Synthesis of glycerol mono-laurate from lauric acid and glycerol for food antibacterial additive

NASA Astrophysics Data System (ADS)

Setianto, W. B.; Wibowo, T. Y.; Yohanes, H.; Illaningtyas, F.; Anggoro, D. D.

2017-05-01

Synthesis of glycerol mono-laurate (GML) has been performed using esterification reaction of glycerol and lauric acid. The reaction was performed at the condition of temperature of 120-140 °C within 7 hour, variation of molar ratio of glycerol - lauric acid, and was using heterogeneous catalyst of zeolist Y. Without catalyst dealumination the maximum acid conversion was 78%, with GML contained in the sample was 38.6%, and it was obtained at the reaction condition of 140 oC, 15wt% catalyst, and 8:1 molar ratio of glycerol - lauric acid. At the same condition, using dealuminated catalyst, the maximum acid conversion was increased up to 98%, with GML contained in the sample was 50.4%. The GML antibacterial activity was examined. It was observed that the GML has antibacterial activity against gram positive bacterial such as B. cereus and S. aureus.

Bardoxolone methyl and kidney function in CKD with type 2 diabetes.

PubMed

Pergola, Pablo E; Raskin, Philip; Toto, Robert D; Meyer, Colin J; Huff, J Warren; Grossman, Eric B; Krauth, Melissa; Ruiz, Stacey; Audhya, Paul; Christ-Schmidt, Heidi; Wittes, Janet; Warnock, David G

2011-07-28

Chronic kidney disease (CKD) associated with type 2 diabetes is the leading cause of kidney failure, with both inflammation and oxidative stress contributing to disease progression. Bardoxolone methyl, an oral antioxidant inflammation modulator, has shown efficacy in patients with CKD and type 2 diabetes in short-term studies, but longer-term effects and dose response have not been determined. In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned 227 adults with CKD (defined as an estimated glomerular filtration rate [GFR] of 20 to 45 ml per minute per 1.73 m(2) of body-surface area) in a 1:1:1:1 ratio to receive placebo or bardoxolone methyl at a target dose of 25, 75, or 150 mg once daily. The primary outcome was the change from baseline in the estimated GFR with bardoxolone methyl, as compared with placebo, at 24 weeks; a secondary outcome was the change at 52 weeks. Patients receiving bardoxolone methyl had significant increases in the mean (±SD) estimated GFR, as compared with placebo, at 24 weeks (with between-group differences per minute per 1.73 m(2) of 8.2±1.5 ml in the 25-mg group, 11.4±1.5 ml in the 75-mg group, and 10.4±1.5 ml in the 150-mg group; P<0.001). The increases were maintained through week 52, with significant differences per minute per 1.73 m(2) of 5.8±1.8 ml, 10.5±1.8 ml, and 9.3±1.9 ml, respectively. Muscle spasms, the most frequent adverse event in the bardoxolone methyl groups, were generally mild and dose-related. Hypomagnesemia, mild increases in alanine aminotransferase levels, and gastrointestinal effects were more common among patients receiving bardoxolone methyl. Bardoxolone methyl was associated with improvement in the estimated GFR in patients with advanced CKD and type 2 diabetes at 24 weeks. The improvement persisted at 52 weeks, suggesting that bardoxolone methyl may have promise for the treatment of CKD. (Funded by Reata Pharmaceuticals; BEAM ClinicalTrials.gov number, NCT00811889.).

Gas chromatographic/mass spectrometric analysis of the essential oil of Houttuynia cordata Thunb by using on-column methylation with tetramethylammonium acetate.

PubMed

Ch, Muhammad Ishtiaq; Wen, Yang F; Cheng, YiYu

2007-01-01

This paper describes a simple and novel on-column derivatization procedure used with gas chromatography/mass spectrometry (GC/MS) for the analysis of essential oil of Houttuynia cordata Thunb (HCT), a traditional Chinese medicine. In the procedure, the essential oil was obtained by hydrodistillation, and the fatty acid components were derivatized with tetramethylammonium acetate (TMAA) at 250 degrees C and identified by GC/MS. Methylation improved the determination of both the fatty acids and the other components in the essential oil of HCT. To obtain optimum methylation conditions, several important factors were investigated with pentadecane as the internal standard and a GC inlet temperature of 250 degres C. Tetramethylammonium hydroxide (TMAH) and TMAA were compared as the derivatization agent, and a 2:1 ratio of TMAA to capric acid was evaluated. Fatty acid methyl esters produced good chromatographic peak shapes and did not interfere with the determination of dodecanal and caryophyllene. TMAA is a neutral methylation reagent, and it yielded no side reactions during derivatization. It was found that the fatty acid content of the essential oil was about 81%; among the methylated fatty acids found were capric acid, methyl (43.66%), methyl laurate (16.15%), methyl hexadecanoate (9.27%), undecanoic acid, methyl (5.62%), methyl oleate (1.98%), and methyl linoleate (1.40%). Other major constituents were (-)-beta-pinene (1.02%), beta-myrcene (1.62%), 1-terpinen-4-ol (1.59%), decanal (1.49%), and 2-undecanone (1.47%). The results obtained demonstrated good efficiency for the procedure. Pure chromatograms allowed quantitation, which was obtained by total volume integration. The on-column derivatization procedure was simple to perform, and it improved the sensitivity, the peak resolution, and the selectivity of the GC/MS determination.

Preparation of fatty acid methyl esters for gas-liquid chromatography[S

PubMed Central

Ichihara, Ken'ichi; Fukubayashi, Yumeto

2010-01-01

A convenient method using commercial aqueous concentrated HCl (conc. HCl; 35%, w/w) as an acid catalyst was developed for preparation of fatty acid methyl esters (FAMEs) from sterol esters, triacylglycerols, phospholipids, and FFAs for gas-liquid chromatography (GC). An 8% (w/v) solution of HCl in methanol/water (85:15, v/v) was prepared by diluting 9.7 ml of conc. HCl with 41.5 ml of methanol. Toluene (0.2 ml), methanol (1.5 ml), and the 8% HCl solution (0.3 ml) were added sequentially to the lipid sample. The final HCl concentration was 1.2% (w/v). This solution (2 ml) was incubated at 45°C overnight or heated at 100°C for 1–1.5 h. The amount of FFA formed in the presence of water derived from conc. HCl was estimated to be <1.4%. The yields of FAMEs were >96% for the above lipid classes and were the same as or better than those obtained by saponification/methylation or by acid-catalyzed methanolysis/methylation using commercial anhydrous HCl/methanol. The method developed here could be successfully applied to fatty acid analysis of various lipid samples, including fish oils, vegetable oils, and blood lipids by GC. PMID:19759389

GeoSciML and EarthResourceML Update, 2012

NASA Astrophysics Data System (ADS)

Richard, S. M.; Commissionthe Management; Application Inte, I.

2012-12-01

CGI Interoperability Working Group activities during 2012 include deployment of services using the GeoSciML-Portrayal schema, addition of new vocabularies to support properties added in version 3.0, improvements to server software for deploying services, introduction of EarthResourceML v.2 for mineral resources, and collaboration with the IUSS on a markup language for soils information. GeoSciML and EarthResourceML have been used as the basis for the INSPIRE Geology and Mineral Resources specifications respectively. GeoSciML-Portrayal is an OGC GML simple-feature application schema for presentation of geologic map unit, contact, and shear displacement structure (fault and ductile shear zone) descriptions in web map services. Use of standard vocabularies for geologic age and lithology enables map services using shared legends to achieve visual harmonization of maps provided by different services. New vocabularies have been added to the collection of CGI vocabularies provided to support interoperable GeoSciML services, and can be accessed through http://resource.geosciml.org. Concept URIs can be dereferenced to obtain SKOS rdf or html representations using the SISSVoc vocabulary service. New releases of the FOSS GeoServer application greatly improve support for complex XML feature schemas like GeoSciML, and the ArcGIS for INSPIRE extension implements similar complex feature support for ArcGIS Server. These improved server implementations greatly facilitate deploying GeoSciML services. EarthResourceML v2 adds features for information related to mining activities. SoilML provides an interchange format for soil material, soil profile, and terrain information. Work is underway to add GeoSciML to the portfolio of Open Geospatial Consortium (OGC) specifications.

Micropolarity and Hydrogen-Bond Donor Ability of Environmentally Friendly Anionic Reverse Micelles Explored by UV/Vis Absorption of a Molecular Probe and FTIR Spectroscopy.

PubMed

Girardi, Valeria R; Silber, Juana J; Falcone, Ruben Darío; Correa, N Mariano

2018-03-19

In the present work we show how two biocompatible solvents, methyl laurate (ML) and isopropyl myristate (IPM), can be used as a less toxic alternative to replace the nonpolar component in a sodium 1,4-bis-2-ethylhexylsulfosuccinate (AOT) reverse micelles (RMs) formulation. In this sense, the micropolarity and the hydrogen-bond ability of the interface were monitored through the use of the solvatochromism of a molecular probe (1-methyl-8-oxyquinolinium betaine, QB) and Fourier transform infrared spectroscopy (FTIR). Our results demonstrate that the micropolarity sensed by QB in ML RMs is lower than in IPM RMs. Additionally, the water molecules form stronger H-bond interactions with the polar head of AOT in ML than in IPM. By FTIR was revealed that more water molecules interact with the interface in ML/AOT RMs. On the other hand, for AOT RMs generated in IPM, the weaker water-surfactant interaction allows the water molecules to establish hydrogen bonds with each other trending to bulk water more easily than in ML RMs, a consequence of the dissimilar penetration of nonpolar solvents into the interfacial region. The penetration process is strongly controlled by the polarity and viscosity of the external solvents. All of these results allow us to characterize these biocompatible systems, providing information about interfacial properties and how they can be altered by changing the external solvent. The ability of the nontoxic solvent to penetrate or not into the AOT interface produces a new interface with attractive properties. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A newly developed lubricant, chitosan laurate, in the manufacture of acetaminophen tablets.

PubMed

Bani-Jaber, Ahmad; Kobayashi, Asuka; Yamada, Kyohei; Haj-Ali, Dana; Uchimoto, Takeaki; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2015-04-10

To study the usefulness of chitosan laurate (CS-LA), a newly developed chitosan salt, as a lubricant, lubrication properties such as the pressure transmission ratio and ejection force were determined at different concentrations of CS-LA in tableting. In addition, tablet properties such as the tensile strength, disintegration time, and dissolution behavior, were also determined. When CS-LA was mixed at concentrations of 0.1%-3.0%, the pressure transmission ratio was increased in a concentration-dependent manner, and the value at a CS-LA concentration of 3% was equal to that of magnesium stearate (Mg-St), a widely used lubricant. Additionally, a reduction in the ejection force was observed at a concentration from 1%, proving that CS-LA has good lubrication performance. A prolonged disintegration time and decreased tensile strength, which are known disadvantages of Mg-St, were not observed with CS-LA. Furthermore, with CS-LA, retardation of dissolution of the drug from the tablets was not observed. Conjugation of CS with LA was found to be quite important for both lubricant and tablet properties. In conclusion, CS-LA should be useful as an alternative lubricant to Mg-St. Copyright © 2015 Elsevier B.V. All rights reserved.

Using VS30 to Estimate Station ML Adjustments (dML)

NASA Astrophysics Data System (ADS)

Yong, A.; Herrick, J.; Cochran, E. S.; Andrews, J. R.; Yu, E.

2017-12-01

Currently, new seismic stations added to a regional seismic network cannot be used to calculate local or Richter magnitude (ML) until a revised region-wide amplitude decay function is developed. The new station must record a minimum number of local and regional events that meet specific amplitude requirements prior to re-calibration of the amplitude decay function. Therefore, there can be significant delay between when a new station starts contributing real-time waveform packets and when the data can be included in magnitude estimation. The station component adjustments (dML; Uhrhammer et al., 2011) are calculated after first inverting for a new regional amplitude decay function, constrained by the sum of dML for long-running stations. Here, we propose a method to calculate an initial dML using known or proxy values of seismic site conditions. For site conditions, we use the time-averaged shear-wave velocity (VS) of the upper 30 m (VS30). We solve for dML as described in Equation (1) by Uhrhammer et al. (2011): ML = log (A) - log A0 (r) + dML, where A is the maximum Wood and Anderson (1925) trace amplitude (mm), r is the distance (km), and dML is the station adjustment. Measured VS30 and estimated dML data are comprised of records from 887 horizontal components (east-west and north-south orientations) from 93 seismic monitoring stations in the California Integrated Seismic Network. VS30 values range from 202 m/s to 1464 m/s and dML range from -1.10 to 0.39. VS30 and dML exhibit a positive correlation coefficient (R = 0.72), indicating that as VS30 increases, dML increases. This implies that greater site amplification (i.e., lower VS30) results in smaller ML. When we restrict VS30 < 760 m/s to focus on dML at soft soil to soft rock sites, R increases to 0.80. In locations where measured VS30 data are unavailable, we evaluate the use of proxy-based VS30 estimates based on geology, topographic slope and terrain classification, as well as other hybridized methods

ML Construction Progress

NASA Image and Video Library

2014-12-17

Modifications continue on the Mobile Launcher, or ML, at the Mobile Launcher Park Site at NASA’s Kennedy Space Center in Florida. Scaffolding, or work platforms, have been installed around the base of the tower on the ML to continue upgrades and modifications to the structure. The ML is being modified and strengthened to accommodate the weight, size and thrust at launch of NASA's Space Launch System, or SLS, and Orion spacecraft. The ML is one of the key elements of ground support equipment that is being upgraded by the Ground Systems Development and Operations Program at Kennedy. The ML will carry the SLS rocket and Orion spacecraft to Launch Pad 39B for its first uncrewed mission, Exploration Mission-1, in 2018.

ML Construction Progress

NASA Image and Video Library

2014-12-17

Modifications continue on the Mobile Launcher, or ML, at the Mobile Launcher Park Site at NASA’s Kennedy Space Center in Florida. A crane is being used to move scaffolding, or work platforms, around the base of the tower on the ML to continue upgrades and modifications to the structure. The ML is being modified and strengthened to accommodate the weight, size and thrust at launch of NASA's Space Launch System, or SLS, and Orion spacecraft. The ML is one of the key elements of ground support equipment that is being upgraded by the Ground Systems Development and Operations Program at Kennedy. The ML will carry the SLS rocket and Orion spacecraft to Launch Pad 39B for its first uncrewed mission, Exploration Mission-1, in 2018.

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

PubMed

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.

ML Construction Progress

NASA Image and Video Library

2014-11-17

Modifications continue on the Mobile Launcher, or ML, at the Mobile Launcher Park Site at NASA’s Kennedy Space Center in Florida. The haunch, a structure that will support the launch vehicle on the ML, arrives by flatbed truck at the park site. The ML is being modified and strengthened to accommodate the weight, size and thrust at launch of NASA's Space Launch System, or SLS, and Orion spacecraft. In 2013, the agency awarded a contract to J.P. Donovan Construction Inc. of Rockledge, Fla., to modify the ML, which is one of the key elements of ground support equipment that is being upgraded by the Ground Systems Development and Operations Program at Kennedy. The existing 24-foot exhaust hole is being enlarged and strengthened for the larger, heavier SLS rocket. The ML will carry the SLS rocket and Orion spacecraft to Launch Pad 39B for its first uncrewed mission, Exploration Mission-1, in 2018.

ML Construction Progress

NASA Image and Video Library

2014-11-17

A water moccasin snake travels across the gravel surface near the Mobile Launcher, or ML, at the Mobile Launcher Park Site at NASA’s Kennedy Space Center in Florida. Nearby, the haunch, a structure that will support the launch vehicle on the ML, arrives by flatbed truck at the park site. The ML is being modified and strengthened to accommodate the weight, size and thrust at launch of NASA's Space Launch System, or SLS, and Orion spacecraft. In 2013, the agency awarded a contract to J.P. Donovan Construction Inc. of Rockledge, Fla., to modify the ML, which is one of the key elements of ground support equipment that is being upgraded by the Ground Systems Development and Operations Program at Kennedy. The existing 24-foot exhaust hole is being enlarged and strengthened for the larger, heavier SLS rocket. The ML will carry the SLS rocket and Orion spacecraft to Launch Pad 39B for its first uncrewed mission, Exploration Mission-1, in 2018.

Preclinical evaluation of 18F-ML-10 to determine timing of apoptotic response to chemotherapy in solid tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demirci, Emre; Ahmed, Rafay; Ocak, Meltem

Here, we investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid ( 18F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model. BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal 18F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, 18F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL) immunohistochemistry assay was performed using tumor samplesmore » of baseline and on days 1, 3, and 7 posttreatment. As a result, treated mice demonstrated increased 18F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L) ratios from the control group mice did not show significant change from baseline ( P > .05); however, T/L ratios of the treatment group showed significant 18F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment ( P < .05), but no significant difference at 1 day posttreatment. In conclusion, 2-(5-Fluoro-pentyl)-2-methyl-malonic acid PET imaging has the potential for early assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment.« less

Preclinical evaluation of 18F-ML-10 to determine timing of apoptotic response to chemotherapy in solid tumors

DOE PAGES

Demirci, Emre; Ahmed, Rafay; Ocak, Meltem; ...

2017-01-10

Here, we investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid ( 18F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model. BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal 18F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, 18F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL) immunohistochemistry assay was performed using tumor samplesmore » of baseline and on days 1, 3, and 7 posttreatment. As a result, treated mice demonstrated increased 18F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L) ratios from the control group mice did not show significant change from baseline ( P > .05); however, T/L ratios of the treatment group showed significant 18F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment ( P < .05), but no significant difference at 1 day posttreatment. In conclusion, 2-(5-Fluoro-pentyl)-2-methyl-malonic acid PET imaging has the potential for early assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment.« less

Enhanced physicochemical properties of chitosan/whey protein isolate composite film by sodium laurate-modified TiO2 nanoparticles.

PubMed

Zhang, Wei; Chen, Jiwang; Chen, Yue; Xia, Wenshui; Xiong, Youling L; Wang, Hongxun

2016-03-15

Chitosan/whey protein isolate film incorporated with sodium laurate-modified TiO2 nanoparticles was developed. The nanocomposite film was characterized by scanning electron microscopy, X-ray diffraction and differential scanning calorimetry, and investigated in physicochemical properties as color, tensile strength, elongation at break, water vapor permeability and water adsorption isotherm. Our results showed that the nanoparticles improved the compatibility of whey protein isolate and chitosan. Addition of nanoparticles increased the whiteness of chitosan/whey protein isolate film, but decreased its transparency. Compared with binary film, the tensile strength and elongation at break of nanocomposite film were increased by 11.51% and 12.01%, respectively, and water vapor permeability was decreased by 7.60%. The equilibrium moisture of nanocomposite film was lower than binary film, and its water sorption isotherm of the nanocomposite film fitted well to Guggenheim-Anderson-deBoer model. The findings contributed to the development of novel food packaging materials. Copyright © 2015 Elsevier Ltd. All rights reserved.

ML 3.1 developer's guide.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sala, Marzio; Hu, Jonathan Joseph; Tuminaro, Raymond Stephen

2004-05-01

ML development was started in 1997 by Ray Tuminaro and Charles Tong. Currently, there are several full- and part-time developers. The kernel of ML is written in ANSI C, and there is a rich C++ interface for Trilinos users and developers. ML can be customized to run geometric and algebraic multigrid; it can solve a scalar or a vector equation (with constant number of equations per grid node), and it can solve a form of Maxwell's equations. For a general introduction to ML and its applications, we refer to the Users Guide [SHT04], and to the ML web site, http://software.sandia.gov/ml.

N-acetylcysteine reverses immunotoxic effects of methyl mercury and augments murine lymphocyte proliferation in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Omara, F.; Fournier, M.; Bernier, J.

1995-12-31

N-Acetylcysteine (NAC) is a thiol antioxidant used clinically to treat chronic inflammatory lung disorders and acetaminophen poisoning in humans. The authors evaluated in vitro the effect of NAC on mitogen-induced blastogenesis in C57BI/6 mouse splenocytes by {sup 3}H-thymidine uptake, and its ability to protect against the immunotoxic effects of methyl mercury on lymphocyte proliferation. Lymphocyte proliferation stimulated by optimal and suboptimal concentrations of concanavalin A (Con A), lipopolysaccharide (LPS), or a combination of calcium ionophore A23187 and phorbol-12-myristate-13-acetate (PMA) were markedly enhanced by NAC. NAC itself was a weak mitogen. The kinetics of the NAC effect on splenocyte proliferation weremore » mitogen dependent. NAC enhanced Con A-induced splenocyte proliferation in a dose-dependent and linear manner but enhanced the LPS-induced response at 50--400 {micro}g/ml of NAC followed by a decline in response to control value at higher concentrations. In splenocytes stimulated with PMA plus A23187, NAC increased proliferation at 50--200 pg/ml followed by a constant response at 200--1,000 {micro}g/ml NAC. When splenocytes were stimulated with higher concentrations of Con A (10 {micro}g/ml) or LPS (150 {micro}g/ml) which markedly suppress splenocyte proliferation, NAC significantly enhanced the Con A-induced response and reversed the inhibitory effect of high concentrations of LPS. NAC also protected lymphocytes against mitogen activation-induced cell death. Methyl mercury at 5 {times} 10{sup {minus}7}--1 {times} 10{sup {minus}6} suppressed Con A- and LPS-induced splenocyte proliferation by over 80%. However, NAC completely reversed the immunotoxic effects of methyl mercury on the mitogen-induced splenocyte proliferation even when the cells were pre-incubated with methyl mercury for 6 or 24 hr before stimulation with the mitogens.« less

Workers Welding on ML

NASA Image and Video Library

2014-02-24

CAPE CANAVERAL, Fla. – Modifications continue on the Mobile Launcher, or ML, at the Mobile Launcher Park Site at NASA’s Kennedy Space Center in Florida. A construction worker prepares a metal beam that will be attached to the ML. In 2013, the agency awarded a contract to J.P. Donovan Construction Inc. of Rockledge, Fla., to modify the ML, which is one of the key elements of ground support equipment that is being upgraded by the Ground Systems Development and Operations Program office at Kennedy. The ML will carry the SLS rocket and Orion spacecraft to Launch Pad 39B for its first mission, Exploration Mission 1, in 2017. Photo credit: NASA/Dimitri Gerondidakis

BindML/BindML+: Detecting Protein-Protein Interaction Interface Propensity from Amino Acid Substitution Patterns.

PubMed

Wei, Qing; La, David; Kihara, Daisuke

2017-01-01

Prediction of protein-protein interaction sites in a protein structure provides important information for elucidating the mechanism of protein function and can also be useful in guiding a modeling or design procedures of protein complex structures. Since prediction methods essentially assess the propensity of amino acids that are likely to be part of a protein docking interface, they can help in designing protein-protein interactions. Here, we introduce BindML and BindML+ protein-protein interaction sites prediction methods. BindML predicts protein-protein interaction sites by identifying mutation patterns found in known protein-protein complexes using phylogenetic substitution models. BindML+ is an extension of BindML for distinguishing permanent and transient types of protein-protein interaction sites. We developed an interactive web-server that provides a convenient interface to assist in structural visualization of protein-protein interactions site predictions. The input data for the web-server are a tertiary structure of interest. BindML and BindML+ are available at http://kiharalab.org/bindml/ and http://kiharalab.org/bindml/plus/ .

The jmzQuantML programming interface and validator for the mzQuantML data standard.

PubMed

Qi, Da; Krishna, Ritesh; Jones, Andrew R

2014-03-01

The mzQuantML standard from the HUPO Proteomics Standards Initiative has recently been released, capturing quantitative data about peptides and proteins, following analysis of MS data. We present a Java application programming interface (API) for mzQuantML called jmzQuantML. The API provides robust bridges between Java classes and elements in mzQuantML files and allows random access to any part of the file. The API provides read and write capabilities, and is designed to be embedded in other software packages, enabling mzQuantML support to be added to proteomics software tools (http://code.google.com/p/jmzquantml/). The mzQuantML standard is designed around a multilevel validation system to ensure that files are structurally and semantically correct for different proteomics quantitative techniques. In this article, we also describe a Java software tool (http://code.google.com/p/mzquantml-validator/) for validating mzQuantML files, which is a formal part of the data standard. © 2014 The Authors. Proteomics published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Association between serum aluminium level and methylation of amyloid precursor protein gene in workers engaged in aluminium electrolysis].

PubMed

Yang, X J; Yuan, Y Z; Niu, Q

2016-04-20

To investigate the association between serum aluminium level and methylation of the promoter region of amyloid precursor protein (APP)gene in workers engaged in aluminium electrolysis. In 2012, 366 electrolysis workers in an aluminium factory were enrolled as exposure group (working years >10 and age >40 years)and divided into low-exposure group and high-exposure group based on the median serum aluminium level. Meanwhile, 102 workers in a cement plant not exposed to aluminium were enrolled as control group. Graphite furnace atomic absorption spectrometry was used to measure serum aluminium level, methylation specific PCR was used to measure the methylation rate of the promoter region of APP gene, and ELI-SA was used to measure the protein expression of APP in lymphocytes in peripheral blood. The exposure group had a significantly higher serum aluminium level than the control group (45.07 μg/L vs 30.51 μg/L, P< 0.01). The exposure group had a significantly lower methylation rate of the promoter region of APP gene than the control group (18.85% vs 25.49%, P=0.025), and the high-exposure group had a significantly lower methylation rate of the promoter region of APP gene than the low-exposure group (15.84% vs 21.85%, P<0.05). The exposure group had a significantly higher protein expression of APP in lymphocytes in peripheral blood than the control group (66.73 ng/ml vs 54.17 ng/ml, P<0.05); compared with the low-exposure group (65.39 ng/ml), the high-exposure group showed an increase in the protein expression of APP in lymphocytes in peripheral blood (67.22 ng/ml), but there was no significant difference between these two groups (P>0.05). The multivariate logistic regression analysis showed that with reference to the control group, low aluminium exposure (OR=1.86, 95% CI 1.67~3.52)and high aluminium exposure (OR=2.98, 95% CI 1.97~4.15)were risk factors for a reduced methylation rate of the promoter region of APP gene. Reduced methylation of the promoter region of APP

jmzML, an open-source Java API for mzML, the PSI standard for MS data.

PubMed

Côté, Richard G; Reisinger, Florian; Martens, Lennart

2010-04-01

We here present jmzML, a Java API for the Proteomics Standards Initiative mzML data standard. Based on the Java Architecture for XML Binding and XPath-based XML indexer random-access XML parser, jmzML can handle arbitrarily large files in minimal memory, allowing easy and efficient processing of mzML files using the Java programming language. jmzML also automatically resolves internal XML references on-the-fly. The library (which includes a viewer) can be downloaded from http://jmzml.googlecode.com.

A Practical Methylation Procedure for (1H)-1,2,4-Triazole (Preprint)

DTIC Science & Technology

2007-06-01

on alkylations with higher molecular weight electrophiles, rather than on synthesizing the methyl homologue, the simple reaction to obtain the...an equivalent of the 25% w/w methanolic sodium methoxide solution with heating to 65 °C for 5 minutes in a 5 mL sealed microwave reaction vessel ...requisite neat iodomethane, and recrimping the 5 mL reaction vessel , the reaction vessel was reinserted into the microwave apparatus . The reaction mixture

Metsulfuron-methyl sorption/desorption behavior on volcanic ash-derived soils. effect of phosphate and pH.

PubMed

Cáceres, Lizethly; Fuentes, Roxana; Escudey, Mauricio; Fuentes, Edwar; Báez, María E

2010-06-09

Metsulfuron-methyl sorption/desorption behavior was studied through batch sorption experiments in three typical volcanic ash-derived soils belonging to Andisol and Ultisol orders. Their distinctive physical and chemical properties are acidic pH and variable surface charge. Organic matter content and mineral composition affected in different ways sorption of metsulfuron-methyl (K(OC) ranging from 113 to 646 mL g(-1)): organic matter and iron and aluminum oxides mainly through hydrophilic rather than hydrophobic interactions in Andisols, and Kaolinite group minerals, as major constituents of Ultisols, and iron and aluminum oxides only through hydrophilic interactions. The Freundlich model described metsulfuron-methyl behavior in all cases (R(2) > 0.992). K(f) values (3.1-14.4 microg(1-1/n) mL(1/n) g(-1)) were higher than those reported for different class of soils including some with variable charge. Hysteresis was more significant in Ultisols. A strong influence of pH and phosphate was established for both kinds of soil, intensive soil fertilization and liming being the most probable scenario for leaching of metsulfuron-methyl, particularly in Ultisols.

DAVE-ML Utility Programs

NASA Technical Reports Server (NTRS)

Jackson, Bruce

2006-01-01

DAVEtools is a set of Java archives that embodies tools for manipulating flight-dynamics models that have been encoded in dynamic aerospace vehicle exchange markup language (DAVE-ML). [DAVE-ML is an application program, written in Extensible Markup Language (XML), for encoding complete computational models of the dynamics of aircraft and spacecraft.

Environmentally evaluated HPLC-ELSD method to monitor enzymatic synthesis of a non-ionic surfactant.

PubMed

Gaber, Yasser; Akerman, Cecilia Orellana; Hatti-Kaul, Rajni

2014-01-01

N-Lauroyl-N-methylglucamide is a biodegradable surfactant derived from renewable resources. In an earlier study, we presented an enzymatic solvent-free method for synthesis of this compound. In the present report, the HPLC method developed to follow the reaction between lauric acid/methyl laurate and N-methyl glucamine (MEG) and its environmental assessment are described. Use of ultraviolet (UV) absorption or refractive index (RI) detectors did not allow the detection of N-methyl glucamine (MEG). With Evaporative light scattering detector ELSD, it was possible to apply a gradient elution, and detect MEG with a limit of detection, LOD = 0.12 μg. A good separation of the peaks: MEG, lauric acid, product (amide) and by-product (amide-ester) was achieved with the gradient program with a run time of 40 min. The setting of ELSD detector was optimized using methyl laurate as the analyte. LC-MS/MS was used to confirm the amide and amide-ester peaks. We evaluated the greenness of the developed method using the freely available software HPLC-Environmental Assessment Tool (HPLC-EAT) and the method got a scoring of 73 HPLC-EAT units, implying that the analytical procedure was more environmentally benign compared to some other methods reported in literature whose HPLC-EAT values scored up to 182. Use of ELSD detector allowed the detection and quantification of the substrates and the reaction products of enzymatic synthesis of the surfactant, N-lauroyl-N-methylglucamide. The developed HPLC method has acceptable environmental profile based on HPLC-EAT evaluation.

Environmentally evaluated HPLC-ELSD method to monitor enzymatic synthesis of a non-ionic surfactant

PubMed Central

2014-01-01

Background N-Lauroyl-N-methylglucamide is a biodegradable surfactant derived from renewable resources. In an earlier study, we presented an enzymatic solvent-free method for synthesis of this compound. In the present report, the HPLC method developed to follow the reaction between lauric acid/methyl laurate and N-methyl glucamine (MEG) and its environmental assessment are described. Results Use of ultraviolet (UV) absorption or refractive index (RI) detectors did not allow the detection of N-methyl glucamine (MEG). With Evaporative light scattering detector ELSD, it was possible to apply a gradient elution, and detect MEG with a limit of detection, LOD = 0.12 μg. A good separation of the peaks: MEG, lauric acid, product (amide) and by-product (amide-ester) was achieved with the gradient program with a run time of 40 min. The setting of ELSD detector was optimized using methyl laurate as the analyte. LC-MS/MS was used to confirm the amide and amide-ester peaks. We evaluated the greenness of the developed method using the freely available software HPLC-Environmental Assessment Tool (HPLC-EAT) and the method got a scoring of 73 HPLC-EAT units, implying that the analytical procedure was more environmentally benign compared to some other methods reported in literature whose HPLC-EAT values scored up to 182. Conclusion Use of ELSD detector allowed the detection and quantification of the substrates and the reaction products of enzymatic synthesis of the surfactant, N-lauroyl-N-methylglucamide. The developed HPLC method has acceptable environmental profile based on HPLC-EAT evaluation. PMID:24914404

Self-reported smoking, serum cotinine, and blood DNA methylation.

PubMed

Zhang, Yan; Florath, Ines; Saum, Kai-Uwe; Brenner, Hermann

2016-04-01

Epigenome-wide profiling of DNA methylation pattern with respect to tobacco smoking has given rise to a new measure of smoking exposure. We investigated the relationships of methylation markers with both cotinine, an established marker of internal smoking exposure, and self-reported smoking. Blood DNA methylation levels across the genome and serum cotinine were measured in 1000 older adults aged 50-75 years. Epigenome-wide scans were performed to identify methylation markers associated with cotinine. The inter-dose-response relationships between the number of cigarettes smoked per day, cotinine concentration, and DNA methylation were modeled by restricted cubic spline regression. Of 61 CpGs that passed the genome-wide significance threshold (p<1.13×10(-7)), 40 CpGs in 25 chromosomal regions were successfully replicated, showing 0.2-3% demethylation per 10ng/ml increases in cotinine. The strongest associations were observed for several loci at AHRR, F2RL3, 2q37.1, 6p21.33, and GFI1 that were previously identified to be related to self-reported smoking. One locus at RAB34 was newly discovered. Both cotinine and methylation markers exhibited non-linear relationships with the number of cigarettes smoked per day, where the highest rates of increase in cotinine and decreases in methylation were observed at low smoking intensity (1-15 cigarettes/day) and plateaued at high smoking intensity (>15-20 cigarettes/day). A clear linear relationship was observed between cotinine concentration and methylation level. Both cotinine and methylation markers showed similar accuracy in distinguishing current from never smoker, but only methylation markers distinguished former from never smoker with high accuracy. Our study corroborates and expands the list of smoking-associated DNA methylation markers. Methylation levels were linearly related to cotinine concentration and provided accurate measures for both current and past smoking exposure. Copyright © 2016 Elsevier Inc. All rights

DNA methylation profiling of genomic DNA isolated from urine in diabetic chronic kidney disease: A pilot study

PubMed Central

Sexton-Oates, Alexandra; Carmody, Jake; Ekinci, Elif I.; Dwyer, Karen M.; Saffery, Richard

2018-01-01

Aim To characterise the genomic DNA (gDNA) yield from urine and quality of derived methylation data generated from the widely used Illuminia Infinium MethylationEPIC (HM850K) platform and compare this with buffy coat samples. Background DNA methylation is the most widely studied epigenetic mark and variations in DNA methylation profile have been implicated in diabetes which affects approximately 415 million people worldwide. Methods QIAamp Viral RNA Mini Kit and QIAamp DNA micro kit were used to extract DNA from frozen and fresh urine samples as well as increasing volumes of fresh urine. Matched buffy coats to the frozen urine were also obtained and DNA was extracted from the buffy coats using the QIAamp DNA Mini Kit. Genomic DNA of greater concentration than 20μg/ml were used for methylation analysis using the HM850K array. Results Irrespective of extraction technique or the use of fresh versus frozen urine samples, limited genomic DNA was obtained using a starting sample volume of 5ml (0–0.86μg/mL). In order to optimize the yield, we increased starting volumes to 50ml fresh urine, which yielded only 0–9.66μg/mL A different kit, QIAamp DNA Micro Kit, was trialled in six fresh urine samples and ten frozen urine samples with inadequate DNA yields from 0–17.7μg/mL and 0–1.6μg/mL respectively. Sufficient genomic DNA was obtained from only 4 of the initial 41 frozen urine samples (10%) for DNA methylation profiling. In comparison, all four buffy coat samples (100%) provided sufficient genomic DNA. Conclusion High quality data can be obtained provided a sufficient yield of genomic DNA is isolated. Despite optimizing various extraction methodologies, the modest amount of genomic DNA derived from urine, may limit the generalisability of this approach for the identification of DNA methylation biomarkers of chronic diabetic kidney disease. PMID:29462136

DNA methylation profiling of genomic DNA isolated from urine in diabetic chronic kidney disease: A pilot study.

PubMed

Lecamwasam, Ashani; Sexton-Oates, Alexandra; Carmody, Jake; Ekinci, Elif I; Dwyer, Karen M; Saffery, Richard

2018-01-01

To characterise the genomic DNA (gDNA) yield from urine and quality of derived methylation data generated from the widely used Illuminia Infinium MethylationEPIC (HM850K) platform and compare this with buffy coat samples. DNA methylation is the most widely studied epigenetic mark and variations in DNA methylation profile have been implicated in diabetes which affects approximately 415 million people worldwide. QIAamp Viral RNA Mini Kit and QIAamp DNA micro kit were used to extract DNA from frozen and fresh urine samples as well as increasing volumes of fresh urine. Matched buffy coats to the frozen urine were also obtained and DNA was extracted from the buffy coats using the QIAamp DNA Mini Kit. Genomic DNA of greater concentration than 20μg/ml were used for methylation analysis using the HM850K array. Irrespective of extraction technique or the use of fresh versus frozen urine samples, limited genomic DNA was obtained using a starting sample volume of 5ml (0-0.86μg/mL). In order to optimize the yield, we increased starting volumes to 50ml fresh urine, which yielded only 0-9.66μg/mL A different kit, QIAamp DNA Micro Kit, was trialled in six fresh urine samples and ten frozen urine samples with inadequate DNA yields from 0-17.7μg/mL and 0-1.6μg/mL respectively. Sufficient genomic DNA was obtained from only 4 of the initial 41 frozen urine samples (10%) for DNA methylation profiling. In comparison, all four buffy coat samples (100%) provided sufficient genomic DNA. High quality data can be obtained provided a sufficient yield of genomic DNA is isolated. Despite optimizing various extraction methodologies, the modest amount of genomic DNA derived from urine, may limit the generalisability of this approach for the identification of DNA methylation biomarkers of chronic diabetic kidney disease.

Optimization of suppository preparation containing sodium laurate and taurine that can safely improve rectal absorption of rebamipide.

PubMed

Miyake, Masateru; Minami, Takanori; Oka, Yoshikazu; Kamada, Naoki; Yamazaki, Hiroyuki; Kato, Yusuke; Mukai, Tadashi; Toguchi, Hajime; Odomi, Masaaki; Ogawara, Ken-ichi; Higaki, Kazutaka; Kimura, Toshikiro

2006-02-01

We previously reported that the fatty base suppository containing sodium laurate (C12) and taurine (Tau) (C12-Tau suppository) could enhance the colonic absorption of rebamipide, a poorly water-soluble and poorly absorbable drug, without any serious mucosal damages in rats. In the preset study, in order to make C12-Tau suppositories available for practical use, the scaling-up studies of animal and formulation size were performed, compared with the suppositories containing sodium caprate (C10) (C10 suppository) at the same amounts as those contained in the commercial products. Twenty-mg C12 improved the dissolution of rebamipide from suppository remarkably and the addition of 30-mg Tau only slightly decreased the dissolution rate. The absorption of rebamipide from rabbit rectum was more markedly improved by suppositories containing C12 than C10 suppositories. Although Tau tended to attenuate the absorption-enhancing effect of C12, several C12-Tau suppositories kept high bioavailability values, which were much higher than control. Histopathological studies showed that Tau exerted the cytoprotective action and that C12-Tau suppositories were better than C10 suppositories in safety. Considering the balance between efficacy and safety, the suppository containing 10- or 20-mg C12 with 30-mg Tau is better than C10 suppositories as commercial products and could be promising for practical use in human.

jqcML: an open-source java API for mass spectrometry quality control data in the qcML format.

PubMed

Bittremieux, Wout; Kelchtermans, Pieter; Valkenborg, Dirk; Martens, Lennart; Laukens, Kris

2014-07-03

The awareness that systematic quality control is an essential factor to enable the growth of proteomics into a mature analytical discipline has increased over the past few years. To this aim, a controlled vocabulary and document structure have recently been proposed by Walzer et al. to store and disseminate quality-control metrics for mass-spectrometry-based proteomics experiments, called qcML. To facilitate the adoption of this standardized quality control routine, we introduce jqcML, a Java application programming interface (API) for the qcML data format. First, jqcML provides a complete object model to represent qcML data. Second, jqcML provides the ability to read, write, and work in a uniform manner with qcML data from different sources, including the XML-based qcML file format and the relational database qcDB. Interaction with the XML-based file format is obtained through the Java Architecture for XML Binding (JAXB), while generic database functionality is obtained by the Java Persistence API (JPA). jqcML is released as open-source software under the permissive Apache 2.0 license and can be downloaded from https://bitbucket.org/proteinspector/jqcml .

Formation of methyl mercury by bacteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamdy, M.K.; Noyes, O.R.

1975-09-01

Twenty-three Hg/sup 2 +/-resistant cultures were isolated from sediment of the Savannah River in Georgia; of these, 14 were gram-negative short rods belonging to the genera Escherichia and Enterobacter, six were gram-positive cocci (three Staphylococcus sp. and three Streptococcus sp.) and three were Bacillus sp. All the Escherichia, Enterobacter, and the Bacillus strain were more resistant to Hg/sup 2 +/ than the strains of staphylococci and streptococci. Adaptation using serial dilutions and concentration gradient agar plant techniques showed that it was possible to select a Hg/sup 2 +/-resistant strain from a parent culture identified as Enterobacter aerogenes. This culture resistedmore » 1200 ..mu..g of Hg/sup 2 +/ per ml of medium and produced methyl mercury from HgCl/sub 2/, but was unable to convert Hg/sup 2 +/ to volatile elemental mercury (Hg/sup 0/). Under constant aeration (i.e., submerged culture), slightly more methyl mercury was formed than in the absence of aeration. Production of methyl mercury was cyclic in nature and slightly decreased if DL-homocysteine was present in media, but increased with methylcobalamine. It is concluded that the bacterial production of methyl mercury may be a means of resistance and detoxification against mercurials in which inorganic Hg/sup 2 +/ is converted to organic form and secreted into the environment. 39 references, 5 figures, 3 tables.« less

Formation of methyl mercury by bacteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamdy, M.K.; Noyes, O.R.

1975-09-01

Twenty-three Hg/sup 2 +/-resistant cultures were isolated from sediment of the Savannah River in Georgia; of these, 14 were gram-negative short rods belonging to the genera Escherichia and Enterobacter, six were gram-positive cocci (three Staphylococcus sp. and three Streptococcus sp.) and three were Bacillus sp. All the Escherichia, Enterobacter, and the Bacillus strain were more resistant to Hg/sup 2 +/ than the strains of staphylococci and streptococci. Adaptation using serial dilutions and concentration gradient agar plate techniques showed that it was possible to select a Hg/sup 2 +/-resistant strain from a parent culture identified as Enterobacter aerogenes. This culture resistedmore » 1,200 ..mu..g of Hg/sup 2 +/ per ml of medium and produced methyl mercury from HgCl/sub 2/, but was unable to convert Hg/sup 2 +/ to volatile elemental mercury (Hg/sup 0/). Under constant aeration (i.e., submerged culture), slightly more methyl mercury was formed than in the absence of aeration. Production of methyl mercury was cycle in nature and slightly decreased if DL-homocysteine was present in media, but increased with methylcobalamine. It is concluded that the bacterial production of methyl mercury may be a means of resistance and detoxification against mercurials in which inorganic Hg/sup 2 +/ is converted to organic form and secreted into the environment.« less

jTraML: an open source Java API for TraML, the PSI standard for sharing SRM transitions.

PubMed

Helsens, Kenny; Brusniak, Mi-Youn; Deutsch, Eric; Moritz, Robert L; Martens, Lennart

2011-11-04

We here present jTraML, a Java API for the Proteomics Standards Initiative TraML data standard. The library provides fully functional classes for all elements specified in the TraML XSD document, as well as convenient methods to construct controlled vocabulary-based instances required to define SRM transitions. The use of jTraML is demonstrated via a two-way conversion tool between TraML documents and vendor specific files, facilitating the adoption process of this new community standard. The library is released as open source under the permissive Apache2 license and can be downloaded from http://jtraml.googlecode.com . TraML files can also be converted online at http://iomics.ugent.be/jtraml .

mzML2ISA & nmrML2ISA: generating enriched ISA-Tab metadata files from metabolomics XML data

PubMed Central

Larralde, Martin; Lawson, Thomas N.; Weber, Ralf J. M.; Moreno, Pablo; Haug, Kenneth; Rocca-Serra, Philippe; Viant, Mark R.; Steinbeck, Christoph; Salek, Reza M.

2017-01-01

Abstract Summary Submission to the MetaboLights repository for metabolomics data currently places the burden of reporting instrument and acquisition parameters in ISA-Tab format on users, who have to do it manually, a process that is time consuming and prone to user input error. Since the large majority of these parameters are embedded in instrument raw data files, an opportunity exists to capture this metadata more accurately. Here we report a set of Python packages that can automatically generate ISA-Tab metadata file stubs from raw XML metabolomics data files. The parsing packages are separated into mzML2ISA (encompassing mzML and imzML formats) and nmrML2ISA (nmrML format only). Overall, the use of mzML2ISA & nmrML2ISA reduces the time needed to capture metadata substantially (capturing 90% of metadata on assay and sample levels), is much less prone to user input errors, improves compliance with minimum information reporting guidelines and facilitates more finely grained data exploration and querying of datasets. Availability and Implementation mzML2ISA & nmrML2ISA are available under version 3 of the GNU General Public Licence at https://github.com/ISA-tools. Documentation is available from http://2isa.readthedocs.io/en/latest/. Contact reza.salek@ebi.ac.uk or isatools@googlegroups.com Supplementary information Supplementary data are available at Bioinformatics online. PMID:28402395

mzML2ISA & nmrML2ISA: generating enriched ISA-Tab metadata files from metabolomics XML data.

PubMed

Larralde, Martin; Lawson, Thomas N; Weber, Ralf J M; Moreno, Pablo; Haug, Kenneth; Rocca-Serra, Philippe; Viant, Mark R; Steinbeck, Christoph; Salek, Reza M

2017-08-15

Submission to the MetaboLights repository for metabolomics data currently places the burden of reporting instrument and acquisition parameters in ISA-Tab format on users, who have to do it manually, a process that is time consuming and prone to user input error. Since the large majority of these parameters are embedded in instrument raw data files, an opportunity exists to capture this metadata more accurately. Here we report a set of Python packages that can automatically generate ISA-Tab metadata file stubs from raw XML metabolomics data files. The parsing packages are separated into mzML2ISA (encompassing mzML and imzML formats) and nmrML2ISA (nmrML format only). Overall, the use of mzML2ISA & nmrML2ISA reduces the time needed to capture metadata substantially (capturing 90% of metadata on assay and sample levels), is much less prone to user input errors, improves compliance with minimum information reporting guidelines and facilitates more finely grained data exploration and querying of datasets. mzML2ISA & nmrML2ISA are available under version 3 of the GNU General Public Licence at https://github.com/ISA-tools. Documentation is available from http://2isa.readthedocs.io/en/latest/. reza.salek@ebi.ac.uk or isatools@googlegroups.com. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Ancestry Dependent DNA Methylation and Influence of Maternal Nutrition

PubMed Central

Mozhui, Khyobeni; Smith, Alicia K.; Tylavsky, Frances A.

2015-01-01

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. PMID:25742137

The XBabelPhish MAGE-ML and XML translator.

PubMed

Maier, Don; Wymore, Farrell; Sherlock, Gavin; Ball, Catherine A

2008-01-18

MAGE-ML has been promoted as a standard format for describing microarray experiments and the data they produce. Two characteristics of the MAGE-ML format compromise its use as a universal standard: First, MAGE-ML files are exceptionally large - too large to be easily read by most people, and often too large to be read by most software programs. Second, the MAGE-ML standard permits many ways of representing the same information. As a result, different producers of MAGE-ML create different documents describing the same experiment and its data. Recognizing all the variants is an unwieldy software engineering task, resulting in software packages that can read and process MAGE-ML from some, but not all producers. This Tower of MAGE-ML Babel bars the unencumbered exchange of microarray experiment descriptions couched in MAGE-ML. We have developed XBabelPhish - an XQuery-based technology for translating one MAGE-ML variant into another. XBabelPhish's use is not restricted to translating MAGE-ML documents. It can transform XML files independent of their DTD, XML schema, or semantic content. Moreover, it is designed to work on very large (> 200 Mb.) files, which are common in the world of MAGE-ML. XBabelPhish provides a way to inter-translate MAGE-ML variants for improved interchange of microarray experiment information. More generally, it can be used to transform most XML files, including very large ones that exceed the capacity of most XML tools.

QuakeML 2.0: Recent developments

NASA Astrophysics Data System (ADS)

Euchner, Fabian; Kästli, Philipp; Heiniger, Lukas; Saul, Joachim; Schorlemmer, Danijel; Clinton, John

2016-04-01

QuakeML is a community-backed data model for seismic event parameter description. Its current version 1.2, released in 2013, has become the gold standard for parametric data dissemination at seismological data centers, and has been adopted as an FDSN standard. It is supported by several popular software products and data services, such as FDSN event web services, QuakePy, and SeisComP3. Work on the successor version 2.0 is under way since 2015. The scope of QuakeML has been expanded beyond event parameter description. Thanks to a modular architecture, many thematic packages have been added, which cover peak ground motion, site and station characterization, hydraulic parameters of borehole injection processes, and macroseismics. The first three packages can be considered near final and implementations of program codes and SQL databases are in productive use at various institutions. A public community review process has been initiated in order to turn them into community-approved standards. The most recent addition is a package for single station quake location, which allows a detailed probabilistic description of event parameters recorded at a single station. This package adds some information elements such as angle of incidence, frequency-dependent phase picks, and dispersion relations. The package containing common data types has been extended with a generic type for probability density functions. While on Earth, single station methods are niche applications, they are of prominent interest in planetary seismology, e.g., the NASA InSight mission to Mars. So far, QuakeML is lacking a description of seismic instrumentation (inventory). There are two existing standards of younger age (FDSN StationXML and SeisComP3 Inventory XML). We discuss their respective strengths, differences, and how they could be combined into an inventory package for QuakeML, thus allowing full interoperability with other QuakeML data types. QuakeML is accompanied by QuakePy, a Python package

Estuarine methylation of tin and its relationship to the microbial sulfur cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilmour, C.C.

This work describes the first quantitative measurement of tin methylation in nature. Central to this research was development of a technique for the determination of methyltin species in sediment with detection limits of about 1 pg per gm dry weight sediment. Methyltin concentrations measured in Chesapeake Bay sediments ranged from 0.005 to 8 ng per gm dry weight sediment, with monomethyltin the predominant species. Estuarine tin methylation occurred only in anoxic, sulfidic sediments and was microbially mediated. Sulfate-reducing bacteria were correlated with methyltin production in sediments, and capable of tin methylation in pure culture without sediment. Conversely, excess sulfide concentrationsmore » inhibited methylation. Sulfate reduction rates and reduced inorganic sulfur distribution between acid-volatile and non-volatile sulfides for Chesapeake sediments were also determined. Monomethyltin was the predominant product of stepwise inorganic tin methylation in sediments and bacterial cultures, with di- and trimethylated tins produced in lesser amounts. Methylation rates based on accumulation of all detectable methyltin species were quite low. Maximum concentrations of methyltins formed were quite low. Maximum concentrations of methyltins formed were 10 ng total methyltins per ml culture, or 4 ng per gm dry weight sediment. Trimethyltin, the most toxic product, was produced in the smallest quantities, never more than 50 pg per gm sediment.« less

Efficient delivery and distribution in skin of chlorogenic acid and resveratrol induced by microemulsion using sucrose laurate.

PubMed

Yutani, Reiko; Kikuchi, Taketomo; Teraoka, Reiko; Kitagawa, Shuji

2014-01-01

To achieve efficient skin delivery of polyphenols, we prepared a novel oil-in-water (o/w)-type microemulsion (MESL) using sucrose laurate as a surfactant and ethanol, isopropyl myristate and water as other components. We examined its usefulness by in vitro studies on skin delivery of chlorogenic acid and resveratrol as hydrophilic and hydrophobic polyphenols using Yucatan micropig skin, and also examined the difference in the distribution of these polyphenols in skin. MESL significantly improved skin incorporation of these polyphenols at all time points examined (6, 20, 40 h) in the epidermis and at 20 and 40 h in the dermis, compared with the microemulsion using Tween 80 as a surfactant component (MEK), although the solubilization capacity of MESL was lower than that of MEK. Using MESL, the incorporation amount in the dermis of each polyphenol increased with time, while the amount in the epidermis was almost constant during the time examined. Incorporation efficiencies into skin of chlorogenic acid and resveratrol induced by MESL at 40 h after application were about 6-fold and 19-fold higher in the epidermis and 3.5-fold and 15-fold higher in the dermis, respectively, than those by MEK. The increase was more prominent for resveratrol. Hydrophilic chlorogenic acid was distributed slightly more in the epidermis, while hydrophobic and smaller-molecular-weight resveratrol was mainly distributed in the dermis. These findings suggest that MESL could be a promising vehicle for the efficient skin delivery of chlorogenic acid and resveratrol, especially for resveratrol to the dermis.

Production of MAG via enzymatic glycerolysis

NASA Astrophysics Data System (ADS)

Jamlus, Norul Naziraa Ahmad; Derawi, Darfizzi; Salimon, Jumat

2015-09-01

Enzymatic glycerolysis of a medium chain methyl ester, methyl laurate was performed using lipase Candida antarctica (Novozyme 435) for 6 hours at 55°C. The percentage of components mixture of product were determined by using gas chromatography technique. The enzymatic reaction was successfully produced monolaurin (45.9 %), dilaurin (47.1 %) and trilaurin (7.0 %) respectively. Thin layer chromatography (TLC) plate also showed a good separation of component spots. Fourier transformation infra-red (FTIR) spectrum showed the presence of ester carbonyl at wavenumber 1739.99 cm-1 and hydrogen bonded O-H at 3512.03 cm-1. The product is potentially to be used as emulsifier and additive in food industry, pharmaceutical, as well as antibacterial.

49 CFR 173.193 - Bromoacetone, methyl bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc.

Code of Federal Regulations, 2010 CFR

2010-10-01

... methyl bromide or methyl chloride mixtures, etc. 173.193 Section 173.193 Transportation Other Regulations... bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc. (a) Bromoacetone must be...) Bromoacetone, methyl bromide, chloropicrin and methyl bromide mixtures, chloropicrin and methyl chloride...

ML Crew Access Arm Move

NASA Image and Video Library

2017-11-10

A heavy-load transport truck carrying the Orion crew access arm makes its way toward the mobile launcher (ML) at NASA's Kennedy Space Center in Florida. The crew access arm will be installed at about the 274-foot level on the mobile launcher tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

ML Crew Access Arm Move

NASA Image and Video Library

2017-11-10

A heavy-load transport truck carrying the Orion crew access arm nears the mobile launcher (ML) at NASA's Kennedy Space Center in Florida. The crew access arm will be installed at about the 274-foot level on the mobile launcher tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

QuakeML - An XML Schema for Seismology

NASA Astrophysics Data System (ADS)

Wyss, A.; Schorlemmer, D.; Maraini, S.; Baer, M.; Wiemer, S.

2004-12-01

We propose an extensible format-definition for seismic data (QuakeML). Sharing data and seismic information efficiently is one of the most important issues for research and observational seismology in the future. The eXtensible Markup Language (XML) is playing an increasingly important role in the exchange of a variety of data. Due to its extensible definition capabilities, its wide acceptance and the existing large number of utilities and libraries for XML, a structured representation of various types of seismological data should in our opinion be developed by defining a 'QuakeML' standard. Here we present the QuakeML definitions for parameter databases and further efforts, e.g. a central QuakeML catalog database and a web portal for exchanging codes and stylesheets.

Predictive value of CpG island methylator phenotype for tumor recurrence in hepatitis B virus-associated hepatocellular carcinoma following liver transplantation

PubMed Central

2010-01-01

Background CpG island methylator phenotype (CIMP), in which multiple genes concordantly methylated, has been demonstrated to be associated with progression, recurrence, as well as overall survival in some types of cancer. Methods We examined the promoter methylation status of seven genes including P16, CDH1, GSTP1, DAPK, XAF1, SOCS1 and SYK in 65 cases of HCC treated with LT by methylation-specific PCR. CIMP+ was defined as having three or more genes that are concordantly methylated. The relationship between CIMP status and clinicopathological parameters, as well as tumor recurrence was further analyzed. Results CIMP+ was more frequent in HCC with AFP > 400 ng/ml than those with AFP ≤ 400 ng/ml (P = 0.017). In addition, patients with CIMP+ were prone to have multiple tumor numbers than those with CIMP- (P = 0.007). Patients with CIMP+ tumors had significantly worse recurrence-free survival (RFS) than patients with CIMP-tumors by Kaplan-Meier estimates (P = 0.004). Multivariate analysis also revealed that CIMP status might be a novel independent prognostic factor of RFS for HCC patients treated with LT (HR: 3.581; 95% CI: 1.473-8.710, P = 0.005). Conclusion Our results suggested that CIMP could serve as a new prognostic biomarker to predict the risk of tumor recurrence in HCC after transplantation. PMID:20678188

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in Parkinson's disease.

PubMed

Louis, Elan D; Michalec, Monika; Jiang, Wendy; Factor-Litvak, Pam; Zheng, Wei

2014-01-01

Parkinson's disease (PD) is a late-life neurodegenerative disease. Genetic and environmental factors play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin that shows structural resemblance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In 2002 and 2007, we demonstrated elevated blood harmane concentrations [HA] in essential tremor (ET) cases. We now assessed whether blood [HA] were elevated in Parkinson's disease (PD) as well. Blood [HA] were quantified by high performance liquid chromatography. Subjects comprised 113 PD cases and 101 controls. Mean log blood [HA] in PD cases was double that of controls (0.59±0.63 g(-10)/ml vs. 0.27±0.63 g(-10)/ml, p<0.001). A non-parametric test on non-transformed data (median blood [HA]=3.31 g(-10)/ml in cases and 1.44 g(-10)/ml in controls) also showed this difference (p<0.001). In unadjusted and then adjusted logistic regression analyses, log blood [HA] was associated with PD (odds ratio [OR]unadjusted 2.31, 95% confidence interval [CI] 1.46-3.67, p<0.001; OR(adjusted) 2.54, 95% CI 1.55-4.16, p<0.001). In PD, log blood [HA] co-varied with family history, being lowest in PD cases with no family history (0.54±0.60 g(-10)/ml) and highest in PD cases with a family history of both ET and PD (0.84±0.68 g(-10)/ml) (p=0.06). Blood harmane appears to be elevated in PD. The finding needs to be reproduced in additional cohorts to assess its generalizability. The higher concentration in familial PD suggests that the mechanism may involve genetic factors. Copyright © 2013 Elsevier Inc. All rights reserved.

Elevated Blood Harmane (1-methyl-9H-pyrido[3,4-b]indole) Concentrations In Parkinson's Disease

PubMed Central

Louis, Elan D.; Michalec, Monika; Jiang, Wendy; Factor-Litvak, Pam; Zheng, Wei

2014-01-01

Background Parkinson's disease (PD) is a late-life neurodegenerative disease. Genetic and environmental factors play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin that shows structural resemblance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Objectives In 2002 and 2007, we demonstrated elevated blood harmane concentrations [HA] in essential tremor (ET) cases. We now assessed whether blood [HA] were elevated in Parkinson's disease (PD) as well. Methods Blood [HA] were quantified by high performance liquid chromatography. Subjects comprised 113 PD cases and 101 controls. Results Mean log blood [HA] in PD cases was double that of controls (0.59 ± 0.63 g −10/ml vs. 0.27 ± 0.63 g−10/ml, p <0.001). A non-parametric test on non-transformed data (median blood [HA] = 3.31 g −10/ml in cases and 1.44 g −10/ml in controls) also showed this difference (p <0.001). In unadjusted and then adjusted logistic regression analyses, log blood [HA] was associated with PD (odds ratio [OR]unadjusted 2.31, 95% confidence interval [CI] 1.46 – 3.67, p <0.001; ORadjusted 2.54, 95% CI 1.55 – 4.16, p <0.001). In PD, log blood [HA] co-varied with family history, being lowest in PD cases with no family history (0.54 ± 0.60 g−10/ml) and highest in PD cases with a family history of both ET and PD (0.84 ± 0.68 g−10/ml)(p = 0.06). Conclusions Blood harmane appears to be elevated in PD. The finding needs to be reproduced in additional cohorts to assess its generalizability. The higher concentration in familial PD suggests that the mechanism may involve genetic factors. PMID:24300779

ML Crew Access Arm Move

NASA Image and Video Library

2017-11-09

The Orion crew access arm, secured on a stand, is being prepared for its move from a storage location at NASA's Kennedy Space Center in Florida, to the mobile launcher (ML) tower near the Vehicle Assembly Building at the center. The crew access arm will be installed at about the 274-foot level on the tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower.

ML Crew Access Arm Move

NASA Image and Video Library

2017-11-09

The Orion crew access arm is secured in a storage location at NASA's Kennedy Space Center in Florida. The access arm will be prepared for its move to the mobile launcher (ML) tower near the Vehicle Assembly Building at the center. The crew access arm will be installed at about the 274-foot level on the tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower.

CellML metadata standards, associated tools and repositories

PubMed Central

Beard, Daniel A.; Britten, Randall; Cooling, Mike T.; Garny, Alan; Halstead, Matt D.B.; Hunter, Peter J.; Lawson, James; Lloyd, Catherine M.; Marsh, Justin; Miller, Andrew; Nickerson, David P.; Nielsen, Poul M.F.; Nomura, Taishin; Subramanium, Shankar; Wimalaratne, Sarala M.; Yu, Tommy

2009-01-01

The development of standards for encoding mathematical models is an important component of model building and model sharing among scientists interested in understanding multi-scale physiological processes. CellML provides such a standard, particularly for models based on biophysical mechanisms, and a substantial number of models are now available in the CellML Model Repository. However, there is an urgent need to extend the current CellML metadata standard to provide biological and biophysical annotation of the models in order to facilitate model sharing, automated model reduction and connection to biological databases. This paper gives a broad overview of a number of new developments on CellML metadata and provides links to further methodological details available from the CellML website. PMID:19380315

Diatomite-supported Pd-M (M=Cu, Co, Ni) bimetal nanocatalysts for selective hydrogenation of long-chain aliphatic esters.

PubMed

Huang, Changliang; Zhang, Hongye; Zhao, Yanfei; Chen, Sha; Liu, Zhimin

2012-11-15

Diatomite supported Pd-M (M=Cu, Co, Ni) bimetal nanocatalysts with various metal compositions were prepared and characterized by means of X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy. It was demonstrated that the metal nanoparticles were uniformly distributed on the support, and their size was centered around 8 nm with a relatively narrow size distribution. The catalysts were used to catalyze hydrogenation of long-chain aliphatic esters, including methyl palmitate, methyl stearate, and methyl laurate. It was indicated that the all diatomite-supported Pd-based bimetal catalysts were active to the selective hydrogenation of long-chain esters to corresponding alcohols at 270°C, originated from the synergistic effect between the metal particles and the diatomite support. For the selective hydrogenation of methyl palmitate, Pd-Cu/diatomite with metal loading of 1% and Pd/Cu=3 displayed the highest performance, giving a 1-hexadecanol yield of 82.9% at the substrate conversion of 98.8%. Copyright © 2012 Elsevier Inc. All rights reserved.

ML Crew Access Arm Move

NASA Image and Video Library

2017-10-16

The Orion crew access arm departs Precision Fabricating and Cleaning in Cocoa, Florida, atop a flatbed truck. The access arm is transported to a storage location at NASA's Kennedy Space Center in Florida. Later this month, the arm will be transported to the mobile launcher (ML) tower at the center. The crew access arm will be located at about the 274-foot level on the tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower.

ML Crew Access Arm Move

NASA Image and Video Library

2017-11-10

The Orion crew access arm is secured on a flatbed transporter for its move from a storage location at NASA's Kennedy Space Center in Florida to the mobile launcher (ML) tower near the Vehicle Assembly Building at the center. The crew access arm will be installed at about the 274-foot level on the mobile launcher tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

ML Crew Access Arm Move

NASA Image and Video Library

2017-11-10

A heavy-load transport truck carries the Orion crew access arm along the NASA Causeway east toward State Road 3 at NASA's Kennedy Space Center in Florida. The access arm will be moved to the mobile launcher (ML) near the Vehicle Assembly Building at the center. The crew access arm will be installed at about the 274-foot level on the tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

Cigarette smoke condensate induces differential expression and promoter methylation profiles of critical genes involved in lung cancer in NL-20 lung cells in vitro: short-term and chronic exposure.

PubMed

Word, Beverly; Lyn-Cook, Lascelles E; Mwamba, Bibi; Wang, Honggang; Lyn-Cook, Beverly; Hammons, George

2013-01-01

Establishing early diagnostic markers of harm is critical for effective prevention programs and regulation of tobacco products. This study examined effects of cigarette smoke condensate (CSC) on expression and promoter methylation profile of critical genes (DAPK, ECAD, MGMT, and RASSF1A) involved in lung cancer development in different human lung cell lines. NL-20 cells were treated with 0.1-100 μg/ml of CSC for 24 to 72 hrs for short-term exposures. DAPK expression or methylation status was not significantly affected. However, CSC treatment resulted in changes in expression and promoter methylation profile of ECAD, MGMT, and RASSF1A. For chronic studies, cells were exposed to 1 or 10 μg/ml CSC up to 28 days. Cells showed morphological changes associated with transformation and changes in invasion capacities and global methylation status. This study provides critical data suggesting that epigenetic changes could serve as an early biomarker of harm due to exposure to cigarette smoke.

In vitro study comparing the ability of mono-octanoin and mono-octanoin plus methyl tert-butyl ether to dissolve biliary stones.

PubMed

Tritapepe, R; Cesana, B

1996-01-01

This in vitro study compared the gallstone dissolution rates of mono-octanoin, mono-octanoin plus 10% distilled water, and mono-octanoin plus methyl tert-butyl ether 2:1. Sixteen stones were treated with each solvent at a slow perfusion rate of 3-4 ml/h and a rapid perfusion rate of 2.5 ml/30 min with 20-sec instillation/aspiration cycles, both with and without bile. The stones were weighed before, and 3, 6, 12 and 24 hrs after the start of treatment: the solvent was changed every 30 min. After 24 hrs of instillation/aspiration without bile, the mono-octanoin/methyl tert-butyl ether mixture reduced the weight of the stones by 93%, mono-octanoin plus water by 63%, and mono-octanoin alone by 52%; with bile, the figures were, respectively, 86%, 42% and 40%. The mono-octanoin/methyl tert-butyl ether mixture thus took approximately half the time needed by the other two preparations to dissolve the stones to the same extent, a finding which may be relevant for the clinical dissolution of bile duct stones.

Model-driven Service Engineering with SoaML

NASA Astrophysics Data System (ADS)

Elvesæter, Brian; Carrez, Cyril; Mohagheghi, Parastoo; Berre, Arne-Jørgen; Johnsen, Svein G.; Solberg, Arnor

This chapter presents a model-driven service engineering (MDSE) methodology that uses OMG MDA specifications such as BMM, BPMN and SoaML to identify and specify services within a service-oriented architecture. The methodology takes advantage of business modelling practices and provides a guide to service modelling with SoaML. The presentation is case-driven and illuminated using the telecommunication example. The chapter focuses in particular on the use of the SoaML modelling language as a means for expressing service specifications that are aligned with business models and can be realized in different platform technologies.

ML Crew Access Arm Move

NASA Image and Video Library

2017-11-10

A heavy-load transport truck carries the Orion crew access arm along the NASA Causeway east toward State Road 3 at NASA's Kennedy Space Center in Florida. The access arm will be moved to the mobile launcher (ML) near the Vehicle Assembly Building at the center. The crew access arm will be installed at about the 274-foot level on the mobile launcher tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

Identification of Differentially Methylated Sites with Weak Methylation Effects

PubMed Central

Tran, Hong; Zhu, Hongxiao; Wu, Xiaowei; Kim, Gunjune; Clarke, Christopher R.; Larose, Hailey; Haak, David C.; Westwood, James H.; Zhang, Liqing

2018-01-01

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 concepts, with

Development of suppository formulation safely improving rectal absorption of rebamipide, a poorly absorbable drug, by utilizing sodium laurate and taurine.

PubMed

Miyake, Masateru; Kamada, Naoki; Oka, Yoshikazu; Mukai, Tadashi; Minami, Takanori; Toguchi, Hajime; Odomi, Masaaki; Ogawara, Ken-ichi; Higaki, Kazutaka; Kimura, Toshikiro

2004-09-14

To develop the safe formulation that can safely improve bioavailability of poorly absorbable drugs and that is practically available, we prepared the suppositories of rebamipide, a poorly soluble and poorly absorbable antiulcer drug, by employing the combinatorial use of sodium laurate (C12), an absorption enhancer, with taurine (Tau) or L-glutamine (L-Gln), an adjuvant exerting the cytoprotective action. Although the dissolution of rebamipide from fatty base (FB) suppository prepared using Witepsol H-15 was very slow, it was remarkably improved by the addition of C12 and L-Gln or Tau into the suppository. On the other hand, the dissolution of rebamipide from water-soluble base (WB) suppository prepared using polyethylene glycol was very rapid and the addition of adjuvants did not influence its dissolution so much. Rectal absorption of rebamipide examined in rats was remarkably improved by FB suppository containing C12 or both C12 and Tau, while the enhancing effect of C12 was relatively small in the case of WB suppositories. Biochemical and histopathological studies have confirmed that FB suppository containing both C12 and Tau or L-Gln did not cause any serious local damage, while FB suppository containing C12 only caused the erosion and shrinkage for a lot of rectal epithelial cells. In conclusion, FB suppository employing the combinatorial use of C12 with Tau could be a promising formulation that is effective and safe enough for poorly absorbable drugs to be practically administered.

Comparison of a 50 mL pycnometer and a 500 mL flask, EURAMET.M.FF.S8 (EURAMET 1297)

NASA Astrophysics Data System (ADS)

Mićić, Ljiljana; Batista, Elsa

2018-01-01

The purpose of this comparison was to compare the results of the participating laboratories in the calibration of 50 mL pycnometer and 500 mL volumetric flask using the gravimetric method. Laboratories were asked to determined the 'contained' volume of the 50 mL pycnometer and of the 500 mL flask at a reference temperature of 20 °C. The gravimetric method was used for both instruments by all laboratories. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

ML 3.0 smoothed aggregation user's guide.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sala, Marzio; Hu, Jonathan Joseph; Tuminaro, Raymond Stephen

2004-05-01

ML is a multigrid preconditioning package intended to solve linear systems of equations Az = b where A is a user supplied n x n sparse matrix, b is a user supplied vector of length n and x is a vector of length n to be computed. ML should be used on large sparse linear systems arising from partial differential equation (PDE) discretizations. While technically any linear system can be considered, ML should be used on linear systems that correspond to things that work well with multigrid methods (e.g. elliptic PDEs). ML can be used as a stand-alone package ormore » to generate preconditioners for a traditional iterative solver package (e.g. Krylov methods). We have supplied support for working with the AZTEC 2.1 and AZTECOO iterative package [15]. However, other solvers can be used by supplying a few functions. This document describes one specific algebraic multigrid approach: smoothed aggregation. This approach is used within several specialized multigrid methods: one for the eddy current formulation for Maxwell's equations, and a multilevel and domain decomposition method for symmetric and non-symmetric systems of equations (like elliptic equations, or compressible and incompressible fluid dynamics problems). Other methods exist within ML but are not described in this document. Examples are given illustrating the problem definition and exercising multigrid options.« less

ML 3.1 smoothed aggregation user's guide.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sala, Marzio; Hu, Jonathan Joseph; Tuminaro, Raymond Stephen

2004-10-01

ML is a multigrid preconditioning package intended to solve linear systems of equations Ax = b where A is a user supplied n x n sparse matrix, b is a user supplied vector of length n and x is a vector of length n to be computed. ML should be used on large sparse linear systems arising from partial differential equation (PDE) discretizations. While technically any linear system can be considered, ML should be used on linear systems that correspond to things that work well with multigrid methods (e.g. elliptic PDEs). ML can be used as a stand-alone package ormore » to generate preconditioners for a traditional iterative solver package (e.g. Krylov methods). We have supplied support for working with the Aztec 2.1 and AztecOO iterative package [16]. However, other solvers can be used by supplying a few functions. This document describes one specific algebraic multigrid approach: smoothed aggregation. This approach is used within several specialized multigrid methods: one for the eddy current formulation for Maxwell's equations, and a multilevel and domain decomposition method for symmetric and nonsymmetric systems of equations (like elliptic equations, or compressible and incompressible fluid dynamics problems). Other methods exist within ML but are not described in this document. Examples are given illustrating the problem definition and exercising multigrid options.« less

AllerML: Markup Language for Allergens

PubMed Central

Ivanciuc, Ovidiu; Gendel, Steven M.; Power, Trevor D.; Schein, Catherine H.; Braun, Werner

2011-01-01

Many concerns have been raised about the potential allergenicity of novel, recombinant proteins into food crops. Guidelines, proposed by WHO/FAO and EFSA, include the use of bioinformatics screening to assess the risk of potential allergenicity or cross-reactivities of all proteins introduced, for example, to improve nutritional value or promote crop resistance. However, there are no universally accepted standards that can be used to encode data on the biology of allergens to facilitate using data from multiple databases in this screening. Therefore, we developed AllerML a markup language for allergens to assist in the automated exchange of information between databases and in the integration of the bioinformatics tools that are used to investigate allergenicity and cross-reactivity. As proof of concept, AllerML was implemented using the Structural Database of Allergenic Proteins (SDAP; http://fermi.utmb.edu/SDAP/) database. General implementation of AllerML will promote automatic flow of validated data that will aid in allergy research and regulatory analysis. PMID:21420460

Note on Conditional Compilation in Standard ML

DTIC Science & Technology

1993-06-01

eOmputer-Science No-te on Coridhitiom Cominliati"I~n Standard ML1 Nicholas Haines Edoardo Biagioni Robert Hiarper mom Brian G. Mimnes June 1993 CMU...CS-93. 11 TIC ELECTE f 00..7733 %goo~~OO Note on Conditioual Compilation in Standard ML Nicholas Haines Edoardo Biagioni Robert Harper Brian G. Milnes

Comparison of the bonding between ML(+) and ML2(+) (M = metal, L = noble gas)

NASA Technical Reports Server (NTRS)

Bauschlicher, Charles W., Jr.; Partridge, Harry; Langhoff, Stephen R.

1990-01-01

Ab initio calculations are reported of the spectroscopic constants for the low-lying states of the molecular ions ML2(+), where M = Li, Na, Mg, V, Fe, Co, Ni and Cu, and where L is usually Ar. Comparison with existing analogous calculations on the ML(+) ions shows how the bonding and binding energy change with the addition of a second noble gas atom. The second binding energy is predicted to be essentially the same as the first for the Li, Na, Mg, and V ions, but larger for the Fe, Co, Ni and Cu ions. The binding energies of the transition metal noble gas ions are not accurately predicted at the SCF level, because correlation is required to describe their M(0)Ln(+) character. All trends can be explained in terms of promotion and hybridization on the metal ion.

Methylation matters

PubMed Central

Costello, J.; Plass, C.

2001-01-01

DNA methylation is not just for basic scientists any more. There is a growing awareness in the medical field that having the correct pattern of genomic methylation is essential for healthy cells and organs. If methylation patterns are not properly established or maintained, disorders as diverse as mental retardation, immune deficiency, and sporadic or inherited cancers may follow. Through inappropriate silencing of growth regulating genes and simultaneous destabilisation of whole chromosomes, methylation defects help create a chaotic state from which cancer cells evolve. Methylation defects are present in cells before the onset of obvious malignancy and therefore cannot be explained simply as a consequence of a deregulated cancer cell. Researchers are now able to detect with exquisite sensitivity the cells harbouring methylation defects, sometimes months or years before the time when cancer is clinically detectable. Furthermore, aberrant methylation of specific genes has been directly linked with the tumour response to chemotherapy and patient survival. Advances in our ability to observe the methylation status of the entire cancer cell genome have led us to the unmistakable conclusion that methylation abnormalities are far more prevalent than expected. This methylomics approach permits the integration of an ever growing repertoire of methylation defects with the genetic alterations catalogued from tumours over the past two decades. Here we discuss the current knowledge of DNA methylation in normal cells and disease states, and how this relates directly to our current understanding of the mechanisms by which tumours arise.


Keywords: methylation; cancer PMID:11333864

Isolation, characterization and mode of antimicrobial action against Vibrio cholerae of methyl gallate isolated from Acacia farnesiana.

PubMed

Sánchez, E; Heredia, N; Camacho-Corona, M Del R; García, S

2013-12-01

The antimicrobial activity of Acacia farnesiana against Vibrio cholerae has been demonstrated; however, no information regarding its active compound or its mechanism of action has been documented. The active compound was isolated from A. farnesiana by bioassay-guided fractionation and identified as methyl gallate by nuclear magnetic resonance (NMR) techniques ((1) H NMR and (13) C NMR). The minimum bactericidal concentration (MBC) of methyl gallate and its effect on membrane integrity, cytoplasmic pH, membrane potential, ATP synthesis and gene expression of cholera toxin (ctx) from V. cholerae were determined. The MBC of methyl gallate ranged from 30 ± 1 to 50 ± 1 μg ml(-1) . Methyl gallate affected cell membrane integrity, causing a decrease in cytoplasmic pH (pHin , from 7·3 to <3·0), and membrane hyperpolarization, and ATP was no longer produced by the treated cells. However, methyl gallate did not affect ctx gene expression. Methyl gallate is a major antimicrobial compound from A. farnesiana that disturbs the membrane activity of V. cholerae. The effects of methyl gallate validate several traditional antimicrobial uses of A. farnesiana, and it is an attractive alternative to control V. cholerae. © 2013 The Society for Applied Microbiology.

jmzIdentML API: A Java interface to the mzIdentML standard for peptide and protein identification data.

PubMed

Reisinger, Florian; Krishna, Ritesh; Ghali, Fawaz; Ríos, Daniel; Hermjakob, Henning; Vizcaíno, Juan Antonio; Jones, Andrew R

2012-03-01

We present a Java application programming interface (API), jmzIdentML, for the Human Proteome Organisation (HUPO) Proteomics Standards Initiative (PSI) mzIdentML standard for peptide and protein identification data. The API combines the power of Java Architecture of XML Binding (JAXB) and an XPath-based random-access indexer to allow a fast and efficient mapping of extensible markup language (XML) elements to Java objects. The internal references in the mzIdentML files are resolved in an on-demand manner, where the whole file is accessed as a random-access swap file, and only the relevant piece of XMLis selected for mapping to its corresponding Java object. The APIis highly efficient in its memory usage and can handle files of arbitrary sizes. The APIfollows the official release of the mzIdentML (version 1.1) specifications and is available in the public domain under a permissive licence at http://www.code.google.com/p/jmzidentml/. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD.

PubMed

Pergola, Pablo E; Krauth, Melissa; Huff, J Warren; Ferguson, Deborah A; Ruiz, Stacey; Meyer, Colin J; Warnock, David G

2011-01-01

Bardoxolone methyl, a novel synthetic triterpenoid, induces Nrf2, a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules. This exploratory multi-center, open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with moderate to severe chronic kidney disease and type 2 diabetes. Patients received 25 mg of bardoxolone methyl daily for 28 days, followed by 75 mg daily for another 28 days. The study achieved its primary efficacy endpoint, as demonstrated by a significant increase from baseline in estimated glomerular filtration rate (eGFR) of 7.2 ml/min/1.73 m2 (p < 0.001). Improvements were seen in approximately 90% of patients and showed a dose- and time-dependent increase in eGFR. The eGFR change paralleled a significant reduction in serum creatinine (-0.3 mg/dl) and blood urea nitrogen (-4.9 mg/dl), along with an increase in creatinine clearance (+14.6 ml/min/1.73 m2), without a change in the 24-hour creatinine excretion rate. Markers of vascular injury and inflammation were improved by treatment with bardoxolone. No life-threatening adverse events or drug-related serious adverse events were reported. The results describe an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl, a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function. Copyright © 2011 S. Karger AG, Basel.

AllerML: markup language for allergens.

PubMed

Ivanciuc, Ovidiu; Gendel, Steven M; Power, Trevor D; Schein, Catherine H; Braun, Werner

2011-06-01

Many concerns have been raised about the potential allergenicity of novel, recombinant proteins into food crops. Guidelines, proposed by WHO/FAO and EFSA, include the use of bioinformatics screening to assess the risk of potential allergenicity or cross-reactivities of all proteins introduced, for example, to improve nutritional value or promote crop resistance. However, there are no universally accepted standards that can be used to encode data on the biology of allergens to facilitate using data from multiple databases in this screening. Therefore, we developed AllerML a markup language for allergens to assist in the automated exchange of information between databases and in the integration of the bioinformatics tools that are used to investigate allergenicity and cross-reactivity. As proof of concept, AllerML was implemented using the Structural Database of Allergenic Proteins (SDAP; http://fermi.utmb.edu/SDAP/) database. General implementation of AllerML will promote automatic flow of validated data that will aid in allergy research and regulatory analysis. Copyright © 2011 Elsevier Inc. All rights reserved.

Identification of endometrial cancer methylation features using combined methylation analysis methods

PubMed Central

Trimarchi, Michael P.; Yan, Pearlly; Groden, Joanna; Bundschuh, Ralf; Goodfellow, Paul J.

2017-01-01

Background 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. Methods 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. Results 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. Conclusion We identified a methylation signature for a �

Divergence, differential methylation and interspersion of melon satellite DNA sequences.

PubMed Central

Shmookler Reis, R; Timmis, J N; Ingle, J

1981-01-01

Melon (Cucumis melo) satellite DNA consists of two components, Q and S, each with a buoyant density in CsCl of 1.707 g/ml, but differing by 9 degrees C in "melting" temperature. These physical properties appear to be in contradiction, since both depend on G + C content. In order to resolve this anomaly, base compositions were directly determined for isolated fractions. the low-"melting" component S contains 41.8% G + C, with 6% of C present as 5-methylcytosine, whereas Q DNA contains 54% G + C, with 41% of C methylated. Analyses of restriction site loss agreed well with the direct determinations of methylation and divergence, and indicated some clustering of methylated sites in Q DNA. Analysis of restricted main-band DNA by hydridization with RNA complementary to Q satellite DNA ("Southern transfer") showed satellite Q tandem arrays interspersed in DNA of main-band density. Sequence divergence and extent of methylation did not appear to depend on whether a repeat array was present as satellite or interspersed in main-band DNA. Hydridization in situ indicated considerable heterogeneity in the genomic proportion of the Q-DNA sequences in melon fruit nuclei, implying over- and under-representation consistent with extensive unequal recombination in satellite Q tandem arrays. The cucumber, Cucumis sativus, contains less than 8% as much Q-homologous DNA per genome as the melon, suggesting rapid evolutionary gain or loss of these tandem repeat sequences. Images Fig. 2. PLATE 1 Fig. 4. Fig. 10. PMID:6172117

Methylation of 23S rRNA Nucleotide G748 by RlmAII Methyltransferase Renders Streptococcus pneumoniae Telithromycin Susceptible

PubMed Central

Sato, Yoshiharu; Shoji, Tatsuma; Yamamoto, Tomoko

2013-01-01

Several posttranscriptional modifications of bacterial rRNAs are important in determining antibiotic resistance or sensitivity. In all Gram-positive bacteria, dimethylation of nucleotide A2058, located in domain V of 23S rRNA, by the dimethyltransferase Erm(B) results in low susceptibility and resistance to telithromycin (TEL). However, this is insufficient to produce high-level resistance to TEL in Streptococcus pneumoniae. Inactivation of the methyltransferase RlmAII, which methylates the N-1 position of nucleotide G748, located in hairpin 35 of domain II of 23S rRNA, results in increased resistance to TEL in erm(B)-carrying S. pneumoniae. Sixteen TEL-resistant mutants (MICs, 16 to 32 μg/ml) were obtained from a clinically isolated S. pneumoniae strain showing low TEL susceptibility (MIC, 2 μg/ml), with mutation resulting in constitutive dimethylation of A2058 because of nucleotide differences in the regulatory region of erm(B) mRNA. Primer extension analysis showed that the degree of methylation at G748 in all TEL-resistant mutants was significantly reduced by a mutation in the gene encoding RlmAII to create a stop codon or change an amino acid residue. Furthermore, RNA footprinting with dimethyl sulfate and a molecular modeling study suggested that methylation of G748 may contribute to the stable interaction of TEL with domain II of 23S rRNA, even after dimethylation of A2058 by Erm(B). This novel finding shows that methylation of G748 by RlmAII renders S. pneumoniae TEL susceptible. PMID:23716046

Methylation of 23S rRNA nucleotide G748 by RlmAII methyltransferase renders Streptococcus pneumoniae telithromycin susceptible.

PubMed

Takaya, Akiko; Sato, Yoshiharu; Shoji, Tatsuma; Yamamoto, Tomoko

2013-08-01

Several posttranscriptional modifications of bacterial rRNAs are important in determining antibiotic resistance or sensitivity. In all Gram-positive bacteria, dimethylation of nucleotide A2058, located in domain V of 23S rRNA, by the dimethyltransferase Erm(B) results in low susceptibility and resistance to telithromycin (TEL). However, this is insufficient to produce high-level resistance to TEL in Streptococcus pneumoniae. Inactivation of the methyltransferase RlmA(II), which methylates the N-1 position of nucleotide G748, located in hairpin 35 of domain II of 23S rRNA, results in increased resistance to TEL in erm(B)-carrying S. pneumoniae. Sixteen TEL-resistant mutants (MICs, 16 to 32 μg/ml) were obtained from a clinically isolated S. pneumoniae strain showing low TEL susceptibility (MIC, 2 μg/ml), with mutation resulting in constitutive dimethylation of A2058 because of nucleotide differences in the regulatory region of erm(B) mRNA. Primer extension analysis showed that the degree of methylation at G748 in all TEL-resistant mutants was significantly reduced by a mutation in the gene encoding RlmA(II) to create a stop codon or change an amino acid residue. Furthermore, RNA footprinting with dimethyl sulfate and a molecular modeling study suggested that methylation of G748 may contribute to the stable interaction of TEL with domain II of 23S rRNA, even after dimethylation of A2058 by Erm(B). This novel finding shows that methylation of G748 by RlmA(II) renders S. pneumoniae TEL susceptible.

Fluorescence-based Sensing of 2,4,6-Trinitrotoluene (TNT) Using a Multi-channeled Poly(methyl methacrylate) (PMMA) Microimmunosensor

DTIC Science & Technology

2010-01-22

Davidson, Y.Y.; McWhorter, C.S.; Soper , S.A.; McCarley, R.L. Surface modification of poly(methyl methacrylate) used in the fabrication of microanalytical...J.; Hupert, M.L.; Patterson, D.; Gottert, J.; McCarley, R.L.; Nikitopoulos, D.; Murphy, M.C.; Soper , S.A. Highly efficient circulating tumor cell

Determination of 5-hydroxy-N-methyl-2-pyrrolidone and 2-hydroxy-N-methylsuccinimide in human plasma and urine using liquid chromatography-electrospray tandem mass spectrometry.

PubMed

Carnerup, M A; Akesson, B; Jönsson, B A

2001-09-15

A method for simultaneous determination of 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) was developed. These compounds are metabolites from N-methyl-2-pyrrolidone (NMP), a powerful and widely used organic solvent. 5-HNMP and 2-HMSI were purified from plasma and urine by solid-phase extraction using Isolute ENV+ columns, and analysed by liquid chromatography coupled to a mass spectrometer fitted with an atmospheric pressure turbo ion spray ionisation interface in the positive ion mode. The method was validated for plasma and urine concentrations from 0.12 to 25 microg/ml. The recoveries for 5-HNMP and 2-HMSI in plasma were 99 and 98%, respectively, and in urine 111 and 106%, respectively. For 5-HNMP and 2-HMSI, the within-day precision in plasma was 1-4 and 3-6%, respectively, and in urine 2-12 and 3-10%, respectively. The corresponding data for the between-day precision was 5 and 3-6%, respectively, and 4-6 and 7-8%, respectively. The detection limit for 5-HNMP was 4 ng/ml in plasma and 120 ng/ml in urine. For 2-HMSI, it was 5 ng/ml in plasma and 85 ng/ml in urine. The method is applicable for analysis of plasma and urine samples from workers exposed to NMP.

Understanding and Evolving the ML Module System

DTIC Science & Technology

2005-05-01

kinds Abstract The ML module system stands as a high-water mark of programming language support for data abstraction. Nevertheless, it is not in a... language of part (3) using the framework of Harper and Stone, in which the meanings of “external” ML programs are interpreted by translation into an...researcher has been influenced to a large degree by their rigorous approach to programming language research and their profound sense of aesthetics. I

Malignant lymphomas (ML) and HIV infection in Tanzania

PubMed Central

2008-01-01

Background HIV infection is reported to be associated with some malignant lymphomas (ML) so called AIDS-related lymphomas (ARL), with an aggressive behavior and poor prognosis. The ML frequency, pathogenicity, clinical patterns and possible association with AIDS in Tanzania, are not well documented impeding the development of preventive and therapeutic strategies. Methods Sections of 176 archival formalin-fixed paraffin-embedded biopsies of ML patients at Muhimbili National Hospital (MNH)/Muhimbili University of Health and Allied Sciences (MUHAS), Tanzania from 1996–2001 were stained for hematoxylin and eosin and selected (70) cases for expression of pan-leucocytic (CD45), B-cell (CD20), T-cell (CD3), Hodgkin/RS cell (CD30), histiocyte (CD68) and proliferation (Ki-67) antigen markers. Corresponding clinical records were also evaluated. Available sera from 38 ML patients were screened (ELISA) for HIV antibodies. Results The proportion of ML out of all diagnosed tumors at MNH during the 6 year period was 4.2% (176/4200) comprising 77.84% non-Hodgkin (NHL) including 19.32% Burkitt's (BL) and 22.16% Hodgkin's disease (HD). The ML tumors frequency increased from 0.42% (1997) to 0.70% (2001) and 23.7% of tested sera from these patients were HIV positive. The mean age for all ML was 30, age-range 3–91 and peak age was 1–20 years. The male:female ratio was 1.8:1. Supra-diaphragmatic presentation was commonest and histological sub-types were mostly aggressive B-cell lymphomas however, no clear cases of primary effusion lymphoma (PEL) and primary central nervous system lymphoma (PCNSL) were diagnosed. Conclusion Malignant lymphomas apparently, increased significantly among diagnosed tumors at MNH between 1996 and 2001, predominantly among the young, HIV infected and AIDS patients. The frequent aggressive clinical and histological presentation as well as the dominant B-immunophenotype and the HIV serology indicate a pathogenic association with AIDS. Therefore, routine

Malignant lymphomas (ML) and HIV infection in Tanzania.

PubMed

Mwakigonja, Amos R; Kaaya, Ephata E; Mgaya, Edward M

2008-06-10

HIV infection is reported to be associated with some malignant lymphomas (ML) so called AIDS-related lymphomas (ARL), with an aggressive behavior and poor prognosis. The ML frequency, pathogenicity, clinical patterns and possible association with AIDS in Tanzania, are not well documented impeding the development of preventive and therapeutic strategies. Sections of 176 archival formalin-fixed paraffin-embedded biopsies of ML patients at Muhimbili National Hospital (MNH)/Muhimbili University of Health and Allied Sciences (MUHAS), Tanzania from 1996-2001 were stained for hematoxylin and eosin and selected (70) cases for expression of pan-leucocytic (CD45), B-cell (CD20), T-cell (CD3), Hodgkin/RS cell (CD30), histiocyte (CD68) and proliferation (Ki-67) antigen markers. Corresponding clinical records were also evaluated. Available sera from 38 ML patients were screened (ELISA) for HIV antibodies. The proportion of ML out of all diagnosed tumors at MNH during the 6 year period was 4.2% (176/4200) comprising 77.84% non-Hodgkin (NHL) including 19.32% Burkitt's (BL) and 22.16% Hodgkin's disease (HD). The ML tumors frequency increased from 0.42% (1997) to 0.70% (2001) and 23.7% of tested sera from these patients were HIV positive. The mean age for all ML was 30, age-range 3-91 and peak age was 1-20 years. The male:female ratio was 1.8:1. Supra-diaphragmatic presentation was commonest and histological sub-types were mostly aggressive B-cell lymphomas however, no clear cases of primary effusion lymphoma (PEL) and primary central nervous system lymphoma (PCNSL) were diagnosed. Malignant lymphomas apparently, increased significantly among diagnosed tumors at MNH between 1996 and 2001, predominantly among the young, HIV infected and AIDS patients. The frequent aggressive clinical and histological presentation as well as the dominant B-immunophenotype and the HIV serology indicate a pathogenic association with AIDS. Therefore, routine HIV screening of all malignant lymphoma

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

PubMed

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

Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease.

PubMed

de Zeeuw, Dick; Akizawa, Tadao; Audhya, Paul; Bakris, George L; Chin, Melanie; Christ-Schmidt, Heidi; Goldsberry, Angie; Houser, Mark; Krauth, Melissa; Lambers Heerspink, Hiddo J; McMurray, John J; Meyer, Colin J; Parving, Hans-Henrik; Remuzzi, Giuseppe; Toto, Robert D; Vaziri, Nosratola D; Wanner, Christoph; Wittes, Janet; Wrolstad, Danielle; Chertow, Glenn M

2013-12-26

Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown. We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m(2) of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes. The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group. Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the

Colorimetric determination of DNase I activity with a DNA-methyl green substrate.

PubMed

Sinicropi, D; Baker, D L; Prince, W S; Shiffer, K; Shak, S

1994-11-01

A simple, high throughput, and precise assay was developed for quantification of deoxyribonuclease I (DNase; IUB 3.1.21.1) activity. The method was adapted from the procedure devised by Kurnick which employs a substrate comprised of highly polymerized native DNA complexed with methyl green. Hydrolysis of the DNA produced unbound methyl green and a decrease in the absorbance of the solution at 620 nm. By adjusting the time and temperature of the reaction, the assay permits quantification of DNase activity over a wide concentration range (0.4 to 8900 ng/ml). Samples and standards were added to the substrate in microtiter plates and were incubated for 1-24 h at 25-37 degrees C to achieve the desired assay range. The DNase activity of the samples was interpolated from a standard curve generated with Pulmozyme recombinant human deoxyribonuclease I (rhDNase). Interassay precision was less than 12% CV and recovery was within 100 +/- 11%. Activity determination by the DNA-methyl green method correlated well with that determined by the widely used "hyperchromicity" method originated by Kunitz, which is based on the increase in absorbance at 260 nm upon hydrolysis of DNA. The DNA-methyl green assay was simpler and more versatile than the hyperchromicity method and was used to characterize the activity of rhDNase and DNase isolated from human urine.

Effective methylation of phosphonic acids related to chemical warfare agents mediated by trimethyloxonium tetrafluoroborate for their qualitative detection and identification by gas chromatography-mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valdez, Carlos A.; Leif, Roald N.; Alcaraz, Armando

The effective methylation of phosphonic acids related to chemical warfare agents (CWAs) employing trimethyloxonium tetrafluoroborate (TMO·BF 4) for their qualitative detection and identification by gas chromatography-mass spectrometry (GC-MS) is presented. The methylation occurs in rapid fashion (1 h) and can be conveniently carried out at ambient temperature, thus providing a safer alternative to the universally employed diazomethane-based methylation protocols. Optimization of the methylation parameters led us to conclude that methylene chloride was the ideal solvent to carry out the derivatization, and that even though methylated products can be observed surfacing after only 1 h, additional time was not found tomore » be detrimental but beneficial to the process particularly when dealing with analytes at low concentrations (~10 μg mL -1). Due to its insolubility in methylene chloride, TMO·BF 4 conveniently settles to the bottom during the reaction and does not produce additional interfering by-products that may further complicate the GC-MS analysis. We demonstrated the method to successfully methylate a variety of Schedule 2 phosphonic acids, including their half esters, resulting in derivatives that were readily detected and identified using the instrument's spectral library. Most importantly, the method was shown to simultaneously methylate a mixture of the organophosphorus-based nerve agent hydrolysis products: pinacolyl methylphosphonate (PMPA), cyclohexyl methylphosphonate (CyMPA) and ethyl methylphosphonate (EMPA) (at a 10 μg mL -1 concentration each) in a fatty acid ester-rich organic matrix (OPCW-PT-O 3) featured in the 38th Organisation for the Prohibition of Chemical Weapons (OPCW) Proficiency Test. Additionally, the protocol was found to effectively methylate N,N-diethylamino ethanesulfonic acid and N,N-diisopropylamino ethanesulfonic acid that are products arising from the oxidative degradation of the V-series agents VR and VX respectively

Effective methylation of phosphonic acids related to chemical warfare agents mediated by trimethyloxonium tetrafluoroborate for their qualitative detection and identification by gas chromatography-mass spectrometry

DOE PAGES

Valdez, Carlos A.; Leif, Roald N.; Alcaraz, Armando

2016-06-01

The effective methylation of phosphonic acids related to chemical warfare agents (CWAs) employing trimethyloxonium tetrafluoroborate (TMO·BF 4) for their qualitative detection and identification by gas chromatography-mass spectrometry (GC-MS) is presented. The methylation occurs in rapid fashion (1 h) and can be conveniently carried out at ambient temperature, thus providing a safer alternative to the universally employed diazomethane-based methylation protocols. Optimization of the methylation parameters led us to conclude that methylene chloride was the ideal solvent to carry out the derivatization, and that even though methylated products can be observed surfacing after only 1 h, additional time was not found tomore » be detrimental but beneficial to the process particularly when dealing with analytes at low concentrations (~10 μg mL -1). Due to its insolubility in methylene chloride, TMO·BF 4 conveniently settles to the bottom during the reaction and does not produce additional interfering by-products that may further complicate the GC-MS analysis. We demonstrated the method to successfully methylate a variety of Schedule 2 phosphonic acids, including their half esters, resulting in derivatives that were readily detected and identified using the instrument's spectral library. Most importantly, the method was shown to simultaneously methylate a mixture of the organophosphorus-based nerve agent hydrolysis products: pinacolyl methylphosphonate (PMPA), cyclohexyl methylphosphonate (CyMPA) and ethyl methylphosphonate (EMPA) (at a 10 μg mL -1 concentration each) in a fatty acid ester-rich organic matrix (OPCW-PT-O 3) featured in the 38th Organisation for the Prohibition of Chemical Weapons (OPCW) Proficiency Test. Additionally, the protocol was found to effectively methylate N,N-diethylamino ethanesulfonic acid and N,N-diisopropylamino ethanesulfonic acid that are products arising from the oxidative degradation of the V-series agents VR and VX respectively

Synthesis and Characterization of Microencapsulated Phase Change Materials with Poly(urea-urethane) Shells Containing Cellulose Nanocrystals.

PubMed

Yoo, Youngman; Martinez, Carlos; Youngblood, Jeffrey P

2017-09-20

The main objective of this study is to develop microencapsulation technology for thermal energy storage incorporating a phase change material (PCM) in a composite wall shell, which can be used to create a stable environment and allow the PCM to undergo phase change without any outside influence. Surface modification of cellulose nanocrystals (CNCs) was conducted by grafting poly(lactic acid) oligomers and oleic acid to improve the dispersion of nanoparticles in a polymeric shell. A microencapsulated phase change material (methyl laurate) with poly(urea-urethane) (PU) composite shells containing the hydrophobized cellulose nanocrystals (hCNCs) was fabricated using an in situ emulsion interfacial polymerization process. The encapsulation process of the PCMs with subsequent interfacial hCNC-PU to form composite microcapsules as well as their morphology, composition, thermal properties, and release rates was examined in this study. Oil soluble Sudan II dye solution in methyl laurate was used as a model hydrophobic fill, representing other latent fills with low partition coefficients, and their encapsulation efficiency as well as dye release rates were measured spectroscopically in a water medium. The influence of polyol content in the PU polymer matrix of microcapsules was investigated. An increase in polyol contents leads to an increase in the mean size of microcapsules but a decrease in the gel content (degree of cross-linking density) and permeability of their shell structure. The encapsulated PCMs for thermal energy storage demonstrated here exhibited promising performance for possible use in building or paving materials in terms of released heat, desired phase transformation temperature, chemical and physical stability, and concrete durability during placement.

Human T lymphocytes express N-methyl-D-aspartate receptors functionally active in controlling T cell activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miglio, Gianluca; Varsaldi, Federica; Lombardi, Grazia

2005-12-30

The aim of this study was to investigate the expression and the functional role of N-methyl-D-aspartate (NMDA) receptors in human T cells. RT-PCR analysis showed that human resting peripheral blood lymphocytes (PBL) and Jurkat T cells express genes encoding for both NR1 and NR2B subunits: phytohemagglutinin (PHA)-activated PBL also expresses both these genes and the NR2A and NR2D genes. Cytofluorimetric analysis showed that NR1 expression increases as a consequence of PHA (10 {mu}g/ml) treatment. D-(-)-2-Amino-5-phosphonopentanoic acid (D-AP5), and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine [(+)-MK 801], competitive and non-competitive NMDA receptor antagonists, respectively, inhibited PHA-induced T cell proliferation, whereas they did not affect IL-2 (10more » U/ml)-induced proliferation of PHA blasts. These effects were due to the prevention of T cell activation (inhibition of cell aggregate formation and CD25 expression), but not to cell cycle arrest or death. These results demonstrate that human T lymphocytes express NMDA receptors, which are functionally active in controlling cell activation.« less

AstroML: Python-powered Machine Learning for Astronomy

NASA Astrophysics Data System (ADS)

Vander Plas, Jake; Connolly, A. J.; Ivezic, Z.

2014-01-01

As astronomical data sets grow in size and complexity, automated machine learning and data mining methods are becoming an increasingly fundamental component of research in the field. The astroML project (http://astroML.org) provides a common repository for practical examples of the data mining and machine learning tools used and developed by astronomical researchers, written in Python. The astroML module contains a host of general-purpose data analysis and machine learning routines, loaders for openly-available astronomical datasets, and fast implementations of specific computational methods often used in astronomy and astrophysics. The associated website features hundreds of examples of these routines being used for analysis of real astronomical datasets, while the associated textbook provides a curriculum resource for graduate-level courses focusing on practical statistics, machine learning, and data mining approaches within Astronomical research. This poster will highlight several of the more powerful and unique examples of analysis performed with astroML, all of which can be reproduced in their entirety on any computer with the proper packages installed.

CytometryML binary data standards

NASA Astrophysics Data System (ADS)

Leif, Robert C.

2005-03-01

CytometryML is a proposed new Analytical Cytology (Cytomics) data standard, which is based on a common set of XML schemas for encoding flow cytometry and digital microscopy text based data types (metadata). CytometryML schemas reference both DICOM (Digital Imaging and Communications in Medicine) codes and FCS keywords. Flow Cytometry Standard (FCS) list-mode has been mapped to the DICOM Waveform Information Object. The separation of the large binary data objects (list mode and image data) from the XML description of the metadata permits the metadata to be directly displayed, analyzed, and reported with standard commercial software packages; the direct use of XML languages; and direct interfacing with clinical information systems. The separation of the binary data into its own files simplifies parsing because all extraneous header data has been eliminated. The storage of images as two-dimensional arrays without any extraneous data, such as in the Adobe Photoshop RAW format, facilitates the development by scientists of their own analysis and visualization software. Adobe Photoshop provided the display infrastructure and the translation facility to interconvert between the image data from commercial formats and RAW format. Similarly, the storage and parsing of list mode binary data type with a group of parameters that are specified at compilation time is straight forward. However when the user is permitted at run-time to select a subset of the parameters and/or specify results of mathematical manipulations, the development of special software was required. The use of CytometryML will permit investigators to be able to create their own interoperable data analysis software and to employ commercially available software to disseminate their data.

Chemically modified maize cobs waste with enhanced adsorption properties upon methyl orange and arsenic.

PubMed

Elizalde-González, María P; Mattusch, J; Wennrich, R

2008-07-01

The surface chemistry of maize naturasorbent was altered in this work by the modifying agents: phosphoric acid and different amines (triethanolamine, diethylenetriamine and 1,4-diaminobutane). Removal of methyl orange (25 mg l(-1)) was <50% by maize corn cobs modified by phosphorylation and higher by the quaternized samples: 68% with the 1,4-diaminobutane and 73% with the diethylenetriamine modificators. Adsorption of arsenite by the samples modified with phosphoric acid/ammonia was 11 microg g(-1), which corresponds to 98% removal from a 550 microg As l(-1) solution for an adsorbent dose of 50 mg ml(-1). The samples modified by phosphoric acid/urea removed 0.4 microg g(-1) arsenate from a 300 mug As l(-1) solution. Adsorption of methyl orange, arsenite and arsenate was superior by the chemically modified maize cobs judged against the initial naturasorbent. For comparison, removal by the commercial anion exchanger was 100% for methyl orange, 45% (5 microg g(-1)) for arsenite and 99% (5 microg g(-1)) for arsenate.

Temperature dependence of the exchange coupling in the Fe(001) whisker/11 ML Cr/20 ML Fe structure

NASA Astrophysics Data System (ADS)

From, M.; Liao, L. X.; Cochran, J. F.; Heinrich, B.

1994-05-01

The exchange coupling between iron layers separated by 11 monolayers (ML) of Cr(001) has been investigated using a structure in which the Cr(001) was grown on a bulk iron whisker Fe(001) surface at a temperature of approximately 300 °C. This temperature was selected to produce near optimum smoothness of the Cr layer. The Cr(001) deposition was followed by the deposition of 20 ML of Fe(001) at room temperature, and by the deposition of a 20 ML Au(001) protective layer. The frequencies corresponding to the magnetic excitations in this structure were measured by means of Brillouin light scattering (BLS). One of the observed frequencies corresponds to a surface mode in the bulk iron whisker. Another observed frequency corresponds to the lowest lying precessional mode of the magnetization in the 20 ML thick Fe(001) thin film. Typically, the thin film frequency exhibits a dependence on applied magnetic field that displays two cusps. The positions of the cusps are dependent on the exchange coupling between the 20 ML Fe film and the bulk iron substrate. The surface mode frequency increases monotonically with increasing field over most of the field range investigated. However, at the field corresponding to the low field cusp in the thin film frequency, the surface mode frequency undergoes an abrupt jump in magnitude. We have used the position of the cusps in the thin film data to deduce values for the bilinear, J1, and biquadratic, J2, coupling terms, where the coupling energy is written in the form EAB=-J1 cos(Δφ)+J2 cos2(Δφ); Δφ is the angle between the thin film and bulk iron magnetizations. Measurements of J1 and J2 have been carried out at six temperatures that span the range 100-350 K. Both J1 and J2 are found to depend strongly on temperature. The data are well described by the quadratic expression J2=-0.54+1.46 ×‖J1‖-0.52×J12, where J1 and J2 are expressed in erg/cm2. The large nonzero intercept and the linear term probably imply a significant intrinsic

CytometryML and other data formats

NASA Astrophysics Data System (ADS)

Leif, Robert C.

2006-02-01

Cytology automation and research will be enhanced by the creation of a common data format. This data format would provide the pathology and research communities with a uniform way for annotating and exchanging images, flow cytometry, and associated data. This specification and/or standard will include descriptions of the acquisition device, staining, the binary representations of the image and list-mode data, the measurements derived from the image and/or the list-mode data, and descriptors for clinical/pathology and research. An international, vendor-supported, non-proprietary specification will allow pathologists, researchers, and companies to develop and use image capture/analysis software, as well as list-mode analysis software, without worrying about incompatibilities between proprietary vendor formats. Presently, efforts to create specifications and/or descriptions of these formats include the Laboratory Digital Imaging Project (LDIP) Data Exchange Specification; extensions to the Digital Imaging and Communications in Medicine (DICOM); Open Microscopy Environment (OME); Flowcyt, an extension to the present Flow Cytometry Standard (FCS); and CytometryML. The feasibility of creating a common data specification for digital microscopy and flow cytometry in a manner consistent with its use for medical devices and interoperability with both hospital information and picture archiving systems has been demonstrated by the creation of the CytometryML schemas. The feasibility of creating a software system for digital microscopy has been demonstrated by the OME. CytometryML consists of schemas that describe instruments and their measurements. These instruments include digital microscopes and flow cytometers. Optical components including the instruments' excitation and emission parts are described. The description of the measurements made by these instruments includes the tagged molecule, data acquisition subsystem, and the format of the list-mode and/or image data. Many

DNA methylation and methylation polymorphism in ecotypes of Jatropha curcas L. using methylation-sensitive AFLP markers.

PubMed

Mastan, Shaik G; Rathore, Mangal S; Bhatt, Vacha D; Chikara, J; Ghosh, A

2014-12-01

We investigated DNA methylation and polymorphism in the methylated DNA using AFLP based methylation-sensitive amplification polymorphism (MS-AFLP) markers in ecotypes of Jatropha curcas L. growing in similar and different geo-ecological conditions. Three ecotypes growing in different geo-ecological conditions with environmental heterogeneity (Group-1) and five ecotypes growing in similar environmental conditions (Group-2) were assessed. In ecotypes growing in group-1, 44.32 % DNA was methylated and of which 93.59 % DNA was polymorphic. While in group-2, 32.27 % DNA was methylated, of which 51.64 % DNA was polymorphic. In site 1 and site 2 of group-1, overall methylation was 18.94 and 22.44 % respectively with difference of 3.5 %, while overall polymorphism was 41.14 and 39.23 % with a difference of 1.91 %. In site 1 and site 2 of group-2, overall methylation was 24.68 and 24.18 % respectively with difference of 0.5 %, while overall polymorphism was 12.19 and 12.65 % with a difference of 0.46 %. The difference of methylation percentage and percentage of methylation polymorphism throughout the genome of J. curcas at site 1 and 2 of group-1 is higher than that of J. curcas at site 1 and 2 of group-2. These results correlated the physico-chemical properties of soil at these sites. The variations of physico-chemical properties of soil at Chorwadla (site 1 in group-1 and site 2 in group-2) compared to the soil at Brahmapur (site 2 in group-1) is higher than that of soil at Neswad (site 1 in group-2). The study suggests that these homologous nucleotide sequences probably play important role in ecotype adaptation to environmental heterogeneity by creating epiallelic variations hence in evolution of ecotypes/clines or forms of species showing phenotypic/genotypic differences in different geographical areas.

The sulfate-reducing bacterium Desulfovibrio desulfuricans ND132 as a model for understanding bacterial mercury methylation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilmour, C C; Elias, Dwayne A; Kucken, A M

2010-01-01

We propose the use of Desulfovibrio sp. ND132 as a model species for understanding the genetics and biochemistry of microbial Hg methylation. ND132 is a dissimilatory sulfate-reducing bacterium (DSRB) that exhibits exceptionally high rates of Hg methylation in culture, but is otherwise a characteristically typical Desulfovibrio strain. The full genome sequence of ND132 will be available soon. ND132 is very similar to other DSRB that are sequenced but do not methylate Hg, allowing comparison for potential methylation genes. Here, we describe the physiological characteristics of the strain, examine its MeHg production capability, and place the strain within the phylogeny ofmore » the Desulfovibrionales using 16S rRNA. We also examine Hg toxicity and the inducibility of MeHg production amongst the DSRB by comparing ND132 to non-methylating DSRB. The optimal growth medium for Hg methylation is pyruvate/fumarate, which supports strong respiratory growth without sulfide production. At moderate Hg concentrations (10 ng/ml), and using TiNTA as a reductant, ND132 methylates about 30% of added HgCl2 during batch culture growth on 40 mM pyruvate/fumarate. Under constant culture conditions, MeHg production is an exponential function of Hg concentration, probably reflecting Hg partitioning between aqueous and solid phases. To help understand how Hg is taken up by this organism, we examined the influence of a variety of small thiol-bearing ligands, as well as select amino acids, on methylation by D. desulfuricans ND132. All thiol bearing ligands tested affected methylation in similar ways, suggesting that Hg uptake by ND132 is not associated with uptake of a specific amino acid. To identify enzymes for the methylation activity, a genetic approach is being pursued. Conjugation from E. coli donors works well that allows the generation of a transposon library of random ND132 mutants. These mutants will be screened for affects on mercury methylation.« less

Laurate Biosensors Image Brain Neurotransmitters In Vivo: Can an Antihypertensive Medication Alter Psychostimulant Behavior?

PubMed

Broderick, Patricia A; Ho, Helen; Wat, Karyn; Murthy, Vivek

2008-07-04

Neuromolecular Imaging (NMI) with novel biosensors enables the selective detection of neurotransmitters in vivo within seconds, on line and in real time. Biosensors remain in place for continuing studies over a period of months. This biotechnological advance is based on conventional electrochemistry; the biosensors detect neurotransmitters by electron transfer. Simply stated, biosensors adsorb electrons from each neurotransmitter at specific oxidation potentials; the current derived from electron transfer is proportional to neurotransmitter concentration. Selective electron transfer properties of these biosensors permit the imaging of neurotransmitters, metabolites and precursors. The novel BRODERICK PROBE ® biosensors we have developed, differ in formulation and detection capabilities from biosensors/electrodes used in conventional electrochemistry/ voltammetry. In these studies, NMI, specifically, the BRODERICK PROBE ® laurate biosensor images neurotransmitter signals within mesolimbic neuronal terminals, nucleus accumbens (NAc); dopamine (DA), serotonin (5-HT), homovanillic acid (HVA) and Ltryptophan (L-TP) are selectively imaged. Simultaneously, we use infrared photobeams to monitor open-field movement behaviors on line with NMI in the same animal subjects. The goals are to investigate integrated neurochemical and behavioral effects of cocaine and caffeine alone and co-administered and further, to use ketanserin to decipher receptor profiles for these psychostimulants, alone and co-administered. The rationale for selecting this medication is: ketanserin (a) is an antihypertensive and cocaine and caffeine produce hypertension and (b) acts at 5-HT 2A/2C receptors, prevalent in NAc and implicated in hypertension and cocaine addiction. Key findings are: (a) the moderate dose of caffeine simultaneously potentiates cocaine's neurochemical and behavioral responses. (b) ketanserin simultaneously inhibits cocaine-increased DA and 5-HT release in NAc and open

Laurate Biosensors Image Brain Neurotransmitters In Vivo: Can an Antihypertensive Medication Alter Psychostimulant Behavior?

PubMed Central

Broderick, Patricia A.; Ho, Helen; Wat, Karyn; Murthy, Vivek

2008-01-01

Neuromolecular Imaging (NMI) with novel biosensors enables the selective detection of neurotransmitters in vivo within seconds, on line and in real time. Biosensors remain in place for continuing studies over a period of months. This biotechnological advance is based on conventional electrochemistry; the biosensors detect neurotransmitters by electron transfer. Simply stated, biosensors adsorb electrons from each neurotransmitter at specific oxidation potentials; the current derived from electron transfer is proportional to neurotransmitter concentration. Selective electron transfer properties of these biosensors permit the imaging of neurotransmitters, metabolites and precursors. The novel BRODERICK PROBE® biosensors we have developed, differ in formulation and detection capabilities from biosensors/electrodes used in conventional electrochemistry/voltammetry. In these studies, NMI, specifically, the BRODERICK PROBE® laurate biosensor images neurotransmitter signals within mesolimbic neuronal terminals, nucleus accumbens (NAc); dopamine (DA), serotonin (5-HT), homovanillic acid (HVA) and L-tryptophan (L-TP) are selectively imaged. Simultaneously, we use infrared photobeams to monitor open-field movement behaviors on line with NMI in the same animal subjects. The goals are to investigate integrated neurochemical and behavioral effects of cocaine and caffeine alone and co-administered and further, to use ketanserin to decipher receptor profiles for these psychostimulants, alone and co-administered. The rationale for selecting this medication is: ketanserin (a) is an antihypertensive and cocaine and caffeine produce hypertension and (b) acts at 5-HT2A/2C receptors, prevalent in NAc and implicated in hypertension and cocaine addiction. Key findings are: (a) the moderate dose of caffeine simultaneously potentiates cocaine's neurochemical and behavioral responses. (b) ketanserin simultaneously inhibits cocaine-increased DA and 5-HT release in NAc and open

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

PubMed

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

2013-06-27

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.

Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease

PubMed Central

de Zeeuw, Dick; Akizawa, Tadao; Audhya, Paul; Bakris, George L.; Chin, Melanie; Christ-Schmidt, Heidi; Goldsberry, Angie; Houser, Mark; Krauth, Melissa; Heerspink, Hiddo J. Lambers; McMurray, John J.; Meyer, Colin J.; Parving, Hans-Henrik; Remuzzi, Giuseppe; Toto, Robert D.; Vaziri, Nosratola D.; Wanner, Christoph; Wittes, Janet; Wrolstad, Danielle; Chertow, Glenn M.

2015-01-01

BACKGROUND Although inhibitors of the renin–angiotensin–aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)–related factor 2 activators further reduce this risk is unknown. METHODS We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m2 of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes. RESULTS The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P = 0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group. CONCLUSIONS Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl

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

PubMed Central

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

Mass spectrometer output file format mzML.

PubMed

Deutsch, Eric W

2010-01-01

Mass spectrometry is an important technique for analyzing proteins and other biomolecular compounds in biological samples. Each of the vendors of these mass spectrometers uses a different proprietary binary output file format, which has hindered data sharing and the development of open source software for downstream analysis. The solution has been to develop, with the full participation of academic researchers as well as software and hardware vendors, an open XML-based format for encoding mass spectrometer output files, and then to write software to use this format for archiving, sharing, and processing. This chapter presents the various components and information available for this format, mzML. In addition to the XML schema that defines the file structure, a controlled vocabulary provides clear terms and definitions for the spectral metadata, and a semantic validation rules mapping file allows the mzML semantic validator to insure that an mzML document complies with one of several levels of requirements. Complete documentation and example files insure that the format may be uniformly implemented. At the time of release, there already existed several implementations of the format and vendors have committed to supporting the format in their products.

QuakeML: Status of the XML-based Seismological Data Exchange Format

NASA Astrophysics Data System (ADS)

Euchner, Fabian; Schorlemmer, Danijel; Kästli, Philipp; Quakeml Working Group

2010-05-01

QuakeML is an XML-based data exchange standard for seismology that is in its fourth year of active community-driven development. The current release (version 1.2) is based on a public Request for Comments process that included contributions from ETH, GFZ, USC, SCEC, USGS, IRIS DMC, EMSC, ORFEUS, GNS, ZAMG, BRGM, Nanometrics, and ISTI. QuakeML has mainly been funded through the EC FP6 infrastructure project NERIES, in which it was endorsed as the preferred data exchange format. Currently, QuakeML services are being installed at several institutions around the globe, including EMSC, ORFEUS, ETH, Geoazur (Europe), NEIC, ANSS, SCEC/SCSN (USA), and GNS Science (New Zealand). Some of these institutions already provide QuakeML earthquake catalog web services. Several implementations of the QuakeML data model have been made. QuakePy, an open-source Python-based seismicity analysis toolkit using the QuakeML data model, is being developed at ETH. QuakePy is part of the software stack used in the Collaboratory for the Study of Earthquake Predictability (CSEP) testing center installations, developed by SCEC. Furthermore, the QuakeML data model is part of the SeisComP3 package from GFZ Potsdam. QuakeML is designed as an umbrella schema under which several sub-packages are collected. The present scope of QuakeML 1.2 covers a basic description of seismic events including picks, arrivals, amplitudes, magnitudes, origins, focal mechanisms, and moment tensors. Work on additional packages (macroseismic information, seismic inventory, and resource metadata) has been started, but is at an early stage. Contributions from the community that help to widen the thematic coverage of QuakeML are highly welcome. Online resources: http://www.quakeml.org, http://www.quakepy.org

WaterML: an XML Language for Communicating Water Observations Data

NASA Astrophysics Data System (ADS)

Maidment, D. R.; Zaslavsky, I.; Valentine, D.

2007-12-01

One of the great impediments to the synthesis of water information is the plethora of formats used to publish such data. Each water agency uses its own approach. XML (eXtended Markup Languages) are generalizations of Hypertext Markup Language to communicate specific kinds of information via the internet. WaterML is an XML language for water observations data - streamflow, water quality, groundwater levels, climate, precipitation and aquatic biology data, recorded at fixed, point locations as a function of time. The Hydrologic Information System project of the Consortium of Universities for the Advancement of Hydrologic Science, Inc (CUAHSI) has defined WaterML and prepared a set of web service functions called WaterOneFLow that use WaterML to provide information about observation sites, the variables measured there and the values of those measurments. WaterML has been submitted to the Open GIS Consortium for harmonization with its standards for XML languages. Academic investigators at a number of testbed locations in the WATERS network are providing data in WaterML format using WaterOneFlow web services. The USGS and other federal agencies are also working with CUAHSI to similarly provide access to their data in WaterML through WaterOneFlow services.

DNA methylation profiling identifies global methylation differences and markers of adrenocortical tumors.

PubMed

Rechache, Nesrin S; Wang, Yonghong; Stevenson, Holly S; Killian, J Keith; Edelman, Daniel C; Merino, Maria; Zhang, Lisa; Nilubol, Naris; Stratakis, Constantine A; Meltzer, Paul S; Kebebew, Electron

2012-06-01

It is not known whether there are any DNA methylation alterations in adrenocortical tumors. The objective of the study was to determine the methylation profile of normal adrenal cortex and benign and malignant adrenocortical tumors. Genome-wide methylation status of CpG regions were determined in normal (n = 19), benign (n = 48), primary malignant (n = 8), and metastatic malignant (n = 12) adrenocortical tissue samples. An integrated analysis of genome-wide methylation and mRNA expression in benign vs. malignant adrenocortical tissue samples was also performed. Methylation profiling revealed the following: 1) that methylation patterns were distinctly different and could distinguish normal, benign, primary malignant, and metastatic tissue samples; 2) that malignant samples have global hypomethylation; and 3) that the methylation of CpG regions are different in benign adrenocortical tumors by functional status. Normal compared with benign samples had the least amount of methylation differences, whereas normal compared with primary and metastatic adrenocortical carcinoma samples had the greatest variability in methylation (adjusted P ≤ 0.01). Of 215 down-regulated genes (≥2-fold, adjusted P ≤ 0.05) in malignant primary adrenocortical tumor samples, 52 of these genes were also hypermethylated. Malignant adrenocortical tumors are globally hypomethylated as compared with normal and benign tumors. Methylation profile differences may accurately distinguish between primary benign and malignant adrenocortical tumors. Several differentially methylated sites are associated with genes known to be dysregulated in malignant adrenocortical tumors.

Methylation of DNA

PubMed Central

Gold, Marvin; Gefter, Malcolm; Hausmann, Rudolph; Hurwitz, Jerard

1966-01-01

The methylated bases of DNA are formed by the transfer of the methyl group from S-adenosylmethionine to a polynucleotide acceptor. This transfer is catalyzed by highly specific enzymes which recognize a limited number of available sites in the DNA. The mechanism for the recognition is presently unknown. In some instances, there is evidence that other cellular components, such as lipopolysaccharides, can influence the methylation reaction. Certain bacteriophages induce new methylases upon infection of their hosts. Phage T3 is unique in establishing an environment in which methylation of neither the phage nor the host nucleic acid can occur. By superinfecting T3-infected cells with other phages, the latter can be obtained with methyl-deficient DNA. Although a great deal is known about the enzymology of the methylation reaction, and there appears to be a strong correlation between the in vitro and in vivo reactions, studies in which DNA is either supermethylated or totally unmethylated have not yielded any insight as to what the possible function of the methylated bases may be. PMID:5338563

ML3: a novel regulator of herbivory-induced responses in Arabidopsis thaliana

PubMed Central

Bejai, Sarosh

2013-01-01

ML (MD2-related lipid recognition) proteins are known to enhance innate immune responses in mammals. This study reports the analysis of the putative ML gene family in Arabidopsis thaliana and suggests a role for the ML3 gene in herbivory-associated responses in plants. Feeding by larvae of the Lepidopteran generalist herbivore Spodoptera littoralis and larvae of the specialist herbivore Plutella xylostella activated ML3 transcription in leaf tissues. ML3 loss-of-function Arabidopsis plants were compromised in the upregulation of herbivory-induced genes and displayed a semi-dwarf phenotype. Herbivory bioassays showed that larvae of S. littoralis fed on ml3 mutant plants gained more weight compared to larvae fed on wild-type plants while larvae of P. xylostella did not show any significant difference. Virus-induced gene silencing of ML3 expression in plants compromised in jasmonic acid (JA) and salicylic acid (SA) signalling revealed a complex role of ML3 in JA/defence signalling affecting both JA- and SA-dependent responses. The data suggest that ML3 is involved in herbivory-mediated responses in Arabidopsis and that it has a potential role in herbivory-associated molecular pattern recognition. PMID:23314818

DNA methylation profiling of esophageal adenocarcinoma using Methylation Ligation-dependent Macroarray (MLM).

PubMed

Guilleret, Isabelle; Losi, Lorena; Chelbi, Sonia T; Fonda, Sergio; Bougel, Stéphanie; Saponaro, Sara; Gozzi, Gaia; Alberti, Loredana; Braunschweig, Richard; Benhattar, Jean

2016-10-14

Most types of cancer cells are characterized by aberrant methylation of promoter genes. In this study, we described a rapid, reproducible, and relatively inexpensive approach allowing the detection of multiple human methylated promoter genes from many tissue samples, without the need of bisulfite conversion. The Methylation Ligation-dependent Macroarray (MLM), an array-based analysis, was designed in order to measure methylation levels of 58 genes previously described as putative biomarkers of cancer. The performance of the design was proven by screening the methylation profile of DNA from esophageal cell lines, as well as microdissected formalin-fixed and paraffin-embedded (FFPE) tissues from esophageal adenocarcinoma (EAC). Using the MLM approach, we identified 32 (55%) hypermethylated promoters in EAC, and not or rarely methylated in normal tissues. Among them, 21promoters were found aberrantly methylated in more than half of tumors. Moreover, seven of them (ADAMTS18, APC, DKK2, FOXL2, GPX3, TIMP3 and WIF1) were found aberrantly methylated in all or almost all the tumor samples, suggesting an important role for these genes in EAC. In addition, dysregulation of the Wnt pathway with hypermethylation of several Wnt antagonist genes was frequently observed. MLM revealed a homogeneous pattern of methylation for a majority of tumors which were associated with an advanced stage at presentation and a poor prognosis. Interestingly, the few tumors presenting less methylation changes had a lower pathological stage. In conclusion, this study demonstrated the feasibility and accuracy of MLM for DNA methylation profiling of FFPE tissue samples. Copyright © 2016 Elsevier Inc. All rights reserved.

The evolution of the CUAHSI Water Markup Language (WaterML)

NASA Astrophysics Data System (ADS)

Zaslavsky, I.; Valentine, D.; Maidment, D.; Tarboton, D. G.; Whiteaker, T.; Hooper, R.; Kirschtel, D.; Rodriguez, M.

2009-04-01

The CUAHSI Hydrologic Information System (HIS, his.cuahsi.org) uses web services as the core data exchange mechanism which provides programmatic connection between many heterogeneous sources of hydrologic data and a variety of online and desktop client applications. The service message schema follows the CUAHSI Water Markup Language (WaterML) 1.x specification (see OGC Discussion Paper 07-041r1). Data sources that can be queried via WaterML-compliant water data services include national and international repositories such as USGS NWIS (National Water Information System), USEPA STORET (Storage & Retrieval), USDA SNOTEL (Snowpack Telemetry), NCDC ISH and ISD(Integrated Surface Hourly and Daily Data), MODIS (Moderate Resolution Imaging Spectroradiometer), and DAYMET (Daily Surface Weather Data and Climatological Summaries). Besides government data sources, CUAHSI HIS provides access to a growing number of academic hydrologic observation networks. These networks are registered by researchers associated with 11 hydrologic observatory testbeds around the US, and other research, government and commercial groups wishing to join the emerging CUAHSI Water Data Federation. The Hydrologic Information Server (HIS Server) software stack deployed at NSF-supported hydrologic observatory sites and other universities around the country, supports a hydrologic data publication workflow which includes the following steps: (1) observational data are loaded from static files or streamed from sensors into a local instance of an Observations Data Model (ODM) database; (2) a generic web service template is configured for the new ODM instance to expose the data as a WaterML-compliant water data service, and (3) the new water data service is registered at the HISCentral registry (hiscentral.cuahsi.org), its metadata are harvested and semantically tagged using concepts from a hydrologic ontology. As a result, the new service is indexed in the CUAHSI central metadata catalog, and becomes

Antibacterial and antifungal efficacy of fatty acid methyl esters from the leaves of Sesuvium portulacastrum L.

PubMed

Chandrasekaran, M; Senthilkumar, A; Venkatesalu, V

2011-07-01

The fatty acid methyl esters (FAME extract) from Sesuvium (S.) portulacastrum was studied for its fatty acid composition and antimicrobial activity against human pathogenic microorganisms. The gas chromatographic analysis of FAME extract revealed the presence of palmitic acid with the highest relative percentage (31.18%), followed by oleic acid (21.15%), linolenic acid (14.18%) linoleic acid (10.63%), myristic acid (6.91%) and behenic acid (2.42%). The saturated fatty acids were higher than the unsaturated fatty acids. FAME extract showed the highest antibacterial and anticandidal activities and moderate antifungal activity against the tested microorganisms. The highest mean zone of inhibition (16.3 mm) and the lowest MIC (0.25 mg/ml) and MBC (0.5 mg/ml) values were recorded against Bacillus subtilis. The lowest mean zone of inhibition (8.8 mm) and the highest MIC (8 mg/ml) and MFC (16 mg/ml) values were recorded against Aspergillus fumigatus and Aspergillus niger. The results of the present study justify the use of S. portulacastrum in traditional medicine and the FAME extract can be used as a potential antimicrobial agent against the tested human pathogenic microorganisms.

CellML and associated tools and techniques.

PubMed

Garny, Alan; Nickerson, David P; Cooper, Jonathan; Weber dos Santos, Rodrigo; Miller, Andrew K; McKeever, Steve; Nielsen, Poul M F; Hunter, Peter J

2008-09-13

We have, in the last few years, witnessed the development and availability of an ever increasing number of computer models that describe complex biological structures and processes. The multi-scale and multi-physics nature of these models makes their development particularly challenging, not only from a biological or biophysical viewpoint but also from a mathematical and computational perspective. In addition, the issue of sharing and reusing such models has proved to be particularly problematic, with the published models often lacking information that is required to accurately reproduce the published results. The International Union of Physiological Sciences Physiome Project was launched in 1997 with the aim of tackling the aforementioned issues by providing a framework for the modelling of the human body. As part of this initiative, the specifications of the CellML mark-up language were released in 2001. Now, more than 7 years later, the time has come to assess the situation, in particular with regard to the tools and techniques that are now available to the modelling community. Thus, after introducing CellML, we review and discuss existing editors, validators, online repository, code generators and simulation environments, as well as the CellML Application Program Interface. We also address possible future directions including the need for additional mark-up languages.

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... methacrylate polymers. 177.2000 Section 177.2000 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic.../methyl methacrylate polymers. The vinylidene chloride/methyl acrylate/methyl methacrylate polymers (CAS...

Hydronium ion motion in nanometer 3-methyl-pentane films

NASA Astrophysics Data System (ADS)

Bell, Richard C.; Wu, Kai; Iedema, Martin J.; Cowin, James P.

2007-07-01

An ion soft-landing approach was applied to study the motion of hydronium (D3O+) and cesium (Cs+) ions from 84to104K in glassy 3-methyl-pentane (3MP) films vapor deposited on Pt(111). Both ions were found to have very similar mobilities in 3MP. The span of ion mobilities probed is from ˜10-18to˜10-13m2V-1s-1. Ion transport in these films was studied as a function of film thickness and electric field strength. The drift velocity was found to be linear with applied field below about 2×108V/m and deviated from linearity above this. To a large extent, D3O+ and Cs+ motion in 3MP was well predicted by a simple continuum-based ion mobility model in films from 25 to 20 000 ML thick (including pronounced perturbations 7 ML from both the vacuum and Pt interfaces). The mobility varied with temperature more slowly than predicted by Stokes' law, which may be due to extended inhomogeneous structures in the 3MP near its glass transition at 77K.

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

PubMed

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

2016-08-06

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

Methylation oligonucleotide microarray: a novel tool to analyze methylation patterns

NASA Astrophysics Data System (ADS)

Hou, Peng; Ji, Meiju; He, Nongyao; Lu, Zuhong

2003-04-01

A new technique to analyze methylation patterns in several adjacent CpG sites was developed and reported here. We selected a 336bp segment of the 5"-untranslated region and the first exon of the p16Ink4a gene, which include the most densely packed CpG fragment of the islands containing 32 CpG dinucleotides, as the investigated target. The probes that include all types of methylation patterns were designed to fabricate a DNA microarray to determine the methylation patterns of seven adjacent CpG dinucleotides sites. High accuracy and reproducibility were observed in several parallel experiments. The results led us to the conclusion that the methylation oligonucleotide microarray can be applied as a novel and powerful tool to map methylation patterns and changes in multiple CpG island loci in a variety of tumors.

DMRfinder: efficiently identifying differentially methylated regions from MethylC-seq data.

PubMed

Gaspar, John M; Hart, Ronald P

2017-11-29

DNA methylation is an epigenetic modification that is studied at a single-base resolution with bisulfite treatment followed by high-throughput sequencing. After alignment of the sequence reads to a reference genome, methylation counts are analyzed to determine genomic regions that are differentially methylated between two or more biological conditions. Even though a variety of software packages is available for different aspects of the bioinformatics analysis, they often produce results that are biased or require excessive computational requirements. DMRfinder is a novel computational pipeline that identifies differentially methylated regions efficiently. Following alignment, DMRfinder extracts methylation counts and performs a modified single-linkage clustering of methylation sites into genomic regions. It then compares methylation levels using beta-binomial hierarchical modeling and Wald tests. Among its innovative attributes are the analyses of novel methylation sites and methylation linkage, as well as the simultaneous statistical analysis of multiple sample groups. To demonstrate its efficiency, DMRfinder is benchmarked against other computational approaches using a large published dataset. Contrasting two replicates of the same sample yielded minimal genomic regions with DMRfinder, whereas two alternative software packages reported a substantial number of false positives. Further analyses of biological samples revealed fundamental differences between DMRfinder and another software package, despite the fact that they utilize the same underlying statistical basis. For each step, DMRfinder completed the analysis in a fraction of the time required by other software. Among the computational approaches for identifying differentially methylated regions from high-throughput bisulfite sequencing datasets, DMRfinder is the first that integrates all the post-alignment steps in a single package. Compared to other software, DMRfinder is extremely efficient and unbiased in

High-Throughput Analysis of Global DNA Methylation Using Methyl-Sensitive Digestion.

PubMed

Shiratori, Hiromi; Feinweber, Carmen; Knothe, Claudia; Lötsch, Jörn; Thomas, Dominique; Geisslinger, Gerd; Parnham, Michael J; Resch, Eduard

2016-01-01

DNA methylation is a major regulatory process of gene transcription, and aberrant DNA methylation is associated with various diseases including cancer. Many compounds have been reported to modify DNA methylation states. Despite increasing interest in the clinical application of drugs with epigenetic effects, and the use of diagnostic markers for genome-wide hypomethylation in cancer, large-scale screening systems to measure the effects of drugs on DNA methylation are limited. In this study, we improved the previously established fluorescence polarization-based global DNA methylation assay so that it is more suitable for application to human genomic DNA. Our methyl-sensitive fluorescence polarization (MSFP) assay was highly repeatable (inter-assay coefficient of variation = 1.5%) and accurate (r2 = 0.99). According to signal linearity, only 50-80 ng human genomic DNA per reaction was necessary for the 384-well format. MSFP is a simple, rapid approach as all biochemical reactions and final detection can be performed in one well in a 384-well plate without purification steps in less than 3.5 hours. Furthermore, we demonstrated a significant correlation between MSFP and the LINE-1 pyrosequencing assay, a widely used global DNA methylation assay. MSFP can be applied for the pre-screening of compounds that influence global DNA methylation states and also for the diagnosis of certain types of cancer.

Identification and characterization of chlorpyrifos-methyl and 3,5,6-trichloro-2-pyridinol degrading Burkholderia sp. strain KR100.

PubMed

Kim, Jun-Ran; Ahn, Young-Joon

2009-07-01

A chlorpyrifos-methyl (CM) degrading bacterium (designated strain KR100) was isolated from a Korean rice paddy soil and was further tested for its sensitivity against eight commercial antibiotics. Based on morphological, biochemical, and molecular characteristics, this bacterium showed greatest similarity to members of the order Burkholderiales and was shown to be most closely related to members of the Burkholderia cepacia group. Strain KR100 hydrolyzed CM to 3,5,6-trichloro-2-pyridinol (TCP) and utilized TCP as the sole source of carbon for its growth. The isolate was also able to degrade chlorpyrifos, dimethoate, fenitrothion, malathion, and monocrotophos at 300 microg/ml but diazinon, dicrotophos, parathion, and parathion-methyl at 100 microg/ml. The ability to degrade CM was found to be encoded on a single plasmid of approximately 50 kb, pKR1. Genes encoding resistance to amphotericin B, polymixin B sulfate, and tetracycline were also located on the plasmid. This bacterium merits further study as a potential biological agent for the remediation of soil, water, or crop contaminated with organophosphorus compounds because of its greater biodegradation activity and its broad specificity against a range of organophosphorus insecticides.

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

NASA Astrophysics Data System (ADS)

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

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

PubMed

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.

CytometryML: a markup language for analytical cytology

NASA Astrophysics Data System (ADS)

Leif, Robert C.; Leif, Stephanie H.; Leif, Suzanne B.

2003-06-01

Cytometry Markup Language, CytometryML, is a proposed new analytical cytology data standard. CytometryML is a set of XML schemas for encoding both flow cytometry and digital microscopy text based data types. CytometryML schemas reference both DICOM (Digital Imaging and Communications in Medicine) codes and FCS keywords. These schemas provide representations for the keywords in FCS 3.0 and will soon include DICOM microscopic image data. Flow Cytometry Standard (FCS) list-mode has been mapped to the DICOM Waveform Information Object. A preliminary version of a list mode binary data type, which does not presently exist in DICOM, has been designed. This binary type is required to enhance the storage and transmission of flow cytometry and digital microscopy data. Index files based on Waveform indices will be used to rapidly locate the cells present in individual subsets. DICOM has the advantage of employing standard file types, TIF and JPEG, for Digital Microscopy. Using an XML schema based representation means that standard commercial software packages such as Excel and MathCad can be used to analyze, display, and store analytical cytometry data. Furthermore, by providing one standard for both DICOM data and analytical cytology data, it eliminates the need to create and maintain special purpose interfaces for analytical cytology data thereby integrating the data into the larger DICOM and other clinical communities. A draft version of CytometryML is available at www.newportinstruments.com.

VarioML framework for comprehensive variation data representation and exchange.

PubMed

Byrne, Myles; Fokkema, Ivo Fac; Lancaster, Owen; Adamusiak, Tomasz; Ahonen-Bishopp, Anni; Atlan, David; Béroud, Christophe; Cornell, Michael; Dalgleish, Raymond; Devereau, Andrew; Patrinos, George P; Swertz, Morris A; Taschner, Peter Em; Thorisson, Gudmundur A; Vihinen, Mauno; Brookes, Anthony J; Muilu, Juha

2012-10-03

Sharing of data about variation and the associated phenotypes is a critical need, yet variant information can be arbitrarily complex, making a single standard vocabulary elusive and re-formatting difficult. Complex standards have proven too time-consuming to implement. The GEN2PHEN project addressed these difficulties by developing a comprehensive data model for capturing biomedical observations, Observ-OM, and building the VarioML format around it. VarioML pairs a simplified open specification for describing variants, with a toolkit for adapting the specification into one's own research workflow. Straightforward variant data can be captured, federated, and exchanged with no overhead; more complex data can be described, without loss of compatibility. The open specification enables push-button submission to gene variant databases (LSDBs) e.g., the Leiden Open Variation Database, using the Cafe Variome data publishing service, while VarioML bidirectionally transforms data between XML and web-application code formats, opening up new possibilities for open source web applications building on shared data. A Java implementation toolkit makes VarioML easily integrated into biomedical applications. VarioML is designed primarily for LSDB data submission and transfer scenarios, but can also be used as a standard variation data format for JSON and XML document databases and user interface components. VarioML is a set of tools and practices improving the availability, quality, and comprehensibility of human variation information. It enables researchers, diagnostic laboratories, and clinics to share that information with ease, clarity, and without ambiguity.

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

Code of Federal Regulations, 2010 CFR

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...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 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...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 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...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 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...

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

PubMed Central

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

2016-01-01

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

Structural and spectroscopic characterization of methyl isocyanate, methyl cyanate, methyl fulminate, and acetonitrile N-oxide using highly correlated ab initio methods.

PubMed

Dalbouha, S; Senent, M L; Komiha, N; Domínguez-Gómez, R

2016-09-28

Various astrophysical relevant molecules obeying the empirical formula C 2 H 3 NO are characterized using explicitly correlated coupled cluster methods (CCSD(T)-F12). Rotational and rovibrational parameters are provided for four isomers: methyl isocyanate (CH 3 NCO), methyl cyanate (CH 3 OCN), methyl fulminate (CH 3 ONC), and acetonitrile N-oxide (CH 3 CNO). A CH 3 CON transition state is inspected. A variational procedure is employed to explore the far infrared region because some species present non-rigidity. Second order perturbation theory is used for the determination of anharmonic frequencies, rovibrational constants, and to predict Fermi resonances. Three species, methyl cyanate, methyl fulminate, and CH 3 CON, show a unique methyl torsion hindered by energy barriers. In methyl isocyanate, the methyl group barrier is so low that the internal top can be considered a free rotor. On the other hand, acetonitrile N-oxide presents a linear skeleton, C 3v symmetry, and free internal rotation. Its equilibrium geometry depends strongly on electron correlation. The remaining isomers present a bend skeleton. Divergences between theoretical rotational constants and previous parameters fitted from observed lines for methyl isocyanate are discussed on the basis of the relevant rovibrational interaction and the quasi-linearity of the molecular skeleton.

Structural and spectroscopic characterization of methyl isocyanate, methyl cyanate, methyl fulminate, and acetonitrile N-oxide using highly correlated ab initio methods

NASA Astrophysics Data System (ADS)

Dalbouha, S.; Senent, M. L.; Komiha, N.; Domínguez-Gómez, R.

2016-09-01

Various astrophysical relevant molecules obeying the empirical formula C2H3NO are characterized using explicitly correlated coupled cluster methods (CCSD(T)-F12). Rotational and rovibrational parameters are provided for four isomers: methyl isocyanate (CH3NCO), methyl cyanate (CH3OCN), methyl fulminate (CH3ONC), and acetonitrile N-oxide (CH3CNO). A CH3CON transition state is inspected. A variational procedure is employed to explore the far infrared region because some species present non-rigidity. Second order perturbation theory is used for the determination of anharmonic frequencies, rovibrational constants, and to predict Fermi resonances. Three species, methyl cyanate, methyl fulminate, and CH3CON, show a unique methyl torsion hindered by energy barriers. In methyl isocyanate, the methyl group barrier is so low that the internal top can be considered a free rotor. On the other hand, acetonitrile N-oxide presents a linear skeleton, C3v symmetry, and free internal rotation. Its equilibrium geometry depends strongly on electron correlation. The remaining isomers present a bend skeleton. Divergences between theoretical rotational constants and previous parameters fitted from observed lines for methyl isocyanate are discussed on the basis of the relevant rovibrational interaction and the quasi-linearity of the molecular skeleton.

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

PubMed

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.

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

PubMed

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.

QuakeML: XML for Seismological Data Exchange and Resource Metadata Description

NASA Astrophysics Data System (ADS)

Euchner, F.; Schorlemmer, D.; Becker, J.; Heinloo, A.; Kästli, P.; Saul, J.; Weber, B.; QuakeML Working Group

2007-12-01

QuakeML is an XML-based data exchange format for seismology that is under development. Current collaborators are from ETH, GFZ, USC, USGS, IRIS DMC, EMSC, ORFEUS, and ISTI. QuakeML development was motivated by the lack of a widely accepted and well-documented data format that is applicable to a broad range of fields in seismology. The development team brings together expertise from communities dealing with analysis and creation of earthquake catalogs, distribution of seismic bulletins, and real-time processing of seismic data. Efforts to merge QuakeML with existing XML dialects are under way. The first release of QuakeML will cover a basic description of seismic events including picks, arrivals, amplitudes, magnitudes, origins, focal mechanisms, and moment tensors. Further extensions are in progress or planned, e.g., for macroseismic information, location probability density functions, slip distributions, and ground motion information. The QuakeML language definition is supplemented by a concept to provide resource metadata and facilitate metadata exchange between distributed data providers. For that purpose, we introduce unique, location-independent identifiers of seismological resources. As an application of QuakeML, ETH Zurich currently develops a Python-based seismicity analysis toolkit as a contribution to CSEP (Collaboratory for the Study of Earthquake Predictability). We follow a collaborative and transparent development approach along the lines of the procedures of the World Wide Web Consortium (W3C). QuakeML currently is in working draft status. The standard description will be subjected to a public Request for Comments (RFC) process and eventually reach the status of a recommendation. QuakeML can be found at http://www.quakeml.org.

The ML Scale in Norway

DTIC Science & Technology

1990-05-31

instead of the earlier value of 2800. The new AfL values have also regressively been related to a data set of Mfs values, yielding the relation Als ...reported until Bath et al . (1976) developed a new local magnitude scale (hereafter for simplicity called Bith’s ML scale) based on Swedish data. The...the data. Originally, a much larger data base was considered, based on available earthquake catalogues since 1971 (Bunguin et al ., 1990). In doing this

VarioML framework for comprehensive variation data representation and exchange

PubMed Central

2012-01-01

Background Sharing of data about variation and the associated phenotypes is a critical need, yet variant information can be arbitrarily complex, making a single standard vocabulary elusive and re-formatting difficult. Complex standards have proven too time-consuming to implement. Results The GEN2PHEN project addressed these difficulties by developing a comprehensive data model for capturing biomedical observations, Observ-OM, and building the VarioML format around it. VarioML pairs a simplified open specification for describing variants, with a toolkit for adapting the specification into one's own research workflow. Straightforward variant data can be captured, federated, and exchanged with no overhead; more complex data can be described, without loss of compatibility. The open specification enables push-button submission to gene variant databases (LSDBs) e.g., the Leiden Open Variation Database, using the Cafe Variome data publishing service, while VarioML bidirectionally transforms data between XML and web-application code formats, opening up new possibilities for open source web applications building on shared data. A Java implementation toolkit makes VarioML easily integrated into biomedical applications. VarioML is designed primarily for LSDB data submission and transfer scenarios, but can also be used as a standard variation data format for JSON and XML document databases and user interface components. Conclusions VarioML is a set of tools and practices improving the availability, quality, and comprehensibility of human variation information. It enables researchers, diagnostic laboratories, and clinics to share that information with ease, clarity, and without ambiguity. PMID:23031277

Histone Arginine Methylation

PubMed Central

Lorenzo, Alessandra Di; Bedford, Mark T.

2012-01-01

Arginine methylation is a common posttranslational modification (PTM). This type of PTM occurs on both nuclear and cytoplasmic proteins, and is particularly abundant on shuttling proteins. In this review, we will focus on one aspect of this PTM: the diverse roles that arginine methylation of the core histone tails play in regulating chromatin function. A family of nine protein arginine methyltransferases (PRMTs) catalyze methylation reactions, and a subset target histones. Importantly, arginine methylation of histone tails can promote or prevent the docking of key transcriptional effector molecules, thus playing a central role in the orchestration of the histone code. PMID:21074527

More Effective Distributed ML via a Stale Synchronous Parallel Parameter Server

PubMed Central

Ho, Qirong; Cipar, James; Cui, Henggang; Kim, Jin Kyu; Lee, Seunghak; Gibbons, Phillip B.; Gibson, Garth A.; Ganger, Gregory R.; Xing, Eric P.

2014-01-01

We propose a parameter server system for distributed ML, which follows a Stale Synchronous Parallel (SSP) model of computation that maximizes the time computational workers spend doing useful work on ML algorithms, while still providing correctness guarantees. The parameter server provides an easy-to-use shared interface for read/write access to an ML model’s values (parameters and variables), and the SSP model allows distributed workers to read older, stale versions of these values from a local cache, instead of waiting to get them from a central storage. This significantly increases the proportion of time workers spend computing, as opposed to waiting. Furthermore, the SSP model ensures ML algorithm correctness by limiting the maximum age of the stale values. We provide a proof of correctness under SSP, as well as empirical results demonstrating that the SSP model achieves faster algorithm convergence on several different ML problems, compared to fully-synchronous and asynchronous schemes. PMID:25400488

Fern-synthesized nanoparticles in the fight against malaria: LC/MS analysis of Pteridium aquilinum leaf extract and biosynthesis of silver nanoparticles with high mosquitocidal and antiplasmodial activity.

PubMed

Panneerselvam, Chellasamy; Murugan, Kadarkarai; Roni, Mathath; Aziz, Al Thabiani; Suresh, Udaiyan; Rajaganesh, Rajapandian; Madhiyazhagan, Pari; Subramaniam, Jayapal; Dinesh, Devakumar; Nicoletti, Marcello; Higuchi, Akon; Alarfaj, Abdullah A; Munusamy, Murugan A; Kumar, Suresh; Desneux, Nicolas; Benelli, Giovanni

2016-03-01

Malaria remains a major public health problem due to the emergence and spread of Plasmodium falciparum strains resistant to chloroquine. There is an urgent need to investigate new and effective sources of antimalarial drugs. This research proposed a novel method of fern-mediated synthesis of silver nanoparticles (AgNP) using a cheap plant extract of Pteridium aquilinum, acting as a reducing and capping agent. AgNP were characterized by UV-vis spectrophotometry, Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). Phytochemical analysis of P. aquilinum leaf extract revealed the presence of phenols, alkaloids, tannins, flavonoids, proteins, carbohydrates, saponins, glycosides, steroids, and triterpenoids. LC/MS analysis identified at least 19 compounds, namely pterosin, hydroquinone, hydroxy-acetophenone, hydroxy-cinnamic acid, 5, 7-dihydroxy-4-methyl coumarin, trans-cinnamic acid, apiole, quercetin 3-glucoside, hydroxy-L-proline, hypaphorine, khellol glucoside, umbelliferose, violaxanthin, ergotamine tartrate, palmatine chloride, deacylgymnemic acid, methyl laurate, and palmitoyl acetate. In DPPH scavenging assays, the IC50 value of the P. aquilinum leaf extract was 10.04 μg/ml, while IC50 of BHT and rutin were 7.93 and 6.35 μg/ml. In mosquitocidal assays, LC50 of P. aquilinum leaf extract against Anopheles stephensi larvae and pupae were 220.44 ppm (larva I), 254.12 ppm (II), 302.32 ppm (III), 395.12 ppm (IV), and 502.20 ppm (pupa). LC50 of P. aquilinum-synthesized AgNP were 7.48 ppm (I), 10.68 ppm (II), 13.77 ppm (III), 18.45 ppm (IV), and 31.51 ppm (pupa). In the field, the application of P. aquilinum extract and AgNP (10 × LC50) led to 100 % larval reduction after 72 h. Both the P. aquilinum extract and AgNP reduced longevity and fecundity of An. stephensi adults. Smoke toxicity experiments conducted against An. stephensi adults showed that P. aquilinum leaf-, stem-, and root-based coils

Using CellML with OpenCMISS to Simulate Multi-Scale Physiology

PubMed Central

Nickerson, David P.; Ladd, David; Hussan, Jagir R.; Safaei, Soroush; Suresh, Vinod; Hunter, Peter J.; Bradley, Christopher P.

2014-01-01

OpenCMISS is an open-source modeling environment aimed, in particular, at the solution of bioengineering problems. OpenCMISS consists of two main parts: a computational library (OpenCMISS-Iron) and a field manipulation and visualization library (OpenCMISS-Zinc). OpenCMISS is designed for the solution of coupled multi-scale, multi-physics problems in a general-purpose parallel environment. CellML is an XML format designed to encode biophysically based systems of ordinary differential equations and both linear and non-linear algebraic equations. A primary design goal of CellML is to allow mathematical models to be encoded in a modular and reusable format to aid reproducibility and interoperability of modeling studies. In OpenCMISS, we make use of CellML models to enable users to configure various aspects of their multi-scale physiological models. This avoids the need for users to be familiar with the OpenCMISS internal code in order to perform customized computational experiments. Examples of this are: cellular electrophysiology models embedded in tissue electrical propagation models; material constitutive relationships for mechanical growth and deformation simulations; time-varying boundary conditions for various problem domains; and fluid constitutive relationships and lumped-parameter models. In this paper, we provide implementation details describing how CellML models are integrated into multi-scale physiological models in OpenCMISS. The external interface OpenCMISS presents to users is also described, including specific examples exemplifying the extensibility and usability these tools provide the physiological modeling and simulation community. We conclude with some thoughts on future extension of OpenCMISS to make use of other community developed information standards, such as FieldML, SED-ML, and BioSignalML. Plans for the integration of accelerator code (graphical processing unit and field programmable gate array) generated from CellML models is also

Signatures of DNA Methylation across Insects Suggest Reduced DNA Methylation Levels in Holometabola

PubMed Central

Provataris, Panagiotis; Meusemann, Karen; Niehuis, Oliver; Grath, Sonja; Misof, Bernhard

2018-01-01

Abstract It has been experimentally shown that DNA methylation is involved in the regulation of gene expression and the silencing of transposable element activity in eukaryotes. The variable levels of DNA methylation among different insect species indicate an evolutionarily flexible role of DNA methylation in insects, which due to a lack of comparative data is not yet well-substantiated. Here, we use computational methods to trace signatures of DNA methylation across insects by analyzing transcriptomic and genomic sequence data from all currently recognized insect orders. We conclude that: 1) a functional methylation system relying exclusively on DNA methyltransferase 1 is widespread across insects. 2) DNA methylation has potentially been lost or extremely reduced in species belonging to springtails (Collembola), flies and relatives (Diptera), and twisted-winged parasites (Strepsiptera). 3) Holometabolous insects display signs of reduced DNA methylation levels in protein-coding sequences compared with hemimetabolous insects. 4) Evolutionarily conserved insect genes associated with housekeeping functions tend to display signs of heavier DNA methylation in comparison to the genomic/transcriptomic background. With this comparative study, we provide the much needed basis for experimental and detailed comparative analyses required to gain a deeper understanding on the evolution and function of DNA methylation in insects. PMID:29697817

Anesthetic efficacy of 1.8 mL versus 3.6 mL of 4% articaine with 1:100,000 epinephrine as a primary buccal infiltration of the mandibular first molar.

PubMed

Martin, Matthew; Nusstein, John; Drum, Melissa; Reader, Al; Beck, Mike

2011-05-01

No study has compared 1.8 mL and 3.6 mL 4% articaine with 1:100,000 epinephrine in a mandibular buccal infiltration of the first molar. The authors conducted a prospective, randomized, single-blind, crossover study comparing the degree of pulpal anesthesia obtained with 1.8 mL and 3.6 mL 4% articaine with 1:100,000 epinephrine as a primary infiltration in the mandibular first molar. Eighty-six asymptomatic adult subjects randomly received a primary mandibular buccal first molar infiltration of 1.8 mL or 3.6 mL 4% articaine with 1:100,000 epinephrine in two separate appointments. The authors used an electric pulp tester to test the first molar for anesthesia in 3-minute cycles for 90 minutes after the injections. Compared with the 1.8-mL volume of 4% articaine with 1:100,000 epinephrine, the 3.6-mL volume showed a statistically higher success rate (70% vs 50%). The anesthetic efficacy of 3.6 mL 4% articaine with 1:100,000 epinephrine is better than 1.8 mL of the same anesthetic solution in a primary mandibular buccal infiltration of the first molar. However, the success rate of 70% is not high enough to support its use as a primary injection technique in the mandibular first molar. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Executing medical logic modules expressed in ArdenML using Drools.

PubMed

Jung, Chai Young; Sward, Katherine A; Haug, Peter J

2012-01-01

The Arden Syntax is an HL7 standard language for representing medical knowledge as logic statements. Despite nearly 2 decades of availability, Arden Syntax has not been widely used. This has been attributed to the lack of a generally available compiler to implement the logic, to Arden's complex syntax, to the challenges of mapping local data to data references in the Medical Logic Modules (MLMs), or, more globally, to the general absence of decision support in healthcare computing. An XML representation (ArdenML) may partially address the technical challenges. MLMs created in ArdenML can be converted into executable files using standard transforms written in the Extensible Stylesheet Language Transformation (XSLT) language. As an example, we have demonstrated an approach to executing MLMs written in ArdenML using the Drools business rule management system. Extensions to ArdenML make it possible to generate a user interface through which an MLM developer can test for logical errors.

Executing medical logic modules expressed in ArdenML using Drools

PubMed Central

Jung, Chai Young; Sward, Katherine A

2011-01-01

The Arden Syntax is an HL7 standard language for representing medical knowledge as logic statements. Despite nearly 2 decades of availability, Arden Syntax has not been widely used. This has been attributed to the lack of a generally available compiler to implement the logic, to Arden's complex syntax, to the challenges of mapping local data to data references in the Medical Logic Modules (MLMs), or, more globally, to the general absence of decision support in healthcare computing. An XML representation (ArdenML) may partially address the technical challenges. MLMs created in ArdenML can be converted into executable files using standard transforms written in the Extensible Stylesheet Language Transformation (XSLT) language. As an example, we have demonstrated an approach to executing MLMs written in ArdenML using the Drools business rule management system. Extensions to ArdenML make it possible to generate a user interface through which an MLM developer can test for logical errors. PMID:22180871

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

PubMed

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

An Ontology for State Analysis: Formalizing the Mapping to SysML

NASA Technical Reports Server (NTRS)

Wagner, David A.; Bennett, Matthew B.; Karban, Robert; Rouquette, Nicolas; Jenkins, Steven; Ingham, Michel

2012-01-01

State Analysis is a methodology developed over the last decade for architecting, designing and documenting complex control systems. Although it was originally conceived for designing robotic spacecraft, recent applications include the design of control systems for large ground-based telescopes. The European Southern Observatory (ESO) began a project to design the European Extremely Large Telescope (E-ELT), which will require coordinated control of over a thousand articulated mirror segments. The designers are using State Analysis as a methodology and the Systems Modeling Language (SysML) as a modeling and documentation language in this task. To effectively apply the State Analysis methodology in this context it became necessary to provide ontological definitions of the concepts and relations in State Analysis and greater flexibility through a mapping of State Analysis into a practical extension of SysML. The ontology provides the formal basis for verifying compliance with State Analysis semantics including architectural constraints. The SysML extension provides the practical basis for applying the State Analysis methodology with SysML tools. This paper will discuss the method used to develop these formalisms (the ontology), the formalisms themselves, the mapping to SysML and approach to using these formalisms to specify a control system and enforce architectural constraints in a SysML model.

Formal Verification of Complex Systems based on SysML Functional Requirements

DTIC Science & Technology

2014-12-23

Formal Verification of Complex Systems based on SysML Functional Requirements Hoda Mehrpouyan1, Irem Y. Tumer2, Chris Hoyle2, Dimitra Giannakopoulou3...requirements for design of complex engineered systems. The proposed ap- proach combines a SysML modeling approach to document and structure safety requirements...methods and tools to support the integration of safety into the design solution. 2.1. SysML for Complex Engineered Systems Traditional methods and tools

Identification of differentially methylated sites with weak methylation effect

USDA-ARS?s Scientific Manuscript database

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 dif...

An overview of the CellML API and its implementation

PubMed Central

2010-01-01

Background CellML is an XML based language for representing mathematical models, in a machine-independent form which is suitable for their exchange between different authors, and for archival in a model repository. Allowing for the exchange and archival of models in a computer readable form is a key strategic goal in bioinformatics, because of the associated improvements in scientific record accuracy, the faster iterative process of scientific development, and the ability to combine models into large integrative models. However, for CellML models to be useful, tools which can process them correctly are needed. Due to some of the more complex features present in CellML models, such as imports, developing code ab initio to correctly process models can be an onerous task. For this reason, there is a clear and pressing need for an application programming interface (API), and a good implementation of that API, upon which tools can base their support for CellML. Results We developed an API which allows the information in CellML models to be retrieved and/or modified. We also developed a series of optional extension APIs, for tasks such as simplifying the handling of connections between variables, dealing with physical units, validating models, and translating models into different procedural languages. We have also provided a Free/Open Source implementation of this application programming interface, optimised to achieve good performance. Conclusions Tools have been developed using the API which are mature enough for widespread use. The API has the potential to accelerate the development of additional tools capable of processing CellML, and ultimately lead to an increased level of sharing of mathematical model descriptions. PMID:20377909

An overview of the CellML API and its implementation.

PubMed

Miller, Andrew K; Marsh, Justin; Reeve, Adam; Garny, Alan; Britten, Randall; Halstead, Matt; Cooper, Jonathan; Nickerson, David P; Nielsen, Poul F

2010-04-08

CellML is an XML based language for representing mathematical models, in a machine-independent form which is suitable for their exchange between different authors, and for archival in a model repository. Allowing for the exchange and archival of models in a computer readable form is a key strategic goal in bioinformatics, because of the associated improvements in scientific record accuracy, the faster iterative process of scientific development, and the ability to combine models into large integrative models.However, for CellML models to be useful, tools which can process them correctly are needed. Due to some of the more complex features present in CellML models, such as imports, developing code ab initio to correctly process models can be an onerous task. For this reason, there is a clear and pressing need for an application programming interface (API), and a good implementation of that API, upon which tools can base their support for CellML. We developed an API which allows the information in CellML models to be retrieved and/or modified. We also developed a series of optional extension APIs, for tasks such as simplifying the handling of connections between variables, dealing with physical units, validating models, and translating models into different procedural languages.We have also provided a Free/Open Source implementation of this application programming interface, optimised to achieve good performance. Tools have been developed using the API which are mature enough for widespread use. The API has the potential to accelerate the development of additional tools capable of processing CellML, and ultimately lead to an increased level of sharing of mathematical model descriptions.

Mercury methylation and demethylation in Hg-contaminated lagoon sediments (Marano and Grado Lagoon, Italy)

NASA Astrophysics Data System (ADS)

Hines, Mark E.; Poitras, Erin N.; Covelli, Stefano; Faganeli, Jadran; Emili, Andrea; Žižek, Suzana; Horvat, Milena

2012-11-01

Mercury (Hg) transformation activities and sulfate (SO42-) reduction were studied in sediments of the Marano and Grado Lagoons in the Northern Adriatic Sea region as part of the "MIRACLE" project. The lagoons, which are sites of clam (Tapes philippinarum) farming, have been receiving excess Hg from the Isonzo River for centuries. Marano Lagoon is also contaminated from a chlor-alkali plant. Radiotracer methods were used to measure mercury methylation (230Hg, 197Hg), methylmercury (MeHg) demethylation (14C-MeHg) and SO42- reduction (35S) in sediment cores collected in autumn, winter and summer. Mercury methylation rate constants ranged from near zero to 0.054 day-1, generally decreased with depth, and were highest in summer. Demethylation rate constants were much higher than methylation reaching values of ˜0.6 day-1 in summer. Demethylation occurred via the oxidative pathway, except in winter when the reductive pathway increased in importance in surficial sediments. Sulfate reduction was also most active in summer (up to 1600 nmol mL-1 day-1) and depth profiles reflected seasonally changing redox conditions near the surface. Methylation and demethylation rate constants correlated positively with SO42- reduction and pore-water Hg concentrations, and inversely with Hg sediment-water partition coefficients indicating the importance of SO42- reduction and Hg dissolution on Hg cycling. Hg transformation rates were calculated using rate constants and concentrations of Hg species. In laboratory experiments, methylation was inhibited by amendments of the SO42--reduction inhibitor molybdate and by nitrate. Lagoon sediments displayed a dynamic seasonal cycle in which Hg dissolution in spring/summer stimulated Hg methylation, which was followed by a net loss of MeHg in autumn from demethylation. Sulfate-reducing bacteria (SRB) tended to be responsible for methylation of Hg and the oxidative demethylation of MeHg. However, during winter in surficial sediments, iron

Polymorphic New World monkeys with more than three M/L cone types

NASA Astrophysics Data System (ADS)

Jacobs, Gerald H.; Deegan, Jess F.

2005-10-01

Most New World (platyrrhine) monkeys have M/L cone photopigment polymorphisms that map directly into individual variations in visual sensitivity and color vision. We used electroretinogram flicker photometry to examine M/L cone photopigments in the New World monkey Callicebus moloch (the dusky Titi). Like other New World monkeys, this species has an M/L cone photopigment polymorphism that reflects the presence of X-chromosome opsin gene alleles. However, unlike other platyrrhines in which three M/L photopigments are typical, Callicebus has a total of five M/L cone photopigments. The peak sensitivity values for these pigments extend across the range from 530 to 562 nm. The result is an enhanced array of potential color vision phenotypes in this species.

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

PubMed Central

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

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

PubMed

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 < 0.0001) colorectal cancers. This trend was also observed in colon polyps (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.

DNA methylation pathways and their crosstalk with histone methylation

PubMed Central

Du, Jiamu; Johnson, Lianna M.; Jacobsen, Steven E.; Patel, Dinshaw J.

2015-01-01

Methylation of DNA and of histone 3 at Lys 9 (H3K9) are highly correlated with gene silencing in eukaryotes from fungi to humans. Both of these epigenetic marks need to be established at specific regions of the genome and then maintained at these sites through cell division. Protein structural domains that specifically recognize methylated DNA and methylated histones are key for targeting enzymes that catalyse these marks to appropriate genome sites. Genetic, genomic, structural and biochemical data reveal connections between these two epigenetic marks, and these domains mediate much of the crosstalk. PMID:26296162

The MBD7 complex promotes expression of methylated transgenes without significantly altering their methylation status

PubMed Central

Li, Dongming; Palanca, Ana Marie S; Won, So Youn; Gao, Lei; Feng, Ying; Vashisht, Ajay A; Liu, Li; Zhao, Yuanyuan; Liu, Xigang; Wu, Xiuyun; Li, Shaofang; Le, Brandon; Kim, Yun Ju; Yang, Guodong; Li, Shengben; Liu, Jinyuan; Wohlschlegel, James A; Guo, Hongwei; Mo, Beixin; Chen, Xuemei; Law, Julie A

2017-01-01

DNA methylation is associated with gene silencing in eukaryotic organisms. Although pathways controlling the establishment, maintenance and removal of DNA methylation are known, relatively little is understood about how DNA methylation influences gene expression. Here we identified a METHYL-CpG-BINDING DOMAIN 7 (MBD7) complex in Arabidopsis thaliana that suppresses the transcriptional silencing of two LUCIFERASE (LUC) reporters via a mechanism that is largely downstream of DNA methylation. Although mutations in components of the MBD7 complex resulted in modest increases in DNA methylation concomitant with decreased LUC expression, we found that these hyper-methylation and gene expression phenotypes can be genetically uncoupled. This finding, along with genome-wide profiling experiments showing minimal changes in DNA methylation upon disruption of the MBD7 complex, places the MBD7 complex amongst a small number of factors acting downstream of DNA methylation. This complex, however, is unique as it functions to suppress, rather than enforce, DNA methylation-mediated gene silencing. DOI: http://dx.doi.org/10.7554/eLife.19893.001 PMID:28452714

ISAC's Gating-ML 2.0 data exchange standard for gating description.

PubMed

Spidlen, Josef; Moore, Wayne; Brinkman, Ryan R

2015-07-01

The lack of software interoperability with respect to gating has traditionally been a bottleneck preventing the use of multiple analytical tools and reproducibility of flow cytometry data analysis by independent parties. To address this issue, ISAC developed Gating-ML, a computer file format to encode and interchange gates. Gating-ML 1.5 was adopted and published as an ISAC Candidate Recommendation in 2008. Feedback during the probationary period from implementors, including major commercial software companies, instrument vendors, and the wider community, has led to a streamlined Gating-ML 2.0. Gating-ML has been significantly simplified and therefore easier to support by software tools. To aid developers, free, open source reference implementations, compliance tests, and detailed examples are provided to stimulate further commercial adoption. ISAC has approved Gating-ML as a standard ready for deployment in the public domain and encourages its support within the community as it is at a mature stage of development having undergone extensive review and testing, under both theoretical and practical conditions. © 2015 International Society for Advancement of Cytometry.

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

PubMed Central

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

2016-01-01

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

The performance review of EEWS(Earthquake Early Warning System) about Gyeongju earthquakes with Ml 5.1 and Ml 5.8 in Korea

NASA Astrophysics Data System (ADS)

Park, Jung-Ho; Chi, Heon-Cheol; Lim, In-Seub; Seong, Yun-Jeong; Park, Jihwan

2017-04-01

EEW(Earthquake Early Warning) service to the public has been officially operated by KMA (Korea Meteorological Administration) from 2015 in Korea. For the KMA's official EEW service, KIGAM has adopted ElarmS from UC Berkeley BSL and modified local magnitude relation, 1-D travel time curves and association procedures with real time waveform from about 201 seismic stations of KMA, KIGAM, KINS and KEPRI. There were two moderate size earthquakes with magnitude Ml 5.1 and Ml 5.8 close to Gyeongju city located at the southeastern part of Korea on Sep. 12. 2016. We have checked the performance of EEWS(Earthquake Early Warning System) named as TrigDB by KIGAM reviewing of these two Gyeongju earthquakes. The nearest station to epicenters of two earthquakes Ml 5.1(35.7697 N, 129.1904 E) and Ml 5.8(35.7632 N, 129.1898 E) was MKL which detected P phases in about 2.1 and 3.6 seconds after the origin times respectively. The first events were issued in 6.3 and 7.0 seconds from each origin time. Because of the unstable results on the early steps due to very few stations and unexpected automated analysis, KMA has the policy to wait for more 20 seconds for confirming the reliability. For these events KMA published EEW alarms in about 26 seconds after origin times with M 5.3 and M 5.9 respectively.

'Benifuuki' green tea containing o-methylated catechin reduces symptoms of Japanese cedar pollinosis: a randomized, double-blind, placebo-controlled trial.

PubMed

Masuda, Sawako; Maeda-Yamamoto, Mari; Usui, Satoko; Fujisawa, Takao

2014-06-01

Methylated catechin, one of the active ingredients in green tea, has been reported to ameliorate allergic reactions. We evaluated the efficacy of 'Benifuuki' green tea, which contains O-methylated epigallocatechin-3-O-[3-O-methyl] gallate (O-methylated EGCG), in alleviating Japanese cedar pollinosis (JCP). The study was a double-blind, randomized, placebo-controlled trial. The subjects with JCP were randomly assigned to drink 700ml of 'Benifuuki' green tea containing O-methylated EGCG or 'Yabukita' green tea (not containing O-methylated EGCG) as a placebo every day from December 2007 through March 2008, which includes the pollen season. The primary outcome was the area under the curve (AUC) of symptom scores during the peak pollen season. Fifty-one adults with JCP participated in the study. Twenty-six subjects were assigned to 'Benifuuki' and 25 to 'Yabukita'. The AUC of symptom score during the peak pollen season in the 'Benifuuki' group was significantly smaller than in the 'Yabukita' group for each of runny nose, itchy eyes, tearing, total nasal symptom score, total ocular symptom score, nasal symptom-medication score and ocular symptom-medication score. The total QOL-related questionnaire score for one week in the peak pollen season was significantly better in the 'Benifuuki' group. Increase in the peripheral eosinophil count in response to pollen exposure was suppressed in the 'Benifuuki' group. No adverse events were reported in either group. 'Benifuuki' green tea containing a large amount of O-methylated EGCG reduced the symptoms of JCP and has potential as a complementary/alternative medicine for treating seasonal allergic rhinitis.

Kinetic and analytic investigations on the formation of N-nitroso-N-methyl-N-cyclohexylamine from bromhexine and nitrite.

PubMed

Schmid, J; Daneck, K; Koss, F W; Eisenbrand, G; Schlemmer, K H

1988-09-01

Bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammoniumhydr ochloride) forms N-nitroso-N-methyl-N-cyclohexylamine (NMCA) under the conditions of the WHO Nitrosation Assay Procedure (NAP-test). The formation kinetics of this compound was investigated. The formation of NMCA depends on the square of the nitrite concentration. The reaction has a narrow pH-optimum at pH 3. The reaction is quick: After 1 h about 70% of the maximum amount of NMCA is formed. To study this reaction kinetics sensitive assays with a detection limit up to 0.5 ng/ml NMCA were developed. The stability of the components of the system, especially that of NMCA and nitrite, were further studied. The latter is rather instable under conditions found in an acidic stomach.

Degradation of cyanidin-3-rutinoside and formation of protocatechuic acid methyl ester in methanol solution by gamma irradiation.

PubMed

Lee, Seung Sik; Kim, Tae Hoon; Lee, Eun Mi; Lee, Min Hee; Lee, Ha Yeong; Chung, Byung Yeoup

2014-08-01

Anthocyanins are naturally occurring phenolic compounds having broad biological activities including anti-mutagenesis and anti-carcinogenesis. We studied the effects and the degradation mechanisms of the most common type of anthocyanins, cyanidin-3-rutinoside (cya-3-rut), by using gamma ray. Cya-3-rut in methanol (1mg/ml) was exposed to gamma-rays from 1 to 10kGy. We found that the reddish colour of cya-3-rut in methanol disappeared gradually in a dose-dependent manner and effectively disappeared (>97%) at 10kGy of gamma ray. Concomitantly, a new phenolic compound was generated and identified as a protocatechuic acid methyl ester by liquid chromatography, (1)H, and (13)C NMR. The formation of protocatechuic acid methyl ester increased with increasing irradiation and the amount of protocatechuic acid methyl ester formed by decomposition of cya-3-rut (20μg) at 10kGy of gamma ray was 1.95μg. In addition, the radical-scavenging activities were not affected by gamma irradiation. Copyright © 2014 Elsevier Ltd. All rights reserved.

QualityML: a dictionary for quality metadata encoding

NASA Astrophysics Data System (ADS)

Ninyerola, Miquel; Sevillano, Eva; Serral, Ivette; Pons, Xavier; Zabala, Alaitz; Bastin, Lucy; Masó, Joan

2014-05-01

The scenario of rapidly growing geodata catalogues requires tools focused on facilitate users the choice of products. Having quality fields populated in metadata allow the users to rank and then select the best fit-for-purpose products. In this direction, we have developed the QualityML (http://qualityml.geoviqua.org), a dictionary that contains hierarchically structured concepts to precisely define and relate quality levels: from quality classes to quality measurements. Generically, a quality element is the path that goes from the higher level (quality class) to the lowest levels (statistics or quality metrics). This path is used to encode quality of datasets in the corresponding metadata schemas. The benefits of having encoded quality, in the case of data producers, are related with improvements in their product discovery and better transmission of their characteristics. In the case of data users, particularly decision-makers, they would find quality and uncertainty measures to take the best decisions as well as perform dataset intercomparison. Also it allows other components (such as visualization, discovery, or comparison tools) to be quality-aware and interoperable. On one hand, the QualityML is a profile of the ISO geospatial metadata standards providing a set of rules for precisely documenting quality indicator parameters that is structured in 6 levels. On the other hand, QualityML includes semantics and vocabularies for the quality concepts. Whenever possible, if uses statistic expressions from the UncertML dictionary (http://www.uncertml.org) encoding. However it also extends UncertML to provide list of alternative metrics that are commonly used to quantify quality. A specific example, based on a temperature dataset, is shown below. The annual mean temperature map has been validated with independent in-situ measurements to obtain a global error of 0.5 ° C. Level 0: Quality class (e.g., Thematic accuracy) Level 1: Quality indicator (e.g., Quantitative

DNA Methylation and Cancer Diagnosis

PubMed Central

Delpu, Yannick; Cordelier, Pierre; Cho, William C.; Torrisani, Jérôme

2013-01-01

DNA methylation is a major epigenetic modification that is strongly involved in the physiological control of genome expression. DNA methylation patterns are largely modified in cancer cells and can therefore be used to distinguish cancer cells from normal tissues. This review describes the main technologies available for the detection and the discovery of aberrantly methylated DNA patterns. It also presents the different sources of biological samples suitable for DNA methylation studies. We discuss the interest and perspectives on the use of DNA methylation measurements for cancer diagnosis through examples of methylated genes commonly documented in the literature. The discussion leads to our consideration for why DNA methylation is not commonly used in clinical practice through an examination of the main requirements that constitute a reliable biomarker. Finally, we describe the main DNA methylation inhibitors currently used in clinical trials and those that exhibit promising results. PMID:23873296

ML Crew Access Arm Move

NASA Image and Video Library

2017-11-10

A heavy-load transport truck carrying the Orion crew access arm passes the Vehicle Assembly Building on its way to the mobile launcher at NASA's Kennedy Space Center in Florida. The access arm will be installed at about the 274-foot level on the mobile launcher tower. It will rotate from its retracted position and interface with the Orion crew hatch location to provide entry to the Orion crew module. The Ground Systems Development and Operations Program is overseeing installation of umbilicals and launch accessories on the ML tower to prepare for Exploration Mission-1.

Simultaneous identification and quantification by liquid chromatography of benzethonium chloride, methyl paraben and triclosan in commercial products labeled as grapefruit seed extract.

PubMed

Avula, B; Dentali, S; Khan, I A

2007-08-01

A HPLC method has been developed which permits the quantification of methyl paraben, benzethonium chloride and triclosan in various samples of grapefruit seed extract (GSE). The best results were obtained with a Phenomenex Gemini C18 column using gradient mobile phase of water (0.1% acetic acid) and acetonitrile (0.1% acetic acid) with a flow rate of 1.0 mL per minute. The detection wavelength was 254 nm for methyl paraben, and 275 nm for benzethonium chloride and triclosan. The main synthetic antimicrobial agent identified in commercial GSE samples was benzethonium chloride in concentrations from 0.29-21.84%. Positive ion electrospray MS of a commercial GSE sample showed a molecular ion at m/z 412 [M+], which matched that of a standard of benzethonium chloride. Triclosan was detected in two samples at 0.009 and 1.13%concentrations; while methyl paraben was not detected in the samples analyzed.

Importing MAGE-ML format microarray data into BioConductor.

PubMed

Durinck, Steffen; Allemeersch, Joke; Carey, Vincent J; Moreau, Yves; De Moor, Bart

2004-12-12

The microarray gene expression markup language (MAGE-ML) is a widely used XML (eXtensible Markup Language) standard for describing and exchanging information about microarray experiments. It can describe microarray designs, microarray experiment designs, gene expression data and data analysis results. We describe RMAGEML, a new Bioconductor package that provides a link between cDNA microarray data stored in MAGE-ML format and the Bioconductor framework for preprocessing, visualization and analysis of microarray experiments. http://www.bioconductor.org. Open Source.

First evidence of DNA methylation in insect Tribolium castaneum: environmental regulation of DNA methylation within heterochromatin.

PubMed

Feliciello, Isidoro; Parazajder, Josip; Akrap, Ivana; Ugarković, Durđica

2013-05-01

DNA methylation has been studied in many eukaryotic organisms, in particular vertebrates, and was implicated in developmental and phenotypic variations. Little is known about the role of DNA methylation in invertebrates, although insects are considered as excellent models for studying the evolution of DNA methylation. In the red flour beetle, Tribolium castaneum (Tenebrionidae, Coleoptera), no evidence of DNA methylation has been found till now. In this paper, a cytosine methylation in Tribolium castaneum embryos was detected by methylation sensitive restriction endonucleases and immuno-dot blot assay. DNA methylation in embryos is followed by a global demethylation in larvae, pupae and adults. DNA demethylation seems to proceed actively through 5-hydroxymethylcytosine, most probably by the action of TET enzyme. Bisulfite sequencing of a highly abundant satellite DNA located in pericentromeric heterochromatin revealed similar profile of cytosine methylation in adults and embryos. Cytosine methylation was not only restricted to CpG sites but was found at CpA, CpT and CpC sites. In addition, complete cytosine demethylation of heterochromatic satellite DNA was induced by heat stress. The results reveal existence of DNA methylation cycling in T. castaneum ranging from strong overall cytosine methylation in embryos to a weak DNA methylation in other developmental stages. Nevertheless, DNA methylation is preserved within heterochromatin during development, indicating its role in heterochromatin formation and maintenance. It is, however, strongly affected by heat stress, suggesting a role for DNA methylation in heterochromatin structure modulation during heat stress response.

78 FR 32157 - Methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate; Exemption from the Requirement of a Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

... assessment of exposures and risks associated with methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate follows... received and the nature of the adverse effects caused by methyl 5-(dimethylamino)-2-methyl-5- oxopentanoate... treatment with methyl 5-(dimethylamino)-2-methyl-5-oxopentanoate. A Mammalian Erythrocyte Micronucleus Test...

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

PubMed

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.

Methyl mercury toxicity in plant cultures: modification of resistance and demethylation by light and/or 2,4-dichlorophenoxyacetic acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Czuba, M.

1987-04-01

Cultures of Daucus carota, Ca-68-10, and Lactuca sativa, Le-67, were grown at increasing methyl mercury (MeHg) concentrations ranging from initial doses of 0.05 to 5.0 micrograms/ml per day for 4 days with or without 0.15 microgram/ml 2,4-dichlorophenoxyacetic acid (2,4-D) in the presence or absence of light. The presence of 2,4-D interacted with light synergistically in the expression of MeHg toxicity within the whole range of concentrations. Demethylation patterns increased or decreased depending on the species, the 2,4-D concentration in the medium, and methyl mercury concentration used in the treatment. Lettuce was more sensitive to this interaction than carrot. In lettuce,more » the presence of 2,4-D in the light lowered the concentration of total Hg (or MeHg) required to reduce growth by 50%, about 13 times relative to that in the dark (i.e., it sensitized the cells). In the absence of 2,4-D the pattern was reversed. In carrot the pattern was similar but less pronounced. This suggests that, in these cell populations, MeHg toxicity is partly a hormone-mediated and light-sensitive event.« less

40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Butyl acrylate, polymer with... acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane. (a... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

Evaluation of ML-MC as a Depth Discriminant in Yellowstone, USA and Italy

NASA Astrophysics Data System (ADS)

Li, Z.; Koper, K. D.; Burlacu, R.; Sun, D.; D'Amico, S.

2017-12-01

Recent work has shown that the difference between two magnitude scales, ML (local Richter magnitude) and MC (coda/duration magnitude), acts as a depth discriminant in Utah. Shallow seismic sources, such as mining induced earthquakes and explosions, have strongly negative ML-MC values, while deeper tectonic earthquakes have ML-MC values near zero. These observations imply that ML-MC might be effective at discriminating small explosions from deeper natural earthquakes at local distances. In this work, we examine seismicity catalogs for the Yellowstone region and Italy to determine if ML-MCacts as a depth discriminant in these regions as well. We identified 4,780 earthquakes that occurred in the Yellowstone region between Sept. 24, 1994 and March 31, 2017 for which both ML and MC were calculated. The ML-MC distribution is well described by a Gaussian function with a mean of 0.102 and a standard deviation of 0.326. We selected a subset of these events with accurate depths and determined mean ML-MC values in various depth bins. An event depth was considered accurate if the formal depth error was less than 2 km and either (1) the nearest station was within one focal depth or (2) the distance to the nearest station was smaller than the bin size. We find that ML-MC decreases as event depths become shallower than about 10 km. Similar to the results for Utah, the decrease is statistically significant and is robust with respect to small changes in bin size and the criteria used to define accurate depths. We used a similar process to evaluate whether ML-MC was a function of source depth for 63,555 earthquakes that occurred between April 16, 2005 and April 30, 2012 in Italy. The ML-MC values in Italy are also well described by a normal distribution, with a mean of -0.477 and standard deviation of 0.315. We again find a statistically significant decrease in ML-MC for shallow earthquakes. In contrast to the Yellowstone results, for Italy ML-MC decreases at a nearly constant rate

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

PubMed

Baur, Brittany; Bozdag, Serdar

2016-01-01

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

Rare A2ML1 variants confer susceptibility to otitis media

PubMed Central

Santos-Cortez, Regie Lyn P.; Chiong, Charlotte M.; Reyes-Quintos, Ma. Rina T.; Tantoco, Ma. Leah C.; Wang, Xin; Acharya, Anushree; Abbe, Izoduwa; Giese, Arnaud P.; Smith, Joshua D.; Allen, E. Kaitlynn; Li, Biao; Cutiongco-de la Paz, Eva Maria; Garcia, Marieflor Cristy; Llanes, Erasmo Gonzalo D.V.; Labra, Patrick John; Gloria-Cruz, Teresa Luisa I.; Chan, Abner L.; Wang, Gao T.; Daly, Kathleen A.; Shendure, Jay; Bamshad, Michael J.; Nickerson, Deborah A.; Patel, Janak A.; Riazuddin, Saima; Sale, Michele M.; Chonmaitree, Tasnee; Ahmed, Zubair M.; Abes, Generoso T.; Leal, Suzanne M.

2015-01-01

A duplication variant within middle-ear-specific gene A2ML1 co-segregates with otitis media in an indigenous Filipino pedigree (LOD score=7.5 at reduced penetrance) and lies within a founder haplotype that is also shared by three otitis-prone European- and Hispanic-American children, but is absent in non-otitis-prone children and >62,000 next-generation sequences. Seven additional A2ML1 variants were identified in six otitis-prone children. Collectively our studies support a role for A2ML1 in the pathophysiology of otitis media. PMID:26121085

Rare A2ML1 variants confer susceptibility to otitis media.

PubMed

Santos-Cortez, Regie Lyn P; Chiong, Charlotte M; Reyes-Quintos, Ma Rina T; Tantoco, Ma Leah C; Wang, Xin; Acharya, Anushree; Abbe, Izoduwa; Giese, Arnaud P; Smith, Joshua D; Allen, E Kaitlynn; Li, Biao; Cutiongco-de la Paz, Eva Maria; Garcia, Marieflor Cristy; Llanes, Erasmo Gonzalo D V; Labra, Patrick John; Gloria-Cruz, Teresa Luisa I; Chan, Abner L; Wang, Gao T; Daly, Kathleen A; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Patel, Janak A; Riazuddin, Saima; Sale, Michele M; Chonmaitree, Tasnee; Ahmed, Zubair M; Abes, Generoso T; Leal, Suzanne M

2015-08-01

A duplication variant within the middle ear-specific gene A2ML1 cosegregates with otitis media in an indigenous Filipino pedigree (LOD score = 7.5 at reduced penetrance) and lies within a founder haplotype that is also shared by 3 otitis-prone European-American and Hispanic-American children but is absent in non-otitis-prone children and >62,000 next-generation sequences. We identified seven additional A2ML1 variants in six otitis-prone children. Collectively, our studies support a role for A2ML1 in the pathophysiology of otitis media.

Nonlinear d10-ML2 Transition-Metal Complexes

PubMed Central

Wolters, Lando P; Bickelhaupt, F Matthias

2013-01-01

We have investigated the molecular geometries of a series of dicoordinated d10-transition-metal complexes ML2 (M=Co−, Rh−, Ir−, Ni, Pd, Pt, Cu+, Ag+, Au+; L=NH3, PH3, CO) using relativistic density functional theory (DFT) at ZORA-BLYP/TZ2P. Not all complexes have the expected linear ligand–metal–ligand (L–M–L) angle: this angle varies from 180° to 128.6° as a function of the metal as well as the ligands. Our main objective is to present a detailed explanation why ML2 complexes can become bent. To this end, we have analyzed the bonding mechanism in ML2 as a function of the L–M–L angle using quantitative Kohn–Sham molecular orbital (MO) theory in combination with an energy decomposition analysis (EDA) scheme. The origin of bent L–M–L structures is π backdonation. In situations of strong π backdonation, smaller angles increase the overlap of the ligand’s acceptor orbital with a higher-energy donor orbital on the metal-ligand fragment, and therefore favor π backdonation, resulting in additional stabilization. The angle of the complexes thus depends on the balance between this additional stabilization and increased steric repulsion that occurs as the complexes are bent. PMID:24551547

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

PubMed

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.

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

PubMed Central

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

2016-01-01

Aim: Development of a sensitive method for DNA methylation profiling and associated mutation detection in clinical samples. Materials & methods: 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. Results: 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. Conclusion: 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. PMID:27337298

qcML: An Exchange Format for Quality Control Metrics from Mass Spectrometry Experiments*

PubMed Central

Walzer, Mathias; Pernas, Lucia Espona; Nasso, Sara; Bittremieux, Wout; Nahnsen, Sven; Kelchtermans, Pieter; Pichler, Peter; van den Toorn, Henk W. P.; Staes, An; Vandenbussche, Jonathan; Mazanek, Michael; Taus, Thomas; Scheltema, Richard A.; Kelstrup, Christian D.; Gatto, Laurent; van Breukelen, Bas; Aiche, Stephan; Valkenborg, Dirk; Laukens, Kris; Lilley, Kathryn S.; Olsen, Jesper V.; Heck, Albert J. R.; Mechtler, Karl; Aebersold, Ruedi; Gevaert, Kris; Vizcaíno, Juan Antonio; Hermjakob, Henning; Kohlbacher, Oliver; Martens, Lennart

2014-01-01

Quality control is increasingly recognized as a crucial aspect of mass spectrometry based proteomics. Several recent papers discuss relevant parameters for quality control and present applications to extract these from the instrumental raw data. What has been missing, however, is a standard data exchange format for reporting these performance metrics. We therefore developed the qcML format, an XML-based standard that follows the design principles of the related mzML, mzIdentML, mzQuantML, and TraML standards from the HUPO-PSI (Proteomics Standards Initiative). In addition to the XML format, we also provide tools for the calculation of a wide range of quality metrics as well as a database format and interconversion tools, so that existing LIMS systems can easily add relational storage of the quality control data to their existing schema. We here describe the qcML specification, along with possible use cases and an illustrative example of the subsequent analysis possibilities. All information about qcML is available at http://code.google.com/p/qcml. PMID:24760958

qcML: an exchange format for quality control metrics from mass spectrometry experiments.

PubMed

Walzer, Mathias; Pernas, Lucia Espona; Nasso, Sara; Bittremieux, Wout; Nahnsen, Sven; Kelchtermans, Pieter; Pichler, Peter; van den Toorn, Henk W P; Staes, An; Vandenbussche, Jonathan; Mazanek, Michael; Taus, Thomas; Scheltema, Richard A; Kelstrup, Christian D; Gatto, Laurent; van Breukelen, Bas; Aiche, Stephan; Valkenborg, Dirk; Laukens, Kris; Lilley, Kathryn S; Olsen, Jesper V; Heck, Albert J R; Mechtler, Karl; Aebersold, Ruedi; Gevaert, Kris; Vizcaíno, Juan Antonio; Hermjakob, Henning; Kohlbacher, Oliver; Martens, Lennart

2014-08-01

Quality control is increasingly recognized as a crucial aspect of mass spectrometry based proteomics. Several recent papers discuss relevant parameters for quality control and present applications to extract these from the instrumental raw data. What has been missing, however, is a standard data exchange format for reporting these performance metrics. We therefore developed the qcML format, an XML-based standard that follows the design principles of the related mzML, mzIdentML, mzQuantML, and TraML standards from the HUPO-PSI (Proteomics Standards Initiative). In addition to the XML format, we also provide tools for the calculation of a wide range of quality metrics as well as a database format and interconversion tools, so that existing LIMS systems can easily add relational storage of the quality control data to their existing schema. We here describe the qcML specification, along with possible use cases and an illustrative example of the subsequent analysis possibilities. All information about qcML is available at http://code.google.com/p/qcml. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood

PubMed Central

Baccarelli, Andrea; Kleinman, Ken P; Burris, Heather H; Litonjua, Augusto A; Rifas-Shiman, Sheryl L; Tarantini, Letizia; Gillman, Matthew W

2012-01-01

Maternal diet affects offspring DNA methylation in animal models, but evidence from humans is limited. We investigated the extent to which gestational intake of methyl donor nutrients affects global DNA methylation in maternal and umbilical cord blood. Among mother-infant pairs in Project Viva, a folate-replete US population, we estimated maternal intakes of vitamin B12, betaine, choline, folate, cadmium, zinc and iron periconceptionally and during the second trimester. We examined associations of these nutrients with DNA methylation, measured as %5-methyl cytosines (%5mC) in Long Interspersed Nuclear Element-1 (LINE-1), in first trimester (n = 830) and second trimester (n = 671) maternal blood and in cord blood at delivery (n = 516). Cord blood methylation was higher for male than female infants {mean [standard deviation (SD)] 84.8 [0.6] vs. 84.4 [0.7]%}. In the multivariable-adjusted model, maternal intake of methyl donor nutrients periconceptionally and during the second trimester of pregnancy was not positively associated with first trimester, second trimester or cord blood LINE-1 methylation. Periconceptional betaine intake was inversely associated with cord blood methylation [regression coefficient = −0.08% (95% confidence interval (CI): −0.14, −0.01)] but this association was attenuated after adjustment for dietary cadmium, which itself was directly associated with first trimester methylation and inversely associated with cord blood methylation. We also found an inverse association between periconceptional choline [−0.10%, 95% CI: −0.17, −0.03 for each SD (∼63 mg/day)] and cord blood methylation in males only. In this folate-replete population, we did not find positive associations between intake of methyl donor nutrients during pregnancy and DNA methylation overall, but among males, higher early pregnancy intakes of choline were associated with lower cord blood methylation. PMID:22430801

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

PubMed

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.

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

PubMed Central

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

Modeling Off-Nominal Behavior in SysML

NASA Technical Reports Server (NTRS)

Day, John C.; Donahue, Kenneth; Ingham, Michel; Kadesch, Alex; Kennedy, Andrew K.; Post, Ethan

2012-01-01

Specification and development of fault management functionality in systems is performed in an ad hoc way - more of an art than a science. Improvements to system reliability, availability, safety and resilience will be limited without infusion of additional formality into the practice of fault management. Key to the formalization of fault management is a precise representation of off-nominal behavior. Using the upcoming Soil Moisture Active-Passive (SMAP) mission for source material, we have modeled the off-nominal behavior of the SMAP system during its initial spin-up activity, using the System Modeling Language (SysML). In the course of developing these models, we have developed generic patterns for capturing off-nominal behavior in SysML. We show how these patterns provide useful ways of reasoning about the system (e.g., checking for completeness and effectiveness) and allow the automatic generation of typical artifacts (e.g., success trees and FMECAs) used in system analyses.

Photocopy of drawing. MODIFICATIONS TO CONVERT ML NO. 3 TO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photocopy of drawing. MODIFICATIONS TO CONVERT ML NO. 3 TO MOBILE LAUNCHER PLATFORM NO. 1. NASA, John F. Kennedy Space Center, Florida. Drawing 79K04401, Reynolds, Smith and Hills, March, 1975. ISOMETRIC: EXISTING ML NO. 3 LAUNCHER. Sheet A1 - Cape Canaveral Air Force Station, Launch Complex 39, Mobile Launcher Platforms, Launcher Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Efficient and scalable synthesis of bardoxolone methyl (cddo-methyl ester).

PubMed

Fu, Liangfeng; Gribble, Gordon W

2013-04-05

Bardoxolone methyl (2-cyano-3,12-dioxooleane-1,9(11)-dien-28-oic acid methyl ester; CDDO-Me) (1), a synthetic oleanane triterpenoid with highly potent anti-inflammatory activity (levels below 1 nM), has completed a successful phase I clinical trial for the treatment of cancer and a successful phase II trial for the treatment of chronic kidney disease in type 2 diabetes patients. Our synthesis of bardoxolone methyl (1) proceeds in ∼50% overall yield in five steps from oleanolic acid (2), requires only one to two chromatographic purifications, and can provide gram quantities of 1.

Methyl salicylate overdose

MedlinePlus

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

DNA methylation in CHO cells.

PubMed

Wippermann, Anna; Noll, Thomas

2017-09-20

Chinese hamster ovary (CHO) cells account for the production of the majority of biopharmaceutical molecules - however, the molecular basis for their versatile properties is not entirely understood yet and the underlying cellular processes need to be characterized in detail. One such process that is supposed to contribute significantly to CHO cell phenotype is methylation of DNA at cytosine residues. DNA methylation was shown to be involved in several central biological processes in humans and to contribute to diseases like cancer. Early studies of DNA methylation in CHO mostly focused on methylation of single recombinant genes and promoters and proved a correlation between DNA methylation status and recombinant gene expression or production stability. More recent publications utilized the CHO genomic and transcriptomic data available since 2011 and provided first insights into the CHO DNA methylation landscape and DNA methylation changes in response to effector molecules or culture conditions. Generally, further genome-wide studies of DNA methylation in CHO will be required to shed light on the relevance of this process regarding biopharmaceuticals production and might, e.g., address a potential link between CHO cell metabolism and DNA methylation or provide novel targets for rational cell line engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

PubMed

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, <20) in each 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) (P< or =0.002). In the other six loci (CHFR, HIC1, IGFBP3, MGMT, MINT31 and WRN), which were not highly specific for CIMP-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.

Separation and determination of methyl tert-butyl ether and its degradation products by a laboratory-constructed micro-cryogenic chromatographic oven.

PubMed

Liu, Jiemin; Jiang, Guibin; Zhou, Qunfang; Liu, Jingfu; Wen, Meijuan

2003-10-01

A laboratory-made micro-cryogenic chromatographic oven was mainly improved in size, which was controlled at 6 x 6 x 2.5 cm. A thermoelectric system was used to cool the capillary column instead of the traditional liquid cryogen. A cold block connected to the cryogenic module was directly solidified at room temperature with thermally conductive adhesive so that the uniformity of transferring heat was greatly improved, and the size of the system was reduced. Moreover, this system was inexpensive and convenient for both operation and control. The newly developed device coupled with headspace solid-phase microextraction (SPME) was successfully applied to the determination of methyl tert-butyl ether (MTBE) and its degradation products. During the analysis procedure, a 65 microm polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber was used to extract MTBE and its degradation products. The extraction was controlled at 50 degrees C for 30 min and the NaCl content in the sample was maintained at 35%. The limits of detection (LODs) ranged from 0.006 microg mL(-1) (for MTBE) to 0.206 microg mL(-1) (for methyl acetate) and the relative standard deviations (RSD%) were below 4%. The spiked recoveries for the developed method were evaluated using various water samples as a matrix.

GeoSciML version 3: A GML application for geologic information

NASA Astrophysics Data System (ADS)

International Union of Geological Sciences., I. C.; Richard, S. M.

2011-12-01

After 2 years of testing and development, XML schema for GeoSciML version 3 are now ready for application deployment. GeoSciML draws from many geoscience data modelling efforts to establish a common suite of feature types to represent information associated with geologic maps (materials, structures, and geologic units) and observations including structure data, samples, and chemical analyses. After extensive testing and use case analysis, in December 2008 the CGI Interoperability Working Group (IWG) released GeoSciML 2.0 as an application schema for basic geological information. GeoSciML 2.0 is in use to deliver geologic data by the OneGeology Europe portal, the Geological Survey of Canada Groundwater Information Network (wet GIN), and the Auscope Mineral Resources portal. GeoSciML to version 3.0 is updated to OGC Geography Markup Language v3.2, re-engineered patterns for association of element values with controlled vocabulary concepts, incorporation of ISO19156 Observation and Measurement constructs for representing numeric and categorical values and for representing analytical data, incorporation of EarthResourceML to represent mineral occurrences and mines, incorporation of the GeoTime model to represent GSSP and stratigraphic time scale, and refactoring of the GeoSciML namespace to follow emerging ISO practices for decoupling of dependencies between standardized namespaces. These changes will make it easier for data providers to link to standard vocabulary and registry services. The depth and breadth of GeoSciML remains largely unchanged, covering the representation of geologic units, earth materials and geologic structures. ISO19156 elements and patterns are used to represent sampling features such as boreholes and rock samples, as well as geochemical and geochronologic measurements. Geologic structures include shear displacement structures (brittle faults and ductile shears), contacts, folds, foliations, lineations and structures with no preferred

missMethyl: an R package for analyzing data from Illumina's HumanMethylation450 platform.

PubMed

Phipson, Belinda; Maksimovic, Jovana; Oshlack, Alicia

2016-01-15

DNA methylation is one of the most commonly studied epigenetic modifications due to its role in both disease and development. The Illumina HumanMethylation450 BeadChip is a cost-effective way to profile >450 000 CpGs across the human genome, making it a popular platform for profiling DNA methylation. Here we introduce missMethyl, an R package with a suite of tools for performing normalization, removal of unwanted variation in differential methylation analysis, differential variability testing and gene set analysis for the 450K array. missMethyl is an R package available from the Bioconductor project at www.bioconductor.org. alicia.oshlack@mcri.edu.au Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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.

Methylated bases in mycoplasmal DNA.

PubMed Central

Razin, A; Razin, S

1980-01-01

The DNAs of four Mycoplasma and one Acholeplasma species were found to contain methylated bases. All of the five species contained 6-methyladenine (m6Ade), the methylated base characteristic of prokaryotic DNA. The extent of methylation of adenine residues in the mycoplasmal DNA ranged from 0.2% in Mycoplasma capricolum to about 2% in Mycoplasma arginini and Mycoplasma hyorhinis with intermediate methylation values for Mycoplasma orale and Acholeplasma laidlawii DNAs. About 5.8% of the cytosine residues in M. hyorhinis DNA were methylated also. Analysis of cell culture DNA for the presence of m6Ade as a means for detection of contamination by mycoplasmas, and the phylogenetic implications of the finding of methylated bases in mycoplasmal DNAs are discussed. PMID:7433124

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

PubMed

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.

iMETHYL: an integrative database of human DNA methylation, gene expression, and genomic variation.

PubMed

Komaki, Shohei; Shiwa, Yuh; Furukawa, Ryohei; Hachiya, Tsuyoshi; Ohmomo, Hideki; Otomo, Ryo; Satoh, Mamoru; Hitomi, Jiro; Sobue, Kenji; Sasaki, Makoto; Shimizu, Atsushi

2018-01-01

We launched an integrative multi-omics database, iMETHYL (http://imethyl.iwate-megabank.org). iMETHYL provides whole-DNA methylation (~24 million autosomal CpG sites), whole-genome (~9 million single-nucleotide variants), and whole-transcriptome (>14 000 genes) data for CD4 + T-lymphocytes, monocytes, and neutrophils collected from approximately 100 subjects. These data were obtained from whole-genome bisulfite sequencing, whole-genome sequencing, and whole-transcriptome sequencing, making iMETHYL a comprehensive database.

Predicting aberrant CpG island methylation

PubMed Central

Feltus, F. A.; Lee, E. K.; Costello, J. F.; Plass, C.; Vertino, P. M.

2003-01-01

Epigenetic silencing associated with aberrant methylation of promoter region CpG islands is one mechanism leading to loss of tumor suppressor function in human cancer. Profiling of CpG island methylation indicates that some genes are more frequently methylated than others, and that each tumor type is associated with a unique set of methylated genes. However, little is known about why certain genes succumb to this aberrant event. To address this question, we used Restriction Landmark Genome Scanning to analyze the susceptibility of 1,749 unselected CpG islands to de novo methylation driven by overexpression of DNA cytosine-5-methyltransferase 1 (DNMT1). We found that although the overall incidence of CpG island methylation was increased in cells overexpressing DNMT1, not all loci were equally affected. The majority of CpG islands (69.9%) were resistant to de novo methylation, regardless of DNMT1 overexpression. In contrast, we identified a subset of methylation-prone CpG islands (3.8%) that were consistently hypermethylated in multiple DNMT1 overexpressing clones. Methylation-prone and methylation-resistant CpG islands were not significantly different with respect to size, C+G content, CpG frequency, chromosomal location, or promoter association. We used DNA pattern recognition and supervised learning techniques to derive a classification function based on the frequency of seven novel sequence patterns that was capable of discriminating methylation-prone from methylation-resistant CpG islands with 82% accuracy. The data indicate that CpG islands differ in their intrinsic susceptibility to de novo methylation, and suggest that the propensity for a CpG island to become aberrantly methylated can be predicted based on its sequence context. PMID:14519846

Predicting aberrant CpG island methylation.

PubMed

Feltus, F A; Lee, E K; Costello, J F; Plass, C; Vertino, P M

2003-10-14

Epigenetic silencing associated with aberrant methylation of promoter region CpG islands is one mechanism leading to loss of tumor suppressor function in human cancer. Profiling of CpG island methylation indicates that some genes are more frequently methylated than others, and that each tumor type is associated with a unique set of methylated genes. However, little is known about why certain genes succumb to this aberrant event. To address this question, we used Restriction Landmark Genome Scanning to analyze the susceptibility of 1,749 unselected CpG islands to de novo methylation driven by overexpression of DNA cytosine-5-methyltransferase 1 (DNMT1). We found that although the overall incidence of CpG island methylation was increased in cells overexpressing DNMT1, not all loci were equally affected. The majority of CpG islands (69.9%) were resistant to de novo methylation, regardless of DNMT1 overexpression. In contrast, we identified a subset of methylation-prone CpG islands (3.8%) that were consistently hypermethylated in multiple DNMT1 overexpressing clones. Methylation-prone and methylation-resistant CpG islands were not significantly different with respect to size, C+G content, CpG frequency, chromosomal location, or promoter association. We used DNA pattern recognition and supervised learning techniques to derive a classification function based on the frequency of seven novel sequence patterns that was capable of discriminating methylation-prone from methylation-resistant CpG islands with 82% accuracy. The data indicate that CpG islands differ in their intrinsic susceptibility to de novo methylation, and suggest that the propensity for a CpG island to become aberrantly methylated can be predicted based on its sequence context.

Validation of a SysML based design for wireless sensor networks

NASA Astrophysics Data System (ADS)

Berrachedi, Amel; Rahim, Messaoud; Ioualalen, Malika; Hammad, Ahmed

2017-07-01

When developing complex systems, the requirement for the verification of the systems' design is one of the main challenges. Wireless Sensor Networks (WSNs) are examples of such systems. We address the problem of how WSNs must be designed to fulfil the system requirements. Using the SysML Language, we propose a Model Based System Engineering (MBSE) specification and verification methodology for designing WSNs. This methodology uses SysML to describe the WSNs requirements, structure and behaviour. Then, it translates the SysML elements to an analytic model, specifically, to a Deterministic Stochastic Petri Net. The proposed approach allows to design WSNs and study their behaviors and their energy performances.

Conformations and Barriers to Methyl Group Internal Rotation in Two Asymmetric Ethers: Propyl Methyl Ether and Butyl Methyl Ether

NASA Astrophysics Data System (ADS)

Long, B. E.; Dechirico, F.; Cooke, S. A.

2012-06-01

The conformational preferences of the O-C-C-C unit are important in many biological systems with the unit generally preferring a gauche configuration compared to an anti configuration. Butyl methyl ether and propyl methyl ether provide very simple systems for this phenomenom to manifest. Pure rotational spectra of the title molecules have been recorded using chirped pulse Fourier transform microwave spectroscopy (CP-FTMW). In the case of butyl methyl ether, only one conformer has been observed. This conformer has torsional angles of COCC = 180°, OCCC = 62° and CCCC = 180° (anti-gauche-anti) and rotational constants of A = 10259.4591(33) MHz, B = 1445.6470(13) MHz, and C = 1356.2944(14) MHz. The rotational spectrum was doubled and has been analyzed to produce an effective barrier to methyl group internal rotation of 780(35) cm-1. A prior rotational spectroscopic study on propyl methyl ether had focused only on the high energy anti-anti conformer. We have analyzed spectra from the lowest energy anti-gauche conformer and the spectroscopic constants will be presented. A summary of the differences in conformational energies and methyl group internal rotation barriers for the class of aliphatic asymmetric ethers will be presented. K. N. Houk, J. E. Eksterowicz, Y.-D. Wu, C. D. Fuglesang, D. B. Mitchell. J. Am. Chem. Soc. 115 (4170), 1993. Hiroshi Kato, Jun Nakagawa, Michiro Hayashi. J. Mol. Spectrosc. 80 (272), 1980.

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

NASA Astrophysics Data System (ADS)

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.

Evolution of DNA Methylation across Insects

PubMed Central

Vogel, Kevin J.; Moore, Allen J.; Schmitz, Robert J.

2017-01-01

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. PMID:28025279

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

PubMed

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.

ANZSoilML: An Australian - New Zealand standard for exchange of soil data

NASA Astrophysics Data System (ADS)

Simons, Bruce; Wilson, Peter; Ritchie, Alistair; Cox, Simon

2013-04-01

The Australian-New Zealand soil information exchange standard (ANZSoilML) is a GML-based standard designed to allow the discovery, query and delivery of soil and landscape data via standard Open Geospatial Consortium (OGC) Web Feature Services. ANZSoilML modifies the Australian soil exchange standard (OzSoilML), which is based on the Australian Soil Information Transfer and Evaluation System (SITES) database design and exchange protocols, to meet the New Zealand National Soils Database requirements. The most significant change was the removal of the lists of CodeList terms in OzSoilML, which were based on the field methods specified in the 'Australian Soil and Land Survey Field Handbook'. These were replaced with empty CodeLists as placeholders to external vocabularies to allow the use of New Zealand vocabularies without violating the data model. Testing of the use of these separately governed Australian and New Zealand vocabularies has commenced. ANZSoilML attempts to accommodate the proposed International Organization for Standardization ISO/DIS 28258 standard for soil quality. For the most part, ANZSoilML is consistent with the ISO model, although major differences arise as a result of: • The need to specify the properties appropriate for each feature type; • The inclusion of soil-related 'Landscape' features; • Allowing the mapping of soil surfaces, bodies, layers and horizons, independent of the soil profile; • Allowing specifying the relationships between the various soil features; • Specifying soil horizons as specialisations of soil layers; • Removing duplication of features provided by the ISO Observation & Measurements standard. The International Union of Soil Sciences (IUSS) Working Group on Soil Information Standards (WG-SIS) aims to develop, promote and maintain a standard to facilitate the exchange of soils data and information. Developing an international exchange standard that is compatible with existing and emerging national and

Synthesis and properties of fatty acid starch esters.

PubMed

Winkler, Henning; Vorwerg, Waltraud; Wetzel, Hendrik

2013-10-15

Being completely bio-based, fatty acid starch esters (FASEs) are attractive materials that represent an alternative to crude oil-based plastics. In this study, two synthesis methods were compared in terms of their efficiency, toxicity and, especially, product solubility with starch laurate (C12) as model compound. Laurates (DS>2) were obtained through transesterification of fatty acid vinylesters in DMSO or reaction with fatty acid chlorides in pyridine. The latter lead to higher DS-values in a shorter reaction time. But due to the much better solubility of the products compared to lauroyl chloride esterified ones, vinylester-transesterification was preferred to optimize reaction parameters, where reaction time could be shortened to 2h. FASEs C6-C18 were also successfully prepared via transesterification. To determine the DS of the resulting starch laurates, the efficient ATR-IR method was compared with common methods (elementary analysis, (1)H NMR). Molar masses (Mw) of the highly soluble starch laurates were analyzed using SEC-MALLS (THF). High recovery rates (>80%) attest to the outstanding solubility of products obtained through transesterification, caused by a slight disintegration during synthesis. Particle size distributions (DLS) demonstrated stable dissolutions in CHCl3 of vinyl laurate esterified - contrary to lauroyl chloride esterified starch. For all highly soluble FASEs (C6-C18), formation of concentrated solutions (10 wt%) is feasible. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evolution of DNA Methylation across Insects.

PubMed

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.

Methyl chloride and methyl bromide emissions from baking: an unrecognized anthropogenic source.

PubMed

Thornton, Brett F; Horst, Axel; Carrizo, Daniel; Holmstrand, Henry

2016-05-01

Methyl chloride and methyl bromide (CH3Cl and CH3Br) are the largest natural sources of chlorine and bromine, respectively, to the stratosphere, where they contribute to ozone depletion. We report the anthropogenic production of CH3Cl and CH3Br during breadbaking, and suggest this production is an abiotic process involving the methyl ester functional groups in pectin and lignin structural polymers of plant cells. Wide variations in baking styles allow only rough estimates of this flux of methyl halides on a global basis. A simple model suggests that CH3Br emissions from breadbaking likely peaked circa 1990 at approximately 200tonnes per year (about 0.3% of industrial production), prior to restrictions on the dough conditioner potassium bromate. In contrast, CH3Cl emissions from breadbaking may be of similar magnitude as acknowledged present-day CH3Cl industrial emissions. Because the mechanisms involve functional groups and compounds widely found in plant materials, this type of methyl halide production may occur in other cooking techniques as well. Copyright © 2016 Elsevier B.V. All rights reserved.

Two-year drinking water carcinogenicity study of methyl tertiary-butyl ether (MTBE) in Wistar rats.

PubMed

Dodd, Darol; Willson, Gabrielle; Parkinson, Horace; Bermudez, Edilberto

2013-07-01

Methyl tertiary-butyl ether (MTBE) has been used as a gasoline additive to reduce tailpipe emissions and its use has been discontinued. There remains a concern that drinking water sources have been contaminated with MTBE. A two-year drinking water carcinogenicity study of MTBE was conducted in Wistar rats (males, 0, 0.5, 3, 7.5 mg ml(-1); and females, 0, 0.5, 3, and 15 mg ml(-1)). Body weights were unaffected and water consumption was reduced in MTBE-exposed males and females. Wet weights of male kidneys were increased at the end of two years of exposure to 7.5 mg ml(-1) MTBE. Chronic progressive nephropathy was observed in males and females, was more severe in males, and was exacerbated in the high MTBE exposure groups. Brain was the only tissue with a statistically significant finding of neoplasms. One astrocytoma (1/50) was found in a female rat (15 mg ml(-1)). The incidence of brain astrocytomas in male rats was 1/50, 1/50, 1/50 and 4/50 for the 0, 0.5, 3 and 7.5 mg ml(-1) exposure groups, respectively. This was a marginally significant statistical trend, but not statistically significant when pairwise comparisons were made or when multiple comparisons were taken into account. The incidence of astrocytoma fell within historical control ranges for Wistar rats, and the brain has not been identified as a target organ following chronic administration of MTBE, ethyl tert-butyl ether, or tertiary butyl alcohol (in drinking water) to mice and rats. We conclude that the astrocytomas observed in this study are not associated with exposure to MTBE. Copyright © 2011 John Wiley & Sons, Ltd.

Histone Lysine Methylation and Neurodevelopmental Disorders.

PubMed

Kim, Jeong-Hoon; Lee, Jang Ho; Lee, Im-Soon; Lee, Sung Bae; Cho, Kyoung Sang

2017-06-30

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.

Choline, Other Methyl-Donors and Epigenetics

PubMed Central

Zeisel, Steven H.

2017-01-01

Choline dietary intake varies such that many people do not achieve adequate intakes. Diet intake of choline can modulate methylation because, via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-adenosylhomocysteine and S-adenosylmethionine. Some of the epigenetic mechanisms that modify gene expression without modifying the genetic code depend on the methylation of DNA or of histones; and diet availability of choline and other methyl-group donors influences both of these methylations. Examples of methyl-donor mediated epigenetic effects include the changes in coat color and body weight in offspring when pregnant agouti mice are fed high choline, high methyl diets; the changes in tail kinking in offspring when pregnant Axin(Fu) mice are fed high choline, high methyl diets; the changes in Cdkn3 methylation and altered brain development that occurs in offspring when pregnant rodents are fed low choline diets. When choline metabolism is disrupted by deleting the gene Bhmt, DNA methylation is affected (especially in a region of chromosome 13), expression of specific genes is suppressed, and liver cancers develop. Better understanding of how nutrients such as choline and methyl-donors influence epigenetic programs has importance for our understanding of not only developmental abnormalities but also for understanding the origins of chronic diseases. PMID:28468239

Choline, Other Methyl-Donors and Epigenetics.

PubMed

Zeisel, Steven

2017-04-29

Choline dietary intake varies such that many people do not achieve adequate intakes. Diet intake of choline can modulate methylation because, via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-adenosylhomocysteine and S-adenosylmethionine. Some of the epigenetic mechanisms that modify gene expression without modifying the genetic code depend on the methylation of DNA or of histones; and diet availability of choline and other methyl-group donors influences both of these methylations. Examples of methyl-donor mediated epigenetic effects include the changes in coat color and body weight in offspring when pregnant agouti mice are fed high choline, high methyl diets; the changes in tail kinking in offspring when pregnant Axin(Fu) mice are fed high choline, high methyl diets; the changes in Cdkn3 methylation and altered brain development that occurs in offspring when pregnant rodents are fed low choline diets. When choline metabolism is disrupted by deleting the gene Bhmt, DNA methylation is affected (especially in a region of chromosome 13), expression of specific genes is suppressed, and liver cancers develop. Better understanding of how nutrients such as choline and methyl-donors influence epigenetic programs has importance for our understanding of not only developmental abnormalities but also for understanding the origins of chronic diseases.

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

PubMed

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.

What triggers differential DNA methylation of genes and TEs: contribution of body methylation?

PubMed

Inagaki, S; Kakutani, T

2012-01-01

Transposable elements (TEs) are epigenetically silenced with extensive DNA methylation. The silent epigenetic marks should, however, be excluded from active genes. By genetic approaches, we study mechanisms to remove the heterochromatin marks from transcribed genes. Based on our observations on control of TE transcription, we propose a possible trigger for the TE-specific accumulation of DNA methylation. A critical difference between TEs and genes could be their responses to the DNA methylation in the internal part of transcribed regions. When their internal region is methylated, genes are still transcribed, but TEs could be silenced, which may reflect the obligatory position of every critical cis-acting element within the TE itself. This initial difference of TEs and genes will be amplified by positive feedback loops to stabilize active or silent states. Thus, the mechanisms to accumulate heterochromatin marks within transcribed regions could provide a trigger to induce differential DNA methylation between genes and TEs.

pymzML--Python module for high-throughput bioinformatics on mass spectrometry data.

PubMed

Bald, Till; Barth, Johannes; Niehues, Anna; Specht, Michael; Hippler, Michael; Fufezan, Christian

2012-04-01

pymzML is an extension to Python that offers (i) an easy access to mass spectrometry (MS) data that allows the rapid development of tools, (ii) a very fast parser for mzML data, the standard data format in MS and (iii) a set of functions to compare or handle spectra. pymzML requires Python2.6.5+ and is fully compatible with Python3. The module is freely available on http://pymzml.github.com or pypi, is published under LGPL license and requires no additional modules to be installed. christian@fufezan.net.

Spectra, chromatograms, Metadata: mzML-the standard data format for mass spectrometer output.

PubMed

Turewicz, Michael; Deutsch, Eric W

2011-01-01

This chapter describes Mass Spectrometry Markup Language (mzML), an XML-based and vendor-neutral standard data format for storage and exchange of mass spectrometer output like raw spectra and peak lists. It is intended to replace its two precursor data formats (mzData and mzXML), which had been developed independently a few years earlier. Hence, with the release of mzML, the problem of having two different formats for the same purposes is solved, and with it the duplicated effort of maintaining and supporting two data formats. The new format has been developed by a broad-based consortium of major instrument vendors, software vendors, and academic researchers under the aegis of the Human Proteome Organisation (HUPO), Proteomics Standards Initiative (PSI), with full participation of the main developers of the precursor formats. This comprehensive approach helped mzML to become a generally accepted standard. Furthermore, the collaborative development insured that mzML has adopted the best features of its precursor formats. In this chapter, we discuss mzML's development history, its design principles and use cases, as well as its main building components. We also present the available documentation, an example file, and validation software for mzML.

Effects of Particulate Matter on Genomic DNA Methylation Content and iNOS Promoter Methylation

PubMed Central

Tarantini, Letizia; Bonzini, Matteo; Apostoli, Pietro; Pegoraro, Valeria; Bollati, Valentina; Marinelli, Barbara; Cantone, Laura; Rizzo, Giovanna; Hou, Lifang; Schwartz, Joel; Bertazzi, Pier Alberto; Baccarelli, Andrea

2009-01-01

Background Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. Objectives We aimed at identifying short- and long-term effects of PM exposure on DNA methylation, a major genomic mechanism of gene expression control, in workers in an electric furnace steel plant with well-characterized exposure to PM with aerodynamic diameters < 10 μm (PM10). Methods We measured global genomic DNA methylation content estimated in Alu and long interspersed nuclear element-1 (LINE-1) repeated elements, and promoter DNA methylation of iNOS (inducible nitric oxide synthase), a gene suppressed by DNA methylation and induced by PM exposure in blood leukocytes. Quantitative DNA methylation analysis was performed through bisulfite PCR pyrosequencing on blood DNA obtained from 63 workers on the first day of a work week (baseline, after 2 days off work) and after 3 days of work (postexposure). Individual PM10 exposure was between 73.4 and 1,220 μg/m3. Results Global methylation content estimated in Alu and LINE-1 repeated elements did not show changes in postexposure measures compared with baseline. PM10 exposure levels were negatively associated with methylation in both Alu [β = −0.19 %5-methylcytosine (%5mC); p = 0.04] and LINE-1 [β = −0.34 %5mC; p = 0.04], likely reflecting long-term PM10 effects. iNOS promoter DNA methylation was significantly lower in postexposure blood samples compared with baseline (difference = −0.61 %5mC; p = 0.02). Conclusions We observed changes in global and gene specific methylation that should be further characterized in future investigations on the effects of PM. PMID:19270791

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

PubMed

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.

40 CFR 721.1025 - Benzenamine, 4-chloro-2-methyl-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine...

Code of Federal Regulations, 2010 CFR

2010-07-01

...-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine, 2-chloro-6-methyl-. 721.1025 Section 721... Benzenamine, 4-chloro-2-methyl-; benzenamine, 4-chloro-2-methyl-, hydrochloride; and ben-zenamine, 2-chloro-6...-, hydrochloride (CAS Number 3165-93-3); and benzenamine, 2-chloro-6-methyl- (CAS Number 87-63-8) are subject to...

Formation of Worm-Like Micelles in Mixed N-Hexadecyl-N-Methylpyrrolidinium Bromide-Based Cationic Surfactant and Anionic Surfactant Systems

PubMed Central

Dai, Caili; Yan, Zhihu; You, Qing; Du, Mingyong; Zhao, Mingwei

2014-01-01

Through the descriptive and rheological characterization of worm-like micelles formed by N-hexadecyl-N-methylpyrrolidinium bromide and sodium laurate, the formation and properties of the worm-like micelles were affected by the concentrations of sodium laurate and temperature. Additionally, cryogenic transmission electron microscopy images further validated the formation of worm-like micelles. PMID:25019152

IBM techexplorer and MathML: Interactive Multimodal Scientific Documents

NASA Astrophysics Data System (ADS)

Diaz, Angel

2001-06-01

The World Wide Web provides a standard publishing platform for disseminating scientific and technical articles, books, journals, courseware, or even homework on the internet; however, the transition from paper to web-based interactive content has brought new opportunities for creating interactive content. Students, scientists, and engineers are now faced with the task of rendering the 2D presentational structure of mathematics, harnessing the wealth of scientific and technical software, and creating truly accessible scientific portals across international boundaries and markets. The recent emergence of World Wide Web Consortium (W3C) standards such as the Mathematical Markup Language (MathML), Language (XSL), and Aural CSS (ACSS) provide a foundation whereby mathematics can be displayed, enlivened, computed, and audio formatted. With interoperability ensured by standards, software applications can be easily brought together to create extensible and interactive scientific content. In this presentation we will provide an overview of the IBM techexplorer Hypermedia Browser, a web browser plug-in and ActiveX control aimed at bringing interactive mathematics to the masses across platforms and applications. We will demonstrate "live" mathematics where documents that contain MathML expressions can be edited and computed right inside your favorite web browser. This demonstration will be generalized as we show how MathML can be used to enliven even PowerPoint presentations. Finally, we will close the loop by demonstrating a novel approach to spoken mathematics based on MathML, DOM, XSL, ACSS, techexplorer, and IBM ViaVoice. By making use of techexplorer as the glue that binds the rendered content to the web browser, the back-end computation software, the Java applets that augment the exposition, and voice-rendering systems such as ViaVoice, authors can indeed create truly extensible and interactive scientific content. For more information see: [http

Ulcer Prevention Effect Of 3,4,5-Tihydroxy-N0-[(2-Methyl-1H-Indol-3yl)Methylidene]Benzohydrazide In HCl/Ethanol-Induced Gastric Mucosal Damage In Rats.

PubMed

Tayeby, Faezeh; Salman, Abbas Abdul Ameer; Kamran, Sareh; Khaing, Si Lay; Salehen, Nur'ain Binti; Mohan, Gokula Mohan A/L Duchiyanda

2017-01-01

The newly synthesized, 3,4,5-Trihydroxy-N 0-[(2-methyl-1H-indol-3-yl)-methylidene] benzohydrazide (TIBH), is an indole and gallic acid derivative. The aim of this research investigation was to evaluate the acute toxicity and the ulcer prevention potential of TIBH in HCl/Ethanol-induced gastric ulcer rat model. Six groups of rats were orally received 5ml/kg of vehicle (1 % Carboxy methyl cellulose) for the normal and ulcer control groups each, Omeprazole (20mg/kg) for positive control, 50 mg/kg, 100 mg/kg and 200 mg/kg of TIBH for experimental groups, respectively. After one hour, instead of rats in the normal group which received 5ml/kg of 1% CMC, other groups received 5ml/kg of HCl/Ethanol. All rats were sacrificed after one additional hour. Gastric juice, gastric mucosa, morphologies of gastric ulcers and protein expressions of both control and treatment groups were evaluated. TIBH showed a ulcer prevention potential by increase of the mucus secretion, decrease of the gastric acidity, up-regulation of HSP70 protein, down-regulation of Bax protein, decrease of the lipid peroxidation and the increase of the Superoxide dismutase (SOD) activity in gastric tissue homogenate. Acute toxicity assay exposed valuable information on the safety of this compound. TIBH had a dose dependent ulcer prevention potential against HCl/Ethanol-triggered gastric ulcer.

Ulcer Prevention Effect Of 3,4,5-Tihydroxy-N0-[(2-Methyl-1H-Indol-3yl)Methylidene]Benzohydrazide In HCl/Ethanol-Induced Gastric Mucosal Damage In Rats

PubMed Central

Tayeby, Faezeh; Salman, Abbas Abdul Ameer; Kamran, Sareh; Khaing, Si Lay; Salehen, Nur'ain Binti; Mohan, Gokula Mohan A/L Duchiyanda

2017-01-01

The newly synthesized, 3,4,5-Trihydroxy-N 0-[(2-methyl-1H-indol-3-yl)-methylidene] benzohydrazide (TIBH), is an indole and gallic acid derivative. The aim of this research investigation was to evaluate the acute toxicity and the ulcer prevention potential of TIBH in HCl/Ethanol-induced gastric ulcer rat model. Six groups of rats were orally received 5ml/kg of vehicle (1 % Carboxy methyl cellulose) for the normal and ulcer control groups each, Omeprazole (20mg/kg) for positive control, 50 mg/kg, 100 mg/kg and 200 mg/kg of TIBH for experimental groups, respectively. After one hour, instead of rats in the normal group which received 5ml/kg of 1% CMC, other groups received 5ml/kg of HCl/Ethanol. All rats were sacrificed after one additional hour. Gastric juice, gastric mucosa, morphologies of gastric ulcers and protein expressions of both control and treatment groups were evaluated. TIBH showed a ulcer prevention potential by increase of the mucus secretion, decrease of the gastric acidity, up-regulation of HSP70 protein, down-regulation of Bax protein, decrease of the lipid peroxidation and the increase of the Superoxide dismutase (SOD) activity in gastric tissue homogenate. Acute toxicity assay exposed valuable information on the safety of this compound. TIBH had a dose dependent ulcer prevention potential against HCl/Ethanol-triggered gastric ulcer. PMID:29200945

Methylation-sensitive amplified polymorphism-based genome-wide analysis of cytosine methylation profiles in Nicotiana tabacum cultivars.

PubMed

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.

PubMed

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.

Conformational analysis and dipole moments of tetra-O-methyl-(+)-catechin and tetra-O-methyl_(-)-epicatechin

Treesearch

W.L. Mattice; F.L. Tobiason; K. Houghlum; A. Shanafelt

1982-01-01

A conformational energy analysis has been performed for tetra-0-methyl-(+)-catechin and tetra-O-methyl-(-)-epicatechin. Rotation was permitted about five C-O bonds and about the single bond connecting two rings. Eighteen rotational isomers each were assigned for tetra-0-methyl-(-)-epicatechin. Relative...

Towards Solvation of a Chiral Alpha-Hydroxy Ester: Broadband Chirp and Narrow Band Cavity Fouirier Transform Microwave Spectroscopy of Methyl Lactate-Water Clusters

NASA Astrophysics Data System (ADS)

Thomas, Javix; Sukhorukov, Oleksandr; Jaeger, Wolfgang; Xu, Yunjie

2013-06-01

Methyl lactate (ML), a chiral alpha-hydroxy ester, has attracted much attention as a prototype system in studies of chirality transfer,[1] solvation effects on chiroptical signatures,[2] and chirality recognition.[3] It has multiple functional groups which can serve both as a hydrogen donor and acceptor. By applying rotational spectroscopy and high level ab initio calculations, we examine the delicate competition between inter- and intramolecular hydrogen-bonding in the ML-water clusters. Broadband rotational spectra obtained with a chirp Fourier transform microwave (FTMW) spectrometer, reveal that the insertion conformations are the most favourable ones in the binary and ternary solvated complexes. In the insertion conformations, the water molecule(s) inserts itself (themselves) into the existing intramolecular hydrogen-bonded ring formed between the alcoholic hydroxyl group and the oxygen of the carbonyl group of ML. The final frequency measurements have been carried out using a cavity based FTMW instrument where internal rotation splittings due to the ester methyl group have also been detected. A number of insertion conformers with subtle structural differences for both the binary and ternary complexes have been identified theoretically. The interconversion dynamics of these conformers and the identification of the most favorable conformers will be discussed. 1. C. Merten, Y. Xu, Angew. Chem. Int. Ed., 2013, 52, 2073 -2076. 2. M. Losada, Y. Xu, Phys. Chem. Chem. Phys., 2007, 9, 3127-3135; Y. Liu, G. Yang, M. Losada, Y. Xu, J. Chem. Phys., 2010, 132, 234513/1-11. 3. A. Zehnacker, M. Suhm, Angew. Chem. Int. Ed. 2008, 47, 6970 - 6992.

Core Stage Inter-Tank Umbilical (CSITU) Lift at ML

NASA Image and Video Library

2017-10-11

A heavy-lift crane and rigging are used to lift the Core Stage Inter-tank Umbilical (CSITU) up to about the 140-foot level of the mobile launcher (ML) tower at NASA's Kennedy Space Center in Florida. The CSITU is moved into place for a fit check of the attachment hardware. The umbilical will then be lowered down and installed permanently on the ML at a later date. The CSITU is a swing-arm umbilical that will connect to the Space Launch System core stage inter-tank. It will provide conditioned air, pressurized gases and power and data connection to the core stage. The Ground Systems Development and Operations Program is overseeing installation of the umbilicals.

DNA Methylation and BMI: Investigating Identified Methylation Sites at HIF3A in a Causal Framework

PubMed Central

Richmond, Rebecca C.; Ward, Mary E.; Fraser, Abigail; Lyttleton, Oliver; McArdle, Wendy L.; Ring, Susan M.; Gaunt, Tom R.; Lawlor, Debbie A.; Davey Smith, George; Relton, Caroline L.

2016-01-01

Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ∼1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation. PMID:26861784

HepML, an XML-based format for describing simulated data in high energy physics

NASA Astrophysics Data System (ADS)

Belov, S.; Dudko, L.; Kekelidze, D.; Sherstnev, A.

2010-10-01

In this paper we describe a HepML format and a corresponding C++ library developed for keeping complete description of parton level events in a unified and flexible form. HepML tags contain enough information to understand what kind of physics the simulated events describe and how the events have been prepared. A HepML block can be included into event files in the LHEF format. The structure of the HepML block is described by means of several XML Schemas. The Schemas define necessary information for the HepML block and how this information should be located within the block. The library libhepml is a C++ library intended for parsing and serialization of HepML tags, and representing the HepML block in computer memory. The library is an API for external software. For example, Matrix Element Monte Carlo event generators can use the library for preparing and writing a header of an LHEF file in the form of HepML tags. In turn, Showering and Hadronization event generators can parse the HepML header and get the information in the form of C++ classes. libhepml can be used in C++, C, and Fortran programs. All necessary parts of HepML have been prepared and we present the project to the HEP community. Program summaryProgram title: libhepml Catalogue identifier: AEGL_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEGL_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU GPLv3 No. of lines in distributed program, including test data, etc.: 138 866 No. of bytes in distributed program, including test data, etc.: 613 122 Distribution format: tar.gz Programming language: C++, C Computer: PCs and workstations Operating system: Scientific Linux CERN 4/5, Ubuntu 9.10 RAM: 1 073 741 824 bytes (1 Gb) Classification: 6.2, 11.1, 11.2 External routines: Xerces XML library ( http://xerces.apache.org/xerces-c/), Expat XML Parser ( http://expat.sourceforge.net/) Nature of problem: Monte Carlo simulation in high

Simulation Experiment Description Markup Language (SED-ML) Level 1 Version 2.

PubMed

Bergmann, Frank T; Cooper, Jonathan; Le Novère, Nicolas; Nickerson, David; Waltemath, Dagmar

2015-09-04

The number, size and complexity of computational models of biological systems are growing at an ever increasing pace. It is imperative to build on existing studies by reusing and adapting existing models and parts thereof. The description of the structure of models is not sufficient to enable the reproduction of simulation results. One also needs to describe the procedures the models are subjected to, as recommended by the Minimum Information About a Simulation Experiment (MIASE) guidelines. This document presents Level 1 Version 2 of the Simulation Experiment Description Markup Language (SED-ML), a computer-readable format for encoding simulation and analysis experiments to apply to computational models. SED-ML files are encoded in the Extensible Markup Language (XML) and can be used in conjunction with any XML-based model encoding format, such as CellML or SBML. A SED-ML file includes details of which models to use, how to modify them prior to executing a simulation, which simulation and analysis procedures to apply, which results to extract and how to present them. Level 1 Version 2 extends the format by allowing the encoding of repeated and chained procedures.

Simulation Experiment Description Markup Language (SED-ML) Level 1 Version 2.

PubMed

Bergmann, Frank T; Cooper, Jonathan; Le Novère, Nicolas; Nickerson, David; Waltemath, Dagmar

2015-06-01

The number, size and complexity of computational models of biological systems are growing at an ever increasing pace. It is imperative to build on existing studies by reusing and adapting existing models and parts thereof. The description of the structure of models is not sufficient to enable the reproduction of simulation results. One also needs to describe the procedures the models are subjected to, as recommended by the Minimum Information About a Simulation Experiment (MIASE) guidelines. This document presents Level 1 Version 2 of the Simulation Experiment Description Markup Language (SED-ML), a computer-readable format for encoding simulation and analysis experiments to apply to computational models. SED-ML files are encoded in the Extensible Markup Language (XML) and can be used in conjunction with any XML-based model encoding format, such as CellML or SBML. A SED-ML file includes details of which models to use, how to modify them prior to executing a simulation, which simulation and analysis procedures to apply, which results to extract and how to present them. Level 1 Version 2 extends the format by allowing the encoding of repeated and chained procedures.

Genome-wide methylation analysis identifies differentially methylated CpG loci associated with severe obesity in childhood.

PubMed

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 < 0.05). The top pathways enriched among the DMCpGs included developmental processes, immune system regulation, regulation of cell signaling, and small GTPase-mediated signal transduction. The associations between the methylation of selected DMCpGs with childhood 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 < 0.01), while 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.

Diguanylate cyclase activity of the Mycobacterium leprae T cell antigen ML1419c

PubMed Central

Rotcheewaphan, Suwatchareeporn; Belisle, John T.; Webb, Kristofor J.; Kim, Hee-Jin; Spencer, John S.

2016-01-01

The second messenger, bis-(3′,5′)-cyclic dimeric guanosine monophosphate (cyclic di-GMP), is involved in the control of multiple bacterial phenotypes, including those that impact host–pathogen interactions. Bioinformatics analyses predicted that Mycobacterium leprae, an obligate intracellular bacterium and the causative agent of leprosy, encodes three active diguanylate cyclases. In contrast, the related pathogen Mycobacterium tuberculosis encodes only a single diguanylate cyclase. One of the M. leprae unique diguanylate cyclases (ML1419c) was previously shown to be produced early during the course of leprosy. Thus, functional analysis of ML1419c was performed. The gene encoding ML1419c was cloned and expressed in Pseudomonas aeruginosa PAO1 to allow for assessment of cyclic di-GMP production and cyclic di-GMP-mediated phenotypes. Phenotypic studies revealed that ml1419c expression altered colony morphology, motility and biofilm formation of P. aeruginosa PAO1 in a manner consistent with increased cyclic di-GMP production. Direct measurement of cyclic di-GMP levels by liquid chromatography–mass spectrometry confirmed that ml1419c expression increased cyclic di-GMP production in P. aeruginosa PAO1 cultures in comparison to the vector control. The observed phenotypes and increased levels of cyclic di-GMP detected in P. aeruginosa expressing ml1419c could be abrogated by mutation of the active site in ML1419c. These studies demonstrated that ML1419c of M. leprae functions as diguanylate cyclase to synthesize cyclic di-GMP. Thus, this protein was renamed DgcA (Diguanylate cyclase A). These results also demonstrated the ability to use P. aeruginosa as a heterologous host for characterizing the function of proteins involved in the cyclic di-GMP pathway of a pathogen refractory to in vitro growth, M. leprae. PMID:27450520

Diguanylate cyclase activity of the Mycobacterium leprae T cell antigen ML1419c.

PubMed

Rotcheewaphan, Suwatchareeporn; Belisle, John T; Webb, Kristofor J; Kim, Hee-Jin; Spencer, John S; Borlee, Bradley R

2016-09-01

The second messenger, bis-(3',5')-cyclic dimeric guanosine monophosphate (cyclic di-GMP), is involved in the control of multiple bacterial phenotypes, including those that impact host-pathogen interactions. Bioinformatics analyses predicted that Mycobacterium leprae, an obligate intracellular bacterium and the causative agent of leprosy, encodes three active diguanylate cyclases. In contrast, the related pathogen Mycobacterium tuberculosis encodes only a single diguanylate cyclase. One of the M. leprae unique diguanylate cyclases (ML1419c) was previously shown to be produced early during the course of leprosy. Thus, functional analysis of ML1419c was performed. The gene encoding ML1419c was cloned and expressed in Pseudomonas aeruginosa PAO1 to allow for assessment of cyclic di-GMP production and cyclic di-GMP-mediated phenotypes. Phenotypic studies revealed that ml1419c expression altered colony morphology, motility and biofilm formation of P. aeruginosa PAO1 in a manner consistent with increased cyclic di-GMP production. Direct measurement of cyclic di-GMP levels by liquid chromatography-mass spectrometry confirmed that ml1419c expression increased cyclic di-GMP production in P. aeruginosa PAO1 cultures in comparison to the vector control. The observed phenotypes and increased levels of cyclic di-GMP detected in P. aeruginosa expressing ml1419c could be abrogated by mutation of the active site in ML1419c. These studies demonstrated that ML1419c of M. leprae functions as diguanylate cyclase to synthesize cyclic di-GMP. Thus, this protein was renamed DgcA (Diguanylate cyclase A). These results also demonstrated the ability to use P. aeruginosa as a heterologous host for characterizing the function of proteins involved in the cyclic di-GMP pathway of a pathogen refractory to in vitro growth, M. leprae.

Reproducible computational biology experiments with SED-ML - The Simulation Experiment Description Markup Language

PubMed Central

2011-01-01

Background The increasing use of computational simulation experiments to inform modern biological research creates new challenges to annotate, archive, share and reproduce such experiments. The recently published Minimum Information About a Simulation Experiment (MIASE) proposes a minimal set of information that should be provided to allow the reproduction of simulation experiments among users and software tools. Results In this article, we present the Simulation Experiment Description Markup Language (SED-ML). SED-ML encodes in a computer-readable exchange format the information required by MIASE to enable reproduction of simulation experiments. It has been developed as a community project and it is defined in a detailed technical specification and additionally provides an XML schema. The version of SED-ML described in this publication is Level 1 Version 1. It covers the description of the most frequent type of simulation experiments in the area, namely time course simulations. SED-ML documents specify which models to use in an experiment, modifications to apply on the models before using them, which simulation procedures to run on each model, what analysis results to output, and how the results should be presented. These descriptions are independent of the underlying model implementation. SED-ML is a software-independent format for encoding the description of simulation experiments; it is not specific to particular simulation tools. Here, we demonstrate that with the growing software support for SED-ML we can effectively exchange executable simulation descriptions. Conclusions With SED-ML, software can exchange simulation experiment descriptions, enabling the validation and reuse of simulation experiments in different tools. Authors of papers reporting simulation experiments can make their simulation protocols available for other scientists to reproduce the results. Because SED-ML is agnostic about exact modeling language(s) used, experiments covering models from

Reproducible computational biology experiments with SED-ML--the Simulation Experiment Description Markup Language.

PubMed

Waltemath, Dagmar; Adams, Richard; Bergmann, Frank T; Hucka, Michael; Kolpakov, Fedor; Miller, Andrew K; Moraru, Ion I; Nickerson, David; Sahle, Sven; Snoep, Jacky L; Le Novère, Nicolas

2011-12-15

The increasing use of computational simulation experiments to inform modern biological research creates new challenges to annotate, archive, share and reproduce such experiments. The recently published Minimum Information About a Simulation Experiment (MIASE) proposes a minimal set of information that should be provided to allow the reproduction of simulation experiments among users and software tools. In this article, we present the Simulation Experiment Description Markup Language (SED-ML). SED-ML encodes in a computer-readable exchange format the information required by MIASE to enable reproduction of simulation experiments. It has been developed as a community project and it is defined in a detailed technical specification and additionally provides an XML schema. The version of SED-ML described in this publication is Level 1 Version 1. It covers the description of the most frequent type of simulation experiments in the area, namely time course simulations. SED-ML documents specify which models to use in an experiment, modifications to apply on the models before using them, which simulation procedures to run on each model, what analysis results to output, and how the results should be presented. These descriptions are independent of the underlying model implementation. SED-ML is a software-independent format for encoding the description of simulation experiments; it is not specific to particular simulation tools. Here, we demonstrate that with the growing software support for SED-ML we can effectively exchange executable simulation descriptions. With SED-ML, software can exchange simulation experiment descriptions, enabling the validation and reuse of simulation experiments in different tools. Authors of papers reporting simulation experiments can make their simulation protocols available for other scientists to reproduce the results. Because SED-ML is agnostic about exact modeling language(s) used, experiments covering models from different fields of research

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.

PubMed

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

Validation of circulating BNP level >1000 pg/ml in all-cause mortality: A retrospective study.

PubMed

Sakamoto, Daisuke; Sakamoto, Shigeru; Kanda, Tsugiyasu

2015-08-01

To determine the primary diseases and prognoses of patients with highly elevated levels of B-type natriuretic peptide (BNP; >1000 pg/ml), with or without heart failure. Medical records and echocardiograms of patients with BNP levels that fell within one of three predetermined categories (>1000 pg/ml, 200-1000 pg/ml and <200 pg/ml) were retrospectively reviewed. There were no significant between-group differences in duration of hospitalization. Patients with BNP levels >1000 pg/ml (n = 103) or 200-1000 pg/ml (n = 100) had significantly worse 3-year survival than those with BNP levels <200 pg/ml (n = 100). The majority of patients (64/103) in the BNP >1000 pg/ml group had heart failure. The main cause of death in patients with other causes of BNP levels >1000 pg/ml (39/103) was community acquired pneumonia. A BNP level >1000 pg/ml has clinical importance in primary care medicine and hospital settings. © The Author(s) 2015.

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor.

PubMed

Louis, Elan D; Jiang, Wendy; Pellegrino, Kathryn M; Rios, Eileen; Factor-Litvak, Pam; Henchcliffe, Claire; Zheng, Wei

2008-03-01

Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors likely play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. In 2002, we demonstrated elevated blood harmane concentrations in an initial sample of 100 ET cases compared to 100 controls. Between 2002 and 2007, we assembled a new and larger sample of ET cases and controls. We now attempt to replicate our previous findings. Cases and controls were frequency-matched on age, gender, and race. Blood harmane concentrations were quantified by high-performance liquid chromatography. Subjects comprised 150 ET cases and 135 controls (mean age 65.3+/-15.5 vs. 65.5+/-14.2 years, p=0.94). Mean log blood harmane concentration was approximately 50% higher in cases than controls (0.50+/-0.54g(-10)/ml vs. 0.35+/-0.62g(-10)/ml, p=0.038). In a logistic regression analysis, log blood harmane concentration was associated with ET (OR(adjusted) 1.56, 95% CI 1.01-2.42, p=0.04), and odds of ET was 1.90 (95% CI 1.07-3.39, p=0.029) in the highest versus lowest log blood harmane tertile. Log blood harmane was highest in ET cases with familial ET (0.53+/-0.57g(-10)/ml), intermediate in cases with sporadic ET (0.43+/-0.45g(-10)/ml) and lowest in controls (0.35+/-0.62g(-10)/ml) (test for trend, p=0.026). Blood harmane appears to be elevated in ET. The higher concentrations in familial ET suggests that the mechanism may involve genetic factors.

Protection against de novo methylation is instrumental in maintaining parent-of-origin methylation inherited from the gametes.

PubMed

Proudhon, Charlotte; Duffié, Rachel; Ajjan, Sophie; Cowley, Michael; Iranzo, Julian; Carbajosa, Guillermo; Saadeh, Heba; Holland, Michelle L; Oakey, Rebecca J; Rakyan, Vardhman K; Schulz, Reiner; Bourc'his, Déborah

2012-09-28

Identifying loci with parental differences in DNA methylation is key to unraveling parent-of-origin phenotypes. By conducting a MeDIP-Seq screen in maternal-methylation free postimplantation mouse embryos (Dnmt3L-/+), we demonstrate that maternal-specific methylation exists very scarcely at midgestation. We reveal two forms of oocyte-specific methylation inheritance: limited to preimplantation, or with longer duration, i.e. maternally imprinted loci. Transient and imprinted maternal germline DMRs (gDMRs) are indistinguishable in gametes and preimplantation embryos, however, de novo methylation of paternal alleles at implantation delineates their fates and acts as a major leveling factor of parent-inherited differences. We characterize two new imprinted gDMRs, at the Cdh15 and AK008011 loci, with tissue-specific imprinting loss, again by paternal methylation gain. Protection against demethylation after fertilization has been emphasized as instrumental in maintaining parent-of-origin methylation inherited from the gametes. Here we provide evidence that protection against de novo methylation acts as an equal major pivot, at implantation and throughout life. Copyright © 2012 Elsevier Inc. All rights reserved.

Protection against De Novo Methylation Is Instrumental in Maintaining Parent-of-Origin Methylation Inherited from the Gametes

PubMed Central

Proudhon, Charlotte; Duffié, Rachel; Ajjan, Sophie; Cowley, Michael; Iranzo, Julian; Carbajosa, Guillermo; Saadeh, Heba; Holland, Michelle L.; Oakey, Rebecca J.; Rakyan, Vardhman K.; Schulz, Reiner; Bourc’his, Déborah

2012-01-01

Summary Identifying loci with parental differences in DNA methylation is key to unraveling parent-of-origin phenotypes. By conducting a MeDIP-Seq screen in maternal-methylation free postimplantation mouse embryos (Dnmt3L-/+), we demonstrate that maternal-specific methylation exists very scarcely at midgestation. We reveal two forms of oocyte-specific methylation inheritance: limited to preimplantation, or with longer duration, i.e. maternally imprinted loci. Transient and imprinted maternal germline DMRs (gDMRs) are indistinguishable in gametes and preimplantation embryos, however, de novo methylation of paternal alleles at implantation delineates their fates and acts as a major leveling factor of parent-inherited differences. We characterize two new imprinted gDMRs, at the Cdh15 and AK008011 loci, with tissue-specific imprinting loss, again by paternal methylation gain. Protection against demethylation after fertilization has been emphasized as instrumental in maintaining parent-of-origin methylation inherited from the gametes. Here we provide evidence that protection against de novo methylation acts as an equal major pivot, at implantation and throughout life. PMID:22902559

Methods of DNA methylation detection

NASA Technical Reports Server (NTRS)

Maki, Wusi Chen (Inventor); Filanoski, Brian John (Inventor); Mishra, Nirankar (Inventor); Rastogi, Shiva (Inventor)

2010-01-01

The present invention provides for methods of DNA methylation detection. The present invention provides for methods of generating and detecting specific electronic signals that report the methylation status of targeted DNA molecules in biological samples.Two methods are described, direct and indirect detection of methylated DNA molecules in a nano transistor based device. In the direct detection, methylated target DNA molecules are captured on the sensing surface resulting in changes in the electrical properties of a nano transistor. These changes generate detectable electronic signals. In the indirect detection, antibody-DNA conjugates are used to identify methylated DNA molecules. RNA signal molecules are generated through an in vitro transcription process. These RNA molecules are captured on the sensing surface change the electrical properties of nano transistor thereby generating detectable electronic signals.

DNA methylation dynamics during early plant life.

PubMed

Bouyer, Daniel; Kramdi, Amira; Kassam, Mohamed; Heese, Maren; Schnittger, Arp; Roudier, François; Colot, Vincent

2017-09-25

Cytosine methylation is crucial for gene regulation and silencing of transposable elements in mammals and plants. While this epigenetic mark is extensively reprogrammed in the germline and early embryos of mammals, the extent to which DNA methylation is reset between generations in plants remains largely unknown. Using Arabidopsis as a model, we uncovered distinct DNA methylation dynamics over transposable element sequences during the early stages of plant development. Specifically, transposable elements and their relics show invariably high methylation at CG sites but increasing methylation at CHG and CHH sites. This non-CG methylation culminates in mature embryos, where it reaches saturation for a large fraction of methylated CHH sites, compared to the typical 10-20% methylation level observed in seedlings or adult plants. Moreover, the increase in CHH methylation during embryogenesis matches the hypomethylated state in the early endosperm. Finally, we show that interfering with the embryo-to-seedling transition results in the persistence of high CHH methylation levels after germination, specifically over sequences that are targeted by the RNA-directed DNA methylation (RdDM) machinery. Our findings indicate the absence of extensive resetting of DNA methylation patterns during early plant life and point instead to an important role of RdDM in reinforcing DNA methylation of transposable element sequences in every cell of the mature embryo. Furthermore, we provide evidence that this elevated RdDM activity is a specific property of embryogenesis.

Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance.

PubMed

Todosijević, Marija N; Savić, Miroslav M; Batinić, Bojan B; Marković, Bojan D; Gašperlin, Mirjana; Ranđelović, Danijela V; Lukić, Milica Ž; Savić, Snežana D

2015-12-30

To elaborate the decisive role of surfactants in promotion of aceclofenac' skin absorption, potentially avoiding irritation, we developed non-ionic microemulsions varying natural or synthetic surfactants: sucrose esters (laurate or myristate) vs. polysorbate 80. A comprehensive physicochemical characterization indicated no significant influence of the solubilized nonsteroidal anti-inflammatory drug on the bicontinuous structure of blank formulations. To evaluate skin tolerability of isopropyl alcohol, a sucrose ester-based microemulsion containing transcutol P as a cosurfactant was also developed. The measured skin parameters strongly depended on the (co)surfactant type, showing higher compatibility of the microemulsions containing sucrose ester and isopropyl alcohol. In vitro release results, in vivo tape stripping and pharmacokinetics in rats confirmed superiority of the sucrose ester- over polysorbate-based microemulsions (total amounts of aceclofenac penetrated 60.81±5.97 and 60.86±3.67 vs. 27.00±5.09μg/cm(2), and its maximum plasma concentrations 275.57±109.49 and 281.31±76.76 vs. 150.23±69.74ng/ml for sucrose laurate- and myristate- vs. polysorbate 80-based microemulsions, respectively). Hence, sugar-based excipients increased delivery of aceclofenac through stratum corneum by increasing its fluidity, showing overall more satisfying safety profiles. In conclusion, sucrose ester-based microemulsions proved to be promising carriers for dermal/transdermal aceclofenac delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

Methyl group transfer upon gas phase decomposition of protonated methyl benzoate and similar compounds.

PubMed

Frański, Rafał; Gierczyk, Błażej; Zalas, Maciej; Jankowski, Wojciech; Hoffmann, Marcin

2018-05-01

Gas phase decompositions of protonated methyl benzoate and its conjugates have been studied by using electrospray ionization-collision induced dissociation-tandem mass spectrometry. Loss of CO 2 molecule, thus transfer of methyl group, has been observed. In order to better understand this process, the theoretical calculations have been performed. For methyl benzoate conjugates, it has been found that position of substituent affects the loss of CO 2 molecule, not the electron donor/withdrawing properties of the substituent. Therefore, electrospray ionization-mass spectrometry in positive ion mode may be useful for differentiation of isomers of methyl benzoate conjugates. Copyright © 2018 John Wiley & Sons, Ltd.

MethylMix 2.0: an R package for identifying DNA methylation genes. | Office of Cancer Genomics

Cancer.gov

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.

Effect of phase symmetry on the NMR spectrum of acetonitrile oriented in a uniaxial-biaxial-uniaxial phase

NASA Astrophysics Data System (ADS)

Deepak, H. S. Vinay; Yelamaggad, C. V.; Khetrapal, C. L.; Ramanathan, K. V.

2016-09-01

We report here the measurement of the Csbnd H and the Hsbnd H dipolar couplings of the methyl group of acetonitrile oriented in the biaxial liquid crystal potassium laurate/1-decanol/water system. These parameters show large variations when measured as a function of temperature. The variations follow the symmetry of the phase as the liquid crystal goes through the sequence of uniaxial - biaxial - uniaxial phases and show a close correspondence to the phase changes that occur in the liquid crystalline solvent coinciding with the onset of biaxiality. The Hsbnd Csbnd H bond angle calculated after incorporating vibrational corrections to the dipolar couplings is discussed in terms of contributions in the case of the biaxial liquid crystal arising from vibration-rotation interaction effects.

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

PubMed

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.

Improved synthetic route to methyl 1-fluoroindan-1-carboxylate (FICA Me ester) and 4-methyl derivatives.

PubMed

Koyanagi, Jyunichi; Kamei, Tomoyo; Ishizaki, Miyuki; Nakamura, Hiroshi; Takahashi, Tamiko

2014-01-01

An improved synthetic route has been developed for the preparation of methyl 1-fluoroindan-1-carboxylate (FICA Me ester) from 1-indanone. Methyl 4-methyl-1-fluoroindan-1-carboxylate (4-Me-FICA Me ester) was also prepared following the same procedure.

Are clinicopathological features of colorectal cancers with methylation in half of CpG island methylator phenotype panel markers different from those of CpG island methylator phenotype-high colorectal cancers?

PubMed

Bae, Jeong Mo; Rhee, Ye-Young; Kim, Kyung Ju; Wen, Xianyu; Song, Young Seok; Cho, Nam-Yun; Kim, Jung Ho; Kang, Gyeong Hoon

2016-01-01

CpG island methylator phenotype (CIMP)-high (CIMP-H) colorectal cancer (CRC) is defined when a tumor shows methylation at greater than or equal to 60% of CIMP panel markers. Although CRCs with methylation at 50% of panel markers are classified as CIMP-low/CIMP-0 tumors, little is known regarding the clinicopathological and molecular features of CRCs with methylation at 4/8 panel markers (4/8 methylated markers) and whether they are akin to CIMP-H or CIMP-low/CIMP-0 CRCs in terms of their clinicopathological or molecular features. A total of 1164 cases of surgically resected CRC were analyzed for their methylation status in 8 CIMP panel markers, and the frequencies of various clinicopathological and molecular features were compared between CRCs with 0/8, 1/8 to 3/8, 4/8, and 5/8 to 8/8 methylated markers. CRCs with 4/8 methylated markers were closer to CRCs with 5/8 to 8/8 methylated markers in terms of sex distribution, mucin production, serration, nodal metastasis, CK7 expression, CK20 loss, and CDX2 loss frequencies and overall survival rate. CRCs with methylation at 4/8 markers were closer to CRCs with 1/8 to 3/8 methylated markers in terms of less frequent right colon location and poor differentiation. CRCs with 4/8 methylated markers showed the shortest overall survival time compared with CRCs with 0/8, 1/8 to 3/8, 4/8, or 5/8 to 8/8 methylated markers. In terms of clinicopathological and molecular features, CRCs with 4/8 methylated markers appeared to be closer to CIMP-H than to CIMP-low/CIMP-0 and would thus be better classified as CIMP-H if the CRCs require classification into either CIMP-H or CIMP-low/CIMP-0. Copyright © 2015 Elsevier Inc. All rights reserved.

NASA Engineering and Safety Center (NESC) Enhanced Melamine (ML) Foam Acoustic Test (NEMFAT)

NASA Technical Reports Server (NTRS)

McNelis, Anne M.; Hughes, William O.; McNelis, Mark E.

2014-01-01

The NASA Engineering and Safety Center (NESC) funded a proposal to achieve initial basic acoustic characterization of ML (melamine) foam, which could serve as a starting point for a future, more comprehensive acoustic test program for ML foam. A project plan was developed and implemented to obtain acoustic test data for both normal and enhanced ML foam. This project became known as the NESC Enhanced Melamine Foam Acoustic Test (NEMFAT). This document contains the outcome of the NEMFAT project.

40 CFR 721.10121 - Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched.

Code of Federal Regulations, 2012 CFR

2012-07-01

...)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched. 721.10121 Section 721.10121 Protection of Environment...)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as poly[oxy(methyl-1,2-ethanediyl)], .alpha...

40 CFR 721.10121 - Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched.

Code of Federal Regulations, 2010 CFR

2010-07-01

...)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched. 721.10121 Section 721.10121 Protection of Environment...)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as poly[oxy(methyl-1,2-ethanediyl)], .alpha...

40 CFR 721.10121 - Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched.

Code of Federal Regulations, 2013 CFR

2013-07-01

...)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched. 721.10121 Section 721.10121 Protection of Environment...)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as poly[oxy(methyl-1,2-ethanediyl)], .alpha...

40 CFR 721.10121 - Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched.

Code of Federal Regulations, 2014 CFR

2014-07-01

...)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched. 721.10121 Section 721.10121 Protection of Environment...)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as poly[oxy(methyl-1,2-ethanediyl)], .alpha...

40 CFR 721.10121 - Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched.

Code of Federal Regulations, 2011 CFR

2011-07-01

...)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched. 721.10121 Section 721.10121 Protection of Environment...)], .alpha.-methyl-.omega.-(4-nonylphenoxy)-, branched. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as poly[oxy(methyl-1,2-ethanediyl)], .alpha...

How does methylation suppress the electron-induced decomposition of 1-methyl-nitroimidazoles?

NASA Astrophysics Data System (ADS)

Kossoski, F.; Varella, M. T. do N.

2017-10-01

The efficient decomposition of nitroimidazoles (NIs) by low energy electrons is believed to underlie their radiosensitizing properties. Recent dissociative electron attachment (DEA) measurements showed that methylation at the N1 site unexpectedly suppresses the electron-induced reactions in 4(5)-NI. We report theoretical results that provide a clear interpretation of that astounding finding. Around 1.5 eV, DEA reactions into several fragments are initiated by a π* resonance, not considered in previous studies. The autoionization lifetime of this anion state, which limits the predissociation dynamics, is considerably shorter in the methylated species, thereby suppressing the DEA signals. On the other hand, the lifetime of the π* resonance located around 3 eV is less affected by methylation, which explains why DEA is still observed at these energies. Our results demonstrate how even a simple methylation can significantly modify the probabilities for DEA reactions, which may be significant for NI-based cancer therapy.

DNA Methylation and BMI: Investigating Identified Methylation Sites at HIF3A in a Causal Framework.

PubMed

Richmond, Rebecca C; Sharp, Gemma C; Ward, Mary E; Fraser, Abigail; Lyttleton, Oliver; McArdle, Wendy L; Ring, Susan M; Gaunt, Tom R; Lawlor, Debbie A; Davey Smith, George; Relton, Caroline L

2016-05-01

Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ∼1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

CytometryML: a data standard which has been designed to interface with other standards

NASA Astrophysics Data System (ADS)

Leif, Robert C.

2007-02-01

Because of the differences in the requirements, needs, and past histories including existing standards of the creating organizations, a single encompassing cytology-pathology standard will not, in the near future, replace the multiple existing or under development standards. Except for DICOM and FCS, these standardization efforts are all based on XML. CytometryML is a collection of XML schemas, which are based on the Digital Imaging and Communications in Medicine (DICOM) and Flow Cytometry Standard (FCS) datatypes. The CytometryML schemas contain attributes that link them to the DICOM standard and FCS. Interoperability with DICOM has been facilitated by, wherever reasonable, limiting the difference between CytometryML and the previous standards to syntax. In order to permit the Resource Description Framework, RDF, to reference the CytometryML datatypes, id attributes have been added to many CytometryML elements. The Laboratory Digital Imaging Project (LDIP) Data Exchange Specification and the Flowcyt standards development effort employ RDF syntax. Documentation from DICOM has been reused in CytometryML. The unity of analytical cytology was demonstrated by deriving a microscope type and a flow cytometer type from a generic cytometry instrument type. The feasibility of incorporating the Flowcyt gating schemas into CytometryML has been demonstrated. CytometryML is being extended to include many of the new DICOM Working Group 26 datatypes, which describe patients, specimens, and analytes. In situations where multiple standards are being created, interoperability can be facilitated by employing datatypes based on a common set of semantics and building in links to standards that employ different syntax.

DNA methylation changes detected by methylation-sensitive amplified polymorphism in two contrasting rice genotypes under salt stress.

PubMed

Wang, Wensheng; Zhao, Xiuqin; Pan, Yajiao; Zhu, Linghua; Fu, Binying; Li, Zhikang

2011-09-20

DNA methylation, one of the most important epigenetic phenomena, plays a vital role in tuning gene expression during plant development as well as in response to environmental stimuli. In the present study, a methylation-sensitive amplified polymorphism (MSAP) analysis was performed to profile DNA methylation changes in two contrasting rice genotypes under salt stress. Consistent with visibly different phenotypes in response to salt stress, epigenetic markers classified as stable inter-cultivar DNA methylation differences were determined between salt-tolerant FL478 and salt-sensitive IR29. In addition, most tissue-specific DNA methylation loci were conserved, while many of the growth stage-dependent DNA methylation loci were dynamic between the two genotypes. Strikingly, salt stress induced a decrease in DNA methylation specifically in roots at the seedling stage that was more profound in IR29 than in the FL478. This result may indicate that demethylation of genes is an active epigenetic response to salt stress in roots at the seedling stage, and helps to further elucidate the implications of DNA methylation in crop growth and development. Copyright © 2011. Published by Elsevier Ltd.

Protein methylation in pea chloroplasts. [Pisum sativum

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1990-07-01

The methylation of chloroplast proteins has been investigated by incubating intact pea (Pisum sativum) chloroplasts with ({sup 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. Onemore » 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 ({sup 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 ({sup 3}H)methyl group.« less

MTHFR methylation moderates the impact of smoking on DNA methylation at AHRR for African American young adults.

PubMed

Beach, Steven R H; Lei, Man Kit; Ong, Mei Ling; Brody, Gene H; Dogan, Meeshanthini V; Philibert, Robert A

2017-09-01

Smoking has been shown to have a large, reliable, and rapid effect on demethylation of AHRR, particularly at cg05575921, suggesting that methylation may be used as an index of cigarette consumption. Because the availability of methyl donors may also influence the degree of demethylation in response to smoking, factors that affect the activity of methylene tetrahydrofolate reductase (MTHFR), a key regulator of methyl group availability, may be of interest. In the current investigation, we examined the extent to which individual differences in methylation of MTHFR moderated the association between smoking and demethylation at cg05575921 as well as at other loci on AHRR associated with a main effect of smoking. Using a discovery sample (AIM, N = 293), and a confirmatory sample (SHAPE, N = 368) of young adult African Americans, degree of methylation of loci in the first exon of MTHFR was associated with amplification of the association between smoking and AHRR demethylation at cg05575921. However, genetic variation at a commonly studied MTHFR variant, C677T, did not influence cg05575921 methylation. The significant interaction between MTHFR methylation and the smoking-induced response at cg05575921 suggests a role for individual differences in methyl cycle regulation in understanding the effects of cigarette consumption on genome wide DNA methylation. © 2017 Wiley Periodicals, Inc.

Methyl bromide determination in selected foods by headspace technique.

PubMed

Daft, J L

1993-01-01

A headspace method used earlier for determining methyl bromide (MB) in assorted nuts and peanut butters has been successfully applied to other foods that could potentially contain traces of this toxic fumigant. The foods tested include 63 off-the-shelf spices and seasonings, 83 table-ready items (grain-based, dried, or highly seasoned), 30 dried fruits and trail mixes, and 38 oil-based items (oil-seeds, cooking oils, or spicy oil-based dressings). Sample headspace gas is produced by blending < or = 50 g sample in 250 +/- 50 mL aqueous solution in a sealed 1000 mL blender cup. After equilibration at 25 degrees C, the headspace is sampled with a gas-tight syringe and injected into a dual column-dual detector gas chromatograph. One determination is made with a 20% OV-101 packed column and a 63Ni electron capture detector (ECD), the other with a GS-Q wide-bore capillary column and a Hall electrolytic conductivity detector (HECD). Of the approximately 200 samples tested, none contained detectable MB residue at a quantitation limit < 100 ng/g sample. All fortified samples yielded MB recovery. Samples were fortified at levels ranging from 78 to 3250 ng MB/g. Recoveries ranged from a mean high of 56% for spices and seasonings to a mean low of 30% for oil-based foods. The overall recovery and CV, including the results from assorted nuts and peanut butters, were 46 and 33%, respectively.

Atmospheric Methyl Chloride

DOE Data Explorer

Khalil, M. A. K. [Portland State Univ., Portland, OR (United States); Rasmussen, R. A. [Oregon Graduate Institute, Portland, OR (USA)

1999-01-01

This data set provides monthly average concentrations of atmospheric methyl chloride taken from seven locations distributed among the polar, middle, and tropical latitudes of both hemispheres. The seven primary sites include Pt. Barrow, Alaska; Cape Kumukahi and Mauna Loa, Hawaii; Cape Matatula, Samoa; Cape Grim, Tasmania; and the South Pole and Palmer Station, Antarctica. Concentration measurements from these seven sites cover a period of 16 years, extending from 1981-1997. Monthly data taken between 1987-1989 from 20 short-term sites and vertical distribution measured at various latitudes are also provided. Air samples were collected from various sites in stainless steel flasks and methyl chloride concentrations were measured using an Electron Capture Gas Chromatograph. Concentrations are reported as mixing ratios in dry air. The concentrations are determined by using a set of calibration standards that are referenced against a primary standard which is also used to establish the absolute concentration. The primary standards were prepared by the investigators in the absence of an available standard from a centralized location. The data are useful in global methyl chloride budget analyses and for determining the atmospheric distribution and trends of methyl chloride and estimating the total emissions at various latitudes.

DocML: A Digital Library of University Data.

ERIC Educational Resources Information Center

Papadakis, Ioannis; Karakoidas, Vassileios; Chrissikopoulos, Vassileios

2002-01-01

Describes DocML, a Web-based digital library of university data that is used to build a system capable of preserving and managing student assignments. Topics include requirements for a digital library of university data; metadata and XML; three-tier architecture; user interface; searching; browsing; content delivery; and administrative issues.…

CpG island methylator phenotype in colorectal cancer

PubMed Central

Toyota, Minoru; Ahuja, Nita; Ohe-Toyota, Mutsumi; Herman, James G.; Baylin, Stephen B.; Issa, Jean-Pierre J.

1999-01-01

Aberrant methylation of promoter region CpG islands is associated with transcriptional inactivation of tumor-suppressor genes in neoplasia. To understand global patterns of CpG island methylation in colorectal cancer, we have used a recently developed technique called methylated CpG island amplification to examine 30 newly cloned differentially methylated DNA sequences. Of these 30 clones, 19 (63%) were progressively methylated in an age-dependent manner in normal colon, 7 (23%) were methylated in a cancer-specific manner, and 4 (13%) were methylated only in cell lines. Thus, a majority of CpG islands methylated in colon cancer are also methylated in a subset of normal colonic cells during the process of aging. In contrast, methylation of the cancer-specific clones was found exclusively in a subset of colorectal cancers, which appear to display a CpG island methylator phenotype (CIMP). CIMP+ tumors also have a high incidence of p16 and THBS1 methylation, and they include the majority of sporadic colorectal cancers with microsatellite instability related to hMLH1 methylation. We thus define a pathway in colorectal cancer that appears to be responsible for the majority of sporadic tumors with mismatch repair deficiency. PMID:10411935

Methylation patterns in marginal zone lymphoma.

PubMed

Arribas, Alberto J; Bertoni, Francesco

Promoter DNA methylation is a major regulator of gene expression and transcription. The identification of methylation changes is important for understanding disease pathogenesis, for identifying prognostic markers and can drive novel therapeutic approaches. In this review we summarize the current knowledge regarding DNA methylation in MALT lymphoma, splenic marginal zone lymphoma, nodal marginal zone lymphoma. Despite important differences in the study design for different publications and the existence of a sole large and genome-wide methylation study for splenic marginal zone lymphoma, it is clear that DNA methylation plays an important role in marginal zone lymphomas, in which it contributes to the inactivation of tumor suppressors but also to the expression of genes sustaining tumor cell survival and proliferation. Existing preclinical data provide the rationale to target the methylation machinery in these disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl.

PubMed

Chin, Melanie P; Wrolstad, Danielle; Bakris, George L; Chertow, Glenn M; de Zeeuw, Dick; Goldsberry, Angie; Linde, Peter G; McCullough, Peter A; McMurray, John J; Wittes, Janet; Meyer, Colin J

2014-12-01

A phase 3 randomized clinical trial was designed to test whether bardoxolone methyl, a nuclear factor erythroid-2-related factor 2 (Nrf2) activator, slows progression to end-stage renal disease in patients with stage 4 chronic kidney disease and type 2 diabetes mellitus. The trial was terminated because of an increase in heart failure in the bardoxolone methyl group; many of the events were clinically associated with fluid retention. We randomized 2,185 patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD) (estimated glomerular filtration rate 15 to <30 mL min(-1) 1.73 m(-2)) to once-daily bardoxolone methyl (20 mg) or placebo. We used classification and regression tree analysis to identify baseline factors predictive of heart failure or fluid overload events. Elevated baseline B-type natriuretic peptide and previous hospitalization for heart failure were identified as predictors of heart failure events; bardoxolone methyl increased the risk of heart failure by 60% in patients with these risk factors. For patients without these baseline characteristics, the risk for heart failure events among bardoxolone methyl- and placebo-treated patients was similar (2%). The same risk factors were also identified as predictors of fluid overload and appeared to be related to other serious adverse events. Bardoxolone methyl contributed to events related to heart failure and/or fluid overload in a subpopulation of susceptible patients with an increased risk for heart failure at baseline. Careful selection of participants and vigilant monitoring of the study drug will be required in any future trials of bardoxolone methyl to mitigate the risk of heart failure and other serious adverse events. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

DNA methylation-based variation between human populations.

PubMed

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.

Host cells and methods for producing 3-methyl-2-buten-1-ol, 3-methyl-3-buten-1-ol, and 3-methyl-butan-1-ol

DOEpatents

Chou, Howard H [Berkeley, CA; Keasling, Jay D [Berkeley, CA

2011-07-26

The invention provides for a method for producing a 5-carbon alcohol in a genetically modified host cell. In one embodiment, the method comprises culturing a genetically modified host cell which expresses a first enzyme capable of catalyzing the dephosphorylation of an isopentenyl pyrophosphate (IPP) or dimethylallyl diphosphate (DMAPP), such as a Bacillus subtilis phosphatase (YhfR), under a suitable condition so that 5-carbon alcohol is 3-methyl-2-buten-1-ol and/or 3-methyl-3-buten-1-ol is produced. Optionally, the host cell may further comprise a second enzyme capable of reducing a 3-methyl-2-buten-1-ol to 3-methyl-butan-1-ol, such as a reductase.

ELUCIDATING THE PATHWAY FOR ARSENIC METHYLATION

EPA Science Inventory

Enzymatically-catalyzed methylation of arsenic is part of a metabolic pathway that converts inorganic arsenic into methylated products. Hence, in humans chronically exposed to inorganic arsenic, methyl and dimethyl arsenic account for most of the arsenic that is excreted in the ...

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Porterfield, Jessica P.; Bross, David H.; Ruscic, Branko

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 (CH 3COOCH 3) and methyl butanoate (CH 3CH 2CH 2COOCH 3) 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 ofmore » 300 – 1600 K were explored. Decomposition of CH 3COOCH 3 commences at 1000 K and the initial products are (CH 2=C=O and CH 3OH). As the micro-reactor is heated to 1300 K, a mixture of (CH 2=C=O and CH 3OH, CH 3, CH 2=O, H, CO, CO 2) appears. The thermal cracking of CH 3CH 2CH 2COOCH 3 begins at 800 K with the formation of (CH 3CH 2CH=C=O, CH 3OH). By 1300 K, the pyrolysis of methyl butanoate yields a complex mixture of (CH 3CH 2CH=C=O, CH 3OH, CH 3, CH 2=O, CO, CO 2, CH 3CH=CH 2, CH 2CHCH 2, CH 2=C=CH 2, HCCCH 2, CH 2=C=C=O, CH 2=CH 2, HCΞCH, CH 2=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 CH 2-COOCH 3. The lowest energy fragmentation will be a 4-center elimination of methanol to form the ketene, RCH=C=O. At higher temperatures, concerted fragmentation to radicals will ensue to produce a mixture of species: (RCH 2 + CO 2 + CH 3) and (RCH 2 + CO + CH 2=O + H). Thermal cracking of the β C-C bond of the methyl ester will generate the radicals (R and H) as well as CH 2=C=O + CH 2=O. The thermochemistry of methyl acetate and its fragmentation products have been obtained via the Active Thermochemical Tables (ATcT) approach, resulting in �

Genome-Wide Methylation Analyses in Glioblastoma Multiforme

PubMed Central

Lai, Rose K.; Chen, Yanwen; Guan, Xiaowei; Nousome, Darryl; Sharma, Charu; Canoll, Peter; Bruce, Jeffrey; Sloan, Andrew E.; Cortes, Etty; Vonsattel, Jean-Paul; Su, Tao; Delgado-Cruzata, Lissette; Gurvich, Irina; Santella, Regina M.; Ostrom, Quinn; Lee, Annette; Gregersen, Peter; Barnholtz-Sloan, Jill

2014-01-01

Few studies had investigated genome-wide methylation in glioblastoma multiforme (GBM). Our goals were to study differential methylation across the genome in gene promoters using an array-based method, as well as repetitive elements using surrogate global methylation markers. The discovery sample set for this study consisted of 54 GBM from Columbia University and Case Western Reserve University, and 24 brain controls from the New York Brain Bank. We assembled a validation dataset using methylation data of 162 TCGA GBM and 140 brain controls from dbGAP. HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486 informative CpG sites in both the discovery and validation datasets. Global methylation levels were assessed by analysis of L1 retrotransposon (LINE1), 5 methyl-deoxycytidine (5m-dC) and 5 hydroxylmethyl-deoxycytidine (5hm-dC) in the discovery dataset. We validated a total of 1548 CpG sites (1307 genes) that were differentially methylated in GBM compared to controls. There were more than twice as many hypomethylated genes as hypermethylated ones. Both the discovery and validation datasets found 5 tumor methylation classes. Pathway analyses showed that the top ten pathways in hypomethylated genes were all related to functions of innate and acquired immunities. Among hypermethylated pathways, transcriptional regulatory network in embryonic stem cells was the most significant. In the study of global methylation markers, 5m-dC level was the best discriminant among methylation classes, whereas in survival analyses, high level of LINE1 methylation was an independent, favorable prognostic factor in the discovery dataset. Based on a pathway approach, hypermethylation in genes that control stem cell differentiation were significant, poor prognostic factors of overall survival in both the discovery and validation datasets. Approaches that targeted these methylated genes may be a future therapeutic goal. PMID:24586730

DNA methylation at hepatitis B viral integrants is associated with methylation at flanking human genomic sequences

PubMed Central

Watanabe, Yoshiyuki; Yamamoto, Hiroyuki; Oikawa, Ritsuko; Toyota, Minoru; Yamamoto, Masakazu; Kokudo, Norihiro; Tanaka, Shinji; Arii, Shigeki; Yotsuyanagi, Hiroshi; Koike, Kazuhiko; Itoh, Fumio

2015-01-01

Integration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)–related hepatocellular carcinoma. However, the molecular details and clinical impact of HBV integration on either human or HBV epigenomes are unknown. Here, we show that methylation of the integrated HBV DNA is related to the methylation status of the flanking human genome. We developed a next-generation sequencing-based method for structural methylation analysis of integrated viral genomes (denoted G-NaVI). This method is a novel approach that enables enrichment of viral fragments for sequencing using unique baits based on the sequence of the HBV genome. We detected integrated HBV sequences in the genome of the PLC/PRF/5 cell line and found variable levels of methylation within the integrated HBV genomes. Allele-specific methylation analysis revealed that the HBV genome often became significantly methylated when integrated into highly methylated host sites. After integration into unmethylated human genome regions such as promoters, however, the HBV DNA remains unmethylated and may eventually play an important role in tumorigenesis. The observed dynamic changes in DNA methylation of the host and viral genomes may functionally affect the biological behavior of HBV. These findings may impact public health given that millions of people worldwide are carriers of HBV. We also believe our assay will be a powerful tool to increase our understanding of the various types of DNA virus-associated tumorigenesis. PMID:25653310

40 CFR 721.1645 - Benzenesulfonic acid, 4-methyl-, reaction products with oxirane mono[(C10-16-alkyloxy)methyl...

Code of Federal Regulations, 2011 CFR

2011-07-01

...-, reaction products with oxirane mono[(C10-16-alkyloxy)methyl] derivatives and 2,2,4(or 2,4,4)-trimethyl-1,6... Specific Chemical Substances § 721.1645 Benzenesulfonic acid, 4-methyl-, reaction products with oxirane...-methyl-, reaction products with oxirane mono[(C10-16-alkyloxy)methyl] derivatives and 2,2,4(or 2,4,4...

40 CFR 721.1645 - Benzenesulfonic acid, 4-methyl-, reaction products with oxirane mono[(C10-16-alkyloxy)methyl...

Code of Federal Regulations, 2010 CFR

2010-07-01

...-, reaction products with oxirane mono[(C10-16-alkyloxy)methyl] derivatives and 2,2,4(or 2,4,4)-trimethyl-1,6... Specific Chemical Substances § 721.1645 Benzenesulfonic acid, 4-methyl-, reaction products with oxirane...-methyl-, reaction products with oxirane mono[(C10-16-alkyloxy)methyl] derivatives and 2,2,4(or 2,4,4...

Controlling DNA methylation: many roads to one modification.

PubMed

Freitag, Michael; Selker, Eric U

2005-04-01

Genetic, biochemical and cytological studies on DNA methylation in several eukaryotic organisms have resulted in leaps of understanding in the past three years. Discoveries of mechanistic links between DNA methylation and histone methylation, and between these processes and RNA interference (RNAi) machineries have reinvigorated the field. The details of the connections between DNA methylation, histone modifications and RNA silencing remain to be elucidated, but it is already clear that no single pathway accounts for all DNA methylation found in eukaryotes. Rather, different taxa use one or more of several general mechanisms to control methylation. Despite recent progress, classic questions remain, including: What are the signals for DNA methylation? Are "de novo" and "maintenance" methylation truly separate processes? How is DNA methylation regulated?

The additional benefit of the ML Flow test to classify leprosy patients.

PubMed

Bührer-Sékula, Samira; Illarramendi, Ximena; Teles, Rose B; Penna, Maria Lucia F; Nery, José Augusto C; Sales, Anna Maria; Oskam, Linda; Sampaio, Elizabeth P; Sarno, Euzenir N

2009-08-01

The use of the skin lesion counting classification leads to both under and over diagnosis of leprosy in many instances. Thus, there is a need to complement this classification with another simple and robust test for use in the field. Data of 202 untreated leprosy patients diagnosed at FIOCRUZ, Rio de Janeiro, Brazil, was analyzed. There were 90 patients classified as PB and 112 classified as MB according to the reference standard. The BI was positive in 111 (55%) patients and the ML Flow test in 116 (57.4%) patients. The ML Flow test was positive in 95 (86%) of the patients with a positive BI. The lesion counting classification was confirmed by both BI and ML Flow tests in 65% of the 92 patients with 5 or fewer lesions, and in 76% of the 110 patients with 6 or more lesions. The combination of skin lesion counting and the ML Flow test results yielded a sensitivity of 85% and a specificity of 87% for MB classification, and correctly classified 86% of the patients when compared to the standard reference. A considerable proportion of the patients (43.5%) with discordant test results in relation to standard classification was in reaction. The use of any classification system has limitations, especially those that oversimplify a complex disease such as leprosy. In the absence of an experienced dermatologist and slit skin smear, the ML Flow test could be used to improve treatment decisions in field conditions.

ELEVATED BLOOD HARMANE (1-METHYL-9H-PYRIDO[3,4-B]INDOLE) CONCENTRATIONS IN ESSENTIAL TREMOR

PubMed Central

Louis, Elan D.; Jiang, Wendy; Pellegrino, Kathryn M.; Rios, Eileen; Factor-Litvak, Pam; Henchcliffe, Claire; Zheng, Wei

2008-01-01

Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors likely play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. In 2002, we demonstrated elevated blood harmane concentrations in an initial sample of 100 ET cases compared to 100 controls. Between 2002 and 2007, we assembled a new and larger sample of ET cases and controls. We now attempt to replicate our previous findings. Cases and controls were frequency-matched on age, gender, and race. Blood harmane concentrations were quantified by high performance liquid chromatography. Subjects comprised 150 ET cases and 135 controls (mean age 65.3 ± 15.5 vs. 65.5 ± 14.2 years, p = 0.94). Mean log blood harmane concentration was ∼50% higher in cases than controls (0.50 ± 0.54 g -10/ml vs. 0.35 ± 0.62 g-10/ml, p = 0.038). In a logistic regression analysis, log blood harmane concentration was associated with ET (ORadjusted 1.56, 95% CI 1.01 - 2.42, p = 0.04), and odds of ET was 1.90 (95% CI 1.07 - 3.39, p = 0.029) in the highest vs. lowest log blood harmane tertile. Log blood harmane was highest in ET cases with familial ET (0.53 ± 0.57 g -10/ml), intermediate in cases with sporadic ET (0.43 ± 0.45 g -10/ml) and lowest in controls (0.35 ± 0.62 g-10/ml) (test for trend, p = 0.026). Blood harmane appears to be elevated in ET. The higher concentrations in familial ET suggests that the mechanism may involve genetic factors. PMID:18242711

The Ml Magnitude Scale In Italy

NASA Astrophysics Data System (ADS)

Gasperini, P.; Lolli, B.; Filippucci, M.; de Simoni, B.

To improve the reliability of Ml magnitude estimates in Italy, we have updated the database of real Wood-Anderson (WA) and of simulated Wood Anderson (SWA) am- plitudes recently revised by Gasperini (2002). This was done by the re-reading of orig- inal WA seismograms, made available by the SISMOS Project of the Istituto Nazionale di Geofisica (INGV), as well as by the analysis of further Very Broad Band (VBB) recordings of the MEDNET network of INGV for the period from 1996 to 1998. The full operability, in the last five years, of a VBB station located exactly at the same site (TRI) of a former WA instrument allowed us to reliably infer a new attenuation function from the joined WA and SWA dataset. We found a significant deviation of the attenuation law from the standard Richter table at distances larger than 400 km where the latter overestimates the magnitude up to about 0.3 units. We also computed regionalized attenuation functions accounting for the differences in the propagation properties of seismic waves between the Adriatic (less attenuating) and Tyrrhenian (more attenuating) sides of the Italian peninsula. Using this improved Ml magnitude database we were also able to further improve the computation of duration (Md) and amplitude (Ma) magnitudes computed from short period vertical seismometers of the INGV as well as to analyze the time variation of the station calibrations. We found that the absolute amplification of INGV stations is underestimated almost exactly by a factor 2 starting from the entering upon in operation of the digital acquisition system at INGV in middle 1984.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-01-01

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

Methylation detection oligonucleotide microarray analysis: a high-resolution method for detection of CpG island methylation

PubMed Central

Kamalakaran, Sitharthan; Kendall, Jude; Zhao, Xiaoyue; Tang, Chunlao; Khan, Sohail; Ravi, Kandasamy; Auletta, Theresa; Riggs, Michael; Wang, Yun; Helland, Åslaug; Naume, Bjørn; Dimitrova, Nevenka; Børresen-Dale, Anne-Lise; Hicks, Jim; Lucito, Robert

2009-01-01

Methylation of CpG islands associated with genes can affect the expression of the proximal gene, and methylation of non-associated CpG islands correlates to genomic instability. This epigenetic modification has been shown to be important in many pathologies, from development and disease to cancer. We report the development of a novel high-resolution microarray that detects the methylation status of over 25 000 CpG islands in the human genome. Experiments were performed to demonstrate low system noise in the methodology and that the array probes have a high signal to noise ratio. Methylation measurements between different cell lines were validated demonstrating the accuracy of measurement. We then identified alterations in CpG islands, both those associated with gene promoters, as well as non-promoter-associated islands in a set of breast and ovarian tumors. We demonstrate that this methodology accurately identifies methylation profiles in cancer and in principle it can differentiate any CpG methylation alterations and can be adapted to analyze other species. PMID:19474344

Role of UHRF1 in de novo DNA methylation in oocytes and maintenance methylation in preimplantation embryos

PubMed Central

Toh, Hidehiro; Ohishi, Hiroaki; Sharif, Jafar; Koseki, Haruhiko; Sasaki, Hiroyuki

2017-01-01

The methylation of cytosine at CG sites in the mammalian genome is dynamically reprogrammed during gametogenesis and preimplantation development. It was previously shown that oocyte-derived DNMT1 (a maintenance methyltransferase) is essential for maintaining and propagating CG methylation at imprinting control regions in preimplantation embryos. In mammalian somatic cells, hemimethylated-CG-binding protein UHRF1 plays a critical role in maintaining CG methylation by recruiting DNMT1 to hemimethylated CG sites. However, the role of UHRF1 in oogenesis and preimplantation development is unknown. In the present study, we show that UHRF1 is mainly, but not exclusively, localized in the cytoplasm of oocytes and preimplantation embryos. However, smaller amounts of UHRF1 existed in the nucleus, consistent with the expected role in DNA methylation. We then generated oocyte-specific Uhrf1 knockout (KO) mice and found that, although oogenesis was itself unaffected, a large proportion of the embryos derived from the KO oocytes died before reaching the blastocyst stage (a maternal effect). Whole genome bisulfite sequencing revealed that blastocysts derived from KO oocytes have a greatly reduced level of CG methylation, suggesting that maternal UHRF1 is essential for maintaining CG methylation, particularly at the imprinting control regions, in preimplantation embryos. Surprisingly, UHRF1 was also found to contribute to de novo CG and non-CG methylation during oocyte growth: in Uhrf1 KO oocytes, transcriptionally-inactive regions gained less methylation, while actively transcribed regions, including the imprinting control regions, were unaffected or only slightly affected. We also found that de novo methylation was defective during the late stage of oocyte growth. To the best of our knowledge, this is the first study to demonstrate the role of UHRF1 in de novo DNA methylation in vivo. Our study reveals multiple functions of UHRF1 during the global epigenetic reprogramming of

SED-ED, a workflow editor for computational biology experiments written in SED-ML.

PubMed

Adams, Richard R

2012-04-15

The simulation experiment description markup language (SED-ML) is a new community data standard to encode computational biology experiments in a computer-readable XML format. Its widespread adoption will require the development of software support to work with SED-ML files. Here, we describe a software tool, SED-ED, to view, edit, validate and annotate SED-ML documents while shielding end-users from the underlying XML representation. SED-ED supports modellers who wish to create, understand and further develop a simulation description provided in SED-ML format. SED-ED is available as a standalone Java application, as an Eclipse plug-in and as an SBSI (www.sbsi.ed.ac.uk) plug-in, all under an MIT open-source license. Source code is at https://sed-ed-sedmleditor.googlecode.com/svn. The application itself is available from https://sourceforge.net/projects/jlibsedml/files/SED-ED/.

Analysis of DNA methylation of perennial ryegrass under drought using the methylation-sensitive amplification polymorphism (MSAP) technique.

PubMed

Tang, Xiao-Mei; Tao, Xiang; Wang, Yan; Ma, Dong-Wei; Li, Dan; Yang, Hong; Ma, Xin-Rong

2014-12-01

Perennial ryegrass (Lolium perenne), an excellent grass for forage and turf, is widespread in temperate regions. Drought is an important factor that limits its growth, distribution, and yield. DNA methylation affects gene expression and plays an important role in adaptation to adverse environments. In this study, the DNA methylation changes in perennial ryegrass under drought stress were assessed using methylation-sensitive amplified polymorphism (MSAP). After 15 days of drought stress treatment, the plant height was less than half of the control, and the leaves were smaller and darker. Genome-wide, a total of 652 CCGG sites were detected by MSAP. The total methylation level was 57.67 and 47.39 % in the control and drought treatment, respectively, indicating a decrease of 10.28 % due to drought exposure. Fifteen differentially displayed DNA fragments in MSAP profiles were cloned for sequencing analysis. The results showed that most of the genes involved in stress responses. The relative expression levels revealed that three demethylated fragments were up-regulated. The expression of a predicted retrotransposon increased significantly, changing from hypermethylation to non-methylation. Although the extent of methylation in two other genes decreased, the sites of methylation remained, and the expression increased only slightly. All of these results suggested that drought stress decreased the total DNA methylation level in perennial ryegrass and demethylation up-regulated related gene expressions and that the extent of methylation was negatively correlated with expression. Overall, the induced epigenetic changes in genome probably are an important regulatory mechanism for acclimating perennial ryegrass to drought and possibly other environmental stresses.

Transgenerational epigenetics: Inheritance of global cytosine methylation and methylation-related epigenetic markers in the shrub Lavandula latifolia.

PubMed

Herrera, Carlos M; Alonso, Conchita; Medrano, Mónica; Pérez, Ricardo; Bazaga, Pilar

2018-04-01

The ecological and evolutionary significance of natural epigenetic variation (i.e., not based on DNA sequence variants) variation will depend critically on whether epigenetic states are transmitted from parents to offspring, but little is known on epigenetic inheritance in nonmodel plants. We present a quantitative analysis of transgenerational transmission of global DNA cytosine methylation (= proportion of all genomic cytosines that are methylated) and individual epigenetic markers (= methylation status of anonymous MSAP markers) in the shrub Lavandula latifolia. Methods based on parent-offspring correlations and parental variance component estimation were applied to epigenetic features of field-growing plants ('maternal parents') and greenhouse-grown progenies. Transmission of genetic markers (AFLP) was also assessed for reference. Maternal parents differed significantly in global DNA cytosine methylation (range = 21.7-36.7%). Greenhouse-grown maternal families differed significantly in global methylation, and their differences were significantly related to maternal origin. Methylation-sensitive amplified polymorphism (MSAP) markers exhibited significant transgenerational transmission, as denoted by significant maternal variance component of marker scores in greenhouse families and significant mother-offspring correlations of marker scores. Although transmission-related measurements for global methylation and MSAP markers were quantitatively lower than those for AFLP markers taken as reference, this study has revealed extensive transgenerational transmission of genome-wide global cytosine methylation and anonymous epigenetic markers in L. latifolia. Similarity of results for global cytosine methylation and epigenetic markers lends robustness to this conclusion, and stresses the value of considering both types of information in epigenetic studies of nonmodel plants. © 2018 Botanical Society of America.

21 CFR 173.385 - Sodium methyl sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium methyl sulfate. 173.385 Section 173.385... CONSUMPTION Specific Usage Additives § 173.385 Sodium methyl sulfate. Sodium methyl sulfate may be present in... pectin by sulfuric acid and methyl alcohol and subsequent treatment with sodium bicarbonate. (b) It does...

Effect of oxygen, methyl mercaptan, and methyl chloride on friction behavior of copper-iron contacts

NASA Technical Reports Server (NTRS)

Buckley, D. H.

1978-01-01

Sliding friction experiments were conducted with an iron rider on a copper disk and a copper rider on an iron disk. The sputter cleaned iron and copper disk surfaces were saturated with oxygen, methyl mercaptan, and methyl chloride at atmospheric pressure. Auger emission spectroscopy was used to monitor the surfaces. Lower friction was obtained in all experiments with the copper rider sliding on the iron disk than when the couple was reversed. For both iron and copper disks, methyl mercaptan gave the best surface coverage and was most effective in reducing friction. For both iron and copper disks, methyl chloride was the least effective in reducing friction. With sliding, copper transferred to iron and iron to copper.

GeoSciML v3.0 - a significant upgrade of the CGI-IUGS geoscience data model

NASA Astrophysics Data System (ADS)

Raymond, O.; Duclaux, G.; Boisvert, E.; Cipolloni, C.; Cox, S.; Laxton, J.; Letourneau, F.; Richard, S.; Ritchie, A.; Sen, M.; Serrano, J.-J.; Simons, B.; Vuollo, J.

2012-04-01

GeoSciML version 3.0 (http://www.geosciml.org), released in late 2011, is the latest version of the CGI-IUGS* Interoperability Working Group geoscience data interchange standard. The new version is a significant upgrade and refactoring of GeoSciML v2 which was released in 2008. GeoSciML v3 has already been adopted by several major international interoperability initiatives, including OneGeology, the EU INSPIRE program, and the US Geoscience Information Network, as their standard data exchange format for geoscience data. GeoSciML v3 makes use of recently upgraded versions of several Open Geospatial Consortium (OGC) and ISO data transfer standards, including GML v3.2, SWE Common v2.0, and Observations and Measurements v2 (ISO 19156). The GeoSciML v3 data model has been refactored from a single large application schema with many packages, into a number of smaller, but related, application schema modules with individual namespaces. This refactoring allows the use and future development of modules of GeoSciML (eg; GeologicUnit, GeologicStructure, GeologicAge, Borehole) in smaller, more manageable units. As a result of this refactoring and the integration with new OGC and ISO standards, GeoSciML v3 is not backwardly compatible with previous GeoSciML versions. The scope of GeoSciML has been extended in version 3.0 to include new models for geomorphological data (a Geomorphology application schema), and for geological specimens, geochronological interpretations, and metadata for geochemical and geochronological analyses (a LaboratoryAnalysis-Specimen application schema). In addition, there is better support for borehole data, and the PhysicalProperties model now supports a wider range of petrophysical measurements. The previously used CGI_Value data type has been superseded in favour of externally governed data types provided by OGC's SWE Common v2 and GML v3.2 data standards. The GeoSciML v3 release includes worked examples of best practice in delivering geochemical

Effects of 15(S)-15-methyl prostaglandin F2 alpha methyl ester-containing silastic discs in male rats.

PubMed

Kimball, F A; Frielink, R D; Porteus, S E

1978-01-01

Silicone rubber discs containing 15(S)-15-methyl prostaglandin F2 alpha ester (15-Me-PGF2 alpha) in the matrix were implanted in the left side of the scrotums of Sprague-Dawley rats. The effect of 1% and 2% drug concentration was examined for 10, 20, or 28 days and compared with the effects of Silastic discs containing no prostaglandin. The discs containing prostaglandin reduced mean testicular and accessory gland weights. Histologically the testes and epididymides showed decreased or absent spermatogenic elements and hypertrophy of the interstitial cell masses in comparison with other cells. Implanted prostaglandin significantly depressed serum testosterone, luteinizing hormone, and follicle-stimulating hormone (FSH) concentrations when 15-Me-PGF2 alpha plasma concentrations exceeded 2 ng/ml. Hormone concentrations returned to control values as drug concentrations declined. FSH concentrations significantly exceeded control values 10 and 20 days after implantation, when prostaglandin concentration was nondetectable. The acute suppression of all three hormones suggest that 15-Me-PGF2 alpha either may act directly on the tests to suppress testosterone production or may suppress testosterone production or may suppress gonadotropin secretion, resulting in depressed testosterone output.

Quantitative DNA methylation analyses reveal stage dependent DNA methylation and association to clinico-pathological factors in breast tumors.

PubMed

Klajic, Jovana; Fleischer, Thomas; Dejeux, Emelyne; Edvardsen, Hege; Warnberg, Fredrik; Bukholm, Ida; Lønning, Per Eystein; Solvang, Hiroko; Børresen-Dale, Anne-Lise; Tost, Jörg; Kristensen, Vessela N

2013-10-05

Aberrant DNA methylation of regulatory genes has frequently been found in human breast cancers and correlated to clinical outcome. In the present study we investigate stage specific changes in the DNA methylation patterns in order to identify valuable markers to understand how these changes affect breast cancer progression. Quantitative DNA methylation analyses of 12 candidate genes ABCB1, BRCCA1, CDKN2A, ESR1, GSTP1, IGF2, MGMT, HMLH1, PPP2R2B, PTEN, RASSF1A and FOXC1 was performed by pyrosequencing a series of 238 breast cancer tissue samples from DCIS to invasive tumors stage I to IV. Significant differences in methylation levels between the DCIS and invasive stage II tumors were observed for six genes RASSF1A, CDKN2A, MGMT, ABCB1, GSTP1 and FOXC1. RASSF1A, ABCB1 and GSTP1 showed significantly higher methylation levels in late stage compared to the early stage breast carcinoma. Z-score analysis revealed significantly lower methylation levels in DCIS and stage I tumors compared with stage II, III and IV tumors. Methylation levels of PTEN, PPP2R2B, FOXC1, ABCB1 and BRCA1 were lower in tumors harboring TP53 mutations then in tumors with wild type TP53. Z-score analysis showed that TP53 mutated tumors had significantly lower overall methylation levels compared to tumors with wild type TP53. Methylation levels of RASSF1A, PPP2R2B, GSTP1 and FOXC1 were higher in ER positive vs. ER negative tumors and methylation levels of PTEN and CDKN2A were higher in HER2 positive vs. HER2 negative tumors. Z-score analysis also showed that HER2 positive tumors had significantly higher z-scores of methylation compared to the HER2 negative tumors. Univariate survival analysis identifies methylation status of PPP2R2B as significant predictor of overall survival and breast cancer specific survival. In the present study we report that the level of aberrant DNA methylation is higher in late stage compared with early stage of invasive breast cancers and DCIS for genes mentioned above.

The ectopic expression of a pectin methyl esterase inhibitor increases pectin methyl esterification and limits fungal diseases in wheat.

PubMed

Volpi, Chiara; Janni, Michela; Lionetti, Vincenzo; Bellincampi, Daniela; Favaron, Francesco; D'Ovidio, Renato

2011-09-01

Cell wall pectin methyl esterification can influence plant resistance because highly methyl-esterified pectin can be less susceptible to the hydrolysis by pectic enzymes such as fungal endopolygalacturonases (PG). Pectin is secreted into the cell wall in a highly methyl-esterified form and, here, is de-methyl esterified by pectin methyl esterase (PME). The activity of PME is controlled by specific protein inhibitors called PMEI; consequently, an increased inhibition of PME by PMEI might modify the pectin methyl esterification. In order to test the possibility of improving wheat resistance by modifying the methyl esterification of pectin cell wall, we have produced durum wheat transgenic lines expressing the PMEI from Actinidia chinensis (AcPMEI). The expression of AcPMEI endows wheat with a reduced endogenous PME activity, and transgenic lines expressing a high level of the inhibitor showed a significant increase in the degree of methyl esterification. These lines showed a significant reduction of disease symptoms caused by the fungal pathogens Bipolaris sorokiniana or Fusarium graminearum. This increased resistance was related to the impaired ability of these fungal pathogens to grow on methyl-esterified pectin and to a reduced activity of the fungal PG to hydrolyze methyl-esterified pectin. In addition to their importance for wheat improvement, these results highlight the primary role of pectin despite its low content in the wheat cell wall.

Occurrence of 7-methyl-7-hexadecenoic acid, the corresponding alcohol, 7-methyl-6-hexadecenoic acid, and 5-methyl-4hexadecenoic acid in sperm whale oils.

PubMed

Pascal, J C; Ackman, R G

1975-08-01

Two sperm whale oils from the northern hemisphere and two from the southern hemisphere were fractionated. Triglyceride and wax esters were examined for fatty acids and alcohols with monoethylenic unsaturation bearing a methyl branch on an ethylenic carbon. The 7-methyl-7-hexadecenoic acid (0.37-1.37%) was accompanied by the corresponding alcohol (0.28-0.72%), but these materials were not accompanied by shorter chain homologues. The 7-methyl-6-hexadecenoic acid was relatively less important (0.23-0.68%), but was accompanied by 5-methyl-4-hexadecenoic acid (0.10-0.39%), and a partially identified C13 compound. Chromatographic properties on silver nitrate impregnated silicic acid TLC and on three GLC liquid phases are reported.

Identifying DNA methylation in a nanochannel

NASA Astrophysics Data System (ADS)

Sun, Xiaoyin; Yasui, Takao; Yanagida, Takeshi; Kaji, Noritada; Rahong, Sakon; Kanai, Masaki; Nagashima, Kazuki; Kawai, Tomoji; Baba, Yoshinobu

2016-01-01

DNA methylation is a stable epigenetic modification, which is well known to be involved in gene expression regulation. In general, however, analyzing DNA methylation requires rather time consuming processes (24-96 h) via DNA replication and protein modification. Here we demonstrate a methodology to analyze DNA methylation at a single DNA molecule level without any protein modifications by measuring the contracted length and relaxation time of DNA within a nanochannel. Our methodology is based on the fact that methylation makes DNA molecules stiffer, resulting in a longer contracted length and a longer relaxation time (a slower contraction rate). The present methodology offers a promising way to identify DNA methylation without any protein modification at a single DNA molecule level within 2 h.

A Formal Modelling Language Extending SysML for Simulation of Continuous and Discrete System

DTIC Science & Technology

2012-11-01

UNCLASSIFIED DSTO-GD-0734 16. A Formal Modelling Language Extending SysML for Simulation of Continuous and Discrete System – Mark Hodson1 and...be conceptual at some level because a one to one mapping with the real system will never exist. SysML is an extension and modification of UML that...simulation, which can provide great insights into the behaviour of complex systems. Although UML and SysML primarily support conceptual modelling they

40 CFR 180.437 - Methyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-p-toluate and methyl 6-(4-isopropyl-4...

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific... for the combined residues of the herbicide methyl 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)-p...

Assessment of changes in DNA methylation by methylation-sensitive amplification polymorphism in Jatropha curcas L. subjected to salinity stress.

PubMed

Mastan, Shaik G; Rathore, Mangal S; Bhatt, Vacha D; Yadav, P; Chikara, J

2012-10-15

The present study assesses the changes in DNA methylation in leaf and root tissues of Jatropha curcas L., induced by salinity stress using methylation sensitive amplification polymorphism (MSAP) markers. Seedlings of 21 days (d) grown under controlled conditions were subjected to 0–100 mM salinity treatment for 24 h (1 d). Immediate changes in DNA methylation and polymorphism in methylated DNA in whole genome of both leaves and roots were assessed using 10 selective combinations of MSAP primers. In root and leaves 70.06% and 57.89% methylation was observed respectively. Similarly 67.22% and 71.21% polymorphism was observed in methylated DNA from root and leaf tissues respectively. Compared with control, the percentage of methylation and methylation polymorphism in roots of plants under different dosages of salinity was found in the order of 50 mM < 25 mM = 100 mM < 75 mM and 75 mM < 25 mM < 50 mM < 100 mM respectively. Similarly percentage of methylation and methylation polymorphism in leaves of plants treated with different levels of salinity was found in order of 75 mM < 25 mM < 50 mM < 100 mM and 50 mM < 25 mM < 100 mM < 75 mM respectively. The MSAP analysis showed that under salt stress homologous nucleotide sequences in genome from control and salt treated plants of J. curcas showed different patterns of methylation; which suggest that these fragments probably play an important role to induce immediate adaptive responses in Jatropha under salinity stress.

Chitin degradation and utilization by virulent Aeromonas hydrophila strain ML10-51K.

PubMed

Zhang, Dunhua; Xu, De-Hai; Qiu, Junqiang; Rasmussen-Ivey, Cody R; Liles, Mark R; Beck, Benjamin H

2017-05-01

Virulent Aeromonas hydrophila (vAh) is one of the most important bacterial pathogens that causes persistent outbreaks of motile Aeromonas septicemia in warm-water fishes. The survivability of this pathogen in aquatic environments is of great concern. The aim of this study was to determine the capability of the vAh strain ML10-51K to degrade and utilize chitin. Genome-wide analysis revealed that ML10-51K encodes a suite of proteins for chitin metabolism. Assays in vitro showed that four chitinases, one chitobiase and one chitin-binding protein were secreted extracellularly and participated in chitin degradation. ML10-51K was shown to be able to use not only N-acetylglucosamine and colloidal chitin but also chitin flakes as sole carbon sources for growth. This study indicates that ML10-51K is a highly chitinolytic bacterium and suggests that the capability of effective chitin utilization could enable the bacterium to attain high densities when abundant chitin is available in aquatic niches.

PCMdb: Pancreatic Cancer Methylation Database

NASA Astrophysics Data System (ADS)

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

2014-02-01

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

The Knock-Limited Performance of Fuel Blends Containing Spiropentane, Methylenecyclobutane, Di-Tert-Butyl Ether, Methyl Tert-Butyl Ether, and Triptane

NASA Technical Reports Server (NTRS)

Meyer, Carl L.

1946-01-01

Tests show that at inlet-air temperatures of 250 deg F and 100 deg F the knock-limited performance of the base fuel of blends, leaded with 4 ml TEL per gallon and containing 20 percent spiropentane, was reduced at fuel/air ratios below 0.085. The 20 percent methylenecyclobutane reduced the knock-limited power of the base fuel at fuel/air ratios below 0.112. Di-tert-butyl ether, methyl-tert-butyl ether, and triptane increased the knock-limited power of the base fuel at all fuel/air ratios and at both temperatures.

DNA methylation in adult diffuse gliomas.

PubMed

LeBlanc, Veronique G; Marra, Marco A

2016-11-01

Adult diffuse gliomas account for the majority of primary malignant brain tumours, and are in most cases lethal. Current therapies are often only marginally effective, and improved options will almost certainly benefit from further insight into the various processes contributing to gliomagenesis and pathology. While molecular characterization of these tumours classifies them on the basis of genetic alterations and chromosomal abnormalities, DNA methylation patterns are increasingly understood to play a role in glioma pathogenesis. Indeed, a subset of gliomas associated with improved survival is characterized by the glioma CpG island methylator phenotype (G-CIMP), which can be induced by the expression of mutant isocitrate dehydrogenase (IDH1/2). Aberrant methylation of particular genes or regulatory elements, within the context of G-CIMP-positive and/or negative tumours, has also been shown to be associated with differential survival. In this review, we provide an overview of the current knowledge regarding the role of DNA methylation in adult diffuse gliomas. In particular, we discuss IDH mutations and G-CIMP, MGMT promoter methylation, DNA methylation-mediated microRNA regulation and aberrant methylation of specific genes or groups of genes. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

40 CFR 721.10122 - 2-Propenoic acid, 2-methyl-, 1,1′-[2-ethyl-2-[[(2-methyl-1-oxo-2-propen-1-yl)oxy]methyl]- 1,3...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 2-Propenoic acid, 2-methyl-, 1,1â²-[2... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10122 2-Propenoic acid, 2-methyl-, 1,1... new uses subject to reporting. (1) The chemical substance identified as 2-propenoic acid, 2-methyl-, 1...

40 CFR 721.10122 - 2-Propenoic acid, 2-methyl-, 1,1′-[2-ethyl-2-[[(2-methyl-1-oxo-2-propen-1-yl)oxy]methyl]- 1,3...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 2-Propenoic acid, 2-methyl-, 1,1â²-[2... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10122 2-Propenoic acid, 2-methyl-, 1,1... new uses subject to reporting. (1) The chemical substance identified as 2-propenoic acid, 2-methyl-, 1...

40 CFR 721.10122 - 2-Propenoic acid, 2-methyl-, 1,1′-[2-ethyl-2-[[(2-methyl-1-oxo-2-propen-1-yl)oxy]methyl]- 1,3...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 2-Propenoic acid, 2-methyl-, 1,1â²-[2... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10122 2-Propenoic acid, 2-methyl-, 1,1... new uses subject to reporting. (1) The chemical substance identified as 2-propenoic acid, 2-methyl-, 1...

Analysis of DNA Methylation of Gracilariopsis lemaneiformis Under Temperature Stress Using the Methylation Sensitive Amplification Polymorphism (MSAP) Technique

NASA Astrophysics Data System (ADS)

Peng, Chong; Sui, Zhenghong; Zhou, Wei; Hu, Yiyi; Mi, Ping; Jiang, Minjie; Li, Xiaodong; Ruan, Xudong

2018-06-01

Gracilariopsis lemaneiformis is an economically important agarophyte, which contains high quality gel and shows a high growth rate. Wild population of G. lemaneiformis displayed resident divergence, though with a low genetic diversity as was revealed by amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) analyses. In addition, different strains of G. lemaneiformis are diverse in morphology. The highly inconsistence between genetic background and physiological characteristics recommends strongly to the regulation at epigenetic level. In this study, the DNA methylation change in G. lemaneiformis among different generation branches and under different temperature stresses was assessed using methylation sensitive amplified polymorphism (MSAP) technique. It was shown that DNA methylation level among different generation branches was diverse. The full and total methylated DNA level was the lowest in the second generation branch and the highest in the third generation. The total methylation level was 61.11%, 60.88% and 64.12% at 15°C, 22°C and 26°C, respectively. Compared with the control group (22°C), the fully methylated and totally methylated ratios were increased in both experiment groups (15°C and 26°C). All of the cytosine methylation/demethylation transform (CMDT) was further analyzed. High temperature treatment could induce more CMDT than low temperature treatment did.

Curcumin modulates DNA methylation in colorectal cancer cells.

PubMed

Link, Alexander; Balaguer, Francesc; Shen, Yan; Lozano, Juan Jose; Leung, Hon-Chiu E; Boland, C Richard; Goel, Ajay

2013-01-01

Recent evidence suggests that several dietary polyphenols may exert their chemopreventive effect through epigenetic modifications. Curcumin is one of the most widely studied dietary chemopreventive agents for colon cancer prevention, however, its effects on epigenetic alterations, particularly DNA methylation, remain unclear. Using systematic genome-wide approaches, we aimed to elucidate the effect of curcumin on DNA methylation alterations in colorectal cancer cells. To evaluate the effect of curcumin on DNA methylation, three CRC cell lines, HCT116, HT29 and RKO, were treated with curcumin. 5-aza-2'-deoxycytidine (5-aza-CdR) and trichostatin A treated cells were used as positive and negative controls for DNA methylation changes, respectively. Methylation status of LINE-1 repeat elements, DNA promoter methylation microarrays and gene expression arrays were used to assess global methylation and gene expression changes. Validation was performed using independent microarrays, quantitative bisulfite pyrosequencing, and qPCR. As expected, genome-wide methylation microarrays revealed significant DNA hypomethylation in 5-aza-CdR-treated cells (mean β-values of 0.12), however, non-significant changes in mean β-values were observed in curcumin-treated cells. In comparison to mock-treated cells, curcumin-induced DNA methylation alterations occurred in a time-dependent manner. In contrast to the generalized, non-specific global hypomethylation observed with 5-aza-CdR, curcumin treatment resulted in methylation changes at selected, partially-methylated loci, instead of fully-methylated CpG sites. DNA methylation alterations were supported by corresponding changes in gene expression at both up- and down-regulated genes in various CRC cell lines. Our data provide previously unrecognized evidence for curcumin-mediated DNA methylation alterations as a potential mechanism of colon cancer chemoprevention. In contrast to non-specific global hypomethylation induced by 5-aza

Curcumin Modulates DNA Methylation in Colorectal Cancer Cells

PubMed Central

Link, Alexander; Balaguer, Francesc; Shen, Yan; Lozano, Juan Jose; Leung, Hon-Chiu E.; Boland, C. Richard; Goel, Ajay

2013-01-01

Aim Recent evidence suggests that several dietary polyphenols may exert their chemopreventive effect through epigenetic modifications. Curcumin is one of the most widely studied dietary chemopreventive agents for colon cancer prevention, however, its effects on epigenetic alterations, particularly DNA methylation, remain unclear. Using systematic genome-wide approaches, we aimed to elucidate the effect of curcumin on DNA methylation alterations in colorectal cancer cells. Materials and Methods To evaluate the effect of curcumin on DNA methylation, three CRC cell lines, HCT116, HT29 and RKO, were treated with curcumin. 5-aza-2′-deoxycytidine (5-aza-CdR) and trichostatin A treated cells were used as positive and negative controls for DNA methylation changes, respectively. Methylation status of LINE-1 repeat elements, DNA promoter methylation microarrays and gene expression arrays were used to assess global methylation and gene expression changes. Validation was performed using independent microarrays, quantitative bisulfite pyrosequencing, and qPCR. Results As expected, genome-wide methylation microarrays revealed significant DNA hypomethylation in 5-aza-CdR-treated cells (mean β-values of 0.12), however, non-significant changes in mean β-values were observed in curcumin-treated cells. In comparison to mock-treated cells, curcumin-induced DNA methylation alterations occurred in a time-dependent manner. In contrast to the generalized, non-specific global hypomethylation observed with 5-aza-CdR, curcumin treatment resulted in methylation changes at selected, partially-methylated loci, instead of fully-methylated CpG sites. DNA methylation alterations were supported by corresponding changes in gene expression at both up- and down-regulated genes in various CRC cell lines. Conclusions Our data provide previously unrecognized evidence for curcumin-mediated DNA methylation alterations as a potential mechanism of colon cancer chemoprevention. In contrast to non

Alternatives to Methyl Bromide (1993)

EPA Pesticide Factsheets

The report examines the alternatives that have been discussed as substitutes for current methyl bromide uses if methyl bromide should no longer be available and discusses the economic implications of such a phaseout.

Function and Evolution of DNA Methylation in Nasonia vitripennis

PubMed Central

Wang, Xu; Wheeler, David; Avery, Amanda; Rago, Alfredo; Choi, Jeong-Hyeon; Colbourne, John K.; Clark, Andrew G.; Werren, John H.

2013-01-01

The parasitoid wasp Nasonia vitripennis is an emerging genetic model for functional analysis of DNA methylation. Here, we characterize genome-wide methylation at a base-pair resolution, and compare these results to gene expression across five developmental stages and to methylation patterns reported in other insects. An accurate assessment of DNA methylation across the genome is accomplished using bisulfite sequencing of adult females from a highly inbred line. One-third of genes show extensive methylation over the gene body, yet methylated DNA is not found in non-coding regions and rarely in transposons. Methylated genes occur in small clusters across the genome. Methylation demarcates exon-intron boundaries, with elevated levels over exons, primarily in the 5′ regions of genes. It is also elevated near the sites of translational initiation and termination, with reduced levels in 5′ and 3′ UTRs. Methylated genes have higher median expression levels and lower expression variation across development stages than non-methylated genes. There is no difference in frequency of differential splicing between methylated and non-methylated genes, and as yet no established role for methylation in regulating alternative splicing in Nasonia. Phylogenetic comparisons indicate that many genes maintain methylation status across long evolutionary time scales. Nasonia methylated genes are more likely to be conserved in insects, but even those that are not conserved show broader expression across development than comparable non-methylated genes. Finally, examination of duplicated genes shows that those paralogs that have lost methylation in the Nasonia lineage following gene duplication evolve more rapidly, show decreased median expression levels, and increased specialization in expression across development. Methylation of Nasonia genes signals constitutive transcription across developmental stages, whereas non-methylated genes show more dynamic developmental expression

Microbial mercury methylation in Antarctic sea ice.

PubMed

Gionfriddo, Caitlin M; Tate, Michael T; Wick, Ryan R; Schultz, Mark B; Zemla, Adam; Thelen, Michael P; Schofield, Robyn; Krabbenhoft, David P; Holt, Kathryn E; Moreau, John W

2016-08-01

Atmospheric deposition of mercury onto sea ice and circumpolar sea water provides mercury for microbial methylation, and contributes to the bioaccumulation of the potent neurotoxin methylmercury in the marine food web. Little is known about the abiotic and biotic controls on microbial mercury methylation in polar marine systems. However, mercury methylation is known to occur alongside photochemical and microbial mercury reduction and subsequent volatilization. Here, we combine mercury speciation measurements of total and methylated mercury with metagenomic analysis of whole-community microbial DNA from Antarctic snow, brine, sea ice and sea water to elucidate potential microbially mediated mercury methylation and volatilization pathways in polar marine environments. Our results identify the marine microaerophilic bacterium Nitrospina as a potential mercury methylator within sea ice. Anaerobic bacteria known to methylate mercury were notably absent from sea-ice metagenomes. We propose that Antarctic sea ice can harbour a microbial source of methylmercury in the Southern Ocean.

Selective Methylation: an Incorrect Hypothesis

PubMed Central

Shugart, Lee

1976-01-01

“Selective methylation,” a hypothesis proposed to explain the discrepancy found in the degree of methyl deficiency of transfer ribonucleic acid, cannot be explained on the basis of some biological phenomenon. PMID:770445

Direct detection of methylation in genomic DNA

PubMed Central

Bart, A.; van Passel, M. W. J.; van Amsterdam, K.; van der Ende, A.

2005-01-01

The identification of methylated sites on bacterial genomic DNA would be a useful tool to study the major roles of DNA methylation in prokaryotes: distinction of self and nonself DNA, direction of post-replicative mismatch repair, control of DNA replication and cell cycle, and regulation of gene expression. Three types of methylated nucleobases are known: N6-methyladenine, 5-methylcytosine and N4-methylcytosine. The aim of this study was to develop a method to detect all three types of DNA methylation in complete genomic DNA. It was previously shown that N6-methyladenine and 5-methylcytosine in plasmid and viral DNA can be detected by intersequence trace comparison of methylated and unmethylated DNA. We extended this method to include N4-methylcytosine detection in both in vitro and in vivo methylated DNA. Furthermore, application of intersequence trace comparison was extended to bacterial genomic DNA. Finally, we present evidence that intrasequence comparison suffices to detect methylated sites in genomic DNA. In conclusion, we present a method to detect all three natural types of DNA methylation in bacterial genomic DNA. This provides the possibility to define the complete methylome of any prokaryote. PMID:16091626

Optical biosensing strategies for DNA methylation analysis.

PubMed

Nazmul Islam, Md; Yadav, Sharda; Hakimul Haque, Md; Munaz, Ahmed; Islam, Farhadul; Al Hossain, Md Shahriar; Gopalan, Vinod; Lam, Alfred K; Nguyen, Nam-Trung; Shiddiky, Muhammad J A

2017-06-15

DNA methylation is an epigenetic modification of DNA, where a methyl group is added at the fifth carbon of the cytosine base to form 5 methyl cytosine (5mC) without altering the DNA sequences. It plays important roles in regulating many cellular processes by modulating key genes expression. Alteration in DNA methylation patterns becomes particularly important in the aetiology of different diseases including cancers. Abnormal methylation pattern could contribute to the pathogenesis of cancer either by silencing key tumor suppressor genes or by activating oncogenes. Thus, DNA methylation biosensing can help in the better understanding of cancer prognosis and diagnosis and aid the development of therapies. Over the last few decades, a plethora of optical detection techniques have been developed for analyzing DNA methylation using fluorescence, Raman spectroscopy, surface plasmon resonance (SPR), electrochemiluminescence and colorimetric readouts. This paper aims to comprehensively review the optical strategies for DNA methylation detection. We also present an overview of the remaining challenges of optical strategies that still need to be focused along with the lesson learnt while working with these techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

Heterogeneity of DNA methylation in multifocal prostate cancer.

PubMed

Serenaite, Inga; Daniunaite, Kristina; Jankevicius, Feliksas; Laurinavicius, Arvydas; Petroska, Donatas; Lazutka, Juozas R; Jarmalaite, Sonata

2015-01-01

Most prostate cancer (PCa) cases are multifocal, and separate foci display histological and molecular heterogeneity. DNA hypermethylation is a frequent alteration in PCa, but interfocal heterogeneity of these changes has not been extensively investigated. Ten pairs of foci from multifocal PCa and 15 benign prostatic hyperplasia (BPH) samples were obtained from prostatectomy specimens, resulting altogether in 35 samples. Methylation-specific PCR (MSP) was used to evaluate methylation status of nine tumor suppressor genes (TSGs), and a set of selected TSGs was quantitatively analyzed for methylation intensity by pyrosequencing. Promoter sequences of the RASSF1 and ESR1 genes were methylated in all paired PCa foci, and frequent (≥75 %) DNA methylation was detected in RARB, GSTP1, and ABCB1 genes. MSP revealed different methylation status of at least one gene in separate foci in 8 out of 10 multifocal tumors. The mean methylation level of ESR1, GSTP1, RASSF1, and RARB differed between the paired foci of all PCa cases. The intensity of DNA methylation in these TSGs was significantly higher in PCa cases than in BPH (p < 0.001). Hierarchical cluster analysis revealed a divergent methylation profile of paired PCa foci, while the foci from separate cases with biochemical recurrence showed similar methylation profile and the highest mean levels of DNA methylation. Our findings suggest that PCa tissue is heterogeneous, as between paired foci differences in DNA methylation status were found. Common epigenetic profile of recurrent tumors can be inferred from our data.

MGMT promoter methylation in Peruvian patients with glioblastoma

PubMed Central

Belmar-Lopez, Carolina; Castaneda, Carlos A; Castillo, Miluska; García-Corrochano, Pamela; Orrego, Enrique; Meléndez, Barbara; Casavilca, Sandro; Flores, Claudio; Orrego, Enrique

2018-01-01

Purpose O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation predicts the outcome and response to alkylating chemotherapy in glioblastoma. The aim of this study is to evaluate the prevalence of MGMT methylation in Peruvian glioblastoma cases. Patients and methods We evaluated retrospectively 50 cases of resected glioblastoma during the period 2008–2013 at Instituto Nacional de Enfermedades Neoplasicas in Peru. Samples consisted of paraffin embedded and frozen tumour tissue. MGMT-promoter methylation status and the expression level of MGMT gene were evaluated by methylation-specific PCR and real-time PCR, respectively. Results Unmethylated, methylated and partially methylated statuses were found in 54%, 20% and 26% of paraffin-embedded samples, respectively. Methylation status was confirmed in the Virgen de la Salud Hospital and frozen samples. There was an association between the status of MGMT-promoter methylation and the level of gene expression (p = 0.001). Methylation was associated with increased progression-free survival (p = 0.002) and overall survival (OS) (p < 0.001). Conclusion MGMT-promoter methylation frequency in Peruvian glioblastoma is similar to that reported in other populations and the detection test has been standardised. PMID:29515653

Methylation of zebularine investigated using density functional theory calculations.

PubMed

Selvam, Lalitha; Chen, Fang Fang; Wang, Feng

2011-07-30

Deoxyribonucleic acid (DNA) methylation is an epigenetic phenomenon, which adds methyl groups into DNA. This study reveals methylation of a nucleoside antibiotic drug 1-(β-D-ribofuranosyl)-2-pyrimidinone (zebularine or zeb) with respect to its methylated analog, 1-(β-D-ribofuranosyl)-5-methyl-2-pyrimidinone (d5) using density functional theory calculations in valence electronic space. Very similar infrared spectra suggest that zeb and d5 do not differ by types of the chemical bonds, but distinctly different Raman spectra of the nucleoside pair reveal that the impact caused by methylation of zeb can be significant. Further valence orbital-based information details on valence electronic structural changes caused by methylation of zebularine. Frontier orbitals in momentum space and position space of the molecules respond differently to methylation. Based on the additional methyl electron density concentration in d5, orbitals affected by the methyl moiety are classified into primary and secondary contributors. Primary methyl contributions include MO8 (57a), MO18 (47a), and MO37 (28a) of d5, which concentrates on methyl and the base moieties, suggest certain connection to their Frontier orbitals. The primary and secondary methyl affected orbitals provide useful information on chemical bonding mechanism of the methylation in zebularine. Copyright © 2011 Wiley Periodicals, Inc.

Methylation profiling identified novel differentially methylated markers including OPCML and FLRT2 in prostate cancer.

PubMed

Wu, Yu; Davison, Jerry; Qu, Xiaoyu; Morrissey, Colm; Storer, Barry; Brown, Lisha; Vessella, Robert; Nelson, Peter; Fang, Min

2016-04-02

To develop new methods to distinguish indolent from aggressive prostate cancers (PCa), we utilized comprehensive high-throughput array-based relative methylation (CHARM) assay to identify differentially methylated regions (DMRs) throughout the genome, including both CpG island (CGI) and non-CGI regions in PCa patients based on Gleason grade. Initially, 26 samples, including 8 each of low [Gleason score (GS) 6] and high (GS ≥7) grade PCa samples and 10 matched normal prostate tissues, were analyzed as a discovery cohort. We identified 3,567 DMRs between normal and cancer tissues, and 913 DMRs distinguishing low from high-grade cancers. Most of these DMRs were located at CGI shores. The top 5 candidate DMRs from the low vs. high Gleason comparison, including OPCML, ELAVL2, EXT1, IRX5, and FLRT2, were validated by pyrosequencing using the discovery cohort. OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low-Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (n=70) vs. those without (n=86) in a third cohort, and they showed no difference in methylation at these DMR loci. When GS 3+4 cases and GS 4+3 cases were compared, OPCML-DMR methylation showed a trend of lower methylation in the recurrence group (n=30) than in the no-recurrence (n=52) group. We conclude that whole-genome methylation profiling with CHARM revealed distinct patterns of differential DNA methylation between normal prostate and PCa tissues, as well as between different risk groups of PCa as defined by Gleason scores. A panel of selected DMRs may serve as novel surrogate biomarkers for Gleason score in PCa.

[Specific features of 2-methyl hydroxybenzene and 3-methyl hydroxybenzene distribution in the organism of warm-blooded animals].

PubMed

Shormanov, B K; Grishenko, V K; Astashkina, A P; Elizarova, M K

2013-01-01

The present work was designed to study the specific features of 2-methyl hydroxybezene and 3-methyl hydroxybenzene distribution after intragastric administration of these toxicants to warm-blooded animals (rats). They were detected in the unmetabolized form in the internal organs and blood of the animals. The levels of 2-methyl hydroxybezene were especially high in the stomach and blood whereas the maximum content of 3-methyl hydroxybenzene was found in brain, blood, small intestines of the poisoned rats.

Nonparametric Bayesian clustering to detect bipolar methylated genomic loci.

PubMed

Wu, Xiaowei; Sun, Ming-An; Zhu, Hongxiao; Xie, Hehuang

2015-01-16

With recent development in sequencing technology, a large number of genome-wide DNA methylation studies have generated massive amounts of bisulfite sequencing data. The analysis of DNA methylation patterns helps researchers understand epigenetic regulatory mechanisms. Highly variable methylation patterns reflect stochastic fluctuations in DNA methylation, whereas well-structured methylation patterns imply deterministic methylation events. Among these methylation patterns, bipolar patterns are important as they may originate from allele-specific methylation (ASM) or cell-specific methylation (CSM). Utilizing nonparametric Bayesian clustering followed by hypothesis testing, we have developed a novel statistical approach to identify bipolar methylated genomic regions in bisulfite sequencing data. Simulation studies demonstrate that the proposed method achieves good performance in terms of specificity and sensitivity. We used the method to analyze data from mouse brain and human blood methylomes. The bipolar methylated segments detected are found highly consistent with the differentially methylated regions identified by using purified cell subsets. Bipolar DNA methylation often indicates epigenetic heterogeneity caused by ASM or CSM. With allele-specific events filtered out or appropriately taken into account, our proposed approach sheds light on the identification of cell-specific genes/pathways under strong epigenetic control in a heterogeneous cell population.

EFEMP1 as a novel DNA methylation marker for prostate cancer: array-based DNA methylation and expression profiling.

PubMed

Kim, Yong-June; Yoon, Hyung-Yoon; Kim, Seon-Kyu; Kim, Young-Won; Kim, Eun-Jung; Kim, Isaac Yi; Kim, Wun-Jae

2011-07-01

Abnormal DNA methylation is associated with many human cancers. The aim of the present study was to identify novel methylation markers in prostate cancer (PCa) by microarray analysis and to test whether these markers could discriminate normal and PCa cells. Microarray-based DNA methylation and gene expression profiling was carried out using a panel of PCa cell lines and a control normal prostate cell line. The methylation status of candidate genes in prostate cell lines was confirmed by real-time reverse transcriptase-PCR, bisulfite sequencing analysis, and treatment with a demethylation agent. DNA methylation and gene expression analysis in 203 human prostate specimens, including 106 PCa and 97 benign prostate hyperplasia (BPH), were carried out. Further validation using microarray gene expression data from the Gene Expression Omnibus (GEO) was carried out. Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was identified as a lead candidate methylation marker for PCa. The gene expression level of EFEMP1 was significantly higher in tissue samples from patients with BPH than in those with PCa (P < 0.001). The sensitivity and specificity of EFEMP1 methylation status in discriminating between PCa and BPH reached 95.3% (101 of 106) and 86.6% (84 of 97), respectively. From the GEO data set, we confirmed that the expression level of EFEMP1 was significantly different between PCa and BPH. Genome-wide characterization of DNA methylation profiles enabled the identification of EFEMP1 aberrant methylation patterns in PCa. EFEMP1 might be a useful indicator for the detection of PCa.

Methylenetetrahydrofolate Reductase Modulates Methyl Metabolism and Lignin Monomer Methylation in Maize.

PubMed

Wu, Zhenying; Ren, Hao; Xiong, Wangdan; Roje, Sanja; Liu, Yuchen; Su, Kunlong; Fu, Chunxiang

2018-05-30

The brown midrib2 (bm2) mutant of maize, with a modified lignin composition, contains a mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. We here show that a MITE transposon insertion caused downregulation of MTHFR with accompanying decrease in 5-methyl-THF and increase in 5, 10-methylene-THF and THF in the bm2 mutant. Furthermore, MTHFR mutation did not change the content of SAM, the methyl group donor involved in the biosynthesis of guaiacyl (G) and syringyl (S) lignins, but increased the level of S-adenosyl homocysteine (SAH), the de-methylation product of SAM. Moreover, competitive inhibition of the maize caffeoyl CoA O-methyltransferase (CCoAOMT) and caffeic acid O-methyltransferase (COMT) enzyme activities by SAH was found, suggesting that SAH/SAM ratio rather than SAM concentration regulates the transmethylation reactions of lignin intermediates. Phenolic profiling revealed that caffeoyl alcohol glucose derivatives accumulated in the mutant, indicating impaired 3-O-methylation of monolignols. A remarkable increase in the unusual catechyl (C) lignin determined in the mutant demonstrates that MTHFR downregulation mainly affects G lignin biosynthesis, consistent with the observation that CCoAOMT is more sensitive to SAH inhibition than COMT. This study which uncovered a novel regulatory mechanism in lignin biosynthesis and may offer an effective approach to utilize lignocellulosic feedstocks in future.

Effects of methyl p-hydroxybenzoate (methyl paraben) on Ca2+ concentration and histamine release in rat peritoneal mast cells

PubMed Central

Fukugasako, Sanae; Ito, Shinichi; Ikemoto, Yoshimi

2003-01-01

Mechanisms of methyl p-hydroxybenzoate (methyl paraben) action in allergic reactions were investigated by measuring the intracellular Ca2+ concentration ([Ca2+]i) and histamine release in rat peritoneal mast cells (RPMCs). In the presence or absence of extracellular Ca2+, methyl paraben (0.1–10 mM) increased [Ca2+]i, in a concentration-dependent manner. Under both the conditions, methyl paraben alone did not evoke histamine release. In RPMCs pretreated with a protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate (PMA) 3 and 10 nM), methyl paraben (0.3–3 mM) induced histamine release. However, a high concentration (10 mM) of the agent did not increase the histamine release. U73122 (0.1 and 0.5 μM), an inhibitor of phospholipase C (PLC), significantly inhibited the methyl paraben-induced histamine release in PMA-pretreated RPMCs. U73343 (0.5 μM), an inactive analogue of U73122, did not inhibit the histamine release caused by methyl paraben. In Ca2+-free solution, PLC inhibitors (U73122 0.1 and 0.5 μM, D609 1–10 μM) inhibited the methyl paraben-induced increase in [Ca2+]i, whereas U73343 (0.5 μM) did not. Xestospongin C (2–20 μM) and 2 aminoethoxydiphenyl borate (30 and 100 μM), blockers of the inositol 1,4,5-trisphosphate (IP3) receptor, inhibited the methyl paraben-induced increase in [Ca2+]i in Ca2+-free solution. In conclusion, methyl paraben causes an increase in [Ca2+]i, which may be due to release of Ca2+ from storage sites by IP3 via activation of PLC in RPMCs. In addition, methyl paraben possibly has some inhibitory effects on histamine release via unknown mechanisms. PMID:12770943

EXTRACTION OF TETRAVALENT PLUTONIUM VALUES WITH METHYL ETHYL KETONE, METHYL ISOBUTYL KETONE ACETOPHENONE OR MENTHONE

DOEpatents

Seaborg, G.T.

1961-08-01

A process is described for extracting tetravalent plutonium from an aqueous acid solution with methyl ethyl ketone, methyl isobutyl ketone, or acetophenone and with the extraction of either tetravalent or hexavalent plutonium into menthone. (AEC)

Is the Fungus Magnaporthe Losing DNA Methylation?

PubMed Central

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

2013-01-01

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

Aberrant DNA methylation patterns in diabetic nephropathy

PubMed Central

2014-01-01

Background The aim of this study was to evaluate whether global levels of DNA methylation status were associated with albuminuria and progression of diabetic nephropathy in a case-control study of 123 patients with type 2 diabetes- 53 patients with albuminuria and 70 patients without albuminuria. Methods The 5-methyl cytosine content was assessed by reverse phase high pressure liquid chromatography (RP-HPLC) of peripheral blood mononuclear cells to determine individual global DNA methylation status in two groups. Results Global DNA methylation levels were significantly higher in patients with albuminuria compared with those in normal range of albuminuria (p = 0.01). There were significant differences in global levels of DNA methylation in relation to albuminuria (p = 0.028) and an interesting pattern of increasing global levels of DNA methylation in terms of albuminuria severity. In patients with micro- and macro albuminuria, we found no significant correlations between global DNA methylation levels and duration of diabetes (p > 0.05). In both sub groups, there were not significant differences between global DNA methylation levels with good and poor glycaemic control (p > 0.05). In addition, in patients with albuminuria, no differences in DNA methylation levels were observed between patients with and without other risk factors including age, gender, hypertension, dyslipidaemia and obesity. Conclusions These data may be helpful in further studies to develop novel biomarkers and new strategies for clinical care of patients at risk of diabetic nephropathy. PMID:25028646

Electrochemical biosensing strategies for DNA methylation analysis.

PubMed

Hossain, Tanvir; Mahmudunnabi, Golam; Masud, Mostafa Kamal; Islam, Md Nazmul; Ooi, Lezanne; Konstantinov, Konstantin; Hossain, Md Shahriar Al; Martinac, Boris; Alici, Gursel; Nguyen, Nam-Trung; Shiddiky, Muhammad J A

2017-08-15

DNA methylation is one of the key epigenetic modifications of DNA that results from the enzymatic addition of a methyl group at the fifth carbon of the cytosine base. It plays a crucial role in cellular development, genomic stability and gene expression. Aberrant DNA methylation is responsible for the pathogenesis of many diseases including cancers. Over the past several decades, many methodologies have been developed to detect DNA methylation. These methodologies range from classical molecular biology and optical approaches, such as bisulfite sequencing, microarrays, quantitative real-time PCR, colorimetry, Raman spectroscopy to the more recent electrochemical approaches. Among these, electrochemical approaches offer sensitive, simple, specific, rapid, and cost-effective analysis of DNA methylation. Additionally, electrochemical methods are highly amenable to miniaturization and possess the potential to be multiplexed. In recent years, several reviews have provided information on the detection strategies of DNA methylation. However, to date, there is no comprehensive evaluation of electrochemical DNA methylation detection strategies. Herein, we address the recent developments of electrochemical DNA methylation detection approaches. Furthermore, we highlight the major technical and biological challenges involved in these strategies and provide suggestions for the future direction of this important field. Copyright © 2017 Elsevier B.V. All rights reserved.

The DNA methylation landscape of human melanoma.

PubMed

Jin, Seung-Gi; Xiong, Wenying; Wu, Xiwei; Yang, Lu; Pfeifer, Gerd P

2015-12-01

Using MIRA-seq, we have characterized the DNA methylome of metastatic melanoma and normal melanocytes. Individual tumors contained several thousand hypermethylated regions. We discovered 179 tumor-specific methylation peaks present in all (27/27) melanomas that may be effective disease biomarkers, and 3113 methylation peaks were seen in >40% of the tumors. We found that 150 of the approximately 1200 tumor-associated methylation peaks near transcription start sites (TSSs) were marked by H3K27me3 in melanocytes. DNA methylation in melanoma was specific for distinct H3K27me3 peaks rather than for broadly covered regions. However, numerous H3K27me3 peak-associated TSS regions remained devoid of DNA methylation in tumors. There was no relationship between BRAF mutations and the number of methylation peaks. Gene expression analysis showed upregulated immune response genes in melanomas presumably as a result of lymphocyte infiltration. Down-regulated genes were enriched for melanocyte differentiation factors; e.g., KIT, PAX3 and SOX10 became methylated and downregulated in melanoma. Copyright © 2015 Elsevier Inc. All rights reserved.

77 FR 20752 - Methyl Bromide; Proposed Pesticide Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-06

... fumigated with methyl bromide requires a tolerance. Without a tolerance or exemption, food or feed... livestock feeding items resulting from fumigation of cottonseed with methyl bromide are covered by existing... produced from cottonseed fumigated with methyl bromide would not contain residues of methyl bromide...

The DaveMLTranslator: An Interface for DAVE-ML Aerodynamic Models

NASA Technical Reports Server (NTRS)

Hill, Melissa A.; Jackson, E. Bruce

2007-01-01

It can take weeks or months to incorporate a new aerodynamic model into a vehicle simulation and validate the performance of the model. The Dynamic Aerospace Vehicle Exchange Markup Language (DAVE-ML) has been proposed as a means to reduce the time required to accomplish this task by defining a standard format for typical components of a flight dynamic model. The purpose of this paper is to describe an object-oriented C++ implementation of a class that interfaces a vehicle subsystem model specified in DAVE-ML and a vehicle simulation. Using the DaveMLTranslator class, aerodynamic or other subsystem models can be automatically imported and verified at run-time, significantly reducing the elapsed time between receipt of a DAVE-ML model and its integration into a simulation environment. The translator performs variable initializations, data table lookups, and mathematical calculations for the aerodynamic build-up, and executes any embedded static check-cases for verification. The implementation is efficient, enabling real-time execution. Simple interface code for the model inputs and outputs is the only requirement to integrate the DaveMLTranslator as a vehicle aerodynamic model. The translator makes use of existing table-lookup utilities from the Langley Standard Real-Time Simulation in C++ (LaSRS++). The design and operation of the translator class is described and comparisons with existing, conventional, C++ aerodynamic models of the same vehicle are given.

Mercury methylation by novel microorganisms from new environments.

PubMed

Gilmour, Cynthia C; Podar, Mircea; Bullock, Allyson L; Graham, Andrew M; Brown, Steven D; Somenahally, Anil C; Johs, Alex; Hurt, Richard A; Bailey, Kathryn L; Elias, Dwayne A

2013-10-15

Microbial mercury (Hg) methylation transforms a toxic trace metal into the highly bioaccumulated neurotoxin methylmercury (MeHg). The lack of a genetic marker for microbial MeHg production has prevented a clear understanding of Hg-methylating organism distribution in nature. Recently, a specific gene cluster (hgcAB) was linked to Hg methylation in two bacteria.1 Here we test if the presence of hgcAB orthologues is a reliable predictor of Hg methylation capability in microorganisms, a necessary confirmation for the development of molecular probes for Hg-methylation in nature. Although hgcAB orthologues are rare among all available microbial genomes, organisms are much more phylogenetically and environmentally diverse than previously thought. By directly measuring MeHg production in several bacterial and archaeal strains encoding hgcAB, we confirmed that possessing hgcAB predicts Hg methylation capability. For the first time, we demonstrated Hg methylation in a number of species other than sulfate- (SRB) and iron- (FeRB) reducing bacteria, including methanogens, and syntrophic, acetogenic, and fermentative Firmicutes. Several of these species occupy novel environmental niches for Hg methylation, including methanogenic habitats such as rice paddies, the animal gut, and extremes of pH and salinity. Identification of these organisms as Hg methylators now links methylation to discrete gene markers in microbial communities.

Promoter methylation profile in gallbladder cancer.

PubMed

Roa, Juan Carlos; Anabalón, Leonardo; Roa, Iván; Melo, Angélica; Araya, Juan Carlos; Tapia, Oscar; de Aretxabala, Xavier; Muñoz, Sergio; Schneider, Barbara

2006-03-01

Methylation in the promoter region of genes is an important mechanism of inactivation of tumor suppressor genes. Our objective was to analyze the methylation pattern of some of the genes involved in carcinogenesis of the gallbladder, examining the immunohistochemical expression of proteins, clinical features, and patient survival time. Twenty cases of gallbladder cancer were selected from the frozen tumor bank. The DNA extracted was analyzed by means of a methylation-specific polymerase chain reaction test for the CDKN2A (p16), MLH1, APC, FHIT, and CDH1 (E-cadherin) genes. Morphological and clinical data and follow-up information were obtained. All cases were in an advanced stage: histologically moderate or poorly differentiated tumors (95%). Methylation of the promoter area of genes was observed in 5%, 20%, 30%, 40%, and 65% of cases, and an altered immunohistochemical pattern (AIP) in 5%, 35%, 21%, 25%, and 66% for the MLH1, CDKN2A, FHIT, APC, and CDH1 genes, respectively. The Kappa concordance index between methylation of the promoter area and AIP for the MLH1 and CDH1 genes was very high (K > 0.75) and substantial for APC (K > 0.45). No correlation was found between survival time and the methylation of the genes studied. The high frequency of gene methylation (with the exception of MLH1) and the high agreement between AIP and methylation of the gene promoter area for the MLH1, APC, and CDH1 genes suggest that the inactivation of tumor suppressor genes and of the genes related to the control of cellular proliferation through this mechanism is involved in gallbladder carcinogenesis.

Molecular correlates with MGMT promoter methylation and silencing support CpG island methylator phenotype-low (CIMP-low) in colorectal cancer.

PubMed

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

2007-11-01

The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer. In contrast, a phenotype with less widespread promoter methylation (CIMP-low) has not been well characterised. O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and silencing have been associated with G>A mutations and microsatellite instability-low (MSI-low). To examine molecular correlates with MGMT methylation/silencing in colorectal cancer. Utilising MethyLight technology, we quantified DNA methylation in MGMT and eight other markers (a CIMP-diagnostic panel; CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) in 920 population-based colorectal cancers. Tumours with both MGMT methylation and loss were correlated positively with MSI-low (p = 0.02), CIMP-high (>or=6/8 methylated CIMP markers, p = 0.005), CIMP-low (1/8-5/8 methylated CIMP markers, p = 0.002, compared to CIMP-0 with 0/8 methylated markers), KRAS G>A mutation (p = 0.02), and inversely with 18q loss of heterozygosity (p = 0.0002). Tumours were classified into nine MSI/CIMP subtypes. Among the CIMP-low group, tumours with both MGMT methylation and loss were far more frequent in MSI-low tumours (67%, 12/18) than MSI-high tumours (5.6%, 1/18; p = 0.0003) and microsatellite stable (MSS) tumours (33%, 52/160; p = 0.008). However, no such relationship was observed among the CIMP-high or CIMP-0 groups. The relationship between MGMT methylation/silencing and MSI-low is limited to only CIMP-low tumours, supporting the suggestion that CIMP-low in colorectal cancer may be a different molecular phenotype from CIMP-high and CIMP-0. Our data support a molecular difference between MSI-low and MSS in colorectal cancer, and a possible link between CIMP-low, MSI-low, MGMT methylation/loss and KRAS mutation.

Implementation of a Goal-Based Systems Engineering Process Using the Systems Modeling Language (SysML)

NASA Technical Reports Server (NTRS)

Patterson, Jonathan D.; Breckenridge, Jonathan T.; Johnson, Stephen B.

2013-01-01

Building upon the purpose, theoretical approach, and use of a Goal-Function Tree (GFT) being presented by Dr. Stephen B. Johnson, described in a related Infotech 2013 ISHM abstract titled "Goal-Function Tree Modeling for Systems Engineering and Fault Management", this paper will describe the core framework used to implement the GFTbased systems engineering process using the Systems Modeling Language (SysML). These two papers are ideally accepted and presented together in the same Infotech session. Statement of problem: SysML, as a tool, is currently not capable of implementing the theoretical approach described within the "Goal-Function Tree Modeling for Systems Engineering and Fault Management" paper cited above. More generally, SysML's current capabilities to model functional decompositions in the rigorous manner required in the GFT approach are limited. The GFT is a new Model-Based Systems Engineering (MBSE) approach to the development of goals and requirements, functions, and its linkage to design. As a growing standard for systems engineering, it is important to develop methods to implement GFT in SysML. Proposed Method of Solution: Many of the central concepts of the SysML language are needed to implement a GFT for large complex systems. In the implementation of those central concepts, the following will be described in detail: changes to the nominal SysML process, model view definitions and examples, diagram definitions and examples, and detailed SysML construct and stereotype definitions.

Druggability of methyl-lysine binding sites

NASA Astrophysics Data System (ADS)

Santiago, C.; Nguyen, K.; Schapira, M.

2011-12-01

Structural modules that specifically recognize—or read—methylated or acetylated lysine residues on histone peptides are important components of chromatin-mediated signaling and epigenetic regulation of gene expression. Deregulation of epigenetic mechanisms is associated with disease conditions, and antagonists of acetyl-lysine binding bromodomains are efficacious in animal models of cancer and inflammation, but little is known regarding the druggability of methyl-lysine binding modules. We conducted a systematic structural analysis of readers of methyl marks and derived a predictive druggability landscape of methyl-lysine binding modules. We show that these target classes are generally less druggable than bromodomains, but that some proteins stand as notable exceptions.

A Metabolic Function for Phospholipid and Histone Methylation.

PubMed

Ye, Cunqi; Sutter, Benjamin M; Wang, Yun; Kuang, Zheng; Tu, Benjamin P

2017-04-20

S-adenosylmethionine (SAM) is the methyl donor for biological methylation modifications that regulate protein and nucleic acid functions. Here, we show that methylation of a phospholipid, phosphatidylethanolamine (PE), is a major consumer of SAM. The induction of phospholipid biosynthetic genes is accompanied by induction of the enzyme that hydrolyzes S-adenosylhomocysteine (SAH), a product and inhibitor of methyltransferases. Beyond its function for the synthesis of phosphatidylcholine (PC), the methylation of PE facilitates the turnover of SAM for the synthesis of cysteine and glutathione through transsulfuration. Strikingly, cells that lack PE methylation accumulate SAM, which leads to hypermethylation of histones and the major phosphatase PP2A, dependency on cysteine, and sensitivity to oxidative stress. Without PE methylation, particular sites on histones then become methyl sinks to enable the conversion of SAM to SAH. These findings reveal an unforeseen metabolic function for phospholipid and histone methylation intrinsic to the life of a cell. Copyright © 2017 Elsevier Inc. All rights reserved.

Roles of Distal and Genic Methylation in the Development of Prostate Tumorigenesis Revealed by Genome-wide DNA Methylation Analysis.

PubMed

Wang, Yao; Jadhav, Rohit Ramakant; Liu, Joseph; Wilson, Desiree; Chen, Yidong; Thompson, Ian M; Troyer, Dean A; Hernandez, Javier; Shi, Huidong; Leach, Robin J; Huang, Tim H-M; Jin, Victor X

2016-02-29

Aberrant DNA methylation at promoters is often linked to tumorigenesis. But many aspects of DNA methylation remain unexplored, including the individual roles of distal and gene body methylation, as well as their collaborative roles with promoter methylation. Here we performed a MBD-seq analysis on prostate specimens classified into low, high, and very high risk group based on Gleason score and TNM stages. We identified gene sets with differential methylation regions (DMRs) in Distal, TSS, gene body and TES. To understand the collaborative roles, TSS was compared with the other three DMRs, resulted in 12 groups of genes with collaborative differential methylation patterns (CDMPs). We found several groups of genes that show opposite methylation patterns in Distal and Genic regions compared to TSS region, and in general they are differentially expressed genes (DEGs) in tumors in TCGA RNA-seq data. IPA (Ingenuity Pathway Analysis) reveals AR/TP53 signaling network to be a major signaling pathway, and survival analysis indicates genes subsets significantly associated with prostate cancer recurrence. Our results suggest that DNA methylation in Distal and Genic regions also plays critical roles in contributing to prostate tumorigenesis, and may act either positively or negatively with TSSs to alter gene regulation in tumors.

Quantitative DNA Methylation Profiling in Cancer.

PubMed

Ammerpohl, Ole; Haake, Andrea; Kolarova, Julia; Siebert, Reiner

2016-01-01

Epigenetic mechanisms including DNA methylation are fundamental for the regulation of gene expression. Epigenetic alterations can lead to the development and the evolution of malignant tumors as well as the emergence of phenotypically different cancer cells or metastasis from one single tumor cell. Here we describe bisulfite pyrosequencing, a technology to perform quantitative DNA methylation analyses, to detect aberrant DNA methylation in malignant tumors.

DNA motifs associated with aberrant CpG island methylation.

PubMed

Feltus, F Alex; Lee, Eva K; Costello, Joseph F; Plass, Christoph; Vertino, Paula M

2006-05-01

Epigenetic silencing involving the aberrant methylation of promoter region CpG islands is widely recognized as a tumor suppressor silencing mechanism in cancer. However, the molecular pathways underlying aberrant DNA methylation remain elusive. Recently we showed that, on a genome-wide level, CpG island loci differ in their intrinsic susceptibility to aberrant methylation and that this susceptibility can be predicted based on underlying sequence context. These data suggest that there are sequence/structural features that contribute to the protection from or susceptibility to aberrant methylation. Here we use motif elicitation coupled with classification techniques to identify DNA sequence motifs that selectively define methylation-prone or methylation-resistant CpG islands. Motifs common to 28 methylation-prone or 47 methylation-resistant CpG island-containing genomic fragments were determined using the MEME and MAST algorithms (). The five most discriminatory motifs derived from methylation-prone sequences were found to be associated with CpG islands in general and were nonrandomly distributed throughout the genome. In contrast, the eight most discriminatory motifs derived from the methylation-resistant CpG islands were randomly distributed throughout the genome. Interestingly, this latter group tended to associate with Alu and other repetitive sequences. Used together, the frequency of occurrence of these motifs successfully discriminated methylation-prone and methylation-resistant CpG island groups with an accuracy of 87% after 10-fold cross-validation. The motifs identified here are candidate methylation-targeting or methylation-protection DNA sequences.

Immunoaffinity Enrichment and Mass Spectrometry Analysis of Protein Methylation

PubMed Central

Guo, Ailan; Gu, Hongbo; Zhou, Jing; Mulhern, Daniel; Wang, Yi; Lee, Kimberly A.; Yang, Vicky; Aguiar, Mike; Kornhauser, Jon; Jia, Xiaoying; Ren, Jianmin; Beausoleil, Sean A.; Silva, Jeffrey C.; Vemulapalli, Vidyasiri; Bedford, Mark T.; Comb, Michael J.

2014-01-01

Protein methylation is a common posttranslational modification that mostly occurs on arginine and lysine residues. Arginine methylation has been reported to regulate RNA processing, gene transcription, DNA damage repair, protein translocation, and signal transduction. Lysine methylation is best known to regulate histone function and is involved in epigenetic regulation of gene transcription. To better study protein methylation, we have developed highly specific antibodies against monomethyl arginine; asymmetric dimethyl arginine; and monomethyl, dimethyl, and trimethyl lysine motifs. These antibodies were used to perform immunoaffinity purification of methyl peptides followed by LC-MS/MS analysis to identify and quantify arginine and lysine methylation sites in several model studies. Overall, we identified over 1000 arginine methylation sites in human cell line and mouse tissues, and ∼160 lysine methylation sites in human cell line HCT116. The number of methylation sites identified in this study exceeds those found in the literature to date. Detailed analysis of arginine-methylated proteins observed in mouse brain compared with those found in mouse embryo shows a tissue-specific distribution of arginine methylation, and extends the types of proteins that are known to be arginine methylated to include many new protein types. Many arginine-methylated proteins that we identified from the brain, including receptors, ion channels, transporters, and vesicle proteins, are involved in synaptic transmission, whereas the most abundant methylated proteins identified from mouse embryo are transcriptional regulators and RNA processing proteins. PMID:24129315

Patterns of cytosine methylation in an elite rice hybrid and its parental lines, detected by a methylation-sensitive amplification polymorphism technique.

PubMed

Xiong, L Z; Xu, C G; Saghai Maroof, M A; Zhang, Q

1999-04-01

DNA methylation is known to play an important role in the regulation of gene expression in eukaryotes. In this study, we assessed the extent and pattern of cytosine methylation in the rice genome, using the technique of methylation-sensitive amplified polymorphism (MSAP), which is a modification of the amplified fragment length polymorphism (AFLP) method that makes use of the differential sensitivity of a pair of isoschizomers to cytosine methylation. The tissues assayed included seedlings and flag leaves of an elite rice hybrid, Shanyou 63, and the parental lines Zhenshan 97 and Minghui 63. In all, 1076 fragments, each representing a recognition site cleaved by either or both of the isoschizomers, were amplified using 16 pairs of selective primers. A total of 195 sites were found to be methylated at cytosines in one or both parents, and the two parents showed approximately the same overall degree of methylation (16.3%), as revealed by the incidence of differential digestion by the isoschizomers. Four classes of patterns were identified in a comparative assay of cytosine methylation in the parents and hybrid; increased methylation was detected in the hybrid compared to the parents at some of the recognition sites, while decreased methylation in the hybrid was detected at other sites. A small proportion of the sites was found to be differentially methylated in seedlings and flag leaves; DNA from young seedlings was methylated to a greater extent than that from flag leaves. Almost all of the methylation patterns detected by MSAP could be confirmed by Southern analysis using the isolated amplified fragments as probes. The results clearly demonstrate that the MSAP technique is highly efficient for large-scale detection of cytosine methylation in the rice genome. We believe that the technique can be adapted for use in other plant species.

Electronic transport in methylated fragments of DNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Almeida, M. L. de; Oliveira, J. I. N.; Lima Neto, J. X.

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

NASA Astrophysics Data System (ADS)

de Almeida, M. L.; 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.; de Moura, F. A. B. F.; Lyra, M. L.

2015-11-01

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.

Genetic Control of Methyl Halide Production in Arabidopsis

NASA Astrophysics Data System (ADS)

Rhew, R. C.; Ostergaard, L.; Saltzman, E. S.; Yanofsky, M. F.

2003-12-01

Methyl chloride and methyl bromide are the primary carriers of natural chlorine and bromine to the stratosphere where they catalyze the destruction of ozone, whereas methyl iodide influences aerosol formation and ozone loss in the troposphere. Methyl bromide is also an agricultural fumigant whose use is scheduled to be phased out by international agreement. Despite the economic and environmental importance of these methyl halides, their natural sources and biological production mechanisms are poorly understood. Currently identified sources include oceans, biomass burning, industrial and agricultural use, fuel combustion, salt marshes, wetlands, rice paddies, certain terrestrial plants and fungi, and abiotic processes. We demonstrate that the model plant Arabidopsis thaliana produces and emits methyl halides and that the enzyme primarily responsible for the production is encoded by the HARMLESS TO OZONE LAYER (HOL) gene located on chromosome II. In mutant plants that have a disruption of the HOL gene, methyl halide production is largely eliminated. A phylogenetic analysis using the HOL gene suggests that the ability to produce methyl halides is widespread among vascular plants. This approach provides a genetic basis for understanding and predicting patterns of methyl halide production by plants.

Mercury methylation by novel microorganisms from new environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilmour, C C; Podar, Mircea; Bullock, Allyson L

2013-01-01

Microbial mercury (Hg) methylation transforms a toxic trace metal into the highly bioaccumulated neurotoxin methylmercury (MeHg). The lack of a genetic marker for microbial MeHg production has prevented a clear understanding of Hg-methylating organism distribution in nature. Recently, a specific gene cluster (hgcAB) was linked to Hg methylation in two bacteria.1 Here we test if the presence of hgcAB orthologues is a reliable predictor of Hg methylation capability in microorganisms, a necessary confirmation for the development of molecular probes for Hg-methylation in nature. Although hgcAB orthologues are rare among all available microbial genomes, organisms are much more phylogenetically and environmentallymore » diverse than previously thought. By directly measuring MeHg production in several bacterial and archaeal strains encoding hgcAB, we confirmed that possessing hgcAB predicts Hg methylation capability. For the first time, we demonstrated Hg methylation in a number of species other than sulfate- (SRB) and iron- (FeRB) reducing bacteria, including methanogens, and syntrophic, acetogenic, and fermentative Firmicutes. Several of these species occupy novel environmental niches for Hg methylation, including methanogenic habitats such as rice paddies, the animal gut, and extremes of pH and salinity. Identification of these organisms as Hg methylators now links methylation to discrete gene markers in microbial communities.« less

40 CFR 721.10491 - Benzenepropanal,.alpha.-methyl-.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Benzenepropanal,.alpha.-methyl-. 721... Substances § 721.10491 Benzenepropanal,.alpha.-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzenepropanal,.alpha.-methyl- (PMN P-05...

40 CFR 721.10491 - Benzenepropanal,.alpha.-methyl-.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Benzenepropanal,.alpha.-methyl-. 721... Substances § 721.10491 Benzenepropanal,.alpha.-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as benzenepropanal,.alpha.-methyl- (PMN P-05...

Simulation Experiment Description Markup Language (SED-ML) Level 1 Version 3 (L1V3).

PubMed

Bergmann, Frank T; Cooper, Jonathan; König, Matthias; Moraru, Ion; Nickerson, David; Le Novère, Nicolas; Olivier, Brett G; Sahle, Sven; Smith, Lucian; Waltemath, Dagmar

2018-03-19

The creation of computational simulation experiments to inform modern biological research poses challenges to reproduce, annotate, archive, and share such experiments. Efforts such as SBML or CellML standardize the formal representation of computational models in various areas of biology. The Simulation Experiment Description Markup Language (SED-ML) describes what procedures the models are subjected to, and the details of those procedures. These standards, together with further COMBINE standards, describe models sufficiently well for the reproduction of simulation studies among users and software tools. The Simulation Experiment Description Markup Language (SED-ML) is an XML-based format that encodes, for a given simulation experiment, (i) which models to use; (ii) which modifications to apply to models before simulation; (iii) which simulation procedures to run on each model; (iv) how to post-process the data; and (v) how these results should be plotted and reported. SED-ML Level 1 Version 1 (L1V1) implemented support for the encoding of basic time course simulations. SED-ML L1V2 added support for more complex types of simulations, specifically repeated tasks and chained simulation procedures. SED-ML L1V3 extends L1V2 by means to describe which datasets and subsets thereof to use within a simulation experiment.

Methylation analysis of polysaccharides: Technical advice.

PubMed

Sims, Ian M; Carnachan, Susan M; Bell, Tracey J; Hinkley, Simon F R

2018-05-15

Glycosyl linkage (methylation) analysis is used widely for the structural determination of oligo- and poly-saccharides. The procedure involves derivatisation of the individual component sugars of a polysaccharide to partially methylated alditol acetates which are analysed and quantified by gas chromatography-mass spectrometry. The linkage positions for each component sugar can be determined by correctly identifying the partially methylated alditol acetates. Although the methods are well established, there are many technical aspects to this procedure and both careful attention to detail and considerable experience are required to achieve a successful methylation analysis and to correctly interpret the data generated. The aim of this article is to provide the technical details and critical procedural steps necessary for a successful methylation analysis and to assist researchers (a) with interpreting data correctly and (b) in providing the comprehensive data required for reviewers to fully assess the work. Copyright © 2018 Elsevier Ltd. All rights reserved.

N-METHYL GROUPS IN BACTERIAL LIPIDS

PubMed Central

Goldfine, Howard; Ellis, Martha E.

1964-01-01

Goldfine, Howard (Harvard Medical School, Boston, Mass.), and Martha E. Ellis. N-methyl groups in bacterial lipids. J. Bacteriol. 87:8–15. 1964.—The ability of bacteria to synthesize lecithin was examined by measuring the incorporation of the methyl group of methionine into the water-soluble moieties obtained on acid hydrolysis of bacterial lipids. Of 21 species examined, mostly of the order Eubacteriales, only 2, Agrobacterium radiobacter and A. rhizogenes, incorporated the methyl group of methionine into lipid-bound choline. Evidence was also obtained for the formation of lipid-bound N-methylethanolamine and N,N′-dimethylethanolamine in these two organisms. Two other species, Clostridium butyricum and Proteus vulgaris, incorporated the methyl group of methionine into lipid-bound N-methylethanolamine, but did not appear to be able to further methylate these lipids to form lecithin. The results of this study lend further strength to the generalization that bacteria, with the exception of the genus Agrobacterium, are unable to synthesize lecithin. PMID:14102879

Use of ceric ammonium sulphate and two dyes, methyl orange and indigo carmine, in the determination of lansoprazole in pharmaceuticals.

PubMed

Basavaiah, Kanakapura; Ramakrishna, Veeraiah; Kumar, Urdigere Rangachar Anil

2007-06-01

Two spectrophotometric methods are proposed for the assay of lansoprazole (LPZ) in bulk drug and in dosage forms using ceric ammonium sulphate (CAS) and two dyes, methyl orange and indigo carmine, as reagents. The methods involve addition of a known excess of CAS to LPZ in acid medium, followed by determination of residual CAS by reacting with a fixed amount of either methyl orange, measuring the absorbance at 520 nm (method A), or indigo carmine, measuring the absorbance at 610 nm (method B). In both methods, the amount of CAS reacted corresponds to the amount of LPZ and the measured absorbance was found to increase linearly with the concentration of LPZ, which is corroborated by the correlation coefficients of 0.9979 and 0.9954 for methods A and B, respectively. The systems obey Beer's law for 0.5-7.0 microg mL(-1) and 0.25-3.0 microg mL(-1) for methods A and B, respectively. The apparent molar absorptivities were calculated to be 3.0 x 10(4) and 4.4 x 10(4) L mol(-1) cm(-1) for methods A and B, respectively. The limits of detection (LOD) and quantification (LOQ) were calculated to be 0.08 and 0.25 microg mL(-1) for method A, and 0.09 and 0.27 microg mLs(-1) for method B, respectively. The intra-day and inter-day precision and accuracy of the methods were evaluated according to the current ICH guidelines. Both methods were of comparable accuracy (er < or = 2 %). Also, both methods are equally precise as shown by the relative standard deviation values < 1.5%. No interference was observed from common pharmaceutical adjuvants. The accuracy of the methods was further ascertained by performing recovery studies using the standard addition method. The methods were successfully applied to the assay of LPZ in capsule preparations and the results were statistically compared with those of the literature UV-spectrophotometric method by applying Student's t-test and F-test.

CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies.

PubMed

Ogino, S; Cantor, M; Kawasaki, T; Brahmandam, M; Kirkner, G J; Weisenberger, D J; Campan, M; Laird, P W; Loda, M; Fuchs, C S

2006-07-01

The concept of CpG island methylator phenotype (CIMP) is not universally accepted. Even if specific clinicopathological features have been associated with CIMP, investigators often failed to demonstrate a bimodal distribution of the number of methylated markers, which would suggest CIMP as a distinct subtype of colorectal cancer. Previous studies primarily used methylation specific polymerase chain reaction which might detect biologically insignificant low levels of methylation. To demonstrate a distinct genetic profile of CIMP colorectal cancer using quantitative DNA methylation analysis that can distinguish high from low levels of DNA methylation. We developed quantitative real time polymerase chain reaction (MethyLight) assays and measured DNA methylation (percentage of methylated reference) of five carefully selected loci (promoters of CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1) in 460 colorectal cancers from large prospective cohorts. There was a clear bimodal distribution of 80 microsatellite instability-high (MSI-H) tumours according to the number of methylated promoters, with no tumours showing 3/5 methylated loci. Thus we defined CIMP as having >or=4/5 methylated loci, and 17% (78) of the 460 tumours were classified as CIMP. CIMP was significantly associated with female sex, MSI, BRAF mutations, and wild-type KRAS. Both CIMP MSI-H tumours and CIMP microsatellite stable (MSS) tumours showed much higher frequencies of BRAF mutations (63% and 54%) than non-CIMP counterparts (non-CIMP MSI-H (0%, p<10(-5)) and non-CIMP MSS tumours (6.6%, p<10(-4)), respectively). CIMP is best characterised by quantitative DNA methylation analysis. CIMP is a distinct epigenotype of colorectal cancer and may be less frequent than previously reported.

RlmCD-mediated U747 methylation promotes efficient G748 methylation by methyltransferase RlmAII in 23S rRNA in Streptococcus pneumoniae; interplay between two rRNA methylations responsible for telithromycin susceptibility

PubMed Central

Shoji, Tatsuma; Takaya, Akiko; Sato, Yoshiharu; Kimura, Satoshi; Suzuki, Tsutomu; Yamamoto, Tomoko

2015-01-01

Adenine at position 752 in a loop of helix 35 from positions 745 to 752 in domain II of 23S rRNA is involved in binding to the ribosome of telithromycin (TEL), a member of ketolides. Methylation of guanine at position 748 by the intrinsic methyltransferase RlmAII enhances binding of telithromycin (TEL) to A752 in Streptococcus pneumoniae. We have found that another intrinsic methylation of the adjacent uridine at position 747 enhances G748 methylation by RlmAII, rendering TEL susceptibility. U747 and another nucleotide, U1939, were methylated by the dual-specific methyltransferase RlmCD encoded by SP_1029 in S. pneumoniae. Inactivation of RlmCD reduced N1-methylated level of G748 by RlmAII in vivo, leading to TEL resistance when the nucleotide A2058, located in domain V of 23S rRNA, was dimethylated by the dimethyltransferase Erm(B). In vitro methylation of rRNA showed that RlmAII activity was significantly enhanced by RlmCD-mediated pre-methylation of 23S rRNA. These results suggest that RlmCD-mediated U747 methylation promotes efficient G748 methylation by RlmAII, thereby facilitating TEL binding to the ribosome. PMID:26365244

Mercury Methylation by the Methanogen Methanospirillum hungatei

PubMed Central

Reinfelder, John R.; Hines, Mark E.

2013-01-01

Methylmercury (MeHg), a neurotoxic substance that accumulates in aquatic food chains and poses a risk to human health, is synthesized by anaerobic microorganisms in the environment. To date, mercury (Hg) methylation has been attributed to sulfate- and iron-reducing bacteria (SRB and IRB, respectively). Here we report that a methanogen, Methanospirillum hungatei JF-1, methylated Hg in a sulfide-free medium at comparable rates, but with higher yields, than those observed for some SRB and IRB. Phylogenetic analyses showed that the concatenated orthologs of the Hg methylation proteins HgcA and HgcB from M. hungatei are closely related to those from known SRB and IRB methylators and that they cluster together with proteins from eight other methanogens, suggesting that these methanogens may also methylate Hg. Because all nine methanogens with HgcA and HgcB orthologs belong to the class Methanomicrobia, constituting the late-evolving methanogenic lineage, methanogenic Hg methylation could not be considered an ancient metabolic trait. Our results identify methanogens as a new guild of Hg-methylating microbes with a potentially important role in mineral-poor (sulfate- and iron-limited) anoxic freshwater environments. PMID:23934484

A DNA methylation fingerprint of 1628 human samples

PubMed Central

Fernandez, Agustin F.; Assenov, Yassen; Martin-Subero, Jose Ignacio; Balint, Balazs; Siebert, Reiner; Taniguchi, Hiroaki; Yamamoto, Hiroyuki; Hidalgo, Manuel; Tan, Aik-Choon; Galm, Oliver; Ferrer, Isidre; Sanchez-Cespedes, Montse; Villanueva, Alberto; Carmona, Javier; Sanchez-Mut, Jose V.; Berdasco, Maria; Moreno, Victor; Capella, Gabriel; Monk, David; Ballestar, Esteban; Ropero, Santiago; Martinez, Ramon; Sanchez-Carbayo, Marta; Prosper, Felipe; Agirre, Xabier; Fraga, Mario F.; Graña, Osvaldo; Perez-Jurado, Luis; Mora, Jaume; Puig, Susana; Prat, Jaime; Badimon, Lina; Puca, Annibale A.; Meltzer, Stephen J.; Lengauer, Thomas; Bridgewater, John; Bock, Christoph; Esteller, Manel

2012-01-01

Most of the studies characterizing DNA methylation patterns have been restricted to particular genomic loci in a limited number of human samples and pathological conditions. Herein, we present a compromise between an extremely comprehensive study of a human sample population with an intermediate level of resolution of CpGs at the genomic level. We obtained a DNA methylation fingerprint of 1628 human samples in which we interrogated 1505 CpG sites. The DNA methylation patterns revealed show this epigenetic mark to be critical in tissue-type definition and stemness, particularly around transcription start sites that are not within a CpG island. For disease, the generated DNA methylation fingerprints show that, during tumorigenesis, human cancer cells underwent a progressive gain of promoter CpG-island hypermethylation and a loss of CpG methylation in non-CpG-island promoters. Although transformed cells are those in which DNA methylation disruption is more obvious, we observed that other common human diseases, such as neurological and autoimmune disorders, had their own distinct DNA methylation profiles. Most importantly, we provide proof of principle that the DNA methylation fingerprints obtained might be useful for translational purposes by showing that we are able to identify the tumor type origin of cancers of unknown primary origin (CUPs). Thus, the DNA methylation patterns identified across the largest spectrum of samples, tissues, and diseases reported to date constitute a baseline for developing higher-resolution DNA methylation maps and provide important clues concerning the contribution of CpG methylation to tissue identity and its changes in the most prevalent human diseases. PMID:21613409

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

PubMed

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.

The Gel Electrophoresis Markup Language (GelML) from the Proteomics Standards Initiative

PubMed Central

Gibson, Frank; Hoogland, Christine; Martinez-Bartolomé, Salvador; Medina-Aunon, J. Alberto; Albar, Juan Pablo; Babnigg, Gyorgy; Wipat, Anil; Hermjakob, Henning; Almeida, Jonas S; Stanislaus, Romesh; Paton, Norman W; Jones, Andrew R

2011-01-01

The Human Proteome Organisation’s Proteomics Standards Initiative (HUPO-PSI) has developed the GelML data exchange format for representing gel electrophoresis experiments performed in proteomics investigations. The format closely follows the reporting guidelines for gel electrophoresis, which are part of the Minimum Information About a Proteomics Experiment (MIAPE) set of modules. GelML supports the capture of metadata (such as experimental protocols) and data (such as gel images) resulting from gel electrophoresis so that laboratories can be compliant with the MIAPE Gel Electrophoresis guidelines, while allowing such data sets to be exchanged or downloaded from public repositories. The format is sufficiently flexible to capture data from a broad range of experimental processes, and complements other PSI formats for mass spectrometry data and the results of protein and peptide identifications to capture entire gel-based proteome workflows. GelML has resulted from the open standardisation process of PSI consisting of both public consultation and anonymous review of the specifications. PMID:20677327

The gel electrophoresis markup language (GelML) from the Proteomics Standards Initiative.

PubMed

Gibson, Frank; Hoogland, Christine; Martinez-Bartolomé, Salvador; Medina-Aunon, J Alberto; Albar, Juan Pablo; Babnigg, Gyorgy; Wipat, Anil; Hermjakob, Henning; Almeida, Jonas S; Stanislaus, Romesh; Paton, Norman W; Jones, Andrew R

2010-09-01

The Human Proteome Organisation's Proteomics Standards Initiative has developed the GelML (gel electrophoresis markup language) data exchange format for representing gel electrophoresis experiments performed in proteomics investigations. The format closely follows the reporting guidelines for gel electrophoresis, which are part of the Minimum Information About a Proteomics Experiment (MIAPE) set of modules. GelML supports the capture of metadata (such as experimental protocols) and data (such as gel images) resulting from gel electrophoresis so that laboratories can be compliant with the MIAPE Gel Electrophoresis guidelines, while allowing such data sets to be exchanged or downloaded from public repositories. The format is sufficiently flexible to capture data from a broad range of experimental processes, and complements other PSI formats for MS data and the results of protein and peptide identifications to capture entire gel-based proteome workflows. GelML has resulted from the open standardisation process of PSI consisting of both public consultation and anonymous review of the specifications.

cluML: A markup language for clustering and cluster validity assessment of microarray data.

PubMed

Bolshakova, Nadia; Cunningham, Pádraig

2005-01-01

cluML is a new markup language for microarray data clustering and cluster validity assessment. The XML-based format has been designed to address some of the limitations observed in traditional formats, such as inability to store multiple clustering (including biclustering) and validation results within a dataset. cluML is an effective tool to support biomedical knowledge representation in gene expression data analysis. Although cluML was developed for DNA microarray analysis applications, it can be effectively used for the representation of clustering and for the validation of other biomedical and physical data that has no limitations.

IGF-II promoter methylation and ovarian cancer prognosis.

PubMed

Beeghly, A C; Katsaros, D; Wiley, A L; Rigault de la Longrais, I A; Prescott, A T; Chen, H; Puopolo, M; Rutherford, T J; Yu, H

2007-10-01

The insulin-like growth factor-II (IGF-II) gene has four promoters that produce distinct transcripts which vary by tissue type and developmental stage. Dysregulation of normal promoter usage has been shown to occur in cancer; DNA methylation regulates promoter use. Thus, we sought to examine if DNA methylation varies among IGF-II promoters in ovarian cancer and if methylation patterns are related to clinical features of the disease. Tumor tissue, clinical data, and follow-up information were collected from 215 patients diagnosed with primary epithelial ovarian cancer. DNA extracted from tumor tissues was analyzed for IGF-II promoter methylation with seven methylation specific PCR (MSP) assays: three for promoter 2 (P2) and two assays each for promoters 3 and 4 (P3 and P4). Methylation was found to vary among the seven assays: 19.3% in P2A, 45.6% in P2B, 50.9% in P2C, 48.4% in P3A, 13.1% in P3B, 5.1% in P4A, and 6.1% in P4B. Methylation in any of the three P2 assays was associated with high tumor grade (P = 0.043), suboptimal debulking (P = 0.036), and disease progression [hazards ratio (HR) = 1.73, 95% confidence interval (CI) 1.09-2.74]. When comparing promoter methylation patterns, differential methylation of P2 and P3 was found to be associated with disease prognosis; patients with P3 but not P2 methylation were less likely to have disease progression (HR = 0.39, 95% CI 0.17-0.91) compared to patients with P2 but not P3 methylation. This study shows that methylation varies among three IGF-II promoters in ovarian cancer and that this variation seems to have biologic implications as it relates to clinical features and prognosis of the disease.

DNA methylation: the future of crime scene investigation?

PubMed

Gršković, Branka; Zrnec, Dario; Vicković, Sanja; Popović, Maja; Mršić, Gordan

2013-07-01

Proper detection and subsequent analysis of biological evidence is crucial for crime scene reconstruction. The number of different criminal acts is increasing rapidly. Therefore, forensic geneticists are constantly on the battlefield, trying hard to find solutions how to solve them. One of the essential defensive lines in the fight against the invasion of crime is relying on DNA methylation. In this review, the role of DNA methylation in body fluid identification and other DNA methylation applications are discussed. Among other applications of DNA methylation, age determination of the donor of biological evidence, analysis of the parent-of-origin specific DNA methylation markers at imprinted loci for parentage testing and personal identification, differentiation between monozygotic twins due to their different DNA methylation patterns, artificial DNA detection and analyses of DNA methylation patterns in the promoter regions of circadian clock genes are the most important ones. Nevertheless, there are still a lot of open chapters in DNA methylation research that need to be closed before its final implementation in routine forensic casework.

DNA Methylation Biomarkers: Cancer and Beyond

PubMed Central

Mikeska, Thomas; Craig, Jeffrey M.

2014-01-01

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. PMID:25229548

Subsets of microsatellite-unstable colorectal cancers exhibit discordance between the CpG island methylator phenotype and MLH1 methylation status.

PubMed

Kim, Jung H; Rhee, Ye-Y; Bae, Jeong-M; Kwon, Hyeong-J; Cho, Nam-Y; Kim, Mi J; Kang, Gyeong H

2013-07-01

Although the presence of MLH1 methylation in microsatellite-unstable colorectal cancer generally indicates involvement of the CpG island methylator phenotype (CIMP) in the development of the tumor, these two conditions do not always correlate. A minority of microsatellite-unstable colorectal cancers exhibit discordance between CIMP and MLH1 methylation statuses. However, the clinicopathological features of such microsatellite-unstable colorectal cancers with discrepant MLH1 methylation and CIMP statuses remain poorly studied. Microsatellite-unstable colorectal cancers (n=220) were analyzed for CIMP and MLH1 methylation statuses using the MethyLight assay. Based on the combinatorial CIMP and MLH1 methylation statuses, the microsatellite-unstable colorectal cancers were grouped into four subtypes (CIMP-high (CIMP-H) MLH1 methylation-positive (MLH1m+), CIMP-H MLH1 methylation-negative, CIMP-low/0 (CIMP-L/0) MLH1m+, and CIMP-L/0 MLH1 methylation-negative), which were compared in terms of their associations with clinicopathological and molecular features. The CIMP-L/0 MLH1 methylation-negative and CIMP-H MLH1m+ subtypes were predominant, comprising 63.6 and 24.1% of total microsatellite-unstable colorectal cancers, respectively. The discordant subtypes, CIMP-H MLH1 methylation-negative and CIMP-L/0 MLH1m+, were found in 5 and 7% of microsatellite-unstable colorectal cancers, respectively. The CIMP-H MLH1 methylation-negative subtype exhibited elevated incidence rates in male patients and was associated with larger tumor size, more frequent loss of MSH2 expression, increased frequency of KRAS mutation, and advanced cancer stage. The CIMP-L/0 MLH1m+ subtype was associated with onset at an earlier age, a predominance of MLH1 loss, and earlier cancer stage. None of the CIMP-L/0 MLH1m+ subtype patients succumbed to death during the follow-up. Our findings suggest that the discordant subtypes of colorectal cancers exhibit distinct clinicopathological and molecular features

Factors associated with aberrant imprint methylation and oligozoospermia

PubMed Central

Kobayashi, Norio; Miyauchi, Naoko; Tatsuta, Nozomi; Kitamura, Akane; Okae, Hiroaki; Hiura, Hitoshi; Sato, Akiko; Utsunomiya, Takafumi; Yaegashi, Nobuo; Nakai, Kunihiko; Arima, Takahiro

2017-01-01

Disturbingly, the number of patients with oligozoospermia (low sperm count) has been gradually increasing in industrialized countries. Epigenetic alterations are believed to be involved in this condition. Recent studies have clarified that intrinsic and extrinsic factors can induce epigenetic transgenerational phenotypes through apparent reprogramming of the male germ line. Here we examined DNA methylation levels of 22 human imprinted loci in a total of 221 purified sperm samples from infertile couples and found methylation alterations in 24.8% of the patients. Structural equation model suggested that the cause of imprint methylation errors in sperm might have been environmental factors. More specifically, aberrant methylation and a particular lifestyle (current smoking, excess consumption of carbonated drinks) were associated with severe oligozoospermia, while aging probably affected this pathology indirectly through the accumulation of PCB in the patients. Next we examined the pregnancy outcomes for patients when the sperm had abnormal imprint methylation. The live-birth rate decreased and the miscarriage rate increased with the methylation errors. Our research will be useful for the prevention of methylation errors in sperm from infertile men, and sperm with normal imprint methylation might increase the safety of assisted reproduction technology (ART) by reducing methylation-induced diseases of children conceived via ART. PMID:28186187

Lysine Methylation of Nuclear Co-repressor Receptor Interacting Protein 140

PubMed Central

Huq, MD Mostaqul; Ha, Sung Gil; Barcelona, Helene; Wei, Li-Na

2009-01-01

Receptor interacting protein 140 (RIP140) undergoes extensive posttranslational modifications (PTMs), including phosphorylation, acetylation, arginine methylation, and pyridoxylation. PTMs affect its sub-cellular distribution, protein-protein interaction, and biological activity in adipocyte differentiation. Arginine methylation on Arg240, Arg650, and Arg948 suppresses the repressive activity of RIP140. Here we find that endogenous RIP140 in differentiated 3T3-L1 cells is also modified by lysine methylation. Three lysine residues, Lys591, Lys653, and Lys757 are mapped as potential methylation sites by mass spectrometry. Site-directed mutagenesis study shows that lysine methylation enhances its gene repressive activity. Mutation of lysine methylation sites enhances arginine methylation, while mutation on arginine methylation sites has little effect on its lysine methylation, suggesting a relationship between lysine methylation and arginine methylation. Kinetic analysis of PTMs of endogenous RIP140 in differentiated 3T3-L1 cells demonstrates sequential modifications on RIP140, initiated from constitutive lysine methylation, followed by increased arginine methylation later in differentiation. This study reveals a potential hierarchy of modifications, at least for lysine and arginine methylation, which bi-directionally regulate the functionality of a non-histone protein. PMID:19216533

40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Butyl acrylate, polymer with... NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.6920 Butyl... butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted silane...

Methylation of ribonucleic acid by the carcinogens dimethyl sulphate, N-methyl-N-nitrosourea and N-methyl-N′-nitro-N-nitrosoguanidine. Comparisons of chemical analyses at the nucleoside and base levels

PubMed Central

Lawley, P. D.; Shah, S. A.

1972-01-01

1. The following methods for hydrolysis of methyl-14C-labelled RNA, and for chromatographic isolation and determination of the products, were investigated: enzymic digestion to nucleosides at pH6 or 8; alkaline hydrolysis and conversion into nucleosides; hydrolysis by acid to pyrimidine nucleotides and purine bases, or completely to bases; chromatography on Dowex 50 (NH4+ form) at pH6 or 8.9, or on Dowex 50 (H+ form), or on Sephadex G-10. 2. The suitability of the various methods for determination of methylation products was assessed. The principal product, 7-methylguanosine, was unstable under the conditions used for determinations of nucleosides. 3- and 7-Methyladenine and 3- and 7-methylguanine are best determined as bases; 1-methyladenine and 3-methylcytosine can be isolated as either nucleosides or bases; O6-methylguanine is unstable under the acid hydrolysis conditions used and can be determined as the nucleoside; 3-methyluracil was detected, but may be derived from methylation of the ionized form of uracil. 3. Differences between the patterns of methylation of RNA and homopolyribonucleotides by the N-methyl-N-nitroso compounds and dimethyl sulphate were found: the nitroso compounds were able to methylate O-6 of guanine, were relatively more reactive at N-7 of adenine and probably at N-3 of guanine, but less reactive at N-1 of adenine, N-3 of cytosine and probably at N-3 of uridine. They probably reacted more with the ribose–phosphate chain, but no products from this were identified. 4. The possible influences of these differences on biological action of the methylating agents is discussed. Nitroso compounds may differ principally in their ability to induce miscoding in the Watson–Crick sense by reaction at O-6 of guanine. Both types of agent may induce miscoding to a lesser extent through methylation at N-3 of guanine; both can methylate N atoms, presumably preventing Watson–Crick hydrogen-bonding. N-Methyl-N-nitrosourea can degrade RNA, possibly

PepArML: A Meta-Search Peptide Identification Platform

PubMed Central

Edwards, Nathan J.

2014-01-01

The PepArML meta-search peptide identification platform provides a unified search interface to seven search engines; a robust cluster, grid, and cloud computing scheduler for large-scale searches; and an unsupervised, model-free, machine-learning-based result combiner, which selects the best peptide identification for each spectrum, estimates false-discovery rates, and outputs pepXML format identifications. The meta-search platform supports Mascot; Tandem with native, k-score, and s-score scoring; OMSSA; MyriMatch; and InsPecT with MS-GF spectral probability scores — reformatting spectral data and constructing search configurations for each search engine on the fly. The combiner selects the best peptide identification for each spectrum based on search engine results and features that model enzymatic digestion, retention time, precursor isotope clusters, mass accuracy, and proteotypic peptide properties, requiring no prior knowledge of feature utility or weighting. The PepArML meta-search peptide identification platform often identifies 2–3 times more spectra than individual search engines at 10% FDR. PMID:25663956

Successive ratio subtraction coupled with constant multiplication spectrophotometric method for determination of hydroquinone in complex mixture with its degradation products, tretinoin and methyl paraben

NASA Astrophysics Data System (ADS)

Elghobashy, Mohamed R.; Bebawy, Lories I.; Shokry, Rafeek F.; Abbas, Samah S.

2016-03-01

A sensitive and selective stability-indicating successive ratio subtraction coupled with constant multiplication (SRS-CM) spectrophotometric method was studied and developed for the spectrum resolution of five component mixture without prior separation. The components were hydroquinone in combination with tretinoin, the polymer formed from hydroquinone alkali degradation, 1,4 benzoquinone and the preservative methyl paraben. The proposed method was used for their determination in their pure form and in pharmaceutical formulation. The zero order absorption spectra of hydroquinone, tretinoin, 1,4 benzoquinone and methyl paraben were determined at 293, 357.5, 245 and 255.2 nm, respectively. The calibration curves were linear over the concentration ranges of 4.00-46.00, 1.00-7.00, 0.60-5.20, and 1.00-7.00 μg mL- 1 for hydroquinone, tretinoin, 1,4 benzoquinone and methyl paraben, respectively. The pharmaceutical formulation was subjected to mild alkali condition and measured by this method resulting in the polymerization of hydroquinone and the formation of toxic 1,4 benzoquinone. The proposed method was validated according to ICH guidelines. The results obtained were statistically analyzed and compared with those obtained by applying the reported method.

Consumption study and identification of methyl salicylate in spicy cassava chips

NASA Astrophysics Data System (ADS)

Nirjana, Marlene; Anggadiredja, Kusnandar; Damayanti, Sophi

2015-09-01

Spicy cassava chips is a popular snack. However, some news in electronic media reported addition of balsam which is a banned food additives in that product to give extra spicy flavor. This study aimed to determine ITB students' pattern of consumption, health problems caused by spicy chips consumption, and knowledge about illicit use of food additives in that product, and identify the main content of balsam namely methyl salicylate in 10 samples of spicy cassava chips taken from inside and outside about ITB campus. A total of 300 questionnaires distributed to ITB students then data processing was performed. Spicy cassava chips sample macerated in 50 mL of methanol for 24 hours at room temperature, filtered and analyzed using gas chromatography capillary column with OV-1, nitrogen carrier gas and flame ionization detector. Based on questionnaires, 292 (97%) of 300 respondents had consumed spicy chips. A total of 247 (85%) from 292 respondents spicy chips consumed less than 3 times a week. A total of 195 respondents (67%) had experienced health problems after eating spicy chips. There were 137 (47%) of the 292 respondents who knew about the illicit addition of food additives into spicy chips; only 35 respondents (12%) who knew about balsam's addition. There were 126 respondents (43%) who did not pay attention to their health because they will keep eating spicy chips despite the addition of banned food additives. Through the verification of the standard addition method in gas chromatography system with a hydrogen pressure of 1.5 bar, injector temperature 200 °C, detector temperature 230 °C, oven temperature 60 °C for 2 minutes and then increased to 230 °C with rate 6 °C/menit; linearity, limit of detection, limit of quantitation, accuracy, precision, and specificity parameters met the acceptance limits. From 10 spicy cassava chips samples which were analyzed, they did not reveal any content of methyl salicylate. Methyl salicylate contained in the positive control

Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood: prospective results from a folate-replete population.

PubMed

Boeke, Caroline E; Baccarelli, Andrea; Kleinman, Ken P; Burris, Heather H; Litonjua, Augusto A; Rifas-Shiman, Sheryl L; Tarantini, Letizia; Gillman, Matthew

2012-03-01

Maternal diet affects offspring DNA methylation in animal models, but evidence from humans is limited. We investigated the extent to which gestational intake of methyl donor nutrients affects global DNA methylation in maternal and umbilical cord blood. Among mother-infant pairs in Project Viva, a folate-replete US population, we estimated maternal intakes of vitamin B12, betaine, choline, folate, cadmium, zinc and iron periconceptionally and during the second trimester. We examined associations of these nutrients with DNA methylation, measured as %5-methyl cytosines (%5mC) in Long Interspersed Nuclear Element-1 (LINE-1), in first trimester (n = 830) and second trimester (n = 671) maternal blood and in cord blood at delivery (n = 516). Cord blood methylation was higher for male than female infants {mean [standard deviation (SD)] 84.8 [0.6] vs. 84.4 [0.7]%}. In the multivariable-adjusted model, maternal intake of methyl donor nutrients periconceptionally and during the second trimester of pregnancy was not positively associated with first trimester, second trimester or cord blood LINE-1 methylation. Periconceptional betaine intake was inversely associated with cord blood methylation [regression coefficient = -0.08% (95% confidence interval (CI): -0.14,-0.01)] but this association was attenuated after adjustment for dietary cadmium, which itself was directly associated with first trimester methylation and inversely associated with cord blood methylation. We also found an inverse association between periconceptional choline [-0.10%, 95% CI: -0.17,-0.03 for each SD (~63 mg/day)] and cord blood methylation in males only. In this folate-replete population, we did not find positive associations between intake of methyl donor nutrients during pregnancy and DNA methylation overall, but among males, higher early pregnancy intakes of choline were associated with lower cord blood methylation.

Transcription factors as readers and effectors of DNA methylation.

PubMed

Zhu, Heng; Wang, Guohua; Qian, Jiang

2016-08-01

Recent technological advances have made it possible to decode DNA methylomes at single-base-pair resolution under various physiological conditions. Many aberrant or differentially methylated sites have been discovered, but the mechanisms by which changes in DNA methylation lead to observed phenotypes, such as cancer, remain elusive. The classical view of methylation-mediated protein-DNA interactions is that only proteins with a methyl-CpG binding domain (MBD) can interact with methylated DNA. However, evidence is emerging to suggest that transcription factors lacking a MBD can also interact with methylated DNA. The identification of these proteins and the elucidation of their characteristics and the biological consequences of methylation-dependent transcription factor-DNA interactions are important stepping stones towards a mechanistic understanding of methylation-mediated biological processes, which have crucial implications for human development and disease.

RlmCD-mediated U747 methylation promotes efficient G748 methylation by methyltransferase RlmAII in 23S rRNA in Streptococcus pneumoniae; interplay between two rRNA methylations responsible for telithromycin susceptibility.

PubMed

Shoji, Tatsuma; Takaya, Akiko; Sato, Yoshiharu; Kimura, Satoshi; Suzuki, Tsutomu; Yamamoto, Tomoko

2015-10-15

Adenine at position 752 in a loop of helix 35 from positions 745 to 752 in domain II of 23S rRNA is involved in binding to the ribosome of telithromycin (TEL), a member of ketolides. Methylation of guanine at position 748 by the intrinsic methyltransferase RlmA(II) enhances binding of telithromycin (TEL) to A752 in Streptococcus pneumoniae. We have found that another intrinsic methylation of the adjacent uridine at position 747 enhances G748 methylation by RlmA(II), rendering TEL susceptibility. U747 and another nucleotide, U1939, were methylated by the dual-specific methyltransferase RlmCD encoded by SP_1029 in S. pneumoniae. Inactivation of RlmCD reduced N1-methylated level of G748 by RlmA(II) in vivo, leading to TEL resistance when the nucleotide A2058, located in domain V of 23S rRNA, was dimethylated by the dimethyltransferase Erm(B). In vitro methylation of rRNA showed that RlmA(II) activity was significantly enhanced by RlmCD-mediated pre-methylation of 23S rRNA. These results suggest that RlmCD-mediated U747 methylation promotes efficient G748 methylation by RlmA(II), thereby facilitating TEL binding to the ribosome. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Dynamic Alu Methylation during Normal Development, Aging, and Tumorigenesis

PubMed Central

Lu, Xuemei

2014-01-01

DNA methylation primarily occurs on CpG dinucleotides and plays an important role in transcriptional regulations during tissue development and cell differentiation. Over 25% of CpG dinucleotides in the human genome reside within Alu elements, the most abundant human repeats. The methylation of Alu elements is an important mechanism to suppress Alu transcription and subsequent retrotransposition. Decades of studies revealed that Alu methylation is highly dynamic during early development and aging. Recently, many environmental factors were shown to have a great impact on Alu methylation. In addition, aberrant Alu methylation has been documented to be an early event in many tumors and Alu methylation levels have been associated with tumor aggressiveness. The assessment of the Alu methylation has become an important approach for early diagnosis and/or prognosis of cancer. This review focuses on the dynamic Alu methylation during development, aging, and tumor genesis. The cause and consequence of Alu methylation changes will be discussed. PMID:25243180

WaterML, an Information Standard for the Exchange of in-situ hydrological observations

NASA Astrophysics Data System (ADS)

Valentine, D.; Taylor, P.; Zaslavsky, I.

2012-04-01

The WaterML 2.0 Standards Working Group (SWG), working within the Open Geospatial Consortium (OGC) and in cooperation with the joint OGC-World Meteorological Organization (WMO) Hydrology Domain Working Group (HDWG), has developed an open standard for the exchange of water observation data; WaterML 2.0. The focus of the standard is time-series data, commonly generated from in-situ style monitoring. This is high value data for hydrological applications such as flood forecasting, environmental reporting and supporting hydrological infrastructure (e.g. dams, supply systems), which is commonly exchanged, but a lack of standards inhibits efficient reuse and automation. The process of developing WaterML required doing a harmonization analysis of existing standards to identify overlapping concepts and come to agreement on a harmonized definition. Generally the formats captured similar requirements, all with subtle differences, such as how time-series point metadata was handled. The in-progress standard WaterML 2.0 incorporates the semantics of the hydrologic information: location, procedure, and observations, and is implemented as an application schema of the Geography Markup Language version 3.2.1, making use of the OGC Observations & Measurements standards. WaterML2.0 is designed as an extensible schema to allow encoding of data to be used in a variety of exchange scenarios. Example areas of usage are: exchange of data for operational hydrological monitoring programs; supporting operation of infrastructure (e.g. dams, supply systems); cross-border exchange of observational data; release of data for public dissemination; enhancing disaster management through data exchange; and exchange in support of national reporting The first phase of WaterML2.0 focused on structural definitions allowing for the transfer of time-series, with less work on harmonization of vocabulary items such as quality codes. Vocabularies from various organizations tend to be specific and take time to

[Applications of DNA methylation markers in forensic medicine].

PubMed

Zhao, Gui-sen; Yang, Qing-en

2005-02-01

DNA methylation is a post-replication modification that is predominantly found in cytosines of the dinucleotide sequence CpG. Epigenetic information is stored in the distribution of the modified base 5-methylcytosine. DNA methylation profiles represent a more chemically and biologically stable source of molecular diagnostic information than RNA or most proteins. Recent advances attest to the great promise of DNA methylation markers as powerful future tools in the clinic. In the past decade, DNA methylation analysis has been revolutionized by two technological advances--bisulphite modification of DNA and methylation-specific polymerase chain reaction (MSP). The methylation pattern of human genome is space-time specific, sex-specific, parent-of-origin specific and disease specific, providing us an alternative way to solve forensic problems.

Collaborations between CpG sites in DNA methylation

NASA Astrophysics Data System (ADS)

Song, You; Ren, Honglei; Lei, Jinzhi

2017-08-01

DNA methylation patterns have profound impacts on genome stability, gene expression and development. The molecular base of DNA methylation patterns has long been focused at single CpG sites level. Here, we construct a kinetic model of DNA methylation with collaborations between CpG sites, from which a correlation function was established based on experimental data. The function consists of three parts that suggest three possible sources of the correlation: movement of enzymes along DNA, collaboration between DNA methylation and nucleosome modification, and global enzyme concentrations within a cell. Moreover, the collaboration strength between DNA methylation and nucleosome modification is universal for mouse early embryo cells. The obtained correlation function provides insightful understanding for the mechanisms of inheritance of DNA methylation patterns.

Analysis of DNA methylation of maize in response to osmotic and salt stress based on methylation-sensitive amplified polymorphism.

PubMed

Tan, Ming-pu

2010-01-01

Water stress is known to alter cytosine methylation, which generally represses transcription. However, little is known about the role of methylation alteration in maize under osmotic stress. Here, methylation-sensitive amplified polymorphism (MSAP) was used to screen PEG- or NaCl-induced methylation alteration in maize seedlings. The sequences of 25 differentially amplified fragments relevant to stress were successfully obtained. Two stress-specific fragments from leaves, LP166 and LPS911, shown to be homologous to retrotransposon Gag-Pol protein genes, suggested that osmotic stress-induced methylation of retrotransposons. Three MSAP fragments, representing drought-induced or salt-induced methylation in leaves, were homologous to a maize aluminum-induced transporter. Besides these, heat shock protein HSP82, Poly [ADP-ribose] polymerase 2, Lipoxygenase, casein kinase (CK2), and dehydration-responsive element-binding (DREB) factor were also homologs of MSAP sequences from salt-treated roots. One MSAP fragment amplified from salt-treated roots, designated RS39, was homologous to the first intron of maize protein phosphatase 2C (zmPP2C), whereas - LS103, absent from salt-treated leaves, was homologous to maize glutathione S-transferases (zmGST). Expression analysis showed that salt-induced intron methylation of root zmPP2C significantly downregulated its expression, while salt-induced demethylation of leaf zmGST weakly upregulated its expression. The results suggested that salinity-induced methylation downregulated zmPP2C expression, a negative regulator of the stress response, while salinity-induced demethylation upregulated zmGST expression, a positive effecter of the stress response. Altered methylation, in response to stress, might also be involved in stress acclimation. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Methylation-Sensitive High Resolution Melting (MS-HRM).

PubMed

Hussmann, Dianna; Hansen, Lise Lotte

2018-01-01

Methylation-Sensitive High Resolution Melting (MS-HRM) is an in-tube, PCR-based method to detect methylation levels at specific loci of interest. A unique primer design facilitates a high sensitivity of the assays enabling detection of down to 0.1-1% methylated alleles in an unmethylated background.Primers for MS-HRM assays are designed to be complementary to the methylated allele, and a specific annealing temperature enables these primers to anneal both to the methylated and the unmethylated alleles thereby increasing the sensitivity of the assays. Bisulfite treatment of the DNA prior to performing MS-HRM ensures a different base composition between methylated and unmethylated DNA, which is used to separate the resulting amplicons by high resolution melting.The high sensitivity of MS-HRM has proven useful for detecting cancer biomarkers in a noninvasive manner in urine from bladder cancer patients, in stool from colorectal cancer patients, and in buccal mucosa from breast cancer patients. MS-HRM is a fast method to diagnose imprinted diseases and to clinically validate results from whole-epigenome studies. The ability to detect few copies of methylated DNA makes MS-HRM a key player in the quest for establishing links between environmental exposure, epigenetic changes, and disease.

21 CFR 173.385 - Sodium methyl sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium methyl sulfate. 173.385 Section 173.385 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... CONSUMPTION Specific Usage Additives § 173.385 Sodium methyl sulfate. Sodium methyl sulfate may be present in...

21 CFR 173.385 - Sodium methyl sulfate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium methyl sulfate. 173.385 Section 173.385 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD... CONSUMPTION Specific Usage Additives § 173.385 Sodium methyl sulfate. Sodium methyl sulfate may be present in...

Cortical DNA methylation maintains remote memory.

PubMed

Miller, Courtney A; Gavin, Cristin F; White, Jason A; Parrish, R Ryley; Honasoge, Avinash; Yancey, Christopher R; Rivera, Ivonne M; Rubio, María D; Rumbaugh, Gavin; Sweatt, J David

2010-06-01

A behavioral memory's lifetime represents multiple molecular lifetimes, suggesting the necessity for a self-perpetuating signal. One candidate is DNA methylation, a transcriptional repression mechanism that maintains cellular memory throughout development. We found that persistent, gene-specific cortical hypermethylation was induced in rats by a single, hippocampus-dependent associative learning experience and pharmacologic inhibition of methylation 1 month after learning disrupted remote memory. We propose that the adult brain utilizes DNA methylation to preserve long-lasting memories.

Regenerating muscle with arginine methylation

PubMed Central

Blanc, Roméo S.; Richard, Stéphane

2017-01-01

ABSTRACT Protein arginine methyltransferase (PRMT) is a family of nine proteins catalyzing the methylation of arginine residues. They were recently shown to be essential for proper regeneration of skeletal muscles. However, the mechanisms triggering the methylation event, as well as how the methylated substrates regulate muscle stem cell function and fate decision remain to be determined. This point-of-view will discuss the recent findings on the specific role of PRMT1, CARM1/PRMT4, PRMT5, and PRMT7 in muscle stem cell fate guidance, and shed light on the future challenges which could help defining the therapeutic potential of PRMT inhibitors against muscular disorders and aging. PMID:28301308

Regenerating muscle with arginine methylation.

PubMed

Blanc, Roméo S; Richard, Stéphane

2017-05-27

Protein arginine methyltransferase (PRMT) is a family of nine proteins catalyzing the methylation of arginine residues. They were recently shown to be essential for proper regeneration of skeletal muscles. However, the mechanisms triggering the methylation event, as well as how the methylated substrates regulate muscle stem cell function and fate decision remain to be determined. This point-of-view will discuss the recent findings on the specific role of PRMT1, CARM1/PRMT4, PRMT5, and PRMT7 in muscle stem cell fate guidance, and shed light on the future challenges which could help defining the therapeutic potential of PRMT inhibitors against muscular disorders and aging.

Quantitative methylation-sensitive arbitrarily primed PCR method to determine differential genomic DNA methylation in Down Syndrome.

PubMed

Chango, Abalo; Abdennebi-Najar, Latifa; Tessier, Frederic; Ferré, Séverine; Do, Sergio; Guéant, Jean-Louis; Nicolas, Jean Pierre; Willequet, Francis

2006-10-20

Relative levels of DNA hypermethylation were quantified in DS individuals using a new method based on a combination of methylation-sensitive arbitrarily primed polymerase chain reaction (MS-AP-PCR) and quantification of DNA fragments with the Agilent 2100 bioanalyzer. Four of the DS individuals had low plasma total homocysteine (tHcy) level (4.3 +/- 0.3 micromol/l) and 4 other had high-tHcy level (14.1 +/- 0.9 micromol/l). Eight healthy control individuals were matched to the DS cases for age, sex, and tHcy levels. We have identified and quantified six hypermethylated fragments. Their sizes ranged from 230-bp to 700-bp. In cases and controls, low-tHcy did not affect methylation level of identified fragments, mean methylation values were 68.0 +/- 39.7% and 52.1 +/- 40.3%, respectively. DNA methylation in DS individuals did not change significantly (59.7+/-34.5%) in response to high-tHcy level in contrast to controls (23.4 +/- 17.7%, P = 0.02). Further, the quantitative MS-AP-PCR using this microfludic system is a useful method for determining differential genomic DNA methylation.

Quantification of the methylation status of the PWS/AS imprinted region: comparison of two approaches based on bisulfite sequencing and methylation-sensitive MLPA.

PubMed

Dikow, Nicola; Nygren, Anders Oh; Schouten, Jan P; Hartmann, Carolin; Krämer, Nikola; Janssen, Bart; Zschocke, Johannes

2007-06-01

Standard methods used for genomic methylation analysis allow the detection of complete absence of either methylated or non-methylated alleles but are usually unable to detect changes in the proportion of methylated and unmethylated alleles. We compare two methods for quantitative methylation analysis, using the chromosome 15q11-q13 imprinted region as model. Absence of the non-methylated paternal allele in this region leads to Prader-Willi syndrome (PWS) whilst absence of the methylated maternal allele results in Angelman syndrome (AS). A proportion of AS is caused by mosaic imprinting defects which may be missed with standard methods and require quantitative analysis for their detection. Sequence-based quantitative methylation analysis (SeQMA) involves quantitative comparison of peaks generated through sequencing reactions after bisulfite treatment. It is simple, cost-effective and can be easily established for a large number of genes. However, our results support previous suggestions that methods based on bisulfite treatment may be problematic for exact quantification of methylation status. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) avoids bisulfite treatment. It detects changes in both CpG methylation as well as copy number of up to 40 chromosomal sequences in one simple reaction. Once established in a laboratory setting, the method is more accurate, reliable and less time consuming.

Dynamic DNA methylation reconfiguration during seed development and germination.

PubMed

Kawakatsu, Taiji; Nery, Joseph R; Castanon, Rosa; Ecker, Joseph R

2017-09-15

Unlike animals, plants can pause their life cycle as dormant seeds. In both plants and animals, DNA methylation is involved in the regulation of gene expression and genome integrity. In animals, reprogramming erases and re-establishes DNA methylation during development. However, knowledge of reprogramming or reconfiguration in plants has been limited to pollen and the central cell. To better understand epigenetic reconfiguration in the embryo, which forms the plant body, we compared time-series methylomes of dry and germinating seeds to publicly available seed development methylomes. Time-series whole genome bisulfite sequencing reveals extensive gain of CHH methylation during seed development and drastic loss of CHH methylation during germination. These dynamic changes in methylation mainly occur within transposable elements. Active DNA methylation during seed development depends on both RNA-directed DNA methylation and heterochromatin formation pathways, whereas global demethylation during germination occurs in a passive manner. However, an active DNA demethylation pathway is initiated during late seed development. This study provides new insights into dynamic DNA methylation reprogramming events during seed development and germination and suggests possible mechanisms of regulation. The observed sequential methylation/demethylation cycle suggests an important role of DNA methylation in seed dormancy.

AstroML: "better, faster, cheaper" towards state-of-the-art data mining and machine learning

NASA Astrophysics Data System (ADS)

Ivezic, Zeljko; Connolly, Andrew J.; Vanderplas, Jacob

2015-01-01

We present AstroML, a Python module for machine learning and data mining built on numpy, scipy, scikit-learn, matplotlib, and astropy, and distributed under an open license. AstroML contains a growing library of statistical and machine learning routines for analyzing astronomical data in Python, loaders for several open astronomical datasets (such as SDSS and other recent major surveys), and a large suite of examples of analyzing and visualizing astronomical datasets. AstroML is especially suitable for introducing undergraduate students to numerical research projects and for graduate students to rapidly undertake cutting-edge research. The long-term goal of astroML is to provide a community repository for fast Python implementations of common tools and routines used for statistical data analysis in astronomy and astrophysics (see http://www.astroml.org).

Transcription factors as readers and effectors of DNA methylation

PubMed Central

Zhu, Heng; Wang, Guohua; Qian, Jiang

2017-01-01

Recent technological advances have made it possible to decode DNA methylomes at single-base-pair resolution under various physiological conditions. Many aberrant or differentially methylated sites have been discovered, but the mechanisms by which changes in DNA methylation lead to observed phenotypes, such as cancer, remain elusive. The classical view of methylation-mediated protein-DNA interactions is that only proteins with a methyl-CpG binding domain (MBD) can interact with methylated DNA. However, evidence is emerging to suggest that transcription factors lacking a MBD can also interact with methylated DNA. The identification of these proteins and the elucidation of their characteristics and the biological consequences of methylation-dependent transcription factor-DNA interactions are important stepping stones towards a mechanistic understanding of methylation-mediated biological processes, which have crucial implications for human development and disease. PMID:27479905

Dishevelled3 is a novel arginine methyl transferase substrate.

PubMed

Bikkavilli, Rama Kamesh; Avasarala, Sreedevi; Vanscoyk, Michelle; Sechler, Marybeth; Kelley, Nicole; Malbon, Craig C; Winn, Robert A

2012-01-01

Dishevelled, a phosphoprotein scaffold, is a central component in all the Wnt-sensitive signaling pathways. In the present study, we report that Dishevelled is post-translationally modified, both in vitro and in vivo, via arginine methylation. We also show protein arginine methyl transferases 1 and 7 as the key enzymes catalyzing Dishevelled methylation. Interestingly, Wnt3a stimulation of F9 teratocarcinoma cells results in reduced Dishevelled methylation. Similarly, the methylation-deficient mutant of Dishevelled, R271K, displayed spontaneous membrane localization and robust activation of Wnt signaling; suggesting that differential methylation of Dishevelled plays an important role in Wnt signaling. Thus arginine methylation is shown to be an important switch in regulation of Dishevelled function and Wnt signaling.

A markup language for electrocardiogram data acquisition and analysis (ecgML)

PubMed Central

Wang, Haiying; Azuaje, Francisco; Jung, Benjamin; Black, Norman

2003-01-01

Background The storage and distribution of electrocardiogram data is based on different formats. There is a need to promote the development of standards for their exchange and analysis. Such models should be platform-/ system- and application-independent, flexible and open to every member of the scientific community. Methods A minimum set of information for the representation and storage of electrocardiogram signals has been synthesised from existing recommendations. This specification is encoded into an XML-vocabulary. The model may aid in a flexible exchange and analysis of electrocardiogram information. Results Based on advantages of XML technologies, ecgML has the ability to present a system-, application- and format-independent solution for representation and exchange of electrocardiogram data. The distinction between the proposal developed by the U.S Food and Drug Administration and ecgML model is given. A series of tools, which aim to facilitate ecgML-based applications, are presented. Conclusions The models proposed here can facilitate the generation of a data format, which opens ways for better and clearer interpretation by both humans and machines. Its structured and transparent organisation will allow researchers to expand and test its capabilities in different application domains. The specification and programs for this protocol are publicly available. PMID:12735790

21 CFR 173.385 - Sodium methyl sulfate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium methyl sulfate. 173.385 Section 173.385... Sodium methyl sulfate. Sodium methyl sulfate may be present in pectin in accordance with the following... subsequent treatment with sodium bicarbonate. (b) It does not exceed 0.1 percent by weight of the pectin. ...

Vapor Pressure of Methyl Salicylate and n-Hexadecane

DTIC Science & Technology

2014-01-01

VAPOR PRESSURE OF METHYL SALICYLATE AND N-HEXADECANE ECBC-TR-1184 David E. Tevault Leonard C. Buettner...REPORT TYPE Final 3. DATES COVERED (From - To) Mar 2000-Dec 2001 4. TITLE AND SUBTITLE Vapor Pressure of Methyl Salicylate and n-Hexadecane 5a...ABSTRACT Vapor pressure data are reported for O-hydroxybenzoic acid, methyl ester, more commonly known as methyl salicylate (MeS), and n-hexadecane in

Methylated spirit burns: an ongoing problem.

PubMed

Jansbeken, J R H; Vloemans, A F P M; Tempelman, F R H; Breederveld, R S

2012-09-01

Despite many educational campaigns we still see burns caused by methylated spirit every year. We undertook a retrospective study to analyse the impact of this problem. We retrospectively collected data of all patients with burns caused by methylated spirit over twelve years from 1996 to 2008. Our main endpoints were: incidence, age, mechanism of injury, total body surface area (TBSA) burned, burn depth, need for surgery and length of hospital stay. Ninety-seven patients with methylated spirit burns were included. During the study period there was no decrease in the number of patients annually admitted to the burn unit with methylated spirit burns. 28% of the patients (n=27) were younger than eighteen years old, 15% (n=15) were ten years old or younger. The most common cause of burns was carelessness in activities involving barbecues, campfires and fondues. Mean TBSA burned was 16% (SD 12.4). 70% (n=68) had full thickness burns. 66% (n=64) needed grafting. Mean length of hospital stay was 23 days (SD 24.7). The use of methylated spirit is an ongoing problem, which continues to cause severe burns in adults and children. Therefore methylated spirit should be banned in households. We suggest sale only in specialised shops, clear labelling and mandatory warnings. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Absolute photoionization cross-section of the methyl radical.

PubMed

Taatjes, Craig A; Osborn, David L; Selby, Talitha M; Meloni, Giovanni; Fan, Haiyan; Pratt, Stephen T

2008-10-02

The absolute photoionization cross-section of the methyl radical has been measured using two completely independent methods. The CH3 photoionization cross-section was determined relative to that of acetone and methyl vinyl ketone at photon energies of 10.2 and 11.0 eV by using a pulsed laser-photolysis/time-resolved synchrotron photoionization mass spectrometry method. The time-resolved depletion of the acetone or methyl vinyl ketone precursor and the production of methyl radicals following 193 nm photolysis are monitored simultaneously by using time-resolved synchrotron photoionization mass spectrometry. Comparison of the initial methyl signal with the decrease in precursor signal, in combination with previously measured absolute photoionization cross-sections of the precursors, yields the absolute photoionization cross-section of the methyl radical; sigma(CH3)(10.2 eV) = (5.7 +/- 0.9) x 10(-18) cm(2) and sigma(CH3)(11.0 eV) = (6.0 +/- 2.0) x 10(-18) cm(2). The photoionization cross-section for vinyl radical determined by photolysis of methyl vinyl ketone is in good agreement with previous measurements. The methyl radical photoionization cross-section was also independently measured relative to that of the iodine atom by comparison of ionization signals from CH3 and I fragments following 266 nm photolysis of methyl iodide in a molecular-beam ion-imaging apparatus. These measurements gave a cross-section of (5.4 +/- 2.0) x 10(-18) cm(2) at 10.460 eV, (5.5 +/- 2.0) x 10(-18) cm(2) at 10.466 eV, and (4.9 +/- 2.0) x 10(-18) cm(2) at 10.471 eV. The measurements allow relative photoionization efficiency spectra of methyl radical to be placed on an absolute scale and will facilitate quantitative measurements of methyl concentrations by photoionization mass spectrometry.

Evaluation of [(11)C]methyl-losartan and [(11)C]methyl-EXP3174 for PET imaging of renal AT1receptor in rats.

PubMed

Ismail, Basma; Hadizad, Tayebeh; Antoun, Rawad; Lortie, Mireille; deKemp, Robert A; Beanlands, Rob S B; DaSilva, Jean N

2015-11-01

The angiotensin II type 1 receptor (AT1R) is responsible for the main effects of the renin-angiotensin system (RAS), and its expression pattern is altered in several diseases. The [(11)C]methylated derivatives of the clinically used AT1R blocker (ARB) losartan and its active metabolite EXP3174, that binds with higher affinity to AT1R, were evaluated as potential PET imaging tracers in rat kidneys. [(11)C]Methyl-losartan and [(11)C]methyl-EXP3174 were synthesized by [(11)C]methylation of the tetrazole-protected analogs using [11C]methyl iodide. Tissue uptake and binding selectivity of [(11)C]methyl-losartan were assessed by ex-vivo biodistribution and in-vitro autoradiography. Radiolabeled metabolites in rat plasma and kidneys were analysed by column-switch HPLC. Both tracers were evaluated with small animal PET imaging. Due to better pharmacokinetics, [(11)C]methyl-EXP3174 was further investigated via PET by co-injection with AT1R antagonist candesartan or the AT2R antagonist PD123,319. Binding selectivity to renal AT1 over AT2 and Mas receptors was demonstrated for [(11)C]methyl-losartan. Plasma metabolite analysis at 10 min revealed stability of [(11)C]methyl-losartan and [(11)C]methyl-EXP3174 with the presence of unchanged tracer at 70.8 ± 9.9% and 81.4 ± 6.0%, of total radioactivity, respectively. Contrary to [(11)C]methyl-losartan, co-injection of candesartan with [(11)C]methyl-EXP3174 reduced the proportion of unchanged tracer (but not metabolites), indicating that these metabolites do not bind to AT1R in rat kidneys. MicroPET images for both radiotracers displayed high kidney-to-background contrast. Candesartan significantly reduced [(11)C]methyl-EXP3174 uptake in the kidney, whereas no difference was observed following PD123,319 indicating binding selectivity for AT1R. [(11)C]Methyl-EXP3174 displayed a favorable binding profile compared to [(11)C]methyl-losartan for imaging renal AT1Rs supporting further studies to assess its full potential as a

N.m.r. studies of the conformation of analogues of methyl beta-lactoside in methyl sulfoxide-d6.

PubMed

Rivera-Sagredo, A; Jiménez-Barbero, J; Martín-Lomas, M

1991-12-16

The 1H- and 13C-n.m.r. spectra of solutions of methyl beta-lactoside (1), all of its monodeoxy derivatives (2, 3, 6-10), the 3-O-methyl derivative (4), and methyl 4-O-beta-D-galactopyranosyl-D-xylopyranoside (5) in methyl sulfoxide-d6 have been analysed. The n.O.e.'s and specific desheildings indicate similar distributions of low-energy conformers, comparable to those in aqueous solution. The major conformer has torsion angles phi H and psi H of 49 degrees and 5 degrees, respectively, with contributions of conformers with phi/psi 24 degrees/-59 degrees, 22 degrees/32 degrees, and 6 degrees/44 degrees.

Study of the Formation and Solution Properties of Worm-Like Micelles Formed Using Both N-Hexadecyl-N-Methylpiperidinium Bromide-Based Cationic Surfactant and Anionic Surfactant

PubMed Central

Yan, Zhihu; Dai, Caili; Feng, Haishun; Liu, Yifei; Wang, Shilu

2014-01-01

The viscoelastic properties of worm-like micelles formed by mixing the cationic surfactant N-hexadecyl-N-methylpiperidinium bromide (C16MDB) with the anionic surfactant sodium laurate (SL) in aqueous solutions were investigated using rheological measurements. The effects of sodium laurate and temperature on the worm-like micelles and the mechanism of the observed shear thinning phenomenon and pseudoplastic behavior were systematically investigated. Additionally, cryogenic transmission electron microscopy images further ascertained existence of entangled worm-like micelles. PMID:25296131

Methyl group turnover on methyl-accepting chemotaxis proteins during chemotaxis by Bacillus subtilis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thoelke, M.S.; Casper, J.M.; Ordal, G.W.

1990-02-05

The addition of attractant to Bacillus subtilis briefly exposed to radioactive methionine causes an increase of labeling of the methyl-accepting chemotaxis proteins. The addition of attractant to cells radiolabeled for longer times shows no change in the extent of methylation. Therefore, the increase in labeling for the briefly labeled cells is due to an increased turnover of methyl groups caused by attractant. All amino acids gave enhanced turnover. This turnover lasted for a prolonged time, probably spanning the period of smooth swimming caused by the attractant addition. Repellent did not affect the turnover when added alone or simultaneously with attractant.more » Thus, for amino acid attractants, the turnover is probably the excitatory signal, which is seen to extend long into or throughout the adaptation period, not just at the start of it.« less

Genome-wide DNA methylation analysis in lung fibroblasts co-cultured with silica-exposed alveolar macrophages.

PubMed

Li, Juan; Yao, Wu; Zhang, Lin; Bao, Lei; Chen, Huiting; Wang, Di; Yue, Zhongzheng; Li, Yiping; Zhang, Miao; Hao, Changfu

2017-05-12

Exposure to crystalline silica is considered to increase the risk of lung fibrosis. The primary effector cell, the myofibroblast, plays an important role in the deposition of extracellular matrix (ECM). DNA methylation change is considered to have a potential effect on myofibroblast differentiation. Therefore, the present study was designed to investigate the genome-wide DNA methylation profiles of lung fibroblasts co-cultured with alveolar macrophages exposed to crystalline silica in vitro. AM/fibroblast co-culture system was established. CCK8 was used to assess the toxicity of AMs. mRNA and protein expression of collagen I, α-SMA, MAPK9 and TGF-β1 of fibroblasts after AMs exposed to 100 μg /ml SiO 2 for 0-, 24-, or 48 h were determined by means of quantitative real-time PCR, immunoblotting and immunohistochemistry. Genomic DNA of fibroblasts was isolated using MeDIP-Seq to sequence. R software, GO, KEGG and Cytoscape were used to analyze the data. SiO 2 exposure increased the expression of collagen I and α-SMA in fibroblasts in co-culture system. Analysis of fibroblast methylome identified extensive methylation changes involved in several signaling pathways, such as the MAPK signaling pathway and metabolic pathways. Several candidates, including Tgfb1 and Mapk9, are hubs who can connect the gene clusters. MAPK9 mRNA expression was significantly higher in fibroblast exposed to SiO 2 in co-culture system for 48 h. MAPK9 protein expression was increased at both 24-h and 48-h treatment groups. TGF-β1 mRNA expression of fibroblast has a time-dependent manner, but we didn't observe the TGF-β1 protein expression. Tgfb1 and Mapk9 are helpful to explore the mechanism of myofibroblast differentiation. The genome-wide DNA methylation profiles of fibroblasts in this experimental silicosis model will be useful for future studies on epigenetic gene regulation during myofibroblast differentiation.

RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models.