Stereoselective synthesis of stable-isotope-labeled amino acids

International Nuclear Information System (INIS)

Unkefer, C.J.; Martinez, R.A.; Silks, L.A. III; Lodwig, S.N.

1994-01-01

For magnetic resonance and vibrational spectroscopies to reach their full potential, they must be used in combination with sophisticated site-specific stable isotope labeling of biological macromolecules. Labeled amino acids are required for the study of the structure and function of enzymes and proteins. Because there are 20 common amino acids, each with its own distinguishing chemistry, they remain a synthetic challenge. The Oppolzer chiral auxiliary provides a general tool with which to approach the synthesis of labeled amino acids. By using the Oppolzer auxiliary, amino acids can be constructed from several small molecules, which is ideal for stable isotope labeling. In addition to directing the stereochemistry at the α-carbon, the camphorsultam can be used for stereo-specific isotope labeling at prochiral centers in amino acids. By using the camphorsultam auxiliary we have the potential to synthesize virtually any isotopomer of all of the common amino acids

Stable isotope dimethyl labelling for quantitative proteomics and beyond

Science.gov (United States)

Hsu, Jue-Liang; Chen, Shu-Hui

2016-01-01

Stable-isotope reductive dimethylation, a cost-effective, simple, robust, reliable and easy-to- multiplex labelling method, is widely applied to quantitative proteomics using liquid chromatography-mass spectrometry. This review focuses on biological applications of stable-isotope dimethyl labelling for a large-scale comparative analysis of protein expression and post-translational modifications based on its unique properties of the labelling chemistry. Some other applications of the labelling method for sample preparation and mass spectrometry-based protein identification and characterization are also summarized. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644970

Protein labelling with stable isotopes: strategies

International Nuclear Information System (INIS)

Lirsac, P.N.; Gilles, N.; Jamin, N.; Toma, F.; Gabrielsen, O.; Boulain, J.C.; Menez, A.

1994-01-01

A protein labelling technique with stable isotopes has been developed at the CEA: a labelled complete medium has been developed, performing as well as the Luria medium, but differing from it because it contains not only free aminated acids and peptides, but also sugars (96% of D-glucopyrannose) and labelled nucleosides. These precursors are produced from a labelled photosynthetic micro-organisms biomass, obtained with micro-algae having incorporated carbon 13, nitrogen 15 and deuterium during their culture. Labelling costs are reduced. 1 fig., 1 tab., 3 refs

Positional enrichment by proton analysis (PEPA). A one-dimensional "1H-NMR approach for "1"3C stable isotope tracer studies in metabolomics

International Nuclear Information System (INIS)

Vinaixa, Maria; Yanes, Oscar; Rodriguez, Miguel A.; Capellades, Jordi; Aivio, Suvi; Stracker, Travis H.; Gomez, Josep; Canyellas, Nicolau

2017-01-01

A novel metabolomics approach for NMR-based stable isotope tracer studies called PEPA is presented, and its performance validated using human cancer cells. PEPA detects the position of carbon label in isotopically enriched metabolites and quantifies fractional enrichment by indirect determination of "1"3C-satellite peaks using 1D-"1H-NMR spectra. In comparison with "1"3C-NMR, TOCSY and HSQC, PEPA improves sensitivity, accelerates the elucidation of "1"3C positions in labeled metabolites and the quantification of the percentage of stable isotope enrichment. Altogether, PEPA provides a novel framework for extending the high-throughput of "1H-NMR metabolic profiling to stable isotope tracing in metabolomics, facilitating and complementing the information derived from 2D-NMR experiments and expanding the range of isotopically enriched metabolites detected in cellular extracts. (copyright 2017 The Authors. Published by Wiley-VCH Verlag GmbH and Co. KGaA.)

Uses of stable isotopes

International Nuclear Information System (INIS)

Axente, Damian

1998-01-01

The most important fields of stable isotope use with examples are presented. These are: 1. Isotope dilution analysis: trace analysis, measurements of volumes and masses; 2. Stable isotopes as tracers: transport phenomena, environmental studies, agricultural research, authentication of products and objects, archaeometry, studies of reaction mechanisms, structure and function determination of complex biological entities, studies of metabolism, breath test for diagnostic; 3. Isotope equilibrium effects: measurement of equilibrium effects, investigation of equilibrium conditions, mechanism of drug action, study of natural processes, water cycle, temperature measurements; 4. Stable isotope for advanced nuclear reactors: uranium nitride with 15 N as nuclear fuel, 157 Gd for reactor control. In spite of some difficulties of stable isotope use, particularly related to the analytical techniques, which are slow and expensive, the number of papers reporting on this subject is steadily growing as well as the number of scientific meetings organized by International Isotope Section and IAEA, Gordon Conferences, and regional meeting in Germany, France, etc. Stable isotope application development on large scale is determined by improving their production technologies as well as those of labeled compound and the analytical techniques. (author)

Calculation of turnover rates in stable-isotope studies

International Nuclear Information System (INIS)

Wootton, R.; Ford, G.C.; Cheng, K.N.; Halliday, D.

1985-01-01

In a comparison of glucose turnover measured with 2 H-glucose and with 13 C-glucose Tserng and Kalhan used five apparently different equations and obtained conflicting answers. There is, however, no difference in principle between the use of a stable isotope as a tracer and the use of a radioactive isotope, and the rate of appearance of tracee in a steady-state system (the turnover) can therefore be shown to be proportional to the equilibrium dilution of the infused tracer. Because the sensitivity of measurement of this dilution made using a gas chromatograph-mass spectrometer is lower than that made by radioactivity measurement, the contribution to the measured turnover rate due to the infusate cannot be neglected, as it usually is in radioisotope work. A convenient calibration curve to establish this dilution is the mole ratio of the pure infusate against the area ratio for the relevant ions. Tserng and Kalhan's apparently conflicting results for glucose-turnover using 13 C-glucose as the tracer can all be shown to amount to approximately 11.6 μmol min -1 kg -1 . This value is only slightly lower (0.05 2 H-glucose as the tracer and supports the use of 13 C-glucose as an alternative. (author)

Bromide as a tracer for studying water movement and nitrate displacement in soils: comparison with stable isotope tracers

International Nuclear Information System (INIS)

Russow, R.; Knappe, S.

1999-01-01

Tracers are an ideal means of studying water movement and associated nitrate displacement. Often bromide is preferred as a tracer because it is considered a representative tracer for water and because, being a conservative tracer (i.e. not involved in chemical and biological soil processes), it can be used for studying anion transport in soils. Moreover, it is less expensive and easier to measure than the stable isotopes deuterium and 15 N. Its great advantage over radioactive tracers (e.g. tritium), which outweighs their extreme sensitivity and ease of measurement and which it has in common with stable isotopes, is that it does not require radiation protection measures. However, there are also constraints on the use of bromide as a tracer in soil/water/plant systems. Our own studies on different soils using D 2 O, bromide and [ 15 N]-nitrate in lysimeters suggest that the above assumptions on bromide tracers need not always be valid under conditions as they prevail in biologically active soils. As the present paper shows, these studies permit a good assessment of the possibilities and limits to these tracers [de

Positional enrichment by proton analysis (PEPA). A one-dimensional {sup 1}H-NMR approach for {sup 13}C stable isotope tracer studies in metabolomics

Energy Technology Data Exchange (ETDEWEB)

Vinaixa, Maria; Yanes, Oscar [Department of Electronic Engineering-Universitat Rovira i Virgili, Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus (Spain); Rodriguez, Miguel A.; Capellades, Jordi [Universitat Rovira i Virgili, Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus (Spain); Aivio, Suvi; Stracker, Travis H. [Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (Spain); Gomez, Josep; Canyellas, Nicolau [Department of Electronic Engineering-, Universitat Rovira i Virgili, Tarragona (Spain)

2017-03-20

A novel metabolomics approach for NMR-based stable isotope tracer studies called PEPA is presented, and its performance validated using human cancer cells. PEPA detects the position of carbon label in isotopically enriched metabolites and quantifies fractional enrichment by indirect determination of {sup 13}C-satellite peaks using 1D-{sup 1}H-NMR spectra. In comparison with {sup 13}C-NMR, TOCSY and HSQC, PEPA improves sensitivity, accelerates the elucidation of {sup 13}C positions in labeled metabolites and the quantification of the percentage of stable isotope enrichment. Altogether, PEPA provides a novel framework for extending the high-throughput of {sup 1}H-NMR metabolic profiling to stable isotope tracing in metabolomics, facilitating and complementing the information derived from 2D-NMR experiments and expanding the range of isotopically enriched metabolites detected in cellular extracts. (copyright 2017 The Authors. Published by Wiley-VCH Verlag GmbH and Co. KGaA.)

Applications of stable isotope tracers to air pollution problems

International Nuclear Information System (INIS)

Kelly, W.R.

1985-01-01

One of the fundamental environmental problems facing the United States is how to effect acid rain abatement in the northeast United States and southeastern Canada in a cost effective manner. There are several key scientific questions that must be addressed in order to design an effective strategy. These questions include the following: (1) where do pollutants from a specified source area go., (2) what chemical transformations occur during transport., and (3) where and how are these pollutants deposited. One approach to address these questions is the use of enriched stable isotopes as intentional tracers of aerosol and sulfur emissions. Isotopic tracers can determine the location and pathways of pollutants in the environment and trace pollutants back to their original source. For an element with n isotopes, it is possible to intentionally tag n-2 sources. (For example, Nd, which has seven isotopes, could be used to tag 5 different aerosol sources). To trace sulfur compounds, the two minor isotopes of sulfur, 33 S and 36 S, could be used. Methods developed at NBS using high precision mass spectrometry permits the detection of the small changes in isotopic composition brought about by the intentional tagging at a source. This may make possible the identification of a source at a particular sampling site

Use of a variable tracer infusion method to determine glucose turnover in humans

International Nuclear Information System (INIS)

Molina, J.M.; Baron, A.D.; Edelman, S.V.; Brechtel, G.; Wallace, P.; Olefsky, J.M.

1990-01-01

The single-compartment pool fraction model, when used with the hyperinsulinemic glucose clamp technique to measure rates of glucose turnover, sometimes underestimates true rates of glucose appearance (Ra) resulting in negative values for hepatic glucose output (HGO). We focused our attention on isotope discrimination and model error as possible explanations for this underestimation. We found no difference in [3-3H] glucose specific activity in samples obtained simultaneously from the femoral artery and vein (2,400 +/- 455 vs. 2,454 +/- 522 dpm/mg) in 6 men during a hyperinsulinemic euglycemic clamp study where insulin was infused at 40 mU.m-2.min-1 for 3 h; therefore, isotope discrimination did not occur. We compared the ability of a constant (0.6 microCi/min) vs. variable tracer infusion method (tracer added to the glucose infusate) to measure non-steady-state Ra during hyperinsulinemic clamp studies. Plasma specific activity fell during the constant tracer infusion studies but did not change from base line during the variable tracer infusion studies. By maintaining a constant plasma specific activity the variable tracer infusion method eliminates uncertainty about changes in glucose pool size. This overcame modeling error and more accurately measures non-steady-state Ra (P less than 0.001 by analysis of variance vs. constant infusion method). In conclusion, underestimation of Ra determined isotopically during hyperinsulinemic clamp studies is largely due to modeling error that can be overcome by use of the variable tracer infusion method. This method allows more accurate determination of Ra and HGO under non-steady-state conditions

Trends in the use of stable isotopes in biochemistry and pharmacology

International Nuclear Information System (INIS)

Matwiyoff, N.A.; Walker, T.E.

1977-01-01

Recent trends in the use of the stable isotopes 13 C, 15 N and 18 O in biochemistry and pharmacology are reviewed with emphasis on the studies that have employed nuclear magnetic resonance (nmr) spectroscopy and mass spectrometry as analytical techniques. Pharmacological studies with drugs and other compounds labelled with stable isotopes have developed in parallel with the rapid progress in the enhancement of sensitivity and selectivity of gas chromatography - mass spectrometric analyses, and have been directed largely to an evaluation of pharmako-kinetics and drug metabolic pathways. In these studies, illustrated with selected samples, isotopically labelled compounds have been used to advantage as internal standards for the mass spectrometric analyses and as in vivo tracers for metabolites. In the broader discipline of biochemistry, stable isotopes and isotopically labelled compounds have been used increasingly in conjuction with both nmr spectroscopy and mass spectrometry in tracer and structural studies. The more recent trends in the use of stable isotopes in these biochemical studies are discussed in the context of the improvements in analytical techniques. Specific examples will be drawn from investigations of the biosynthesis of natural products by micro-organisms; the protein, fat and carbohydrate fluxes in humans; and the structure and function of enzymes, membranes and other macro-molecular assemblages. The potential for the future development of stable isotopes in biochemistry and pharmacology are considered briefly, together with some of the problems that must be solved if their considerable potential is to be realized. (author)

Multiple stable isotope tracer technique for studying the metabolic kinetics of amino acids in hepatic failure

Energy Technology Data Exchange (ETDEWEB)

Zongqin, Xia; Tengchang, Dai; Jianhua, Zhang; Yaer, Hu; Bingyao, Yu; Xingrong, Xu; Guanlu, Huang; Gengrong, Shen; Yaqiu, Zhou; Hong, Yu

1987-08-01

In order to study the mechanism of the imbalance of amino acid metabolism during hepatic failure, a stable isotope tracer method for observing simultaneously the metabolic kinetics of several amino acids has been established. /sup 15/N-L-Ala, (2,3-D/sub 3/)-Leu and (2,3-D/sub 3/)-Phe were chosen as nonessential, branched chain and aromatic amino acids. A single iv injection of 40 mg N-Ala, 20 mg deuterated Leu and 20 mg deuterated Phe was given to each human subject. Blood samples were taken just before and at different times (up to 60 min) after the injection. Total free amino acids were isolated from the plasma with a small dowex 50 x 8 column and converted to trifluoroacetyl derivatives. Their abundances were then analyzed with a GC-MS system and typical double exponential time course curves were found for all the three labelled amino acids. A two-pool model was designed and applied for compartmental analysis. Significant changes were found in the kinetic parameters of Phe and Leu in patients with fulminant hepatitis or heptic cirrhosis. The half-lives of both Phe pools were longer and the pool sizes were larger than normal subjects, while the half-lives and pool sizes of Leu changes in the opposite direction. No marked change was found in Ala. The significance of intracellular imbalance of Phe and Leu metabolism was discussed. It is evident that the combination of GCMS technique and multiple-tracers labelled with stable isotopes is of great potential for similar purposes.

Stable-label intravenous glucose tolerance test minimal model

International Nuclear Information System (INIS)

Avogaro, A.; Bristow, J.D.; Bier, D.M.; Cobelli, C.; Toffolo, G.

1989-01-01

The minimal model approach to estimating insulin sensitivity (Sl) and glucose effectiveness in promoting its own disposition at basal insulin (SG) is a powerful tool that has been underutilized given its potential applications. In part, this has been due to its inability to separate insulin and glucose effects on peripheral uptake from their effects on hepatic glucose inflow. Prior enhancements, with radiotracer labeling of the dosage, permit this separation but are unsuitable for use in pregnancy and childhood. In this study, we labeled the intravenous glucose tolerance test (IVGTT) dosage with [6,6- 2 H 2 ]glucose, [2- 2 H]glucose, or both stable isotopically labeled glucose tracers and modeled glucose kinetics in six postabsorptive, nonobese adults. As previously found with the radiotracer model, the tracer-estimated S*l derived from the stable-label IVGTT was greater than Sl in each case except one, and the tracer-estimated SG* was less than SG in each instance. More importantly, however, the stable-label IVGTT estimated each parameter with an average precision of +/- 5% (range 3-9%) compared to average precisions of +/- 74% (range 7-309%) for SG and +/- 22% (range 3-72%) for Sl. In addition, because of the different metabolic fates of the two deuterated tracers, there were minor differences in basal insulin-derived measures of glucose effectiveness, but these differences were negligible for parameters describing insulin-stimulated processes. In conclusion, the stable-label IVGTT is a simple, highly precise means of assessing insulin sensitivity and glucose effectiveness at basal insulin that can be used to measure these parameters in individuals of all ages, including children and pregnant women

Stable isotopes as tracers for radionuclides

International Nuclear Information System (INIS)

Giussani, A.; Bartolo, D. de; Cantone, M.C.; Zilker, T.; Greim, H.; Roth, P.; Werner, E.

2000-01-01

The assessment of internal dose after incorporation of radionuclides requires as input data the knowledge of the uptake into the systemic circulation, the distribution and retention in selected organs, the excretion pathways. Realistic biokinetic models are needed for reliable estimates, correct interpretation of bioassay measurements, appropriate decision-making in radiological emergencies. For many radionuclides, however, the biokinetic models currently recommended are often generic, with very few specific parameters, due to the lack of experimental human data. The use of stable isotopes as tracers enables to determine important biokinetic parameters such as the fractional uptake, the clearance from the transfer compartment, the excretion patterns under experimentally controlled conditions. The subjects investigated are not exposed to any radiation risk, so this technique enables to obtain biokinetic information also for sensitive groups of the population, such as children or pregnant women, and to determine age- and gender-specific model parameters. Sophisticated analytical method, able to discriminate and quantitate different isotopes of the same element in complex matrices such as biological fluids, have to be purposely developed and optimized. Activation analysis and mass spectrometry are the most proper techniques of choice. Experiments were conducted with molybdenum, tellurium, ruthenium and zirconium. Activation analysis with protons, thermal ionization mass spectrometry and inductively coupled mass spectrometry were employed for the determination of stable isotopes of these elements in blood plasma and urine samples. Several deviations from the predictions of the ICRP models were observed. For example, modifications to the current model for molybdenum have been suggested on the basis of these results. The dose coefficients to the target regions calculated with this proposed model are even of one order of magnitude different than the ICRP estimates

Recycling of an amino acid label with prolonged isotope infusion: Implications for kinetic studies

International Nuclear Information System (INIS)

Schwenk, W.F.; Tsalikian, E.; Beaufrere, B.; Haymond, M.W.

1985-01-01

To investigate whether recycling of a labeled amino acid would occur after 24 h of infusion, two groups of normal volunteers were infused with [ 3 H]leucine and alpha-[ 14 C]-ketoisocaproate for 4 h and [ 2 H 3 ]leucine for either 4 or 24 h (groups I and II, respectively). Entry of [ 2 H 3 ]leucine at steady state into the plasma space was indistinguishable from its infusion rate for group I but 30% higher (P less than 0.001) than this rate for group II, demonstrating significant recycling of label. After discontinuation of the infusions, isotope disappearance from the plasma space was followed for 2 h. The 3 H and 14 C decay data for both groups suggest that plasma leucine and alpha- ketoisocaproate are derived from a single intracellular pool in the postabsorptive state. In group I, the 3 H and 2 H labels decayed identically; whereas, in group II, the decay of [ 2 H 3 ]-leucine and alpha- [ 2 H 3 ]ketoisocaproate was slower (P less than 0.01) than the decay of [ 3 H]leucine and alpha-[ 3 H]ketoisocaproate, confirming re-entry of label after a 24-h infusion. Therefore kinetic values calculated from models assuming no recycling of labeled amino acids are most likely not quantitative and must be interpreted with care when flux does not change or decreases

Radio-isotopic tracers

International Nuclear Information System (INIS)

Wolfangel, R.G.

1976-01-01

The invention concerns the dispersions that may be used for preparing radio-isotopic tracers, technetium labelled dispersions, processes for preparing these dispersions and their use as tracers. Technetium 99m sulphur colloids are utilized as scintillation tracers to give a picture of the reticulo-endothelial system, particularly the liver and spleen. A dispersion is provided which only requires the addition of a radioactive nuclide to form a radioactively labelled dispersion that can be injected as a tracer. It is formed of a colloid of tin sulphur dispersed in an aqueous buffer solution. Such a reagent has the advantage of being safe and reliable and is easier to use. The colloid can be prepared more quickly since additions of several different reagents are avoided. There is no need to heat up and no sulphuretted hydrogen, which is a toxic gas, is used [fr

Overcoming interference with the detection of a stable isotopically labeled microtracer in the evaluation of beclabuvir absolute bioavailability using a concomitant microtracer approach.

Science.gov (United States)

Jiang, Hao; Titsch, Craig; Zeng, Jianing; Jones, Barry; Joyce, Philip; Gandhi, Yash; Turley, Wesley; Burrell, Richard; Aubry, Anne F; Arnold, Mark E

2017-09-05

The oral absolute bioavailability of beclabuvir in healthy subjects was determined using a microdose (100μg) of the stable isotopically labeled tracer via intravenous (IV) infusion started after oral dosing of beclabuvir (150mg). To simultaneously analyze the concentrations of the IV microtracer ([ 13 C 6 ]beclabuvir) and beclabuvir in plasma samples, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method was initially developed. Surprisingly beclabuvir significantly interfered with the IV microtracer detection when using the selected reaction monitoring (SRM) in the assay. An interfering component from the drug substance was observed using a high resolution mass spectrometer (HRMS). The mass-to-charge (m/z) of the interfering component was -32ppm different from the nominal value for the IV microtracer and thus could not be differentiated in the SRM assay by the unit mass resolution. To overcome this interference, we evaluated two approaches by either monitoring an alternative product ion using the SRM assay or isolating the interfering component using the parallel reaction monitoring (PRM) assay on the HRMS. This case study has demonstrated two practical approaches for overcoming interferences with the detection of stable isotopically labeled IV microtracers in the evaluation of absolute bioavailability, which provides users the flexibility in using either LC-MS/MS or HRMS to mitigate unpredicted interferences in the assay to support microtracer absolute bioavailability studies. Copyright © 2017 Elsevier B.V. All rights reserved.

The synthesis of a tritium, carbon-14, and stable isotope-labeled cathepsin C inhibitors.

Science.gov (United States)

Allen, Paul; Bragg, Ryan A; Caffrey, Moya; Ericsson, Cecilia; Hickey, Michael J; Kingston, Lee P; Elmore, Charles S

2017-02-01

As part of a medicinal chemistry program aimed at developing a highly potent and selective cathepsin C inhibitor, tritium, carbon-14, and stable isotope-labeled materials were required. The synthesis of tritium-labeled methanesulfonate 5 was achieved via catalytic tritiolysis of a chloro precursor, albeit at a low radiochemical purity of 67%. Tritium-labeled AZD5248 was prepared via a 3-stage synthesis, utilizing amide-directed hydrogen isotope exchange. Carbon-14 and stable isotope-labeled AZD5248 were successfully prepared through modifications of the medicinal chemistry synthetic route, enabling the use of available labeled intermediates. Copyright © 2016 John Wiley & Sons, Ltd.

Co-ordinated research programme on applications of stable isotope tracers in human nutrition research

International Nuclear Information System (INIS)

1992-01-01

This document provides a very brief report on the final Research Co-ordination Meeting of this Co-ordinated Research Project (CRP): the final report on the CRP will be published by the IAEA in the IAEA-TECDOC series. The present document contains a detailed proposal for a new Co-ordinated Research Programme on ''Stable Isotope Tracer Techniques for Studies on Protein-Energy Interactions'', and a brief series of notes on stable isotopic methods for investigating protein and amino-acid metabolism in man. Refs

Stable isotope usage in developing countries: Safe tracer tools to measure human nutritional status

International Nuclear Information System (INIS)

Klein, P.D.; Klein, E.R.

1987-01-01

How many calories are used when a nursing mother feeds her infant? How much milk does an infant receive in one week? What is the impact of the environment on the energy needs of children? How adequately does dietary protein sustain the synthesis of body constituents? What types of foods best nourish a child recovering from intestinal diseases such as diarrhoea? Quantitative answers to questions such as these can be obtained from the use of stable, non-radioactive isotopic tracers. Answers to these questions are important in assessing the nutritional status of infants, children, pregnant women and nursing mothers, as well as that of individuals who subsist on marginal food supplies. Because stable isotopic tracers are completely safe and without hazard, they can be used freely in health, nutrition, and agriculture studies in all populations

Stable isotopic labeling-based quantitative targeted glycomics (i-QTaG).

Science.gov (United States)

Kim, Kyoung-Jin; Kim, Yoon-Woo; Kim, Yun-Gon; Park, Hae-Min; Jin, Jang Mi; Hwan Kim, Young; Yang, Yung-Hun; Kyu Lee, Jun; Chung, Junho; Lee, Sun-Gu; Saghatelian, Alan

2015-01-01

Mass spectrometry (MS) analysis combined with stable isotopic labeling is a promising method for the relative quantification of aberrant glycosylation in diseases and disorders. We developed a stable isotopic labeling-based quantitative targeted glycomics (i-QTaG) technique for the comparative and quantitative analysis of total N-glycans using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). We established the analytical procedure with the chemical derivatizations (i.e., sialic acid neutralization and stable isotopic labeling) of N-glycans using a model glycoprotein (bovine fetuin). Moreover, the i-QTaG using MALDI-TOF MS was evaluated with various molar ratios (1:1, 1:2, 1:5) of (13) C6 /(12) C6 -2-aminobenzoic acid-labeled glycans from normal human serum. Finally, this method was applied to direct comparison of the total N-glycan profiles between normal human sera (n = 8) and prostate cancer patient sera (n = 17). The intensities of the N-glycan peaks from i-QTaG method showed a good linearity (R(2) > 0.99) with the amount of the bovine fetuin glycoproteins. The ratios of relative intensity between the isotopically 2-AA labeled N-glycans were close to the theoretical molar ratios (1:1, 1:2, 1:5). We also demonstrated that the up-regulation of the Lewis antigen (~82%) in sera from prostate cancer patients. In this proof-of-concept study, we demonstrated that the i-QTaG method, which enables to achieve a reliable comparative quantitation of total N-glycans via MALDI-TOF MS analysis, has the potential to diagnose and monitor alterations in glycosylation associated with disease states or biotherapeutics. © 2015 American Institute of Chemical Engineers.

Advances in stable isotope assisted labeling strategies with information science.

Science.gov (United States)

Kigawa, Takanori

2017-08-15

Stable-isotope (SI) labeling of proteins is an essential technique to investigate their structures, interactions or dynamics by nuclear magnetic resonance (NMR) spectroscopy. The assignment of the main-chain signals, which is the fundamental first step in these analyses, is usually achieved by a sequential assignment method based on triple resonance experiments. Independently of the triple resonance experiment-based sequential assignment, amino acid-selective SI labeling is beneficial for discriminating the amino acid type of each signal; therefore, it is especially useful for the signal assignment of difficult targets. Various combinatorial selective labeling schemes have been developed as more sophisticated labeling strategies. In these strategies, amino acids are represented by combinations of SI labeled samples, rather than simply assigning one amino acid to one SI labeled sample as in the case of conventional amino acid-selective labeling. These strategies have proven to be useful for NMR analyses of difficult proteins, such as those in large complex systems, in living cells, attached or integrated into membranes, or with poor solubility. In this review, recent advances in stable isotope assisted labeling strategies will be discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

A free-air system for long-term stable carbon isotope labeling of adult forest trees

Science.gov (United States)

Stable carbon (C) isotopes, in particular employed in labeling experiments, are an ideal tool to broaden our understanding of C dynamics in trees and forest ecosystems. Here, we present a free-air exposure system, named isoFACE, designed for long-term stable C isotope labeling in...

Suitable activated stable nuclide tracer technique and its applications in biology and medicine

International Nuclear Information System (INIS)

Zhang Weicheng

1989-01-01

Stable isotopes as tracers in biology and medicine have been more extensively used. Mass spectrometry has been a classic technique in the analysis of stable isotopes because it is very sensitive and precise. Activation analysis has recently been introduced as an analytical tool. Its fast speed and simplicity is a great advantage for handling large batches of samples in isotopic tracer experiments. The combination of enriched stable isotope tracer studies and activation analysis techniques has become an ideal and reliable technique, especially in the fields of biology and medicine. This paper presents a survey of the fundamental principle, the character and the applications in biology and medicine for the suitable activated stable isotope tracer techniques

Choice of infusion-sampling mode for tracer studies of free fatty acid metabolism

International Nuclear Information System (INIS)

Jensen, M.D.; Rogers, P.J.; Ellman, M.G.; Miles, J.M.

1988-01-01

To determine the preferred infusion-sampling mode for isotopic studies of free fatty acid (FFA) metabolism, tracer [( 14 C]palmitate) was infused into the left ventricle of five anesthetized dogs, and tracee ([ 3 H]palmitate) was infused into three separate peripheral veins of each dog. The [ 14 C]palmitate specific activity (SA) was lower in mixed venous than arterial blood, and [ 3 H]palmitate SA was equal in both sites. The actual infusion rate of [ 3 H]palmitate [2.15 +/- 0.31 X 10(5) disintegrations/min (dpm).kg-1.min-1] could be accurately predicted (2.14 +/- 0.32 X 10(5) dpm.kg-1.min-1) using the known [ 14 C]palmitate infusion rate and the arterial plasma [ 14 C]-to-[ 3 H]palmitate ratio. In contrast, the mixed venous [ 14 C]-to-[ 3 H]palmitate ratio resulted in overestimates (P less than 0.05) of the actual [ 3 H]palmitate infusion rate. In summary, venous tracer infusion with arterial blood sampling for FFA tracer studies provides the most accurate estimates of tracee rate of appearance

Tracer studies with aortic infusion result in improper tracer distribution

International Nuclear Information System (INIS)

Wisneski, J.A.; Brooks, G.A.; Neese, R.A.; Stanley, W.C.; Morris, D.L.; Gertz, E.W.

1986-01-01

It has been suggested that lactate turnover can be accurately assessed by infusing radioactive lactate tracer into the aorta and sampling blood in the vena cava. However, there may be streaming of newly infused tracer in the aorta, resulting in a nonuniform arterial specific activity (SA). Furthermore vena caval blood may not be representative of mixed venous blood. The authors examined this problem in 7 anesthetized dogs with sampling catheters in the pulmonary (PA), carotid (CA), and femoral (FA) arteries, and the superior (SVC) and inferior (IVC) vena cavi. [1- 14 C]lactate was continuously infused into the left ventricle through a catheter introduced through the femoral artery. The same SA (dpm/μmol) was found in the CA and FA, indicating adequate mixing of newly infused tracer with trace. Three dogs showed differences between SVC, IVC and PA, suggesting a mixed venous sample can not be obtained from the VC. When the catheter was moved into the aorta, wide differences in SA appeared between the CA and FA, clearly reflecting streaming of tracer. These differences also appeared in the SVC and IVC. In conclusion, adequate mixing does not occur between tracer and trace in arterial blood with aortic infusion. Further, VC sampling will not give a consistent mixed venous SA. Therefore, for practical reasons, aortic tracer infusion with vena caval sampling will lead to erroneous turnover values

Expeditious syntheses of stable and radioactive isotope-labeled anticonvulsant agent, JNJ-26990990, and its metabolites.

Science.gov (United States)

Lin, Ronghui; Weaner, Larry E; Hoerr, David C; Salter, Rhys; Gong, Yong

2013-01-01

Syntheses of stable and radioactive isotope-labeled anticonvulsant agent, JNJ-26990990, that is, N-(benzo[b]thien-3-ylmethyl)-sulfamide and its metabolites are described. [(13)C(15)N]Benzo[b]thiophene-3-carbonitrile was first prepared by coupling of 3-bromo-benzo[b]thiophene with [(13)C(15)N]-copper cyanide. The resultant [(13)C(15)N]benzo[b]thiophene-3-carbonitrile was reduced with lithium aluminum deuteride to give [(13)CD2(15)N]benzo[b]thiophen-3-yl-methylamine; which was then coupled with sulfamide to afford [(13)CD2(15)N]-N-(benzo[b]thien-3-ylmethyl)-sulfamide, the stable isotope-labeled compound with four stable isotope atoms. Direct oxidation of [(13)CD2(15)N]-N-(benzo[b]thien-3-ylmethyl)-sulfamide with hydrogen peroxide and peracetic acid gave the stable isotope-labeled sulfoxide and sulfone metabolites. On the other hand, radioactive (14)C-labeled N-(benzo[b]thien-3-ylmethyl)-sulfamide was prepared conveniently by sequential coupling of 3-bromo-benzo[b]thiophene with [(14)C]-copper cyanide, reduction of the carbonitrile to carboxaldehyde, and reductive amination with sulfamide. Copyright © 2013 John Wiley & Sons, Ltd.

Subcellular SIMS imaging of isotopically labeled amino acids in cryogenically prepared cells

International Nuclear Information System (INIS)

Chandra, Subhash

2004-01-01

Ion microscopy is a potentially powerful technique for localization of isotopically labeled molecules. In this study, L-arginine and phenylalanine amino acids labeled with stable isotopes 13 C and 15 N were localized in cultured cells with the ion microscope at 500 nm spatial resolution. Cells were exposed to the labeled amino acids and cryogenically prepared. SIMS analyses were made in fractured freeze-dried cells. A dynamic distribution was observed from labeled arginine-treated LLC-PK 1 kidney cells at mass 28 ( 13 C 15 N) in negative secondaries, revealing cell-to-cell heterogeneity and preferential accumulation of the amino acid (or its metabolite) in the nucleus and nucleolus of some cells. The smaller nucleolus inside the nucleus was clearly resolved in SIMS images and confirmed by correlative light microscopy. The distribution of labeled phenylalanine contrasted with arginine as it was rather homogeneously distributed in T98G human glioblastoma cells. Images of 39 K, 23 Na and 40 Ca were also recorded to confirm the reliability of sample preparation and authenticity of the observed amino acid distributions. These observations indicate that SIMS techniques can provide a valuable technology for subcellular localization of nitrogen-containing molecules in proteomics since nitrogen does not have a radionuclide tracer isotope. Amino acids labeled with stable isotopes can be used as tracers for studying their transport and metabolism in distinct subcellular compartments with SIMS. Further studies of phenylalanine uptake in human glioblastoma cells may have special significance in boron neutron capture therapy (BNCT) as a boron analogue of phenylalanine, boronophenylalanine is a clinically approved compound for the treatment of brain tumors

Subcellular SIMS imaging of isotopically labeled amino acids in cryogenically prepared cells

Energy Technology Data Exchange (ETDEWEB)

Chandra, Subhash

2004-06-15

Ion microscopy is a potentially powerful technique for localization of isotopically labeled molecules. In this study, L-arginine and phenylalanine amino acids labeled with stable isotopes {sup 13}C and {sup 15}N were localized in cultured cells with the ion microscope at 500 nm spatial resolution. Cells were exposed to the labeled amino acids and cryogenically prepared. SIMS analyses were made in fractured freeze-dried cells. A dynamic distribution was observed from labeled arginine-treated LLC-PK{sub 1} kidney cells at mass 28 ({sup 13}C{sup 15}N) in negative secondaries, revealing cell-to-cell heterogeneity and preferential accumulation of the amino acid (or its metabolite) in the nucleus and nucleolus of some cells. The smaller nucleolus inside the nucleus was clearly resolved in SIMS images and confirmed by correlative light microscopy. The distribution of labeled phenylalanine contrasted with arginine as it was rather homogeneously distributed in T98G human glioblastoma cells. Images of {sup 39}K, {sup 23}Na and {sup 40}Ca were also recorded to confirm the reliability of sample preparation and authenticity of the observed amino acid distributions. These observations indicate that SIMS techniques can provide a valuable technology for subcellular localization of nitrogen-containing molecules in proteomics since nitrogen does not have a radionuclide tracer isotope. Amino acids labeled with stable isotopes can be used as tracers for studying their transport and metabolism in distinct subcellular compartments with SIMS. Further studies of phenylalanine uptake in human glioblastoma cells may have special significance in boron neutron capture therapy (BNCT) as a boron analogue of phenylalanine, boronophenylalanine is a clinically approved compound for the treatment of brain tumors.

Synthesis of 14C-labeled and stable isotope-labeled CGS 16617

International Nuclear Information System (INIS)

Chaudhuri, N.K.; Markus, B.; Sung Mingsang

1988-01-01

The synthesis of a 14 C-labeled and two stable isotope-labeled analogs of CGS 16617 is described. The synthetic method involved the preparation of tetrahydro-3-bromo-1-benzazepin-2-one, labeled with a 14 C or four deuterium atoms, followed by introduction of two side chains at 1- and 3-positions. The labeled bromobenzazepinones were prepared by Beckmann rearrangement of bromo-oximes of α-tetralones, obtained by cyclization of labeled benzenebutanoic acids. The 14 C-labeled acid was prepared by hydrolysis of the nitrile, prepared by reaction of 3-bromopropylbenzene and K 14 CN. The tetradeutero acid was prepared from ethyl phenylpropynoate by catalytic reduction of the triple bond with deuterium gas, followed by reduction of the deuterated ester with lithium aluminium hydride and conversion of the resulting alcohol into the carboxylic acid. The acetic acid side chain was introduced by N-alkylation with ethyl bromoacetate or ethyl bromoacetate-1, 2- 13 C 2 followed by hydrolysis, and the L-lysine side chain, by reaction with L-(-)-3-amino-ε-caprolactam followed by hydrolysis of the caprolactam ring. (author)

French days on stable isotopes

International Nuclear Information System (INIS)

2000-01-01

These first French days on stable isotopes took place in parallel with the 1. French days of environmental chemistry. Both conferences had common plenary sessions. The conference covers all aspects of the use of stable isotopes in the following domains: medicine, biology, environment, tracer techniques, agronomy, food industry, geology, petroleum geochemistry, cosmo-geochemistry, archaeology, bio-geochemistry, hydrology, climatology, nuclear and particle physics, astrophysics, isotope separations etc.. Abstracts available on CD-Rom only. (J.S.)

Applications of isotopes. [Need and cost of stable iotopes for use as tracers in biomedical and environmental studies

Energy Technology Data Exchange (ETDEWEB)

Kirby-Smith, J.S.

1976-01-01

Current and potential applications of stable isotopes as tracers in a number of biomedical and environmental areas are discussed. It is pointed out that a wide variety of problems exist in these fields whose solutions in principle are amenable to the isotopic approach. The number and diversity of these problems as well as the unique role stable isotopes can play in their solution illustrate the importance of achieving and maintaining a broad inventory of isotopic species. Experience has demonstrated unequivocally an additional overriding requirement for widespread exploration of stable isotopes by the scientific and technical community, i.e., the need for low cost availability of the materials in quantity. Some representative applications of /sup 12/C, /sup 13/C, /sup 14/N, /sup 15/N, /sup 16/O, /sup 17/O, and /sup 18/O are discussed.

Metabolic studies in man using stable isotopes

International Nuclear Information System (INIS)

Faust, H.; Jung, K.; Krumbiegel, P.

1993-01-01

In this project, stable isotope compounds and stable isotope pharmaceuticals were used (with emphasis on the application of 15 N) to study several aspects of nitrogen metabolism in man. Of the many methods available, the 15 N stable isotope tracer technique holds a special position because the methodology for application and nitrogen isotope analysis is proven and reliable. Valid routine methods using 15 N analysis by emission spectrometry have been demonstrated. Several methods for the preparation of biological material were developed during our participation in the Coordinated Research Programme. In these studies, direct procedures (i.e. use of diluted urine as a samples without chemical preparation) or rapid isolation methods were favoured. Within the scope of the Analytical Quality Control Service (AQCS) enriched stable isotope reference materials for medical and biological studies were prepared and are now available through the International Atomic Energy Agency. The materials are of special importance as the increasing application of stable isotopes as tracers in medical, biological and agricultural studies has focused interest on reliable measurements of biological material of different origin. 24 refs

Copper absorption from foods labelled intrinsically and extrinsically with Cu-65 stable isotope.

Science.gov (United States)

Harvey, L J; Dainty, J R; Beattie, J H; Majsak-Newman, G; Wharf, S G; Reid, M D; Fairweather-Tait, S J

2005-03-01

To determine copper absorption from copper containing foods labelled either intrinsically or extrinsically with a highly enriched Cu-65 stable isotope label. A longitudinal cross-over study. The study was conducted at the Institute of Food Research, Human Nutrition Unit, Norwich, UK. Subjects were recruited locally via advertisements placed around the Norwich Research Park. A total of 10 volunteers (nine female, one male) took part in the study, but not all volunteers completed each of the test meals. A highly enriched Cu-65 stable isotope label was administered to volunteers in the form of a reference dose or in breakfast test meals consisting of red wine, soya beans, mushrooms or sunflower seeds. Faecal monitoring and mass spectrometry techniques were used to estimate the relative quantities of copper absorbed from the different test meals. True copper absorption from the reference dose (54%) was similar to extrinsically labelled red wine (49%) and intrinsically labelled sunflower seeds (52%), but significantly higher than extrinsically labelled mushrooms (35%), intrinsically (29%) and extrinsically (15%) labelled soya beans and extrinsically labelled sunflower seed (32%) test meals. The use of Cu-65 extrinsic labels in copper absorption studies requires validation according to the food being examined; intrinsic and extrinsic labelling produced significantly different results for sunflower seeds.

Amyloid-β Plaques in Clinical Alzheimer’s Disease Brain Incorporate Stable Isotope Tracer In Vivo and Exhibit Nanoscale Heterogeneity

Science.gov (United States)

Wildburger, Norelle C.; Gyngard, Frank; Guillermier, Christelle; Patterson, Bruce W.; Elbert, Donald; Mawuenyega, Kwasi G.; Schneider, Theresa; Green, Karen; Roth, Robyn; Schmidt, Robert E.; Cairns, Nigel J.; Benzinger, Tammie L. S.; Steinhauser, Matthew L.; Bateman, Randall J.

2018-01-01

Alzheimer’s disease (AD) is a neurodegenerative disorder with clinical manifestations of progressive memory decline and loss of executive function and language. AD affects an estimated 5.3 million Americans alone and is the most common form of age-related dementia with a rapidly growing prevalence among the aging population—those 65 years of age or older. AD is characterized by accumulation of aggregated amyloid-beta (Aβ) in the brain, which leads to one of the pathological hallmarks of AD—Aβ plaques. As a result, Aβ plaques have been extensively studied after being first described over a century ago. Advances in brain imaging and quantitative measures of Aβ in biological fluids have yielded insight into the time course of plaque development decades before and after AD symptom onset. However, despite the fundamental role of Aβ plaques in AD, in vivo measures of individual plaque growth, growth distribution, and dynamics are still lacking. To address this question, we combined stable isotope labeling kinetics (SILK) and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging in an approach termed SILK–SIMS to resolve plaque dynamics in three human AD brains. In human AD brain, plaques exhibit incorporation of a stable isotope tracer. Tracer enrichment was highly variable between plaques and the spatial distribution asymmetric with both quiescent and active nanometer sub-regions of tracer incorporation. These data reveal that Aβ plaques are dynamic structures with deposition rates over days indicating a highly active process. Here, we report the first, direct quantitative measures of in vivo deposition into plaques in human AD brain. Our SILK–SIMS studies will provide invaluable information on plaque dynamics in the normal and diseased brain and offer many new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development. PMID:29623063

Amyloid-β Plaques in Clinical Alzheimer’s Disease Brain Incorporate Stable Isotope Tracer In Vivo and Exhibit Nanoscale Heterogeneity

Directory of Open Access Journals (Sweden)

Norelle C. Wildburger

2018-03-01

Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder with clinical manifestations of progressive memory decline and loss of executive function and language. AD affects an estimated 5.3 million Americans alone and is the most common form of age-related dementia with a rapidly growing prevalence among the aging population—those 65 years of age or older. AD is characterized by accumulation of aggregated amyloid-beta (Aβ in the brain, which leads to one of the pathological hallmarks of AD—Aβ plaques. As a result, Aβ plaques have been extensively studied after being first described over a century ago. Advances in brain imaging and quantitative measures of Aβ in biological fluids have yielded insight into the time course of plaque development decades before and after AD symptom onset. However, despite the fundamental role of Aβ plaques in AD, in vivo measures of individual plaque growth, growth distribution, and dynamics are still lacking. To address this question, we combined stable isotope labeling kinetics (SILK and nanoscale secondary ion mass spectrometry (NanoSIMS imaging in an approach termed SILK–SIMS to resolve plaque dynamics in three human AD brains. In human AD brain, plaques exhibit incorporation of a stable isotope tracer. Tracer enrichment was highly variable between plaques and the spatial distribution asymmetric with both quiescent and active nanometer sub-regions of tracer incorporation. These data reveal that Aβ plaques are dynamic structures with deposition rates over days indicating a highly active process. Here, we report the first, direct quantitative measures of in vivo deposition into plaques in human AD brain. Our SILK–SIMS studies will provide invaluable information on plaque dynamics in the normal and diseased brain and offer many new avenues for investigation into pathological mechanisms of the disease, with implications for therapeutic development.

The conversion of phenylalanine to tyrosine in man. Direct measurement by continuous intravenous tracer infusions of L-[ring-2H5]phenylalanine and L-[1-13C] tyrosine in the postabsorptive state

International Nuclear Information System (INIS)

Clarke, J.T.; Bier, D.M.

1982-01-01

Steady state phenylalanine and tyrosine turnover and the rate of conversion of phenylalanine of tyrosine in vivo were determined in 6 healthy postabsorptive adult volunteers. Continuous infusions of tracer amounts of L-[ring- 2 H5]phenylalanine were determined intravenously for 13-14 hr. After 9-10 hr, a priming dose followed by a continuous infusion of L-[1- 13 C]tyrosine was added and maintained, along with the [ 2 H5]phenylalanine infusion, for 4 hr. Venous plasma samples were obtained before the initiation of each infusion and every 30 min during the course of the combined [ 2 H5]phenylalanine and [ 13 C]tyrosine infusion for determination of isotopic enrichments of [ 2 H5]phenylalanine, [ 13 C]tyrosine, and [ 2 H4]tyrosine by gas chromatograph-mass spectrometric analysis of the N-trifluoroacetyl-, methyl ester derivatives of the amino acids. Calculated from the observed enrichments, free phenylalanine and tyrosine turnover rates were 36.1 +/- 5.1 mumole . kg-1 . h-1 and 39.8 +/- 3.5 mumole . kg-1 . h-1, respectively. Phenylalanine was converted to tyrosine at the rate of 5.83 +/- 0.59 mumole . kg-1 . h-1, accounting for approximately 16% of either the phenylalanine or the tyrosine flux. The results indicate that the normal basal steady state phenylalanine hydroxylase activity in vivo in man is lower than that obtained from phenylalanine loading studies. This supports the existence of some type of substance activation of the enzyme as reflected in the previously reported exponential relationship between phenylalanine concentration and phenylalanine hydroxylase activity in vitro. The use of continuous simultaneous infusions of tracer amounts of stable isotope-labeled phenylalanine and tyrosine provides a direct means for studying physiological regulation of phenylalanine hydroxylase activity in vivo

Identification of fentanyl metabolites in rat urine by gas chromatography-mass spectrometry with stable-isotope tracers

Energy Technology Data Exchange (ETDEWEB)

Goromaru, T.; Matsuura, H.; Furuta, T.; Baba, S.; Yoshimura, N.; Miyawaki, T.; Sameshima, T.

The metabolites of fentanyl (l), which has been widely used as a neuroleptic analgesic agent, were identified in urine of rats by gas chromatography-mass spectrometry combined with a stable-isotope tracer technique. After the oral administration of an equimolar mixture of l and deuterium-labeled l (l/l-d5), the urinary metabolites were extracted with chloroform at pH 9.0. Extracts were derivatized and analyzed by GC/MS. Metabolites were identified by the presence of doublet ion peaks separated by 5 amu, and chemical structures were established from analyses of fragmentation pathways. The metabolites were identified as 4-N-(N-propionylanilino)-piperidine, 4-N-(N-hydroxypropionylanilino)piperidine, 4-N-(N-propionylanilino) hydroxypiperidine, 1-(2-phenethyl)-4-N-(N-hydroxypropionylanilino)piperidine and 1-(2-phenethyl)-4-N-(N-propionylanilino)hydroxypiperidine. These metabolites, together with unchanged l, were also detected in urine of rats receiving l/l-d5 intravenously, by selected-ion monitoring of the specific cluster ions.

Applications of C and N stable isotopes to ecological and environmental studies in seagrass ecosystems

Energy Technology Data Exchange (ETDEWEB)

Lepoint, Gilles [Centre MARE, Laboratoire d' Oceanologie, Institut de Chimie, B6, Universite de Liege, B-4000 Liege (Belgium)]. E-mail: g.lepoint@ulg.ac.be; Dauby, Patrick [Centre MARE, Laboratoire d' Oceanologie, Institut de Chimie, B6, Universite de Liege, B-4000 Liege (Belgium); Institut Royal des Sciences Naturelles de Belgique, rue Vautier, B1000 Brussels (Belgium); Gobert, Sylvie [Centre MARE, Laboratoire d' Oceanologie, Institut de Chimie, B6, Universite de Liege, B-4000 Liege (Belgium)

2004-12-01

Stable isotopes of carbon and nitrogen are increasingly used in marine ecosystems, for ecological and environmental studies. Here, we examine some applications of stable isotopes as ecological integrators or tracers in seagrass ecosystem studies. We focus on both the use of natural isotope abundance as food web integrators or environmental tracers and on the use of stable isotopes as experimental tools. As ecosystem integrators, stable isotopes have helped to elucidate the general structure of trophic webs in temperate, Mediterranean and tropical seagrass ecosystems. As environmental tracers, stable isotopes have proven their utility in sewage impact measuring and mapping. However, to make such environmental studies more comprehensible, future works on understanding of basic reasons for variations of N and C stable isotopes in seagrasses should be encouraged. At least, as experimental tracers, stable isotopes allow the study of many aspects of N and C cycles at the scale of a plant or at the scale of the seagrass ecosystem.

Biomedical research applications of electromagnetically separated enriched stable isotopes

International Nuclear Information System (INIS)

Lambrecht, R.M.

1982-01-01

The current and projected annual requirements through 1985 for stable isotopes enriched by electromagnetic separation methods were reviewed for applications in various types of biomedical research: (1) medical radiosotope production, labeled compounds, and potential radiopharmaceuticals; (2) nutrition, food science, and pharmacology; (3) metallobiochemistry and environmental toxicology; (4) nuclear magnetic resonance, electron paramagnetic resonance, and Moessbauer spectroscopy in biochemical, biophysical, and biomedical research; and (5) miscellaneous advances in radioactive and non-radioactive tracer technology. Radioisotopes available from commercial sources or routinely used in clinical nuclear medicine were excluded. Priorities and summaries are based on statements in the references and from answers to a survey conducted in the fall of 1981. Current requirements for enriched stable isotopes in biomedical research are not being satisfied. Severe shortages exist for 26 Mg, 43 Ca, 70 Zn, 76 Se, 78 Se, 102 Pd, 111 Cd, 113 Cd, and 190 Os. Many interesting and potentially important investigations in biomedical research require small quantities of specific elements at high isotopic enrichments

SAIL--stereo-array isotope labeling.

Science.gov (United States)

Kainosho, Masatsune; Güntert, Peter

2009-11-01

Optimal stereospecific and regiospecific labeling of proteins with stable isotopes enhances the nuclear magnetic resonance (NMR) method for the determination of the three-dimensional protein structures in solution. Stereo-array isotope labeling (SAIL) offers sharpened lines, spectral simplification without loss of information and the ability to rapidly collect and automatically evaluate the structural restraints required to solve a high-quality solution structure for proteins up to twice as large as before. This review gives an overview of stable isotope labeling methods for NMR spectroscopy with proteins and provides an in-depth treatment of the SAIL technology.

13C metabolic flux analysis: optimal design of isotopic labeling experiments.

Science.gov (United States)

Antoniewicz, Maciek R

2013-12-01

Measuring fluxes by 13C metabolic flux analysis (13C-MFA) has become a key activity in chemical and pharmaceutical biotechnology. Optimal design of isotopic labeling experiments is of central importance to 13C-MFA as it determines the precision with which fluxes can be estimated. Traditional methods for selecting isotopic tracers and labeling measurements did not fully utilize the power of 13C-MFA. Recently, new approaches were developed for optimal design of isotopic labeling experiments based on parallel labeling experiments and algorithms for rational selection of tracers. In addition, advanced isotopic labeling measurements were developed based on tandem mass spectrometry. Combined, these approaches can dramatically improve the quality of 13C-MFA results with important applications in metabolic engineering and biotechnology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Utilization of stable isotopes in medicine

International Nuclear Information System (INIS)

1980-11-01

The ten lectures given at this round table are presented together with a discussion. Five lectures, relating to studies in which deuterium oxide was employed as a tracer of body water, dealt with pulmonary water measurements in man and animals, the total water pool in adipose subjects, and liquid compartments in children undergoing hemodyalisis. The heavy water is analysed by infrared spectrometry and a new double spectrodoser is described. Two studies using 13 C as tracer, described the diagnosis of liver troubles and diabetes respectively. A general review of the perspectives of the application of stable isotopes in clinical medicine is followed by a comparison of the use of stable and radioactive isotopes in France [fr

Stable-isotope-labeled carbohydrates and nucleosides: Synthesis and applications in chemistry and biology

Energy Technology Data Exchange (ETDEWEB)

Serianni, A.S. [Univ. of Notre Dame, IN (United States)

1994-12-01

Carbohydrates play important roles in many key biochemical processes in living cells. For example, they are metabolized to produce energy, mediate cell-cell recognition, and play an indirect role (as constituents of DNA and RNA) in DNA replication, RNA transcription, and protein synthesis. These roles, and others of comparable biochemical significance, have been studied to varying extends with the use of stable isotopically labeled molecules, usually in conjunction with NMR spectroscopy and/or mass spectrometry. For example, carbohydrate metabolism has been monitored in vitro and in vivo with the use of isotopically labeled compounds. Molecular aspects of cell-cell recognition, mediated by cell-surface glycoproteins and glycolipids, have been probed through NMR studies of isotopically labeled oligosaccharides. More recently, the solution behavior of DNA and RNA has been examined through the use of labeled oligonucleotides. In all of these pursuits, the effort and expense to prepare labeled molecules, both of which can be substantial, are more than offset by the wealth of information derived from these studies. This information often cannot be accessed, or can be accessed only with great difficulty, using natural (unlabeled) compounds.

Stable-isotope-labeled carbohydrates and nucleosides: Synthesis and applications in chemistry and biology

International Nuclear Information System (INIS)

Serianni, A.S.

1994-01-01

Carbohydrates play important roles in many key biochemical processes in living cells. For example, they are metabolized to produce energy, mediate cell-cell recognition, and play an indirect role (as constituents of DNA and RNA) in DNA replication, RNA transcription, and protein synthesis. These roles, and others of comparable biochemical significance, have been studied to varying extends with the use of stable isotopically labeled molecules, usually in conjunction with NMR spectroscopy and/or mass spectrometry. For example, carbohydrate metabolism has been monitored in vitro and in vivo with the use of isotopically labeled compounds. Molecular aspects of cell-cell recognition, mediated by cell-surface glycoproteins and glycolipids, have been probed through NMR studies of isotopically labeled oligosaccharides. More recently, the solution behavior of DNA and RNA has been examined through the use of labeled oligonucleotides. In all of these pursuits, the effort and expense to prepare labeled molecules, both of which can be substantial, are more than offset by the wealth of information derived from these studies. This information often cannot be accessed, or can be accessed only with great difficulty, using natural (unlabeled) compounds

The Use of Stable Isotope Tracers to Quantify the Transit Time Distribution of Water

Science.gov (United States)

Gray, T. M.; Troch, P. A. A.

2016-12-01

Water pollution is an important societal problem because it can have harmful effects on human and ecological health. In order to improve water quality, scientists must develop land management methods that can avoid or mitigate environmental pollution. State of the art tools to develop such methods are flow and transport models that trace water and other solutes through the landscape. These models deliver important information that can lead to remediation efforts, and improve the quality of water for humans, plants, and animals. However, these models may be difficult to apply since many details about the catchment may not be available. Instead, a lumped approach is often used to find the water transit time using stable isotope tracers such as 18O and 2H that are naturally applied by precipitation to a catchment. The transit time distribution of water is an important indicator for the amount of solutes soil water and groundwater can contain, and thus a predictor of water quality. We conducted a 2-week long experiment using a tilted weighing lysimeter at Biosphere 2 to observe the breakthrough curves of deuterium and specific artificial DNA particles. We show that hydrological parameters can be computed in order to provide an estimate for the transit time distribution of deuterium. The convolution integral is then used to determine the distribution of the water transit time in the system. Unfortunately, stable isotopes such as deuterium make it difficult to pinpoint a specific flowpath since they naturally occur in the environment. Recent studies have shown that DNA tracers are able to trace water through the landscape. We found that DNA has a similar breakthrough curve happening at similar timescales as the deuterium. Therefore, DNA tracers may be able to identify sources of nonpoint source pollution in the future.

Stable isotope applications in biomolecular structure and mechanisms. A meeting to bring together producers and users of stable-isotope-labeled compounds to assess current and future needs

International Nuclear Information System (INIS)

Trewhella, J.; Cross, T.A.; Unkefer, C.J.

1994-12-01

Knowledge of biomolecular structure is a prerequisite for understanding biomolecular function, and stable isotopes play an increasingly important role in structure determination of biological molecules. The first Conference on Stable Isotope Applications in Biomolecular Structure and Mechanisms was held in Santa Fe, New Mexico, March 27--31, 1994. More than 120 participants from 8 countries and 44 institutions reviewed significant developments, discussed the most promising applications for stable isotopes, and addressed future needs and challenges. Participants focused on applications of stable isotopes for studies of the structure and function of proteins, peptides, RNA, and DNA. Recent advances in NMR techniques neutron scattering, EPR, and vibrational spectroscopy were highlighted in addition to the production and synthesis of labeled compounds. This volume includes invited speaker and poster presentations as well as a set of reports from discussion panels that focused on the needs of the scientific community and the potential roles of private industry, the National Stable Isotope Resource, and the National High Magnetic Field Laboratory in serving those needs. This is the leading abstract. Individual papers are processed separately for the database

Stable isotope applications in biomolecular structure and mechanisms. A meeting to bring together producers and users of stable-isotope-labeled compounds to assess current and future needs

Energy Technology Data Exchange (ETDEWEB)

Trewhella, J.; Cross, T.A.; Unkefer, C.J. [eds.

1994-12-01

Knowledge of biomolecular structure is a prerequisite for understanding biomolecular function, and stable isotopes play an increasingly important role in structure determination of biological molecules. The first Conference on Stable Isotope Applications in Biomolecular Structure and Mechanisms was held in Santa Fe, New Mexico, March 27--31, 1994. More than 120 participants from 8 countries and 44 institutions reviewed significant developments, discussed the most promising applications for stable isotopes, and addressed future needs and challenges. Participants focused on applications of stable isotopes for studies of the structure and function of proteins, peptides, RNA, and DNA. Recent advances in NMR techniques neutron scattering, EPR, and vibrational spectroscopy were highlighted in addition to the production and synthesis of labeled compounds. This volume includes invited speaker and poster presentations as well as a set of reports from discussion panels that focused on the needs of the scientific community and the potential roles of private industry, the National Stable Isotope Resource, and the National High Magnetic Field Laboratory in serving those needs. This is the leading abstract. Individual papers are processed separately for the database.

Noninvasive imaging of protein metabolic labeling in single human cells using stable isotopes and Raman microscopy

NARCIS (Netherlands)

van Manen, H.J.; Lenferink, Aufrid T.M.; Otto, Cornelis

2008-01-01

We have combined nonresonant Raman microspectroscopy and spectral imaging with stable isotope labeling by amino acids in cell culture (SILAC) to selectively detect the incorporation of deuterium-labeled phenylalanine, tyrosine, and methionine into proteins in intact, single HeLa cells. The C−D

Synthesis of 15N isotope labeled alanine

International Nuclear Information System (INIS)

Oliveira, Claudineia R. de; Bendassolli, Jose Albertino; Sant'Ana, Carlos Roberto; Tagliassachi, Romulo Barbieri; Maximo, Everaldo; Prestes, Clelber Vieira

2005-01-01

The application of light chemical elements and their stable isotopes in biological studies have been increased over the last years. The use of 15 N labeled amino acids is an important tool for elucidation of peptides structures. This paper describe a method for the synthesis of 15 N isotope labeled alanine at lower costs than international ones, as well as the details of the recovery system of the nitrogen residues. In the present work an amination of α-haloacids, with the bromopropionic carboxylic acid and labeled aqua ammonia ( 15 NH 3 aq) was carried out. In order to avoid eventually losses of 15 NH 3 , special cares were adopted, since the production cost is high. Although the acquisition cost of the 13 N (radioactive) labeled compounds is lower, the obtained stable tracer will allow the accomplishment of important studies of the nitrogen cycling in living things, less occupational and environment hazards, and the time limitation problems in field studies. The tests took place in triplicates with NH 3 (aq) being employed. With the establishment of the system for 15 NH 3 recovery, an average of 94 % of the ammonia employed in the synthesis process was recovered. The purity of the amino acid was state determined by TLC (Thin Layer Chromatography) and HPLC (High-Performance Liquid Chromatography) with a fluorescence detector. The Rf and the retention time of the synthesized sample were similar the sigma standard. Finally, regarding the established conditions, it was possible to obtain the alanine with a production cost about 40 % lower than the international price. (author)

Protein-based stable isotope probing.

Science.gov (United States)

Jehmlich, Nico; Schmidt, Frank; Taubert, Martin; Seifert, Jana; Bastida, Felipe; von Bergen, Martin; Richnow, Hans-Hermann; Vogt, Carsten

2010-12-01

We describe a stable isotope probing (SIP) technique that was developed to link microbe-specific metabolic function to phylogenetic information. Carbon ((13)C)- or nitrogen ((15)N)-labeled substrates (typically with >98% heavy label) were used in cultivation experiments and the heavy isotope incorporation into proteins (protein-SIP) on growth was determined. The amount of incorporation provides a measure for assimilation of a substrate, and the sequence information from peptide analysis obtained by mass spectrometry delivers phylogenetic information about the microorganisms responsible for the metabolism of the particular substrate. In this article, we provide guidelines for incubating microbial cultures with labeled substrates and a protocol for protein-SIP. The protocol guides readers through the proteomics pipeline, including protein extraction, gel-free and gel-based protein separation, the subsequent mass spectrometric analysis of peptides and the calculation of the incorporation of stable isotopes into peptides. Extraction of proteins and the mass fingerprint measurements of unlabeled and labeled fractions can be performed in 2-3 d.

UNiquant, a Program for Quantitative Proteomics Analysis Using Stable Isotope Labeling

Energy Technology Data Exchange (ETDEWEB)

Huang, Xin; Tolmachev, Aleksey V.; Shen, Yulei; Liu, Miao; Huang, Lin; Zhang, Zhixin; Anderson, Gordon A.; Smith, Richard D.; Chan, Wing C.; Hinrichs, Steven; Fu, Kai; Ding, Shi-Jian

2011-03-04

We present UNiquant, a new software program for analyzing stable isotope labeling (SIL) based quantitative proteomics data. UNiquant surpassed the performance of two other platforms, MaxQuant and Mascot Distiller, using complex proteome mixtures having either known or unknown heavy/light ratios. UNiquant is compatible with a broad spectrum of search engines and SIL methods, providing outstanding peptide pair identification and accurate measurement of the relative peptide/protein abundance.

Stable isotopes

International Nuclear Information System (INIS)

Brazier, J.L.; Guinamant, J.L.

1995-01-01

According to the progress which has been realised in the technology of separating and measuring isotopes, the stable isotopes are used as preferable 'labelling elements' for big number of applications. The isotopic composition of natural products shows significant variations as a result of different reasons like the climate, the seasons, or their geographic origins. So, it was proved that the same product has a different isotopic composition of alimentary and agriculture products. It is also important in detecting the pharmacological and medical chemicals. This review article deals with the technology, like chromatography and spectrophotometry, adapted to this aim, and some important applications. 17 refs. 6 figs

Adaptation of a Commonly Used, Chemically Defined Medium for Human Embryonic Stem Cells to Stable Isotope Labeling with Amino Acids in Cell Culture

DEFF Research Database (Denmark)

Liberski, A. R.; Al-Noubi, M. N.; Rahman, Z. H.

2013-01-01

Metabolic labeling with stable isotopes is a prominent technique for comparative quantitative proteomics, and stable isotope labeling with amino acids in cell culture (SILAC) is the most commonly used approach. SILAC is, however, traditionally limited to simple tissue culture regimens and only ra...

Application of zinc isotope tracer technology in tracing soil heavy metal pollution

Science.gov (United States)

Norbu, Namkha; Wang, Shuguang; Xu, Yan; Yang, Jianqiang; Liu, Qiang

2017-08-01

Recent years the soil heavy metal pollution has become increasingly serious, especially the zinc pollution. Due to the complexity of this problem, in order to prevent and treat the soil pollution, it's crucial to accurately and quickly find out the pollution sources and control them. With the development of stable isotope tracer technology, it's able to determine the composition of zinc isotope. Based on the theory of zinc isotope tracer technique, and by means of doing some latest domestic and overseas literature research about the zinc isotope multi-receiving cups of inductively coupled plasma mass spectrometer (MC-ICP-MS) testing technology, this paper summarized the latest research results about the pollution tracer of zinc isotope, and according to the deficiencies and existing problems of previous research, made outlooks of zinc isotope fractionation mechanism, repository establishment and tracer multiple solutions.

Isotope and chemical tracers in groundwater hydrology

International Nuclear Information System (INIS)

Kendall, C.; Stewart, M.K.; Morgenstern, U.; Trompetter, V.

1999-01-01

The course sessions cover: session 1, Fundamentals of stable and radioactive isotopes; session 2, Stable oxygen and hydrogen isotopes in hydrology: background, examples, sampling strategy; session 3, Catchment studies using oxygen and hydrogen isotopes: background - the hydrologic water balance, evapotranspiration - the lion's share, runoff generation - new water/old water fractions, groundwater recharge - the crumbs; session 4, Isotopes in catchment hydrology: survey of applications, future developments; session 5, Applications of tritium in hydrology: background and measurement, interpretation, examples; session 6, Case studies using mixing models: Hutt Valley groundwater system, an extended mixing model for simulating tracer transport in the unsaturated zone; session 7, Groundwater dating using CFC concentrations: background, sampling and measurement, use and applications; session 8, Groundwater dating with carbon-14: background, sampling and measurement, use and applications; session 9, NZ case studies: Tauranga warm springs, North Canterbury Plains groundwater; session 10, Stable carbon and nitrogen isotopes: background and examples, biological applications of C-N-S isotopes; session 11, New developments in isotope hydrology: gas isotopes, compound specific applications, age dating of sediments etc; session 12, NZ case studies: North Canterbury Plains groundwater (continued), Waimea Plains groundwater. (author). refs., figs

Isotopically labelled pyrimidines and purines

International Nuclear Information System (INIS)

Balaban, A.T.; Bally, I.

1987-01-01

Among the three diazines, pyrimidine is by far the most important one because its derivatives uracil, thymine and cytosine are constituents of the ubiquitous deoxynucleic acids (DNA) and ribonucleic acids (RNA). Other derivatives of pyrimidine without condensed rings include barbiturates, alloxan, orotic acid and thiamine or vitamin B 1 . From the polycyclic derivatives of pyrimidine such as pteridine, alloxazine, and purine, the latter, through its derivatives adenine and guanine complete the list of bases which occur in DNA and RNA: in addition, other purine derivatives such as hypoxanthine, xanthine, theobromine, theophylline, caffeine and uric acid are important natural products with biological activity. The paper presents methods for preparing isotopically labeled pyrimidines as well as purine derivatives. For convenience, the authors describe separately carbon-labeled with radioisotopes 11 C (T 1/2 = 20.3 min) and 14 C (T 1/2 = 5736 years) or the stable isotope 13 C (natural abundance 1.1%) and then hydrogen-labeled systems with the radioisotope 3 H ≡ T (T 1/2 = 12.346 years) or with the stable isotope 2 H ≡ D (natural abundance 0.015%). We do not separate stable from radioactive isotopes because the synthetic methods are identical for the same element; however, the introduction of hydrogen isotopes into organic molecules is often performed by reactions such as isotope exchange which cannot take place in the case of carbon isotopes

Isotopic marking and tracers

International Nuclear Information System (INIS)

Morel, F.

1997-01-01

The use of radioactive isotopes as tracers in biology has been developed thanks to the economic generation of the required isotopes in accelerators and nuclear reactors, and to the multiple applications of tracers in the life domain; the most usual isotopes employed in biology are carbon, hydrogen, phosphorus and sulfur isotopes, because these elements are present in most of organic molecules. Most of the life science knowledge appears to be dependent to the extensive use of nuclear tools and radioactive tracers; the example of the utilization of radioactive phosphorus marked ATP to study the multiple reactions with proteins, nucleic acids, etc., is given

Investigation of mercury-containing proteins by enriched stable isotopic tracer and size-exclusion chromatography hyphenated to inductively coupled plasma-isotope dilution mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Shi Junwen [Laboratory for Bio-Environmental Health Sciences of Nanoscale Materials and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China)]|[Graduate School of the Chinese Academy of Sciences, Beijing 100049 (China); Feng Weiyue [Laboratory for Bio-Environmental Health Sciences of Nanoscale Materials and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China)]. E-mail: fengwy@mail.ihep.ac.cn; Wang Meng [Laboratory for Bio-Environmental Health Sciences of Nanoscale Materials and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China)]|[Graduate School of the Chinese Academy of Sciences, Beijing 100049 (China); Zhang Fang [Graduate School of the Chinese Academy of Sciences, Beijing 100049 (China); Li Bai [Laboratory for Bio-Environmental Health Sciences of Nanoscale Materials and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China); Wang Bing; Zhu Motao [Laboratory for Bio-Environmental Health Sciences of Nanoscale Materials and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China)]|[Graduate School of the Chinese Academy of Sciences, Beijing 100049 (China); Chai Zhifang [Laboratory for Bio-Environmental Health Sciences of Nanoscale Materials and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China)]|[Institute of Nuclear Technology, Shenzhen University, Shenzhen 518060 (China)]|[Institute of Nanochemistry and Nanosafety, Shanghai University, Shanghai (China)

2007-01-30

In order to investigate trace mercury-containing proteins in maternal rat and their offspring, a method of enriched stable isotopic tracer ({sup 196}Hg and {sup 198}Hg) combined with size-exclusion chromatography (SEC) coupled to inductively coupled plasma-isotope dilution mass spectrometry (ICP-IDMS) was developed. Prior to the analysis, {sup 196}Hg- and {sup 198}Hg-enriched methylmercury was administrated to the pregnant rats. Then the mercury-containing proteins in serum and brain cytosol of the dam and pup rats were separated by size-exclusion columns and the mercury was detected by ICP-MS. The ICP-MS spectrogram of the tracing samples showed significantly elevated {sup 196}Hg and {sup 198}Hg isotopic signals compared with the natural ones, indicating that the detection sensitivity could be increased by the tracer method. The contents of mercury in chromatographic fractions of the dam and pup rat brain cytosol were quantitatively estimated by post-column reverse ID-ICP-MS. The quantitative speciation differences of mercury in brain cytosol between the dam and pup rats were observed, indicating that such studies could be useful for toxicological estimation. Additionally, the isotopic ratio measurement of {sup 198}Hg/{sup 202}Hg in the tracing samples could be used to identify the artifact mercury species caused in the analytical procedure. The study demonstrates that the tracer method combined with high-performance liquid chromatography (HPLC)-ICP-IDMS could provide reliably qualitative and quantitative information on mercury-containing proteins in organisms.

Investigation of mercury-containing proteins by enriched stable isotopic tracer and size-exclusion chromatography hyphenated to inductively coupled plasma-isotope dilution mass spectrometry

International Nuclear Information System (INIS)

Shi Junwen; Feng Weiyue; Wang Meng; Zhang Fang; Li Bai; Wang Bing; Zhu Motao; Chai Zhifang

2007-01-01

In order to investigate trace mercury-containing proteins in maternal rat and their offspring, a method of enriched stable isotopic tracer ( 196 Hg and 198 Hg) combined with size-exclusion chromatography (SEC) coupled to inductively coupled plasma-isotope dilution mass spectrometry (ICP-IDMS) was developed. Prior to the analysis, 196 Hg- and 198 Hg-enriched methylmercury was administrated to the pregnant rats. Then the mercury-containing proteins in serum and brain cytosol of the dam and pup rats were separated by size-exclusion columns and the mercury was detected by ICP-MS. The ICP-MS spectrogram of the tracing samples showed significantly elevated 196 Hg and 198 Hg isotopic signals compared with the natural ones, indicating that the detection sensitivity could be increased by the tracer method. The contents of mercury in chromatographic fractions of the dam and pup rat brain cytosol were quantitatively estimated by post-column reverse ID-ICP-MS. The quantitative speciation differences of mercury in brain cytosol between the dam and pup rats were observed, indicating that such studies could be useful for toxicological estimation. Additionally, the isotopic ratio measurement of 198 Hg/ 202 Hg in the tracing samples could be used to identify the artifact mercury species caused in the analytical procedure. The study demonstrates that the tracer method combined with high-performance liquid chromatography (HPLC)-ICP-IDMS could provide reliably qualitative and quantitative information on mercury-containing proteins in organisms

Stable isotope studies of nicotine kinetics and bioavailability

International Nuclear Information System (INIS)

Benowitz, N.L.; Jacob, P. III; Denaro, C.; Jenkins, R.

1991-01-01

The stable isotope-labeled compound 3',3'-dideuteronicotine was used to investigate the disposition kinetics of nicotine in smokers, the systemic absorption of nicotine from cigarette smoke, and the bioavailability of nicotine ingested as oral capsules. Blood levels of labeled nicotine could be measured for 9 hours after a 30-minute intravenous infusion. Analysis of disposition kinetics in 10 healthy men revealed a multiexponential decline after the end of an infusion, with an elimination half-life averaging 203 minutes. This half-life was longer than that previously reported, indicating the presence of a shallow elimination phase. Plasma clearance averaged 14.6 ml/min/kg. The average intake of nicotine per cigarette was 2.29 mg. A cigarette smoke-monitoring system that directly measured particulate matter in smoke was evaluated in these subjects. Total particulate matter, number of puffs on the cigarette, total puff volume, and time of puffing correlated with the intake of nicotine from smoking. The oral bioavailability of nicotine averaged 44%. This bioavailability is higher than expected based on the systemic clearance of nicotine and suggests that there may be significant extrahepatic metabolism of nicotine

Cooperation of CMEA member states in the field of the manufacture and use of stable isotopes and compounds thus labelled

International Nuclear Information System (INIS)

Ertel, G.; Ewald, G.

1977-01-01

The contribution presents a survey of scientific-technical cooperation of CMEA member states in the field of stable isotopes, it deals with the specialization of stable isotope production and compounds thus labelled, and gives the prospects for further development of this cooperation. (HK) [de

Bromide as a tracer for studying water movement and nitrate displacement in soils: comparison with stable isotope tracers; Bromid als Tracer zur Untersuchung der Wasserbewegung und der Nitratverlagerung in Boeden: Vergleich mit stabilisotopen Tracern

Energy Technology Data Exchange (ETDEWEB)

Russow, R.; Knappe, S. [UFZ - Umweltforschungszentrum Leipzig-Halle GmbH, Bad Lauchstaedt (Germany). Sektion Bodenforschung

1999-02-01

Tracers are an ideal means of studying water movement and associated nitrate displacement. Often bromide is preferred as a tracer because it is considered a representative tracer for water and because, being a conservative tracer (i.e. not involved in chemical and biological soil processes), it can be used for studying anion transport in soils. Moreover, it is less expensive and easier to measure than the stable isotopes deuterium and {sup 15}N. Its great advantage over radioactive tracers (e.g. tritium), which outweighs their extreme sensitivity and ease of measurement and which it has in common with stable isotopes, is that it does not require radiation protection measures. However, there are also constraints on the use of bromide as a tracer in soil/water/plant systems. Our own studies on different soils using D{sub 2}O, bromide and [{sup 15}N]-nitrate in lysimeters suggest that the above assumptions on bromide tracers need not always be valid under conditions as they prevail in biologically active soils. As the present paper shows, these studies permit a good assessment of the possibilities and limits to these tracers. [Deutsch] Fuer die Untersuchung der Wasserbewegung sowie der daran gekoppelten Nitrat-Verlagerung ist der Einsatz von Tracern das Mittel der Wahl. Dabei wird Bromid als Tracer haeufig bevorzugt, da es allgemein als ein repraesentativer Tracer fuer Wasser und als konservativer Tracer (nicht involviert in chemische und biologische Bodenprozesse) zur Untersuchung des Anionentransportes in Boeden angesehen wird und es gegenueber den stabilen Isotopen Deuterium und {sup 15}N billiger und einfacher zu bestimmen ist. Gegenueber den radioaktiven Tracern (z.B. Tritium), die zwar sehr empfindlich und einfach messbar sind, besteht der grosse Vorteil, dass, wie bei den stabilen Isotopen, keine Strahlenschutzmassnahmen ergriffen werden muessen. Es gibt jedoch auch einschraenkende Hinweise fuer die Verwendung von Bromid als Tracer im System Boden

Stable isotope labeling of glycoprotein expressed in silkworms using immunoglobulin G as a test molecule

Energy Technology Data Exchange (ETDEWEB)

Yagi, Hirokazu [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan); Nakamura, Masatoshi [National Institute of Agrobiological Sciences, Genetic Resources Conservation Research Unit, Genetic Resources Center (Japan); Yokoyama, Jun [Taiyo Nippon Sanso Corporation, Tsukuba Laboratories (Japan); Zhang, Ying; Yamaguchi, Takumi [National Institutes of Natural Sciences, Institute for Molecular Science and Okazaki Institute for Integrative Bioscience (Japan); Kondo, Sachiko [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan); Kobayashi, Jun [Yamaguchi University, Department of Biological and Environmental Sciences, Faculty of Agriculture (Japan); Kato, Tatsuya; Park, Enoch Y. [Shizuoka University, Laboratory of Biotechnology, Research Institute of Green Science and Technology (Japan); Nakazawa, Shiori [Nagoya University, Sugashima Marine Biological Laboratory, Graduate School of Science (Japan); Hashii, Noritaka; Kawasaki, Nana [National Institute of Health Sciences, Division of Biological Chemistry and Biologicals (Japan); Kato, Koichi, E-mail: kkato@phar.nagoya-cu.ac.jp [Nagoya City University, Faculty and Graduate School of Pharmaceutical Sciences (Japan)

2015-06-15

Silkworms serve as promising bioreactors for the production of recombinant proteins, including glycoproteins and membrane proteins, for structural and functional protein analyses. However, lack of methodology for stable isotope labeling has been a major deterrent to using this expression system for nuclear magnetic resonance (NMR) structural biology. Here we developed a metabolic isotope labeling technique using commercially available silkworm larvae. The fifth instar larvae were infected with baculoviruses for co-expression of recombinant human immunoglobulin G (IgG) as a test molecule, with calnexin as a chaperone. They were subsequently reared on an artificial diet containing {sup 15}N-labeled yeast crude protein extract. We harvested 0.1 mg of IgG from larva with a {sup 15}N-enrichment ratio of approximately 80 %. This allowed us to compare NMR spectral data of the Fc fragment cleaved from the silkworm-produced IgG with those of an authentic Fc glycoprotein derived from mammalian cells. Therefore, we successfully demonstrated that our method enables production of isotopically labeled glycoproteins for NMR studies.

Development of new technology for the use of stable isotopic tracers in the study of human health and disease

International Nuclear Information System (INIS)

Hacyey, D.L.; Klein, P.D.; Szczepanik, P.A.; Niu, W.; Stellaard, F.; Tserng, K.Y.

1977-01-01

This program has five major aspects: first, the development of analytical instrumentation of requisite sensitivity, stability, and simplicity to conduct stable isotope measurements in a routine manner; second, the development of appropriately labeled compounds for metabolic investigations, initially through custom syntheses but eventually through commercial sources; third, development of analytical methodology to isolate, purify, and determine the isotopic content of specific organic compounds reflecting metabolic processes or disease states; fourth, collaborative development of clinical applications and testing on a routine basis, through a network of clinical centers around the country; and finally, the collection and dissemination of stable isotope information on an international scale through survey publications and conferences

In vivo trace element speciation study by using enriched stable isotopic tracer technique

International Nuclear Information System (INIS)

Feng Weiyue; Chai Zhifang; Shi Junwen; Ding Wenjun

2005-01-01

In contrast to the radioactive tracer method, the enriched stable isotopic technique used in life sciences will not cause radiation damage to cells and its operation will be no radioactive risk, In our laboratory, the enriched stable isotopes Cr-50, Hg-196 and Hg-198 combined with biochemical separation, neutron activation analysis (NAA) and inductively coupled plasma mass spectrometry (ICP-IVIS) have been used to investigate the element speciation in vivo. Chromium (Cr) is proposed to act as a potentiator of insulin action in animals and human beings. Its deficiency induces the symptoms resembling diabetes and its supplement can alleviate these symptoms. However, as the concentration of Cr in vivo is usually at ultratrace level(- ng/g), its speciation study is usually difficult, since it is almost impossible to avoid the exogenous Cr contamination caused by separation and determination processes. Therefore, in this study, 50 Cr 2 O 3 with 94.2% 50 Cr was used as a tracer combined with gel chromatography to study the Cr speciation in serum, liver, urine and other tissues of healthy and diabetic rats. The Cr concentrations can be determined via 50 Cr(n, γ) 51 Cr by NAA, which is ideally suited for the ultratrace element analyses due to its high precision, accuracy and sensitivity. Such research have found that the most quantity of chromium in vivo is mainly combined with high molecular weight proteins, which is later identified as transferrin and low molecular weight protein is mainly excreted from urine. Mercury is listed by the International Program of Chemical Safety as one of the six most dangerous chemicals in the global environment. Mercury compounds in the environment are often difficult to degrade. However, the mechanism on mercury toxicity to developing children following long term and low dose of mercury exposure is still not clear. Therefore, high sensitive method in vivo needs to be developed to study such low level mercury toxicity to fetus In this

Analysis of stable isotope assisted metabolomics data acquired by GC-MS

International Nuclear Information System (INIS)

Wei, Xiaoli; Shi, Biyun; Koo, Imhoi; Yin, Xinmin; Lorkiewicz, Pawel; Suhail, Hamid; Rattan, Ramandeep; Giri, Shailendra; McClain, Craig J.

2017-01-01

Stable isotope assisted metabolomics (SIAM) measures the abundance levels of metabolites in a particular pathway using stable isotope tracers (e.g., 13 C, 18 O and/or 15 N). We report a method termed signature ion approach for analysis of SIAM data acquired on a GC-MS system equipped with an electron ionization (EI) ion source. The signature ion is a fragment ion in EI mass spectrum of a derivatized metabolite that contains all atoms of the underivatized metabolite, except the hydrogen atoms lost during derivatization. In this approach, GC-MS data of metabolite standards were used to recognize the signature ion from the EI mass spectra acquired from stable isotope labeled samples, and a linear regression model was used to deconvolute the intensity of overlapping isotopologues. A mixture score function was also employed for cross-sample chromatographic peak list alignment to recognize the chromatographic peaks generated by the same metabolite in different samples, by simultaneously evaluating the similarity of retention time and EI mass spectrum of two chromatographic peaks. Analysis of a mixture of 16 13 C-labeled and 16 unlabeled amino acids showed that the signature ion approach accurately identified and quantified all isotopologues. Analysis of polar metabolite extracts from cells respectively fed with uniform 13 C-glucose and 13 C-glutamine further demonstrated that this method can also be used to analyze the complex data acquired from biological samples. - Highlights: • A signature ion approach is developed for analysis of stable isotope GC-MS data. • GC-MS data of compound standards are used for selection of the signature ion. • Linear regression model is used to deconvolute the overlapping isotopologue peaks. • The developed method was tested by known compounds and biological samples.

Application of stable isotopes and isotope pattern deconvolution-ICPMS to speciation of endogenous and exogenous Fe and Se in rats

International Nuclear Information System (INIS)

Gonzalez Iglesias, H.; Fernandez-Sanchez, M.L.; Garcia Alonso, J.I.; Lopez Sastre, J.B.; Sanz-Medel, A.

2009-01-01

Full text: Enriched stable isotopes are crucial to study essential trace element metabolism (e.g. Se, Fe) in biological systems. Measuring isotope ratios by ICPMS and using appropriate mathematical calculations, based on isotope pattern deconvolution (IPD) may provide quantitative data about endogenous and exogenous essential or toxic elements and their metabolism. In this work, IPD was applied to explore the feasibility of using two Se (or Fe) enriched stable isotopes, one as metabolic tracer and the other as quantitation tracer, to discriminate between the endogenous and supplemented Se (or Fe) species in rat fluids by collision cell ICPMS coupled to HPLC separation. (author)

Earth mechanisms (fluid and solid), life mechanisms and stable isotope tracers. Isotopes and biology, a great project

International Nuclear Information System (INIS)

Fromageot, P.

1997-01-01

Historical and recent review of the development and use of radioactive isotopes for biological studies in France: study of the intermediate metabolism with 14 C tracers in organic molecules; study and biosynthesis of macromolecules (DNA, RNA and polynucleotides) through the use of marked nucleotides; tracer proteins for use in NMR and protein engineering, use of tritium for the study of hormonal regulation

Surface oceanographic fronts influencing deep-sea biological activity: Using fish stable isotopes as ecological tracers

Science.gov (United States)

Louzao, Maite; Navarro, Joan; Delgado-Huertas, Antonio; de Sola, Luis Gil; Forero, Manuela G.

2017-06-01

Ecotones can be described as transition zones between neighbouring ecological systems that can be shaped by environmental gradients over a range of space and time scales. In the marine environment, the detection of ecotones is complex given the highly dynamic nature of marine systems and the paucity of empirical data over ocean-basin scales. One approach to overcome these limitations is to use stable isotopes from animal tissues since they can track spatial oceanographic variability across marine systems and, in turn, can be used as ecological tracers. Here, we analysed stable isotopes of deep-sea fishes to assess the presence of ecological discontinuities across the western Mediterranean. We were specifically interested in exploring the connection between deep-sea biological activity and particular oceanographic features (i.e., surface fronts) occurring in the pelagic domain. We collected samples for three different abundant deep-sea species in May 2004 from an experimental oceanographic trawling cruise (MEDITS): the Mictophydae jewel lanternfish Lampanyctus crocodilus and two species of the Gadidae family, the silvery pout Gadiculus argenteus and the blue whiting Micromesistius poutassou. The experimental survey occurred along the Iberian continental shelf and the upper and middle slopes, from the Strait of Gibraltar in the SW to the Cape Creus in the NE. The three deep-sea species were highly abundant throughout the study area and they showed geographic variation in their isotopic values, with decreasing values from north to south disrupted by an important change point around the Vera Gulf. Isotopic latitudinal gradients were explained by pelagic oceanographic conditions along the study area and confirm the existence of an ecotone at the Vera Gulf. This area could be considered as an oceanographic boundary where waters of Atlantic origin meet Mediterranean surface waters forming important frontal structures such as the Almeria-Oran front. In fact, our results

Single-well reactive tracer test and stable isotope analysis for determination of microbial activity in a fast hydrocarbon-contaminated aquifer

International Nuclear Information System (INIS)

Burbery, L.; Cassiani, G.; Andreotti, G.; Ricchiuto, T.; Semple, K.T.

2004-01-01

Single-well reactive tracer tests, such as the push-pull test are useful tools for characterising in-situ bioattenuation processes in contaminated aquifers. However, the analytical models that are used to interpret push-pull data may be over-simplified, and potentially overlook important processes responsible for the frequent discrepancy between predicted and observed results obtained from push-pull tests. In this study, the limitations underlying the push-pull test methodology were investigated and were supported with results from a push-pull test conducted in a sulphate-reducing aquifer contaminated by crude oil. Poor ( 20% mass recoveries were achieved. Push-pull test data collected from sulphate-reducing aquifers indicate that the assumption of a well-mixed batch reactor system is incorrect and that reaction rates obtained from push-pull tests in such systems may be affected by the extraction regime implemented. Evidence of microbial respiration of the reactive tracer was provided by stable sulphur isotope analysis, from which an isotope fractionation factor of +9.9±8.1%o was estimated. The stable isotope data support the argument that reaction rates calculated using push-pull tests are not uniformly distributed in space and time and are likely to be influenced by heterogeneities in the flow field. - Reaction rates calculated by push-pull tests are not uniformly distributed in time and space

Stable-carbon isotope variability in tree foliage and wood

International Nuclear Information System (INIS)

Leavitt, S.W.; Long, A.

1986-01-01

This study documents variation of stable-carbon isotope ratios ( 13 C/ 12 C) in trees of genera Juniperus and Pinus under field conditions. Results are from cellulose analysis on leaves, twigs, and wood from a number of localities in the southwestern US. Substantial variability, typically 1-3%, exists among leaves, within wood (radially, vertically, circumferentially), and between individuals at a site. These results may help guide sampling in tracer-type studies with stable-carbon isotope ratios and aid in the interpretation of isotopic results from such studies

Tracer measured substrate turnover requires arterial sampling downstream of infusion site

International Nuclear Information System (INIS)

Stanley, W.C.; Neese, R.A.; Gertz, E.W.; Wisneski, J.A.; Morris, D.L.; Brooks, G.A.

1986-01-01

Measurement of metabolite turnover (Rt) with radioactive tracers is done by either infusing tracer venously and sampling specific activity (SA) arterially (V-A modes), or by infusing into the aorta and sampling venous blood (A-V mode). Using the Fick principle, the necessity for using the V-A mode can be demonstrated. If tracer is infused into the left ventricle, in a steady state the Rt is the product of arterial trace concentration, the cardiac output, and the tracer extraction ratio for the whole body. This is expressed as: Rt = Ca x Qx ((*Ca - *Cv)/*Ca) (Eq1) where C=trace concentration (μmol/ml), *C=tracer conc. (dpm/ml), a=arterial, v-=mixed venous, and Q=cardiac output (ml/min). Rearranging the equation: Rt = Qx(*Ca - *Cv)/SAa = F/SAa (Eq2) where SAa is *Ca/Ca, and Qx (*Ca-*Cv) equals the infusion rate (F). The authors compared Eqs1 and 2 (Rt = F/SAa) in 3 anesthetized dogs in which [1- 14 C] lactate was infused into the left ventricle, and blood was sampled arterially downstream from the infusion site and in the pulmonary artery. Eqs 1 and 2 gave similar results for Rt (45.9 vs. 43.9 μmol/kg min), while substituting SAv for SAa (A-V mode) into Eq 2 gave a higher Rt (53.6). When SAv (A-V mode) is used, the specific activity seen by the tissues (SAa) is not considered in the calculation of Rt. Therefore, only the V-A mode meets the requirements for tracer measured metabolite turnover

Determination of steady state and nonsteady-state glycerol kinetics in humans using deuterium-labeled tracer

International Nuclear Information System (INIS)

Beylot, M.; Martin, C.; Beaufrere, B.; Riou, J.P.; Mornex, R.

1987-01-01

Using deuterium-labeled glycerol as tracer and gas-liquid chromatography-mass spectrometry techniques for the determination of isotopic enrichment, we have developed a simple and ethically acceptable method of determining glycerol appearance rate in humans under steady-state and nonsteady-state conditions. In normal subjects, the appearance rate of glycerol in the post-absorptive state was 2.22 +/- 0.20 mumol X kg-1 X min-1, a value in agreement with those reported in studies with radioactively labeled tracers. The ratio nonesterified fatty acid (NEFA) appearance rate/glycerol appearance rate ranged from 1.95 to 3.40. In insulin-dependent diabetic patients with a mild degree of metabolic control, the appearance rate of glycerol was 2.48 +/- 0.29 mumol X kg-1 X min-1. The volume of distribution of glycerol, determined by the bolus injection technique, was (mean) 0.306 l X kg-1 in normal subjects and 0.308 l X kg-1 in insulin-independent diabetic patients. To evaluate the usefulness of the method for determination of glycerol kinetics in nonsteady-state conditions, we infused six normal subjects with natural glycerol and calculated the isotopically determined glycerol appearance rate using a single compartment model (volume of distribution 0.31 l X kg-1). During these tests, the expected glycerol appearance rates were successively 5.03 +/- 0.33, 7.48 +/- 0.39, 9.94 +/- 0.34, 7.48 +/- 0.39, and 5.03 +/- 0.33 mumol +/- kg-1 X min-1, whereas the corresponding isotopically determined appearance rates were 4.62 +/- 0.45, 6.95 +/- 0.56, 10.85 +/- 0.51, 7.35 +/- 0.34, and 5.28 +/- 0.12 mumol X kg-1 X min-1

The use of stable isotopes in medicinal chemistry

International Nuclear Information System (INIS)

Halliday, D.; Thompson, G.N.

1988-01-01

Stable isotopes have been employed increasingly as tracers over the last decade both to provide the clinician with the opportunity to broaden, in a quantitative manner, discrete areas of diagnosis and research, and the clinical chemist with definitive methodology for specific analyte analysis. These non-radioactive 'heavy' isotopes contain one or more extra neutrons in the nucleus compared with their more abundant 'lighter' analogues. Impetus in the application of stable isotopes for in vivo studies has come from an increased awareness of the possible harmful effects in the use of radionuclides, and a realisation of several positive advantages conferred by the use of stable isotopes in their own right - certain elements of clinical importance (especially nitrogen) lack a useable radio-nuclide equivalent; use of a 'cocktail' of stable isotopes permits a range of studies to be performed in the same patient simultaneously and, within specific constraints, serial studies can be performed in the same patients. (author)

Identification of miRNA targets with stable isotope labeling by amino acids in cell culture

DEFF Research Database (Denmark)

Vinther, Jeppe; Hedegaard, Mads Marquardt; Gardner, Paul Phillip

2006-01-01

miRNAs are small noncoding RNAs that regulate gene expression. We have used stable isotope labeling by amino acids in cell culture (SILAC) to investigate the effect of miRNA-1 on the HeLa cell proteome. Expression of 12 out of 504 investigated proteins was repressed by miRNA-1 transfection...

Determining synthesis rates of individual proteins in zebrafish (Danio rerio) with low levels of a stable isotope labelled amino acid.

Science.gov (United States)

Geary, Bethany; Magee, Kieran; Cash, Phillip; Young, Iain S; Whitfield, Phillip D; Doherty, Mary K

2016-05-01

The zebrafish is a powerful model organism for the analysis of human cardiovascular development and disease. Understanding these processes at the protein level not only requires changes in protein concentration to be determined but also the rate at which these changes occur on a protein-by-protein basis. The ability to measure protein synthesis and degradation rates on a proteome-wide scale, using stable isotope labelling in conjunction with mass spectrometry is now a well-established experimental approach. With the advent of more selective and sensitive mass spectrometers, it is possible to accurately measure lower levels of stable isotope incorporation, even when sample is limited. In order to challenge the sensitivity of this approach, we successfully determined the synthesis rates of over 600 proteins from the cardiac muscle of the zebrafish using a diet where either 30% or 50% of the L-leucine was replaced with a stable isotope labelled analogue ([(2) H7 ]L-leucine]. It was possible to extract sufficient protein from individual zebrafish hearts to determine the incorporation rate of the label into hundreds of proteins simultaneously, with the two labelling regimens showing a good correlation of synthesis rates. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multitracer Stable Isotope Quantification of Arginase and Nitric Oxide Synthase Activity in a Mouse Model of Pseudomonas Lung Infection

Directory of Open Access Journals (Sweden)

Hartmut Grasemann

2014-01-01

Full Text Available Cystic fibrosis airways are deficient for L-arginine, a substrate for nitric oxide synthases (NOSs and arginases. The rationale for this study was to quantify NOS and arginase activity in the mouse lung. Anesthetized unventilated mice received a primed constant stable isotope intravenous infusion containing labeled L-arginine, ornithine, and citrulline. The isotopic enrichment of each of the infused isotopomers and its product amino acids were measured in plasma and organ homogenates using liquid chromatography-tandem mass spectrometry. The effect of infection was studied three days after direct tracheal instillation of Pseudomonas-coated agar beads. In the infusion model, lung infection resulted in a significant (28-fold increase in NOS activity in lung but not in trachea, kidney, liver, or plasma. Absolute rates of arginase activity in solid tissues could not be calculated in this model. In an isolated lung perfusion model used for comparison increased NOS activity in infected lungs was confirmed (28.5-fold and lung arginase activity was increased 9.7-fold. The activity of L-arginine metabolizing enzymes can be measured using stable isotope conversion in the mouse. Accumulation of L-ornithine in the whole mouse model hindered the exact quantification of arginase activity in the lung, a problem that was overcome utilizing an isolated lung perfusion model.

Quantitative imaging of subcellular metabolism with stable isotopes and multi-isotope imaging mass spectrometry

Science.gov (United States)

Steinhauser, Matthew L.; Lechene, Claude P.

2014-01-01

Multi-isotope imaging mass spectrometry (MIMS) is the quantitative imaging of stable isotope labels in cells with a new type of secondary ion mass spectrometer (NanoSIMS). The power of the methodology is attributable to (i) the immense advantage of using non-toxic stable isotope labels, (ii) high resolution imaging that approaches the resolution of usual transmission electron microscopy and (iii) the precise quantification of label down to 1 part-per-million and spanning several orders of magnitude. Here we review the basic elements of MIMS and describe new applications of MIMS to the quantitative study of metabolic processes including protein and nucleic acid synthesis in model organisms ranging from microbes to humans. PMID:23660233

Use of stable isotope techniques in soil organic matter studies

International Nuclear Information System (INIS)

Gerzabek, M.H.

1998-01-01

Plants differ distinctly in their C-isotopic composition. The largest differences occur between plant species with different photosynthetic pathways. C 3 - and C 4 -plants are differentiated by approximately 1.4% on the δ-scale (approx. -2.7% 13 C versus -1.3% 13 C). Modern elemental analyser - mass spectrometer combinations reach accuracies of at least 0.01% δ 13 C. Therefore, the difference between C 3 and C 4 plants is sufficient to be used for tracer studies. Several investigations of soil organic mater (SOM) turnover under field conditions were undertaken using the fact that the vegetation cover changed between C 3 and C 4 plants. The discrimination between SOM originating from indigenous vegetation (forest, C 3 ) and sugar cane (C 4 ) after 50 years of cropping introducing two SOM compartments of different stability was described. Another example is the change from prairie vegetation (C 4 ) to different C 3 -crops and the evaluation of the carbon origin at or near equilibrium. More recent studies use 15 N-labelled C 4 -plant residues or 13 C-labelled C 3 -plants to elucidate the fate of carbon and nitrogen in soils developed under C 3 -vegetation. Both in situ experiments and laboratory incubations were used to evaluate carbon and nitrogen fluxes from crop residues. Physical fractionation of bulk soil into particle sizes proved to be of advantage to follow short and long-term dynamics of crop residues within SOM. Changes in the natural abundance of 13 C and 15 N within soil profiles can elucidate leaching or mineralization of humic substances. Changes in the natural abundance of stable isotopes are also possible due to the application of organic manures, quantification, however is not easy because of the small isotopic differences between soil and manure carbon and nitrogen. 15 N labelling of soil nitrogen has been widely used in the last two decades to quantify biological nitrogen fixation. Considerable progress has been made due to the isotope dilution

Stable isotope labeling – Liquid chromatography/mass spectrometry for quantitative analysis of androgenic and progestagenic steroids

International Nuclear Information System (INIS)

Guo, Ning; Liu, Ping; Ding, Jun; Zheng, Shu-Jian; Yuan, Bi-Feng; Feng, Yu-Qi

2016-01-01

Steroid hormones play important roles in mammal at very low concentrations and are associated with numerous endocrinology and oncology diseases. Therefore, quantitative analysis of steroid hormones can provide crucial information for uncovering underlying mechanisms of steroid hormones related diseases. In the current study, we developed a sensitive method for the detection of steroid hormones (progesterone, dehydroepiandrosterone, testosterone, pregnenolone, 17-hydroxyprogesterone, androstenedione and 17α-hydroxypregnenolone) in body fluids by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this respect, a pair of isotopes labeling reagents, Girard reagent P (GP) and d_5-Girard reagent P (d_5-GP), were synthesized and utilized to label steroid hormones in follicular fluid samples and steroid hormone standards, respectively. The heavy labeled standards were used as internal standards for quantification to minimize quantitation deviation in MS analysis due to the matrix and ion suppression effects. The ionization efficiencies of steroid hormones were greatly improved by 4–504 folds through the introduction of a permanent charged moiety of quaternary ammonium from GP. Using the developed method, we successfully quantified steroid hormones in human follicular fluid. We found that the contents of testosterone and androstenedione exhibited significant increase while the content of pregnenolone had significant decrease in follicular fluid of polycystic ovarian syndrome (PCOS) patients compared with healthy controls, indicating that these steroid hormones with significant change may contribute to the pathogenesis of PCOS. Taken together, the developed stable isotope labeling coupled LC-ESI-MS/MS analysis demonstrated to be a promising method for the sensitive and accurate determination of steroid hormones, which may facilitate the in-depth investigation of steroid hormones related

Stable isotope labeling – Liquid chromatography/mass spectrometry for quantitative analysis of androgenic and progestagenic steroids

Energy Technology Data Exchange (ETDEWEB)

Guo, Ning; Liu, Ping; Ding, Jun; Zheng, Shu-Jian; Yuan, Bi-Feng; Feng, Yu-Qi, E-mail: yqfeng@whu.edu.cn

2016-01-28

Steroid hormones play important roles in mammal at very low concentrations and are associated with numerous endocrinology and oncology diseases. Therefore, quantitative analysis of steroid hormones can provide crucial information for uncovering underlying mechanisms of steroid hormones related diseases. In the current study, we developed a sensitive method for the detection of steroid hormones (progesterone, dehydroepiandrosterone, testosterone, pregnenolone, 17-hydroxyprogesterone, androstenedione and 17α-hydroxypregnenolone) in body fluids by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this respect, a pair of isotopes labeling reagents, Girard reagent P (GP) and d{sub 5}-Girard reagent P (d{sub 5}-GP), were synthesized and utilized to label steroid hormones in follicular fluid samples and steroid hormone standards, respectively. The heavy labeled standards were used as internal standards for quantification to minimize quantitation deviation in MS analysis due to the matrix and ion suppression effects. The ionization efficiencies of steroid hormones were greatly improved by 4–504 folds through the introduction of a permanent charged moiety of quaternary ammonium from GP. Using the developed method, we successfully quantified steroid hormones in human follicular fluid. We found that the contents of testosterone and androstenedione exhibited significant increase while the content of pregnenolone had significant decrease in follicular fluid of polycystic ovarian syndrome (PCOS) patients compared with healthy controls, indicating that these steroid hormones with significant change may contribute to the pathogenesis of PCOS. Taken together, the developed stable isotope labeling coupled LC-ESI-MS/MS analysis demonstrated to be a promising method for the sensitive and accurate determination of steroid hormones, which may facilitate the in-depth investigation of steroid hormones

Plant mutation breeding and application of isotopic tracer in Chinese agriculture

International Nuclear Information System (INIS)

Liang Qu

1993-03-01

The progress and achievements made in plant mutation breeding and application of isotopic tracer in Chinese agriculture are outlined. Plant mutation breeding is well developed not only in improvement of crops but also in methodology of mutation induction. More than 325 mutant varieties and hundreds of various valuable mutants of 29 different species have been obtained. The mutant cultivars released have covered more than 10 million hectares in total area. The systematic studies on methodology such as techniques for mutagenic treatment, development of various mutagens, screening and selecting techniques of mutation etc. have been carried out in China. The techniques of radioisotopic tracer used in many research fields are described. Application of isotopic tracer in studies of fertilization and plant nutrition, environment protection, nitrogen-fixation, animal production and diagnosis of diseases, and so on, have made great achievements and benefits in China. Many kinds of labelled compounds, especially of labelled agro-chemicals have been synthesized in the Institute for Application of Atomic Energy (IAAE). Chinese Academy of Agricultural Sciences (CAAS). The proposals for the region cooperation in Asia on application of atomic energy in agriculture are included

The synthesis of tritium, carbon-14 and stable isotope labelled selective estrogen receptor degraders.

Science.gov (United States)

Bragg, Ryan A; Bushby, Nick; Ericsson, Cecilia; Kingston, Lee P; Ji, Hailong; Elmore, Charles S

2016-09-01

As part of a Medicinal Chemistry program aimed at developing an orally bioavailable selective estrogen receptor degrader, a number of tritium, carbon-14, and stable isotope labelled (E)-3-[4-(2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl]prop-2-enoic acids were required. This paper discusses 5 synthetic approaches to this compound class. Copyright © 2016 John Wiley & Sons, Ltd.

Stable isotope-resolved metabolomics and applications for drug development

Science.gov (United States)

Fan, Teresa W-M.; Lorkiewicz, Pawel; Sellers, Katherine; Moseley, Hunter N.B.; Higashi, Richard M.; Lane, Andrew N.

2012-01-01

Advances in analytical methodologies, principally nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), during the last decade have made large-scale analysis of the human metabolome a reality. This is leading to the reawakening of the importance of metabolism in human diseases, particularly cancer. The metabolome is the functional readout of the genome, functional genome, and proteome; it is also an integral partner in molecular regulations for homeostasis. The interrogation of the metabolome, or metabolomics, is now being applied to numerous diseases, largely by metabolite profiling for biomarker discovery, but also in pharmacology and therapeutics. Recent advances in stable isotope tracer-based metabolomic approaches enable unambiguous tracking of individual atoms through compartmentalized metabolic networks directly in human subjects, which promises to decipher the complexity of the human metabolome at an unprecedented pace. This knowledge will revolutionize our understanding of complex human diseases, clinical diagnostics, as well as individualized therapeutics and drug response. In this review, we focus on the use of stable isotope tracers with metabolomics technologies for understanding metabolic network dynamics in both model systems and in clinical applications. Atom-resolved isotope tracing via the two major analytical platforms, NMR and MS, has the power to determine novel metabolic reprogramming in diseases, discover new drug targets, and facilitates ADME studies. We also illustrate new metabolic tracer-based imaging technologies, which enable direct visualization of metabolic processes in vivo. We further outline current practices and future requirements for biochemoinformatics development, which is an integral part of translating stable isotope-resolved metabolomics into clinical reality. PMID:22212615

A theory of stable-isotope dilution mass spectrometry

International Nuclear Information System (INIS)

Pickup, J.F.; McPherson, C.K.

1977-01-01

In order to perform quantitative analysis using stable isotope dilution with mass spectrometry, an equation is derived which describes the relationship between the relative proportions of natural and labelled material and measured isotope ratios

Application of Stable Isotope Signatures in Food Traceability

International Nuclear Information System (INIS)

Nazaratul Ashifa Abdullah Salim; Roslanzairi Mostapha; Zainon Othman

2016-01-01

Stable isotope analysis has widely been used to trace the origin of organic materials in various fields, such as geochemistry, biochemistry, archaeology and petroleum. In past a decade, it has also become an important tool for food traceability study. The globalisation of food markets and the relative ease which food commodities are transported through and between countries and continents means that consumers are increasingly concerned about the origin of the foods they eat. The natural abundance of stable isotope variation such as carbon, nitrogen, hydrogen and oxygen are used as geographic tracers or marker to determine the geographic origin of fruits, crop, vegetables and food products from animal. The isotopic compositions of plant materials reflect various factors such as isotopic compositions of source materials and their assimilation processes as well as growth environments. This paper will discuss on stable carbon and nitrogen isotopic compositions in rice that been determined by Isotope Ratio Mass Spectrometry, advantages, limitations and potential of other analysis applications that can be incorporated in food traceability system. (author)

DNA stable-isotope probing (DNA-SIP).

Science.gov (United States)

Dunford, Eric A; Neufeld, Josh D

2010-08-02

DNA stable-isotope probing (DNA-SIP) is a powerful technique for identifying active microorganisms that assimilate particular carbon substrates and nutrients into cellular biomass. As such, this cultivation-independent technique has been an important methodology for assigning metabolic function to the diverse communities inhabiting a wide range of terrestrial and aquatic environments. Following the incubation of an environmental sample with stable-isotope labelled compounds, extracted nucleic acid is subjected to density gradient ultracentrifugation and subsequent gradient fractionation to separate nucleic acids of differing densities. Purification of DNA from cesium chloride retrieves labelled and unlabelled DNA for subsequent molecular characterization (e.g. fingerprinting, microarrays, clone libraries, metagenomics). This JoVE video protocol provides visual step-by-step explanations of the protocol for density gradient ultracentrifugation, gradient fractionation and recovery of labelled DNA. The protocol also includes sample SIP data and highlights important tips and cautions that must be considered to ensure a successful DNA-SIP analysis.

Use of stable sulphur isotopes to monitor directly the behaviour of sulphur in coal during thermal desulphurization

Science.gov (United States)

Liu, Chao-Li; Hackley, Keith C.; Coleman, D.D.

1987-01-01

A method has been developed using stable sulphur isotope analyses to monitor the behaviour of sulphur forms in a coal during thermal desulphurization. In this method, the natural stable isotopic composition of the pyritic and organic sulphur in coal is used as a tracer to follow their mobility during the desulphurization process. This tracer method is based on the fact that the isotopic compositions of pyritic and organic sulphur are significantly different in some coals. Isotopic results of pyrolysis experiments at temperatures ranging from 350 to 750 ??C indicate that the sulphur released with the volatiles is predominantly organic sulphur. The pyritic sulphur is evolved in significant quantities only when pyrolysis temperatures exceed 500 ??C. The presence of pyrite seems to have no effect on the amount of organic sulphur evolved during pyrolysis. The chemical and isotopic mass balances achieved from three different samples of the Herrin (No. 6) coal of the Illinois Basin demonstrate that this stable isotope tracer method is quantitative. The main disadvantage of this tracing technique is that not all coals contain isotopically distinct organic and pyritic sulphur. ?? 1987.

Stable isotopes - separation and application

International Nuclear Information System (INIS)

Lockhart, I.M.

1980-01-01

In this review, methods used for the separation of stable isotopes ( 12 C, 13 C, 14 N, 15 N, 16 O, 17 O, 18 O, 34 S) will be described. The synthesis of labelled compounds, techniques for detection and assay, and areas of application will also be discussed. Particular attention will be paid to the isotopes of carbon, nitrogen, and oxygen; to date, sulphur isotopes have only assumed a minor role. The field of deuterium chemistry is too extensive for adequate treatment; it will therefore be essentially excluded. (author)

Stable isotopes: essential tools in biological and medical research

Energy Technology Data Exchange (ETDEWEB)

Klein, P. D.; Hachey, D. L.; Kreek, M. J.; Schoeller, D. A.

1977-01-01

Recent developments in the use of the stable isotopes, /sup 13/C, /sup 15/N, /sup 17/O, and /sup 18/O, as tracers in research studies in the fields of biology, medicine, pharmacology, and agriculture are briefly reviewed. (CH)

Stable Oxygen-18 and Deuterium Isotopes

DEFF Research Database (Denmark)

Müller, Sascha

The application of stable Oxygen-18 (18O) and Deuterium (2H) isotopes, as a tracer for fluxes between different compartments of the water cycle was subject of the present PhD-thesis. During a three year period, temporal data from a wide range of water cycle constituents was collected from...... the Skjern River catchment, Denmark. The presented applications focused on studying the isotopic 'input signal' to the hydrosphere in the form of precipitation, the isotopic 'output signal' with its related dynamic processes at a coastal saltwater-freshwater interface (groundwater isotopes) and the temporal...... development within a given lowland headwater catchment (stream water isotopes). Based on our investigations on the precipitation isotopic composition a local meteoric water line (LMWL) was constructed and expressed as: δ2H=7.4 δ18O + 5.36‰. Moreover, we showed that under maritime temperature climate influence...

Simple, rapid method for the preparation of isotopically labeled formaldehyde

Science.gov (United States)

Hooker, Jacob Matthew [Port Jefferson, NY; Schonberger, Matthias [Mains, DE; Schieferstein, Hanno [Aabergen, DE; Fowler, Joanna S [Bellport, NY

2011-10-04

Isotopically labeled formaldehyde (*C.sup..sctn.H.sub.2O) is prepared from labeled methyl iodide (*C.sup..sctn.H.sub.3I) by reaction with an oxygen nucleophile having a pendant leaving group. The mild and efficient reaction conditions result in good yields of *C.sup..sctn.H.sub.2O with little or no *C isotopic dilution. The simple, efficient production of .sup.11CH.sub.2O is described. The use of the .sup.11CH.sub.2O for the formation of positron emission tomography tracer compounds is described. The reaction can be incorporated into automated equipment available to radiochemistry laboratories. The isotopically labeled formaldehyde can be used in a variety of reactions to provide radiotracer compounds for imaging studies as well as for scintillation counting and autoradiography.

Analysis of stable isotope data to estimate vitamin A body stores

International Nuclear Information System (INIS)

2008-06-01

Vitamin A deficiency (VAD) is a serious public health problem in most developing countries. Because of the detrimental effects of vitamin A deficiency on human health, accurate assessment of vitamin A status is necessary to develop and evaluate intervention programmes. The IAEA is providing technical support to its Member States to use stable isotope dilution techniques to develop and evaluate programmes aimed at reducing vitamin A deficiency in populations. The stable isotope dilution technique, in contrast to other methods, have the potential to provide a quantitative estimate of vitamin A concentration across the continuum of status, from deficient to excess vitamin A body stores. In 2004 the IAEA, the United States Agency for International Development (USAID) and HarvestPlus initiated the Vitamin A Tracer Task Force, made up of international experts. HarvestPlus is a Global Challenge Program of the Consultative Group on International Agricultural Research (CGIAR). It is coordinated by the Centro Internacional de Agricultura Tropical (CIAT), a not-for-profit organization that conducts socially and environmentally progressive research aimed at reducing hunger and poverty and preserving natural resources in developing countries, located in Colombia, and the International Food Policy Research Institute (IFPRI), located in the United States of America and whose mission is to provide policy solutions aimed at reducing hunger and malnutrition in developing countries. The role of the Vitamin A Tracer Task Force was to prepare three complementary publications on the use of stable isotope dilution techniques to assess vitamin A body stores. The first publication entitled 'Appropriate Use of Vitamin A Tracer (Stable Isotope) Methodology' was published in 2004 by USAID/International Life Sciences Institute (ILSI) through the Micronutrient Global Leadership (MGL) project with co-sponsorship of IAEA and HarvestPlus. The second handbook is on 'Vitamin A Tracer Dilution

Stable isotopes applied as water tracers for infiltration experiment

International Nuclear Information System (INIS)

Liu Xiaoyan; Chen Jiansheng; Sun Xiaoxu; Su Zhiguo

2011-01-01

The δD and δ 18 O vertical profiles of soil water were measured prior to and after a rainfall event. Mechanisms of soil water movement were deciphered by comparing the soil water isotope profiles with the isotopic composition of precipitation. The results show that evaporation at the upper depth led to enrichment of the heavy isotopes. Compared to the loess profile, the shallow soil water of sand profile is relatively enriched in D and 18 O due to macro-pore and low water-holding capacity. The precipitation is infiltrated into soil in piston mode, accompanied with significant mixing of older soil water. The preferential fluid flow in loess was observed at depths of 0-20 cm, caused by cracks in the depths. The hydrogen and oxygen isotopic compositions in outflow are close to the precipitation, which shows a mixing of the precipitation and old soil water, and indicates that the isotopic composition of outflow water is mainly controlled by that of the precipitation. The δD and δ 18 O in outflow decreased with time until stable δ values of outflow are close to those of the precipitation. (authors)

Closing the gap between T-cell life span estimates from stable isotope-labeling studies in mice and humans

NARCIS (Netherlands)

Westera, Liset; Drylewicz, Julia; den Braber, Ineke; Mugwagwa, Tendai; van der Maas, Iris; Kwast, Lydia; Volman, Thomas; van de Weg-Schrijver, Elise H. R.; Bartha, István; Spierenburg, Gerrit; Gaiser, Koos; Ackermans, Mariëtte T.; Asquith, Becca; de Boer, Rob J.; Tesselaar, Kiki; Borghans, José A. M.

2013-01-01

Quantitative knowledge of the turnover of different leukocyte populations is a key to our understanding of immune function in health and disease. Much progress has been made thanks to the introduction of stable isotope labeling, the state-of-the-art technique for in vivo quantification of cellular

Stable isotope geochemistry : definitions, terminology, measurement and some applications

International Nuclear Information System (INIS)

Faure, K.

2014-01-01

In 1936, Alfred Nier produced the first precise measurement of isotope abundance ratios and his design still remains the basis of stable isotope mass spectrometry. With this gift from the physicists for routine measurement of isotope ratios, earth scientists began to explore the natural variations of isotopes. Thus began a new era in geoscience research with the hydrological cycle and marine palaeoclimatic research being the first topics to be investigated. Stable isotope measurements have been applied to many fundamental problems in geochemistry, petrology, and paleoclimatology, as well as related fields in archaeology, anthropology, physical chemistry, biology and forensic sciences. These applications can be broadly classified into four main types: 1. Thermometry: Formation temperatures of rock and mineral systems are determined on the basis of temperature-dependent fractionations of the isotopic ratios between two or more cogenetic phases. 2. Tracers: Reservoirs like the ocean, the mantle, meteoric waters and organic matter have distinct stable isotope signatures that can be used to trace the origin of rocks, fluids, contaminants etc. 3. Reaction mechanism: Distinctions can be made between diffusion and recrystallization, open and closed systems and bacterial and thermogenic processes. 4. Chemostratigraphy: Abrupt changes (excursions) in the stable isotope ratios of ocean sediments and certain terrestrial materials can be used as stratigraphic markers. (author)

Stable isotope geochemistry: definitions, terminology, measurement and some applications

International Nuclear Information System (INIS)

Faure, K.

2015-01-01

In 1936, Alfred Nier produced the first precise measurement of isotope abundance ratios and his design still remains the basis of stable isotope mass spectrometry. With this gift from the physicists for routine measurement of isotope ratios, earth scientists began to explore the natural variations of isotopes. Thus began a new era in geoscience research with the hydrological cycle and marine palaeoclimatic research being the first topics to be investigated. Stable isotope measurements have been applied to many fundamental problems in geochemistry, petrology, and paleoclimatology, as well as related fields in archaeology, anthropology, physical chemistry, biology and forensic sciences. These applications can be broadly classified into four main types: 1. Thermometry: Formation temperatures of rock and mineral systems are determined on the basis of temperature-dependent fractionations of the isotopic ratios between two or more cogenetic phases. 2. Tracers: Reservoirs like the ocean, the mantle, meteoric waters and organic matter have distinct stable isotope signatures that can be used to trace the origin of rocks, fluids, contaminants etc. 3. Reaction mechanism: Distinctions can be made between diffusion and recrystallization, open and closed systems and bacterial and thermogenic processes. 4. Chemostratigraphy: Abrupt changes (excursions) in the stable isotope ratios of ocean sediments and certain terrestrial materials can be used as stratigraphic markers. (author).

Stable isotope geochemistry : definitions, terminology, measurement and some applications

International Nuclear Information System (INIS)

Faure, K.

2016-01-01

In 1936, Alfred Nier produced the first precise measurement of isotope abundance ratios and his design still remains the basis of stable isotope mass spectrometry. With this gift from the physicists for routine measurement of isotope ratios, earth scientists began to explore the natural variations of isotopes. Thus began a new era in geoscience research with the hydrological cycle and marine palaeoclimatic research being the first topics to be investigated. Stable isotope measurements have been applied to many fundamental problems in geochemistry, petrology, and paleoclimatology, as well as related fields in archaeology, anthropology, physical chemistry, biology and forensic sciences. These applications can be broadly classified into four main types: 1. Thermometry: Formation temperatures of rock and mineral systems are determined on the basis of temperature-dependent fractionations of the isotopic ratios between two or more cogenetic phases. 2. Tracers: Reservoirs like the ocean, the mantle, meteoric waters and organic matter have distinct stable isotope signatures that can be used to trace the origin of rocks, fluids, contaminants etc. 3. Reaction mechanism: Distinctions can be made between diffusion and recrystallization, open and closed systems and bacterial and thermogenic processes. 4. Chemostratigraphy: Abrupt changes (excursions) in the stable isotope ratios of ocean sediments and certain terrestrial materials can be used as stratigraphic markers. (author).

Application of Stable Isotope-Assisted Metabolomics for Cell Metabolism Studies

Science.gov (United States)

You, Le; Zhang, Baichen; Tang, Yinjie J.

2014-01-01

The applications of stable isotopes in metabolomics have facilitated the study of cell metabolisms. Stable isotope-assisted metabolomics requires: (1) properly designed tracer experiments; (2) stringent sampling and quenching protocols to minimize isotopic alternations; (3) efficient metabolite separations; (4) high resolution mass spectrometry to resolve overlapping peaks and background noises; and (5) data analysis methods and databases to decipher isotopic clusters over a broad m/z range (mass-to-charge ratio). This paper overviews mass spectrometry based techniques for precise determination of metabolites and their isotopologues. It also discusses applications of isotopic approaches to track substrate utilization, identify unknown metabolites and their chemical formulas, measure metabolite concentrations, determine putative metabolic pathways, and investigate microbial community populations and their carbon assimilation patterns. In addition, 13C-metabolite fingerprinting and metabolic models can be integrated to quantify carbon fluxes (enzyme reaction rates). The fluxome, in combination with other “omics” analyses, may give systems-level insights into regulatory mechanisms underlying gene functions. More importantly, 13C-tracer experiments significantly improve the potential of low-resolution gas chromatography-mass spectrometry (GC-MS) for broad-scope metabolism studies. We foresee the isotope-assisted metabolomics to be an indispensable tool in industrial biotechnology, environmental microbiology, and medical research. PMID:24957020

Characterization and relative quantification of phospholipids based on methylation and stable isotopic labeling[S

Science.gov (United States)

Cai, Tanxi; Shu, Qingbo; Liu, Peibin; Niu, Lili; Guo, Xiaojing; Ding, Xiang; Xue, Peng; Xie, Zhensheng; Wang, Jifeng; Zhu, Nali; Wu, Peng; Niu, Lili; Yang, Fuquan

2016-01-01

Phospholipids (PLs), one of the lipid categories, are not only the primary building blocks of cellular membranes, but also can be split to produce products that function as second messengers in signal transduction and play a pivotal role in numerous cellular processes, including cell growth, survival, and motility. Here, we present an integrated novel method that combines a fast and robust TMS-diazomethane-based phosphate derivatization and isotopic labeling strategy, which enables simultaneous profiling and relative quantification of PLs from biological samples. Our results showed that phosphate methylation allows fast and sensitive identification of the six major PL classes, including their lysophospholipid counterparts, under positive ionization mode. The isotopic labeling of endogenous PLs was achieved by deuterated diazomethane, which was generated through acid-catalyzed hydrogen/deuterium (H/D) exchange and methanolysis of TMS-diazomethane during the process of phosphate derivatization. The measured H/D ratios of unlabeled and labeled PLs, which were mixed in known proportions, indicated that the isotopic labeling strategy is capable of providing relative quantitation with adequate accuracy, reproducibility, and a coefficient of variation of 9.1%, on average. This novel method offers unique advantages over existing approaches and presents a powerful tool for research of PL metabolism and signaling. PMID:26733148

Chloroformate derivatization for tracing the fate of Amino acids in cells and tissues by multiple stable isotope resolved metabolomics (mSIRM).

Science.gov (United States)

Yang, Ye; Fan, Teresa W-M; Lane, Andrew N; Higashi, Richard M

2017-07-11

Amino acids have crucial roles in central metabolism, both anabolic and catabolic. To elucidate these roles, steady-state concentrations of amino acids alone are insufficient, as each amino acid participates in multiple pathways and functions in a complex network, which can also be compartmentalized. Stable Isotope-Resolved Metabolomics (SIRM) is an approach that uses atom-resolved tracking of metabolites through biochemical transformations in cells, tissues, or whole organisms. Using different elemental stable isotopes to label multiple metabolite precursors makes it possible to resolve simultaneously the utilization of these precursors in a single experiment. Conversely, a single precursor labeled with two (or more) different elemental isotopes can trace the allocation of e.g. C and N atoms through the network. Such dual-label experiments however challenge the resolution of conventional mass spectrometers, which must distinguish the neutron mass differences among different elemental isotopes. This requires ultrahigh resolution Fourier transform mass spectrometry (UHR-FTMS). When combined with direct infusion nano-electrospray ion source (nano-ESI), UHR-FTMS can provide rapid, global, and quantitative analysis of all possible mass isotopologues of metabolites. Unfortunately, very low mass polar metabolites such as amino acids can be difficult to analyze by current models of UHR-FTMS, plus the high salt content present in typical cell or tissue polar extracts may cause unacceptable ion suppression for sources such as nano-ESI. Here we describe a modified method of ethyl chloroformate (ECF) derivatization of amino acids to enable rapid quantitative analysis of stable isotope labeled amino acids using nano-ESI UHR-FTMS. This method showed excellent linearity with quantifiable limits in the low nanomolar range represented in microgram quantities of biological specimens, which results in extracts with total analyte abundances in the low to sub-femtomole range. We have

Application of Stable Isotope Signatures in Food Traceability

International Nuclear Information System (INIS)

Nazaratul Ashifa Abdullah Salim; Roslanzairi Mostapha; Zainon Othman; Nor Afiqah Harun; Mohd Suhaimi Hamzah; Shamsiah Abdul Rahman; Md Suhaimi Elias; Salmah Moosa

2015-01-01

Stable isotope analysis has widely been used to trace the origin of organic materials in various fields, such as geochemistry, biochemistry, archaeology and petroleum. In past a decade, it has also become an important tool for food traceability study. The globalization of food markets and the relative ease with which food commodities are transported through and between countries and continents, means that consumers are increasingly concerned about the origin of the foods they eat. The natural abundance isotope variation such as carbon, nitrogen, hydrogen and oxygen are use as geographic tracers or marker to determine the geographic origin of fruits, crop, vegetables and food products from animal. The isotopic compositions of plant materials reflect various factors such as isotopic compositions of source materials and their assimilation processes as well as growth environments. This paper will discuss on stable carbon and nitrogen isotopic compositions in rice, advantages, limitations and potential of other analysis applications that can be incorporated in food traceability system. (author)

Validation of 13CO2 breath analysis as a measurement of demethylation of stable isotope labeled aminopyrine in man

International Nuclear Information System (INIS)

Schneider, J.F.; Schoeller, D.A.; Nemchausky, B.; Bayer, J.L.; Klein, P.

1978-01-01

Interval sampling of expired breath as a simple, non-invasive assessment of the effect of liver disease upon hepatic microsomal drug metabolism, has been demonstrated with [ 14 C] dimethylaminoantipyrine (aminopyrine). In order to eliminate radiation risk the authors have validated the use of aminopyrine labeled with the stable, non-radioactive isotope 13 C. Simultaneous oral administration of both [ 14 C]- and [ 13 C] aminopyrine to five adult subjects without liver disease as well as five patients with known liver disease, resulted in the excretion of label at nearly identical rates in both individual time collections (r=0.94) as well as cumulative excretion for three hours (r=0.97). An oral dose of 2-mg/kg of [ 13 C) aminopyrine resulted in rates of production of 13 CO 2 significantly greater than baseline variations in 13 CO 2 production in the fasting, resting subject. Measurements of a single peak value at one half hour correlated closely with the determination of cumulative appearance over three hours (r=0.96). A consistent reproducible increase in the peak production of 13 CO 2 was observed when five patients received phenobarbital. Stable isotope labeled aminopyrine may be used to detect the effects of disease and treatment upon hepatic N-demethylation activity in human subjects without incurring any risk from radiation. Furthermore, the availability of another isotopic carbon label should make possible the study of direct drug-drug interaction utilizing CO 2 analysis. (Auth.)

Isotopically labelled benzodiazepines

International Nuclear Information System (INIS)

Liebman, A.A.

1987-01-01

This paper reports on the benzodiazepines which are a class of therapeutic agents. Improvements in the analytical methodology in the areas of biochemistry and pharmacology were significant, particularly in the application of chromatographic and spectroscopic techniques. In addition, the discovery and subsequent development of tritium and carbon-14 as an analytical tool in the biological sciences were essentially post-world war II phenomena. Thus, as these new chemical entities were found to be biologically active, they could be prepared in labeled form for metabolic study, biological half-life determination (pharmacokinetics), tissue distribution study, etc. This use of tracer methodology has been liberally applied to the benzodiazepines and also more recently to the study of receptor-ligand interactions, in which tritium, carbon-11 or fluorine-18 isotopes have been used. The history of benzodiazepines as medicinal agents is indeed an interesting one; an integral part of that history is their use in just about every conceivable labeled form

iMS2Flux – a high–throughput processing tool for stable isotope labeled mass spectrometric data used for metabolic flux analysis

Directory of Open Access Journals (Sweden)

Poskar C Hart

2012-11-01

Full Text Available Abstract Background Metabolic flux analysis has become an established method in systems biology and functional genomics. The most common approach for determining intracellular metabolic fluxes is to utilize mass spectrometry in combination with stable isotope labeling experiments. However, before the mass spectrometric data can be used it has to be corrected for biases caused by naturally occurring stable isotopes, by the analytical technique(s employed, or by the biological sample itself. Finally the MS data and the labeling information it contains have to be assembled into a data format usable by flux analysis software (of which several dedicated packages exist. Currently the processing of mass spectrometric data is time-consuming and error-prone requiring peak by peak cut-and-paste analysis and manual curation. In order to facilitate high-throughput metabolic flux analysis, the automation of multiple steps in the analytical workflow is necessary. Results Here we describe iMS2Flux, software developed to automate, standardize and connect the data flow between mass spectrometric measurements and flux analysis programs. This tool streamlines the transfer of data from extraction via correction tools to 13C-Flux software by processing MS data from stable isotope labeling experiments. It allows the correction of large and heterogeneous MS datasets for the presence of naturally occurring stable isotopes, initial biomass and several mass spectrometry effects. Before and after data correction, several checks can be performed to ensure accurate data. The corrected data may be returned in a variety of formats including those used by metabolic flux analysis software such as 13CFLUX, OpenFLUX and 13CFLUX2. Conclusion iMS2Flux is a versatile, easy to use tool for the automated processing of mass spectrometric data containing isotope labeling information. It represents the core framework for a standardized workflow and data processing. Due to its flexibility

Contribution of stable isotopes to the study of pharmacokinetics of magnesium salts; Apport des isotopes stables a l'etude de la pharmacocinetique de sels de magnesium

Energy Technology Data Exchange (ETDEWEB)

Benech, H

1999-05-28

The use of stable isotopes as labels is becoming an attractive tool for the study of magnesium behavior in humans. It has been used two stable isotopes of magnesium, {sup 25}Mg and {sup 26}Mg, to measure the absolute bioavailability of a pharmaceutical form of magnesium. (N.C.)

Development of uniformly stable isotope labeling system in higher plants for hetero-nuclear NMR experiments in vitro and in vivo

International Nuclear Information System (INIS)

Kikuchi, J.

2005-01-01

Full text: Novel methods for measurement of living systems are making new breakthroughs in life science. In the era of the metabolome (analysis of all measurable metabolites), a MS-based approach is considered to be the major technology, whereas a NMR-based method is recognized as minor technology due to its low sensitivity. Therefore, my laboratory is currently focusing to develop novel methodologies for an NMR-based metabolomics. This will be achieved by uniform stable isotope labeling of higher plants allowing application of multi-dimensional NMR experiments used in protein structure determination. Using these novel methods, I will analyze the dynamic molecular networks inside tissues. Especially, use of stable isotope labeling methods has enormous advantage for discrimination of incorporated or de novo synthesized compounds. Furthermore, potentiality of in vivo-NMR metabolomics will be discussed in the conference. (author)

Stable isotopes

International Nuclear Information System (INIS)

Evans, D.K.

1986-01-01

Seventy-five percent of the world's stable isotope supply comes from one producer, Oak Ridge Nuclear Laboratory (ORNL) in the US. Canadian concern is that foreign needs will be met only after domestic needs, thus creating a shortage of stable isotopes in Canada. This article describes the present situation in Canada (availability and cost) of stable isotopes, the isotope enrichment techniques, and related research programs at Chalk River Nuclear Laboratories (CRNL)

Advisory group meeting on stable isotope labelled compounds in biomedical studies

International Nuclear Information System (INIS)

Vera Ruiz, H.; Parr, R.M.

1985-11-01

The programme of the meeting was restricted to topics involving applications of stable isotopes of the lighter elements (H, C, N, O). The current status of stable isotope techniques and applications in nutritional and biomedical studies, the applicability of these techniques in developing countries and the IAEA's future programmes on this topic were discussed

Stable isotope geochemistry : definitions, terminology, measurement and some applications

International Nuclear Information System (INIS)

Faure, K.

2009-01-01

In 1936, Alfred Nier produced the first precise measurement of isotope abundance ratios and his design still remains the basis of stable isotope mass spectrometry. With this gift from the physicists for routine measurement of isotope ratios, earth scientists began to explore the natural variations of isotopes. Thus began a new era in geoscience research with the hydrological cycle and marine palaeolimatic research being the first topics to be investigated. Stable isotope measurements have been applied to many fundamental problems in geochemistry, petrology, and paleoclimatology, as well as related fields in archaeology, anthropology, physical chemistry, biology and forensic sciences. These applications can be broadly classified into four main types: 1. Thermometry: Formation temperatures of rock and mineral systems are determined on the basis of temperature-dependent fractionations of the isotopic ratios between two or more cogenetic phases. 2. Tracers: Reservoirs like the ocean, the mantle, meteroic waters and organic matter have distinct stable isotope signatures that can be used to trace the origin of rocks, fluids, contaminants etc. 3. Reaction mechanism: Distinctions can be made between diffusion and recrystallization, open and closed systems and bacterial and thermogenic processes. 4. Chemostratigraphy: Abrupt changes (excursions) in the stable isotope ratios of ocean sediments and certain terrestrial materials can be used as stratigraphic markers. (author). 56 refs., 11 figs., 2 tabs.

Stable isotope geochemistry : definitions, terminology, measurement and some applications

International Nuclear Information System (INIS)

Faure, K.

2012-01-01

In 1936, Alfred Nier produced the first precise measurement of isotope abundance ratios and his design still remains the basis of stable isotope mass spectrometry. With this gift from the physicists for routine measurement of isotope ratios, earth scientists began to explore the natural variations of isotopes. Thus began a new era in geoscience research with the hydrological cycle and marine palaeoclimatic research being the first topics to be investigated. Stable isotope measurements have been applied to many fundamental problems in geochemistry, petrology, and paleoclimatology, as well as related fields in archaeology, anthropology, physical chemistry, biology and forensic sciences. These applications can be broadly classified into four main types: 1. Thermometry: Formation temperatures of rock and mineral systems are determined on the basis of temperature-dependent fractionations of the isotopic ratios between two or more cogenetic phases. 2. Tracers: Reservoirs like the ocean, the mantle, meteoric waters and organic matter have distinct stable isotope signatures that can be used to trace the origin of rocks, fluids, contaminants etc. 3. Reaction mechanism: Distinctions can be made between diffusion and recrystallization, open and closed systems and bacterial and thermogenic processes. 4. Chemostratigraphy: Abrupt changes (excursions) in the stable isotope ratios of ocean sediments and certain terrestrial materials can be used as stratigraphic markers. (author). 89 refs., 12 figs., 2 tabs.

Stable isotope geochemistry : definitions, terminology, measurement and some applications

International Nuclear Information System (INIS)

Faure, K.

2008-01-01

In 1936, Alfred Nier produced the first precise measurement of isotope abundance ratios and his design still remains the basis of stable isotope mass spectrometry. With this gift from the physicists for routine measurement of isotope ratios, earth scientists began to explore the natural variations of isotopes. Thus began a new era in geoscience research with the hydrological cycle and marine palaeolimatic research being the first topics to be investigated. Stable isotope measurements have been applied to many fundamental problems in geochemistry, petrology, and paleoclimatology, as well as related fields in archaeology, anthropology, physical chemistry, biology and forensic sciences. These applications can be broadly classified into four main types: 1. Thermometry: Formation temperatures of rock and mineral systems are determined on the basis of temperature-dependent fractionations of the isotopic ratios between two or more cogenetic phases. 2. Tracers: Reservoirs like the ocean, the mantle, meteroic waters and organic matter have distinct stable isotope signatures that can be used to trace the origin of rocks, fluids, contaminants etc. 3. Reaction mechanism: Distinctions can be made between diffusion and recrystallization, open and closed systems and bacterial and thermogenic processes. 4. Chemostratigraphy: Abrupt changes (excursions) in the stable isotope ratios of ocean sediments and certain terrestrial materials can be used as stratigraphic markers. (author). 56 refs., 11 figs., 2 tabs

Stable isotope geochemistry : definitions, terminology, measurement and some applications

International Nuclear Information System (INIS)

Faure, K.

2009-01-01

In 1936, Alfred Nier produced the first precise measurement of isotope abundance ratios and his design still remains the basis of stable isotope mass spectrometry. With this gift from the physicists for routine measurement of isotope ratios, earth scientists began to explore the natural variations of isotopes. Thus began a new era in geoscience research with the hydrological cycle and marine palaeolimatic research being the first topics to be investigated. Stable isotope measurements have been applied to many fundamental problems in geochemistry, petrology, and paleoclimatology, as well as related fields in archaeology, anthropology, physical chemistry, biology and forensic sciences. These applications can be broadly classified into four main types: 1. Thermometry: Formation temperatures of rock and mineral systems are determined on the basis of temperature-dependent fractionations of the isotopic ratios between two or more cogenetic phases. 2. Tracers: Reservoirs like the ocean, the mantle, meteroic waters and organic matter have distinct stable isotope signatures that can be used to trace the origin of rocks, fluids, contaminants etc. 3. Reaction mechanism: Distinctions can be made between diffusion and recrystallization, open and closed systems and bacterial and thermogenic processes. 4. Chemostratigraphy: Abrupt changes (excursions) in the stable isotope ratios of ocean sediments and certain terrestrial materials can be used as stratigraphic markers. (author). 56 refs., 11 figs., 2 tabs

Stable isotope geochemistry : definitions, terminology, measurement and some applications

International Nuclear Information System (INIS)

Faure, K.

2013-01-01

In 1936, Alfred Nier produced the first precise measurement of isotope abundance ratios and his design still remains the basis of stable isotope mass spectrometry. With this gift from the physicists for routine measurement of isotope ratios, earth scientists began to explore the natural variations of isotopes. Thus began a new era in geoscience research with the hydrological cycle and marine palaeoclimatic research being the first topics to be investigated. Stable isotope measurements have been applied to many fundamental problems in geochemistry, petrology, and paleoclimatology, as well as related fields in archaeology, anthropology, physical chemistry, biology and forensic sciences. These applications can be broadly classified into four main types: 1. Thermometry: Formation temperatures of rock and mineral systems are determined on the basis of temperature-dependent fractionations of the isotopic ratios between two or more cogenetic phases. 2. Tracers: Reservoirs like the ocean, the mantle, meteoric waters and organic matter have distinct stable isotope signatures that can be used to trace the origin of rocks, fluids, contaminants etc. 3. Reaction mechanism: Distinctions can be made between diffusion and recrystallization, open and closed systems and bacterial and thermogenic processes. 4. Chemostratigraphy: Abrupt changes (excursions) in the stable isotope ratios of ocean sediments and certain terrestrial materials can be used as stratigraphic markers. (author). 91 refs., 12 figs., 2 tabs.

Synthesis of isotopically modified ZnO nanoparticles and their potential as nanotoxicity tracers

International Nuclear Information System (INIS)

Dybowska, Agnieszka D.; Croteau, Marie-Noele; Misra, Superb K.; Berhanu, Deborah; Luoma, Samuel N.; Christian, Paul; O'Brien, Paul; Valsami-Jones, Eugenia

2011-01-01

Understanding the behavior of engineered nanoparticles in the environment and within organisms is perhaps the biggest obstacle to the safe development of nanotechnologies. Reliable tracing is a particular issue for nanoparticles such as ZnO, because Zn is an essential element and a common pollutant thus present at elevated background concentrations. We synthesized isotopically enriched (89.6%) with a rare isotope of Zn ( 67 Zn) ZnO nanoparticles and measured the uptake of 67 Zn by L. stagnalis exposed to diatoms amended with the particles. Stable isotope technique is sufficiently sensitive to determine the uptake of Zn at an exposure equivalent to lower concentration range ( -1 ). Without a tracer, detection of newly accumulated Zn is significant at Zn exposure concentration only above 5000 μg g -1 which represents some of the most contaminated Zn conditions. Only by using a tracer we can study Zn uptake at a range of environmentally realistic exposure conditions. - ZnO nanoparticles with distinct isotopic composition can be tailor synthesized to be used as tracers of environmental fate and uptake by organisms.

Methods of 15N tracer research in biological systems

International Nuclear Information System (INIS)

Hirschberg, K.; Faust, H.

1985-01-01

The application of the stable isotope 15 N is of increasing importance in different scientific disciplines, especially in medicine, agriculture, and the biosciences. The close correlation between the growing interest and improvements of analytical procedures resulted in remarkable advances in the 15 N tracer technique. On the basis of the latest results of 15 N tracer research in life sciences and agriculture methods of 15 N tracer research in biological systems are compiled. The 15 N methodology is considered under three headings: Chemical analysis with a description of methods of sample preparation (including different separation and isolation methods for N-containing substances of biological and agricultural origin) and special procedures converting ammonia to molecular nitrogen. Isotopic analysis with a review on the most important methods of isotopic analysis of nitrogen: mass spectrometry (including the GC-MS technique), emission spectrometry, NMR spectroscopy, and other analytical procedures. 15 N-tracer techniques with a consideration of the role of the isotope dilution analysis as well as different labelling techniques and the mathematical interpretation of tracer data (modelling, N turnover experiments). In these chapters also sources of errors in chemical and isotopic analysis, the accuracy of the different methods and its importance on tracer experiments are discussed. Procedures for micro scale 15 N analysis and aspects of 15 N analysis on the level of natural abundance are considered. Furthermore some remarks on isotope effects in 15 N tracer experiments are made. (author)

Contribution of stable isotopes to the study of pharmacokinetics of magnesium salts; Apport des isotopes stables a l'etude de la pharmacocinetique de sels de magnesium

Energy Technology Data Exchange (ETDEWEB)

Benech, H

1999-05-28

The use of stable isotopes as labels is becoming an attractive tool for the study of magnesium behavior in humans. It has been used two stable isotopes of magnesium, {sup 25}Mg and {sup 26}Mg, to measure the absolute bioavailability of a pharmaceutical form of magnesium. (N.C.)

Stable isotope geochemistry : definitions, terminology, measurement and some applications

International Nuclear Information System (INIS)

Faure, K.

2004-01-01

Stable isotope measurements have been applied to many fundamental problems in geochemistry, petrology, and paleoclimatology, as well as related fields in archaeology, anthropology, physical chemistry, biology and forensic sciences. These applications can be broadly classified into four main types: thermometry, tracers, reaction mechanisms and chemostratigraphy. 52 refs., 11 figs., 2 tabs

Isotopes as tracers of the oceanic circulation: Results from the World Ocean Circulation Experiment

International Nuclear Information System (INIS)

Schlosser, P.; Jenkins, W.J.; Key, R.; Lupton, J.

2002-01-01

During the past decades, natural and anthropogenic isotopes such as tritium ( 3 H), radiocarbon ( 14 C), 3 He, or the stable isotopes of water have been used in studies of the dynamics of natural systems. Early applications of tracers to studies of the ocean were directed at determination of circulation patterns and mean residence times of specific water masses, as well as estimates of mixing coefficients. These exploratory studies suggested that tracers can add significantly to our understanding of the oceanic circulation. In order to fully exploit this potential, the first global tracer study, the GEochemical Ocean SECtions Study (GEOSECS), was launched. From the GEOSECS results it was immediately apparent that very close coordination of tracer programs with physical oceanography studies is required for full utilization of tracer data. During the 1980s plans for the World OCean Experiment (WOCE) were developed. As part of its Hydrographic Program (WHP), especially during the one-time survey, a set of tracers were measured on a global scale with unprecedented spatial resolution (both lateral and vertical). The original plan included a larger number of tracers (CFCs, 3 H/ 3 He, 14 C, 39 Ar, stable isotopes of water, helium isotopes, 228 Ra, 90 Sr, 137 Cs, 85 Kr) than could actually be measured systematically (CFCs, 3 H/ 3 He, 14 C, H 2 18 O/H 2 16 O, helium isotopes). Nevertheless, the resulting data set, which presently is under evaluation, exceeds those obtained from pre-WOCE tracer studies by a wide margin. In this contribution, we describe the existing WOCE data set and demonstrate the type of results that can be expected from its interpretation on the basis of a few selected examples. These examples include: (1) the application of tritium and 3 He to studies of the ventilation of the upper waters in the Pacific Ocean, (2) the spreading of intermediate water in the Pacific and Indian oceans as derived from the distribution of 3 He, and (3) the evaluation of

Escherichia coli cell-free protein synthesis and isotope labeling of mammalian proteins.

Science.gov (United States)

Terada, Takaho; Yokoyama, Shigeyuki

2015-01-01

This chapter describes the cell-free protein synthesis method, using an Escherichia coli cell extract. This is a cost-effective method for milligram-scale protein production and is particularly useful for the production of mammalian proteins, protein complexes, and membrane proteins that are difficult to synthesize by recombinant expression methods, using E. coli and eukaryotic cells. By adjusting the conditions of the cell-free method, zinc-binding proteins, disulfide-bonded proteins, ligand-bound proteins, etc., may also be produced. Stable isotope labeling of proteins can be accomplished by the cell-free method, simply by using stable isotope-labeled amino acid(s) in the cell-free reaction. Moreover, the cell-free protein synthesis method facilitates the avoidance of stable isotope scrambling and dilution over the recombinant expression methods and is therefore advantageous for amino acid-selective stable isotope labeling. Site-specific stable isotope labeling is also possible with a tRNA molecule specific to the UAG codon. By the cell-free protein synthesis method, coupled transcription-translation is performed from a plasmid vector or a PCR-amplified DNA fragment encoding the protein. A milligram quantity of protein can be produced with a milliliter-scale reaction solution in the dialysis mode. More than a thousand solution structures have been determined by NMR spectroscopy for uniformly labeled samples of human and mouse functional domain proteins, produced by the cell-free method. Here, we describe the practical aspects of mammalian protein production by the cell-free method for NMR spectroscopy. © 2015 Elsevier Inc. All rights reserved.

Environmental Monitoring of Agro-Ecosystem Using Environmental Isotope Tracer Technology

International Nuclear Information System (INIS)

Chung, Byung Yeoup; Kim, Jae Sung; Cho, Jae Young

2004-10-01

This report has provided the counterparts the knowledge and skills on the use of environmental isotope tracer technology for obtaining valuable information on agricultural non-point pollution source in agro-ecosystem. The contamination from agricultural watersheds has been brought into attention as a potential contaminant of streams and tributaries, since majority of them caused water quality degradation, eutrophication of reservoir and negative effect on agro-environment. To prevent the contamination from these watersheds, it is necessary to find out the source of the contamination. However, accurate contaminants outflows from various types of non-point sources have not yet been elucidated due to the fact that the extent of non-point source contaminants related to uncontrollable climatic events and irrigation conditions may differ greatly from place to place and year to year. The dominant use of isotopes in environmental ecosystem research in the last few decades has been to trace sources of waters and solutes. The environmental isotope tracer technology using stable isotopes such as oxygen, hydrogen, carbon, nitrogen, and sulfur has extensively been used for tracing the fate of environmental pollutants and for identification of environmental pollutants sources in agro-ecosystems

Elucidation of oxidation and degradation products of oxygen containing fuel components by combined use of a stable isotopic tracer and mass spectrometry.

Science.gov (United States)

Frauscher, Marcella; Besser, Charlotte; Allmaier, Günter; Dörr, Nicole

2017-11-15

In order to reveal the degradation products of oxygen-containing fuel components, in particular fatty acid methyl esters, a novel approach was developed to characterize the oxidation behaviour. Combination of artificial alteration under pressurized oxygen atmosphere, a stable isotopic tracer, and gas chromatography electron impact mass spectrometry (GC-EI-MS) was used to obtain detailed information on the formation of oxidation products of (9Z), (12Z)-octadecadienoic acid methyl ester (C18:2 ME). Thereby, biodiesel simulating model compound C18:2 ME was oxidized in a rotating pressurized vessel standardized for lubricant oxidation tests (RPVOT), i.e., artificially altered, under 16 O 2 as well as 18 O 2 atmosphere. Identification of the formed degradation products, mainly carboxylic acids of various chain lengths, alcohols, ketones, and esters, was performed by means of GC-EI-MS. Comparison of mass spectra of compounds under both atmospheres revealed not only the degree of oxidation and the origin of oxygen atoms, but also the sites of oxidative attack and bond cleavage. Hence, the developed and outlined strategy based on a gas-phase stable isotopic tracer and mass spectrometry provides insight into the degradation of oxygen-containing fuels and fuel components by means of the accurate differentiation of oxygen origin in a degradation product. Copyright © 2017 Elsevier B.V. All rights reserved.

Reassessment of primed constant-infusion tracer method to measure urea kinetics

International Nuclear Information System (INIS)

Jahoor, F.; Wolfe, R.R.

1987-01-01

The validity of the primed constant-infusion tracer technique to make short-term measurements of urea production rates (R/sub a/) in humans in a physiological steady state and during disruption of steady state was evaluated. Four subjects received a primed constant infusion (P/I = 560 min) of [ 13 C]urea for 8 h. A plateau in urea enrichment was reached after 2 h and maintained throughout. When [ 13 C]- and [ 18 O]urea were simultaneously infused into four subjects at P/I ratios of 560:1 and 360:1, respectively, both tracers reached plateau enrichment at the same time (2-4 h). The enrichment at plateau was a function of the infusion rate rather than the priming dose, and calculated urea R/sub a/ was the same with either prime. In five additional experiments the technique responded acutely to a physiological perturbation (alanine infusion) in a dose-dependent manner. The results confirm that this technique is appropriate for short-term measurements of urea R/sub a/, and the requirement for accuracy in estimating the priming dose is not impractically stringent

Synthesis of stable isotopically labeled peptides with filter-assisted enzymatic labeling for the diagnosis of hepatitis B virus infection utilizing mass spectrometry-based proteomics strategy

International Nuclear Information System (INIS)

Tsai, Hsing-Fen; Hsiao, He-Hsuan

2017-01-01

A facile method for the preparation of stable isotopically labeled peptides was developed by means of filter-assisted tryptic "1"6O/"1"8O water labeling, which could be directly applied to the determination of hepatitis B virus infection from human serum with tandem mass spectrometry. Tryptic peptides of hepatitis B surface antigen or hepatitis B e antigen from different subtypes of hepatitis B virus were synthesized with traditional solid-phase peptide synthesis as potential biomarkers. Trypsin catalyzed oxygen-18 exchange at their amidated c-terminus of arginine or lysine residue. The protease catalyzed oxygen-18 to oxygen-16 back exchange reaction was eliminated due to the complete removal of trypsin by the centrifugal filter containing a thin membrane associated with molecular weight cut-off of 10 KDa. The synthetic isotopic peptides were spiked into trichloroacetic acid/acetone precipitated human serum as internal standards and were selectively detected with multiplexed parallel reaction monitoring on a hybrid quadrupole-orbitrap mass spectrometer. The limit of detection for all synthetic peptides were in the range of 0.09 fmol–1.13 fmol. The results indicated that the peptide YLWEWASVR derived from hepatitis B surface antigen was quantified approximately 200 fmol per μl serum and may serve as a diagnostic biomarker for the detection of hepatitis B virus infected disease. - Highlights: • Facile synthesis of an inexpensive and highly reproducible stable isotopically labeled peptides. • Complete incorporation of two "1"8O atoms into synthesized peptides with filter-assisted enzymatic labeling. • Targeted analysis with parallel reaction monitoring assay for the disease diagnosis.

Synthesis of stable isotopically labeled peptides with filter-assisted enzymatic labeling for the diagnosis of hepatitis B virus infection utilizing mass spectrometry-based proteomics strategy

Energy Technology Data Exchange (ETDEWEB)

Tsai, Hsing-Fen; Hsiao, He-Hsuan, E-mail: hhhsiao@dragon.nchu.edu.tw

2017-03-01

A facile method for the preparation of stable isotopically labeled peptides was developed by means of filter-assisted tryptic {sup 16}O/{sup 18}O water labeling, which could be directly applied to the determination of hepatitis B virus infection from human serum with tandem mass spectrometry. Tryptic peptides of hepatitis B surface antigen or hepatitis B e antigen from different subtypes of hepatitis B virus were synthesized with traditional solid-phase peptide synthesis as potential biomarkers. Trypsin catalyzed oxygen-18 exchange at their amidated c-terminus of arginine or lysine residue. The protease catalyzed oxygen-18 to oxygen-16 back exchange reaction was eliminated due to the complete removal of trypsin by the centrifugal filter containing a thin membrane associated with molecular weight cut-off of 10 KDa. The synthetic isotopic peptides were spiked into trichloroacetic acid/acetone precipitated human serum as internal standards and were selectively detected with multiplexed parallel reaction monitoring on a hybrid quadrupole-orbitrap mass spectrometer. The limit of detection for all synthetic peptides were in the range of 0.09 fmol–1.13 fmol. The results indicated that the peptide YLWEWASVR derived from hepatitis B surface antigen was quantified approximately 200 fmol per μl serum and may serve as a diagnostic biomarker for the detection of hepatitis B virus infected disease. - Highlights: • Facile synthesis of an inexpensive and highly reproducible stable isotopically labeled peptides. • Complete incorporation of two {sup 18}O atoms into synthesized peptides with filter-assisted enzymatic labeling. • Targeted analysis with parallel reaction monitoring assay for the disease diagnosis.

Contribution of stable isotopes to the study of pharmacokinetics of magnesium salts

International Nuclear Information System (INIS)

Benech, H.

1999-01-01

The use of stable isotopes as labels is becoming an attractive tool for the study of magnesium behavior in humans. It has been used two stable isotopes of magnesium, 25 Mg and 26 Mg, to measure the absolute bioavailability of a pharmaceutical form of magnesium. (N.C.)

Gluconeogenesis from labeled carbon: estimating isotope dilution

International Nuclear Information System (INIS)

Kelleher, J.K.

1986-01-01

To estimate the rate of gluconeogenesis from steady-state incorporation of labeled 3-carbon precursors into glucose, isotope dilution must be considered so that the rate of labeling of glucose can be quantitatively converted to the rate of gluconeogenesis. An expression for the value of this isotope dilution can be derived using mathematical techniques and a model of the tricarboxylic acid (TCA) cycle. The present investigation employs a more complex model than that used in previous studies. This model includes the following pathways that may affect the correction for isotope dilution: 1) flux of 3-carbon precursor to the oxaloacetate pool via acetyl-CoA and the TCA cycle; 2) flux of 4- or 5-carbon compounds into the TCA cycle; 3) reversible flux between oxaloacetate (OAA) and pyruvate and between OAA and fumarate; 4) incomplete equilibrium between OAA pools; and 5) isotope dilution of 3-carbon tracers between the experimentally measured pool and the precursor for the TCA-cycle OAA pool. Experimental tests are outlined which investigators can use to determine whether these pathways are significant in a specific steady-state system. The study indicated that flux through these five pathways can significantly affect the correction for isotope dilution. To correct for the effects of these pathways an alternative method for calculating isotope dilution is proposed using citrate to relate the specific activities of acetyl-CoA and OAA

Synthesis of isotopically modified ZnO nanoparticles and their potential as nanotoxicity tracers

Energy Technology Data Exchange (ETDEWEB)

Dybowska, Agnieszka D., E-mail: a.dybowska@nhm.ac.u [Department of Mineralogy, Natural History Museum London, Cromwell Road, London, SW7 5BD (United Kingdom); Croteau, Marie-Noele [U.S. Geological Survey, 345 Middlefield Road, MS 496, Menlo Park, CA 94025 (United States); Misra, Superb K.; Berhanu, Deborah [Department of Mineralogy, Natural History Museum London, Cromwell Road, London, SW7 5BD (United Kingdom); Luoma, Samuel N. [Department of Mineralogy, Natural History Museum London, Cromwell Road, London, SW7 5BD (United Kingdom); U.S. Geological Survey, 345 Middlefield Road, MS 496, Menlo Park, CA 94025 (United States); Christian, Paul; O' Brien, Paul [School of Chemistry, University of Manchester, M13 9PL, Manchester (United Kingdom); Valsami-Jones, Eugenia [Department of Mineralogy, Natural History Museum London, Cromwell Road, London, SW7 5BD (United Kingdom)

2011-01-15

Understanding the behavior of engineered nanoparticles in the environment and within organisms is perhaps the biggest obstacle to the safe development of nanotechnologies. Reliable tracing is a particular issue for nanoparticles such as ZnO, because Zn is an essential element and a common pollutant thus present at elevated background concentrations. We synthesized isotopically enriched (89.6%) with a rare isotope of Zn ({sup 67}Zn) ZnO nanoparticles and measured the uptake of {sup 67}Zn by L. stagnalis exposed to diatoms amended with the particles. Stable isotope technique is sufficiently sensitive to determine the uptake of Zn at an exposure equivalent to lower concentration range (<15 {mu}g g{sup -1}). Without a tracer, detection of newly accumulated Zn is significant at Zn exposure concentration only above 5000 {mu}g g{sup -1} which represents some of the most contaminated Zn conditions. Only by using a tracer we can study Zn uptake at a range of environmentally realistic exposure conditions. - ZnO nanoparticles with distinct isotopic composition can be tailor synthesized to be used as tracers of environmental fate and uptake by organisms.

Isotope ratios as pollutant source and behaviour indicators

International Nuclear Information System (INIS)

1975-01-01

Recent years have witnessed significant advances in isotope techniques for identifying origins and for studying the behaviour of trace contaminants and pollutants of the environment under actual existing environmental conditions. Improvements in the supply of stable isotopes and their labelled compounds, instrumental analysis and information on stable or radioactive isotopic ratios of existing environmental contaminants as a function of origin or behaviour have provided relatively new tools for the environmental scientist. While variations in natural or existing environmental stable and radioactive nuclides could be regarded as 'background noise' in conventional tracer experiments they promised unique information about sources and behaviour to those who listened carefully. (author)

Stable isotope ratio measurements in hydrogen, nitrogen, and oxygen using Raman scattering

International Nuclear Information System (INIS)

Harney, R.C.; Bloom, S.D.; Milanovich, F.P.

1975-01-01

A method for measuring stable isotope ratios using laser Raman scattering was developed which may prove of significant utility and benefit in stable isotope tracer studies. Crude isotope ratio measurements obtained with a low-power laser indicate that with current technology it should be possible to construct an isotope ratio measurement system using laser Raman scattering that is capable of performing 0.1 percent accuracy isotope ratio measurements of 16 O/ 18 O in natural abundance oxygen gas or 14 N/ 15 N in natural abundance nitrogen gas in times less than two minutes per sample. Theory pertinent to the technique, designs of specific isotope ratio spectrometer systems, and data relating to isotope ratio measurements in hydrogen, nitrogen, and oxygen are presented. In addition, the current status of several studies utilizing this technique is discussed. (auth)

Stable lead isotopes as a tracer in coastal waters

International Nuclear Information System (INIS)

Stukas, V.J.; Wong, C.S.

1981-01-01

The natural abundances of the stable isotopes of lead are used to identify natural and industrial sources of lead in the coastal waters of British Columbia, Canada. The 206 Pb/ 207 Pb ratios, used to characterize the lead source, had values of approx. 1.24 for coastal oceanic water, approx. 1.22 for fjord waters receiving lead from mine tailings, and approx. 1.163 for waters near urban centers. The lead concentration data are in agreement with presently accepted seawater values

Shifts in rotifer life history in response to stable isotope enrichment: testing theories of isotope effects on organismal growth

Science.gov (United States)

2017-01-01

In ecology, stable isotope labelling is commonly used for tracing material transfer in trophic interactions, nutrient budgets and biogeochemical processes. The main assumption in this approach is that the enrichment with a heavy isotope has no effect on the organism growth and metabolism. This assumption is, however, challenged by theoretical considerations and experimental studies on kinetic isotope effects in vivo. Here, I demonstrate profound changes in life histories of the rotifer Brachionus plicatilis fed 15N-enriched algae (0.4–5.0 at%); i.e. at the enrichment levels commonly used in ecological studies. These findings support theoretically predicted effects of heavy isotope enrichment on growth, metabolism and ageing in biological systems and underline the importance of accounting for such effects when using stable isotope labelling in experimental studies. PMID:28405367

Stable nuclide tracer studies and human amino acid requirements. A summary

International Nuclear Information System (INIS)

Young, V.R.

1994-01-01

The nutritional requirements for proteins have been estimated for various age groups. The current status of knowledge concerning the quantitative needs for specific indispensable amino acids was reviewed and it was concluded that, except for infants, current values for pre-school children, school age children and healthy adults are based on limited experimental data and/or on results from nitrogen balance determinations which are open to serious question regarding their nutritional significance. A review of 13 C-labelled tracer studies carried out in MIT laboratories was undertaken to demonstrate the applicability of stable nuclide tracer studies for purposes of determining the amino acid requirements of humans. 5 refs

Stable isotope labelling with amino acids in cell culture for human embryonic stem cell proteomic analysis

DEFF Research Database (Denmark)

Harkness, Linda; Prokhorova, Tatyana A; Kassem, Moustapha

2012-01-01

The identification and quantitative measurements of proteins in human embryonic stem cells (hESC) is a fast growing interdisciplinary area with an enormous impact on understanding the biology of hESC and the mechanism controlling self-renewal and differentiation. Using a quantitative mass...... spectroscopic method of stable isotope labelling with amino acids during cell culture (SILAC), we are able to analyse differential expression of proteins from different cellular compartments and to identify intracellular signalling pathways involved in self-renewal and differentiation. In this chapter, we...

Pharmacokinetics of lidocaine and bupivacaine and stable isotope labelled analogues : a study in healthy volunteers

NARCIS (Netherlands)

Burm, A.G.D.; de Boer, A G; van Kleef, J.W.; Vermeulen, N P; de Leede, L G; Spierdijk, J; Breimer, D D

1988-01-01

The pharmacokinetics of lidocaine and bupivacaine and tri-deuteromethyl-labelled lidocaine and bupivacaine were investigated in healthy volunteers. The deuterium-labelled and the unlabelled form of the drug to be investigated were simultaneously infused in 10 min. Plasma concentrations were

Modification degrees at specific sites on heparan sulphate: an approach to measure chemical modifications on biological molecules with stable isotope labelling

Science.gov (United States)

Wu, Zhengliang L.; Lech, Miroslaw

2005-01-01

Chemical modification of biological molecules is a general mechanism for cellular regulation. A quantitative approach has been developed to measure the extent of modification on HS (heparan sulphates). Sulphation on HS by sulphotransferases leads to variable sulphation levels, which allows cells to tune their affinities to various extracellular proteins, including growth factors. With stable isotope labelling and HPLC-coupled MS, modification degrees at various O-sulphation sites could be determined. A bovine kidney HS sample was first saturated in vitro with 34S by an OST (O-sulphotransferase), then digested with nitrous acid and analysed with HPLC-coupled MS. The 34S-labelled oligosaccharides were identified based on their unique isotope clusters. The modification degrees at the sulphotransferase recognition sites were obtained by calculating the intensities of isotopic peaks in the isotope clusters. The modification degrees at 3-OST-1 and 6-OST-1 sites were examined in detail. This approach can also be used to study other types of chemical modifications on biological molecules. PMID:15743272

Systematic NMR Analysis of Stable Isotope Labeled Metabolite Mixtures in Plant and Animal Systems: Coarse Grained Views of Metabolic Pathways

Science.gov (United States)

Chikayama, Eisuke; Suto, Michitaka; Nishihara, Takashi; Shinozaki, Kazuo; Hirayama, Takashi; Kikuchi, Jun

2008-01-01

Background Metabolic phenotyping has become an important ‘bird's-eye-view’ technology which can be applied to higher organisms, such as model plant and animal systems in the post-genomics and proteomics era. Although genotyping technology has expanded greatly over the past decade, metabolic phenotyping has languished due to the difficulty of ‘top-down’ chemical analyses. Here, we describe a systematic NMR methodology for stable isotope-labeling and analysis of metabolite mixtures in plant and animal systems. Methodology/Principal Findings The analysis method includes a stable isotope labeling technique for use in living organisms; a systematic method for simultaneously identifying a large number of metabolites by using a newly developed HSQC-based metabolite chemical shift database combined with heteronuclear multidimensional NMR spectroscopy; Principal Components Analysis; and a visualization method using a coarse-grained overview of the metabolic system. The database contains more than 1000 1H and 13C chemical shifts corresponding to 142 metabolites measured under identical physicochemical conditions. Using the stable isotope labeling technique in Arabidopsis T87 cultured cells and Bombyx mori, we systematically detected >450 HSQC peaks in each 13C-HSQC spectrum derived from model plant, Arabidopsis T87 cultured cells and the invertebrate animal model Bombyx mori. Furthermore, for the first time, efficient 13C labeling has allowed reliable signal assignment using analytical separation techniques such as 3D HCCH-COSY spectra in higher organism extracts. Conclusions/Significance Overall physiological changes could be detected and categorized in relation to a critical developmental phase change in B. mori by coarse-grained representations in which the organization of metabolic pathways related to a specific developmental phase was visualized on the basis of constituent changes of 56 identified metabolites. Based on the observed intensities of 13C atoms of

Insights from quantitative metaproteomics and protein-stable isotope probing into microbial ecology.

Science.gov (United States)

von Bergen, Martin; Jehmlich, Nico; Taubert, Martin; Vogt, Carsten; Bastida, Felipe; Herbst, Florian-Alexander; Schmidt, Frank; Richnow, Hans-Hermann; Seifert, Jana

2013-10-01

The recent development of metaproteomics has enabled the direct identification and quantification of expressed proteins from microbial communities in situ, without the need for microbial enrichment. This became possible by (1) significant increases in quality and quantity of metagenome data and by improvements of (2) accuracy and (3) sensitivity of modern mass spectrometers (MS). The identification of physiologically relevant enzymes can help to understand the role of specific species within a community or an ecological niche. Beside identification, relative and absolute quantitation is also crucial. We will review label-free and label-based methods of quantitation in MS-based proteome analysis and the contribution of quantitative proteome data to microbial ecology. Additionally, approaches of protein-based stable isotope probing (protein-SIP) for deciphering community structures are reviewed. Information on the species-specific metabolic activity can be obtained when substrates or nutrients are labeled with stable isotopes in a protein-SIP approach. The stable isotopes ((13)C, (15)N, (36)S) are incorporated into proteins and the rate of incorporation can be used for assessing the metabolic activity of the corresponding species. We will focus on the relevance of the metabolic and phylogenetic information retrieved with protein-SIP studies and for detecting and quantifying the carbon flux within microbial consortia. Furthermore, the combination of protein-SIP with established tools in microbial ecology such as other stable isotope probing techniques are discussed.

Progress in stable isotope analysis and new possibilities of clinical investigations

International Nuclear Information System (INIS)

Roth, E.

1989-01-01

The use of stable isotopes in medicine rests on three possibilities offered by labelling: identification of an element, a molecule, or a fragment of a molecule along its biological pathway; quantification of biological pools by isotopic dilution; measurement of metabolization rates, and more generally of clearances. Whenever a corporal function experiences a disregulation reflected either by changes in metabolic activity or modifications of the importance of pools of certain molecules, the possibility exists of making use of isotopes in diagnosis. Examples of practical applications of stable isotopes are given and analytical problems that had to be solved are underlined

Protein retention assessment of four levels of poultry by-product substitution of fishmeal in rainbow trout (Oncorhynchus mykiss) diets using stable isotopes of nitrogen (δ15N) as natural tracers.

Science.gov (United States)

Badillo, Daniel; Herzka, Sharon Z; Viana, Maria Teresa

2014-01-01

This is second part from an experiment where the nitrogen retention of poultry by-product meal (PBM) compared to fishmeal (FM) was evaluated using traditional indices. Here a quantitative method using stable isotope ratios of nitrogen (δ(15)N values) as natural tracers of nitrogen incorporation into fish biomass is assessed. Juvenile rainbow trout (Oncorhynchus mykiss) were fed for 80 days on isotopically distinct diets in which 0, 33, 66 and 100% of FM as main protein source was replaced by PBM. The diets were isonitrogenous, isolipidic and similar in gross energy content. Fish in all treatments reached isotopic equilibrium by the end of the experiment. Two-source isotope mixing models that incorporated the isotopic composition of FM and PBM as well as that of formulated feeds, empirically derived trophic discrimination factors and the isotopic composition of fish that had reached isotopic equilibrium to the diets were used to obtain a quantitative estimate of the retention of each source of nitrogen. Fish fed the diets with 33 and 66% replacement of FM by PBM retained poultry by-product meal roughly in proportion to its level of inclusion in the diets, whereas no differences were detected in the protein efficiency ratio. Coupled with the similar biomass gain of fishes fed the different diets, our results support the inclusion of PBM as replacement for fishmeal in aquaculture feeds. A re-feeding experiment in which all fish were fed a diet of 100% FM for 28 days indicated isotopic turnover occurred very fast, providing further support for the potential of isotopic ratios as tracers of the retention of specific protein sources into fish tissues. Stable isotope analysis is a useful tool for studies that seek to obtain quantitative estimates of the retention of different protein sources.

Synthesis of isotopically modified ZnO nanoparticles and their potential as nanotoxicity tracers.

Science.gov (United States)

Dybowska, Agnieszka D; Croteau, Marie-Noele; Misra, Superb K; Berhanu, Deborah; Luoma, Samuel N; Christian, Paul; O'Brien, Paul; Valsami-Jones, Eugenia

2011-01-01

Understanding the behavior of engineered nanoparticles in the environment and within organisms is perhaps the biggest obstacle to the safe development of nanotechnologies. Reliable tracing is a particular issue for nanoparticles such as ZnO, because Zn is an essential element and a common pollutant thus present at elevated background concentrations. We synthesized isotopically enriched (89.6%) with a rare isotope of Zn (67Zn) ZnO nanoparticles and measured the uptake of 67Zn by L. stagnalis exposed to diatoms amended with the particles. Stable isotope technique is sufficiently sensitive to determine the uptake of Zn at an exposure equivalent to lower concentration range (<15 μg g(-1)). Without a tracer, detection of newly accumulated Zn is significant at Zn exposure concentration only above 5000 μg g(-1) which represents some of the most contaminated Zn conditions. Only by using a tracer we can study Zn uptake at a range of environmentally realistic exposure conditions. Copyright © 2010 Elsevier Ltd. All rights reserved.

Synthesis of isotopically modified ZnO nanoparticles and their potential as nanotoxicity tracers

Science.gov (United States)

Dybowska, A.D.; Croteau, M.-N.; Misra, S.K.; Berhanu, D.; Luoma, S.N.; Christian, P.; O'Brien, P.; Valsami-Jones, E.

2011-01-01

Understanding the behavior of engineered nanoparticles in the environment and within organisms is perhaps the biggest obstacle to the safe development of nanotechnologies. Reliable tracing is a particular issue for nanoparticles such as ZnO, because Zn is an essential element and a common pollutant thus present at elevated background concentrations. We synthesized isotopically enriched (89.6%) with a rare isotope of Zn (67Zn) ZnO nanoparticles and measured the uptake of 67Zn by L. stagnalis exposed to diatoms amended with the particles. Stable isotope technique is sufficiently sensitive to determine the uptake of Zn at an exposure equivalent to lower concentration range (<15 ??g g-1). Without a tracer, detection of newly accumulated Zn is significant at Zn exposure concentration only above 5000 ??g g-1 which represents some of the most contaminated Zn conditions. Only by using a tracer we can study Zn uptake at a range of environmentally realistic exposure conditions. ?? 2010 Elsevier Ltd. All rights reserved.

Formation of Hydroxymethyl DNA Adducts in Rats Orally Exposed to Stable Isotope Labeled Methanol

Science.gov (United States)

Lu, Kun; Gul, Husamettin; Upton, Patricia B.; Moeller, Benjamin C.; Swenberg, James A.

2012-01-01

Methanol is a large volume industrial chemical and widely used solvent and fuel additive. Methanol’s well known toxicity and use in a wide spectrum of applications has raised long-standing environmental issues over its safety, including its carcinogenicity. Methanol has not been listed as a carcinogen by any regulatory agency; however, there are debates about its carcinogenic potential. Formaldehyde, a metabolite of methanol, has been proposed to be responsible for the carcinogenesis of methanol. Formaldehyde is a known carcinogen and actively targets DNA and protein, causing diverse DNA and protein damage. However, formaldehyde-induced DNA adducts arising from the metabolism of methanol have not been reported previously, largely due to the absence of suitable DNA biomarkers and the inability to differentiate what was due to methanol compared with the substantial background of endogenous formaldehyde. Recently, we developed a unique approach combining highly sensitive liquid chromatography-mass spectrometry methods and exposure to stable isotope labeled chemicals to simultaneously quantify formaldehyde-specific endogenous and exogenous DNA adducts. In this study, rats were exposed daily to 500 or 2000 mg/kg [13CD4]-methanol by gavage for 5 days. Our data demonstrate that labeled formaldehyde arising from [13CD4]-methanol induced hydroxymethyl DNA adducts in multiple tissues in a dose-dependent manner. The results also demonstrated that the number of exogenous DNA adducts was lower than the number of endogenous hydroxymethyl DNA adducts in all tissues of rats administered 500 mg/kg per day for 5 days, a lethal dose to humans, even after incorporating an average factor of 4 for reduced metabolism due to isotope effects of deuterium-labeled methanol into account. PMID:22157354

Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer.

Science.gov (United States)

Yang, Lijun; Kress, Benjamin T; Weber, Harris J; Thiyagarajan, Meenakshisundaram; Wang, Baozhi; Deane, Rashid; Benveniste, Helene; Iliff, Jeffrey J; Nedergaard, Maiken

2013-05-01

Neurodegenerative diseases such as Alzheimer's are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30-180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans.

Using stable isotopes of nitrogen and carbon to study seabird ecology: applications in the Mediterranean seabird community

Directory of Open Access Journals (Sweden)

Manuela G. Forero

2003-07-01

Full Text Available The application of the stable isotope technique to ecological studies is becoming increasingly widespread. In the case of seabirds, stable isotopes of nitrogen and carbon have been mainly used as dietary tracers. This approach relieson the fact that food web isotopic signatures are reflected in the tissues of the consumer. In addition to the study of trophic ecology, stable isotopes have been used to track the movement of seabirds across isotopic gradients, as individuals moving between isotopically distinct foodwebs can carry with them information on the location of previous feeding areas. Studies applying the stable isotope methodology to the study of seabird ecology show a clear evolution from broad and descriptive approaches to detailed and individual-based analyses. The purpose of this article is to show the different fields of application of stable isotopes to the study of the seabird ecology. Finally, we illustrate the utility of this technique by considering the particularities of the Mediterranean seabird community, suggesting different ecological questions and conservation problems that could be addressed by using the stable isotope approach in this community.

Mass spectrometric studies of stable isotope-labelled carboxylic acid derivatives

International Nuclear Information System (INIS)

Andersson, B.Aa.; Dinger, F.; Dinh-Nguyen, N.

1975-01-01

Low resolution mass spectra of deuterium and carbon-13 labelled fatty acid pyrrolidides are discussed. The simple fragmentation pattern of pyrrolidides makes them superior to other derivatives, regarding location of isotopes. Deuteriation of ethylenic fatty acid pyrrolidides therefore seems to be an improved method to locate carbon-carbon double bonds by mass spectrometry. (author)

Effect of Different Carbon Substrates on Nitrate Stable Isotope Fractionation During Microbial Denitrification

DEFF Research Database (Denmark)

Wunderlich, Anja; Meckenstock, Rainer; Einsiedl, Florian

2012-01-01

-labeled water and 18O-labeled nitrite were added to the microcosm experiments to study the effect of putative backward reactions of nitrite to nitrate on the stable isotope fractionation. We found no evidence for a reverse reaction. Significant variations of the stable isotope enrichment factor ε were observed......In batch experiments, we studied the isotope fractionation in N and O of dissolved nitrate during dentrification. Denitrifying strains Thauera aromatica and “Aromatoleum aromaticum strain EbN1” were grown under strictly anaerobic conditions with acetate, benzoate, and toluene as carbon sources. 18O...... of nitrate transport across the cell wall compared to the kinetics of the intracellular nitrate reduction step of microbial denitrification....

Stable isotope utilization for research on human nutrition

International Nuclear Information System (INIS)

Desjeux, J.F.

1994-01-01

In the framework of nutritional molecule metabolism research, this paper presents the various stable isotopes used as labels for biological molecules, the reasons for their application in human nutritional study (mainly because of their non toxicity) and the various analysis methods (isotope ratio mass spectrometry, coupled gaseous chromatography and mass spectrometry, nuclear magnetic resonance). Several application examples in nutrition research are then discussed: metabolic conversion measurement for a molecule into its different metabolites, energetic losses. 23 refs

Chlorine isotopes potential as geo-chemical tracers

Digital Repository Service at National Institute of Oceanography (India)

Shirodkar, P.V.; Pradhan, U.K.; Banerjee, R.

The potential of chlorine isotopes as tracers of geo-chemical processes of earth and the oceans is highlighted based on systematic studies carried out in understanding the chlorine isotope fractionation mechanism, its constancy in seawater and its...

Use of labeled compounds in tracer experiments

International Nuclear Information System (INIS)

Anon.

1991-01-01

The use of radiotracers in research has become common. This chapter looks at some of the underlying assumptions and advantages of labeled compounds: advantages of radiotracers; availability of suitable tracers and labeled compounds; purity of labeled compounds; autoradiolysis; storage of labeled compounds; detection systems for chromatography and electrophoretic methods. 14 refs., 2 figs

You are not always what we think you eat: selective assimilation across multiple whole-stream isotopic tracer studies

Science.gov (United States)

W. K. Dodds; S. M. Collins; S. K. Hamilton; J. L. Tank; S. Johnson; J. R. Webster; K. S. Simon; M. R. Whiles; H. M. Rantala; W. H. McDowell; S. D. Peterson; T. Riis; C. L. Crenshaw; S. A. Thomas; P. B. Kristensen; B. M. Cheever; A. S. Flecker; N. A. Griffiths; T. Crowl; E. J. Rosi-Marshall; R. El-Sabaawi; E. Martí

2014-01-01

Analyses of 21 15N stable isotope tracer experiments, designed to examine food web dynamics in streams around the world, indicated that the isotopic composition of food resources assimilated by primary consumers (mostly invertebrates) poorly reflected the presumed food sources. Modeling indicated that consumers assimilated only 33–50% of the N...

Synthesis of {sup 15}N isotope labeled alanine; Sintese da alanina enriquecida com {sup 15}N

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Claudineia R. de; Bendassolli, Jose Albertino; Sant' Ana, Carlos Roberto; Tagliassachi, Romulo Barbieri; Maximo, Everaldo; Prestes, Clelber Vieira [Centro de Energia Nuclear na Agricultura (CENA), Piracicaba, SP (Brazil). Dept. de Isotopos Estaveis]. E-mail: crolivei@cena.usp.br

2005-07-01

The application of light chemical elements and their stable isotopes in biological studies have been increased over the last years. The use of {sup 15}N labeled amino acids is an important tool for elucidation of peptides structures. This paper describe a method for the synthesis of {sup 15}N isotope labeled alanine at lower costs than international ones, as well as the details of the recovery system of the nitrogen residues. In the present work an amination of {alpha}-haloacids, with the bromopropionic carboxylic acid and labeled aqua ammonia ({sup 15}NH{sub 3} aq) was carried out. In order to avoid eventually losses of {sup 15}NH{sub 3}, special cares were adopted, since the production cost is high. Although the acquisition cost of the {sup 13}N (radioactive) labeled compounds is lower, the obtained stable tracer will allow the accomplishment of important studies of the nitrogen cycling in living things, less occupational and environment hazards, and the time limitation problems in field studies. The tests took place in triplicates with NH{sub 3} (aq) being employed. With the establishment of the system for {sup 15}NH{sub 3} recovery, an average of 94 % of the ammonia employed in the synthesis process was recovered. The purity of the amino acid was state determined by TLC (Thin Layer Chromatography) and HPLC (High-Performance Liquid Chromatography) with a fluorescence detector. The Rf and the retention time of the synthesized sample were similar the sigma standard. Finally, regarding the established conditions, it was possible to obtain the alanine with a production cost about 40 % lower than the international price. (author)

Stable isotope N-phosphoryl amino acids labeling for quantitative profiling of amine-containing metabolites using liquid chromatography mass spectrometry.

Science.gov (United States)

Zhang, Shanshan; Shi, Jinwen; Shan, Changkai; Huang, Chengting; Wu, Yile; Ding, Rong; Xue, Yuhua; Liu, Wen; Zhou, Qiang; Zhao, Yufen; Xu, Pengxiang; Gao, Xiang

2017-07-25

Stable isotope chemical labeling liquid chromatography-mass spectrometry (LC-MS) is a powerful strategy for comprehensive metabolomics profiling, which can improve metabolites coverage and quantitative information for exploration of metabolic regulation in complex biological systems. In the current work, a novel stable isotope N-phosphoryl amino acids labeling strategy (SIPAL) has been successful developed for quantitative profiling of amine-containing metabolites in urine based on organic phosphorus chemistry. Two isotopic reagents, 16 O 2 - and 18 O 2 -N-diisopropyl phosphoryl l-alanine N-hydroxysuccinimide esters ( 16 O/ 18 O-DIPP-L-Ala-NHS), were firstly synthesized in high yields for labeling the amine-containing metabolites. The performance of SIPAL strategy was tested by analyzing standard samples including 20 l-amino acids, 10 d-amino acids and small peptides by using LC-MS. We observed highly efficient and selective labeling for SIPAL strategy within 15 min in a one-pot derivatization reaction under aqueous reaction conditions. The introduction of a neutral phosphate group at N-terminus can increase the proton affinity and overall hydrophobicity of targeted metabolites, leading to the better ionization efficiency in electrospray ionization processes and chromatographic separations of hydrophilic metabolites on reversed-phase column. Furthermore, the chiral metabolites, such as d-amino acids, could be converted to diastereomers after SIPAL and successfully separated on regular reversed-phase column. The chirality of labeled enantiomers can be determined by using different detection methods such as 31 P NMR, UV, and MS, demonstrating the potential application of SIPAL strategy. In addition, absolute quantification of chiral metabolites in biological samples can be easily achieved by using SIPAL strategy. For this purpose, urine samples collected from a healthy volunteer were analyzed by using LC-ESI-Orbitrap MS. Over 300 pairs of different amine

Isotopic and geochemical tracers for fingerprinting process-affected waters in the oil sands industry: a pilot study

Energy Technology Data Exchange (ETDEWEB)

Gibson, J.J.; Birks, S.J.; Moncur, M.; Yi, Y.; Tattrie, K.; Jasechko, S.; Richardson, K.; Eby, P. [Alberta Innovates - Technology Futures (Canada)

2011-04-15

During 2009 and 2010, Alberta Innovates - Technology Futures carried out a pilot study for Alberta Environment to examine the possibility of labeling process affected water from oil sands operations with isotropic and geochemical tracers. For the study, 3 oil sands operators furnished logistical support and personnel, 39 samples were gathered and several isotope tracers were measured. In addition, geotechnical analyses were performed and the presence of organic compounds in the samples was scanned using Fourier transform ion cyclotron resonance mass spectrometry. Results showed that the selected tracers were able to label water sources in some locations, however they cannot be used as a universal method and a case by case approach needs to be adopted. This study pointed out that Fourier transform ion cyclotron resonance mass spectrometry is the best way to construct a dataset for use in identification of process affected waters.

Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) Applied to Quantitative Proteomics of Bacillus subtilis

DEFF Research Database (Denmark)

Soufi, Boumediene; Kumar, C.; Gnad, F.

2010-01-01

We applied stable isotope labeling by amino acids in cell culture (SILAC) to large-scale quantitative proteomics analyses of the model bacterium Bacillus subtilis in two physiological conditions: growth on succinate and growth under phosphate starvation. Using a B. subtilis strain auxotrophic...... of the most comprehensive quantitative proteomics studies in bacteria, covering more than 75% of the B. subtilis genes expressed in the log phase of growth. Furthermore, we detect and quantify dynamics of 35 Ser/Thr/Tyr phosphorylation sites under growth on succinate, and 10 phosphorylation sites under...

Conceptualisation of Snowpack Isotope Dynamics in Spatially Distributed Tracer-Aided Runoff Models in Snow Influenced Northern Cathments

Science.gov (United States)

Ala-aho, P. O. A.; Tetzlaff, D.; Laudon, H.; McNamara, J. P.; Soulsby, C.

2016-12-01

We use the Spatially distributed Tracer-Aided Rainfall-Runoff (STARR) modelling framework to explore non-stationary flow and isotope response in three northern headwater catchments. The model simulates dynamic, spatially variable tracer concentration in different water stores and fluxes within a catchment, which can constrain internal catchment mixing processes, flow paths and associated water ages. To date, a major limitation in using such models in snow-dominated catchments has been the difficulties in paramaterising the isotopic transformations in snowpack accumulation and melt. We use high quality long term datasets for hydrometrics and stable water isotopes collected in three northern study catchments for model calibration and testing. The three catchments exhibit different hydroclimatic conditions, soil and vegetation types, and topographic relief, which brings about variable degree of snow dominance across the catchments. To account for the snow influence we develop novel formulations to estimate the isotope evolution in the snowpack and melt. Algorithms for the isotopic evolution parameterize an isotopic offset between snow evaporation and melt fluxes and the remaining snow storage. The model for each catchment is calibrated to match both streamflow and tracer concentration at the stream outlet to ensure internal consistency of the system behaviour. The model is able to reproduce the streamflow along with the spatio-temporal differences in tracer concentrations across the three studies catchments reasonably well. Incorporating the spatially distributed snowmelt processes and associated isotope transformations proved essential in capturing the stream tracer reponse for strongly snow-influenced cathments. This provides a transferrable tool which can be used to understand spatio-temporal variability of mixing and water ages for different storages and flow paths in other snow influenced, environments.

You are not always what we think you eat. Selective assimilation across multiple whole-stream isotopic tracer studies

International Nuclear Information System (INIS)

Dodds, W. K.; Collins, S. M.; Hamilton, S. K.; Johnson, S.; Webster, J. R.; Simon, K. S.; Whiles, M. R.; Rantala, H. M.; McDowell, W. H.; Peterson, S. D.; Riis, T.; Crenshaw, C. L.; Thomas, S. A.; Kristensen, P. B.; Cheever, B. M.; Flecker, A. S.; Griffiths, N. A.; Crowl, T.; Rosi-Marshall, E. J.; El-Sabaawi, R.; Marti, E.

2014-01-01

Analyses of 21 15 N stable isotope tracer experiments, designed to examine food web dynamics in streams around the world, indicated that the isotopic composition of food resources assimilated by primary consumers (mostly invertebrates) poorly reflected the presumed food sources. Modeling indicated that consumers assimilated only 33-50% of the N available in sampled food sources such as decomposing leaves, epilithon, and fine particulate detritus over feeding periods of weeks or more. Thus, common methods of sampling food sources consumed by animals in streams do not sufficiently reflect the pool of N they assimilate. Lastly, Isotope tracer studies, combined with modeling and food separation techniques, can improve estimation of N pools in food sources that are assimilated by consumers

New insights to the use of ethanol in automotive fuels: a stable isotopic tracer for fossil- and bio-fuel combustion inputs to the atmosphere.

Science.gov (United States)

Giebel, Brian M; Swart, Peter K; Riemer, Daniel D

2011-08-01

Ethanol is currently receiving increased attention because of its use as a biofuel or fuel additive and because of its influence on air quality. We used stable isotopic ratio measurements of (13)C/(12)C in ethanol emitted from vehicles and a small group of tropical plants to establish ethanol's δ(13)C end-member signatures. Ethanol emitted in exhaust is distinctly different from that emitted by tropical plants and can serve as a unique stable isotopic tracer for transportation-related inputs to the atmosphere. Ethanol's unique isotopic signature in fuel is related to corn, a C4 plant and the primary source of ethanol in the U.S. We estimated a kinetic isotope effect (KIE) for ethanol's oxidative loss in the atmosphere and used previous assumptions with respect to the fractionation that may occur during wet and dry deposition. A small number of interpretive model calculations were used for source apportionment of ethanol and to understand the associated effects resulting from atmospheric removal. The models incorporated our end-member signatures and ambient measurements of ethanol, known or estimated source strengths and removal magnitudes, and estimated KIEs associated with atmospheric removal processes for ethanol. We compared transportation-related ethanol signatures to those from biogenic sources and used a set of ambient measurements to apportion each source contribution in Miami, Florida-a moderately polluted, but well ventilated urban location.

Stable sulfur and oxygen isotopes as geochemical tracers of sulfate in karst waters

Science.gov (United States)

Sun, Jing; Kobayashi, Tatsuaki; Strosnider, William H. J.; Wu, Pan

2017-08-01

Karst water resources, which are extremely sensitive to mining activities, are critical for the support of human societies and ecological systems in many regions worldwide. In order to determine the sources and fate of dissolved sulfate in low-pH karst waters, hydrochemical variations of karst waters with and without acid mine drainage (AMD) impacts were investigated along with stable isotope dynamics. As expected, hydrochemical characteristics and isotopic compositions of the AMD and AMD-downstream water (ADW) were dramatically different from that of the non-AMD-impacted water (NAW). The sources of sulfur isotopes in sulfate were predominantly pyrite oxidation for the AMD and ADW, and atmospheric deposition for the NAW. Based on the general isotope-balance model, the relative proportions of sulfate oxygen derived from water and air were calculated. The mean proportion of sulfate oxygen derived from water in ADW was roughly double that of AMD. This suggests that the sulfate associated with AMD is predominantly influenced by aerobic pyrite oxidation, while that of ADW is likely affected by the dissolution of pyrite under anaerobic conditions in reservoir sediment. This observation was coincident with the noted variations of hydrochemical characteristics and was supported by principal component analysis. These results provide a better understanding of how stable isotopes of sulfate and water can be used to track mining contamination in karst aquifers, which could benefit remediation planning for these distinctive systems.

Reliable LC-MS quantitative glycomics using iGlycoMab stable isotope labeled glycans as internal standards.

Science.gov (United States)

Zhou, Shiyue; Tello, Nadia; Harvey, Alex; Boyes, Barry; Orlando, Ron; Mechref, Yehia

2016-06-01

Glycans have numerous functions in various biological processes and participate in the progress of diseases. Reliable quantitative glycomic profiling techniques could contribute to the understanding of the biological functions of glycans, and lead to the discovery of potential glycan biomarkers for diseases. Although LC-MS is a powerful analytical tool for quantitative glycomics, the variation of ionization efficiency and MS intensity bias are influencing quantitation reliability. Internal standards can be utilized for glycomic quantitation by MS-based methods to reduce variability. In this study, we used stable isotope labeled IgG2b monoclonal antibody, iGlycoMab, as an internal standard to reduce potential for errors and to reduce variabililty due to sample digestion, derivatization, and fluctuation of nanoESI efficiency in the LC-MS analysis of permethylated N-glycans released from model glycoproteins, human blood serum, and breast cancer cell line. We observed an unanticipated degradation of isotope labeled glycans, tracked a source of such degradation, and optimized a sample preparation protocol to minimize degradation of the internal standard glycans. All results indicated the effectiveness of using iGlycoMab to minimize errors originating from sample handling and instruments. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry

International Nuclear Information System (INIS)

Esteban, N.V.; Loughlin, T.; Yergey, A.L.; Zawadzki, J.K.; Booth, J.D.; Winterer, J.C.; Loriaux, D.L.

1991-01-01

Growth retardation as well as the development of Cushingoid features in adrenally insufficient patients treated with the currently accepted replacement dose of cortisol (33-41 mumol/day.m2; 12-15 mg/m2.day) prompted us to reevaluate the cortisol production rate (FPR) in normal subjects and patients with Cushing's syndrome, using a recently developed thermospray liquid chromatography-mass spectrometry method. The stable isotope [9,12,12-2H3]cortisol was infused continuously for 31 h at about 5% of the anticipated FPR. Blood samples were obtained at 20-min intervals for 24 h, spun, and pooled in 4-h groups. Tracer dilution in plasma was determined by liquid chromatography/mass spectrometry. The method was validated with controlled infusions in 6 patients with adrenal insufficiency. Results from 12 normal volunteers revealed a FPR of 27.3 +/- 7.5 mumol/day (9.9 +/- 2.7 mg/day) or 15.7 mumol/day.m2; 5.7 mg/m2. day. A previously unreported circadian variation in FPR was observed. Patients with Cushing's syndrome demonstrated unequivocal elevation of FPR and cortisol concentration correlated during each sample period in normal volunteers, indicating that cortisol secretion, rather than metabolism, is mainly responsible for changes in plasma cortisol. Our data suggest that the FPR in normal subjects may be lower than previously believed

Measurement of protein digestibility in humans by a dual-tracer method.

Science.gov (United States)

Devi, Sarita; Varkey, Aneesia; Sheshshayee, M S; Preston, Thomas; Kurpad, Anura V

2018-06-01

Recent evaluations of the risk of dietary protein deficiency have indicated that protein digestibility may be a key limiting factor in the provision of indispensable amino acids (IAAs), particularly for vulnerable populations living in challenging environments where intestinal dysfunction may exist. Since the digestion of protein occurs only in the small intestine, and the metabolic activity of colonic bacteria confounds measurements at the fecal level, there is a need to develop noninvasive protein digestibility measurements at the ileal level. We used a dual-tracer method with stable isotopes to characterize the digestibility of uniformly labeled [13C]-spirulina protein as a standard protein, in comparison to a mixture of 2H-labeled crystalline amino acids, and then demonstrated the use of this standard protein to measure the digestibility of selected legumes (chick pea and mung bean) through the use of proteins that were intrinsically labeled with 2H. The digestibility of uniformly labeled [13C]-spirulina was first measured in 6 healthy volunteers (3 males and 3 females) by feeding it along with a standard mixture of 2H-labeled amino acids, in a dual-tracer, plateau-fed test meal approach. Next, intrinsically labeled legume protein digestibility was studied with a similar dual-tracer approach, with uniformly labeled [13C]-spirulina as the standard, when processed differently before consumption. The average digestibility of IAA in spirulina protein was 85.2%. The average IAA digestibility of intrinsically 2H-labeled chick pea and mung bean protein was 56.6% and 57.7%, respectively. Dehulling of mung bean before ingestion increased the average IAA digestibility by 9.9% in comparison to whole mung bean digestibility. An innovative, minimally invasive "dual-stable-isotope" method was developed to measure protein digestibility, in which the ingestion of an intrinsically 2H-labeled test protein along with a 13C-labeled standard protein of known digestibility allows

Water stable isotopes: application to the water cycle and climate variations study

International Nuclear Information System (INIS)

Risi, C.

2009-12-01

The stable isotopic composition of water (H 2 16 , HDO, H 2 18 , H 2 17 ) is a promising tracer of the present day water cycle and past climates. While the isotopic composition recorded in polar ice core have long been used to reconstruct past temperatures, however, what controls the isotopic composition of the tropical precipitation is more complex. The goal of this thesis is thus to better understand the processes that affect the isotopic composition of tropical precipitation and atmospheric water, more particularly in the tropics. Since most of the tropical precipitation arises from atmospheric convection, and most isotopic archives are on land, we focus more particularly on the impact of convective and land surface processes. In turn, what can be learned about convection and land surface processes using isotopic measurements? Can they help constrain their representation in models? At the inter-annual to climate change scale, what information about the tropical climate variability is recorded in isotopic signals observed in archives? First, we investigate the influence of convection on water stable isotopes. We use both (1) numerical modeling, with a hierarchy of models (single column model, two-dimensional model of squall lines, general circulation model) and (2) data analysis, using isotopic data from rain collected in the Sahel during the African Monsoon Multidisciplinary Analysis campaign, at the event and intra-event scales. These studies highlight the strong impact of convection on the precipitation composition, and stress the importance of rain evaporation and convective or meso-scale subsidence in controlling the rain isotopic composition. Convection also plays an important role on isotopic profiles in the upper troposphere-lower stratosphere. Second, we study what information about climatic variability is recorded by water stable isotopes in precipitation. We analyze simulations of present day and past climates with LMDZ, and evaluate to what extent

Sci-Fri AM: Imaging - 09: Serial estimation of cross-talk for correction in dual-isotope imaging with dynamic tracers.

Science.gov (United States)

Wells, R G; Lockwood, J; Wei, L; Duan, D; Fernando, P; Bensimon, C; Ruddy, T D

2012-07-01

The recent radioisotope shortage has led to interest in non-Tc99m-based tracers. We have developed a novel I-123-labelled myocardial perfusion imaging tracer. We compare the I123-tracer to the clinical standard of Tc99m tetrofosmin in vivo in a rat model using a small-animal SPECT/CT camera. SPECT distinguishes different isotopes based on the different energies of the emitted gamma rays and thus allows simultaneous comparison of two tracer distributions in the same animal. Dual-isotope imaging is complicated by cross-talk between the energy windows of the isotopes. Standard energy-window-based correction methods are difficult to employ because of the proximity in energy of Tc99m (140keV) and I123 (159keV). Imaging the second tracer's energy window prior to its injection provides an estimate of the cross-talk. However, this estimate is only accurate if the tracer distribution is static. We use serial imaging prior to the introduction of the second tracer to estimate the dynamics of the first tracer and interpolate the cross-talk images to provide a more accurate correction. We used rat models of myocardial disease (n=3). I123 tracer was injected and imaged for one hour at 20min intervals. The Tc99m tetrofosmin was then injected and 30min later, a dual-isotope image was obtained. The impact of this approach is assessed by comparing the differences in the Tc99m-tetrofosmin image using this method with correction by simple correction for physical decay. The interpolative approach improves the accuracy of the correction by 2%-5% and thereby enhances the comparison of the two tracers. © 2012 American Association of Physicists in Medicine.

Glucose tracer, kinetics and turnover in monkeys and chickens infused with ethanol, 1,3-butanediol, or fructose

International Nuclear Information System (INIS)

Armstrong, M.K.

1985-01-01

Mixtures of (2- 3 H) and (U- 14 C) glucose were injected as single doses into fasted cynomolgus monkeys to assess glucose tracer kinetics and obtain rates of turnover. Data were treated by stochastic and compartmental analyses and results from both analyses closely agreed. However, (2- 3 H) data analyzed by the compartmental analysis required three pools to fit the glucose disappearance curve while (6- 3 H) data fit a two or three pool model equally well. Turnover rates averaged 4.9-4.0, and 3.0 mg/min x kg -1 body weight with (2- 3 H), 6- 3 H) and (U- 14 C) glucose tracers, respectively. The data heuristically suggest that the slow turnover pool that was necessary to fit (2- 3 H) glucose data is related to isotope discrimination. The effects of four treatment solutions on (6- 3 H) glucose metabolism in monkeys were examined. The solutions and their rates of infusion (umoles/min x kg -1 ) were: (1) ethanol, 110; (2) 1,3-butanediol, 110; (3) fructose, 30; and (4) ethanol pus fructose, 110 and 30, respectively. The glucose clearance rate was lowest during the ethanol plus fructose infusions. Ethanol infusions (222 or 444 umoles/min x kg -1 body weight) in chickens (1500 g) fasted 64 hours did not cause hypoglycemia although the high dose slightly decreased the rate of glucose turnover 15% (14.0 versus 12.0 mg/min x kg -1 ). It was further found that neither the hepatic cytosolic nor the mitochondrial redox state significantly changed in chickens infused with the high dose of ethanol. The unchanged hepatic metabolite ratios in chickens are consistent with their unusual resistance to ethanol-induced hypoglycemia

Lipolytic response to glucose infusion in human subjects

International Nuclear Information System (INIS)

Wolfe, R.R.; Peters, E.J.

1987-01-01

The authors have determined the effect of various rates of glucose infusion on the rates of release of glycerol (R/sub a/ glycerol), free fatty acids (R/sub a/ FFA), and on energy metabolism in normal human volunteers. Plasma kinetics were determined with use of the stable isotopic tracers D-5-glycerol and [1- 13 C]palmitate, and energy metabolism was determined by indirect calorimetry. The effect of glucose infusion on R/sub a/ glycerol and R/sub a/ FFA was dose-dependent. At 4 mg x kg -1 x min -1 , both R/sub a/ glycerol and R/sub a/ FFA were suppressed; at 8 mg x kg -1 x min -1 , R/sub a/ FFA was even more depressed, but R/sub a/ glycerol was similar to the value during the 4 mg x kg -1 x min -1 infusion. At all infusion rates tested, the amount of potential energy available from the sum of the glucose infusion and endogenously mobilized fat was always greater than when no glucose was infused. Glucose decreased fat mobilization by both inhibiting lipolysis and stimulating reesterification, thus causing a significant increase in triglyceride-fatty acid substrate cycling within the adipose tissue. Plasma insulin was determined by radioimmunoassay

Applications of stable isotopes

International Nuclear Information System (INIS)

Letolle, R.; Mariotti, A.; Bariac, T.

1991-06-01

This report reviews the historical background and the properties of stable isotopes, the methods used for their measurement (mass spectrometry and others), the present technics for isotope enrichment and separation, and at last the various present and foreseeable application (in nuclear energy, physical and chemical research, materials industry and research; tracing in industrial, medical and agronomical tests; the use of natural isotope variations for environmental studies, agronomy, natural resources appraising: water, minerals, energy). Some new possibilities in the use of stable isotope are offered. A last chapter gives the present state and forecast development of stable isotope uses in France and Europe

Evaluation of stable isotope labelling strategies for the quantitation of CP4 EPSPS in genetically modified soya

Energy Technology Data Exchange (ETDEWEB)

Ocana, Mireia Fernandez [Centre for Chemical and Bioanalytical Sciences, Royal Holloway, University of London, Egham TW20 0EX (United Kingdom)], E-mail: Mireia.FernandezOcana@pfizer.com; Fraser, Paul D. [Centre for Chemical and Bioanalytical Sciences, Royal Holloway, University of London, Egham TW20 0EX (United Kingdom); Patel, Raj K.P.; Halket, John M. [Specialist Bioanalytical Services Ltd., Royal Holloway, University of London, Egham TW20 0EX (United Kingdom); Bramley, Peter M. [Centre for Chemical and Bioanalytical Sciences, Royal Holloway, University of London, Egham TW20 0EX (United Kingdom)

2009-02-16

The introduction of genetically modified (GM) crops into the market has raised a general alertness relating to the control and safety of foods. The applicability of protein separation hyphenated to mass spectrometry to identify the bacterial enolpyruvylshikimate-3-phosphate synthase (CP4 EPSPS) protein expressed in GM crops has been previously reported [M.F. Ocana, P.D. Fraser, R.K.P. Patel, J.M. Halket, P.M. Bramley, Rapid Commun. Mass Spectrom. 21 (2007) 319.]. Herein, we investigate the suitability of two strategies that employ heavy stable isotopes, i.e. AQUA and iTRAQ, to quantify different levels of CP4 EPSPS in up to four GM preparations. Both quantification strategies showed potential to determine whether the presence of GM material is above the limits established by the European Union. The AQUA quantification procedure involved protein solubilisation/fractionation and subsequent separation using SDS-PAGE. A segment of the gel in which the protein of interest was located was excised, the stable isotope labeled peptide added at a known concentration and proteolytic digestion initiated. Following recovery of the peptides, on-line separation and detection using LC-MS was carried out. A similar approach was used for the iTRAQ workflow with the exception that proteins were digested in solution and generated tryptic peptides were chemically tagged. Both procedures demonstrated the potential for quantitative detection at 0.5% (w/w) GM soya which is a level below the current European Union's threshold for food-labelling. In this context, a comparison between the two procedures is provided within the present study.

Evaluation of stable isotope labelling strategies for the quantitation of CP4 EPSPS in genetically modified soya

International Nuclear Information System (INIS)

Ocana, Mireia Fernandez; Fraser, Paul D.; Patel, Raj K.P.; Halket, John M.; Bramley, Peter M.

2009-01-01

The introduction of genetically modified (GM) crops into the market has raised a general alertness relating to the control and safety of foods. The applicability of protein separation hyphenated to mass spectrometry to identify the bacterial enolpyruvylshikimate-3-phosphate synthase (CP4 EPSPS) protein expressed in GM crops has been previously reported [M.F. Ocana, P.D. Fraser, R.K.P. Patel, J.M. Halket, P.M. Bramley, Rapid Commun. Mass Spectrom. 21 (2007) 319.]. Herein, we investigate the suitability of two strategies that employ heavy stable isotopes, i.e. AQUA and iTRAQ, to quantify different levels of CP4 EPSPS in up to four GM preparations. Both quantification strategies showed potential to determine whether the presence of GM material is above the limits established by the European Union. The AQUA quantification procedure involved protein solubilisation/fractionation and subsequent separation using SDS-PAGE. A segment of the gel in which the protein of interest was located was excised, the stable isotope labeled peptide added at a known concentration and proteolytic digestion initiated. Following recovery of the peptides, on-line separation and detection using LC-MS was carried out. A similar approach was used for the iTRAQ workflow with the exception that proteins were digested in solution and generated tryptic peptides were chemically tagged. Both procedures demonstrated the potential for quantitative detection at 0.5% (w/w) GM soya which is a level below the current European Union's threshold for food-labelling. In this context, a comparison between the two procedures is provided within the present study

Stable isotope composition of environmental water and food products as a tracer of origin

International Nuclear Information System (INIS)

Wierzchnicki, R.; Owczarczyk, A.; Soltyk, W.

2004-01-01

The paper is the review of Institute of Nuclear Chemistry and Technology (INCT) activity in application of stable isotope ratios (especially D/H and 18 O/ 16 O) for environmental studies and food origin control. INCT has at disposal since 1998, a high class instrument - Isotope Ratio Mass Spectrometer, Delta Plus, Finnigan MAT, Germany - suitable to perform such measurements. (author)

Statistical dynamic imaging of RI-labeled tracer from list-mode PET data

International Nuclear Information System (INIS)

Tanimoto, Michiaki; Kuroda, Yoshihiro; Oshiro, Osamu; Watabe, Hiroshi; Kuroda, Tomohiro

2009-01-01

Positron emission tomography (PET) can be used in physiological analysis to illustrate physiological states by visualizing the accumulation of radioisotope (RI)-labeled tracer in specific organs or tissues. PET obtains spatio-temporal statistics in the form of list-mode data. However, conventional imaging techniques, which sum up list-mode data over a given time period, cannot depict detailed temporal dynamics of the RI-labeled tracer. In this study, a spatio-temporal analysis approach was employed to visualize the temporal flow dynamics of RI-labeled tracer from the obtained list-mode data. Experiments to assess the visualization of simulated RI-labeled tracer dynamics as well as RI-labeled tracer dynamics in a vascular phantom showed that the proposed method successfully depicted detailed temporal flow dynamics that could not be visualized using conventional methods. (author)

Optimal sample to tracer ratio for isotope dilution mass spectrometry: the polyisotopic case

International Nuclear Information System (INIS)

Laszlo, G.; Ridder, P. de; Goldman, A.; Cappis, J.; Bievre, P. de

1991-01-01

The Isotope Dilution Mass Spectrometry (IDMS) measurement technique provides a means for determining the unknown amount of various isotopes of an element in a sample solution of known mass. The sample solution is mixed with an auxiliary solution, or tracer, containing a known amount of the same element having the same isotopes but of different relative abundances or isotopic composition and the induced change in the isotopic composition measured by isotope mass spectrometry. The technique involves the measurement of the abundance ratio of each isotope to a (same) reference isotope in the sample solution, in the tracer solution and in the blend of the sample and tracer solution. These isotope ratio measurements, the known element amount in the tracer and the known mass of sample solution are used to calculate the unknown amount of one isotope in the sample solution. Subsequently the unknown amount of element is determined. The purpose of this paper is to examine the optimization of the ratio of the estimated unknown amount of element in the sample solution to the known amount of element in the tracer solution in order to minimize the relative uncertainty in the determination of the unknown amount of element

Stable isotopes. Enriched wheat: a new chance for nutrition research

International Nuclear Information System (INIS)

Chagvardieff, P.

1996-01-01

The Department of Plant Eco-physiology (DEV) from the CEA/Life Sciences Department of Cadarache (France) has artificially produced two kg of carbon 13 labelled wheat for nutrition research. It is the first successful stable isotope labelling of complex nutriments with a 10% enrichment in carbon 13. This wheat has been used for the manufacturing of pastas to follow the assimilation of nutrients by the organism. This short paper gives some details about the experimental procedure of labelled wheat cultivation. (J.S.)

Labelled compounds for agrochemical residue studies in developing countries

International Nuclear Information System (INIS)

1977-01-01

Potential applications of stable and radioactive isotopic tracers for assessing undesirable contaminants in agriculture, fisheries and food are discussed as related to developing countries. Sources and types of residues are considered, and their local implications; also, the availability of suitably labelled compounds, including possible international cooperation to facilitate more centralized and economic preparation, and the distribution of labelled intermediates and compounds for use by local scientists. The provision of training courses and their syllabus are reviewed. Experience in the Joint FAO/IAEA chemical residue and pollution programme has indicated a need for longer-lived radioisotopically labelled pesticides (insecticides, acaricides, fungicides, herbicides, fumigants, etc.) for studying their behaviour. 15 N-, 13 C- or 2 H-labelled fertilizers and fertilizer additives such as nitrification inhibitors will shortly be needed, for studying the behaviour of fertilizer nitrogen residues, and their regulation and conservation, under conditions prevailing in the developing countries. Compounds labelled with stable isotopes are considered particularly valuable under field conditions. The report reviews the present situation and presents specific recommendations to the Directors General of FAO and IAEA

Stable isotopes in human nutrition research. Final report on an IAEA co-ordinated research programme, Vienna, Austria, 1993

International Nuclear Information System (INIS)

1993-01-01

The Co-ordinated Research Programme (CRP) on Applications of Stable Isotope Tracers in Human Nutrition Research was established by the Agency in October 1988 and was completed in 1992. At various times during this period the CRP encompassed 16 participants in 16 countries. Its general objective was to help establish competence in the use of stable isotope techniques, particularly in developing countries, and particularly with reference to applications of 2 H, 13 C, 15 N, and 18 O in human nutrition research. Thereby it was hoped that it would be possible (i) to identify centres and scientists throughout the developing world who could use stable isotopes in human nutrition research, (ii) to assess the need for methodological adaptations for isotope-based methods in developing countries, and (iii) to advance the competence of the participants in using stable isotopes as tracers of human metabolism. In addition it was expected that the CRP would make a study of some major questions which have been identified by international groups of nutrition experts, particularly in areas relating to energy and protein metabolism. This document comprises copies of the working papers submitted by all CRP participants who contributed a final report on their project. These reports include details of the rationale, methods, results and interpretations from each of the respective studies. Refs, figs and tabs

The Oxygen Isotopic Composition of Phosphate: A Tracer for Phosphate Sources and Cycling

Energy Technology Data Exchange (ETDEWEB)

Mclaughlin, K. [Southern California Coastal Water Research Project, Costa Mesa, University of California, CA (United States); Young, M. B.; Paytan, A.; Kendall, C. [U.S. Geological Survey, University of California, CA (United States)

2013-05-15

Phosphorus (P) is a limiting macro-nutrient for primary productivity and anthropogenic P-loading to aquatic ecosystems is one of the leading causes of eutrophication in many ecosystems throughout the world. Because P has only one stable isotope, traditional isotope techniques are not possible for tracing sources and cycling of P in aquatic systems. However, much of the P in nature is bonded to four oxygen (O) atoms as orthophosphate (PO{sub 4}{sup 3-}). The P-O bonds in orthophosphate are strongly resistant to inorganic hydrolysis and do not exchange oxygen with water without biological mediation (enzyme-mediated recycling). Thus, the oxygen isotopic composition of dissolved inorganic phosphate ({delta}{sup 18}O{sub p}) may be used as a tracer for phosphate sources and cycling in aquatic ecosystems. Recently, several studies have been conducted utilizing {delta}{sup 18}O{sub p} as a tracer for phosphate sources and cycling in various aquatic environments. Specifically, work to date indicates that {delta}{sup 18}O{sub p} is useful for determining sources of phosphate to aquatic systems if these sources have unique isotopic signatures and phosphate cycling within the system is limited compared to input fluxes. In addition, because various processes imprint specific fractionation effects, the {delta}{sup 18}O{sub p} tracer can be utilized to determine the degree of phosphorous cycling and processing through the biomass. This chapter reviews several of these studies and discusses the potential to utilize the {delta}{sup 18}O{sub p} of phosphate in rivers and streams. (author)

Production of isotopically labeled heterologous proteins in non-E. coli prokaryotic and eukaryotic cells

International Nuclear Information System (INIS)

Takahashi, Hideo; Shimada, Ichio

2010-01-01

The preparation of stable isotope-labeled proteins is necessary for the application of a wide variety of NMR methods, to study the structures and dynamics of proteins and protein complexes. The E. coli expression system is generally used for the production of isotope-labeled proteins, because of the advantages of ease of handling, rapid growth, high-level protein production, and low cost for isotope-labeling. However, many eukaryotic proteins are not functionally expressed in E. coli, due to problems related to disulfide bond formation, post-translational modifications, and folding. In such cases, other expression systems are required for producing proteins for biomolecular NMR analyses. In this paper, we review the recent advances in expression systems for isotopically labeled heterologous proteins, utilizing non-E. coli prokaryotic and eukaryotic cells.

Stable isotope tracer marking of individual boll weevils

International Nuclear Information System (INIS)

James, W.D.; Showler, A.T.; Armstrong, J.S.; Westbrook, J.K.

2006-01-01

Stable isotope markers have been used to study animal nutrition for several decades and more recently to study the foraging and cultural habits of imported fire ants. In this work, we have extended that effort to evaluate the potential for marking boll weevils, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae), with the rare earth element samarium to aid in studies of insect invasion and pest eradication protocols. Neutron activation analysis (NAA) was performed on the marked boll weevils as well as plant material from the cotton squares on which the insects were fed. Samarium levels in non-dosed insects average about 20 ng/g or about 100 pg total element per insect. Our computed average determination limit was 36 pg samarium/weevil. The determination limit for cotton plant squares and leaves averaged 3.5 ng/g and 8.2 ng/g, respectively. These initial results indicate the NAA method is capable of identifying individual marked insects which have assimilated 1 ng of samarium, a ten-fold increase in content over average blank values. (author)

Stable isotope studies

International Nuclear Information System (INIS)

Ishida, T.

1992-01-01

The research has been in four general areas: (1) correlation of isotope effects with molecular forces and molecular structures, (2) correlation of zero-point energy and its isotope effects with molecular structure and molecular forces, (3) vapor pressure isotope effects, and (4) fractionation of stable isotopes. 73 refs, 38 figs, 29 tabs

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

Science.gov (United States)

Rhew, R. C.

2011-12-01

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

Proceedings of the atmospheric tracers and tracer application workshop

International Nuclear Information System (INIS)

Barr, S.; Gedayloo, T.

1979-12-01

In addition to presentations by participating members a general discussion was held in order to summarize and outline the goals and objectives of the workshop. A number of new low level background tracers such as heavy methanes, perfluorocarbons, multiply labeled isotopes such as 13 C 18 O 2 , helium 3, in addition to sample collection techniques and analytical methods for various tracers were discussed. This report is a summary of discussions and papers presented at this workshop

Simultaneous determination of the intravenous and oral pharmacokinetic parameters of D,L-verapamil using stable isotope-labelled verapamil.

Science.gov (United States)

Eichelbaum, M; Somogyi, A; von Unruh, G E; Dengler, H J

1981-01-01

Following i.v. administration, the plasma concentration-time curve of verapamil could best be described by either a mono- or biexponential equation. Total plasma clearance (1.26 1/min) approached liver blood flow (1.51/min), so it can be concluded that its clearance is liver blood flow-dependent. Although absorption was almost complete after oral administration, absolute bioavailability (20%) was low, due to extensive hepatic first-pass metabolism. The approach using stable isotope-labelled and unlabelled drug permits simultaneous administration by the intravascular and extravascular routes, thus allowing determination of absolute bioavailability in a single experiment.

Intra-arterial and intraportal infusion liver scintigraphy using 99mTc-labeled colloid

International Nuclear Information System (INIS)

Inoue, Yusuke; Ohtake, Tohru; Momose, Toshimitsu; Watanabe, Toshiaki; Kosaka, Noboru; Nishikawa, Jun-ichi; Sasaki, Yasuhito; Sawada, Toshio; Muto, Tetsuichiro

1991-01-01

Intra-arterial infusion liver scintigraphy was performed in 11 patients with primary or metastatic liver tumor. and intraportal infusion liver scintigraphy was performed in 6 patients for prophylaxis of liver metastasis from colorectal cancer. 99m Tc-Sn colloid or 99m Tc-phytate was administered through the catheter of which tip was placed in the portal vein or the hepatic artery, and then liver image was obtained. When 99m Tc-phytate was infused intra-arterially, significant amount of the infused tracer passed through the liver and we could not get sufficient information to assess the distribution of drug administered through the catheter. On the other hand, intraportal infusion liver scintigraphy using 99m Tc-Sn colloid or 99m Tc-phytate and intra-arterial infusion liver scintigraphy using 99m Tc-Sn colloid revealed heterogenity of liver uptake, tracer uptake in spleen, low uptake area corresponding to the liver tumor and high uptake area around it. The findings will be clinically useful, and these methods are thought to be helpful to confirm the satisfactory drug distribution. (author)

Isotopes as tracers in a contaminated fractured chalk aquitard

Science.gov (United States)

Nativ, R.; Adar, E.

2003-04-01

Clusters of industrial plants often generate contaminant plumes with several potential sources. Prevention of further pollution and designing suitable remedial measures require identification of the contributing source among all potential ones and the sorting of currently active sources from historical ones. In the study area, an industrial complex in the Negev desert, Israel, the lateral spread of groundwater contamination combined with water level patterns and the location of wastewater storage lagoons and treatment facilities posed a serious monitoring problem. Because (1) wastewater from all plants was mixed through a central wastewater pipeline and spread in various ways and means throughout the site, and (2) a groundwater mounding area was formed upgradient of the site, the contribution of potentially contaminating individual downgradient facilities could not be inferred using site-specific contaminants and/or the increased hydraulic head. Stable isotopes of oxygen, hydrogen and sulfur, as well as tritium, proved to be an efficient monitoring tool. Isotopic characterization of the two end members, namely, the natural, uncontaminated groundwater in off-site wells, and the industrial wastewater, provided the criteria for constraining a contaminating source when several alternative sources appeared viable. The isotopic fractionation of oxygen and hydrogen isotopes could be tied to the various disposal phases of the industrial wastewater. The presented case studies illustrate the important role of isotopes as tracers at contaminated sites.

Using isotopes to constrain water flux and age estimates in snow-influenced catchments using the STARR (Spatially distributed Tracer-Aided Rainfall–Runoff model

Directory of Open Access Journals (Sweden)

P. Ala-aho

2017-10-01

Full Text Available Tracer-aided hydrological models are increasingly used to reveal fundamentals of runoff generation processes and water travel times in catchments. Modelling studies integrating stable water isotopes as tracers are mostly based in temperate and warm climates, leaving catchments with strong snow influences underrepresented in the literature. Such catchments are challenging, as the isotopic tracer signals in water entering the catchments as snowmelt are typically distorted from incoming precipitation due to fractionation processes in seasonal snowpack. We used the Spatially distributed Tracer-Aided Rainfall–Runoff (STARR model to simulate fluxes, storage, and mixing of water and tracers, as well as estimating water ages in three long-term experimental catchments with varying degrees of snow influence and contrasting landscape characteristics. In the context of northern catchments the sites have exceptionally long and rich data sets of hydrometric data and – most importantly – stable water isotopes for both rain and snow conditions. To adapt the STARR model for sites with strong snow influence, we used a novel parsimonious calculation scheme that takes into account the isotopic fractionation through snow sublimation and snowmelt. The modified STARR setup simulated the streamflows, isotope ratios, and snow pack dynamics quite well in all three catchments. From this, our simulations indicated contrasting median water ages and water age distributions between catchments brought about mainly by differences in topography and soil characteristics. However, the variable degree of snow influence in catchments also had a major influence on the stream hydrograph, storage dynamics, and water age distributions, which was captured by the model. Our study suggested that snow sublimation fractionation processes can be important to include in tracer-aided modelling for catchments with seasonal snowpack, while the influence of fractionation during snowmelt

Mercury and stable isotopes (δ15N and δ13C as tracers during the ontogeny of Trichiurus lepturus

Directory of Open Access Journals (Sweden)

Ana Paula Madeira Di Beneditto

Full Text Available This study applies total mercury (THg concentration and stable isotope signature (δ15N and δ13C to evaluate the trophic status and feeding ground of Trichiurus lepturus during its ontogeny in northern Rio de Janeiro, south-eastern Brazil. The trophic position of T. lepturus is detected well by THg and δ15N as the sub-adult planktivorous specimens are distinct from the adult carnivorous specimens. The δ13C signatures suggest a feeding ground associated with marine coastal waters that are shared by fish in different ontogenetic phases. The diet tracers indicated that the fish feeding habits do not vary along seasons of the year, probably reflecting the prey availability in the study area. This fish has economic importance and the concentration of THg was compared to World Health Organization limit, showing that the adult specimens of T. lepturus are very close to the tolerable limit for safe regular ingestion.

Classification-based quantitative analysis of stable isotope labeling by amino acids in cell culture (SILAC) data.

Science.gov (United States)

Kim, Seongho; Carruthers, Nicholas; Lee, Joohyoung; Chinni, Sreenivasa; Stemmer, Paul

2016-12-01

Stable isotope labeling by amino acids in cell culture (SILAC) is a practical and powerful approach for quantitative proteomic analysis. A key advantage of SILAC is the ability to simultaneously detect the isotopically labeled peptides in a single instrument run and so guarantee relative quantitation for a large number of peptides without introducing any variation caused by separate experiment. However, there are a few approaches available to assessing protein ratios and none of the existing algorithms pays considerable attention to the proteins having only one peptide hit. We introduce new quantitative approaches to dealing with SILAC protein-level summary using classification-based methodologies, such as Gaussian mixture models with EM algorithms and its Bayesian approach as well as K-means clustering. In addition, a new approach is developed using Gaussian mixture model and a stochastic, metaheuristic global optimization algorithm, particle swarm optimization (PSO), to avoid either a premature convergence or being stuck in a local optimum. Our simulation studies show that the newly developed PSO-based method performs the best among others in terms of F1 score and the proposed methods further demonstrate the ability of detecting potential markers through real SILAC experimental data. No matter how many peptide hits the protein has, the developed approach can be applicable, rescuing many proteins doomed to removal. Furthermore, no additional correction for multiple comparisons is necessary for the developed methods, enabling direct interpretation of the analysis outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Investigating Unsaturated Zone Travel Times with Tritium and Stable Isotopes

Science.gov (United States)

Visser, A.; Thaw, M.; Van der Velde, Y.

2017-12-01

Travel times in the unsaturated zone are notoriously difficult to assess. Travel time tracers relying on the conservative transport of dissolved (noble) gases (tritium-helium, CFCs or SF6) are not applicable. Large water volume requirements of other cosmogenic radioactive isotopes (sulfur-35, sodium-22) preclude application in the unsaturated zone. Prior investigations have relied on models, introduced tracers, profiles of stable isotopes or tritium, or a combination of these techniques. Significant unsaturated zone travel times (UZTT) complicate the interpretation of stream water travel time tracers by ranked StorAge Selection (rSAS) functions. Close examination of rSAS functions in a sloping soil lysimeter[1] show the effect of the UZTT on the shape of the rSAS cumulative distribution function. We studied the UZTT at the Southern Sierra Critical Zone Observatory (SS-CZO) using profiles of tritium and stable isotopes (18O and 2H) in the unsaturated zone, supported by soil water content data. Tritium analyses require 100-500 mL of soil water and therefore large soil samples (1-5L), and elaborate laboratory procedures (oven drying, degassing and noble gas mass spectrometry). The high seasonal and interannual variability in precipitation of the Mediterranean climate, variable snow pack and high annual ET/P ratios lead to a dynamic hydrology in the deep unsaturated soils and regolith and highly variable travel time distributions. Variability of the tritium concentration in precipitation further complicates direct age estimates. Observed tritium profiles (>3 m deep) are interpreted in terms of advective and dispersive vertical transport of the input variability and radioactive decay of tritium. Significant unsaturated zone travel times corroborate previously observed low activities of short-lived cosmogenic radioactive nuclides in stream water. Under these conditions, incorporating the UZTT is critical to adequately reconstruct stream water travel time distributions. 1

Using miniature osmotic infusion pumps to maintain tritiated thymidine exposure to cells in culture

International Nuclear Information System (INIS)

Neely, J.E.; Hake, D.A.

1982-01-01

To provide a constant level of tracer doses of tritiated thymidine to cultured cells during continuous infusion, miniature osmotic infusion pumps were used to provide replacement thymidine. By determining the loss of isotope from the media during nonreplacement, the rate of constant infusion replacement to maintain thymidine levels was calculated. The replacement rates were similar for the three cell lines examined and allowed a standard osmotic pump infusion

Trace contaminants of agriculture, fisheries and food with particular reference to isotope studies

International Nuclear Information System (INIS)

Winteringham, F.P.W.

1977-01-01

Growing world population, industrilization and intensification of agricultural and fisheries practices have greatly increased the need during recent decades to protect the resources concerned, and the quality of food and agricultural environment. These trends have also resulted in a growing range of trace contaminants and excessive nutrient problems of agriculture and fisheries. Isotopic tracer and nuclear analytical techniques are powerful and often unique tools for the study and control of the problems, especially in relation to trace elements, nutrients and contaminants. In addition to the conventional use of radioactive and stable isotopes as tracers there appears to be considerable scope for the use of environmental or natural isotope ratio techniques and the use of labelled reagents and substrates as monitoring tools. Representative applications are described. (author)

Co-ordinated research programme applications of stable isotope tracers in human nutrition research

International Nuclear Information System (INIS)

1992-01-01

The objective of this Co-ordinated Research Programme is to help establish competence in the use of stable isotope techniques, particularly in developing countries. This report summarizes the discussions that took, place during the Second Research Co-ordination Meeting, held in Bangalore in November 1990. Working papers presented by the participants are included as annexes. Refs, figs and tabs

Development of Stable Isotope Technology

International Nuclear Information System (INIS)

Jeong, Do Young; Kim, Cheol Jung; Han, Jae Min

2009-03-01

KAERI has obtained an advanced technology with singular originality for laser stable isotope separation. Objectives for this project are to get production technology of Tl-203 stable isotope used for medical application and are to establish the foundation of the pilot system, while we are taking aim at 'Laser Isotope Separation Technology to make resistance to the nuclear proliferation'. And we will contribute to ensuring a nuclear transparency in the world society by taking part in a practical group of NSG and being collaboration with various international groups related to stable isotope separation technology

Calcium stable isotope geochemistry

Energy Technology Data Exchange (ETDEWEB)

Gausonne, Nikolaus [Muenster Univ. (Germany). Inst. fuer Mineralogie; Schmitt, Anne-Desiree [Strasbourg Univ. (France). LHyGeS/EOST; Heuser, Alexander [Bonn Univ. (Germany). Steinmann-Inst. fuer Geologie, Mineralogie und Palaeontologie; Wombacher, Frank [Koeln Univ. (Germany). Inst. fuer Geologie und Mineralogie; Dietzel, Martin [Technische Univ. Graz (Austria). Inst. fuer Angewandte Geowissenschaften; Tipper, Edward [Cambridge Univ. (United Kingdom). Dept. of Earth Sciences; Schiller, Martin [Copenhagen Univ. (Denmark). Natural History Museum of Denmark

2016-08-01

This book provides an overview of the fundamentals and reference values for Ca stable isotope research, as well as current analytical methodologies including detailed instructions for sample preparation and isotope analysis. As such, it introduces readers to the different fields of application, including low-temperature mineral precipitation and biomineralisation, Earth surface processes and global cycling, high-temperature processes and cosmochemistry, and lastly human studies and biomedical applications. The current state of the art in these major areas is discussed, and open questions and possible future directions are identified. In terms of its depth and coverage, the current work extends and complements the previous reviews of Ca stable isotope geochemistry, addressing the needs of graduate students and advanced researchers who want to familiarize themselves with Ca stable isotope research.

Calcium stable isotope geochemistry

International Nuclear Information System (INIS)

Gausonne, Nikolaus; Schmitt, Anne-Desiree; Heuser, Alexander; Wombacher, Frank; Dietzel, Martin; Tipper, Edward; Schiller, Martin

2016-01-01

This book provides an overview of the fundamentals and reference values for Ca stable isotope research, as well as current analytical methodologies including detailed instructions for sample preparation and isotope analysis. As such, it introduces readers to the different fields of application, including low-temperature mineral precipitation and biomineralisation, Earth surface processes and global cycling, high-temperature processes and cosmochemistry, and lastly human studies and biomedical applications. The current state of the art in these major areas is discussed, and open questions and possible future directions are identified. In terms of its depth and coverage, the current work extends and complements the previous reviews of Ca stable isotope geochemistry, addressing the needs of graduate students and advanced researchers who want to familiarize themselves with Ca stable isotope research.

Labeling of fruitflies and their identification by tracer activation

International Nuclear Information System (INIS)

Haisch, A.; Forster, S.; Staerk, H.

1975-01-01

A technique was worked out to label and identify cherry fruit flies (Rhagoletic cerasi L.) in large numbers. For that purpose, the tracers dysprosium and samarium were mingled with a carrier substance (silica gel) which, mixed with silica sand, formed the substrate for emergence. The flies, the pupae of which were in this substrate, took up with their ptilinum-labeled silica gel during their crawling through the sand up to the surface. The tracer was detected after its activation by neutron irradiation

Proposal for a coordination research programme (CRP) of the International Atomic Energy Agency (IAEA) on stable isotope tracer techniques for studies on protein-energy interactions

International Nuclear Information System (INIS)

Shetty, P.; James, W.P.T.

1993-01-01

This Report provides a rationale and justification for the initiation of a Coordinated Research programme to support studies using stable isotopic tracer techniques to address priority areas of human protein-energy interactions with special emphasis on the problems of human nutrition in developing countries. The Report suggests a modus for establishing such a practically oriented Coordinated Research Programme under the aegis of the International Atomic Energy Agency with concrete suggestions for its organization and the identification of probable participants in such a programme. The likely sources of additional funding to sustain such an activity viable for a period of 4 to 5 years are also indicated. 8 refs

Quantitation of stable isotopic tracers of calcium by fast atom bombardment mass spectrometry

International Nuclear Information System (INIS)

Jiang, X.; Smith, D.L.

1987-01-01

Instrumentation and methodology developed for quantitation of stable isotopic traces in urine are described. Calcium is isolated from urine as the insoluble oxalate salt which is subsequently dissolved in hydrochloric acid. The isotopic content of the acid solution is determined by use of a conventional mass spectrometer equipped with a fast atom bombardment ion source. Calcium ions are desorbed from the sample surface by a beam of high-energy xenon atoms and detected with a high-resolution mass spectrometer. A data acquisition system has been developed to control the mass spectrometer and record the ion signals. Detailed analysis of potential sources of error indicates that the precision of the method is presently limited primarily by an isotope effect that occurs during ion desorption. Results presented here demonstrate that the relative abundances of calcium isotopes in urine can be determined with high precision (coefficient of variation < 0.2%) and that the method is a viable alternative to conventional thermal ionization mass spectrometry. The method is especially attractive because it uses a conventional high-resolution mass spectrometer which is routinely used for analysis of organic substances

Tests of intestinal absorption using carbon-14-labeled isotopes

International Nuclear Information System (INIS)

Fromm, H.; Sarva, R.P.

1983-01-01

Beta radiation-emitting isotopes are being used increasingly in diagnostic gastroenterology for the study of absorption. The major reason for the popularity of radioisotopes is that their use is convenient for patient and physician alike. They often obviate naso- or orointestinal intubation and the collection, storage, and analysis of stool. The radioactivity used for the studies of digestive and absorptive processes is small and is not hazardous. In spite of the safety of the radiolabeled compounds, their use is restricted in children and pregnant women. Therefore, for most tests, promising alternative methods that make use of the stable isotope of carbon, /sup 13/C, instead of the radioactive /sup 14/C have been developed. The analysis of stable isotopes requires more sophisticated technology than that of radioactive compounds, however. Only a few centers presently are equipped and staffed to analyze stable isotopes on a routine basis. In contrast, the analysis of radioactive isotopes has become a routine procedure in almost ever major laboratory. The last decade has brought the development of several radioactive absorption tests. The clinically most useful tests relate to the study of bile acid, fat, lactose, and xylose absorption. All of these tests utilize the excretion rate of /sup 14/CO/sub 2/ in breath after ingestion of a /sup 14/C-labeled compound as a measure of the rate of its absorption or malabsorption

Preferential flow pathways revealed by field based stable isotope analysis of CO2 by mid-infrared laser spectroscopy

Science.gov (United States)

van Geldern, Robert; Nowak, Martin; Zimmer, Martin; Szizybalski, Alexandra; Myrttinen, Anssi; Barth, Johannes A. C.; Jost, Hj

2016-04-01

A newly developed and commercially available isotope ratio laser spectrometer for CO2 analyses has been tested during a 10-day field monitoring campaign at the Ketzin pilot site for CO2 storage in northern Germany. The laser instrument is based on tunable laser direct absorption in the mid-infrared. The instrument recorded a continuous 10-day carbon stable isotope data set with 30 minutes resolution directly on-site in a field-based laboratory container during a tracer experiment. To test the instruments performance and accuracy the monitoring campaign was accompanied by daily CO2 sampling for laboratory analyses with isotope ratio mass spectrometry (IRMS). The carbon stable isotope ratios measured by conventional IRMS technique and by the new mid-infrared laser spectrometer agree remarkably well within 2σ analytical precision (<0.3 ‰). This proves the capability of the new mid-infrared direct absorption technique to measure high precision and accurate real-time table isotope data directly in the field. The injected CO2 tracer had a distinct δ13C value that was largely different from the reservoir background value. The laser spectroscopy data revealed a prior to this study unknown, intensive dynamic with fast changing δ13C values. The arrival pattern of the tracer suggest that the observed fluctuations were probably caused by migration along separate and distinct preferential flow paths between injection well and observation well. The new technique might contribute to a better tracing of the migration of the underground CO2 plume and help to ensure the long-term integrity of the reservoir.

A Combined Radio- and Stable-Isotopic Study of a California Coastal Aquifer System

Directory of Open Access Journals (Sweden)

Michael Land

2013-04-01

Full Text Available Stable and radioactive tracers were utilized in concert to characterize geochemical processes in a complex coastal groundwater system and to provide constraints on the kinetics of rock/water interactions. Groundwater samples from wells within the Dominguez Gap region of Los Angeles County, California were analyzed for a suite of major cations (Na+, K+, Mg2+, Ca2+ and anions (Cl−, SO42−, silica, alkalinity, select trace elements (Ba, B, Sr, dissolved oxygen, stable isotopes of hydrogen (δD, oxygen (δ18O, dissolved inorganic carbon (δ13CDIC, and radioactive isotopes (3H, 222Rn and 223,224,226,228Ra. In the study area, groundwater may consist of a complex mixture of native groundwater, intruded seawater, non-native injected water, and oil-field brine water. In some wells, Cl− concentrations attained seawater-like values and in conjunction with isotopically heavier δ18O values, these tracers provide information on the extent of seawater intrusion and/or mixing with oil-field brines. Groundwater 3H above 1 tritium unit (TU was observed only in a few select wells close to the Dominguez Gap area and most other well groundwater was aged pre-1952. Based on an initial 14C value for the study site of 90 percent modern carbon (pmc, groundwater age estimates likely extend beyond 20 kyr before present and confirm deep circulation of some native groundwater through multiple aquifers. Enriched values of groundwater δ13CDIC in the absence of SO42− imply enhanced anaerobic microbial methanogenesis. While secular equilibrium was observed for 234U/238U (activity ratios ~1 in host matrices, strong isotopic fractionation in these groundwater samples can be used to obtain information of adsorption/desorption kinetics. Calculated Ra residence times are short, and the associated desorption rate constant is about three orders of magnitude slower than that of the adsorption rate constant. Combined stable- and radio-isotopic results provide unique insights

Tracing metal–silicate segregation and late veneer in the Earth and the ureilite parent body with palladium stable isotopes

DEFF Research Database (Denmark)

Creech, J. B.; Moynier, F.; Bizzarro, Martin

2017-01-01

Stable isotope studies of highly siderophile elements (HSE) have the potential to yield valuable insights into a range of geological processes. In particular, the strong partitioning of these elements into metal over silicates may lead to stable isotope fractionation during metal......–silicate segregation, making them sensitive tracers of planetary differentiation processes. We present the first techniques for the precise determination of palladium stable isotopes by MC-ICPMS using a 106Pd–110Pd double-spike to correct for instrumental mass fractionation. Results are expressed as the per mil...... (‰) difference in the 106Pd/105Pd ratio (δ106Pd) relative to an in-house solution standard (Pd_IPGP) in the absence of a certified Pd isotopic standard. Repeated analyses of the Pd isotopic composition of the chondrite Allende demonstrate the external reproducibility of the technique of ±0.032‰ on δ106Pd. Using...

Application of Stable Isotope in Detection of Veterinary Drug Residues

International Nuclear Information System (INIS)

Wang Wei; Liu Zhanfeng; Du Xiaoning

2010-01-01

In recent years, there has happened a series of significant food safety events worldwide, which lower down consumers' confidence in food safety, and they are taking increasing care about the sources of their foods. The safety problem of animal-origin foods has become a global topic for discussion. Therefore, it is a pressing task to establish a precise, sensitive and reliable method for analyzing veterinary drug residue. An introduction of the present status regarding veterinary drug residue analysis was made in the paper, and it briefly summarized the limit of detection (LOD) and quantification (LOQ) which could be reached in veterinary drug residue analysis by isotopic internal standard method domestically and abroad. The paper also made a review of the progress in applied research of stable isotope labeled compound in veterinary drug residue analysis of, such as, antibiotic medicines, furans and sulfonamides. The paper elucidated the great importance of the application of stable isotopes in the sane development of China's food safety system. (authors)

Glucose and protein kinetics in patients undergoing colorectal surgery: perioperative amino acid versus hypocaloric dextrose infusion.

Science.gov (United States)

Lugli, Andrea Kopp; Schricker, Thomas; Wykes, Linda; Lattermann, Ralph; Carli, Franco

2010-11-01

Surgical injury provokes a stress response that leads to a catabolic state and, when prolonged, interferes with the postoperative recovery process. This study tests the impact of 2 nutrition support regimens on protein and glucose metabolism as part of an integrated approach in the perioperative period incorporating epidural analgesia in 18 nondiabetic patients undergoing colorectal surgery. To test the hypothesis that parenteral amino acid infusion (amino acid group, n = 9) maintains glucose homeostasis while maintaining normoglycemia and reduces proteolysis compared with infusion of dextrose alone (DEX group, n = 9), glucose and protein kinetics were measured before and on the second day after surgery using a stable isotope tracer technique. Postoperatively, the rate of appearance of glucose was higher (P dextrose alone. Copyright © 2010 Elsevier Inc. All rights reserved.

Water enriched in the rare stable isotopes : Preparation, measurement and applications

NARCIS (Netherlands)

Faghihi, Vahideh

2016-01-01

The subject of this thesis is water with increased abundances of the rare stable isotopes 2H and 18O (and to some extent also 17O). Such artificially enriched (or "labelled") waters are often used in biomedicine, for establishing the total amount of body water (and thus body composition) of humans

Melatonin labeled with hydrogen isotopes

International Nuclear Information System (INIS)

Dmitrevskaya, L.I.; Smushkevich, Yu.I.; Kurkovskaya, L.N.; Ponomarenko, N.K.; Suvorov, N.N.

1989-01-01

A study has been made of isotope exchange between melatonin and deuterium (D 2 O) or tritium (HTO) oxide under different conditions. The ease of isotope exchange for the indole ring hydrogens of melatonin in an acidic medium decreases over the series H 4 > H 2 H 6 >> H 7 , enabling the authors to process a route for production of melatonin labeled with hydrogen isotopes at positions 4,6, and 2 of the indole ring. A method has been suggested for producing melatonin labeled with hydrogen isotopes at position 2 by desulfurization of 2-(2,4-dinitro-phenylsulfenyl)melatonin at Ni(Re) (D)

Melatonin labelled by hydrogen isotopes

International Nuclear Information System (INIS)

Dmitrevskaya, L.I.; Smushkevich, Yu.I.; Kurkovskaya, L.N.; Ponomarenko, N.K.; Suvorov, N.N.

1988-01-01

Isotope exchange of melatonin with deuterium (D 2 O) and tritium (HTO) oxides under different conditions is studied. Simplicity of isotope exchange of hydrogens of the indole ring of melatonin in the acidic medium decreases in series H 4 >H 2 >H 6 >>H 7 , that permits to suggest the way of melatonin preparation labelled by hydrogen isotopes in positions 4,6 and 2 of the indole ring. The way of melatonin preparation labelled by hydrogen isotopes in position 2 according to the reaction of desulfation 2-(2,4-dinitrophenylsulphenyl) melatonin at catalyst Ni(Re)(D) is suggested

Stable water isotope and surface heat flux simulation using ISOLSM: Evaluation against in-situ measurements

KAUST Repository

Cai, Mick Y.; Wang, Lixin; Parkes, Stephen; Strauss, Josiah; McCabe, Matthew; Evans, Jason P.; Griffiths, Alan D.

2015-01-01

The stable isotopes of water are useful tracers of water sources and hydrological processes. Stable water isotope-enabled land surface modeling is a relatively new approach for characterizing the hydrological cycle, providing spatial and temporal variability for a number of hydrological processes. At the land surface, the integration of stable water isotopes with other meteorological measurements can assist in constraining surface heat flux estimates and discriminate between evaporation (E) and transpiration (T). However, research in this area has traditionally been limited by a lack of continuous in-situ isotopic observations. Here, the National Centre for Atmospheric Research stable isotope-enabled Land Surface Model (ISOLSM) is used to simulate the water and energy fluxes and stable water isotope variations. The model was run for a period of one month with meteorological data collected from a coastal sub-tropical site near Sydney, Australia. The modeled energy fluxes (latent heat and sensible heat) agreed reasonably well with eddy covariance observations, indicating that ISOLSM has the capacity to reproduce observed flux behavior. Comparison of modeled isotopic compositions of evapotranspiration (ET) against in-situ Fourier Transform Infrared spectroscopy (FTIR) measured bulk water vapor isotopic data (10. m above the ground), however, showed differences in magnitude and temporal patterns. The disparity is due to a small contribution from local ET fluxes to atmospheric boundary layer water vapor (~1% based on calculations using ideal gas law) relative to that advected from the ocean for this particular site. Using ISOLSM simulation, the ET was partitioned into E and T with 70% being T. We also identified that soil water from different soil layers affected T and E differently based on the simulated soil isotopic patterns, which reflects the internal working of ISOLSM. These results highlighted the capacity of using the isotope-enabled models to discriminate

Stable water isotope and surface heat flux simulation using ISOLSM: Evaluation against in-situ measurements

KAUST Repository

Cai, Mick Y.

2015-04-01

The stable isotopes of water are useful tracers of water sources and hydrological processes. Stable water isotope-enabled land surface modeling is a relatively new approach for characterizing the hydrological cycle, providing spatial and temporal variability for a number of hydrological processes. At the land surface, the integration of stable water isotopes with other meteorological measurements can assist in constraining surface heat flux estimates and discriminate between evaporation (E) and transpiration (T). However, research in this area has traditionally been limited by a lack of continuous in-situ isotopic observations. Here, the National Centre for Atmospheric Research stable isotope-enabled Land Surface Model (ISOLSM) is used to simulate the water and energy fluxes and stable water isotope variations. The model was run for a period of one month with meteorological data collected from a coastal sub-tropical site near Sydney, Australia. The modeled energy fluxes (latent heat and sensible heat) agreed reasonably well with eddy covariance observations, indicating that ISOLSM has the capacity to reproduce observed flux behavior. Comparison of modeled isotopic compositions of evapotranspiration (ET) against in-situ Fourier Transform Infrared spectroscopy (FTIR) measured bulk water vapor isotopic data (10. m above the ground), however, showed differences in magnitude and temporal patterns. The disparity is due to a small contribution from local ET fluxes to atmospheric boundary layer water vapor (~1% based on calculations using ideal gas law) relative to that advected from the ocean for this particular site. Using ISOLSM simulation, the ET was partitioned into E and T with 70% being T. We also identified that soil water from different soil layers affected T and E differently based on the simulated soil isotopic patterns, which reflects the internal working of ISOLSM. These results highlighted the capacity of using the isotope-enabled models to discriminate

Diurnal variations of organic molecular tracers and stable carbon isotopic compositions in atmospheric aerosols over Mt. Tai in North China Plain: an influence of biomass burning

Science.gov (United States)

Fu, P. Q.; Kawamura, K.; Chen, J.; Li, J.; Sun, Y. L.; Liu, Y.; Tachibana, E.; Aggarwal, S. G.; Okuzawa, K.; Tanimoto, H.; Kanaya, Y.; Wang, Z. F.

2012-04-01

Organic tracer compounds of tropospheric aerosols, as well as organic carbon (OC), elemental carbon (EC), water-soluble organic carbon (WSOC), and stable carbon isotope ratios (δ13C) of total carbon (TC) have been investigated for aerosol samples collected during early and late periods of Mount Tai eXperiment 2006 (MTX2006) field campaign in North China Plain. Total solvent extracts were investigated by gas chromatography/mass spectrometry. More than 130 organic compounds were detected in the aerosol samples. They were grouped into twelve organic compound classes, including biomass burning tracers, biogenic primary sugars, biogenic secondary organic aerosol (SOA) tracers, and anthropogenic tracers such as phthalates, hopanes and polycyclic aromatic hydrocarbons (PAHs). In early June when the field burning activities of wheat straws in North China Plain were very active, the total identified organics (2090 ± 1170 ng m-3) were double those in late June (926 ± 574 ng m-3). All the compound classes were more abundant in early June than in late June, except phthalate esters, which were higher in late June. Levoglucosan (88-1210 ng m-3, 403 ng m-3) was found as the most abundant single compound in early June, while diisobutyl phthalate was the predominant species in late June. During the biomass-burning period in early June, the diurnal trends of most of the primary and secondary organic aerosol tracers were characterized by the concentration peaks observed at mid-night or in early morning, while in late June most of the organic species peaked in late afternoon. This suggests that smoke plumes from biomass burning can uplift the aerosol particulate matter to a certain altitude and then transported to and encountered the summit of Mt. Tai during nighttime. On the basis of the tracer-based method for the estimation of biomass-burning OC, fungal-spore OC and biogenic secondary organic carbon (SOC), we estimate that an average of 24% (up to 64%) of the OC in the Mt. Tai

Co-ordinated research programme on applications of stable isotope tracers in human nutrition research

International Nuclear Information System (INIS)

1989-01-01

This Co-ordinated Research Programme (CRP) was formally established by the Agency in October 1988, and has since then expanded to encompass 13 participants in 13 countries. Its general objective is to help establish competence in the use of stable isotope techniques, particularly in developing countries, and particularly with reference to applications of 2 H, 13 C, 15 N, and 18 O. This report summarizes the discussions that took place during the first Research Co-ordination Meeting (RCM). Working papers (progress reports) presented by the participants are included as annexes together with a preliminary report on the results of a series of intercomparison exercises involving enriched stable isotope reference materials containing 2 H, 13 C, 15 N and 18 O. For the future it was agreed that more work needs to be done to harmonize the analytical techniques being used, and to obtain support for new CRPs relating to human energy expenditure studies in pregnancy, lactation, growth and other conditions, and to studies of nitrogen turnover in relation to malnutrition and liver function. Refs, figs and tabs

Stable isotopes and elasmobranchs: tissue types, methods, applications and assumptions.

Science.gov (United States)

Hussey, N E; MacNeil, M A; Olin, J A; McMeans, B C; Kinney, M J; Chapman, D D; Fisk, A T

2012-04-01

Stable-isotope analysis (SIA) can act as a powerful ecological tracer with which to examine diet, trophic position and movement, as well as more complex questions pertaining to community dynamics and feeding strategies or behaviour among aquatic organisms. With major advances in the understanding of the methodological approaches and assumptions of SIA through dedicated experimental work in the broader literature coupled with the inherent difficulty of studying typically large, highly mobile marine predators, SIA is increasingly being used to investigate the ecology of elasmobranchs (sharks, skates and rays). Here, the current state of SIA in elasmobranchs is reviewed, focusing on available tissues for analysis, methodological issues relating to the effects of lipid extraction and urea, the experimental dynamics of isotopic incorporation, diet-tissue discrimination factors, estimating trophic position, diet and mixing models and individual specialization and niche-width analyses. These areas are discussed in terms of assumptions made when applying SIA to the study of elasmobranch ecology and the requirement that investigators standardize analytical approaches. Recommendations are made for future SIA experimental work that would improve understanding of stable-isotope dynamics and advance their application in the study of sharks, skates and rays. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Stable isotope analysis in primatology: a critical review.

Science.gov (United States)

Sandberg, Paul A; Loudon, James E; Sponheimer, Matt

2012-11-01

Stable isotope analysis has become an important tool in ecology over the last 25 years. A wealth of ecological information is stored in animal tissues in the relative abundances of the stable isotopes of several elements, particularly carbon and nitrogen, because these isotopes navigate through ecological processes in predictable ways. Stable carbon and nitrogen isotopes have been measured in most primate taxonomic groups and have yielded information about dietary content, dietary variability, and habitat use. Stable isotopes have recently proven useful for addressing more fine-grained questions about niche dynamics and anthropogenic effects on feeding ecology. Here, we discuss stable carbon and nitrogen isotope systematics and critically review the published stable carbon and nitrogen isotope data for modern primates with a focus on the problems and prospects for future stable isotope applications in primatology. © 2012 Wiley Periodicals, Inc.

Applications of stable isotopes of 2H, 13C and 15N to clinical problems

International Nuclear Information System (INIS)

Klein, P.D.; Szczepanik, P.A.; Hachey, D.L.

1974-01-01

The function of the Argonne Program is to provide synthetic, analytical instrumental capability in a core facility for the clinical investigator who needs to use 2 H, 13 C, or 15 N labelled compounds for metabolic or clinical research on pregnant women, newborn infants, young children, or for mass screening. To carry out such application development, there were six stages which were recurrent steps in every application. Five fundamental strategies should be adopted to establish the use of stable isotopes in clinical work. The instrument required for measurements was a combined gas chromatograph-mass spectrometer, and its use was schematically illustrated. Some of the successful experiences with compounds labelled by stable isotopes, such as deuterium labelled chenodeoxycholic acid, and respective 13 C and 15 N-labelled glycine were described. Deutrium labelled bile acid enabled easy and safe determination of the size of the bile acid pool and the replacement rate, providing clearer diagnoses for cholestatic liver disease and gallstones. 13 C and 15 N labelled compounds were used in clinical studies, of children with genetic disorders of amino acid metabolism, i.e., non ketotic hyperflycinemia, B 12 -responsive methyl malonic acidemia, and Lesch-Nyhan syndrome. 15 N-labelled glycine was also studied in a child with Lesch-Nyhan syndrome. (Mukohata, S.)

The Use of P isotope in the ecology and source environment research: A review

International Nuclear Information System (INIS)

Chu Qun; Feng Gu

2012-01-01

The use of tracers are widely to plant-soil-manue duction-environment systems which study activity of phosphorus, forms changes, utilization and changes. It induces the development of ecology and source environment. This review shows the approaches of tracer in plant-soil-manue duction-environment systems which include direct labeling technique, indirect labeling technique or exposed directly. The use of stable isotopes of oxygen in phosphate made it possible to quantify the phosphrous cycling under field conditions and water system. But it is limited in plant and soil systems. NMR techniques was widely used to study the changes of phosphorus forms. It supplies a new tools to quality and quantity of different forms of paraphos. (authors)

The use of P isotope in the ecology and source environment research: a review

International Nuclear Information System (INIS)

Chu Qun; Feng Gu

2011-01-01

The use of tracers are widely to plant-soi-manue duction-environment systems which study activity of phosphorus, forms changes, utilization and changes. It induces the development of ecology and sorce environment. This review shows the approache of tracer in plant-soi-manue duction-environment systems which include direct labeling technique, indirect labeling technique or exposed directly. The use of stable isotopes of oxygen in phosphate made it possible to quantify the phosphrus cycling under field canditions and aer system. But it is limited in plant and soil systems. NMR techniques was widely used to study the changes of phosphorus forms. It supplies a new tools to qanlity and quantity of diffrenct forms of phophrus. (authors)

Forensic Stable Isotope Biogeochemistry

Science.gov (United States)

Cerling, Thure E.; Barnette, Janet E.; Bowen, Gabriel J.; Chesson, Lesley A.; Ehleringer, James R.; Remien, Christopher H.; Shea, Patrick; Tipple, Brett J.; West, Jason B.

2016-06-01

Stable isotopes are being used for forensic science studies, with applications to both natural and manufactured products. In this review we discuss how scientific evidence can be used in the legal context and where the scientific progress of hypothesis revisions can be in tension with the legal expectations of widely used methods for measurements. Although this review is written in the context of US law, many of the considerations of scientific reproducibility and acceptance of relevant scientific data span other legal systems that might apply different legal principles and therefore reach different conclusions. Stable isotopes are used in legal situations for comparing samples for authenticity or evidentiary considerations, in understanding trade patterns of illegal materials, and in understanding the origins of unknown decedents. Isotope evidence is particularly useful when considered in the broad framework of physiochemical processes and in recognizing regional to global patterns found in many materials, including foods and food products, drugs, and humans. Stable isotopes considered in the larger spatial context add an important dimension to forensic science.

Recent developments in application of stable isotope analysis on agro-product authenticity and traceability.

Science.gov (United States)

Zhao, Yan; Zhang, Bin; Chen, Gang; Chen, Ailiang; Yang, Shuming; Ye, Zhihua

2014-02-15

With the globalisation of agro-product markets and convenient transportation of food across countries and continents, the potential for distribution of mis-labelled products increases accordingly, highlighting the need for measures to identify the origin of food. High quality food with identified geographic origin is a concern not only for consumers, but also for agriculture farmers, retailers and administrative authorities. Currently, stable isotope ratio analysis in combination with other chemical methods gradually becomes a promising approach for agro-product authenticity and traceability. In the last five years, a growing number of research papers have been published on tracing agro-products by stable isotope ratio analysis and techniques combining with other instruments. In these reports, the global variety of stable isotope compositions has been investigated, including light elements such as C, N, H, O and S, and heavy isotopes variation such as Sr and B. Several factors also have been considered, including the latitude, altitude, evaporation and climate conditions. In the present paper, an overview is provided on the authenticity and traceability of the agro-products from both animal and plant sources by stable isotope ratio analysis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Stable Isotope Analyses of water and Aqueous Solutions by Conventional Dual-inlet Mass Spectrometry

Energy Technology Data Exchange (ETDEWEB)

Horita, Juske [ORNL; Kendall, C. [U.S. Geological Survey, Menlo Park, CA

2004-01-01

The foundation of various analytical methods for the stable isotope composition of water and other aqueous samples (natural abundance, {sup 1}H : {sup 2}H (D) = 99.985 : 0.015 atom%, and {sup 16}O : {sup 17}O : {sup 18}O = 99.762 : 0.038 : 0.200 atom%) was established during the Manhatten Project in the U.S.A., when large amounts of heavy water were produced for nuclear reactors (see Kirshenbaum, 1951, for a detailed account). From early on, there was great interest in the oxygen and hydrogen isotopic compositions of water, because they are the ideal tracers of water sources and reactions. The increased analytical precisions made possible by the subsequent development of modern gas-source isotope-ratio mass spectrometers with dual-inlets and multi-collectors, have caused the proliferation of new analytical methods and applications for the oxygen and hydrogen isotopic compositions of water. These stable isotopes have found wide applications in basic as well as applied sciences (chemistry, geology, hydrology, biology, medical sciences, and food sciences). This is because water is ubiquitous, is an essential and predominant ingredient of living organisms, and is perhaps the most reactive compound in the Earth.

A new technique for the evaluation of the capacity of the gastrointestinal tract to assimilate foods by using a stable isotope of nitrogen (15N)

International Nuclear Information System (INIS)

Takemiya, Muneyasu; Fujita, Yoshikuni; Yazima, Yoshitada; Okabe, Haruya

1983-01-01

A new technique is introduced for the evaluation of the capacity of the gastrointestinal tract to assimilate foods by using a stable isotope of nitrogen ( 15 N) as a tracer. Four groups of male Wistar rats were fed 15 N-labeled rice for one day following a basal diet, composed of 87% poudered rice. Then, 15 N-labeled rice was switched to basal diet again for the next seven days. The four groups of rats consisted of: Group A-three pancreatic duct-ligated rats; Group B-four sham operated rats; Group C-five control rats and Group D-seven Streptozotocin-treated (20mg/kg) rats. The 15 N contents were measured in the stool, urine and sera collected before feeding of 15 N-labeled rice and one, three and seven days thereafter. In group A, the rate of 15 N excretion into the stools, i.e., the amount of 15 N in the stools against the total amount of 15 N consumed, was higher as compared to the control group throughout the period of the study. On the contrary, the rate of urinary excretion of 15 N as well as the contents of 15 N in the urine and sera were apparently lower. In group D, the rate of 15 N excretion into the stools as well as the contents of 15 N in the sera and urine showed no difference as compared to the control group. The rate of 15 N excretion into the urine, however, was apparently higher than that of the control group throughout the period of the study. These results indicate that this stable isotope of nitrogen ( 15 N), which clearly reveals the existence of malabsorption of pancreatic origin, is valuable as a tracer for assimilation studies and technically applicable for clinical use. We have found no evidence of malassimilation in rats with Streptozotocin-induced diabetes in spite of the presence of previous reports that assert the existence of pancreatic exocrine dysfunction in these animals. (author)

Zinc absorption study using an enriched stable isotope (70Zn)

International Nuclear Information System (INIS)

Li Gongpan.

1990-04-01

A weaning food from fermented soybean was prepared for increasing the bioavailability of zinc. The zinc absorption was compared with that of a weaning food from non-fermented soybean and normal staple food. A stable isotope tracer technique ( 70 Zn) and neutron activation were used for determining the absorption of zinc. Nine children aged 7 to 18 months were tested. Zinc bioavailability of weaning food from fermented soybean is higher than that of normal weaning food. The weight increment and zinc nutrition of children having weaning food from fermented soybean are improved by this diet. 5 tabs

Determination of zinc stable isotopes in biological materials using isotope dilution inductively coupled plasma mass spectrometry

International Nuclear Information System (INIS)

Patterson, K.Y.; Veillon, Claude

1992-01-01

A method is described for using isotope dilution to determine both the amount of natural zinc and enriched isotopes of zinc in biological samples. Isotope dilution inductively coupled plasma mass spectrometry offers a way to quantify not only the natural zinc found in a sample but also the enriched isotope tracers of zinc. Accurate values for the enriched isotopes and natural zinc are obtained by adjusting the mass count rate data for measurable instrumental biases. Analytical interferences from the matrix are avoided by extracting the zinc from the sample matrix using diethylammonium diethyldithiocarbamate. The extraction technique separates the zinc from elements which form interfering molecular ions at the same nominal masses as the zinc isotopes. Accuracy of the method is verified using standard reference materials. The detection limit is 0.06 μg Zn per sample. Precision of the abundance ratios range from 0.3-0.8%. R.S.D. for natural zinc concentrations is about 200-600 μg g -1 . The accuracy and precision of the measurements make it possible to follow enriched isotopic tracers of zinc in biological samples in metabolic tracer studies. (author). 19 refs.; 1 fig., 4 tabs

Diurnal variations of organic molecular tracers and stable carbon isotopic composition in atmospheric aerosols over Mt. Tai in the North China Plain: an influence of biomass burning

Science.gov (United States)

Fu, P. Q.; Kawamura, K.; Chen, J.; Li, J.; Sun, Y. L.; Liu, Y.; Tachibana, E.; Aggarwal, S. G.; Okuzawa, K.; Tanimoto, H.; Kanaya, Y.; Wang, Z. F.

2012-09-01

Organic tracer compounds, as well as organic carbon (OC), elemental carbon (EC), water-soluble organic carbon (WSOC), and stable carbon isotope ratios (δ13C) of total carbon (TC) have been investigated in aerosol samples collected during early and late periods of the Mount Tai eXperiment 2006 (MTX2006) field campaign in the North China Plain. Total solvent-extractable fractions were investigated by gas chromatography/mass spectrometry. More than 130 organic compounds were detected in the aerosol samples. They were grouped into twelve organic compound classes, including biomass burning tracers, biogenic primary sugars, biogenic secondary organic aerosol (SOA) tracers, and anthropogenic tracers such as phthalates, hopanes and polycyclic aromatic hydrocarbons (PAHs). In early June when the field burning activities of wheat straws in the North China Plain were very active, the total identified organics (2090 ± 1170 ng m-3) were double those in late June (926 ± 574 ng m-3). All the compound classes were more abundant in early June than in late June, except phthalate esters, which were higher in late June. Levoglucosan (88-1210 ng m-3, mean 403 ng m-3) was found as the most abundant single compound in early June, while diisobutyl phthalate was the predominant species in late June. During the biomass-burning period in early June, the diurnal trends of most of the primary and secondary organic aerosol tracers were characterized by the concentration peaks observed at mid-night or in early morning, while in late June most of the organic species peaked in late afternoon. This suggests that smoke plumes from biomass burning can uplift the aerosol particulate matter to a certain altitude, which could be further transported to and encountered the summit of Mt. Tai during nighttime. On the basis of the tracer-based method for the estimation of biomass-burning OC, fungal-spore OC and biogenic secondary organic carbon (SOC), we estimate that an average of 24% (up to 64%) of the

Stable isotope research pool inventory

International Nuclear Information System (INIS)

1984-03-01

This report contains a listing of electromagnetically separated stable isotopes which are available at the Oak Ridge National Laboratory for distribution for nondestructive research use on a loan basis. This inventory includes all samples of stable isotopes in the Research Materials Collection and does not designate whether a sample is out on loan or is in reprocessing. For some of the high abundance naturally occurring isotopes, larger amounts can be made available; for example, Ca-40 and Fe-56

Stable isotopes of water as a natural tracer for infiltration into urban sewer systems

Science.gov (United States)

Kracht, O.; Gresch, M.; de Bénédittis, J.; Prigiobbe, V.; Gujer, W.

2003-04-01

An adequate understanding of the hydraulic interaction between leaky sewers and groundwater is essential for the sustainable management of both sewer systems and aquifers in urbanized areas. Undesirable infiltration of groundwater into sewers can contribute over 50% of the total discharge and is detrimental to treatment plant efficiency. On the other hand, in many European cities groundwater surface levels seem to be particularly controlled by the drainage effect of permeable sewer systems. However, nowadays methods for the quantification of these exchange processes are still subject to considerable uncertainties due to their underlying assumptions. The frequently used assumption that the night time minimum in the diurnal wastewater hydrograph is equal to the "parasitic discharge" has to be reconsidered to today's patterns of human life as well as to the long residence time of wastewater in the sewer networks of modern cities. The suitability of stable water isotopes as a natural tracer to differentiate the origin of water in the sewer ("real" wastewater or infiltrating groundwater) is currently investigated in three different catchment areas. The studies are carried out within the framework of the European research project APUSS (Assessing Infiltration and Exfiltration on the Performance of Urban Sewer Systems): 1) The village of Rümlang (Zürich, Switzerland) is predominantly served with drinking water from the Lake Zürich. A large fraction of the lakes water is derived from precipitation in the Alps. This drinking water represents the intrinsic provenience of the wastewater with an δ18O value around -11,5 per mill and δ^2H value around -82 per mill vs. SMOW. In contrast, the local groundwater is originating from precipitation in a moderate altitude of about 450 m above sea level and shows comparatively enriched mean δ18O values of -9,7 per mill and δ^2H values of -70 per mill with only small natural variations. The isotopic separation between these

Radiation dose estimates for carbon-11-labelled PET tracers

International Nuclear Information System (INIS)

Aart, Jasper van der; Hallett, William A.; Rabiner, Eugenii A.; Passchier, Jan; Comley, Robert A.

2012-01-01

Introduction: Carbon-11-labelled positron emission tomography (PET) tracers commonly used in biomedical research expose subjects to ionising radiation. Dosimetry is the measurement of radiation dose, but also commonly refers to the estimation of health risk associated with ionising radiation. This review describes radiation dosimetry of carbon-11-labelled molecules in the context of current PET research and the most widely used regulatory guidelines. Methods: A MEDLINE literature search returned 42 articles; 32 of these were based on human PET data dealing with radiation dosimetry of carbon-11 molecules. Radiation burden expressed as effective dose and maximum absorbed organ dose was compared between tracers. Results: All but one of the carbon-11-labelled PET tracers have an effective dose under 9 μSv/MBq, with a mean of 5.9 μSv/MBq. Data show that serial PET scans in a single subject are feasible for the majority of radiotracers. Conclusion: Although differing in approach, the two most widely used regulatory frameworks (those in the USA and the EU) do not differ substantially with regard to the maximum allowable injected activity per PET study. The predictive validity of animal dosimetry models is critically discussed in relation to human dosimetry. Finally, empirical PET data are related to human dose estimates based on homogenous distribution, generic models and maximum cumulated activities. Despite the contribution of these models to general risk estimation, human dosimetry studies are recommended where continued use of a new PET tracer is foreseen.

Stable isotope research pool inventory

International Nuclear Information System (INIS)

1982-01-01

This report contains a listing of electromagnetically separated stable isotopes which are available for distribution within the United States for nondestructive research use from the Oak Ridge National Laboratory on a loan basis. This inventory includes all samples of stable isotopes in the Material Research Collection and does not designate whether a sample is out on loan or in reprocessing. For some of the high abundance naturally occurring isotopes, larger amounts can be made available; for example, Ca-40 and Fe-56

Investigating Uranium Mobility Using Stable Isotope Partitioning of 238U/235U and a Reactive Transport Model

Science.gov (United States)

Bizjack, M.; Johnson, T. M.; Druhan, J. L.; Shiel, A. E.

2015-12-01

We report a numerical reactive transport model which explicitly incorporates the effectively stable isotopes of uranium (U) and the factors that influence their partitioning in bioactive systems. The model reproduces trends observed in U isotope ratios and concentration measurements from a field experiment, thereby improving interpretations of U isotope ratios as a tracer for U reactive transport. A major factor contributing to U storage and transport is its redox state, which is commonly influenced by the availability of organic carbon to support metal-reducing microbial communities. Both laboratory and field experiments have demonstrated that biogenic reduction of U(VI) fractionates the stable isotope ratio 238U/235U, producing an isotopically heavy solid U(IV) product. It has also been shown that other common reactive transport processes involving U do not fractionate isotopes to a consistently measurable level, which suggests the capacity to quantify the extent of bioreduction occurring in groundwater containing U using 238U/235U ratios. A recent study of a U bioremediation experiment at the Rifle IFRC site (Colorado, USA) applied Rayleigh distillation models to quantify U stable isotope fractionation observed during acetate amendment. The application of these simplified models were fit to the observations only by invoking a "memory-effect," or a constant source of low-concentration, unfractionated U(VI). In order to more accurately interpret the measured U isotope ratios, we present a multi-component reactive transport model using the CrunchTope software. This approach is capable of quantifying the cycling and partitioning of individual U isotopes through a realistic network of transport and reaction pathways including reduction, oxidation, and microbial growth. The model incorporates physical heterogeneity of the aquifer sediments through zones of decreased permeability, which replicate the observed bromide tracer, major ion chemistry, U concentration, and U

Problems and prospects in future applications of stable isotopes in the life sciences and medicine

International Nuclear Information System (INIS)

Matwiyoff, N.A.; Unkefer, C.J.; Walker, T.E.

1982-01-01

In the last decade, there has been a resurgence of interest in the use of stable isotopes of carbon, oxygen, and nitrogen in the life sciences and medicine fueled by the increased availability of the isotopes and isotopically labeled compounds and of instruments for their detection. Accelerated development of 13 C, 15 N, and 17 18 O can be expected in the future for studies of drug bioavailability, nutrition and body protein economy, viability of organs for transplant, and for non-invasive tests of metabolic diseases and dysfunctions. These accelerated developments depend on continued improvements in nmr and ms instrumentation and in methods for the synthesis of isotopically labeled compounds. The main part of this paper explores the possibilities of biosynthesis for the selective enrichment of natural products, especially amino acids, with 13 C

New developments in the use of stable activable tracers in environmental science

International Nuclear Information System (INIS)

Loveland, W.; Keasler, K.; Ghannam, L.; Borovik, A.

1980-01-01

Recent developments in the use of stable activable tracers (SATs) in environmental science are reported. (A stable activable tracer is a stable material injected into a system under study and whose concentration is measured by post-sampling activation analysis.) The activable nuclear parts of the tracers studied have been rare earth nuclides with short-lived activation products or Cu. To trace the fate of fluid-bound pollutants (and/or water masses) in marine waters, we have used anionic DTPA complexes of the rare earths. These tracers were shown to be stable (80 to 90% nondissociated) in extensive laboratory tests involving solutions of the tracer in estuarine water including large amounts of marine sediments. Results of a field study in which the flushing time and other hydrological characteristics of an estuarine marina were measured by simultaneously using a fluorescent dye and a SAT are presented. To trace the path of potentially toxic organic molecules, three stable activable tracers, dysprosium(III)-trisacetylacetonate DY(acac) 3 3H 2 O), dysprosium(III)-trisdibenzoylmethane (DY(dbm) 3 H 2 O and copper oxinate Cu (C 9 H 6 ON) 2 were synthesized. Their octanol/water partition coefficients and their solubility in water were measured and used to correlate the tracer species and its biological activity with that of known toxic materials. In a project to demonstrate the simple use of SATs to trace the origin of common insecticides and herbicides, seven common insecticides and herbicides were marked with anionic rare earth DTPA complexes and shown to be detectable at dilutions of 1 part in 10 12 . Two arsenical herbicides were chosen for further study and the tracer/herbicide ratio was shown to remain constant in samples of herbicide material collected on plant surfaces and runoff waters in the environment for long periods

LabData database sub-systems for post-processing and quality control of stable isotope and gas chromatography measurements

Science.gov (United States)

Suckow, A. O.

2013-12-01

Measurements need post-processing to obtain results that are comparable between laboratories. Raw data may need to be corrected for blank, memory, drift (change of reference values with time), linearity (dependence of reference on signal height) and normalized to international reference materials. Post-processing parameters need to be stored for traceability of results. State of the art stable isotope correction schemes are available based on MS Excel (Geldern and Barth, 2012; Gröning, 2011) or MS Access (Coplen, 1998). These are specialized to stable isotope measurements only, often only to the post-processing of a special run. Embedding of algorithms into a multipurpose database system was missing. This is necessary to combine results of different tracers (3H, 3He, 2H, 18O, CFCs, SF6...) or geochronological tools (Sediment dating e.g. with 210Pb, 137Cs), to relate to attribute data (submitter, batch, project, geographical origin, depth in core, well information etc.) and for further interpretation tools (e.g. lumped parameter modelling). Database sub-systems to the LabData laboratory management system (Suckow and Dumke, 2001) are presented for stable isotopes and for gas chromatographic CFC and SF6 measurements. The sub-system for stable isotopes allows the following post-processing: 1. automated import from measurement software (Isodat, Picarro, LGR), 2. correction for sample-to sample memory, linearity, drift, and renormalization of the raw data. The sub-system for gas chromatography covers: 1. storage of all raw data 2. storage of peak integration parameters 3. correction for blank, efficiency and linearity The user interface allows interactive and graphical control of the post-processing and all corrections by export to and plot in MS Excel and is a valuable tool for quality control. The sub-databases are integrated into LabData, a multi-user client server architecture using MS SQL server as back-end and an MS Access front-end and installed in four

Stable isotope mass spectrometry in petroleum exploration

International Nuclear Information System (INIS)

Mathur, Manju

1997-01-01

The stable isotope mass spectrometry plays an important role to evaluate the stable isotopic composition of hydrocarbons. The isotopic ratios of certain elements in petroleum samples reflect certain characteristics which are useful for petroleum exploration

Carbon allocation belowground in Pinus pinaster using stable carbon isotope pulse labeling technique

Science.gov (United States)

Dannoura, M.; Bosc, A.; Chipeaux, C.; Sartore, M.; Lambrot, C.; Trichet, P.; Bakker, M.; Loustau, D.; Epron, D.

2010-12-01

Carbon allocation belowground competes with aboveground growth and biomass production. In the other hand, it contributes to resource acquisition such as nutrient, water and carbon sequestration in soil. Thus, a better characterization of carbon flow from plant to soil and its residence time within each compartment is an important issue for understanding and modeling forest ecosystem carbon budget. 13C pulse labeling of whole crown was conducted at 4 seasons to study the fate of assimilated carbon by photosynthesis into the root on 12 year old Pinus pinaster planted in the INRA domain of Pierroton. Maritime pine is the most widely planted species in South-West Europe. Stem, root and soil CO2 effluxes and their isotope composition were measured continuously by tunable diode laser absorption spectroscopy with a trace gas analyzer (TGA 100A; Campbell Scientific) coupled to flow-through chambers. 13CO2 recovery and peak were observed in respiration of each compartment after labeling. It appeared sequentially from top of stem to bottom, and to coarse root. The maximum velocity of carbon transfer was calculated as the difference in time lag of recovery between two positions on the trunk or on the root. It ranged between 0.08-0.2 m h-1 in stem and between 0.04-0.12 m h-1 in coarse root. This velocity was higher in warmer season, and the difference between time lag of recovery and peak increased after first frost. Photosynthates arrived underground 1.5 to 5 days after labeling, at similar time in soil CO2 effluxes and coarse root respiration. 0.08-1.4 g of carbon was respired per tree during first 20 days following labeling. It presented 0.6 -10% of 13C used for labeling and it is strongly related to seasons. The isotope signal was detected in fine root organs and microbial biomass by periodical core sampling. The peak was observed 6 days after labeling in early summer while it was delayed more than 10 days in autumn and winter with less amount of carbon allocated

Deciphering systemic wound responses of the pumpkin extrafascicular phloem by metabolomics and stable isotope-coded protein labeling.

Science.gov (United States)

Gaupels, Frank; Sarioglu, Hakan; Beckmann, Manfred; Hause, Bettina; Spannagl, Manuel; Draper, John; Lindermayr, Christian; Durner, Jörg

2012-12-01

In cucurbits, phloem latex exudes from cut sieve tubes of the extrafascicular phloem (EFP), serving in defense against herbivores. We analyzed inducible defense mechanisms in the EFP of pumpkin (Cucurbita maxima) after leaf damage. As an early systemic response, wounding elicited transient accumulation of jasmonates and a decrease in exudation probably due to partial sieve tube occlusion by callose. The energy status of the EFP was enhanced as indicated by increased levels of ATP, phosphate, and intermediates of the citric acid cycle. Gas chromatography coupled to mass spectrometry also revealed that sucrose transport, gluconeogenesis/glycolysis, and amino acid metabolism were up-regulated after wounding. Combining ProteoMiner technology for the enrichment of low-abundance proteins with stable isotope-coded protein labeling, we identified 51 wound-regulated phloem proteins. Two Sucrose-Nonfermenting1-related protein kinases and a 32-kD 14-3-3 protein are candidate central regulators of stress metabolism in the EFP. Other proteins, such as the Silverleaf Whitefly-Induced Protein1, Mitogen Activated Protein Kinase6, and Heat Shock Protein81, have known defensive functions. Isotope-coded protein labeling and western-blot analyses indicated that Cyclophilin18 is a reliable marker for stress responses of the EFP. As a hint toward the induction of redox signaling, we have observed delayed oxidation-triggered polymerization of the major Phloem Protein1 (PP1) and PP2, which correlated with a decline in carbonylation of PP2. In sum, wounding triggered transient sieve tube occlusion, enhanced energy metabolism, and accumulation of defense-related proteins in the pumpkin EFP. The systemic wound response was mediated by jasmonate and redox signaling.

Stable isotope research pool inventory

International Nuclear Information System (INIS)

1980-12-01

This report contains a listing of electromagnetically separated stable isotopes which are available for distribution within the United States for non-destructive research use from the Oak Ridge National Laboratory on a loan basis. This inventory includes all samples of stable isotopes in the Materials Research Collection and does not designate whether a sample is out on loan or in reprocessing

Stable Isotope Group 1982 progress report

International Nuclear Information System (INIS)

Stewart, M.K.

1983-06-01

The work of the Stable Isotope Group of the Institute of Nuclear Sciences during 1982, in the fields of isotope geology, isotope hydrology, geochronology, isotope biology and mass spectrometer instrumentation, is described

Feasibility of laser-separation of 36S and its use as an atmospheric tracer

International Nuclear Information System (INIS)

Herman, I.P.

1981-01-01

This report addresses one of the possible uses of isotopic tracers, produced by laser-assisted iostope separation, in the investigation of pollution problems. Specifically, the use of laser-produced sulfur isotopes to analyze the acid rain situation is considered as it is a most important application of this technique. The proposed use of isotopically-labelled SO 2 , in particular of 36 SO 2 , as a tracer can help elucidate the chemical and transport facets in a unified experiment. Separation of a sufficient quantity of the rare 36 S isotope to perform several of these tracer studies appears to be practical and economical. This overall process is certainly deserving of further investigation

NMR-based stable isotope resolved metabolomics in systems biochemistry

International Nuclear Information System (INIS)

Fan, Teresa W-M.; Lane, Andrew N.

2011-01-01

An important goal of metabolomics is to characterize the changes in metabolic networks in cells or various tissues of an organism in response to external perturbations or pathologies. The profiling of metabolites and their steady state concentrations does not directly provide information regarding the architecture and fluxes through metabolic networks. This requires tracer approaches. NMR is especially powerful as it can be used not only to identify and quantify metabolites in an unfractionated mixture such as biofluids or crude cell/tissue extracts, but also determine the positional isotopomer distributions of metabolites derived from a precursor enriched in stable isotopes such as 13 C and 15 N via metabolic transformations. In this article we demonstrate the application of a variety of 2-D NMR editing experiments to define the positional isotopomers of compounds present in polar and non-polar extracts of human lung cancer cells grown in either [U– 13 C]-glucose or [U– 13 C, 15 N]-glutamine as source tracers. The information provided by such experiments enabled unambiguous reconstruction of metabolic pathways, which is the foundation for further metabolic flux modeling.

Simultaneous speciation of endogenous and exogenous elements by HPLC/ICP-MS with enriched stable isotopes

International Nuclear Information System (INIS)

Suzuki, K.T.

1996-01-01

High performance liquid chromatography (HPLC)/inductively coupled argon plasma-mass spectrometry (ICP-MS) was introduced to investigate the distributions of selenium (Se) in biological fluids. The method was to determine both the natural abundance of Se and an enriched stable isotope of Se used as a tracer. The distributions of Se in plasma and in urine specimens were determined in Wistar rats on various Se diets with and without an intravenous injection of 82 Se-selenite. Although the distribution of natural abundance Se (endogenous Se) in the plasma was affected little by the nutritional status of Se, that in the urine gave a Se peak depending on the nutritional status of Se, and the peak was identified as methylselenol. When 82 Se-selenite was injected in excess into rats given three different Se diets (Se-deficient, Se-adequate, Se-excessive), three Se peaks occurred in the HPLC chromatogram of the urine samples, corresponding to selenite, methylselenol and trimethylselenonium ion in the order of elution, and the intensities of the tracer peaks reflected the nutritional status. These results indicate that the HPLC/ICP-MS method is a powerful analytical tool for specifying Se-containing biological constituents, both natural abundance and enriched stable isotopes. Methylselenol in urine is proposed to be a sensitive and Se-specific biological indicator for diagnosing the nutritional status of Se. Furthermore, it was shown that an enriched stable isotope such as 82 Se-selenite was shown to be used for the same purpose, and that 82 Se-methylselenol and 82 Se-trimethylselenonium ion in urine were more sensitive indicators of the Se status of the rats. (author)

Stable Isotope Group 1983 progress report

International Nuclear Information System (INIS)

Stewart, M.K.

1984-06-01

The work of the Stable Isotope Group of the Institute of Nuclear Sciences in the fields of isotope geology, isotope hydrology, geochronology, isotope biology and related fields, and mass spectrometer instrumentation, during 1983, is described

Stable isotopes in Lithuanian bioarcheological material

Science.gov (United States)

Skipityte, Raminta; Jankauskas, Rimantas; Remeikis, Vidmantas

2015-04-01

Investigation of bioarcheological material of ancient human populations allows us to understand the subsistence behavior associated with various adaptations to the environment. Feeding habits are essential to the survival and growth of ancient populations. Stable isotope analysis is accepted tool in paleodiet (Schutkowski et al, 1999) and paleoenvironmental (Zernitskaya et al, 2014) studies. However, stable isotopes can be useful not only in investigating human feeding habits but also in describing social and cultural structure of the past populations (Le Huray and Schutkowski, 2005). Only few stable isotope investigations have been performed before in Lithuanian region suggesting a quite uniform diet between males and females and protein intake from freshwater fish and animal protein. Previously, stable isotope analysis has only been used to study a Stone Age population however, more recently studies have been conducted on Iron Age and Late medieval samples (Jacobs et al, 2009). Anyway, there was a need for more precise examination. Stable isotope analysis were performed on human bone collagen and apatite samples in this study. Data represented various ages (from 5-7th cent. to 18th cent.). Stable carbon and nitrogen isotope analysis on medieval populations indicated that individuals in studied sites in Lithuania were almost exclusively consuming C3 plants, C3 fed terrestrial animals, and some freshwater resources. Current investigation demonstrated social differences between elites and country people and is promising in paleodietary and daily life reconstruction. Acknowledgement I thank prof. dr. G. Grupe, Director of the Anthropological and Palaeoanatomical State Collection in Munich for providing the opportunity to work in her laboratory. The part of this work was funded by DAAD. Antanaitis-Jacobs, Indre, et al. "Diet in early Lithuanian prehistory and the new stable isotope evidence." Archaeologia Baltica 12 (2009): 12-30. Le Huray, Jonathan D., and Holger

Visualizing Microbial Biogeochemistry: NanoSIMS and Stable Isotope Probing (Invited)

Science.gov (United States)

Pett-Ridge, J.; Weber, P. K.

2009-12-01

Linking phylogenetic information to function in microbial communities is a key challenge for microbial ecology. Isotope-labeling experiments provide a useful means to investigate the ecophysiology of microbial populations and cells in the environment and allow measurement of nutrient transfers between cell types, symbionts and consortia. The combination of Nano-Secondary Ion Mass Spectrometry (NanoSIMS) analysis, in situ labeling and high resolution microscopy allows isotopic analysis to be linked to phylogeny and morphology and holds great promise for fine-scale studies of microbial systems. In NanoSIMS analysis, samples are sputtered with an energetic primary beam (Cs+, O-) liberating secondary ions that are separated by the mass spectrometer and detected in a suite of electron multipliers. Five isotopic species may be analyzed concurrently with spatial resolution as fine as 50nm. A high sensitivity isotope ratio ‘map’ can then be generated for the analyzed area. NanoSIMS images of 13C, 15N and Mo (a nitrogenase co-factor) localization in diazotrophic cyanobacteria show how cells differentially allocate resources within filaments and allow calculation of nutrient uptake rates on a cell by cell basis. Images of AM fungal hyphae-root and cyanobacteria-rhizobia associations indicate the mobilization and sharing (stealing?) of newly fixed C and N. In a related technique, “El-FISH”, stable isotope labeled biomass is probed with oligonucleotide-elemental labels and then imaged by NanoSIMS. In microbial consortia and cyanobacterial mats, this technique helps link microbial structure and function simultaneously even in systems with unknown and uncultivated microbes. Finally, the combination of re-engineered universal 16S oligonucleotide microarrays with NanoSIMS analyses may allow microbial identity to be linked to functional roles in complex systems such as mats and cellulose degrading hindgut communities. These newly developed methods provide correlated

A new method for the labelling of proteins with radioactive arsenic isotopes

Energy Technology Data Exchange (ETDEWEB)

Jennewein, M. [Institute of Nuclear Chemistry, Johannes Gutenberg University of Mainz, Fritz-Strassmann-Weg 2, 55128 Mainz (Germany); Hermanne, A. [VUB Cyclotron, University of Brussels, Laarbeeklaan 103, 1090 Brussels (Belgium); Mason, R.P. [Department of Radiology, Advanced Radiological Sciences, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas (United States); Thorpe, P.E. [Department of Pharmacology and Simmons and Hamon Cancer Centers, University of Texas Southwestern Medical Center at Dallas, Dallas, TX (United States); Roesch, F. [Institute of Nuclear Chemistry, Johannes Gutenberg University of Mainz, Fritz-Strassmann-Weg 2, 55128 Mainz (Germany)]. E-mail: frank.roesch@uni-mainz.de

2006-12-20

Radioarsenic labelled radiopharmaceuticals could be a valuable asset to positron emission tomography. In particular, the long half-lives of {sup 72}As (T{sub 1/2}=26h) and {sup 74}As (T{sub 1/2}=17.8d) allow to investigate slow physiological or metabolical processes, like the enrichment and distribution of monoclonal antibodies (mab) in tumour tissue. In this work, a new method for the labelling of proteins with various radioactive arsenic isotopes was developed. For this purpose, two proteins, namely a chimeric IgG{sub 3} monoclonal antibody, ch3G4, directed against anionic phospholipids, and Rituxan (Rituximab), were labelled as a proof of principle with no-carrier-added radioarsenic isotopes ({sup 74}As and {sup 77}As). The developed labelling chemistry gives high yields (>99.9%), is reliable and could easily be transferred to automated labelling systems in a clinical environment. At least for the mab used in this work, this route of radioarsenic labelling does not affect the immunoreactivity of the product. The arsenic label stays stable for up to 72h at the molecular mass of the monoclonal antibody, which is in particular relevant to follow the pharmacology and pharmacokinetics of the labelled mab for several days.

Quantification of isotope-labelled and unlabelled folates in plasma, ileostomy and food samples.

Science.gov (United States)

Büttner, Barbara E; Öhrvik, Veronica E; Witthöft, Cornelia M; Rychlik, Michael

2011-01-01

New stable isotope dilution assays were developed for the simultaneous quantitation of [(13)C(5)]-labelled and unlabelled 5-methyltetrahydrofolic acid, 5-formyltetrahydrofolic acid, folic acid along with unlabelled tetrahydrofolic acid and 10-formylfolic acid in clinical samples deriving from human bioavailability studies, i.e. plasma, ileostomy samples, and food. The methods were based on clean-up by strong anion exchange followed by LC-MS/MS detection. Deuterated analogues of the folates were applied as the internal standards in the stable isotope dilution assays. Assay sensitivity was sufficient to detect all relevant folates in the respective samples as their limits of detection were below 0.62 nmol/L in plasma and below 0.73 μg/100 g in food or ileostomy samples. Quantification of the [(13)C(5)]-label in clinical samples offers the possibility to differentiate between folate from endogenous body pools and the administered dose when executing bioavailability trials.

Diurnal variations of organic molecular tracers and stable carbon isotopic composition in atmospheric aerosols over Mt. Tai in the North China Plain: an influence of biomass burning

Directory of Open Access Journals (Sweden)

P. Q. Fu

2012-09-01

Full Text Available Organic tracer compounds, as well as organic carbon (OC, elemental carbon (EC, water-soluble organic carbon (WSOC, and stable carbon isotope ratios (δ¹³C of total carbon (TC have been investigated in aerosol samples collected during early and late periods of the Mount Tai eXperiment 2006 (MTX2006 field campaign in the North China Plain. Total solvent-extractable fractions were investigated by gas chromatography/mass spectrometry. More than 130 organic compounds were detected in the aerosol samples. They were grouped into twelve organic compound classes, including biomass burning tracers, biogenic primary sugars, biogenic secondary organic aerosol (SOA tracers, and anthropogenic tracers such as phthalates, hopanes and polycyclic aromatic hydrocarbons (PAHs. In early June when the field burning activities of wheat straws in the North China Plain were very active, the total identified organics (2090 ± 1170 ng m⁻³ were double those in late June (926 ± 574 ng m⁻³. All the compound classes were more abundant in early June than in late June, except phthalate esters, which were higher in late June. Levoglucosan (88–1210 ng m⁻³, mean 403 ng m⁻³ was found as the most abundant single compound in early June, while diisobutyl phthalate was the predominant species in late June. During the biomass-burning period in early June, the diurnal trends of most of the primary and secondary organic aerosol tracers were characterized by the concentration peaks observed at mid-night or in early morning, while in late June most of the organic species peaked in late afternoon. This suggests that smoke plumes from biomass burning can uplift the aerosol particulate matter to a certain altitude, which could be further transported to and encountered the summit of Mt. Tai during nighttime. On the basis of the tracer-based method for the estimation of biomass-burning OC, fungal-spore OC and biogenic secondary

Stable isotopes and biomarkers in microbial ecology

NARCIS (Netherlands)

Boschker, H.T.S.; Middelburg, J.J.

2002-01-01

The use of biomarkers in combination with stable isotope analysis is a new approach in microbial ecology and a number of papers on a variety of subjects have appeared. We will first discuss the techniques for analysing stable isotopes in biomarkers, primarily gas chromatography-combustion-isotope

Proceedings of Tracer 3. International Conference on Tracers and Tracing Methods

International Nuclear Information System (INIS)

2004-01-01

Tracer 3 conference is a continuation of former Tracer 1 (1998) and Tracer 2 (2001) conferences organized by CNRS - Nancy France. The objective of this 3rd conference is presentation of different aspects of tracer method applications and development of tracer methodology.The new field of activity presented at the Conference was application of stable isotopes as natural tracers for investigations of environmental processes. The conference gave the possibility for scientific information exchange between specialists from different fields of activity such as chemical engineering, chemistry, bioengineering, environmental engineering, hydrology, civil engineering, metallurgy, etc. The presentations were divided into groups covering the principal items of Conference. Section A. Fundamental development - RTD and tracer methodology, - RTD methodology and Computational Fluid Dynamics (CFD), - New tracers and detectors. Section B. Industrial applications - Environment, - Geology, hydrogeology and oil field applications, - Civil engineering, mineral engineering and metallurgy applications, - Food engineering and bioengineering, - Material engineering, - Chemical engineering. During the Conference INIS promotion materials were exposed by INIS liaison officer for Poland

Proceedings of Tracer 3. International Conference on Tracers and Tracing Methods

Energy Technology Data Exchange (ETDEWEB)

NONE

2004-07-01

Tracer 3 conference is a continuation of former Tracer 1 (1998) and Tracer 2 (2001) conferences organized by CNRS - Nancy France. The objective of this 3rd conference is presentation of different aspects of tracer method applications and development of tracer methodology.The new field of activity presented at the Conference was application of stable isotopes as natural tracers for investigations of environmental processes. The conference gave the possibility for scientific information exchange between specialists from different fields of activity such as chemical engineering, chemistry, bioengineering, environmental engineering, hydrology, civil engineering, metallurgy, etc. The presentations were divided into groups covering the principal items of Conference. Section A. Fundamental development - RTD and tracer methodology, - RTD methodology and Computational Fluid Dynamics (CFD), - New tracers and detectors. Section B. Industrial applications - Environment, - Geology, hydrogeology and oil field applications, - Civil engineering, mineral engineering and metallurgy applications, - Food engineering and bioengineering, - Material engineering, - Chemical engineering. During the Conference INIS promotion materials were exposed by INIS liaison officer for Poland.

Isotopic Analysis of Fingernails as a USGS Open House Demonstration of the Use of Stable Isotopes in Foodweb Studies

Science.gov (United States)

Silva, S. R.; Kendall, C.; Young, M. B.; Choy, D.

2011-12-01

The USGS Isotope Tracers Project uses stable isotopes and tritium to add a unique dimension of chemical information to a wide range of environmental investigations. The use and application of isotopes is usually an unfamiliar and even esoteric topic to the general public. Therefore during three USGS open house events, as a public outreach effort, we demonstrated the use of stable isotopes by analyzing nitrogen and carbon isotopes from very small fragments of fingernail from willing participants. We titled the exhibit "You Are What You Eat". The results from all participants were plotted on a graph indicating the general influence of different food groups on the composition of body tissues as represented by fingernails. All participants were assigned a number and no personal-identification information was collected. A subset of participants provided us with an estimate of the number of days a week various foods were eaten and if they were vegetarians, vegans or non-vegetarians. Volunteers from our research group were on hand to explain and discuss fundamental concepts such as how foods attain their isotopic composition, the difference between C3 and C4 plants, the effects of assimilation, trophic enrichment, and the various uses of stable isotopes in environmental studies. The results of the fingernail analyses showed the variation of the range of isotopic compositions among about 400 people at each event, the distinct influence of C4 plants (mainly corn and cane sugar) on our carbon isotopic composition, and the isotopic differences between vegetarians and non vegetarians among other details (http://wwwrcamnl.wr.usgs.gov/isoig/projects/fingernails/). A poll of visitors attending the open house event in 2006 indicated that "You Are What You Eat" was among the most popular exhibits. Following the first two open house events we were contacted by a group of researchers from Brazil who had completed a very similar study. Our collaboration resulted in a publication in

Stable isotope enrichment: Current and future potential

International Nuclear Information System (INIS)

Tracy, J.G.; Aaron, W.S.

1992-01-01

Oak Ridge National Laboratory (ORNL) operates the Isotope Enrichment Facility for the purpose of providing enriched stable isotopes, selected radioactive isotopes (including the actinides), and isotope-related materials and services for use in various research applications. ORNL is responsible for isotope enrichment and the distribution of approximately 225 nongaseous stable isotopes from 50 multi-isotopic elements. Many enriched isotope products are of prime importance in the fabrication of nuclear targets and the subsequent production of special radionuclides. State-of-the-art techniques to achieve special isotopic, chemical, and physical requirements are performed at ORNL This report describes the status and capabilities of the Isotope Enrichment Facility and the Isotope Research Materials Laboratory as well as emphasizing potential advancements in enrichment capabilities

Stable isotope enrichment - current and future potential

International Nuclear Information System (INIS)

Tracy, J.G.; Aaron, W.S.

1993-01-01

Oak Ridge National Laboratory (ORNL) operates the Isotope Enrichment Facility for the purpose of providing enriched stable isotopes, selected radioactive isotopes (including the actinides), and isotope-related materials and services for use in various research applications. ORNL is responsible for isotope enrichment and the distribution of approximately 225 nongaseous stable isotopes from 50 multi-isotopic elements. Many enriched isotope products are of prime importance in the fabrication of nuclear targets and the subsequent production of special radionuclides. State-of-the-art techniques to achieve special isotopic, chemical, and physical requirements are performed at ORNL. This report describes the status and capabilities of the Isotope Enrichment Facility and the Isotope Research Materials Laboratory as well as emphasizing potential advancements in enrichment capabilities. (orig.)

Development of stable isotope manufacturing in Russia

International Nuclear Information System (INIS)

Pokidychev, A.; Pokidycheva, M.

1999-01-01

For the past 25 years, Russia has relied heavily on the electromagnetic separation process for the production of middle and heavy mass stable isotopes. The separation of most light isotopes had been centered in Georgia which, after the collapse of the USSR, left Russia without this capability. In the mid-1970s, development of centrifuge technology for the separation of stable isotopes was begun. Alternative techniques such as laser separation, physical-chemical methods, and ion cyclotron resonance have also been investigated. Economic considerations have played a major role in the development and current status of the stable isotope enrichment capabilities of Russia

Tracing metal-silicate segregation and late veneer in the Earth and the ureilite parent body with palladium stable isotopes

Science.gov (United States)

Creech, J. B.; Moynier, F.; Bizzarro, M.

2017-11-01

Stable isotope studies of highly siderophile elements (HSE) have the potential to yield valuable insights into a range of geological processes. In particular, the strong partitioning of these elements into metal over silicates may lead to stable isotope fractionation during metal-silicate segregation, making them sensitive tracers of planetary differentiation processes. We present the first techniques for the precise determination of palladium stable isotopes by MC-ICPMS using a 106Pd-110Pd double-spike to correct for instrumental mass fractionation. Results are expressed as the per mil (‰) difference in the 106Pd/105Pd ratio (δ106Pd) relative to an in-house solution standard (Pd_IPGP) in the absence of a certified Pd isotopic standard. Repeated analyses of the Pd isotopic composition of the chondrite Allende demonstrate the external reproducibility of the technique of ±0.032‰ on δ106Pd. Using these techniques, we have analysed Pd stable isotopes from a range of terrestrial and extraterrestrial samples. We find that chondrites define a mean δ106Pdchondrite = -0.19 ± 0.05‰. Ureilites reveal a weak trend towards heavier δ106Pd with decreasing Pd content, similar to recent findings based on Pt stable isotopes (Creech et al., 2017), although fractionation of Pd isotopes is significantly less than for Pt, possibly related to its weaker metal-silicate partitioning behaviour and the limited field shift effect. Terrestrial mantle samples have a mean δ106Pdmantle = -0.182 ± 0.130‰, which is consistent with a late-veneer of chondritic material after core formation.

Laser Spectroscopic Analysis of Liquid Water Samples for Stable Hydrogen and Oxygen Isotopes

International Nuclear Information System (INIS)

2009-01-01

Stable isotope ratios of hydrogen and oxygen are tracers of choice for water cycle processes in hydrological, atmospheric and ecological studies. The use of isotopes has been limited to some extent because of the relatively high cost of isotope ratio mass spectrometers and the need for specialized operational skills. Here, the results of performance testing of a recently developed laser spectroscopic instrument for measuring stable hydrogen and oxygen isotope ratios of water samples are described, along with a procedure for instrument installation and operation. Over the last four years, the IAEA Water Resources Programme conducted prototype and production model testing of these instruments and this publication is the outcome of those efforts. One of the main missions of the IAEA is to promote the use of peaceful applications of isotope and nuclear methods in Member States and this publication is intended to facilitate the use of laser absorption based instruments for hydrogen and oxygen stable isotope analyses of liquid water samples for hydrological and other studies. The instrument uses off-axis integrated cavity output spectroscopy to measure absolute abundances of 2 HHO, HH 18 O, and HHO via laser absorption. Test results using a number of natural and synthetic water standards and samples with a large range of isotope values demonstrate adequate precision and accuracy (e.g. precisions of 1 per mille for δ 2 H and 0.2 per mille for δ 18 O). The laser instrument has much lower initial and maintenance costs than mass spectrometers and is substantially easier to operate. Thus, these instruments have the potential to bring about a paradigm shift in isotope applications by enabling researchers in all fields to measure isotope ratios by themselves. The appendix contains a detailed procedure for the installation and operation of the instrument. Using the procedure, new users should be able to install the instrument in less than two hours. It also provides step

The choice of label and measurement technique in tracer studies of body protein metabolism in man

International Nuclear Information System (INIS)

James, W.P.T.; Sender, P.M.; Garlick, P.J.; Waterlow, J.C.

1975-01-01

The turnover of non-serum proteins in man has had limited study despite the physiological importance of maintaining the balance between synthesis and breakdown of body proteins. Body protein is usually considered as a single pool and breakdown rates are often measured by monitoring excreted label at intervals after pulse labelling with radioactive or 15 N amino acids. No label has yet been used for measuring tissue protein breakdown in man which is free from the major problem of label re-utilization. All measurements of breakdown rates, eg. with 75 Se-selenomethionine, 15 N- or 14 C-glycine, give rate constants which are too low. The heterogeneity of body proteins also means that an estimate of the weighted average breakdown rate can only be obtained after following the excretion of isotope for a long period, perhaps of the order of 3-4 half-lives which, for man, would be 100 days after labelling. We therefore use infusions with either 14 C- or 15 N-labelled amino acids to measure breakdown and synthesis rates: these values are less affected by problems of protein heterogeneity. Single injection techniques are subject to more error than constant infusions of label because of the difficulty of defining the precursor activity. 15 N labelling need not be confined to essential amino acids if total protein rather than amino acid turnover is studied: the latter involves measurements of the labelled amino acid itself which is difficult with 15 N because of the small amounts of free amino acid nitrogen available. Carbon labelling of non-essential amino acids is unsuitable for studies of protein turnover and the choice of the position of the label on the molecule is important when labelled essential amino acids are employed. Short-term changes in protein metabolism are evaluated better with amino acids with a small pool size; the equilibration time in the excretory bicarbonate pool is also shorter than in the urea pool so that 15 N is less useful than carbon labelling. We

Authentically radiolabelled Mn(II) complexes as bimodal PET/MR tracers

Energy Technology Data Exchange (ETDEWEB)

Vanasschen, Christian; Brandt, Marie; Ermert, Johannes [Institute of Neuroscience and Medicine, INM-5 - Nuclear Chemistry, Forschungszentrum Jülich (Germany); Neumaier, Bernd [Institute for Radiochemistry and Experimental Molecular Imaging, Medical Clinics, University of Cologne (Germany); Coenen, Heinz H [Institute of Neuroscience and Medicine, INM-5 - Nuclear Chemistry, Forschungszentrum Jülich (Germany)

2015-05-18

The development of small molecule bimodal PET/MR tracers is mainly hampered by the lack of dedicated preparation methods. Authentic radiolabelling of MR contrast agents ensures easy access to such probes: a ligand, chelating a paramagnetic metal ion (e.g. Mn2+) and the corresponding PET isotope (e.g. 52gMn), leads to a “cocktail mixture” where both imaging reporters exhibit the same pharmacokinetics. Paramagnetic [55Mn(CDTA)]2- shows an excellent compromise between thermodynamic stability, kinetic inertness and MR contrast enhancement. Therefore, the aim of this study was to develop new PET/MR tracers by labelling CDTA ligands with paramagnetic manganese and the β+-emitter 52gMn. N.c.a. 52gMn (t1/2: 5.6 d; Eβ+: 575.8 keV (29.6%)) was produced by proton irradiation of a natCr target followed by cation-exchange chromatography. CDTA was radiolabelled with n.c.a. 52gMn2+ in NaOAc buffer (pH 6) at RT. The complex was purified by RP-HPLC and its stability tested in PBS and blood plasma at 37°C. The redox stability was assessed by monitoring the T1 relaxation (20 MHz) in HEPES buffer (pH 7.4). A functionalized CDTA ligand was synthesized in 5 steps. [52gMn(CDTA)]2- was quantitatively formed within 30 min at RT. The complex was stable for at least 6 days in PBS and blood plasma at 37°C and no oxidation occurred within 7 months storage at RT. Labelling CDTA with an isotopic 52g/55Mn2+ mixture led to the corresponding bimodal PET/MR tracer. Furthermore, a functionalized CDTA ligand was synthesized with an overall yield of 18-25%. [52g/55Mn(CDTA)]2-, the first manganese-based bimodal PET/MR tracer prepared, exhibits excellent stability towards decomplexation and oxidation. This makes the functionalized CDTA ligand highly suitable for designing PET/MR tracers with high relaxivity or targeting properties.

Authentically radiolabelled Mn(II) complexes as bimodal PET/MR tracers

International Nuclear Information System (INIS)

Vanasschen, Christian; Brandt, Marie; Ermert, Johannes; Neumaier, Bernd; Coenen, Heinz H

2015-01-01

The development of small molecule bimodal PET/MR tracers is mainly hampered by the lack of dedicated preparation methods. Authentic radiolabelling of MR contrast agents ensures easy access to such probes: a ligand, chelating a paramagnetic metal ion (e.g. Mn2+) and the corresponding PET isotope (e.g. 52gMn), leads to a “cocktail mixture” where both imaging reporters exhibit the same pharmacokinetics. Paramagnetic [55Mn(CDTA)]2- shows an excellent compromise between thermodynamic stability, kinetic inertness and MR contrast enhancement. Therefore, the aim of this study was to develop new PET/MR tracers by labelling CDTA ligands with paramagnetic manganese and the β+-emitter 52gMn. N.c.a. 52gMn (t1/2: 5.6 d; Eβ+: 575.8 keV (29.6%)) was produced by proton irradiation of a natCr target followed by cation-exchange chromatography. CDTA was radiolabelled with n.c.a. 52gMn2+ in NaOAc buffer (pH 6) at RT. The complex was purified by RP-HPLC and its stability tested in PBS and blood plasma at 37°C. The redox stability was assessed by monitoring the T1 relaxation (20 MHz) in HEPES buffer (pH 7.4). A functionalized CDTA ligand was synthesized in 5 steps. [52gMn(CDTA)]2- was quantitatively formed within 30 min at RT. The complex was stable for at least 6 days in PBS and blood plasma at 37°C and no oxidation occurred within 7 months storage at RT. Labelling CDTA with an isotopic 52g/55Mn2+ mixture led to the corresponding bimodal PET/MR tracer. Furthermore, a functionalized CDTA ligand was synthesized with an overall yield of 18-25%. [52g/55Mn(CDTA)]2-, the first manganese-based bimodal PET/MR tracer prepared, exhibits excellent stability towards decomplexation and oxidation. This makes the functionalized CDTA ligand highly suitable for designing PET/MR tracers with high relaxivity or targeting properties.

Inhibition of endogenous lactate turnover with lactate infusion in humans

International Nuclear Information System (INIS)

Searle, G.L.; Feingold, K.R.; Hsu, F.S.; Clark, O.H.; Gertz, E.W.; Stanley, W.C.

1989-01-01

The extent to which lactate infusion may inhibit endogenous lactate production, though previously considered, has never been critically assessed. To examine this proposition, single injection tracer methodology (U- 14 C Lactate) has been used for the estimation of lactate kinetics in 12 human subjects under basal conditions and with the infusion of sodium lactate. The basal rate of lactate turnover was measured on a day before the study with lactate infusion, and averaged 63.7 + 5.5 mg/kg/h. Six of these individuals received a stable lactate infusion at an approximate rate of 160 mg/kg/h, while the remaining six individuals were infused at the approximate rate of 100 mg/kg/h. It has been found that stable lactate infused at rates approximating 160 mg/kg/h consistently produced a complete inhibition of endogenous lactate production. Infusion of lactate at 100 mg/kg/h caused a lesser and more variable inhibition of endogenous lactate production (12% to 64%). In conclusion, lactate infusion significantly inhibits endogenous lactate production

LC/MS Method for the Determination of Stable Isotope Labeled Promethazine in Human Plasma

Science.gov (United States)

Zuwei, Wang; Boyd, Jason; Berens, Kurt L.; Putcha, Lakshmi

2004-01-01

Promethazine (PMZ) is taken by astronauts orally (PO), intramuscularly (IM) or rectally (PR) for space motion sickness. LC/MS method was developed with off-line solid phase extraction to measure plasma concentrations of PMZ given as stable isotope-labeled (SIL) formulations by the three different routes of administration simultaneously. Samples (0.5ml) were loaded on to Waters Oasis HLB co-polymer cartridges and eluted with 1.0 mL methanol. HPLC separation of the eluted sample was performed using an Agilent Zorbax SB-CN column (50 x 2.1 mm) at a flow rate of 0.2 mL/min for 6 min. Acetonitrile/ ammonium acetate (30 mM) in water (3:2, v/v), pH 5.6 plus or minus 0.1, was used as the mobile phase for separation. Concentrations of PMZ, PMZ-d4 and PMZ-d7 and chlorpromazine (internal standard) were determined using a Micromass ZMD single quadrupole mass spectrometer with Electrospray Ionization (ESI). ESI mass spectra were acquired in positive ion mode with selected ion monitoring of [M+ H]dot plus. The method is rapid, reproducible and the assay specific parameters are listed in a table. A novel, sensitive and specific method for the measurement of PMZ and SIL PMZ in human plasma is reported.

Using stable isotopes of carbon and nitrogen as in-situ tracers for monitoring the natural attenuation of explosives

National Research Council Canada - National Science Library

Miyares, Paul H

1999-01-01

The use of carbon and nitrogen stable isotope measurements from TNT was examined as a possible tool for monitoring the natural attenuation of TNT incubation studies of spiked soil samples were conducted...

Strontium isotopes as natural tracers in reservoir oilfield and in groundwater systems

International Nuclear Information System (INIS)

Santos, Marcos E.; Palmieri, Helena E.L.; Moreira, Rubens M.

2009-01-01

The radioactive beta (β - ) decay of 87 Rb to 87 Sr is an important isotope system that has been widely applied for geochronological purposes and in identifying ground water sources, aquifer interactions and as a tracer for a secondary recovery process in offshore oilfields via seawater injection. The 87 Sr/ 86 Sr ratio of present seawater is constant worldwide, while formation waters in hydrocarbon reservoirs have various values are in most cases higher than modern seawater. This can be the basis for a natural tracer technique aiming at evaluating the performance of seawater injection processes by evaluating the 87 Sr/ 86 Sr ratio and the total Sr content of formation waters in the reservoir prior to injection, followed by monitoring these values in the produced water as injection proceeds. Inductively Couple Plasma Mass Spectrometry ICP-MS is a technique that has potential to be used in studies with tracers in the environment in the determination of isotope ratios and element traces in a sample. This work describes the methodology that will be used for the determination of variations in the isotopic composition of Sr and presents the preliminary results obtained determination of the strontium isotope ratios ( 87 Sr/ 86 Sr) using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). (author)

General physical fundamentals of isotope hydrology

International Nuclear Information System (INIS)

Moser, H.; Rauert, W.

1976-01-01

A description is given of the measurement and measuring units of stable isotopes, the physical properties, measurement and measuring units of radioactive isotopes, the fundamentals of the tracer technique, the environmental isotope distribution in the hydrosphere and the radiation protection in isotope hydrological investigations. (HK) [de

Intravascular streaming and variable delivery to brain following carotid artery infusions in the Sprague-Dawley rat

International Nuclear Information System (INIS)

Saris, S.C.; Wright, D.C.; Oldfield, E.H.; Blasberg, R.G.

1988-01-01

Intracarotid artery infusions in animals are commonly performed in studies of the blood-brain barrier and in chemotherapy trials. Implicit in the analysis of these experiments is that the infusate will be distributed to the territory of the internal carotid artery in a manner that is proportional to blood flow. Fifteen Sprague-Dawley rats were studied to determine if poor infusate mixing with blood due to intravascular streaming occurred during intracarotid artery drug infusions and if it could be eliminated with fast retrograde infusion. In three experimental groups, a radiolabeled flow tracer-- 14 C-iodoantipyrine (IAP)--was infused retrograde through the external carotid artery into the common carotid artery at slow, medium, and fast rates (0.45, 1.5, and 5.0 ml/min). In a control group, IAP was injected intravenously (i.v.). Local isotope concentrations in the brain were determined by quantitative autoradiography, and the variability of isotope delivery was assessed in the frontoparietal cortex, temporal cortex, and caudate putamen of all animals. Streaming phenomena were manifest in all selected anatomic areas after the slow and medium rates of intraarterial infusion. After fast intracarotid infusion or i.v. injection, there was uniform distribution of isotope in the same brain regions

Applications of stable isotopes in clinical pharmacology

NARCIS (Netherlands)

Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

2011-01-01

This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the

Using stable isotope tracers to assess hydrological flow paths, residence times and landscape influences in a nested mesoscale catchment

Directory of Open Access Journals (Sweden)

P. Rodgers

2005-01-01

Full Text Available δ18O measurements in precipitation and stream waters were used to investigate hydrological flow paths and residence times at nested spatial scales in the mesoscale (233 km2 River Feugh catchment in the northeast of Scotland over the 2001-2002 hydrological year. Precipitation δ18O exhibited strong seasonal variation, which although significantly damped within the catchment, was reflected in stream water at six sampling sites. This allowed δ18O variations to be used to infer the relative influence of soil-derived storm flows with a seasonally variable isotopic signature, and groundwater of apparently more constant isotopic composition. Periodic regression analysis was then used to examine the sub-catchment difference using an exponential flow model to provide indicative estimates of mean stream water residence times, which varied between approximately 3 and 14 months. This showed that the effects of increasing scale on estimated mean stream water residence time was minimal beyond that of the smallest (ca. 1 km2 headwater catchment scale. Instead, the interaction of catchment soil cover and topography appeared to be the dominant controlling influence. Where sub-catchments had extensive peat coverage, responsive hydrological pathways produced seasonally variable δ18O signatures in runoff with short mean residence times (ca. 3 months. In contrast, areas dominated by steeper slopes, more freely draining soils and larger groundwater storage in shallow valley-bottom aquifers, deeper flow paths allow for more effective mixing and damping of δ18O indicating longer residence times (>12 months. These insights from δ18O measurements extend the hydrological understanding of the Feugh catchment gained from previous geochemical tracer studies, and demonstrate the utility of isotope tracers in investigating the interaction of hydrological processes and catchment characteristics at larger spatial scales.

Stable isotope research pool inventory

International Nuclear Information System (INIS)

1986-08-01

This report contains a listing of electromagnetically separated stable isotopes which are available at the Oak Ridge National Laboratory for distribution for nondestructive research use on a loan basis. This inventory includes all samples of stable isotopes in the Research Materials Collection and does not designate whether a sample is out on loan or is in reprocessing. For some of the high-abundance, naturally occurring isotopes, larger amounts can be made available; for example, Ca-40 and Fe-56. All requests for the loan of samples should be submitted with a summary of the purpose of the loan to: Iotope Distribution Office, Oak Ridge National Laboratory, P.O. Box X, Oak Ridge, Tennessee 37831. Requests from non-DOE contractors and from foreign institutions require DOE approval

Metal Stable Isotope Tagging: Renaissance of Radioimmunoassay for Multiplex and Absolute Quantification of Biomolecules.

Science.gov (United States)

Liu, Rui; Zhang, Shixi; Wei, Chao; Xing, Zhi; Zhang, Sichun; Zhang, Xinrong

2016-05-17

The unambiguous quantification of biomolecules is of great significance in fundamental biological research as well as practical clinical diagnosis. Due to the lack of a detectable moiety, the direct and highly sensitive quantification of biomolecules is often a "mission impossible". Consequently, tagging strategies to introduce detectable moieties for labeling target biomolecules were invented, which had a long and significant impact on studies of biomolecules in the past decades. For instance, immunoassays have been developed with radioisotope tagging by Yalow and Berson in the late 1950s. The later languishment of this technology can be almost exclusively ascribed to the use of radioactive isotopes, which led to the development of nonradioactive tagging strategy-based assays such as enzyme-linked immunosorbent assay, fluorescent immunoassay, and chemiluminescent and electrochemiluminescent immunoassay. Despite great success, these strategies suffered from drawbacks such as limited spectral window capacity for multiplex detection and inability to provide absolute quantification of biomolecules. After recalling the sequences of tagging strategies, an apparent question is why not use stable isotopes from the start? A reasonable explanation is the lack of reliable means for accurate and precise quantification of stable isotopes at that time. The situation has changed greatly at present, since several atomic mass spectrometric measures for metal stable isotopes have been developed. Among the newly developed techniques, inductively coupled plasma mass spectrometry is an ideal technique to determine metal stable isotope-tagged biomolecules, for its high sensitivity, wide dynamic linear range, and more importantly multiplex and absolute quantification ability. Since the first published report by our group, metal stable isotope tagging has become a revolutionary technique and gained great success in biomolecule quantification. An exciting research highlight in this area

Mercury bio magnification in the Atlantic spotted dolphin (Stenella frontalis) food chain, using nitrogen stable isotope as an ecological tracer

International Nuclear Information System (INIS)

Kehrig, Helena A; Baptista, Gilberto; Di Beneditto, Ana Paula M; Almeida, Marcelo G; Rezende, Carlos E; Siciliano, Salvatore; De Moura, Jailson F; Moreira, Isabel

2017-01-01

An assessment of mercury (Hg) concentrations and nitrogen stable isotope (δ"1"5N) was conducted in the food chain of the Atlantic spotted dolphin (Stenella frontalis), including phytoplankton, zooplankton, planktivorous fish and its major prey (predatory fish and a single species of cephalopod), that compose a tropical trophic chain of the Brazilian southeastern coast. Tissue concentrations of Hg in a voracious predator fish, the largehead hairtail (Trichiurus lepturus), one of the dolphin's prey, were 9.8 times lower than median concentrations found in dolphin tissues. δ"1"5N values in predatory fish were found to be lower to those of its predator the spotted dolphin. Isotopic data suggested significant differences for ? 15N along the trophic chain, with the top predator (dolphin) exhibiting heavier value, followed by the voracious predator fish and the benthonic carnivorous fish, the whitemouth croaker (Micropogonias furnieri). Phytoplankton displayed the lightest δ"1"5N, followed by zooplankton and the planktophagous fish, the lebranche mullet (Mugil liza). This fish species and the cephalopod showed the lowest median Hg concentration. All links of the entire trophic chain presented trophic transfer of Hg with a biomagnification factor higher than 1. A significant relationship was found between the log Hg concentration and trophic level (TL) of all evaluated species, with a positive slope (β= 0.87). The calculated trophic magnification factor (TMF7.44) indicates that Hg concentration increased per TL, and also that the entire coastal food chain from the South Atlantic Ocean presented a biomagnification power of Hg within a range previously reported for tropical coastal ecosystems. Key words: Marine mammal, coastal aquatic biota, toxic element, biotransference, ecological tracer

Conditional CO2 flux analysis of a managed grassland with the aid of stable isotopes

Science.gov (United States)

Zeeman, M. J.; Tuzson, B.; Emmenegger, L.; Knohl, A.; Buchmann, N.; Eugster, W.

2009-04-01

Short statured managed ecosystems, such as agricultural grasslands, exhibit high temporal changes in carbon dioxide assimilation and respiration fluxes for which measurements of the net CO2 flux, e.g. by using the eddy covariance (EC) method, give only limited insight. We have therefore adopted a recently proposed concept for conditional EC flux analysis of forest to grasslands, in order to identify and quantify daytime sub-canopy respiration fluxes. To validate the concept, high frequency (≈5 Hz) stable carbon isotope analyis of CO2 was used. We made eddy covariance measurements of CO2 and its isotopologues during four days in August 2007, using a novel quantum cascade laser absorption spectrometer, capable of high time resolution stable isotope analysis. The effects of a grass cut during the measurement period could be detected and resulted in a sub-canopy source conditional flux classification, for which the isotope composition of the CO2 could be confirmed to be of a respiration source. However, the conditional flux method did not work for an undisturbed grassland canopy. We attribute this to the flux measurement height that was chosen well above the roughness sublayer, where the natural isotopic tracer (δ13C) of respiration was too well mixed with background air.

Stable isotopes back-track the origin of alabaster from the 'Ulrich Epitaph', Güstrow, Germany

Science.gov (United States)

Böttcher, Michael E.; Fuchs, Arnold; Gehre, Matthias; Krempler, Michael; Cooper, Anthony H.

2017-04-01

Natural calcium sulphate minerals (like gypsum, in the variety of 'alabaster') have been used for a long time for art and ornamental works despite its high solubility in aqueous solution due to its easy way of recovery and handling. To identify different European source provenances, geochemical and stable isotope forensic methods have been applied, thereby defining historical pathways of trade. A detailed geochemical characterization of both alabaster samples from the monument and potential sources is a pre-requisite for a backtracking material sources. Several tracers have been tested in the past identifiying the coupled sulfur and oxygen isotope composition of the sulfate molecule in the evaporite minerals to be highly characteristic. In the present study, we analyzed the stable sulfur and oxygen isotope composition of raw alabaster from the famous Ulrich Epithaph in Güstrow, Northeastern Germany, and compared the results with new measurements from one of the major European contributors of alabaster in the 16th century, the Cellaston quarry, Derbyshire (England) and literature data for further potential Spanish and Frensh source quarries (Kloppmann et a., 2014; Archaeometry, 56). We found that the stable sulfur and oxygen isotope signatures of alabaster from the Ulrich Epitaph indicate the origin from the Upper Triassic (Keuper) evaporites of the English Cellaston quarry and are not related to other potential alabaster sources. This further illustrates the alabaster trade way between England and Germany in the late 16th century.

Bicarbonate as tracer for plant assimilated C and homogeneity of 14C and 15N distribution in ryegrass and white clover tissue by alternative labeling approaches

DEFF Research Database (Denmark)

Rasmussen, Jim; Kusliene, Gedrime; Jacobsen, Ole Stig

2013-01-01

that 15N also had a heterogeneous distribution (up to two orders of magnitude). Conclusion Bicarbonate can efficiently be used to introduce 14C or 13C into plant via the leaf-labeling method. Both 14C and 15N showed heterogeneous distribution in the plant, although the distribution of 15N was more even......Aims: Application of carbon (C) and nitrogen (N) isotopes is an essential tool to study C and N flows in plant-soil-microorganisms systems. When targeting single plants in a community the tracers need to be added via e.g., leaf-labeling or stem-feeding approaches. In this study we: (i) investigated...... if bicarbonate can be used to introduce 14C (or 13C) into white clover and ryegrass, and (ii) compared the patterns of 14C and 15N allocation in white clover and ryegrass to evaluate the homogeneity of tracer distribution after two alternative labeling approaches. Methods Perennial ryegrass and white clover were...

Applications of isotopes

International Nuclear Information System (INIS)

Kirby-Smith, J.S.

1976-01-01

Current and potential applications of stable isotopes as tracers in a number of biomedical and environmental areas are discussed. It is pointed out that a wide variety of problems exist in these fields whose solutions in principle are amenable to the isotopic approach. The number and diversity of these problems as well as the unique role stable isotopes can play in their solution illustrate the importance of achieving and maintaining a broad inventory of isotopic species. Experience has demonstrated unequivocally an additional overriding requirement for widespread exploration of stable isotopes by the scientific and technical community, i.e., the need for low cost availability of the materials in quantity. Some representative applications of 12 C, 13 C, 14 N, 15 N, 16 O, 17 O, and 18 O are discussed

18O isotopic tracer studies of silicon oxidation in dry oxygen

International Nuclear Information System (INIS)

Han, C.J.

1986-01-01

Oxidation of silicon in dry oxygen has been an important process in the integrated circuit industry for making gate insulators on metal-oxide-semiconductory (MOS) devices. This work examines this process using isotopic tracers of oxygen to determine the transport mechanisms of oxygen through silicon dioxide. Oxides were grown sequentially using mass-16 and mass-18 oxygen gas sources to label the oxygen molecules from each step. The resulting oxides are analyzed using secondary ion mass spectrometry (SIMS). The results of these analyses suggest two oxidant species are present during the oxidation, each diffuses and oxidizes separately during the process. A model from this finding using a sum of two linear-parabolic growth rates, each representing the growth rate from one of the oxidants, describes the reported oxidation kinetics in the literature closely. A fit of this relationship reveals excellent fits to the data for oxide thicknesses ranging from 30 A to 1 μm and for temperatures ranging from 800 to 1200 0 C. The mass-18 oxygen tracers also enable a direct observation of the oxygen solubility in the silicon dioxide during a dry oxidation process. The SIMS profiles establish a maximum solubility for interstitial oxygen at 1000 0 C at 2 x 10 20 cm -3 . Furthermore, the mass-18 oxygen profiles show negligible network diffusion during an 1000 0 C oxidation

Stable isotope views on ecosystem function: challenging or challenged?

Science.gov (United States)

Resco, Víctor; Querejeta, José I; Ogle, Kiona; Voltas, Jordi; Sebastià, Maria-Teresa; Serrano-Ortiz, Penélope; Linares, Juan C; Moreno-Gutiérrez, Cristina; Herrero, Asier; Carreira, José A; Torres-Cañabate, Patricia; Valladares, Fernando

2010-06-23

Stable isotopes and their potential for detecting various and complex ecosystem processes are attracting an increasing number of scientists. Progress is challenging, particularly under global change scenarios, but some established views have been challenged. The IX meeting of the Spanish Association of Terrestrial Ecology (AAET, Ubeda, 18-22 October 2009) hosted a symposium on the ecology of stable isotopes where the linear mixing model approach of partitioning sinks and sources of carbon and water fluxes within an ecosystem was challenged, and new applications of stable isotopes for the study of plant interactions were evaluated. Discussion was also centred on the need for networks that monitor ecological processes using stable isotopes and key ideas for fostering future research with isotopes.

Application of heavy stable isotopes in forensic isotope geochemistry: A review

International Nuclear Information System (INIS)

Aggarwal, Jugdeep; Habicht-Mauche, Judith; Juarez, Chelsey

2008-01-01

Light stable isotopes have been used for many years to characterize the source and transport of materials. More recently heavy isotope systems such as Sr, Nd and Pb have been added to this list in order to aid source identification. With the advent of multiple collector ICP-MS, the range of isotopic tools now available has increased considerably, however, until the isotope systematics of these new non-traditional isotope systems have become better understood, they will not be as useful in characterizing material source and transportation. Applications using heavy metal stable isotopes (mostly traditional heavy isotopes) have reached most avenues in science, including earth sciences, archaeology, anthropology, animal physiology, ecology and toxicology. This field will continue to grow as new applications are developed and techniques become simpler and quicker. This paper provides a review of how this field has grown and presents two new applications using Pb and Sr isotopes in glazes to determine the source of ore used in glazes, and using Sr isotopes to determine the origin of undocumented deceased Mexican border crossers

Application of heavy stable isotopes in forensic isotope geochemistry: A review

Energy Technology Data Exchange (ETDEWEB)

Aggarwal, Jugdeep [W.M. Keck Isotope Laboratory, Department of Earth Sciences, University of California, Santa Cruz, CA 95064 (United States)], E-mail: jaggarwal@pmc.ucsc.edu; Habicht-Mauche, Judith; Juarez, Chelsey [Department of Anthropology, University of California, Santa Cruz, CA 95064 (United States)

2008-09-15

Light stable isotopes have been used for many years to characterize the source and transport of materials. More recently heavy isotope systems such as Sr, Nd and Pb have been added to this list in order to aid source identification. With the advent of multiple collector ICP-MS, the range of isotopic tools now available has increased considerably, however, until the isotope systematics of these new non-traditional isotope systems have become better understood, they will not be as useful in characterizing material source and transportation. Applications using heavy metal stable isotopes (mostly traditional heavy isotopes) have reached most avenues in science, including earth sciences, archaeology, anthropology, animal physiology, ecology and toxicology. This field will continue to grow as new applications are developed and techniques become simpler and quicker. This paper provides a review of how this field has grown and presents two new applications using Pb and Sr isotopes in glazes to determine the source of ore used in glazes, and using Sr isotopes to determine the origin of undocumented deceased Mexican border crossers.

Applications of stable isotope analysis in mammalian ecology.

Science.gov (United States)

Walter, W David; Kurle, Carolyn M; Hopkins, John B

2014-01-01

In this editorial, we provide a brief introduction and summarize the 10 research articles included in this Special Issue on Applications of stable isotope analysis in mammalian ecology. The first three articles report correction and discrimination factors that can be used to more accurately estimate the diets of extinct and extant mammals using stable isotope analysis. The remaining seven applied research articles use stable isotope analysis to address a variety of wildlife conservation and management questions from the oceans to the mountains.

A stable isotope approach for the quantification of sewer infiltration.

Science.gov (United States)

Kracht, Oliver; Gresch, Markus; Gujert, Willi

2007-08-15

Extraneous flows in wastewater collection systems are conventionally evaluated solely on the consideration of discharge hydrographs, which often involves a great degree of subjectivity and oversimplification. To obtain reliable information on the material fluxes within the urban environment, the use of intrinsic tracers can be the optimal choice. We demonstrate the successful use of naturally occurring stable isotopes of water (18O/16O and D/H) to accurately quantify extraneous discharge of groundwater in a combined sewer network. Fresh water supply from a distant hydrological regime provided usable isotopic separations between drinking water (proxy for real foul sewage) and local groundwater (proxy for sewer infiltration) of 1.8 per thousand in delta18O and 11.7 per thousand in 62H. Diurnal variation of wastewater isotopic composition reflected both the varying rates of foul sewage production and irregular dispersion effects in the pipe network. The latter suggest the existence of larger cumulative backwater zone volumes, which have not been attended to yet. Infiltrating groundwater contributed 39% (95% confidence interval = +/- 2.5%) of the total daily dry weather wastewater discharge. This paper discusses all relevant aspects for practical application of the method. It presents a comprehensive framework for uncertainty analysis and details on the detection and discrimination of possibly interfering effects.

Quantification of long-term wastewater fluxes at the surface water/groundwater-interface: an integrative model perspective using stable isotopes and acesulfame.

Science.gov (United States)

Engelhardt, I; Barth, J A C; Bol, R; Schulz, M; Ternes, T A; Schüth, C; van Geldern, R

2014-01-01

The suitability of acesulfame to trace wastewater-related surface water fluxes from streams into the hyporheic and riparian zones over long-term periods was investigated. The transport behavior of acesulfame was compared with the transport of water stable isotopes (δ(18)O or δ(2)H). A calibrated model based on a joint inversion of temperature, acesulfame, and piezometric pressure heads was employed in a model validation using data sets of acesulfame and water stable isotopes collected over 5months in a stream and groundwater. The spatial distribution of fresh water within the groundwater resulting from surface water infiltration was estimated by computing groundwater ages and compared with the predicted acesulfame plume obtained after 153day simulation time. Both, surface water ratios calculated with a mixing equation from water stable isotopes and simulated acesulfame mass fluxes, were investigated for their ability to estimate the contribution of wastewater-related surface water inflow within groundwater. The results of this study point to limitations for the application of acesulfame to trace surface water-groundwater interactions properly. Acesulfame completely missed the wastewater-related surface water volumes that still remained in the hyporheic zone under stream-gaining conditions. In contrast, under stream-losing conditions, which developed after periods of stagnating hydraulic exchange, acesulfame based predictions lead to an overestimation of the surface water volume of up to 25% in the riparian zone. If slow seepage velocities prevail a proportion of acesulfame might be stored in smaller pores, while when released under fast flowing water conditions it will travel further downstream with the groundwater flow direction. Therefore, under such conditions acesulfame can be a less-ideal tracer in the hyporheic and riparian zones and additional monitoring with other environmental tracers such as water stable isotopes is highly recommended. © 2013 Elsevier

Quantification of long-term wastewater fluxes at the surface water/groundwater-interface: An integrative model perspective using stable isotopes and acesulfame

Energy Technology Data Exchange (ETDEWEB)

Engelhardt, I., E-mail: i.engelhardt@fz-juelich.de [Forschungszentrum Jülich, Institute of Bio- and Geosciences, Agrosphere — IBG-3 (Germany); Technical University of Darmstadt, Institute of Applied Geosciences (Germany); Barth, J.A.C. [GeoZentrum Nordbayern, University of Erlangen-Nuremberg (Germany); Bol, R. [Forschungszentrum Jülich, Institute of Bio- and Geosciences, Agrosphere — IBG-3 (Germany); Schulz, M.; Ternes, T.A. [Federal Institute of Hydrology (BfG) (Germany); Schüth, C. [Technical University of Darmstadt, Institute of Applied Geosciences (Germany); van Geldern, R. [GeoZentrum Nordbayern, University of Erlangen-Nuremberg (Germany)

2014-01-01

The suitability of acesulfame to trace wastewater-related surface water fluxes from streams into the hyporheic and riparian zones over long-term periods was investigated. The transport behavior of acesulfame was compared with the transport of water stable isotopes (δ{sup 18}O or δ{sup 2}H). A calibrated model based on a joint inversion of temperature, acesulfame, and piezometric pressure heads was employed in a model validation using data sets of acesulfame and water stable isotopes collected over 5 months in a stream and groundwater. The spatial distribution of fresh water within the groundwater resulting from surface water infiltration was estimated by computing groundwater ages and compared with the predicted acesulfame plume obtained after 153 day simulation time. Both, surface water ratios calculated with a mixing equation from water stable isotopes and simulated acesulfame mass fluxes, were investigated for their ability to estimate the contribution of wastewater-related surface water inflow within groundwater. The results of this study point to limitations for the application of acesulfame to trace surface water–groundwater interactions properly. Acesulfame completely missed the wastewater-related surface water volumes that still remained in the hyporheic zone under stream-gaining conditions. In contrast, under stream-losing conditions, which developed after periods of stagnating hydraulic exchange, acesulfame based predictions lead to an overestimation of the surface water volume of up to 25% in the riparian zone. If slow seepage velocities prevail a proportion of acesulfame might be stored in smaller pores, while when released under fast flowing water conditions it will travel further downstream with the groundwater flow direction. Therefore, under such conditions acesulfame can be a less-ideal tracer in the hyporheic and riparian zones and additional monitoring with other environmental tracers such as water stable isotopes is highly recommended

Stable isotopes and the environment

International Nuclear Information System (INIS)

Krouse, H.R.

1990-01-01

Whereas traditionally, stable isotope research has been directed towards resource exploration and development, it is finding more frequent applications in helping to assess the impacts of resource utilization upon ecosystems. Among the many pursuits, two themes are evident: tracing the transport and conversions of pollutants in the environment and better understanding of the interplay among environmental receptors, e.g. food web studies. Stable isotope data are used primarily to identify the presence of pollutants in the environment and with a few exceptions, the consequence of their presence must be assessed by other techniques. Increasing attention has been given to the isotopic composition of humans with many potential applications in areas such as paleodiets, medicine, and criminology. In this brief overview examples are used from the Pacific Rim to illustrate the above concepts. 26 refs., 1 tab., 3 figs

Enriching stable isotopes: Alternative use for Urenco technology

International Nuclear Information System (INIS)

Rakhorst, H.; de Jong, P.G.T.; Dawson, P.D.

1996-01-01

The International Urenco Group utilizes a technologically advanced centrifuge process to enrich uranium in the fissionable isotope 235 U. The group operates plants in the United Kingdom, the Netherlands, and Germany and currently holds a 10% share of the multibillion dollar world enrichment market. In the early 1990s, Urenco embarked on a strategy of building on the company's uniquely advanced centrifuge process and laser isotope separation (LIS) experience to enrich nonradioactive isotopes colloquially known as stable isotopes. This paper summarizes the present status of Urenco's stable isotopes business

Stable isotope views on ecosystem function: challenging or challenged?

Science.gov (United States)

Resco, Víctor; Querejeta, José I.; Ogle, Kiona; Voltas, Jordi; Sebastià, Maria-Teresa; Serrano-Ortiz, Penélope; Linares, Juan C.; Moreno-Gutiérrez, Cristina; Herrero, Asier; Carreira, José A.; Torres-Cañabate, Patricia; Valladares, Fernando

2010-01-01

Stable isotopes and their potential for detecting various and complex ecosystem processes are attracting an increasing number of scientists. Progress is challenging, particularly under global change scenarios, but some established views have been challenged. The IX meeting of the Spanish Association of Terrestrial Ecology (AAET, Úbeda, 18–22 October 2009) hosted a symposium on the ecology of stable isotopes where the linear mixing model approach of partitioning sinks and sources of carbon and water fluxes within an ecosystem was challenged, and new applications of stable isotopes for the study of plant interactions were evaluated. Discussion was also centred on the need for networks that monitor ecological processes using stable isotopes and key ideas for fostering future research with isotopes. PMID:20015858

Slow and preferential flow in the unsaturated zone and its impact on stable isotope composition

International Nuclear Information System (INIS)

Seiler, K.P.

2001-01-01

Stable isotope methods (δ 18 O and δ 2 H) have been used investigate the importance of bypass flow in the unsaturated zone which leads to unproductive water loss during flood irrigation. Field experiments have been carried out in Jordan and Pakistan in order to determine the occurrence of bypass flow, its amount and its velocity compared to piston flow. Results show that there is not only an advective component of flow (bypass flow) but a diffusive tracer exchange between piston and bypass flow. Infiltration calculations and analysis of tracer distributions are used to show that at the research sites, bypass flow amounts to about 25% of water recharged during winter. This estimate is important as it provides an assessment of the amount of water that passes the root zone and directly recharges groundwater. (author)

Cell-free expression and stable isotope labelling strategies for membrane proteins

International Nuclear Information System (INIS)

Sobhanifar, Solmaz; Reckel, Sina; Junge, Friederike; Schwarz, Daniel; Kai, Lei; Karbyshev, Mikhail; Loehr, Frank; Bernhard, Frank; Doetsch, Volker

2010-01-01

Membrane proteins are highly underrepresented in the structural data-base and remain one of the most challenging targets for functional and structural elucidation. Their roles in transport and cellular communication, furthermore, often make over-expression toxic to their host, and their hydrophobicity and structural complexity make isolation and reconstitution a complicated task, especially in cases where proteins are targeted to inclusion bodies. The development of cell-free expression systems provides a very interesting alternative to cell-based systems, since it circumvents many problems such as toxicity or necessity for the transportation of the synthesized protein to the membrane, and constitutes the only system that allows for direct production of membrane proteins in membrane-mimetic environments which may be suitable for liquid state NMR measurements. The unique advantages of the cell-free expression system, including strong expression yields as well as the direct incorporation of almost any combination of amino acids with very little metabolic scrambling, has allowed for the development of a wide-array of isotope labelling techniques which facilitate structural investigations of proteins whose spectral congestion and broad line-widths may have earlier rendered them beyond the scope of NMR. Here we explore various labelling strategies in conjunction with cell-free developments, with a particular focus on α-helical transmembrane proteins which benefit most from such methods.

Indium-111 tropolone, a new tracer for platelet labeling

International Nuclear Information System (INIS)

Dewanjee, M.K.; Rao, S.A.; Rosemark, J.A.; Chowdhury, S.; Didisheim, P.

1982-01-01

Platelets have been labeled with a new neutral, lipid-soluble metal complex of indium 111 ( 111 In) and tropolone. Unlike oxine, which is soluble in ethyl alcohol, tropolone is soluble in isotonic saline. Platelet labeling with 111 In tropolone can be performed in both acid-citrate-dextrose (ACD) plasma and ACD saline within two hours. Labeling efficiency has been 80% to 90%. 111 In tropolone in ACD saline and ACD plasma at tropolone concentrations of 5 and 10 micrograms/ml, respectively, and incubation of the platelets with the tracer at room temperature for 20 minutes were optimal conditions for labeling. The authors have developed an ACD-saline kit for convenient preparation of 111 In-labeled platelets. No adverse effect of 111 In tropolone on platelets has been observed in studies of biodistribution, recovery, and survival of platelets in rabbits and dogs

Indium-111 tropolone, a new tracer for platelet labeling

International Nuclear Information System (INIS)

Dewanjee, M.K.; Rao, S.A.; Rosemark, J.A.; Chowdhury, S.; Didisheim, P.

1982-01-01

Platelets have been labeled with a new neutral, lipid-soluble metal complex of indium 111 ( 111 In) and tropolone. Unlike oxine, which is soluble in ethyl alcohol, tropolone is soluble in isotonic saline. Platelet labeling with 111 In tropolone can be performed in both acid-citrate-dextrose (ACD) plasma and ACD saline within two hours. Labeling efficiency has been 80% to 90%. 111 In tropolone in ACD saline and ACD plasma at tropolone concentrations of 5 to 10 μg/ml, respectively, and incubation of the platelets with the tracer at room temperature for 20 minutes were optimal conditions for labeling. The authors have developed an ACD-saline kit for convenient preparation of 111 In-labeled platelets. No adverse effect of 111 In tropolone on platelets has been observed in studies of biodistribution, recovery, and survival of platelets in rabbits and dogs

Isotopically labelled vitamin D derivatives and processes for preparing same

International Nuclear Information System (INIS)

Deluca, H.R.; Schnoes, H.K.; Napoli, J.L.; Fivizzani, M.A.

1981-01-01

This invention relates to 26,27-isotopically labelled vitamin D 3 compounds, including radiolabelled vitamin D 3 compounds of high specific activity, methods for their preparation, and intermediates obtained in their synthesis. The method involves reacting an ester of a 26,27-dinor-vitamin D-25-carboxylic acid with an isotopically labelled methyl Grignard reagent or methyl lithium reagent to obtain a 26,27-isotopically labelled compound in which at least some of the H atoms and/or C atoms are heavy isotopes. (author)

Failure to label baboon milk intrinsically with iron

International Nuclear Information System (INIS)

Figueroa-Colon, R.; Elwell, J.H.; Jackson, E.; Osborne, J.W.; Fomon, S.J.

1989-01-01

The widely held belief that 50% of the iron in human milk is absorbed is based on studies that have used an extrinsic radioactive iron tag. To determine the validity of an extrinsic tag, it is necessary to label the milk intrinsically with one isotope and to compare absorption of this isotope with absorption of another isotope added as the extrinsic tag. We chose the baboon as a model and infused 59Fe intravenously. In each of three attempts we failed to label the milk intrinsically

Measuring Protein Synthesis Rate In Living Object Using Flooding Dose And Constant Infusion Methods

OpenAIRE

Ulyarti, Ulyarti

2018-01-01

Constant infusion is a method used for measuring protein synthesis rate in living object which uses low concentration of amino acid tracers. Flooding dose method is another technique used to measure the rate of protein synthesis which uses labelled amino acid together with large amount of unlabelled amino acid.  The latter method was firstly developed to solve the problem in determination of precursor pool arise from constant infusion method.  The objective of this writing is to com...

Fifty years of radiochemical tracers

International Nuclear Information System (INIS)

Evans, E.A.

1992-01-01

During the past 50 years radiochemical tracers, usually in the form of isotopically labelled organic compounds, have been essential tools to further advance our knowledge at the frontiers of a great variety of scientific developments in the life sciences. This plenary lecture reviews necessarily selected highlights in the synthesis and applications of such radiochemical tracers. Included are examples where important advances, made possible by using radiochemicals, have contributed to improving the quality of life on this planet. The principal radioisotopes involved, 14 C, 3 H, 35 S, 32 P, 125 I, are all relatively safe to handle and are commercially available at maximum theoretical specific activity (carrier free). The compounds labeled with these radioisotopes are used in many fields of research which include biosynthesis and biotechnology studies, cell biology, drug metabolism, clinical research and environmental applications, and are briefly reviewed. (author). 55 refs

Stable isotope composition of human fingernails from Slovakia

International Nuclear Information System (INIS)

Grolmusová, Zuzana; Rapčanová, Anna; Michalko, Juraj; Čech, Peter; Veis, Pavel

2014-01-01

Stable isotope composition of human fingernails has proven to be useful for documenting human dietary information and geographical patterns in archeological, forensic, anthropological and biological studies. Therefore, it is of interest to detect all factors influencing the stable isotopic composition in the certain regions in the world. Carbon and nitrogen isotope data of human fingernail keratin from 52 individuals from Slovakia were reported in this study. The online combustion and continuous flow isotope-ratio mass spectrometer Delta V Advantage was used for δ 13 C and δ 15 N analysis of fingernail keratin samples from 24 vegetarian and 28 omnivorous individuals. A group of people with frequent meat consumption showed enrichment in 13 C and 15 N isotopes in fingernails. A similar trend was observed with increasing seafood in an individual's diet. Moreover a significant difference was revealed between smokers and nonsmokers for both δ 13 C and δ 15 N values. These data were compared to previously published δ 13 C and δ 15 N fingernail values from across the globe. This study brings new information on the stable isotope signature of individuals from Slovakia and characterizes the Central European region for the first time. The stable isotope composition of fingernails is influenced by the frequency of meat and seafood consumption as well as smoking. - Highlights: • This study deals with stable isotope analyses of fingernails from Slovak volunteers. • δ 13 C and δ 15 N values of vegetarian and omnivore fingernails were compared. • Influence of sex, diet and smoking was studied

Sequencing of Isotope-Labeled Small RNA Using Femtosecond Laser Ablation Time-of-Flight Mass Spectrometry

Science.gov (United States)

Kurata-Nishimura, Mizuki; Ando, Yoshinari; Kobayashi, Tohru; Matsuo, Yukari; Suzuki, Harukazu; Hayashizaki, Yoshihide; Kawai, Jun

2010-04-01

A novel method for the analysis of sequences of small RNAs using nucleotide triphosphates labeled with stable isotopes has been developed using time-of-flight mass spectroscopy combined with femtosecond laser ablation (fsLA-TOF-MS). Small RNAs synthesized with nucleotides enriched in 13C and 15N were efficiently atomized and ionized by single-shot fsLA and the isotope ratios 13C/12C and 15N/14N were evaluated using the TOF-MS method. By comparing the isotope ratios among four different configurations, the number of nucleotide contents of the control RNA sample were successfully reproduced.

Measurement of Hepatic Protein Fractional Synthetic Rate with Stable Isotope Labeling Technique in Thapsigargin Stressed HepG2 Cells

Science.gov (United States)

Song, Juquan; Zhang, Xiao-jun; Boehning, Darren; Brooks, Natasha C.; Herndon, David N.; Jeschke, Marc G.

2012-01-01

Severe burn-induced liver damage and dysfunction is associated with endoplasmic reticulum (ER) stress. ER stress has been shown to regulate global protein synthesis. In the current study, we induced ER stress in vitro and estimated the effect of ER stress on hepatic protein synthesis. The aim was two-fold: (1) to establish an in vitro model to isotopically measure hepatic protein synthesis and (2) to evaluate protein fractional synthetic rate (FSR) in response to ER stress. Human hepatocellular carcinoma cells (HepG2) were cultured in medium supplemented with stable isotopes 1,2-13C2-glycine and L-[ring-13C6]phenylalanine. ER stress was induced by exposing the cells to 100 nM of thapsigargin (TG). Cell content was collected from day 0 to 14. Alterations in cytosolic calcium were measured by calcium imaging and ER stress markers were confirmed by Western blotting. The precursor and product enrichments were detected by GC-MS analysis for FSR calculation. We found that the hepatic protein FSR were 0.97±0.02 and 0.99±0.05%/hr calculated from 1,2-13C2-glycine and L-[ring-13C6]phenylalanine, respectively. TG depleted ER calcium stores and induced ER stress by upregulating p-IRE-1 and Bip. FSR dramatically decreased to 0.68±0.03 and 0.60±0.06%/hr in the TG treatment group (pisotope tracer incorporation technique is a useful method for studying the effects of ER stress on hepatic protein synthesis. PMID:22298954

Field ionization mass spectrometry (FIMS) applied to tracer studies and isotope dilution analysis

International Nuclear Information System (INIS)

Anbar, M.; Heck, H.d'A.; McReynolds, J.H.; St John, G.A.

1975-01-01

The nonfragmenting nature of field ionization mass spectrometry makes it a preferred technique for the isotopic analysis of multilabeled organic compounds. The possibility of field ionization of nonvolatile thermolabile materials significantly extends the potential uses of this technique beyond those of conventional ionization methods. Multilabeled tracers may be studied in biological systems with a sensitivity comparable to that of radioactive tracers. Isotope dilution analysis may be performed reliably by this technique down to picogram levels. These techniques will be illustrated by a number of current studies using multilabeled metabolites and drugs. The scope and limitations of the methodology are discussed

Gas phase thermal diffusion of stable isotopes

International Nuclear Information System (INIS)

Eck, C.F.

1979-01-01

The separation of stable isotopes at Mound Facility is reviewed from a historical perspective. The historical development of thermal diffusion from a laboratory process to a separation facility that handles all the noble gases is described. In addition, elementary thermal diffusion theory and elementary cascade theory are presented along with a brief review of the uses of stable isotopes

Use of isotopic tracers in pesticide and environmental contamination research

International Nuclear Information System (INIS)

Casida, J.E.

1976-01-01

The era of synthetic organic pesticides, starting with DDT and the herbicide 2,4-D about 1940, coincides with that of rapid advances in radiotracer applications. This is indeed fortunate since isotopic experiments are an essential step in evaluating each new pesticide and in continually reassessing older compounds for safety and most efficient utilization. This research is carried out in all developed nations with important supplementation on local problems or use conditions from investigations in the developing countries. Several slides will help illustrate the sequence of studies for establishing the disposition and fate of pesticides and other environmental contaminants.It is clear that very little of the pesticide ever contacts the pest. Pesticide chemicals are generally applied at dosages of 0.2 to 2 kilogram per hectare from one to five or more times per crop season. Less than 0.01% of an insecticide is absorbed or ingested by the pest insect. The remaining amount, more than 99.99%, is an environmental contaminant, a portion of which is a potential residue in food, feed and fibre. Isotopic research is critical in understanding or solving several aspects of the problem. The isotopic label is introduced into the chemical by synthesis in a commercial or university laboratory or in a national or regional atomic research centre. The most common radioisotopes used are tritium, 14carbon, 32phosphorus, 35sulphur and 36chlorine. Stable isotopes are becoming increasingly important in pesticide research, particularly carbon 13, nitrogen 15 and oxygen 18. The initial studies usually involve administration of the 14 carbon-labelled pesticide to rats, which are then held in metabolism cages that allow separate collection of expired gases, urine and faeces. The products in the excreta are identified by various chromatographic and spectroscopic techniques. The persistence of the chemical and its metabolites in various tissues is also determined to make sure that the material

Custom synthesis of isotope-labelled Apis mellifera Pheromone

International Nuclear Information System (INIS)

Conanan, Aida P.; Cortes, Nicole Marie A.; Daguno, Cristel Lyn R.; Templonuevo, Jose Angelo A.; Sucgang, Raymond J.

2012-01-01

The object of this study is to determine the optimum conditions for the synthesis of the isotope-labelled isopentyl acetate. Isopentyl acetate is widely used as a raw material in industries, in syntheses, and is utilized as a sex attractant (pheromone) by the bee species, Apis mellifera. The isotope labelling of isopentyl acetate will allow tracking of the fate and movement of the isopentyl acetate in the environment, in chemical transformations, and in biological systems. Esterification by alcoholysis of acetic acid was optimized for the preparation of Carbon-14( 14 C)-labelled isopentyl acetate from 14 C-labelled acetic acid and isoamyl alcohol. The different conditions studied were: (1) The effects of acid catalysis and/or reflux on the incorporation and retention of the isotope label on the product. The efficiency of label incorporation and retention was determined through the beta radioactivity of Carbon 14 in each of the synthetic constructs. Determination of the beta radioactivity concentration of 14 C in the isopentyl acetate product was done using low level liquid scintillation spectrometry. Each of the synthetic products was mixed with Ultima Gold scintillation cocktail in a low potassium glass scintillation vial, and analysed in a low-level Wallac 1414 scintillation counter. The application of catalysis without reflux resulted in the highest yield (35%). The same condition also resulted in the highest abundance of carbon isotope label with 2.40 Bequerels per cubic centimetre, Bq/cc (measurement unit for radioactivity). (author)

Metabolism and pharmacokinetic of cyclo-peptides and peptides. Use of radioelement and stable isotopes

International Nuclear Information System (INIS)

Aninat, C.

2003-10-01

More and more peptides and proteins are used in therapeutic. Three mainly techniques are used for pharmacokinetic and metabolism studies: immunoassay, radioactively labeled molecules and mass spectrometry. In the first part of this work, we have used uniformly labelled peptides (C-peptide and insulin) with stables ( 13 C, 15 N, and 13 C/ 15 N) or radioactive ( 14 C) isotopes to investigated these kind of studies. These works are based on isotope dilution mass spectrometry assay. In a second time we have investigated the metabolism of a particular cyclo-peptides families composed of two amino acids: the diketo-piperazine. These compounds are found in mammals and in microorganisms. There are not recognized by proteolytic enzymes. We have estimated if the main enzymes implicated in the metabolism of xenobiotics, the P450 cytochrome mono-oxygenases, were able to recognized them

Culture of microalgae Spirulina platensis with isotope stable Carbon-13

International Nuclear Information System (INIS)

Cronemberger, Luiz C.A.; Costa, Vladimir E.

2017-01-01

Gastric emptying time abnormalities cause complications that affect the quality of life in humans and scintigraphy is the gold standard for this diagnosis. However its application has restrictions due to the use of the radiopharmaceutical 99m Tc. An alternative to this method is the stable carbon isotope respiratory test. This is a non-radioactive, noninvasive technique with no contraindications. Its application varies according to the substrate used. For evaluation of gastric emptying time one of the substrates that can be used in the respiratory test is Spirulina platensis labeled at 97% carbon atoms with the stable isotope carbon-13 ( 13 C). In Brazil, there is no production of this substrate and its high cost (US$475.00/g, excluding import taxes) makes it difficult to apply the test. Thus, the objective of the work is to cultivate labeled S. platensis at 97% of 13 C for use in the respiratory test for gastric emptying and to establish optimization parameters for the best cost-benefit of this culture. In the cultivation process the microalgae will be kept in a closed sterilized glass volumetric flask, with deionized water and a pure 13 C source. The light (photoperiod 12h light / dark), pH (∼ 9.5) and temperature (30 deg C) will be controlled and after 35-40 days of growth, the cyanobacteria will be lyophilized and ground for the acquisition of a powder that will be analyzed by IRMS and compared to S. platensis, which will be our reference standard

Stable isotope probing to study functional components of complex microbial ecosystems.

Science.gov (United States)

Mazard, Sophie; Schäfer, Hendrik

2014-01-01

This protocol presents a method of dissecting the DNA or RNA of key organisms involved in a specific biochemical process within a complex ecosystem. Stable isotope probing (SIP) allows the labelling and separation of nucleic acids from community members that are involved in important biochemical transformations, yet are often not the most numerically abundant members of a community. This pure culture-independent technique circumvents limitations of traditional microbial isolation techniques or data mining from large-scale whole-community metagenomic studies to tease out the identities and genomic repertoires of microorganisms participating in biological nutrient cycles. SIP experiments can be applied to virtually any ecosystem and biochemical pathway under investigation provided a suitable stable isotope substrate is available. This versatile methodology allows a wide range of analyses to be performed, from fatty-acid analyses, community structure and ecology studies, and targeted metagenomics involving nucleic acid sequencing. SIP experiments provide an effective alternative to large-scale whole-community metagenomic studies by specifically targeting the organisms or biochemical transformations of interest, thereby reducing the sequencing effort and time-consuming bioinformatics analyses of large datasets.

A new methodology involving stable isotope tracer to compare short- and long- term selenium mobility in soils

Science.gov (United States)

Tolu, Julie; Thiry, Yves; Potin-gautier, Martine; Le hécho, Isabelle; Bueno, Maïté

2013-04-01

Selenium is an element of environmental concern given its dual beneficial and toxic character to animal and human health. Its radioactive isotope 79Se, a fission product of 235U, is considered critical in safety assessment of nuclear waste repositories in case of leakage and hypothetical soil contamination. Therefore, Se species transformations and interactions with soil components have to be clearly understood to predict its dispersion in the biosphere (e.g., accumulation in soils, migration to waters, transfer to living organisms). While natural Se interactions with soils run over centuries to millennia time scales, transformations and partitioning are generally studied with short-term experiments (often inferior to 1 month) after Se addition. The influence of slower, long-term processes involved in Se speciation and mobility in soils is thus not properly accounted for. We tested if using ambient Se would be relevant for long-term risk assessment while added Se would be more representative of short-term contamination impact. For that purpose, we developed a new methodology to trace the differential reactivity of ambient and spiked Se at trace level (µg kg-1) in soils. It combined the use of a stable isotopically enriched tracer with our previous published analytical method based on specific extractions and HPLC-ICP-MS to determine trace Se species partition in different soil phases. Given that soil extracts contains very high concentrations of various elements interfering Se (e.g., Fe, Cl, Br), the ICP-MS parameters and mathematical corrections were optimized to cope with such interferences. Following optimization, three correct and accurate (<2%) isotope ratios were obtained with 77Se, 78Se, 80Se and 82Se. The optimized method was then applied to an arable and a forest soil submitted to an aging process (drying/wetting cycles) during three months, to which 77Se(IV) was previously added. The results showed that ambient Se was at steady state in terms of water

Lead isotope ratios as a tracer for lead contamination sources: A lake Andong case study

Directory of Open Access Journals (Sweden)

Kim Y. H

2013-04-01

Full Text Available The objective of this study was to evaluate stable Pb isotope signatures as a tracer for Pb contamination in Lake Andong. For Pb isotope analysis, we collected water and sediment from Lake Andong, particles in the air, soils, and stream water, mine tailings, sludge and wastewater from zinc smelting around lake Andong watershed. The results showed that Pb isotope ratios (206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb for zinc concentrate were 18.809 ± 0.322, 15.650 ± 0.062, and 38.728 ± 0.421, respectively. In wastewater, isotopic ratio values (206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb were 17.363 ± 0.133, 15.550 ± 0.025, and 37.217 ± 0.092, respectively. Additionally, isotopic ratio values (206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb for sludge were 17.515 ± 0.155, 15.537 ± 0.018, and 37.357 ± 0.173, respectively. These values were similar to those in zinc and lead concentrate originated from Canada and South America. In contrast, Pb isotope ratios of soil, tailings and sediment from Lake Andong were similar to those of Korean ore. Atmospheric particles showed different patterns of Pb isotope ratios from sediments, soils, and zinc smelting and this needs further investigation in order to identify atmospheric Pb sources.

Blood cells kinetics by stable tracers assayed by XRF-analysis and by radioactive tracers

International Nuclear Information System (INIS)

Cesareo, R.; Del Principe, D.; Tallarida, B.

1980-01-01

Stable rubidium, as an analogue of potassium, has been employed to label human and rabbit red cells and platelets. The concentration of rubidium bound to the cells, which are deposited on filter paper disks, is assayed by a simple version of the X-ray fluorescence equipment, characterized by a 1 mCi Cd-109 radioisotopic source, a xenon-filled proportional detector and a single-channel-analyzer. Survival curves of platelets and of red-cells labelled with stable Rb were determined by measuring the Rb concentration in the labelled cells, withdrawn at different times. The fluorescent counts are linearly proportional to the mass of rubidium per unit area of the filter. The sensitivity of the XRF technique is about 0.05 μg/cm 2 in a measuring time of 500 s. The mean quantity of Rb incorporated by the platelets is of about 5-10 μg for human platelets labelled ''in vitro'', of about 30-50 μg for rabbit platelets labelled in vivo and of about 0.5 mg for rabbit red cell labelled in vivo. The following half-time values were deduced: Tsub(1/2) = 35-45 h for human platelets labelled in ''in vitro''. Tsub(1/2) = 22 +- 3 h for rabbit platelets labelled ''in vivo''. Tsub(1/2) = 310 +- 15 h for rabbit red cells labelled ''in vivo''. The next step of our studies is to label ''in vivo'' human red cells and human platelets. (author)

Marine Biogenic Minerals Hold Clues About Changes in Ocean Chemistry and Climate: Some Important Lessons Learned from Studies of Stable and Radioactive Isotopes of Be and Al

Directory of Open Access Journals (Sweden)

Devendra Lal

2002-01-01

Full Text Available The elements Be and Al exhibit very short residence time in ocean waters, and therefore serve as useful tracers for the study of biogeochemical processes in seawater. A unique feature of these tracers is that nuclear interactions of cosmic rays in the atmosphere produce appreciable amounts of two radioactive isotopes, 10Be (with a half-life of 1.5 my and 26Al (with a half-life of 0.7 my, which are introduced in the hydrosphere, cryosphere, and lithosphere via precipitation. Thus, these elements are labeled by their respective radioactive isotopes, which help quantitative tagging of their biogeochemical cycles. Finally, as we report here, several marine organisms incorporate them in their skeletal shells in certain fixed proportions to their concentrations in the seawater, so that it seems possible to study changes in the ocean chemistry and climate over the past several million years. We summarize here the recent discovery by Dong et al.[9] of significant enrichments of intrinsic Be and Al in marine foraminiferal calcite and coral aragonite, and of Al in opal (radiolarians and aragonite (corals, which should make it possible to determine 10Be/Be and 26Al/Al in oceans in the past. We also summarize their measured 10Be/9Be in foraminiferal calcite in Pacific Ocean cores, which reveal that the concentrations and ratios of the stable and cosmogenic isotopes of Be and Al have varied significantly in the past 30 ky. The implications of these results are discussed.

Stable isotope composition of human fingernails from Slovakia

Energy Technology Data Exchange (ETDEWEB)

Grolmusová, Zuzana, E-mail: zuzana.grolmusova@geology.sk [Comenius University in Bratislava, Faculty of Mathematics, Physics and Informatics, Department of Experimental Physics, Mlynská dolina F2, 842 48 Bratislava (Slovakia); State Geological Institute of Dionýz Štúr, Laboratory of Isotope Geology, Mlynská dolina 1, 817 04 Bratislava (Slovakia); Rapčanová, Anna [Comenius University in Bratislava, Faculty of Mathematics, Physics and Informatics, Department of Experimental Physics, Mlynská dolina F2, 842 48 Bratislava (Slovakia); Michalko, Juraj; Čech, Peter [State Geological Institute of Dionýz Štúr, Laboratory of Isotope Geology, Mlynská dolina 1, 817 04 Bratislava (Slovakia); Veis, Pavel [Comenius University in Bratislava, Faculty of Mathematics, Physics and Informatics, Department of Experimental Physics, Mlynská dolina F2, 842 48 Bratislava (Slovakia); State Geological Institute of Dionýz Štúr, Laboratory of Isotope Geology, Mlynská dolina 1, 817 04 Bratislava (Slovakia)

2014-10-15

Stable isotope composition of human fingernails has proven to be useful for documenting human dietary information and geographical patterns in archeological, forensic, anthropological and biological studies. Therefore, it is of interest to detect all factors influencing the stable isotopic composition in the certain regions in the world. Carbon and nitrogen isotope data of human fingernail keratin from 52 individuals from Slovakia were reported in this study. The online combustion and continuous flow isotope-ratio mass spectrometer Delta V Advantage was used for δ{sup 13}C and δ{sup 15}N analysis of fingernail keratin samples from 24 vegetarian and 28 omnivorous individuals. A group of people with frequent meat consumption showed enrichment in {sup 13}C and {sup 15}N isotopes in fingernails. A similar trend was observed with increasing seafood in an individual's diet. Moreover a significant difference was revealed between smokers and nonsmokers for both δ{sup 13}C and δ{sup 15}N values. These data were compared to previously published δ{sup 13}C and δ{sup 15}N fingernail values from across the globe. This study brings new information on the stable isotope signature of individuals from Slovakia and characterizes the Central European region for the first time. The stable isotope composition of fingernails is influenced by the frequency of meat and seafood consumption as well as smoking. - Highlights: • This study deals with stable isotope analyses of fingernails from Slovak volunteers. • δ{sup 13}C and δ{sup 15}N values of vegetarian and omnivore fingernails were compared. • Influence of sex, diet and smoking was studied.

Deciphering Systemic Wound Responses of the Pumpkin Extrafascicular Phloem by Metabolomics and Stable Isotope-Coded Protein Labeling1[C][W

Science.gov (United States)

Gaupels, Frank; Sarioglu, Hakan; Beckmann, Manfred; Hause, Bettina; Spannagl, Manuel; Draper, John; Lindermayr, Christian; Durner, Jörg

2012-01-01

In cucurbits, phloem latex exudes from cut sieve tubes of the extrafascicular phloem (EFP), serving in defense against herbivores. We analyzed inducible defense mechanisms in the EFP of pumpkin (Cucurbita maxima) after leaf damage. As an early systemic response, wounding elicited transient accumulation of jasmonates and a decrease in exudation probably due to partial sieve tube occlusion by callose. The energy status of the EFP was enhanced as indicated by increased levels of ATP, phosphate, and intermediates of the citric acid cycle. Gas chromatography coupled to mass spectrometry also revealed that sucrose transport, gluconeogenesis/glycolysis, and amino acid metabolism were up-regulated after wounding. Combining ProteoMiner technology for the enrichment of low-abundance proteins with stable isotope-coded protein labeling, we identified 51 wound-regulated phloem proteins. Two Sucrose-Nonfermenting1-related protein kinases and a 32-kD 14-3-3 protein are candidate central regulators of stress metabolism in the EFP. Other proteins, such as the Silverleaf Whitefly-Induced Protein1, Mitogen Activated Protein Kinase6, and Heat Shock Protein81, have known defensive functions. Isotope-coded protein labeling and western-blot analyses indicated that Cyclophilin18 is a reliable marker for stress responses of the EFP. As a hint toward the induction of redox signaling, we have observed delayed oxidation-triggered polymerization of the major Phloem Protein1 (PP1) and PP2, which correlated with a decline in carbonylation of PP2. In sum, wounding triggered transient sieve tube occlusion, enhanced energy metabolism, and accumulation of defense-related proteins in the pumpkin EFP. The systemic wound response was mediated by jasmonate and redox signaling. PMID:23085839

Carbon-11 and Fluorine-18 Labeled Amino Acid Tracers for Positron Emission Tomography Imaging of Tumors

Science.gov (United States)

Sun, Aixia; Liu, Xiang; Tang, Ganghua

2017-12-01

Tumor cells have an increased nutritional demand for amino acids(AAs) to satisfy their rapid proliferation. Positron-emitting nuclide labeled AAs are interesting probes and are of great importance for imaging tumors using positron emission tomography (PET). Carbon-11 and fluorine-18 labeled AAs include the [1-11C] amino acids, labeling alpha-C- amino acids, the branched-chain of amino acids and N-substituted carbon-11 labeled amino acids. These tracers target protein synthesis or amino acid(AA) transport, and their uptake mechanism mainly involves AA transport. AA PET tracers have been widely used in clinical settings to image brain tumors, neuroendocrine tumors, prostate cancer, breast cancer, non–small cell lung cancer (NSCLC) and hepatocellular carcinoma. This review focuses on the fundamental concepts and the uptake mechanism of AAs, AA PET tracers and their clinical applications.

A new high-quality set of singly (H-2) and doubly (H-2 and O-18) stable isotope labeled reference waters for biomedical and other isotope-labeled research

NARCIS (Netherlands)

Faghihi, V.; Verstappen-Dumoulin, B. M. A. A.; Jansen, H. G.; van Dijk, G.; Aerts-Bijma, A. T.; Kerstel, E. R. T.; Groening, M.; Meijer, H. A. J.

2015-01-01

RATIONALE: Research using water with enriched levels of the rare stable isotopes of hydrogen and/or oxygen requires well-characterized enriched reference waters. The International Atomic Energy Agency (IAEA) did have such reference waters available, but these are now exhausted. New reference waters

Custom isotope-labelling of apis mellifera pheromone

International Nuclear Information System (INIS)

Conanan, Aida P.; Cortes, Nicole Marie A.; Daguno, Cristel Lyn R.; Templonuevo, Jose Angelo A.; Sucgang, Raymond J.

2012-01-01

The object of this study is to determine the optimum conditions for the synthesis of isotope-labelled isoamyl acetate. Esterification by alcoholysis of acetic acid was optimized for the preparation of Carbon - 14 ( 14 C)-labelled isopentyl acetate from 14 C-labelled acetic acid and isopentyl alcohol. The optimization procedure defined the effects of catalysis, reflux time, and temperature. The application of catalysis without reflux resulted to the highest yield (40%); the same condition also resulted to the highest abundance of carbon isotope label with 2.40 disintegrations per minute per cubic centimetre, DPM/cc (measurement unit for radioactivity). Determination of the beta radioactivity concentration of 14 C in the isopentyl acetate product was done using low level liquid scintillation spectrometry. Each of the synthetic constructs was mixed with Ultima Gold scintillation cocktail in a glass scintillation vial, and analysed in a low-level Wallac 1414 scintillation counter. Samples were counted for 2 hours in a chamber temperature maintained at 14 degree centegrade. The catalysed reaction without reflux was established to be the most efficient scheme for the radiolabelling. The radiolabelled isoamyl acetate can give way to the synthesis of more complex substances which can be then tracked when they are introduced to a system through the carbon isotope label. (author)

Tracer monitoring of enhanced oil recovery projects

Directory of Open Access Journals (Sweden)

Kleven R.

2013-05-01

Full Text Available In enhanced oil recovery (EOR, chemicals are injected into the oil reservoir, either to increase macroscopic sweep efficiency, or to reduce remaining oil saturation in swept zones. Tracers can be used to identify reservoirs that are specifically suited for EOR operations. Injection of a selection of partitioning tracers, combined with frequent sample analysis of produced fluids, provides information suited for estimation of residual oil saturation. Tracers can also be used to evaluate and optimize the application of EOR chemicals in the reservoir. Suitable tracers will follow the EOR chemicals and assist in evaluation of retention, degradation or trapping. In addition to field applications, tracers also have a large potential as a tool to perform mechanistic studies of EOR chemicals in laboratory experiments. By labelling EOR chemicals with radioactive isotopes of elements such as H, C and S, detailed studies of transport mechanisms can be carried out. Co-injection of labelled compounds in dynamic flooding experiments in porous media will give information about retention or separation of the unique compounds constituting the chemical formulation. Separation of such compounds may be detrimental to obtaining the EOR effect expected. The paper gives new information of specific methods, and discusses current status for use of tracers in EOR operations.

In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis

International Nuclear Information System (INIS)

Gholamrezanezhad, Ali; Mirpour, Sahar; Bagheri, Mohammad; Mohamadnejad, Mehdi; Alimoghaddam, Kamran; Abdolahzadeh, Leila; Saghari, Mohsen; Malekzadeh, Reza

2011-01-01

Background: Several animal and few human studies suggest the beneficial role of bone marrow mesenchymal stem cells (MSCs) in liver cirrhosis. However, little is known about the fate of MSCs after infusion in cirrhotic patients. We evaluated stem cell biodistribution after peripheral infusion of MSCs in four cirrhotic patients. Methods: After three passages of MSCs, the patients received a total of 250-400x10 6 cells, of which only 50% of the cells were labeled. Specific activities of 0.21-0.67 MBq/10 6 cells were maintained for the injected labeled MSCs. Planar whole-body acquisitions (anterior/posterior projections) were acquired immediately following infusion as well as at 2 h, 4 h, 6 h, 24 h, 48 h, 7th and 10th days after cell infusion. Results: After intravenous infusion, the radioactivity was first observed to accumulate in the lungs. During the following hours to days, the radioactivity gradually increased in the liver and spleen, with spleen uptake exceeding that in the liver in all patients. Region-of-interest analysis showed that the percentage of cells homing to the liver (following decay and background corrections and geometric mean calculation) increased from 0.0%-2.8% at immediately post-infusion images to 13.0-17.4% in 10th-day post-infusion. Similarly, the residual activities in the spleen increased from 2.0%-10.2% at immediately post-infusion images to 30.1%-42.2% in 10th-day post-infusion. During the same period, the residual activities in the lungs decreased from 27.0-33.5% to 2.0-5.4%. Conclusion: The infusion of MSCs labeled with 111 In-oxine through a peripheral vein is safe in cirrhosis. Cell labeling with 111 In-oxine is a suitable method for tracking MSC distribution after infusion.

The status of applying stable isotope in the studies of environmental science

International Nuclear Information System (INIS)

Bai Zhipeng; Zhang Liwen; Zhu Tan; Feng Yinchang

2007-01-01

The stable isotope composition is characteristic in the pollution source, and it is relatively fixed in the process of transferring and reaction. At present the precise analysis result of stable isotope ratio can be obtained easily. So the stable isotopes can be applied to the pollution affair arbitration and source study. The concept and analytical method of stable isotopes are introduced. The research status of the stable isotopes in the field of environmental science and the isotope fractionation is reviewed. (authors)

Use of radioactive tracers in dynamic sedimentology

International Nuclear Information System (INIS)

Tola, Francois.

1982-01-01

In the first part, developments in the use of radioactive tracers in sedimentology are recalled together with the corresponding fields of application and the identities of the main users. The state-of-the-art in France is also discussed; The main characteristics of the method are then described and compared with those of more classical methods. The results that can be obtained with tracer methods are then outlined. The criteria employed to establish the granulometry characteristics of the tracer, the particular radioisotope to be used, and the masses and activities involved, are treated. A list is then given of the main isotopes available in France and their characteristics. The various different labelling techniques employed are studied together with their respective advantages and disadvantages. The special case of pelitic sediments is mentioned. The use of reduced model isotope generators, double labelling and applications to studies of the mud plug in the Gironde Estuary are also discussed. The methods and materials used for injecting and detecting tracers are described, emphasis being given to the economic factors associated with the use of radioactive tracers in sedimentology. The second part of the report contains two chapters: - studies of transport by driftage: presentation and analysis of results and the application of the Count Rate Balance method to obtain quantitative information on transport; - studies of in-suspension transport of fine sediments in the sea: the procedures adopted from the moment when the tracer is introduced up to the time when the results are analyzed and interpreted, enables the trajectories and mean velocities of the transported sediments to be determined together with their degree of dilution and their settling speeds and rates; it is also possible to investigate the evolution and horizontal dispersion of the sediments in this way. Results from recent experiments are presented in both parts of the report

Axonal collateral-collateral transport of tract tracers in brain neurons: false anterograde labelling and useful tool.

Science.gov (United States)

Chen, S; Aston-Jones, G

1998-02-01

It is well established that some neuroanatomical tracers may be taken up by local axonal terminals and transported to distant axonal collaterals (e.g., transganglionic transport in dorsal root ganglion cells). However, such collateral-collateral transport of tracers has not been systematically examined in the central nervous system. We addressed this issue with four neuronal tracers--biocytin, biotinylated dextran amine, cholera toxin B subunit, and Phaseolus vulgaris-leucoagglutinin--in the cerebellar cortex. Labelling of distant axonal collaterals in the cerebellar cortex (indication of collateral-collateral transport) was seen after focal iontophoretic microinjections of each of the four tracers. However, collateral-collateral transport properties differed among these tracers. Injection of biocytin or Phaseolus vulgaris-leucoagglutinin in the cerebellar cortex yielded distant collateral labelling only in parallel fibres. In contrast, injection of biotinylated dextran amine or cholera toxin B subunit produced distant collateral labelling of climbing fibres and mossy fibres, as well as parallel fibres. The present study is the first systematic examination of collateral-collateral transport following injection of anterograde tracers in brain. Such collateral-collateral transport may produce false-positive conclusions regarding neural connections when using these tracers for anterograde transport. However, this property may also be used as a tool to determine areas that are innervated by common distant afferents. In addition, these results may indicate a novel mode of chemical communication in the nervous system.

Stable isotope customer list and summary of shipments:

International Nuclear Information System (INIS)

Tracy, J.G.

1988-03-01

This compilation is published as an aid to those concerned with the separation and sale of stable isotopes. The information is divided into four sections: alphabetical lists of domestic and foreign customers;alphabetical lists of isotopes and services;alphabetical lists of states and countries;tabulation of the shipments, quantities, and dollars for each isotope and dollars for services divided into domestic, foreign, and DOE project categories. During FY 1987 sales of stable isotope products and services were made to 272 differnt customers, of whom 159 were domestic and 113 were foreign, representing 18 different foreign countries. The total revenue was $3,785,609 of which 12.3% was from sales to DOE project customers, 60.4% was from sales to other domestic customers, and 27.3% was from sales to foreign customers. this represented sales of 189 different stable isotopes plus associated services and was a 16.5% increase over FY 1986

[Fractionation of hydrogen stable isotopes in the human body].

Science.gov (United States)

Siniak, Iu E; Grigor'ev, A I; Skuratov, V M; Ivanova, S M; Pokrovskiĭ, B G

2006-01-01

Fractionation of hydrogen stable isotopes was studied in 9 human subjects in a chamber with normal air pressure imitating a space cabin. Mass-spectrometry of isotopes in blood, urine, saliva, and potable water evidenced increases in the contents of heavy H isotope (deuterium) in the body liquids as compared with water. These results support one of the theories according to which the human organism eliminates heavy stable isotopes of biogenous chemical elements.

Tellurium stable isotope fractionation in chondritic meteorites and some terrestrial samples

Science.gov (United States)

Fehr, Manuela A.; Hammond, Samantha J.; Parkinson, Ian J.

2018-02-01

New methodologies employing a 125Te-128Te double-spike were developed and applied to obtain high precision mass-dependent tellurium stable isotope data for chondritic meteorites and some terrestrial samples by multiple-collector inductively coupled plasma mass spectrometry. Analyses of standard solutions produce Te stable isotope data with a long-term reproducibility (2SD) of 0.064‰ for δ130/125Te. Carbonaceous and enstatite chondrites display a range in δ130/125Te of 0.9‰ (0.2‰ amu-1) in their Te stable isotope signature, whereas ordinary chondrites present larger Te stable isotope fractionation, in particular for unequilibrated ordinary chondrites, with an overall variation of 6.3‰ for δ130/125Te (1.3‰ amu-1). Tellurium stable isotope variations in ordinary chondrites display no correlation with Te contents or metamorphic grade. The large Te stable isotope fractionation in ordinary chondrites is likely caused by evaporation and condensation processes during metamorphism in the meteorite parent bodies, as has been suggested for other moderately and highly volatile elements displaying similar isotope fractionation. Alternatively, they might represent a nebular signature or could have been produced during chondrule formation. Enstatite chondrites display slightly more negative δ130/125Te compared to carbonaceous chondrites and equilibrated ordinary chondrites. Small differences in the Te stable isotope composition are also present within carbonaceous chondrites and increase in the order CV-CO-CM-CI. These Te isotope variations within carbonaceous chondrites may be due to mixing of components that have distinct Te isotope signatures reflecting Te stable isotope fractionation in the early solar system or on the parent bodies and potentially small so-far unresolvable nucleosynthetic isotope anomalies of up to 0.27‰. The Te stable isotope data of carbonaceous and enstatite chondrites displays a general correlation with the oxidation state and hence might

New stable isotope method to measure protein digestibility and response to pancreatic enzyme intake in cystic fibrosis.

Science.gov (United States)

Engelen, M P K J; Com, G; Anderson, P J; Deutz, N E P

2014-12-01

Adequate protein intake and digestion are necessary to prevent muscle wasting in cystic fibrosis (CF). Accurate and easy-to-use methodology to quantify protein maldigestion is lacking in CF. To measure protein digestibility and the response to pancreatic enzyme intake in CF by using a new stable isotope methodology. In 19 CF and 8 healthy subjects, protein digestibility was quantified during continuous (sip) feeding for 6 h by adding (15)N-labeled spirulina protein and L-[ring-(2)H5]phenylalanine (PHE) to the nutrition and measuring plasma ratio [(15)N]PHE to [(2)H5]PHE. Pancreatic enzymes were ingested after 2 h in CF and the response in protein digestibility was assessed. To exclude difference in mucosal function, postabsorptive whole-body citrulline (CIT) production rate was measured by L-[5-(13)C-5,5-(2)H2]-CIT pulse and blood samples were taken to analyze tracer-tracee ratios. Protein digestibility was severely reduced in the CF group (47% of healthy subjects; P digestibility in CF until 90% of values obtained by healthy subjects. Maximal digestibility was reached at 100 min and maintained for 80 min. Stratification into CF children (n = 10) and adults showed comparable values for protein digestibility and similar kinetic responses to pancreatic enzyme intake. Whole-body citrulline production was elevated in CF indicating preserved mucosal function. Protein digestibility is severely compromised in patients with CF as measured by this novel and easy-to-use stable isotope approach. Pancreatic enzymes are able to normalize protein digestibility in CF, albeit with a severe delay. Registration ClinicalTrials.gov = NCT01494909. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

18F-labelled annexin V: a PET tracer for apoptosis imaging

International Nuclear Information System (INIS)

Murakami, Yoshihiro; Tatsumi, Mitsuyoshi; Ichise, Rikiya; Nishimura, Shintaro; Takamatsu, Hiroyuki; Noda, Akihiro; Taki, Junichi; Tait, Jonathan F.

2004-01-01

Annexin V can be used to detect apoptotic cells in vitro and in vivo, based on its ability to identify extracellular phosphatidylserine, which arises during apoptosis. In the present study, we examined the synthesis of fluorine-18 labelled annexin V as a positron emission tomography tracer for apoptosis imaging. The distribution of [ 18 F]annexin V and technetium-99m labelled annexin V, a well-characterised SPET tracer for apoptosis imaging, was compared. [ 18 F]annexin V was synthesised using N-succinimidyl 4-[ 18 F]fluorobenzoate as an 18 F labelling reagent. Synthesised and purified [ 18 F]annexin V was confirmed by SDS-PAGE. In an ex vivo imaging experiment, [ 18 F]annexin V was intravenously injected into rats 24 h after the induction of myocardial ischaemia, and accumulation in the left ventricle was examined. [ 18 F]annexin V accumulated in the infarct area of the left ventricle, where apoptotic cells were observed. In separate experiments, [ 18 F]annexin V or [ 99m Tc]annexin V was intravenously injected into ischaemic or normal animals, and the distribution of the tracers was compared. In ischaemic animals, accumulation of [ 18 F]annexin V and [ 99m Tc]annexin V in the infarct area was about threefold higher than in the non-infarct area. Furthermore, the ratio of accumulation in the normal heart to the blood radioactivity was not significantly different between the tracers. In normal animals, however, the uptake of [ 18 F]annexin V in the liver, spleen and kidney was much lower than that of [ 99m Tc]annexin V. The low uptake of [ 18 F]annexin V in these organs might represent an advantage over [ 99m Tc]annexin V. (orig.)

Comparative analysis of monoclonal antibody N-glycosylation using stable isotope labelling and UPLC-fluorescence-MS.

Science.gov (United States)

Millán Martín, Silvia; Delporte, Cédric; Farrell, Amy; Navas Iglesias, Natalia; McLoughlin, Niaobh; Bones, Jonathan

2015-03-07

A twoplex method using (12)C6 and (13)C6 stable isotope analogues (Δmass = 6 Da) of 2-aminobenzoic acid (2-AA) is described for quantitative analysis of N-glycans present on monoclonal antibodies and other glycoproteins using ultra performance liquid chromatography with sequential fluorescence and accurate mass tandem quadrupole time of flight (QToF) mass spectrometric detection.

The Use of Stable Water Isotopes as Tracers in Soil Aquifer Treatment (SAT and in Regional Water Systems

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Ido Negev

2017-01-01

Full Text Available This study examines the feasibility of tracing and quantifying the progress of different water sources along the water–effluent–SAT (Soil Aquifer Treatment chain using 2H and 18O isotopes. The research was conducted at the Dan Region Reclamation Plant (Shafdan, which reclaims ~135 MCM/year of effluent for irrigation. Water samples representing different stages along the chain were taken in two surveys during 2010–2011 and 2014. δ18O and δ2H values were used for mixing ratios (MR calculations, and compared with calculated MRs using chloride and carbamazepine concentrations. The results showed a relative enrichment of 18O and 2H in the Israeli water system compared to the regional groundwater, due to the addition of massive quantities of desalinated water. A linear correlation for δ2H vs. δ18O with a slope of 4.5 was found for the different freshwater sources and their mixing products, suggesting evaporation-mixing effects. MR values indicate on the spreading of new type of effluent originating from desalinated water in the aquifer. A dilution model explains the isotopic compositions in the water system and of the Shafdan effluents. Water isotopes have an advantage over other tracers, due to the ability to predict their ratio in the supply system and in the effluent, based on mass balance calculations and on knowledge of water supply volumes.

Lead and stable Pb-isotope characteristics of tropical soils in north-eastern Brazil

International Nuclear Information System (INIS)

Schucknecht, Anne; Matschullat, Jörg; Reimann, Clemens

2011-01-01

Stable Pb-isotope ratios are widely used as tracers for Pb-sources in the environment. Recently, a few publications have challenged the predominating view of environmental applications of Pb-isotopes. Present applications of Pb-isotopic tracers in soils largely represent the northern hemisphere. This study focuses on tropical soils from Paraíba, north-eastern Brazil. Lead concentrations and Pb-isotopic signatures (both 7N HNO 3 ) were determined at 30 sites along a 327 km E–W-transect, from the Atlantic coast at João Pessoa to some kilometers west of Patos, to identify possible processes for the observed (and anticipated) distribution pattern. Thirty samples each of litter (ORG) and top mineral soil (TOP) were taken on pasture land at suitable distance from roads or other potential contamination sources. Lead-content was determined by inductively-coupled plasma atomic emission spectrometry (ICP-AES) and the ratios of 206 Pb/ 207 Pb, 206 Pb/ 208 Pb, and 208 Pb/ 207 Pb by ICP-sector field mass spectrometry (ICP-SFMS). Both sample materials show similarly low Pb-concentrations with a lower median in the ORG samples (ORG 3.4 mg kg −1 versus TOP 6.9 mg kg −1 ). The 206 Pb/ 207 Pb ratios revealed a large spread along the transect with median 206 Pb/ 207 Pb ratios of 1.160 (ORG) and 1.175 (TOP). The 206 Pb/ 207 Pb ratios differ noticeably between sample sites located in the Atlantic Forest biome along the coast and sample sites in the inland Caatinga biome. The “forest” sites were characterised by a significant lower median and a lower spread in the 206 Pb/ 207 Pb and 206 Pb/ 208 Pb ratios compared to the Caatinga sites. Results indicate a very restricted influence of anthropogenic activities (individual sites only). The main process influencing the spatial variability of Pb-isotope ratios is supposed to be precipitation-dependent bioproductivity and weathering.

Tracing wastewater effluents in surface and groundwaters: a couple approach with organic/inorganic tracers and isotopes

Science.gov (United States)

Petelet-Giraud, Emmanuelle; Baran, Nicole; Soulier, Coralie

2017-04-01

In the context of land use change, the origins of contamination of water resources are often multiple, including for a single chemical element or molecule. For instance, excess of nitrates in both surface and groundwater can originate from agricultural practices and wastewater effluents. The discrimination of the origins and vectors of contamination in the environment is both an environmental and societal issue in order to define an integrated water resources management at the catchment or water body scale by implementing appropriate measures to effectively struggle against pollution. The objective of this study is to define a methodology for the identification of a "domestic wastewater" contamination within surface waters and groundwater. An ideal tracer should be conservative, persistent in the different water compartments, present in quantity above the detection limit and originate from a single type of pollution source. There is, however, no ideal tracer in the strict sense. Indeed, even chloride which is present in quantity in wastewater, and which behaves conservatively in the environment, is not an univocal tracer of wastewater, as it may come from atmospheric inputs, from the dissolution of evaporitic rocks, from the salting of roads or from fertilizers. To overcome this limitation, in this study, we propose a multi-tracer approach (chemical and isotopic) to identify and validate the relevance of foreseen tracers. Among the relevant tracers of wastewater, the following may be used for their intrinsic or combined discriminant power: 1) organic effluent tracers: nitrogen contents and isotopic ratios of nitrogen and oxygen of nitrates; 2) tracer of detergents: boron contents and boron isotopes; 3) pharmaceuticals tracers: e.g. carbamazepine, ibuprofen, paracetamol, gadolinium anomaly; 4) life-style tracers: e.g. caffeine. The originality of the study relies on small capacities wastewater treatment plants without tertiary treatment process. Results on a

Using Stable Isotopes of Carbon and Nitrogen to Mark Wild Populations of Anopheles and Aedes Mosquitoes in South-Eastern Tanzania.

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Mercy A Opiyo

Full Text Available Marking wild mosquitoes is important for understanding their ecology, behaviours and role in disease transmission. Traditional insect marking techniques include using fluorescent dyes, protein labels, radioactive labels and tags, but such techniques have various limitations; notably low marker retention and inability to mark wild mosquitoes at source. Stable isotopes are gaining wide spread use for non-invasive marking of arthropods, permitting greater understanding of mosquito dispersal and responses to interventions. We describe here a simple technique for marking naturally-breeding malaria and dengue vectors using stable isotopes of nitrogen (15N and carbon (13C, and describe potential field applications.We created man-made aquatic mosquito habitats and added either 15N-labelled potassium nitrate or 13C-labelled glucose, leaving non-adulterated habitats as controls. We then allowed wild mosquitoes to lay eggs in these habitats and monitored their development in situ. Pupae were collected promptly as they appeared and kept in netting cages. Emergent adults (in pools of ~4 mosquitoes/pool and individually stored pupae were desiccated and analysed using Isotope Ratio Mass Spectrometry (IRMS.Anopheles gambiae s.l and Aedes spp. from enriched 13C and enriched 15N larval habitats had significantly higher isotopic levels than controls (P = 0.005, and both isotopes produced sufficient distinction between marked and unmarked mosquitoes. Mean δ15N for enriched females and males were 275.6±65.1 and 248.0±54.6, while mean δ15N in controls were 2.1±0.1 and 3.9±1.7 respectively. Similarly, mean δ13C for enriched females and males were 36.08±5.28 and 38.5±6.86, compared to -4.3±0.2 and -7.9±3.6 in controls respectively. Mean δ15N and δ13C was significantly higher in any pool containing at least one enriched mosquito compared to pools with all unenriched mosquitoes, P<0.001. In all cases, there were variations in standardized isotopic ratios

Identifying and quantifying proteolytic events and the natural N terminome by terminal amine isotopic labeling of substrates.

Science.gov (United States)

Kleifeld, Oded; Doucet, Alain; Prudova, Anna; auf dem Keller, Ulrich; Gioia, Magda; Kizhakkedathu, Jayachandran N; Overall, Christopher M

2011-09-22

Analysis of the sequence and nature of protein N termini has many applications. Defining the termini of proteins for proteome annotation in the Human Proteome Project is of increasing importance. Terminomics analysis of protease cleavage sites in degradomics for substrate discovery is a key new application. Here we describe the step-by-step procedures for performing terminal amine isotopic labeling of substrates (TAILS), a 2- to 3-d (depending on method of labeling) high-throughput method to identify and distinguish protease-generated neo-N termini from mature protein N termini with all natural modifications with high confidence. TAILS uses negative selection to enrich for all N-terminal peptides and uses primary amine labeling-based quantification as the discriminating factor. Labeling is versatile and suited to many applications, including biochemical and cell culture analyses in vitro; in vivo analyses using tissue samples from animal and human sources can also be readily performed. At the protein level, N-terminal and lysine amines are blocked by dimethylation (formaldehyde/sodium cyanoborohydride) and isotopically labeled by incorporating heavy and light dimethylation reagents or stable isotope labeling with amino acids in cell culture labels. Alternatively, easy multiplex sample analysis can be achieved using amine blocking and labeling with isobaric tags for relative and absolute quantification, also known as iTRAQ. After tryptic digestion, N-terminal peptide separation is achieved using a high-molecular-weight dendritic polyglycerol aldehyde polymer that binds internal tryptic and C-terminal peptides that now have N-terminal alpha amines. The unbound naturally blocked (acetylation, cyclization, methylation and so on) or labeled mature N-terminal and neo-N-terminal peptides are recovered by ultrafiltration and analyzed by tandem mass spectrometry (MS/MS). Hierarchical substrate winnowing discriminates substrates from the background proteolysis products and

Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling

Science.gov (United States)

2012-01-01

Background Abnormal proteostasis due to alterations in protein turnover has been postulated to play a central role in several neurodegenerative diseases. Therefore, the development of techniques to quantify protein turnover in the brain is critical for understanding the pathogenic mechanisms of these diseases. We have developed a bolus stable isotope-labeling kinetics (SILK) technique coupled with multiple reaction monitoring mass spectrometry to measure the clearance of proteins in the mouse brain. Results Cohorts of mice were pulse labeled with 13 C6-leucine and the brains were isolated after pre-determined time points. The extent of label incorporation was measured over time using mass spectrometry to measure the ratio of labeled to unlabeled apolipoprotein E (apoE) and amyloid β (Aβ). The fractional clearance rate (FCR) was then calculated by analyzing the time course of disappearance for the labeled protein species. To validate the technique, apoE clearance was measured in mice that overexpress the low-density lipoprotein receptor (LDLR). The FCR in these mice was 2.7-fold faster than wild-type mice. To demonstrate the potential of this technique for understanding the pathogenesis of neurodegenerative disease, we applied our SILK technique to determine the effect of ATP binding cassette A1 (ABCA1) on both apoE and Aβ clearance. ABCA1 had previously been shown to regulate both the amount of apoE in the brain, along with the extent of Aβ deposition, and represents a potential molecular target for lowering brain amyloid levels in Alzheimer's disease patients. The FCR of apoE was increased by 1.9- and 1.5-fold in mice that either lacked or overexpressed ABCA1, respectively. However, ABCA1 had no effect on the FCR of Aβ, suggesting that ABCA1 does not regulate Aβ metabolism in the brain. Conclusions Our SILK strategy represents a straightforward, cost-effective, and efficient method to measure the clearance of proteins in the mouse brain. We expect that

Comparison of a Label-Free Quantitative Proteomic Method Based on Peptide Ion Current Area to the Isotope Coded Affinity Tag Method

Directory of Open Access Journals (Sweden)

Young Ah Goo

2008-01-01

Full Text Available Recently, several research groups have published methods for the determination of proteomic expression profiling by mass spectrometry without the use of exogenously added stable isotopes or stable isotope dilution theory. These so-called label-free, methods have the advantage of allowing data on each sample to be acquired independently from all other samples to which they can later be compared in silico for the purpose of measuring changes in protein expression between various biological states. We developed label free software based on direct measurement of peptide ion current area (PICA and compared it to two other methods, a simpler label free method known as spectral counting and the isotope coded affinity tag (ICAT method. Data analysis by these methods of a standard mixture containing proteins of known, but varying, concentrations showed that they performed similarly with a mean squared error of 0.09. Additionally, complex bacterial protein mixtures spiked with known concentrations of standard proteins were analyzed using the PICA label-free method. These results indicated that the PICA method detected all levels of standard spiked proteins at the 90% confidence level in this complex biological sample. This finding confirms that label-free methods, based on direct measurement of the area under a single ion current trace, performed as well as the standard ICAT method. Given the fact that the label-free methods provide ease in experimental design well beyond pair-wise comparison, label-free methods such as our PICA method are well suited for proteomic expression profiling of large numbers of samples as is needed in clinical analysis.

In vivo tracking of {sup 111}In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis

Energy Technology Data Exchange (ETDEWEB)

Gholamrezanezhad, Ali, E-mail: agholam1@jhmi.edu [Research Institute for Nuclear Medicine. Shariati Hospital. Tehran University of Medical Sciences, Tehran, 14114 (Iran, Islamic Republic of); Mirpour, Sahar [Research Institute for Nuclear Medicine. Shariati Hospital. Tehran University of Medical Sciences, Tehran, 14114 (Iran, Islamic Republic of); Bagheri, Mohammad; Mohamadnejad, Mehdi [Digestive Disease Research Center. Shariati Hospital. Tehran University of Medical Sciences, Tehran, 14114 (Iran, Islamic Republic of); Alimoghaddam, Kamran [Hematology and BMT Research Center. Shariati Hospital. Tehran University of Medical Sciences, Tehran, 14114 (Iran, Islamic Republic of); Abdolahzadeh, Leila [Digestive Disease Research Center. Shariati Hospital. Tehran University of Medical Sciences, Tehran, 14114 (Iran, Islamic Republic of); Saghari, Mohsen [Research Institute for Nuclear Medicine. Shariati Hospital. Tehran University of Medical Sciences, Tehran, 14114 (Iran, Islamic Republic of); Malekzadeh, Reza [Digestive Disease Research Center. Shariati Hospital. Tehran University of Medical Sciences, Tehran, 14114 (Iran, Islamic Republic of)

2011-10-15

Background: Several animal and few human studies suggest the beneficial role of bone marrow mesenchymal stem cells (MSCs) in liver cirrhosis. However, little is known about the fate of MSCs after infusion in cirrhotic patients. We evaluated stem cell biodistribution after peripheral infusion of MSCs in four cirrhotic patients. Methods: After three passages of MSCs, the patients received a total of 250-400x10{sup 6} cells, of which only 50% of the cells were labeled. Specific activities of 0.21-0.67 MBq/10{sup 6} cells were maintained for the injected labeled MSCs. Planar whole-body acquisitions (anterior/posterior projections) were acquired immediately following infusion as well as at 2 h, 4 h, 6 h, 24 h, 48 h, 7th and 10th days after cell infusion. Results: After intravenous infusion, the radioactivity was first observed to accumulate in the lungs. During the following hours to days, the radioactivity gradually increased in the liver and spleen, with spleen uptake exceeding that in the liver in all patients. Region-of-interest analysis showed that the percentage of cells homing to the liver (following decay and background corrections and geometric mean calculation) increased from 0.0%-2.8% at immediately post-infusion images to 13.0-17.4% in 10th-day post-infusion. Similarly, the residual activities in the spleen increased from 2.0%-10.2% at immediately post-infusion images to 30.1%-42.2% in 10th-day post-infusion. During the same period, the residual activities in the lungs decreased from 27.0-33.5% to 2.0-5.4%. Conclusion: The infusion of MSCs labeled with {sup 111}In-oxine through a peripheral vein is safe in cirrhosis. Cell labeling with {sup 111}In-oxine is a suitable method for tracking MSC distribution after infusion.

Climatic signals in multiple highly resolved stable isotope records from Greenland

DEFF Research Database (Denmark)

Vinther, Bo Møllesøe; Dahl-Jensen, Dorthe; Johnsen, Sigfus Johann

2010-01-01

are found to correspond better with winter stable isotope data than with summer or annual average stable isotope data it is suggested that a strong local Greenland temperature signal can be extracted from the winter stable isotope data even on centennial to millennial time scales. Udgivelsesdato: Feb....

Hydroponic isotope labeling of entire plants and high-performance mass spectrometry for quantitative plant proteomics.

Science.gov (United States)

Bindschedler, Laurence V; Mills, Davinia J S; Cramer, Rainer

2012-01-01

Hydroponic isotope labeling of entire plants (HILEP) combines hydroponic plant cultivation and metabolic labeling with stable isotopes using (15)N-containing inorganic salts to label whole and mature plants. Employing (15)N salts as the sole nitrogen source for HILEP leads to the production of healthy-looking plants which contain (15)N proteins labeled to nearly 100%. Therefore, HILEP is suitable for quantitative plant proteomic analysis, where plants are grown in either (14)N- or (15)N-hydroponic media and pooled when the biological samples are collected for relative proteome quantitation. The pooled (14)N-/(15)N-protein extracts can be fractionated in any suitable way and digested with a protease for shotgun proteomics, using typically reverse phase liquid chromatography nanoelectrospray ionization tandem mass spectrometry (RPLC-nESI-MS/MS). Best results were obtained with a hybrid ion trap/FT-MS mass spectrometer, combining high mass accuracy and sensitivity for the MS data acquisition with speed and high-throughput MS/MS data acquisition, increasing the number of proteins identified and quantified and improving protein quantitation. Peak processing and picking from raw MS data files, protein identification, and quantitation were performed in a highly automated way using integrated MS data analysis software with minimum manual intervention, thus easing the analytical workflow. In this methodology paper, we describe how to grow Arabidopsis plants hydroponically for isotope labeling using (15)N salts and how to quantitate the resulting proteomes using a convenient workflow that does not require extensive bioinformatics skills.

Strontium stable isotope behaviour accompanying basalt weathering

Science.gov (United States)

Burton, K. W.; Parkinson, I. J.; Gíslason, S. G. R.

2016-12-01

The strontium (Sr) stable isotope composition of rivers is strongly controlled by the balance of carbonate to silicate weathering (Krabbenhöft et al. 2010; Pearce et al. 2015). However, rivers draining silicate catchments possess distinctly heavier Sr stable isotope values than their bedrock compositions, pointing to significant fractionation during weathering. Some have argued for preferential release of heavy Sr from primary phases during chemical weathering, others for the formation of secondary weathering minerals that incorporate light isotopes. This study presents high-precision double-spike Sr stable isotope data for soils, rivers, ground waters and estuarine waters from Iceland, reflecting both natural weathering and societal impacts on those environments. The bedrock in Iceland is dominantly basaltic, d88/86Sr ≈ +0.27, extending to lighter values for rhyolites. Geothermal waters range from basaltic Sr stable compositions to those akin to seawater. Soil pore waters reflect a balance of input from primary mineral weathering, precipitation and litter recycling and removal into secondary phases and vegetation. Rivers and ground waters possess a wide range of d88/86Sr compositions from +0.101 to +0.858. Elemental and isotope data indicate that this fractionation primarily results from the formation or dissolution of secondary zeolite (d88/86Sr ≈ +0.10), but also carbonate (d88/86Sr ≈ +0.22) and sometimes anhydrite (d88/86Sr ≈ -0.73), driving the residual waters to heavier or lighter values, respectively. Estuarine waters largely reflect mixing with seawater, but are also be affected by adsorption onto particulates, again driving water to heavy values. Overall, these data indicate that the stability and nature of secondary weathering phases, exerts a strong control on the Sr stable isotope composition of silicate rivers. [1] Krabbenhöft et al. (2010) Geochim. Cosmochim. Acta 74, 4097-4109. [2] Pearce et al. (2015) Geochim. Cosmochim. Acta 157, 125-146.

RNA–Stable-Isotope Probing Shows Utilization of Carbon from Inulin by Specific Bacterial Populations in the Rat Large Bowel

Science.gov (United States)

Lawley, Blair; Munro, Karen; Sims, Ian M.; Lee, Julian; Butts, Christine A.; Roy, Nicole

2014-01-01

Knowledge of the trophisms that underpin bowel microbiota composition is required in order to understand its complex phylogeny and function. Stable-isotope (13C)-labeled inulin was added to the diet of rats on a single occasion in order to detect utilization of inulin-derived substrates by particular members of the cecal microbiota. Cecal digesta from Fibruline-inulin-fed rats was collected prior to (0 h) and at 6, 12, 18 and 24 h following provision of the [13C]inulin diet. RNA was extracted from these cecal specimens and fractionated in isopycnic buoyant density gradients in order to detect 13C-labeled nucleic acid originating in bacterial cells that had metabolized the labeled dietary constituent. RNA extracted from specimens collected after provision of the labeled diet was more dense than 0-h RNA. Sequencing of 16S rRNA genes amplified from cDNA obtained from these fractions showed that Bacteroides uniformis, Blautia glucerasea, Clostridium indolis, and Bifidobacterium animalis were the main users of the 13C-labeled substrate. Culture-based studies of strains of these bacterial species enabled trophisms associated with inulin and its hydrolysis products to be identified. B. uniformis utilized Fibruline-inulin for growth, whereas the other species used fructo-oligosaccharide and monosaccharides. Thus, RNA–stable-isotope probing (RNA-SIP) provided new information about the use of carbon from inulin in microbiota metabolism. PMID:24487527

Insights into Ancient Human Populations and their Environment through Stable Isotope Analysis

Science.gov (United States)

Macko, S. A.

2011-12-01

Fundamental to the understanding of human history is the ability to make interpretations based on artifacts and other remains which are used to gather information about an ancient population. Sequestered in the organic matrices of these remains can be information concerning incidence of disease, population interactions, genetic defects and diet. Stable isotopes have long been used to interpret diet and trophic interactions in modern ecosystems. We suggest that the isotope compositions of a commonly overlooked material, human hair, is an ideal tool to be used in gleaning information, especially on human diets, about ancient civilizations. Hair can be well-preserved and is amenable to routine measurements of 13C, 15N and 34S isotope analyses and distinguishing sources of nutrition. We have isotopically characterized hair from both modern and ancient individuals. There is a wide diversity in isotope values owing, at least partially, to the levels of seafood, corn-fed animals and other grains in diet. Using these isotope tracers, new information regarding historical figures (George Washington, 1799 AD) to perhaps the most ancient of mummies, the Chinchorro of Chile (more than 7000 BP) as well as the Moche of Peru (1500 BP) and the best preserved mummy, the Neolithic Ice Man of the Oetztaler Alps (5200 BP), have been deciphered. It appears that the often-overlooked hair in archaeological sites represents a significant approach for understanding ancient human communities and their environments, as well as new perspectives on our use of our own modern nutritional sources.

Isotopic Abundance and Chemical Purity Analysis of Stable Isotope Deuterium Labeled Sudan I

Directory of Open Access Journals (Sweden)

CAI Yin-ping;LEI Wen;ZHENG Bo;DU Xiao-ning

2014-02-01

Full Text Available It is important that to analysis of the isotopic abundance and chemical purity of Sudan I-D5, which is the internal standard of isotope dilution mass spectrometry. The isotopic abundance of Sudan I-D5 is detected by “mass cluster” classification method and LC-MS. The repeatability and reproducibility experiments were carried out by using different mass spectrometers and different operators. The RSD was less than 0.1%, so the repeatability and reproducibility were satisfactory. The accuracy and precision of the isotopic abundance analysis method was good with the results of F test and t test. The high performance liquid chromatography (HPLC had been used for detecting the chemical purity of Sudan I-D5 as external standard method.

Use of stable and radioactive isotopes in the determination of the recharge rate in Djeffara aquifer system southern Tunisia

International Nuclear Information System (INIS)

Trabelisi, R.; Zouari, K.

2012-12-01

Southern Tunisia is characterized by the presence of several hydrogeological basins, which extend over Tunisian borders. The Djeffara aquifer is one of the most important aquifer systems n this area and contains several interconnected aquifer levels. Stable (δ 2 H, δ 18 O and δ 13 C) and radioactive isotopes (1 4C , 3 H ) have been used to evaluate recharge mechanisms and groundwater residence time in the Djeffara multi-aquifer. Thesis aquifer presents two compartments, the first one ( west of the Medenine fault system) is unconfined with a well defined isotope fingerprint, the second compartment is deeper and confined multi- tracer results show groundwater of different origins, and ages , and that tectonic features control ground water flows. The unconfined part was mostly recharged during the Holocene. The recharge rates of this aquifer, inferred by 1 4C ages, are variable and could reach 3.5 mm/year. However, stable isotope composition and 1 4 'C content of the confined groundwater indicates carrier recharge during late pelistocene cold periods. (Author)

Stable isotope deltas: Tiny, yet robust signatures in nature

Science.gov (United States)

Brand, Willi A.; Coplen, Tyler B.

2012-01-01

Although most of them are relatively small, stable isotope deltas of naturally occurring substances are robust and enable workers in anthropology, atmospheric sciences, biology, chemistry, environmental sciences, food and drug authentication, forensic science, geochemistry, geology, oceanography, and paleoclimatology to study a variety of topics. Two fundamental processes explain the stable isotope deltas measured in most terrestrial systems: isotopic fractionation and isotope mixing. Isotopic fractionation is the result of equilibrium or kinetic physicochemical processes that fractionate isotopes because of small differences in physical or chemical properties of molecular species having different isotopes. It is shown that the mixing of radioactive and stable isotope end members can be modelled to provide information on many natural processes, including 14C abundances in the modern atmosphere and the stable hydrogen and oxygen isotopic compositions of the oceans during glacial and interglacial times. The calculation of mixing fractions using isotope balance equations with isotope deltas can be substantially in error when substances with high concentrations of heavy isotopes (e.g. 13C, 2H, and 18O ) are mixed. In such cases, calculations using mole fractions are preferred as they produce accurate mixing fractions. Isotope deltas are dimensionless quantities. In the International System of Units (SI), these quantities have the unit 1 and the usual list of prefixes is not applicable. To overcome traditional limitations with expressing orders of magnitude differences in isotope deltas, we propose the term urey (symbol Ur), after Harold C. Urey, for the unit 1. In such a manner, an isotope delta value expressed traditionally as−25 per mil can be written as−25 mUr (or−2.5 cUr or−0.25 dUr; the use of any SI prefix is possible). Likewise, very small isotopic differences often expressed in per meg ‘units’ are easily included (e.g. either+0.015 ‰ or+15 per meg

Stable isotope probing in the metagenomics era: a bridge towards improved bioremediation

Science.gov (United States)

Uhlik, Ondrej; Leewis, Mary-Cathrine; Strejcek, Michal; Musilova, Lucie; Mackova, Martina; Leigh, Mary Beth; Macek, Tomas

2012-01-01

Microbial biodegradation and biotransformation reactions are essential to most bioremediation processes, yet the specific organisms, genes, and mechanisms involved are often not well understood. Stable isotope probing (SIP) enables researchers to directly link microbial metabolic capability to phylogenetic and metagenomic information within a community context by tracking isotopically labeled substances into phylogenetically and functionally informative biomarkers. SIP is thus applicable as a tool for the identification of active members of the microbial community and associated genes integral to the community functional potential, such as biodegradative processes. The rapid evolution of SIP over the last decade and integration with metagenomics provides researchers with a much deeper insight into potential biodegradative genes, processes, and applications, thereby enabling an improved mechanistic understanding that can facilitate advances in the field of bioremediation. PMID:23022353

Simulation and interpretation of inter-well tracer tests

Directory of Open Access Journals (Sweden)

Dugstad Øyvind

2013-05-01

Full Text Available In inter-well tracer tests (IWTT, chemical compounds or radioactive isotopes are used to label injection water and gas to establish well connections and fluid patterns in petroleum reservoirs. Tracer simulation is an invaluable tool to ease the interpretation of IWTT results and is also required for assisted history matching application of tracer data. In this paper we present a new simulation technique to analyse and interpret tracer results. Laboratory results are used to establish and test formulations of the tracer conservation equations, and the technique is used to provide simulated tracer responses that are compared with observed tracer data from an extensive tracer program. The implemented tracer simulation methodology use a fast post-processing of previously simulated reservoir simulation runs. This provides a fast, flexible and powerful method for analysing gas tracer behaviour in reservoirs. We show that simulation time for tracers can be reduced by factor 100 compared to solving the tracer flow equations simultaneously with the reservoir fluid flow equations. The post-processing technique, combined with a flexible built-in local tracer-grid refinement is exploited to reduce numerical smearing, particularly severe for narrow tracer pulses.

Plasma Protein Turnover Rates in Rats Using Stable Isotope Labeling, Global Proteomics, and Activity-Based Protein Profiling

Energy Technology Data Exchange (ETDEWEB)

Smith, Jordan N.; Tyrrell, Kimberly J.; Hansen, Joshua R.; Thomas, Dennis G.; Murphree, Taylor A.; Shukla, Anil K.; Luders, Teresa; Madden, James M.; Li, Yunying; Wright, Aaron T.; Piehowski, Paul D.

2017-12-06

Protein turnover is important for general health on cellular and organism scales providing a strategy to replace old, damaged, or dysfunctional proteins. Protein turnover also informs of biomarker kinetics, as a better understanding of synthesis and degradation of proteins increases the clinical utility of biomarkers. Here, turnover rates of plasma proteins in rats were measured in vivo using a pulse-chase stable isotope labeling experiment. During the pulse, rats (n=5) were fed 13C6-labeled lysine (“heavy”) feed for 23 days to label proteins. During the chase, feed was changed to an unlabeled equivalent feed (“light”), and blood was repeatedly sampled from rats over 10 time points for 28 days. Plasma samples were digested with trypsin, and analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). MaxQuant was used to identify peptides and proteins, and quantify heavy:light lysine ratios. A system of ordinary differential equations was used to calculate protein turnover rates. Using this approach, 273 proteins were identified, and turnover rates were quantified for 157 plasma proteins with half-lives ranging 0.3-103 days. For the ~70 most abundant proteins, variability in turnover rates among rats was low (median coefficient of variation: 0.09). Activity-based protein profiling was applied to pooled plasma samples to enrich serine hydrolases using a fluorophosphonate (FP2) activity-based probe. This enrichment resulted in turnover rates for an additional 17 proteins. This study is the first to measure global plasma protein turnover rates in rats in vivo, measure variability of protein turnover rates in any animal model, and utilize activity-based protein profiling for enhancing measurements of targeted, low-abundant proteins, such as those commonly used as biomarkers. Measured protein turnover rates will be important for understanding of the role of protein turnover in cellular and organism health as well as increasing the utility of protein

Benzylic rearrangement stable isotope labeling for quantitation of guanidino and ureido compounds in thyroid tissues by liquid chromatography-electrospray ionization mass spectrometry

International Nuclear Information System (INIS)

Fan, Ruo-Jing; Guan, Qing; Zhang, Fang; Leng, Jia-Peng; Sun, Tuan-Qi; Guo, Yin-Long

2016-01-01

Benzylic rearrangement stable isotope labeling (BRSIL) was explored to quantify the guanidino and ureido compounds (GCs and UCs). This method employed a common reagent, benzil, to label the guanidino and ureido groups through nucleophilic attacking then benzylic migrating. The use of BRSIL was investigated in the analysis of five GCs (creatine, L-arginine, homoarginine, 4-guanidinobutyric acid, and methylguanidine) and two UCs (urea and citrulline). The labeling was found simple and specific. The introduction of bi-phenyl group and the generation of nitrogen heterocyclic ring in the benzil-d0/d5 labeled GCs and UCs improved the retention behaviors in liquid chromatography (LC) and increased the sensitivity of electrospray ionization mass spectrometry (ESI MS) detection. The fragment ion pairs of m/z 182/187 and m/z 210/215 from the benzil-d0/d5 tags facilitated the discovery of potential GCs and UCs candidates residing in biological matrices. The use of BRSIL combined with LC-ESI MS was applied for simultaneously quantitation of GCs and UCs in thyroid tissues. It was demonstrated that nine GCs and UCs were detected, six of which were further quantified based on corresponding standards. It was concluded that five GCs and UCs (L-arginine, homoarginine, 4-guanidinobutyric acid, methylguanidine, and citrulline) were statistically significantly different (p < 0.05) between the para-carcinoma and carcinoma thyroid tissue samples. - Highlights: • A common reagent, benzil-d0/d5 was employed to label the GCs and UCs through BRSIL. • The benzil-d0/d5 labeling improved the retention behavior in RPLC and increased the sensitivity by ESI MS detection. • BRSIL coupled with LC-ESI MS was applied to the qualitation and quantitation of GCs and UCs in thyroid tissues.

Benzylic rearrangement stable isotope labeling for quantitation of guanidino and ureido compounds in thyroid tissues by liquid chromatography-electrospray ionization mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Fan, Ruo-Jing [State Key Laboratory of Organmetallic Chemistry and National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China); Guan, Qing [Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 (China); Zhang, Fang, E-mail: fzhang@sioc.ac.cn [State Key Laboratory of Organmetallic Chemistry and National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China); Leng, Jia-Peng [State Key Laboratory of Organmetallic Chemistry and National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China); Sun, Tuan-Qi, E-mail: tuanqisun@163.com [Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 (China); Guo, Yin-Long, E-mail: ylguo@sioc.ac.cn [State Key Laboratory of Organmetallic Chemistry and National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 (China)

2016-02-18

Benzylic rearrangement stable isotope labeling (BRSIL) was explored to quantify the guanidino and ureido compounds (GCs and UCs). This method employed a common reagent, benzil, to label the guanidino and ureido groups through nucleophilic attacking then benzylic migrating. The use of BRSIL was investigated in the analysis of five GCs (creatine, L-arginine, homoarginine, 4-guanidinobutyric acid, and methylguanidine) and two UCs (urea and citrulline). The labeling was found simple and specific. The introduction of bi-phenyl group and the generation of nitrogen heterocyclic ring in the benzil-d0/d5 labeled GCs and UCs improved the retention behaviors in liquid chromatography (LC) and increased the sensitivity of electrospray ionization mass spectrometry (ESI MS) detection. The fragment ion pairs of m/z 182/187 and m/z 210/215 from the benzil-d0/d5 tags facilitated the discovery of potential GCs and UCs candidates residing in biological matrices. The use of BRSIL combined with LC-ESI MS was applied for simultaneously quantitation of GCs and UCs in thyroid tissues. It was demonstrated that nine GCs and UCs were detected, six of which were further quantified based on corresponding standards. It was concluded that five GCs and UCs (L-arginine, homoarginine, 4-guanidinobutyric acid, methylguanidine, and citrulline) were statistically significantly different (p < 0.05) between the para-carcinoma and carcinoma thyroid tissue samples. - Highlights: • A common reagent, benzil-d0/d5 was employed to label the GCs and UCs through BRSIL. • The benzil-d0/d5 labeling improved the retention behavior in RPLC and increased the sensitivity by ESI MS detection. • BRSIL coupled with LC-ESI MS was applied to the qualitation and quantitation of GCs and UCs in thyroid tissues.

Studies of radioisotope tracer technique and its applications to pesticide sciences in China

International Nuclear Information System (INIS)

Jia Minghong; Chen Qing; Zheng Ran

1996-05-01

The improper use of chemical pesticides has resulted in serious environmental problems and food pollutions, affecting the ecosystem balance and human being health. There are more and more scientists and research institutions being engaged in the area of radioisotope tracer techniques for pesticide sciences in China. So far, more than 80 labeled compounds, including insecticides, fungicides, acaricides, herbicides, metabolic intermediates, fertilizer and biological agents, etc. have been synthesized at the laboratory for application of isotopes in Institute for Application of Atomic Energy, Chinese Academy of Agricultural Sciences. Over past several years, the great achievements have been made in the researches of radioisotope tracer techniques and their applications to pesticide sciences in China, especially in the researches for isotopic labeling, residues, degradation and metabolism of pesticides in plant and animal, behavior and fate of pesticides in environment, and techniques for safe application of pesticide, and so on. The researches of radioisotope tracer techniques and their applications to pesticide sciences in China in the past years are briefly introduced. Some problems are put forward and the development in future is predicted. (1 tab.)

13C- and 15N-labelled non-biogenic compounds used as stable isotope drugs for human liver function tests

International Nuclear Information System (INIS)

Krumbiegel, P.

1989-01-01

As a result of liver diseases, the elimination of certain drugs is retarded. After labelling a suitable drug with 13 C, the 13 CO 2 elimination rate serves as a liver function parameter. Current contributions to the 13 CO 2 breath test method are reviewed and related to the 14 CO 2 breath test proposals. In spite of several advantages of 13 C-labelled agents, some dissatisfaction has remained with the tests, especially at using them with infants. It is the necessity of face masks and the uncertainty to consider endogeneous CO 2 contributions diluting the exhaled 13 CO 2 . The problems are avoided if the other molecule site of the drug is labelled which is known to be eliminated via urine. With 15 N as a tracer, a suitable urine test using [ 15 N]-methacetin as agent has been proposed and put into practice. (author)

Optimizing sample pretreatment for compound-specific stable carbon isotopic analysis of amino sugars in marine sediment

Science.gov (United States)

Zhu, R.; Lin, Y.-S.; Lipp, J. S.; Meador, T. B.; Hinrichs, K.-U.

2014-09-01

Amino sugars are quantitatively significant constituents of soil and marine sediment, but their sources and turnover in environmental samples remain poorly understood. The stable carbon isotopic composition of amino sugars can provide information on the lifestyles of their source organisms and can be monitored during incubations with labeled substrates to estimate the turnover rates of microbial populations. However, until now, such investigation has been carried out only with soil samples, partly because of the much lower abundance of amino sugars in marine environments. We therefore optimized a procedure for compound-specific isotopic analysis of amino sugars in marine sediment, employing gas chromatography-isotope ratio mass spectrometry. The whole procedure consisted of hydrolysis, neutralization, enrichment, and derivatization of amino sugars. Except for the derivatization step, the protocol introduced negligible isotopic fractionation, and the minimum requirement of amino sugar for isotopic analysis was 20 ng, i.e., equivalent to ~8 ng of amino sugar carbon. Compound-specific stable carbon isotopic analysis of amino sugars obtained from marine sediment extracts indicated that glucosamine and galactosamine were mainly derived from organic detritus, whereas muramic acid showed isotopic imprints from indigenous bacterial activities. The δ13C analysis of amino sugars provides a valuable addition to the biomarker-based characterization of microbial metabolism in the deep marine biosphere, which so far has been lipid oriented and biased towards the detection of archaeal signals.

A Computational Drug Metabolite Detection Using the Stable Isotopic Mass-Shift Filtering with High Resolution Mass Spectrometry in Pioglitazone and Flurbiprofen

Directory of Open Access Journals (Sweden)

Yohei Miyamoto

2013-09-01

Full Text Available The identification of metabolites in drug discovery is important. At present, radioisotopes and mass spectrometry are both widely used. However, rapid and comprehensive identification is still laborious and difficult. In this study, we developed new analytical software and employed a stable isotope as a tool to identify drug metabolites using mass spectrometry. A deuterium-labeled compound and non-labeled compound were both metabolized in human liver microsomes and analyzed by liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS. We computationally aligned two different MS data sets and filtered ions having a specific mass-shift equal to masses of labeled isotopes between those data using our own software. For pioglitazone and flurbiprofen, eight and four metabolites, respectively, were identified with calculations of mass and formulas and chemical structural fragmentation analysis. With high resolution MS, the approach became more accurate. The approach detected two unexpected metabolites in pioglitazone, i.e., the hydroxypropanamide form and the aldehyde hydrolysis form, which other approaches such as metabolite-biotransformation list matching and mass defect filtering could not detect. We demonstrated that the approach using computational alignment and stable isotopic mass-shift filtering has the ability to identify drug metabolites and is useful in drug discovery.

Deuterium used as artificial tracer in column studies under saturated water flow conditions

Science.gov (United States)

Koeniger, P.; Geiges, M.; Leibundgut, Ch.

2003-04-01

In contrast to numerous investigations using deuterium as an environmental tracer, hydrological investigations with deuterium-labelled water are rather rare. Currently applications in groundwater studies are restricted due to increasing costs of spiking large water quantities but an application as intelligent tracer might be of advantage especially in combination with other tracers and under distinct environmental conditions. Therefore deuterium was applied as artificial tracer in column experiments that are well proved as a tool to characterise tracer behaviour in recent studies. Deuterium was tested in comparison to the more familiar conservative tracer fluorescein. Varying experimental conditions, e.g. column length (0.5, 1.0, 1.5 m), initial tracer concentration (0.01, 0.02, 0.2 mg) and flow velocity (1.5 to 6.0 m/d) were used to investigate tracer behaviour under saturated water flow conditions. Deuterium was analysed using an H/Device with chrome reduction connected to an isotope ratio mass spectrometer and expressed in relative concentrations [per mill V-SMOW]. Theoretical tracer breakthrough curves were calculated using a one dimensional dispersion model. The results indicate higher mean transport velocities and smaller dispersion for deuterium in all experiments. Due to different molecule properties that also determine the interaction of soil substrate and tracer, deuterium indicates a more conservative transport behaviour. Deuterium is non-toxic, completely soluble, chemically and biologically stable and not subject to light-influenced decay. Furthermore, it shows promise for investigations of water flow in the unsaturated zone, and of interactions of water in soil-plant-atmosphere systems. A further discussion of problems, together with possibilities for applying deuterium as an artificial tracer, will be presented.

Potential use of stable isotope and fatty acid analyses for traceability of geographic origins of jumbo squid (Dosidicus gigas).

Science.gov (United States)

Gong, Yi; Li, Yunkai; Chen, Xinjun; Chen, Ling

2018-04-15

Squid is an important seafood resource for Asian and European countries. With the continuous development of processed squid products, an effective traceability system has become increasingly prominent. Here, we attempt to trace the fishery products of the main target species, jumbo squid (Dosidicus gigas), by using biochemical tracers. Carbon and nitrogen isotope ratios (δ 13 C and δ 15 N values) and fatty acid profiles were identified in squid from three harvest locations in the eastern Pacific Ocean by isotope ratio mass spectrometry and gas chromatography/mass spectrometry, respectively. Comparative analysis was used to evaluate the geographic variations in tracers and to identify the suitable discriminatory variables among origins. Significant spatial variations were found in isotopic values and fatty acid profiles in squid muscle tissues, possibly because of different food availability and/or oceanographic conditions that each group experiences at a given location. The stepwise discriminant analysis indicated that δ 15 N, C16:1n7, C17:1n7, C18:2n6, C20:1 and C20:4n6 were effective variables at differentiating origin. Combined use of stable isotope ratios and fatty acid analyses could trace geographic origins of jumbo squid. This study provides an alternative approach for improving authenticity evaluation of commercial squid products. Copyright © 2018 John Wiley & Sons, Ltd.

Factors controlling stable isotope composition of European precipitation

International Nuclear Information System (INIS)

Rozanski, K.; Sonntag, C.; Muennich, K.O.

1982-01-01

The seasonal and spatial variations of stable isotope ratios in present day European precipitation are simulated with a simple multibox model of the mean west-east horizontal transport of the atmospheric water vapour across the European continent. Isotope fractionation during the formation of precipitation leads to an increasing depletion of heavy isotopes in the residual air moisture as it moves towards the centre of the continent. This isotopic depletion is partly compensated, particularly in summer, by evapotranspiration, which is assumed to transfer soil water into the atmosphere without isotope fractionation. The model estimates are based on horizontal water vapour flux data, varying seasonally between 88 and 130 kg m -1 s -1 for the Atlantic coast region, and on the monthly precipitation, evapotranspiration and surface air temperature data available for various locations in Europe. Both continental and seasonal temperature effects observed in the stable isotope composition of European precipitation are fairly well reproduced by the model. The calculations show that the isotopic composition of local precipitation is primarily controlled by regional scale processes, i.e. by the water vapour transport patterns into the continent, and by the average precipitation-evapotranspiration history of the air masses precipitating at a given place. Local parameters such as the surface and/or cloud base temperature or the amount of precipitation modify the isotope ratios only slightly. Implications of the model predictions for the interpretation of stable isotope ratios in earlier periods as they are preserved in ice cores and in groundwater are also discussed. (Auth.)

Differential Isotope Labeling of Glycopeptides for Accurate Determination of Differences in Site-Specific Glycosylation.

Science.gov (United States)

Pabst, Martin; Benešová, Iva; Fagerer, Stephan R; Jacobsen, Mathias; Eyer, Klaus; Schmidt, Gregor; Steinhoff, Robert; Krismer, Jasmin; Wahl, Fabian; Preisler, Jan; Zenobi, Renato

2016-01-04

We introduce a stable isotope labeling approach for glycopeptides that allows a specific glycosylation site in a protein to be quantitatively evaluated using mass spectrometry. Succinic anhydride is used to specifically label primary amino groups of the peptide portion of the glycopeptides. The heavy form (D4(13)C4) provides an 8 Da mass increment over the light natural form (H4(12)C4), allowing simultaneous analysis and direct comparison of two glycopeptide profiles in a single MS scan. We have optimized a protocol for an in-solution trypsin digestion, a one-pot labeling procedure, and a post-labeling solid-phase extraction to obtain purified and labeled glycopeptides. We provide the first demonstration of this approach by comparing IgG1 Fc glycopeptides from polyclonal IgG samples with respect to their galactosylation and sialylation patterns using MALDI MS and LC-ESI-MS.

Environmental radionuclides tracers and timers of terrestrial processes

CERN Document Server

Froehlich, Klaus

2009-01-01

The book presents a state-of-the-art summary of knowledge on the use of radionuclides to study processes and systems in the continental part of the Earth's environment. It is conceived as a companion to the two volumes of this series, which deal with isotopes as tracers in the marine environment (Livingston, Marine Radioactivity) and with the radioecology of natural and man-made terrestrial systems (Shaw, Radioactivity in Terrestrial Ecosystems). Although the book focuses on natural and anthropogenic radionuclides (radioactive isotopes), it also refers to stable environmental isotopes, which i

Stable isotope geochemistry : definitions, terminology, measurement and some applications