61 results on '"Jensen DJ"'
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2. Metal structures in four dimensions
- Author
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Søren Schmidt and Jensen, Dj
3. Smoothing turbulence-induced power fluctuations in large wind farms by optimal control of the rotating kinetic energy of the turbines
- Author
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Simon De Rijcke, Johan Driesen, Johan Meyers, Bak, C, Bechmann, A, Bingol, F, Dellwik, E, Dimitrov, N, Giebel, G, Hansen, MOL, Jensen, DJ, Larsen, G, Madsen, HA, Mann, J, Natarajan, A, Rathmann, O, Sathe, A, Sorensen, JN, and Sorensen, NN
- Subjects
History ,Engineering ,business.industry ,Turbulence ,Optimal control ,7. Clean energy ,Computer Science Applications ,Education ,Power (physics) ,Boundary layer ,Control theory ,Benchmark (computing) ,Torque ,business ,Energy (signal processing) ,Smoothing - Abstract
In the current study, we use a large-eddy simulation of a wind-farm boundary layer to generate the fluctuating wind fields that are observed at different turbines in the wind farm. Using these wind fields as inputs, we focus on the development of a benchmark framework in which we explore the trade-off between high energy extraction and low variability using optimal control of multiple turbines subject to a turbulent wind field. The controls variables that are optimized are the electric torque and the pitch angles of the individual turbines over time horizons of 10 minutes. Moreover, both optimal control of individual turbines and coordinated optimal control of groups of turbines are investigated. Optimal control results are presented in terms of Pareto fronts that show optimal trade-offs between energy extraction and power smoothing. We find that power variations can be significantly reduced with limited loss of extracted energy. Moreover, coordinated control can effectively reduce fluctuations over longer time scales. For instance, considering 24 optimally coordinated turbines, variability at a time scale of 50 seconds is reduced 4 times more than the normal statistical reduction of 24 uncoordinated turbines. © Published under licence by IOP Publishing Ltd. ispartof: Journal of Physics: Conference Series vol:524 issue:1 ispartof: The Science of Making Torque from Wind location:Lyngby date:18 Jun - 20 Jun 2014 status: published
- Published
- 2014
4. Wind farm performance in conventionally neutral atmospheric boundary layers with varying inversion strengths
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Dries Allaerts, Johan Meyers, Bak, C, Bechmann, A, Bingol, F, Dellwik, E, Dimitrov, N, Giebel, G, Hansen, MOL, Jensen, DJ, Larsen, G, Madsen, HA, Mann, J, Natarajan, A, Rathmann, O, Sathe, A, Sorensen, JN, and Sorensen, NN
- Subjects
Physics ,History ,Wind power ,010504 meteorology & atmospheric sciences ,business.industry ,Planetary boundary layer ,Wind stress ,Inversion (meteorology) ,Atmospheric sciences ,01 natural sciences ,7. Clean energy ,010305 fluids & plasmas ,Computer Science Applications ,Education ,Physics::Fluid Dynamics ,Boundary layer ,Wind profile power law ,Log wind profile ,0103 physical sciences ,Capping inversion ,Astrophysics::Solar and Stellar Astrophysics ,business ,Physics::Atmospheric and Oceanic Physics ,0105 earth and related environmental sciences - Abstract
In this study we consider large wind farms in a conventionally neutral atmospheric boundary layer. In large wind farms the energy extracted by the turbines is dominated by downward vertical turbulent transport of kinetic energy from the airflow above the farm. However, atmospheric boundary layers are almost always capped by an inversion layer which slows down the entrainment rate and counteracts boundary layer growth. In a suite of large eddy simulations the effect of the strength of the capping inversion on the boundary layer and on the performance of a large wind farm is investigated. For simulations with and without wind turbines the results indicate that the boundary layer growth is effectively limited by the capping inversion and that the entrainment rate depends strongly on the inversion strength. The power output of wind farms is shown to decrease for increasing inversions. © Published under licence by IOP Publishing Ltd. ispartof: Journal of Physics: Conference Series vol:524 issue:1 ispartof: The Science of Making Torque from Wind location:Lyngby date:18 Jun - 20 Jun 2014 status: published
- Published
- 2014
- Full Text
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5. Effect of Selection of Design Parameters on the Optimization of a Horizontal Axis Wind Turbine via Genetic Algorithm
- Author
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Emre Alpman, Alpman, Emre, Bak, C, Bechmann, A, Bingol, F, Dellwik, E, Dimitrov, N, Giebel, G, Hansen, MOL, Jensen, DJ, Larsen, G, Madsen, HA, Mann, J, Natarajan, A, Rathmann, O, Sathe, A, Sorensen, JN, and Sorensen, NN
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Horizontal axis ,History ,Mathematical optimization ,Engineering ,education.field_of_study ,Turbine blade ,business.industry ,Population ,Bézier curve ,Stall (fluid mechanics) ,Aerodynamics ,Turbine ,Computer Science Applications ,Education ,law.invention ,law ,Twist angle ,business ,education ,Algorithm - Abstract
The effect of selecting the twist angle and chord length distributions on the wind turbine blade design was investigated by performing aerodynamic optimization of a two-bladed stall regulated horizontal axis wind turbine. Twist angle and chord length distributions were defined using Bezier curve using 3, 5, 7 and 9 control points uniformly distributed along the span. Optimizations performed using a micro-genetic algorithm with populations composed of 5, 10, 15, 20 individuals showed that, the number of control points clearly affected the outcome of the process; however the effects were different for different population sizes. The results also showed the superiority of micro-genetic algorithm over a standard genetic algorithm, for the selected population sizes. Optimizations were also performed using a macroevolutionary algorithm and the resulting best blade design was compared with that yielded by micro-genetic algorithm.
- Published
- 2014
6. Numerical simulations of flow fields through conventionally controlled wind turbines & wind farms
- Author
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Johan Meyers, Ali Emre Yilmaz, Bak, C, Bechmann, A, Bingol, F, Dellwik, E, Dimitrov, N, Giebel, G, Hansen, MOL, Jensen, DJ, Larsen, G, Madsen, HA, Mann, J, Natarajan, A, Rathmann, O, Sathe, A, Sorensen, JN, and Sorensen, NN
- Subjects
History ,Engineering ,Wind power ,business.industry ,Rotor (electric) ,Blade pitch ,Rotational speed ,7. Clean energy ,Turbine ,Wind speed ,Computer Science Applications ,Education ,law.invention ,Physics::Fluid Dynamics ,Wind profile power law ,Control theory ,law ,business - Abstract
In the current study, an Actuator-Line Model (ALM) is implemented in our in-house pseudo-spectral LES solver SP-WIND, including a turbine controller. Below rated wind speed, turbines are controlled by a standard-torque-controller aiming at maximum power extraction from the wind. Above rated wind speed, the extracted power is limited by a blade pitch controller which is based on a proportional-integral type control algorithm. This model is used to perform a series of single turbine and wind farm simulations using the NREL 5MW turbine. First of all, we focus on below-rated wind speed, and investigate the effect of the farm layout on the controller calibration curves. These calibration curves are expressed in terms of nondimensional torque and rotational speed, using the mean turbine-disk velocity as reference. We show that this normalization leads to calibration curves that are independent of wind speed, but the calibration curves do depend on the farm layout, in particular for tightly spaced farms. Compared to turbines in a lone-standing set-up, turbines in a farm experience a different wind distribution over the rotor due to the farm boundary-layer interaction. We demonstrate this for fully developed wind-farm boundary layers with aligned turbine arrangements at different spacings (5D, 7D, 9D). Further we also compare calibration curves obtained from full farm simulations with calibration curves that can be obtained at a much lower cost using a minimal flow unit. © Published under licence by IOP Publishing Ltd. ispartof: Journal of Physics: Conference Series vol:524 issue:1 ispartof: The Science of Making Torque from Wind location:Lyngby date:18 Jun - 20 Jun 2014 status: published
- Published
- 2014
7. Volumetric scans of wind turbine wakes performed with three simultaneous wind LiDARs under different atmospheric stability regimes
- Author
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Giacomo Valerio Iungo, Fernando Porté-Agel, Bak, C, Bechmann, A, Mann, J, Natarajan, A, Rathmann, O, Sathe, A, Sorensen, Jn, Sorensen, Nn, Bingol, F, Dellwik, E, Dimitrov, N, Giebel, G, Hansen, Mol, Jensen, Dj, Larsen, G, and Madsen, Ha
- Subjects
History ,Wind gradient ,Wind power ,Meteorology ,business.industry ,Planetary boundary layer ,Wind stress ,Atmospheric sciences ,Wind speed ,Computer Science Applications ,Education ,Geography ,Wind profile power law ,Log wind profile ,Wind shear ,business - Abstract
Aerodynamic optimization of wind farm layout is a crucial task to reduce wake effects on downstream wind turbines, thus to maximize wind power harvesting. However, downstream evolution and recovery of wind turbine wakes are strongly affected by the characteristics of the incoming atmospheric boundary layer (ABL) flow, such as wind shear and turbulence intensity, which are in turn affected by the ABL thermal stability. In order to characterize the downstream evolution of wakes produced by full-scale wind turbines under different atmospheric conditions, wind velocity measurements were performed with three wind LiDARs. The volumetric scans are performed by continuously sweeping azimuthal and elevation angles of the LiDARs in order to cover a 3D volume that includes the wind turbine wake. The minimum wake velocity deficit is then evaluated as a function of the downstream location for different atmospheric conditions. It is observed that the ABL thermal stability has a significant effect on the wake evolution, and the wake recovers faster under convective conditions.
- Published
- 2014
8. The effect of atmospheric stability on wind-turbine wakes: A large-eddy simulation study
- Author
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Mahdi Abkar, Fernando Porté-Agel, Bak, C, Bechmann, A, Mann, J, Natarajan, A, Rathmann, O, Sathe, A, Sorensen, Jn, Sorensen, Nn, Bingol, F, Dellwik, E, Dimitrov, N, Giebel, G, Hansen, Mol, Jensen, Dj, Larsen, G, and Madsen, Ha
- Subjects
Physics ,History ,Turbulence ,Flow (psychology) ,Wake ,Atmospheric sciences ,Convective Boundary Layer ,Turbine ,Computer Science Applications ,Education ,Physics::Fluid Dynamics ,Turbulence kinetic energy ,Atmospheric instability ,Large eddy simulation - Abstract
In this study, large-eddy simulation is used to investigate the influence of atmospheric stability on wind-turbine wakes. In the simulations, tuning-free Lagrangian scale- dependent dynamic models are used to model the subgrid-scale turbulent fluxes, while the turbine-induced forces are parameterized with an actuator-disk model. Emphasis is placed on studying the structure and characteristics of turbine wake in the cases where the incident flow to the turbine has the same mean velocity at the hub height but different thermal stability condition. The simulation results show that the atmospheric stability has a significant effect on the spatial distribution of the mean velocity deficit and turbulent fluxes in the wake region. In particular, in the convective boundary layer, the wake recovers faster, and the locations of the maximum turbulence intensity and turbulent stresses are closer to the turbine compared with the neutral and stable cases.
9. 3D microscopy at the nanoscale reveals unexpected lattice rotations in deformed nickel.
- Author
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He Q, Schmidt S, Zhu W, Wu G, Huang T, Zhang L, Jensen DJ, Feng Z, Godfrey A, and Huang X
- Abstract
In polycrystalline metals, plastic deformation is accompanied by lattice rotations resulting from dislocation glide. Following these rotations in three dimensions requires nondestructive methods that so far have been limited to grain sizes at the micrometer scale. We tracked the rotations of individual grains in nanograined nickel by using three-dimensional orientation mapping in a transmission electron microscope before and after in situ nanomechanical testing. Many of the larger-size grains underwent unexpected lattice rotations, which we attributed to a reversal of rotation during unloading. This inherent reversible rotation originated from a back stress-driven dislocation slip process that was more active for larger grains. These results provide insights into the fundamental deformation mechanisms of nanograined metals and will help to guide strategies for material design and engineering applications.
- Published
- 2023
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10. Response to Letter-to-the-editor, concerning the article entitled "Common opioids and stimulants in autopsy and DUID cases: A comparison of measured concentrations."
- Author
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Hermansen SK and Christoffersen DJ
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- Autopsy, Analgesics, Opioid, Central Nervous System Stimulants
- Published
- 2023
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11. Common opioids and stimulants in autopsy and DUID cases: A comparison of measured concentrations.
- Author
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Hermansen SK and Christoffersen DJ
- Subjects
- Amphetamine, Analgesics, Opioid, Autopsy, Coma, Heroin, Humans, Methadone, Morphine, Substance Abuse Detection methods, Central Nervous System Stimulants, Cocaine, N-Methyl-3,4-methylenedioxyamphetamine, Substance-Related Disorders
- Abstract
Quantitative results from toxicological analyses of autopsy material are widely compared to ranges in reference works to determine if drug concentrations are in relevant levels for establishing intoxication. This study compares concentrations of commonly used opioids and stimulants from drug addict autopsies and driving under the influence of drugs (DUID) cases to supplement current knowledge of the possible span and overlaps of measured concentrations. The study included whole-blood results from forensic autopsies of drug addicts performed from 2015 to 2020 (n = 220) and DUID cases from 2015 to 2019 (n = 7088). The focus was on heroin/morphine, methadone, cocaine, amphetamine and MDMA concentrations because these drugs are commonly encountered in both fatal intoxications and DUID cases and the potential for abuse is well known. In the DUID group, the opioids heroin/morphine and methadone and the stimulants amphetamine and MDMA were often seen in concentrations above the reported lower comatose-fatal level whereas cocaine was almost always below. Thus, based on our data, the potential for false assessment of intoxication cases when comparing to reported comatose-fatal limits appears greatest on lower end concentrations of heroin/morphine, methadone, amphetamine and MDMA, whereas false assessment of cocaine appears less likely because most control cases are below reported comatose-fatal levels., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
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12. RNA profiles reveal signatures of future health and disease in pregnancy.
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Rasmussen M, Reddy M, Nolan R, Camunas-Soler J, Khodursky A, Scheller NM, Cantonwine DE, Engelbrechtsen L, Mi JD, Dutta A, Brundage T, Siddiqui F, Thao M, Gee EPS, La J, Baruch-Gravett C, Santillan MK, Deb S, Ame SM, Ali SM, Adkins M, DePristo MA, Lee M, Namsaraev E, Gybel-Brask DJ, Skibsted L, Litch JA, Santillan DA, Sazawal S, Tribe RM, Roberts JM, Jain M, Høgdall E, Holzman C, Quake SR, Elovitz MA, and McElrath TF
- Subjects
- Female, Humans, Predictive Value of Tests, Pregnancy, Retrospective Studies, Sensitivity and Specificity, Cell-Free Nucleic Acids blood, Pre-Eclampsia diagnosis, Pre-Eclampsia genetics, RNA blood
- Abstract
Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden
1 . Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method2 . cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia., (© 2022. The Author(s).)- Published
- 2022
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13. Increased risk of fatal intoxication and polypharmacy among psychiatric patients at death.
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Reuss CF, Hasselstrøm JB, Linnet K, Christoffersen DJ, Leth PM, Boel LWT, and Banner J
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- Denmark epidemiology, Female, Humans, Illicit Drugs poisoning, Male, Middle Aged, Prospective Studies, Mentally Ill Persons statistics & numerical data, Poisoning mortality, Polypharmacy, Substance-Related Disorders mortality
- Abstract
Patients suffering from psychiatric disorders have an excess mortality and a shorter life span expectancy compared to the general population. Furthermore, they are treated with multiple drugs and are known to have an increased risk of drug abuse. In this study, we aimed at investigating the pharmaceutical drug and drug of abuse profiles of the deceased included in the Danish prospective autopsy-based forensic study on psychiatric patients, SURVIVE. Using the postmortem systematic toxicological analysis results, we identified 129 different consumed compounds in our population (n = 443). Polypharmacy (≥5 compounds) was detected in 39.5% of the deceased. Deceased with a psychiatric diagnosis or who died from a fatal intoxication had significantly more compounds at the time of their death compared to having either no psychiatric diagnosis or another cause of death, respectively. Evidence of drug abuse was present, as 29.8% of our total population had consumed either methadone or illicit drugs of abuse, excluding tetrahydrocannabinol. Of those deceased with a psychiatric diagnosis, 33.6% had either consumed methadone or illicit drugs of abuse, a greater number than those without a psychiatric diagnosis. Fatal intoxication was the most frequent cause of death (40.6%) with methadone as the major intoxicant. Here, we found that those without a psychiatric diagnosis had fewer fatal pharmaceutical drug intoxications compared to the psychiatric diagnosis groups. Our findings add further context to understanding the excess mortality of psychiatric patents, since there is an increased occurrence of fatal intoxication, polypharmacy, and drug abuse in this population., (© 2020 American Academy of Forensic Sciences.)
- Published
- 2021
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14. The proanthocyanin-related transcription factors MYBC1 and WRKY44 regulate branch points in the kiwifruit anthocyanin pathway.
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Peng Y, Thrimawithana AH, Cooney JM, Jensen DJ, Espley RV, and Allan AC
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- Actinidia classification, Actinidia genetics, Amino Acid Motifs, Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System metabolism, Flavonoids biosynthesis, Fruit metabolism, Phylogeny, Pigments, Biological biosynthesis, Plant Leaves metabolism, Plant Proteins biosynthesis, Plant Proteins genetics, Plants, Genetically Modified, Promoter Regions, Genetic genetics, Recombinant Proteins metabolism, Species Specificity, Nicotiana metabolism, Transcriptome, Actinidia metabolism, Anthocyanins biosynthesis, Gene Expression Regulation, Plant, Plant Proteins physiology, Transcription Factors physiology
- Abstract
The groups of plant flavonoid metabolites termed anthocyanins and proanthocyanins (PA) are responsible for pigmentation in seeds, flowers and fruits. Anthocyanins and PAs are produced by a pathway of enzymes which are transcriptionally regulated by transcription factors (TFs) that form the MYB-bHLH-WD40 (MBW) complex. In this study, transcriptomic analysis of purple-pigmented kiwifruit skin and flesh tissues identified MYBC1, from subgroup 5 of the R2R3 MYB family, and WRKY44 (highly similar to Arabidopsis TTG2) as candidate activators of the anthocyanin pathway. Transient over-expression of MYBC1 and WRKY44 induced anthocyanin accumulation in tobacco leaves. Dual luciferase promoter activation assays revealed that both MYBC1 and WRKY44 were able to strongly activate the promoters of the kiwifruit F3'H and F3'5'H genes. These enzymes are branch points of the pathway which specifies the type of anthocyanin accumulated. Stable over-expression of MYBC1 and WRKY44 in kiwifruit calli activated the expression of F3'5'H and PA-related biosynthetic genes as well as increasing levels of PAs. These results suggest that while previously characterised anthocyanin activator MYBs regulate the overall anthocyanin biosynthesis pathway, the PA-related TFs, MYBC1 and WRKY44, more specifically regulate key branch points. This adds a layer of regulatory control that potentially balances anthocyanin and PA levels.
- Published
- 2020
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15. THC-influenced drivers in the new Danish 3-level offense system.
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Hermansen SK, Pedersen TR, and Christoffersen DJ
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- Adolescent, Adult, Aged, Criminals statistics & numerical data, Denmark, Female, Forensic Toxicology, Gas Chromatography-Mass Spectrometry, Humans, Male, Middle Aged, Young Adult, Criminals legislation & jurisprudence, Driving Under the Influence legislation & jurisprudence, Driving Under the Influence statistics & numerical data, Dronabinol blood
- Abstract
Objective: The objectives of the study were to describe the distribution of tetrahydrocannabinol (THC)-influenced drivers in a new Danish 3-level offense system and discuss the consequences of the changed legislation. Methods: By request of the police, blood of individuals suspected of driving under the influence of drugs (DUID) in Funen and Southern Jutland was sampled by medical staff and shipped to the Section of Forensic Toxicology of the University of Southern Denmark in Odense. Samples from individuals suspected for driving under the influence of cannabis (DUIC) were stored at 5 °C prior to immediate analysis, and THC content in whole-blood samples was established by gas chromatography-mass spectrometry analysis. Quantitative results for blood THC levels were available from 2017 and 2018, resulting in 2,206 eligible cases. Data before and after the legal change on December 15, 2017, were extracted from the department's laboratory information management system. Results: With the new graduated sanctions introduced in December 2017, 70% of the DUIC suspects faced milder sanctions. The number of DUIC cases has been increasing and has almost doubled in the last 4 years, from 648 cases in 2015 to 1,206 in 2018. Correspondingly, the total number of DUID cases increased by 80% from 898 cases in 2015 to 1,614 cases in 2018. The concentration of THC in blood was above the legal limit of 0.001 mg/kg in 73% of the cases; 18% had concentrations categorized as low, 32% as medium, and 22% as high. Conclusion: We found that more than two-thirds of the THC offenders faced milder sanctions compared to before the new legislation, suggesting that the new graduated legislation has had a significant impact. The current trend is a steadily increasing number of DUID cases. We believe that the continual increase is caused by a combination of factors, including increased police awareness and training of police personnel along with improved roadside screening abilities.
- Published
- 2020
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16. Consumption of an Anthocyanin-Rich Extract Made From New Zealand Blackcurrants Prior to Exercise May Assist Recovery From Oxidative Stress and Maintains Circulating Neutrophil Function: A Pilot Study.
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Hurst RD, Lyall KA, Roberts JM, Perthaner A, Wells RW, Cooney JM, Jensen DJ, Burr NS, and Hurst SM
- Abstract
Aim: To evaluate blackcurrant anthocyanin-rich extract (BAE) consumption on time- and dose-dependent plasma anthocyanin bioavailability and conduct a pilot study to explore the potential effect of BAE in promoting recovery from exercise-induced oxidative stress, and maintenance of circulating neutrophil function. Methods: Time- and dose-dependent blackcurrant anthocyanin bioavailability was assessed using LC-MS in 12 participants over 6 h after the ingestion of a placebo or BAE containing 0.8, 1.6, or 3.2 mg/kg total anthocyanins. In a separate pilot intervention exercise trial, 32 participants consumed either a placebo or 0.8, 1.6, or 3.2 mg/kg BAE (8 individuals per group), and then 1 h later performed a 30 min row at 70% VO
2 max. Blood was collected during the trial for oxidative, antioxidant, inflammatory, and circulating neutrophil status. Results: Consumption of BAE caused a time- and dose-dependent increase in plasma anthocyanins, peaking at 2 h after ingestion of 3.2 mg/kg BAE (217 ± 69 nM). BAE consumed 1 h prior to a 30 min row had no effect on plasma antioxidant status but hastened the recovery from exercise-induced oxidative stress: By 2 h recovery, consumption of 1.6 mg/kg BAE prior to exercise caused a significant ( P < 0.05) 34 and 32% decrease in post-exercise plasma oxidative capacity and protein carbonyl levels, respectively, compared to placebo. BAE consumption prior to exercise dose-dependently attenuated a small, yet significant ( P < 0.01) transient 13 ± 2% decline in circulating neutrophils observed in the placebo group immediately post-exercise. Furthermore, the timed consumption of either 1.6 or 3.2 mg/kg BAE attenuated a 17 ± 2.4% ( P < 0.05) decline in neutrophil phagocytic capability of opsonised FITC- Escherichia coli observed 6 h post-exercise in the placebo group. Similarly, a dose-dependent increase in neutrophil surface expression of complement receptor-3 complex (CR3, critical for effective phagocytosis of opsonised microbes), was observed 6 h post-exercise in both 1.6 and 3.2 mg/kg BAE intervention groups. Conclusions: Consumption of BAE (>1.6 mg/kg) 1 h prior to exercise facilitated recovery from exercise-induced oxidative stress and preserved circulating neutrophil function. This study provides data to underpin a larger study designed to evaluate the efficacy of timed BAE consumption on post-exercise recovery and innate immunity.- Published
- 2019
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17. Early results of a surgeon-led, perioperative surgical home.
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Powell AC, Thearle MS, Cusick M, Sanderson DJ, Van Lew H, Lee C, and Kieran JA
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- Adult, Aged, Arizona, Female, Humans, Male, Middle Aged, Outcome and Process Assessment, Health Care, Perioperative Care methods, Perioperative Care statistics & numerical data, Pilot Projects, Quality Improvement statistics & numerical data, Retrospective Studies, Health Services, Indigenous organization & administration, Indians, North American, Patient Care Team organization & administration, Patient-Centered Care organization & administration, Perioperative Care standards, Quality Improvement organization & administration, Surgeons organization & administration
- Abstract
Background: The Perioperative Surgical Home is a novel care model designed to provide patient-centered, high-quality surgical care. In 2013, we implemented POSH, a pilot Peri-Operative Surgical Home at Phoenix Indian Medical Center (PIMC), an Indian Health Service hospital, as a quality improvement project. After 2 y, we sought to quantify the impact of POSH on the quality of surgical care at PIMC., Materials and Methods: We conducted a retrospective review of 33 surgical patients who underwent surgery at PIMC through the POSH process between 2013 and 2015 matched to 64 historical controls with similar operations. Study patients underwent surgery via the POSH treatment process. Primary outcomes were composite measures of (1) care standards and (2) care goals. Success was defined as meeting seven of nine care standards and six of eight care goals., Results and Discussion: The mean number of care standards met was 8.1 ± 1.0 versus 4.2 ± 1.4 (P < 0.001) and the mean number of care goals met was 6.7 ± 0.8 versus 6.1 ± 1.1 (P = 0.005) for POSH patients and historical controls, respectively. Patients participating in the POSH model were 8.6 (95% confidence interval: 3.5-22.3) and 1.5 (95% confidence interval: 1.2-1.9) times more likely to meet the minimum number of care standards and goals, respectively. Fourteen of the study patients (42%) would not have been offered surgery at PIMC before POSH due to elevated surgical risk., Conclusions: POSH may have improved quality of surgical care at PIMC while expanding services to more complex patients. POSH may present an opportunity for improved surgical quality in resource-constrained environments., (Published by Elsevier Inc.)
- Published
- 2017
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18. PROMIS for Orthopaedic Outcomes Measurement.
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Brodke DJ, Saltzman CL, and Brodke DS
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- Ankle physiopathology, Humans, Psychometrics, Software, Spine physiopathology, Upper Extremity physiopathology, Information Systems, Orthopedic Procedures standards, Patient Reported Outcome Measures
- Abstract
Patient-reported outcome measures have become important tools for assessing health status in a variety of patient populations. Many historically or commonly used patient-reported outcome measures in orthopaedics are narrow in scope and are limited by the burden associated with their administration, making them useful only for specific populations. The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to overcome these limitations. The system was developed using item response theory, which allows for reliable and efficient estimation of underlying health traits using targeted item banks to assess physical function in the upper and lower extremities. PROMIS has been validated in patient populations with orthopaedic disorders of the foot and ankle, upper extremity, and spine and has demonstrated a marked improvement in measurement characteristics and reduced patient and administrative burden. PROMIS Physical Function measures are useful for assessing orthopaedic outcomes and are superior to legacy measures in several key populations.
- Published
- 2016
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19. Item Response Theory and Computerized Adaptive Testing for Orthopaedic Outcomes Measures.
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Brodke DJ, Hung M, and Bozic KJ
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- Calibration, Humans, Musculoskeletal Diseases complications, Psychometrics, Software, Information Systems, Orthopedics, Patient Reported Outcome Measures, Symptom Assessment methods
- Abstract
The use of patient-reported outcome measures (PROMs) to objectively and quantifiably assess patient symptomatology allows tracking of symptoms over time, measurement of the effect of healthcare interventions, and performance of cost-effectiveness analyses to assess and compare the value of treatment options. Many of the PROMs historically used had limited versatility because they were developed using classical test theory, which generates static tests that are not comparable with other measures assessing similar outcomes. Recently developed PROMs, however, were designed according to the principles of the newer item response theory (IRT), which allows for the creation of dynamic instruments deliverable in a variety of forms that are readily comparable with similar measures. IRT also enables computerized adaptive testing to decrease the burden of using PROMs by allowing rapid and complete data acquisition. IRT-based instruments are suitable for patient care and research and have been validated in a variety of populations, many of which are relevant to orthopaedic populations.
- Published
- 2016
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20. Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18.
- Author
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Wynn JL, Wilson CS, Hawiger J, Scumpia PO, Marshall AF, Liu JH, Zharkikh I, Wong HR, Lahni P, Benjamin JT, Plosa EJ, Weitkamp JH, Sherwood ER, Moldawer LL, Ungaro R, Baker HV, Lopez MC, McElroy SJ, Colliou N, Mohamadzadeh M, and Moore DJ
- Subjects
- Animals, Animals, Newborn, Antibodies, Monoclonal therapeutic use, Female, Male, Mice, Mice, Inbred C57BL, Molecular Targeted Therapy methods, Neonatal Sepsis pathology, Treatment Outcome, Interleukin-17 antagonists & inhibitors, Interleukin-17 immunology, Interleukin-18 immunology, Neonatal Sepsis immunology, Neonatal Sepsis therapy, Survival Rate
- Abstract
Interleukin (IL)-18 is an important effector of innate and adaptive immunity, but its expression must also be tightly regulated because it can potentiate lethal systemic inflammation and death. Healthy and septic human neonates demonstrate elevated serum concentrations of IL-18 compared with adults. Thus, we determined the contribution of IL-18 to lethality and its mechanism in a murine model of neonatal sepsis. We find that IL-18-null neonatal mice are highly protected from polymicrobial sepsis, whereas replenishing IL-18 increased lethality to sepsis or endotoxemia. Increased lethality depended on IL-1 receptor 1 (IL-1R1) signaling but not adaptive immunity. In genome-wide analyses of blood mRNA from septic human neonates, expression of the IL-17 receptor emerged as a critical regulatory node. Indeed, IL-18 administration in sepsis increased IL-17A production by murine intestinal γδT cells as well as Ly6G(+) myeloid cells, and blocking IL-17A reduced IL-18-potentiated mortality to both neonatal sepsis and endotoxemia. We conclude that IL-17A is a previously unrecognized effector of IL-18-mediated injury in neonatal sepsis and that disruption of the deleterious and tissue-destructive IL-18/IL-1/IL-17A axis represents a novel therapeutic approach to improve outcomes for human neonates with sepsis.
- Published
- 2016
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21. Sweet Poisons: Honeys Contaminated with Glycosides of the Neurotoxin Tutin.
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Larsen L, Joyce NI, Sansom CE, Cooney JM, Jensen DJ, and Perry NB
- Subjects
- Food Contamination analysis, Glycosides chemistry, Glycosides poisoning, Molecular Structure, Neurotoxins blood, Neurotoxins pharmacokinetics, Nuclear Magnetic Resonance, Biomolecular, Picrotoxin analysis, Picrotoxin chemistry, Picrotoxin pharmacology, Sesquiterpenes analysis, Sesquiterpenes chemistry, Glycosides analysis, Honey analysis, Picrotoxin analogs & derivatives, Sesquiterpenes pharmacology
- Abstract
Poisonings due to consumption of honeys containing plant toxins have been reported widely. One cause is the neurotoxin tutin, an oxygenated sesquiterpene picrotoxane, traced back to honeybees (Apis mellifera) collecting honeydew produced by passionvine hoppers (Scolypopa australis) feeding on sap of the poisonous shrub tutu (Coriaria spp.). However, a pharmacokinetic study suggested that unidentified conjugates of tutin were also present in such honeys. We now report the discovery, using ion trap LC-MS, of two tutin glycosides and their purification and structure determination as 2-(β-d-glucopyranosyl)tutin (4) and 2-[6'-(α-d-glucopyranosyl)-β-d-glucopyranosyl]tutin (5). These compounds were used to develop a quantitative triple quadrupole LC-MS method for honey analysis, which showed the presence of tutin (3.6 ± 0.1 μg/g honey), hyenanchin (19.3 ± 0.5), tutin glycoside (4) (4.9 ± 0.4), and tutin diglycoside (5) (4.9 ± 0.1) in one toxic honey. The ratios of 4 and 5 to tutin varied widely in other tutin-containing honeys. The glycosidation of tutin may represent detoxification by one or both of the insects involved in the food chain from plant to honey.
- Published
- 2015
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22. Unusual immuno-modulatory triterpene-caffeates in the skins of russeted varieties of apples and pears.
- Author
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Andre CM, Larsen L, Burgess EJ, Jensen DJ, Cooney JM, Evers D, Zhang J, Perry NB, and Laing WA
- Subjects
- Adult, Cell Line, Humans, Macrophages drug effects, Macrophages immunology, Middle Aged, NF-kappa B immunology, Anti-Inflammatory Agents pharmacology, Caffeic Acids pharmacology, Fruit chemistry, Malus chemistry, Plant Extracts pharmacology, Pyrus chemistry, Triterpenes pharmacology
- Abstract
Three triterpene-caffeates have been isolated from skins of a russeted apple cultivar "Merton Russet" and identified by LC-MS and NMR as betulinic acid-3-cis-caffeate, betulinic acid-3-trans-caffeate, and oleanolic acid-3-trans-caffeate. Betulinic acid-3-trans-caffeate and oleanolic acid-3-trans-caffeate were also found in russeted pear skins. These compounds have not been previously reported in apples or pears, or in any other foods. Their presence was related to suberized tissue as they were only found in russet portions of the partially russeted apple cultivar "Cox's Orange Pippin" and were not detected in the waxy apple cultivar "Royal Gala". High concentrations of betulinic acid-3-trans-caffeate were found in the bark of both "Merton Russet" and "Royal Gala" trees. The three triterpene-caffeates showed anti-inflammatory activity in vitro, inhibiting NF-κB activation with IC50's of 6-9 μM. Betulinic acid-3-trans-caffeate, the predominant compound in the apples, was immuno-modulatory at around 10 μM in the in vitro and ex vivo bioassays, boosting production of the pro-inflammatory cytokine TNFα in cells stimulated with bacterial lipopolysaccharides.
- Published
- 2013
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23. Blackcurrant proanthocyanidins augment IFN-gamma-induced suppression of IL-4 stimulated CCL26 secretion in alveolar epithelial cells.
- Author
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Hurst SM, McGhie TK, Cooney JM, Jensen DJ, Gould EM, Lyall KA, and Hurst RD
- Subjects
- Anti-Inflammatory Agents, Non-Steroidal analysis, Anti-Inflammatory Agents, Non-Steroidal chemistry, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Asthma prevention & control, Catechin analogs & derivatives, Catechin pharmacology, Cell Line, Chemokine CCL26, Chemokines, CC genetics, Epithelial Cells drug effects, Epithelial Cells metabolism, Fruit chemistry, Gene Expression Regulation drug effects, Humans, Interferon-gamma agonists, Interleukin-13 antagonists & inhibitors, Interleukin-13 pharmacology, Interleukin-4 antagonists & inhibitors, Osmolar Concentration, Phosphorylation drug effects, Plant Extracts chemistry, Proanthocyanidins analysis, Proanthocyanidins chemistry, Pulmonary Alveoli metabolism, RNA, Messenger metabolism, Recombinant Proteins pharmacology, STAT6 Transcription Factor metabolism, Time Factors, Chemokines, CC metabolism, Interferon-gamma pharmacology, Interleukin-4 pharmacology, Plant Extracts pharmacology, Proanthocyanidins pharmacology, Pulmonary Alveoli drug effects, Ribes chemistry
- Abstract
Epidemiological studies reveal that fruit consumption reduces the prevalence of airway inflammation and childhood asthma. In particular, blackcurrant polyphenolic extracts have been shown to alleviate lung inflammation. Since IL-4-stimulated eotaxin-3 (CCL26) secretion is a major factor in the continuous eosinophil recruitment observed in atopic asthma, our focus was to evaluate the effectiveness of blackcurrant polyphenolic compounds on CCL26 secretion in human alveolar epithelial cells. Our results indicate that a proanthocyanin-enriched blackcurrant extract (BC-P), but not anthocyanin-enriched blackcurrant extract suppressed both IL-4- and IL-13-stimulated CCL26 secretion in a dose-dependent manner. Furthermore pre-incubation of cells with BC-P caused a time-dependent suppression of IL-4-stimulated CCL26 secretion. Moreover, epigallocatechin (EGC), and to a lesser extent epicatechin, metabolites identified in the proanthocyanidin extract, suppressed IL-4-stimulated CCL26 secretion. EGC was also effective at reducing the cellular phosphorylated STAT-6/STAT-6 ratio. Furthermore, both BC-P and purified EGC potentiated the ability of IFN-gamma to suppress IL-4-stimulated CCL26 secretion. The progression of an allergic immune response is complex, identifying plant compounds that target specific cellular events and complement the body's own immune actions is important for the development of functional foods. Our findings support the potential for blackcurrant polyphenolic compounds to reduce eosinophil recruitment and alleviate eosinophilic-driven airway inflammation.
- Published
- 2010
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24. Blueberry fruit polyphenolics suppress oxidative stress-induced skeletal muscle cell damage in vitro.
- Author
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Hurst RD, Wells RW, Hurst SM, McGhie TK, Cooney JM, and Jensen DJ
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- Animals, Anthocyanins analysis, Anthocyanins chemistry, Anthocyanins isolation & purification, Antioxidants analysis, Antioxidants chemistry, Antioxidants isolation & purification, Biomarkers metabolism, Cell Differentiation drug effects, Cell Line, Creatine Kinase metabolism, Dose-Response Relationship, Drug, Flavonoids analysis, Flavonoids chemistry, Flavonoids isolation & purification, Glycosides analysis, Glycosides chemistry, Glycosides pharmacology, Ionophores toxicity, Lactate Dehydrogenases metabolism, Muscle Fibers, Skeletal cytology, Muscle Fibers, Skeletal drug effects, Muscle Fibers, Skeletal enzymology, Muscle, Skeletal enzymology, Phenols analysis, Phenols chemistry, Phenols isolation & purification, Phytotherapy, Plant Extracts chemistry, Plant Extracts isolation & purification, Plant Extracts pharmacology, Polyphenols, Rats, Reactive Oxygen Species analysis, Time Factors, Antioxidants pharmacology, Blueberry Plants chemistry, Flavonoids pharmacology, Fruit chemistry, Muscle, Skeletal drug effects, Oxidative Stress drug effects, Phenols pharmacology
- Abstract
Skeletal muscle damage can result from disease and unaccustomed or excessive exercise. Muscle dysfunction occurs via an increased level of reactive oxygen species and hence there is potential in antioxidants as amelioration strategies. We explored the putative benefit of fruit polyphenolic extracts in reducing the susceptibility of skeletal muscle cells to oxidative stress. Muscle myotubes were simultaneously challenged with fruit extracts (1-50 microg/mL) and calcium ionophore (A23187), hydrogen peroxide, or 2,4-dinitrophenol and damage monitored by release of cytosolic enzymes. A blueberry fruit extract displayed a potent and significant dose-dependent protective capacity. Evaluation of the protective capacity of anthocyanin sub-extracts of blueberry fruit and pure individual glycosides, with identification of extract polyphenolic components using MS, suggested that malvidin galactoside and/or glucoside were the active compounds. These in vitro data support the concept that blueberry fruits or derived foods rich in malvidin glycosides may be beneficial in alleviating muscle damage caused by oxidative stress. More research on the benefits of blueberry fruit consumption in human intervention studies is warranted.
- Published
- 2010
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25. Chemical composition and in vitro anti-inflammatory activity of apple phenolic extracts and of their sub-fractions.
- Author
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Lauren DR, Smith WA, Adaim A, Cooney JM, Wibisono R, Jensen DJ, Zhang J, and Skinner MA
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- Animals, Cell Line, Cell Survival drug effects, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Flavonoids analysis, Flavonoids chemistry, Flavonoids pharmacology, Glycosides analysis, Glycosides chemistry, Glycosides pharmacology, Inflammation drug therapy, Inflammation Mediators metabolism, Inhibitory Concentration 50, Lipopolysaccharides toxicity, Macrophages drug effects, Macrophages metabolism, Mice, Phenols chemistry, Phenols pharmacology, Phytotherapy, Powders, Reproducibility of Results, Anti-Inflammatory Agents, Non-Steroidal chemistry, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Fruit chemistry, Malus chemistry, Phenols analysis, Plant Extracts chemistry, Plant Extracts pharmacology
- Abstract
Apple extract powders from three different manufacturers were investigated for their anti-inflammatory activity, their total phenolic content, and their chemical composition. The samples represented two production batches for two products and a single batch of a third. The samples showed similar, but clearly different, anti-inflammatory activities, and had substantially different total phenolic contents, and different chemical compositions. Differences in chemical composition for batches of the same product were significant, although not as great as differences between products. The samples were fractionated into chemical classes. The most active fractions were those that contained epicatechin, catechin with phloridzin and quercetin glycosides, or those that contained procyanidin polymers. It was not possible to link activity to the presence of individual components or combinations of these. If fruit extracts are to be reliably linked to validated health benefits, then the source materials, the extraction processes, and the final composition of such products need to be more clearly defined than at present.
- Published
- 2009
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26. Environmental regulation of leaf colour in red 35S:PAP1 Arabidopsis thaliana.
- Author
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Rowan DD, Cao M, Lin-Wang K, Cooney JM, Jensen DJ, Austin PT, Hunt MB, Norling C, Hellens RP, Schaffer RJ, and Allan AC
- Subjects
- Anthocyanins chemistry, Anthocyanins metabolism, Arabidopsis genetics, Arabidopsis radiation effects, Arabidopsis Proteins, Biomass, Cluster Analysis, Flavonols chemistry, Flavonols metabolism, Gene Expression Regulation, Plant, Genes, Plant, Genes, Regulator, Glycosides chemistry, Glycosides metabolism, Light, Pancreatitis-Associated Proteins, Plant Leaves radiation effects, Temperature, Transcription Factors genetics, Arabidopsis physiology, Environment, Pigmentation radiation effects, Plant Leaves physiology, Transcription Factors metabolism
- Abstract
* High-temperature, low-light (HTLL) treatment of 35S:PAP1 Arabidopsis thaliana over-expressing the PAP1 (Production of Anthocyanin Pigment 1) gene results in reversible reduction of red colouration, suggesting the action of additional anthocyanin regulators. High-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LCMS) and Affimetrix-based microarrays were used to measure changes in anthocyanin, flavonoids, and gene expression in response to HTLL. * HTLL treatment of control and 35S:PAP1 A. thaliana resulted in a reversible reduction in the concentrations of major anthocyanins despite ongoing over-expression of the PAP1 MYB transcription factor. Twenty-one anthocyanins including eight cis-coumaryl esters were identified by LCMS. The concentrations of nine anthocyanins were reduced and those of three were increased, consistent with a sequential process of anthocyanin degradation. Analysis of gene expression showed down-regulation of flavonol and anthocyanin biosynthesis and of transport-related genes within 24 h of HTLL treatment. No catabolic genes up-regulated by HTLL were found. * Reductions in the concentrations of anthocyanins and down-regulation of the genes of anthocyanin biosynthesis were achieved by environmental manipulation, despite ongoing over-expression of PAP1. Quantitative PCR showed reduced expression of three genes (TT8, TTG1 and EGL3) of the PAP1 transcriptional complex, and increased expression of the potential transcriptional repressors AtMYB3, AtMYB6 and AtMYBL2 coincided with HTLL-induced down-regulation of anthocyanin biosynthesis. * HTLL treatment offers a model system with which to explore anthocyanin catabolism and to discover novel genes involved in the environmental control of anthocyanins.
- Published
- 2009
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27. Antifungal saponins from Paris polyphylla Smith.
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Deng D, Lauren DR, Cooney JM, Jensen DJ, Wurms KV, Upritchard JE, Cannon RD, Wang MZ, and Li MZ
- Subjects
- Molecular Structure, Saponins chemistry, Antifungal Agents isolation & purification, Drugs, Chinese Herbal chemistry, Liliaceae chemistry, Saponins isolation & purification
- Abstract
Three steroidal saponins, including one new and two known compounds, were isolated from the rhizomes of Paris polyphylla Smith. One- and two-dimensional NMR, LC-MS, and interpretation of hydrolytic cleavage experiments led to the identification of the structure of the new saponin as ( 25R)-spirost-5-ene-3 beta,17 alpha-diol (pennogenin) 3- O-{ O- alpha- L-rhamnopyranosyl-(1-->2)- O-[ O- beta-xylopyranosyl-(1-->5)- alpha- L-arabinofuranosyl-(1-->4)]- beta- D-glucopyranoside}. The isolated saponins were evaluated for their antifungal activity against Cladosporium cladosporioides and Candida species and showed comparable activity to chemicals used in some commercial products.
- Published
- 2008
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28. Preparative enzymatic synthesis of glucuronides of zearalenone and five of its metabolites.
- Author
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Stevenson DE, Hansen RP, Loader JI, Jensen DJ, Cooney JM, Wilkins AL, and Miles CO
- Subjects
- Animals, Cattle, Glucuronides chemistry, Magnetic Resonance Spectroscopy, Models, Molecular, Zearalenone chemistry, Zearalenone metabolism, Glucuronides biosynthesis, Glucuronosyltransferase metabolism, Zearalenone biosynthesis
- Abstract
The resorcylic acid lactones zearalenone ( 1), alpha-zearalenol ( 2), beta-zearalenol ( 3), alpha-zearalanol (zeranol) ( 4), beta-zearalanol (taleranol) ( 5), and zearalanone ( 6) were converted to their glucuronides on a preparative scale in good yields. Reactions were conducted with bovine uridine 5'-diphosphoglucuronyl transferase (UDPGT) as catalyst and uridine 5'-diphosphoglucuronic acid (UDPGA) as cofactor. The glucuronides were isolated by column chromatography and characterized by NMR spectroscopy and mass spectrometry. Although the principal products were 4- O-glucuronides (i.e., linkage through a phenolic hydroxyl), significant quantities of the 6'- O-glucuronides (i.e., linkage through the aliphatic hydroxyl) of alcohols 2, 4, and 5 were also isolated. In the case of 3, the 2- O-glucuronide was isolated as the minor product. Overall isolated yields of glucuronides, performed on a 20-50 mg scale, were typically ca. 80% based on the resorcylic acid lactone starting material. LC-UV-MS (2) analysis of purified specimens revealed MS (2) fragmentations useful for defining the point of attachment of the glucuronide moiety to the zearalenone nucleus.
- Published
- 2008
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29. Semisynthesis of S-desoxybrevetoxin-B2 and brevetoxin-B2, and assessment of their acute toxicities.
- Author
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Selwood AI, Ginkel Rv, Wilkins AL, Munday R, Ramsdell JS, Jensen DJ, Cooney JM, and Miles CO
- Subjects
- Animals, Female, Lethal Dose 50, Marine Toxins toxicity, Mice, Sulfhydryl Compounds chemistry, Marine Toxins chemical synthesis, Marine Toxins chemistry, Oxocins chemistry
- Abstract
Brevetoxins are neurotoxins associated with blooms of marine algae such as Karenia brevis and can accumulate in the marine food chain, causing intoxication of marine animals and people consuming seafood. Brevetoxin-B2 ( 5) is a toxic metabolite produced in shellfish exposed to algae that contain brevetoxin-B ( 1). S-Desoxybrevetoxin-B2 ( 4) has been proposed as a cometabolite produced during this transformation, and while LC-MS analyses suggest its presence in shellfish, it has not yet been isolated and characterized. Studies on these materials are severely constrained by the difficulty of obtaining and purifying them from natural sources. We have developed a convenient one-pot conversion of commercially available brevetoxin-B ( 1) into S-desoxybrevetoxin-B2 ( 4), and a simple method for converting 4 into brevetoxin-B2 ( 5). Full NMR and mass-spectral characterization of 4 and 5 confirmed their structures and showed that the ratio of diastereoisomers in the synthetic 4 and 5 was similar to that observed in naturally contaminated shellfish. The LD 50 values for 4, 5, and dihydrobrevetoxin-B ( 6) by ip injection in mice were 211, 400, and 250 microg/kg, respectively. The methodology for synthesis of brevetoxin metabolites should greatly facilitate toxicological, biochemical and immunochemical studies of these substances, as well as the production of analytical standards.
- Published
- 2008
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30. Comparison of enzymically glucuronidated flavonoids with flavonoid aglycones in an in vitro cellular model of oxidative stress protection.
- Author
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Stevenson DE, Cooney JM, Jensen DJ, Wibisono R, Adaim A, Skinner MA, and Zhang J
- Subjects
- Cell Line, Tumor, Cell Survival drug effects, Humans, Antioxidants pharmacology, Flavonoids pharmacology, Glucuronides pharmacology, Hydrogen Peroxide pharmacology, Oxidative Stress drug effects
- Abstract
This study modeled, in vitro, the potential effect of conjugative (phase II) metabolism on the cytoprotective capacity of fruit flavonoids against oxidative stress. Flavonoid aglycones were compared with their corresponding isomeric mixtures of glucuronides for their ability to enhance the survival of cultured human Jurkat T and neuroblastoma cells stressed with hydrogen peroxide. Various polyphenolic compounds were tested as substrates in vitro for an ovine liver glucuronyl transferase preparation. Flavonoids and their glycoside derivatives were found to be good substrates, whereas phenolic acids were either poor or nonsubstrates. Five common flavonoids were glucuronidated to prepare mixtures for bioassay testing. Glucuronidation generally weakened the cytoprotective capacities of flavonoids (in the presence of H(2)O(2)), but some compounds were weakened much more than others. The concentration that halved cell death was well below 0.5 microM for most flavonoids tested, but glucuronidation increased median effective concentration values to a range of 1-16 microM. This compares with the generally accepted physiological range (0.1-10 microM) for circulating dietary polyphenolics detected in the body. Therefore, some flavonoids may retain a reduced cytoprotective capacity in vitro, after glucuronidation, whereas others may be effectively inactivated.
- Published
- 2008
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31. Convenient large-scale purification of yessotoxin from Protoceratium reticulatum culture and isolation of a novel furanoyessotoxin.
- Author
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Loader JI, Hawkes AD, Beuzenberg V, Jensen DJ, Cooney JM, Wilkins AL, Fitzgerald JM, Briggs LR, and Miles CO
- Subjects
- Animals, Chromatography, High Pressure Liquid, Ethers, Cyclic chemistry, Magnetic Resonance Spectroscopy, Molecular Structure, Oxocins chemistry, Spectrometry, Mass, Electrospray Ionization, Dinoflagellida metabolism, Ethers, Cyclic isolation & purification, Mollusk Venoms, Oxocins isolation & purification
- Abstract
Yessotoxins from a large-scale culture (226 L) of Protoceratium reticulatum strain CAWD129 were harvested by filtration followed by solid-phase extraction. The extract was purified by column chromatography over basic alumina and reverse-phase flash chromatography to afford pure yessotoxin (193 mg). Isolation of yessotoxin was greatly facilitated by selection of a strain which did not produce analogues that interfered with yessotoxin isolation. In addition to yessotoxin, numerous minor yessotoxins were detected by LC-MS in other fractions. From one of these, an early eluting minor analogue with the same molecular weight as yessotoxin and a similar mass spectrometric fragmentation pattern was isolated. This analogue was identified by NMR and mass spectrometry as a novel yessotoxin analogue containing a furan ring in the side chain. This finding reveals biosynthetic flexibility of the yessotoxin pathway in P. reticulatum and confirms earlier findings of production of many minor yessotoxin analogues by this alga. Production of these analogues appeared to be a constitutive trait of P. reticulatum CAWD129.
- Published
- 2007
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32. Comparison of the relative recovery of polyphenolics in two fruit extracts from a model of degradation during digestion and metabolism.
- Author
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Stevenson DE, Cooney JM, Jensen DJ, Zhang J, and Wibisono R
- Subjects
- Anthocyanins analysis, Blueberry Plants chemistry, Chlorogenic Acid analysis, Chlorogenic Acid metabolism, Digestion, Glucuronides metabolism, Hydrogen-Ion Concentration, Hydrolysis, Malus chemistry, Models, Biological, Phloretin analysis, Phloretin metabolism, Polyphenols, Quercetin analysis, Quercetin metabolism, Species Specificity, Flavonoids analysis, Flavonoids metabolism, Fruit chemistry, Phenols analysis, Phenols metabolism, Plant Extracts chemistry
- Abstract
To simulate the effects of digestion and metabolism on the survival of different polyphenolic compounds, extracts of blueberry and apple were deglycosylated by acid hydrolysis, followed by enzymic glucuronidation under neutral conditions, yielding approximately 5% overall recovery of polyphenolics. The major polyphenolics before and after the treatment were compared, to estimate which species are likely to be present in the intestinal lumen, undegraded and available for absorption, after consumption of the fruit. Whereas blueberry extract consisted predominantly of anthocyanins, epicatechin and caffeoyl quinate esters, the major components of the treated extract were quercetin glucuronides and (unglucuronidated) caffeoyl quinates, with only traces of anthocyanidin derivatives. In apple extract, compositional changes were less marked, but caffeoyl quinates, procyanidins and quercetin were enriched at the expense of caffeic acid, epicatechin and catechin. Hydrophobic compounds like phloretin and quercetin were extensively glucuronidated, whereas caffeic acid and caffeoyl quinate were not. These results suggest that the major polyphenolic components of a fruit are not necessarily the most important contributors to any health benefits because the polyphenolic composition in the intestinal lumen and consequently, in the circulation, may be considerably different.
- Published
- 2007
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33. Peripherally administered desacetyl alpha-MSH and alpha-MSH both influence postnatal rat growth and associated rat hypothalamic protein expression.
- Author
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Wu CS, Greenwood DR, Cooney JM, Jensen DJ, Tatnell MA, Cooper GJ, and Mountjoy KG
- Subjects
- Animals, Animals, Newborn, Body Weight drug effects, Chromatography, Liquid, Electrophoresis, Polyacrylamide Gel, Hypothalamus drug effects, Injections, Subcutaneous, Mass Spectrometry, Organ Size drug effects, Rats, Growth drug effects, Hypothalamus metabolism, Nerve Tissue Proteins biosynthesis, alpha-MSH pharmacology
- Abstract
Desacetyl alpha-MSH predominates over alpha-MSH during development, but whether it is biologically active and has a physiological role is unclear. We compared the effects of 0.3 microg.g(-1).day(-1) desacetyl alpha-MSH with that of 0.3 microg.g(-1).day(-1) alpha-MSH on postnatal body growth by administering the peptides subcutaneously daily for postnatal days 0-14 and also used a two-dimensional gel electrophoresis gel-based proteomic approach to analyze protein changes in hypothalami, the relay center for body weight and growth regulation, after 14 days of treatment. We found that the growth rate between days 1 and 10 was significantly decreased by desacetyl alpha-MSH but not by alpha-MSH, but by day 14, a time reported for development of a mature pattern of hypothalamic innervation, both peptides had significantly increased neonatal growth compared with PBS-treated control rats. Desacetyl alpha-MSH significantly increased spleen weight, but alpha-MSH had no effect. alpha-MSH significantly decreased kidney weight, but desacetyl alpha-MSH had no effect. Both desacetyl alpha-MSH and alpha-MSH significantly decreased brain weight. By 14 days, both peptides significantly changed expression of a number of hypothalamic proteins, specifically metabolic enzymes, cytoskeleton, signaling, and stress response proteins. We show that peripherally administered desacetyl alpha-MSH is biologically active and induces responses that can differ from those for alpha-MSH. In conclusion, desacetyl alpha-MSH appears to be an important regulator of neonatal rat growth.
- Published
- 2006
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34. Methylated polyphenols are poor "chemical" antioxidants but can still effectively protect cells from hydrogen peroxide-induced cytotoxicity.
- Author
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Deng D, Zhang J, Cooney JM, Skinner MA, Adaim A, Jensen DJ, and Stevenson DE
- Subjects
- Dose-Response Relationship, Drug, Humans, Hydrogen Peroxide pharmacology, Hydroxybenzoates pharmacology, Jurkat Cells, Methylation, Oxidants pharmacology, Polyphenols, Reactive Oxygen Species antagonists & inhibitors, Reactive Oxygen Species metabolism, Antioxidants pharmacology, Cytoprotection, Flavonoids pharmacology, Hydrogen Peroxide toxicity, Oxidants toxicity, Phenols pharmacology
- Abstract
Several polyphenolic compounds, including flavonoids and phenolic acids, were compared with their per-methylated forms in both chemical and cell-based assays for antioxidant capacity. Methylation largely eliminated "chemical" antioxidant capacity, according to ferric reducing antioxidant power and oxygen radical absorbance capacity assays. Methylation, however, only moderately reduced protection of human Jurkat cells in culture, from hydrogen peroxide-mediated cytotoxicity, at physiologically relevant concentrations. Neither methylated nor un-methylated compounds were detectably metabolized by the cells. It appears that the protective mechanism of polyphenolic antioxidants against high concentrations of hydrogen peroxide in human cells may be largely unrelated to chemical antioxidant capacity.
- Published
- 2006
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35. Isolation and identification of pectenotoxins-13 and -14 from Dinophysis acuta in New Zealand.
- Author
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Miles CO, Wilkins AL, Hawkes AD, Jensen DJ, Selwood AI, Beuzenberg V, Mackenzie AL, Cooney JM, and Holland PT
- Subjects
- Animals, Chromatography, High Pressure Liquid, Dinoflagellida metabolism, Furans chemistry, Macrolides, Marine Toxins chemistry, Molecular Structure, Pyrans chemistry, Spectrometry, Mass, Electrospray Ionization, Dinoflagellida chemistry, Furans isolation & purification, Marine Toxins isolation & purification, Pyrans isolation & purification
- Abstract
Two novel pectenotoxins (PTXs), PTX-13 and -14, were isolated from extracts of Dinophysis acuta collected from the west coast of South Island, New Zealand. The compounds were identified as oxidized analogues of PTX-2 by NMR spectroscopic and LC-MS studies. PTX-13 (32R-hydroxyPTX-2) corresponds to the unidentified analogue PTX-11x reported by [Suzuki et al., 2003. Liquid chromatography-mass spectrometry of spiroketal stereoisomers of pectenotoxins and the analysis of novel pectenotoxin isomers in the toxic dinoflagellate Dinophysis acuta from New Zealand. J. Chromatogr. A 992, 141-150]. PTX-13 underwent slow deuteration at the 13beta-position during NMR analysis. PTX-14 corresponds to the 32,36-dehydration product of PTX-13, and may be an artifact.
- Published
- 2006
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36. Isolation and identification of a cis-C8-diol-ester of okadaic acid from Dinophysis acuta in New Zealand.
- Author
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Miles CO, Wilkins AL, Hawkes AD, Jensen DJ, Cooney JM, Larsen K, Petersen D, Rise F, Beuzenberg V, and Lincoln Mackenzie A
- Subjects
- Animals, Chromatography, High Pressure Liquid, Esterification, Furans pharmacology, Hepatopancreas metabolism, Hydrolysis drug effects, Macrolides, Magnetic Resonance Spectroscopy, Marine Toxins chemistry, Molecular Structure, Okadaic Acid analogs & derivatives, Okadaic Acid analysis, Pyrans pharmacology, Spectrometry, Mass, Electrospray Ionization, Dinoflagellida chemistry, Marine Toxins isolation & purification, Okadaic Acid isolation & purification, Pyrans chemistry
- Abstract
A cis-isomer of a C(8)-diol ester of okadaic acid (1) was isolated during large-scale purification of pectenotoxins (PTXs) from extracts of Dinophysis acuta collected from the west coast of South Island, New Zealand. The compound was identified by NMR spectroscopic and liquid chromatography-mass spectrometry (LC-MS) studies, and is the first reported cis-isomer of an okadaic acid C(8)-diol-ester identified in Dinophysis. The more abundant trans-C(8)-diol ester of okadaic acid (2) isolated from the same Dinophysis extract was rapidly hydrolyzed to okadaic acid in vitro by the supernatant from green-lipped mussel hepatopancreas.
- Published
- 2006
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37. Isolation of yessotoxin 32-O-[beta-L-arabinofuranosyl-(5'-->1'')-beta-L-arabinofuranoside] from Protoceratium reticulatum.
- Author
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Miles CO, Wilkins AL, Selwood AI, Hawkes AD, Jensen DJ, Cooney JM, Beuzenberg V, and MacKenzie AL
- Subjects
- Animals, Models, Molecular, Molecular Structure, Oxocins chemistry, Mollusk Venoms chemistry, Mollusk Venoms isolation & purification, Oxocins isolation & purification
- Abstract
Yessotoxin 32-O-[beta-L-arabinofuranosyl-(5'-->1'')-beta-L-arabinofuranoside] (3) was isolated from extracts of Protoceratium reticulatum during a large scale isolation of yessotoxin (1). The structure was characterized by mass spectrometry and NMR spectroscopy. Di-glycoside-3, along with the corresponding mono-glycoside (2) were detected in cultures of P. reticulatum originating from Europe and New Zealand, suggesting that production of arabinosides of 1 is a normal feature of this alga. Formation of multiply charged anions and fragmentation of 3 occurred much more readily than for 1 and 2 under the LC-MS conditions used in this study.
- Published
- 2006
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38. Production of 7-epi-pectenotoxin-2 seco acid and assessment of its acute toxicity to mice.
- Author
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Miles CO, Wilkins AL, Munday JS, Munday R, Hawkes AD, Jensen DJ, Cooney JM, and Beuzenberg V
- Subjects
- Animals, Bivalvia metabolism, Chromatography, High Pressure Liquid, Female, Furans chemistry, Hydrolysis, Macrolides, Magnetic Resonance Spectroscopy, Mice, Pyrans chemistry, Shellfish analysis, Shellfish toxicity, Furans metabolism, Furans toxicity, Pyrans metabolism, Pyrans toxicity
- Abstract
Pectenotoxins (PTXs) accumulate in shellfish feeding on dinoflagellates of the genus Dinophysis, so that humans can be exposed to these toxins through shellfish consumption. Some PTXs are toxic to experimental animals, whereas others are of much lower toxicity. Pectenotoxin-2, the most abundant PTX from most Dinophysis spp., is rapidly metabolized by most shellfish to a mixture of pectenotoxin-2 seco acid (2) and 7-epi-pectenotoxin-2 seco acid (1). A mixture of 1 and 2 was produced during purification of an extract from in vitro enzymatic hydrolysis of pectenotoxin-2. These were separated by preparative HPLC, and the structure of 1 was confirmed by one- and two-dimensional 1H and 13C NMR spectroscopy and LC-MS3 analyses. No toxic changes were recorded in mice injected intraperitoneally with 1 or 2 at a dose of 5000 microg/kg. PTX seco acids are therefore unlikely to be of consequence to human consumers at the concentrations found in contaminated shellfish.
- Published
- 2006
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39. Identification of pectenotoxin-11 as 34S-hydroxypectenotoxin-2, a new pectenotoxin analogue in the toxic dinoflagellate Dinophysis acuta from New Zealand.
- Author
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Suzuki T, Walter JA, LeBlanc P, MacKinnon S, Miles CO, Wilkins AL, Munday R, Beuzenberg V, MacKenzie AL, Jensen DJ, Cooney JM, and Quilliam MA
- Subjects
- Animals, Injections, Intraperitoneal, Lethal Dose 50, Macrolides, Magnetic Resonance Spectroscopy, Marine Toxins administration & dosage, Marine Toxins toxicity, Mice, Models, Molecular, Molecular Conformation, New Zealand, Sensitivity and Specificity, Spectrometry, Mass, Electrospray Ionization, Spectrophotometry, Ultraviolet, Stereoisomerism, Time Factors, Dinoflagellida chemistry, Furans chemistry, Furans isolation & purification, Marine Toxins chemistry, Pyrans chemistry, Pyrans isolation & purification
- Abstract
A new pectenotoxin, which has been named pectenotoxin-11 (PTX11), was isolated from the dinoflagellate Dinophysis acuta collected from the west coast of New Zealand. The structure of PTX11 was determined as 34S-hydroxypectenotoxin-2 by tandem mass spectrometry and UV and NMR spectroscopy. PTX11 appears to be only the third pectenotoxin identified as a natural biosynthetic product from algae after pectenotoxin-2 and pectenotoxin-12. The LD50 of PTX11 determined by mouse intraperitoneal injection was 244 microg/kg. The LD(min) of PTX11 in these experiments was 250 microg/kg. No signs of toxicity were recorded in mice following an oral dose of PTX11 at 5000 microg/kg. No diarrhea was observed in any of the animals administered with the test substance by either route of administration. Unlike pectenotoxin-2 (PTX2), PTX11 was not readily hydrolyzed to its corresponding seco acid by enzymes from homogenized green-lipped mussel (Perna canaliculus) hepatopancreas.
- Published
- 2006
- Full Text
- View/download PDF
40. Identification of 45-hydroxy-46,47-dinoryessotoxin, 44-oxo-45,46,47-trinoryessotoxin, and 9-methyl-42,43,44,45,46,47,55-heptanor-38-en-41-oxoyessotoxin, and partial characterization of some minor yessotoxins, from Protoceratium reticulatum.
- Author
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Miles CO, Wilkins AL, Hawkes AD, Selwood AI, Jensen DJ, Cooney JM, Beuzenberg V, and MacKenzie AL
- Subjects
- Animals, Molecular Structure, Mollusk Venoms, Dinoflagellida chemistry, Ethers, Cyclic chemistry, Ethers, Cyclic isolation & purification, Oxocins chemistry, Oxocins isolation & purification
- Abstract
Preparative HPLC purification of a side-fraction obtained during purification of 44,55-dihydroxyyessotoxin (6) afforded fractions containing previously unidentified yessotoxin analogues. Careful analysis of these fractions by HPLC-UV, LC-MS3, and NMR spectroscopy, revealed the identities of some of these analogues as 45-hydroxy-46,47-dinoryessotoxin (1), 44-oxo-45,46,47-trinoryessotoxin (2) and 9-methyl-42,43,44,45,46,47,55-heptanor-38-en-41-oxoyessotoxin (5). Numerous other analogues were present but could only be characterized by HPLC-UV and LC-MS3 due to their low abundance. The HPLC-UV and LC-MS3 data confirm the presence of large numbers of yessotoxin analogues, some of which may be oxidative degradation products, in extracts of Protoceratium reticulatum. Compound-1 is the first 46,47-dinoryessotoxin to be identified.
- Published
- 2006
- Full Text
- View/download PDF
41. Isolation and identification of (44-R,S)-44,55-dihydroxyyessotoxin from Protoceratium reticulatum, and its occurrence in extracts of shellfish from New Zealand, Norway and Canada.
- Author
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Finch SC, Wilkins AL, Hawkes AD, Jensen DJ, MacKenzie AL, Beuzenberg V, Quilliam MA, Olseng CD, Samdal IA, Aasen J, Selwood AI, Cooney JM, Sandvik M, and Miles CO
- Subjects
- Animals, Canada, Chemical Fractionation, Chromatography, Liquid, Ethers, Cyclic chemistry, Magnetic Resonance Spectroscopy, Marine Toxins chemistry, Mass Spectrometry, Mollusk Venoms, New Zealand, Norway, Oxocins chemistry, Dinoflagellida chemistry, Ethers, Cyclic isolation & purification, Marine Toxins isolation & purification, Oxocins isolation & purification, Shellfish parasitology, Shellfish toxicity
- Abstract
44,55-Dihydroxyyessotoxin (1) was isolated from extracts of Protoceratium reticulatum and identified by analysis of its one- and two-dimensional NMR and mass spectra. In addition, LC-MS methods revealed the presence of compounds tentatively identified as (44-R,S)-44,55-dihydroxy-41a-homoyessotoxin (2) and (44-R,S)-44,55-dihydroxy-9-methyl-41a-homoyessotoxin (3). LC-MS analyses indicate that 1 is a constituent of P. reticulatum in New Zealand and Norway, and it was present in three species of mussels from New Zealand, Norway, and Canada.
- Published
- 2005
- Full Text
- View/download PDF
42. Polyhydroxylated amide analogs of yessotoxin from Protoceratium reticulatum.
- Author
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Miles CO, Wilkins AL, Hawkes AD, Selwood AI, Jensen DJ, Munday R, Cooney JM, and Beuzenberg V
- Subjects
- Animals, Ethers, Cyclic chemistry, Ethers, Cyclic pharmacology, Female, Mice, Molecular Structure, Oxocins chemistry, Oxocins pharmacology, Ethers, Cyclic isolation & purification, Mollusk Venoms chemistry, Oxocins isolation & purification
- Abstract
Two analogs of yessotoxin were isolated from extracts of a culture of Protoceratium reticulatum. The structures of the analogs were identified as trihydroxylated amides of 41a-homoyessotoxin (1) and 9-methyl-41a-homoyessotoxin (2) by one- and two-dimensional 1H and 13C NMR spectroscopy and LC-MS3 analyses. Structures were further confirmed by micro-scale chemical conversions combined with LC-MS3 analyses. No toxic effects were recorded in mice injected intraperitoneally with 2 at a dose of 5000 microg/kg.
- Published
- 2005
- Full Text
- View/download PDF
43. Isolation of 41a-homoyessotoxin and the identification of 9-methyl-41a-homoyessotoxin and nor-ring A-yessotoxin from Protoceratium reticulatum.
- Author
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Miles CO, Wilkins AL, Jensen DJ, Cooney JM, Quilliam MA, Aasen J, and MacKenzie AL
- Subjects
- Animals, Chemical Fractionation, Dinoflagellida chemistry, Molecular Structure, Spectrometry, Mass, Electrospray Ionization, Dinoflagellida metabolism, Ethers, Cyclic chemistry, Ethers, Cyclic isolation & purification, Mollusk Venoms chemistry, Oxocins chemistry, Oxocins isolation & purification
- Abstract
41a-homoyessotoxin (1), a new analogue of yessotoxin (7), was isolated from extracts of Protoceratium reticulatum grown in culture. In addition, 9-methyl-41a-homoyessotoxin (2) and a nor-ring A-yessotoxin (3) were identified as the major components of a mixed fraction. The structural information was initially obtained from LC-UV and LC-MS3 chromatograms, with subsequent definitive structure determination by NMR, LC-MS/MS, and high-resolution MS. Full 1H and indirectly detected 13C NMR assignments for all but two carbon atoms were obtained from ca. 100 microg of 1. Full 1H NMR assignments for 2 and 3 and identification of three new heptanor-41-oxo-analogues of 3 (4-6) during LC-MS3 analysis of a fraction containing 1-3 and 7 are also reported.
- Published
- 2004
- Full Text
- View/download PDF
44. A novel pectenotoxin, PTX-12, in Dinophysis spp. and shellfish from Norway.
- Author
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Miles CO, Wilkins AL, Samdal IA, Sandvik M, Petersen D, Quilliam MA, Naustvoll LJ, Rundberget T, Torgersen T, Hovgaard P, Jensen DJ, and Cooney JM
- Subjects
- Animals, Food Contamination, Marine Toxins chemistry, Mass Spectrometry methods, Molecular Structure, Pyrans chemistry, Spiro Compounds chemistry, Dinoflagellida chemistry, Marine Toxins analysis, Pyrans analysis, Spiro Compounds analysis
- Abstract
Two novel pectenotoxins (PTXs) were detected by LC-MS in solid phase extracts of net hauls taken at Flødevigen, Norway, in June 2002 that were dominated by Dinophysis acuminata and Dinophysis norvegica. The new compounds were isolated as minor components from a large collection of a Dinophysis acuta-dominated bloom obtained from Skjer, Sognefjorden, Norway, in October 2002. LC-MS and NMR analyses revealed that the new components, 36S-PTX-12 and 36R-PTX-12, occurred as a pair of equilibrating diastereoisomers differing from PTX-2 in that they contained an exocylic olefinic methylene rather than a methyl group at C-38. Analyses of shellfish extracts revealed that PTX-12 accumulated in Norwegian blue mussels (Mytilus edulis) and cockles (Cerastoderma edule), along with PTX-12 seco acids occurring as a complex mixture of diastereoisomers. LC-MS analysis of algal cells picked from the net haul from Flødevigen revealed that PTX-12 predominated in D. acuta and D. norvegica, whereas PTX-2 was the predominant pectenotoxin in D. acuminata. Preliminary observations indicate that the relative contents of PTX-2 and PTX-12 vary between sites and years in Norway, even within a single species of Dinophysis. Our data also suggest that heterotrophic dinoflagellates may accumulate toxins from their prey.
- Published
- 2004
- Full Text
- View/download PDF
45. Isolation of a 1,3-enone isomer of heptanor-41-oxoyessotoxin from Protoceratium reticulatum cultures.
- Author
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Miles CO, Wilkins AL, Hawkes AD, Selwood A, Jensen DJ, Aasen J, Munday R, Samdal IA, Briggs LR, Beuzenberg V, and MacKenzie AL
- Subjects
- Ammonia metabolism, Animals, Biological Assay, Chromatography, High Pressure Liquid, Chromatography, Liquid, Environmental Monitoring, Ethers, Cyclic toxicity, Isomerism, Magnetic Resonance Spectroscopy, Mass Spectrometry, Mice, Models, Molecular, New Zealand, Norway, Toxicity Tests, Acute, Bivalvia metabolism, Dinoflagellida metabolism, Ethers, Cyclic chemistry, Ethers, Cyclic isolation & purification
- Abstract
The 1,3-enone isomer (1) of heptanor-41-oxoyessotoxin (2) was isolated from extracts of Protoceratium reticulatum during large-scale production of yessotoxin (4). We found that 2 readily isomerizes to 1 in the presence of dilute ammonia and present evidence for the existence of 40-epi-2 (3) that also isomerizes to 1. 1-3 were detected by LC-MS methods both in extracts of P. reticulatum cultures and in mussels contaminated with yessotoxins. The isomerization of 2 and 3 into 1 occurs so readily that purification on basic alumina needs to be conducted carefully. No toxic effects were recorded in mice injected intraperitoneally with 1 at a dose of 5,000 microg/kg.
- Published
- 2004
- Full Text
- View/download PDF
46. Watching the growth of bulk grains during recrystallization of deformed metals.
- Author
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Schmidt S, Nielsen SF, Gundlach C, Margulies L, Huang X, and Jensen DJ
- Abstract
We observed the in situ growth of a grain during recrystallization in the bulk of a deformed sample. We used the three-dimensional x-ray diffraction microscope located at the European Synchrotron Radiation Facility in Grenoble, France. The results showed a very heterogeneous growth pattern, contradicting the classical assumption of smooth and spherical growth of new grains during recrystallization. This type of in situ bulk measurement opens up the possibility of obtaining experimental data on scientific topics that before could only be analyzed theoretically on the basis of the statistical characterization of microstructures. For recrystallization, the in situ method includes direct measurements of nucleation and boundary migration through a deformed matrix.
- Published
- 2004
- Full Text
- View/download PDF
47. Isolation of pectenotoxin-2 from Dinophysis acuta and its conversion to pectenotoxin-2 seco acid, and preliminary assessment of their acute toxicities.
- Author
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Miles CO, Wilkins AL, Munday R, Dines MH, Hawkes AD, Briggs LR, Sandvik M, Jensen DJ, Cooney JM, Holland PT, Quilliam MA, MacKenzie AL, Beuzenberg V, and Towers NR
- Subjects
- Administration, Oral, Animals, Female, Furans administration & dosage, Furans metabolism, Furans toxicity, Hydrolysis, Injections, Intraperitoneal, Lethal Dose 50, Macrolides, Marine Toxins administration & dosage, Marine Toxins metabolism, Mice, Pyrans administration & dosage, Pyrans metabolism, Pyrans toxicity, Dinoflagellida, Furans isolation & purification, Marine Toxins isolation & purification, Marine Toxins toxicity, Pyrans isolation & purification
- Abstract
We have developed a simple and effective method for isolating pectenotoxin-2 (PTX-2) from Dinophysis cells collected from a natural bloom. A two-step extraction procedure followed by two column chromatography steps produced PTX-2 in high purity suitable for use as an analytical standard and for toxicological studies. Incubation of purified PTX-2 with the supernatant from ultracentrifuged blue (Mytilus edulis) or Greenshell (Perna canaliculus) mussel hepatopancreas homogenate caused rapid conversion to pectenotoxin-2 seco acid (PTX-2 SA). Purification of PTX-2 SA was achieved by solvent extraction followed by column chromatography. PTX-2 and PTX-2 SA were fully characterized by LC-MS and NMR, and full (1)H and (13)C NMR assignments were obtained. Okadaic acid C(8)-diol ester was isolated during the purification of PTX-2, and its identity confirmed by NMR and LC-MS analyses. Pectenotoxin-2 seco acid methyl ester, identified by LC-MS, was also produced during the hydrolytic procedure due to the presence of methanol. PTX-2 was acutely toxic to mice by i.p. injection (LD(50)=219 microg/kg) but no effects were seen with PTX-2 SA at 5000 microg/kg. Neither PTX-2 nor PTX-2 SA was overtly toxic to mice by the oral route at doses up to 5000 microg/kg. No diarrhea was observed in mice dosed with either compound, suggesting that pectenotoxins do not belong in the diarrhetic shellfish poison group.
- Published
- 2004
- Full Text
- View/download PDF
48. Anthocyanin glycosides from berry fruit are absorbed and excreted unmetabolized by both humans and rats.
- Author
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McGhie TK, Ainge GD, Barnett LE, Cooney JM, and Jensen DJ
- Subjects
- Absorption, Animals, Anthocyanins chemistry, Anthocyanins urine, Chromatography, High Pressure Liquid, Glycosides urine, Humans, Rats, Anthocyanins pharmacokinetics, Fruit chemistry, Glycosides pharmacokinetics
- Abstract
Anthocyanins, the red/blue pigments found in plants, are polyphenolic compounds consumed by humans and are part of a normal diet. Recent studies have shown that anthocyanins have substantial bioactivity including antioxidant activity and therefore may have beneficial effects on human health. Anthocyanins are a group of over 500 compounds of diverse structures containing different core phenolic aglycons and conjugated with sugars in a variety of glycosylation patterns. In this study, we have investigated the bioabsorption of 15 anthocyanins with structures containing different aglycons and conjugated sugars extracted from blueberry, boysenberry, black raspberry, and blackcurrant in both humans and rats. Intact and unmetabolized anthocyanins were detected in urine of rats and humans following dosing for all molecular structures investigated, thus demonstrating that anthocyanins with diverse molecular structure and from different dietary sources are bioavailable at diet relevant dosage rates. In addition, the relative concentrations of anthocyanins detected in urine following dosing varied, indicating that differences in bioavailability are due to variations in chemical structure. Our results suggest that the nature of the sugar conjugate and the phenolic aglycon are both important determinants of anthocyanin absorption and excretion in rats and humans.
- Published
- 2003
- Full Text
- View/download PDF
49. Efficient method for determining the glycyrrhizin content of fresh and dried roots, and root extracts, of Glycyrrhiza species.
- Author
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Lauren DR, Jensen DJ, Douglas JA, and Follett JM
- Subjects
- Spectrophotometry, Ultraviolet, Chromatography, High Pressure Liquid methods, Glycyrrhiza chemistry, Glycyrrhizic Acid analysis, Plant Roots chemistry
- Abstract
A reliable and efficient method suitable for the selective analysis of the glycyrrhizin content of fresh and dried roots of Glycyrrhiza species and of root extracts is described. The method was optimised for recovery and analysis of glycyrrhizin after conversion to its aglycone, 18 beta-glycyrrhetinic acid. The reversed-phase HPLC system was developed using a sterically protected C8 column that allowed UV detection of the aglycone at 254 mm without interference from co-occurring components. The average recovery through the method was determined at 83%, with a range of 65-99%. Analysis of 150 dried root samples gave levels of glycyrrhizin consistent with earlier reported values. A comparison of post-harvest treatment conditions. showed that the drying of root samples at up to 65 degrees C did not result in any measurable reduction in glycyrrhizin.
- Published
- 2001
- Full Text
- View/download PDF
50. Guidelines for Institutional Animal Care and Use Committees: consideration of alternatives.
- Author
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Stokes WS and Jensen DJ
- Published
- 1995
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