Study of methylation sites and factors in contaminated aquatic systems in the Amazon using an optimized radiochemical technique

International Nuclear Information System (INIS)

Davee Guimaraes, Jean Remy

2002-01-01

Measurements of net 203 Hg methylation potentials were made in a set of floodplain lakes of the Tapajos river, Brazilian Amazon, on roots of the floating macrophyte Paspalurn sp. during the wet and dry seasons. Water physico-chemical parameters and C, N, and C and N isotopic ratios on root -associated periphyton were also determined. We confirmed the high Hg methylation potentials in roots of Paspalurn sp. and other macrophyte species (up to 22%) but observed that the intra and inter-lake variations in root methylation potentials are high, even when sampling one single macrophyte species. Correlations between Hg methylation in roots of Paspalurn sp and other measured parameters are low, possibly due to the limited data set available so far. Other tracer techniques have been recently introduced in this study, such as measurements of bacterial activity estimated by tritiated leucine uptake and sulfate-reduction measurements 35 S0 4 uptake, and it is expected that they will contribute to the understanding of the environmental parameters controlling Hg methylation in the studied water systems. (author)

Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer.

Science.gov (United States)

White-Al Habeeb, Nicole M A; Ho, Linh T; Olkhov-Mitsel, Ekaterina; Kron, Ken; Pethe, Vaijayanti; Lehman, Melanie; Jovanovic, Lidija; Fleshner, Neil; van der Kwast, Theodorus; Nelson, Colleen C; Bapat, Bharati

2014-09-15

Epigenetic silencing mediated by CpG methylation is a common feature of many cancers. Characterizing aberrant DNA methylation changes associated with tumor progression may identify potential prognostic markers for prostate cancer (PCa). We treated two PCa cell lines, 22Rv1 and DU-145 with the demethylating agent 5-Aza 2'-deoxycitidine (DAC) and global methylation status was analyzed by performing methylation-sensitive restriction enzyme based differential methylation hybridization strategy followed by genome-wide CpG methylation array profiling. In addition, we examined gene expression changes using a custom microarray. Gene Set Enrichment Analysis (GSEA) identified the most significantly dysregulated pathways. In addition, we assessed methylation status of candidate genes that showed reduced CpG methylation and increased gene expression after DAC treatment, in Gleason score (GS) 8 vs. GS6 patients using three independent cohorts of patients; the publically available The Cancer Genome Atlas (TCGA) dataset, and two separate patient cohorts. Our analysis, by integrating methylation and gene expression in PCa cell lines, combined with patient tumor data, identified novel potential biomarkers for PCa patients. These markers may help elucidate the pathogenesis of PCa and represent potential prognostic markers for PCa patients.

Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors.

Directory of Open Access Journals (Sweden)

Hector Hernandez-Vargas

Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is characterized by late detection and fast progression, and it is believed that epigenetic disruption may be the cause of its molecular and clinicopathological heterogeneity. A better understanding of the global deregulation of methylation states and how they correlate with disease progression will aid in the design of strategies for earlier detection and better therapeutic decisions. METHODS AND FINDINGS: We characterized the changes in promoter methylation in a series of 30 HCC tumors and their respective surrounding tissue and identified methylation signatures associated with major risk factors and clinical correlates. A wide panel of cancer-related gene promoters was analyzed using Illumina bead array technology, and CpG sites were then selected according to their ability to classify clinicopathological parameters. An independent series of HCC tumors and matched surrounding tissue was used for validation of the signatures. We were able to develop and validate a signature of methylation in HCC. This signature distinguished HCC from surrounding tissue and from other tumor types, and was independent of risk factors. However, aberrant methylation of an independent subset of promoters was associated with tumor progression and etiological risk factors (HBV or HCV infection and alcohol consumption. Interestingly, distinct methylation of an independent panel of gene promoters was strongly correlated with survival after cancer therapy. CONCLUSION: Our study shows that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression stage, with potential clinical applications in diagnosis and prognosis.

Heterogeneity in white blood cells has potential to confound DNA methylation measurements.

Directory of Open Access Journals (Sweden)

Bjorn T Adalsteinsson

Full Text Available Epigenetic studies are commonly conducted on DNA from tissue samples. However, tissues are ensembles of cells that may each have their own epigenetic profile, and therefore inter-individual cellular heterogeneity may compromise these studies. Here, we explore the potential for such confounding on DNA methylation measurement outcomes when using DNA from whole blood. DNA methylation was measured using pyrosequencing-based methodology in whole blood (n = 50-179 and in two white blood cell fractions (n = 20, isolated using density gradient centrifugation, in four CGIs (CpG Islands located in genes HHEX (10 CpG sites assayed, KCNJ11 (8 CpGs, KCNQ1 (4 CpGs and PM20D1 (7 CpGs. Cellular heterogeneity (variation in proportional white blood cell counts of neutrophils, lymphocytes, monocytes, eosinophils and basophils, counted by an automated cell counter explained up to 40% (p<0.0001 of the inter-individual variation in whole blood DNA methylation levels in the HHEX CGI, but not a significant proportion of the variation in the other three CGIs tested. DNA methylation levels in the two cell fractions, polymorphonuclear and mononuclear cells, differed significantly in the HHEX CGI; specifically the average absolute difference ranged between 3.4-15.7 percentage points per CpG site. In the other three CGIs tested, methylation levels in the two fractions did not differ significantly, and/or the difference was more moderate. In the examined CGIs, methylation levels were highly correlated between cell fractions. In summary, our analysis detects region-specific differential DNA methylation between white blood cell subtypes, which can confound the outcome of whole blood DNA methylation measurements. Finally, by demonstrating the high correlation between methylation levels in cell fractions, our results suggest a possibility to use a proportional number of a single white blood cell type to correct for this confounding effect in analyses.

Characterization of a novel and potentially lethal designer drug (±)-cis-para-methyl-4-methylaminorex (4,4'-DMAR, or 'Serotoni').

Science.gov (United States)

Brandt, Simon D; Baumann, Michael H; Partilla, John S; Kavanagh, Pierce V; Power, John D; Talbot, Brian; Twamley, Brendan; Mahony, Olivia; O'Brien, John; Elliott, Simon P; Archer, Roland P; Patrick, Julian; Singh, Kuldip; Dempster, Nicola M; Cosbey, Simon H

2014-01-01

During the second half of 2013, a total of 26 deaths involving para-methyl-4-methylaminorex (4,4'-DMAR) were reported to the European Monitoring Centre for Drugs and Drug Addiction. While aminorex and 4-methylaminorex (4-MAR) are known psychostimulants, nothing is known about the comparatively new para-methyl analog. Analytical characterization of two independent samples obtained from online vendors confirmed the presence of the (±)-cis isomer that also appeared to be associated with at least 18 of the 26 deaths. Extensive characterizations included crystal structure analysis, single, tandem, and high-resolution mass spectrometry, liquid and gas chromatography, and nuclear magnetic resonance spectroscopy. For the work described here, both the (±)-cis and (±)-trans racemates were also synthesized, confirming that the differentiation between these two forms was straight-forward. Monoamine transporter activity was studied using rat brain synaptosomes which included the comparison with d-amphetamine, aminorex and (±)-cis-4-MAR. (±)-cis-4,4'-DMAR was a potent, efficacious substrate-type releaser at transporters for dopamine, norepinephrine and serotonin with EC50 values of 8.6 ± 1.1 nM (DAT), 26.9 ± 5.9 nM (NET) and 18.5 ± 2.8 nM (SERT), respectively. The potency of (±)-cis-4,4'-DMAR at DAT and NET rivalled that of other psychomotor stimulant drugs like d-amphetamine and aminorex. However, (±)-cis-4,4'-DMAR had much more potent actions at SERT and activity at SERT varied more than 100-fold across the four drugs. The potent releasing activity of (±)-cis-4,4'-DMAR at all three monoamine transporters predicts a potential for serious side-effects such as psychotic symptoms, agitation, hyperthermia and cardiovascular stimulation, especially after high-dose exposure or following combination with other psychostimulants. Copyright © 2014 John Wiley & Sons, Ltd.

Mercury methylation rates of biofilm and plankton microorganisms from a hydroelectric reservoir in French Guiana.

Science.gov (United States)

Huguet, L; Castelle, S; Schäfer, J; Blanc, G; Maury-Brachet, R; Reynouard, C; Jorand, F

2010-02-15

The Petit-Saut ecosystem is a hydroelectric reservoir covering 365km(2) of flooded tropical forest. This reservoir and the Sinnamary Estuary downstream of the dam are subject to significant mercury methylation. The mercury methylation potential of plankton and biofilm microorganisms/components from different depths in the anoxic reservoir water column and from two different sites along the estuary was assessed. For this, reservoir water and samples of epiphytic biofilms from the trunk of a submerged tree in the anoxic water column and from submerged branches in the estuary were batch-incubated from 1h to 3 months with a nominal 1000ng/L spike of Hg(II) chloride enriched in (199)Hg. Methylation rates were determined for different reservoir and estuarine communities under natural nutrient (reservoir water, estuary freshwater) and artificial nutrient (culture medium) conditions. Methylation rates in reservoir water incubations were the highest with plankton microorganisms sampled at -9.5m depth (0.5%/d) without addition of biofilm components. Mercury methylation rates of incubated biofilm components were strongly enhanced by nutrient addition. The results suggested that plankton microorganisms strongly contribute to the total Hg methylation in the Petit-Saut reservoir and in the Sinnamary Estuary. Moreover, specific methylation efficiencies (%Me(199)Hg(net)/cell) suggested that plankton microorganisms could be more efficient methylating actors than biofilm consortia and that their methylation efficiency may be reduced in the presence of biofilm components. Extrapolation to the reservoir scale of the experimentally determined preliminary methylation efficiencies suggested that plankton microorganisms in the anoxic water column could produce up to 27mol MeHg/year. Taking into account that (i) demethylation probably occurs in the reservoir and (ii) that the presence of biofilm components may limit the methylation efficiency of plankton microorganisms, this result is

Variable Methylation Potential in Preterm Placenta: Implication for Epigenetic Programming of the Offspring.

Science.gov (United States)

Khot, Vinita V; Chavan-Gautam, Preeti; Mehendale, Savita; Joshi, Sadhana R

2017-06-01

Children born preterm are reported to be at increased risk of developing noncommunicable diseases in later life. Altered placental DNA methylation patterns are implicated in fetal programming of adult diseases. Our earlier animal studies focus on micronutrients (folic acid, vitamin B 12 ) and long-chain polyunsaturated fatty acids (LCPUFAs) that interact in the 1 carbon cycle, thereby influencing methylation reactions. Our previous studies in women delivering preterm show altered plasma levels of micronutrients and lower plasma LCPUFA levels. We postulate that alterations in the micronutrient metabolism may affect the regulation of enzymes, methionine adenosyltransferase ( MAT2A), and SAH-hydrolase ( AHCY), involved in the production of methyl donor S-adenosylmethionine (SAM), thereby influencing the methylation potential (MP) in the placenta of women delivering preterm. The present study, therefore, examines the mRNA, protein levels of enzymes ( MAT2A and AHCY), SAM, S-adenosylhomocysteine (SAH) levels, and global DNA methylation levels from preterm (n = 73) and term (n = 73) placentae. The enzyme messenger RNA (mRNA) levels were analyzed by real-time quantitative polymerase chain reaction, protein levels by enzyme-linked immunosorbent assay, and SAM-SAH levels by high-performance liquid chromatography. The mRNA levels for MAT2A and AHCY are higher ( P programming of the developing fetus.

Thermal Decomposition of Potential Ester Biofuels. Part I: Methyl Acetate and Methyl Butanoate

Energy Technology Data Exchange (ETDEWEB)

Porterfield, Jessica P.; Bross, David H.; Ruscic, Branko; Thorpe, James H.; Nguyen, Thanh Lam; Baraban, Joshua H.; Stanton, John F.; Daily, John W.; Ellison, G. Barney

2017-06-09

Two methyl esters have been examined as models for the pyrolysis of biofuels. Dilute samples (0.06 - 0.13%) of methyl acetate (CH₃COOCH₃) and methyl butanoate (CH₃CH₂CH₂COOCH₃) were entrained in (He, Ar) carrier gas and decomposed in a set of flash-pyrolysis micro-reactors. The pyrolysis products resulting from the methyl esters were detected and identified by vacuum ultraviolet photoionization mass spectrometry. Complementary product identification was provided by matrix infrared absorption spectroscopy. Pyrolysis pressures in the pulsed micro-reactor were roughly 20 Torr and residence times through the reactors were approximately 25 - 150 µs. Reactor temperatures of 300 – 1600 K were explored. Decomposition of CH₃COOCH₃ commences at 1000 K and the initial products are (CH₂=C=O and CH₃OH). As the micro-reactor is heated to 1300 K, a mixture of (CH₂=C=O and CH₃OH, CH₃, CH₂=O, H, CO, CO₂) appears. The thermal cracking of CH₃CH₂CH₂COOCH₃ begins at 800 K with the formation of (CH₃CH₂CH=C=O, CH₃OH). By 1300 K, the pyrolysis of methyl butanoate yields a complex mixture of (CH₃CH₂CH=C=O, CH₃OH, CH₃, CH₂=O, CO, CO₂, CH₃CH=CH₂, CH₂CHCH₂, CH₂=C=CH₂, HCCCH₂, CH₂=C=C=O, CH₂=CH₂, HCΞCH, CH₂=C=O). Based on the results from the thermal cracking of methyl acetate and methyl butanoate, we predict several important decomposition channels for the pyrolysis of fatty acid methyl esters, R CH₂-COOCH₃. The lowest energy fragmentation will be a 4-center elimination of methanol to form the ketene, RCH=C=O. At higher temperatures, concerted

Net global warming potential and greenhouse gas intensity influenced by irrigation, tillage, crop rotation, and nitrogen fertilization

Science.gov (United States)

Little information exists about sources and sinks of greenhouse gases (GHGs) affected by management practices to account for net emissions from agroecosystems. We evaluated the effects of irrigation, tillage, crop rotation, and N fertilization on net global warming potential (GWP) and greenhouse gas...

Mercury methylation influenced by areas of past mercury mining in the Terlingua district, Southwest Texas, USA

International Nuclear Information System (INIS)

Gray, John E.; Hines, Mark E.; Biester, Harald

2006-01-01

Speciation and microbial transformation of Hg was studied in mine waste from abandoned Hg mines in SW Texas to evaluate the potential for methyl-Hg production and degradation in mine wastes. In mine waste samples, total Hg, ionic Hg 2+ , Hg 0 , methyl-Hg, organic C, and total S concentrations were measured, various Hg compounds were identified using thermal desorption pyrolysis, and potential rates of Hg methylation and methyl-Hg demethylation were determined using isotopic-tracer methods. These data are the first reported for Hg mines in this region. Total Hg and methyl-Hg concentrations were also determined in stream sediment collected downstream from two of the mines to evaluate transport of Hg and methylation in surrounding ecosystems. Mine waste contains total Hg and methyl-Hg concentrations as high as 19,000 μg/g and 1500 ng/g, respectively, which are among the highest concentrations reported at Hg mines worldwide. Pyrolysis analyses show that mine waste contains variable amounts of cinnabar, metacinnabar, Hg 0 , and Hg sorbed onto particles. Methyl-Hg concentrations in mine waste correlate positively with ionic Hg 2+ , organic C, and total S, which are geochemical parameters that influence processes of Hg cycling and methylation. Net methylation rates were as high as 11,000 ng/g/day, indicating significant microbial Hg methylation at some sites, especially in samples collected inside retorts. Microbially-mediated methyl-Hg demethylation was also observed in many samples, but where both methylation and demethylation were found, the potential rate of methylation was faster. Total Hg concentrations in stream sediment samples were generally below the probable effect concentration of 1.06 μg/g, the Hg concentration above which harmful effects are likely to be observed in sediment dwelling organisms; whereas total Hg concentrations in mine waste samples were found to exceed this concentration, although this is a sediment quality guideline and is not directly

Widespread promoter methylation of synaptic plasticity genes in long-term potentiation in the adult brain in vivo.

Science.gov (United States)

Maag, Jesper L V; Kaczorowski, Dominik C; Panja, Debabrata; Peters, Timothy J; Bramham, Clive R; Wibrand, Karin; Dinger, Marcel E

2017-03-23

DNA methylation is a key modulator of gene expression in mammalian development and cellular differentiation, including neurons. To date, the role of DNA modifications in long-term potentiation (LTP) has not been explored. To investigate the occurrence of DNA methylation changes in LTP, we undertook the first detailed study to describe the methylation status of all known LTP-associated genes during LTP induction in the dentate gyrus of live rats. Using a methylated DNA immunoprecipitation (MeDIP)-array, together with previously published matched RNA-seq and public histone modification data, we discover widespread changes in methylation status of LTP-genes. We further show that the expression of many LTP-genes is correlated with their methylation status. We show that these correlated genes are enriched for RNA-processing, active histone marks, and specific transcription factors. These data reveal that the synaptic activity-evoked methylation changes correlates with pre-existing activation of the chromatin landscape. Finally, we show that methylation of Brain-derived neurotrophic factor (Bdnf) CpG-islands correlates with isoform switching from transcripts containing exon IV to exon I. Together, these data provide the first evidence of widespread regulation of methylation status in LTP-associated genes.

DNA methylation, microRNAs, and their crosstalk as potential biomarkers in hepatocellular carcinoma

Science.gov (United States)

Anwar, Sumadi Lukman; Lehmann, Ulrich

2014-01-01

Epigenetic alterations have been identified as a major characteristic in human cancers. Advances in the field of epigenetics have contributed significantly in refining our knowledge of molecular mechanisms underlying malignant transformation. DNA methylation and microRNA expression are epigenetic mechanisms that are widely altered in human cancers including hepatocellular carcinoma (HCC), the third leading cause of cancer related mortality worldwide. Both DNA methylation and microRNA expression patterns are regulated in developmental stage specific-, cell type specific- and tissue-specific manner. The aberrations are inferred in the maintenance of cancer stem cells and in clonal cell evolution during carcinogenesis. The availability of genome-wide technologies for DNA methylation and microRNA profiling has revolutionized the field of epigenetics and led to the discovery of a number of epigenetically silenced microRNAs in cancerous cells and primary tissues. Dysregulation of these microRNAs affects several key signalling pathways in hepatocarcinogenesis suggesting that modulation of DNA methylation and/or microRNA expression can serve as new therapeutic targets for HCC. Accumulative evidence shows that aberrant DNA methylation of certain microRNA genes is an event specifically found in HCC which correlates with unfavorable outcomes. Therefore, it can potentially serve as a biomarker for detection as well as for prognosis, monitoring and predicting therapeutic responses in HCC. PMID:24976726

Whole-genome methylation caller designed for methyl- DNA ...

African Journals Online (AJOL)

etchie

2013-02-20

Feb 20, 2013 ... Key words: Methyl-DNA immunoprecipitation, next-generation sequencing, Hidden ... its response to environmental cues. .... have a great potential to become the most cost-effective ... hg18 reference genome (set to 0 if not present in retrieved reads). ..... DNA methylation patterns and epigenetic memory.

Total- and methyl-mercury concentrations and methylation rates across the freshwater to hypersaline continuum of the Great Salt Lake, Utah, USA

Science.gov (United States)

Johnson, William P.; Swanson, Neil; Black, Brooks; Rudd, Abigail; Carling, Gregory; Fernandez, Diego P.; Luft, John; Van Leeuwen, Jim; Marvin-DiPasquale, Mark C.

2015-01-01

We examined mercury (Hg) speciation in water and sediment of the Great Salt Lake and surrounding wetlands, a locale spanning fresh to hypersaline and oxic to anoxic conditions, in order to test the hypothesis that spatial and temporal variations in Hg concentration and methylation rates correspond to observed spatial and temporal trends in Hg burdens previously reported in biota. Water column, sediment, and pore water concentrations of methylmercury (MeHg) and total mercury (THg), as well as related aquatic chemical parameters were examined. Inorganic Hg(II)-methylation rates were determined in selected water column and sediment subsamples spiked with inorganic divalent mercury (204Hg(II)). Net production of Me204Hg was expressed as apparent first-order rate constants for methylation (kmeth), which were also expanded to MeHg production potential (MPP) rates via combination with tin reducible ‘reactive’ Hg(II) (Hg(II)R) as a proxy for bioavailable Hg(II). Notable findings include: 1) elevated Hg concentrations previously reported in birds and brine flies were spatially proximal to the measured highest MeHg concentrations, the latter occurring in the anoxic deep brine layer (DBL) of the Great Salt Lake; 2) timing of reduced Hg(II)-methylation rates in the DBL (according to both kmeth and MPP) coincides with reduced Hg burdens among aquatic invertebrates (brine shrimp and brine flies) that act as potential vectors of Hg propagation to the terrestrial ecosystem; 3) values ofkmeth were found to fall within the range reported by other studies; and 4) MPP rates were on the lower end of the range reported in methodologically comparable studies, suggesting the possibility that elevated MeHg in the anoxic deep brine layer results from its accumulation and persistence in this quasi-isolated environment, due to the absence of light (restricting abiotic photo demethylation) and/or minimal microbiological demethylation.

Net-baryon-, net-proton-, and net-charge kurtosis in heavy-ion collisions within a relativistic transport approach

International Nuclear Information System (INIS)

Nahrgang, Marlene; Schuster, Tim; Stock, Reinhard; Mitrovski, Michael; Bleicher, Marcus

2012-01-01

We explore the potential of net-baryon, net-proton and net-charge kurtosis measurements to investigate the properties of hot and dense matter created in relativistic heavy-ion collisions. Contrary to calculations in a grand-canonical ensemble we explicitly take into account exact electric and baryon charge conservation on an event-by-event basis. This drastically limits the width of baryon fluctuations. A simple model to account for this is to assume a grand-canonical distribution with a sharp cut-off at the tails. We present baseline predictions of the energy dependence of the net-baryon, net-proton and net-charge kurtosis for central (b≤2.75 fm) Pb+Pb/Au+Au collisions from E lab =2A GeV to √(s NN )=200 GeV from the UrQMD model. While the net-charge kurtosis is compatible with values around zero, the net-baryon number decreases to large negative values with decreasing beam energy. The net-proton kurtosis becomes only slightly negative for low √(s NN ). (orig.)

A genome-wide methylation study on obesity Differential variability and differential methylation

NARCIS (Netherlands)

Xu, Xiaojing; Su, Shaoyong; Barnes, Vernon A.; De Miguel, Carmen; Pollock, Jennifer; Ownby, Dennis; Shi, Huidong; Zhu, Haidong; Snieder, Harold; Wang, Xiaoling

2013-01-01

Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common

Effects of damming on the distribution and methylation of mercury in Wujiang River, Southwest China.

Science.gov (United States)

Zhao, Lei; Guo, Yanna; Meng, Bo; Yao, Heng; Feng, Xinbin

2017-10-01

Newly built reservoirs are regarded as sensitive ecosystem for mercury (Hg) methylation. A comprehensive study was conducted to understand the influence of damming on the distribution and methylation of Hg within a river-reservoir ecosystem in Wujiang River Basin (WRB), Southwest China. Hg species in inflow-outflow rivers of six cascade reservoirs were analyzed each month during 2006. Mean concentrations of total Hg (THg) and methylmercury (MeHg) in river water in WRB were 3.41 ± 1.98 ng L -1 and 0.15 ± 0.06 ng L -1 , respectively. THg and particulate Hg (PHg) concentrations in outflow rivers of reservoirs significantly decreased after dam construction, suggesting that a considerable amount of PHg was intercepted by way of sedimentation. However, the influence of damming on the distributions of dissolved Hg (DHg) and reactive Hg (RHg) in rivers was less pronounced. MeHg concentrations in outflow rivers of the older reservoirs significantly increased compared to inflow rivers with the maximum increasing factor of 92%, indicating the active net Hg methylation in the reservoirs. However, the difference between MeHg in inflow rivers and outflow rivers were less pronounced in the newly constructed reservoirs, indicating that these reservoirs were not active sites of Hg methylation. The construction of the cascade reservoirs resulted in the elevation of MeHg in several sections of the Wujiang River, which attributed to the net Hg methylation in reservoirs and discharge of MeHg from hypolimnion. MeHg-enriched water in outflow rivers from hypolimnetic water could be transported to downstream, posing potential threat to the aquatic food web and human health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Origin of methyl torsional potential barrier – An overview

Indian Academy of Sciences (India)

Unknown

This paper presents the evolution of views on methyl internal rotation ... recognized in the early years of quantum theory.1 Since then, detailed experimental and ..... C−C bond in the methyl conjugated molecules is an important factor for barrier.

Net sulfur mineralization potential in Swedish arable soils in relation to long-term treatment history and soil properties

DEFF Research Database (Denmark)

Boye, Kristin; Nilsson, S Ingvar; Eriksen, Jørgen

2009-01-01

accumulated net S mineralization (SAccMin) and a number of soil physical and chemical properties were determined. Treatments and soil differences in SAccMin, as well as correlations with soil variables, were tested with single and multivariate analyses. Long-term FYM application resulted in a significantly (p......The long-term treatment effect (since 1957-1966) of farmyard manure (FYM) application compared with crop residue incorporation was investigated in five soils (sandy loam to silty clay) with regards to the net sulfur (S) mineralization potential. An open incubation technique was used to determine...... = 0.012) higher net S mineralization potential, although total amounts of C, N, and S were not significantly (p soils within this treatment. The measured soil variables were not significantly correlated...

The potential of centrifugal casting for the production of near net shape uranium parts

International Nuclear Information System (INIS)

Robertson, E.

1993-09-01

This report was written to provide a detailed summary of a literature survey on the near net shape casting process of centrifugal casting. Centrifugal casting is one potential casting method which could satisfy the requirements of the LANL program titled Near Net Shape Casting of Uranium for Reduced Environmental, Safety and Health Impact. In this report, centrifugal casting techniques are reviewed and an assessment of the ability to achieve the near net shape and waste minimization goals of the LANL program by using these techniques is made. Based upon the literature reviewed, it is concluded that if properly modified for operation within a vacuum, vertical or horizontal centrifugation could be used to safely cast uranium for the production of hollow, cylindrical parts. However, for the production of components of geometries other than hollow tubes, vertical centrifugation could be combined with other casting methods such as semi-permanent mold or investment casting

Importance of Dissolved Neutral Hg-Sulfides, Energy Rich Organic Matter and total Hg Concentrations for Methyl Mercury Production in Sediments

Science.gov (United States)

Drott, A.; Skyllberg, U.

2007-12-01

Methyl mercury (MeHg) is the mercury form that biomagnifies to the greatest extent in aquatic food webs. Therefore information about factors determining MeHg concentrations is critical for accurate risk assessment of contaminated environments. The concentration of MeHg in wetlands and sediments is the net result of: 1) methylation rates, 2) demethylation rates, and 3) input/output processes. In this study, the main controls on Hg methylation rates and total concentrations of MeHg, were investigated at eight sites in Sweden with sediments that had been subjected to local Hg contamination either as Hg(0), or as phenyl-Hg. Sediments were selected to represent a gradient in total Hg concentration, temperature climate, salinity, primary productivity, and organic C content and quality. Most sediments were high in organic matter content due to wood fibre efflux from pulp and paper industry. The pore water was analysed for total Hg, MeHg, DOC, H2S(aq), pH, DOC, Cl and Br. The chemical speciation of Hg(II) and MeHg in pore water was calculated using equilibrium models. Potential methylation and demethylation rates in sediments were determined in incubation experiments at 23° C under N2(g) for 48 h, after addition of isotopically enriched 201Hg(II) and Me204Hg. In all surface (0-20 cm) sediments there was a significant (pdetermined specific potential methylation rate constant (Km, day-1) and % MeHg (concentrations of MeHg normalized to total Hg) in the sediment. This indicates that MeHg production overruled degradation and input/output processes of MeHg in surface sediments, and that % MeHg in surface sediments may be used as a proxy for net production of MeHg. To our knowledge, these are the first data showing significant positive relationships between short term (48 h) MeHg production and longer term accumulation of MeHg, across a range of sites with different properties (1). If MeHg was not normalized to total Hg, the relationship was not significant. For sub-sets of

Differential Radiosensitizing Potential of Temozolomide in MGMT Promoter Methylated Glioblastoma Multiforme Cell Lines

International Nuclear Information System (INIS)

Nifterik, Krista A. van; Berg, Jaap van den; Stalpers, Lukas J.A.; Lafleur, M. Vincent M.; Leenstra, Sieger; Slotman, Ben J.; Hulsebos, Theo J.M.; Sminia, Peter

2007-01-01

Purpose: To investigate the radiosensitizing potential of temozolomide (TMZ) for human glioblastoma multiforme (GBM) cell lines using single-dose and fractionated γ-irradiation. Methods and Materials: Three genetically characterized human GBM cell lines (AMC-3046, VU-109, and VU-122) were exposed to various single (0-6 Gy) and daily fractionated doses (2 Gy per fraction) of γ-irradiation. Repeated TMZ doses were given before and concurrent with irradiation treatment. Immediately plated clonogenic cell-survival curves were determined for both the single-dose and the fractionated irradiation experiments. To establish the net effect of clonogenic cell survival and cell proliferation, growth curves were determined, expressed as the number of surviving cells. Results: All three cell lines showed MGMT promoter methylation, lacked MGMT protein expression, and were sensitive to TMZ. The isotoxic TMZ concentrations used were in a clinically feasible range of 10 μmol/L (AMC-3046), 3 μmol/L (VU-109), and 2.5 μmol/L (VU-122). Temozolomide was able to radiosensitize two cell lines (AMC 3046 and VU-122) using single-dose irradiation. A reduction in the number of surviving cells after treatment with the combination of TMZ and fractionated irradiation was seen in all three cell lines, but only AMC 3046 showed a radiosensitizing effect. Conclusions: This study on TMZ-sensitive GBM cell lines shows that TMZ can act as a radiosensitizer and is at least additive to γ-irradiation. Enhancement of the radiation response by TMZ seems to be independent of the epigenetically silenced MGMT gene

Mercury methylation coupled to iron reduction by dissimilatory iron-reducing bacteria.

Science.gov (United States)

Si, Youbin; Zou, Yan; Liu, Xiaohong; Si, Xiongyuan; Mao, Jingdong

2015-03-01

Iron reduction and mercury methylation by dissimilatory iron-reducing bacteria (DIRB), Geobacter sulfurreducens and Shewanella oneidensis, were studied, and the relationship of mercury methylation coupled to iron reduction was determined. The ability of both bacteria for reducing iron was tested, and Fe(III) reduction occurred with the highest rate when ferric oxyhydroxide was used as a terminal electron acceptor. G. sulfurreducens had proven to mediate the production of methylmercury (MeHg), and a notable increase of MeHg following the addition of inorganic Hg was observed. When the initial concentration of HgCl2 was 500nM, about 177.03nM of MeHg was determined at 8d after G. sulfurreducens inoculation. S. oneidensis was tested negligible for Hg methylation and only 12.06nM of MeHg was determined. Iron reduction could potentially influence Hg methylation rates. The increase in MeHg was consistent with high rate of iron reduction, indicating that Fe(III) reduction stimulated the formation of MeHg. Furthermore, the net MeHg concentration increased at low Fe(III) additions from 1.78 to 3.57mM, and then decreased when the added Fe(III) was high from 7.14 to 17.85mM. The mercury methylation rate was suppressed with high Fe(III) additions, which might have been attributable to mercury complexation and low availability. Copyright © 2014 Elsevier Ltd. All rights reserved.

Potentiation of insulin release in response to amino acid methyl esters correlates to activation of islet glutamate dehydrogenase activity

DEFF Research Database (Denmark)

Kofod, Hans; Lernmark, A; Hedeskov, C J

1986-01-01

Column perifusion of mouse pancreatic islets was used to study the ability of amino acids and their methyl esters to influence insulin release and activate islet glutamate dehydrogenase activity. In the absence of L-glutamine, L-serine and the methyl ester of L-phenylalanine, but neither L...... glutamate dehydrogenase activity showed that only the two methyl esters of L-phenylalanine and L-serine activated the enzyme. It is concluded that the mechanism by which methyl esters of amino acids potentiate insulin release is most likely to be mediated by the activation of pancreatic beta-cell glutamate...

Status of Net Metering: Assessing the Potential to Reach Program Caps

Energy Technology Data Exchange (ETDEWEB)

Heeter, J.; Gelman, R.; Bird, L.

2014-09-01

Several states are addressing the issue of net metering program caps, which limit the total amount of net metered generating capacity that can be installed in a state or utility service territory. In this analysis, we examine net metering caps to gain perspective on how long net metering will be available in various jurisdictions under current policies. We also surveyed state practices and experience to understand important policy design considerations.

NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer

Directory of Open Access Journals (Sweden)

Shen Shourong

2010-04-01

Full Text Available Abstract Background Nasopharyngeal carcinoma associated gene 6 (NGX6 is down-regulated in most colon cancer cell lines and tumor tissues when compared with their normal tissue samples. As a novel suppress tumor gene, it could inhibit colon cancer cell growth and cell cycle progression. However, little is known about the transcriptional mechanisms controlling NGX6 gene expression. Recent findings suggest that epigenetic inactivation of multiple tumor suppressor genes plays an important role in the tumorigenesis of colorectal carcinoma (CRC. In this study, we explored the role of DNA methylation in regulation of NGX6 transcription. Methods In the present study, we cloned the NGX6 promoter with characteristics of a CpG island by luciferase reporter assay. Then, the CpG methylation status around the NGX6 promoter region in colon cancer cell lines and colorectal tumor tissues was examined by methylation-specific PCR and bisulfite DNA sequencing. Finally, 5-Aza-2'-deoxycytidine (5-Aza-dC treatment was used to confirm the correlation between NGX6 promoter methylation and its gene inactivation. Results The sequence spanning positions -157 to +276 was identified as the NGX6 promoter, in which no canonical TATA boxes were found, while two CAAT boxes and GC boxes were discovered. Methylation status was observed more frequently in 40 colorectal cancer samples than in 40 adjacent normal mucosa samples (18/40 versus 7/40; P Conclusions Down-regulation of NGX6 gene is related to the promoter methylation. DNA methylation of NGX6 promoter might be a potential molecular marker for diagnosis or prognosis, or serve as a therapeutic target.

Potential area for floating net fishery in Lake Toba

Science.gov (United States)

Rustini, H. A.; Harsono, E.; Ridwansyah, I.

2018-02-01

Lake Toba in North Sumatera, Indonesia, is now designated to be a world-class tourism destination. Aside from its infrastructure development, this largest lake in the Southeast Asia needs to be restored, especially its water quality. While an oligotrophic status is required for tourism purposes, several studies showed that Toba is mesotrophic at its best and hyper-eutrophic at its worst. Numerous studies and reports blame floating net fishery (FNF) for water quality decline in Lake Toba and propose limitation for its production. While the central government allowed FNF to be positioned in certain areas according to its depth and distance from the lakeshore, increasing number of FNF means adding more nutrients to the lake and thus may inhibit the lake’s restoration process. Hence, it is important to identify which areas are potential for FNF location to assist the authorities to regulate FNF. This study used SPOT-6, SPOT-7, and Pleiades satellite imagery to locate the position of existing FNF and to analyse the result to identify a potential location for FNF.

Independent Review of Simulation of Net Infiltration for Present-Day and Potential Future Climates

Energy Technology Data Exchange (ETDEWEB)

Review Panel: Soroosh Sorooshian, Ph.D., Panel Chairperson, University of California, Irvine; Jan M. H. Hendrickx, Ph.D., New Mexico Institute of Mining and Technology; Binayak P. Mohanty, Ph.D., Texas A& M University; Scott W. Tyler, Ph.D., University of Nevada, Reno; Tian-Chyi Jim Yeh, Ph.D., University of Arizona -- ORISE Review Facilitators: Robert S. Turner, Ph.D., Technical Review Group Manager, Oak Ridge Institute for Science and Education; Brian R. Herndon, Project Manager, Oak Ridge Institute for Science and Education; Russ Manning, Technical Writer/Editor, Haselwood Enterprises, Inc.

2008-08-30

The DOE Office of Civilian Radioactive Waste Management (OCRWM) tasked Oak Ridge Institute for Science and Education (ORISE) with providing an independent expert review of the documented model and prediction results for net infiltration of water into the unsaturated zone at Yucca Mountain. The specific purpose of the model, as documented in the report MDL-NBS-HS-000023, Rev. 01, is “to provide a spatial representation, including epistemic and aleatory uncertainty, of the predicted mean annual net infiltration at the Yucca Mountain site ...” (p. 1-1) The expert review panel assembled by ORISE concluded that the model report does not provide a technically credible spatial representation of net infiltration at Yucca Mountain. Specifically, the ORISE Review Panel found that: • A critical lack of site-specific meteorological, surface, and subsurface information prevents verification of (i) the net infiltration estimates, (ii) the uncertainty estimates of parameters caused by their spatial variability, and (iii) the assumptions used by the modelers (ranges and distributions) for the characterization of parameters. The paucity of site-specific data used by the modeling team for model implementation and validation is a major deficiency in this effort. • The model does not incorporate at least one potentially important hydrologic process. Subsurface lateral flow is not accounted for by the model, and the assumption that the effect of subsurface lateral flow is negligible is not adequately justified. This issue is especially critical for the wetter climate periods. This omission may be one reason the model results appear to underestimate net infiltration beneath wash environments and therefore imprecisely represent the spatial variability of net infiltration. • While the model uses assumptions consistently, such as uniform soil depths and a constant vegetation rooting depth, such assumptions may not be appropriate for this net infiltration simulation because they

Independent Review of Simulation of Net Infiltration for Present-Day and Potential Future Climates

International Nuclear Information System (INIS)

Review Panel: Soroosh Sorooshian, Jan M. H. Hendrickx; Binayak P. Mohanty, Scott W. Tyler; Tian-Chyi Jim Yeh; Robert S. Turner; Brian R. Herndon; Russ Manning

2008-01-01

The DOE Office of Civilian Radioactive Waste Management (OCRWM) tasked Oak Ridge Institute for Science and Education (ORISE) with providing an independent expert review of the documented model and prediction results for net infiltration of water into the unsaturated zone at Yucca Mountain. The specific purpose of the model, as documented in the report MDL-NBS-HS-000023, Rev. 01, is 'to provide a spatial representation, including epistemic and aleatory uncertainty, of the predicted mean annual net infiltration at the Yucca Mountain site' (p. 1-1). The expert review panel assembled by ORISE concluded that the model report does not provide a technically credible spatial representation of net infiltration at Yucca Mountain. Specifically, the ORISE Review Panel found that: A critical lack of site-specific meteorological, surface, and subsurface information prevents verification of (1) the net infiltration estimates, (2) the uncertainty estimates of parameters caused by their spatial variability, and (3) the assumptions used by the modelers (ranges and distributions) for the characterization of parameters. The paucity of site-specific data used by the modeling team for model implementation and validation is a major deficiency in this effort. The model does not incorporate at least one potentially important hydrologic process. Subsurface lateral flow is not accounted for by the model, and the assumption that the effect of subsurface lateral flow is negligible is not adequately justified. This issue is especially critical for the wetter climate periods. This omission may be one reason the model results appear to underestimate net infiltration beneath wash environments and therefore imprecisely represent the spatial variability of net infiltration. While the model uses assumptions consistently, such as uniform soil depths and a constant vegetation rooting depth, such assumptions may not be appropriate for this net infiltration simulation because they oversimplify a complex

Mercury methylation and reduction potentials in marine water: An improved methodology using {sup 197}Hg radiotracer

Energy Technology Data Exchange (ETDEWEB)

Koron, Neza [National Institute of Biology, Marine Biology Station, Fornace 41, 6330 Piran (Slovenia); Bratkic, Arne [Department of Environmental Sciences, ' Jozef Stefan' Institute, Jamova 39, 1000 Ljubljana (Slovenia); Ribeiro Guevara, Sergio, E-mail: ribeiro@cab.cnea.gov.ar [Laboratorio de Analisis por Activacion Neutronica, Centro Atomico Bariloche, Av. Bustillo km 9.5, 8400 Bariloche (Argentina); Vahcic, Mitja; Horvat, Milena [Department of Environmental Sciences, ' Jozef Stefan' Institute, Jamova 39, 1000 Ljubljana (Slovenia)

2012-01-15

A highly sensitive laboratory methodology for simultaneous determination of methylation and reduction of spiked inorganic mercury (Hg{sup 2+}) in marine water labelled with high specific activity radiotracer ({sup 197}Hg prepared from enriched {sup 196}Hg stable isotope) was developed. A conventional extraction protocol for methylmercury (CH{sub 3}Hg{sup +}) was modified in order to significantly reduce the partitioning of interfering labelled Hg{sup 2+} into the final extract, thus allowing the detection of as little as 0.1% of the Hg{sup 2+} spike transformed to labelled CH{sub 3}Hg{sup +}. The efficiency of the modified CH{sub 3}Hg{sup +} extraction procedure was assessed by radiolabelled CH{sub 3}Hg{sup +} spikes corresponding to concentrations of methylmercury between 0.05 and 4 ng L{sup -1}. The recoveries were 73.0{+-}6.0% and 77.5{+-}3.9% for marine and MilliQ water, respectively. The reduction potential was assessed by purging and trapping the radiolabelled elemental Hg in a permanganate solution. The method allows detection of the reduction of as little as 0.001% of labelled Hg{sup 2+} spiked to natural waters. To our knowledge, the optimised methodology is among the most sensitive available to study the Hg methylation and reduction potential, therefore allowing experiments to be done at spikes close to natural levels (1-10 ng L{sup -1}). - Highlights: Black-Right-Pointing-Pointer Inorganic mercury methylation and reduction in marine water were studied. Black-Right-Pointing-Pointer High specific activity {sup 197}Hg was used to label Hg{sup 2+} spikes at natural levels. Black-Right-Pointing-Pointer Methylmercury extraction had 73% efficiency for 0.05-4 ng L{sup -1} levels. Black-Right-Pointing-Pointer High sensibility to assess methylation potentials, below 0.1% of the spike. Black-Right-Pointing-Pointer High sensibility also for reduction potentials, as low as 0.001% of the spike.

NetSig

DEFF Research Database (Denmark)

Horn, Heiko; Lawrence, Michael S; Chouinard, Candace R

2018-01-01

Methods that integrate molecular network information and tumor genome data could complement gene-based statistical tests to identify likely new cancer genes; but such approaches are challenging to validate at scale, and their predictive value remains unclear. We developed a robust statistic (Net......Sig) that integrates protein interaction networks with data from 4,742 tumor exomes. NetSig can accurately classify known driver genes in 60% of tested tumor types and predicts 62 new driver candidates. Using a quantitative experimental framework to determine in vivo tumorigenic potential in mice, we found that Net......Sig candidates induce tumors at rates that are comparable to those of known oncogenes and are ten-fold higher than those of random genes. By reanalyzing nine tumor-inducing NetSig candidates in 242 patients with oncogene-negative lung adenocarcinomas, we find that two (AKT2 and TFDP2) are significantly amplified...

Potential of DNA methylation in rectal cancer as diagnostic and prognostic biomarkers

Science.gov (United States)

Exner, Ruth; Pulverer, Walter; Diem, Martina; Spaller, Lisa; Woltering, Laura; Schreiber, Martin; Wolf, Brigitte; Sonntagbauer, Markus; Schröder, Fabian; Stift, Judith; Wrba, Fritz; Bergmann, Michael; Weinhäusel, Andreas; Egger, Gerda

2015-01-01

Background: Aberrant DNA methylation is more prominent in proximal compared with distal colorectal cancers. Although a number of methylation markers were identified for colon cancer, yet few are available for rectal cancer. Methods: DNA methylation differences were assessed by a targeted DNA microarray for 360 marker candidates between 22 fresh frozen rectal tumour samples and 8 controls and validated by microfluidic high-throughput and methylation-sensitive qPCR in fresh frozen and formalin-fixed paraffin-embedded (FFPE) samples, respectively. The CpG island methylator phenotype (CIMP) was assessed by MethyLight in FFPE material from 78 patients with pT2 and pT3 rectal adenocarcinoma. Results: We identified and confirmed two novel three-gene signatures in fresh frozen samples that can distinguish tumours from adjacent tissue as well as from blood with a high sensitivity and specificity of up to 1 and an AUC of 1. In addition, methylation of individual CIMP markers was associated with specific clinical parameters such as tumour stage, therapy or patients' age. Methylation of CDKN2A was a negative prognostic factor for overall survival of patients. Conclusions: The newly defined methylation markers will be suitable for early disease detection and monitoring of rectal cancer. PMID:26335606

Potential of DNA methylation in rectal cancer as diagnostic and prognostic biomarkers

OpenAIRE

Exner, Ruth; Pulverer, Walter; Diem, Martina; Spaller, Lisa; Woltering, Laura; Schreiber, Martin; Wolf, Brigitte; Sonntagbauer, Markus; Schr?der, Fabian; Stift, Judith; Wrba, Fritz; Bergmann, Michael; Weinh?usel, Andreas; Egger, Gerda

2015-01-01

Background: Aberrant DNA methylation is more prominent in proximal compared with distal colorectal cancers. Although a number of methylation markers were identified for colon cancer, yet few are available for rectal cancer. Methods: DNA methylation differences were assessed by a targeted DNA microarray for 360 marker candidates between 22 fresh frozen rectal tumour samples and 8 controls and validated by microfluidic high-throughput and methylation-sensitive qPCR in fresh frozen and formalin-...

Automated sequence- and stereo-specific assignment of methyl-labeled proteins by paramagnetic relaxation and methyl-methyl nuclear overhauser enhancement spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Venditti, Vincenzo; Fawzi, Nicolas L.; Clore, G. Marius, E-mail: mariusc@mail.nih.gov [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Laboratory of Chemical Physics (United States)

2011-11-15

Methyl-transverse relaxation optimized spectroscopy is rapidly becoming the preferred NMR technique for probing structure and dynamics of very large proteins up to {approx}1 MDa in molecular size. Data interpretation, however, necessitates assignment of methyl groups which still presents a very challenging and time-consuming process. Here we demonstrate that, in combination with a known 3D structure, paramagnetic relaxation enhancement (PRE), induced by nitroxide spin-labels incorporated at only a few surface-exposed engineered cysteines, provides fast, straightforward and robust access to methyl group resonance assignments, including stereoassignments for the methyl groups of leucine and valine. Neither prior assignments, including backbone assignments, for the protein, nor experiments that transfer magnetization between methyl groups and the protein backbone, are required. PRE-derived assignments are refined by 4D methyl-methyl nuclear Overhauser enhancement data, eliminating ambiguities and errors that may arise due to the high sensitivity of PREs to the potential presence of sparsely-populated transient states.

Grazing alters net ecosystem C fluxes and the global warming potential of a subtropical pasture.

Science.gov (United States)

Gomez-Casanovas, Nuria; DeLucia, Nicholas J; Bernacchi, Carl J; Boughton, Elizabeth H; Sparks, Jed P; Chamberlain, Samuel D; DeLucia, Evan H

2018-03-01

The impact of grazing on C fluxes from pastures in subtropical and tropical regions and on the environment is uncertain, although these systems account for a substantial portion of global C storage. We investigated how cattle grazing influences net ecosystem CO 2 and CH 4 exchange in subtropical pastures using the eddy covariance technique. Measurements were made over several wet-dry seasonal cycles in a grazed pasture, and in an adjacent pasture during the first three years of grazer exclusion. Grazing increased soil wetness but did not affect soil temperature. By removing aboveground biomass, grazing decreased ecosystem respiration (R eco ) and gross primary productivity (GPP). As the decrease in R eco was larger than the reduction in GPP, grazing consistently increased the net CO 2 sink strength of subtropical pastures (55, 219 and 187 more C/m 2 in 2013, 2014, and 2015). Enteric ruminant fermentation and increased soil wetness due to grazers, increased total net ecosystem CH 4 emissions in grazed relative to ungrazed pasture (27-80%). Unlike temperate, arid, and semiarid pastures, where differences in CH 4 emissions between grazed and ungrazed pastures are mainly driven by enteric ruminant fermentation, our results showed that the effect of grazing on soil CH 4 emissions can be greater than CH 4 produced by cattle. Thus, our results suggest that the interactions between grazers and soil hydrology affecting soil CH 4 emissions play an important role in determining the environmental impacts of this management practice in a subtropical pasture. Although grazing increased total net ecosystem CH 4 emissions and removed aboveground biomass, it increased the net storage of C and decreased the global warming potential associated with C fluxes of pasture by increasing its net CO 2 sink strength. © 2017 by the Ecological Society of America.

Pro asynchronous programming with .NET

CERN Document Server

Blewett, Richard; Ltd, Rock Solid Knowledge

2014-01-01

Pro Asynchronous Programming with .NET teaches the essential skill of asynchronous programming in .NET. It answers critical questions in .NET application development, such as: how do I keep my program responding at all times to keep my users happy how do I make the most of the available hardware how can I improve performanceIn the modern world, users expect more and more from their applications and devices, and multi-core hardware has the potential to provide it. But it takes carefully crafted code to turn that potential into responsive, scalable applications.With Pro Asynchronous Programming

A new method to describe two-phase solvent extraction based on net transport potential derived as linear combinations of forward and reverse constituents

International Nuclear Information System (INIS)

Nabeshima, Masahiro

1998-01-01

With the view to avoiding the difficulties encountered in estimating thermodynamic activities of the multiple chemical species in two-phase liquid system, a set of forward, reverse, net and total transport potentials are defined to represent the chemical state of a transferring solute during transient using bulk concentrations. The net transport potential corresponds to that in the conventional two-film model of diffusion-controlled processes. The overall driving forces of mass transport are redefined as the derivatives of the relevant transport potentials differentiated with respect to a state variable newly defined in terms of the bulk concentrations of the solute contained in both phases. Net and total quantities, i.e. transport potentials, overall driving forces and the molar fluxes are obtained as linear combinations of those for forward and reverse directions. The topical features presented by these quantities and their mutual relations are discussed in detail. The experimental new overall transport coefficient for U(VI) varied in accord with the changes in the theoretical net transport potential and overall driving force. The present method permits describing the extractive mass transport consistently both to forward and reverse directions of transport. (author)

Experimental vapor pressures (from 1 Pa to 100 kPa) of six saturated Fatty Acid Methyl Esters (FAMEs): Methyl hexanoate, methyl octanoate, methyl decanoate, methyl dodecanoate, methyl tetradecanoate and methyl hexadecanoate

International Nuclear Information System (INIS)

Sahraoui, Lakhdar; Khimeche, Kamel; Dahmani, Abdallah; Mokbel, Ilham; Jose, Jacques

2016-01-01

Highlight: • Vapor-liquid equilibria, Enthalpy of Vaporization, saturated Fatty Acid Methyl Ester. - Abstract: Vapor pressures of six saturated Fatty Acid Methyl Esters (FAMEs), methyl hexanoate (or methyl caproate), methyl octanoate (or methyl caprylate), Methyl decanoate (or methyl caprate), methyl dodecanoate (or methyl laurate), methyl tetradecanoate (or methyl myristate), and methyl hexadecanoate (or methyl palmitate) were measured from 1 Pa to 100 kPa and at temperature range between 262 and 453 K using a static apparatus. The experimental data (P-T) were compared with the available literature data.

In silico identification of BIM-1 (2-methyl-1H-indol-3-yl) as a potential ...

African Journals Online (AJOL)

In silico identification of BIM-1 (2-methyl-1H-indol-3-yl) as a potential therapeutic agent against elevated protein kinase C beta associated diseases. U Saeed, N Nawaz, Y Waheed, N Chaudry, HT Bhatti, S Urooj, H Waheed, M Ashraf, UHK Naizi ...

Trans-methylation reactions in plants: focus on the activated methyl cycle.

Science.gov (United States)

Rahikainen, Moona; Alegre, Sara; Trotta, Andrea; Pascual, Jesús; Kangasjärvi, Saijaliisa

2018-02-01

Trans-methylation reactions are vital in basic metabolism, epigenetic regulation, RNA metabolism, and posttranslational control of protein function and therefore fundamental in determining the physiological processes in all living organisms. The plant kingdom is additionally characterized by the production of secondary metabolites that undergo specific hydroxylation, oxidation and methylation reactions to obtain a wide array of different chemical structures. Increasing research efforts have started to reveal the enzymatic pathways underlying the biosynthesis of complex metabolites in plants. Further engineering of these enzymatic machineries offers significant possibilities in the development of bio-based technologies, but necessitates deep understanding of their potential metabolic and regulatory interactions. Trans-methylation reactions are tightly coupled with the so-called activated methyl cycle (AMC), an essential metabolic circuit that maintains the trans-methylation capacity in all living cells. Tight regulation of the AMC is crucial in ensuring accurate trans-methylation reactions in different subcellular compartments, cell types, developmental stages and environmental conditions. This review addresses the organization and posttranslational regulation of the AMC and elaborates its critical role in determining metabolic regulation through modulation of methyl utilization in stress-exposed plants. © 2017 Scandinavian Plant Physiology Society.

Evolution of DNA Methylation across Insects.

Science.gov (United States)

Bewick, Adam J; Vogel, Kevin J; Moore, Allen J; Schmitz, Robert J

2017-03-01

DNA methylation contributes to gene and transcriptional regulation in eukaryotes, and therefore has been hypothesized to facilitate the evolution of plastic traits such as sociality in insects. However, DNA methylation is sparsely studied in insects. Therefore, we documented patterns of DNA methylation across a wide diversity of insects. We predicted that underlying enzymatic machinery is concordant with patterns of DNA methylation. Finally, given the suggestion that DNA methylation facilitated social evolution in Hymenoptera, we tested the hypothesis that the DNA methylation system will be associated with presence/absence of sociality among other insect orders. We found DNA methylation to be widespread, detected in all orders examined except Diptera (flies). Whole genome bisulfite sequencing showed that orders differed in levels of DNA methylation. Hymenopteran (ants, bees, wasps and sawflies) had some of the lowest levels, including several potential losses. Blattodea (cockroaches and termites) show all possible patterns, including a potential loss of DNA methylation in a eusocial species whereas solitary species had the highest levels. Species with DNA methylation do not always possess the typical enzymatic machinery. We identified a gene duplication event in the maintenance DNA methyltransferase 1 (DNMT1) that is shared by some Hymenoptera, and paralogs have experienced divergent, nonneutral evolution. This diversity and nonneutral evolution of underlying machinery suggests alternative DNA methylation pathways may exist. Phylogenetically corrected comparisons revealed no evidence that supports evolutionary association between sociality and DNA methylation. Future functional studies will be required to advance our understanding of DNA methylation in insects. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The methyl rotational potentials of Ga(CH sub 3) sub 3 derived by neutron spectroscopy

CERN Document Server

Prager, M; Parker, S F; Desmedt, A; Lechner, R E

2002-01-01

High resolution neutron spectra of Ga(CH sub 3) sub 3 show tunnelling transitions between 4.5 and 19 mu eV. The spectrum can be explained within the single-particle model on the basis of the monoclinic C2/c (Z = 16) low temperature crystal structure of Ga(CH sub 3) sub 3 with six inequivalent methyl groups in the unit cell. The overlapping tunnelling lines prevent the extraction of temperature dependent linewidths which would allow us to assign the librational energies measured in the phonon density of states. Classical rotational motion is studied by quasielastic neutron scattering. Three activation energies could be extracted. Methyl librations, tunnelling energies and barrier heights are combined with consistent intensities into rotational potentials. Only the concerted application of all spectroscopic techniques yields a conclusive description.

The Potential for Increasing Net Incomes on Limited-Resource Farms in Eastern Kentucky. Research Report 24.

Science.gov (United States)

Stewart, Fred J.; And Others

The study identified possibilities for improving farm incomes on limited-resource farms in eastern Kentucky. Objectives were to describe farm operations of full-time Appalachian farmers who had gross sales of less than $5,000 in 1972, estimate potential increases in net farm incomes from given resources, and identify nonresource constraints on…

The Potential for Forestry to Reduce Net CO2 Emissions

International Nuclear Information System (INIS)

Eriksson, Erik

2006-01-01

Forestry may have an important role to play in attempts to reduce atmospheric CO 2 levels, since countries may choose to account for forest management activities to fulfil their commitments under the Kyoto Protocol. However, the effectiveness of such efforts may depend on the forest management strategies applied. This thesis is based on four separate studies in which the potential for forest management strategies to decrease net CO 2 emissions was considered. Long-term field experiments and models were used to: evaluate the impact of different thinning regimes; study broad-leaved stands growing on abandoned farmland with different rotation lengths; predict the effects of using different rotation lengths on carbon accumulation and fossil fuel substitution; and perform an integrated analysis of forest management practices and the potential to substitute fossil fuels by wood products. To evaluate the effects of the management regimes considered, carbon stocks in the investigated stands and the potential of the resulting biomass to substitute fossil fuel were estimated. No significant differences were found in biomass production between the thinning regimes for Norway spruce (Picea abies (L.) Karst.) stands, but the standing biomass was significantly larger in unthinned stands, indicating that to maximize the carbon stock in tree biomass thinnings should be avoided. For Scots pine (Pinus sylvestris L.), thinned and fertilized stands produced significantly more biomass (2.60-2.72 ton d.w./ha/yr) than unthinned and unfertilized stands (2.17-2.34 ton d.w./ha/yr) in the northern regions. These findings indicate that fertilization might be a viable measure to increase production of biomass with the potential to replace fossil fuel and energy-intensive material. In addition, for broad-leaved trees stands on abandoned farmland, management regimes with a short rotation were found to be better for maximizing the substitution of fossil fuel than regimes with a long rotation

DNA methylation

DEFF Research Database (Denmark)

Williams, Kristine; Christensen, Jesper; Helin, Kristian

2012-01-01

DNA methylation is involved in key cellular processes, including X-chromosome inactivation, imprinting and transcriptional silencing of specific genes and repetitive elements. DNA methylation patterns are frequently perturbed in human diseases such as imprinting disorders and cancer. The recent...... discovery that the three members of the TET protein family can convert 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) has provided a potential mechanism leading to DNA demethylation. Moreover, the demonstration that TET2 is frequently mutated in haematopoietic tumours suggests that the TET...... proteins are important regulators of cellular identity. Here, we review the current knowledge regarding the function of the TET proteins, and discuss various mechanisms by which they contribute to transcriptional control. We propose that the TET proteins have an important role in regulating DNA methylation...

Simulation of net infiltration and potential recharge using a distributed-parameter watershed model of the Death Valley region, Nevada and California

Science.gov (United States)

Hevesi, Joseph A.; Flint, Alan L.; Flint, Lorraine E.

2003-01-01

This report presents the development and application of the distributed-parameter watershed model, INFILv3, for estimating the temporal and spatial distribution of net infiltration and potential recharge in the Death Valley region, Nevada and California. The estimates of net infiltration quantify the downward drainage of water across the lower boundary of the root zone and are used to indicate potential recharge under variable climate conditions and drainage basin characteristics. Spatial variability in recharge in the Death Valley region likely is high owing to large differences in precipitation, potential evapotranspiration, bedrock permeability, soil thickness, vegetation characteristics, and contributions to recharge along active stream channels. The quantity and spatial distribution of recharge representing the effects of variable climatic conditions and drainage basin characteristics on recharge are needed to reduce uncertainty in modeling ground-water flow. The U.S. Geological Survey, in cooperation with the Department of Energy, developed a regional saturated-zone ground-water flow model of the Death Valley regional ground-water flow system to help evaluate the current hydrogeologic system and the potential effects of natural or human-induced changes. Although previous estimates of recharge have been made for most areas of the Death Valley region, including the area defined by the boundary of the Death Valley regional ground-water flow system, the uncertainty of these estimates is high, and the spatial and temporal variability of the recharge in these basins has not been quantified. To estimate the magnitude and distribution of potential recharge in response to variable climate and spatially varying drainage basin characteristics, the INFILv3 model uses a daily water-balance model of the root zone with a primarily deterministic representation of the processes controlling net infiltration and potential recharge. The daily water balance includes precipitation

Structure, bioactivity, and synthesis of methylated flavonoids.

Science.gov (United States)

Wen, Lingrong; Jiang, Yueming; Yang, Jiali; Zhao, Yupeng; Tian, Miaomiao; Yang, Bao

2017-06-01

Methylated flavonoids are an important type of natural flavonoid derivative with potentially multiple health benefits; among other things, they have improved bioavailability compared with flavonoid precursors. Flavonoids have been documented to have broad bioactivities, such as anticancer, immunomodulation, and antioxidant activities, that can be elevated, to a certain extent, by methylation. Understanding the structure, bioactivity, and bioavailability of methylated flavonoids, therefore, is an interesting topic with broad potential applications. Though methylated flavonoids are widely present in plants, their levels are usually low. Because developing efficient techniques to produce these chemicals would likely be beneficial, we provide an overview of their chemical and biological synthesis. © 2017 New York Academy of Sciences.

Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures.

Science.gov (United States)

Schwalbe, E C; Hicks, D; Rafiee, G; Bashton, M; Gohlke, H; Enshaei, A; Potluri, S; Matthiesen, J; Mather, M; Taleongpong, P; Chaston, R; Silmon, A; Curtis, A; Lindsey, J C; Crosier, S; Smith, A J; Goschzik, T; Doz, F; Rutkowski, S; Lannering, B; Pietsch, T; Bailey, S; Williamson, D; Clifford, S C

2017-10-18

Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation.

Surface potential of methyl isobutyl carbinol adsorption layer at the air/water interface.

Science.gov (United States)

Phan, Chi M; Nakahara, Hiromichi; Shibata, Osamu; Moroi, Yoshikiyo; Le, Thu N; Ang, Ha M

2012-01-26

The surface potential (ΔV) and surface tension (γ) of MIBC (methyl isobutyl carbinol) were measured on the subphase of pure water and electrolyte solutions (NaCl at 0.02 and 2 M). In contrast to ionic surfactants, it was found that surface potential gradually increased with MIBC concentration. The ΔV curves were strongly influenced by the presence of NaCl. The available model in literature, in which surface potential is linearly proportional to surface excess, failed to describe the experimental data. Consequently, a new model, employing a partial charge of alcohol adsorption layer, was proposed. The new model predicted the experimental data consistently for MIBC in different NaCl solutions. However, the model required additional information for ionic impurity to predict adsorption in the absence of electrolyte. Such inclusion of impurities is, however, unnecessary for industrial applications. The modeling results successfully quantify the influence of electrolytes on surface potential of MIBC, which is critical for froth stability.

Calculation of baryon chemical potential and strangeness chemical potential in resonance matter

International Nuclear Information System (INIS)

Fu Yuanyong; Hu Shouyang; Lu Zhongdao

2006-01-01

Based on the high energy heavy-ion collisions statistical model, the baryon chemical potential and strangeness chemical potential are calculated for resonance matter with net baryon density and net strangeness density under given temperature. Furthermore, the relationship between net baryon density, net strangeness density and baryon chemical potential, strangeness chemical potential are analyzed. The results show that baryon chemical potential and strangeness chemical potential increase with net baryon density and net strangeness density increasing, the change of net baryon density affects baryon chemical potential and strangeness chemical potential more strongly than the change of net strangeness density. (authors)

Genome-wide, Single-Cell DNA Methylomics Reveals Increased Non-CpG Methylation during Human Oocyte Maturation

Directory of Open Access Journals (Sweden)

Bo Yu

2017-07-01

Full Text Available The establishment of DNA methylation patterns in oocytes is a highly dynamic process marking gene-regulatory events during fertilization, embryonic development, and adulthood. However, after epigenetic reprogramming in primordial germ cells, how and when DNA methylation is re-established in developing human oocytes remains to be characterized. Here, using single-cell whole-genome bisulfite sequencing, we describe DNA methylation patterns in three different maturation stages of human oocytes. We found that while broad-scale patterns of CpG methylation have been largely established by the immature germinal vesicle stage, localized changes continue into later development. Non-CpG methylation, on the other hand, undergoes a large-scale, generalized remodeling through the final stage of maturation, with the net overall result being the accumulation of methylation as oocytes mature. The role of the genome-wide, non-CpG methylation remodeling in the final stage of oocyte maturation deserves further investigation.

Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression

NARCIS (Netherlands)

van der Wijst, Monique G. P.; van Tilburg, Amanda Y.; Ruiters, Marcel H. J.; Rots, Marianne G.

2017-01-01

Like the nucleus, mitochondria contain their own DNA and recent reports provide accumulating evidence that also the mitochondrial DNA (mtDNA) is subjective to DNA methylation. This evidence includes the demonstration of mitochondria-localised DNA methyltransferases and demethylases, and the

Prospects and potential of fatty acid methyl esters of some non-traditional seed oils for use as biodiesel in India

Energy Technology Data Exchange (ETDEWEB)

Mohibbe Azam, M.; Waris, Amtul; Nahar, N.M. [Central Arid Zone Research Institute, Jodhpur 342003 (India)

2005-10-01

Fatty acid profiles of seed oils of 75 plant species having 30% or more fixed oil in their seed/kernel were examined. Saponification number (SN), iodine value (IV) and cetane number (CN) of fatty acid methyl esters of oils were empirically determined and they varied from 169.2 to 312.5, 4.8 to 212 and 20.56 to 67.47, respectively. Fatty acid compositions, IV and CN were used to predict the quality of fatty acid methyl esters of oil for use as biodiesel. Fatty acid methyl ester of oils of 26 species including Azadirachta indica, Calophyllum inophyllum, Jatropha curcas and Pongamia pinnata were found most suitable for use as biodiesel and they meet the major specification of biodiesel standards of USA, Germany and European Standard Organization. The fatty acid methyl esters of another 11 species meet the specification of biodiesel standard of USA only. These selected plants have great potential for biodiesel. (author)

Prospects and potential of fatty acid methyl esters of some non-traditional seed oils for use as biodiesel in India

International Nuclear Information System (INIS)

Mohibbe Azam, M.; Waris, Amtul; Nahar, N.M.

2005-01-01

Fatty acid profiles of seed oils of 75 plant species having 30% or more fixed oil in their seed/kernel were examined. Saponification number (SN), iodine value (IV) and cetane number (CN) of fatty acid methyl esters of oils were empirically determined and they varied from 169.2 to 312.5, 4.8 to 212 and 20.56 to 67.47, respectively. Fatty acid compositions, IV and CN were used to predict the quality of fatty acid methyl esters of oil for use as biodiesel. Fatty acid methyl ester of oils of 26 species including Azadirachta indica, Calophyllum inophyllum, Jatropha curcas and Pongamia pinnata were found most suitable for use as biodiesel and they meet the major specification of biodiesel standards of USA, Germany and European Standard Organization. The fatty acid methyl esters of another 11 species meet the specification of biodiesel standard of USA only. These selected plants have great potential for biodiesel

Net energy gain from DT fusion

International Nuclear Information System (INIS)

Buende, R.

1985-01-01

The net energy which can be gained from an energy raw material by means of a certain conversion system is deduced as the figure-of-merit which adequately characterizes the net energy balance of utilizing an energy source. This potential net energy gain is determined for DT fusion power plants. It is represented as a function of the degree of exploitation of the energy raw material lithium ore and is compared with the net energy which can be gained with LW and FBR power plants by exploiting uranium ore. The comparison clearly demonstrates the net energetic advantage of DT fusion. A sensitivity study shows that this holds even if the energy expenditure for constructing and operating is drastically increased

Methyl-Analyzer--whole genome DNA methylation profiling.

Science.gov (United States)

Xin, Yurong; Ge, Yongchao; Haghighi, Fatemeh G

2011-08-15

Methyl-Analyzer is a python package that analyzes genome-wide DNA methylation data produced by the Methyl-MAPS (methylation mapping analysis by paired-end sequencing) method. Methyl-MAPS is an enzymatic-based method that uses both methylation-sensitive and -dependent enzymes covering >80% of CpG dinucleotides within mammalian genomes. It combines enzymatic-based approaches with high-throughput next-generation sequencing technology to provide whole genome DNA methylation profiles. Methyl-Analyzer processes and integrates sequencing reads from methylated and unmethylated compartments and estimates CpG methylation probabilities at single base resolution. Methyl-Analyzer is available at http://github.com/epigenomics/methylmaps. Sample dataset is available for download at http://epigenomicspub.columbia.edu/methylanalyzer_data.html. fgh3@columbia.edu Supplementary data are available at Bioinformatics online.

Electronic transport in methylated fragments of DNA

Energy Technology Data Exchange (ETDEWEB)

Almeida, M. L. de; Oliveira, J. I. N.; Lima Neto, J. X.; Gomes, C. E. M.; Fulco, U. L., E-mail: umbertofulco@gmail.com; Albuquerque, E. L. [Departamento de Biofísica e Farmacologia, Universidade Federal do Rio Grande do Norte, 59072-970 Natal-RN (Brazil); Freire, V. N. [Departamento de Física, Universidade Federal do Ceará, 60455-760 Fortaleza, CE (Brazil); Caetano, E. W. S. [Instituto Federal de Educação, Ciência e Tecnologia do Ceará, 60040-531 Fortaleza, CE (Brazil); Moura, F. A. B. F. de; Lyra, M. L. [Instituto de Física, Universidade Federal de Alagoas, 57072-900 Maceió-AL (Brazil)

2015-11-16

We investigate the electronic transport properties of methylated deoxyribonucleic-acid (DNA) strands, a biological system in which methyl groups are added to DNA (a major epigenetic modification in gene expression), sandwiched between two metallic platinum electrodes. Our theoretical simulations apply an effective Hamiltonian based on a tight-binding model to obtain current-voltage curves related to the non-methylated/methylated DNA strands. The results suggest potential applications in the development of novel biosensors for molecular diagnostics.

Electronic transport in methylated fragments of DNA

International Nuclear Information System (INIS)

Almeida, M. L. de; Oliveira, J. I. N.; Lima Neto, J. X.; Gomes, C. E. M.; Fulco, U. L.; Albuquerque, E. L.; Freire, V. N.; Caetano, E. W. S.; Moura, F. A. B. F. de; Lyra, M. L.

2015-01-01

We investigate the electronic transport properties of methylated deoxyribonucleic-acid (DNA) strands, a biological system in which methyl groups are added to DNA (a major epigenetic modification in gene expression), sandwiched between two metallic platinum electrodes. Our theoretical simulations apply an effective Hamiltonian based on a tight-binding model to obtain current-voltage curves related to the non-methylated/methylated DNA strands. The results suggest potential applications in the development of novel biosensors for molecular diagnostics

Immunosuppressive potential of bardoxolone methyl using a modified murine local lymph node assay (LLNA).

Science.gov (United States)

Kitsukawa, Mika; Tsuchiyama, Hiromi; Maeda, Akihisa; Oshida, Keiyu; Miyamoto, Yohei

2014-08-01

2-Cyano-3, 12-dioxooleana-1, 9-dien-28-oic acid methyl ester (CDDO-Me; bardoxolone methyl) is one of the synthetic oleanane triterpenoids (SOs). It is known that it is the strongest Nrf2/ARE signaling inducer of SOs and slightly inhibits immune response. Little was known about the immunomodulatory action of CDDO-Me in vivo. We assessed its immunosuppressive potential by using the modified mouse lymph node assay (LLNA) including immunosuppression-related gene expression analysis. In the modified LLNA, CDDO-Me showed a significant decrease in lymph node weight and changes in expressions of the immunosuppression-related genes, Zfp459 and Fmo2. It has been already reported that a decrease in lymph node weight was induced by several types of immunosuppressive chemicals such as calcineurin inhibitors, antimetabolites, steroids, and alkylators. In addition, changes in Zfp459 and Fmo2 expression was reported in response after only treatment of antimetabolites. From these results, CDDO-Me is considered to have an immunosuppressive action and similar mechanism to antimetabolites.

Experimental hut evaluation of bednets treated with an organophosphate (chlorpyrifos-methyl or a pyrethroid (lambdacyhalothrin alone and in combination against insecticide-resistant Anopheles gambiae and Culex quinquefasciatus mosquitoes

Directory of Open Access Journals (Sweden)

Corbel Vincent

2005-05-01

Full Text Available Abstract Background Pyrethroid resistant mosquitoes are becoming increasingly common in parts of Africa. It is important to identify alternative insecticides which, if necessary, could be used to replace or supplement the pyrethroids for use on treated nets. Certain compounds of an earlier generation of insecticides, the organophosphates may have potential as net treatments. Methods Comparative studies of chlorpyrifos-methyl (CM, an organophosphate with low mammalian toxicity, and lambdacyhalothrin (L, a pyrethroid, were conducted in experimental huts in Côte d'Ivoire, West Africa. Anopheles gambiae and Culex quinquefasciatus mosquitoes from the area are resistant to pyrethroids and organophosphates (kdr and insensitive acetylcholinesterase Ace.1R. Several treatments and application rates on intact or holed nets were evaluated, including single treatments, mixtures, and differential wall/ceiling treatments. Results and Conclusion All of the treatments were effective in reducing blood feeding from sleepers under the nets and in killing both species of mosquito, despite the presence of the kdr and Ace.1R genes at high frequency. In most cases, the effects of the various treatments did not differ significantly. Five washes of the nets in soap solution did not reduce the impact of the insecticides on A. gambiae mortality, but did lead to an increase in blood feeding. The three combinations performed no differently from the single insecticide treatments, but the low dose mixture performed encouragingly well indicating that such combinations might be used for controlling insecticide resistant mosquitoes. Mortality of mosquitoes that carried both Ace.1R and Ace.1S genes did not differ significantly from mosquitoes that carried only Ace.1S genes on any of the treated nets, indicating that the Ace.1R allele does not confer effective resistance to chlorpyrifos-methyl under the realistic conditions of an experimental hut.

Isomorphism of 2-methylnaphthalene and 2-halonaphthalenes as a revealer of a special interaction between methyl and halogen

Science.gov (United States)

Calvet, T.; Cuevas-Diarte, M. A.; Haget, Y.; Mondieig, D.; Kok, I. C.; Verdonk, M. L.; Van Miltenburg, J. C.; Oonk, H. A. J.

1999-03-01

The systems 2-methylnaphthalene+2-chloronaphthalene and 2-methylnaphthalene+2-bromonaphthalene belong to the exceptional group of binary systems where the formation of mixed crystals goes together with a solid-liquid phase diagram with a maximum. For these systems a thermodynamic analysis is presented which is based on new phase diagram and thermochemical data. The excess Gibbs energies, excess enthalpies, and excess entropies of the mixed crystalline state all are negative. These properties correspond to a net attraction between methyl and substituted halogen. Additional evidence of such an attraction is given by the outcome of a statistical search on intermolecular contacts, in the crystalline state of pure substances, among methyl+halogen, halogen+halogen, and methyl+methyl.

Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

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Barbara Banelli

Full Text Available Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months. Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

Impacts of Activated Carbon Amendment on Hg Methylation, Demethylation and Microbial Activity in Marsh Soils

Science.gov (United States)

Gilmour, C. C.; Ghosh, U.; Santillan, E. F. U.; Soren, A.; Bell, J. T.; Butera, D.; McBurney, A. W.; Brown, S.; Henry, E.; Vlassopoulos, D.

2015-12-01

In-situ sorbent amendments are a low-impact approach for remediation of contaminants in sediments, particular in habitats like wetlands that provide important ecosystem services. Laboratory microcosm trials (Gilmour et al. 2013) and early field trials show that activated carbon (AC) can effectively increase partitioning of both inorganic Hg and methylmercury to the solid phase. Sediment-water partitioning can serve as a proxy for Hg and MeHg bioavailability in soils. One consideration in using AC in remediation is its potential impact on organisms. For mercury, a critical consideration is the potential impact on net MeHg accumulation and bioavailability. In this study, we specifically evaluated the impact of AC on rates of methylmercury production and degradation, and on overall microbial activity, in 4 different Hg-contaminated salt marsh soils. The study was done over 28 days in anaerobic, sulfate-reducing slurries. A double label of enriched mercury isotopes (Me199Hg and inorganic 201Hg) was used to separately follow de novo Me201Hg production and Me199Hg degradation. AC amendments decreased both methylation and demethylation rate constants relative to un-amended controls, but the impact on demethylation was stronger. The addition of 5% (dry weight) regenerated AC to soil slurries drove demethylation rate constants to nearly zero; i.e. MeHg sorption to AC almost totally blocked its degradation. The net impact was increased solid phase MeHg concentrations in some of the soil slurries with the highest methylation rate constants. However, the net impact of AC amendments was to increase MeHg (and inorganic Hg) partitioning to the soil phase and decrease concentrations in the aqueous phase. AC significantly decreased aqueous phase inorganic Hg and MeHg concentrations after 28 days. Overall, the efficacy of AC in reducing aqueous MeHg was highest in the soils with the highest MeHg concentrations. The AC addition did not significantly impact microbial activity, as

Methylated genes as new cancer biomarkers.

LENUS (Irish Health Repository)

Duffy, M J

2012-02-01

Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene methylation need to be standardised, simplified and evaluated in external quality assurance programmes. It is concluded that methylated genes have the potential to provide a new generation of cancer biomarkers.

A novel method to quantify local CpG methylation density by regional methylation elongation assay on microarray

Directory of Open Access Journals (Sweden)

Qiao Yingjuan

2008-01-01

Full Text Available Abstract Background DNA methylation based techniques are important tools in both clinical diagnostics and therapeutics. But most of these methods only analyze a few CpG sites in a target region. Indeed, difference of site-specific methylation may also lead to a change of methylation density in many cases, and it has been found that the density of methylation is more important than methylation of single CpG site for gene silencing. Results We have developed a novel approach for quantitative analysis of CpG methylation density on the basis of microarray-based hybridization and incorporation of Cy5-dCTP into the Cy3 labeled target DNA by using Taq DNA Polymerase on microarray. The quantification is achieved by measuring Cy5/Cy3 signal ratio which is proportional to methylation density. This methylation-sensitive technique, termed RMEAM (regional methylation elongation assay on microarray, provides several advantages over existing methods used for methylation analysis. It can determine an exact methylation density of the given region, and has potential of high throughput. We demonstrate a use of this method in determining the methylation density of the promoter region of the tumor-related gene MLH1, TERT and MGMT in colorectal carcinoma patients. Conclusion This technique allows for quantitative analysis of regional methylation density, which is the representative of all allelic methylation patterns in the sample. The results show that this technique has the characteristics of simplicity, rapidness, specificity and high-throughput.

Implications of DNA Methylation in Parkinson’s Disease

Directory of Open Access Journals (Sweden)

Ernesto Miranda-Morales

2017-07-01

Full Text Available It has been 200 years since Parkinson’s disease (PD was first described, yet many aspects of its etiopathogenesis remain unclear. PD is a progressive and complex neurodegenerative disorder caused by genetic and environmental factors including aging, nutrition, pesticides and exposure to heavy metals. DNA methylation may be altered in response to some of these factors; therefore, it is proposed that epigenetic mechanisms, particularly DNA methylation, can have a fundamental role in gene–environment interactions that are related with PD. Epigenetic changes in PD-associated genes are now widely studied in different populations, to discover the mechanisms that contribute to disease development and identify novel biomarkers for early diagnosis and future pharmacological treatment. While initial studies sought to find associations between promoter DNA methylation and the regulation of associated genes in PD brain tissue, more recent studies have described concordant DNA methylation patterns between blood and brain tissue DNA. These data justify the use of peripheral blood samples instead of brain tissue for epigenetic studies. Here, we summarize the current data about DNA methylation changes in PD and discuss the potential of DNA methylation as a potential biomarker for PD. Additionally, we discuss environmental and nutritional factors that have been implicated in DNA methylation. Although the search for significant DNA methylation changes and gene expression analyses of PD-associated genes have yielded inconsistent and contradictory results, epigenetic modifications remain under investigation for their potential to reveal the link between environmental risk factors and the development of PD.

[Effects of plastic film mulching and nitrogen application rate on net global warming potential in semiarid rain-fed maize cropland].

Science.gov (United States)

Liu, Jian Can; Wang, Ze Lin; Yue, Shan Chao; Li, Shi Qing

2018-04-01

A one-year field experiment was conducted to evaluate the effects of plastic film mulching (FM) and nitrogen application rates applied to rain-fed maize fields on net global warming potential (Net GWP) and greenhouse gas intensity (GHGI) at the Changwu Agricultural and Ecological Experimental Station. Both GWP and GHGI were affected by the plastic film mulching and nitrogen application rate. Under the FM treatment, maize yield ranged from 1643 to 16699 kg·hm -2 , the net GWP (CO 2 -eq) ranged from 595 to 4376 kg·hm -2 ·a -1 , and the GHGI (CO 2 -eq) ranged from 213 to 358 kg·t -1 . The grain yield of maize, net GWP and GHGI for the UM (no mulching) treatment were 956 to 8821 kg·hm -2 , 342 to 4004 kg·hm -2 ·a -1 and 204 to 520 kg·t -1 , respectively. The results suggested that plastic film mulching could simultaneously improve grain yield and decrease GHGI in rain-fed cropland along with nitrogen fertilizer of 250 kg·hm -2 .

Net metering in British Columbia : white paper

International Nuclear Information System (INIS)

Berry, T.

2003-01-01

Net metering was described as being the reverse registration of an electricity customer's revenue meter when interconnected with a utility's grid. It is a provincial policy designed to encourage small-distributed renewable power generation such as micro-hydro, solar energy, fuel cells, and larger-scale wind energy. It was noted that interconnection standards for small generation is an important issue that must be addressed. The British Columbia Utilities Commission has asked BC Hydro to prepare a report on the merits of net metering in order to support consultations on a potential net metering tariff application by the utility. This report provides information on net metering with reference to experience in other jurisdictions with net metering, and the possible costs and benefits associated with net metering from both a utility and consumer perspective. Some of the barriers and policy considerations for successful implementation of net metering were also discussed. refs., tabs., figs

Prooxidant/Antioxidant Ratio (ProAntidex as a Better Index of Net Free Radical Scavenging Potential

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Hwee Ming Cheng

2010-11-01

Full Text Available The antioxidant activity of several Malaysian plant extracts was analyzed simultaneously with their pro-oxidant capacity. This ratio represents an index (ProAntidex of the net free radical scavenging ability of whole plant extracts. We observed that ethanolic extracts of Nephelium lappaceum peel, Fragaria x ananassa leaf, Lawsonia inermis leaf, Syzygium aqueum leaf and grape seed had a lower Pro-Antidex than the commercially available Emblica™ extract which is an antioxidant agent with very low pro-oxidant activity. Among the aqueous extracts, Lawsonia inermis leaf, Nephelium mutobile leaf and grape seed had lower pro-oxidant activity compared to the Emblica™ extract. Among these extracts, aqueous extract of Nephelium mutobile leaf had a very low index of 0.05 compared to 0.69 for Emblica™. Most of the extracts had a far lower ProAntidex compared to the Vitamin C. The index enables us to identify extracts with high net free radical scavenging activity potential. The ProAntidex is beneficial as a screening parameter to the food industries and healthcare.

A genome-wide methylation study on obesity: differential variability and differential methylation.

Science.gov (United States)

Xu, Xiaojing; Su, Shaoyong; Barnes, Vernon A; De Miguel, Carmen; Pollock, Jennifer; Ownby, Dennis; Shi, Hidong; Zhu, Haidong; Snieder, Harold; Wang, Xiaoling

2013-05-01

Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common complex disease. We analyzed genome-wide methylation profiles of over 470,000 CpGs in peripheral blood samples from 48 obese and 48 lean African-American youth aged 14-20 y old. A substantial number of differentially variable CpG sites (DVCs), using statistics based on variances, as well as a substantial number of differentially methylated CpG sites (DMCs), using statistics based on means, were identified. Similar to the findings in cancers, DVCs generally exhibited an outlier structure and were more variable in cases than in controls. By randomly splitting the current sample into a discovery and validation set, we observed that both the DVCs and DMCs identified from the first set could independently predict obesity status in the second set. Furthermore, both the genes harboring DMCs and the genes harboring DVCs showed significant enrichment of genes identified by genome-wide association studies on obesity and related diseases, such as hypertension, dyslipidemia, type 2 diabetes and certain types of cancers, supporting their roles in the etiology and pathogenesis of obesity. We generalized the recent finding on methylation variability in cancer research to obesity and demonstrated that differential variability is also an important feature of obesity-related methylation changes. Future studies on the epigenetics of obesity will benefit from both statistics based on means and statistics based on variances.

Mercury methylation and demethylation by periphyton biofilms and their host in a fluvial wetland of the St. Lawrence River (QC, Canada)

International Nuclear Information System (INIS)

Hamelin, Stéphanie; Planas, Dolors; Amyot, Marc

2015-01-01

Wetlands in large rivers are important sites of production of the neurotoxin methylmercury (MeHg), and the periphyton growing on wetland macrophytes are increasingly recognized as key players in this production and transfer in food webs. Information is lacking about mercury methylation (K m ) and demethylation (K d ) rates in periphytic biofilms from the Northern Hemisphere, as well as about the drivers of net MeHg production, hampering ecosystem modeling of Hg cycling. Mercury methylation and demethylation rates were measured in periphytic biofilms growing on submerged plants in a shallow fluvial lake located in a temperate cold region (St. Lawrence River, Quebec, Canada). Incubations were performed in situ within macrophyte beds using low-level spikes of 199 HgO and Me 200 Hg stable isotopes as tracers. A direct relationship was observed between K m (0.002 to 0.137 d −1 ) and [MeHg] in periphyton. A similar relationship was found between K d (0.096 to 0.334 d −1 ) and [inorganic Hg]. Periphyton of Lake St. Pierre reached high levels of net MeHg production that were two orders of magnitude higher than those found in local sediment. This production varied through the plant growing season and was mainly driven by environmental variables such as depth of growth, available light, dissolved oxygen, temperature, plant community structure, and productivity of the habitat. - Highlights: • Periphyton Hg methylation and demethylation were studied in a large fluvial lake. • Addition of stable Hg isotopes was used to obtain in situ rates for these processes. • Net methylation was higher in periphyton than in local sediments. • Methylation and demethylation rates fluctuated during the summer. • Key drivers of rates were depth, light, temperature, and community structure

Mercury methylation and demethylation by periphyton biofilms and their host in a fluvial wetland of the St. Lawrence River (QC, Canada)

Energy Technology Data Exchange (ETDEWEB)

Hamelin, Stéphanie; Planas, Dolors [GRIL, Département de sciences biologiques, Université du Québec à Montréal, C.P. 8888, Succursale Centre-Ville, Montreal, Quebec H3C 3P8 (Canada); Amyot, Marc [GRIL, Département de sciences biologiques, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, Quebec H3C 3J7 (Canada)

2015-04-15

Wetlands in large rivers are important sites of production of the neurotoxin methylmercury (MeHg), and the periphyton growing on wetland macrophytes are increasingly recognized as key players in this production and transfer in food webs. Information is lacking about mercury methylation (K{sub m}) and demethylation (K{sub d}) rates in periphytic biofilms from the Northern Hemisphere, as well as about the drivers of net MeHg production, hampering ecosystem modeling of Hg cycling. Mercury methylation and demethylation rates were measured in periphytic biofilms growing on submerged plants in a shallow fluvial lake located in a temperate cold region (St. Lawrence River, Quebec, Canada). Incubations were performed in situ within macrophyte beds using low-level spikes of {sup 199}HgO and Me{sup 200}Hg stable isotopes as tracers. A direct relationship was observed between K{sub m} (0.002 to 0.137 d{sup −1}) and [MeHg] in periphyton. A similar relationship was found between K{sub d} (0.096 to 0.334 d{sup −1}) and [inorganic Hg]. Periphyton of Lake St. Pierre reached high levels of net MeHg production that were two orders of magnitude higher than those found in local sediment. This production varied through the plant growing season and was mainly driven by environmental variables such as depth of growth, available light, dissolved oxygen, temperature, plant community structure, and productivity of the habitat. - Highlights: • Periphyton Hg methylation and demethylation were studied in a large fluvial lake. • Addition of stable Hg isotopes was used to obtain in situ rates for these processes. • Net methylation was higher in periphyton than in local sediments. • Methylation and demethylation rates fluctuated during the summer. • Key drivers of rates were depth, light, temperature, and community structure.

Infraspecific DNA methylation polymorphism in cotton (Gossypium hirsutum L.).

Science.gov (United States)

Keyte, Anna L; Percifield, Ryan; Liu, Bao; Wendel, Jonathan F

2006-01-01

Cytosine methylation is important in the epigenetic regulation of gene expression and development in plants and has been implicated in silencing duplicate genes after polyploid formation in several plant groups. Relatively little information exists, however, on levels and patterns of methylation polymorphism (MP) at homologous loci within species. Here we explored the levels and patterns of methylation-polymorphism diversity at CCGG sites within allotetraploid cotton, Gossypium hirsutum, using a methylation-sensitive amplified fragment length polymorphism screen and a selected set of 20 G. hirsutum accessions for which we have information on genetic polymorphism levels and relationships. Methylation and MP exist at high levels within G. hirsutum: of 150 HpaII/MspI sites surveyed, 48 were methylated at the inner cytosine (32%) and 32 of these were polymorphic (67%). Both these values are higher than comparable measures of genetic diversity using restriction fragment length polymorphisms. The high percentage of methylation-polymorphic sites and potential relationship to gene expression underscore the potential significance of MP within and among populations. We speculate that biased correlation of methylation-polymorphic sites and genes in cotton may be a consequence of polyploidy and the attendant doubling of all genes.

Efficacy of mosquito nets treated with a pyrethroid-organophosphorous mixture against Kdr- and Kdr+ malaria vectors (Anopheles gambiae

Directory of Open Access Journals (Sweden)

Darriet F.

2003-12-01

Full Text Available In order to prevent the resistance of Anopheles gambiae s.l. to pyrethroids from spreading too quickly and to lengthen the effectiveness of insecticide impregnated mosquito nets, it has recently been suggested to use mixtures of insecticides that have different modes of action. This study presents the results obtained with tulle mosquito nets treated with bifenthrin (a pyrethroid] and chlorpyrifos-methyl (an organophosphorous both separately and in mixture on two strains of An. gambiae, one sensitive to all insecticides, and the other resistant to pyrethroids. The values of KDt50 and KDt95 and the mortality induced with the mixture of bifenthrin (25 mg/m2 and chlorpyrifos-methyl (4.5 mg/m2 show a significant synergistic effect on the strain of An. gambiae susceptible to insecticides. However, the tested combination does not induce any synergistic effect on the VKPR strain selected with permethrin, but only enhances the effectiveness of the two insecticides taken separately.

DNA methylation and temperature stress in an Antarctic polychaete, Spiophanes tcherniai.

Science.gov (United States)

Marsh, Adam G; Pasqualone, Annamarie A

2014-01-01

Epigenetic modifications of DNA and histones are a primary mechanism by which gene expression activities may be modified in response to environmental stimuli. Here we characterize patterns of methyl-cytosine composition in the marine polychaete Spiophanes tcherniai from McMurdo Sound, Antarctica. We cultured adult worms at two temperatures, -1.5°C (ambient control) and +4°C (warm treatment), for 4 weeks. We observed a rapid capacity for S. tcherniai organismal respiration rates and underlying catalytic rates of citrate synthase at +4°C to return to control levels in less than 4 weeks. We profiled changes in the methylation states of CpG sites in these treatments using an NGS strategy to computationally reconstruct and quantify methylation status across the genome. In our analysis we recovered 120,000 CpG sites in assembled contigs from both treatments. Of those, we were able to align 28,000 CpG sites in common between the two sample groups. In comparing these aligned sites between treatments, only 3000 (11%) evidenced a change in methylation state, but over 85% of changes involved a gain of a 5-methyl group on a CpG site (net increase in methyation). The ability to score CpG sites as partially methylated among gDNA copies in a sample opens up a new avenue for assessing DNA methylation responses to changing environments. By quantitatively distinguishing a "mixed" population of copies of one CpG site, we can begin to identify dynamic, non-binary, continuous-response reactions in DNA methylation intensity or density that previously may have been overlooked as noise.

DNA Methylation and Temperature Stress in an Antarctic Polychaete, Spiophanes tcherniai

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Adam G. Marsh

2014-05-01

Full Text Available Epigenetic modifications of DNA and histones are a primary mechanism by which gene expression activities may be modified in response to environmental stimuli. Here we characterize patterns of methyl-cytosine composition in the marine polychaete emph{Spiophanes tcherniai} from McMurdo Sound, Antarctica. We cultured adult worms at two temperatures, -1.5 C (ambient control and +4 C (warm treatment, for four weeks. We observed a rapid capacity for emph{S. tcherniai} organismal respiration rates and underlying catalytic rates of citrate synthase to acclimate at +4 C and return to control levels. We profiled changes in the methylation states of CpG sites in these treatments using an NGS strategy to computationally reconstruct and quantify methylation status across the genome. In our analysis we recovered 120,000 CpG sites in assembled contigs from both treatments. Of those, we were able to align 28,000 CpG sites in common between the two sample groups. In comparing these aligned sites between treatments, only 3,000 (11% evidenced a change in methylation state, but over 85% of changes involved a gain of a 5-methyl group on a CpG site (net increase in methyation. The ability to score CpG sites as partially methylated among gDNA copies in a sample opens up a new avenue for assessing DNA methylation responses to changing environments. By quantitatively distinguishing a ``mixed'' population of copies of one CpG site, we can begin to identify dynamic, non-binary, continuous-response reactions in DNA methylation intensity or density that previously may have been overlooked as noise.

Towards new information resources for public health--from WordNet to MedicalWordNet.

Science.gov (United States)

Fellbaum, Christiane; Hahn, Udo; Smith, Barry

2006-06-01

In the last two decades, WordNet has evolved as the most comprehensive computational lexicon of general English. In this article, we discuss its potential for supporting the creation of an entirely new kind of information resource for public health, viz. MedicalWordNet. This resource is not to be conceived merely as a lexical extension of the original WordNet to medical terminology; indeed, there is already a considerable degree of overlap between WordNet and the vocabulary of medicine. Instead, we propose a new type of repository, consisting of three large collections of (1) medically relevant word forms, structured along the lines of the existing Princeton WordNet; (2) medically validated propositions, referred to here as medical facts, which will constitute what we shall call MedicalFactNet; and (3) propositions reflecting laypersons' medical beliefs, which will constitute what we shall call the MedicalBeliefNet. We introduce a methodology for setting up the MedicalWordNet. We then turn to the discussion of research challenges that have to be met to build this new type of information resource. We build a database of sentences relevant to the medical domain. The sentences are generated from WordNet via its relations as well as from medical statements broken down into elementary propositions. Two subcorpora of sentences are distinguished, MedicalBeliefNet and MedicalFactNet. The former is rated for assent by laypersons; the latter for correctness by medical experts. The sentence corpora will be valuable for a variety of applications in information retrieval as well as in research in linguistics and psychology with respect to the study of expert and non-expert beliefs and their linguistic expressions. Our work has to meet several considerable challenges. These include accounting for the distinction between medical experts and laypersons, the social issues of expert-layperson communication in different media, the linguistic aspects of encoding medical knowledge, and

Avocado and olive oil methyl esters

International Nuclear Information System (INIS)

Knothe, Gerhard

2013-01-01

Biodiesel, the mono-alkyl esters of vegetable oils, animal fats or other triacylglycerol-containing materials and an alternative to conventional petroleum-based diesel fuel, has been derived from a variety of feedstocks. Numerous feedstocks have been investigated as potential biodiesel sources, including commodity oils, however, the methyl esters of avocado and olive oil would likely be suitable as biodiesel fuel. In order to expand the database and comprehensive evaluation of the properties of vegetable oil esters, in this work the fuel-related properties of avocado and olive oil methyl esters, which exhibit similar fatty acid profiles including high oleic acid content, are determined. The cetane numbers of avocado oil methyl esters and olive oil methyl esters are relatively high, determined as 59.2 and 62.5, respectively, due to their elevated content of methyl oleate. Other properties are well within the ranges specified in biodiesel standards. The cloud points of both esters are slightly above 0 °C due to their content of saturated esters, especially methyl palmitate. Overall, avocado and olive oil yield methyl esters with fuel properties comparable to methyl esters from other commodity vegetable oils. The 1 H and 13 C NMR spectra of avocado and olive oil methyl esters are reported. -- Highlights: • Methyl esters of avocado and olive oil meet biodiesel fuel standards. • Provides comparison for methyl esters of other vegetable oils with high oleic content. • Discusses and compares present results with prior literature

Comparison of net global warming potential and greenhouse gas intensity affected by management practices in two dryland cropping sites

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Little is known about the effect of management practices on net global warming potential (GWP) and greenhouse gas intensity (GHGI) that account for all sources and sinks of greenhouse gas (GHG) emissions in dryland cropping systems. The objective of this study was to compare the effect of a combinat...

Prognostic DNA Methylation Markers for Prostate Cancer

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Siri H. Strand

2014-09-01

Full Text Available Prostate cancer (PC is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181 and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC.

Epigenetics in Alzheimer's Disease: Perspective of DNA Methylation.

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Qazi, Talal Jamil; Quan, Zhenzhen; Mir, Asif; Qing, Hong

2018-02-01

Research over the years has shown that causes of Alzheimer's disease are not well understood, but over the past years, the involvement of epigenetic mechanisms in the developing memory formation either under pathological or physiological conditions has become clear. The term epigenetics represents the heredity of changes in phenotype that are independent of altered DNA sequences. Different studies validated that cytosine methylation of genomic DNA decreases with age in different tissues of mammals, and therefore, the role of epigenetic factors in developing neurological disorders in aging has been under focus. In this review, we summarized and reviewed the involvement of different epigenetic mechanisms especially the DNA methylation in Alzheimer's disease (AD), late-onset Alzheimer's disease (LOAD), familial Alzheimer's disease (FAD), and autosomal dominant Alzheimer's disease (ADAD). Down to the minutest of details, we tried to discuss the methylation patterns like mitochondrial DNA methylation and ribosomal DNA (rDNA) methylation. Additionally, we mentioned some therapeutic approaches related to epigenetics, which could provide a potential cure for AD. Moreover, we reviewed some recent studies that validate DNA methylation as a potential biomarker and its role in AD. We hope that this review will provide new insights into the understanding of AD pathogenesis from the epigenetic perspective especially from the perspective of DNA methylation.

Bridging the gap between protein carboxyl methylation and phospholipid methylation to understand glucose-stimulated insulin secretion from the pancreatic beta cell.

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Kowluru, Anjaneyulu

2008-01-15

Recent findings have implicated post-translational modifications at C-terminal cysteines [e.g., methylation] of specific proteins [e.g., G-proteins] in glucose-stimulated insulin secretion [GSIS]. Furthermore, methylation at the C-terminal leucine of the catalytic subunit of protein phosphatase 2A [PP2Ac] has also been shown to be relevant for GSIS. In addition to these two classes of protein methyl transferases, a novel class of glucose-activated phospholipid methyl transferases have also been identified in the beta cell. These enzymes catalyze three successive methylations of phosphatidylethanolamine to yield phosphatidylcholine. The "newly formed" phosphatidylcholine is felt to induce alterations in the membrane fluidity, which might favor vesicular fusion with the plasma membrane for the exocytosis of insulin. The objectives of this commentary are to: (i) review the existing evidence on the regulation, by glucose and other insulin secretagogues, of post-translational carboxylmethylation [CML] of specific proteins in the beta cell; (ii) discuss the experimental evidence, which implicates regulation, by glucose and other insulin secretagogues, of phosphatidylethanolamine methylation in the islet beta cell; (iii) propose a model for potential cross-talk between the protein and lipid methylation pathways in the regulation of GSIS and (iv) highlight potential avenues for future research, including the development of specific pharmacological inhibitors to further decipher regulatory roles for these methylation reactions in islet beta cell function.

Clinical Utility of promoter methylation of the tumor suppressor ...

African Journals Online (AJOL)

Aim: Aim is to examine the potential usefulness of blood based methylation specific polymerase chain reaction (MSP) of methylated DKK3 and RASSF1A genes in early detection of breast cancer. Method: Methylation status of DKK3 and RASSF1 was investigated in forty breast cancer patients, twenty fibroadenoma patients ...

Genome-Wide DNA Methylation Profiles of Phlegm-Dampness Constitution

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Haiqiang Yao

2018-03-01

Full Text Available Background/Aims: Metabolic diseases are leading health concerns in today’s global society. In traditional Chinese medicine (TCM, one body type studied is the phlegm-dampness constitution (PC, which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown. Methods: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs. Eight volunteers had PC and 4 had balanced constitutions. Results: Methylation data indicated a genome-scale hyper-methylation pattern in PC. We located 288 differentially methylated probes (DMPs. A total of 256 genes were mapped, and some of these were metabolic-related. SQSTM1, DLGAP2 and DAB1 indicated diabetes mellitus; HOXC4 and SMPD3, obesity; and GRWD1 and ATP10A, insulin resistance. According to Ingenuity Pathway Analysis (IPA, differentially methylated genes were abundant in multiple metabolic pathways. Conclusion: Our results suggest the potential risk for metabolic disorders in individuals with PC. We also explain the clinical characteristics of PC with DNA methylation features.

On the potential of models for location and scale for genome-wide DNA methylation data.

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Wahl, Simone; Fenske, Nora; Zeilinger, Sonja; Suhre, Karsten; Gieger, Christian; Waldenberger, Melanie; Grallert, Harald; Schmid, Matthias

2014-07-03

With the help of epigenome-wide association studies (EWAS), increasing knowledge on the role of epigenetic mechanisms such as DNA methylation in disease processes is obtained. In addition, EWAS aid the understanding of behavioral and environmental effects on DNA methylation. In terms of statistical analysis, specific challenges arise from the characteristics of methylation data. First, methylation β-values represent proportions with skewed and heteroscedastic distributions. Thus, traditional modeling strategies assuming a normally distributed response might not be appropriate. Second, recent evidence suggests that not only mean differences but also variability in site-specific DNA methylation associates with diseases, including cancer. The purpose of this study was to compare different modeling strategies for methylation data in terms of model performance and performance of downstream hypothesis tests. Specifically, we used the generalized additive models for location, scale and shape (GAMLSS) framework to compare beta regression with Gaussian regression on raw, binary logit and arcsine square root transformed methylation data, with and without modeling a covariate effect on the scale parameter. Using simulated and real data from a large population-based study and an independent sample of cancer patients and healthy controls, we show that beta regression does not outperform competing strategies in terms of model performance. In addition, Gaussian models for location and scale showed an improved performance as compared to models for location only. The best performance was observed for the Gaussian model on binary logit transformed β-values, referred to as M-values. Our results further suggest that models for location and scale are specifically sensitive towards violations of the distribution assumption and towards outliers in the methylation data. Therefore, a resampling procedure is proposed as a mode of inference and shown to diminish type I error rate in

Structure, function and carcinogenicity of metabolites of methylated and non-methylated polycyclic aromatic hydrocarbons: a comprehensive review.

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Flesher, James W; Lehner, Andreas F

2016-01-01

The Unified Theory of PAH Carcinogenicity accommodates the activities of methylated and non-methylated polycyclic aromatic hydrocarbons (PAHs) and states that substitution of methyl groups on meso-methyl substituted PAHs with hydroxy, acetoxy, chloride, bromide or sulfuric acid ester groups imparts potent cancer producing properties. It incorporates specific predictions from past researchers on the mechanism of carcinogenesis by methyl-substituted hydrocarbons, including (1) requirement for metabolism to an ArCH2X type structure where X is a good leaving group and (2) biological substitution of a meso-methyl group at the most reactive center in non-methylated hydrocarbons. The Theory incorporates strong inferences of Fieser: (1) The mechanism of carcinogenesis involves a specific metabolic substitution of a hydrocarbon at its most reactive center and (2) Metabolic elimination of a carcinogen is a detoxifying process competitive with that of carcinogenesis and occurring by a different mechanism. According to this outlook, chemical or biochemical substitution of a methyl group at the reactive meso-position of non-methylated hydrocarbons is the first step in the mechanism of carcinogenesis for most, if not all, PAHs and the most potent metabolites of PAHs are to be found among the meso methyl-substituted hydrocarbons. Some PAHs and their known or potential metabolites and closely related compounds have been tested in rats for production of sarcomas at the site of subcutaneous injection and the results strongly support the specific predictions of the Unified Theory.

Histone Lysine Methylation in Diabetic Nephropathy

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Guang-dong Sun

2014-01-01

Full Text Available Diabetic nephropathy (DN belongs to debilitating microvascular complications of diabetes and is the leading cause of end-stage renal diseases worldwide. Furthermore, outcomes from the DCCT/EDIC study showed that DN often persists and progresses despite intensive glucose control in many diabetes patients, possibly as a result of prior episode of hyperglycemia, which is called “metabolic memory.” The underlying mechanisms responsible for the development and progression of DN remain poorly understood. Activation of multiple signaling pathways and key transcription factors can lead to aberrant expression of DN-related pathologic genes in target renal cells. Increasing evidence suggests that epigenetic mechanisms in chromatin such as DNA methylation, histone acetylation, and methylation can influence the pathophysiology of DN and metabolic memory. Exciting researches from cell culture and experimental animals have shown that key histone methylation patterns and the related histone methyltransferases and histone demethylases can play important roles in the regulation of inflammatory and profibrotic genes in renal cells under diabetic conditions. Because histone methylation is dynamic and potentially reversible, it can provide a window of opportunity for the development of much-needed novel therapeutic potential for DN in the future. In this minireview, we discuss recent advances in the field of histone methylation and its roles in the pathogenesis and progression of DN.

Co-polymerization of methyl methacrylate and styrene via surfactant-free emulsion polymerization, as a potential material for photonic crystal application

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Kassim, Syara; Zahari, Siti Balqis; Tahrin, Rabiatul Addawiyah Azwa; Harun, Noor Aniza

2017-09-01

Photonic crystals are being the great interest of researcher to studies due to a variety of potential application for the interaction of light including the solar cells, optical sensors and paints. In order to evaluate the fabrication of photonic crystals thin film, a free-emulsifier emulsion copolymerization of styrene and methyl methacrylate was carried out. By using the self -assembly approach, this method offers the opportunity to produce crystalline polymer sphere in more ease operation, low cost and environmental friendly. The influences of the mixing ratio of monomer and amount of initiators were studied. In advance, the presence of styrene as co-monomer had improved the thermal degradation of polymer methyl methacrylate. While in changing the mixing ratio of styrene and methyl methacrylate resulted in particle size of the sphere. The size of polymer particles slightly increased on increasing volume of styrene monomer ratio. This occurred because the properties of styrene in water where it sparingly soluble and lead to coagulation of particles. This simple, yet effective method for preparing functional complex 3D structures has the potential to be used generically to fabricate a variety of functional porous 3D structures that could find application not only in new or improved photonic crystal (PC) devices but also in areas such as catalysis, solar cell, separation, fuel cells technology, microelectronics and optoelectronics.

Seeing the sink beneath the source: an improved stable isotope tracer method for measuring highly variable gross fluxes of methyl halides

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Rhew, R. C.

2011-12-01

Measuring methyl bromide (CH3Br) and methyl chloride (CH3Cl) fluxes in terrestrial ecosystems is complicated by the presence of simultaneous production (typically associated with plants and/or fungi) and consumption (typically associated with soils). Thus, specific sites within an ecosystem can act as either a net source or net sink, depending on season, soil conditions, or vegetative cover. To interpret the highly variable net fluxes found in many of these ecosystems, a stable isotope tracer technique has been developed to measure gross fluxes of CH3Br and CH3Cl. This method entails adding small amounts of 13CH3Br and 13CH3Cl to an incubation chamber, monitoring the headspace concentration changes of both 13C and 13C isotopologues, and applying a box model to simultaneously solve for gross production and consumption. Over the last decade, this technique has been successfully applied to laboratory soil incubations and field studies from a variety of ecosystems, including boreal forest, annual grasslands, shortgrass steppe, oak-savanna woodland, and Arctic tundra. These studies demonstrate that gross uptake rates are strongly affected by soil moisture within ecosystems but are on average much lower than previously estimated, and that gross production rates are highly dependent on plant species enclosed, with minor production within the soils as well. Measuring gross uptake rates is more challenging in ecosystems with large net emissions of methyl halides, such as coastal salt marshes, rice fields and certain grassland sites. Using the tallgrass prairie of Kansas as a case study, four slightly different models to calculate gross fluxes are compared. These models are largely in agreement except at sites with large emissions (i.e., sites with Amorpha shrubs), where one of the models most robustly quantifies gross consumption. This improved stable isotope tracer method is used to track the separate responses of gross production and gross consumption of methyl halides

Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles.

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Aiba, Toshiki; Saito, Toshiyuki; Hayashi, Akiko; Sato, Shinji; Yunokawa, Harunobu; Maruyama, Toru; Fujibuchi, Wataru; Kurita, Hisaka; Tohyama, Chiharu; Ohsako, Seiichiroh

2017-03-09

It has been pointed out that environmental factors or chemicals can cause diseases that are developmental in origin. To detect abnormal epigenetic alterations in DNA methylation, convenient and cost-effective methods are required for such research, in which multiple samples are processed simultaneously. We here present methylated site display (MSD), a unique technique for the preparation of DNA libraries. By combining it with amplified fragment length polymorphism (AFLP) analysis, we developed a new method, MSD-AFLP. Methylated site display libraries consist of only DNAs derived from DNA fragments that are CpG methylated at the 5' end in the original genomic DNA sample. To test the effectiveness of this method, CpG methylation levels in liver, kidney, and hippocampal tissues of mice were compared to examine if MSD-AFLP can detect subtle differences in the levels of tissue-specific differentially methylated CpGs. As a result, many CpG sites suspected to be tissue-specific differentially methylated were detected. Nucleotide sequences adjacent to these methyl-CpG sites were identified and we determined the methylation level by methylation-sensitive restriction endonuclease (MSRE)-PCR analysis to confirm the accuracy of AFLP analysis. The differences of the methylation level among tissues were almost identical among these methods. By MSD-AFLP analysis, we detected many CpGs showing less than 5% statistically significant tissue-specific difference and less than 10% degree of variability. Additionally, MSD-AFLP analysis could be used to identify CpG methylation sites in other organisms including humans. MSD-AFLP analysis can potentially be used to measure slight changes in CpG methylation level. Regarding the remarkable precision, sensitivity, and throughput of MSD-AFLP analysis studies, this method will be advantageous in a variety of epigenetics-based research.

Horizontal ichthyoplankton tow-net system with unobstructed net opening

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Nester, Robert T.

1987-01-01

The larval fish sampler described here consists of a modified bridle, frame, and net system with an obstruction-free net opening and is small enough for use on boats 10 m or less in length. The tow net features a square net frame attached to a 0.5-m-diameter cylinder-on-cone plankton net with a bridle designed to eliminate all obstructions forward of the net opening, significantly reducing currents and vibrations in the water directly preceding the net. This system was effective in collecting larvae representing more than 25 species of fish at sampling depths ranging from surface to 10 m and could easily be used at greater depths.

Relationship between methylation status of vitamin D-related genes, vitamin D levels, and methyl-donor biochemistry

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Emma Louise Beckett

2016-12-01

Full Text Available Vitamin D is known for its role in the regulation of gene expression via the vitamin D receptor, a nuclear transcription factor. More recently, a role for vitamin D in regulating DNA methylation has been identified as an additional mechanism of modulation of gene expression. How methylation status influences vitamin D metabolism and response pathways is not yet clear. Therefore, we aimed to assess the relationship between plasma 25-hydroxycholecalciferol (25(OHD and the methylation status of vitamin D metabolism enzyme genes (CYP2R1, CYP27B1 and CYP24A1 and the vitamin D receptor gene (VDR. This analysis was conducted in the context of dietary vitamin D, and background methyl donor related biochemistry, with adjustment for several dietary and lifestyle variables. Percentage methylation at CpG sites was assessed in peripheral blood cells using methylation sensitive and dependent enzymes and qPCR. Standard analytical techniques were used to determine plasma 25(OHD and homocysteine, and serum folate and B12, with the relationship to methylation status assessed using multi-variable regression analysis. CYP2R1 and VDR methylation were found to be independent predictors of plasma 25(OHD, when adjusted for vitamin D intake and other lifestyle variables. CYP24A1 was related to plasma 25(OHD directly, but not in the context of vitamin D intake. Methyl-group donor biochemistry was associated with the methylation status of some genes, but did not alter the relationship between methylation and plasma 25(OHD. Modulation of methylation status of CYP2R1, CYP24A1 and VDR in response to plasma 25(OHD may be part of feedback loops involved in maintaining vitamin D homeostasis, and may explain a portion of the variance in plasma 25(OHD levels in response to intake and sun exposure. Methyl-group donor biochemistry, while a potential independent modulator, did not alter this effect.

Methylation screening of the TGFBI promoter in human lung and prostate cancer by methylation-specific PCR

International Nuclear Information System (INIS)

Shah, Jinesh N; Shao, Genze; Hei, Tom K; Zhao, Yongliang

2008-01-01

Hypermethylation of the TGFBI promoter has been shown to correlate with decreased expression of this gene in human tumor cell lines. In this study, we optimized a methylation-specific polymerase chain reaction (MSP) method and investigated the methylation status of the TGFBI promoter in human lung and prostate cancer specimens. Methylation-specific primers were designed based on the methylation profiles of the TGFBI promoter in human tumor cell lines, and MSP conditions were optimized for accurate and efficient amplification. Genomic DNA was isolated from lung tumors and prostatectomy tissues of prostate cancer patients, bisulfite-converted, and analyzed by MSP. Among 50 lung cancer samples, 44.0% (22/50) harbored methylated CpG sites in the TGFBI promoter. An analysis correlating gene methylation status with clinicopathological cancer features revealed that dense methylation of the TGFBI promoter was associated with a metastatic phenotype, with 42.9% (6/14) of metastatic lung cancer samples demonstrating dense methylation vs. only 5.6% (2/36) of primary lung cancer samples (p < 0.05). Similar to these lung cancer results, 82.0% (41/50) of prostate cancer samples harbored methylated CpG sites in the TGFBI promoter, and dense methylation of the promoter was present in 38.9% (7/18) of prostate cancer samples with the feature of locoregional invasiveness vs. only 19.4% (6/31) of prostate cancer samples without locoregional invasiveness (p < 0.05). Furthermore, promoter hypermethylation correlated with highly reduced expression of the TGFBI gene in human lung and prostate tumor cell lines. We successfully optimized a MSP method for the precise and efficient screening of TGFBI promoter methylation status. Dense methylation of the TGFBI promoter correlated with the extent of TGFBI gene silencing in tumor cell lines and was related to invasiveness of prostate tumors and metastatic status of lung cancer tumors. Thus, TGFBI promoter methylation can be used as a potential

MOURA magnetometer for Mars MetNet Precursor Mission. Its potential for an in situ magnetic environment and surface characterization

Energy Technology Data Exchange (ETDEWEB)

Diaz Michelena, M.; Sanz, R.; Fernandez, A.B.; Manuel, V. de; Cerdan, M.F.; Apestigue, V.; Arruego, I.; Azcue, J.; Dominguez, J.A.; Gonzalez, M.; Guerrero, H.; Sabau, M.; Kilian, R.; Baeza, O.; Ros, F.; Vazquez, M.; Tordesillas, J.M.; Covisa, P.; Aguado, J.

2016-07-01

MOURA magnetometer and gradiometer is part of the scientific instrumentation for Mars MetNet Precursor mission. This work describes the objective of the investigation, summarizes the work done in the design and development of the sensor as well as its calibration, and shows the demonstration campaigns to show the potential of such instrument for planetary landers and rovers. (Author)

Higher-moment measurements of net-kaon, net-charge and net-proton multiplicity distributions at STAR

International Nuclear Information System (INIS)

Sarkar, Amal

2014-01-01

In this paper, we report the measurements of the various moments, such as mean, standard deviation (σ), skewness (S) and kurtosis (κ) of the net-kaon, net-charge and net-proton multiplicity distributions at mid-rapidity in Au + Au collisions from √(s NN )=7.7 to 200 GeV with the STAR experiment at RHIC. This work has been done with the aim to locate the critical point on the QCD phase diagram. These moments and their products are related to the thermodynamic susceptibilities of conserved quantities such as net baryon number, net charge, and net strangeness as well as to the correlation length of the system which diverges in an ideal infinite thermodynamic system at the critical point. For a finite system, existing for a finite time, a non-monotonic behavior of these variables would indicate the presence of the critical point. Furthermore, we also present the moment products Sσ, κσ 2 of net-kaon, net-charge and net-proton multiplicity distributions as a function of collision centrality and energy. The energy and the centrality dependence of higher moments and their products have been compared with different models

Anti-N-Methyl-D-aspartate Receptor Encephalitis: A Severe, Potentially Reversible Autoimmune Encephalitis

Science.gov (United States)

Liu, Cai-yun; Zheng, Xiang-Yu; Ma, Chi

2017-01-01

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is potentially lethal, but it is also a treatable autoimmune disorder characterized by prominent psychiatric and neurologic symptoms. It is often accompanied with teratoma or other neoplasm, especially in female patients. Anti-NMDAR antibodies in cerebrospinal fluid (CSF) and serum are characteristic features of the disease, thereby suggesting a pathogenic role in the disease. Here, we summarize recent studies that have clearly documented that both clinical manifestations and the antibodies may contribute to early diagnosis and multidisciplinary care. The clinical course of the disorder is reversible and the relapse could occur in some patients. Anti-NMDAR encephalitis coexisting with demyelinating disorders makes the diagnosis more complex; thus, clinicians should be aware of the overlapping diseases. PMID:28698711

DNA methylation-based variation between human populations.

Science.gov (United States)

Kader, Farzeen; Ghai, Meenu

2017-02-01

Several studies have proved that DNA methylation affects regulation of gene expression and development. Epigenome-wide studies have reported variation in methylation patterns between populations, including Caucasians, non-Caucasians (Blacks), Hispanics, Arabs, and numerous populations of the African continent. Not only has DNA methylation differences shown to impact externally visible characteristics, but is also a potential biomarker for underlying racial health disparities between human populations. Ethnicity-related methylation differences set their mark during early embryonic development. Genetic variations, such as single-nucleotide polymorphisms and environmental factors, such as age, dietary folate, socioeconomic status, and smoking, impacts DNA methylation levels, which reciprocally impacts expression of phenotypes. Studies show that it is necessary to address these external influences when attempting to differentiate between populations since the relative impacts of these factors on the human methylome remain uncertain. The present review summarises several reported attempts to establish the contribution of differential DNA methylation to natural human variation, and shows that DNA methylation could represent new opportunities for risk stratification and prevention of several diseases amongst populations world-wide. Variation of methylation patterns between human populations is an exciting prospect which inspires further valuable research to apply the concept in routine medical and forensic casework. However, trans-generational inheritance needs to be quantified to decipher the proportion of variation contributed by DNA methylation. The future holds thorough evaluation of the epigenome to understand quantification, heritability, and the effect of DNA methylation on phenotypes. In addition, methylation profiling of the same ethnic groups across geographical locations will shed light on conserved methylation differences in populations.

CpG Methylation Analysis—Current Status of Clinical Assays and Potential Applications in Molecular Diagnostics

Science.gov (United States)

Sepulveda, Antonia R.; Jones, Dan; Ogino, Shuji; Samowitz, Wade; Gulley, Margaret L.; Edwards, Robin; Levenson, Victor; Pratt, Victoria M.; Yang, Bin; Nafa, Khedoudja; Yan, Liying; Vitazka, Patrick

2009-01-01

Methylation of CpG islands in gene promoter regions is a major molecular mechanism of gene silencing and underlies both cancer development and progression. In molecular oncology, testing for the CpG methylation of tissue DNA has emerged as a clinically useful tool for tumor detection, outcome prediction, and treatment selection, as well as for assessing the efficacy of treatment with the use of demethylating agents and monitoring for tumor recurrence. In addition, because CpG methylation occurs early in pre-neoplastic tissues, methylation tests may be useful as markers of cancer risk in patients with either infectious or inflammatory conditions. The Methylation Working Group of the Clinical Practice Committee of the Association of Molecular Pathology has reviewed the current state of clinical testing in this area. We report here our summary of both the advantages and disadvantages of various methods, as well as the needs for standardization and reporting. We then conclude by summarizing the most promising areas for future clinical testing in cancer molecular diagnostics. PMID:19541921

Net Neutrality: Media Discourses and Public Perception

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Christine Quail

2010-01-01

Full Text Available This paper analyzes media and public discourses surrounding net neutrality, with particular attention to public utility philosophy, from a critical perspective. The article suggests that further public education about net neutrality would be beneficial. The first portion of this paper provides a survey of the existing literature surrounding net neutrality, highlighting the contentious debate between market-based and public interest perspectives. In order to contextualize the debate, an overview of public utility philosophy is provided, shedding light on how the Internet can be conceptualized as a public good. Following this discussion, an analysis of mainstream media is presented, exploring how the media represents the issue of net neutrality and whether or not the Internet is discussed through the lens of public utility. To further examine how the net neutrality debate is being addressed, and to see the potential impacts of media discourses on the general public, the results of a focus group are reported and analyzed. Finally, a discussion assesses the implications of the net neutrality debate as presented through media discourses, highlighting the future of net neutrality as an important policy issue.

Identification of Differentially Methylated Sites with Weak Methylation Effects

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Hong Tran

2018-02-01

Full Text Available Deoxyribonucleic acid (DNA methylation is an epigenetic alteration crucial for regulating stress responses. Identifying large-scale DNA methylation at single nucleotide resolution is made possible by whole genome bisulfite sequencing. An essential task following the generation of bisulfite sequencing data is to detect differentially methylated cytosines (DMCs among treatments. Most statistical methods for DMC detection do not consider the dependency of methylation patterns across the genome, thus possibly inflating type I error. Furthermore, small sample sizes and weak methylation effects among different phenotype categories make it difficult for these statistical methods to accurately detect DMCs. To address these issues, the wavelet-based functional mixed model (WFMM was introduced to detect DMCs. To further examine the performance of WFMM in detecting weak differential methylation events, we used both simulated and empirical data and compare WFMM performance to a popular DMC detection tool methylKit. Analyses of simulated data that replicated the effects of the herbicide glyphosate on DNA methylation in Arabidopsis thaliana show that WFMM results in higher sensitivity and specificity in detecting DMCs compared to methylKit, especially when the methylation differences among phenotype groups are small. Moreover, the performance of WFMM is robust with respect to small sample sizes, making it particularly attractive considering the current high costs of bisulfite sequencing. Analysis of empirical Arabidopsis thaliana data under varying glyphosate dosages, and the analysis of monozygotic (MZ twins who have different pain sensitivities—both datasets have weak methylation effects of <1%—show that WFMM can identify more relevant DMCs related to the phenotype of interest than methylKit. Differentially methylated regions (DMRs are genomic regions with different DNA methylation status across biological samples. DMRs and DMCs are essentially the same

Forensic DNA methylation profiling from evidence material for investigative leads

Science.gov (United States)

Lee, Hwan Young; Lee, Soong Deok; Shin, Kyoung-Jin

2016-01-01

DNA methylation is emerging as an attractive marker providing investigative leads to solve crimes in forensic genetics. The identification of body fluids that utilizes tissue-specific DNA methylation can contribute to solving crimes by predicting activity related to the evidence material. The age estimation based on DNA methylation is expected to reduce the number of potential suspects, when the DNA profile from the evidence does not match with any known person, including those stored in the forensic database. Moreover, the variation in DNA implicates environmental exposure, such as cigarette smoking and alcohol consumption, thereby suggesting the possibility to be used as a marker for predicting the lifestyle of potential suspect. In this review, we describe recent advances in our understanding of DNA methylation variations and the utility of DNA methylation as a forensic marker for advanced investigative leads from evidence materials. [BMB Reports 2016; 49(7): 359-369] PMID:27099236

Automated sequence- and stereo-specific assignment of methyl-labeled proteins by paramagnetic relaxation and methyl–methyl nuclear overhauser enhancement spectroscopy

International Nuclear Information System (INIS)

Venditti, Vincenzo; Fawzi, Nicolas L.; Clore, G. Marius

2011-01-01

Methyl-transverse relaxation optimized spectroscopy is rapidly becoming the preferred NMR technique for probing structure and dynamics of very large proteins up to ∼1 MDa in molecular size. Data interpretation, however, necessitates assignment of methyl groups which still presents a very challenging and time-consuming process. Here we demonstrate that, in combination with a known 3D structure, paramagnetic relaxation enhancement (PRE), induced by nitroxide spin-labels incorporated at only a few surface-exposed engineered cysteines, provides fast, straightforward and robust access to methyl group resonance assignments, including stereoassignments for the methyl groups of leucine and valine. Neither prior assignments, including backbone assignments, for the protein, nor experiments that transfer magnetization between methyl groups and the protein backbone, are required. PRE-derived assignments are refined by 4D methyl–methyl nuclear Overhauser enhancement data, eliminating ambiguities and errors that may arise due to the high sensitivity of PREs to the potential presence of sparsely-populated transient states.

Propagation characteristic of THz wave in camouflage net material

Science.gov (United States)

Dong, Hailong; Wang, Jiachun; Chen, Zongsheng; Lin, Zhidan; Zhao, Dapeng; Liu, Ruihuang

2017-10-01

Terahertz (THz) radar system, with excellent potentials such as high-resolution and strong penetration capability, is promising in the field of anti-camouflage. Camouflage net is processed by cutting the camouflage net material, which is fabricated on pre-processing substrate by depositing coatings with camouflage abilities in different bands, such as visible, infrared and radar. In this paper, we concentrate on the propagation characteristic of THz wave in camouflage net material. Firstly, function and structure of camouflage net were analyzed. Then the advantage and appliance of terahertz time-domain spectroscopy (THz-TDS) was introduced. And the relevant experiments were conducted by utilizing THz-TDS. The results obtained indicate that THz wave has better penetration capacity in camouflage net material, which demonstrates the feasibility of using THz radar to detect those targets covered with camouflage net.

Dynamics and design of space nets for orbital capture

CERN Document Server

Yang, Leping; Zhen, Ming; Liu, Haitao

2017-01-01

This book covers the topics of theoretical principles, dynamics model and algorithm, mission analysis, system design and experimental studies of space nets system, aiming to provide an initial framework in this field and serve as a ready reference for those interested. Space nets system represents a forefront field in future development of aerospace technologies. However, it involves new challenges and problems such as nonlinear and distorted nets structure, complex rigid flexible coupling dynamics, orbital transfer of space flexible composite and dynamics control. Currently, no comprehensive books on space nets dynamics and design are available, so potential readers can get to know the working mechanism, dynamics elements, and mission design of the space nets system from a Chinese perspective.

Whole-genome methylation caller designed for methyl- DNA ...

African Journals Online (AJOL)

etchie

2013-02-20

Feb 20, 2013 ... Our method uses a single-CpG-resolution, whole-genome methylation ... Key words: Methyl-DNA immunoprecipitation, next-generation sequencing, ...... methylation is prevalent in embryonic stem cells andmaybe mediated.

Net alkalinity and net acidity 2: Practical considerations

Science.gov (United States)

Kirby, C.S.; Cravotta, C.A.

2005-01-01

The pH, alkalinity, and acidity of mine drainage and associated waters can be misinterpreted because of the chemical instability of samples and possible misunderstandings of standard analytical method results. Synthetic and field samples of mine drainage having various initial pH values and concentrations of dissolved metals and alkalinity were titrated by several methods, and the results were compared to alkalinity and acidity calculated based on dissolved solutes. The pH, alkalinity, and acidity were compared between fresh, unoxidized and aged, oxidized samples. Data for Pennsylvania coal mine drainage indicates that the pH of fresh samples was predominantly acidic (pH 2.5-4) or near neutral (pH 6-7); ??? 25% of the samples had pH values between 5 and 6. Following oxidation, no samples had pH values between 5 and 6. The Standard Method Alkalinity titration is constrained to yield values >0. Most calculated and measured alkalinities for samples with positive alkalinities were in close agreement. However, for low-pH samples, the calculated alkalinity can be negative due to negative contributions by dissolved metals that may oxidize and hydrolyze. The Standard Method hot peroxide treatment titration for acidity determination (Hot Acidity) accurately indicates the potential for pH to decrease to acidic values after complete degassing of CO2 and oxidation of Fe and Mn, and it indicates either the excess alkalinity or that required for neutralization of the sample. The Hot Acidity directly measures net acidity (= -net alkalinity). Samples that had near-neutral pH after oxidation had negative Hot Acidity; samples that had pH mine drainage treatment can lead to systems with insufficient Alkalinity to neutralize metal and H+ acidity and is not recommended. The use of net alkalinity = -Hot Acidity titration is recommended for the planning of mine drainage treatment. The use of net alkalinity = (Alkalinitymeasured - Aciditycalculated) is recommended with some cautions

DNA Methylation Biomarkers: Cancer and Beyond

Directory of Open Access Journals (Sweden)

Thomas Mikeska

2014-09-01

Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

Analysis of RET promoter CpG island methylation using methylation-specific PCR (MSP), pyrosequencing, and methylation-sensitive high-resolution melting (MS-HRM): impact on stage II colon cancer patient outcome.

Science.gov (United States)

Draht, Muriel X G; Smits, Kim M; Jooste, Valérie; Tournier, Benjamin; Vervoort, Martijn; Ramaekers, Chantal; Chapusot, Caroline; Weijenberg, Matty P; van Engeland, Manon; Melotte, Veerle

2016-01-01

Already since the 1990s, promoter CpG island methylation markers have been considered promising diagnostic, prognostic, and predictive cancer biomarkers. However, so far, only a limited number of DNA methylation markers have been introduced into clinical practice. One reason why the vast majority of methylation markers do not translate into clinical applications is lack of independent validation of methylation markers, often caused by differences in methylation analysis techniques. We recently described RET promoter CpG island methylation as a potential prognostic marker in stage II colorectal cancer (CRC) patients of two independent series. In the current study, we analyzed the RET promoter CpG island methylation of 241 stage II colon cancer patients by direct methylation-specific PCR (MSP), nested-MSP, pyrosequencing, and methylation-sensitive high-resolution melting (MS-HRM). All primers were designed as close as possible to the same genomic region. In order to investigate the effect of different DNA methylation assays on patient outcome, we assessed the clinical sensitivity and specificity as well as the association of RET methylation with overall survival for three and five years of follow-up. Using direct-MSP and nested-MSP, 12.0 % (25/209) and 29.6 % (71/240) of the patients showed RET promoter CpG island methylation. Methylation frequencies detected by pyrosequencing were related to the threshold for positivity that defined RET methylation. Methylation frequencies obtained by pyrosequencing (threshold for positivity at 20 %) and MS-HRM were 13.3 % (32/240) and 13.8 % (33/239), respectively. The pyrosequencing threshold for positivity of 20 % showed the best correlation with MS-HRM and direct-MSP results. Nested-MSP detected RET promoter CpG island methylation in deceased patients with a higher sensitivity (33.1 %) compared to direct-MSP (10.7 %), pyrosequencing (14.4 %), and MS-HRM (15.4 %). While RET methylation frequencies detected by nested

Identification of endometrial cancer methylation features using combined methylation analysis methods.

Directory of Open Access Journals (Sweden)

Michael P Trimarchi

Full Text Available DNA methylation is a stable epigenetic mark that is frequently altered in tumors. DNA methylation features are attractive biomarkers for disease states given the stability of DNA methylation in living cells and in biologic specimens typically available for analysis. Widespread accumulation of methylation in regulatory elements in some cancers (specifically the CpG island methylator phenotype, CIMP can play an important role in tumorigenesis. High resolution assessment of CIMP for the entire genome, however, remains cost prohibitive and requires quantities of DNA not available for many tissue samples of interest. Genome-wide scans of methylation have been undertaken for large numbers of tumors, and higher resolution analyses for a limited number of cancer specimens. Methods for analyzing such large datasets and integrating findings from different studies continue to evolve. An approach for comparison of findings from a genome-wide assessment of the methylated component of tumor DNA and more widely applied methylation scans was developed.Methylomes for 76 primary endometrial cancer and 12 normal endometrial samples were generated using methylated fragment capture and second generation sequencing, MethylCap-seq. Publically available Infinium HumanMethylation 450 data from The Cancer Genome Atlas (TCGA were compared to MethylCap-seq data.Analysis of methylation in promoter CpG islands (CGIs identified a subset of tumors with a methylator phenotype. We used a two-stage approach to develop a 13-region methylation signature associated with a "hypermethylator state." High level methylation for the 13-region methylation signatures was associated with mismatch repair deficiency, high mutation rate, and low somatic copy number alteration in the TCGA test set. In addition, the signature devised showed good agreement with previously described methylation clusters devised by TCGA.We identified a methylation signature for a "hypermethylator phenotype" in

Implications of bio-efficacy and persistence of insecticides when indoor residual spraying and long-lasting insecticide nets are combined for malaria prevention.

Science.gov (United States)

Okumu, Fredros O; Chipwaza, Beatrice; Madumla, Edith P; Mbeyela, Edgar; Lingamba, Geoffrey; Moore, Jason; Ntamatungro, Alex J; Kavishe, Deo R; Moore, Sarah J

2012-11-19

Bio-efficacy and residual activity of insecticides used for indoor residual spraying (IRS) and long-lasting insecticide nets (LLINs) were assessed against laboratory-reared and wild populations of the malaria vector, Anopheles arabiensis in south eastern Tanzania. Implications of the findings are examined in the context of potential synergies and redundancies where IRS and LLINs are combined. Bioassays were conducted monthly for six months on three LLIN types (Olyset® PermaNet 2.0®,and Icon Life®) and three IRS treatments (2 g/m2 pirimiphos-methyl, 2 g/m2 DDT and 0.03 g/m2 lambda-cyhalothrin, sprayed on mud walls and palm ceilings of experimental huts). Tests used susceptible laboratory-reared An. arabiensis exposed in cones (nets and IRS) or wire balls (nets only). Susceptibility of wild populations was assessed using WHO diagnostic concentrations and PCR for knock-down resistance (kdr) genes. IRS treatments killed ≥ 85% of mosquitoes exposed on palm ceilings and ≥ 90% of those exposed on mud walls, but up to 50% of this toxicity decayed within 1-3 months, except for DDT. By 6th month, only 7.5%, 42.5% and 30.0% of mosquitoes died when exposed to ceilings sprayed with pirimiphos-methyl, DDT or lambda-cyhalothrin respectively, while 12.5%, 36.0% and 27.5% died after exposure to mud walls sprayed with the same insecticides. In wire-ball assays, mortality decreased from 98.1% in 1st month to 92.6% in 6th month in tests on PermaNet 2.0®, from 100% to 61.1% on Icon Life® and from 93.2% to 33.3% on Olyset® nets. In cone bioassays, mortality reduced from 92.8% in 1st month to 83.3% in 6th month on PermaNet 2.0®, from 96.9% to 43.80% on Icon Life® and from 85.6% to 14.6% on Olyset®. Wild An. arabiensis were 100% susceptible to DDT, 95.8% to deltamethrin, 90.2% to lambda cyhalothrin and 95.2% susceptible to permethrin. No kdr gene mutations were detected. In bioassays where sufficient contact with treated surfaces is assured, LLINs and IRS kill high

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models

Science.gov (United States)

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com.

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

Science.gov (United States)

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

Methodological considerations regarding the use of inorganic 197Hg(II) radiotracer to assess mercury methylation potential rates in lake sediment

International Nuclear Information System (INIS)

Perez Catan, Soledad; Guevara, Sergio Ribeiro; Marvin-DiPasquale, Mark; Magnavacca, Cecilia; Cohen, Isaac Marcos; Arribere, Maria

2007-01-01

Methodological considerations on the determination of benthic methyl-mercury (CH 3 Hg) production potentials were investigated on lake sediment, using 197 Hg radiotracer. Three methods to arrest bacterial activity were compared: flash freezing, thermal sterilization, and γ-irradiation. Flash freezing showed similar CH 3 Hg recoveries as thermal sterilization, which was both 50% higher than the recoveries obtained with γ-ray irradiation. No additional radiolabel was recovered in kill-control samples after an additional 24 or 65 h of incubation, suggesting that all treatments were effective at arresting Hg(II)-methylating bacterial activity, and that the initial recoveries are likely due to non-methylated 197 Hg(II) carry-over in the organic extraction and/or [ 197 Hg]CH 3 Hg produced via abiotic reactions. Two CH 3 Hg extraction methods from sediment were compared: (a) direct extraction into toluene after sediment leaching with CuSO 4 and HCl and (b) the same extraction with an additional back-extraction step to thiosulphate. Similar information was obtained with both methods, but the low efficiency observed and the extra work associated with the back-extraction procedure represent significant disadvantages, even tough the direct extraction involves higher Hg(II) carry over

Petri Nets

Indian Academy of Sciences (India)

In a computer system, for example, typical discrete events ... This project brought out a series of influential reports on Petri net theory in the mid and late ... Technology became a leading centre for Petri net research and from then on, Petri nets ...

Standardization of radiochemical techniques aiming the study of Hg volatilization and methylation in water and sediment of gold mining areas in the Amazon region

International Nuclear Information System (INIS)

Guimaraes, Jean Remy Davee

1992-09-01

Methylation of inorganic Hg in aquatic systems is a key process in the environmental cycling of this metal, not yet studied in tropical conditions. Radiochemical techniques were adapted and simplified, aiming at the study of Hg volatilization and methylation in water and sediment of gold mining areas in the Amazon region. Preliminary experiments showed, in 35 days volatilization of up to 32 % of 203 Hg 2+ added to aqueous solutions. Acid K 2 Cr 2 0 7 0.1 M solutions were not effective in 203 Hg 0 trapping and the latter was highly and irreversibly absorbed by a variety of synthetic materials commonly used in laboratory work. Considerably simplified versions of the Furutani and Rudd (1980) radiochemical technique for the determination of methylation rates in environmental samples were developed and showed efficiencies close to 90 % in tests with methyl- 2 0 3 H g standards. In-situ incubations of surface sediments were performed in the Madeira River gold mining region, Rondonia State, Brazil, and potential net Hg methylation rates (MR) of up to 1 %.g-1.h-1 were found in black-water affluent like the Mutum-Parana and Jamari rivers and in the Samuel reservoir. MRs in the Madeira River sediments were lower, ranging 10-5 to 10-3 %.g-1.h-1 . MRs obtained in incubations of samples some weeks after collection were one or two orders of magnitude lower than those resulting from in-situ incubations. Methylation in autoclaved samples was close to minimum detectable rates. MRs in surface water samples was in all cases < 7.10-7 %.ml-1.h-1. The determination of the predominant methylation sites will allow a better standardization of the technique described herein, suitable for MR determinations even under the unfavorable conditions prevailing in the Amazon region. (author)

Genetic and DNA methylation changes in cotton (Gossypium genotypes and tissues.

Directory of Open Access Journals (Sweden)

Kenji Osabe

Full Text Available In plants, epigenetic regulation is important in normal development and in modulating some agronomic traits. The potential contribution of DNA methylation mediated gene regulation to phenotypic diversity and development in cotton was investigated between cotton genotypes and various tissues. DNA methylation diversity, genetic diversity, and changes in methylation context were investigated using methylation-sensitive amplified polymorphism (MSAP assays including a methylation insensitive enzyme (BsiSI, and the total DNA methylation level was measured by high-performance liquid chromatography (HPLC. DNA methylation diversity was greater than the genetic diversity in the selected cotton genotypes and significantly different levels of DNA methylation were identified between tissues, including fibre. The higher DNA methylation diversity (CHG methylation being more diverse than CG methylation in cotton genotypes suggest epigenetic regulation may be important for cotton, and the change in DNA methylation between fibre and other tissues hints that some genes may be epigenetically regulated for fibre development. The novel approach using BsiSI allowed direct comparison between genetic and epigenetic diversity, and also measured CC methylation level that cannot be detected by conventional MSAP.

Genetic and DNA methylation changes in cotton (Gossypium) genotypes and tissues.

Science.gov (United States)

Osabe, Kenji; Clement, Jenny D; Bedon, Frank; Pettolino, Filomena A; Ziolkowski, Lisa; Llewellyn, Danny J; Finnegan, E Jean; Wilson, Iain W

2014-01-01

In plants, epigenetic regulation is important in normal development and in modulating some agronomic traits. The potential contribution of DNA methylation mediated gene regulation to phenotypic diversity and development in cotton was investigated between cotton genotypes and various tissues. DNA methylation diversity, genetic diversity, and changes in methylation context were investigated using methylation-sensitive amplified polymorphism (MSAP) assays including a methylation insensitive enzyme (BsiSI), and the total DNA methylation level was measured by high-performance liquid chromatography (HPLC). DNA methylation diversity was greater than the genetic diversity in the selected cotton genotypes and significantly different levels of DNA methylation were identified between tissues, including fibre. The higher DNA methylation diversity (CHG methylation being more diverse than CG methylation) in cotton genotypes suggest epigenetic regulation may be important for cotton, and the change in DNA methylation between fibre and other tissues hints that some genes may be epigenetically regulated for fibre development. The novel approach using BsiSI allowed direct comparison between genetic and epigenetic diversity, and also measured CC methylation level that cannot be detected by conventional MSAP.

Methylation of food commodities during fumigation with methyl bromide

International Nuclear Information System (INIS)

Starratt, A.N.; Bond, E.J.

1990-01-01

Sites of methylation in several commodities (wheat, oatmeal, peanuts, almonds, apples, oranges, maize, alfalfa and potatoes) during fumigation with 14 C-methyl bromide were studied. Differences were observed in levels of the major volatiles: methanol, dimethyl sulphide and methyl mercaptan, products of O- and S-methylation, resulting from treatment of the fumigated materials with 1N sodium hydroxide. In studies of maize and wheat, histidine was the amino acid which underwent the highest level of N-methylation. (author). 24 refs, 3 tabs

Modeling of Biometric Identification System Using the Colored Petri Nets

Science.gov (United States)

Petrosyan, G. R.; Ter-Vardanyan, L. A.; Gaboutchian, A. V.

2015-05-01

In this paper we present a model of biometric identification system transformed into Petri Nets. Petri Nets, as a graphical and mathematical tool, provide a uniform environment for modelling, formal analysis, and design of discrete event systems. The main objective of this paper is to introduce the fundamental concepts of Petri Nets to the researchers and practitioners, both from identification systems, who are involved in the work in the areas of modelling and analysis of biometric identification types of systems, as well as those who may potentially be involved in these areas. In addition, the paper introduces high-level Petri Nets, as Colored Petri Nets (CPN). In this paper the model of Colored Petri Net describes the identification process much simpler.

DNA Methylation: An Epigenetic Risk Factor in Preterm Birth

Science.gov (United States)

Menon, Ramkumar; Conneely, Karen N.; Smith, Alicia K.

2012-01-01

Spontaneous preterm birth (PTB; birth prior to 37 weeks of gestation) is a complex phenotype with multiple risk factors that complicate our understanding of its etiology. A number of recent studies have supported the hypothesis that epigenetic modifications such as DNA methylation induced by pregnancy-related risk factors may influence the risk of PTB or result in changes that predispose a neonate to adult-onset diseases. The critical role of timing of gene expression in the etiology of PTB makes it a highly relevant disorder in which to examine the potential role of epigenetic changes. Because changes in DNA methylation patterns can result in long-term consequences, it is of critical interest to identify the epigenetic patterns associated with adverse pregnancy outcomes. This review examines the potential role of DNA methylation as a risk factor for PTB and discusses several issues and limitations that should be considered when planning DNA methylation studies. PMID:22228737

The potential of net zero energy buildings (NZEBs) concept at design stage for healthcare buildings towards sustainable development

Science.gov (United States)

Hazli Abdellah, Roy; Asrul Nasid Masrom, Md; Chen, Goh Kai; Mohamed, Sulzakimin; Omar, Roshartini

2017-11-01

The focus on net-zero energy buildings (NZEBs) has been widely analysed and discussed particularly when European Union Parliament are progressively moving towards regulation that promotes the improvement of energy efficiency (EE). Additionally, it also to reduce energy consumption through the recast of the EU Directive on Energy Performance of Buildings (EPBD) in which all new buildings to be “nearly Zero-Energy” Buildings by 2020. Broadly, there is a growing trend to explore the feasibility of net zero energy in healthcare sector as the level energy consumption for healthcare sector is found significantly high. Besides that, healthcare buildings energy consumption also exceeds of many other nondomestic building types, and this shortcoming is still undetermined yet especially for developing countries. This paper aims to review the potential of NZEBs in healthcare buildings by considering its concept in design features. Data are gathered through a comprehensive energy management literature review from previous studies. The review is vital to encourage construction players to increase their awareness, practices, and implementation of NZEBs in healthcare buildings. It suggests that NZEBs concept has a potential to be adapted in healthcare buildings through emphasizing of passive approach as well as the utilization of energy efficiency systems and renewable energy systems in buildings. This paper will provide a basis knowledge for construction key players mainly architects to promote NZEBs concept at design stage for healthcare buildings development.

A global meta-analysis on the impact of management practices on net global warming potential and greenhouse gas intensity from cropland soils

Science.gov (United States)

Agricultural practices contribute significant amount of greenhouse gas (GHG) emissions, but little is known about their effects on net global warming potential (GWP) and greenhouse gas intensity (GHGI) that account for all sources and sinks of carbon dioxide emissions per unit area or crop yield. Se...

Effects of soil type, moisture content, redox potential and methyl bromide fumigation on Kd values of radio-selenium in soil

International Nuclear Information System (INIS)

Ashworth, D.J.; Moore, J.; Shaw, G.

2008-01-01

Understanding the processes that determine the solid-liquid partitioning (K d value) of Se is of fundamental importance in assessing the risk associated with the disposal of radio-selenium-containing waste. Using a mini-column (rather than batch) approach, K d values for 75 Se were determined over time in relation to soil moisture content (field capacity or saturated), redox potential and methyl bromide fumigation (used to disrupt the soil microbial population) in three contrasting soil types: clay loam, organic and sandy loam. The K d values were generally in the range 50-500 L kg -1 , with mean soil K d increasing with increasing organic matter content. Saturation with water lowered the measured redox potentials in the soils. However, only in the sandy loam soil did redox potential become negative, and this led to an increase in 75 Se K d value in this soil. Comparison of the data with the Eh-pH stability diagram for Se suggested that such strong reduction may have been consistent with the formation of the insoluble Se species, selenide. These findings, coupled with the fact that methyl bromide fumigation had no discernible effect on 75 Se K d value in the sandy loam soil, suggest that geochemical, rather than microbial, processes controlled 75 Se partitioning. The inter-relations between soil moisture content, redox potential and Se speciation should be considered in the modelling and assessment of radioactive Se fate and transport in the environment

Net shape powder processing of aluminium

International Nuclear Information System (INIS)

Schaffer, G.B.

2000-01-01

The increasing interest in light weight materials coupled to the need for cost-effective processing have combined to create a significant opportunity for aluminium powder metallurgy. Net shape processing of aluminium using the classical press-and-sinter powder metallurgy technique is a unique and important metal-forming method which is cost effective in producing complex parts at, or very close to, final dimensions. This paper provides an overview of the net shape powder processing of aluminium. Current research is critically reviewed and the future potential is briefly considered

The equivalency between logic Petri workflow nets and workflow nets.

Science.gov (United States)

Wang, Jing; Yu, ShuXia; Du, YuYue

2015-01-01

Logic Petri nets (LPNs) can describe and analyze batch processing functions and passing value indeterminacy in cooperative systems. Logic Petri workflow nets (LPWNs) are proposed based on LPNs in this paper. Process mining is regarded as an important bridge between modeling and analysis of data mining and business process. Workflow nets (WF-nets) are the extension to Petri nets (PNs), and have successfully been used to process mining. Some shortcomings cannot be avoided in process mining, such as duplicate tasks, invisible tasks, and the noise of logs. The online shop in electronic commerce in this paper is modeled to prove the equivalence between LPWNs and WF-nets, and advantages of LPWNs are presented.

The Equivalency between Logic Petri Workflow Nets and Workflow Nets

Science.gov (United States)

Wang, Jing; Yu, ShuXia; Du, YuYue

2015-01-01

Logic Petri nets (LPNs) can describe and analyze batch processing functions and passing value indeterminacy in cooperative systems. Logic Petri workflow nets (LPWNs) are proposed based on LPNs in this paper. Process mining is regarded as an important bridge between modeling and analysis of data mining and business process. Workflow nets (WF-nets) are the extension to Petri nets (PNs), and have successfully been used to process mining. Some shortcomings cannot be avoided in process mining, such as duplicate tasks, invisible tasks, and the noise of logs. The online shop in electronic commerce in this paper is modeled to prove the equivalence between LPWNs and WF-nets, and advantages of LPWNs are presented. PMID:25821845

Ontological Annotation with WordNet

Energy Technology Data Exchange (ETDEWEB)

Sanfilippo, Antonio P.; Tratz, Stephen C.; Gregory, Michelle L.; Chappell, Alan R.; Whitney, Paul D.; Posse, Christian; Paulson, Patrick R.; Baddeley, Bob; Hohimer, Ryan E.; White, Amanda M.

2006-06-06

Semantic Web applications require robust and accurate annotation tools that are capable of automating the assignment of ontological classes to words in naturally occurring text (ontological annotation). Most current ontologies do not include rich lexical databases and are therefore not easily integrated with word sense disambiguation algorithms that are needed to automate ontological annotation. WordNet provides a potentially ideal solution to this problem as it offers a highly structured lexical conceptual representation that has been extensively used to develop word sense disambiguation algorithms. However, WordNet has not been designed as an ontology, and while it can be easily turned into one, the result of doing this would present users with serious practical limitations due to the great number of concepts (synonym sets) it contains. Moreover, mapping WordNet to an existing ontology may be difficult and requires substantial labor. We propose to overcome these limitations by developing an analytical platform that (1) provides a WordNet-based ontology offering a manageable and yet comprehensive set of concept classes, (2) leverages the lexical richness of WordNet to give an extensive characterization of concept class in terms of lexical instances, and (3) integrates a class recognition algorithm that automates the assignment of concept classes to words in naturally occurring text. The ensuing framework makes available an ontological annotation platform that can be effectively integrated with intelligence analysis systems to facilitate evidence marshaling and sustain the creation and validation of inference models.

Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data

Directory of Open Access Journals (Sweden)

Tsang Percy CK

2006-08-01

Full Text Available Abstract Background Epigenetic gene silencing is one of the major causes of carcinogenesis. Its widespread occurrence in cancer genome could inactivate many cellular pathways including DNA repair, cell cycle control, apoptosis, cell adherence, and detoxification. The abnormal promoter methylation might be a potential molecular marker for cancer management. Methods For rapid identification of potential targets for aberrant methylation in gynecological cancers, methylation status of the CpG islands of 34 genes was determined using pooled DNA approach and methylation-specific PCR. Pooled DNA mixture from each cancer type (50 cervical cancers, 50 endometrial cancers and 50 ovarian cancers was made to form three test samples. The corresponding normal DNA from the patients of each cancer type was also pooled to form the other three control samples. Methylated alleles detected in tumors, but not in normal controls, were indicative of aberrant methylation in tumors. Having identified potential markers, frequencies of methylation were further analyzed in individual samples. Markers identified are used to correlate with clinico-pathological data of tumors using χ2 or Fisher's exact test. Results APC and p16 were hypermethylated across the three cancers. MINT31 and PTEN were hypermethylated in cervical and ovarian cancers. Specific methylation was found in cervical cancer (including CDH1, DAPK, MGMT and MINT2, endometrial cancer (CASP8, CDH13, hMLH1 and p73, and ovarian cancer (BRCA1, p14, p15, RIZ1 and TMS1. The frequencies of occurrence of hypermethylation in 4 candidate genes in individual samples of each cancer type (DAPK, MGMT, p16 and PTEN in 127 cervical cancers; APC, CDH13, hMLH1 and p16 in 60 endometrial cancers; and BRCA1, p14, p16 and PTEN in 49 ovarian cancers were examined for further confirmation. Incidence varied among different genes and in different cancer types ranging from the lowest 8.2% (PTEN in ovarian cancer to the highest 56

Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data

International Nuclear Information System (INIS)

Yang, Hui-Juan; Liu, Vincent WS; Wang, Yue; Tsang, Percy CK; Ngan, Hextan YS

2006-01-01

Epigenetic gene silencing is one of the major causes of carcinogenesis. Its widespread occurrence in cancer genome could inactivate many cellular pathways including DNA repair, cell cycle control, apoptosis, cell adherence, and detoxification. The abnormal promoter methylation might be a potential molecular marker for cancer management. For rapid identification of potential targets for aberrant methylation in gynecological cancers, methylation status of the CpG islands of 34 genes was determined using pooled DNA approach and methylation-specific PCR. Pooled DNA mixture from each cancer type (50 cervical cancers, 50 endometrial cancers and 50 ovarian cancers) was made to form three test samples. The corresponding normal DNA from the patients of each cancer type was also pooled to form the other three control samples. Methylated alleles detected in tumors, but not in normal controls, were indicative of aberrant methylation in tumors. Having identified potential markers, frequencies of methylation were further analyzed in individual samples. Markers identified are used to correlate with clinico-pathological data of tumors using χ 2 or Fisher's exact test. APC and p16 were hypermethylated across the three cancers. MINT31 and PTEN were hypermethylated in cervical and ovarian cancers. Specific methylation was found in cervical cancer (including CDH1, DAPK, MGMT and MINT2), endometrial cancer (CASP8, CDH13, hMLH1 and p73), and ovarian cancer (BRCA1, p14, p15, RIZ1 and TMS1). The frequencies of occurrence of hypermethylation in 4 candidate genes in individual samples of each cancer type (DAPK, MGMT, p16 and PTEN in 127 cervical cancers; APC, CDH13, hMLH1 and p16 in 60 endometrial cancers; and BRCA1, p14, p16 and PTEN in 49 ovarian cancers) were examined for further confirmation. Incidence varied among different genes and in different cancer types ranging from the lowest 8.2% (PTEN in ovarian cancer) to the highest 56.7% (DAPK in cervical cancer). Aberrant methylation

Analysis of genuine saving and potential green net national income. Portugal, 1990-2005

International Nuclear Information System (INIS)

Mota, Rui Pedro; Domingos, Tiago; Martins, Victor

2010-01-01

The context of this paper is the measurement of welfare and weak sustainability (defined as non-declining utility) in dynamic economies, i.e., comprehensive or green accounting. We estimate green net national income (GNNI) and genuine saving (GS) for Portugal, for the years 1990 to 2005, accounting for the disamenity of air pollution emissions, the depreciation of commercial forests and the value of time, discussing the implications of the assumptions underlying the inclusion of these terms in the green accounting model. The influence of short-run cycles is analyzed by estimating GNNI excluding business cycles. Our results suggest that business cycles affect the sustainability message of GNNI. We find that potential GNNI is growing and GS is positive in the analyzed period, thereby not indicating a weak sustainability problem in Portugal, although both depict a trend towards unsustainability. Excluding technological progress there is a contradiction in the sustainability message of GNNI and GS. (author)

Analysis of genuine saving and potential green net national income. Portugal, 1990-2005

Energy Technology Data Exchange (ETDEWEB)

Mota, Rui Pedro; Domingos, Tiago [Environment and Energy Section, DEM, Instituto Superior Tecnico (Portugal); Martins, Victor [Department of Economics, Instituto Superior de Economia e Gestao (Portugal)

2010-08-15

The context of this paper is the measurement of welfare and weak sustainability (defined as non-declining utility) in dynamic economies, i.e., comprehensive or green accounting. We estimate green net national income (GNNI) and genuine saving (GS) for Portugal, for the years 1990 to 2005, accounting for the disamenity of air pollution emissions, the depreciation of commercial forests and the value of time, discussing the implications of the assumptions underlying the inclusion of these terms in the green accounting model. The influence of short-run cycles is analyzed by estimating GNNI excluding business cycles. Our results suggest that business cycles affect the sustainability message of GNNI. We find that potential GNNI is growing and GS is positive in the analyzed period, thereby not indicating a weak sustainability problem in Portugal, although both depict a trend towards unsustainability. Excluding technological progress there is a contradiction in the sustainability message of GNNI and GS. (author)

CLIMATIC FORECASTING OF NET INFILTRATION AT YUCCA MOUNTAIN, USING ANALOGUE METEOROLOGICAL DATA

International Nuclear Information System (INIS)

B. Faybishenko

2005-01-01

Net infiltration is a key hydrologic parameter that controls the rate of deep percolation through the unsaturated zone, the groundwater recharge, radionuclide transport, and seepage into the underground tunnels. Because net infiltration is largely affected by climatic conditions, future changes in climatic conditions will potentially alter net infiltration. The objectives of this presentation are to: (1) Present a conceptual model and a semi-empirical approach for regional, climatic forecasting of net infiltration, based on the precipitation and temperature data from analogue meteorological stations, and (2) Demonstrate the results of forecasting net infiltration for future climates--interglacial, monsoon and glacial--over the Yucca Mountain region for the period of 500,000 years. Calculations of the net infiltration were performed using a modified Budyko's water-balance model, for which potential evapotranspiration was evaluated from the temperature-based Thornthwaite formula. (Both Budyko's and Thornthwaite's formulae have been used broadly in hydrological studies.) The results of calculations were used for ranking net infiltration, along with the aridity and precipitation-effectiveness (P-E) indexes, for future climatic scenarios. Using this approach, we determined a general trend of increasing net infiltration from the present-day (interglacial) climate to monsoon, intermediate (glacial transition), and then to the glacial climate. Ranking of the aridity and P-E indexes is practically the same as that of net infiltration. The validation of the computed net infiltration rates yielded a good match with other field and modeling study results of groundwater recharge and net infiltration evaluation

MethylMix 2.0: an R package for identifying DNA methylation genes.

Science.gov (United States)

Cedoz, Pierre-Louis; Prunello, Marcos; Brennan, Kevin; Gevaert, Olivier

2018-04-14

DNA methylation is an important mechanism regulating gene transcription, and its role in carcinogenesis has been extensively studied. Hyper and hypomethylation of genes is a major mechanism of gene expression deregulation in a wide range of diseases. At the same time, high-throughput DNA methylation assays have been developed generating vast amounts of genome wide DNA methylation measurements. We developed MethylMix, an algorithm implemented in R to identify disease specific hyper and hypomethylated genes. Here we present a new version of MethylMix that automates the construction of DNA-methylation and gene expression datasets from The Cancer Genome Atlas (TCGA). More precisely, MethylMix 2.0 incorporates two major updates: the automated downloading of DNA methylation and gene expression datasets from TCGA and the automated preprocessing of such datasets: value imputation, batch correction and CpG sites clustering within each gene. The resulting datasets can subsequently be analyzed with MethylMix to identify transcriptionally predictive methylation states. We show that the Differential Methylation Values created by MethylMix can be used for cancer subtyping. olivier.gevaert@stanford.edu. https://bioconductor.org/packages/release/bioc/manuals/MethylMix/man/MethylMix.pdf. MethylMix 2.0 was implemented as an R package and is available in bioconductor.

Global DNA methylation analysis using methyl-sensitive amplification polymorphism (MSAP).

Science.gov (United States)

Yaish, Mahmoud W; Peng, Mingsheng; Rothstein, Steven J

2014-01-01

DNA methylation is a crucial epigenetic process which helps control gene transcription activity in eukaryotes. Information regarding the methylation status of a regulatory sequence of a particular gene provides important knowledge of this transcriptional control. DNA methylation can be detected using several methods, including sodium bisulfite sequencing and restriction digestion using methylation-sensitive endonucleases. Methyl-Sensitive Amplification Polymorphism (MSAP) is a technique used to study the global DNA methylation status of an organism and hence to distinguish between two individuals based on the DNA methylation status determined by the differential digestion pattern. Therefore, this technique is a useful method for DNA methylation mapping and positional cloning of differentially methylated genes. In this technique, genomic DNA is first digested with a methylation-sensitive restriction enzyme such as HpaII, and then the DNA fragments are ligated to adaptors in order to facilitate their amplification. Digestion using a methylation-insensitive isoschizomer of HpaII, MspI is used in a parallel digestion reaction as a loading control in the experiment. Subsequently, these fragments are selectively amplified by fluorescently labeled primers. PCR products from different individuals are compared, and once an interesting polymorphic locus is recognized, the desired DNA fragment can be isolated from a denaturing polyacrylamide gel, sequenced and identified based on DNA sequence similarity to other sequences available in the database. We will use analysis of met1, ddm1, and atmbd9 mutants and wild-type plants treated with a cytidine analogue, 5-azaC, or zebularine to demonstrate how to assess the genetic modulation of DNA methylation in Arabidopsis. It should be noted that despite the fact that MSAP is a reliable technique used to fish for polymorphic methylated loci, its power is limited to the restriction recognition sites of the enzymes used in the genomic

Coloured Petri Nets

DEFF Research Database (Denmark)

Jensen, Kurt

1987-01-01

The author describes a Petri net model, called coloured Petri nets (CP-nets), by means of which it is possible to describe large systems without having to cope with unnecessary details. The author introduces CP-nets and provide a first impression of their modeling power and the suitability...

Net one, net two: the primary care network income statement.

Science.gov (United States)

Halley, M D; Little, A W

1999-10-01

Although hospital-owned primary care practices have been unprofitable for most hospitals, some hospitals are achieving competitive advantage and sustainable practice operations. A key to the success of some has been a net income reporting tool that separates practice operating expenses from the costs of creating and operating a network of practices to help healthcare organization managers, physicians, and staff to identify opportunities to improve the network's financial performance. This "Net One, Net Two" reporting allows operations leadership to be held accountable for Net One expenses and strategic leadership to be held accountable for Net Two expenses.

Methyl jasmonate affects phenolic metabolism and gene expression in blueberry (Vaccinium corymbosum).

Science.gov (United States)

Cocetta, Giacomo; Rossoni, Mara; Gardana, Claudio; Mignani, Ilaria; Ferrante, Antonio; Spinardi, Anna

2015-02-01

Blueberry (Vaccinium corymbosum) is a fruit very much appreciated by consumers for its antioxidant potential and health-promoting traits. Its beneficial potential properties are mainly due to a high content of anthocyanins and their amount can change after elicitation with methyl jasmonate. The aim of this work is to evaluate the changes in expression of several genes, accumulation of phenolic compounds and alterations in antioxidant potential in two different blueberry cultivars ('Duke' and 'Blueray') in response to methyl jasmonate (0.1 mM). Results showed that 9 h after treatment, the expression of phenylalanine ammonium lyase, chalcone synthase and anthocyanidin synthase genes was stimulated more in the 'Blueray' variety. Among the phenols measured an increase was recorded also for epicatechin and anthocyanin concentrations. 'Duke' is a richer sourche of anthocyanins compared to 'Blueray', treatment with methyl jasmonate promoted in 'Blueray' an increase in pigments as well as in the antioxidant potential, especially in fully ripe berries, but treated 'Duke' berries had greater levels, which were not induced by methyl jasmonate treatment. In conclusion, methyl jasmonate was, in some cases, an effective elicitor of phenolic metabolism and gene expression in blueberry, though with different intensity between cultivars. © 2014 Scandinavian Plant Physiology Society.

Influence of rice straw amendment on mercury methylation and nitrification in paddy soils

International Nuclear Information System (INIS)

Liu, Yu-Rong; Dong, Ji-Xin; Han, Li-Li; Zheng, Yuan-Ming; He, Ji-Zheng

2016-01-01

Currently, rice straw return in place of burning is becoming more intensive in China than observed previously. However, little is known on the effect of returned rice straw on mercury (Hg) methylation and microbial activity in contaminated paddy fields. Here, we conduct a microcosm experiment to evaluate the effect of rice straw amendment on the Hg methylation and potential nitrification in two paddy soils with distinct Hg levels. Our results show that amended rice straw enhanced Hg methylation for relatively high Hg content soil, but not for low Hg soil, spiking the same additional fresh Hg. methylmercury (MeHg) concentration was significantly correlated to the dissolved organic carbon (DOC) content and relative abundance of dominant microbes associated with Hg methylation. Similarly, amended rice straw was found to only enhance the potential nitrification rate in soil with relatively high Hg content. These findings provide evidence that amended rice straw differentially modulates Hg methylation and nitrification in Hg contaminated soils possibly resulting from different characteristics in the soil microbial community. This highlights that caution should be taken when returning rice straw to contaminated paddy fields, as this practice may increase the risk of more MeHg production. Main finding: Rice straw amendment enhanced both Hg methylation and nitrification potential in the relatively high, but not low, Hg soil. - Highlights: • Rice straw enhanced Hg methylation in relatively high Hg content paddy soils. • Microbial community directly correlated to the Hg methylation. • Mercury methylation in soils depend on Hg bioavailability and microbial activities. • Hg input affects microbial community associated with decomposition of rice straw.

DNA Methylation as a Biomarker for Preeclampsia

Energy Technology Data Exchange (ETDEWEB)

Anderson, Cindy M.; Ralph, Jody L.; Wright, Michelle L.; Linggi, Bryan E.; Ohm, Joyce E.

2014-10-01

Background: Preeclampsia contributes significantly to pregnancy-associated morbidity and mortality as well as future risk of cardiovascular disease in mother and offspring, and preeclampsia in offspring. The lack of reliable methods for early detection limits the opportunities for prevention, diagnosis, and timely treatment. Purpose: The purpose of this study was to explore distinct DNA methylation patterns associated with preeclampsia in both maternal cells and fetal-derived tissue that represent potential biomarkers to predict future preeclampsia and inheritance in children. Method: A convenience sample of nulliparous women (N = 55) in the first trimester of pregnancy was recruited for this prospective study. Genome-wide DNA methylation was quantified in first-trimester maternal peripheral white blood cells and placental chorionic tissue from normotensive women and those with preeclampsia (n = 6/group). Results: Late-onset preeclampsia developed in 12.7% of women. Significant differences in DNA methylation were identified in 207 individual linked cytosine and guanine (CpG) sites in maternal white blood cells collected in the first trimester (132 sites with gain and 75 sites with loss of methylation), which were common to approximately 75% of the differentially methylated CpG sites identified in chorionic tissue of fetal origin. Conclusion: This study is the first to identify maternal epigenetic targets and common targets in fetal-derived tissue that represent putative biomarkers for early detection and heritable risk of preeclampsia. Findings may pave the way for diagnosis of preeclampsia prior to its clinical presentation and acute damaging effects, and the potential for prevention of the detrimental long-term sequelae.

DNA methylation in states of cell physiology and pathology.

Directory of Open Access Journals (Sweden)

Lech Chyczewski

2007-10-01

Full Text Available DNA methylation is one of epigenetic mechanisms regulating gene expression. The methylation pattern is determined during embryogenesis and passed over to differentiating cells and tissues. In a normal cell, a significant degree of methylation is characteristic for extragenic DNA (cytosine within the CG dinucleotide while CpG islands located in gene promoters are unmethylated, except for inactive genes of the X chromosome and the genes subjected to genomic imprinting. The changes in the methylation pattern, which may appear as the organism age and in early stages of cancerogenesis, may lead to the silencing of over ninety endogenic genes. It has been found, that these disorders consist not only of the methylation of CpG islands, which are normally unmethylated, but also of the methylation of other dinucleotides, e.g. CpA. Such methylation has been observed in non-small cell lung cancer, in three regions of the exon 5 of the p53 gene (so-called "non-CpG" methylation. The knowledge of a normal methylation process and its aberrations appeared to be useful while searching for new markers enabling an early detection of cancer. With the application of the Real-Time PCR technique (using primers for methylated and unmethylated sequences five new genes which are potential biomarkers of lung cancer have been presented.

[THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

Science.gov (United States)

Mikhailenko, D S; Kushlinskii, N E

2016-02-01

All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers.

Potentiation of 2,5-hexanedione neurotoxicity by methyl ethyl ketone

International Nuclear Information System (INIS)

Ralston, W.H.; Hilderbrand, R.L.; Uddin, D.E.; Andersen, M.E.; Gardier, R.W.

1985-01-01

Chronic oral administration of a combination of 2.2 mmol methyl ethyl ketone (MEK) and 2.2 mmol 2,5-hexanedione (2,5-HD)/kg/day, 5 days/week resulted in more rapid onset of motor deficits than did chronic dosing with 2.2 mmol 2,5-HD/kg/day alone. In kinetic studies blood time courses of 2,5-HD were determined in rats in the presence and absence of MEK. Concomitant administration of MEK reduced blood 2,5-HD clearance and increased the area under the curve (AUC) for the blood 2,5-HD. In companion experiments with 2,5-[1,6- 14 C]HD as a tracer, neural and nonneural tissues were examined 72 hr following the last treatment at Weeks 1, 2, and 3 of chronic administration of 2,5-HD alone or in combination with an equimolar dose of MEK. Rats treated with 2,5-[ 14 C]HD alone or in combination with MEK demonstrated no difference in total or trichloroacetic acid-precipitable radioactivity in blood, in liver homogenates, or in neurofilament-enriched fractions from sciatic nerve and spinal cord. The data support a suggestion that the potentiation of hexacarbon neurotoxicity by MEK is the result of the persistence of the neurotoxic metabolite in the blood and not the enhanced metabolism of parent hexacarbon to 2,5-HD

Assessment of the Mutagenic Potential of Carbon Disulfide, Carbon Tetrachloride, Dichloromethane, Ethylene Dichloride, and Methyl Bromide: A Comparative Analysis in Relation to Ethylene Dibromide

Science.gov (United States)

The document provides an evaluation of the mutagenic potential of five alternative fumigants to ethylene dibromide(EDB). These include carbon disulfide(CS2), carbon tetrachloride(CCl4), dichloromethane(DCM), ethylene dichloride(EDC), and methyl bromide (MB). Of the five proposed ...

[PHI regulates histone methylation and acetylation in Burkitt lymphoma Daudi cell line].

Science.gov (United States)

Hong, Ling-Ling; Ma, Xu-Dong; Huang, Yi-Qun

2011-02-01

This study was purposed to investigate the effects of phenylhexyl isothiocyanate (PHI) on Burkitt lymphoma Daudi cell line and regulation of histone acetylation and methylation in Daudi cells, and to explore the potential mechanism. The apoptotic rate of Daudi cells treated with PHI was measured by flow cytometry, the changes of histone H3 and H4 acetylation, histone H3K9 and H3K4 methylation in Daudi cells treated with PHI were detected by Western blot. The results showed that PHI could induce apoptosis of Daudi cells, increased the acetylation level of H3 and H4, enhanced the methylation of H3K4, but reduced the methylation of H3K9. It is concluded that the PHI can up-regulate the acetylation level of histone H3 associated with transcription stimulation and the methylation of histone H3K4, down-regulate the methylation on histone H3K9 associated with transcription inhibition, promotes the apoptosis of Daudi cells. PHI may be a potential agent for target therapy of lymphoma.

Implications of bio-efficacy and persistence of insecticides when indoor residual spraying and long-lasting insecticide nets are combined for malaria prevention

Directory of Open Access Journals (Sweden)

Okumu Fredros O

2012-11-01

Full Text Available Abstract Background Bio-efficacy and residual activity of insecticides used for indoor residual spraying (IRS and long-lasting insecticide nets (LLINs were assessed against laboratory-reared and wild populations of the malaria vector, Anopheles arabiensis in south eastern Tanzania. Implications of the findings are examined in the context of potential synergies and redundancies where IRS and LLINs are combined. Methods Bioassays were conducted monthly for six months on three LLIN types (Olyset® PermaNet 2.0®,and Icon Life® and three IRS treatments (2 g/m2 pirimiphos-methyl, 2 g/m2 DDT and 0.03 g/m2 lambda-cyhalothrin, sprayed on mud walls and palm ceilings of experimental huts. Tests used susceptible laboratory-reared An. arabiensis exposed in cones (nets and IRS or wire balls (nets only. Susceptibility of wild populations was assessed using WHO diagnostic concentrations and PCR for knock-down resistance (kdr genes. Results IRS treatments killed ≥ 85% of mosquitoes exposed on palm ceilings and ≥ 90% of those exposed on mud walls, but up to 50% of this toxicity decayed within 1–3 months, except for DDT. By 6th month, only 7.5%, 42.5% and 30.0% of mosquitoes died when exposed to ceilings sprayed with pirimiphos-methyl, DDT or lambda-cyhalothrin respectively, while 12.5%, 36.0% and 27.5% died after exposure to mud walls sprayed with the same insecticides. In wire-ball assays, mortality decreased from 98.1% in 1st month to 92.6% in 6th month in tests on PermaNet 2.0®, from 100% to 61.1% on Icon Life® and from 93.2% to 33.3% on Olyset® nets. In cone bioassays, mortality reduced from 92.8% in 1st month to 83.3% in 6th month on PermaNet 2.0®, from 96.9% to 43.80% on Icon Life® and from 85.6% to 14.6% on Olyset®. Wild An. arabiensis were 100% susceptible to DDT, 95.8% to deltamethrin, 90.2% to lambda cyhalothrin and 95.2% susceptible to permethrin. No kdr gene mutations were detected. Conclusions In bioassays where sufficient contact with

Systemic effects of chronically administered methyl prednisolonate and methyl 17-deoxyprednisolonate.

Science.gov (United States)

Olejniczak, E; Lee, H J

1984-06-01

The systemic activities of methyl prednisolonate and methyl 17-deoxyprednisolonate (1) were studied in rats. Methyl 17-deoxyprednisolonate produced significant changes in the amount of sodium ion (decreased) and potassium ion (increased) in urine; however, methyl prednisolonate had no effect on electrolyte balance. Both methyl prednisolonate and methyl 17-deoxyprednisolonate had no effect on liver glycogen content, plasma corticosterone level and relative adrenal weight. In contrast, the parent compound prednisolone caused a significant decrease in liver glycogen content, plasma corticosterone level and relative adrenal weight.

Meta-analysis of the association between APC promoter methylation and colorectal cancer.

Science.gov (United States)

Ding, Zhenyu; Jiang, Tong; Piao, Ying; Han, Tao; Han, Yaling; Xie, Xiaodong

2015-01-01

Previous studies investigating the association between adenomatous polyposis coli (APC) gene promoter methylation and colorectal cancer (CRC) have yielded conflicting results. The aim of this study was to comprehensively evaluate the potential application of the detection of APC promoter methylation to the prevention and treatment of CRC. PubMed, Embase, and MEDLINE (results updated to October 2014) were searched for relevant studies. The effect size was defined as the weighted odds ratio (OR), which was calculated using either the fixed-effects or random-effects model. Prespecified subgroup and sensitivity analyses were conducted to evaluate potential heterogeneity among the included studies. Nineteen studies comprising 2,426 participants were selected for our meta-analysis. The pooled results of nine studies comprising a total of 740 subjects indicated that APC promoter methylation was significantly associated with CRC risk (pooled OR 5.53; 95% confidence interval [CI] 3.50-8.76; PAPC promoter methylation and the presence of CRC metastasis, and the pooled OR was 0.80 (95% CI 0.44-1.46; P=0.47). A meta-analysis conducted with four studies with a total of 467 patients found no significant correlation between APC promoter methylation and the presence of colorectal adenoma (pooled OR 1.85; 95% CI 0.67-5.10; P=0.23). No significant correlation between APC promoter methylation and patients' Dukes' stage, TNM stage, differentiation grade, age, or sex was identified. In conclusion, APC promoter methylation was found to be significantly associated with a higher risk of developing CRC. The findings indicate that APC promoter methylation may be a potential biomarker for the carcinogenesis of CRC.

Association of season of birth with DNA methylation and allergic disease

NARCIS (Netherlands)

Lockett, G. A.; Soto-Ramirez, N.; Ray, M. A.; Everson, T. M.; Xu, C-J.; Patil, V. K.; Terry, W.; Kaushal, A.; Rezwan, F. I.; Ewart, S. L.; Gehring, U.; Postma, D. S.; Koppelman, G. H.; Arshad, S. H.; Zhang, H.; Karmaus, W.; Holloway, J. W.

Background Season of birth influences allergy risk; however, the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie

Type 1 Diabetes TrialNet--an international collaborative clinical trials network.

Science.gov (United States)

Skyler, Jay S; Greenbaum, Carla J; Lachin, John M; Leschek, Ellen; Rafkin-Mervis, Lisa; Savage, Peter; Spain, Lisa

2008-12-01

Type 1 Diabetes TrialNet is an international consortium of clinical research centers aimed at the prevention or delay of type 1 diabetes (T1D). The fundamental goal of TrialNet is to counter the T1D disease process by immune modulation and/or enhancement of beta cell proliferation and regeneration. To achieve this goal, TrialNet researchers are working to better understand the natural history of the disease, to identify persons at risk, and to clinically evaluate novel therapies that balance potential risks and benefits. The particular focus is on studies of preventive measures. In addition, TrialNet evaluates therapies in individuals with newly diagnosed T1D with preserved beta cell function to help determine the risk/benefit profile and gain an initial assessment of potential efficacy in preservation of beta cell function, so that promising agents can be studied in prevention trials. In addition, TrialNet evaluates methodologies that enhance the conduct of its clinical trials, which includes tests of outcome assessment methodology, the evaluation of surrogate markers, and mechanistic studies laying the foundation for future clinical trials.

Theoretical spectroscopic characterization at low temperatures of S-methyl thioformate and O-methyl thioformate

International Nuclear Information System (INIS)

Senent, M. L.; Puzzarini, C.; Hochlaf, M.; Domínguez-Gómez, R.; Carvajal, M.

2014-01-01

Highly correlated ab initio methods are employed to determine spectroscopic properties at low temperatures of two S-analogs of methyl formate: S-methyl thioformate CH 3 -S-CHO (MSCHO) and O-methyl thioformate CH 3 -O-CHS (MOCHS). Both species are detectable and they are expected to play an important role in Astrochemistry. Molecular properties are compared with those of the O-analog, methyl formate. Both isomers present two conformers cis and trans. cis-CH 3 -S-CHO represents the most stable structure lying 4372.2 cm −1 below cis-CH 3 -O-CHS. The energy difference between the cis and trans forms is drastically lower for MSCHO (1134 cm −1 ) than for MOCHS (1963.6 cm −1 ). Harmonic and anharmonic fundamentals and the corresponding intensities, as well as the rotational constants for the ground vibrational and first excited torsional states and the centrifugal distortions constants, are provided. Low torsional energy levels have been obtained by solving variationally a two dimensional Hamiltonian expressed in terms of the two torsional degrees of freedom. The corresponding 2D potential energy surfaces have been computed at the CCSD(T)/aug-cc-pVTZ level of theory. The methyl torsional barriers V 3 (cis) are determined to be 139.7 cm −1 (CH 3 -S-CHO) and 670.4 cm −1 (CH 3 -O-CHS). The A/E splitting of ground torsional state has been estimated to be 0.438 cm −1 for CH 3 -S-CHO and negligible for CH 3 -O-CHS

Methyl Methacrylate and Alpha-Methyl Styrene: New Strategy for Synthesis of Bloc Copolymers for Use in Potential Biomedical Applications Generated by an Ecologic Catalyst Called Maghnite (Algerian MMT

Directory of Open Access Journals (Sweden)

Moulkheir Ayat

2016-10-01

Full Text Available A new model for synthesis of the plastics, block copolymers were prepared from methyl methacrylate (MMA and alpha-methyl styrene (α-MS by cationic copolymerization in the presence of a new and efficient catalyst of “Maghnite-Na” at 0 °C in bulk. In this paper, the copolymerization of α-MS and MMA was induced in heterogeneous phase catalyzed by Maghnite-Na was investigated under suitable conditions. The “Maghnite-Na” is a montmorillonite sheet silicate clay, with exchanged sodium cations to produce Na-Montmorillonite (Na+-MMT obtained from Tlemcen, Algeria, was investigated to remove heavy metal ion from wastewater as an efficient catalyst for cationic polymerization of many vinylic and heterocyclic monomers. The synthesized copolymer were characterized by Nuclear Magnetic Resonance (NMR-1H, NMR-13C, FT-IR spectroscopy, Differential Scanning Calorimetry (DSC, and Gel Permeation Chromatography (GPC to elucidate structural characteristics and thermal properties of the resulting copolymers. The structure compositions of “MMT”, “H+-MMT” and “Na+-MMT” have been developed. The effect of the MMA/α-MS molar ratio on the rate of copolymerization, the amount of catalyst, temperature and time of copolymerization on yield of copolymers was studied. The yield of copolymerization depends on the amount of Na+-MMT used and the reaction time. The kinetic studies indicated that the polymerization rate is first order with respect to monomer concentration. A possible mechanism of this cationic polymerization is discussed based on the results of the 1H-NMR Spectroscopic analysis of these model reactions. A cationic mechanism for the reaction studies showed that monomer was inserted into the growing chains. Copyright © 2016 BCREC GROUP. All rights reserved Received: 2nd May 2015; Revised: 24th February 2016; Accepted: 15th March 2016 How to Cite: Ayat, M., Belbachir, M., Rahmouni, A. (2016. Methyl Methacrylate and Alpha-Methyl Styrene: New

MethPrimer: designing primers for methylation PCRs.

Science.gov (United States)

Li, Long-Cheng; Dahiya, Rajvir

2002-11-01

DNA methylation is an epigenetic mechanism of gene regulation. Bisulfite- conversion-based PCR methods, such as bisulfite sequencing PCR (BSP) and methylation specific PCR (MSP), remain the most commonly used techniques for methylation mapping. Existing primer design programs developed for standard PCR cannot handle primer design for bisulfite-conversion-based PCRs due to changes in DNA sequence context caused by bisulfite treatment and many special constraints both on the primers and the region to be amplified for such experiments. Therefore, the present study was designed to develop a program for such applications. MethPrimer, based on Primer 3, is a program for designing PCR primers for methylation mapping. It first takes a DNA sequence as its input and searches the sequence for potential CpG islands. Primers are then picked around the predicted CpG islands or around regions specified by users. MethPrimer can design primers for BSP and MSP. Results of primer selection are delivered through a web browser in text and in graphic view.

Association of season of birth with DNA methylation and allergic disease

NARCIS (Netherlands)

Lockett, G. A.; Soto-Ramirez, N.; Ray, M. A.; Everson, T. M.; Xu, C-J.; Patil, V. K.; Terry, W.; Kaushal, A.; Rezwan, F. I.; Ewart, S. L.; Gehring, U.; Postma, D. S.; Koppelman, G. H.; Arshad, S. H.; Zhang, H.; Karmaus, W.; Holloway, J. W.

BackgroundSeason of birth influences allergy risk; however, the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the

Quantitative analysis of DNA methylation in chronic lymphocytic leukemia patients.

Science.gov (United States)

Lyko, Frank; Stach, Dirk; Brenner, Axel; Stilgenbauer, Stephan; Döhner, Hartmut; Wirtz, Michaela; Wiessler, Manfred; Schmitz, Oliver J

2004-06-01

Changes in the genomic DNA methylation level have been found to be closely associated with tumorigenesis. In order to analyze the relation of aberrant DNA methylation to clinical and biological risk factors, we have determined the cytosine methylation level of 81 patients diagnosed with chronic lymphocytic leukemia (CLL). The analysis was based on DNA hydrolysis followed by derivatization of the 2'-desoxyribonucleoside-3'-monophosphates with BODIPY FL EDA. Derivatives were separated by micellar electrokinetic chromatography, and laser-induced fluorescence was used for detection. We analyzed potential correlations between DNA methylation levels and numerous patient parameters, including clinical observations and biological data. As a result, we observed a significant correlation with the immunoglobulin variable heavy chain gene (VH) mutation status. This factor has been repeatedly proposed as a reliable prognostic marker for CLL, which suggests that the methylation level might be a valuable factor in determining the prognostic outcome of CLL. We are now in the process of refining our method to broaden its application potential. In this context, we show here that the oxidation of the fluorescence marker in the samples and the evaporation of methanol in the electrolytes can be prevented by a film of paraffin oil. In summary, our results thus establish capillary electrophoresis as a valuable tool for analyzing the DNA methylation status of clinical samples.

Rhodotorulaglutinis phenylalanine/tyrosine ammonia lyase enzyme catalyzed synthesis of the methyl ester of para-hydroxycinnamic acid and its potential antibacterial activity

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Marybeth C MacDonald

2016-03-01

Full Text Available Biotransformation of L-tyrosine methyl ester (L-TM to the methyl ester of para- hydroxycinnamic acid (p-HCAM using Rhodotorula glutinis yeast phenylalanine/tyrosine ammonia lyase (PTAL; EC 4.3.1.26 enzyme was successfully demonstrated for the first time; progress of the reaction was followed by spectrophotometric determination at 315 nm. The following conditions were optimized for maximal formation of p-HCAM: pH (8.5, temperature (37 C, speed of agitation (50 rpm, enzyme concentration (0.080 µM, and substrate concentration (0.50 mM. Under these conditions, the yield of the reaction was ~15% in 1 h incubation period and ~63% after an overnight (~18 h incubation period. The product (p-HCAM of the reaction of PTAL with L-TM was confirmed using Nuclear Magnetic Resonance spectroscopy (NMR. Fourier Transform Infra-Red spectroscopy (FTIR was carried out to rule out potential hydrolysis of p-HCAM during overnight incubation. Potential antibacterial activity of p-HCAM was tested against several strains of Gram positive and Gram negative bacteria. This study describes a synthetically useful transformation, and could have future clinical and industrial applications.

Zebrafish embryos as a screen for DNA methylation modifications after compound exposure

Energy Technology Data Exchange (ETDEWEB)

Bouwmeester, Manon C.; Ruiter, Sander; Lommelaars, Tobias; Sippel, Josefine; Hodemaekers, Hennie M. [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Brandhof, Evert-Jan van den [Center for Environmental Quality, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Pennings, Jeroen L.A. [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands); Kamstra, Jorke H. [Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Jelinek, Jaroslav [Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA (United States); Issa, Jean-Pierre J. [Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA (United States); Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX (United States); Legler, Juliette [Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Ven, Leo T.M. van der, E-mail: leo.van.der.ven@rivm.nl [Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven (Netherlands)

2016-01-15

Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin, arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis. - Highlights: • Compound induced effects on DNA methylation in zebrafish embryos • Global methylation not an informative biomarker • Minimal genome

Zebrafish embryos as a screen for DNA methylation modifications after compound exposure

International Nuclear Information System (INIS)

Bouwmeester, Manon C.; Ruiter, Sander; Lommelaars, Tobias; Sippel, Josefine; Hodemaekers, Hennie M.; Brandhof, Evert-Jan van den; Pennings, Jeroen L.A.; Kamstra, Jorke H.; Jelinek, Jaroslav; Issa, Jean-Pierre J.; Legler, Juliette; Ven, Leo T.M. van der

2016-01-01

Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin, arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis. - Highlights: • Compound induced effects on DNA methylation in zebrafish embryos • Global methylation not an informative biomarker • Minimal genome

Mass distribution of free insecticide-treated nets do not interfere with continuous net distribution in Tanzania.

Science.gov (United States)

Eze, Ikenna C; Kramer, Karen; Msengwa, Amina; Mandike, Renata; Lengeler, Christian

2014-05-27

To protect the most vulnerable groups from malaria (pregnant women and infants) the Tanzanian Government introduced a subsidy (voucher) scheme in 2004, on the basis of a public-private partnership. These vouchers are provided to pregnant women at their first antenatal care visit and mothers of infants at first vaccination. The vouchers are redeemed at registered retailers for a long-lasting insecticidal net against the payment of a modest top-up price. The present work analysed a large body of data from the Tanzanian National Voucher Scheme, focusing on interactions with concurrent mass distribution campaigns of free nets. In an ecologic study involving all regions of Tanzania, voucher redemption data for the period 2007-2011, as well as data on potential determinants of voucher redemption were analysed. The four outcome variables were: pregnant woman and infant voucher redemption rates, use of treated bed nets by all household members and by under- five children. Each of the outcomes was regressed with selected determinants, using a generalized estimating equation model and accounting for regional data clustering. There was a consistent improvement in voucher redemption rates over the selected time period, with rates >80% in 2011. The major determinants of redemption rates were the top-up price paid by the voucher beneficiary, the retailer- clinic ratio, and socio-economic status. Improved redemption rates after 2009 were most likely due to reduced top-up prices (following a change in policy). Redemption rates were not affected by two major free net distribution campaigns. During this period, there was a consistent improvement in net use across all the regions, with rates of up to 75% in 2011. The key components of the National Treated Nets Programme (NATNETS) seem to work harmoniously, leading to a high level of net use in the entire population. This calls for the continuation of this effort in Tanzania and for emulation by other countries with endemic malaria.

The Fine LINE: Methylation Drawing the Cancer Landscape

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Isabelle R. Miousse

2015-01-01

Full Text Available LINE-1 (L1 is the most abundant mammalian transposable element that comprises nearly 20% of the genome, and nearly half of the mammalian genome has stemmed from L1-mediated mobilization. Expression and retrotransposition of L1 are suppressed by complex mechanisms, where the key role belongs to DNA methylation. Alterations in L1 methylation may lead to aberrant expression of L1 and have been described in numerous diseases. Accumulating evidence clearly indicates that loss of global DNA methylation observed in cancer development and progression is tightly associated with hypomethylation of L1 elements. Significant progress achieved in the last several years suggests that such parameters as L1 methylation status can be potentially utilized as clinical biomarkers for determination of the disease stage and in predicting the disease-free survival in cancer patients. In this paper, we summarize the current knowledge on L1 methylation, with specific emphasis given to success and challenges on the way of introduction of L1 into clinical practice.

A Potential Synergy between Incomplete Arsenic Methylation Capacity and Demographic Characteristics on the Risk of Hypertension: Findings from a Cross-Sectional Study in an Arsenic-Endemic Area of Inner Mongolia, China

Directory of Open Access Journals (Sweden)

Yongfang Li

2015-03-01

Full Text Available Inefficient arsenic methylation capacity has been associated with various health hazards induced by arsenic. In this study, we aimed to explore the interaction effect of lower arsenic methylation capacity with demographic characteristics on hypertension risk. A total of 512 adult participants (126 hypertension subjects and 386 non-hypertension subjects residing in an arsenic-endemic area in Inner Mongolia, China were included. Urinary levels of inorganic arsenic (iAs, monomethylarsonic acid (MMA, and dimethylarsinic acid (DMA were measured for all subjects. The percentage of urinary arsenic metabolites (iAs%, MMA%, and DMA%, primary methylation index (PMI and secondary methylation index (SMI were calculated to assess arsenic methylation capacity of individuals. Results showed that participants carrying a lower methylation capacity, which is characterized by lower DMA% and SMI, have a higher risk of hypertension compared to their corresponding references after adjusting for multiple confounders. A potential synergy between poor arsenic methylation capacity (higher MMA%, lower DMA% and SMI and older age or higher BMI were detected. The joint effects of higher MMA% and lower SMI with cigarette smoking also suggest some evidence of synergism. The findings of present study indicated that inefficient arsenic methylation capacity was associated with hypertension and the effect might be enhanced by certain demographic factors.

Methodological considerations regarding the use of inorganic {sup 197}Hg(II) radiotracer to assess mercury methylation potential rates in lake sediment

Energy Technology Data Exchange (ETDEWEB)

Perez Catan, Soledad [Laboratorio de Analisis por Activacion Neutronica, Comision Nacional de Energia Atomica, Centro Atomico Bariloche, 8400 Bariloche (Argentina); Guevara, Sergio Ribeiro [Laboratorio de Analisis por Activacion Neutronica, Comision Nacional de Energia Atomica, Centro Atomico Bariloche, 8400 Bariloche (Argentina)], E-mail: ribeiro@cab.cnea.gov.ar; Marvin-DiPasquale, Mark [US Geological Survey, 345 Middlefield Rd./MS 480, Menlo Park, CA 94025 (United States); Magnavacca, Cecilia [Centro Atomico Ezeiza, Comision Nacional de Energia Atomica, Presbitero Gonzalez y Aragon No. 15, B1802AYA, Ezeiza, Buenos Aires (Argentina); Cohen, Isaac Marcos [Departamento de Ingenieria Quimica, Facultad Regional Buenos Aires, Universidad Tecnologica Nacional, Medrano 951 (C1179AAQ) Buenos Aires (Argentina); Arribere, Maria [Laboratorio de Analisis por Activacion Neutronica, Comision Nacional de Energia Atomica, Centro Atomico Bariloche, 8400 Bariloche (Argentina)

2007-09-15

Methodological considerations on the determination of benthic methyl-mercury (CH{sub 3}Hg) production potentials were investigated on lake sediment, using {sup 197}Hg radiotracer. Three methods to arrest bacterial activity were compared: flash freezing, thermal sterilization, and {gamma}-irradiation. Flash freezing showed similar CH{sub 3}Hg recoveries as thermal sterilization, which was both 50% higher than the recoveries obtained with {gamma}-ray irradiation. No additional radiolabel was recovered in kill-control samples after an additional 24 or 65 h of incubation, suggesting that all treatments were effective at arresting Hg(II)-methylating bacterial activity, and that the initial recoveries are likely due to non-methylated {sup 197}Hg(II) carry-over in the organic extraction and/or [{sup 197}Hg]CH{sub 3}Hg produced via abiotic reactions. Two CH{sub 3}Hg extraction methods from sediment were compared: (a) direct extraction into toluene after sediment leaching with CuSO{sub 4} and HCl and (b) the same extraction with an additional back-extraction step to thiosulphate. Similar information was obtained with both methods, but the low efficiency observed and the extra work associated with the back-extraction procedure represent significant disadvantages, even tough the direct extraction involves higher Hg(II) carry over.

Automating Ontological Annotation with WordNet

Energy Technology Data Exchange (ETDEWEB)

Sanfilippo, Antonio P.; Tratz, Stephen C.; Gregory, Michelle L.; Chappell, Alan R.; Whitney, Paul D.; Posse, Christian; Paulson, Patrick R.; Baddeley, Bob L.; Hohimer, Ryan E.; White, Amanda M.

2006-01-22

Semantic Web applications require robust and accurate annotation tools that are capable of automating the assignment of ontological classes to words in naturally occurring text (ontological annotation). Most current ontologies do not include rich lexical databases and are therefore not easily integrated with word sense disambiguation algorithms that are needed to automate ontological annotation. WordNet provides a potentially ideal solution to this problem as it offers a highly structured lexical conceptual representation that has been extensively used to develop word sense disambiguation algorithms. However, WordNet has not been designed as an ontology, and while it can be easily turned into one, the result of doing this would present users with serious practical limitations due to the great number of concepts (synonym sets) it contains. Moreover, mapping WordNet to an existing ontology may be difficult and requires substantial labor. We propose to overcome these limitations by developing an analytical platform that (1) provides a WordNet-based ontology offering a manageable and yet comprehensive set of concept classes, (2) leverages the lexical richness of WordNet to give an extensive characterization of concept class in terms of lexical instances, and (3) integrates a class recognition algorithm that automates the assignment of concept classes to words in naturally occurring text. The ensuing framework makes available an ontological annotation platform that can be effectively integrated with intelligence analysis systems to facilitate evidence marshaling and sustain the creation and validation of inference models.

Application of deconvolution interferometry with both Hi-net and KiK-net data

Science.gov (United States)

Nakata, N.

2013-12-01

Application of deconvolution interferometry to wavefields observed by KiK-net, a strong-motion recording network in Japan, is useful for estimating wave velocities and S-wave splitting in the near surface. Using this technique, for example, Nakata and Snieder (2011, 2012) found changed in velocities caused by Tohoku-Oki earthquake in Japan. At the location of the borehole accelerometer of each KiK-net station, a velocity sensor is also installed as a part of a high-sensitivity seismograph network (Hi-net). I present a technique that uses both Hi-net and KiK-net records for computing deconvolution interferometry. The deconvolved waveform obtained from the combination of Hi-net and KiK-net data is similar to the waveform computed from KiK-net data only, which indicates that one can use Hi-net wavefields for deconvolution interferometry. Because Hi-net records have a high signal-to-noise ratio (S/N) and high dynamic resolution, the S/N and the quality of amplitude and phase of deconvolved waveforms can be improved with Hi-net data. These advantages are especially important for short-time moving-window seismic interferometry and deconvolution interferometry using later coda waves.

CpG Methylation Analysis of HPV16 in Laser Capture Microdissected Archival Tissue and Whole Tissue Sections from High Grade Anal Squamous Intraepithelial Lesions: A Potential Disease Biomarker.

Directory of Open Access Journals (Sweden)

Monica Molano

Full Text Available Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC are associated with human papillomavirus (HPV. Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS and laser capture microdissected (LCM tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL.

Migration and risk: net migration in marginal ecosystems and hazardous areas

International Nuclear Information System (INIS)

De Sherbinin, Alex; Levy, Marc; Adamo, Susana; MacManus, Kytt; Yetman, Greg; Mara, Valentina; Razafindrazay, Liana; Aichele, Cody; Pistolesi, Linda; Goodrich, Benjamin; Srebotnjak, Tanja

2012-01-01

The potential for altered ecosystems and extreme weather events in the context of climate change has raised questions concerning the role that migration plays in either increasing or reducing risks to society. Using modeled data on net migration over three decades from 1970 to 2000, we identify sensitive ecosystems and regions at high risk of climate hazards that have seen high levels of net in-migration and out-migration over the time period. This paper provides a literature review on migration related to ecosystems, briefly describes the methodology used to develop the estimates of net migration, then uses those data to describe the patterns of net migration for various ecosystems and high risk regions. The study finds that negative net migration generally occurs over large areas, reflecting its largely rural character, whereas areas of positive net migration are typically smaller, reflecting its largely urban character. The countries with largest population such as China and India tend to drive global results for all the ecosystems found in those countries. Results suggest that from 1970 to 2000, migrants in developing countries have tended to move out of marginal dryland and mountain ecosystems and out of drought-prone areas, and have moved towards coastal ecosystems and areas that are prone to floods and cyclones. For North America results are reversed for dryland and mountain ecosystems, which saw large net influxes of population in the period of record. Uncertainties and potential sources of error in these estimates are addressed. (letter)

Theoretical spectroscopic characterization at low temperatures of S-methyl thioformate and O-methyl thioformate

Energy Technology Data Exchange (ETDEWEB)

Senent, M. L., E-mail: senent@iem.cfmac.csic.es [Departamento de Química y Física Teóricas, Instituto de Estructura de la Materia, IEM-C.S.I.C., Serrano 121, Madrid 28006 (Spain); Puzzarini, C., E-mail: cristina.puzzarini@unibo.it [Dipartimento di Chimica G. Ciamician, Università di Bologna, Via F. Selmi 2, I-40126 Bologna (Italy); Hochlaf, M., E-mail: hochlaf@univ-mlv.fr [Laboratoire de Modélisation et Simulation Multi Echelle, Université Paris-Est, MSME UMR 8208 CNRS, 5 boulevard Descartes, 77454 Marne-la-Vallée (France); Domínguez-Gómez, R., E-mail: rosa.dominguez@upm.es [Departamento de Ingeniería Civil, Cátedra de Química, E.U.I.T. Obras Públicas, Universidad Politécnica de Madrid, Madrid (Spain); Carvajal, M., E-mail: miguel.carvajal@dfa.uhu.es [Departamento de Física Aplicada, Facultad de Ciencias Experimentales, Unidad Asociada IEM-CSIC-U.Huelva, Universidad de Huelva, 21071 Huelva (Spain)

2014-09-14

Highly correlated ab initio methods are employed to determine spectroscopic properties at low temperatures of two S-analogs of methyl formate: S-methyl thioformate CH{sub 3}-S-CHO (MSCHO) and O-methyl thioformate CH{sub 3}-O-CHS (MOCHS). Both species are detectable and they are expected to play an important role in Astrochemistry. Molecular properties are compared with those of the O-analog, methyl formate. Both isomers present two conformers cis and trans. cis-CH{sub 3}-S-CHO represents the most stable structure lying 4372.2 cm{sup −1} below cis-CH{sub 3}-O-CHS. The energy difference between the cis and trans forms is drastically lower for MSCHO (1134 cm{sup −1}) than for MOCHS (1963.6 cm{sup −1}). Harmonic and anharmonic fundamentals and the corresponding intensities, as well as the rotational constants for the ground vibrational and first excited torsional states and the centrifugal distortions constants, are provided. Low torsional energy levels have been obtained by solving variationally a two dimensional Hamiltonian expressed in terms of the two torsional degrees of freedom. The corresponding 2D potential energy surfaces have been computed at the CCSD(T)/aug-cc-pVTZ level of theory. The methyl torsional barriers V{sub 3}(cis) are determined to be 139.7 cm{sup −1} (CH{sub 3}-S-CHO) and 670.4 cm{sup −1} (CH{sub 3}-O-CHS). The A/E splitting of ground torsional state has been estimated to be 0.438 cm{sup −1} for CH{sub 3}-S-CHO and negligible for CH{sub 3}-O-CHS.

DNA methylation regulates expression of VEGF-C, and S-adenosylmethionine is effective for VEGF-C methylation and for inhibiting cancer growth

Energy Technology Data Exchange (ETDEWEB)

Da, M.X. [Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou (China); Zhang, Y.B. [Department of Surgery, Ningxia Medical University, Yinchuan (China); Yao, J.B. [Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou (China); Duan, Y.X. [Department of Surgery, Ningxia Medical University, Yinchuan (China)

2014-09-30

DNA hypomethylation may activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-adenosylmethionine (SAM) is a methyl donor in numerous methylation reactions and acts as an inhibitor of intracellular demethylase activity, which results in hypermethylation of DNA. The main objectives of this study were to determine whether DNA hypomethylation correlated with vascular endothelial growth factor-C (VEGF-C) expression, and the effect of SAM on VEGF-C methylation and gastric cancer growth inhibition. VEGF-C expression was assayed by Western blotting and RT-qPCR in gastric cancer cells, and by immunohistochemistry in tumor xenografts. VEGF-C methylation was assayed by bisulfite DNA sequencing. The effect of SAM on cell apoptosis was assayed by flow cytometry analyses and its effect on cancer growth was assessed in nude mice. The VEGF-C promoters of MGC-803, BGC-823, and SGC-7901 gastric cancer cells, which normally express VEGF-C, were nearly unmethylated. After SAM treatment, the VEGF-C promoters in these cells were highly methylated and VEGF-C expression was downregulated. SAM also significantly inhibited tumor growth in vitro and in vivo. DNA methylation regulates expression of VEGF-C. SAM can effectively induce VEGF-C methylation, reduce the expression of VEGF-C, and inhibit tumor growth. SAM has potential as a drug therapy to silence oncogenes and block the progression of gastric cancer.

Potentialities of aberrantly methylated circulating DNA for diagnostics and post-treatment follow-up of lung cancer patients.

Science.gov (United States)

Ponomaryova, Anastasia A; Rykova, Elena Yu; Cherdyntseva, Nadezda V; Skvortsova, Tatiana E; Dobrodeev, Alexey Yu; Zav'yalov, Alexander A; Bryzgalov, Leonid O; Tuzikov, Sergey A; Vlassov, Valentin V; Laktionov, Pavel P

2013-09-01

To date, aberrant DNA methylation has been shown to be one of the most common and early causes of malignant cell transformation and tumors of different localizations, including lung cancer. Cancer cell-specific methylated DNA has been found in the blood of cancer patients, indicating that cell-free DNA circulating in the blood (cirDNA) is a convenient tumor-associated DNA marker that can be used as a minimally invasive diagnostic test. In the current study, we investigated the methylation status in blood samples of 32 healthy donors and 60 lung cancer patients before and after treatment with neoadjuvant chemotherapy followed by total tumor resection. Using quantitative methylation-specific PCR, we found that the index of methylation (IM), calculated as IM = 100 × [copy number of methylated/(copy number of methylated + unmethylated gene)], for the RASSF1A and RARB2 genes in the cirDNA isolated from blood plasma and cell-surface-bound cirDNA was elevated 2- to 3-fold in lung cancer patients compared with healthy donors. Random forest classification tree model based on these variables combined (RARB2 and RASSF1A IM in both plasma and cell-surface-bound cirDNA) lead to NSCLC patients' and healthy subjects' differentiation with 87% sensitivity and 75% specificity. An association of increased IM values with an advanced stage of non-small-cell lung cancer was found for RARB2 but not for RASSF1A. Chemotherapy and total tumor resection resulted in a significant decrease in the IM for RARB2 and RASSF1A, in both cirDNA fractions, comparable to the IM level of healthy subjects. Importantly, a rise in the IM for RARB2 was detected in patients within the follow-up period, which manifested in disease relapse at 9 months, confirmed with instrumental and pathologic methods. Our data indicate that quantitative analysis of the methylation status of the RARB2 and RASSF1A tumor suppressor genes in both cirDNA fractions is a useful tool for lung cancer diagnostics, evaluation of cancer

DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumors

International Nuclear Information System (INIS)

Amatruda, James F; Frazier, A Lindsay; Poynter, Jenny N; Ross, Julie A; Christensen, Brock; Fustino, Nicholas J; Chen, Kenneth S; Hooten, Anthony J; Nelson, Heather; Kuriger, Jacquelyn K; Rakheja, Dinesh

2013-01-01

Aberrant DNA methylation is a prominent feature of many cancers, and may be especially relevant in germ cell tumors (GCTs) due to the extensive epigenetic reprogramming that occurs in the germ line during normal development. We used the Illumina GoldenGate Cancer Methylation Panel to compare DNA methylation in the three main histologic subtypes of pediatric GCTs (germinoma, teratoma and yolk sac tumor (YST); N = 51) and used recursively partitioned mixture models (RPMM) to test associations between methylation pattern and tumor and demographic characteristics. We identified genes and pathways that were differentially methylated using generalized linear models and Ingenuity Pathway Analysis. We also measured global DNA methylation at LINE1 elements and evaluated methylation at selected imprinted loci using pyrosequencing. Methylation patterns differed by tumor histology, with 18/19 YSTs forming a distinct methylation class. Four pathways showed significant enrichment for YSTs, including a human embryonic stem cell pluripotency pathway. We identified 190 CpG loci with significant methylation differences in mature and immature teratomas (q < 0.05), including a number of CpGs in stem cell and pluripotency-related pathways. Both YST and germinoma showed significantly lower methylation at LINE1 elements compared with normal adjacent tissue while there was no difference between teratoma (mature and immature) and normal tissue. DNA methylation at imprinted loci differed significantly by tumor histology and location. Understanding methylation patterns may identify the developmental stage at which the GCT arose and the at-risk period when environmental exposures could be most harmful. Further, identification of relevant genetic pathways could lead to the development of new targets for therapy

Modeling of the oxidation of methyl esters—Validation for methyl hexanoate, methyl heptanoate, and methyl decanoate in a jet-stirred reactor

Science.gov (United States)

Glaude, Pierre Alexandre; Herbinet, Olivier; Bax, Sarah; Biet, Joffrey; Warth, Valérie; Battin-Leclerc, Frédérique

2013-01-01

The modeling of the oxidation of methyl esters was investigated and the specific chemistry, which is due to the presence of the ester group in this class of molecules, is described. New reactions and rate parameters were defined and included in the software EXGAS for the automatic generation of kinetic mechanisms. Models generated with EXGAS were successfully validated against data from the literature (oxidation of methyl hexanoate and methyl heptanoate in a jet-stirred reactor) and a new set of experimental results for methyl decanoate. The oxidation of this last species was investigated in a jet-stirred reactor at temperatures from 500 to 1100 K, including the negative temperature coefficient region, under stoichiometric conditions, at a pressure of 1.06 bar and for a residence time of 1.5 s: more than 30 reaction products, including olefins, unsaturated esters, and cyclic ethers, were quantified and successfully simulated. Flow rate analysis showed that reactions pathways for the oxidation of methyl esters in the low-temperature range are similar to that of alkanes. PMID:23710076

Modeling of the oxidation of methyl esters-Validation for methyl hexanoate, methyl heptanoate, and methyl decanoate in a jet-stirred reactor.

Science.gov (United States)

Glaude, Pierre Alexandre; Herbinet, Olivier; Bax, Sarah; Biet, Joffrey; Warth, Valérie; Battin-Leclerc, Frédérique

2010-11-01

The modeling of the oxidation of methyl esters was investigated and the specific chemistry, which is due to the presence of the ester group in this class of molecules, is described. New reactions and rate parameters were defined and included in the software EXGAS for the automatic generation of kinetic mechanisms. Models generated with EXGAS were successfully validated against data from the literature (oxidation of methyl hexanoate and methyl heptanoate in a jet-stirred reactor) and a new set of experimental results for methyl decanoate. The oxidation of this last species was investigated in a jet-stirred reactor at temperatures from 500 to 1100 K, including the negative temperature coefficient region, under stoichiometric conditions, at a pressure of 1.06 bar and for a residence time of 1.5 s: more than 30 reaction products, including olefins, unsaturated esters, and cyclic ethers, were quantified and successfully simulated. Flow rate analysis showed that reactions pathways for the oxidation of methyl esters in the low-temperature range are similar to that of alkanes.

Identification of methylated genes associated with aggressive clinicopathological features in mantle cell lymphoma.

Directory of Open Access Journals (Sweden)

Anna Enjuanes

Full Text Available BACKGROUND: Mantle cell lymphoma (MCL is genetically characterized by the t(11;14(q13;q32 translocation and a high number of secondary chromosomal alterations. The contribution of DNA methylation to MCL lymphomagenesis is not well known. We sought to identify epigenetically silenced genes in these tumours that might have clinical relevance. METHODOLOGY/PRINCIPAL FINDINGS: To identify potential methylated genes in MCL we initially investigated seven MCL cell lines treated with epigenetic drugs and gene expression microarray profiling. The methylation status of selected candidate genes was validated by a quantitative assay and subsequently analyzed in a series of primary MCL (n = 38. After pharmacological reversion we identified 252 potentially methylated genes. The methylation analysis of a subset of these genes (n = 25 in the MCL cell lines and normal B lymphocytes confirmed that 80% of them were methylated in the cell lines but not in normal lymphocytes. The subsequent analysis in primary MCL identified five genes (SOX9, HOXA9, AHR, NR2F2, and ROBO1 frequently methylated in these tumours. The gene methylation events tended to occur in the same primary neoplasms and correlated with higher proliferation, increased number of chromosomal abnormalities, and shorter survival of the patients. CONCLUSIONS: We have identified a set of genes whose methylation degree and gene expression levels correlate with aggressive clinicopathological features of MCL. Our findings also suggest that a subset of MCL might show a CpG island methylator phenotype (CIMP that may influence the behaviour of the tumours.

High-resolution analysis of cytosine methylation in ancient DNA.

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Bastien Llamas

Full Text Available Epigenetic changes to gene expression can result in heritable phenotypic characteristics that are not encoded in the DNA itself, but rather by biochemical modifications to the DNA or associated chromatin proteins. Interposed between genes and environment, these epigenetic modifications can be influenced by environmental factors to affect phenotype for multiple generations. This raises the possibility that epigenetic states provide a substrate for natural selection, with the potential to participate in the rapid adaptation of species to changes in environment. Any direct test of this hypothesis would require the ability to measure epigenetic states over evolutionary timescales. Here we describe the first single-base resolution of cytosine methylation patterns in an ancient mammalian genome, by bisulphite allelic sequencing of loci from late Pleistocene Bison priscus remains. Retrotransposons and the differentially methylated regions of imprinted loci displayed methylation patterns identical to those derived from fresh bovine tissue, indicating that methylation patterns are preserved in the ancient DNA. Our findings establish the biochemical stability of methylated cytosines over extensive time frames, and provide the first direct evidence that cytosine methylation patterns are retained in DNA from ancient specimens. The ability to resolve cytosine methylation in ancient DNA provides a powerful means to study the role of epigenetics in evolution.

MicroRNA-137 promoter methylation in oral lichen planus and oral squamous cell carcinoma

DEFF Research Database (Denmark)

Dang, Jun; Bian, Yong-qian; Sun, Jian-yong

2013-01-01

and patients with oral squamous cell carcinoma (OSCC). A total of 20 OLP and 12 patients with OSCC as well as 10 healthy subjects were subjected to miR-137 promoter methylation analysis using methylation-specific PCR (MSP). To address the malignancy prediction potential from miR-137 promoter methylation status...

An 11bp region with stem formation potential is essential for de novo DNA methylation of the RPS element.

Directory of Open Access Journals (Sweden)

Matthew Gentry

Full Text Available The initiation of DNA methylation in Arabidopsis is controlled by the RNA-directed DNA methylation (RdDM pathway that uses 24nt siRNAs to recruit de novo methyltransferase DRM2 to the target site. We previously described the REPETITIVE PETUNIA SEQUENCE (RPS fragment that acts as a hot spot for de novo methylation, for which it requires the cooperative activity of all three methyltransferases MET1, CMT3 and DRM2, but not the RdDM pathway. RPS contains two identical 11nt elements in inverted orientation, interrupted by a 18nt spacer, which resembles the features of a stemloop structure. The analysis of deletion/substitution derivatives of this region showed that deletion of one 11nt element RPS is sufficient to eliminate de novo methylation of RPS. In addition, deletion of a 10nt region directly adjacent to one of the 11nt elements, significantly reduced de novo methylation. When both 11nt regions were replaced by two 11nt elements with altered DNA sequence but unchanged inverted repeat homology, DNA methylation was not affected, indicating that de novo methylation was not targeted to a specific DNA sequence element. These data suggest that de novo DNA methylation is attracted by a secondary structure to which the two 11nt elements contribute, and that the adjacent 10nt region influences the stability of this structure. This resembles the recognition of structural features by DNA methyltransferases in animals and suggests that similar mechanisms exist in plants.

Net Neutrality

DEFF Research Database (Denmark)

Savin, Andrej

2017-01-01

Repealing “net neutrality” in the US will have no bearing on Internet freedom or security there or anywhere else.......Repealing “net neutrality” in the US will have no bearing on Internet freedom or security there or anywhere else....

Annotating Coloured Petri Nets

DEFF Research Database (Denmark)

Lindstrøm, Bo; Wells, Lisa Marie

2002-01-01

Coloured Petri nets (CP-nets) can be used for several fundamentally different purposes like functional analysis, performance analysis, and visualisation. To be able to use the corresponding tool extensions and libraries it is sometimes necessary to include extra auxiliary information in the CP......-net. An example of such auxiliary information is a counter which is associated with a token to be able to do performance analysis. Modifying colour sets and arc inscriptions in a CP-net to support a specific use may lead to creation of several slightly different CP-nets – only to support the different uses...... of the same basic CP-net. One solution to this problem is that the auxiliary information is not integrated into colour sets and arc inscriptions of a CP-net, but is kept separately. This makes it easy to disable this auxiliary information if a CP-net is to be used for another purpose. This paper proposes...

In silico mining identifies IGFBP3 as a novel target of methylation in prostate cancer.

LENUS (Irish Health Repository)

Perry, A S

2007-05-21

Promoter hypermethylation is central in deregulating gene expression in cancer. Identification of novel methylation targets in specific cancers provides a basis for their use as biomarkers of disease occurrence and progression. We developed an in silico strategy to globally identify potential targets of promoter hypermethylation in prostate cancer by screening for 5\\' CpG islands in 631 genes that were reported as downregulated in prostate cancer. A virtual archive of 338 potential targets of methylation was produced. One candidate, IGFBP3, was selected for investigation, along with glutathione-S-transferase pi (GSTP1), a well-known methylation target in prostate cancer. Methylation of IGFBP3 was detected by quantitative methylation-specific PCR in 49\\/79 primary prostate adenocarcinoma and 7\\/14 adjacent preinvasive high-grade prostatic intraepithelial neoplasia, but in only 5\\/37 benign prostatic hyperplasia (P < 0.0001) and in 0\\/39 histologically normal adjacent prostate tissue, which implies that methylation of IGFBP3 may be involved in the early stages of prostate cancer development. Hypermethylation of IGFBP3 was only detected in samples that also demonstrated methylation of GSTP1 and was also correlated with Gleason score > or =7 (P=0.01), indicating that it has potential as a prognostic marker. In addition, pharmacological demethylation induced strong expression of IGFBP3 in LNCaP prostate cancer cells. Our concept of a methylation candidate gene bank was successful in identifying a novel target of frequent hypermethylation in early-stage prostate cancer. Evaluation of further relevant genes could contribute towards a methylation signature of this disease.

Validation of methylation-sensitive high-resolution melting (MS-HRM) for the detection of stool DNA methylation in colorectal neoplasms.

Science.gov (United States)

Xiao, Zhujun; Li, Bingsheng; Wang, Guozhen; Zhu, Weisi; Wang, Zhongqiu; Lin, Jinfeng; Xu, Angao; Wang, Xinying

2014-04-20

Methylation-sensitive high-resolution melting (MS-HRM) is a new technique for assaying DNA methylation, but its feasibility for assaying stool in patients with colorectal cancer (CRC) is unknown. First, the MS-HRM and methylation-specific PCR (MSP) detection limits were tested. Second, the methylation statuses of SFRP2 and VIM were analyzed in stool samples by MS-HRM, and in matching tumor and normal colon tissues via bisulfite sequencing PCR (BSP). Third, a case-control study evaluated the diagnostic sensitivity and specificity of MS-HRM relative to results obtained with MSP and the fecal immunochemical test (FIT). Finally, the linearity and reproducibility of MS-HRM were assessed. The detection limits of MS-HRM and MSP were 1% and 5%, respectively. The diagnostic sensitivities of MS-HRM (87.3%, 55/63) in stool and BSP in matching tumor tissue (92.1%, 58/63) were highly consistent (κ=0.744). The MS-HRM assay detected 92.5% (37/40) methylation in CRCs, 94.4% (34/36) in advanced adenomas, and 8.8% (5/57) in normal controls. The results of MS-HRM analysis were stable and reliable and showed fairly good linearity for both SFRP2 (PHRM shows potential for CRC screening. Copyright © 2014 Elsevier B.V. All rights reserved.

Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer

Science.gov (United States)

Shigeyasu, Kunitoshi; Nagasaka, Takeshi; Mori, Yoshiko; Yokomichi, Naosuke; Kawai, Takashi; Fuji, Tomokazu; Kimura, Keisuke; Umeda, Yuzo; Kagawa, Shunsuke; Goel, Ajay; Fujiwara, Toshiyoshi

2015-01-01

Background To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown. Methods This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox’s proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1 methylation status in relation to overall survival (OS). Results By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088), better tumor differentiation (P = 0.0267) and CIMP-high and MLH1 3' methylated status (P = 0.0312). Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis. Conclusions CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer. PMID:26121593

Clinical Significance of MLH1 Methylation and CpG Island Methylator Phenotype as Prognostic Markers in Patients with Gastric Cancer.

Directory of Open Access Journals (Sweden)

Kunitoshi Shigeyasu

Full Text Available To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP and microsatellite instability (MSI have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown.This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox's proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1 methylation status in relation to overall survival (OS.By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088, better tumor differentiation (P = 0.0267 and CIMP-high and MLH1 3' methylated status (P = 0.0312. Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis.CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer.

Targeting Net Zero Energy at Marine Corps Base Hawaii, Kaneohe Bay: Preprint

Energy Technology Data Exchange (ETDEWEB)

Burman, K.; Kandt, A.; Lisell, L.; Booth, S.

2012-05-01

This paper summarizes the results of an NREL assessment of Marine Corps Base Hawaii (MCBH), Kaneohe Bay to appraise the potential of achieving net zero energy status through energy efficiency, renewable energy, and hydrogen vehicle integration. In 2008, the U.S. Department of Defense's U.S. Pacific Command partnered with the U.S. Department of Energy's (DOE's) National Renewable Energy Laboratory (NREL) to assess opportunities for increasing energy security through renewable energy and energy efficiency at Hawaii military installations. DOE selected Marine Corps Base Hawaii (MCBH), Kaneohe Bay, to receive technical support for net zero energy assessment and planning funded through the Hawaii Clean Energy Initiative (HCEI). NREL performed a comprehensive assessment to appraise the potential of MCBH Kaneohe Bay to achieve net zero energy status through energy efficiency, renewable energy, and hydrogen vehicle integration. This paper summarizes the results of the assessment and provides energy recommendations. The analysis shows that MCBH Kaneohe Bay has the potential to make significant progress toward becoming a net zero installation. Wind, solar photovoltaics, solar hot water, and hydrogen production were assessed, as well as energy efficiency technologies. Deploying wind turbines is the most cost-effective energy production measure. If the identified energy projects and savings measures are implemented, the base will achieve a 96% site Btu reduction and a 99% source Btu reduction. Using excess wind and solar energy to produce hydrogen for a fleet and fuel cells could significantly reduce energy use and potentially bring MCBH Kaneohe Bay to net zero. Further analysis with an environmental impact and interconnection study will need to be completed. By achieving net zero status, the base will set an example for other military installations, provide environmental benefits, reduce costs, increase energy security, and exceed its energy goals and mandates.

Controls on the variability of net infiltration to desert sandstone

Science.gov (United States)

Heilweil, Victor M.; McKinney, Tim S.; Zhdanov, Michael S.; Watt, Dennis E.

2007-01-01

As populations grow in arid climates and desert bedrock aquifers are increasingly targeted for future development, understanding and quantifying the spatial variability of net infiltration becomes critically important for accurately inventorying water resources and mapping contamination vulnerability. This paper presents a conceptual model of net infiltration to desert sandstone and then develops an empirical equation for its spatial quantification at the watershed scale using linear least squares inversion methods for evaluating controlling parameters (independent variables) based on estimated net infiltration rates (dependent variables). Net infiltration rates used for this regression analysis were calculated from environmental tracers in boreholes and more than 3000 linear meters of vadose zone excavations in an upland basin in southwestern Utah underlain by Navajo sandstone. Soil coarseness, distance to upgradient outcrop, and topographic slope were shown to be the primary physical parameters controlling the spatial variability of net infiltration. Although the method should be transferable to other desert sandstone settings for determining the relative spatial distribution of net infiltration, further study is needed to evaluate the effects of other potential parameters such as slope aspect, outcrop parameters, and climate on absolute net infiltration rates.

Biochar amendment reduces paddy soil nitrogen leaching but increases net global warming potential in Ningxia irrigation, China.

Science.gov (United States)

Wang, Yongsheng; Liu, Yansui; Liu, Ruliang; Zhang, Aiping; Yang, Shiqi; Liu, Hongyuan; Zhou, Yang; Yang, Zhengli

2017-05-09

The efficacy of biochar as an environmentally friendly agent for non-point source and climate change mitigation remains uncertain. Our goal was to test the impact of biochar amendment on paddy rice nitrogen (N) uptake, soil N leaching, and soil CH 4 and N 2 O fluxes in northwest China. Biochar was applied at four rates (0, 4.5, 9 and13.5 t ha -1 yr -1 ). Biochar amendment significantly increased rice N uptake, soil total N concentration and the abundance of soil ammonia-oxidizing archaea (AOA), but it significantly reduced the soil NO 3 - -N concentration and soil bulk density. Biochar significantly reduced NO 3 - -N and NH 4 + -N leaching. The C2 and C3 treatments significantly increased the soil CH 4 flux and reduced the soil N 2 O flux, leading to significantly increased net global warming potential (GWP). Soil NO 3 - -N rather than NH 4 + -N was the key integrator of the soil CH 4 and N 2 O fluxes. Our results indicate that a shift in abundance of the AOA community and increased rice N uptake are closely linked to the reduced soil NO 3 - -N concentration under biochar amendment. Furthermore, soil NO 3 - -N availability plays an important role in regulating soil inorganic N leaching and net GWP in rice paddies in northwest China.

Learning Visual Basic NET

CERN Document Server

Liberty, Jesse

2009-01-01

Learning Visual Basic .NET is a complete introduction to VB.NET and object-oriented programming. By using hundreds of examples, this book demonstrates how to develop various kinds of applications--including those that work with databases--and web services. Learning Visual Basic .NET will help you build a solid foundation in .NET.

Net Zero Energy Military Installations: A Guide to Assessment and Planning

Energy Technology Data Exchange (ETDEWEB)

Booth, S.; Barnett, J.; Burman, K.; Hambrick, J.; Westby, R.

2010-08-01

The U.S. Department of Defense (DoD) recognizes the strategic importance of energy to its mission, and is working to reduce energy consumption and enhance energy self-sufficiency by drawing on local clean energy sources. A joint initiative formed between DoD and the U.S. Department of Energy (DOE) in 2008 to address military energy use led to a task force to examine the potential for net zero energy military installations, which would produce as much energy on site as they consume in buildings, facilities, and fleet vehicles. This report presents an assessment and planning process to examine military installations for net zero energy potential. Net Zero Energy Installation Assessment (NZEIA) presents a systematic framework to analyze energy projects at installations while balancing other site priorities such as mission, cost, and security.

Effect of O-methylated and glucuronosylated flavonoids from Tamarix gallica on α-glucosidase inhibitory activity: structure-activity relationship and synergistic potential.

Science.gov (United States)

Ben Hmidene, Asma; Smaoui, Abderrazak; Abdelly, Chedly; Isoda, Hiroko; Shigemori, Hideyuki

2017-03-01

O-Methylated and glucuronosylated flavonoids were isolated from Tamarix gallica as α-glucosidase inhibitors. Structure-activity relationship of these flavonoids suggests that catechol moiety and glucuronic acid at C-3 are factors in the increase in α-glucosidase inhibitory activity. Furthermore, rhamnetin, tamarixetin, rhamnazin, KGlcA, KGlcA-Me, QGlcA, and QGlcA-Me exhibit synergistic potential when applied with a very low concentration of acarbose to α-glucosidase from rat intestine.

DNA methylation of angiotensin II receptor gene in nonalcoholic steatohepatitis-related liver fibrosis.

Science.gov (United States)

Asada, Kiyoshi; Aihara, Yosuke; Takaya, Hiroaki; Noguchi, Ryuichi; Namisaki, Tadashi; Moriya, Kei; Uejima, Masakazu; Kitade, Mitsuteru; Mashitani, Tsuyoshi; Takeda, Kosuke; Kawaratani, Hideto; Okura, Yasushi; Kaji, Kosuke; Douhara, Akitoshi; Sawada, Yasuhiko; Nishimura, Norihisa; Seki, Kenichiro; Mitoro, Akira; Yamao, Junichi; Yoshiji, Hitoshi

2016-10-08

To clarify whether Agtr1a methylation is involved in the development of nonalcoholic steatohepatitis (NASH)-related liver fibrosis in adult rats. A choline-deficient amino acid (CDAA) diet model was employed for methylation analysis of NASH-related liver fibrosis. Agtr1a methylation levels were measured in the livers of CDAA- and control choline-sufficient amino acid (CSAA)-fed rats for 8 and 12 wk using quantitative methylation-specific PCR. Hepatic stellate cells (HSCs) were isolated by collagenase digestion of the liver, followed by centrifugation of the crude cell suspension through a density gradient. Agtr1a methylation and its gene expression were also analyzed during the activation of HSCs. The mean levels of Agtr1a methylation in the livers of CDAA-fed rats (11.5% and 18.6% at 8 and 12 wk, respectively) tended to be higher ( P = 0.06 and 0.09, respectively) than those in the livers of CSAA-fed rats (2.1% and 5.3% at 8 and 12 wk, respectively). Agtr1a was not methylated at all in quiescent HSCs, but was clearly methylated in activated HSCs (13.8%, P < 0.01). Interestingly, although Agtr1a was hypermethylated, the Agtr1a mRNA level increased up to 2.2-fold ( P < 0.05) in activated HSCs compared with that in quiescent HSCs, suggesting that Agtr1a methylation did not silence its expression but instead had the potential to upregulate its expression. These findings indicate that Agtr1a methylation and its upregulation of gene expression are associated with the development of NASH-related liver fibrosis. This is the first study to show that DNA methylation is potentially involved in the regulation of a renin-angiotensin system-related gene expression during liver fibrosis.

Aberrantly methylated DNA as a biomarker in breast cancer.

Science.gov (United States)

Kristiansen, Søren; Jørgensen, Lars M; Guldberg, Per; Sölétormos, György

2013-01-01

Aberrant DNA hypermethylation at gene promoters is a frequent event in human breast cancer. Recent genome-wide studies have identified hundreds of genes that exhibit differential methylation between breast cancer cells and normal breast tissue. Due to the tumor-specific nature of DNA hypermethylation events, their use as tumor biomarkers is usually not hampered by analytical signals from normal cells, which is a general problem for existing protein tumor markers used for clinical assessment of breast cancer. There is accumulating evidence that DNA-methylation changes in breast cancer patients occur early during tumorigenesis. This may open up for effective screening, and analysis of blood or nipple aspirate may later help in diagnosing breast cancer. As a more detailed molecular characterization of different types of breast cancer becomes available, the ability to divide patients into subgroups based on DNA biomarkers may improve prognosis. Serial monitoring of DNA-methylation markers in blood during treatment may be useful, particularly when the cancer burden is below the detection level for standard imaging techniques. Overall, aberrant DNA methylation has a great potential as a versatile biomarker tool for screening, diagnosis, prognosis and monitoring of breast cancer. Standardization of methods and biomarker panels will be required to fully exploit this clinical potential.

Pro-Nets versus No-Nets: Differences in Urban Older Adults' Predilections for Internet Use

Science.gov (United States)

Cresci, M. Kay; Yarandi, Hossein N.; Morrell, Roger W.

2010-01-01

Enthusiasm for information technology (IT) is growing among older adults. Many older adults enjoy IT and the Internet (Pro-Nets), but others have no desire to use it (No-Nets). This study found that Pro-Nets and No-Nets were different on a number of variables that might predict IT use. No-Nets were older, had less education and income, were…

Methylation diet and methyl group genetics in risk for adenomatous polyp occurrence

Directory of Open Access Journals (Sweden)

Mark Lucock

2015-06-01

Conclusion: A methylation diet influences methyl group synthesis in the regulation of blood homocysteine level, and is modulated by genetic interactions. Methylation-related nutrients also interact with key genes to modify risk of AP, a precursor of colorectal cancer. Independent of diet, two methylation-related genes (A2756G-MS and A66G-MSR were directly associated with AP occurrence.

Information Thermodynamics of Cytosine DNA Methylation.

Directory of Open Access Journals (Sweden)

Robersy Sanchez

Full Text Available 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

Reactions of guanine with methyl chloride and methyl bromide: O6-methylation versus charge transfer complex formation

Science.gov (United States)

Shukla, P. K.; Mishra, P. C.; Suhai, S.

Density functional theory (DFT) at the B3LYP/6-31+G* and B3LYP/AUG-cc-pVDZ levels was employed to study O6-methylation of guanine due to its reactions with methyl chloride and methyl bromide and to obtain explanation as to why the methyl halides cause genotoxicity and possess mutagenic and carcinogenic properties. Geometries of the various isolated species involved in the reactions, reactant complexes (RCs), and product complexes (PCs) were optimized in gas phase. Transition states connecting the reactant complexes with the product complexes were also optimized in gas phase at the same levels of theory. The reactant complexes, product complexes, and transition states were solvated in aqueous media using the polarizable continuum model (PCM) of the self-consistent reaction field theory. Zero-point energy (ZPE) correction to total energy and the corresponding thermal energy correction to enthalpy were made in each case. The reactant complexes of the keto form of guanine with methyl chloride and methyl bromide in water are appreciably more stable than the corresponding complexes involving the enol form of guanine. The nature of binding in the product complexes was found to be of the charge transfer type (O6mG+ · X-, X dbond Cl, Br). Binding of HCl, HBr, and H2O molecules to the PCs obtained with the keto form of guanine did not alter the positions of the halide anions in the PCs, and the charge transfer character of the PCs was also not modified due to this binding. Further, the complexes obtained due to the binding of HCl, HBr, and H2O molecules to the PCs had greater stability than the isolated PCs. The reaction barriers involved in the formation of PCs were found to be quite high (?50 kcal/mol). Mechanisms of genotoxicity, mutagenesis and carcinogenesis caused by the methyl halides appear to involve charge transfer-type complex formation. Thus the mechanisms of these processes involving the methyl halides appear to be quite different from those that involve the

Squaroglitter: A 3,4-Connected Carbon Net

KAUST Repository

Prasad, Dasari L. V. K.

2013-08-13

Theoretical calculations are presented on a new hypothetical 3,4-connected carbon net (called squaroglitter) incorporating 1,4 cyclohexadiene units. The structure has tetragonal space group P4/mmm (No. 123) symmetry. The optimized geometry shows normal distances, except for some elongated bonds in the cyclobutane ring substructures in the network. Squaroglitter has an indirect bandgap of about 1.0 eV. The hypothetical lattice, whose density is close to graphite, is more stable than other 3,4-connected carbon nets. A relationship to a (4,4)nanotube is explored, as is a potential threading of the lattice with metal needles. © 2013 American Chemical Society.

TreeNetViz: revealing patterns of networks over tree structures.

Science.gov (United States)

Gou, Liang; Zhang, Xiaolong Luke

2011-12-01

Network data often contain important attributes from various dimensions such as social affiliations and areas of expertise in a social network. If such attributes exhibit a tree structure, visualizing a compound graph consisting of tree and network structures becomes complicated. How to visually reveal patterns of a network over a tree has not been fully studied. In this paper, we propose a compound graph model, TreeNet, to support visualization and analysis of a network at multiple levels of aggregation over a tree. We also present a visualization design, TreeNetViz, to offer the multiscale and cross-scale exploration and interaction of a TreeNet graph. TreeNetViz uses a Radial, Space-Filling (RSF) visualization to represent the tree structure, a circle layout with novel optimization to show aggregated networks derived from TreeNet, and an edge bundling technique to reduce visual complexity. Our circular layout algorithm reduces both total edge-crossings and edge length and also considers hierarchical structure constraints and edge weight in a TreeNet graph. These experiments illustrate that the algorithm can reduce visual cluttering in TreeNet graphs. Our case study also shows that TreeNetViz has the potential to support the analysis of a compound graph by revealing multiscale and cross-scale network patterns. © 2011 IEEE

Experiments and simulation of a net closing mechanism for tether-net capture of space debris

Science.gov (United States)

Sharf, Inna; Thomsen, Benjamin; Botta, Eleonora M.; Misra, Arun K.

2017-10-01

This research addresses the design and testing of a debris containment system for use in a tether-net approach to space debris removal. The tether-net active debris removal involves the ejection of a net from a spacecraft by applying impulses to masses on the net, subsequent expansion of the net, the envelopment and capture of the debris target, and the de-orbiting of the debris via a tether to the chaser spacecraft. To ensure a debris removal mission's success, it is important that the debris be successfully captured and then, secured within the net. To this end, we present a concept for a net closing mechanism, which we believe will permit consistently successful debris capture via a simple and unobtrusive design. This net closing system functions by extending the main tether connecting the chaser spacecraft and the net vertex to the perimeter and around the perimeter of the net, allowing the tether to actuate closure of the net in a manner similar to a cinch cord. A particular embodiment of the design in a laboratory test-bed is described: the test-bed itself is comprised of a scaled-down tether-net, a supporting frame and a mock-up debris. Experiments conducted with the facility demonstrate the practicality of the net closing system. A model of the net closure concept has been integrated into the previously developed dynamics simulator of the chaser/tether-net/debris system. Simulations under tether tensioning conditions demonstrate the effectiveness of the closure concept for debris containment, in the gravity-free environment of space, for a realistic debris target. The on-ground experimental test-bed is also used to showcase its utility for validating the dynamics simulation of the net deployment, and a full-scale automated setup would make possible a range of validation studies of other aspects of a tether-net debris capture mission.

Gene transcription profiles, global DNA methylation and potential transgenerational epigenetic effects related to Zn exposure history in Daphnia magna

International Nuclear Information System (INIS)

Vandegehuchte, Michiel B.; De Coninck, Dieter; Vandenbrouck, Tine; De Coen, Wim M.; Janssen, Colin R.

2010-01-01

A reduced level of DNA methylation has recently been described in both Zn-exposed and non-exposed offspring of Daphnia magna exposed to Zn. The hypothesis examined in this study is that DNA hypomethylation has an effect on gene transcription. A second hypothesis is that accumulative epigenetic effects can affect gene transcription in non-exposed offspring from parents with an exposure history of more than one generation. Transcriptional gene regulation was studied with a cDNA microarray. In the exposed and non-exposed hypomethylated daphnids, a large proportion of common genes were similarly up- or down-regulated, indicating a possible effect of the DNA hypomethylation. Two of these genes can be mechanistically involved in DNA methylation reduction. The similar transcriptional regulation of two and three genes in the F 0 and F 1 exposed daphnids on one hand and their non-exposed offspring on the other hand, could be the result of a one-generation temporary transgenerational epigenetic effect, which was not accumulative. - Zn-induced DNA hypomethylation is related to gene transcription in Daphnia magna and Zn exposure potentially induced limited temporary transgenerational effects on gene transcription.

Mercury methylation and bacterial activity associated to tropical phytoplankton

International Nuclear Information System (INIS)

Coelho-Souza, Sergio A.; Guimaraes, Jean R.D.; Mauro, Jane B.N.; Miranda, Marcio R.; Azevedo, Sandra M.F.O.

2006-01-01

The methylated form of mercury (Hg), methylmercury (MeHg), is one of the most toxic pollutants. Biotic and/or abiotic methylation, often associated to sulfate-reducing bacteria metabolism, occurs in aquatic environments and in many tropical areas, mostly in the periphyton associated to floating macrophyte roots. Data about mercury methylation by phytoplankton are scarce and the aim of this study was to verify the biotic influence in the methylation process in Microcystis aeruginosa and Sineccocystis sp. laboratory strains and in natural populations of phytoplankton from two different aquatic systems, the mesotrophic Ribeirao das Lajes reservoir and hypereutrophic oligohaline Jacarepagua lagoon, Rio de Janeiro state, Brazil. Adapted radiochemical techniques were used to measure sulfate-reduction, mercury methylation and bacterial activity in phytoplankton samples. Methyl- 203 Hg formation from added inorganic 203 Hg and 3 H-Leucine uptake were measured by liquid scintillation as well as sulfate-reduction, estimated as H 2 35 S produced from added Na 2 35 SO 4 . There was no significant difference in low methylation potentials (0.37%) among the two cyanobacterium species studied in laboratory conditions. At Ribeirao das Lajes reservoir, there was no significant difference in methylation, bacterial activity and sulfate-reduction of surface sediment between the sampling points. Methylation in sediments (3-4%) was higher than in phytoplankton (1.5%), the opposite being true for bacterial activity (sediment mean 6.6 against 150.3 nmol gdw -1 h -1 for phytoplankton samples). At Jacarepagua lagoon, an expressive bacterial activity (477.1 x 10 3 nmol gdw -1 h -1 at a concentration of 1000 nM leucine) and sulfate-reduction (∼21% H 2 35 S trapped) associated to phytoplankton (mostly cyanobacteria M. aeruginosa) was observed, but mercury methylation was not detected

Mercury methylation and bacterial activity associated to tropical phytoplankton

Energy Technology Data Exchange (ETDEWEB)

Coelho-Souza, Sergio A. [Laboratorio de Tracadores Wolfgang Pfeiffer, SL 62, Instituto de Biofisica Carlos Chagas Filho, Bloco G, Ilha do Fundao, Universidade Federal do Rio de Janeiro (IBCCF/UFRJ), RJ, CEP 21949-900 (Brazil); Guimaraes, Jean R.D. [Laboratorio de Tracadores Wolfgang Pfeiffer, SL 62, Instituto de Biofisica Carlos Chagas Filho, Bloco G, Ilha do Fundao, Universidade Federal do Rio de Janeiro (IBCCF/UFRJ), RJ, CEP 21949-900 (Brazil)]. E-mail: jeanrdg@biof.ufrj.br; Mauro, Jane B.N. [Laboratorio de Tracadores Wolfgang Pfeiffer, SL 62, Instituto de Biofisica Carlos Chagas Filho, Bloco G, Ilha do Fundao, Universidade Federal do Rio de Janeiro (IBCCF/UFRJ), RJ, CEP 21949-900 (Brazil); Miranda, Marcio R. [Laboratorio de Tracadores Wolfgang Pfeiffer, SL 62, Instituto de Biofisica Carlos Chagas Filho, Bloco G, Ilha do Fundao, Universidade Federal do Rio de Janeiro (IBCCF/UFRJ), RJ, CEP 21949-900 (Brazil); Azevedo, Sandra M.F.O. [Laboratorio de Ecofisiologia e Toxicologia de Cianobacterias, IBCCF/UFRJ, RJ (Brazil)

2006-07-01

The methylated form of mercury (Hg), methylmercury (MeHg), is one of the most toxic pollutants. Biotic and/or abiotic methylation, often associated to sulfate-reducing bacteria metabolism, occurs in aquatic environments and in many tropical areas, mostly in the periphyton associated to floating macrophyte roots. Data about mercury methylation by phytoplankton are scarce and the aim of this study was to verify the biotic influence in the methylation process in Microcystis aeruginosa and Sineccocystis sp. laboratory strains and in natural populations of phytoplankton from two different aquatic systems, the mesotrophic Ribeirao das Lajes reservoir and hypereutrophic oligohaline Jacarepagua lagoon, Rio de Janeiro state, Brazil. Adapted radiochemical techniques were used to measure sulfate-reduction, mercury methylation and bacterial activity in phytoplankton samples. Methyl-{sup 203}Hg formation from added inorganic {sup 203}Hg and {sup 3}H-Leucine uptake were measured by liquid scintillation as well as sulfate-reduction, estimated as H{sub 2} {sup 35}S produced from added Na{sub 2} {sup 35}SO{sub 4}. There was no significant difference in low methylation potentials (0.37%) among the two cyanobacterium species studied in laboratory conditions. At Ribeirao das Lajes reservoir, there was no significant difference in methylation, bacterial activity and sulfate-reduction of surface sediment between the sampling points. Methylation in sediments (3-4%) was higher than in phytoplankton (1.5%), the opposite being true for bacterial activity (sediment mean 6.6 against 150.3 nmol gdw{sup -1} h{sup -1} for phytoplankton samples). At Jacarepagua lagoon, an expressive bacterial activity (477.1 x 10{sup 3} nmol gdw{sup -1} h{sup -1} at a concentration of 1000 nM leucine) and sulfate-reduction ({approx}21% H{sub 2} {sup 35}S trapped) associated to phytoplankton (mostly cyanobacteria M. aeruginosa) was observed, but mercury methylation was not detected.

21 CFR 177.2000 - Vinylidene chloride/methyl acrylate/methyl methacrylate polymers.

Science.gov (United States)

2010-04-01

... methacrylate polymers. 177.2000 Section 177.2000 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...: POLYMERS Substances for Use as Basic Components of Single and Repeated Use Food Contact Surfaces § 177.2000 Vinylidene chloride/methyl acrylate/methyl methacrylate polymers. The vinylidene chloride/methyl acrylate...

Improving methyl ketone production in Escherichia coli by heterologous expression of NADH-dependent FabG

DEFF Research Database (Denmark)

Goh, Ee Been; Chen, Yan; Petzold, Christopher J.

2018-01-01

balance, as fatty acid-derived pathways face the systematic metabolic challenge of net NADPH consumption (in large part, resulting from the key fatty acid biosynthetic enzyme FabG [β-ketoacyl-ACP reductase]) and net NADH production. In this study, we attempted to mitigate cofactor imbalance...... by heterologously expressing NADH-dependent, rather than NADPH-dependent, versions of FabG identified in previous studies. Of the four NADH-dependent versions of FabG tested in our previously best-reported methyl ketone-producing strain (EGS1895), the version from Acholeplasma laidlawii (Al_FabG) showed...... for the base strain (EGS1895) under fermentation conditions optimized in this study. Shotgun proteomic data for strains EGS2920 and EGS1895 during fed-batch fermentation were consistent with the goal of alleviating NADPH limitation through expression of Al_FabG. For example, relative to strain EGS1895, strain...

Petri nets - part 1: concepts and application areas

International Nuclear Information System (INIS)

Sivertsen, Terje

2004-03-01

There exist a number of models, languages, methods, and tools that support the specification and analysis of system requirements. One important class comprises graphical methods based on the concept of Petri nets. Due to the wide variety of applications, these methods are relevant also in research and applications outside the digital systems safety domain. The present report constitutes the first of three parts of a unified exposition of graphical methods based on the concept of Petri nets. The report provides an introduction to basic concepts of Petri nets and an overview of a wide variety of application areas. The second part of the trilogy will present a number of techniques and tools. The third part will focus on analysis. Petri nets have been proposed for a wide variety of applications, and new areas are considered as new challenges emerge from scientific, technological, and social developments. The wide variety of application areas reflects a broad interest in Petri nets, coming from diverse directions. Empirically, as well as theoretically, there are good reasons to claim that Petri nets are applicable for many different kinds of problems. What is common to the different applications and problems addressed is the need for a formalism that allows adequate representation of important system characteristics like concurrency, asyncronicity, distribution, parallelism, and non-determinism. Several of the references in the report discuss NPP-related applications, or applications with great potentials for technology transfer from other areas to the nuclear domain. (Author)

Turkey's net energy consumption

International Nuclear Information System (INIS)

Soezen, Adnan; Arcaklioglu, Erol; Oezkaymak, Mehmet

2005-01-01

The main goal of this study is to develop the equations for forecasting net energy consumption (NEC) using an artificial neural-network (ANN) technique in order to determine the future level of energy consumption in Turkey. In this study, two different models were used in order to train the neural network. In one of them, population, gross generation, installed capacity and years are used in the input layer of the network (Model 1). Other energy sources are used in input layer of network (Model 2). The net energy consumption is in the output layer for two models. Data from 1975 to 2003 are used for the training. Three years (1981, 1994 and 2003) are used only as test data to confirm this method. The statistical coefficients of multiple determinations (R 2 -value) for training data are equal to 0.99944 and 0.99913 for Models 1 and 2, respectively. Similarly, R 2 values for testing data are equal to 0.997386 and 0.999558 for Models 1 and 2, respectively. According to the results, the net energy consumption using the ANN technique has been predicted with acceptable accuracy. Apart from reducing the whole time required, with the ANN approach, it is possible to find solutions that make energy applications more viable and thus more attractive to potential users. It is also expected that this study will be helpful in developing highly applicable energy policies

Near-Net Forging Technology Demonstration Program

Science.gov (United States)

Hall, I. Keith

1996-01-01

Significant advantages in specific mechanical properties, when compared to conventional aluminum (Al) alloys, make aluminum-lithium (Al-Li) alloys attractive candidate materials for use in cryogenic propellant tanks and dry bay structures. However, the cost of Al-Li alloys is typically five times that of 2219 aluminum. If conventional fabrication processes are employed to fabricate launch vehicle structure, the material costs will restrict their utilization. In order to fully exploit the potential cost and performance benefits of Al-Li alloys, it is necessary that near-net manufacturing methods be developed to off-set or reduce raw material costs. Near-net forging is an advanced manufacturing method that uses elevated temperature metal movement (forging) to fabricate a single piece, near-net shape, structure. This process is termed 'near-net' because only a minimal amount of post-forge machining is required. The near-net forging process was developed to reduce the material scrap rate (buy-to-fly ratio) and fabrication costs associated with conventional manufacturing methods. The goal for the near-net forging process, when mature, is to achieve an overall cost reduction of approximately 50 percent compared with conventional manufacturing options for producing structures fabricated from Al-Li alloys. This NASA Marshall Space Flight Center (MSFC) sponsored program has been a part of a unique government / industry partnership, coordinated to develop and demonstrate near-net forging technology. The objective of this program was to demonstrate scale-up of the near-net forging process. This objective was successfully achieved by fabricating four integrally stiffened, 170- inch diameter by 20-inch tall, Al-Li alloy 2195, Y-ring adapters. Initially, two 2195 Al-Li ingots were converted and back extruded to produce four cylindrical blockers. Conventional ring rolling of the blockers was performed to produce ring preforms, which were then contour ring rolled to produce

DNA Methylation and Methylation Polymorphism in Genetically Stable In vitro Regenerates of Jatropha curcas L. Using Methylation-Sensitive AFLP Markers.

Science.gov (United States)

Rathore, Mangal S; Jha, Bhavanath

2016-03-01

The present investigation aimed to evaluate the degree and pattern of DNA methylation using methylation-sensitive AFLP (MS-AFLP) markers in genetically stable in vitro regenerates of Jatropha curcas L.. The genetically stable in vitro regenerates were raised through direct organogenesis via enhanced axillary shoot bud proliferation (Protocol-1) and in vitro-derived leaf regeneration (Protocol-2). Ten selective combinations of MS-AFLP primers produced 462 and 477 MS-AFLP bands in Protocol-1 (P-1) and Protocol-2 (P-2) regenerates, respectively. In P-1 regenerates, 15.8-31.17 % DNA was found methylated with an average of 25.24 %. In P-2 regenerates, 15.93-32.7 % DNA was found methylated with an average of 24.11 %. Using MS-AFLP in P-1 and P-2 regenerates, 11.52-25.53 % and 13.33-25.47 % polymorphism in methylated DNA was reported, respectively. Compared to the mother plant, P-1 regenerates showed hyper-methylation while P-2 showed hypo-methylation. The results clearly indicated alternation in degree and pattern of DNA methylation; hence, epigenetic instability in the genetically stable in vitro regenerates of J. curcas, developed so far using two different regeneration systems and explants of two different origins. The homologous nucleotide fragments in genomes of P-1 and P-2 regenerates showing methylation re-patterning might be involved in immediate adaptive responses and developmental processes through differential regulation of transcriptome under in vitro conditions.

Winnowing DNA for rare sequences: highly specific sequence and methylation based enrichment.

Directory of Open Access Journals (Sweden)

Jason D Thompson

Full Text Available Rare mutations in cell populations are known to be hallmarks of many diseases and cancers. Similarly, differential DNA methylation patterns arise in rare cell populations with diagnostic potential such as fetal cells circulating in maternal blood. Unfortunately, the frequency of alleles with diagnostic potential, relative to wild-type background sequence, is often well below the frequency of errors in currently available methods for sequence analysis, including very high throughput DNA sequencing. We demonstrate a DNA preparation and purification method that through non-linear electrophoretic separation in media containing oligonucleotide probes, achieves 10,000 fold enrichment of target DNA with single nucleotide specificity, and 100 fold enrichment of unmodified methylated DNA differing from the background by the methylation of a single cytosine residue.

Winnowing DNA for rare sequences: highly specific sequence and methylation based enrichment.

Science.gov (United States)

Thompson, Jason D; Shibahara, Gosuke; Rajan, Sweta; Pel, Joel; Marziali, Andre

2012-01-01

Rare mutations in cell populations are known to be hallmarks of many diseases and cancers. Similarly, differential DNA methylation patterns arise in rare cell populations with diagnostic potential such as fetal cells circulating in maternal blood. Unfortunately, the frequency of alleles with diagnostic potential, relative to wild-type background sequence, is often well below the frequency of errors in currently available methods for sequence analysis, including very high throughput DNA sequencing. We demonstrate a DNA preparation and purification method that through non-linear electrophoretic separation in media containing oligonucleotide probes, achieves 10,000 fold enrichment of target DNA with single nucleotide specificity, and 100 fold enrichment of unmodified methylated DNA differing from the background by the methylation of a single cytosine residue.

Analysis of DNA methylation in Arabidopsis thaliana based on methylation-sensitive AFLP markers.

Science.gov (United States)

Cervera, M T; Ruiz-García, L; Martínez-Zapater, J M

2002-12-01

AFLP analysis using restriction enzyme isoschizomers that differ in their sensitivity to methylation of their recognition sites has been used to analyse the methylation state of anonymous CCGG sequences in Arabidopsis thaliana. The technique was modified to improve the quality of fingerprints and to visualise larger numbers of scorable fragments. Sequencing of amplified fragments indicated that detection was generally associated with non-methylation of the cytosine to which the isoschizomer is sensitive. Comparison of EcoRI/ HpaII and EcoRI/ MspI patterns in different ecotypes revealed that 35-43% of CCGG sites were differentially digested by the isoschizomers. Interestingly, the pattern of digestion among different plants belonging to the same ecotype is highly conserved, with the rate of intra-ecotype methylation-sensitive polymorphisms being less than 1%. However, pairwise comparisons of methylation patterns between samples belonging to different ecotypes revealed differences in up to 34% of the methylation-sensitive polymorphisms. The lack of correlation between inter-ecotype similarity matrices based on methylation-insensitive or methylation-sensitive polymorphisms suggests that whatever the mechanisms regulating methylation may be, they are not related to nucleotide sequence variation.

Integrating livestock manure with a corn-soybean bioenergy cropping system improves short-term carbon sequestration rates and net global warming potential

International Nuclear Information System (INIS)

Thelen, K.D.; Fronning, B.E.; Kravchenko, A.; Min, D.H.; Robertson, G.P.

2010-01-01

Carbon cycling and the global warming potential (GWP) of bioenergy cropping systems with complete biomass removal are of agronomic and environmental concern. Corn growers who plan to remove corn stover as a feedstock for the emerging cellulosic ethanol industry will benefit from carbon amendments such as manure and compost, to replace carbon removed with the corn stover. The objective of this research was to determine the effect of beef cattle feedlot manure and composted dairy manure on short-term carbon sequestration rates and net global warming potential (GWP) in a corn-soybean rotation with complete corn-stover removal. Field experiments consisting of a corn-soybean rotation with whole-plant corn harvest, were conducted near East Lansing, MI over a three-year period beginning in 2002. Compost and manure amendments raised soil carbon (C) at a level sufficient to overcome the C debt associated with manure production, manure collection and storage, land application, and post-application field emissions. The net GWP in carbon dioxide equivalents for the manure and compost amended cropping systems was -934 and -784 g m -2 y -1 , respectively, compared to 52 g m -2 y -1 for the non-manure amended synthetic fertilizer check. This work further substantiates the environmental benefits associated with renewable fuels and demonstrates that with proper management, the integration of livestock manures in biofuel cropping systems can enhance greenhouse gas (GHG) remediation.

Are one or two dangerous? Methyl salicylate exposure in toddlers.

Science.gov (United States)

Davis, Jonathan E

2007-01-01

Serious toxicity can result from exposure to small amounts of methyl salicylate. Methyl salicylate is widely available as a component in many over-the-counter brands of creams, ointments, lotions, liniments and medicated oils intended for topical application to relieve musculoskeletal aches and pains. Among the most potent forms of methyl salicylate is oil of wintergreen (98% methyl salicylate). Other products with varying concentrations of methyl salicylate are ubiquitous throughout many parts of the world, including a number of products marketed as Asian herbal remedies. The toxic potential of all of these formulations is often underestimated by health care providers and the general public. A comprehensive review of the existing medical literature on methyl salicylate poisoning was performed, and data compiled over the past two decades by the American Association of Poison Control Centers (AAPCC) was examined. Methyl salicylate continues to be a relatively common source of pediatric exposures. Persistent reports of life-threatening and fatal toxicity were found. In children less than 6 years of age, a teaspoon (5 mL) or less of oil of wintergreen has been implicated in several well-documented deaths. More needs to be done to educate both health care providers and the general public regarding the dangers of these widely available formulations.

The application of methylation specific electrophoresis (MSE to DNA methylation analysis of the 5' CpG island of mucin in cancer cells

Directory of Open Access Journals (Sweden)

Yokoyama Seiya

2012-02-01

Full Text Available Abstract Background Methylation of CpG sites in genomic DNA plays an important role in gene regulation and especially in gene silencing. We have reported mechanisms of epigenetic regulation for expression of mucins, which are markers of malignancy potential and early detection of human neoplasms. Epigenetic changes in promoter regions appear to be the first step in expression of mucins. Thus, detection of promoter methylation status is important for early diagnosis of cancer, monitoring of tumor behavior, and evaluating the response of tumors to targeted therapy. However, conventional analytical methods for DNA methylation require a large amount of DNA and have low sensitivity. Methods Here, we report a modified version of the bisulfite-DGGE (denaturing gradient gel electrophoresis using a nested PCR approach. We designated this method as methylation specific electrophoresis (MSE. The MSE method is comprised of the following steps: (a bisulfite treatment of genomic DNA, (b amplification of the target DNA by a nested PCR approach and (c applying to DGGE. To examine whether the MSE method is able to analyze DNA methylation of mucin genes in various samples, we apply it to DNA obtained from state cell lines, ethanol-fixed colonic crypts and human pancreatic juices. Result The MSE method greatly decreases the amount of input DNA. The lower detection limit for distinguishing different methylation status is Conclusions The MSE method can provide a qualitative information of methylated sequence profile. The MSE method allows sensitive and specific analysis of the DNA methylation pattern of almost any block of multiple CpG sites. The MSE method can be applied to analysis of DNA methylation status in many different clinical samples, and this may facilitate identification of new risk markers.

Life cycle energy efficiency and potentials of biodiesel production from palm oil in Thailand

International Nuclear Information System (INIS)

Papong, Seksan; Chom-In, Tassaneewan; Noksa-nga, Soottiwan

2010-01-01

Biodiesel production from palm oil has been considered one of the most promising renewable resources for transportation fuel in Thailand. The objective of this study was to analyze the energy performance and potential of the palm oil methyl ester (PME) production in Thailand. The PME system was divided into four stages: the oil palm plantation, transportation, crude palm oil (CPO) production, and transesterification into biodiesel. The results showed that the highest fossil-based energy consumption was in the transesterification process, followed by the plantation, transportation, and CPO production. A net energy value and net energy ratio (NER) of 24.0 MJ/FU and 2.5, respectively, revealed that the PME system was quite energy efficient. In addition, if all the by-products from the CPO production (such as empty fruit branches, palm kernel shells, and biogas) were considered in terms of energy sources, the NER would be more than 3.0. The PME can be a viable substitute for diesel and can decrease the need for oil imports. Based on B100 demand in 2008, PME can be substituted for 478 million liters of diesel. Moreover, with palm oil output potential and B5 implementation, it can be substituted for 1134 million liters of diesel. (author)

The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma.

Directory of Open Access Journals (Sweden)

Fumiharu Ohka

Full Text Available Gliomas are the most frequently occurring primary brain tumor in the central nervous system of adults. Glioblastoma multiformes (GBMs, WHO grade 4 have a dismal prognosis despite the use of the alkylating agent, temozolomide (TMZ, and even low grade gliomas (LGGs, WHO grade 2 eventually transform to malignant secondary GBMs. Although GBM patients benefit from promoter hypermethylation of the O(6-methylguanine-DNA methyltransferase (MGMT that is the main determinant of resistance to TMZ, recent studies suggested that MGMT promoter methylation is of prognostic as well as predictive significance for the efficacy of TMZ. Glioma-CpG island methylator phenotype (G-CIMP in the global genome was shown to be a significant predictor of improved survival in patients with GBM. Collectively, we hypothesized that MGMT promoter methylation might reflect global DNA methylation. Additionally in LGGs, the significance of MGMT promoter methylation is still undetermined. In the current study, we aimed to determine the correlation between clinical, genetic, and epigenetic profiles including LINE-1 and different cancer-related genes and the clinical outcome in newly diagnosed 57 LGG and 54 GBM patients. Here, we demonstrated that (1 IDH1/2 mutation is closely correlated with MGMT promoter methylation and 1p/19q codeletion in LGGs, (2 LINE-1 methylation levels in primary and secondary GBMs are lower than those in LGGs and normal brain tissues, (3 LINE-1 methylation is proportional to MGMT promoter methylation in gliomas, and (4 higher LINE-1 methylation is a favorable prognostic factor in primary GBMs, even compared to MGMT promoter methylation. As a global DNA methylation marker, LINE-1 may be a promising marker in gliomas.

Methylation profiling in individuals with Russell-Silver syndrome.

Science.gov (United States)

Peñaherrera, Maria S; Weindler, Susanne; Van Allen, Margot I; Yong, Siu-Li; Metzger, Daniel L; McGillivray, Barbara; Boerkoel, Cornelius; Langlois, Sylvie; Robinson, Wendy P

2010-02-01

Russell-Silver syndrome (RSS) is a heterogeneous disorder associated with pre- and post-natal growth restriction and relative macrocephaly. Involvement of imprinted genes on both chromosome 7 and 11p15.5 has been reported. To further characterize the role of epimutations in RSS we evaluated the methylation status at both 11p15.5 imprinting control regions (ICRs): ICR1 associated with H19/IGF2 expression and ICR2 (KvDMR1) associated with CDKN1C expression in a series of 35 patients with RSS. We also evaluated methylation at the promoter regions of other imprinted genes involved in growth such as PLAGL1 (6q24), GCE (7q21), and PEG10 (7q21) in this series of 35 patients with RSS. Thirteen of the 35 patient samples, but none of 22 controls, showed methylation levels at ICR1 that were more than 2 SD below the mean for controls. Three RSS patients were highly methylated at the SCGE promoter, all of which were diagnosed with upd(7)mat. To identify further potential global methylation changes in RSS patients, a subset of 22 patients were evaluated at 1505 CpG sites by the Illumina GoldenGate methylation array. Among the few CpG sites displaying a significant difference between RSS patients and controls, was a CpG associated with the H19 promoter. No other sites associated with known imprinted genes were identified as abnormally methylated in RSS patients by this approach. While the association of hypomethylation of the H19/IGF2 ICR1 is clear, the continuous distribution of methylation values among the patients and controls complicates the establishment of clear cut-offs for clinical diagnosis. Copyright 2010 Wiley-Liss, Inc.

Recognition of methylated DNA through methyl-CpG binding domain proteins

DEFF Research Database (Denmark)

Zou, Xueqing; Ma, Wen; Solov'yov, Ilia

2012-01-01

DNA methylation is a key regulatory control route in epigenetics, involving gene silencing and chromosome inactivation. It has been recognized that methyl-CpG binding domain (MBD) proteins play an important role in interpreting the genetic information encoded by methylated DNA (mDNA). Although...... the function of MBD proteins has attracted considerable attention and is well characterized, the mechanism underlying mDNA recognition by MBD proteins is still poorly understood. In this article, we demonstrate that the methyl-CpG dinucleotides are recognized at the MBD-mDNA interface by two MBD arginines...

Changes in genomic methylation patterns during the formation of triploid asexual dandelion lineages

NARCIS (Netherlands)

Verhoeven, K.J.F.; Van Dijk, P.J.; Biere, A.

2010-01-01

DNA methylation is an epigenetic mechanism that has the potential to affect plant phenotypes and that is responsive to environmental and genomic stresses such as hybridization and polyploidization. We explored de novo methylation variation that arises during the formation of triploid asexual

Net-infiltration map of the Navajo Sandstone outcrop area in western Washington County, Utah

Science.gov (United States)

Heilweil, Victor M.; McKinney, Tim S.

2007-01-01

As populations grow in the arid southwestern United States and desert bedrock aquifers are increasingly targeted for future development, understanding and quantifying the spatial variability of net infiltration and recharge becomes critically important for inventorying groundwater resources and mapping contamination vulnerability. A Geographic Information System (GIS)-based model utilizing readily available soils, topographic, precipitation, and outcrop data has been developed for predicting net infiltration to exposed and soil-covered areas of the Navajo Sandstone outcrop of southwestern Utah. The Navajo Sandstone is an important regional bedrock aquifer. The GIS model determines the net-infiltration percentage of precipitation by using an empirical equation. This relation is derived from least squares linear regression between three surficial parameters (soil coarseness, topographic slope, and downgradient distance from outcrop) and the percentage of estimated net infiltration based on environmental tracer data from excavations and boreholes at Sand Hollow Reservoir in the southeastern part of the study area.Processed GIS raster layers are applied as parameters in the empirical equation for determining net infiltration for soil-covered areas as a percentage of precipitation. This net-infiltration percentage is multiplied by average annual Parameter-elevation Regressions on Independent Slopes Model (PRISM) precipitation data to obtain an infiltration rate for each model cell. Additionally, net infiltration on exposed outcrop areas is set to 10 percent of precipitation on the basis of borehole net-infiltration estimates. Soils and outcrop net-infiltration rates are merged to form a final map.Areas of low, medium, and high potential for ground-water recharge have been identified, and estimates of net infiltration range from 0.1 to 66 millimeters per year (mm/yr). Estimated net-infiltration rates of less than 10 mm/yr are considered low, rates of 10 to 50 mm/yr are

Complexity Metrics for Workflow Nets

DEFF Research Database (Denmark)

Lassen, Kristian Bisgaard; van der Aalst, Wil M.P.

2009-01-01

analysts have difficulties grasping the dynamics implied by a process model. Recent empirical studies show that people make numerous errors when modeling complex business processes, e.g., about 20 percent of the EPCs in the SAP reference model have design flaws resulting in potential deadlocks, livelocks......, etc. It seems obvious that the complexity of the model contributes to design errors and a lack of understanding. It is not easy to measure complexity, however. This paper presents three complexity metrics that have been implemented in the process analysis tool ProM. The metrics are defined...... for a subclass of Petri nets named Workflow nets, but the results can easily be applied to other languages. To demonstrate the applicability of these metrics, we have applied our approach and tool to 262 relatively complex Protos models made in the context of various student projects. This allows us to validate...

ROOT.NET: Using ROOT from .NET languages like C# and F#

Science.gov (United States)

Watts, G.

2012-12-01

ROOT.NET provides an interface between Microsoft's Common Language Runtime (CLR) and .NET technology and the ubiquitous particle physics analysis tool, ROOT. ROOT.NET automatically generates a series of efficient wrappers around the ROOT API. Unlike pyROOT, these wrappers are statically typed and so are highly efficient as compared to the Python wrappers. The connection to .NET means that one gains access to the full series of languages developed for the CLR including functional languages like F# (based on OCaml). Many features that make ROOT objects work well in the .NET world are added (properties, IEnumerable interface, LINQ compatibility, etc.). Dynamic languages based on the CLR can be used as well, of course (Python, for example). Additionally it is now possible to access ROOT objects that are unknown to the translation tool. This poster will describe the techniques used to effect this translation, along with performance comparisons, and examples. All described source code is posted on the open source site CodePlex.

ROOT.NET: Using ROOT from .NET languages like C and F

International Nuclear Information System (INIS)

Watts, G

2012-01-01

ROOT.NET provides an interface between Microsoft's Common Language Runtime (CLR) and .NET technology and the ubiquitous particle physics analysis tool, ROOT. ROOT.NET automatically generates a series of efficient wrappers around the ROOT API. Unlike pyROOT, these wrappers are statically typed and so are highly efficient as compared to the Python wrappers. The connection to .NET means that one gains access to the full series of languages developed for the CLR including functional languages like F (based on OCaml). Many features that make ROOT objects work well in the .NET world are added (properties, IEnumerable interface, LINQ compatibility, etc.). Dynamic languages based on the CLR can be used as well, of course (Python, for example). Additionally it is now possible to access ROOT objects that are unknown to the translation tool. This poster will describe the techniques used to effect this translation, along with performance comparisons, and examples. All described source code is posted on the open source site CodePlex.

Kismeth: Analyzer of plant methylation states through bisulfite sequencing

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Martienssen Robert A

2008-09-01

Full Text Available Abstract Background There is great interest in probing the temporal and spatial patterns of cytosine methylation states in genomes of a variety of organisms. It is hoped that this will shed light on the biological roles of DNA methylation in the epigenetic control of gene expression. Bisulfite sequencing refers to the treatment of isolated DNA with sodium bisulfite to convert unmethylated cytosine to uracil, with PCR converting the uracil to thymidine followed by sequencing of the resultant DNA to detect DNA methylation. For the study of DNA methylation, plants provide an excellent model system, since they can tolerate major changes in their DNA methylation patterns and have long been studied for the effects of DNA methylation on transposons and epimutations. However, in contrast to the situation in animals, there aren't many tools that analyze bisulfite data in plants, which can exhibit methylation of cytosines in a variety of sequence contexts (CG, CHG, and CHH. Results Kismeth http://katahdin.mssm.edu/kismeth is a web-based tool for bisulfite sequencing analysis. Kismeth was designed to be used with plants, since it considers potential cytosine methylation in any sequence context (CG, CHG, and CHH. It provides a tool for the design of bisulfite primers as well as several tools for the analysis of the bisulfite sequencing results. Kismeth is not limited to data from plants, as it can be used with data from any species. Conclusion Kismeth simplifies bisulfite sequencing analysis. It is the only publicly available tool for the design of bisulfite primers for plants, and one of the few tools for the analysis of methylation patterns in plants. It facilitates analysis at both global and local scales, demonstrated in the examples cited in the text, allowing dissection of the genetic pathways involved in DNA methylation. Kismeth can also be used to study methylation states in different tissues and disease cells compared to a reference sequence.

Identification of DNA methylation biomarkers from Infinium arrays

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Richard D Emes

2012-08-01

Full Text Available Epigenetic modifications of DNA, such as cytosine methylation are differentially abundant in diseases such as cancer. A goal for clinical research is finding sites that are differentially methylated between groups of samples to act as potential biomarkers for disease outcome. However, clinical samples are often limited in availability, represent a heterogeneous collection of cells or are of uncertain clinical class. Array based methods for identification of methylation provide a cost effective method to survey a proportion of the methylome at single base resolution. The Illumina Infinium array has become a popular and reliable high throughput method in this field and are proving useful in the identification of biomarkers for disease. Here, we compare a commonly used statistical test with a new intuitive and flexible computational approach to quickly detect differentially methylated sites. The method rapidly identifies and ranks candidate lists with greatest inter-group variability whilst controlling for intra-group variability. Intuitive and biologically relevant filters can be imposed to quickly identify sites and genes of interest.

DNA methylation patterns provide insight into epigenetic regulation in the Pacific oyster (Crassostrea gigas

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Gavery Mackenzie R

2010-08-01

Full Text Available Abstract Background DNA methylation is an epigenetic mechanism with important regulatory functions in animals. While the mechanism itself is evolutionarily ancient, the distribution and function of DNA methylation is diverse both within and among phylogenetic groups. Although DNA methylation has been well studied in mammals, there are limited data on invertebrates, particularly molluscs. Here we characterize the distribution and investigate potential functions of DNA methylation in the Pacific oyster (Crassostrea gigas. Results Methylation sensitive PCR and bisulfite sequencing PCR approaches were used to identify CpG methylation in C. gigas genes and demonstrated that this species possesses intragenic methylation. In silico analysis of CpGo/e ratios in publicly available sequence data suggests that DNA methylation is a common feature of the C. gigas genome, and that specific functional categories of genes have significantly different levels of methylation. Conclusions The Pacific oyster genome displays intragenic DNA methylation and contains genes necessary for DNA methylation in animals. Results of this investigation suggest that DNA methylation has regulatory functions in Crassostrea gigas, particularly in gene families that have inducible expression, including those involved in stress and environmental responses.

QML-AiNet: An immune network approach to learning qualitative differential equation models.

Science.gov (United States)

Pang, Wei; Coghill, George M

2015-02-01

In this paper, we explore the application of Opt-AiNet, an immune network approach for search and optimisation problems, to learning qualitative models in the form of qualitative differential equations. The Opt-AiNet algorithm is adapted to qualitative model learning problems, resulting in the proposed system QML-AiNet. The potential of QML-AiNet to address the scalability and multimodal search space issues of qualitative model learning has been investigated. More importantly, to further improve the efficiency of QML-AiNet, we also modify the mutation operator according to the features of discrete qualitative model space. Experimental results show that the performance of QML-AiNet is comparable to QML-CLONALG, a QML system using the clonal selection algorithm (CLONALG). More importantly, QML-AiNet with the modified mutation operator can significantly improve the scalability of QML and is much more efficient than QML-CLONALG.

Using Sulfate-Amended Sediment Slurry Batch Reactors to Evaluate Mercury Methylation

International Nuclear Information System (INIS)

Harmon, S.M.

2003-01-01

In the methylated form, mercury represents a concern to public health primarily through the consumption of contaminated fish tissue. Research conducted on the methylation of mercury strongly suggests the process is microbial in nature and facilitated principally by sulfate-reducing bacteria. This study addressed the potential for mercury methylation by varying sulfate treatments and wetland-based soil in microbial slurry reactors with available inorganic mercury. Under anoxic laboratory conditions conducive to growth of naturally occurring sulfate-reducing bacteria in the soil, it was possible to evaluate how various sulfate additions influenced the methylation of inorganic mercury added to overlying water. Treatments included sulfate amendments ranging FR-om 25 to 500 mg/L (0.26 to 5.2 mM) above the soil's natural sulfate level. This study also provided an assessment of mercury methylation relative to sulfate-reducing bacterial population growth and subsequent sulfide production. Mercury methylation in sulfate treatments did not exceed that of the non-amended control during a 35-day incubation. However, increases in methylmercury concentration were linked to bacterial growth and sulfate reduction. A time lag in methylation in the highest treatment correlated with an equivalent lag in bacterial growth

beta-Methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart.

Science.gov (United States)

DeGrado, T R; Holden, J E; Ng, C K; Raffel, D M; Gatley, S J

1989-01-01

The use of 15-p-iodophenyl-beta-methyl-pentadecanoic acid (beta Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both beta Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, beta Me-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond beta Me-IPPA-CoA in the oxidative pathway.

beta. -methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart

Energy Technology Data Exchange (ETDEWEB)

DeGrado, T.R.; Holden, J.E.; Ng, C.K.; Raffel, D.M.; Gatley, S.J.

1989-02-01

The use of 15-p-iodophenyl-..beta..-methyl-pentadecanoic acid (..beta..Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both ..beta..Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2(5(4-chlorophenyl)pentyl)oxirane-2-carboxylate (POCA). In contrast, ..beta..Me-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond ..beta..Me-IPPA-CoA in the oxidative pathway.

Dopamine transporter binding in rat striatum: a comparison of [O-methyl-{sup 11}C]{beta}-CFT and [N-methyl-{sup 11}C]{beta}-CFT

Energy Technology Data Exchange (ETDEWEB)

Yoder, Karmen K.; Hutchins, Gary D.; Mock, Bruce H.; Fei, Xiangshu; Winkle, Wendy L. [Department of Radiology, Indiana University School of Medicine, L3-208, Indianapolis, IN 46202 (United States); Gitter, Bruce D.; Territo, Paul R. [Lilly Center for Anatomical and Molecular Imaging, Integrative Biology Division, Lilly Research Laboratories, Greenfield, IN 46140 (United States); Zheng Qihuang [Department of Radiology, Indiana University School of Medicine, L3-208, Indianapolis, IN 46202 (United States)], E-mail: qzheng@iupui.edu

2009-01-15

Introduction: Positron emission tomography scanning with radiolabeled phenyltropane cocaine analogs is important for quantifying the in vivo density of monoamine transporters, including the dopamine transporter (DAT). [{sup 11}C]{beta}-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [{sup 11}C]{beta}-CFT is commonly labeled at the N-methyl position. However, labeling of [{sup 11}C]{beta}-CFT at the O-methyl position is a simpler procedure and results in a shorter synthesis time [desirable in small-animal studies, where specific activity (SA) is crucial]. In this study, we sought to validate that the O-methylated form of [{sup 11}C]{beta}-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form. Methods: Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-{sup 11}C]{beta}-CFT and once with [O-methyl-{sup 11}C]{beta}-CFT. DAT binding potentials (BP{identical_to}B'{sub avail}/K{sub d}) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function. Results: [N-Methyl-{sup 11}C]{beta}-CFT and [O-methyl-{sup 11}C]{beta}-CFT were synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical purity was >99%. SA at end of bombardment was 258{+-}30 GBq/{mu}mol. Average BP values for right and left striata with [N-methyl-{sup 11}C]{beta}-CFT were 1.16{+-}0.08 and 1.23{+-}0.14, respectively. BP values for [O-methyl-{sup 11}C]{beta}-CFT were 1.18{+-}0.08 (right) and 1.22{+-}0.16 (left). Paired t tests demonstrated that labeling position did not affect striatal DAT BP. Conclusions: These results suggest that [O-methyl-{sup 11}C]{beta}-CFT is quantitatively equivalent to [N-methyl-{sup 11}C]{beta}-CFT in the rat striatum.

Lysine methyltransferase G9a is not required for DNMT3A/3B anchoring to methylated nucleosomes and maintenance of DNA methylation in somatic cells

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Sharma Shikhar

2012-01-01

Full Text Available Abstract Background DNA methylation, histone modifications and nucleosome occupancy act in concert for regulation of gene expression patterns in mammalian cells. Recently, G9a, a H3K9 methyltransferase, has been shown to play a role in establishment of DNA methylation at embryonic gene targets in ES cells through recruitment of de novo DNMT3A/3B enzymes. However, whether G9a plays a similar role in maintenance of DNA methylation in somatic cells is still unclear. Results Here we show that G9a is not essential for maintenance of DNA methylation in somatic cells. Knockdown of G9a has no measurable effect on DNA methylation levels at G9a-target loci. DNMT3A/3B remain stably anchored to nucleosomes containing methylated DNA even in the absence of G9a, ensuring faithful propagation of methylated states in cooperation with DNMT1 through somatic divisions. Moreover, G9a also associates with nucleosomes in a DNMT3A/3B and DNA methylation-independent manner. However, G9a knockdown synergizes with pharmacologic inhibition of DNMTs resulting in increased hypomethylation and inhibition of cell proliferation. Conclusions Taken together, these data suggest that G9a is not involved in maintenance of DNA methylation in somatic cells but might play a role in re-initiation of de novo methylation after treatment with hypomethylating drugs, thus serving as a potential target for combinatorial treatments strategies involving DNMTs inhibitors.

Maternal intake of methyl-group donors affects DNA methylation of metabolic genes in infants.

Science.gov (United States)

Pauwels, Sara; Ghosh, Manosij; Duca, Radu Corneliu; Bekaert, Bram; Freson, Kathleen; Huybrechts, Inge; Langie, Sabine A S; Koppen, Gudrun; Devlieger, Roland; Godderis, Lode

2017-01-01

Maternal nutrition during pregnancy and infant nutrition in the early postnatal period (lactation) are critically involved in the development and health of the newborn infant. The Maternal Nutrition and Offspring's Epigenome (MANOE) study was set up to assess the effect of maternal methyl-group donor intake (choline, betaine, folate, methionine) on infant DNA methylation. Maternal intake of dietary methyl-group donors was assessed using a food-frequency questionnaire (FFQ). Before and during pregnancy, we evaluated maternal methyl-group donor intake through diet and supplementation (folic acid) in relation to gene-specific ( IGF2 DMR, DNMT1 , LEP , RXRA ) buccal epithelial cell DNA methylation in 6 months old infants ( n  = 114) via pyrosequencing. In the early postnatal period, we determined the effect of maternal choline intake during lactation (in mothers who breast-fed for at least 3 months) on gene-specific buccal DNA methylation ( n  = 65). Maternal dietary and supplemental intake of methyl-group donors (folate, betaine, folic acid), only in the periconception period, was associated with buccal cell DNA methylation in genes related to growth ( IGF2 DMR), metabolism ( RXRA ), and appetite control ( LEP ). A negative association was found between maternal folate and folic acid intake before pregnancy and infant LEP (slope = -1.233, 95% CI -2.342; -0.125, p  = 0.0298) and IGF2 DMR methylation (slope = -0.706, 95% CI -1.242; -0.107, p  = 0.0101), respectively. Positive associations were observed for maternal betaine (slope = 0.875, 95% CI 0.118; 1.633, p  = 0.0241) and folate (slope = 0.685, 95% CI 0.245; 1.125, p  = 0.0027) intake before pregnancy and RXRA methylation. Buccal DNMT1 methylation in the infant was negatively associated with maternal methyl-group donor intake in the first and second trimester of pregnancy and negatively in the third trimester. We found no clear association between maternal choline intake

INMARSAT-C SafetyNET

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Tsunamis 406 EPIRB's National Weather Service Marine Forecasts INMARSAT-C SafetyNET Marine Forecast Offices greater danger near shore or any shallow waters? NATIONAL WEATHER SERVICE PRODUCTS VIA INMARSAT-C SafetyNET Inmarsat-C SafetyNET is an internationally adopted, automated satellite system for promulgating

Abiotic Formation of Methyl Halides in the Terrestrial Environment

Science.gov (United States)

Keppler, F.

2011-12-01

Methyl chloride and methyl bromide are the most abundant chlorine and bromine containing organic compounds in the atmosphere. Since both compounds have relatively long tropospheric lifetimes they can effectively transport halogen atoms from the Earth's surface, where they are released, to the stratosphere and following photolytic oxidation form reactive halogen gases that lead to the chemical destruction of ozone. Methyl chloride and methyl bromide account for more than 20% of the ozone-depleting halogens delivered to the stratosphere and are predicted to grow in importance as the chlorine contribution to the stratosphere from anthropogenic CFCs decline. Today methyl chloride and methyl bromide originate mainly from natural sources with only a minor fraction considered to be of anthropogenic origin. However, until as recently as 2000 most of the methyl chloride and methyl bromide input to the atmosphere was considered to originate from the oceans, but investigations in recent years have clearly demonstrated that terrestrial sources such as biomass burning, wood-rotting fungi, coastal salt marshes, tropical vegetation and organic matter degradation must dominate the atmospheric budgets of these trace gases. However, many uncertainties still exist regarding strengths of both sources and sinks, as well as the mechanisms of formation of these naturally occurring halogenated gases. A better understanding of the atmospheric budget of both methyl chloride and methyl bromide is therefore required for reliable prediction of future ozone depletion. Biotic and abiotic methylation processes of chloride and bromide ion are considered to be the dominant pathways of formation of these methyl halides in nature. In this presentation I will focus on abiotic formation processes in the terrestrial environment and the potential parameters that control their emissions. Recent advances in our understanding of the abiotic formation pathway of methyl halides will be discussed. This will

Extensive Lysine Methylation in Hyperthermophilic Crenarchaea: Potential Implications for Protein Stability and Recombinant Enzymes

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Catherine H. Botting

2010-01-01

Full Text Available In eukarya and bacteria, lysine methylation is relatively rare and is catalysed by sequence-specific lysine methyltransferases that typically have only a single-protein target. Using RNA polymerase purified from the thermophilic crenarchaeum Sulfolobus solfataricus, we identified 21 methyllysines distributed across 9 subunits of the enzyme. The modified lysines were predominantly in α-helices and showed no conserved sequence context. A limited survey of the Thermoproteus tenax proteome revealed widespread modification with 52 methyllysines in 30 different proteins. These observations suggest the presence of an unusual lysine methyltransferase with relaxed specificity in the crenarchaea. Since lysine methylation is known to enhance protein thermostability, this may be an adaptation to a thermophilic lifestyle. The implications of this modification for studies and applications of recombinant crenarchaeal enzymes are discussed.

Quantum net dynamics

International Nuclear Information System (INIS)

Finkelstein, D.

1989-01-01

The quantum net unifies the basic principles of quantum theory and relativity in a quantum spacetime having no ultraviolet infinities, supporting the Dirac equation, and having the usual vacuum as a quantum condensation. A correspondence principle connects nets to Schwinger sources and further unifies the vertical structure of the theory, so that the functions of the many hierarchic levels of quantum field theory (predicate algebra, set theory, topology,hor-ellipsis, quantum dynamics) are served by one in quantum net dynamics

Protein methylation in pea chloroplasts

International Nuclear Information System (INIS)

Niemi, K.J.; Adler, J.; Selman, B.R.

1990-01-01

The methylation of chloroplast proteins has been investigated by incubating intact pea (Pisum sativum) chloroplasts with [ 3 H-methyl]-S-adenosylmethionine. Incubation in the light increases the amount of methylation in both the thylakoid and stromal fractions. Numerous thylakoid proteins serve as substrates for the methyltransfer reactions. Three of these thylakoid proteins are methylated to a significantly greater extent in the light than in the dark. The primary stromal polypeptide methylated is the large subunit of ribulose bisphosphate carboxylase/oxygenase. One other stromal polypeptide is also methylated much more in the light than in the dark. Two distinct types of protein methylation occur. One methylinkage is stable to basic conditions whereas a second type is base labile. The base-stable linkage is indicative of N-methylation of amino acid residues while base-lability is suggestive of carboxymethylation of amino acid residues. Labeling in the light increases the percentage of methylation that is base labile in the thylakoid fraction while no difference is observed in the amount of base-labile methylations in light-labeled and dark-labeled stromal proteins. Also suggestive of carboxymethylation is the detection of volatile [ 3 H]methyl radioactivity which increases during the labeling period and is greater in chloroplasts labeled in the light as opposed to being labeled in the dark; this implies in vivo turnover of the [ 3 H]methyl group

High-level Petri Nets

DEFF Research Database (Denmark)

various journals and collections. As a result, much of this knowledge is not readily available to people who may be interested in using high-level nets. Within the Petri net community this problem has been discussed many times, and as an outcome this book has been compiled. The book contains reprints...... of some of the most important papers on the application and theory of high-level Petri nets. In this way it makes the relevant literature more available. It is our hope that the book will be a useful source of information and that, e.g., it can be used in the organization of Petri net courses. To make......High-level Petri nets are now widely used in both theoretical analysis and practical modelling of concurrent systems. The main reason for the success of this class of net models is that they make it possible to obtain much more succinct and manageable descriptions than can be obtained by means...

Epigenomic profiling of DNA methylation in paired prostate cancer versus adjacent benign tissue.

Science.gov (United States)

Geybels, Milan S; Zhao, Shanshan; Wong, Chao-Jen; Bibikova, Marina; Klotzle, Brandy; Wu, Michael; Ostrander, Elaine A; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L

2015-12-01

Aberrant DNA methylation may promote prostate carcinogenesis. We investigated epigenome-wide DNA methylation profiles in prostate cancer (PCa) compared to adjacent benign tissue to identify differentially methylated CpG sites. The study included paired PCa and adjacent benign tissue samples from 20 radical prostatectomy patients. Epigenetic profiling was done using the Infinium HumanMethylation450 BeadChip. Linear models that accounted for the paired study design and False Discovery Rate Q-values were used to evaluate differential CpG methylation. mRNA expression levels of the genes with the most differentially methylated CpG sites were analyzed. In total, 2,040 differentially methylated CpG sites were identified in PCa versus adjacent benign tissue (Q-value Cancer Genome Atlas (TCGA) data provided confirmatory evidence for our findings. This study of PCa versus adjacent benign tissue showed many differentially methylated CpGs and regions in and outside gene promoter regions, which may potentially be used for the development of future epigenetic-based diagnostic tests or as therapeutic targets. © 2015 Wiley Periodicals, Inc.

Genome-wide methylation analysis identified sexually dimorphic methylated regions in hybrid tilapia

Science.gov (United States)

Wan, Zi Yi; Xia, Jun Hong; Lin, Grace; Wang, Le; Lin, Valerie C. L.; Yue, Gen Hua

2016-01-01

Sexual dimorphism is an interesting biological phenomenon. Previous studies showed that DNA methylation might play a role in sexual dimorphism. However, the overall picture of the genome-wide methylation landscape in sexually dimorphic species remains unclear. We analyzed the DNA methylation landscape and transcriptome in hybrid tilapia (Oreochromis spp.) using whole genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq). We found 4,757 sexually dimorphic differentially methylated regions (DMRs), with significant clusters of DMRs located on chromosomal regions associated with sex determination. CpG methylation in promoter regions was negatively correlated with the gene expression level. MAPK/ERK pathway was upregulated in male tilapia. We also inferred active cis-regulatory regions (ACRs) in skeletal muscle tissues from WGBS datasets, revealing sexually dimorphic cis-regulatory regions. These results suggest that DNA methylation contribute to sex-specific phenotypes and serve as resources for further investigation to analyze the functions of these regions and their contributions towards sexual dimorphisms. PMID:27782217

DNA sequence explains seemingly disordered methylation levels in partially methylated domains of Mammalian genomes.

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Dimos Gaidatzis

2014-02-01

Full Text Available For the most part metazoan genomes are highly methylated and harbor only small regions with low or absent methylation. In contrast, partially methylated domains (PMDs, recently discovered in a variety of cell lines and tissues, do not fit this paradigm as they show partial methylation for large portions (20%-40% of the genome. While in PMDs methylation levels are reduced on average, we found that at single CpG resolution, they show extensive variability along the genome outside of CpG islands and DNase I hypersensitive sites (DHS. Methylation levels range from 0% to 100% in a roughly uniform fashion with only little similarity between neighboring CpGs. A comparison of various PMD-containing methylomes showed that these seemingly disordered states of methylation are strongly conserved across cell types for virtually every PMD. Comparative sequence analysis suggests that DNA sequence is a major determinant of these methylation states. This is further substantiated by a purely sequence based model which can predict 31% (R(2 of the variation in methylation. The model revealed CpG density as the main driving feature promoting methylation, opposite to what has been shown for CpG islands, followed by various dinucleotides immediately flanking the CpG and a minor contribution from sequence preferences reflecting nucleosome positioning. Taken together we provide a reinterpretation for the nucleotide-specific methylation levels observed in PMDs, demonstrate their conservation across tissues and suggest that they are mainly determined by specific DNA sequence features.

The effects of rape residue mulching on net global warming potential and greenhouse gas intensity from no-tillage paddy fields.

Science.gov (United States)

Zhang, Zhi-Sheng; Cao, Cou-Gui; Guo, Li-Jin; Li, Cheng-Fang

2014-01-01

A field experiment was conducted to provide a complete greenhouse gas (GHG) accounting for global warming potential (GWP), net GWP, and greenhouse gas intensity (GHGI) from no-tillage (NT) paddy fields with different amounts of oilseed rape residue mulch (0, 3000, 4000, and 6000 kg dry matter (DM) ha(-1)) during a rice-growing season after 3 years of oilseed rape-rice cultivation. Residue mulching treatments showed significantly more organic carbon (C) density for the 0-20 cm soil layer at harvesting than no residue treatment. During a rice-growing season, residue mulching treatments sequestered significantly more organic C from 687 kg C ha(-1) season(-1) to 1654 kg C ha(-1) season(-1) than no residue treatment. Residue mulching significantly increased emissions of CO2 and N2O but decreased CH4 emissions. Residue mulching treatments significantly increased GWP by 9-30% but significantly decreased net GWP by 33-71% and GHGI by 35-72% relative to no residue treatment. These results suggest that agricultural economic viability and GHG mitigation can be achieved simultaneously by residue mulching on NT paddy fields in central China.

Aberrant TET1 Methylation Closely Associated with CpG Island Methylator Phenotype in Colorectal Cancer.

Science.gov (United States)

Ichimura, Norihisa; Shinjo, Keiko; An, Byonggu; Shimizu, Yasuhiro; Yamao, Kenji; Ohka, Fumiharu; Katsushima, Keisuke; Hatanaka, Akira; Tojo, Masayuki; Yamamoto, Eiichiro; Suzuki, Hiromu; Ueda, Minoru; Kondo, Yutaka

2015-08-01

Inactivation of methylcytosine dioxygenase, ten-eleven translocation (TET) is known to be associated with aberrant DNA methylation in cancers. Tumors with a CpG island methylator phenotype (CIMP), a distinct subgroup with extensive DNA methylation, show characteristic features in the case of colorectal cancer. The relationship between TET inactivation and CIMP in colorectal cancers is not well understood. The expression level of TET family genes was compared between CIMP-positive (CIMP-P) and CIMP-negative (CIMP-N) colorectal cancers. Furthermore, DNA methylation profiling, including assessment of the TET1 gene, was assessed in colorectal cancers, as well as colon polyps. The TET1 was silenced by DNA methylation in a subset of colorectal cancers as well as cell lines, expression of which was reactivated by demethylating agent. TET1 methylation was more frequent in CIMP-P (23/55, 42%) than CIMP-N (2/113, 2%, P CIMP-P, 16/40, 40%; CIMP-N, 2/24, 8%; P = 0.002), suggesting that TET1 methylation is an early event in CIMP tumorigenesis. TET1 methylation was significantly associated with BRAF mutation but not with hMLH1 methylation in the CIMP-P colorectal cancers. Colorectal cancers with TET1 methylation have a significantly greater number of DNA methylated genes and less pathological metastasis compared to those without TET1 methylation (P = 0.007 and 0.045, respectively). Our data suggest that TET1 methylation may contribute to the establishment of a unique pathway in respect to CIMP-mediated tumorigenesis, which may be incidental to hMLH1 methylation. In addition, our findings provide evidence that TET1 methylation may be a good biomarker for the prediction of metastasis in colorectal cancer. ©2015 American Association for Cancer Research.

Evaluating genome-wide DNA methylation changes in mice by Methylation Specific Digital Karyotyping

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Maruoka Shuichiro

2008-12-01

Full Text Available Abstract Background The study of genome-wide DNA methylation changes has become more accessible with the development of various array-based technologies though when studying species other than human the choice of applications are limited and not always within reach. In this study, we adapted and tested the applicability of Methylation Specific Digital Karyotyping (MSDK, a non-array based method, for the prospective analysis of epigenetic changes after perinatal nutritional modifications in a mouse model of allergic airway disease. MSDK is a sequenced based method that allows a comprehensive and unbiased methylation profiling. The method generates 21 base pairs long sequence tags derived from specific locations in the genome. The resulting tag frequencies determine in a quantitative manner the methylation level of the corresponding loci. Results Genomic DNA from whole lung was isolated and subjected to MSDK analysis using the methylation-sensitive enzyme Not I as the mapping enzyme and Nla III as the fragmenting enzyme. In a pair wise comparison of the generated mouse MSDK libraries we identified 158 loci that are significantly differentially methylated (P-value = 0.05 after perinatal dietary changes in our mouse model. Quantitative methylation specific PCR and sequence analysis of bisulfate modified genomic DNA confirmed changes in methylation at specific loci. Differences in genomic MSDK tag counts for a selected set of genes, correlated well with changes in transcription levels as measured by real-time PCR. Furthermore serial analysis of gene expression profiling demonstrated a dramatic difference in expressed transcripts in mice exposed to perinatal nutritional changes. Conclusion The genome-wide methylation survey applied in this study allowed for an unbiased methylation profiling revealing subtle changes in DNA methylation in mice maternally exposed to dietary changes in methyl-donor content. The MSDK method is applicable for mouse models

Divergence of gene body DNA methylation and evolution of plant duplicate genes.

Directory of Open Access Journals (Sweden)

Jun Wang

Full Text Available 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.

Planning of nets

International Nuclear Information System (INIS)

Carberry, M

1996-01-01

The paper is about the planning of nets in areas of low density like it is the case of the rural areas. The author includes economic and technological aspects, planning of nets, demands and management among others

Catalytic hydrodeoxygenation of methyl-substituted phenols: correlations of kinetic parameters with molecular properties.

Science.gov (United States)

Massoth, F E; Politzer, P; Concha, M C; Murray, J S; Jakowski, J; Simons, Jack

2006-07-27

The hydrodeoxygenation of methyl-substituted phenols was carried out in a flow microreactor at 300 degrees C and 2.85 MPa hydrogen pressure over a sulfided CoMo/Al(2)O(3) catalyst. The primary reaction products were methyl-substituted benzene, cyclohexene, cyclohexane, and H(2)O. Analysis of the results suggests that two independent reaction paths are operative, one leading to aromatics and the other to partially or completely hydrogenated cyclohexanes. The reaction data were analyzed using Langmuir-Hinshelwood kinetics to extract the values of the reactant-to-catalyst adsorption constant and of the rate constants characterizing the two reaction paths. The adsorption constant was found to be the same for both reactions, suggesting that a single catalytic site center is operative in both reactions. Ab initio electronic structure calculations were used to evaluate the electrostatic potentials and valence orbital ionization potentials for all of the substituted phenol reactants. Correlations were observed between (a) the adsorption constant and the two reaction rate constants measured for various methyl-substitutions and (b) certain moments of the electrostatic potentials and certain orbitals' ionization potentials of the isolated phenol molecules. On the basis of these correlations to intrinsic reactant-molecule properties, a reaction mechanism is proposed for each pathway, and it is suggested that the dependencies of adsorption and reaction rates upon methyl-group substitution are a result of the substituents' effects on the electrostatic potential and orbitals rather than geometric (steric) effects.

A nonparametric Bayesian approach for clustering bisulfate-based DNA methylation profiles.

Science.gov (United States)

Zhang, Lin; Meng, Jia; Liu, Hui; Huang, Yufei

2012-01-01

DNA methylation occurs in the context of a CpG dinucleotide. It is an important epigenetic modification, which can be inherited through cell division. The two major types of methylation include hypomethylation and hypermethylation. Unique methylation patterns have been shown to exist in diseases including various types of cancer. DNA methylation analysis promises to become a powerful tool in cancer diagnosis, treatment and prognostication. Large-scale methylation arrays are now available for studying methylation genome-wide. The Illumina methylation platform simultaneously measures cytosine methylation at more than 1500 CpG sites associated with over 800 cancer-related genes. Cluster analysis is often used to identify DNA methylation subgroups for prognosis and diagnosis. However, due to the unique non-Gaussian characteristics, traditional clustering methods may not be appropriate for DNA and methylation data, and the determination of optimal cluster number is still problematic. A Dirichlet process beta mixture model (DPBMM) is proposed that models the DNA methylation expressions as an infinite number of beta mixture distribution. The model allows automatic learning of the relevant parameters such as the cluster mixing proportion, the parameters of beta distribution for each cluster, and especially the number of potential clusters. Since the model is high dimensional and analytically intractable, we proposed a Gibbs sampling "no-gaps" solution for computing the posterior distributions, hence the estimates of the parameters. The proposed algorithm was tested on simulated data as well as methylation data from 55 Glioblastoma multiform (GBM) brain tissue samples. To reduce the computational burden due to the high data dimensionality, a dimension reduction method is adopted. The two GBM clusters yielded by DPBMM are based on data of different number of loci (P-value < 0.1), while hierarchical clustering cannot yield statistically significant clusters.

Programming NET Web Services

CERN Document Server

Ferrara, Alex

2007-01-01

Web services are poised to become a key technology for a wide range of Internet-enabled applications, spanning everything from straight B2B systems to mobile devices and proprietary in-house software. While there are several tools and platforms that can be used for building web services, developers are finding a powerful tool in Microsoft's .NET Framework and Visual Studio .NET. Designed from scratch to support the development of web services, the .NET Framework simplifies the process--programmers find that tasks that took an hour using the SOAP Toolkit take just minutes. Programming .NET

Preclinical and clinical evaluation of O-[11C]methyl-L-tyrosine for tumor imaging by positron emission tomography

International Nuclear Information System (INIS)

Ishiwata, Kiichi; Tsukada, Hideo; Kubota, Kazuo; Nariai, Tadashi; Harada, Norihiro; Kawamura, Kazunori; Kimura, Yuichi; Oda, Keiichi; Iwata, Ren; Ishii, Kenji

2005-01-01

We performed preclinical and clinical studies of O-[ 11 C]methyl-L-tyrosine, a potential tracer for imaging amino acid transport of tumors by positron emission tomography (PET). Examinations of the radiation-absorbed dose by O-[ 11 C]methyl-L-tyrosine and the acute toxicity and mutagenicity of O-methyl-L-tyrosine showed suitability of the tracer for clinical use. The whole-body imaging of monkeys and healthy humans by PET showed low uptake of O-[ 11 C]methyl-L-tyrosine in all normal organs except for the urinary track and bladder, suggesting that the O-[ 11 C]methyl-L-tyrosine PET has the potential for tumor imaging in the whole-body. Finally, the brain tumor imaging was preliminarily demonstrated

SchNet - A deep learning architecture for molecules and materials

Science.gov (United States)

Schütt, K. T.; Sauceda, H. E.; Kindermans, P.-J.; Tkatchenko, A.; Müller, K.-R.

2018-06-01

Deep learning has led to a paradigm shift in artificial intelligence, including web, text, and image search, speech recognition, as well as bioinformatics, with growing impact in chemical physics. Machine learning, in general, and deep learning, in particular, are ideally suitable for representing quantum-mechanical interactions, enabling us to model nonlinear potential-energy surfaces or enhancing the exploration of chemical compound space. Here we present the deep learning architecture SchNet that is specifically designed to model atomistic systems by making use of continuous-filter convolutional layers. We demonstrate the capabilities of SchNet by accurately predicting a range of properties across chemical space for molecules and materials, where our model learns chemically plausible embeddings of atom types across the periodic table. Finally, we employ SchNet to predict potential-energy surfaces and energy-conserving force fields for molecular dynamics simulations of small molecules and perform an exemplary study on the quantum-mechanical properties of C20-fullerene that would have been infeasible with regular ab initio molecular dynamics.

Integrating livestock manure with a corn-soybean bioenergy cropping system improves short-term carbon sequestration rates and net global warming potential

Energy Technology Data Exchange (ETDEWEB)

Thelen, K.D.; Fronning, B.E.; Kravchenko, A.; Min, D.H.; Robertson, G.P. [Michigan State University, East Lansing, MI 48824 (United States)

2010-07-15

Carbon cycling and the global warming potential (GWP) of bioenergy cropping systems with complete biomass removal are of agronomic and environmental concern. Corn growers who plan to remove corn stover as a feedstock for the emerging cellulosic ethanol industry will benefit from carbon amendments such as manure and compost, to replace carbon removed with the corn stover. The objective of this research was to determine the effect of beef cattle feedlot manure and composted dairy manure on short-term carbon sequestration rates and net global warming potential (GWP) in a corn-soybean rotation with complete corn-stover removal. Field experiments consisting of a corn-soybean rotation with whole-plant corn harvest, were conducted near East Lansing, MI over a three-year period beginning in 2002. Compost and manure amendments raised soil carbon (C) at a level sufficient to overcome the C debt associated with manure production, manure collection and storage, land application, and post-application field emissions. The net GWP in carbon dioxide equivalents for the manure and compost amended cropping systems was -934 and -784 g m{sup -2} y{sup -1}, respectively, compared to 52 g m{sup -2} y{sup -1} for the non-manure amended synthetic fertilizer check. This work further substantiates the environmental benefits associated with renewable fuels and demonstrates that with proper management, the integration of livestock manures in biofuel cropping systems can enhance greenhouse gas (GHG) remediation. (author)

Observation on the biodegradation and bioremediation potential of methyl t-butyl ether

International Nuclear Information System (INIS)

Salanitro, J.; Wisniewski, H.; McAllister, P.

1995-01-01

There have been few reports documenting evidence for the biodegradation of the fuel oxygenate alkyl ether, methyl t-butyl ether (MTBE) in groundwater, soils, and biosludges. Partial (or complete) microbial breakdown of MTBE has been observed in an anaerobic subsoil, a river sediment under methanogenic conditions, a cyclohexane-degrading bacterial consortium and a pure culture of the methylotroph, Methylisnus trichosporium OB3b. An aerobic bacterial enrichment (BC-1) isolated from an industrial transient (non-accumulating) metabolic intermediate. The studies suggest that MTBE is cleaved by BC-1 to TBA which is then metabolized via isopropanol and acetone. There is little information on the occurrence of indigenous MTBE-degraders in groundwater, soils and activated sludges. Preliminary evidence has been obtained, however, from a marketing terminal groundwater site that naturally-occurring MTBE-degraders are present in some monitoring wells. Microcosm experiments with groundwater from this aquifer show that MTBE is aerobically degraded (no TBA formed) with a first-order decay rate (0.31/day) similar to BTEX. Also, MTBE did not inhibit the intrinsic biodegradation potential of BTEX in groundwater microcosms. In summary, the data presented indicate that MTBE biodegradation has been observed in some environmental media. Further work is needed to assess the feasibility of using indigenous or derived aerobic and anaerobic MTBE-degrading cultures for treating fuel ethers in groundwaters or wastewater with in-situ or ex-situ bioremediation technologies

Methylation signature of lymph node metastases in breast cancer patients

International Nuclear Information System (INIS)

Barekati, Zeinab; Radpour, Ramin; Lu, Qing; Bitzer, Johannes; Zheng, Hong; Toniolo, Paolo; Lenner, Per; Zhong, Xiao Yan

2012-01-01

Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers. The quantitative methylation analysis was performed using the SEQUENOM’s EpiTYPER™ assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The quantitative DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for the APC, BIN1, BMP6, BRCA1, CST6, ESR-b, P16, PTEN and TIMP3 promoter regions (P<0.05). Among those candidate methylated genes, APC, BMP6, BRCA1 and P16 displayed higher methylation proportion in the matched lymph node metastasis than that found in the normal tissue (P<0.05). The pathway analysis revealed that BMP6, BRCA1 and P16 have a role in prevention of neoplasm metastasis. The results of the present study showed methylation heterogeneity between primary tumors and metastatic lesion. The contribution of aberrant methylation alterations of BMP6, BRCA1 and P16 genes in lymph node metastasis might provide a further clue to establish useful biomarkers for screening metastasis

Ancestry dependent DNA methylation and influence of maternal nutrition.

Directory of Open Access Journals (Sweden)

Khyobeni Mozhui

Full Text Available There is extensive variation in DNA methylation between individuals and ethnic groups. These differences arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we compare genome-wide DNA methylation in neonatal cord blood from African American (AA; N = 112 and European American (EA; N = 91 participants of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood. Our goal is to determine if there are replicable ancestry-specific methylation patterns that may implicate risk factors for diseases that have differential prevalence between populations. To identify the most robust ancestry-specific CpG sites, we replicate our results in lymphoblastoid cell lines from Yoruba African and CEPH European panels of HapMap. We also evaluate the influence of maternal nutrition--specifically, plasma levels of vitamin D and folate during pregnancy--on methylation in newborns. We define stable ancestry-dependent methylation of genes that include tumor suppressors and cell cycle regulators (e.g., APC, BRCA1, MCC. Overall, there is lower global methylation in African ancestral groups. Plasma levels of 25-hydroxy vitamin D are also considerably lower among AA mothers and about 60% of AA and 40% of EA mothers have concentrations below 20 ng/ml. Using a weighted correlation analysis, we define a network of CpG sites that is jointly modulated by ancestry and maternal vitamin D. Our results show that differences in DNA methylation patterns are remarkably stable and maternal micronutrients can exert an influence on the child epigenome.

From intervention to impact: modelling the potential mortality impact achievable by different long-lasting, insecticide-treated net delivery strategies

Directory of Open Access Journals (Sweden)

Okell Lucy C

2012-09-01

Full Text Available Abstract Background The current target of universal access to long-lasting, insecticide-treated nets (LLIN is 80% coverage to reduce malaria deaths by 75% by 2015. So far, campaigns have been the main channel for large-scale delivery of LLINs, however the World Health Organization has recommended that equal priority should be given to delivery via routine antenatal care (ANC and immunization systems (EPI to target pregnant women and children from birth. These various channels of LLIN delivery are targeted to children of different ages. Since risk of mortality varies with child age and LLIN effectiveness declines with net age, it was hypothesized that the age at which a child receives a new LLIN, and therefore the delivery channel, is important in optimizing the health impact of a net. Methods A simple dynamic mathematical model was developed of delivery and impact of LLINs among children under five years of age and their household members, incorporating data on age-specific malaria death rates, net use by household structure, and net efficacy over time. Results The presented analysis finds that supplementing a universal mass campaign with extra ANC delivery would achieve a 1.4 times higher mortality reduction than campaign delivery alone, reflecting that children born in the years between campaigns would otherwise have access to old nets or no nets at an age of high risk. The relative advantage of supplementary ANC delivery is still present though smaller if malaria transmission levels are lower or if there is a strong mass effect achieved by mass campaigns. Conclusion These results indicate that LLIN delivery policies must take into account the age of greatest malaria risk. Emphasis should be placed on supporting routine delivery of LLINs to young children as well as campaigns.

The analysis of methyl salicylate and salicylic acid from Chinese herbal medicine ingestion.

Science.gov (United States)

Parker, Dawn; Martinez, Christina; Stanley, Christina; Simmons, Jerry; McIntyre, Iain M

2004-04-01

This paper presents a multi-drug fatality in which methyl salicylate was ingested. It is presented to inform the toxicological community that a particularly expeditious method of detection for methyl salicylate exists. Previously published methods for the analysis of methyl salicylate include a gas chromatographic-mass spectrometric method and an alkaline/acidic extraction followed by high-performance liquid chromatographic (HPLC) analysis. This article describes a method for analyzing methyl salicylate using HPLC, in which a simple, rapid extraction procedure is used. Using a previously published HPLC method, methyl salicylate and salicylic acid were easily identified in biological specimens. Methyl salicylate and salicylic acid were detected using an extraction solution of acetonitrile coupled with internal standard and then analyzed by HPLC-diode-array detection. Because of its concentrated liquid form, methyl salicylate ingestion can cause rapid onset salicylate toxicity. As the potentially fatal methyl salicylate forms are readily available and easily found on drugstore shelves, the need to rapidly detect and quantitate salicylic acid concentrations that are due to methyl salicylate ingestion may arise. In the case presented, the peripheral blood concentration of salicylic acid from methyl salicylate ingestion was 320 mg/L, and the concentration in gastric contents was 820 mg. It alone was not the cause of death, however. The discovery of the ability to detect and quantitate methyl salicylate was due to its suspected ingestion.

MethylMeter(®): bisulfite-free quantitative and sensitive DNA methylation profiling and mutation detection in FFPE samples.

Science.gov (United States)

McCarthy, David; Pulverer, Walter; Weinhaeusel, Andreas; Diago, Oscar R; Hogan, Daniel J; Ostertag, Derek; Hanna, Michelle M

2016-06-01

Development of a sensitive method for DNA methylation profiling and associated mutation detection in clinical samples. Formalin-fixed and paraffin-embedded tumors received by clinical laboratories often contain insufficient DNA for analysis with bisulfite or methylation sensitive restriction enzymes-based methods. To increase sensitivity, methyl-CpG DNA capture and Coupled Abscription PCR Signaling detection were combined in a new assay, MethylMeter(®). Gliomas were analyzed for MGMT methylation, glioma CpG island methylator phenotype and IDH1 R132H. MethylMeter had 100% assay success rate measuring all five biomarkers in formalin-fixed and paraffin-embedded tissue. MGMT methylation results were supported by survival and mRNA expression data. MethylMeter is a sensitive and quantitative method for multitarget DNA methylation profiling and associated mutation detection. The MethylMeter-based GliomaSTRAT assay measures methylation of four targets and one mutation to simultaneously grade gliomas and predict their response to temozolomide. This information is clinically valuable in management of gliomas.

Data error effects on net radiation and evapotranspiration estimation

International Nuclear Information System (INIS)

Llasat, M.C.; Snyder, R.L.

1998-01-01

The objective of this paper is to evaluate the potential error in estimating the net radiation and reference evapotranspiration resulting from errors in the measurement or estimation of weather parameters. A methodology for estimating the net radiation using hourly weather variables measured at a typical agrometeorological station (e.g., solar radiation, temperature and relative humidity) is presented. Then the error propagation analysis is made for net radiation and for reference evapotranspiration. Data from the Raimat weather station, which is located in the Catalonia region of Spain, are used to illustrate the error relationships. The results show that temperature, relative humidity and cloud cover errors have little effect on the net radiation or reference evapotranspiration. A 5°C error in estimating surface temperature leads to errors as big as 30 W m −2 at high temperature. A 4% solar radiation (R s ) error can cause a net radiation error as big as 26 W m −2 when R s ≈ 1000 W m −2 . However, the error is less when cloud cover is calculated as a function of the solar radiation. The absolute error in reference evapotranspiration (ET o ) equals the product of the net radiation error and the radiation term weighting factor [W = Δ(Δ1+γ)] in the ET o equation. Therefore, the ET o error varies between 65 and 85% of the R n error as air temperature increases from about 20° to 40°C. (author)

New Synthesis, Structure and Analgesic Properties of Methyl 1-R-4-Methyl-2,2-Dioxo-1H-2λ6,1-Benzothiazine-3-Carboxylates

Directory of Open Access Journals (Sweden)

Liliana Azotla-Cruz

2017-01-01

Full Text Available According to the principles of the methodology of bioisosteric replacements a series of methyl 1-R-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates has been obtained as potential analgesics. In addition, a fundamentally new strategy for the synthesis of compounds of this chemical class involving the introduction of N-alkyl substituent at the final stage in 2,1-benzothiazine nucleus already formed has been proposed. Using nuclear magnetic resonance (NMR spectroscopy, mass spectrometry and X-ray diffraction analysis it has been proven that in the DMSO/K2CO3 system the reaction of methyl 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate and alkyl halides leads to formation of N-substituted derivatives with good yields regardless of the structure of the alkylating agent. The peculiarities of NMR (1Н and 13С spectra of the compounds synthesized, their mass spectrometric behavior and the spatial structure are discussed. In N-benzyl derivative the ability to form a monosolvate with methanol has been found. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick it has been determined that replacement of 4-ОН-group in methyl 1-R-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates for the methyl group is actually bioisosteric since all methyl 1-R-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates synthesized demonstrated a statistically significant analgesic effect. The majority of the substances can inhibit the thermal pain response much more effective than piroxicam in the same dose. Under the same conditions as an analgesic the N-methyl-substituted analog exceeds not only piroxicam, but more active meloxicam as well. Therefore, it deserves in-depth biological studies on other experimental models.

Game Coloured Petri Nets

DEFF Research Database (Denmark)

Westergaard, Michael

2006-01-01

This paper introduces the notion of game coloured Petri nets. This allows the modeler to explicitly model what parts of the model comprise the modeled system and what parts are the environment of the modeled system. We give the formal definition of game coloured Petri nets, a means of reachability...... analysis of this net class, and an application of game coloured Petri nets to automatically generate easy-to-understand visualizations of the model by exploiting the knowledge that some parts of the model are not interesting from a visualization perspective (i.e. they are part of the environment...

Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation.

Science.gov (United States)

Yehuda, Rachel; Daskalakis, Nikolaos P; Bierer, Linda M; Bader, Heather N; Klengel, Torsten; Holsboer, Florian; Binder, Elisabeth B

2016-09-01

The involvement of epigenetic mechanisms in intergenerational transmission of stress effects has been demonstrated in animals but not in humans. Cytosine methylation within the gene encoding for FK506 binding protein 5 (FKBP5) was measured in Holocaust survivors (n = 32), their adult offspring (n = 22), and demographically comparable parent (n = 8) and offspring (n = 9) control subjects, respectively. Cytosine-phosphate-guanine sites for analysis were chosen based on their spatial proximity to the intron 7 glucocorticoid response elements. Holocaust exposure had an effect on FKBP5 methylation that was observed in exposed parents as well in their offspring. These effects were observed at bin 3/site 6. Interestingly, in Holocaust survivors, methylation at this site was higher in comparison with control subjects, whereas in Holocaust offspring, methylation was lower. Methylation levels for exposed parents and their offspring were significantly correlated. In contrast to the findings at bin 3/site 6, offspring methylation at bin 2/sites 3 to 5 was associated with childhood physical and sexual abuse in interaction with an FKBP5 risk allele previously associated with vulnerability to psychological consequences of childhood adversity. The findings suggest the possibility of site specificity to environmental influences, as sites in bins 3 and 2 were differentially associated with parental trauma and the offspring's own childhood trauma, respectively. FKBP5 methylation averaged across the three bins examined was associated with wake-up cortisol levels, indicating functional relevance of the methylation measures. This is the first demonstration of an association of preconception parental trauma with epigenetic alterations that is evident in both exposed parent and offspring, providing potential insight into how severe psychophysiological trauma can have intergenerational effects. Published by Elsevier Inc.

Insight into the theoretical and experimental studies of 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone N(4)-methyl-N(4)- phenylthiosemicarbazone - A potential NLO material

Science.gov (United States)

Sangeetha, K. G.; Aravindakshan, K. K.; Safna Hussan, K. P.

2017-12-01

The synthesis, geometrical parameters, spectroscopic studies, optimised molecular structure, vibrational analysis, Mullikan population analysis, MEP, NBO, frontier molecular orbitals and NLO effects of 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone N-(4)-methyl-N-(4)-phenylthiosemicarbazone, C25H23N5OS (L1) have been communicated in this paper. A combined experimental and theoretical approach was used to explore the structure and properties of the compound. For computational studies, Gaussian 09 program was used. Starting geometry of molecule was taken from X-ray refinement data and has been optimized by using DFT (B3LYP) method with the 6-31+G (d, p) basis sets. NBO analysis gave insight into the strongly delocalized structure, responsible for the nonlinearity and hence the stability of the molecule. Frontier molecular orbitals have been defined to forecast the global reactivity descriptors of L1. The computed first-order hyperpolarizability (β) of the compound is 2 times higher than that of urea and this account for its nonlinear optical property. Simultaneously, a molecular docking study of the compound was performed using GLIDE Program. For this, three biological enzymes, histone deacetylase, ribonucleotide reductase and DNA methyl transferase, were selected as receptor molecules.

Differential DNA Methylation Patterns Are Related to Phellogen Origin and Quality of Quercus suber Cork.

Science.gov (United States)

Inácio, Vera; Barros, Pedro M; Costa, Augusta; Roussado, Cristóvão; Gonçalves, Elsa; Costa, Rita; Graça, José; Oliveira, M Margarida; Morais-Cecílio, Leonor

2017-01-01

DNA methylation is thought to influence Quercus suber cork quality, which is the main constraint for its economic valorisation. However, a deep knowledge of the cytosine methylation patterns disclosing the epigenetic variability of trees with different cork quality types is totally missing. This study investigates the hypothesis that variations in DNA methylation contribute to differences in cork cellular characteristics directly related to original or traumatic phellogen activity. We used MSAPs (Methylation Sensitive Amplified Polymorphism) to assess DNA methylation patterns of cork and leaf tissues of Q. suber adult trees growing in three cork oak stands. The relationship between the detected polymorphisms and the diversity of cork quality traits was explored by a marker-trait analysis focusing on the most relevant quality characteristics. Populations differed widely in cork quality, but only slightly in degree of epigenetic differentiation. Four MSAP markers (1.3% of the total) were significantly associated with the most noteworthy quality traits: wood inclusions (nails) and porosity. This evidence supports the potential role of cytosine methylation in the modulation of differential phellogen activity either involved in localized cell death or in pore production, resulting in different cork qualities. Although, the underlying basis of the methylation polymorphism of loci affecting cork quality traits remain unclear, the disclosure of markers statistically associated with cork quality strengthens the potential role of DNA methylation in the regulation of these traits, namely at the phellogen level.

DNA Methylation and Gene Expression Profiling of Ewing Sarcoma Primary Tumors Reveal Genes That Are Potential Targets of Epigenetic Inactivation

Directory of Open Access Journals (Sweden)

Nikul Patel

2012-01-01

Full Text Available The role of aberrant DNA methylation in Ewing sarcoma is not completely understood. The methylation status of 503 genes in 52 formalin-fixed paraffin-embedded EWS tumors and 3 EWS cell lines was compared to human mesenchymal stem cell primary cultures (hMSCs using bead chip methylation analysis. Relative expression of methylated genes was assessed in 5-Aza-2-deoxycytidine-(5-AZA-treated EWS cell lines and in a cohort of primary EWS samples and hMSCs by gene expression and quantitative RT-PCR. 129 genes demonstrated statistically significant hypermethylation in EWS tumors compared to hMSCs. Thirty-six genes were profoundly methylated in EWS and unmethylated in hMSCs. 5-AZA treatment of EWS cell lines resulted in upregulation of expression of hundreds of genes including 162 that were increased by at least 2-fold. The expression of 19 of 36 candidate hypermethylated genes was increased following 5-AZA. Analysis of gene expression from an independent cohort of tumors confirmed decreased expression of six of nineteen hypermethylated genes (AXL, COL1A1, CYP1B1, LYN, SERPINE1, and VCAN. Comparing gene expression and DNA methylation analyses proved to be an effective way to identify genes epigenetically regulated in EWS. Further investigation is ongoing to elucidate the role of these epigenetic alterations in EWS pathogenesis.

Coloured Petri Nets

DEFF Research Database (Denmark)

Jensen, Kurt

1991-01-01

This paper describes how Coloured Petri Nets (CP-nets) have been developed — from being a promising theoretical model to being a full-fledged language for the design, specification, simulation, validation and implementation of large software systems (and other systems in which human beings and...

Net zero water

CSIR Research Space (South Africa)

Lindeque, M

2013-01-01

Full Text Available the national grid. The unfortunate situation with water is that there is no replacement technology for water. Water can be supplied from many different sources. A net zero energy development will move closer to a net zero water development by reducing...

Video studies of passage by Anopheles gambiae mosquitoes through holes in a simulated bed net: effects of hole size, hole orientation and net environment.

Science.gov (United States)

Sutcliffe, James; Colborn, Kathryn L

2015-05-13

Holes in netting provide potential routes for mosquitoes to enter ITNs. Despite this, there is little information on how mosquitoes respond to holes in bed nets and how their responses are affected by hole size, shape and orientation or by ambient conditions around the net. Female Anopheles gambiae (G3) were recorded in a simulated bed net consisting of two sizes of untreated netting-covered behavioural arenas placed above and beside (to simulate the bed net roof and sides respectively) the experimenter who was a source of host cues from 'inside' the net. A round hole of 9 mm or 13 mm diameter was cut into the centre of the netting of each arena. Videos of unfed female mosquitoes in arenas were analysed for time spent flying, walking and standing still and for exit through the hole. The effects of the experimenter on temperature and relative humidity around the simulated net were also measured. Mosquitoes were significantly more active in overhead arenas than in arenas to the side. Hole passage was significantly more likely in smaller arenas than larger ones and for larger holes than smaller ones. In arenas to the side, hole passage rate through small holes was about 50% less likely than what could be explained by area alone. Passage rate through holes in overhead arenas was consistent with hole area. Temperature in arenas did not strongly reflect the experimenter's presence in the simulated net. Relative humidity and absolute humidity in overhead arenas, but not in arenas to the side, were immediately affected by experimenter presence. Higher levels of activity in overhead arenas than in arenas to the side were likely due to the rising heat and humidity plume from the experimenter. Lower than expected passage rates through smaller vertically oriented holes may have been be due to an edge effect that does not apply to horizontally oriented holes. Results suggest that current methods of assessing the importance of physical damage to ITNs may not accurately reflect

CpG island methylator phenotype-low (CIMP-low) colorectal cancer shows not only few methylated CIMP-high-specific CpG islands, but also low-level methylation at individual loci.

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Kawasaki, Takako; Ohnishi, Mutsuko; Nosho, Katsuhiko; Suemoto, Yuko; Kirkner, Gregory J; Meyerhardt, Jeffrey A; Fuchs, Charles S; Ogino, Shuji

2008-03-01

The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct phenotype in colorectal cancer. However, the concept of CIMP-low with less extensive CpG island methylation is still evolving. Our aim is to examine whether density of methylation in individual CpG islands was different between CIMP-low and CIMP-high tumors. Utilizing MethyLight technology and 889 population-based colorectal cancers, we quantified DNA methylation (methylation index, percentage of methylated reference) at 14 CpG islands, including 8 CIMP-high-specific loci (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1). Methylation positivity in each locus was defined as methylation index>4. Low-level methylation (methylation index>0, CIMP-high-specific locus was significantly more common in 340 CIMP-low tumors (1/8-5/8 methylation-positive loci) than 133 CIMP-high tumors (> or =6/8 methylation-positive loci) and 416 CIMP-0 tumors (0/8 methylation-positive loci) (PCIMP-high, low-level methylation, was not persistently more prevalent in CIMP-low tumors. In conclusion, compared to CIMP-high and CIMP-0 tumors, CIMP-low colorectal cancers show not only few methylated CIMP-high-specific CpG islands, but also more frequent low-level methylation at individual loci. Our data may provide supporting evidence for a difference in pathogenesis of DNA methylation between CIMP-low and CIMP-high tumors.

Higher-order organisation of extremely amplified, potentially functional and massively methylated 5S rDNA in European pikes (Esox sp.).

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Symonová, Radka; Ocalewicz, Konrad; Kirtiklis, Lech; Delmastro, Giovanni Battista; Pelikánová, Šárka; Garcia, Sonia; Kovařík, Aleš

2017-05-18

Pikes represent an important genus (Esox) harbouring a pre-duplication karyotype (2n = 2x = 50) of economically important salmonid pseudopolyploids. Here, we have characterized the 5S ribosomal RNA genes (rDNA) in Esox lucius and its closely related E. cisalpinus using cytogenetic, molecular and genomic approaches. Intragenomic homogeneity and copy number estimation was carried out using Illumina reads. The higher-order structure of rDNA arrays was investigated by the analysis of long PacBio reads. Position of loci on chromosomes was determined by FISH. DNA methylation was analysed by methylation-sensitive restriction enzymes. The 5S rDNA loci occupy exclusively (peri)centromeric regions on 30-38 acrocentric chromosomes in both E. lucius and E. cisalpinus. The large number of loci is accompanied by extreme amplification of genes (>20,000 copies), which is to the best of our knowledge one of the highest copy number of rRNA genes in animals ever reported. Conserved secondary structures of predicted 5S rRNAs indicate that most of the amplified genes are potentially functional. Only few SNPs were found in genic regions indicating their high homogeneity while intergenic spacers were more heterogeneous and several families were identified. Analysis of 10-30 kb-long molecules sequenced by the PacBio technology (containing about 40% of total 5S rDNA) revealed that the vast majority (96%) of genes are organised in large several kilobase-long blocks. Dispersed genes or short tandems were less common (4%). The adjacent 5S blocks were directly linked, separated by intervening DNA and even inverted. The 5S units differing in the intergenic spacers formed both homogeneous and heterogeneous (mixed) blocks indicating variable degree of homogenisation between the loci. Both E. lucius and E. cisalpinus 5S rDNA was heavily methylated at CG dinucleotides. Extreme amplification of 5S rRNA genes in the Esox genome occurred in the absence of significant pseudogenisation

To What Extent Does DNA Methylation Affect Phenotypic Variation in Cattle?

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Stephanie McKAY

2015-07-01

Full Text Available DNA methylation is an environmentally influenced epigenetic modification that regulates gene transcription and has the potential to influence variation in economically important phenotypes in agricultural species. We have utilized a novel approach to evaluate the relationship between genetic and epigenetic variation and downstream phenotypes. To begin with, we have integrated RNA-Seq and methyl binding domain sequencing (MBD-Seq data in order to determine the extent to which DNA methylation affects phenotypic variation in economically important traits of cattle. MBD-Seq is a technique that involves the sample enrichment of methylated genomic regions followed by their next-generation sequencing. This study utilized Illumina next generation sequencing technology to perform both RNA-Seq and MBD-Seq. NextGENe software (SoftGenetics, State College, PA was employed for quality trimming and aligning the sequence reads to the UMD3.1 bovine reference genome, generating counts of matched reads and methylated peak identification. Subsequently, we identified and quantified genome-wide methylated regions and characterized the extent of differential methylation and differential expression between two groups of animals with extreme phenotypes. The program edgeR from the R software package (version 3.0.1 was employed for identifying differentially methylated regions and regions of differential expression. Finally, Partial Correlation with Information Theory (PCIT was performed to identify transcripts and methylation events that exhibit differential hubbing. A differential hub is defined as a gene network hub that is more highly connected in one treatment group than the other. This analysis produced every possible pair-wise interaction that subsequently enabled us to look at network interactions of how methylation affects expression. (co-expression, co-methylation, methylation x expression. Genomic regions of interest derived from this analysis were then aligned

Origin and fate of 4-methyl steroid hydrocarbons. I. Diagenesis of 4-methyl sterenes

Energy Technology Data Exchange (ETDEWEB)

Wolff, G.A.; Lamb, N.A.; Maxwell, J.R.

1986-03-01

Treatment of 4-methylcholest-4-ene under mild acid conditions at low temperatures gives chemical evidence for certain features seen in the distributions of sedimentary 4-methyl steroid hydrocarbons, and further indicates that many low temperature diagenetic reactions of steroids are explicable in terms of acid catalyzed rearrangements. Specifically, the results provide: (i) Indirect evidence that the 4-ene skeleton is a key intermediate in the dehydration of 4-methyl stanols in sediments. (ii) An explanation for the distribution of 4-methyl sterenes and A-nor sterenes in the lacustrine Messel shale (Eocene). (iii) An explanation for the presence of 4..beta..-methyl steranes in relatively immature sedimentary rocks, despite the precursor stanols having the 4..cap alpha..-methyl configuration. With increasing maturity in the Paris Basin shales (Lower Toarcian), the less stable 4..beta..-methyl steranes decrease gradually in abundance relative to their 4..cap alpha..-methyl counterparts, at a rate fairly similar to the change in pristane stereochemistry.

Analysis of DNA Cytosine Methylation Patterns Using Methylation-Sensitive Amplification Polymorphism (MSAP).

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Guevara, María Ángeles; de María, Nuria; Sáez-Laguna, Enrique; Vélez, María Dolores; Cervera, María Teresa; Cabezas, José Antonio

2017-01-01

Different molecular techniques have been developed to study either the global level of methylated cytosines or methylation at specific gene sequences. One of them is the methylation-sensitive amplified polymorphism technique (MSAP) which is a modification of amplified fragment length polymorphism (AFLP). It has been used to study methylation of anonymous CCGG sequences in different fungi, plants, and animal species. The main variation of this technique resides on the use of isoschizomers with different methylation sensitivity (such as HpaII and MspI) as a frequent-cutter restriction enzyme. For each sample, MSAP analysis is performed using both EcoRI/HpaII- and EcoRI/MspI-digested samples. A comparative analysis between EcoRI/HpaII and EcoRI/MspI fragment patterns allows the identification of two types of polymorphisms: (1) methylation-insensitive polymorphisms that show common EcoRI/HpaII and EcoRI/MspI patterns but are detected as polymorphic amplified fragments among samples and (2) methylation-sensitive polymorphisms which are associated with the amplified fragments that differ in their presence or absence or in their intensity between EcoRI/HpaII and EcoRI/MspI patterns. This chapter describes a detailed protocol of this technique and discusses the modifications that can be applied to adjust the technology to different species of interest.

Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.

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Bartlett, Thomas E; Zaikin, Alexey; Olhede, Sofia C; West, James; Teschendorff, Andrew E; Widschwendter, Martin

2013-01-01

Epigenetic processes--including DNA methylation--are increasingly seen as having a fundamental role in chronic diseases like cancer. It is well known that methylation levels at particular genes or loci differ between normal and diseased tissue. Here we investigate whether the intra-gene methylation architecture is corrupted in cancer and whether the variability of levels of methylation of individual CpGs within a defined gene is able to discriminate cancerous from normal tissue, and is associated with heterogeneous tumour phenotype, as defined by gene expression. We analysed 270985 CpGs annotated to 18272 genes, in 3284 cancerous and 681 normal samples, corresponding to 14 different cancer types. In doing so, we found novel differences in intra-gene methylation pattern across phenotypes, particularly in those genes which are crucial for stem cell biology; our measures of intra-gene methylation architecture are a better determinant of phenotype than measures based on mean methylation level alone (K-S test [Formula: see text] in all 14 diseases tested). These per-gene methylation measures also represent a considerable reduction in complexity, compared to conventional per-CpG beta-values. Our findings strongly support the view that intra-gene methylation architecture has great clinical potential for the development of DNA-based cancer biomarkers.

Inelastic neutron scattering study of methyl groups rotation in some methylxanthines

Science.gov (United States)

Prager, M.; Pawlukojc, A.; Wischnewski, A.; Wuttke, J.

2007-12-01

The three isomeric dimethylxanthines and trimethylxanthine are studied by neutron spectroscopy up to energy transfers of 100meV at energy resolutions ranging from 0.7μeV to some meV. The loss of elastic intensity with increasing temperature can be modeled by quasielastic methyl rotation. The number of inequivalent methyl groups is in agreement with those of the room temperature crystal structures. Activation energies are obtained. In the case of theophylline, a doublet tunneling band is observed at 15.1 and 17.5μeV. In theobromine, a single tunneling band at 0.3μeV is found. Orientational disorder in caffeine leads to a 2.7μeV broad distribution of tunneling bands around the elastic line. At the same time, broad low energy phonon spectra characterize an orientational glassy state with weak methyl rotational potentials. Librational energies of the dimethylxanthines are clearly seen in the phonon densities of states. Rotational potentials can be derived which explain consistently all observables. While their symmetry in general is threefold, theophylline shows a close to sixfold potential reflecting a mirror symmetry.

Evidence for methyl group transfer between the methyl-accepting chemotaxis proteins in Bacillus subtilis

International Nuclear Information System (INIS)

Bedale, W.A.; Nettleton, D.O.; Sopata, C.S.; Thoelke, M.S.; Ordal, G.W.

1988-01-01

The authors present evidence for methyl (as methyl or methoxy) transfer from the methyl-accepting chemotaxis proteins H1 and possibly H3 of Bacillus subtilis to the methyl-accepting chemotaxis protein H2. This methyl transfer, which has been observed in vitro was strongly stimulated by the chemoattractant aspartate and thus may plan an important role in the sensory processing system of this organism. Although radiolabeling of H1 and H3 began at once after the addition of [ 3 H] methionine, radiolabeling of H2 showed a lag. Furthermore, the addition of excess nonradioactive methionine caused immediate exponential delabeling of H1 and H3 while labeling of H2 continued to increase. Methylation of H2 required the chemotactic methyltransferase, probably to first methylate H1 and H3. Aspartate caused increased labeling of H2 and strongly decreased labeling of H1 and H3 after the addition of nonradioactive methionine. Without the addition of nonradioactive methionine, aspartate caused demethylation of H1 and to a lesser extent H3, with an approximately equal increase of methylation of H2

[Analysis of genomic DNA methylation level in radish under cadmium stress by methylation-sensitive amplified polymorphism technique].

Science.gov (United States)

Yang, Jin-Lan; Liu, Li-Wang; Gong, Yi-Qin; Huang, Dan-Qiong; Wang, Feng; He, Ling-Li

2007-06-01

The level of cytosine methylation induced by cadmium in radish (Raphanus sativus L.) genome was analysed using the technique of methylation-sensitive amplified polymorphism (MSAP). The MSAP ratios in radish seedling exposed to cadmium chloride at the concentration of 50, 250 and 500 mg/L were 37%, 43% and 51%, respectively, and the control was 34%; the full methylation levels (C(m)CGG in double strands) were at 23%, 25% and 27%, respectively, while the control was 22%. The level of increase in MSAP and full methylation indicated that de novo methylation occurred in some 5'-CCGG sites under Cd stress. There was significant positive correlation between increase of total DNA methylation level and CdCl(2) concentration. Four types of MSAP patterns: de novo methylation, de-methylation, atypical pattern and no changes of methylation pattern were identified among CdCl(2) treatments and the control. DNA methylation alteration in plants treated with CdCl(2) was mainly through de novo methylation.

Multiflavor string-net models

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Lin, Chien-Hung

2017-05-01

We generalize the string-net construction to multiple flavors of strings, each of which is labeled by the elements of an Abelian group Gi. The same flavor of strings can branch, while different flavors of strings can cross one another and thus they form intersecting string nets. We systematically construct the exactly soluble lattice Hamiltonians and the ground-state wave functions for the intersecting string-net condensed phases. We analyze the braiding statistics of the low-energy quasiparticle excitations and find that our model can realize all the topological phases as the string-net model with group G =∏iGi . In this respect, our construction provides various ways of building lattice models which realize topological order G , corresponding to different partitions of G and thus different flavors of string nets. In fact, our construction concretely demonstrates the Künneth formula by constructing various lattice models with the same topological order. As an example, we construct the G =Z2×Z2×Z2 string-net model which realizes a non-Abelian topological phase by properly intersecting three copies of toric codes.

Reaction products from N-methyl-N-nitrosourea and deoxyribonucleic acid containing thymidine residues. Synthesis and identification of a new methylation product, O4-methyl-thymidine

Science.gov (United States)

Lawley, P. D.; Orr, D. J.; Shah, S. A.; Farmer, P. B.; Jarman, M.

1973-01-01

1. DNA was treated with N-methyl-N-nitrosourea at pH7–8, 37°C, degraded to yield 3- and 7-methylpurines and deoxyribonucleosides and the reaction products were separated by chromatography on ion-exchange resins. The following methods for identification and determination of products were used: with unlabelled N-methyl-N-nitrosourea, u.v. absorption; use of methyl-14C-labelled N-methyl-N-nitrosourea and use of [14C]thymine-labelled DNA. 2. The synthesis of O4-methylthymidine and its identification by u.v. and mass spectroscopy are reported. 3. 3-Methylthymidine and O4-methylthymidine were found as methylation products from N-methyl-N-nitrosourea with thymidine and with DNA, in relatively small yields. Unidentified products containing thymine were found in enzymic digests of N-methyl-N-nitrosourea-treated DNA, which may be phosphotriesters. 4. The possible role of formation of methylthymines in mutagenesis by N-methyl-N-nitrosourea is discussed. PMID:4798180

DNA Methylation as a Biomarker for Body Fluid Identification

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Rania Gomaa

2017-12-01

Full Text Available Currently, available identification techniques for forensic samples are either enzyme or protein based, which can be subjected to degradation, thus limiting its storage potentials. Epigenetic changes arising due to DNA methylation and histone acetylation can be used for body fluid identification. Markers DACT1, USP49, ZC3H12D, FGF7, cg23521140, cg17610929, chromosome 4 (25287119–25287254, chromosome 11 (72085678–72085798, 57171095–57171236, 1493401–1493538, and chromosome 19 (47395505–47395651 are currently being used for semen identification. Markers cg26107890, cg20691722, cg01774894 and cg14991487 are used to differentiate saliva and vaginal secretions from other body fluids. However, such markers show overlapping methylation pattern. This review article aimed to highlight the feasibility of using DNA methylation of certain genetic markers in body fluid identification and its implications for forensic investigations. The reviewed articles have employed molecular genetics techniques such as Bisulfite sequencing PCR (BSP, methylation specific PCR (MSP, Pyrosequencing, Combined Bisulfite Restriction Analysis (COBRA, Methylation-sensitive Single Nucleotide Primer Extension (SNuPE, and Multiplex SNaPshot Microarray. Bioinformatics software such as MATLAB and BiQ Analyzer has been used. Biological fluids have different methylation patterns and thus, this difference can be used to identify the nature of the biological fluid found at the crime scene. Using DNA methylation to identify the body fluids gives accurate results without consumption of the trace evidence and requires a minute amount of DNA for analysis. Recent studies have incorporated next-generation sequencing aiming to find out more reliable markers that can differentiate between different body fluids. Nonetheless, new DNA methylation markers are yet to be discovered to accurately differentiate between saliva and vaginal secretions with high confidence. Epigenetic changes are

Preclinical and clinical evaluation of O-[{sup 11}C]methyl-L-tyrosine for tumor imaging by positron emission tomography

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Ishiwata, Kiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0022 (Japan)]. E-mail: ishiwata@pet.tmig.or.jp; Tsukada, Hideo [Central Research Laboratory, Hamamatsu Photonics K.K., Hamakita 434-8601 (Japan); Kubota, Kazuo [Department of Radiology, Division of Nuclear Medicine, International Medical Center of Japan, Shinjuku-ku, Tokyo 162-8655 (Japan); Nariai, Tadashi [Department of Neurosurgery, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519 (Japan); Harada, Norihiro [Department of Radiology, Division of Nuclear Medicine, International Medical Center of Japan, Shinjuku-ku, Tokyo 162-8655 (Japan); Kawamura, Kazunori [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0022 (Japan); SHI Accelerator Service Ltd., Shinagawa-ku, Tokyo 141-8686 (Japan); Kimura, Yuichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0022 (Japan); Oda, Keiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0022 (Japan); Iwata, Ren [CYRIC, Tohoku University, Aoba-ku, Sendai 980-8578 (Japan); Ishii, Kenji [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0022 (Japan)

2005-04-01

We performed preclinical and clinical studies of O-[{sup 11}C]methyl-L-tyrosine, a potential tracer for imaging amino acid transport of tumors by positron emission tomography (PET). Examinations of the radiation-absorbed dose by O-[{sup 11}C]methyl-L-tyrosine and the acute toxicity and mutagenicity of O-methyl-L-tyrosine showed suitability of the tracer for clinical use. The whole-body imaging of monkeys and healthy humans by PET showed low uptake of O-[{sup 11}C]methyl-L-tyrosine in all normal organs except for the urinary track and bladder, suggesting that the O-[{sup 11}C]methyl-L-tyrosine PET has the potential for tumor imaging in the whole-body. Finally, the brain tumor imaging was preliminarily demonstrated.

Rare, but challenging tumors: NET

International Nuclear Information System (INIS)

Ivanova, D.; Balev, B.

2013-01-01

Full text: Introduction: Gastroenteropancreatic Neuroendocrine Tumors (GEP - NET) are a heterogeneous group of tumors with different locations and many different clinical, histological, and imaging performance. In a part of them a secretion of various organic substances is present. The morbidity of GEP - NET in the EU is growing, and this leads to increase the attention to them. What you will learn: Imaging methods used for localization and staging of GEP - NET, characteristics of the study’s protocols; Classification of GEP - NET; Demonstration of typical and atypical imaging features of GEP - NET in patients registered at the NET Center at University Hospital ‘St. Marina’, Varna; Features of metastatic NET, The role of imaging in the evaluation of treatment response and follow-up of the patients. Discussion: The image semiotics analysis is based on 19 cases of GEP - NET registered NET Center at University Hospital ‘St. Marina’. The main imaging method is multidetector CT (MDCT), and magnetic resonance imaging (MRI ) has advantages in the evaluation of liver lesions and the local prevalence of anorectal tumors. In patients with advanced disease and liver lesions the assessment of skeletal involvement (MRI/ nuclear medical method) is mandatory. The majority of GEP - NET have not any specific imaging findings. Therefore it is extremely important proper planning and conducting of the study (MDCT and MR enterography; accurate assessment phase of scanning, positive and negative contrast). Conclusion: GEP - NET is a major diagnostic challenge due to the absence of typical imaging characteristics and often an overlap with those of the tumors of different origin can be observed. Therefore, a good knowledge of clinical and imaging changes occurring at different locations is needed. MDCT is the basis for the diagnosis, staging and follow-up of these neoplasms

Limitations of shallow nets approximation.

Science.gov (United States)

Lin, Shao-Bo

2017-10-01

In this paper, we aim at analyzing the approximation abilities of shallow networks in reproducing kernel Hilbert spaces (RKHSs). We prove that there is a probability measure such that the achievable lower bound for approximating by shallow nets can be realized for all functions in balls of reproducing kernel Hilbert space with high probability, which is different with the classical minimax approximation error estimates. This result together with the existing approximation results for deep nets shows the limitations for shallow nets and provides a theoretical explanation on why deep nets perform better than shallow nets. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis of [methyl-14C]crotonobetaine from DL-[methyl-14C]carnitine

International Nuclear Information System (INIS)

Loester, H.; Seim, H.

1996-01-01

The causes of carnitine deficiency syndromes are not completely understood, but decomposition of L-carnitine in vivo is likely to be involved. Carnitine is metabolized to γ-butyrobetaine, and crotonobetaine is probably an intermediate in this pathway. To validate experimentally the precursor-product relationship between the three physiologically occuring γ-betaines - L-carnitine, crotonobetaine, γ-butyrobetaine - labelling with stable or radioactive isotopes became necessary. Methyl-labelled carnitine isomers (L(-)-, D(+)- or DL-) or γ-butyrobetaine can be easily synthesized by methylation of 4-amino-3-hydroxybutyric acid isomers or 4-aminobutyric acid, respectively. Because of problems with the 4-aminocrotonic acid, we synthesized labelled crotonbetaine from labelled carnitine. Thus, DL-[methyl- 14 C]carnitine was dehydrated by reaction with concentrated sulfuric acid. After removal of the latter the products were separated and purified by ion exchange chromatography on DOWEX 50 WX8 (200 - 400 mesh) and gradient elution with hydrochloric acid. In addition to the labelled main product [methyl- 14 C]crotonobetaine (yield about 50 %), [methyl- 14 C]glycine betaine and [methyl- 14 C]acetonyl-trimethylammonium (ATMA) were formed. The end products were identified by combined thin layer chromatography/autoradiography and quantified by liquid scintillation counting. (Author)

Internet Safety and Malaysian Students: A Study of Female Undergraduates and Their Net Pals

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Cheong Lee Mei, Dianne

2007-12-01

Full Text Available Malaysian female undergraduates are perceived as able to rationally evaluate and estimate risks towards Net pals. Friendship is secured online while deception and fraud are revealed offline. Based on what they have been informed, the female undergraduates may know their Net pals’ likes and dislikes but the invisible cyber veil does not allow them to penetrate the illusion and accurately evaluate a person’s character and personality. This study examined how Malaysian female undergraduates use the Internet, perceive risks in meeting Net pals and the safety awareness surrounding cyber friendship. Responses of 118 female undergraduates (43% from UiTM, 30% from UM, 27% from MMU to a survey indicated that Net pals were befriended through chat rooms and websites. More than half of the female undergraduates would have a face-to-face meeting with their Net pals without the knowledge of relevant parties and have done at least one potentially unsafe behaviour. If the extent and level of Internet safety awareness is known, the problem of Internet deception that might lead to potential social problems such as rape and sexual abuse can be effectively addressed.

Human active X-specific DNA methylation events showing stability across time and tissues

Science.gov (United States)

Joo, Jihoon Eric; Novakovic, Boris; Cruickshank, Mark; Doyle, Lex W; Craig, Jeffrey M; Saffery, Richard

2014-01-01

The phenomenon of X chromosome inactivation in female mammals is well characterised and remains the archetypal example of dosage compensation via monoallelic expression. The temporal series of events that culminates in inactive X-specific gene silencing by DNA methylation has revealed a ‘patchwork' of gene inactivation along the chromosome, with approximately 15% of genes escaping. Such genes are therefore potentially subject to sex-specific imbalance between males and females. Aside from XIST, the non-coding RNA on the X chromosome destined to be inactivated, very little is known about the extent of loci that may be selectively silenced on the active X chromosome (Xa). Using longitudinal array-based DNA methylation profiling of two human tissues, we have identified specific and widespread active X-specific DNA methylation showing stability over time and across tissues of disparate origin. Our panel of X-chromosome loci subject to methylation on Xa reflects a potentially novel mechanism for controlling female-specific X inactivation and sex-specific dimorphisms in humans. Further work is needed to investigate these phenomena. PMID:24713664

Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation.

Science.gov (United States)

Dou, John; Schmidt, Rebecca J; Benke, Kelly S; Newschaffer, Craig; Hertz-Picciotto, Irva; Croen, Lisa A; Iosif, Ana-Maria; LaSalle, Janine M; Fallin, M Daniele; Bakulski, Kelly M

2018-01-01

Cord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells, generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability. We evaluated differences in cell composition and DNA methylation between cord blood buffy coat and whole cord blood samples. Cord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in eight individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition. DNA methylation PCs were associated with individual (P PC1 = 1.4 × 10 -9 ; P PC2 = 2.9 × 10 -5 ; P PC3 = 3.8 × 10 -5 ; P PC4 = 4.2 × 10 -6 ; P PC5 = 9.9 × 10 -13 , P PC6 = 1.3 × 10 -11 ) and not with sample type (P PC1-6 >0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired samples ranged from r = 0.66 to r = 0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (five sites had unadjusted Pcoat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.

The application of methylation specific electrophoresis (MSE) to DNA methylation analysis of the 5' CpG island of mucin in cancer cells

International Nuclear Information System (INIS)

Yokoyama, Seiya; Yonezawa, Suguru; Kitamoto, Sho; Yamada, Norishige; Houjou, Izumi; Sugai, Tamotsu; Nakamura, Shin-ichi; Arisaka, Yoshifumi; Takaori, Kyoichi; Higashi, Michiyo

2012-01-01

Methylation of CpG sites in genomic DNA plays an important role in gene regulation and especially in gene silencing. We have reported mechanisms of epigenetic regulation for expression of mucins, which are markers of malignancy potential and early detection of human neoplasms. Epigenetic changes in promoter regions appear to be the first step in expression of mucins. Thus, detection of promoter methylation status is important for early diagnosis of cancer, monitoring of tumor behavior, and evaluating the response of tumors to targeted therapy. However, conventional analytical methods for DNA methylation require a large amount of DNA and have low sensitivity. Here, we report a modified version of the bisulfite-DGGE (denaturing gradient gel electrophoresis) using a nested PCR approach. We designated this method as methylation specific electrophoresis (MSE). The MSE method is comprised of the following steps: (a) bisulfite treatment of genomic DNA, (b) amplification of the target DNA by a nested PCR approach and (c) applying to DGGE. To examine whether the MSE method is able to analyze DNA methylation of mucin genes in various samples, we apply it to DNA obtained from state cell lines, ethanol-fixed colonic crypts and human pancreatic juices. The MSE method greatly decreases the amount of input DNA. The lower detection limit for distinguishing different methylation status is < 0.1% and the detectable minimum amount of DNA is 20 pg, which can be obtained from only a few cells. We also show that MSE can be used for analysis of challenging samples such as human isolated colonic crypts or human pancreatic juices, from which only a small amount of DNA can be extracted. The MSE method can provide a qualitative information of methylated sequence profile. The MSE method allows sensitive and specific analysis of the DNA methylation pattern of almost any block of multiple CpG sites. The MSE method can be applied to analysis of DNA methylation status in many different clinical

Association of Tissue-Specific DNA Methylation Alterations with α-Thalassemia Southeast Asian Deletion

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Tanapat Pangeson

2017-11-01

Full Text Available In the wild-type allele, DNA methylation levels of 10 consecutive CpG sites adjacent to the upstream 5′-breakpoint of α-thalassemia Southeast Asian (SEA deletion are not different between placenta and leukocytes. However, no previous study has reported the map of DNA methylation in the SEA allele. This report aims to show that the SEA mutation is associated with DNA methylation changes, resulting in differential methylation between placenta and leukocytes. Methylation-sensitive high-resolution analysis was used to compare DNA methylation among placenta, leukocytes, and unmethylated control DNA. The result indicates that the DNA methylation between placenta and leukocyte DNA is different and shows that the CpG status of both is not fully unmethylated. Mapping of individual CpG sites was performed by targeted bisulfite sequencing. The DNA methylation level of the 10 consecutive CpG sites was different between placenta and leukocyte DNA. When the 10th CpG of the mutation allele was considered as a hallmark for comparing DNA methylation level, it was totally different from the unmethylated 10th CpG of the wild-type allele. Finally, the distinct DNA methylation patterns between both DNA were extracted. In total, 24 patterns were found in leukocyte samples and 9 patterns were found in placenta samples. This report shows that the large deletion is associated with DNA methylation change. In further studies for clinical application, the distinct DNA methylation pattern might be a potential marker for detecting cell-free fetal DNA.

Clinical Utility of promoter methylation of the tumor suppressor genes DKK3, and RASSF1A in breast cancer patients

Directory of Open Access Journals (Sweden)

Marwa H. Saied

2018-04-01

Full Text Available Background: DNA methylation is the commonest known epigenetic change that results in silencing of tumor suppressor genes. Promoter methylation of tumor suppressor genes has the potential for early detection of breast cancer. Aim: Aim is to examine the potential usefulness of blood based methylation specific polymerase chain reaction (MSP of methylated DKK3 and RASSF1A genes in early detection of breast cancer. Method: Methylation status of DKK3 and RASSF1 was investigated in forty breast cancer patients, twenty fibroadenoma patients and twenty healthy ladies as control group using MSP. Results: Methylation of DKK3 promoter was found in 22.5% of breast cancer patients, while DKK3 methylation was absent in both fibroadenoma patients and control group. Similarly, methylation of RASSF1 promoter was found in 17.5% of breast cancer patients and in none of fibroadenoma and control group. Conclusion: Promoter methylation of DKK3 and RASSF1 was found in breast cancer patients while absent in control group suggesting that tumorspecific methylation of the two genes (DKK3 and RASSF1A might be a valuable biomarker for the early detection of breast cancer. Keywords: DNA methylation, Breast cancer, DKK3, RASSF1

Methyl methacrylate oligomerically-modified clay and its poly(methyl methacrylate) nanocomposites

International Nuclear Information System (INIS)

Zheng Xiaoxia; Jiang, David D.; Wilkie, Charles A.

2005-01-01

A methyl methacrylate oligomerically-modified clay was used to prepare poly(methyl methacrylate) clay nanocomposites by melt blending and the effect of the clay loading level on the modified clay and corresponding nanocomposite was studied. These nanocomposites were characterized by X-ray diffraction, transmission electron microscopy, thermogravimetric analysis and cone calorimetry. The results show a mixed intercalated/delaminated morphology with good nanodispersion. The compatibility between the methylacrylate-subsituted clay and poly(methyl methacrylate) (PMMA) are greatly improved compared to other oligomerically-modified clays

The effect of netting solidity ratio and inclined angle on the hydrodynamic characteristics of knotless polyethylene netting

Science.gov (United States)

Tang, Hao; Hu, Fuxiang; Xu, Liuxiong; Dong, Shuchuang; Zhou, Cheng; Wang, Xuefang

2017-10-01

Knotless polyethylene (PE) netting has been widely used in aquaculture cages and fishing gears, especially in Japan. In this study, the hydrodynamic coefficient of six knotless PE netting panels with different solidity ratios were assessed in a flume tank under various attack angles of netting from 0° (parallel to flow) to 90° (perpendicular to flow) and current speeds from 40 cm s-1 to 130 cm s-1. It was found that the drag coefficient was related to Reynolds number, solidity ratio and attack angle of netting. The solidity ratio was positively related with drag coefficient for netting panel perpendicular to flow, whereas when setting the netting panel parallel to the flow the opposite result was obtained. For netting panels placed at an angle to the flow, the lift coefficient reached the maximum at an attack angle of 50° and then decreased as the attack angle further increased. The solidity ratio had a dual influence on drag coefficient of inclined netting panels. Compared to result in the literature, the normal drag coefficient of knotless PE netting measured in this study is larger than that of nylon netting or Dyneema netting.

Methyl halide fluxes from tropical plants under controlled radiation and temperature regimes

Science.gov (United States)

Blei, Emanuel; Yokouchi, Yoko; Saito, Takuya; Nozoe, Susumu

2015-04-01

Methyl halides (CH3Cl, CH3Br, CH3I) contribute significantly to the halogen burden of the atmosphere and have the potential to influence the stratospheric ozone layer through their catalytic effect in the Chapman cycle. As such they have been studied over the years, and many plants and biota have been examined for their potential to act as a source of these gases. One of the potentially largest terrestrial sources identified was tropical vegetation such as tropical ferns and Dipterocarp trees. Most of these studies concentrated on the identification and quantification of such fluxes rather than their characteristics and often the chambers used in these studies were either opaque or only partially transparent to the full solar spectrum. Therefore it is not certain to which degree emissions of methyl halides are innate to the plants and how much they might vary due to radiation or temperature conditions inside the enclosures. In a separate development it had been proposed that UV-radiation could cause live plant materials to be become emitters of methane even under non-anoxic conditions. As methane is chemically very similar to methyl halides and had been proposed to be produced from methyl-groups ubiquitously found in plant cell material there is a relatively good chance that such a production mechanism would also apply to methyl halides. To test whether radiation can affect elevated emissions of methyl halides from plant materials and to distinguish this from temperature effects caused by heat build-up in chambers a set of controlled laboratory chamber enclosures under various radiation and temperature regimes was conducted on four different tropical plant species (Magnolia grandiflora, Cinnamonum camphora, Cyathea lepifera, Angiopteris lygodiifolia), the latter two of which had previously been identified as strong methyl halide emitters. Abscised leaf samples of these species were subjected to radiation treatments such UV-B, UV-A and broad spectrum radiation

Usability of human Infinium MethylationEPIC BeadChip for mouse DNA methylation studies.

Science.gov (United States)

Needhamsen, Maria; Ewing, Ewoud; Lund, Harald; Gomez-Cabrero, David; Harris, Robert Adam; Kular, Lara; Jagodic, Maja

2017-11-15

The advent of array-based genome-wide DNA methylation methods has enabled quantitative measurement of single CpG methylation status at relatively low cost and sample input. Whereas the use of Infinium Human Methylation BeadChips has shown great utility in clinical studies, no equivalent tool is available for rodent animal samples. We examined the feasibility of using the new Infinium MethylationEPIC BeadChip for studying DNA methylation in mouse. In silico, we identified 19,420 EPIC probes (referred as mEPIC probes), which align with a unique best alignment score to the bisulfite converted reference mouse genome mm10. Further annotation revealed that 85% of mEPIC probes overlapped with mm10.refSeq genes at different genomic features including promoters (TSS1500 and TSS200), 1st exons, 5'UTRs, 3'UTRs, CpG islands, shores, shelves, open seas and FANTOM5 enhancers. Hybridization of mouse samples to Infinium Human MethylationEPIC BeadChips showed successful measurement of mEPIC probes and reproducibility between inter-array biological replicates. Finally, we demonstrated the utility of mEPIC probes for data exploration such as hierarchical clustering. Given the absence of cost and labor convenient genome-wide technologies in the murine system, our findings show that the Infinium MethylationEPIC BeadChip platform is suitable for investigation of the mouse methylome. Furthermore, we provide the "mEPICmanifest" with genomic features, available to users of Infinium Human MethylationEPIC arrays for mouse samples.

Use of bed nets and factors that influence bed net use among Jinuo Ethnic Minority in southern China.

Science.gov (United States)

Xu, Jian-wei; Liao, Yuan-mei; Liu, Hui; Nie, Ren-hua; Havumaki, Joshua

2014-01-01

Insecticide-treated nets (ITNs) are an integral part of vector control recommendations for malaria elimination in China. This study investigated the extent to which bed nets were used and which factors influence bed net use among Jinuo Ethnic Minority in China-Myanmar-Laos border areas. This study combined a quantitative household questionnaire survey and qualitative semi-structured in-depth interviews (SDI). Questionnaires were administered to 352 heads of households. SDIs were given to 20 key informants. The bed net to person ratio was 1∶2.1 (i.e., nearly one net for every two people), however only 169 (48.0%) households owned at least one net and 623 (47.2%) residents slept under bed nets the prior night. The percentages of residents who regularly slept under nets (RSUN) and slept under nets the prior night (SUNPN) were similar (48.0% vs. 47.2%, P>0.05), however the percentage correct use of nets (CUN) was significantly lower (34.5%, Pcash income per person (ACIP) was an independent factor that influenced bed net use (PHigh bed net availability does not necessarily mean higher coverage or bed net use. Household income, house type and knowledge of the ability of bed nets to prevent malaria are all independent factors that influence bed net use among Jinuo Ethnic Minority.

The Effects of Rape Residue Mulching on Net Global Warming Potential and Greenhouse Gas Intensity from No-Tillage Paddy Fields

Science.gov (United States)

Zhang, Zhi-Sheng; Cao, Cou-Gui; Guo, Li-Jin; Li, Cheng-Fang

2014-01-01

A field experiment was conducted to provide a complete greenhouse gas (GHG) accounting for global warming potential (GWP), net GWP, and greenhouse gas intensity (GHGI) from no-tillage (NT) paddy fields with different amounts of oilseed rape residue mulch (0, 3000, 4000, and 6000 kg dry matter (DM) ha−1) during a rice-growing season after 3 years of oilseed rape-rice cultivation. Residue mulching treatments showed significantly more organic carbon (C) density for the 0–20 cm soil layer at harvesting than no residue treatment. During a rice-growing season, residue mulching treatments sequestered significantly more organic C from 687 kg C ha−1 season−1 to 1654 kg C ha−1 season−1 than no residue treatment. Residue mulching significantly increased emissions of CO2 and N2O but decreased CH4 emissions. Residue mulching treatments significantly increased GWP by 9–30% but significantly decreased net GWP by 33–71% and GHGI by 35–72% relative to no residue treatment. These results suggest that agricultural economic viability and GHG mitigation can be achieved simultaneously by residue mulching on NT paddy fields in central China. PMID:25140329

Fusion through the NET

International Nuclear Information System (INIS)

Spears, B.

1987-01-01

The paper concerns the next generation of fusion machines which are intended to demonstrate the technical viability of fusion. In Europe, the device that will follow on from JET is known as NET - the Next European Torus. If the design programme for NET proceeds, Europe could start to build the machine in 1994. The present JET programme hopes to achieve breakeven in the early 1990's. NET hopes to reach ignition in the next century, and so lay the foundation for a demonstration reactor. A description is given of the technical specifications of the components of NET, including: the first wall, the divertors to protect the wall, the array of magnets that provide the fields containing the plasma, the superconducting magnets, and the shield of the machine. NET's research programme is briefly outlined, including the testing programme to optimise conditions in the machine to achieve ignition, and its safety work. (U.K.)

Bisulfite sequencing reveals that Aspergillus flavus holds a hollow in DNA methylation.

Directory of Open Access Journals (Sweden)

Si-Yang Liu

Full Text Available Aspergillus flavus first gained scientific attention for its production of aflatoxin. The underlying regulation of aflatoxin biosynthesis has been serving as a theoretical model for biosynthesis of other microbial secondary metabolites. Nevertheless, for several decades, the DNA methylation status, one of the important epigenomic modifications involved in gene regulation, in A. flavus remains to be controversial. Here, we applied bisulfite sequencing in conjunction with a biological replicate strategy to investigate the DNA methylation profiling of A. flavus genome. Both the bisulfite sequencing data and the methylome comparisons with other fungi confirm that the DNA methylation level of this fungus is negligible. Further investigation into the DNA methyltransferase of Aspergillus uncovers its close relationship with RID-like enzymes as well as its divergence with the methyltransferase of species with validated DNA methylation. The lack of repeat contents of the A. flavus' genome and the high RIP-index of the small amount of remanent repeat potentially support our speculation that DNA methylation may be absent in A. flavus or that it may possess de novo DNA methylation which occurs very transiently during the obscure sexual stage of this fungal species. This work contributes to our understanding on the DNA methylation status of A. flavus, as well as reinforces our views on the DNA methylation in fungal species. In addition, our strategy of applying bisulfite sequencing to DNA methylation detection in species with low DNA methylation may serve as a reference for later scientific investigations in other hypomethylated species.

DNA methylation modifications associated with chronic fatigue syndrome.

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Wilfred C de Vega

Full Text Available Chronic Fatigue Syndrome (CFS, also known as myalgic encephalomyelitis, is a complex multifactorial disease that is characterized by the persistent presence of fatigue and other particular symptoms for a minimum of 6 months. Symptoms fail to dissipate after sufficient rest and have major effects on the daily functioning of CFS sufferers. CFS is a multi-system disease with a heterogeneous patient population showing a wide variety of functional disabilities and its biological basis remains poorly understood. Stable alterations in gene function in the immune system have been reported in several studies of CFS. Epigenetic modifications have been implicated in long-term effects on gene function, however, to our knowledge, genome-wide epigenetic modifications associated with CFS have not been explored. We examined the DNA methylome in peripheral blood mononuclear cells isolated from CFS patients and healthy controls using the Illumina HumanMethylation450 BeadChip array, controlling for invariant probes and probes overlapping polymorphic sequences. Gene ontology (GO and network analysis of differentially methylated genes was performed to determine potential biological pathways showing changes in DNA methylation in CFS. We found an increased abundance of differentially methylated genes related to the immune response, cellular metabolism, and kinase activity. Genes associated with immune cell regulation, the largest coordinated enrichment of differentially methylated pathways, showed hypomethylation within promoters and other gene regulatory elements in CFS. These data are consistent with evidence of multisystem dysregulation in CFS and implicate the involvement of DNA modifications in CFS pathology.

NetView technical research

Science.gov (United States)

1993-01-01

This is the Final Technical Report for the NetView Technical Research task. This report is prepared in accordance with Contract Data Requirements List (CDRL) item A002. NetView assistance was provided and details are presented under the following headings: NetView Management Systems (NMS) project tasks; WBAFB IBM 3090; WPAFB AMDAHL; WPAFB IBM 3084; Hill AFB; McClellan AFB AMDAHL; McClellan AFB IBM 3090; and Warner-Robins AFB.

DNA methylation fingerprint of neuroblastoma reveals new biological and clinical insights

Directory of Open Access Journals (Sweden)

Soledad Gómez

2015-09-01

We have analyzed the DNA methylome of neuroblastoma using high-density microarrays (Infinium Human Methylation 450k BeadChip to define the epigenetic landscape of this pediatric tumor and its potential clinicopathological impact. Here, we provide the detail of methods and quality control parameters of the microarray data used for the study. Methylation data has been deposited at NCBI Gene Expression Omnibus data repository, accession number GSE54719; superseries record GSE54721.

Maternal Methyl-Group Donor Intake and Global DNA (HydroxyMethylation before and during Pregnancy

Directory of Open Access Journals (Sweden)

Sara Pauwels

2016-08-01

Full Text Available It is still unclear to which extent methyl-group intake during pregnancy can affect maternal global DNA (hydroxylmethylation. 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 (hydroxymethylation 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 (hydroxymethylation 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 (hydroxymethylation 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 (hydroxymethylation was found and women with higher methyl-group intake showed higher methylation in the third trimester, and not in earlier phases of pregnancy.

Efficacy of PermaNet® 3.0 and PermaNet® 2.0 nets against laboratory-reared and wild Anopheles gambiae sensu lato populations in northern Tanzania.

Science.gov (United States)

Kweka, Eliningaya J; Lyaruu, Lucile J; Mahande, Aneth M

2017-01-18

Mosquitoes have developed resistance against pyrethroids, the only class of insecticides approved for use on long-lasting insecticidal nets (LLINs). The present study sought to evaluate the efficacy of the pyrethroid synergist PermaNet® 3.0 LLIN versus the pyrethroid-only PermaNet® 2.0 LLIN, in an East African hut design in Lower Moshi, northern Tanzania. In this setting, resistance to pyrethroid insecticides has been identified in Anopheles gambiae mosquitoes. Standard World Health Organization bioefficacy evaluations were conducted in both laboratory and experimental huts. Experimental hut evaluations were conducted in an area where there was presence of a population of highly pyrethroid-resistant An. arabiensis mosquitoes. All nets used were subjected to cone bioassays and then to experimental hut trials. Mosquito mortality, blood-feeding inhibition and personal protection rate were compared between untreated nets, unwashed LLINs and LLINs that were washed 20 times. Both washed and unwashed PermaNet® 2.0 and PermaNet® 3.0 LLINs had knockdown and mortality rates of 100% against a susceptible strain of An. gambiae sensu stricto. The adjusted mortality rate of the wild mosquito population after use of the unwashed PermaNet® 3.0 and PermaNet® 2.0 nets was found to be higher than after use of the washed PermaNet® 2.0 and PermaNet® 3.0 nets. Given the increasing incidence of pyrethroid resistance in An. gambiae mosquitoes in Tanzania, we recommend that consideration is given to its distribution in areas with pyrethroid-resistant malaria vectors within the framework of a national insecticide-resistance management plan.

PODATKOVNE STORITVE ADO.NET IN ADO.NET ENTITY FRAMEWORK

OpenAIRE

Volavc, Franc

2012-01-01

V diplomskem delu smo predstavili Microsoftovi ogrodji ADO.NET in ADO.NET Entity Framework. Preučili in analizirali smo metode za dostop do podatkovnih virov, ki jih ponujata ogrodji, ter nato te ugotovitve preslikati v odločitveno drevo, katero bo programerjem in razvijalcem informacijskih sistemov pomagalo pri odločanju glede pristopa za dostop do podatkovnih virov. Ker bomo v diplomskem delu predstavili Microsoftovi ogrodji, bomo posledično omejeni zgolj na Microsoftovo tehnologijo, se pra...

Theoretical study of the regioselectivity of the interaction of 3-methyl-4-pyrimidone and 1-methyl-2-pyrimidone with Lewis acids.

Science.gov (United States)

Kasende, Okuma Emile; Muya, Jules Tshishimbi; Broeckaert, Lies; Maes, Guido; Geerlings, Paul

2012-08-23

A density functional theory (DFT) study is performed to determine the stability of the complexes formed between either the N or O site of 3-methyl-4-pyrimidone and 1-methyl-2-pyrimidone molecules and different ligands. The studied ligands are boron and alkali Lewis acids, namely, B(CH(3))(3), HB(CH(3))(2), H(2)B(CH(3)), BH(3), H(2)BF, HBF(2), BF(3), Li(+), Na(+), and K(+). The acids are divided into two groups according to their hardness. The reactivity predictions, according to the molecular electrostatic potential (MEP) map and the natural bond orbital (NBO) analysis, are in agreement with the calculated relative stabilities. Our findings reveal a strong regioselectivity with borane and its derivatives preferring the nitrogen site in both pyrimidone isomers, while a preference for oxygen is observed for the alkali acids in the 3-methyl-4-pyrimidone molecule. The complexation of 1-methyl-2-pyrimidone with these hard alkali acids does not show any discrimination between the two sites due to the presence of a continuous delocalized density region between the nitrogen and the oxygen atoms. The preference of boron Lewis acids toward the N site is due to the stronger B-N bond as compared to the B-O bond. The influence of fluorine or methyl substitution on the boron atom is discussed through natural orbital analysis (NBO) concentrating on the overlap of the boron empty p-orbital with the F lone pairs and methyl hyperconjugation, respectively. The electrophilicity of the boron acids gives a good overall picture of the interaction capabilities with the Lewis base.

Transmission of epi-alleles with MET1-dependent dense methylation in Arabidopsis thaliana.

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Michael Watson

Full Text Available DNA methylation in plants targets cytosines in three sequence contexts, CG, CHG and CHH (H representing A, C or T. Each of these patterns has traditionally been associated with distinct DNA methylation pathways with CHH methylation being controlled by the RNA dependent DNA methylation (RdDM pathway employing small RNAs as a guide for the de novo DOMAINS REARRANGED METHYLTRANSFERASE (DRM2, and maintenance DNA METHYLTRANSFERASE1 (MET1 being responsible for faithful propagation of CG methylation. Here we report an unusual 'dense methylation' pattern under the control of MET1, with methylation in all three sequence contexts. We identified epi-alleles of dense methylation at a non coding RNA locus (At4g15242 in Arabidopsis ecotypes, with distinct dense methylation and expression characteristics, which are stably maintained and transmitted in genetic crosses and which can be heritably altered by depletion of MET1. This suggests that, in addition to its classical CG maintenance function, at certain loci MET1 plays a role in creating transcriptional diversity based on the generation of independent epi-alleles. Database inspection identified several other loci with MET1-dependent dense methylation patterns. Arabidopsis ecotypes contain distinct epi-alleles of these loci with expression patterns that inversely correlate with methylation density, predominantly within the transcribed region. In Arabidopsis, dense methylation appears to be an exception as it is only found at a small number of loci. Its presence does, however, highlight the potential for MET1 as a contributor to epigenetic diversity, and it will be interesting to investigate the representation of dense methylation in other plant species.

Blanket testing in NET

International Nuclear Information System (INIS)

Chazalon, M.; Daenner, W.; Libin, B.

1989-01-01

The testing stages in NET for the performance assessment of the various breeding blanket concepts developed at the present time in Europe for DEMO (LiPb and ceramic blankets) and the requirements upon NET to perform these tests are reviewed. Typical locations available in NET for blanket testing are the central outboard segments and the horizontal ports of in-vessel sectors. These test positions will be connectable with external test loops. The number of test loops (helium, water, liquid metal) will be such that each major class of blankets can be tested in NET. The test positions, the boundary conditions and the external test loops are identified and the requirements for test blankets are summarized (author). 6

Longitudinal changes in glucocorticoid receptor exon 1F methylation and psychopathology after military deployment.

Science.gov (United States)

Schür, R R; Boks, M P; Rutten, B P F; Daskalakis, N P; de Nijs, L; van Zuiden, M; Kavelaars, A; Heijnen, C J; Joëls, M; Kahn, R S; Geuze, E; Vermetten, E; Vinkers, C H

2017-07-25

Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucocorticoid receptor exon 1 F region (GR-1 F ) for trauma-related psychopathology. We conducted a longitudinal study to examine GR-1 F methylation changes over time in relation to trauma exposure and the development of post-deployment psychopathology. GR-1 F methylation (52 loci) was quantified using pyrosequencing in whole blood of 92 military men 1 month before and 6 months after a 4-month deployment period to Afghanistan. GR-1 F methylation overall (mean methylation and the number of methylated loci) and functional methylation (methylation at loci associated with GR exon 1 F expression) measures were examined. We first investigated the effect of exposure to potentially traumatic events during deployment on these measures. Subsequently, changes in GR-1 F methylation were related to changes in mental health problems (total Symptom Checklist-90 score) and posttraumatic stress disorder (PTSD) symptoms (Self-Report Inventory for PTSD). Trauma exposure during deployment was associated with an increase in all methylation measures, but development of mental health problems 6 months after deployment was only significantly associated with an increased functional methylation. Emergence of post-deployment PTSD symptoms was not related to increased functional methylation over time. Pre-deployment methylation levels did not predict post-deployment psychopathology. To our knowledge, this is the first study to prospectively demonstrate trauma-related increases in GR-1 F methylation, and it shows that only increases at specific functionally relevant sites predispose for post-deployment psychopathology.

Dietary and supplemental maternal methyl-group donor intake and cord blood DNA methylation.

Science.gov (United States)

Pauwels, Sara; Ghosh, Manosij; Duca, Radu Corneliu; Bekaert, Bram; Freson, Kathleen; Huybrechts, Inge; A S Langie, Sabine; Koppen, Gudrun; Devlieger, Roland; Godderis, Lode

2017-01-02

Maternal nutrition is critically involved in the development and health of the fetus. We evaluated maternal methyl-group donor intake through diet (methionine, betaine, choline, folate) and supplementation (folic acid) before and during pregnancy in relation to global DNA methylation and hydroxymethylation and gene specific (IGF2 DMR, DNMT1, LEP, RXRA) cord blood methylation. A total of 115 mother-infant pairs were enrolled in the MAternal Nutrition and Offspring's Epigenome (MANOE) study. The intake of methyl-group donors was assessed using a food-frequency questionnaire. LC-MS/MS and pyrosequencing were used to measure global and gene specific methylation, respectively. Dietary intake of methyl-groups before and during pregnancy was associated with changes in LEP, DNMT1, and RXRA cord blood methylation. Statistically significant higher cord blood LEP methylation was observed when mothers started folic acid supplementation more than 6 months before conception compared with 3-6 months before conception (34.6 ± 6.3% vs. 30.1 ± 3.6%, P = 0.011, LEP CpG1) or no folic acid used before conception (16.2 ± 4.4% vs. 13.9 ± 3%, P = 0.036 for LEP CpG3 and 24.5 ± 3.5% vs. 22.2 ± 3.5%, P = 0.045 for LEP mean CpG). Taking folic acid supplements during the entire pregnancy resulted in statistically significantly higher cord blood RXRA methylation as compared with stopping supplementation in the second trimester (12.3 ± 1.9% vs. 11.1 ± 2%, P = 0.008 for RXRA mean CpG). To conclude, long-term folic acid use before and during pregnancy was associated with higher LEP and RXRA cord blood methylation, respectively. To date, pregnant women are advised to take a folic acid supplement of 400 µg/day from 4 weeks before until 12 weeks of pregnancy. Our results suggest significant epigenetic modifications when taking a folic acid supplement beyond the current advice.

Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease

DEFF Research Database (Denmark)

Cloos, Paul A C; Christensen, Jesper; Agger, Karl

2008-01-01

The enzymes catalyzing lysine and arginine methylation of histones are essential for maintaining transcriptional programs and determining cell fate and identity. Until recently, histone methylation was regarded irreversible. However, within the last few years, several families of histone...... demethylases erasing methyl marks associated with gene repression or activation have been identified, underscoring the plasticity and dynamic nature of histone methylation. Recent discoveries have revealed that histone demethylases take part in large multiprotein complexes synergizing with histone deacetylases......, histone methyltransferases, and nuclear receptors to control developmental and transcriptional programs. Here we review the emerging biochemical and biological functions of the histone demethylases and discuss their potential involvement in human diseases, including cancer....

A panel of genes methylated with high frequency in colorectal cancer

International Nuclear Information System (INIS)

Mitchell, Susan M; Beetson, Iain; Rand, Keith N; McEvoy, Aidan; Thomas, Melissa L; Baker, Rohan T; Wattchow, David A; Young, Graeme P; Lockett, Trevor J; Pedersen, Susanne K; LaPointe, Lawrence C; Ross, Jason P; Molloy, Peter L; Drew, Horace R; Ho, Thu; Brown, Glenn S; Saunders, Neil FW; Duesing, Konsta R; Buckley, Michael J; Dunne, Rob

2014-01-01

The development of colorectal cancer (CRC) is accompanied by extensive epigenetic changes, including frequent regional hypermethylation particularly of gene promoter regions. Specific genes, including SEPT9, VIM1 and TMEFF2 become methylated in a high fraction of cancers and diagnostic assays for detection of cancer-derived methylated DNA sequences in blood and/or fecal samples are being developed. There is considerable potential for the development of new DNA methylation biomarkers or panels to improve the sensitivity and specificity of current cancer detection tests. Combined epigenomic methods – activation of gene expression in CRC cell lines following DNA demethylating treatment, and two novel methods of genome-wide methylation assessment – were used to identify candidate genes methylated in a high fraction of CRCs. Multiplexed amplicon sequencing of PCR products from bisulfite-treated DNA of matched CRC and non-neoplastic tissue as well as healthy donor peripheral blood was performed using Roche 454 sequencing. Levels of DNA methylation in colorectal tissues and blood were determined by quantitative methylation specific PCR (qMSP). Combined analyses identified 42 candidate genes for evaluation as DNA methylation biomarkers. DNA methylation profiles of 24 of these genes were characterised by multiplexed bisulfite-sequencing in ten matched tumor/normal tissue samples; differential methylation in CRC was confirmed for 23 of these genes. qMSP assays were developed for 32 genes, including 15 of the sequenced genes, and used to quantify methylation in tumor, adenoma and non-neoplastic colorectal tissue and from healthy donor peripheral blood. 24 of the 32 genes were methylated in >50% of neoplastic samples, including 11 genes that were methylated in 80% or more CRCs and a similar fraction of adenomas. This study has characterised a panel of 23 genes that show elevated DNA methylation in >50% of CRC tissue relative to non-neoplastic tissue. Six of these genes

Synthesis and characteristics in tumor-bearing mice of N-[11C]methyl-1-deoxynojirimycin and N-[11C]methyl-1-deoxymannojirimycin

International Nuclear Information System (INIS)

Ishiwata, Kiichi; Sasaki, Toru; Ishii, Shin-ichi; Senda, Michio; Seki, Hiroyuki; Kitasato Univ.; Nozaki, Tadashi

1993-01-01

N-[ 11 C]Methyl-1-deoxynojirimycin ([ 11 C]MDNM) and N-[ 11 C]methyl-1-deoxymannojirimycin ([ 11 C]MDMM) were prepared by 11 C-methylation of 1-deoxynojirimycin (DNM) and 1-deoxymannojirimycin (DMM), which are specific inhibitors of glucosidase and mannosidase, respectively. In mice bearing Ehrich ascitic tumor, the highest uptake of the [ 11 C]MDNM was observed in the kidney, followed by the liver and small intestine, while the tumour uptake was moderate. By MDNM loading, saturable uptake was observed in these tissues. In homogenates of the kidney and tumor tissues, a considerable amount of radioactivity was detected in a high-molecular weight fraction. These results demonstrate that the [ 11 C]MDNM has a potential for imaging the glucosidase activity by positron emission tomography. On the other hand, [ 11 C]MDMM showed lower uptake than [ 11 C]MDNM in the kidney, liver and small intestine and no effect of carrier DMM, suggesting that the [ 11 C]MDMM would not reflect mannosidase activity. (Author)

Detection of DNA methylation changes in micropropagated banana plants using methylation-sensitive amplification polymorphism (MSAP).

Science.gov (United States)

Peraza-Echeverria, S; Herrera-Valencia, V A.; Kay, A -J.

2001-07-01

The extent of DNA methylation polymorphisms was evaluated in micropropagated banana (Musa AAA cv. 'Grand Naine') derived from either the vegetative apex of the sucker or the floral apex of the male inflorescence using the methylation-sensitive amplification polymorphism (MSAP) technique. In all, 465 fragments, each representing a recognition site cleaved by either or both of the isoschizomers were amplified using eight combinations of primers. A total of 107 sites (23%) were found to be methylated at cytosine in the genome of micropropagated banana plants. In plants micropropagated from the male inflorescence explant 14 (3%) DNA methylation events were polymorphic, while plants micropropagated from the sucker explant produced 8 (1.7%) polymorphisms. No DNA methylation polymorphisms were detected in conventionally propagated banana plants. These results demonstrated the usefulness of MSAP to detect DNA methylation events in micropropagated banana plants and indicate that DNA methylation polymorphisms are associated with micropropagation.

β-methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart

International Nuclear Information System (INIS)

DeGrado, T.R.; Holden, J.E.; Ng, C.K.; Raffel, D.M.; Gatley, S.J.

1989-01-01

The use of 15-p-iodophenyl-β-methyl-pentadecanoic acid (βMe-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both βMe-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, βMe-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond βMe-IPPA-CoA in the oxidative pathway. (orig.)

Current Status and Future Prospect of K-NET and KiK-net

Science.gov (United States)

Aoi, S.; Kunugi, T.; Suzuki, W.; Nakamura, H.; Fujiwara, H.

2014-12-01

During 18 years since the deployment of K-NET following the Kobe earthquake, our attention has mainly focused on rapidity of the data collection and an unfailing and reliable observation. In this presentation, we review three generations of the instruments employed by K-NET and KiK-net from these two points of view.At beginning of the 2000's, we newly developed the second generation instruments (K-NET02, K-NET02A, KiK-net06) to replace the first generation instruments (K-NET95, SMAC-MDK) employed when the networks were constructed in the 1990's. These instruments have an automatic dial-out function. It takes typically 2-5 s to establish communication and a few seconds to send the pre-trigger data. After that, data is available typically within a 1.5 s delay. Not only waveform data but also strong motion indexes such as real-time intensity, PGA, PGV, PGD, and response spectra are continuously sent once a second.After the 2011 Tohoku earthquake, we have developed the third generation instruments (K-NET11, KiK-net11) and have replaced almost half of the all stations country wide. Main improvement of this instrument is more unfailing and reliable observation. Because we have often experienced very large ground motions (e.g. 45 records exceeding gravity), the maximum measureable range was expanded from 2000 gal to 4000 gal for the second generation instrument, and to 8000 gal for the third. For the third generation instrument, in case of power failure, observation (including transmission of data) works for seven days thanks to the backup battery, while for the second generation instruments it works only for one day. By adding an oblique component to the three-component accelerometers, we could automatically distinguish shaking data from noise such as electric pulses which may cause a false alarm in EEW. Implementation to guarantee the continuity of observation under severe conditions such as during the Tohoku earthquake is very important, as well as a highly efficient

DNA methylation signatures for prediction of biochemical recurrence after radical prostatectomy of clinically localized prostate cancer

DEFF Research Database (Denmark)

Haldrup, Christa; Mundbjerg, Kamilla; Vestergaard, Else Marie

2013-01-01

Purpose Diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, causing overtreatment of indolent PC and risk of delayed treatment of aggressive PC. Here, we identify six novel candidate DNA methylation markers for PC with promising diagnostic and prognostic potential. Methods...... Microarray-based screening and bisulfite sequencing of 20 nonmalignant and 29 PC tissue specimens were used to identify new candidate DNA hypermethylation markers for PC. Diagnostic and prognostic potential was evaluated in 35 nonmalignant prostate tissue samples, 293 radical prostatectomy (RP) samples...... into low- and high-methylation subgroups, was trained in cohort 1 (HR, 1.91; 95% CI, 1.26 to 2.90) and validated in cohort 2 (HR, 2.33; 95% CI, 1.31 to 4.13). Conclusion We identified six novel candidate DNA methylation markers for PC. C1orf114 hypermethylation and a three-gene methylation signature were...

Quantitative Methylation Profiles for Multiple Tumor Suppressor Gene Promoters in Salivary Gland Tumors

Science.gov (United States)

Durr, Megan L.; Mydlarz, Wojciech K.; Shao, Chunbo; Zahurak, Marianna L.; Chuang, Alice Y.; Hoque, Mohammad O.; Westra, William H.; Liegeois, Nanette J.; Califano, Joseph A.; Sidransky, David; Ha, Patrick K.

2010-01-01

Background Methylation profiling of tumor suppressor gene (TSGs) promoters is quickly becoming a powerful diagnostic tool for the early detection, prognosis, and even prediction of clinical response to treatment. Few studies address this in salivary gland tumors (SGTs); hence the promoter methylation profile of various TSGs was quantitatively assessed in primary SGT tissue to determine if tumor-specific alterations could be detected. Methodology DNA isolated from 78 tumor and 17 normal parotid gland specimens was assayed for promoter methylation status of 19 TSGs by fluorescence-based, quantitative methylation-specific PCR (qMSP). The data were utilized in a binary fashion as well as quantitatively (using a methylation quotient) allowing for better profiling and interpretation of results. Principal Findings The average number of methylation events across the studied genes was highest in salivary duct carcinoma (SDC), with a methylation value of 9.6, compared to the normal 4.5 (ptrend for increasing methylation in APC, Mint 1, PGP9.5, RAR-β, and Timp3. Conclusions/Significance Screening promoter methylation profiles in SGTs showed considerable heterogeneity. The methylation status of certain markers was surprisingly high in even normal salivary tissue, confirming the need for such controls. Several TSGs were found to be associated with malignant SGTs, especially SDC. Further study is needed to evaluate the potential use of these associations in the detection, prognosis, and therapeutic outcome of these rare tumors. PMID:20520817

Markets, voucher subsidies and free nets combine to achieve high bed net coverage in rural Tanzania

Directory of Open Access Journals (Sweden)

Gerrets Rene PM

2008-06-01

Full Text Available Abstract Background Tanzania has a well-developed network of commercial ITN retailers. In 2004, the government introduced a voucher subsidy for pregnant women and, in mid 2005, helped distribute free nets to under-fives in small number of districts, including Rufiji on the southern coast, during a child health campaign. Contributions of these multiple insecticide-treated net delivery strategies existing at the same time and place to coverage in a poor rural community were assessed. Methods Cross-sectional household survey in 6,331 members of randomly selected 1,752 households of 31 rural villages of Demographic Surveillance System in Rufiji district, Southern Tanzania was conducted in 2006. A questionnaire was administered to every consenting respondent about net use, treatment status and delivery mechanism. Findings Net use was 62.7% overall, 87.2% amongst infants (0 to1 year, 81.8% amongst young children (>1 to 5 years, 54.5% amongst older children (6 to 15 years and 59.6% amongst adults (>15 years. 30.2% of all nets had been treated six months prior to interview. The biggest source of nets used by infants was purchase from the private sector with a voucher subsidy (41.8%. Half of nets used by young children (50.0% and over a third of those used by older children (37.2% were obtained free of charge through the vaccination campaign. The largest source of nets amongst the population overall was commercial purchase (45.1% use and was the primary means for protecting adults (60.2% use. All delivery mechanisms, especially sale of nets at full market price, under-served the poorest but no difference in equity was observed between voucher-subsidized and freely distributed nets. Conclusion All three delivery strategies enabled a poor rural community to achieve net coverage high enough to yield both personal and community level protection for the entire population. Each of them reached their relevant target group and free nets only temporarily

Human Papillomavirus DNA Methylation as a Biomarker for Cervical Precancer: Consistency across 12 Genotypes and Potential Impact on Management of HPV-Positive Women.

Science.gov (United States)

Clarke, Megan A; Gradissimo, Ana; Schiffman, Mark; Lam, Jessica; Sollecito, Christopher C; Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy; Raine-Bennett, Tina R; Castle, Philip E; Wentzensen, Nicolas; Burk, Robert D

2018-05-01

Purpose: Human papillomavirus (HPV) DNA methylation testing is a promising triage option for women testing HPV positive during cervical cancer screening. However, the extent to which methylation indicates precancer for all 12 carcinogenic HPV types has not been evaluated. Experimental Design: In this nested case-control study, we tested up to 30 cases of precancer [cervical intraepithelial neoplasia grade 3 (CIN3)/adenocarcinoma in situ (AIS)] and 30 normal controls for each carcinogenic type (single infections with 16/18/31/33/35/39/45/51/52/56/58/59). Next-generation bisulfite sequencing was performed on CpG sites within the L1 and L2 genes. We calculated differences in methylation, ORs, and AUC. Using a fixed sensitivity of 80%, we evaluated the specificity and the risk of CIN3/AIS for best performing CpG sites, and compared the performance of an explorative multi-type methylation assay with current triage strategies. Results: Methylation was positively associated with CIN3/AIS across all 12 types. AUCs for the top sites ranged from 0.71 (HPV51 and HPV56) to 0.86 (HPV18). A combined 12-type methylation assay had the highest Youden index (0.46), compared with cytology (0.31) and a 5-type methylation assay, including only previously described types (0.26). The 12-type methylation assay had higher sensitivity (80% vs. 76.6%) and lower test positivity compared with cytology (38.5% vs. 48.7%). The risk of CIN3/AIS was highest for methylation positives and lowest for cytology or HPV16/18 positives. Conclusions: HPV DNA methylation is a general phenomenon marking the transition from HPV infection to precancer for all 12 carcinogenic types. Development of a combined multitype methylation assay may serve as a triage test for HPV-positive women. Clin Cancer Res; 24(9); 2194-202. ©2018 AACR . ©2018 American Association for Cancer Research.

The origin and fate of 4-methyl steroid hydrocarbons. I. Diagenesis of 4-methyl sterenes

Science.gov (United States)

Wolff, George A.; Lamb, Neil A.; Maxwell, James R.

1986-03-01

Treatment of 4-methylcholest-4-ene under mild acid conditions at low temperatures gives chemical evidence for certain features seen in the distributions of sedimentary 4-methyl steroid hydrocarbons, and further indicates that many low temperature diagenetic reactions of steroids are explicable in terms of acid catalysed rearrangements. Specifically, the results provide: (i) Indirect evidence that the 4-ene skeleton is a key intermediate in the dehydration of 4-methyl stanols in sediments. (ii) An explanation for the distribution of 4-methyl sterenes and A-nor sterenes in the lacustrine Messel shale (Eocene). (iii) An explanation for the presence of 4β-methyl steranes in relatively immature sedimentary rocks, despite the precursor stanols having the 4α-methyl configuration. With increasing maturity in the Paris Basin shales (Lower Toarcian), the less stable 4β-methyl steranes decrease gradually in abundance relative to their 4α-methyl counterparts, at a rate fairly similar to the change in pristane stereochemistry.

[Novel Approaches in DNA Methylation Studies - MS-HRM Analysis and Electrochemistry].

Science.gov (United States)

Bartošík, M; Ondroušková, E

Cytosine methylation in DNA is an epigenetic mechanism regulating gene expression and plays a vital role in cell differentiation or proliferation. Tumor cells often exhibit aberrant DNA methylation, e.g. hypermethylation of tumor suppressor gene promoters. New methods, capable of determining methylation status of specific DNA sequences, are thus being developed. Among them, MS-HRM (methylation-specific high resolution melting) and electrochemistry offer relatively inexpensive instrumentation, fast assay times and possibility of screening multiple samples/DNA regions simultaneously. MS-HRM is due to its sensitivity and simplicity an interesting alternative to already established techniques, including methylation-specific PCR or bisulfite sequencing. Electrochemistry, when combined with suitable electroactive labels and electrode surfaces, has been applied in several unique strategies for discrimination of cytosines and methylcytosines. Both techniques were successfully tested in analysis of DNA methylation within promoters of important tumor suppressor genes and could thus help in achieving more precise diagnostics and prognostics of cancer. Aberrant methylation of promoters has already been described in hundreds of genes associated with tumorigenesis and could serve as important biomarker if new methods applicable into clinical practice are sufficiently advanced.Key words: DNA methylation - 5-methylcytosine - HRM analysis - melting temperature - DNA duplex - electrochemistry - nucleic acid hybridizationThis work was supported by MEYS - NPS I - LO1413.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 6. 5. 2016Accepted: 16. 5. 2016.

Detection and discrimination of maintenance and de novo CpG methylation events using MethylBreak.

Science.gov (United States)

Hsu, William; Mercado, Augustus T; Hsiao, George; Yeh, Jui-Ming; Chen, Chung-Yung

2017-05-15

Understanding the principles governing the establishment and maintenance activities of DNA methyltransferases (DNMTs) can help in the development of predictive biomarkers associated with genetic disorders and diseases. A detection system was developed that distinguishes and quantifies methylation events using methylation-sensitive endonucleases and molecular beacon technology. MethylBreak (MB) is a 22-mer oligonucleotide with one hemimethylated and two unmethylated CpG sites, which are also recognition sites for Sau96I and SacII, and is attached to a fluorophore and a quencher. Maintenance methylation was quantified by fluorescence emission due to the digestion of SacII when the hemimethylated CpG site is methylated, which inhibits Sau96I cleavage. The signal difference between SacII digestion of both MB substrate and maintenance methylated MB corresponds to de novo methylation event. Our technology successfully discriminated and measured both methylation activities at different concentrations of MB and achieved a high correlation coefficient of R 2 =0.997. Additionally, MB was effectively applied to normal and cancer cell lines and in the analysis of enzymatic kinetics and RNA inhibition of recombinant human DNMT1. Copyright © 2017 Elsevier B.V. All rights reserved.

Initial CAD investigations for NET

International Nuclear Information System (INIS)

Katz, F.; Leinemann, K.; Ludwig, A.; Marek, U.; Olbrich, W.; Schlechtendahl, E.G.

1985-11-01

This report summarizes the work done under contract no. 164/84-7/FU-D-/NET between the Commission of the European Communities and KfK during the period from June 1, 1984, through May 31, 1985. The following topics are covered in this report: Initial modelling of NET version NET2A, CAD system extension for remote handling studies, analysis of the CAD information structure, work related to the transfer of CAD information between KfK and the NET team. (orig.) [de

Perceptions on the effect of small electric fans on comfort inside bed nets in southern Ghana: a qualitative study.

Science.gov (United States)

Jaeger, Mulako S; Briët, Olivier J T; Keating, Joseph; Ahorlu, Collins K; Yukich, Joshua O; Oppong, Samuel; Nardini, Peter; Pfeiffer, Constanze

2016-12-01

Long-lasting insecticidal nets (LLINs) are known to be highly effective in reducing malaria transmission, morbidity and mortality. However, among those owning an LLIN, use rates are often suboptimal. A reported barrier to bed net use is discomfort due to heat. This qualitative study was part of a larger evaluation conducted in communities without electricity in rural Ghana to assess whether 0.8 W solar powered net fans can increase net use. Twenty-three key informant interviews with household heads in the study communities in Shai-Osudoku District, southern Ghana, were conducted from July to August 2015. The purpose of the interviews was to obtain insight into perceptions of participants about the net fan system in relation to LLIN use. While all study participants reported using LLINs, with mosquito nuisance prevention as the prime motivation, heat was also mentioned as a key barrier to net use. Respondents appreciated the net fans because they improved comfort inside bed nets. The LED light on the fan stand became the main source of light at night and positively influenced the perception of the intervention as a whole. The general acceptance of the net fan system by the study participants highlights the potential of the intervention to improve comfort inside mosquito nets. This, therefore, has a potential to increase bed net use in areas with low access to electricity.

Forensic individual age estimation with DNA: From initial approaches to methylation tests.

Science.gov (United States)

Freire-Aradas, A; Phillips, C; Lareu, M V

2017-07-01

Individual age estimation is a key factor in forensic science analysis that can provide very useful information applicable to criminal, legal, and anthropological investigations. Forensic age inference was initially based on morphological inspection or radiography and only later began to adopt molecular approaches. However, a lack of accuracy or technical problems hampered the introduction of these DNA-based methodologies in casework analysis. A turning point occurred when the epigenetic signature of DNA methylation was observed to gradually change during an individual´s lifespan. In the last four years, the number of publications reporting DNA methylation age-correlated changes has gradually risen and the forensic community now has a range of age methylation tests applicable to forensic casework. Most forensic age predictor models have been developed based on blood DNA samples, but additional tissues are now also being explored. This review assesses the most widely adopted genes harboring methylation sites, detection technologies, statistical age-predictive analyses, and potential causes of variation in age estimates. Despite the need for further work to improve predictive accuracy and establishing a broader range of tissues for which tests can analyze the most appropriate methylation sites, several forensic age predictors have now been reported that provide consistency in their prediction accuracies (predictive error of ±4 years); this makes them compelling tools with the potential to contribute key information to help guide criminal investigations. Copyright © 2017 Central Police University.

Adsorption, desorption and mobility of metsulfuron-methyl in soils of the oil palm agroecosystem in Malaysia.

Science.gov (United States)

Ismail, B S; Ooi, K E

2012-05-01

Laboratory experiments were conducted to evaluate adsorption, desorption and mobility of metsulfuron-methyl in soils of the oil palm agroecosystem consisting of the Bernam, Selangor, Rengam and Bongor soil series. The lowest adsorption of metsulfuron-methyl occurred in the Bongor soil (0.366 ml g(-1)), and the highest in the Bemam soil (2.837 ml g(-1). The K(fads) (Freundlich) values of metsulfuron-methyl were 0.366, 0.560, 1.570 and 2.837 ml g(-1) in Bongor, Rengam, Selangor and Bemam soil, respectively. The highest K(fdes) value of metsulfuron-methyl, observed in the Bemam soil, was 2.563 indicating low desorption 0.280 (relatively strong retention). In contrast, the lowest K(fdes) value of 0.564 was observed for the Bongor soil, which had the lowest organic matter (1.43%) and clay content (13.2%). Soil organic matter and clay content were the main factors affecting the adsorption of metsulfuron-methyl. The results of the soil column leaching studies suggested that metsulfuron-methyl has a moderate potential for mobility in the Bernam and Bongor soil series with 19.3% and 39%, respectively for rainfall at 200 mm. However, since metsulfuron-methyl is applied at a very low rate (the maximum field application rate used was 30 g ha(-1)) and is susceptible to biodegradation, the potential forground water contamination is low.

Promoter DNA methylation pattern identifies prognostic subgroups in childhood T-cell acute lymphoblastic leukemia.

Directory of Open Access Journals (Sweden)

Magnus Borssén

Full Text Available BACKGROUND: Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided. DESIGN AND METHODS: Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n = 43 using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n = 32. RESULTS: Based on CpG island methylator phenotype (CIMP, T-ALL samples were subgrouped as CIMP+ (high methylation and CIMP- (low methylation. CIMP- T-ALL patients had significantly worse overall and event free survival (p = 0.02 and p = 0.001, respectively compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes. CONCLUSIONS: We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL.

NetBeans IDE 8 cookbook

CERN Document Server

Salter, David

2014-01-01

If you're a Java developer of any level using NetBeans and want to learn how to get the most out of NetBeans, then this book is for you. Learning how to utilize NetBeans will provide a firm foundation for your Java application development.

The Net Advance of Physics

Science.gov (United States)

THE NET ADVANCE OF PHYSICS Review Articles and Tutorials in an Encyclopædic Format Established 1995 [Link to MIT] Computer support for The Net Advance of Physics is furnished by The Massachusetts Newest Additions SPECIAL FEATURES: Net Advance RETRO: Nineteenth Century Physics History of Science

Geissoschizine methyl ether, a corynanthean-type indole alkaloid from Uncaria rhynchophylla as a potential acetylcholinesterase inhibitor.

Science.gov (United States)

Yang, Zhong-Duo; Duan, Dong-Zhu; Du, Juan; Yang, Ming-Jun; Li, Shuo; Yao, Xiao-Jun

2012-01-01

Geissoschizine methyl ether (1), a newly discovered strong acetylcholinesterase (AChE) inhibitor, along with six weakly active alkaloids, vallesiachotamine (2), hisuteine (3), hirsutine (4), isorhynchophylline (5), cisocorynoxeine (6) and corynoxeine (7) have been isolated from Uncaria rhynchophylla. Geissoschizine methyl ether (1) inhibited 50% of AChE activity at concentrations of 3.7 ± 0.3 µg mL(-1) while the IC(50) value of physostigmine as a standard was 0.013 ± 0.002 µg mL(-1). The mode of AChE inhibition by 1 was reversible and non-competitive. In addition, molecular modelling was performed to explore the binding mode of inhibitor 1 at the active site of AChE.

Genome-wide DNA methylation patterns in wild samples of two morphotypes of threespine stickleback (Gasterosteus aculeatus).

Science.gov (United States)

Smith, Gilbert; Smith, Carl; Kenny, John G; Chaudhuri, Roy R; Ritchie, Michael G

2015-04-01

Epigenetic marks such as DNA methylation play important biological roles in gene expression regulation and cellular differentiation during development. To examine whether DNA methylation patterns are potentially associated with naturally occurring phenotypic differences, we examined genome-wide DNA methylation within Gasterosteus aculeatus, using reduced representation bisulfite sequencing. First, we identified highly methylated regions of the stickleback genome, finding such regions to be located predominantly within genes, and associated with genes functioning in metabolism and biosynthetic processes, cell adhesion, signaling pathways, and blood vessel development. Next, we identified putative differentially methylated regions (DMRs) of the genome between complete and low lateral plate morphs of G. aculeatus. We detected 77 DMRs that were mainly located in intergenic regions. Annotations of genes associated with these DMRs revealed potential functions in a number of known divergent adaptive phenotypes between G. aculeatus ecotypes, including cardiovascular development, growth, and neuromuscular development. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Experimental and computational approaches of a novel methyl (2E)-2-{[N-(2-formylphenyl)(4-methylbenzene)sulfonamido]methyl}-3-(4-chlorophenyl)prop-2-enoate: A potential antimicrobial agent and an inhibition of penicillin-binding protein

Science.gov (United States)

Murugavel, S.; Vetri velan, V.; Kannan, Damodharan; Bakthadoss, Manickam

2016-07-01

The title compound methyl(2E)-2-{[N-(2-formylphenyl) (4-methylbenzene)sulfonamido]methyl}-3-(4-chlorophenyl) prop-2-enoate (MFMSC) has been synthesized and single crystals were grown by slow evaporation solution growth technique at room temperature. Structural and vibrational spectroscopic studies were carried out by using single crystal X-ray diffraction, FT-IR and NMR spectral analysis together with DFT method using GAUSSIAN'03 software. The detailed interpretation of the vibrational spectra has been carried out by VEDA program. NBO analysis, Mulliken charge analysis, HOMO-LUMO, MEP, Global chemical reactivity descriptors and thermodynamic properties have been analyzed. The hyperpolarisability calculation reveals the present material has a reasonably good propensity for nonlinear optical activity. The obtained antimicrobial activity results indicate that the compound shows good to moderate activity against all tested bacterial and fungal pathogens. A computational study was also carried out to predict the drug-likeness and ADMET properties of the title compound. Due to the different potential biological activity of the title compound, molecular docking study is also reported and the compound might exhibit inhibitory activity against penicillin-binding protein PBP-2X.

Improved netting

International Nuclear Information System (INIS)

Bramley, A.; Clabburn, R.J.T.

1976-01-01

A method is described for producing netting composed of longitudinal and transverse threads of irradiation cross linked thermoplastic material, the threads being joined together at their crossings by moulded masses of cross linked thermoplastic material. The thread may be formed of polyethylene filaments, subjected to a radiation dose of 15 to 25 MR. The moulding can be conducted at 245 0 to 260 0 C or higher. The product is claimed to be an improved quality of netting, with bonds of increased strength between crossing threads. (U.K.)

Mobility and molecular ions of dimethyl methyl phosphonate, methyl salicylate and acetone

Science.gov (United States)

Nowak, D. M.

1983-06-01

The mobilities of positive and negative reactant ions are reported for (H2O)nH(+); (H2O)2O2 and (H2O)2CO3(-) ion clusters. The formation of positive DMMP monomer and dimer is reported, and equilbria molecular reactions are reported. Acetone is reported as forming a dimer at 81 ppb with a reduced mobility (K sub o) of 1.82, Methyl salicylate is shown to form a protonated and hydrated positive monomer. Mixtures of DMMP and methyl salicylate with acetone showed a substantial change in DMMP ion clustering and little or no change in the methyl salicylate mobility spectra. Negative ions were not observed for DMMP, methyl salicylate, acetone and the mixtures under the conditions reported.

Net alkalinity and net acidity 1: Theoretical considerations

International Nuclear Information System (INIS)

Kirby, Carl S.; Cravotta, Charles A.

2005-01-01

Net acidity and net alkalinity are widely used, poorly defined, and commonly misunderstood parameters for the characterization of mine drainage. The authors explain theoretical expressions of 3 types of alkalinity (caustic, phenolphthalein, and total) and acidity (mineral, CO 2 , and total). Except for rarely-invoked negative alkalinity, theoretically defined total alkalinity is closely analogous to measured alkalinity and presents few practical interpretation problems. Theoretically defined 'CO 2 -acidity' is closely related to most standard titration methods with an endpoint pH of 8.3 used for determining acidity in mine drainage, but it is unfortunately named because CO 2 is intentionally driven off during titration of mine-drainage samples. Using the proton condition/mass-action approach and employing graphs to illustrate speciation with changes in pH, the authors explore the concept of principal components and how to assign acidity contributions to aqueous species commonly present in mine drainage. Acidity is defined in mine drainage based on aqueous speciation at the sample pH and on the capacity of these species to undergo hydrolysis to pH 8.3. Application of this definition shows that the computed acidity in mgL -1 as CaCO 3 (based on pH and analytical concentrations of dissolved Fe II , Fe III , Mn, and Al in mgL -1 ):acidity calculated =50{1000(10 -pH )+[2(Fe II )+3(Fe III )]/56+2(Mn) /55+3(Al)/27}underestimates contributions from HSO 4 - and H + , but overestimates the acidity due to Fe 3+ and Al 3+ . However, these errors tend to approximately cancel each other. It is demonstrated that 'net alkalinity' is a valid mathematical construction based on theoretical definitions of alkalinity and acidity. Further, it is shown that, for most mine-drainage solutions, a useful net alkalinity value can be derived from: (1) alkalinity and acidity values based on aqueous speciation (2) measured alkalinity minus calculated acidity, or (3) taking the negative of the

Net alkalinity and net acidity 1: Theoretical considerations

Science.gov (United States)

Kirby, C.S.; Cravotta, C.A.

2005-01-01

Net acidity and net alkalinity are widely used, poorly defined, and commonly misunderstood parameters for the characterization of mine drainage. The authors explain theoretical expressions of 3 types of alkalinity (caustic, phenolphthalein, and total) and acidity (mineral, CO2, and total). Except for rarely-invoked negative alkalinity, theoretically defined total alkalinity is closely analogous to measured alkalinity and presents few practical interpretation problems. Theoretically defined "CO 2-acidity" is closely related to most standard titration methods with an endpoint pH of 8.3 used for determining acidity in mine drainage, but it is unfortunately named because CO2 is intentionally driven off during titration of mine-drainage samples. Using the proton condition/mass- action approach and employing graphs to illustrate speciation with changes in pH, the authors explore the concept of principal components and how to assign acidity contributions to aqueous species commonly present in mine drainage. Acidity is defined in mine drainage based on aqueous speciation at the sample pH and on the capacity of these species to undergo hydrolysis to pH 8.3. Application of this definition shows that the computed acidity in mg L -1 as CaCO3 (based on pH and analytical concentrations of dissolved FeII, FeIII, Mn, and Al in mg L -1):aciditycalculated=50{1000(10-pH)+[2(FeII)+3(FeIII)]/56+2(Mn)/ 55+3(Al)/27}underestimates contributions from HSO4- and H+, but overestimates the acidity due to Fe3+ and Al3+. However, these errors tend to approximately cancel each other. It is demonstrated that "net alkalinity" is a valid mathematical construction based on theoretical definitions of alkalinity and acidity. Further, it is shown that, for most mine-drainage solutions, a useful net alkalinity value can be derived from: (1) alkalinity and acidity values based on aqueous speciation, (2) measured alkalinity minus calculated acidity, or (3) taking the negative of the value obtained in a

Climatic Forecasting of Net Infiltration at Yucca Mountain Using Analogue Meteorological Data

International Nuclear Information System (INIS)

B. Faybishenko

2006-01-01

At Yucca Mountain, Nevada, future changes in climatic conditions will most likely alter net infiltration, or the drainage below the bottom of the evapotranspiration zone within the soil profile or flow across the interface between soil and the densely welded part of the Tiva Canyon Tuff. The objectives of this paper are to: (a) develop a semi-empirical model and forecast average net infiltration rates, using the limited meteorological data from analogue meteorological stations, for interglacial (present day), and future monsoon, glacial transition, and glacial climates over the Yucca Mountain region, and (b) corroborate the computed net-infiltration rates by comparing them with the empirically and numerically determined groundwater recharge and percolation rates through the unsaturated zone from published data. In this paper, the author presents an approach for calculations of net infiltration, aridity, and precipitation-effectiveness indices, using a modified Budyko's water-balance model, with reference-surface potential evapotranspiration determined from the radiation-based Penman (1948) formula. Results of calculations show that net infiltration rates are expected to generally increase from the present-day climate to monsoon climate, to glacial transition climate, and then to the glacial climate. The forecasting results indicate the overlap between the ranges of net infiltration for different climates. For example, the mean glacial net-infiltration rate corresponds to the upper-bound glacial transition net infiltration, and the lower-bound glacial net infiltration corresponds to the glacial transition mean net infiltration. Forecasting of net infiltration for different climate states is subject to numerous uncertainties-associated with selecting climate analogue sites, using relatively short analogue meteorological records, neglecting the effects of vegetation and surface runoff and runon on a local scale, as well as possible anthropogenic climate changes

Proof Nets for Lambek Calculus

NARCIS (Netherlands)

Roorda, Dirk

1992-01-01

The proof nets of linear logic are adapted to the non-commutative Lambek calculus. A different criterion for soundness of proof nets is given, which gives rise to new algorithms for proof search. The order sensitiveness of the Lambek calculus is reflected by the planarity condition on proof nets;

Potential roles of DNA methylation in the initiation and establishment of replicative senescence revealed by array-based methylome and transcriptome analyses.

Directory of Open Access Journals (Sweden)

Mizuho Sakaki

Full Text Available Cellular senescence is classified into two groups: replicative and premature senescence. Gene expression and epigenetic changes are reported to differ between these two groups and cell types. Normal human diploid fibroblast TIG-3 cells have often been used in cellular senescence research; however, their epigenetic profiles are still not fully understood. To elucidate how cellular senescence is epigenetically regulated in TIG-3 cells, we analyzed the gene expression and DNA methylation profiles of three types of senescent cells, namely, replicatively senescent, ras-induced senescent (RIS, and non-permissive temperature-induced senescent SVts8 cells, using gene expression and DNA methylation microarrays. The expression of genes involved in the cell cycle and immune response was commonly either down- or up-regulated in the three types of senescent cells, respectively. The altered DNA methylation patterns were observed in replicatively senescent cells, but not in prematurely senescent cells. Interestingly, hypomethylated CpG sites detected on non-CpG island regions ("open sea" were enriched in immune response-related genes that had non-CpG island promoters. The integrated analysis of gene expression and methylation in replicatively senescent cells demonstrated that differentially expressed 867 genes, including cell cycle- and immune response-related genes, were associated with DNA methylation changes in CpG sites close to the transcription start sites (TSSs. Furthermore, several miRNAs regulated in part through DNA methylation were found to affect the expression of their targeted genes. Taken together, these results indicate that the epigenetic changes of DNA methylation regulate the expression of a certain portion of genes and partly contribute to the introduction and establishment of replicative senescence.

Bed net use and associated factors in a rice farming community in Central Kenya

Directory of Open Access Journals (Sweden)

Kabuage Lucy

2009-04-01

Full Text Available Abstract Background Use of insecticide-treated nets (ITNs continues to offer potential strategy for malaria prevention in endemic areas. However their effectiveness, sustainability and massive scale up remain a factor of socio-economic and cultural variables of the local community which are indispensable during design and implementation stages. Methods An ethnographic household survey was conducted in four study villages which were purposefully selected to represent socio-economic and geographical diversity. In total, 400 households were randomly selected from the four study villages. Quantitative and qualitative information of the respondents were collected by use of semi-structured questionnaires and focus group discussions. Results Malaria was reported the most frequently occurring disease in the area (93% and its aetiology was attributed to other non-biomedical causes like stagnant water (16%, and long rains (13%. Factors which significantly caused variation in bed net use were occupant relationship to household head (χ2 = 105.705; df 14; P = 0.000, Age (χ2 = 74.483; df 14; P = 0.000, village (χ2 = 150.325; df 6; P = 0.000, occupation (χ2 = 7.955; df 3; P = 0.047, gender (χ2 = 4.254; df 1; P = 0.039 and education levels of the household head or spouse (χ2 = 33.622; df 6; P = 0.000. The same variables determined access and conditions of bed nets at household level. Protection against mosquito bite (95% was the main reason cited for using bed nets in most households while protection against malaria came second (54%. Colour, shape and affordability were some of the key potential factors which determined choice, use and acceptance of bed nets in the study area. Conclusion The study highlights potential social and economic variables important for effective and sustainable implementation of bed nets-related programmes in Sub-Saharan Africa.

Properties of porous netted materials

International Nuclear Information System (INIS)

Daragan, V.D.; Drozdov, B.G.; Kotov, A.Yu.; Mel'nikov, G.N.; Pustogarov, A.V.

1987-01-01

Hydraulic and strength characteristics, efficient heat conduction and inner heat exchange coefficient are experimentally studied for porous netted materials on the base of the brass nets as dependent on porosity, cell size and method of net laying. Results of the studies are presented. It is shown that due to anisotropy of the material properties the hydraulic resistance in the direction parallel to the nets plane is 1.3-1.6 times higher than in the perpendicular one. Values of the effective heat conduction in the direction perpendicular to the nets plane at Π>0.45 agree with the data from literature, at Π<0.45 a deviation from the calculated values is marked in the direction of the heat conduction decrease

Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

Energy Technology Data Exchange (ETDEWEB)

Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj [Division of Clinical Embryology, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal 576 104 (India); Kalthur, Sneha Guruprasad; D' Souza, Antony Sylvan [Department of Anatomy, Kasturba Medical College, Manipal University, Manipal 576 104 (India); Shetty, Pallavi K.; Mutalik, Srinivas [Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576 104 (India); Kalthur, Guruprasad, E-mail: guru.kalthur@manipal.edu [Division of Clinical Embryology, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal 576 104 (India); Adiga, Satish Kumar [Division of Clinical Embryology, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal 576 104 (India)

2014-09-15

Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA

Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

International Nuclear Information System (INIS)

Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj; Kalthur, Sneha Guruprasad; D'Souza, Antony Sylvan; Shetty, Pallavi K.; Mutalik, Srinivas; Kalthur, Guruprasad; Adiga, Satish Kumar

2014-01-01

Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA

Critical threshold levels of DNA methyltransferase 1 are required to maintain DNA methylation across the genome in human cancer cells.

Science.gov (United States)

Cai, Yi; Tsai, Hsing-Chen; Yen, Ray-Whay Chiu; Zhang, Yang W; Kong, Xiangqian; Wang, Wei; Xia, Limin; Baylin, Stephen B

2017-04-01

Reversing DNA methylation abnormalities and associated gene silencing, through inhibiting DNA methyltransferases (DNMTs) is an important potential cancer therapy paradigm. Maximizing this potential requires defining precisely how these enzymes maintain genome-wide, cancer-specific DNA methylation. To date, there is incomplete understanding of precisely how the three DNMTs, 1, 3A, and 3B, interact for maintaining DNA methylation abnormalities in cancer. By combining genetic and shRNA depletion strategies, we define not only a dominant role for DNA methyltransferase 1 (DNMT1) but also distinct roles of 3A and 3B in genome-wide DNA methylation maintenance. Lowering DNMT1 below a threshold level is required for maximal loss of DNA methylation at all genomic regions, including gene body and enhancer regions, and for maximally reversing abnormal promoter DNA hypermethylation and associated gene silencing to reexpress key genes. It is difficult to reach this threshold with patient-tolerable doses of current DNMT inhibitors (DNMTIs). We show that new approaches, like decreasing the DNMT targeting protein, UHRF1, can augment the DNA demethylation capacities of existing DNA methylation inhibitors for fully realizing their therapeutic potential. © 2017 Cai et al.; Published by Cold Spring Harbor Laboratory Press.

A case study: The economic cost of net metering in Maryland: Who bears the economic burden?

International Nuclear Information System (INIS)

Cook, C.; Cross, J.

1999-01-01

The Maryland legislature approved net-metering legislation for residential consumer generators with photovoltaic systems during 1997. Before the legislation passed, the Maryland Energy Administration (MEA) examined its potential economic impact on both the affected utilities and consumer ratepayers--with and without net-metered PV systems. The MEA discovered that the impact on the affected utility is minimal when the net-metered PV capacity is limited to a small percentage of utility peak load. The analysis also determined that the cost burden on other customers under a net-metered scenario is likewise limited. For Maryland's largest investor-owned utility, the maximum amount of any cross-subsidy (or cost) on a per customer basis is 46 cents annually. Furthermore, their analysis showed that when distribution system savings and environmental externalities are incorporated, net-metered customers may actually subsidize other utility customers. The MEA analysis also determined that about 50% of the value of the energy produced is lost if net metering is not available to those customers with grid tied PV systems. Over the long term, most if not all of any potential cost is borne by other residential customers, not utility shareholders. Finally, the additional cost burden to the utility under net metering--compensating the consumer at the retail rate versus the avoided cost rate--is less than expected when one considers the administrative costs associated with a dual-metered billing approach

DNA methylation levels associated with race and childhood asthma severity.

Science.gov (United States)

Chan, Marcia A; Ciaccio, Christina E; Gigliotti, Nicole M; Rezaiekhaligh, Mo; Siedlik, Jacob A; Kennedy, Kevin; Barnes, Charles S

2017-10-01

Asthma is a common chronic childhood disease worldwide. Socioeconomic status, genetic predisposition and environmental factors contribute to its incidence and severity. A disproportionate number of children with asthma are economically disadvantaged and live in substandard housing with potential indoor environmental exposures such as cockroaches, dust mites, rodents and molds. These exposures may manifest through epigenetic mechanisms that can lead to changes in relevant gene expression. We examined the association of global DNA methylation levels with socioeconomic status, asthma severity and race/ethnicity. We measured global DNA methylation in peripheral blood of children with asthma enrolled in the Kansas City Safe and Healthy Homes Program. Inclusion criteria included residing in the same home for a minimum of 4 days per week and total family income of less than 80% of the Kansas City median family income. DNA methylation levels were quantified by an immunoassay that assessed the percentage of 5-methylcytosine. Our results indicate that overall, African American children had higher levels of global DNA methylation than children of other races/ethnicities (p = 0.029). This difference was more pronounced when socioeconomic status and asthma severity were coupled with race/ethnicity (p = 0.042) where low-income, African American children with persistent asthma had significantly elevated methylation levels relative to other races/ethnicities in the same context (p = 0.006, Hedges g = 1.14). Our study demonstrates a significant interaction effect among global DNA methylation levels, asthma severity, race/ethnicity, and socioeconomic status.

Understanding Net Zero Energy Buildings

DEFF Research Database (Denmark)

Salom, Jaume; Widén, Joakim; Candanedo, José

2011-01-01

Although several alternative definitions exist, a Net-Zero Energy Building (Net ZEB) can be succinctly described as a grid-connected building that generates as much energy as it uses over a year. The “net-zero” balance is attained by applying energy conservation and efficiency measures...... and by incorporating renewable energy systems. While based on annual balances, a complete description of a Net ZEB requires examining the system at smaller time-scales. This assessment should address: (a) the relationship between power generation and building loads and (b) the resulting interaction with the power grid...

History-dependent stochastic Petri nets

NARCIS (Netherlands)

Schonenberg, H.; Sidorova, N.; Aalst, van der W.M.P.; Hee, van K.M.; Pnueli, A.; Virbitskaite, I.; Voronkov, A.

2010-01-01

Stochastic Petri Nets are a useful and well-known tool for performance analysis. However, an implicit assumption in the different types of Stochastic Petri Nets is the Markov property. It is assumed that a choice in the Petri net only depends on the current state and not on earlier choices. For many

A DNA methylation microarray-based study identifies ERG as a gene commonly methylated in prostate cancer.

Science.gov (United States)

Schwartzman, Jacob; Mongoue-Tchokote, Solange; Gibbs, Angela; Gao, Lina; Corless, Christopher L; Jin, Jennifer; Zarour, Luai; Higano, Celestia; True, Lawrence D; Vessella, Robert L; Wilmot, Beth; Bottomly, Daniel; McWeeney, Shannon K; Bova, G Steven; Partin, Alan W; Mori, Motomi; Alumkal, Joshi

2011-10-01

DNA methylation of promoter regions is a common event in prostate cancer, one of the most common cancers in men worldwide. Because prior reports demonstrating that DNA methylation is important in prostate cancer studied a limited number of genes, we systematically quantified the DNA methylation status of 1505 CpG dinucleotides for 807 genes in 78 paraffin-embedded prostate cancer samples and three normal prostate samples. The ERG gene, commonly repressed in prostate cells in the absence of an oncogenic fusion to the TMPRSS2 gene, was one of the most commonly methylated genes, occurring in 74% of prostate cancer specimens. In an independent group of patient samples, we confirmed that ERG DNA methylation was common, occurring in 57% of specimens, and cancer-specific. The ERG promoter is marked by repressive chromatin marks mediated by polycomb proteins in both normal prostate cells and prostate cancer cells, which may explain ERG's predisposition to DNA methylation and the fact that tumors with ERG DNA methylation were more methylated, in general. These results demonstrate that bead arrays offer a high-throughput method to discover novel genes with promoter DNA methylation such as ERG, whose measurement may improve our ability to more accurately detect prostate cancer.

DNA methylation and memory formation.

Science.gov (United States)

Day, Jeremy J; Sweatt, J David

2010-11-01

Memory formation and storage require long-lasting changes in memory-related neuronal circuits. Recent evidence indicates that DNA methylation may serve as a contributing mechanism in memory formation and storage. These emerging findings suggest a role for an epigenetic mechanism in learning and long-term memory maintenance and raise apparent conundrums and questions. For example, it is unclear how DNA methylation might be reversed during the formation of a memory, how changes in DNA methylation alter neuronal function to promote memory formation, and how DNA methylation patterns differ between neuronal structures to enable both consolidation and storage of memories. Here we evaluate the existing evidence supporting a role for DNA methylation in memory, discuss how DNA methylation may affect genetic and neuronal function to contribute to behavior, propose several future directions for the emerging subfield of neuroepigenetics, and begin to address some of the broader implications of this work.

Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation.

Directory of Open Access Journals (Sweden)

Yasuko eKikuchi

2013-12-01

Full Text Available Cancer arises through accumulation of epigenetic and genetic alteration. Aberrant promoter methylation is a common epigenetic mechanism of gene silencing in cancer cells. We here performed genome-wide analysis of DNA methylation of promoter regions by Infinium HumanMethylation27 BeadChip, using 14 clinical papillary thyroid cancer samples and 10 normal thyroid samples. Among the 14 papillary cancer cases, 11 showed frequent aberrant methylation, but the other three cases showed no aberrant methylation at all. Distribution of the hypermethylation among cancer samples was non-random, which implied existence of a subset of preferentially methylated papillary thyroid cancer. Among 25 frequently methylated genes, methylation status of six genes (HIST1H3J, POU4F2, SHOX2, PHKG2, TLX3, HOXA7 was validated quantitatively by pyrosequencing. Epigenetic silencing of these genes in methylated papillary thyroid cancer cell lines was confirmed by gene re-expression following treatment with 5-aza-2'-deoxycytidine and trichostatin A, and detected by real-time RT-PCR. Methylation of these six genes was validated by analysis of additional 20 papillary thyroid cancer and 10 normal samples. Among the 34 cancer samples in total, 26 cancer samples with preferential methylation were significantly associated with mutation of BRAF/RAS oncogene (P=0.04, Fisher’s exact test. Thus we identified new genes with frequent epigenetic hypermethylation in papillary thyroid cancer, two subsets of either preferentially methylated or hardly methylated papillary thyroid cancer, with a concomitant occurrence of oncogene mutation and gene methylation. These hypermethylated genes may constitute potential biomarkers for papillary thyroid cancer.

Pro ASP.NET 4 in VB 2010

CERN Document Server

MacDonald, Matthew; Freeman, Adam; Szpuszta, Mario; Agarwal, Vidya Vrat

2010-01-01

ASP.NET 4 is the latest version of Microsoft's revolutionary ASP.NET technology. It is the principal standard for creating dynamic web pages on the Windows platform. Pro ASP.NET 4 in VB 2010 raises the bar for high-quality, practical advice on learning and deploying Microsoft's dynamic web solution. This new edition is updated with everything you need to come to grips with the latest version of ASP.NET, including coverage of ASP.NET MVC, ASP.NET AJAX 4, ASP.NET Dynamic Data, and Silverlight 3. Seasoned .NET professionals Matthew MacDonald and Mario Szpuszta explain how you can get the most fro

FlipADAM: a potential new SPECT imaging agent for the serotonin transporter

Energy Technology Data Exchange (ETDEWEB)

Wang, Julie L.; Deutsch, Eric C. [Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Oya, Shunichi [Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Kung, Hank F., E-mail: kunghf@gmail.co [Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States)

2010-07-15

Introduction: Single photon emission computed tomography (SPECT) imaging of the serotonin transporter (SERT) in the brain is a useful tool for examining normal physiological functions and disease states involving the serotonergic system. The goal of this study was to develop an improved SPECT radiotracer with faster kinetics than the current leading SPECT tracer, [{sup 123}I]ADAM, for selective SERT imaging. Methods: The in vitro binding affinities of (2-(2'-((dimethylamino)methyl)-4'-iodophenylthio)benzenamine) (FlipADAM) (1c), were determined using Hampshire pig kidney cells stably overexpressing the serotonin, norepinephrine (NET) or dopamine transporter (DAT). Localization of [{sup 125}I]FlipADAM (1c) was evaluated through biodistribution and autoradiography in male Sprague Dawley rats, and the specificity of binding was assessed by injecting selective SERT or NET inhibitors prior to [{sup 125}I]FlipADAM (1c). Results: FlipADAM (1c) displayed a high binding affinity for SERT (K{sub i}=1.0 nM) and good selectivity over NET and DAT binding (43-fold and 257-fold, respectively). [{sup 125}I]FlipADAM (1c) successfully penetrated the blood brain barrier, as evidenced by the brain uptake at 2 min (1.75% dose/g). [{sup 125}I]FlipADAM(1c) also had a good target to non-target (hypothalamus/cerebellum) ratio of 3.35 at 60 min post-injection. In autoradiography studies, [{sup 125}I]FlipADAM (1c) showed selective localization in SERT-rich brain regions such as the thalamic nuclei, amygdala, dorsal raphe nuclei and other areas. Conclusion: [{sup 125}I]FlipADAM (1c) exhibited faster clearance from the brain and time to binding equilibrium when compared to [{sup 125}I]2-(2'-((dimethylamino)methyl)-phenylthio)-5-iodophenylamine [{sup 125}I]ADAM (1b) and a higher target to non-target ratio when compared to [{sup 125}I]5-iodo-2-(2'-((dimethylamino)methyl)-phenylthio)benzyl alcohol [{sup 125}I]IDAM (1a). Therefore, [{sup 123}I]FlipADAM (1c) may be an improved

DNA methylation in metabolic disorders

DEFF Research Database (Denmark)

Barres, Romain; Zierath, Juleen R

2011-01-01

DNA methylation is a major epigenetic modification that controls gene expression in physiologic and pathologic states. Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. Recent reports...... have provided evidence that environmental factors at all ages could modify DNA methylation in somatic tissues, which suggests that DNA methylation is a more dynamic process than previously appreciated. Because of the importance of lifestyle factors in metabolic disorders, DNA methylation provides...... a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. This article considers the current evidence that defines a role for DNA methylation in metabolic disorders....

Histone Lysine Methylation and Neurodevelopmental Disorders

Directory of Open Access Journals (Sweden)

Jeong-Hoon Kim

2017-06-01

Full Text Available Methylation of several lysine residues of histones is a crucial mechanism for relatively long-term regulation of genomic activity. Recent molecular biological studies have demonstrated that the function of histone methylation is more diverse and complex than previously thought. Moreover, studies using newly available genomics techniques, such as exome sequencing, have identified an increasing number of histone lysine methylation-related genes as intellectual disability-associated genes, which highlights the importance of accurate control of histone methylation during neurogenesis. However, given the functional diversity and complexity of histone methylation within the cell, the study of the molecular basis of histone methylation-related neurodevelopmental disorders is currently still in its infancy. Here, we review the latest studies that revealed the pathological implications of alterations in histone methylation status in the context of various neurodevelopmental disorders and propose possible therapeutic application of epigenetic compounds regulating histone methylation status for the treatment of these diseases.

Economic Investigation of Community-Scale Versus Building Scale Net-Zero Energy

Energy Technology Data Exchange (ETDEWEB)

Fernandez, Nicholas; Katipamula, Srinivas; Brambley, Michael R.; Reddy, T. A.

2009-12-31

The study presented in this report examines issues concerning whether achieving net-zero energy performance at the community scale provides economic and potentially overall efficiency advantages over strategies focused on individual buildings.

Implications of net energy-return-on-investment for a low-carbon energy transition

Science.gov (United States)

King, Lewis C.; van den Bergh, Jeroen C. J. M.

2018-04-01

Low-carbon energy transitions aim to stay within a carbon budget that limits potential climate change to 2 °C—or well below—through a substantial growth in renewable energy sources alongside improved energy efficiency and carbon capture and storage. Current scenarios tend to overlook their low net energy returns compared to the existing fossil fuel infrastructure. Correcting from gross to net energy, we show that a low-carbon transition would probably lead to a 24-31% decline in net energy per capita by 2050, which implies a strong reversal of the recent rising trends of 0.5% per annum. Unless vast end-use efficiency savings can be achieved in the coming decades, current lifestyles might be impaired. To maintain the present net energy returns, solar and wind renewable power sources should grow two to three times faster than in other proposals. We suggest a new indicator, `energy return on carbon', to assist in maximizing the net energy from the remaining carbon budget.

Gamma irradiation does not induce detectable changes in DNA methylation directly following exposure of human cells.

Directory of Open Access Journals (Sweden)

Christoph Lahtz

Full Text Available Environmental chemicals and radiation have often been implicated in producing alterations of the epigenome thus potentially contributing to cancer and other diseases. Ionizing radiation, released during accidents at nuclear power plants or after atomic bomb explosions, is a potentially serious health threat for the exposed human population. This type of high-energy radiation causes DNA damage including single- and double-strand breaks and induces chromosomal rearrangements and mutations, but it is not known if ionizing radiation directly induces changes in the epigenome of irradiated cells. We treated normal human fibroblasts and normal human bronchial epithelial cells with different doses of γ-radiation emitted from a cesium 137 ((137Cs radiation source. After a seven-day recovery period, we analyzed global DNA methylation patterns in the irradiated and control cells using the methylated-CpG island recovery assay (MIRA in combination with high-resolution microarrays. Bioinformatics analysis revealed only a small number of potential methylation changes with low fold-difference ratios in the irradiated cells. These minor methylation differences seen on the microarrays could not be verified by COBRA (combined bisulfite restriction analysis or bisulfite sequencing of selected target loci. Our study shows that acute γ-radiation treatment of two types of human cells had no appreciable direct effect on DNA cytosine methylation patterns in exposed cells.

NetFCM: A Semi-Automated Web-Based Method for Flow Cytometry Data Analysis

DEFF Research Database (Denmark)

Frederiksen, Juliet Wairimu; Buggert, Marcus; Karlsson, Annika C.

2014-01-01

data analysis has become more complex and labor-intensive than previously. We have therefore developed a semi-automatic gating strategy (NetFCM) that uses clustering and principal component analysis (PCA) together with other statistical methods to mimic manual gating approaches. NetFCM is an online...... tool both for subset identification as well as for quantification of differences between samples. Additionally, NetFCM can classify and cluster samples based on multidimensional data. We tested the method using a data set of peripheral blood mononuclear cells collected from 23 HIV-infected individuals...... corresponding to those obtained by manual gating strategies. These data demonstrate that NetFCM has the potential to identify relevant T cell populations by mimicking classical FCM data analysis and reduce the subjectivity and amount of time associated with such analysis. (c) 2014 International Society...

NASA Net Zero Energy Buildings Roadmap

Energy Technology Data Exchange (ETDEWEB)

Pless, S.; Scheib, J.; Torcellini, P.; Hendron, B.; Slovensky, M.

2014-10-01

In preparation for the time-phased net zero energy requirement for new federal buildings starting in 2020, set forth in Executive Order 13514, NASA requested that the National Renewable Energy Laboratory (NREL) to develop a roadmap for NASA's compliance. NASA detailed a Statement of Work that requested information on strategic, organizational, and tactical aspects of net zero energy buildings. In response, this document presents a high-level approach to net zero energy planning, design, construction, and operations, based on NREL's first-hand experience procuring net zero energy construction, and based on NREL and other industry research on net zero energy feasibility. The strategic approach to net zero energy starts with an interpretation of the executive order language relating to net zero energy. Specifically, this roadmap defines a net zero energy acquisition process as one that sets an aggressive energy use intensity goal for the building in project planning, meets the reduced demand goal through energy efficiency strategies and technologies, then adds renewable energy in a prioritized manner, using building-associated, emission- free sources first, to offset the annual energy use required at the building; the net zero energy process extends through the life of the building, requiring a balance of energy use and production in each calendar year.

RESTful NET

CERN Document Server

Flanders, Jon

2008-01-01

RESTful .NET is the first book that teaches Windows developers to build RESTful web services using the latest Microsoft tools. Written by Windows Communication Foundation (WFC) expert Jon Flanders, this hands-on tutorial demonstrates how you can use WCF and other components of the .NET 3.5 Framework to build, deploy and use REST-based web services in a variety of application scenarios. RESTful architecture offers a simpler approach to building web services than SOAP, SOA, and the cumbersome WS- stack. And WCF has proven to be a flexible technology for building distributed systems not necessa

DNA methylation in inflammatory genes among children with obstructive sleep apnea.

Science.gov (United States)

Kim, Jinkwan; Bhattacharjee, Rakesh; Khalyfa, Abdelnaby; Kheirandish-Gozal, Leila; Capdevila, Oscar Sans; Wang, Yang; Gozal, David

2012-02-01

Pediatric obstructive sleep apnea (OSA) leads to multiple end-organ morbidities that are mediated by the cumulative burden of oxidative stress and inflammation. Because not all children with OSA exhibit increased systemic inflammation, genetic and environmental factors may be affecting patterns of DNA methylation in genes subserving inflammatory functions. DNA from matched children with OSA with and without high levels of high-sensitivity C-reactive protein (hsCRP) were assessed for DNA methylation levels of 24 inflammatory-related genes. Primer-based polymerase chain reaction assays in a case-control setting involving 47 OSA cases and 31 control subjects were conducted to confirm the findings; hsCRP and myeloid-related protein (MRP) 8/14 levels were also assayed. Forkhead box P3 (FOXP3) and interferon regulatory factor 1 (IRF1) showed higher methylation in six children with OSA and high hsCRP levels compared with matched children with OSA and low hsCRP levels (P DNA methylation levels compared with children with OSA and low CRP levels and control subjects. IRF1 did not exhibit significant differences. FOXP3 DNA methylation levels correlated with hsCRP and MRP 8/14 levels and with apnea-hypopnea index (AHI), BMI z score, and apolipoprotein B levels. A stepwise multiple regression model showed that AHI was independently associated with FOXP3 DNA methylation levels (P gene, which regulates expression of T regulatory lymphocytes, is more likely to display increased methylation among children with OSA who exhibit increased systemic inflammatory responses. Thus, epigenetic modifications may constitute an important determinant of inflammatory phenotype in OSA, and FOXP3 DNA methylation levels may provide a potential biomarker for end-organ vulnerability.

Getting to Net Zero

Energy Technology Data Exchange (ETDEWEB)

2016-09-01

The technology necessary to build net zero energy buildings (NZEBs) is ready and available today, however, building to net zero energy performance levels can be challenging. Energy efficiency measures, onsite energy generation resources, load matching and grid interaction, climatic factors, and local policies vary from location to location and require unique methods of constructing NZEBs. It is recommended that Components start looking into how to construct and operate NZEBs now as there is a learning curve to net zero construction and FY 2020 is just around the corner.

Net Zero Energy Buildings

DEFF Research Database (Denmark)

Marszal, Anna Joanna; Bourrelle, Julien S.; Gustavsen, Arild

2010-01-01

and identify possible renewable energy supply options which may be considered in calculations. Finally, the gap between the methodology proposed by each organisation and their respective national building code is assessed; providing an overview of the possible changes building codes will need to undergo......The international cooperation project IEA SHC Task 40 / ECBCS Annex 52 “Towards Net Zero Energy Solar Buildings”, attempts to develop a common understanding and to set up the basis for an international definition framework of Net Zero Energy Buildings (Net ZEBs). The understanding of such buildings...

Pro NET Best Practices

CERN Document Server

Ritchie, Stephen D

2011-01-01

Pro .NET Best Practices is a practical reference to the best practices that you can apply to your .NET projects today. You will learn standards, techniques, and conventions that are sharply focused, realistic and helpful for achieving results, steering clear of unproven, idealistic, and impractical recommendations. Pro .NET Best Practices covers a broad range of practices and principles that development experts agree are the right ways to develop software, which includes continuous integration, automated testing, automated deployment, and code analysis. Whether the solution is from a free and

Effects of β-hydroxy β-methyl butyrate supplementation to sows in late gestation on absorption and hepatic metabolism of glucose and amino acids during transition

DEFF Research Database (Denmark)

Flummer, Christine; Lyby, H; Storli, K S

2012-01-01

A multicatheter sow model was established to study the effects of dietary β-hydroxy β-methyl butyrate (HMB) supplementation on net portal flux (NPF) and net hepatic flux (NHF) of HMB, glucose, and the AA Ala, Gly, Ile, Leu, Phe, Tyr, and Val. Eight second parity sows were fitted with permanent...... the experiment, and 4 HMB sows were fed the control diet supplemented with 15 mg Ca(HMB)2/kg BW mixed in one third of the morning meal from day –10 until parturition. Net portal flux of HMB was affected by treatment (Trt; P HMB sows at 6.9 mmol/h 30 min after the morning meal...... and then decreased towards preprandial level (0.0 mmol/h) 3.5 h after the meal, revealing that dietary HMB was rapidly absorbed from the intestine. The NHF of HMB tended to be affected by Trt (P = 0.06) showing a small hepatic uptake of HMB (1.1 mmol/h) in HMB sows. Net portal flux of glucose and all measured AA...

ASP.NET web API build RESTful web applications and services on the .NET framework

CERN Document Server

Kanjilal, Joydip

2013-01-01

This book is a step-by-step, practical tutorial with a simple approach to help you build RESTful web applications and services on the .NET framework quickly and efficiently.This book is for ASP.NET web developers who want to explore REST-based services with C# 5. This book contains many real-world code examples with explanations whenever necessary. Some experience with C# and ASP.NET 4 is expected.

The distribution of triclosan and methyl-triclosan in marine sediments of Barker Inlet, South Australia.

Science.gov (United States)

Fernandes, Milena; Shareef, Ali; Kookana, Rai; Gaylard, Sam; Hoare, Sonja; Kildea, Tim

2011-04-01

In this work, we investigated the transport and burial of triclosan and its methylated derivative, in surface sediments near the mouth of Barker Inlet in South Australia. The most likely source of this commonly used bactericide to the area is a wastewater outfall discharging at the confluence of the inlet with marine waters. Triclosan was detected in all samples, at concentrations (5-27 μg kg(-1)) comparable to values found in other surface sediments under the influence of marine wastewater outfalls. Its dispersal was closely associated with fine and organic-rich fractions of the sediments. Methyl-triclosan was detected in approximately half of the samples at concentrations compound was linked to both wastewater discharges and biological methylation of the parent compound. Wastewater-borne methyl-triclosan had a smaller spatial footprint than triclosan and was mostly deposited in close proximity to the outfall. In situ methylation of triclosan likely occurs at deeper depositional sites, whereas the absence of methyl-triclosan from shallower sediments was potentially explained by photodegradation of the parent compound. Based on partition equilibrium, a concentration of triclosan in the order of 1 μg L(-1) was estimated in sediment porewaters, a value lower than the threshold reported for harmful effects to occur in the couple of species of marine phytoplankton investigated to date. Methyl-triclosan presents a greater potential for bioaccumulation than triclosan, but the implications of its occurrence to aquatic ecosystem health are difficult to predict given the lack of ecotoxicological data in the current literature.

Methylation-sensitive amplified polymorphism-based genome-wide analysis of cytosine methylation profiles in Nicotiana tabacum cultivars.

Science.gov (United States)

Jiao, J; Wu, J; Lv, Z; Sun, C; Gao, L; Yan, X; Cui, L; Tang, Z; Yan, B; Jia, Y

2015-11-26

This study aimed to investigate cytosine methylation profiles in different tobacco (Nicotiana tabacum) cultivars grown in China. Methylation-sensitive amplified polymorphism was used to analyze genome-wide global methylation profiles in four tobacco cultivars (Yunyan 85, NC89, K326, and Yunyan 87). Amplicons with methylated C motifs were cloned by reamplified polymerase chain reaction, sequenced, and analyzed. The results show that geographical location had a greater effect on methylation patterns in the tobacco genome than did sampling time. Analysis of the CG dinucleotide distribution in methylation-sensitive polymorphic restriction fragments suggested that a CpG dinucleotide cluster-enriched area is a possible site of cytosine methylation in the tobacco genome. The sequence alignments of the Nia1 gene (that encodes nitrate reductase) in Yunyan 87 in different regions indicate that a C-T transition might be responsible for the tobacco phenotype. T-C nucleotide replacement might also be responsible for the tobacco phenotype and may be influenced by geographical location.

DNA methylation in sugarcane somaclonal variants assessed through methylation-sensitive amplified polymorphism.

Science.gov (United States)

Francischini, J H M B; Kemper, E L; Costa, J B; Manechini, J R V; Pinto, L R

2017-05-04

Micropropagation is an important tool for large-scale multiplication of plant superior genotypes. However, somaclonal variation is one of the drawbacks of this process. Changes in DNA methylation have been widely reported as one of the main causes of somaclonal variations in plants. In order to investigate the occurrence of changes in the methylation pattern of sugarcane somaclonal variants, the MSAP (methylation-sensitive amplified polymorphism) technique was applied to micro-propagated plantlets sampled at the third subculture phase. The mother plant, in vitro normal plantlets, and in vitro abnormal plantlets (somaclonal variants) of four sugarcane clones were screened against 16 MSAP selective primers for EcoRI/MspI and EcoRI/HpaII restriction enzymes. A total of 1005 and 1200 MSAP-derived markers with polymorphism percentages of 28.36 and 40.67 were obtained for EcoRI/HpaII and EcoRI/MspI restriction enzyme combinations, respectively. The genetic similarity between the mother plant and the somaclonal variants ranged from 0.877 to 0.911 (EcoRI/MspI) and from 0.928 to 0.955 (EcoRI/HpaII). Most of the MASPs among mother plant and micro-propagated plantlets were derived from EcoRI/MspI restriction enzymes suggesting alteration due to gain or loss of internal cytosine methylation. A higher rate of loss of methylation (hypomethylation) than gain of methylation (hypermethylation) was observed in the abnormal in vitro sugarcane plantlets. Although changes in the methylation pattern were also observed in the in vitro normal plantlets, they were lower than those observed for the in vitro abnormal plantlets. The MASP technique proved to be a promising tool to early assessment of genetic fidelity of micro-propagated sugarcane plants.

Translating Colored Control Flow Nets into Readable Java via Annotated Java Workflow Nets

DEFF Research Database (Denmark)

Lassen, Kristian Bisgaard; Tjell, Simon

2007-01-01

In this paper, we present a method for developing Java applications from Colored Control Flow Nets (CCFNs), which is a special kind of Colored Petri Nets (CPNs) that we introduce. CCFN makes an explicit distinction between the representation of: The system, the environment of the system, and the ......In this paper, we present a method for developing Java applications from Colored Control Flow Nets (CCFNs), which is a special kind of Colored Petri Nets (CPNs) that we introduce. CCFN makes an explicit distinction between the representation of: The system, the environment of the system......, and the interface between the system and the environment. Our translation maps CCFNs into Anno- tated Java Workflow Nets (AJWNs) as an intermediate step, and these AJWNs are finally mapped to Java. CCFN is intended to enforce the modeler to describe the system in an imperative manner which makes the subsequent...... translation to Java easier to define. The translation to Java preserves data dependencies and control-flow aspects of the source CCFN. This paper contributes to the model-driven software development paradigm, by showing how to model a system, environment, and their interface, as a CCFN and presenting a fully...

Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood.

Science.gov (United States)

Huang, R C; Garratt, E S; Pan, H; Wu, Y; Davis, E A; Barton, S J; Burdge, G C; Godfrey, K M; Holbrook, J D; Lillycrop, K A

2015-01-01

Childhood obesity is a major public health issue. Here we investigated whether differential DNA methylation was associated with childhood obesity. We studied DNA methylation profiles in whole blood from 78 obese children (mean BMI Z-score: 2.6) and 71 age- and sex-matched controls (mean BMI Z-score: 0.1). DNA samples from obese and control groups were pooled and analyzed using the Infinium HumanMethylation450 BeadChip array. Comparison of the methylation profiles between obese and control subjects revealed 129 differentially methylated CpG (DMCpG) loci associated with 80 unique genes that had a greater than 10% difference in methylation (P-value obesity were validated using sodium bisulfite pyrosequencing across loci within the FYN, PIWIL4, and TAOK3 genes in individual subjects. Three CpG loci within FYN were hypermethylated in obese individuals (all P obesity was associated with lower methylation of CpG loci within PIWIL4 (P = 0.003) and TAOK3 (P = 0.001). After building logistic regression models, we determined that a 1% increase in methylation in TAOK3, multiplicatively decreased the odds of being obese by 0.91 (95% CI: 0.86 - 0.97), and an increase of 1% methylation in FYN CpG3, multiplicatively increased the odds of being obese by 1.03 (95% CI: 0.99 - 1.07). In conclusion, these findings provide evidence that childhood obesity is associated with specific DNA methylation changes in whole blood, which may have utility as biomarkers of obesity risk.

Programming NET 35

CERN Document Server

Liberty, Jesse

2009-01-01

Bestselling author Jesse Liberty and industry expert Alex Horovitz uncover the common threads that unite the .NET 3.5 technologies, so you can benefit from the best practices and architectural patterns baked into the new Microsoft frameworks. The book offers a Grand Tour" of .NET 3.5 that describes how the principal technologies can be used together, with Ajax, to build modern n-tier and service-oriented applications. "

Sleep quality and methylation status of core circadian rhythm genes among nurses and midwives.

Science.gov (United States)

Bukowska-Damska, Agnieszka; Reszka, Edyta; Kaluzny, Pawel; Wieczorek, Edyta; Przybek, Monika; Zienolddiny, Shanbeh; Peplonska, Beata

2017-01-01

ABSTARCT Poor sleep quality or sleep restriction is associated with sleepiness and concentration problems. Moreover, chronic sleep restriction may affect metabolism, hormone secretion patterns and inflammatory responses. Limited recent reports suggest a potential link between sleep deprivation and epigenetic effects such as changes in DNA methylation profiles. The aim of the present study was to assess the potential association between poor sleep quality or sleep duration and the levels of 5-methylcytosine in the promoter regions of PER1, PER2, PER3, BMAL1, CLOCK, CRY1 CRY2 and NPAS2 genes, taking into account rotating night work and chronotype as potential confounders or modifiers. A cross-sectional study was conducted on 710 nurses and midwives (347 working on rotating nights and 363 working only during the day) aged 40-60 years. Data from in-person interviews about sleep quality, chronotype and potential confounders were used. Sleep quality and chronotype were assessed using Pittsburgh Sleep Quality Questionnaire (PSQI) and Morningness-Eveningness Questionnaire (MEQ), respectively. Morning blood samples were collected. The methylation status of the circadian rhythm genes was determined via quantitative methylation-specific real-time PCR assays (qMSP) reactions using DNA samples derived from leucocytes. The proportional odds regression model was fitted to quantify the relationship between methylation index (MI) as the dependent variable and sleep quality or sleep duration as the explanatory variable. Analyses were carried out for the total population as well as for subgroups of women stratified by the current system of work (rotating night shift/day work) and chronotype (morning type/intermediate type/evening type). A potential modifying effect of the system of work or the chronotype was examined using the likelihood ratio test. No significant findings were observed in the total study population. Subgroup analyses revealed two statistically significant

Net metering: zero electricity bill

International Nuclear Information System (INIS)

Mangi, A.; Khan, Z.

2011-01-01

Worldwide move towards renewable energy sources, environmental concerns and decentralization of the power sector have made net metering an attractive option for power generation at small scale. This paper discusses the net metering, economical issues of renewable sources in Pakistan, technical aspects, installation suitability according to varying terrain, existing utility rules and formulation of legislation for net metering making it economically attractive. (author)

Near Net Manufacturing Using Thin Gage Friction Stir Welding

Science.gov (United States)

Takeshita, Jennifer; Potter, David; Holquin, Michael

2006-01-01

Friction Stir Welding (FSW) and near net spin forming of FSW aluminumn blanks were investigated for large-scale pressure vessel applications. With a specific focus on very thin gage 2xxx and 7xxx aluminum alloys, the program concentrated on the following: the criteria used for material selection, a potential manufacturing flow, and the effectiveness and associated risks of near net spin forming. Discussion will include the mechanical properties of the friction stir welds and the parent material from before and after the spin forming process. This effort was performed under a NASA Space Exploration initiative focused on increasing the affordability, reliability and performance of pressure vessels larger than 10 ft. diameter.

Biodiversity offsets and the challenge of achieving no net loss.

Science.gov (United States)

Gardner, Toby A; VON Hase, Amrei; Brownlie, Susie; Ekstrom, Jonathan M M; Pilgrim, John D; Savy, Conrad E; Stephens, R T Theo; Treweek, Jo; Ussher, Graham T; Ward, Gerri; Ten Kate, Kerry

2013-12-01

Businesses, governments, and financial institutions are increasingly adopting a policy of no net loss of biodiversity for development activities. The goal of no net loss is intended to help relieve tension between conservation and development by enabling economic gains to be achieved without concomitant biodiversity losses. biodiversity offsets represent a necessary component of a much broader mitigation strategy for achieving no net loss following prior application of avoidance, minimization, and remediation measures. However, doubts have been raised about the appropriate use of biodiversity offsets. We examined what no net loss means as a desirable conservation outcome and reviewed the conditions that determine whether, and under what circumstances, biodiversity offsets can help achieve such a goal. We propose a conceptual framework to substitute the often ad hoc approaches evident in many biodiversity offset initiatives. The relevance of biodiversity offsets to no net loss rests on 2 fundamental premises. First, offsets are rarely adequate for achieving no net loss of biodiversity alone. Second, some development effects may be too difficult or risky, or even impossible, to offset. To help to deliver no net loss through biodiversity offsets, biodiversity gains must be comparable to losses, be in addition to conservation gains that may have occurred in absence of the offset, and be lasting and protected from risk of failure. Adherence to these conditions requires consideration of the wider landscape context of development and offset activities, timing of offset delivery, measurement of biodiversity, accounting procedures and rule sets used to calculate biodiversity losses and gains and guide offset design, and approaches to managing risk. Adoption of this framework will strengthen the potential for offsets to provide an ecologically defensible mechanism that can help reconcile conservation and development. Balances de Biodiversidad y el Reto de No Obtener P�

Climatic Forecasting of Net Infiltration at Yucca Mountain Using Analogue Meteorological Data

International Nuclear Information System (INIS)

Faybishenko, Boris

2005-01-01

At Yucca Mountain, NV, future changes in climatic conditions will probably alter net infiltration, drainage below the bottom of the evapotranspiration zone within the soil profile, or flow across the interface between soil and the densely welded part of the Tiva Canyon Tuff. The objectives of this study were to: (1) develop a semiempirical model and forecast average net infiltration rates, using the limited meteorological data from analog meteorological stations, for interglacial(present day), and future monsoon, glacial transition, and glacial climates over the Yucca Mountain region; and (2) corroborate the computed net infiltration rates by comparing them with the empirically and numerically determined groundwater recharge and percolation rates through the unsaturated zone from published data. This study approached calculations of net infiltration, aridity, and precipitation effectiveness indices using a modified Budyko's water-balance model, with reference-surface potential evapotranspiration determined from the radiation-based Penman formula. Results of calculations show that net infiltration rates are expected to generally increase from the present-day climate to monsoon climate, to glacial transition climate, and then to the glacial climate, following a power law relationship between net infiltration and precipitation. The forecasting results indicate the overlap between the ranges of net infiltration for different climates. Forecasting of net infiltration for different climate states is subject to numerous uncertainties associated with selecting climate analog sites, using relatively short analog meteorological records, neglecting the effects of vegetation and surface runoff and run-on on a local scale, as well as possible anthropogenically induced climate changes

Demand and willingness-to-pay for bed nets in Tanzania: results from a choice experiment.

Science.gov (United States)

Gingrich, Chris D; Ricotta, Emily; Kahwa, Amos; Kahabuka, Catherine; Koenker, Hannah

2017-07-14

Universal coverage campaigns for long-lasting insecticide-treated nets do not always reach the goal of one net for every two household members, and even when ownership of at least one net per household is high, many households may not own enough nets. The retail market provides these households options for replacing or increasing the number of nets they own with products that best fit their needs since a variety of net shapes, sizes, and colours are available. Hence, it is important to understand the factors affecting private net demand. This study explores private demand for nets in Tanzania using a discrete choice experiment. The experiment provides participants the option to buy nets with their own money, and thus should prove more accurate than a hypothetical survey of net preferences. Nearly 800 participants sampled in two regions showed an overall strong demand for nets, with 40% choosing to buy a net across all seven combinations of net prices and characteristics such as size, shape, and insecticide treatment. Only 8% of all participants chose not to buy a single net. A key factor influencing demand was whether a participant's household currently owned sufficient nets for all members, with rural participants showing lower net coverage and greater demand than urban participants. Both poor and less poor households showed strong evidence of making purchase decisions based on more than price alone. Mean willingness-to-pay values for a net started at US$1.10 and grew by US$0.50-1.40 for various attributes such as rectangular shape, large size, and insecticide treatment. The impact of price on demand was negative but small, with elasticity values between -0.25 and -0.45. The results suggest that private demand for nets in Tanzania could potentially supplement future coverage campaigns. Net manufacturers and retailers should advertise and promote consumers' preferred net attributes to improve sales and further expand net access and coverage. To overcome household

miRNA-Processing Gene Methylation and Cancer Risk.

Science.gov (United States)

Joyce, Brian T; Zheng, Yinan; Zhang, Zhou; Liu, Lei; Kocherginsky, Masha; Murphy, Robert; Achenbach, Chad J; Musa, Jonah; Wehbe, Firas; Just, Allan; Shen, Jincheng; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A; Hou, Lifang

2018-05-01

Background: Dysregulation of miRNA and methylation levels are epigenetic hallmarks of cancer, potentially linked via miRNA-processing genes. Studies have found genetic alterations to miRNA-processing genes in cancer cells and human population studies. Our objective was to prospectively examine changes in DNA methylation of miRNA-processing genes and their associations with cancer risk. Methods: We examined cohort data from the Department of Veterans' Affairs Normative Aging Study. Participants were assessed every 3 to 5 years starting in 1999 through 2013 including questionnaires, medical record review, and blood collection. Blood from 686 consenting participants was analyzed using the Illumina 450K BeadChip array to measure methylation at CpG sites throughout the genome. We selected 19 genes based on a literature review, with 519 corresponding CpG sites. We then used Cox proportional hazards models to examine associations with cancer incidence, and generalized estimating equations to examine associations with cancer prevalence. Associations at false discovery rate time to cancer development (positively for cg06751583, inversely for cg23230564 and cg21034183), whereas methylation of one CpG site ( DROSHA : cg16131300) was positively associated with cancer prevalence. Conclusions: DNA methylation of DROSHA , a key miRNA-processing gene, and TNRC6B may play a role in early carcinogenesis. Impact: Changes in miRNA processing may exert multiple effects on cancer development, including protecting against it via altered global miRNAs, and may be a useful early detection biomarker of cancer. Cancer Epidemiol Biomarkers Prev; 27(5); 550-7. ©2018 AACR . ©2018 American Association for Cancer Research.

Refined global methyl halide budgets with respect to rapeseed (Brassica napus) by life-cycle measurements

Science.gov (United States)

Jiao, Y.; Acdan, J.; Xu, R.; Deventer, M. J.; Rhew, R. C.

2017-12-01

A precise quantification of global methyl halide budgets is needed to evaluate the ozone depletion potential of these compounds and to predict future changes of stratospheric ozone. However, the global budgets of methyl halides are not balanced between currently identified and quantified sources and sinks. Our study re-evaluated the methyl bromide budget from global cultivated rapeseed (Brassica napus) through life-cycle flux measurements both in the greenhouse and in the field, yielding a methyl bromide emission rate that scales globally to 1.0 - 1.2 Gg yr-1. While this indicates a globally significant source, it is much smaller than the previously widely cited value of 5 - 6 Gg yr-1(Mead et al., 2008), even taking into account the near tripling of annual global yield of rapeseed since the previous evaluation was conducted. Our study also evaluated the methyl chloride and methyl iodide emission levels from rapeseed, yielding emission rates that scale to 5.4 Gg yr-1 for methyl chloride and 1.8 Gg yr-1 of methyl iodide. The concentrations of the methyl donor SAM (S-adenosyl methionine) and the resultant product SAH (S-Adenosyl-L-homocysteine) were also analyzed to explore their role in biogenic methyl halide formation. Halide gradient incubations showed that the magnitude of methyl halide emissions from rapeseed is highly correlated to soil halide levels, thus raising the concern that the heterogeneity of soil halide contents geographically should be considered when extrapolating to global budget.

THE DEVELOPMENT OF MARINE SPATIAL PLANNING AND ITS APPLICATION FOR FLOATING FISH NET CULTURE

Directory of Open Access Journals (Sweden)

Dewayany Sutrisno

2017-01-01

Full Text Available Marine spatial planning has become the crucial issues for an archipelagic state such as Indonesia. The global market demand on marine economic species has been initiated the exploitation of the marine species which will become the hindrance in maintaining the sustainable marine biodiversity. Besides that, the degradation of marine species will also become the problem for traditional fishermen. Therefore, a model has to be employed to spatially manage the coastal waters as the alternative for fishermen activities during closed seasons, such as floating fish net culture.  The aim of this study was to develop marine spatial planning model based on ecological approach in order to identify the potentiality of marine waters for marine culture such as floating fish net culture. The method for the model consisted of social assessment using the Delphi for developing the rule of marine planning for floating fish net culture and the spatial analysis technique for determining the model of marine spatial planning for floating fish net culture. The area of Kupang Bay waters, East Nusa Tenggara was used as the study area. The result indicated that the model can be used to sustainable marine spatial planning, especially for floating fish net culture. The model considered the aspects of potential area for marine culture, the management of zonation and transportation lanes, the conservation and protected area and the strategic area. Application in Kupang bay illustrated the aspect of technology input such as raceways since the majority of the area of Kupang Bay waters is classified as medium potential. Further research still needs to optimum the application of model to others marine area.