate DNA sequences. The effects of non-CpG methylation on transcriptional regulation were validated by cell-based luciferase assay at protein level. The mechanisms of non-CpG methylation influencing DNA-protein interactions were investigated by crystallographic analyses and molecular dynamics simulation. With BisChIP-seq assays in HEK-293T cells, we found that GR can recognize highly methylated sites within chromatin in cells. Therefore, we conclude that non-CpG methylation of DNA can provide a mechanism for regulating gene expression through directly affecting the binding of TFs. PMID:27385050

  7. The effects of cytosine methylation on general transcription factors

    NASA Astrophysics Data System (ADS)

    Jin, Jianshi; Lian, Tengfei; Gu, Chan; Yu, Kai; Gao, Yi Qin; Su, Xiao-Dong

    2016-07-01

    DNA methylation on CpG sites is the most common epigenetic modification. Recently, methylation in a non-CpG context was found to occur widely on genomic DNA. Moreover, methylation of non-CpG sites is a highly controlled process, and its level may vary during cellular development. To study non-CpG methylation effects on DNA/protein interactions, we have chosen three human transcription factors (TFs): glucocorticoid receptor (GR), brain and muscle ARNT-like 1 (BMAL1) - circadian locomotor output cycles kaput (CLOCK) and estrogen receptor (ER) with methylated or unmethylated DNA binding sequences, using single-molecule and isothermal titration calorimetry assays. The results demonstrated that these TFs interact with methylated DNA with different effects compared with their cognate DNA sequences. The effects of non-CpG methylation on transcriptional regulation were validated by cell-based luciferase assay at protein level. The mechanisms of non-CpG methylation influencing DNA-protein interactions were investigated by crystallographic analyses and molecular dynamics simulation. With BisChIP-seq assays in HEK-293T cells, we found that GR can recognize highly methylated sites within chromatin in cells. Therefore, we conclude that non-CpG methylation of DNA can provide a mechanism for regulating gene expression through directly affecting the binding of TFs.

  8. Enrichment-based DNA methylation analysis using next-generation sequencing: sample exclusion, estimating changes in global methylation, and the contribution of replicate lanes

    PubMed Central

    2012-01-01

    Background DNA methylation is an important epigenetic mark and dysregulation of DNA methylation is associated with many diseases including cancer. Advances in next-generation sequencing now allow unbiased methylome profiling of entire patient cohorts, greatly facilitating biomarker discovery and presenting new opportunities to understand the biological mechanisms by which changes in methylation contribute to disease. Enrichment-based sequencing assays such as MethylCap-seq are a cost effective solution for genome-wide determination of methylation status, but the technical reliability of methylation reconstruction from raw sequencing data has not been well characterized. Methods We analyze three MethylCap-seq data sets and perform two different analyses to assess data quality. First, we investigate how data quality is affected by excluding samples that do not meet quality control cutoff requirements. Second, we consider the effect of additional reads on enrichment score, saturation, and coverage. Lastly, we verify a method for the determination of the global amount of methylation from MethylCap-seq data by comparing to a spiked-in control DNA of known methylation status. Results We show that rejection of samples based on our quality control parameters leads to a significant improvement of methylation calling. Additional reads beyond ~13 million unique aligned reads improved coverage, modestly improved saturation, and did not impact enrichment score. Lastly, we find that a global methylation indicator calculated from MethylCap-seq data correlates well with the global methylation level of a sample as obtained from a spike-in DNA of known methylation level. Conclusions We show that with appropriate quality control MethylCap-seq is a reliable tool, suitable for cohorts of hundreds of patients, that provides reproducible methylation information on a feature by feature basis as well as information about the global level of methylation. PMID:23281662

  9. Asymmetric synthesis and absolute stereochemistry of a labdane-type diterpenoid isolated from the rhizomes of Isodan yuennanensis.

    PubMed

    Deng, Heping; Cao, Wei; Zhang, Zhijiang; Liu, Bo

    2016-07-14

    The first synthesis of a labdane-type diterpenoid isolated from Isodon yuennanensis was achieved in fourteen steps from commercially available starting material, (+)-sclareolide. The synthesis features the Barton nitrite ester reaction to introduce an oxime at the angular methyl group and the Jones oxidation to construct the lactone segment. By comparison of the optical rotation of our synthetic sample and the natural sample, the absolute stereochemistry of the natural diterpenoid has been determined. PMID:27251032

  10. Determination of the absolute configuration of mono-saccharides in complex carbohydrates by capillary G.L.C.

    PubMed

    Gerwig, G J; Kamerling, J P; Vliegenthart, J F

    1979-12-01

    The absolute configuration of neutral monosaccharides, 2-acetamido-2-deoxy sugars, and uronic acids can be determined by capillary g.l.c. on SE-30 after glycosidation with (-)-2-butanol and protection of the remaining polar groups. The method is illustrated by application to mixtures of the constituent sugars of the capsular polysaccharide from Klebsiella type 57, alpha 1-acid glycoprotein, mucus glycoproteins, and the methylated, acidic polysaccharide from the coccoliths of Emiliania huxleyi (Lohmann) Kamptner. PMID:519653

  11. ENZYMOLOGY OF ARSENIC METHYLATION

    EPA Science Inventory

    Enzymology of Arsenic Methylation

    David J. Thomas, Pharmacokinetics Branch, Experimental Toxicology Division, National
    Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park...

  12. Methyl salicylate overdose

    MedlinePlus

    Deep heating rubs overdose; Oil of wintergreen overdose ... These products contain methyl salicylate: Deep-heating creams used to relieve sore muscles and joints (Ben Gay, Icy Hot) Oil of wintergreen Solutions for vaporizers Other products ...

  13. Genome-wide mapping of DNA methylation in the human malaria parasite Plasmodium falciparum

    PubMed Central

    Ponts, Nadia; Fu, Lijuan; Harris, Elena Y.; Zhang, Jing; Chung, Duk-Won D.; Cervantes, Michael C.; Prudhomme, Jacques; Atanasova-Penichon, Vessela; Zehraoui, Enric; Bunnik, Evelien; Rodrigues, Elisandra M.; Lonardi, Stefano; Hicks, Glenn R.; Wang, Yinsheng; Le Roch, Karine G.

    2014-01-01

    SUMMARY Cytosine DNA methylation is an epigenetic mark in most eukaryotic cells that regulates numerous processes, including gene expression and stress responses. We performed a genome-wide analysis of DNA methylation in the human malaria parasite Plasmodium falciparum. We mapped the positions of methylated cytosines and identified a single functional DNA methyltransferase, PfDNMT, that may mediate these genomic modifications. These analyses revealed that the malaria genome is asymmetrically methylated, in which only one DNA strand is methylated, and shares common features with undifferentiated plant and mammalian cells. Notably, core promoters are hypomethylated and transcript levels correlate with intra-exonic methylation. Additionally, there are sharp methylation transitions at nucleosome and exon-intron boundaries. These data suggest that DNA methylation could regulate virulence gene expression and transcription elongation. Furthermore, the broad range of action of DNA methylation and uniqueness of PfDNMT suggest that the methylation pathway is a potential target for anti-malarial strategies. PMID:24331467

  14. Gene Body Methylation Patterns in Daphnia Are Associated with Gene Family Size

    PubMed Central

    Asselman, Jana; De Coninck, Dieter I. M.; Pfrender, Michael E.; De Schamphelaere, Karel A. C.

    2016-01-01

    The relation between gene body methylation and gene function remains elusive. Yet, our understanding of this relationship can contribute significant knowledge on how and why organisms target specific gene bodies for methylation. Here, we studied gene body methylation patterns in two Daphnia species. We observed both highly methylated genes and genes devoid of methylation in a background of low global methylation levels. A small but highly significant number of genes was highly methylated in both species. Remarkably, functional analyses indicate that variation in methylation within and between Daphnia species is primarily targeted to small gene families whereas large gene families tend to lack variation. The degree of sequence similarity could not explain the observed pattern. Furthermore, a significant negative correlation between gene family size and the degree of methylation suggests that gene body methylation may help regulate gene family expansion and functional diversification of gene families leading to phenotypic variation. PMID:27017526

  15. Inheritance of Cytosine Methylation.

    PubMed

    Tillo, Desiree; Mukherjee, Sanjit; Vinson, Charles

    2016-11-01

    There are numerous examples of parental transgenerational inheritance that is epigenetic. The informational molecules include RNA, chromatin modifications, and cytosine methylation. With advances in DNA sequencing technologies, the molecular and epigenetic mechanisms mediating these effects are now starting to be uncovered. This mini-review will highlight some of the examples of epigenetic inheritance, the establishment of cytosine methylation in sperm, and recent genomic studies linking sperm cytosine methylation to epigenetic effects on offspring. A recent paper examining changes in diet and sperm cytosine methylation from pools of eight animals each, found differences between a normal diet, a high fat diet, and a low protein diet. However, epivariation between individuals within a group was greater than the differences between groups obscuring any potential methylation changes linked to diet. Learning more about epivariation may help unravel the mechanisms that regulate cytosine methylation. In addition, other experimental and genetic systems may also produce more dramatic changes in the sperm methylome, making it easier to unravel potential transgenerational phenomena. J. Cell. Physiol. 231: 2346-2352, 2016. © 2016 Wiley Periodicals, Inc. PMID:26910768

  16. Clock time is absolute and universal

    NASA Astrophysics Data System (ADS)

    Shen, Xinhang

    2015-09-01

    A critical error is found in the Special Theory of Relativity (STR): mixing up the concepts of the STR abstract time of a reference frame and the displayed time of a physical clock, which leads to use the properties of the abstract time to predict time dilation on physical clocks and all other physical processes. Actually, a clock can never directly measure the abstract time, but can only record the result of a physical process during a period of the abstract time such as the number of cycles of oscillation which is the multiplication of the abstract time and the frequency of oscillation. After Lorentz Transformation, the abstract time of a reference frame expands by a factor gamma, but the frequency of a clock decreases by the same factor gamma, and the resulting multiplication i.e. the displayed time of a moving clock remains unchanged. That is, the displayed time of any physical clock is an invariant of Lorentz Transformation. The Lorentz invariance of the displayed times of clocks can further prove within the framework of STR our earth based standard physical time is absolute, universal and independent of inertial reference frames as confirmed by both the physical fact of the universal synchronization of clocks on the GPS satellites and clocks on the earth, and the theoretical existence of the absolute and universal Galilean time in STR which has proved that time dilation and space contraction are pure illusions of STR. The existence of the absolute and universal time in STR has directly denied that the reference frame dependent abstract time of STR is the physical time, and therefore, STR is wrong and all its predictions can never happen in the physical world.

  17. Achieving Climate Change Absolute Accuracy in Orbit

    NASA Technical Reports Server (NTRS)

    Wielicki, Bruce A.; Young, D. F.; Mlynczak, M. G.; Thome, K. J; Leroy, S.; Corliss, J.; Anderson, J. G.; Ao, C. O.; Bantges, R.; Best, F.; Bowman, K.; Brindley, H.; Butler, J. J.; Collins, W.; Dykema, J. A.; Doelling, D. R.; Feldman, D. R.; Fox, N.; Huang, X.; Holz, R.; Huang, Y.; Jennings, D.; Jin, Z.; Johnson, D. G.; Jucks, K.; Kato, S.; Kratz, D. P.; Liu, X.; Lukashin, C.; Mannucci, A. J.; Phojanamongkolkij, N.; Roithmayr, C. M.; Sandford, S.; Taylor, P. C.; Xiong, X.

    2013-01-01

    The Climate Absolute Radiance and Refractivity Observatory (CLARREO) mission will provide a calibration laboratory in orbit for the purpose of accurately measuring and attributing climate change. CLARREO measurements establish new climate change benchmarks with high absolute radiometric accuracy and high statistical confidence across a wide range of essential climate variables. CLARREO's inherently high absolute accuracy will be verified and traceable on orbit to Système Internationale (SI) units. The benchmarks established by CLARREO will be critical for assessing changes in the Earth system and climate model predictive capabilities for decades into the future as society works to meet the challenge of optimizing strategies for mitigating and adapting to climate change. The CLARREO benchmarks are derived from measurements of the Earth's thermal infrared spectrum (5-50 micron), the spectrum of solar radiation reflected by the Earth and its atmosphere (320-2300 nm), and radio occultation refractivity from which accurate temperature profiles are derived. The mission has the ability to provide new spectral fingerprints of climate change, as well as to provide the first orbiting radiometer with accuracy sufficient to serve as the reference transfer standard for other space sensors, in essence serving as a "NIST [National Institute of Standards and Technology] in orbit." CLARREO will greatly improve the accuracy and relevance of a wide range of space-borne instruments for decadal climate change. Finally, CLARREO has developed new metrics and methods for determining the accuracy requirements of climate observations for a wide range of climate variables and uncertainty sources. These methods should be useful for improving our understanding of observing requirements for most climate change observations.

  18. The National Geodetic Survey absolute gravity program

    NASA Astrophysics Data System (ADS)

    Peter, George; Moose, Robert E.; Wessells, Claude W.

    1989-03-01

    The National Geodetic Survey absolute gravity program will utilize the high precision afforded by the JILAG-4 instrument to support geodetic and geophysical research, which involves studies of vertical motions, identification and modeling of other temporal variations, and establishment of reference values. The scientific rationale of these objectives is given, the procedures used to collect gravity and environmental data in the field are defined, and the steps necessary to correct and remove unwanted environmental effects are stated. In addition, site selection criteria, methods of concomitant environmental data collection and relative gravity observations, and schedule and logistics are discussed.

  19. An absolute radius scale for Saturn's rings

    NASA Technical Reports Server (NTRS)

    Nicholson, Philip D.; Cooke, Maren L.; Pelton, Emily

    1990-01-01

    Radio and stellar occultation observations of Saturn's rings made by the Voyager spacecraft are discussed. The data reveal systematic discrepancies of almost 10 km in some parts of the rings, limiting some of the investigations. A revised solution for Saturn's rotation pole has been proposed which removes the discrepancies between the stellar and radio occultation profiles. Corrections to previously published radii vary from -2 to -10 km for the radio occultation, and +5 to -6 km for the stellar occultation. An examination of spiral density waves in the outer A Ring supports that the revised absolute radii are in error by no more than 2 km.

  20. Characterization of the DARA solar absolute radiometer

    NASA Astrophysics Data System (ADS)

    Finsterle, W.; Suter, M.; Fehlmann, A.; Kopp, G.

    2011-12-01

    The Davos Absolute Radiometer (DARA) prototype is an Electrical Substitution Radiometer (ESR) which has been developed as a successor of the PMO6 type on future space missions and ground based TSI measurements. The DARA implements an improved thermal design of the cavity detector and heat sink assembly to minimize air-vacuum differences and to maximize thermal symmetry of measuring and compensating cavity. The DARA also employs an inverted viewing geometry to reduce internal stray light. We will report on the characterization and calibration experiments which were carried out at PMOD/WRC and LASP (TRF).

  1. Absolute calibration of the Auger fluorescence detectors

    SciTech Connect

    Bauleo, P.; Brack, J.; Garrard, L.; Harton, J.; Knapik, R.; Meyhandan, R.; Rovero, A.C.; Tamashiro, A.; Warner, D.

    2005-07-01

    Absolute calibration of the Pierre Auger Observatory fluorescence detectors uses a light source at the telescope aperture. The technique accounts for the combined effects of all detector components in a single measurement. The calibrated 2.5 m diameter light source fills the aperture, providing uniform illumination to each pixel. The known flux from the light source and the response of the acquisition system give the required calibration for each pixel. In the lab, light source uniformity is studied using CCD images and the intensity is measured relative to NIST-calibrated photodiodes. Overall uncertainties are presently 12%, and are dominated by systematics.

  2. Absolute angular positioning in ultrahigh vacuum

    SciTech Connect

    Schief, H.; Marsico, V.; Kern, K.

    1996-05-01

    Commercially available angular resolvers, which are routinely used in machine tools and robotics, are modified and adapted to be used under ultrahigh-vacuum (UHV) conditions. They provide straightforward and reliable measurements of angular positions for any kind of UHV sample manipulators. The corresponding absolute reproducibility is on the order of 0.005{degree}, whereas the relative resolution is better than 0.001{degree}, as demonstrated by high-resolution helium-reflectivity measurements. The mechanical setup and possible applications are discussed. {copyright} {ital 1996 American Institute of Physics.}

  3. Absolute method of measuring magnetic susceptibility

    USGS Publications Warehouse

    Thorpe, A.; Senftle, F.E.

    1959-01-01

    An absolute method of standardization and measurement of the magnetic susceptibility of small samples is presented which can be applied to most techniques based on the Faraday method. The fact that the susceptibility is a function of the area under the curve of sample displacement versus distance of the magnet from the sample, offers a simple method of measuring the susceptibility without recourse to a standard sample. Typical results on a few substances are compared with reported values, and an error of less than 2% can be achieved. ?? 1959 The American Institute of Physics.

  4. Absolute Priority for a Vehicle in VANET

    NASA Astrophysics Data System (ADS)

    Shirani, Rostam; Hendessi, Faramarz; Montazeri, Mohammad Ali; Sheikh Zefreh, Mohammad

    In today's world, traffic jams waste hundreds of hours of our life. This causes many researchers try to resolve the problem with the idea of Intelligent Transportation System. For some applications like a travelling ambulance, it is important to reduce delay even for a second. In this paper, we propose a completely infrastructure-less approach for finding shortest path and controlling traffic light to provide absolute priority for an emergency vehicle. We use the idea of vehicular ad-hoc networking to reduce the imposed travelling time. Then, we simulate our proposed protocol and compare it with a centrally controlled traffic light system.

  5. Determination of the absolute contours of optical flats

    NASA Technical Reports Server (NTRS)

    Primak, W.

    1969-01-01

    Emersons procedure is used to determine true absolute contours of optical flats. Absolute contours of standard flats are determined and a comparison is then made between standard and unknown flats. Contour differences are determined by deviation of Fizeau fringe.

  6. GNSS Absolute Antenna Calibration at the National Geodetic Survey

    NASA Astrophysics Data System (ADS)

    Bilich, A. L.; Mader, G. L.

    2009-12-01

    GNSS applications now routinely demand measurement and instrument biases at the centimeter to millimeter level in order to achieve the high precision and accuracy required for geodetic position solutions. One of these biases is the antenna phase center, the point of signal reception for a GNSS antenna. It has been well established that phase center patterns differ between antenna models and manufacturers; additional research suggests that the addition of a radome or the choice of antenna mount can significantly alter those a priori phase center patterns. As baseline lengths increase, or with antenna mixing, phase center effects on carrier phase data become more pronounced. To meet the needs of the high-precision GNSS community, the National Geodetic Survey (NGS) has constructed an absolute antenna calibration facility which uses field measurements and actual GNSS satellite signals to determine antenna phase center patterns. A pan/tilt motor changes the orientation of the antenna under test; signals are received at a wide range of angles, allowing computation of a robust phase center pattern. Ultimately, this facility will be used to measure antenna phase center variations of commonly-used geodetic GNSS antennas, as well as antennas submitted by users. The phase center patterns will be publicly available and disseminated in both the ANTEX and NGS formats. We provide information on the observation models and strategy currently used to generate NGS absolute calibrations, and propose some future refinements. We discuss the multipath mitigation strategy currently in use, and provide examples of antenna calibrations from the NGS facility. These examples are compared to the NGS relative calibrations as well as absolute calibrations generated by other organizations.

  7. Mercury methylation in periphyton of the Florida Everglades

    USGS Publications Warehouse

    Cleckner, L.B.; Gilmour, C.C.; Hurley, J.P.; Krabbenhoft, D.P.

    1999-01-01

    Trophic accumulation of mercury (Hg) in aquatic ecosystems is of global concern due to health effects associated with eating fish with elevated Hg levels. The methylated form of Hg bioaccumulates so it is important to understand how inorganic Hg is transformed to methylmercury in the environment. Here, a new site for Hg methylation, the periphyton communities that are prevalent in the Florida Everglades, is described. It is hypothesized that periphyton communities that support an active microbial sulfur cycle support Hg methylation. This new methylation site has implications for trophic transfer of methylmercury since periphyton can be the base of the food web in aquatic ecosystems.

  8. Standardization of the cumulative absolute velocity

    SciTech Connect

    O'Hara, T.F.; Jacobson, J.P. )

    1991-12-01

    EPRI NP-5930, A Criterion for Determining Exceedance of the Operating Basis Earthquake,'' was published in July 1988. As defined in that report, the Operating Basis Earthquake (OBE) is exceeded when both a response spectrum parameter and a second damage parameter, referred to as the Cumulative Absolute Velocity (CAV), are exceeded. In the review process of the above report, it was noted that the calculation of CAV could be confounded by time history records of long duration containing low (nondamaging) acceleration. Therefore, it is necessary to standardize the method of calculating CAV to account for record length. This standardized methodology allows consistent comparisons between future CAV calculations and the adjusted CAV threshold value based upon applying the standardized methodology to the data set presented in EPRI NP-5930. The recommended method to standardize the CAV calculation is to window its calculation on a second-by-second basis for a given time history. If the absolute acceleration exceeds 0.025g at any time during each one second interval, the earthquake records used in EPRI NP-5930 have been reanalyzed and the adjusted threshold of damage for CAV was found to be 0.16g-set.

  9. Absolute rates of hole transfer in DNA.

    PubMed

    Senthilkumar, Kittusamy; Grozema, Ferdinand C; Guerra, Célia Fonseca; Bickelhaupt, F Matthias; Lewis, Frederick D; Berlin, Yuri A; Ratner, Mark A; Siebbeles, Laurens D A

    2005-10-26

    Absolute rates of hole transfer between guanine nucleobases separated by one or two A:T base pairs in stilbenedicarboxamide-linked DNA hairpins were obtained by improved kinetic analysis of experimental data. The charge-transfer rates in four different DNA sequences were calculated using a density-functional-based tight-binding model and a semiclassical superexchange model. Site energies and charge-transfer integrals were calculated directly as the diagonal and off-diagonal matrix elements of the Kohn-Sham Hamiltonian, respectively, for all possible combinations of nucleobases. Taking into account the Coulomb interaction between the negative charge on the stilbenedicarboxamide linker and the hole on the DNA strand as well as effects of base pair twisting, the relative order of the experimental rates for hole transfer in different hairpins could be reproduced by tight-binding calculations. To reproduce quantitatively the absolute values of the measured rate constants, the effect of the reorganization energy was taken into account within the semiclassical superexchange model for charge transfer. The experimental rates could be reproduced with reorganization energies near 1 eV. The quantum chemical data obtained were used to discuss charge carrier mobility and hole-transport equilibria in DNA. PMID:16231945

  10. Transient absolute robustness in stochastic biochemical networks.

    PubMed

    Enciso, German A

    2016-08-01

    Absolute robustness allows biochemical networks to sustain a consistent steady-state output in the face of protein concentration variability from cell to cell. This property is structural and can be determined from the topology of the network alone regardless of rate parameters. An important question regarding these systems is the effect of discrete biochemical noise in the dynamical behaviour. In this paper, a variable freezing technique is developed to show that under mild hypotheses the corresponding stochastic system has a transiently robust behaviour. Specifically, after finite time the distribution of the output approximates a Poisson distribution, centred around the deterministic mean. The approximation becomes increasingly accurate, and it holds for increasingly long finite times, as the total protein concentrations grow to infinity. In particular, the stochastic system retains a transient, absolutely robust behaviour corresponding to the deterministic case. This result contrasts with the long-term dynamics of the stochastic system, which eventually must undergo an extinction event that eliminates robustness and is completely different from the deterministic dynamics. The transiently robust behaviour may be sufficient to carry out many forms of robust signal transduction and cellular decision-making in cellular organisms. PMID:27581485

  11. Absolute Electron Extraction Efficiency of Liquid Xenon

    NASA Astrophysics Data System (ADS)

    Kamdin, Katayun; Mizrachi, Eli; Morad, James; Sorensen, Peter

    2016-03-01

    Dual phase liquid/gas xenon time projection chambers (TPCs) currently set the world's most sensitive limits on weakly interacting massive particles (WIMPs), a favored dark matter candidate. These detectors rely on extracting electrons from liquid xenon into gaseous xenon, where they produce proportional scintillation. The proportional scintillation from the extracted electrons serves to internally amplify the WIMP signal; even a single extracted electron is detectable. Credible dark matter searches can proceed with electron extraction efficiency (EEE) lower than 100%. However, electrons systematically left at the liquid/gas boundary are a concern. Possible effects include spontaneous single or multi-electron proportional scintillation signals in the gas, or charging of the liquid/gas interface or detector materials. Understanding EEE is consequently a serious concern for this class of rare event search detectors. Previous EEE measurements have mostly been relative, not absolute, assuming efficiency plateaus at 100%. I will present an absolute EEE measurement with a small liquid/gas xenon TPC test bed located at Lawrence Berkeley National Laboratory.

  12. Sentinel-2/MSI absolute calibration: first results

    NASA Astrophysics Data System (ADS)

    Lonjou, V.; Lachérade, S.; Fougnie, B.; Gamet, P.; Marcq, S.; Raynaud, J.-L.; Tremas, T.

    2015-10-01

    Sentinel-2 is an optical imaging mission devoted to the operational monitoring of land and coastal areas. It is developed in partnership between the European Commission and the European Space Agency. The Sentinel-2 mission is based on a satellites constellation deployed in polar sun-synchronous orbit. It will offer a unique combination of global coverage with a wide field of view (290km), a high revisit (5 days with two satellites), a high resolution (10m, 20m and 60m) and multi-spectral imagery (13 spectral bands in visible and shortwave infra-red domains). CNES is involved in the instrument commissioning in collaboration with ESA. This paper reviews all the techniques that will be used to insure an absolute calibration of the 13 spectral bands better than 5% (target 3%), and will present the first results if available. First, the nominal calibration technique, based on an on-board sun diffuser, is detailed. Then, we show how vicarious calibration methods based on acquisitions over natural targets (oceans, deserts, and Antarctica during winter) will be used to check and improve the accuracy of the absolute calibration coefficients. Finally, the verification scheme, exploiting photometer in-situ measurements over Lacrau plain, is described. A synthesis, including spectral coherence, inter-methods agreement and temporal evolution, will conclude the paper.

  13. Absolute Spectrophotometry of 237 Open Cluster Stars

    NASA Astrophysics Data System (ADS)

    Clampitt, L.; Burstein, D.

    1994-12-01

    We present absolute spectrophotometry of 237 stars in 7 nearby open clusters: Hyades, Pleiades, Alpha Persei, Praesepe, Coma Berenices, IC 4665, and M 39. The observations were taken using the Wampler single-channel scanner (Wampler 1966) on the Crossley 0.9m telescope at Lick Observatory from July 1973 through December 1974. 21 bandpasses spanning the spectral range 3500 Angstroms to 7780 Angstroms were observed for each star, with bandwiths ranging from 32Angstroms to 64 Angstroms. Data are standardized to the Hayes--Latham (1975) system. Our measurements are compared to filter colors on the Johnson BV, Stromgren ubvy, and Geneva U V B_1 B_2 V_1 G systems, as well as to spectrophotometry of a few stars published by Gunn, Stryker & Tinsley and in the Spectrophotometric Standards Catalog (Adelman; as distributed by the NSSDC). Both internal and external comparisons to the filter systems indicate a formal statistical accuracy per bandpass of 0.01 to 0.02 mag, with apparent larger ( ~ 0.03 mag) differences in absolute calibration between this data set and existing spectrophotometry. These data will comprise part of the spectrophotometry that will be used to calibrate the Beijing-Arizona-Taipei-Connecticut Color Survey of the Sky (see separate paper by Burstein et al. at this meeting).

  14. DNA methylation in fibrosis.

    PubMed

    Dowson, Christopher; O'Reilly, Steven

    2016-09-01

    Fibrosis is characterised by an exuberant wound healing response and the major cell type responsible is the myofibroblast. The myofibroblast is typified by excessive ECM production and contractile activity and is demarcated by alpha-smooth muscle actin expression. What has recently come to light is that the activation of the fibroblast to myofibroblast may be under epigenetic control, specifically methylation. Methylation of DNA is a conserved mechanism to precisely regulate gene expression in a specific context. Hypermethylation leads to gene repression and hypomethylation results in gene induction. Methylation abnormalities have recently been uncovered in fibrosis, both organ specific and widespread fibrosis. The fact that these methylation changes are rapid and reversible lends themselves amenable to therapeutic intervention. This review considers the role of methylation in fibrosis and the activation of the myofibroblasts and how this could be targeted for fibrosis. Fibrosis is of course currently intractable to therapeutics and is a leading cause of morbidity and mortality and is an urgent unmet clinical need. PMID:27346523

  15. A Conceptual Approach to Absolute Value Equations and Inequalities

    ERIC Educational Resources Information Center

    Ellis, Mark W.; Bryson, Janet L.

    2011-01-01

    The absolute value learning objective in high school mathematics requires students to solve far more complex absolute value equations and inequalities. When absolute value problems become more complex, students often do not have sufficient conceptual understanding to make any sense of what is happening mathematically. The authors suggest that the…

  16. Using, Seeing, Feeling, and Doing Absolute Value for Deeper Understanding

    ERIC Educational Resources Information Center

    Ponce, Gregorio A.

    2008-01-01

    Using sticky notes and number lines, a hands-on activity is shared that anchors initial student thinking about absolute value. The initial point of reference should help students successfully evaluate numeric problems involving absolute value. They should also be able to solve absolute value equations and inequalities that are typically found in…

  17. 20 CFR 404.1205 - Absolute coverage groups.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Absolute coverage groups. 404.1205 Section... INSURANCE (1950- ) Coverage of Employees of State and Local Governments What Groups of Employees May Be Covered § 404.1205 Absolute coverage groups. (a) General. An absolute coverage group is a...

  18. PTEN methylation involved in benzene-induced hematotoxicity.

    PubMed

    Yang, Jing; Zuo, Xin; Bai, Wenlin; Niu, Piye; Tian, Lin; Gao, Ai

    2014-06-01

    It is well known that benzene is a hematotoxic carcinogen. PTEN promoter methylation is a representative example of transcriptional silencing of tumor suppressor genes. However, the effect of PTEN methylation on benzene-induced hematotoxicity has not yet been elucidated. In this study, the animal model of benzene hematotoxicity was successfully established. WBC significantly decreased in experimental groups (P < 0.01). Compared with the control group, the weight of rats increased slowly and even declined with increasing doses of benzene in the benzene-treated groups. An increase in the level of PTEN methylation was observed in the low dose group, and PTEN methylation level increased significantly in a dose-dependent manner. However, it was interesting that PTEN mRNA expression increased in the low dose group, but declined with increasing doses of benzene. The decrease of tumor suppressor function caused by PTEN methylation may be an important mechanism of benzene hematotoxicity. Furthermore, lymphoblast cell line F32 was incubated by benzene and then treated with 5-aza and TSA, alone or in combination. A dramatic decrease in the PTEN mRNA expression and a significant increase of PTEN methylation level in benzene-treated cells were also shown. PTEN mRNA expression was up regulated and PTEN methylation level was reduced by the epigenetic inhibitors, 5-aza and TSA. In conclusion, PTEN methylation is involved in benzene-induced hematotoxicity through suppressing PTEN mRNA expression. PMID:24680972

  19. Linking Low-Level Stable Isotope Fractionation to Expression of the Cytochrome P450 Monooxygenase-Encoding ethB Gene for Elucidation of Methyl tert-Butyl Ether Biodegradation in Aerated Treatment Pond Systems▿ †

    PubMed Central

    Jechalke, Sven; Rosell, Mònica; Martínez-Lavanchy, Paula M.; Pérez-Leiva, Paola; Rohwerder, Thore; Vogt, Carsten; Richnow, Hans H.

    2011-01-01

    Multidimensional compound-specific stable isotope analysis (CSIA) was applied in combination with RNA-based molecular tools to characterize methyl tertiary (tert-) butyl ether (MTBE) degradation mechanisms occurring in biofilms in an aerated treatment pond used for remediation of MTBE-contaminated groundwater. The main pathway for MTBE oxidation was elucidated by linking the low-level stable isotope fractionation (mean carbon isotopic enrichment factor [ɛC] of −0.37‰ ± 0.05‰ and no significant hydrogen isotopic enrichment factor [ɛH]) observed in microcosm experiments to expression of the ethB gene encoding a cytochrome P450 monooxygenase able to catalyze the oxidation of MTBE in biofilm samples both from the microcosms and directly from the ponds. 16S rRNA-specific primers revealed the presence of a sequence 100% identical to that of Methylibium petroleiphilum PM1, a well-characterized MTBE degrader. However, neither expression of the mdpA genes encoding the alkane hydroxylase-like enzyme responsible for MTBE oxidation in this strain nor the related MTBE isotope fractionation pattern produced by PM1 could be detected, suggesting that this enzyme was not active in this system. Additionally, observed low inverse fractionation of carbon (ɛC of +0.11‰ ± 0.03‰) and low fractionation of hydrogen (ɛH of −5‰ ± 1‰) in laboratory experiments simulating MTBE stripping from an open surface water body suggest that the application of CSIA in field investigations to detect biodegradation may lead to false-negative results when volatilization effects coincide with the activity of low-fractionating enzymes. As shown in this study, complementary examination of expression of specific catabolic genes can be used as additional direct evidence for microbial degradation activity and may overcome this problem. PMID:21148686

  20. [DNA methylation in obesity].

    PubMed

    Pokrywka, Małgorzata; Kieć-Wilk, Beata; Polus, Anna; Wybrańska, Iwona

    2014-01-01

    The number of overweight and obese people is increasing at an alarming rate, especially in the developed and developing countries. Obesity is a major risk factor for diabetes, cardiovascular disease, and cancer, and in consequence for premature death. The development of obesity results from the interplay of both genetic and environmental factors, which include sedentary life style and abnormal eating habits. In the past few years a number of events accompanying obesity, affecting expression of genes which are not directly connected with the DNA base sequence (e.g. epigenetic changes), have been described. Epigenetic processes include DNA methylation, histone modifications such as acetylation, methylation, phosphorylation, ubiquitination, and sumoylation, as well as non-coding micro-RNA (miRNA) synthesis. In this review, the known changes in the profile of DNA methylation as a factor affecting obesity and its complications are described. PMID:25531701

  1. Communication: The absolute shielding scales of oxygen and sulfur revisited

    SciTech Connect

    Komorovsky, Stanislav; Repisky, Michal; Malkin, Elena; Ruud, Kenneth; Gauss, Jürgen

    2015-03-07

    We present an updated semi-experimental absolute shielding scale for the {sup 17}O and {sup 33}S nuclei. These new shielding scales are based on accurate rotational microwave data for the spin–rotation constants of H{sub 2}{sup 17}O [Puzzarini et al., J. Chem. Phys. 131, 234304 (2009)], C{sup 17}O [Cazzoli et al., Phys. Chem. Chem. Phys. 4, 3575 (2002)], and H{sub 2}{sup 33}S [Helgaker et al., J. Chem. Phys. 139, 244308 (2013)] corrected both for vibrational and temperature effects estimated at the CCSD(T) level of theory as well as for the relativistic corrections to the relation between the spin–rotation constant and the absolute shielding constant. Our best estimate for the oxygen shielding constants of H{sub 2}{sup 17}O is 328.4(3) ppm and for C{sup 17}O −59.05(59) ppm. The relativistic correction for the sulfur shielding of H{sub 2}{sup 33}S amounts to 3.3%, and the new sulfur shielding constant for this molecule is 742.9(4.6) ppm.

  2. Simulation of absolute amplitudes of ultrasound signals using equivalent circuits.

    PubMed

    Johansson, Jonny; Martinsson, Pär-Erik; Delsing, Jerker

    2007-10-01

    Equivalent circuits for piezoelectric devices and ultrasonic transmission media can be used to cosimulate electronics and ultrasound parts in simulators originally intended for electronics. To achieve efficient system-level optimization, it is important to simulate correct, absolute amplitude of the ultrasound signal in the system, as this determines the requirements on the electronics regarding dynamic range, circuit noise, and power consumption. This paper presents methods to achieve correct, absolute amplitude of an ultrasound signal in a simulation of a pulse-echo system using equivalent circuits. This is achieved by taking into consideration loss due to diffraction and the effect of the cable that connects the electronics and the piezoelectric transducer. The conductive loss in the transmission line that models the propagation media of the ultrasound pulse is used to model the loss due to diffraction. Results show that the simulated amplitude of the echo follows measured values well in both near and far fields, with an offset of about 10%. The use of a coaxial cable introduces inductance and capacitance that affect the amplitude of a received echo. Amplitude variations of 60% were observed when the cable length was varied between 0.07 m and 2.3 m, with simulations predicting similar variations. The high precision in the achieved results show that electronic design and system optimization can rely on system simulations alone. This will simplify the development of integrated electronics aimed at ultrasound systems. PMID:18019234

  3. Use of Absolute and Comparative Performance Feedback in Absolute and Comparative Judgments and Decisions

    ERIC Educational Resources Information Center

    Moore, Don A.; Klein, William M. P.

    2008-01-01

    Which matters more--beliefs about absolute ability or ability relative to others? This study set out to compare the effects of such beliefs on satisfaction with performance, self-evaluations, and bets on future performance. In Experiment 1, undergraduate participants were told they had answered 20% correct, 80% correct, or were not given their…

  4. Dietary toxicity of calcium beta-hydroxy-beta-methyl butyrate (CaHMB).

    PubMed

    Baxter, J H; Carlos, J L; Thurmond, J; Rehani, R N; Bultman, J; Frost, D

    2005-12-01

    HMB, 3-hydroxy-3-methyl butyrate, is of interest as a dietary supplement and a possible component of functional and medical foods. The purpose of this study was to evaluate the toxicity of the calcium salt of HMB, calcium 3-hydroxy-3-methyl butyrate (CaHMB, monohydrate, food grade), when administered daily in the diet of rats for at least 90 days. Male and female Crl:CD (SD)IGS BR animals were assigned to four groups. Each group received diets containing the carrier or 1%, 2%, or 5% of CaHMB mixed with diet. Assessment of toxicity was based on mortality, clinical observations, body weights, food consumption, and clinical and anatomic pathology evaluations. Administration of CaHMB in basal diet for 91 days was tolerated well. There were no unscheduled sacrifices or deaths. There were no CaHMB-related adverse effects on clinical observations, body weights, food consumption, clinical chemistry, hematology, absolute or relative organ weights, or macroscopic or microscopic observations. A statistically significant increase in inorganic phosphorous was observed in male animals in the 5% feeding group; however, this effect was not considered adverse. Based on the results of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 5% of CaHMB mixed with diet (3.49 g/kg BW for males and 4.16 g/kg BW for females). PMID:16006030

  5. DNA methylation and healthy human aging.

    PubMed

    Jones, Meaghan J; Goodman, Sarah J; Kobor, Michael S

    2015-12-01

    The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next-generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site-specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age-related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining 'epigenetic age' for human health and outline some important caveats to existing and future studies. PMID:25913071

  6. Childhood Maltreatment and Methylation of FKBP5

    PubMed Central

    Tyrka, Audrey R.; Ridout, Kathryn K.; Parade, Stephanie H.; Paquette, Alison; Marsit, Carmen J.; Seifer, Ronald

    2016-01-01

    A growing body of evidence suggests that alterations of the stress response system may be a mechanism by which childhood maltreatment alters risk for psychopathology. FK506 binding protein 51 (FKBP5) binds to the glucocorticoid receptor and alters its ability to respond to stress signaling. The aim of the present study was to examine methylation of the FKBP5 gene (FKBP5), and the role of an FKBP5 genetic variant, in relation to childhood maltreatment in a sample of impoverished preschool-aged children. One hundred seventy-four families, including n=69 with child welfare documentation of moderate-severe maltreatment in the past six months, participated in this study. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of two CpG sites in intron 7 of FKBP5 was measured via sodium bisulfite pyrosequencing. Maltreated children had significantly lower levels of methylation at both CpG sites (p<.05). Lifetime contextual stress exposure showed a trend for lower levels of methylation at one of the sites, and a trend for an interaction with the FKBP5 polymorphism. A composite adversity variable was associated with lower levels of methylation at one of the sites as well (p<.05). FKBP5 alters glucocorticoid receptor responsiveness and FKBP5 gene methylation may be a mechanism of the bio-behavioral effects of adverse exposures in young children. PMID:26535949

  7. MAGSAT: Vector magnetometer absolute sensor alignment determination

    NASA Technical Reports Server (NTRS)

    Acuna, M. H.

    1981-01-01

    A procedure is described for accurately determining the absolute alignment of the magnetic axes of a triaxial magnetometer sensor with respect to an external, fixed, reference coordinate system. The method does not require that the magnetic field vector orientation, as generated by a triaxial calibration coil system, be known to better than a few degrees from its true position, and minimizes the number of positions through which a sensor assembly must be rotated to obtain a solution. Computer simulations show that accuracies of better than 0.4 seconds of arc can be achieved under typical test conditions associated with existing magnetic test facilities. The basic approach is similar in nature to that presented by McPherron and Snare (1978) except that only three sensor positions are required and the system of equations to be solved is considerably simplified. Applications of the method to the case of the MAGSAT Vector Magnetometer are presented and the problems encountered discussed.

  8. Absolute geostrophic currents in global tropical oceans

    NASA Astrophysics Data System (ADS)

    Yang, Lina; Yuan, Dongliang

    2016-03-01

    A set of absolute geostrophic current (AGC) data for the period January 2004 to December 2012 are calculated using the P-vector method based on monthly gridded Argo profiles in the world tropical oceans. The AGCs agree well with altimeter geostrophic currents, Ocean Surface Current Analysis-Real time currents, and moored current-meter measurements at 10-m depth, based on which the classical Sverdrup circulation theory is evaluated. Calculations have shown that errors of wind stress calculation, AGC transport, and depth ranges of vertical integration cannot explain non-Sverdrup transport, which is mainly in the subtropical western ocean basins and equatorial currents near the Equator in each ocean basin (except the North Indian Ocean, where the circulation is dominated by monsoons). The identified non-Sverdrup transport is thereby robust and attributed to the joint effect of baroclinicity and relief of the bottom (JEBAR) and mesoscale eddy nonlinearity.

  9. Absolute Measurement of Electron Cloud Density

    SciTech Connect

    Covo, M K; Molvik, A W; Cohen, R H; Friedman, A; Seidl, P A; Logan, G; Bieniosek, F; Baca, D; Vay, J; Orlando, E; Vujic, J L

    2007-06-21

    Beam interaction with background gas and walls produces ubiquitous clouds of stray electrons that frequently limit the performance of particle accelerator and storage rings. Counterintuitively we obtained the electron cloud accumulation by measuring the expelled ions that are originated from the beam-background gas interaction, rather than by measuring electrons that reach the walls. The kinetic ion energy measured with a retarding field analyzer (RFA) maps the depressed beam space-charge potential and provides the dynamic electron cloud density. Clearing electrode current measurements give the static electron cloud background that complements and corroborates with the RFA measurements, providing an absolute measurement of electron cloud density during a 5 {micro}s duration beam pulse in a drift region of the magnetic transport section of the High-Current Experiment (HCX) at LBNL.

  10. Absolute instability of a viscous hollow jet

    NASA Astrophysics Data System (ADS)

    Gañán-Calvo, Alfonso M.

    2007-02-01

    An investigation of the spatiotemporal stability of hollow jets in unbounded coflowing liquids, using a general dispersion relation previously derived, shows them to be absolutely unstable for all physical values of the Reynolds and Weber numbers. The roots of the symmetry breakdown with respect to the liquid jet case, and the validity of asymptotic models are here studied in detail. Asymptotic analyses for low and high Reynolds numbers are provided, showing that old and well-established limiting dispersion relations [J. W. S. Rayleigh, The Theory of Sound (Dover, New York, 1945); S. Chandrasekhar, Hydrodynamic and Hydromagnetic Stability (Dover, New York, 1961)] should be used with caution. In the creeping flow limit, the analysis shows that, if the hollow jet is filled with any finite density and viscosity fluid, a steady jet could be made arbitrarily small (compatible with the continuum hypothesis) if the coflowing liquid moves faster than a critical velocity.

  11. Stitching interferometry: recent results and absolute calibration

    NASA Astrophysics Data System (ADS)

    Bray, Michael

    2004-02-01

    Stitching Interferometry is a method of analysing large optical components using a standard "small" interferometer. This result is obtained by taking multiple overlapping images of the large component, and numerically "stitching" these sub-apertures together. We have already reported the industrial use our Stitching Interferometry systems (Previous SPIE symposia), but experimental results had been lacking because this technique is still new, and users needed to get accustomed to it before producing reliable measurements. We now have more results. We will report user comments and show new, unpublished results. We will discuss sources of error, and show how some of these can be reduced to arbitrarily small values. These will be discussed in some detail. We conclude with a few graphical examples of absolute measurements performed by us.

  12. Absolute nonlocality via distributed computing without communication

    NASA Astrophysics Data System (ADS)

    Czekaj, Ł.; Pawłowski, M.; Vértesi, T.; Grudka, A.; Horodecki, M.; Horodecki, R.

    2015-09-01

    Understanding the role that quantum entanglement plays as a resource in various information processing tasks is one of the crucial goals of quantum information theory. Here we propose an alternative perspective for studying quantum entanglement: distributed computation of functions without communication between nodes. To formalize this approach, we propose identity games. Surprisingly, despite no signaling, we obtain that nonlocal quantum strategies beat classical ones in terms of winning probability for identity games originating from certain bipartite and multipartite functions. Moreover we show that, for a majority of functions, access to general nonsignaling resources boosts success probability two times in comparison to classical ones for a number of large enough outputs. Because there are no constraints on the inputs and no processing of the outputs in the identity games, they detect very strong types of correlations: absolute nonlocality.

  13. The CHH motif in sugar beet satellite DNA: a modulator for cytosine methylation.

    PubMed

    Zakrzewski, Falk; Schubert, Veit; Viehoever, Prisca; Minoche, André E; Dohm, Juliane C; Himmelbauer, Heinz; Weisshaar, Bernd; Schmidt, Thomas

    2014-06-01

    Methylation of DNA is important for the epigenetic silencing of repetitive DNA in plant genomes. Knowledge about the cytosine methylation status of satellite DNAs, a major class of repetitive DNA, is scarce. One reason for this is that arrays of tandemly arranged sequences are usually collapsed in next-generation sequencing assemblies. We applied strategies to overcome this limitation and quantified the level of cytosine methylation and its pattern in three satellite families of sugar beet (Beta vulgaris) which differ in their abundance, chromosomal localization and monomer size. We visualized methylation levels along pachytene chromosomes with respect to small satellite loci at maximum resolution using chromosome-wide fluorescent in situ hybridization complemented with immunostaining and super-resolution microscopy. Only reduced methylation of many satellite arrays was obtained. To investigate methylation at the nucleotide level we performed bisulfite sequencing of 1569 satellite sequences. We found that the level of methylation of cytosine strongly depends on the sequence context: cytosines in the CHH motif show lower methylation (44-52%), while CG and CHG motifs are more strongly methylated. This affects the overall methylation of satellite sequences because CHH occurs frequently while CG and CHG are rare or even absent in the satellite arrays investigated. Evidently, CHH is the major target for modulation of the cytosine methylation level of adjacent monomers within individual arrays and contributes to their epigenetic function. This strongly indicates that asymmetric cytosine methylation plays a role in the epigenetic modification of satellite repeats in plant genomes. PMID:24661787

  14. Novel features of telomere biology revealed by the absence of telomeric DNA methylation.

    PubMed

    Vega-Vaquero, Alejandro; Bonora, Giancarlo; Morselli, Marco; Vaquero-Sedas, María I; Rubbi, Liudmilla; Pellegrini, Matteo; Vega-Palas, Miguel A

    2016-08-01

    Cytosine methylation regulates the length and stability of telomeres, which can affect a wide variety of biological features, including cell differentiation, development, or illness. Although it is well established that subtelomeric regions are methylated, the presence of methylated cytosines at telomeres has remained controversial. Here, we have analyzed multiple bisulfite sequencing studies to address the methylation status of Arabidopsis thaliana telomeres. We found that the levels of estimated telomeric DNA methylation varied among studies. Interestingly, we estimated higher levels of telomeric DNA methylation in studies that produced C-rich telomeric strands with lower efficiency. However, these high methylation estimates arose due to experimental limitations of the bisulfite technique. We found a similar phenomenon for mitochondrial DNA: The levels of mitochondrial DNA methylation detected were higher in experiments with lower mitochondrial read production efficiencies. Based on experiments with high telomeric C-rich strand production efficiencies, we concluded that Arabidopsis telomeres are not methylated, which was confirmed by methylation-dependent restriction enzyme analyses. Thus, our studies indicate that telomeres are refractory to de novo DNA methylation by the RNA-directed DNA methylation machinery. This result, together with previously reported data, reveals that subtelomeric DNA methylation controls the homeostasis of telomere length. PMID:27405804

  15. Metabolic production of methylated selenium species requires adequate methylation status

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity negatively impacts methylation status and markers of methylation status vary according to selenium status in supplemented subjects. We have proposed that disruptions in methylation capacity induced by obesity compromise demonstrable anti-cancer effects of Se supplementation. In order to addr...

  16. DNA methylation dynamics in mouse preimplantation embryos revealed by mass spectrometry

    PubMed Central

    Okamoto, Yoshinori; Yoshida, Naoko; Suzuki, Toru; Shimozawa, Nobuhiro; Asami, Maki; Matsuda, Tomonari; Kojima, Nakao; Perry, Anthony C. F.; Takada, Tatsuyuki

    2016-01-01

    Following fertilization in mammals, paternal genomic 5-methyl-2′-deoxycytidine (5 mC) content is thought to decrease via oxidation to 5-hydroxymethyl-2′-deoxycytidine (5 hmC). This reciprocal model of demethylation and hydroxymethylation is inferred from indirect, non-quantitative methods. We here report direct quantification of genomic 5 mC and 5 hmC in mouse embryos by small scale liquid chromatographic tandem mass spectrometry (SMM). Profiles of absolute 5 mC levels in embryos produced by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) were almost identical. By 10 h after fertilization, 5 mC levels had declined by ~40%, consistent with active genomic DNA demethylation. Levels of 5 mC in androgenotes (containing only a paternal genome) and parthenogenotes (containing only a maternal genome) underwent active 5 mC loss in the first 6 h, showing that both parental genomes can undergo demethylation independently. We found no evidence for net loss of 5 mC 10–48 h after fertilization, implying that any passive ‘demethylation’ following DNA replication was balanced by active 5 mC maintenance methylation. However, levels of 5 mC declined during development after 48 h, to 1% (measured as a fraction of G-residues) in blastocysts (~96 h). 5 hmC levels were consistently low (<0.2% of G-residues) throughout development in normal diploid embryos. This work directly quantifies the dynamics of global genomic DNA modification in mouse preimplantation embryos, suggesting that SMM will be applicable to other biomedical situations with limiting sample sizes. PMID:26750605

  17. DNA methylation dynamics in mouse preimplantation embryos revealed by mass spectrometry.

    PubMed

    Okamoto, Yoshinori; Yoshida, Naoko; Suzuki, Toru; Shimozawa, Nobuhiro; Asami, Maki; Matsuda, Tomonari; Kojima, Nakao; Perry, Anthony C F; Takada, Tatsuyuki

    2016-01-01

    Following fertilization in mammals, paternal genomic 5-methyl-2'-deoxycytidine (5 mC) content is thought to decrease via oxidation to 5-hydroxymethyl-2'-deoxycytidine (5 hmC). This reciprocal model of demethylation and hydroxymethylation is inferred from indirect, non-quantitative methods. We here report direct quantification of genomic 5 mC and 5 hmC in mouse embryos by small scale liquid chromatographic tandem mass spectrometry (SMM). Profiles of absolute 5 mC levels in embryos produced by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) were almost identical. By 10 h after fertilization, 5 mC levels had declined by ~40%, consistent with active genomic DNA demethylation. Levels of 5 mC in androgenotes (containing only a paternal genome) and parthenogenotes (containing only a maternal genome) underwent active 5 mC loss in the first 6 h, showing that both parental genomes can undergo demethylation independently. We found no evidence for net loss of 5 mC 10-48 h after fertilization, implying that any passive 'demethylation' following DNA replication was balanced by active 5 mC maintenance methylation. However, levels of 5 mC declined during development after 48 h, to 1% (measured as a fraction of G-residues) in blastocysts (~96 h). 5 hmC levels were consistently low (<0.2% of G-residues) throughout development in normal diploid embryos. This work directly quantifies the dynamics of global genomic DNA modification in mouse preimplantation embryos, suggesting that SMM will be applicable to other biomedical situations with limiting sample sizes. PMID:26750605

  18. STATISTICAL COMPARISON OF THE EFFECT OF RELATIVE AND ABSOLUTE HUMIDITY ON FIXED-BED CARBON ADSORPTION CAPACITY

    EPA Science Inventory

    The paper describes statistical methods used to evaluate data for toluene (at several typical operating temperatures and humidity levels) and to determine which measure of humidity (relative or absolute) is more important in determining carbon adsorption efficiency. The water con...

  19. Mineralisation studies of 14C-labelled metsulfuron-methyl, tribenuron-methyl, chlorsulfuron and thifensulfuron-methyl in one Danish soil and groundwater sediment profile.

    PubMed

    Andersen, S M; Hertz, P B; Holst, T; Bossi, R; Jacobsen, C S

    2001-11-01

    Bacterial mineralisation of four sulfonylurea herbicides at 20 microg kg(-1) in a sandy soil from nine different depths in a sandy soil horizon (5-780 cm) was investigated in laboratory studies. Metsulfuron-methyl, chlorsulfuron, and tribenuron-methyl were 14C-labelled in the sulfonamide ring, while thifensulfuron-methyl was labelled in the thiophene ring. The highest mineralised amount in 126 days was observed for metsulfuron-methyl (40%) followed by tribenuron-methyl (25%), and thifensulfuron-methyl (11%). Chlorsulfuron showed low mineralisation in all the soils tested (<4%). Mineralisation of the herbicides metsulfuron-methyl and tribenuron-methyl varied according to soil depth (upper profile: 5-70 cm, and lower profile: 165-780 cm) and were proven faster in soil taken from depths 5-7 and 30-35 cm, and slower in depths 45-50 and 70-75 cm. Mineralisation was absent in the lower profile (165-780 cm). As an indicator of microbial activity bacterial counts were taken at the experimental start; these counts grouped in three levels: highest in the surface layer (5-7 cm), slightly lower in the depths 30-75 cm, and lowest in the lower profile (165-780 cm). Residual concentrations of metsulfuron-methyl correlated to the accumulated amount mineralised, with high residual concentrations in soil showing low mineralisation. Also chlorsulfuron showed high residual concentrations with increasing depth in the upper profile, but the relatively high dissipation at 30-35 cm and lower one at 45-50 cm could not be related with the lack of mineralisation. This shows that hydrolysis occurs, but mineralisation of the chloro-substituted sulfonamide is restricted. Tribenuron-methyl and thifensulfuron-methyl could not be detected due to interference with other compounds. PMID:11695596

  20. DNA Methylation in Osteoarthritis

    PubMed Central

    den Hollander, Wouter; Meulenbelt, Ingrid

    2015-01-01

    Osteoarthritis (OA) is a prevalent disease of articular joints and primarily characterized by degradation and calcification of articular cartilage. Presently, no effective treatment other than pain relief exists and patients ultimately need to undergo replacement surgery of the affected joint. During disease progression articular chondrocytes, the single cell type present in articular cartilage, show altered transcriptional profiles and undergo phenotypic changes that resemble the terminal differentiation route apparent in growth plate chondrocytes. Hence, given its prominent function in both regulating gene expression and maintaining cellular phenotypes, DNA methylation of CpG dinucleotides is intensively studied in the context of OA. An increasing number of studies have been published that employed a targeted approach on genes known to play a role in OA pathophysiology. As of such, it has become clear that OA responsive DNA methylation changes seem to mediate disease associated aberrant gene expression. Furthermore, established OA susceptibility alleles such as GDF5 and DIO2 appear to confer OA risk via DNA methylation and respective pathophysiological expression changes. In more recent years, genome wide profiling of DNA methylation in OA affected articular cartilage has emerged as a powerful tool to address the epigenetic changes in their entirety, which has resulted in the identification of putative patient subgroups as well as generic OA associated pathways. PMID:27019616

  1. DNA Methylation in Osteoarthritis.

    PubMed

    den Hollander, Wouter; Meulenbelt, Ingrid

    2015-12-01

    Osteoarthritis (OA) is a prevalent disease of articular joints and primarily characterized by degradation and calcification of articular cartilage. Presently, no effective treatment other than pain relief exists and patients ultimately need to undergo replacement surgery of the affected joint. During disease progression articular chondrocytes, the single cell type present in articular cartilage, show altered transcriptional profiles and undergo phenotypic changes that resemble the terminal differentiation route apparent in growth plate chondrocytes. Hence, given its prominent function in both regulating gene expression and maintaining cellular phenotypes, DNA methylation of CpG dinucleotides is intensively studied in the context of OA. An increasing number of studies have been published that employed a targeted approach on genes known to play a role in OA pathophysiology. As of such, it has become clear that OA responsive DNA methylation changes seem to mediate disease associated aberrant gene expression. Furthermore, established OA susceptibility alleles such as GDF5 and DIO2 appear to confer OA risk via DNA methylation and respective pathophysiological expression changes. In more recent years, genome wide profiling of DNA methylation in OA affected articular cartilage has emerged as a powerful tool to address the epigenetic changes in their entirety, which has resulted in the identification of putative patient subgroups as well as generic OA associated pathways. PMID:27019616

  2. Nutrients and DNA Methylation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epigenetics is a new mechanism responsible for development, aging, and disease process such as cancer development. One major epigenetic phenomenon is DNA methylation, which attributes to gene expression and integrity. Deepening the knowledge on one-carbon metabolism is very important to understandin...

  3. Thiophanate-methyl

    Integrated Risk Information System (IRIS)

    Thiophanate - methyl ; CASRN 23564 - 05 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcino

  4. Pirimiphos-methyl

    Integrated Risk Information System (IRIS)

    Pirimiphos - methyl ; CASRN 29232 - 93 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinog

  5. Methyl isobutyl ketone (MIBK)

    Integrated Risk Information System (IRIS)

    Methyl Isobutyl Ketone ( MIBK ) ; CASRN 108 - 10 - 1 ; Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for

  6. Haloxyfop-methyl

    Integrated Risk Information System (IRIS)

    Haloxyfop - methyl ; CASRN 69806 - 40 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinoge

  7. Methyl ethyl ketone (MEK)

    Integrated Risk Information System (IRIS)

    Methyl ethyl ketone ( MEK ) ( CASRN 78 - 93 - 3 ) Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Nonc

  8. Chloromethyl methyl ether (CMME)

    Integrated Risk Information System (IRIS)

    Chloromethyl methyl ether ( CMME ) ; CASRN 107 - 30 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments fo

  9. Kenaf methyl esters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Additional or alternative feedstocks are one of the major areas of interest regarding biodiesel. In this paper, for the first time, the fuel properties of kenaf (Hibiscus cannabinus L.) seed oil methyl esters are comprehensively reported. This biodiesel is also relatively unique by containing small ...

  10. Kapok oil methyl esters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The increased need for biodiesel feedstocks has caused various vegetable oils to be examined for this purpose. In the present work, the methyl esters of kapok (Ceiba pentandra) oil were prepared. The essential fuel properties were comprehensively determined and evaluated in comparison to specificati...

  11. Utilizing Gold Nanoparticle Probes to Visually Detect DNA Methylation.

    PubMed

    Chen, Kui; Zhang, Mingyi; Chang, Ya-Nan; Xia, Lin; Gu, Weihong; Qin, Yanxia; Li, Juan; Cui, Suxia; Xing, Gengmei

    2016-12-01

    The surface plasmon resonance (SPR) effect endows gold nanoparticles (GNPs) with the ability to visualize biomolecules. In the present study, we designed and constructed a GNP probe to allow the semi-quantitative analysis of methylated tumor suppressor genes in cultured cells. To construct the probe, the GNP surfaces were coated with single-stranded DNA (ssDNA) by forming Au-S bonds. The ssDNA contains a thiolated 5'-end, a regulatory domain of 12 adenine nucleotides, and a functional domain with absolute pairing with methylated p16 sequence (Met-p16). The probe, paired with Met-p16, clearly changed the color of aggregating GNPs probe in 5 mol/L NaCl solution. Utilizing the probe, p16 gene methylation in HCT116 cells was semi-quantified. Further, the methylation of E-cadherin, p15, and p16 gene in Caco2, HepG2, and HCT116 cell lines were detected by the corresponding probes, constructed with three domains. This simple and cost-effective method was useful for the diagnosis of DNA methylation-related diseases. PMID:27325520

  12. Utilizing Gold Nanoparticle Probes to Visually Detect DNA Methylation

    NASA Astrophysics Data System (ADS)

    Chen, Kui; Zhang, Mingyi; Chang, Ya-Nan; Xia, Lin; Gu, Weihong; Qin, Yanxia; Li, Juan; Cui, Suxia; Xing, Gengmei

    2016-06-01

    The surface plasmon resonance (SPR) effect endows gold nanoparticles (GNPs) with the ability to visualize biomolecules. In the present study, we designed and constructed a GNP probe to allow the semi-quantitative analysis of methylated tumor suppressor genes in cultured cells. To construct the probe, the GNP surfaces were coated with single-stranded DNA (ssDNA) by forming Au-S bonds. The ssDNA contains a thiolated 5'-end, a regulatory domain of 12 adenine nucleotides, and a functional domain with absolute pairing with methylated p16 sequence (Met- p16). The probe, paired with Met- p16, clearly changed the color of aggregating GNPs probe in 5 mol/L NaCl solution. Utilizing the probe, p16 gene methylation in HCT116 cells was semi-quantified. Further, the methylation of E-cadherin, p15, and p16 gene in Caco2, HepG2, and HCT116 cell lines were detected by the corresponding probes, constructed with three domains. This simple and cost-effective method was useful for the diagnosis of DNA methylation-related diseases.

  13. Formation of methyl iodide on a natural manganese oxide.

    PubMed

    Allard, Sébastien; Gallard, Hervé; Fontaine, Claude; Croué, Jean-Philippe

    2010-08-01

    This paper demonstrates that manganese oxides can initiate the formation of methyl iodide, a volatile compound that participates to the input of iodine into the atmosphere. The formation of methyl iodide was investigated using a natural manganese oxide in batch experiments for different conditions and concentrations of iodide, natural organic matter (NOM) and manganese oxide. Methyl iodide was formed at concentrations methyl iodide increased with increasing initial concentrations of iodide ion and Mn sand and when pH decreased from 7 to 5. The hydrophilic NOM isolate exhibited the lowest yield of methyl iodide whereas hydrophobic NOM isolates such as Suwannee River HPOA fraction produced the highest concentration of methyl iodide. The formation of methyl iodide could take place through the oxidation of NOM on manganese dioxide in the presence of iodide. However, the implication of elemental iodine cannot be excluded at acidic pH. Manganese oxides can then participate with ferric oxides to the formation of methyl iodide in soils and sediments. The formation of methyl iodide is unlikely in technical systems such as drinking water treatment i.e. for ppt levels of iodide and low contact times with manganese oxides. PMID:20580399

  14. Methylation Alterations at Imprinted Genes Detected Among Long Term Shiftworkers

    PubMed Central

    Jacobs, Daniel I.; Hansen, Johnni; Fu, Alan; Stevens, Richard G.; Tjonneland, Anne; Vogel, Ulla B.; Zheng, Tongzhang; Zhu, Yong

    2016-01-01

    Exposure to light at night through shiftwork has been linked to alterations in DNA methylation and increased risk of cancer development. Using an Illumina Infinium Methylation Assay, we analyzed methylation levels of 397 CpG sites in the promoter regions of 56 normally imprinted genes to investigate whether shiftwork is associated with alteration of methylation patterns. Methylation was significantly higher at 20 CpG sites and significantly lower at 30 CpG sites (P < 0.05) in 10 female long-term shiftworkers as compared to 10 female age- and folate intake-matched day workers. The strongest evidence for altered methylation patterns in shiftworkers was observed for DLX5, IGF2AS, and TP73 based on the magnitude of methylation change and consistency in the direction of change across multiple CpG sites, and consistent results were observed using quantitative DNA methylation analysis. We conclude that long-term shiftwork may alter methylation patterns at imprinted genes, which may be an important mechanism by which shiftwork has carcinogenic potential and warrants further investigation. PMID:23193016

  15. miRNA and methylation: a multifaceted liaison.

    PubMed

    Chhabra, Ravindresh

    2015-01-19

    miRNAs and DNA methylation are both critical regulators of gene expression. Aberration in miRNA expression or DNA methylation is a causal factor for numerous pathological conditions. DNA methylation can inhibit the transcription of miRNAs, just like coding genes, by methylating the CpG islands in the promoter regions of miRNAs. Conversely, certain miRNAs can directly target DNA methyltransferases and bring about their inhibition, thereby affecting the whole genome methylation pattern. Recently, methylation patterns have also been revealed in mRNA. Surprisingly, the two most commonly studied methylation states in mRNA (m6A and m5C) are found to be enriched in 3'-UTRs (untranslated regions), the target site for the majority of miRNAs. Whereas m5C is reported to stabilise mRNA, m6A has a destabilising effect on mRNA. However, the effect of mRNA methylation on its interaction with miRNAs is largely unexplored. The review highlights the complex interplay between microRNA and methylation at DNA and mRNA level. PMID:25469751

  16. DNA Methylation is Developmentally Regulated for Genes Essential for Cardiogenesis

    PubMed Central

    Chamberlain, Alyssa A.; Lin, Mingyan; Lister, Rolanda L.; Maslov, Alex A.; Wang, Yidong; Suzuki, Masako; Wu, Bingruo; Greally, John M.; Zheng, Deyou; Zhou, Bin

    2014-01-01

    Background DNA methylation is a major epigenetic mechanism altering gene expression in development and disease. However, its role in the regulation of gene expression during heart development is incompletely understood. The aim of this study is to reveal DNA methylation in mouse embryonic hearts and its role in regulating gene expression during heart development. Methods and Results We performed the genome‐wide DNA methylation profiling of mouse embryonic hearts using methyl‐sensitive, tiny fragment enrichment/massively parallel sequencing to determine methylation levels at ACGT sites. The results showed that while global methylation of 1.64 million ACGT sites in developing hearts remains stable between embryonic day (E) 11.5 and E14.5, a small fraction (2901) of them exhibit differential methylation. Gene Ontology analysis revealed that these sites are enriched at genes involved in heart development. Quantitative real‐time PCR analysis of 350 genes with differential DNA methylation showed that the expression of 181 genes is developmentally regulated, and 79 genes have correlative changes between methylation and expression, including hyaluronan synthase 2 (Has2). Required for heart valve formation, Has2 expression in the developing heart valves is downregulated at E14.5, accompanied with increased DNA methylation in its enhancer. Genetic knockout further showed that the downregulation of Has2 expression is dependent on DNA methyltransferase 3b, which is co‐expressed with Has2 in the forming heart valve region, indicating that the DNA methylation change may contribute to the Has2 enhancer's regulating function. Conclusions DNA methylation is developmentally regulated for genes essential to heart development, and abnormal DNA methylation may contribute to congenital heart disease. PMID:24947998

  17. The negative regulators of Wnt pathway-DACH1, DKK1, and WIF1 are methylated in oral and oropharyngeal cancer and WIF1 methylation predicts shorter survival.

    PubMed

    Paluszczak, Jarosław; Sarbak, Joanna; Kostrzewska-Poczekaj, Magdalena; Kiwerska, Katarzyna; Jarmuż-Szymczak, Małgorzata; Grenman, Reidar; Mielcarek-Kuchta, Daniela; Baer-Dubowska, Wanda

    2015-04-01

    The deregulation of Wnt signaling has recently emerged as one of the drivers of head and neck cancers. This is frequently related to the methylation of several antagonists of this pathway. This study aimed at the assessment of the profile of methylation of Wnt pathway antagonists and the determination of the prognostic value of the methylation of selected genes in oral carcinomas. The methylation of DACH1, DKK1, LKB1, PPP2R2B, RUNX3, SFRP2, and WIF-1 was analyzed in 16 oral squamous cell carcinoma cell lines using the methylation-specific polymerase chain reaction. The methylation of selected genes was further analyzed in tumor sections from 43 primary oral carcinoma patients. The analysis of oral carcinoma cell lines showed very frequent methylation of SFRP2 and WIF-1 and also a less frequent methylation of DACH1 and DKK1. On the other hand, RUNX3 was methylated only in one cell line, while LKB1 and PPP2R2B were not methylated in any of the cell lines. The biallelic methylation of DKK1 correlated with the low level of expression of this gene. Further evaluation of the methylation of DACH1, DKK1, and WIF1 in a clinical patient group confirmed the frequent methylation of WIF1 and intermediate or low frequency of methylation of DACH1 or DKK1, respectively. Importantly, the methylation of WIF-1 correlated with shorter survival in oral cancer patients. Overall, the methylation of the antagonists of Wnt pathway is frequently detected in oral squamous cell carcinomas. The methylation of WIF1 may be considered a prognostic marker in oral cancers. PMID:25487617

  18. A three-axis SQUID-based absolute vector magnetometer

    NASA Astrophysics Data System (ADS)

    Schönau, T.; Zakosarenko, V.; Schmelz, M.; Stolz, R.; Anders, S.; Linzen, S.; Meyer, M.; Meyer, H.-G.

    2015-10-01

    We report on the development of a three-axis absolute vector magnetometer suited for mobile operation in the Earth's magnetic field. It is based on low critical temperature dc superconducting quantum interference devices (LTS dc SQUIDs) with sub-micrometer sized cross-type Josephson junctions and exhibits a white noise level of about 10 fT/Hz1/2. The width of superconducting strip lines is restricted to less than 6 μm in order to avoid flux trapping during cool-down in magnetically unshielded environment. The long-term stability of the flux-to-voltage transfer coefficients of the SQUID electronics is investigated in detail and a method is presented to significantly increase their reproducibility. We further demonstrate the long-term operation of the setup in a magnetic field varying by about 200 μT amplitude without the need for recalibration.

  19. The neurocognitive components of pitch processing: insights from absolute pitch.

    PubMed

    Wilson, Sarah J; Lusher, Dean; Wan, Catherine Y; Dudgeon, Paul; Reutens, David C

    2009-03-01

    The natural variability of pitch naming ability in the population (known as absolute pitch or AP) provides an ideal method for investigating individual differences in pitch processing and auditory knowledge formation and representation. We have demonstrated the involvement of different cognitive processes in AP ability that reflects varying skill expertise in the presence of similar early age of onset of music tuition. These processes were related to different regions of brain activity, including those involved in pitch working memory (right prefrontal cortex) and the long-term representation of pitch (superior temporal gyrus). They reflected expertise through the use of context dependent pitch cues and the level of automaticity of pitch naming. They impart functional significance to structural asymmetry differences in the planum temporale of musicians and establish a neurobiological basis for an AP template. More generally, they indicate variability of knowledge representation in the presence of environmental fostering of early cognitive development that translates to differences in cognitive ability. PMID:18663250

  20. The Neurocognitive Components of Pitch Processing: Insights from Absolute Pitch

    PubMed Central

    Lusher, Dean; Wan, Catherine Y.; Dudgeon, Paul; Reutens, David C.

    2009-01-01

    The natural variability of pitch naming ability in the population (known as absolute pitch or AP) provides an ideal method for investigating individual differences in pitch processing and auditory knowledge formation and representation. We have demonstrated the involvement of different cognitive processes in AP ability that reflects varying skill expertise in the presence of similar early age of onset of music tuition. These processes were related to different regions of brain activity, including those involved in pitch working memory (right prefrontal cortex) and the long-term representation of pitch (superior temporal gyrus). They reflected expertise through the use of context dependent pitch cues and the level of automaticity of pitch naming. They impart functional significance to structural asymmetry differences in the planum temporale of musicians and establish a neurobiological basis for an AP template. More generally, they indicate variability of knowledge representation in the presence of environmental fostering of early cognitive development that translates to differences in cognitive ability. PMID:18663250

  1. Lunar eclipse photometry: absolute luminance measurements and modeling.

    PubMed

    Hernitschek, Nina; Schmidt, Elmar; Vollmer, Michael

    2008-12-01

    The Moon's time-dependent luminance was determined during the 9 February 1990 and 3 March 2007 total lunar eclipses by using calibrated, industry standard photometers. After the results were corrected to unit air mass and to standard distances for both Moon and Sun, an absolute calibration was accomplished by using the Sun's known luminance and a pre-eclipse lunar albedo of approximately 13.5%. The measured minimum level of brightness in the total phase of both eclipses was relatively high, namely -3.32 m(vis) and -1.7 m(vis), which hints at the absence of pronounced stratospheric aerosol. The light curves were modeled in such a way as to let the Moon move through an artificial Earth shadow composed of a multitude of disk and ring zones, containing a relative luminance data set from an atmospheric radiative transfer calculation. PMID:19037352

  2. A three-axis SQUID-based absolute vector magnetometer

    SciTech Connect

    Schönau, T.; Schmelz, M.; Stolz, R.; Anders, S.; Linzen, S.; Meyer, H.-G.; Zakosarenko, V.; Meyer, M.

    2015-10-15

    We report on the development of a three-axis absolute vector magnetometer suited for mobile operation in the Earth’s magnetic field. It is based on low critical temperature dc superconducting quantum interference devices (LTS dc SQUIDs) with sub-micrometer sized cross-type Josephson junctions and exhibits a white noise level of about 10 fT/Hz{sup 1/2}. The width of superconducting strip lines is restricted to less than 6 μm in order to avoid flux trapping during cool-down in magnetically unshielded environment. The long-term stability of the flux-to-voltage transfer coefficients of the SQUID electronics is investigated in detail and a method is presented to significantly increase their reproducibility. We further demonstrate the long-term operation of the setup in a magnetic field varying by about 200 μT amplitude without the need for recalibration.

  3. State estimation and absolute image registration for geosynchronous satellites

    NASA Technical Reports Server (NTRS)

    Nankervis, R.; Koch, D. W.; Sielski, H.

    1980-01-01

    Spacecraft state estimation and the absolute registration of Earth images acquired by cameras onboard geosynchronous satellites are described. The basic data type of the procedure consists of line and element numbers of image points called landmarks whose geodetic coordinates, relative to United States Geodetic Survey topographic maps, are known. A conventional least squares process is used to estimate navigational parameters and camera pointing biases from observed minus computed landmark line and element numbers. These estimated parameters along with orbit and attitude dynamic models are used to register images, using an automated grey level correlation technique, inside the span represented by the landmark data. In addition, the dynamic models can be employed to register images outside of the data span in a near real time mode. An important application of this mode is in support of meteorological studies where rapid data reduction is required for the rapid tracking and predicting of dynamic phenomena.

  4. Monitoring Groundwater Variations Using a Portable Absolute Gravimeter

    NASA Astrophysics Data System (ADS)

    Fukuda, Yoichi; Nishijima, Jun; Hasegawa, Takashi; Sofyan, Yayan; Taniguchi, Makoto; Abidin, Hasanuddin Z.; Delinom, Robert M.

    2010-05-01

    In urbanized areas, one of the urgent problems is to monitor the groundwater variations especially connected with land subsidence. Although the groundwater variations are usually measured by water level meters, gravity measurements can provide us additional information about the water mass movements which should be beneficial for the analyses of groundwater flow and the managements of water resources as well. Therefore, in order to establish a new technique to monitor the groundwater variations by means of the gravity measurements, we investigated the applicability of a portable type absolute gravimeter (Micro-G LaCoste Inc. A10-017). We will report the results of some test measurements in Japan, and the outline of the surveys in Jakarta, Indonesia. As for the absolute gravity measurements, FG-5 of MGL would be more popular. FG-5 is a high precision absolute gravimeter with a 2ugal-accuracy for laboratory use, while the nominal accuracy of A-10 is 10ugal (measurement precision: ±5ugal). In spite of the disadvantage, A-10 is well suited for the field surveys because it is much smaller than FG-5 and can be operated with 12VDC power. The repeated measurements using A10-017 in Kyushu University show good correlations between the measured gravity values and the groundwater levels in nearby observation wells. In a geothermal plant of Takigami, we also observed the gravity changes associated with the cycle of the geothermal fluid. All these test measurements have proved that the gravimeter can achieve a 10ugal (10nm/s2) or better accuracy in the field surveys. In Jakarta, Indonesia, excess groundwater pumping is going on and it causes land subsidence. To reveal the associated gravity changes, we conducted the first gravity survey in August 2008 and the second survey in July 2009. Mainly due to the instrumental troubles during the 2008 surveys, we have not obtained enough reliable data yet. Nevertheless the result obtained so far suggested the gravity increases in the

  5. A DNA methylation fingerprint of 1628 human samples

    PubMed Central

    Fernandez, Agustin F.; Assenov, Yassen; Martin-Subero, Jose Ignacio; Balint, Balazs; Siebert, Reiner; Taniguchi, Hiroaki; Yamamoto, Hiroyuki; Hidalgo, Manuel; Tan, Aik-Choon; Galm, Oliver; Ferrer, Isidre; Sanchez-Cespedes, Montse; Villanueva, Alberto; Carmona, Javier; Sanchez-Mut, Jose V.; Berdasco, Maria; Moreno, Victor; Capella, Gabriel; Monk, David; Ballestar, Esteban; Ropero, Santiago; Martinez, Ramon; Sanchez-Carbayo, Marta; Prosper, Felipe; Agirre, Xabier; Fraga, Mario F.; Graña, Osvaldo; Perez-Jurado, Luis; Mora, Jaume; Puig, Susana; Prat, Jaime; Badimon, Lina; Puca, Annibale A.; Meltzer, Stephen J.; Lengauer, Thomas; Bridgewater, John; Bock, Christoph; Esteller, Manel

    2012-01-01

    Most of the studies characterizing DNA methylation patterns have been restricted to particular genomic loci in a limited number of human samples and pathological conditions. Herein, we present a compromise between an extremely comprehensive study of a human sample population with an intermediate level of resolution of CpGs at the genomic level. We obtained a DNA methylation fingerprint of 1628 human samples in which we interrogated 1505 CpG sites. The DNA methylation patterns revealed show this epigenetic mark to be critical in tissue-type definition and stemness, particularly around transcription start sites that are not within a CpG island. For disease, the generated DNA methylation fingerprints show that, during tumorigenesis, human cancer cells underwent a progressive gain of promoter CpG-island hypermethylation and a loss of CpG methylation in non-CpG-island promoters. Although transformed cells are those in which DNA methylation disruption is more obvious, we observed that other common human diseases, such as neurological and autoimmune disorders, had their own distinct DNA methylation profiles. Most importantly, we provide proof of principle that the DNA methylation fingerprints obtained might be useful for translational purposes by showing that we are able to identify the tumor type origin of cancers of unknown primary origin (CUPs). Thus, the DNA methylation patterns identified across the largest spectrum of samples, tissues, and diseases reported to date constitute a baseline for developing higher-resolution DNA methylation maps and provide important clues concerning the contribution of CpG methylation to tissue identity and its changes in the most prevalent human diseases. PMID:21613409

  6. Density of Jatropha curcas Seed Oil and its Methyl Esters: Measurement and Estimations

    NASA Astrophysics Data System (ADS)

    Veny, Harumi; Baroutian, Saeid; Aroua, Mohamed Kheireddine; Hasan, Masitah; Raman, Abdul Aziz; Sulaiman, Nik Meriam Nik

    2009-04-01

    Density data as a function of temperature have been measured for Jatropha curcas seed oil, as well as biodiesel jatropha methyl esters at temperatures from above their melting points to 90 ° C. The data obtained were used to validate the method proposed by Spencer and Danner using a modified Rackett equation. The experimental and estimated density values using the modified Rackett equation gave almost identical values with average absolute percent deviations less than 0.03% for the jatropha oil and 0.04% for the jatropha methyl esters. The Janarthanan empirical equation was also employed to predict jatropha biodiesel densities. This equation performed equally well with average absolute percent deviations within 0.05%. Two simple linear equations for densities of jatropha oil and its methyl esters are also proposed in this study.

  7. Cell-Wide DNA De-Methylation and Re-Methylation of Purkinje Neurons in the Developing Cerebellum.

    PubMed

    Zhou, Feng C; Resendiz, Marisol; Lo, Chiao-Ling; Chen, Yuanyuan

    2016-01-01

    Global DNA de-methylation is thought to occur only during pre-implantation and gametogenesis in mammals. Scalable, cell-wide de-methylation has not been demonstrated beyond totipotent stages. Here, we observed a large scale de-methylation and subsequent re-methylation (CDR) (including 5-methylcytosine (5mC) and 5-hydroxylmethylcytosine (5hmC)) in post-mitotic cerebellar Purkinje cells (PC) through the course of normal development. Through single cell immuno-identification and cell-specific quantitative methylation assays, we demonstrate that the CDR event is an intrinsically scheduled program, occurring in nearly every PC. Meanwhile, cerebellar granule cells and basket interneurons adopt their own DNA methylation program, independent of PCs. DNA de-methylation was further demonstrated at the gene level, on genes pertinent to PC development. The PC, being one of the largest neurons in the brain, may showcase an amplified epigenetic cycle which may mediate stage transformation including cell cycle arrest, vast axonal-dendritic growth, and synaptogenesis at the onset of neuronal specificity. This discovery is a key step toward better understanding the breadth and role of DNA methylation and de-methylation during neural ontology. PMID:27583369

  8. Shotgun Bisulfite Sequencing of the Betula platyphylla Genome Reveals the Tree’s DNA Methylation Patterning

    PubMed Central

    Su, Chang; Wang, Chao; He, Lin; Yang, Chuanping; Wang, Yucheng

    2014-01-01

    DNA methylation plays a critical role in the regulation of gene expression. Most studies of DNA methylation have been performed in herbaceous plants, and little is known about the methylation patterns in tree genomes. In the present study, we generated a map of methylated cytosines at single base pair resolution for Betula platyphylla (white birch) by bisulfite sequencing combined with transcriptomics to analyze DNA methylation and its effects on gene expression. We obtained a detailed view of the function of DNA methylation sequence composition and distribution in the genome of B. platyphylla. There are 34,460 genes in the whole genome of birch, and 31,297 genes are methylated. Conservatively, we estimated that 14.29% of genomic cytosines are methylcytosines in birch. Among the methylation sites, the CHH context accounts for 48.86%, and is the largest proportion. Combined transcriptome and methylation analysis showed that the genes with moderate methylation levels had higher expression levels than genes with high and low methylation. In addition, methylated genes are highly enriched for the GO subcategories of binding activities, catalytic activities, cellular processes, response to stimulus and cell death, suggesting that methylation mediates these pathways in birch trees. PMID:25514241

  9. DIETARY METHYL MERCURY EXPOSURE IN AMERICAN KESTRELS; PILOT STUDY

    EPA Science Inventory

    Anthropogenic mercury emissions have increased atmospheric mercury levels about threefold since the advent of industrial activity. Atmospheric deposition is the primary source of mercury in the environment hence mercury contamination has increased in similar fashion. Methyl mercu...

  10. DNA Methylation Screening and Analysis

    PubMed Central

    Sant, Karilyn E.; Nahar, Muna S.; Dolinoy, Dana C.

    2013-01-01

    DNA methylation is an epigenetic form of gene regulation that is universally important throughout the life course, especially during in utero and postnatal development. DNA methylation aids in cell cycle regulation and cellular differentiation processes. Previous studies have demonstrated that DNA methylation profiles may be altered by diet and the environment, and that these profiles are especially vulnerable during development. Thus, it is important to understand the role of DNA methylation in developmental governance and subsequent disease progression. A variety of molecular methods exist to assay for global, gene-specific, and epigenome-wide methylation. Here we describe these methods and discuss their relative strengths and limitations. PMID:22669678

  11. Gyrokinetic Statistical Absolute Equilibrium and Turbulence

    SciTech Connect

    Jian-Zhou Zhu and Gregory W. Hammett

    2011-01-10

    A paradigm based on the absolute equilibrium of Galerkin-truncated inviscid systems to aid in understanding turbulence [T.-D. Lee, "On some statistical properties of hydrodynamical and magnetohydrodynamical fields," Q. Appl. Math. 10, 69 (1952)] is taken to study gyrokinetic plasma turbulence: A finite set of Fourier modes of the collisionless gyrokinetic equations are kept and the statistical equilibria are calculated; possible implications for plasma turbulence in various situations are discussed. For the case of two spatial and one velocity dimension, in the calculation with discretization also of velocity v with N grid points (where N + 1 quantities are conserved, corresponding to an energy invariant and N entropy-related invariants), the negative temperature states, corresponding to the condensation of the generalized energy into the lowest modes, are found. This indicates a generic feature of inverse energy cascade. Comparisons are made with some classical results, such as those of Charney-Hasegawa-Mima in the cold-ion limit. There is a universal shape for statistical equilibrium of gyrokinetics in three spatial and two velocity dimensions with just one conserved quantity. Possible physical relevance to turbulence, such as ITG zonal flows, and to a critical balance hypothesis are also discussed.

  12. Absolute surface energy for zincblende semiconductors

    NASA Astrophysics Data System (ADS)

    Zhang, S. B.; Wei, Su-Huai

    2003-03-01

    Recent advance in nanosciences requires the determination of surface (or facet) energy of semiconductors, which is often difficult due to the polar nature of some of the most important surfaces such as the (111)A/(111)B surfaces. Several approaches have been developed in the past [1-3] to deal with the problem but an unambiguous division of the polar surface energies is yet to come [2]. Here we show that an accurate division is indeed possible for the zincblende semiconductors and will present the results for GaAs, ZnSe, and CuInSe2 [4], respectively. A general trend emerges, relating the absolute surface energy to the ionicity of the bulk materials. [1] N. Chetty and R. M. Martin, Phys. Rev. B 45, 6074 (1992). [2] N. Moll, et al., Phys. Rev. B 54, 8844 (1996). [3] S. Mankefors, Phys. Rev. B 59, 13151 (1999). [4] S. B. Zhang and S.-H. Wei, Phys. Rev. B 65, 081402 (2002).

  13. Climate Absolute Radiance and Refractivity Observatory (CLARREO)

    NASA Technical Reports Server (NTRS)

    Leckey, John P.

    2015-01-01

    The Climate Absolute Radiance and Refractivity Observatory (CLARREO) is a mission, led and developed by NASA, that will measure a variety of climate variables with an unprecedented accuracy to quantify and attribute climate change. CLARREO consists of three separate instruments: an infrared (IR) spectrometer, a reflected solar (RS) spectrometer, and a radio occultation (RO) instrument. The mission will contain orbiting radiometers with sufficient accuracy, including on orbit verification, to calibrate other space-based instrumentation, increasing their respective accuracy by as much as an order of magnitude. The IR spectrometer is a Fourier Transform spectrometer (FTS) working in the 5 to 50 microns wavelength region with a goal of 0.1 K (k = 3) accuracy. The FTS will achieve this accuracy using phase change cells to verify thermistor accuracy and heated halos to verify blackbody emissivity, both on orbit. The RS spectrometer will measure the reflectance of the atmosphere in the 0.32 to 2.3 microns wavelength region with an accuracy of 0.3% (k = 2). The status of the instrumentation packages and potential mission options will be presented.

  14. Absolute decay width measurements in 16O

    NASA Astrophysics Data System (ADS)

    Wheldon, C.; Ashwood, N. I.; Barr, M.; Curtis, N.; Freer, M.; Kokalova, Tz; Malcolm, J. D.; Spencer, S. J.; Ziman, V. A.; Faestermann, Th; Krücken, R.; Wirth, H.-F.; Hertenberger, R.; Lutter, R.; Bergmaier, A.

    2012-09-01

    The reaction 126C(63Li, d)168O* at a 6Li bombarding energy of 42 MeV has been used to populate excited states in 16O. The deuteron ejectiles were measured using the high-resolution Munich Q3D spectrograph. A large-acceptance silicon-strip detector array was used to register the recoil and break-up products. This complete kinematic set-up has enabled absolute α-decay widths to be measured with high-resolution in the 13.9 to 15.9 MeV excitation energy regime in 16O; many for the first time. This energy region spans the 14.4 MeV four-α breakup threshold. Monte-Carlo simulations of the detector geometry and break-up processes yield detection efficiencies for the two dominant decay modes of 40% and 37% for the α+12C(g.s.) and a+12C(2+1) break-up channels respectively.

  15. Absolute calibration of forces in optical tweezers

    NASA Astrophysics Data System (ADS)

    Dutra, R. S.; Viana, N. B.; Maia Neto, P. A.; Nussenzveig, H. M.

    2014-07-01

    Optical tweezers are highly versatile laser traps for neutral microparticles, with fundamental applications in physics and in single molecule cell biology. Force measurements are performed by converting the stiffness response to displacement of trapped transparent microspheres, employed as force transducers. Usually, calibration is indirect, by comparison with fluid drag forces. This can lead to discrepancies by sizable factors. Progress achieved in a program aiming at absolute calibration, conducted over the past 15 years, is briefly reviewed. Here we overcome its last major obstacle, a theoretical overestimation of the peak stiffness, within the most employed range for applications, and we perform experimental validation. The discrepancy is traced to the effect of primary aberrations of the optical system, which are now included in the theory. All required experimental parameters are readily accessible. Astigmatism, the dominant effect, is measured by analyzing reflected images of the focused laser spot, adapting frequently employed video microscopy techniques. Combined with interface spherical aberration, it reveals a previously unknown window of instability for trapping. Comparison with experimental data leads to an overall agreement within error bars, with no fitting, for a broad range of microsphere radii, from the Rayleigh regime to the ray optics one, for different polarizations and trapping heights, including all commonly employed parameter domains. Besides signaling full first-principles theoretical understanding of optical tweezers operation, the results may lead to improved instrument design and control over experiments, as well as to an extended domain of applicability, allowing reliable force measurements, in principle, from femtonewtons to nanonewtons.

  16. Absolute spectrophotometry of northern compact planetary nebulae

    NASA Astrophysics Data System (ADS)

    Wright, S. A.; Corradi, R. L. M.; Perinotto, M.

    2005-06-01

    We present medium-dispersion spectra and narrowband images of six northern compact planetary nebulae (PNe): BoBn 1, DdDm 1, IC 5117, M 1-5, M 1-71, and NGC 6833. From broad-slit spectra, total absolute fluxes and equivalent widths were measured for all observable emission lines. High signal-to-noise emission line fluxes of Hα, Hβ, [Oiii], [Nii], and HeI may serve as emission line flux standards for northern hemisphere observers. From narrow-slit spectra, we derive systemic radial velocities. For four PNe, available emission line fluxes were measured with sufficient signal-to-noise to probe the physical properties of their electron densities, temperatures, and chemical abundances. BoBn 1 and DdDm 1, both type IV PNe, have an Hβ flux over three sigma away from previous measurements. We report the first abundance measurements of M 1-71. NGC 6833 measured radial velocity and galactic coordinates suggest that it is associated with the outer arm or possibly the galactic halo, and its low abundance ([O/H]=1.3× 10-4) may be indicative of low metallicity within that region.

  17. Measurement of Histone Methylation Dynamics by One-Carbon Metabolic Isotope Labeling and High-energy Collisional Dissociation Methylation Signature Ion Detection

    PubMed Central

    Tang, Hui; Tian, Bing; Brasier, Allan R.; Sowers, Lawrence C.; Zhang, Kangling

    2016-01-01

    Accumulating evidence suggests that cellular metabolites and nutrition levels control epigenetic modifications, including histone methylation. However, it is not currently possible to measure the metabolic control of histone methylation. Here we report a novel detection method to monitor methyl transfer from serine to histones through the one-carbon metabolic pathway, using stable-isotope labeling and detection of lysine methylation signature ions generated in high-energy-dissociation (HCD) tandem mass spectrometry. This method is a long-needed tool to study the metabolic control of histone methylation. PMID:27530234

  18. Trophic Status Controls Mercury Methylation Pathways in Northern Peats

    NASA Astrophysics Data System (ADS)

    Hines, M. E.; Zhang, L.; Barkay, T.; Krabbenhoft, D. P.; Schaefer, J.; Hu, H.; Sidelinger, W.; Liu, X.; Wang, Y.

    2015-12-01

    Methyl mercury (MeHg) can be produced by a variety of microbes including syntrophs, methanogens, acetogens, and fermenters, besides sulfate (SO42-, SRB) and iron- reducing bacteria. Many freshwater wetlands are deficient in electron acceptors that support the traditional respiratory pathways of methylation, yet they accumulate high levels of MeHg. To investigate methylation in these wetlands and to connect these pathways with vegetation and microbial communities, incubation experiments were conducted using peats from 26 sites in Alaska. The sites were clustered using multiple factor analysis based on pH, temp, CH4 and volatile fatty acids production rates, and surface vegetation composition. Three clusters were generated and corresponded to three trophic levels that were manifested by three pH levels (3.5, 4.5, and 5). Hg methylation activity in laboratory incubations was determined using the short-lived radioisotope 197Hg. In the low pH, Sphagnum-dominated cluster, methylation rates were less than 1% day-1 and likely conducted by primary fermenters. Conversely, the high pH trophic cluster dominated by Carex aquatilis and active syntrophy exhibited Hg methylation rates as high as 12% day-1. In intermediate sites, rich in Sphagnum magellanicum with less Carex, a gradient in syntrophy and Hg methylation paths was observed. Amendments with process-stimulators and inhibitors revealed no evidence of SO42- reduction, but suggested that SRB, metabolizing either syntrophically with methanogens and/or by fermentation, likely methylated Hg. While on going metatranscriptomics studies are required to verify the role of syntrophs, fermenters, and methanogens as methylators, these results revealed that Hg methylation pathways change greatly along trophic gradients with a dominance of respiratory pathways in mineral-rich sites, syntrophy dominance in intermediate sites, and fermentation dominance in nutrient-poor sites.

  19. Divergence of Gene Body DNA Methylation and Evolution of Plant Duplicate Genes

    PubMed Central

    Wang, Jun; Marowsky, Nicholas C.; Fan, Chuanzhu

    2014-01-01

    It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between duplicate genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of duplicate genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica) genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences) of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for duplicate genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes. PMID:25310342

  20. Absolute nuclear material assay using count distribution (LAMBDA) space

    DOEpatents

    Prasad, Mano K.; Snyderman, Neal J.; Rowland, Mark S.

    2015-12-01

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  1. Absolute nuclear material assay using count distribution (LAMBDA) space

    DOEpatents

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2012-06-05

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  2. Absolute Gravimetry in Fennoscandia - A Contribution to Understanding Postglacial Uplift

    NASA Astrophysics Data System (ADS)

    Pettersen, B. R.; Timmen, L.; Gitlein, O.; Muller, J.; Denker, H.; Makinen, J.; Bilker, M.; Lysaker, D. I.; Omang, O. C.; Svendsen, J. G.; Wilmes, H.; Falk, R.; Reinhold, A.; Hoppe, W.; Scherneck, H.; Lidberg, M.; Engen, B.; Kristiansen, O.; Engfeldt, A.; Strykowski, G.; Forsberg, R.; Klopping, F.; Sasagawa, G.

    2005-12-01

    The Fennoscandian postglacial uplift has been mapped geometrically using precise levelling, tide gauges, and networks of permanent GPS stations. The results identify major uplift rates at sites located around the northern part of the Gulf of Bothnia. The vertical motions decay in all directions away from this central location. An oval shaped zero uplift isoline tracks the general western and northern coastline of Norway and the Kola peninsula. It returns southwest through Russian Karelia and touches the southern tip of Sweden and northern Denmark. The uplift area (as measured by present day motions) has its major axis in the direction of southwest to northeast and covers a distance of about 2000 km. Absolute gravimetry was made in Finland and Norway in 1976 with a rise-and fall instrument. A decade later the number of gravity stations was expanded by JILAg-5, in Finland from 1988, in Norway from 1991, and in Sweden from 1992. FG5 was introduced in these three countries in 1993 (7 stations) and continued with an extended campaign in 1995 (12 stations). In 2003 a project was initiated by IfE, Hannover to collect observations simultaneously with GRACE on an annual cycle. New instruments were acquired by IfE (FG5-220), FGI (FG5-221), and UMB (FG5-226). New absolute gravity stations were established by the national mapping agencies in Denmark, Norway, and Sweden. The total number of prepared sites in Fennoscandia is now about 30. Most of them are co-located with permanent GPS, for many of which time series of several years are now available. Along the coast there are nearby tide gauge stations, many of which have time series of several decades. We describe the observing network, procedures, auxiliary observations, and discuss results obtained for selected sites. We compare the gravity results from different instruments and discuss the challenges of combining and validating such data products. Examples are shown where temporal gravity change may be compared to

  3. The absolute disparity anomaly and the mechanism of relative disparities.

    PubMed

    Chopin, Adrien; Levi, Dennis; Knill, David; Bavelier, Daphne

    2016-06-01

    There has been a long-standing debate about the mechanisms underlying the perception of stereoscopic depth and the computation of the relative disparities that it relies on. Relative disparities between visual objects could be computed in two ways: (a) using the difference in the object's absolute disparities (Hypothesis 1) or (b) using relative disparities based on the differences in the monocular separations between objects (Hypothesis 2). To differentiate between these hypotheses, we measured stereoscopic discrimination thresholds for lines with different absolute and relative disparities. Participants were asked to judge the depth of two lines presented at the same distance from the fixation plane (absolute disparity) or the depth between two lines presented at different distances (relative disparity). We used a single stimulus method involving a unique memory component for both conditions, and no extraneous references were available. We also measured vergence noise using Nonius lines. Stereo thresholds were substantially worse for absolute disparities than for relative disparities, and the difference could not be explained by vergence noise. We attribute this difference to an absence of conscious readout of absolute disparities, termed the absolute disparity anomaly. We further show that the pattern of correlations between vergence noise and absolute and relative disparity acuities can be explained jointly by the existence of the absolute disparity anomaly and by the assumption that relative disparity information is computed from absolute disparities (Hypothesis 1). PMID:27248566

  4. The absolute disparity anomaly and the mechanism of relative disparities

    PubMed Central

    Chopin, Adrien; Levi, Dennis; Knill, David; Bavelier, Daphne

    2016-01-01

    There has been a long-standing debate about the mechanisms underlying the perception of stereoscopic depth and the computation of the relative disparities that it relies on. Relative disparities between visual objects could be computed in two ways: (a) using the difference in the object's absolute disparities (Hypothesis 1) or (b) using relative disparities based on the differences in the monocular separations between objects (Hypothesis 2). To differentiate between these hypotheses, we measured stereoscopic discrimination thresholds for lines with different absolute and relative disparities. Participants were asked to judge the depth of two lines presented at the same distance from the fixation plane (absolute disparity) or the depth between two lines presented at different distances (relative disparity). We used a single stimulus method involving a unique memory component for both conditions, and no extraneous references were available. We also measured vergence noise using Nonius lines. Stereo thresholds were substantially worse for absolute disparities than for relative disparities, and the difference could not be explained by vergence noise. We attribute this difference to an absence of conscious readout of absolute disparities, termed the absolute disparity anomaly. We further show that the pattern of correlations between vergence noise and absolute and relative disparity acuities can be explained jointly by the existence of the absolute disparity anomaly and by the assumption that relative disparity information is computed from absolute disparities (Hypothesis 1). PMID:27248566

  5. Viral genome methylation as an epigenetic defense against geminiviruses.

    PubMed

    Raja, Priya; Sanville, Bradley C; Buchmann, R Cody; Bisaro, David M

    2008-09-01

    Geminiviruses encapsidate single-stranded DNA genomes that replicate in plant cell nuclei through double-stranded DNA intermediates that associate with cellular histone proteins to form minichromosomes. Like most plant viruses, geminiviruses are targeted by RNA silencing and encode suppressor proteins such as AL2 and L2 to counter this defense. These related proteins can suppress silencing by multiple mechanisms, one of which involves interacting with and inhibiting adenosine kinase (ADK), a cellular enzyme associated with the methyl cycle that generates S-adenosyl-methionine, an essential methyltransferase cofactor. Thus, we hypothesized that the viral genome is targeted by small-RNA-directed methylation. Here, we show that Arabidopsis plants with mutations in genes encoding cytosine or histone H3 lysine 9 (H3K9) methyltransferases, RNA-directed methylation pathway components, or ADK are hypersensitive to geminivirus infection. We also demonstrate that viral DNA and associated histone H3 are methylated in infected plants and that cytosine methylation levels are significantly reduced in viral DNA isolated from methylation-deficient mutants. Finally, we demonstrate that Beet curly top virus L2- mutant DNA present in tissues that have recovered from infection is hypermethylated and that host recovery requires AGO4, a component of the RNA-directed methylation pathway. We propose that plants use chromatin methylation as a defense against DNA viruses, which geminiviruses counter by inhibiting global methylation. In addition, our results establish that geminiviruses can be useful models for genome methylation in plants and suggest that there are redundant pathways leading to cytosine methylation. PMID:18596098

  6. Effects of Trophic Status on Mercury Methylation Pathways in Peatlands

    NASA Astrophysics Data System (ADS)

    Hines, M. E.; Zhang, L.; Sampath, S.; Hu, R.; Barkay, T.

    2014-12-01

    Methyl mercury (MeHg) is a bioaccumulative toxicant. It was believed to be produced by sulfate (SO4)- and iron- reducing bacteria (SRB and FeRB), but recent studies suggest that organisms that possess the gene cluster (hgcAB) can methylate Hg, which includes other microbial groups besides SRB and FeRB. Many areas known to accumulate high levels of MeHg are freshwater wetlands that lack sufficient electron acceptors to support the production of MeHg. To test the hypothesis that oligotrophic wetlands are able to methylate Hg by pathways that are not respiratory, peat was collected from three wetland sites in Alaska and three in Massachusetts that represented a trophic gradient. We determined rates of gas (CH4, CO2, H2) and LMW organic acid (formate, acetate, propionate, butyrate) formation, and rates of Hg methylation using the short-lived radioisotope 197Hg (half life 2.67 days). Two temperate sites exhibited strong terminal respiration (methanogenesis) and syntrophy, while the Alaskan sites and an oligotrophic temperate site exhibited low rates of both. Primary fermentation was an important process in the latter sites. Hg methylation was most active at the minerotrophic sites that exhibited active syntrophy and methanogenesis. Methylation decreased greatly in the presence of a methanogenic inhibitor and was stimulated by H2 indicating that methanogens and perhaps syntrophs were primary methylators. In the oligotrophic sites, the addition of SO4 stimulated methylation while a SO4 reduction inhibitor decreased methylation. There was no evidence of SO4 reduction in these samples suggesting that methylation was conducted by SRB that were metabolizing via fermentation and not SO4 reduction. While further studies are required to decipher the role of syntrophs including SRB varieties such as Syntrophobacter sp., these results indicate that fermentative bacteria may be able to significantly methylate Hg in wetlands that do not support anaerobic respiration.

  7. Orion Absolute Navigation System Progress and Challenge

    NASA Technical Reports Server (NTRS)

    Holt, Greg N.; D'Souza, Christopher

    2012-01-01

    The absolute navigation design of NASA's Orion vehicle is described. It has undergone several iterations and modifications since its inception, and continues as a work-in-progress. This paper seeks to benchmark the current state of the design and some of the rationale and analysis behind it. There are specific challenges to address when preparing a timely and effective design for the Exploration Flight Test (EFT-1), while still looking ahead and providing software extensibility for future exploration missions. The primary onboard measurements in a Near-Earth or Mid-Earth environment consist of GPS pseudo-range and delta-range, but for future explorations missions the use of star-tracker and optical navigation sources need to be considered. Discussions are presented for state size and composition, processing techniques, and consider states. A presentation is given for the processing technique using the computationally stable and robust UDU formulation with an Agee-Turner Rank-One update. This allows for computational savings when dealing with many parameters which are modeled as slowly varying Gauss-Markov processes. Preliminary analysis shows up to a 50% reduction in computation versus a more traditional formulation. Several state elements are discussed and evaluated, including position, velocity, attitude, clock bias/drift, and GPS measurement biases in addition to bias, scale factor, misalignment, and non-orthogonalities of the accelerometers and gyroscopes. Another consideration is the initialization of the EKF in various scenarios. Scenarios such as single-event upset, ground command, and cold start are discussed as are strategies for whole and partial state updates as well as covariance considerations. Strategies are given for dealing with latent measurements and high-rate propagation using multi-rate architecture. The details of the rate groups and the data ow between the elements is discussed and evaluated.

  8. Evaluation of the Absolute Regional Temperature Potential

    NASA Technical Reports Server (NTRS)

    Shindell, D. T.

    2012-01-01

    The Absolute Regional Temperature Potential (ARTP) is one of the few climate metrics that provides estimates of impacts at a sub-global scale. The ARTP presented here gives the time-dependent temperature response in four latitude bands (90-28degS, 28degS-28degN, 28-60degN and 60-90degN) as a function of emissions based on the forcing in those bands caused by the emissions. It is based on a large set of simulations performed with a single atmosphere-ocean climate model to derive regional forcing/response relationships. Here I evaluate the robustness of those relationships using the forcing/response portion of the ARTP to estimate regional temperature responses to the historic aerosol forcing in three independent climate models. These ARTP results are in good accord with the actual responses in those models. Nearly all ARTP estimates fall within +/-20%of the actual responses, though there are some exceptions for 90-28degS and the Arctic, and in the latter the ARTP may vary with forcing agent. However, for the tropics and the Northern Hemisphere mid-latitudes in particular, the +/-20% range appears to be roughly consistent with the 95% confidence interval. Land areas within these two bands respond 39-45% and 9-39% more than the latitude band as a whole. The ARTP, presented here in a slightly revised form, thus appears to provide a relatively robust estimate for the responses of large-scale latitude bands and land areas within those bands to inhomogeneous radiative forcing and thus potentially to emissions as well. Hence this metric could allow rapid evaluation of the effects of emissions policies at a finer scale than global metrics without requiring use of a full climate model.

  9. Absolute optical surface measurement with deflectometry

    NASA Astrophysics Data System (ADS)

    Li, Wansong; Sandner, Marc; Gesierich, Achim; Burke, Jan

    Deflectometry utilises the deformation and displacement of a sample pattern after reflection from a test surface to infer the surface slopes. Differentiation of the measurement data leads to a curvature map, which is very useful for surface quality checks with sensitivity down to the nanometre range. Integration of the data allows reconstruction of the absolute surface shape, but the procedure is very error-prone because systematic errors may add up to large shape deviations. In addition, there are infinitely many combinations for slope and object distance that satisfy a given observation. One solution for this ambiguity is to include information on the object's distance. It must be known very accurately. Two laser pointers can be used for positioning the object, and we also show how a confocal chromatic distance sensor can be used to define a reference point on a smooth surface from which the integration can be started. The used integration algorithm works without symmetry constraints and is therefore suitable for free-form surfaces as well. Unlike null testing, deflectometry also determines radius of curvature (ROC) or focal lengths as a direct result of the 3D surface reconstruction. This is shown by the example of a 200 mm diameter telescope mirror, whose ROC measurements by coordinate measurement machine and deflectometry coincide to within 0.27 mm (or a sag error of 1.3μm). By the example of a diamond-turned off-axis parabolic mirror, we demonstrate that the figure measurement uncertainty comes close to a well-calibrated Fizeau interferometer.

  10. Absolute determination of local tropospheric OH concentrations

    NASA Technical Reports Server (NTRS)

    Armerding, Wolfgang; Comes, Franz-Josef

    1994-01-01

    Long path absorption (LPA) according to Lambert Beer's law is a method to determine absolute concentrations of trace gases such as tropospheric OH. We have developed a LPA instrument which is based on a rapid tuning of the light source which is a frequency doubled dye laser. The laser is tuned across two or three OH absorption features around 308 nm with a scanning speed of 0.07 cm(exp -1)/microsecond and a repetition rate of 1.3 kHz. This high scanning speed greatly reduces the fluctuation of the light intensity caused by the atmosphere. To obtain the required high sensitivity the laser output power is additionally made constant and stabilized by an electro-optical modulator. The present sensitivity is of the order of a few times 10(exp 5) OH per cm(exp 3) for an acquisition time of a minute and an absorption path length of only 1200 meters so that a folding of the optical path in a multireflection cell was possible leading to a lateral dimension of the cell of a few meters. This allows local measurements to be made. Tropospheric measurements have been carried out in 1991 resulting in the determination of OH diurnal variation at specific days in late summer. Comparison with model calculations have been made. Interferences are mainly due to SO2 absorption. The problem of OH self generation in the multireflection cell is of minor extent. This could be shown by using different experimental methods. The minimum-maximum signal to noise ratio is about 8 x 10(exp -4) for a single scan. Due to the small size of the absorption cell the realization of an open air laboratory is possible in which by use of an additional UV light source or by additional fluxes of trace gases the chemistry can be changed under controlled conditions allowing kinetic studies of tropospheric photochemistry to be made in open air.

  11. Absolute Radiometric Calibration of KOMPSAT-3A

    NASA Astrophysics Data System (ADS)

    Ahn, H. Y.; Shin, D. Y.; Kim, J. S.; Seo, D. C.; Choi, C. U.

    2016-06-01

    This paper presents a vicarious radiometric calibration of the Korea Multi-Purpose Satellite-3A (KOMPSAT-3A) performed by the Korea Aerospace Research Institute (KARI) and the Pukyong National University Remote Sensing Group (PKNU RSG) in 2015.The primary stages of this study are summarized as follows: (1) A field campaign to determine radiometric calibrated target fields was undertaken in Mongolia and South Korea. Surface reflectance data obtained in the campaign were input to a radiative transfer code that predicted at-sensor radiance. Through this process, equations and parameters were derived for the KOMPSAT-3A sensor to enable the conversion of calibrated DN to physical units, such as at-sensor radiance or TOA reflectance. (2) To validate the absolute calibration coefficients for the KOMPSAT-3A sensor, we performed a radiometric validation with a comparison of KOMPSAT-3A and Landsat-8 TOA reflectance using one of the six PICS (Libya 4). Correlations between top-of-atmosphere (TOA) radiances and the spectral band responses of the KOMPSAT-3A sensors at the Zuunmod, Mongolia and Goheung, South Korea sites were significant for multispectral bands. The average difference in TOA reflectance between KOMPSAT-3A and Landsat-8 image over the Libya 4, Libya site in the red-green-blue (RGB) region was under 3%, whereas in the NIR band, the TOA reflectance of KOMPSAT-3A was lower than the that of Landsat-8 due to the difference in the band passes of two sensors. The KOMPSAT-3Aensor includes a band pass near 940 nm that can be strongly absorbed by water vapor and therefore displayed low reflectance. Toovercome this, we need to undertake a detailed analysis using rescale methods, such as the spectral bandwidth adjustment factor.

  12. The Case for Absolute Ligand Discrimination: Modeling Information Processing and Decision by Immune T Cells

    NASA Astrophysics Data System (ADS)

    François, Paul; Altan-Bonnet, Grégoire

    2016-03-01

    Some cells have to take decision based on the quality of surroundings ligands, almost irrespective of their quantity, a problem we name "absolute discrimination". An example of absolute discrimination is recognition of not-self by immune T Cells. We show how the problem of absolute discrimination can be solved by a process called "adaptive sorting". We review several implementations of adaptive sorting, as well as its generic properties such as antagonism. We show how kinetic proofreading with negative feedback implement an approximate version of adaptive sorting in the immune context. Finally, we revisit the decision problem at the cell population level, showing how phenotypic variability and feedbacks between population and single cells are crucial for proper decision.

  13. Dual Functions of the RFTS Domain of Dnmt1 in Replication-Coupled DNA Methylation and in Protection of the Genome from Aberrant Methylation

    PubMed Central

    Kimura, Hironobu; Sharif, Jafar; Muto, Masahiro; Koseki, Haruhiko; Takahashi, Saori; Suetake, Isao; Tajima, Shoji

    2015-01-01

    In mammals, DNA methylation plays important roles in embryogenesis and terminal differentiation via regulation of the transcription-competent chromatin state. The methylation patterns are propagated to the next generation during replication by maintenance DNA methyltransferase, Dnmt1, in co-operation with Uhrf1. In the N-terminal regulatory region, Dnmt1 contains proliferating cell nuclear antigen (PCNA)-binding and replication foci targeting sequence (RFTS) domains, which are thought to contribute to maintenance methylation during replication. To determine the contributions of the N-terminal regulatory domains to the DNA methylation during replication, Dnmt1 lacking the RFTS and/or PCNA-binding domains was ectopically expressed in embryonic stem cells, and then the effects were analyzed. Deletion of both the PCNA-binding and RFTS domains did not significantly affect the global DNA methylation level. However, replication-dependent DNA methylation of the differentially methylated regions of three imprinted genes, Kcnq1ot1/Lit1, Peg3, and Rasgrf1, was impaired in cells expressing the Dnmt1 with not the PCNA-binding domain alone but both the PCNA-binding and RFTS domains deleted. Even in the absence of Uhrf1, which is a prerequisite factor for maintenance DNA methylation, Dnmt1 with both the domains deleted apparently maintained the global DNA methylation level, whilst the wild type and the forms containing the RFTS domain could not perform global DNA methylation under the conditions used. This apparent maintenance of the global DNA methylation level by the Dnmt1 lacking the RFTS domain was dependent on its own DNA methylation activity as well as the presence of de novo-type DNA methyltransferases. We concluded that the RFTS domain, not the PCNA-binding domain, is solely responsible for the replication-coupled DNA methylation. Furthermore, the RFTS domain acts as a safety lock by protecting the genome from replication-independent DNA methylation. PMID:26383849

  14. Regulation of N-methyl-D-aspartate receptor expression and N-methyl-D-aspartate-induced cellular response during chronic hypoxia in differentiated rat PC12 cells.

    PubMed

    Kobayashi, S; Millhorn, D E

    2000-01-01

    The purpose of the present study was to examine the effect of chronic hypoxia on N-methyl-D-aspartate-mediated cellular responses in differentiated PC12 cells. PC12 cells were differentiated by treatment with nerve growth factor. Patch-clamp analysis in differentiated PC12 cells showed that extracellularly applied N-methyl-D-aspartate induced an inward current that was abolished by the presence of the N-methyl-D-aspartate receptor antagonist MK-801. Results from Ca(2+) imaging experiments showed that N-methyl-D-aspartate induced an elevation in intracellular free Ca(2+) which was also abolished by MK-801. We also examined the effect of hypoxia on the N-methyl-D-aspartate-induced current in nerve growth factor-treated cells. We found that the N-methyl-D-aspartate-induced inward current and the N-methyl-D-aspartate-induced elevation in intracellular free Ca(2+) were markedly attenuated by chronic hypoxia. We next examined the possibility that the reduced N-methyl-D-aspartate responsiveness was due to down-regulation of N-methyl-D-aspartate receptor levels. Northern blot and immunoblot analyses showed that both messenger RNA and protein levels for N-methyl-D-aspartate receptor subunit 1 were markedly decreased during hypoxia. However, the messenger RNA for N-methyl-D-aspartate receptor subunit 2C was increased, whereas the protein level for subunit 2C did not change. Our results indicate that differentiated PC12 cells express functional N-methyl-D-aspartate receptors and that chronic exposure to hypoxia attenuates the N-methyl-D-aspartate-induced Ca(2+) accumulation in these cells via down-regulation of N-methyl-D-aspartate receptor subunit 1. This mechanism may play an important role in protecting PC12 cells against hypoxic stress. PMID:11113364

  15. New DNA methylation markers and global DNA hypomethylation are associated with oral cancer development.

    PubMed

    Foy, Jean-Philippe; Pickering, Curtis R; Papadimitrakopoulou, Vassiliki A; Jelinek, Jaroslav; Lin, Steven H; William, William N; Frederick, Mitchell J; Wang, Jing; Lang, Wenhua; Feng, Lei; Zhang, Li; Kim, Edward S; Fan, You H; Hong, Waun K; El-Naggar, Adel K; Lee, J Jack; Myers, Jeffrey N; Issa, Jean-Pierre; Lippman, Scott M; Mao, Li; Saintigny, Pierre

    2015-11-01

    DNA promoter methylation of tumor suppressor genes and global DNA hypomethylation are common features of head and neck cancers. Our goal was to identify early DNA methylation changes in oral premalignant lesions (OPL) that may serve as predictive markers of developing oral squamous cell carcinoma (OSCC). Using high-throughput DNA methylation profiles of 24 OPLs, we found that the top 86 genes differentially methylated between patients who did or did not develop OSCC were simultaneously hypermethylated, suggesting that a CpG island methylation phenotype may occur early during OSCC development. The vast majority of the 86 genes were nonmethylated in normal tissues and hypermethylated in OSCC versus normal mucosa. We used pyrosequencing in a validation cohort of 44 patients to evaluate the degree of methylation of AGTR1, FOXI2, and PENK promoters CpG sites that were included in the top 86 genes and of LINE1 repetitive element methylation, a surrogate of global DNA methylation. A methylation index was developed by averaging the percent methylation of AGTR1, FOXI2, and PENK promoters; patients with a high methylation index had a worse oral cancer-free survival (P = 0.0030). On the other hand, patients with low levels of LINE1 methylation had a significantly worse oral cancer-free survival (P = 0.0153). In conclusion, AGTR1, FOXI2, and PENK promoter methylation and LINE1 hypomethylation may be associated with an increased risk of OSCC development in patients with OPLs. PMID:26342026

  16. Differential Methylation during Maize Leaf Growth Targets Developmentally Regulated Genes1[C][W][OPEN

    PubMed Central

    Candaele, Jasper; Demuynck, Kirin; Mosoti, Douglas; Beemster, Gerrit T.S.; Inzé, Dirk; Nelissen, Hilde

    2014-01-01

    DNA methylation is an important and widespread epigenetic modification in plant genomes, mediated by DNA methyltransferases (DMTs). DNA methylation is known to play a role in genome protection, regulation of gene expression, and splicing and was previously associated with major developmental reprogramming in plants, such as vernalization and transition to flowering. Here, we show that DNA methylation also controls the growth processes of cell division and cell expansion within a growing organ. The maize (Zea mays) leaf offers a great tool to study growth processes, as the cells progressively move through the spatial gradient encompassing the division zone, transition zone, elongation zone, and mature zone. Opposite to de novo DMTs, the maintenance DMTs were transcriptionally regulated throughout the growth zone of the maize leaf, concomitant with differential CCGG methylation levels in the four zones. Surprisingly, the majority of differentially methylated sequences mapped on or close to gene bodies and not to repeat-rich loci. Moreover, especially the 5′ and 3′ regions of genes, which show overall low methylation levels, underwent differential methylation in a developmental context. Genes involved in processes such as chromatin remodeling, cell cycle progression, and growth regulation, were differentially methylated. The presence of differential methylation located upstream of the gene anticorrelated with transcript expression, while gene body differential methylation was unrelated to the expression level. These data indicate that DNA methylation is correlated with the decision to exit mitotic cell division and to enter cell expansion, which adds a new epigenetic level to the regulation of growth processes. PMID:24488968

  17. The methylation status of plant genomic DNA influences PCR efficiency.

    PubMed

    Kiselev, K V; Dubrovina, A S; Tyunin, A P

    2015-03-01

    During the polymerase chain reaction (PCR), which is a versatile and widely used method, certain DNA sequences are rapidly amplified through thermocycling. Although there are numerous protocols of PCR optimization for different applications, little is known about the effect of DNA modifications, such as DNA methylation, on PCR efficiency. Recent studies show that cytosine methylation alters DNA mechanical properties and suggest that DNA methylation may directly or indirectly influence the effectiveness of DNA amplification during PCR. In the present study, using plant DNA, we found that highly methylated plant DNA genomic regions were amplified with lower efficiencies compared to that for the regions methylated at a lower level. The correlation was observed when amplifying stilbene synthase (STS1, STS10) genes of Vitis amurensis, the Actin2 gene of Arabidopsis thaliana, the internal transcribed spacer (AtITS), and tRNAPro of A. thaliana. The level of DNA methylation within the analyzed DNA regions has been analyzed with bisulfite sequencing. The obtained data show that efficient PCRs of highly methylated plant DNA regions can be hampered. Proteinase K treatment of the plant DNA prior to PCR and using HotTaq DNA polymerase improved amplification of the highly methylated plant DNA regions. We suggest that increased DNA denaturation temperatures of the highly methylated DNA and contamination with DNA-binding proteins contribute to the hampered PCR amplification of highly methylated DNA. The data show that it is necessary to use current DNA purification protocols and commercial kits with caution to ensure appropriate PCR product yield and prevent bias toward unmethylated DNA amplification in PCRs. PMID:25506767

  18. Mid-infrared absolute spectral responsivity scale based on an absolute cryogenic radiometer and an optical parametric oscillator laser

    NASA Astrophysics Data System (ADS)

    Zhao, Kun; Shi, Xueshun; Chen, Haidong; Liu, Yulong; Liu, Changming; Chen, Kunfeng; Li, Ligong; Gan, Haiyong; Ma, Chong

    2016-06-01

    We are reporting on a laser-based absolute spectral responsivity scale in the mid-infrared spectral range. By using a mid-infrared tunable optical parametric oscillator as the laser source, the absolute responsivity scale has been established by calibrating thin-film thermopile detectors against an absolute cryogenic radiometer. The thin-film thermopile detectors can be then used as transfer standard detectors. The extended uncertainty of the absolute spectral responsivity measurement has been analyzed to be 0.58%–0.68% (k  =  2).

  19. Conformation-Selective Methylation of Geminivirus DNA ▿

    PubMed Central

    Paprotka, T.; Deuschle, K.; Metzler, V.; Jeske, H.

    2011-01-01

    Geminiviruses with small circular single-stranded DNA genomes replicate in plant cell nuclei by using various double-stranded DNA (dsDNA) intermediates: distinct open circular and covalently closed circular as well as heterogeneous linear DNA. Their DNA may be methylated partially at cytosine residues, as detected previously by bisulfite sequencing and subsequent PCR. In order to determine the methylation patterns of the circular molecules, the DNAs of tomato yellow leaf curl Sardinia virus (TYLCSV) and Abutilon mosaic virus were investigated utilizing bisulfite treatment followed by rolling circle amplification. Shotgun sequencing of the products yielded a randomly distributed 50% rate of C maintenance after the bisulfite reaction for both viruses. However, controls with unmethylated single-stranded bacteriophage DNA resulted in the same level of C maintenance. Only one short DNA stretch within the C2/C3 promoter of TYLCSV showed hyperprotection of C, with the protection rate exceeding the threshold of the mean value plus 1 standard deviation. Similarly, the use of methylation-sensitive restriction enzymes suggested that geminiviruses escape silencing by methylation very efficiently, by either a rolling circle or recombination-dependent replication mode. In contrast, attempts to detect methylated bases positively by using methylcytosine-specific antibodies detected methylated DNA only in heterogeneous linear dsDNA, and methylation-dependent restriction enzymes revealed that the viral heterogeneous linear dsDNA was methylated preferentially. PMID:21835804

  20. Tocopherol, carotene, phenolic contents and antibacterial properties of rose essential oil, hydrosol and absolute.

    PubMed

    Ulusoy, Seyhan; Boşgelmez-Tinaz, Gülgün; Seçilmiş-Canbay, Hale

    2009-11-01

    The antioxidant and antibacterial activities, and total phenolic contents of Rosa damascena Mill. flower extracts (absolute, essential oil and hydrosol) were investigated. The chemical compositions of these extracts were analysed by GC-MS. Phenylethyl alcohol (78.38%) was found to be the main constituent of rose absolute, while citrenellol and geraniol were the major compounds (>55%) of rose essential oil and hydrosol. Tocopherol and carotene levels were determined by high performance liquid chromatography (HPLC) analysis. The levels of beta carotene (422.3+/-35.6 ppm), alpha tocopherol (2397.1+/-72.5 ppm) and gamma tocopherol (343.1+/-28.4 ppm) of rose absolute were found to be higher than that of essential oil and hydrosol. Their total phenolic contents were also evaluated. The total phenolic content of the tested extracts varied from 5.2 to 2134.3 GAE/mg L(-1). Rose absolute and essential oil contained high levels of phenolics and demonstrated strong antibacterial activity against Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538), Chromobacterium violaceum (ATCC 12472) and Erwinia carotovora (ATCC 39048) strains. PMID:19688375

  1. Predictors and Consequences of Global DNA Methylation in Cord Blood and at Three Years

    PubMed Central

    Herbstman, Julie B.; Wang, Shuang; Perera, Frederica P.; Lederman, Sally A.; Vishnevetsky, Julia; Rundle, Andrew G.; Hoepner, Lori A.; Qu, Lirong; Tang, Deliang

    2013-01-01

    DNA methylation changes have been implicated in many common chronic diseases leading to the hypothesis that environmental and age-related DNA methylation changes within individuals are involved in disease etiology. Few studies have examined DNA methylation changes within an individual over time and all of these studies have been conducted in adults. Here, we aim to characterize how global DNA methylation changes from birth to age three within a longitudinal birth cohort study and to determine whether there are consistent predictors of DNA methylation levels measured three years apart. We measured global DNA methylation in the same children at birth (cord blood) and again at three years of age among 165 children, using an immunoassay. We found that on average, DNA methylation was significantly higher in blood at age 3-years than in cord blood (p<0.01). However, for any individual child, the difference was less than would be expected by chance. We found that pre-pregnancy BMI was negatively predictive of both cord and three-year DNA methylation, even after statistical adjustment to account for the correlation between cord blood and three-year DNA methylation. The biologic implications of small changes in global DNA methylation are unknown. However, the observation that global DNA methylation levels persist within an individual from birth to age three supports the belief that factors that influence global DNA methylation, including pre-pregnancy BMI, may confer long-term effects. PMID:24023780

  2. A survey of DNA methylation across social insect species, life stages, and castes reveals abundant and caste-associated methylation in a primitively social wasp

    NASA Astrophysics Data System (ADS)

    Weiner, Susan A.; Galbraith, David A.; Adams, Dean C.; Valenzuela, Nicole; Noll, Fernando B.; Grozinger, Christina M.; Toth, Amy L.

    2013-08-01

    DNA methylation plays an important role in the epigenetic control of developmental and behavioral plasticity, with connections to the generation of striking phenotypic differences between castes (larger, reproductive queens and smaller, non-reproductive workers) in honeybees and ants. Here, we provide the first comparative investigation of caste- and life stage-associated DNA methylation in several species of bees and vespid wasps displaying different levels of social organization. Our results reveal moderate levels of DNA methylation in most bees and wasps, with no clear relationship to the level of sociality. Strikingly, primitively social Polistes dominula paper wasps show unusually high overall DNA methylation and caste-related differences in site-specific methylation. These results suggest DNA methylation may play a role in the regulation of behavioral and physiological differences in primitively social species with more flexible caste differences.

  3. Assessment of DNA methylation changes in tissue culture of Brassica napus.

    PubMed

    Gao, Y; Ran, L; Kong, Y; Jiang, J; Sokolov, V; Wang, Y

    2014-11-01

    Plant tissue culture, as a fundamental technique for genetic engineering, has great potential of epigenetic variation, of which DNA methylation is well known of importance to genome activity. We assessed DNA methylation level of explants during tissue culture of Brassica napus (cv. Yangyou 9), using high-performance liquid chromatography (HPLC) assisted quantification. By detecting methylation levels in hypocotyls cultured in mediums with different concentrations of hormones, we found dissected tissue:cultured with 0.1 mg/L 2,4-D and 1.0 mg/L 6-BA, presented the lowest methylation level and highest induction rate of callus (91.0%). Different time point of cultured explants also showed obvious methylation variations, explants cultured after 6 and 21 days exhibited methylation ratios of 4.33 and 8.07%, respectively. Whereas, the methylation ratio raised to 38.7% after 30 days cultivation, indicating that methylation level of hypocotyls ranged during tissue culture. Moreover, we observed that the methylation level in callus is the highest during regeneration of rape-seed, following the regenerated plantlets and hypocotyls. This paper indicated the function of hormones and differentiation of callus is relevant to the methylation levels during tissue culture. PMID:25739287

  4. Combined absolute and relative gravity measurement for microgravity monitoring in Aso volcanic field

    NASA Astrophysics Data System (ADS)

    Sofyan, Yayan; Nishijima, Jun; Yoshikawa, Shin; Fujimitsu, Yasuhiro; Kagiyama, Tsuneomi; Fukuda, Yoichi

    2014-05-01

    Absolute measurement with a portable A10-017 absolute gravimeter at some benchmarks in the Aso volcanic field are valuable for reducing uncertainties of regional gravity variations and will be useful for delineating the long term trends of gravity changes. A10 absolute gravimeter is a new generation of portable absolute instrument and has accuracy 10 microGal. To further the development of a high precision gravity data, we also conducted measurement using two relative gravimeter (Scintrex CG-5 [549] and LaCoste type G-1016) to be combined with an A10 absolute gravimeter. The using absolute gravimeter along with relative gravimeter can reduce drift correction factor and improve the result of gravity change data in microgravity monitoring. Microgravity monitoring is a valued tool for mapping the redistribution of subsurface mass and for assessing changes in the fluid as a dynamic process in volcanic field. Gravity changes enable the characterization of subsurface processes: i.e., the mass of the intrusion or hydrothermal flow. A key assumption behind gravity monitoring is that changes in earth's gravity reflect mass-transport processes at depth [1]. The absolute gravity network was installed at seven benchmarks using on May 2010, which re-occupied in October 2010, and June 2011. The relative gravity measurements were performed at 28 benchmarks in one month before the eruption on May 2011 and then followed by series of gravity monitoring after the eruption in every three to five months. Gravity measurements covered the area more than 60 km2 in the west side of Aso caldera. Some gravity benchmarks were measured using both absolute and relative gravimeter and is used as the reference benchmarks. In longer time period, the combined gravity method will improve the result of gravity change data for monitoring in the Aso volcanic field. As a result, the gravity changes detected the hydrothermal flow in the subsurface which has a correlation to water level fluctuation in the

  5. Identification of DNA methylation of SOX9 in cervical cancer using methylated-CpG island recovery assay.

    PubMed

    Wu, Jian-Hong; Liang, Xue-Ai; Wu, Yu-Mei; Li, Feng-Shuang; Dai, Yin-Mei

    2013-01-01

    The aim of the present study was to identify novel methylation markers for cervical cancer screening and to test the clinical application of the most promising biomarker in cervical scrapings. Methylated-CpG island recovery assay-based microarray analysis was carried out on a discovery set consisting of cervical cancer tissue and normal cervical tissue to identify significantly hypermethylated genes. Five hundred and four CpG islands, corresponding to 378 genes, were differentially methylated between cervical cancer tissue and normal cervical tissue. Among them, 30 genes were significantly hypermethylated. Of the 30 genes, SOX9, PKLR and DLX4 were selected for further validation by direct bisulfite sequencing. The SOX9 gene revealed complete methylation in the cervical cancer tissue and complete non-methylation in the normal control tissue. A TaqMan-based real-time PCR assay was performed to detect the methylation levels of the SOX9 gene in 156 cervical scrapings, including 48 normal cervical scrapings, 30 scrapings with cervical intraepithelial neoplasia 1 (CIN1), 30 scrapings with CIN2-3 and 48 scrapings with squamous cell carcinoma (SCC). The methylation levels (methylation score) of the SOX9 gene increased significantly with the severity of cervical squamous lesions. The area under the receiver operating characteristic (ROC) curve (AUC) revealed that the methylation score of the SOX9 gene could be used to segregate SCC/CIN2-3 from CIN1/normal (AUC, 0.961; p=0.000). At the optimal cut-off value, a sensitivity of 92.3% and a specificity of 89.7% were obtained. In conclusion, SOX9 methylation is frequently involved in cervical carcinogenesis, and may provide a valuable molecular biomarker for early detection of cervical cancer. PMID:23064448

  6. Supplementary and Enrichment Series: Absolute Value. Teachers' Commentary. SP-25.

    ERIC Educational Resources Information Center

    Bridgess, M. Philbrick, Ed.

    This is one in a series of manuals for teachers using SMSG high school supplementary materials. The pamphlet includes commentaries on the sections of the student's booklet, answers to the exercises, and sample test questions. Topics covered include addition and multiplication in terms of absolute value, graphs of absolute value in the Cartesian…

  7. Supplementary and Enrichment Series: Absolute Value. SP-24.

    ERIC Educational Resources Information Center

    Bridgess, M. Philbrick, Ed.

    This is one in a series of SMSG supplementary and enrichment pamphlets for high school students. This series is designed to make material for the study of topics of special interest to students readily accessible in classroom quantity. Topics covered include absolute value, addition and multiplication in terms of absolute value, graphs of absolute…

  8. Novalis' Poetic Uncertainty: A "Bildung" with the Absolute

    ERIC Educational Resources Information Center

    Mika, Carl

    2016-01-01

    Novalis, the Early German Romantic poet and philosopher, had at the core of his work a mysterious depiction of the "absolute." The absolute is Novalis' name for a substance that defies precise knowledge yet calls for a tentative and sensitive speculation. How one asserts a truth, represents an object, and sets about encountering things…

  9. Chiral separation, configurational identification and antihypertensive evaluation of (±)-7,8-dihydroxy-3-methyl-isochromanone-4.

    PubMed

    Bai, Renren; Liu, Jie; Zhu, Yao; Yang, Xue; Yang, Chen; Kong, Lingyi; Wang, Xiaobing; Zhang, Hengyuan; Yao, Hequan; Shen, Mingqin; Wu, Xiaoming; Xu, Jinyi

    2012-10-15

    (±)-7,8-Dihydroxy-3-methyl-isochromanone-4 [(±)-XJP] is a natural antihypertensive product contained in banana (Musa sapientum L.) peel. (-)-XJP and (+)-XJP were first obtained by chiral resolution, meanwhile circular dichroism (CD) calculations and chiral synthesis were employed to investigate the absolute configuration. The results indicated that the absolute configuration of (+)-XJP is S-configured and the absolute configuration of (-)-XJP is R-configured. Furthermore, the evaluation of antihypertensive effects in vivo proved that R-(-)-XJP was more potent than S-(+)-XJP and [(±)-XJP]. PMID:22963765

  10. Protection against de novo methylation is instrumental in maintaining parent-of-origin methylation inherited from the gametes.

    PubMed

    Proudhon, Charlotte; Duffié, Rachel; Ajjan, Sophie; Cowley, Michael; Iranzo, Julian; Carbajosa, Guillermo; Saadeh, Heba; Holland, Michelle L; Oakey, Rebecca J; Rakyan, Vardhman K; Schulz, Reiner; Bourc'his, Déborah

    2012-09-28

    Identifying loci with parental differences in DNA methylation is key to unraveling parent-of-origin phenotypes. By conducting a MeDIP-Seq screen in maternal-methylation free postimplantation mouse embryos (Dnmt3L-/+), we demonstrate that maternal-specific methylation exists very scarcely at midgestation. We reveal two forms of oocyte-specific methylation inheritance: limited to preimplantation, or with longer duration, i.e. maternally imprinted loci. Transient and imprinted maternal germline DMRs (gDMRs) are indistinguishable in gametes and preimplantation embryos, however, de novo methylation of paternal alleles at implantation delineates their fates and acts as a major leveling factor of parent-inherited differences. We characterize two new imprinte