The production of coenzyme Q10 in microorganisms.

PubMed

Cluis, Corinne P; Pinel, Dominic; Martin, Vincent J

2012-01-01

Coenzyme Q10 has emerged as a valuable molecule for pharmaceutical and cosmetic applications. Therefore, research into producing and optimizing coenzyme Q10 via microbial fermentation is ongoing. There are two major paths being explored for maximizing production of this molecule to commercially advantageous levels. The first entails using microbes that naturally produce coenzyme Q10 as fermentation biocatalysts and optimizing the fermentation parameters in order to reach industrial levels of production. However, the natural coenzyme Q10-producing microbes tend to be intractable for industrial fermentation settings. The second path to coenzyme Q10 production being explored is to engineer Escherichia coli with the ability to biosynthesize this molecule in order to take advantage of its more favourable fermentation characteristics and the well-understood array of genetic tools available for this bacteria. Although many studies have attempted to over-produce coenzyme Q10 in E. coli through genetic engineering, production titres still remain below those of the natural coenzyme Q10-producing microorganisms. Current research is providing the knowledge needed to alleviate the bottlenecks involved in producing coenzyme Q10 from an E. coli strain platform and the fermentation parameters that could dramatically increase production titres from natural microbial producers. Synthesizing the lessons learned from both approaches may be the key towards a more cost-effective coenzyme Q10 industry.

Prebiotic syntheses of vitamin coenzymes: I. Cysteamine and 2-mercaptoethanesulfonic acid (coenzyme M)

NASA Technical Reports Server (NTRS)

Miller, S. L.; Schlesinger, G.

1993-01-01

The reaction of NH3 and SO3(2-) with ethylene sulfide is shown to be a prebiotic synthesis of cysteamine and 2-mercaptoethanesulfonic acid (coenzyme M). A similar reaction with ethylene imine would give cysteamine and taurine. Ethylene oxide would react with NH3 and N(CH3)3 to give the phospholipid components ethanolamine and choline. The prebiotic sources of ethylene sulfide, ethylene imine and ethylene oxide are discussed. Cysteamine itself is not a suitable thioester for metabolic processes because of acyl transfer to the amino group, but this can be prevented by using an amide of cysteamine. The use of cysteamine in coenzyme A may have been due to its prebiotic abundance. The facile prebiotic synthesis of both cysteamine and coenzyme M suggests that they were involved in very early metabolic pathways.

Coenzyme Q10 for heart failure.

PubMed

Madmani, Mohammed E; Yusuf Solaiman, Ahmad; Tamr Agha, Khalil; Madmani, Yasser; Shahrour, Yasser; Essali, Adib; Kadro, Waleed

2014-06-02

Coenzyme Q10, or ubiquinone, is a non-prescription nutritional supplement. It is a fat-soluble molecule that acts as an electron carrier in mitochondria and as a coenzyme for mitochondrial enzymes. Coenzyme Q10 deficiency may be associated with a multitude of diseases including heart failure. The severity of heart failure correlates with the severity of coenzyme Q10 deficiency. Emerging data suggest that the harmful effects of reactive oxygen species are increased in patients with heart failure and coenzyme Q10 may help to reduce these toxic effects because of its antioxidant activity. Coenzyme Q10 may also have a role in stabilising myocardial calcium-dependent ion channels and preventing the consumption of metabolites essential for adenosine-5'-triphosphate (ATP) synthesis. Coenzyme Q10, although not a primary recommended treatment, could be beneficial to patients with heart failure. Several randomised controlled trials have compared coenzyme Q10 to other therapeutic modalities, but no systematic review of existing randomised trials has been conducted. To review the safety and efficacy of coenzyme Q10 in heart failure. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE OVID (1950 to January Week 3 2013) and EMBASE OVID (1980 to 2013 Week 03) on 24 January 2013; Web of Science with Conference Proceedings (1970 to January 2013) and CINAHL Plus (1981 to January 2013) on 25 January 2013; and AMED (Allied and Complementary Medicine) (1985 to January 2013) on 28 January 2013. We applied no language restrictions. We included randomised controlled trials of either parallel or cross-over design that assessed the beneficial and harmful effects of coenzyme Q10 in patients with heart failure. When cross-over studies were identified, we considered data only from the first phase. Two authors independently extracted data from the included studies onto a pre-designed data extraction form. We then entered the data into Review

Prebiotic syntheses of vitamin coenzymes: II. Pantoic acid, pantothenic acid, and the composition of coenzyme A

NASA Technical Reports Server (NTRS)

Miller, S. L.; Schlesinger, G.

1993-01-01

Pantoic acid can by synthesized in good prebiotic yield from isobutyraldehyde or alpha-ketoisovaleric acid + H2CO + HCN. Isobutyraldehyde is the Strecker precursor to valine and alpha-ketoisovaleric acid is the valine transamination product. Mg2+ and Ca2+ as well as several transition metals are catalysts for the alpha-ketoisovaleric acid reaction. Pantothenic acid is produced from pantoyl lactone (easily formed from pantoic acid) and the relatively high concentrations of beta-alanine that would be formed on drying prebiotic amino acid mixtures. There is no selectivity for this reaction over glycine, alanine, or gamma-amino butyric acid. The components of coenzyme A are discussed in terms of ease of prebiotic formation and stability and are shown to be plausible choices, but many other compounds are possible. The gamma-OH of pantoic acid needs to be capped to prevent decomposition of pantothenic acid. These results suggest that coenzyme A function was important in the earliest metabolic pathways and that the coenzyme A precursor contained most of the components of the present coenzyme.

Artificial Enzymes with Thiazolium and Imidazolium Coenzyme Mimics

PubMed Central

Zhao, Huanyu; Foss, Frank W.; Breslow, Ronald

2009-01-01

Hydrophobic thiazolium and imidazolium coenzyme mimics in the presence of modified-polyethylenimine enzyme mimics catalyze the benzoin condensation 2300–3300 times faster than the coenzyme mimics alone. Polycationic enzyme mimics provide not only a hydrophobic binding domain for coenzyme and substrate, but also electrostatic stabilization of anionic species that arise along the reaction pathway of the benzoin condensation. PMID:18763766

Production of a Brassica napus low-molecular mass acyl-coenzyme A-binding protein in Arabidopsis alters the acyl-coenzyme A pool and acyl composition of oil in seeds

USDA-ARS?s Scientific Manuscript database

Low-molecular mass (10 kD) cytosolic acyl-coenzyme A-binding protein (ACBP) has a substantial influence over fatty acid (FA) composition in oilseeds, possibly via an effect on the partitioning of acyl groups between elongation and desaturation pathways. Previously, we demonstrated that the expressio...

Better than Nature: Nicotinamide Biomimetics That Outperform Natural Coenzymes.

PubMed

Knaus, Tanja; Paul, Caroline E; Levy, Colin W; de Vries, Simon; Mutti, Francesco G; Hollmann, Frank; Scrutton, Nigel S

2016-01-27

The search for affordable, green biocatalytic processes is a challenge for chemicals manufacture. Redox biotransformations are potentially attractive, but they rely on unstable and expensive nicotinamide coenzymes that have prevented their widespread exploitation. Stoichiometric use of natural coenzymes is not viable economically, and the instability of these molecules hinders catalytic processes that employ coenzyme recycling. Here, we investigate the efficiency of man-made synthetic biomimetics of the natural coenzymes NAD(P)H in redox biocatalysis. Extensive studies with a range of oxidoreductases belonging to the "ene" reductase family show that these biomimetics are excellent analogues of the natural coenzymes, revealed also in crystal structures of the ene reductase XenA with selected biomimetics. In selected cases, these biomimetics outperform the natural coenzymes. "Better-than-Nature" biomimetics should find widespread application in fine and specialty chemicals production by harnessing the power of high stereo-, regio-, and chemoselective redox biocatalysts and enabling reactions under mild conditions at low cost.

Better than Nature: Nicotinamide Biomimetics That Outperform Natural Coenzymes

PubMed Central

2016-01-01

The search for affordable, green biocatalytic processes is a challenge for chemicals manufacture. Redox biotransformations are potentially attractive, but they rely on unstable and expensive nicotinamide coenzymes that have prevented their widespread exploitation. Stoichiometric use of natural coenzymes is not viable economically, and the instability of these molecules hinders catalytic processes that employ coenzyme recycling. Here, we investigate the efficiency of man-made synthetic biomimetics of the natural coenzymes NAD(P)H in redox biocatalysis. Extensive studies with a range of oxidoreductases belonging to the “ene” reductase family show that these biomimetics are excellent analogues of the natural coenzymes, revealed also in crystal structures of the ene reductase XenA with selected biomimetics. In selected cases, these biomimetics outperform the natural coenzymes. “Better-than-Nature” biomimetics should find widespread application in fine and specialty chemicals production by harnessing the power of high stereo-, regio-, and chemoselective redox biocatalysts and enabling reactions under mild conditions at low cost. PMID:26727612

Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

PubMed

Rodriguez-Perez, N; Schiavi, E; Frei, R; Ferstl, R; Wawrzyniak, P; Smolinska, S; Sokolowska, M; Sievi, N A; Kohler, M; Schmid-Grendelmeier, P; Michalovich, D; Simpson, K D; Hessel, E M; Jutel, M; Martin-Fontecha, M; Palomares, O; Akdis, C A; O'Mahony, L

2017-11-01

Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Longevity of major coenzymes allows minimal de novo synthesis in microorganisms.

PubMed

Hartl, Johannes; Kiefer, Patrick; Meyer, Fabian; Vorholt, Julia A

2017-05-15

Coenzymes are vital for cellular metabolism and act on the full spectrum of enzymatic reactions. Intrinsic chemical reactivity, enzyme promiscuity and high flux through their catalytic cycles make coenzymes prone to damage. To counteract such compromising factors and ensure stable levels of functional coenzymes, cells use a complex interplay between de novo synthesis, salvage, repair and degradation. However, the relative contribution of these factors is currently unknown, as is the overall stability of coenzymes in the cell. Here, we use dynamic 13 C-labelling experiments to determine the half-life of major coenzymes of Escherichia coli. We find that coenzymes such as pyridoxal 5-phosphate, flavins, nicotinamide adenine dinucleotide (phosphate) and coenzyme A are remarkably stable in vivo and allow biosynthesis close to the minimal necessary rate. In consequence, they are essentially produced to compensate for dilution by growth and passed on over generations of cells. Exceptions are antioxidants, which are short-lived, suggesting an inherent requirement for increased renewal. Although the growth-driven turnover of stable coenzymes is apparently subject to highly efficient end-product homeostasis, we exemplify that coenzyme pools are propagated in excess in relation to actual growth requirements. Additional testing of Bacillus subtilis and Saccharomyces cerevisiae suggests that coenzyme longevity is a conserved feature in biology.

Ocean acidification alters temperature and salinity preferences in larval fish.

PubMed

Pistevos, Jennifer C A; Nagelkerken, Ivan; Rossi, Tullio; Connell, Sean D

2017-02-01

Ocean acidification alters the way in which animals perceive and respond to their world by affecting a variety of senses such as audition, olfaction, vision and pH sensing. Marine species rely on other senses as well, but we know little of how these might be affected by ocean acidification. We tested whether ocean acidification can alter the preference for physicochemical cues used for dispersal between ocean and estuarine environments. We experimentally assessed the behavioural response of a larval fish (Lates calcarifer) to elevated temperature and reduced salinity, including estuarine water of multiple cues for detecting settlement habitat. Larval fish raised under elevated CO 2 concentrations were attracted by warmer water, but temperature had no effect on fish raised in contemporary CO 2 concentrations. In contrast, contemporary larvae were deterred by lower salinity water, where CO 2 -treated fish showed no such response. Natural estuarine water-of higher temperature, lower salinity, and containing estuarine olfactory cues-was only preferred by fish treated under forecasted high CO 2 conditions. We show for the first time that attraction by larval fish towards physicochemical cues can be altered by ocean acidification. Such alterations to perception and evaluation of environmental cues during the critical process of dispersal can potentially have implications for ensuing recruitment and population replenishment. Our study not only shows that freshwater species that spend part of their life cycle in the ocean might also be affected by ocean acidification, but that behavioural responses towards key physicochemical cues can also be negated through elevated CO 2 from human emissions.

Mitochondrial Targeted Coenzyme Q, Superoxide, and Fuel Selectivity in Endothelial Cells

PubMed Central

Fink, Brian D.; O'Malley, Yunxia; Dake, Brian L.; Ross, Nicolette C.; Prisinzano, Thomas E.; Sivitz, William I.

2009-01-01

Background Previously, we reported that the “antioxidant” compound “mitoQ” (mitochondrial-targeted ubiquinol/ubiquinone) actually increased superoxide production by bovine aortic endothelial (BAE) cell mitochondria incubated with complex I but not complex II substrates. Methods and Results To further define the site of action of the targeted coenzyme Q compound, we extended these studies to include different substrate and inhibitor conditions. In addition, we assessed the effects of mitoquinone on mitochondrial respiration, measured respiration and mitochondrial membrane potential in intact cells, and tested the intriguing hypothesis that mitoquinone might impart fuel selectivity in intact BAE cells. In mitochondria respiring on differing concentrations of complex I substrates, mitoquinone and rotenone had interactive effects on ROS consistent with redox cycling at multiple sites within complex I. Mitoquinone increased respiration in isolated mitochondria respiring on complex I but not complex II substrates. Mitoquinone also increased oxygen consumption by intact BAE cells. Moreover, when added to intact cells at 50 to 1000 nM, mitoquinone increased glucose oxidation and reduced fat oxidation, at doses that did not alter membrane potential or induce cell toxicity. Although high dose mitoquinone reduced mitochondrial membrane potential, the positively charged mitochondrial-targeted cation, decyltriphenylphosphonium (mitoquinone without the coenzyme Q moiety), decreased membrane potential more than mitoquinone, but did not alter fuel selectivity. Therefore, non-specific effects of the positive charge were not responsible and the quinone moiety is required for altered nutrient selectivity. Conclusions In summary, the interactive effects of mitoquinone and rotenone are consistent with redox cycling at more than one site within complex I. In addition, mitoquinone has substrate dependent effects on mitochondrial respiration, increases repiration by intact cells

Mitochondrial targeted coenzyme Q, superoxide, and fuel selectivity in endothelial cells.

PubMed

Fink, Brian D; O'Malley, Yunxia; Dake, Brian L; Ross, Nicolette C; Prisinzano, Thomas E; Sivitz, William I

2009-01-01

Previously, we reported that the "antioxidant" compound "mitoQ" (mitochondrial-targeted ubiquinol/ubiquinone) actually increased superoxide production by bovine aortic endothelial (BAE) cell mitochondria incubated with complex I but not complex II substrates. To further define the site of action of the targeted coenzyme Q compound, we extended these studies to include different substrate and inhibitor conditions. In addition, we assessed the effects of mitoquinone on mitochondrial respiration, measured respiration and mitochondrial membrane potential in intact cells, and tested the intriguing hypothesis that mitoquinone might impart fuel selectivity in intact BAE cells. In mitochondria respiring on differing concentrations of complex I substrates, mitoquinone and rotenone had interactive effects on ROS consistent with redox cycling at multiple sites within complex I. Mitoquinone increased respiration in isolated mitochondria respiring on complex I but not complex II substrates. Mitoquinone also increased oxygen consumption by intact BAE cells. Moreover, when added to intact cells at 50 to 1000 nM, mitoquinone increased glucose oxidation and reduced fat oxidation, at doses that did not alter membrane potential or induce cell toxicity. Although high dose mitoquinone reduced mitochondrial membrane potential, the positively charged mitochondrial-targeted cation, decyltriphenylphosphonium (mitoquinone without the coenzyme Q moiety), decreased membrane potential more than mitoquinone, but did not alter fuel selectivity. Therefore, non-specific effects of the positive charge were not responsible and the quinone moiety is required for altered nutrient selectivity. In summary, the interactive effects of mitoquinone and rotenone are consistent with redox cycling at more than one site within complex I. In addition, mitoquinone has substrate dependent effects on mitochondrial respiration, increases repiration by intact cells, and alters fuel selectivity favoring glucose over

Manipulation Detection and Preference Alterations in a Choice Blindness Paradigm

PubMed Central

Taya, Fumihiko; Gupta, Swati; Farber, Ilya; Mullette-Gillman, O'Dhaniel A.

2014-01-01

Objectives It is commonly believed that individuals make choices based upon their preferences and have access to the reasons for their choices. Recent studies in several areas suggest that this is not always the case. In choice blindness paradigms, two-alternative forced-choice in which chosen-options are later replaced by the unselected option, individuals often fail to notice replacement of their chosen option, confabulate explanations for why they chose the unselected option, and even show increased preferences for the unselected-but-replaced options immediately after choice (seconds). Although choice blindness has been replicated across a variety of domains, there are numerous outstanding questions. Firstly, we sought to investigate how individual- or trial-factors modulated detection of the manipulations. Secondly, we examined the nature and temporal duration (minutes vs. days) of the preference alterations induced by these manipulations. Methods Participants performed a computerized choice blindness task, selecting the more attractive face between presented pairs of female faces, and providing a typewritten explanation for their choice on half of the trials. Chosen-face cue manipulations were produced on a subset of trials by presenting the unselected face during the choice explanation as if it had been selected. Following all choice trials, participants rated the attractiveness of each face individually, and rated the similarity of each face pair. After approximately two weeks, participants re-rated the attractiveness of each individual face online. Results Participants detected manipulations on only a small proportion of trials, with detections by fewer than half of participants. Detection rates increased with the number of prior detections, and detection rates subsequent to first detection were modulated by the choice certainty. We show clear short-term modulation of preferences in both manipulated and non-manipulated explanation trials compared to choice

Mirtazapine and ketanserin alter preference for gambling-like schedules of reinforcement in rats.

PubMed

Persons, Amanda L; Tedford, Stephanie E; Celeste Napier, T

2017-07-03

Drug and behavioral addictions have overlapping features, e.g., both manifest preference for larger, albeit costlier, reinforcement options in cost/benefit decision-making tasks. Our prior work revealed that the mixed-function serotonergic compound, mirtazapine, attenuates behaviors by rats motivated by abused drugs. To extend this work to behavioral addictions, here we determined if mirtazapine and/or ketanserin, another mixed-function serotonin-acting compound, can alter decision-making in rats that is independent of drug (or food)-motivated reward. Accordingly, we developed a novel variable-ratio task in rats wherein intracranial self-stimulation was used as the positive reinforcer. Using lever pressing for various levels of brain stimulation, the operant task provided choices between a small brain stimulation current delivered on a fixed-ratio schedule (i.e., a predictable reward) and a large brain stimulation delivered following an unpredictable number of responses (i.e., a variable-ratio schedule). This task allowed for demonstration of individualized preference and detection of shifts in motivational influences during a pharmacological treatment. Once baseline preference was established, we determined that pretreatment with mirtazapine or ketanserin significantly decreased preference for the large reinforcer presented after gambling-like schedules of reinforcement. When the rats were tested the next day without drug, preference for the unpredictable large reinforcer option was restored. These data demonstrate that mirtazapine and ketanserin can reduce preference for larger, costlier reinforcement options, and illustrate the potential for these drugs to alter behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

Coenzyme Q10 (PDQ®)—Health Professional Version

Cancer.gov

Coenzyme Q10 is a dietary supplement, and use of it as a treatment for cancer in humans has been investigated in only a limited manner. Get detailed information about Coenzyme Q10 use in cancer in this summary for clinicians.

Coenzyme Q10 (PDQ®)—Patient Version

Cancer.gov

Coenzyme Q10 is naturally made by the body and can be taken as a pill or injection. Studies have shown it to help protect the heart from damaging side effects of doxorubicin and to stimulate the immune system in cancer patients. Read about the results of clinical trials in cancer patients using coenzyme Q10 in this expert-reviewed summary.

Profiling Redox and Energy Coenzymes in Whole Blood, Tissue and Cells Using NMR Spectroscopy.

PubMed

Gowda, G A Nagana

2018-05-14

Coenzymes of cellular redox reactions and cellular energy, as well as antioxidants mediate biochemical reactions fundamental to the functioning of all living cells. Conventional analysis methods lack the opportunity to evaluate these important redox and energy coenzymes and antioxidants in a single step. Major coenzymes include redox coenzymes: NAD⁺ (oxidized nicotinamide adenine dinucleotide), NADH (reduced nicotinamide adenine dinucleotide), NADP⁺ (oxidized nicotinamide adenine dinucleotide phosphate) and NADPH (reduced nicotinamide adenine dinucleotide phosphate); energy coenzymes: ATP (adenosine triphosphate), ADP (adenosine diphosphate) and AMP (adenosine monophosphate); and antioxidants: GSSG (oxidized glutathione) and GSH (reduced glutathione). We show here that a simple ¹H NMR experiment can measure these coenzymes and antioxidants in tissue and whole blood apart from a vast pool of other metabolites. In addition, focused on the goal of identification of coenzymes in subcellular fractions, we demonstrate analysis of coenzymes in the cytoplasm using breast cancer cells. Owing to their unstable nature, or low concentrations, most of the coenzymes either evade detection or lose their integrity when established sample preparation and analysis methods are used. To overcome this challenge, here we describe the development of new methods to detect these molecules without affecting the integrity of other metabolites. We used an array of 1D and 2D NMR methods, chemical shift databases, pH measurements and spiking with authentic compounds to establish the identity of peaks for the coenzymes and antioxidants in NMR spectra. Interestingly, while none of the coenzymes and antioxidants were detected in plasma, they were abundant in whole blood. Considering that the coenzymes and antioxidants represent a sensitive measure of human health and risk for numerous diseases, the presented NMR methods to measure them in one step potentially open new opportunities in the

[Effect of procaine and procaine metabolites on coenzyme A and acetyl coenzyme A concentration in various tissues of the rat].

PubMed

Kietzmann, M; Kaemmerer, K

1989-01-01

In rats treated with procaine hydrochloride, diethylaminoethanol, monoethylaminoethanol, ethanolamine, as well as a combination of procaine hydrochloride and haematoporphyrine the ratio of acetyl coenzyme A and coenzyme A clearly was enhanced in the liver and to a minor extent in the cerebellum. In the tissue of cerebral cortex, heart, muscle and duodenum no corresponding effects were demonstrated. These findings, showing a further intermediary effect of orally administered procaine, can be interpreted as an influence in intermediary energy utilisation.

[Combination treatment with coenzyme Q10 and simvastatin in patients with coronary atherosclerosis].

PubMed

Chapidze G E; Kapanadze, S D; Dolidze, N K; Latsabidze, N E; Bakhutashvili, Z V

2006-01-01

In order to assess efficacy of one of natural antioxidants--coenzyme Q10 (90 mg daily) and its combination with simvastatin (10 mg daily) 44 outpatients with coronary atherosclerosis were examined. Twenty four patients had undergone coronary artery bypass surgery, 12--coronary angioplasty and in 8 coronary heart disease was confirmed by angiography. Duration of treatment was 12 weeks. Positive effects of coenzyme Q10 was particularly expressed in relation to antiatherogenic fraction of cholesterol which increased by 23%. Index of atherogenicity decreased by 27%. At the background of coenzyme Q10 treatment 30% reduction in plasma lipoperoxide levels occurred demonstrating potentially independent role of coenzyme Q10 in positive modification of oxidative stress. Coenzyme Q10 revealed antiaggregatory ability. It was not related to the improvement of endothelial function. Normalization of plasma nitric oxide concentrations was achieved only with combination of coenzyme Q10 and simvastatin. This fact may be explained by positive action of statins on endothelial function.

GABA(A) receptor modulation during adolescence alters adult ethanol intake and preference in rats.

PubMed

Hulin, Mary W; Amato, Russell J; Winsauer, Peter J

2012-02-01

To address the hypothesis that GABA(A) receptor modulation during adolescence may alter the abuse liability of ethanol during adulthood, the effects of adolescent administration of both a positive and negative GABA(A) receptor modulator on adult alcohol intake and preference were assessed. Three groups of adolescent male rats received 12 injections of lorazepam (3.2 mg/kg), dehydroepiandrosterone (DHEA, 56 mg/kg), or vehicle on alternate days starting on postnatal day (PD) 35. After this time, the doses were increased to 5.6 and 100 mg/kg, respectively, for 3 more injections on alternate days. Subjects had access to 25 to 30 g of food daily, during the period of the first 6 injections, and 18 to 20 g thereafter. Food intake of each group was measured 60 minutes after food presentation, which occurred immediately after drug administration on injection days or at the same time of day on noninjection days. When subjects reached adulthood (PD 88), ethanol preference was determined on 2 separate occasions, an initial 3-day period and a 12-day period, in which increasing concentrations of ethanol were presented. During each preference test, intake of water, saccharin, and an ethanol/saccharin solution was measured after each 23-hour access period. During adolescence, lorazepam increased 60-minute food intake, and this effect was enhanced under the more restrictive feeding schedule. DHEA had the opposite effect on injection days, decreasing food intake compared with noninjection days. In adulthood, the lorazepam-treated group preferred the 2 lowest concentrations of ethanol/saccharin more than saccharin alone compared with vehicle-treated subjects, which showed no preference for any concentration of ethanol/saccharin over saccharin. DHEA-treated subjects showed no preference among the 3 solutions. These data demonstrate that GABA(A) receptor modulation during adolescence can alter intake and preference for ethanol in adulthood and highlights the importance of drug history

Effect of coenzyme q10 on myopathic symptoms in patients treated with statins.

PubMed

Caso, Giuseppe; Kelly, Patricia; McNurlan, Margaret A; Lawson, William E

2007-05-15

Treatment of hypercholesterolemia with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) is effective in the primary and secondary prevention of cardiovascular disease. However, statin use is often associated with a variety of muscle-related symptoms or myopathies. Myopathy may be related in part to statin inhibition of the endogenous synthesis of coenzyme Q10, an essential cofactor for mitochondrial energy production. The aim of this study is to determine whether coenzyme Q10 supplementation would reduce the degree of muscle pain associated with statin treatment. Patients with myopathic symptoms were randomly assigned in a double-blinded protocol to treatment with coenzyme Q10 (100 mg/day, n = 18) or vitamin E (400 IU/day, n = 14) for 30 days. Muscle pain and pain interference with daily activities were assessed before and after treatment. After a 30-day intervention, pain severity decreased by 40% (p <0.001) and pain interference with daily activities decreased by 38% (p <0.02) in the group treated with coenzyme Q10. In contrast, no changes in pain severity (+9%, p = NS) or pain interference with daily activities (-11%, p = NS) was observed in the group treated with vitamin E. In conclusion, results suggest that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment. Thus, coenzyme Q10 supplementation may offer an alternative to stopping treatment with these vital drugs.

Elucidation of the biosynthesis of the methane catalyst coenzyme F430

PubMed Central

Moore, Simon J.; Sowa, Sven T.; Schuchardt, Christopher; Deery, Evelyne; Lawrence, Andrew D.; Ramos, José Vazquez; Billig, Susan; Birkemeyer, Claudia; Chivers, Peter T.; Howard, Mark J.; Rigby, Stephen E. J.; Layer, Gunhild; Warren, Martin J.

2017-01-01

Summary Methane biogenesis in methanogens is mediated by methyl-coenzyme M reductase, an enzyme that is also responsible for the utilisation of methane through anaerobic methane oxidation. The enzyme employs an ancillary factor called coenzyme F430, a nickel-containing modified tetrapyrrole that promotes catalysis through a novel methyl radical/Ni(II)-thiolate intermediate. However, the biosynthesis of coenzyme F430 from the common primogenitor uroporphyrinoge III, incorporating 11 steric centres into the macrocycle, has remained poorly understood although the pathway must involve chelation, amidation, macrocyclic ring reduction, lactamisation and carbocyclic ring formation. We have now identified the proteins that catalyse coenzyme F430 biosynthesis from sirohydrochlorin, termed CfbA-E, and shown their activity. The research completes our understanding of how nature is able to construct its repertoire of tetrapyrrole-based life pigments, permitting the development of recombinant systems to utilise these metalloprosthetic groups more widely. PMID:28225763

Potential role of coenzyme Q10 in facilitating recovery from statin-induced rhabdomyolysis.

PubMed

Wang, L W; Jabbour, A; Hayward, C S; Furlong, T J; Girgis, L; Macdonald, P S; Keogh, A M

2015-04-01

Rhabdomyolysis is a rare, but serious complication of statin therapy, and represents the most severe end of the spectrum of statin-induced myotoxicity. We report a case where coenzyme Q10 facilitated recovery from statin-induced rhabdomyolysis and acute renal failure, which had initially persisted despite statin cessation and haemodialysis. This observation is biologically plausible due to the recognised importance of coenzyme Q10 in mitochondrial bioenergetics within myocytes, and the fact that statins inhibit farnesyl pyrophosphate production, a biochemical step crucial for coenzyme Q10 synthesis. Coenzyme Q10 is generally well tolerated, and may potentially benefit patients with statin-induced rhabdomyolysis. © 2015 Royal Australasian College of Physicians.

Combination Therapy with Glucan and Coenzyme Q10 in Murine Experimental Autoimmune Disease and Cancer.

PubMed

Vetvicka, Vaclav; Vetvickova, Jana

2018-06-01

Coenzyme Q 10 is a well-accepted anti-oxidant agent known to play a protective role in various physiological and disease processes. Recently, Coenzyme Q 10 is gaining attention as a substance with significant anti-inflammatory properties. β-Glucan is the most studied immunomodulator with significant synergetic effects with numerous bioactive molecules. We aimed to evaluate the possible synergistic effects of simultaneous use of coenzyme Q 10 with the well-established immune modulator, β-glucan, on immune reactions and cancer development. Coenzyme Q 10 and β-glucan were used, both in vivo and in vitro, and their effects were evaluated using phagocytosis and cytokine secretion. Our study confirmed the strong anti-inflammatory effects of coenzyme Q 10 and showed that these effects were further potentiated with the addition of β-glucan. The anticancer effects of coenzyme Q 10 were less pronounced, but stronger, with the addition of β-glucan. There is significant synergy between coenzyme Q 10 and β-glucan. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

ANTAGONISTIC EFFECTS OF 6-MERCAPTOPURINE AND COENZYME A ON MITOCHONDRIA AND MITOSIS IN TISSUE CULTURE

PubMed Central

Biesele, John J.

1955-01-01

The partial mitotic inhibition caused by 6-mercaptopurine in tissue cultures of Crocker mouse sarcoma 180 and embryonic mouse skin is blocked by co-enzyme A. 6-Mercaptopurine and coenzyme A also have opposite effects on mitochondrial morphology. Mitochondria in cells treated with 6-mercaptopurine become thin and fragmented. Coenzyme A blocks this effect, and alone coenzyme A makes for longer and thicker mitochondria. 6-Mercaptopurine inhibits lipogenesis in embryo skin fibroblasts, and this inhibition is partly counteracted by coenzyme A, which by itself makes for a greater accumulation of lipid droplets in the cytoplasm. It is suggested that at least one part of the action by which 6-mercaptopurine decreases mitotic incidence in tissue cultures may be an interference on the part of 6-mercaptopurine, acting as an antimetabolite of coenzyme A, in mitochondrial function related to cell division. PMID:14381434

Neutron study of B 12 coenzyme at 15 K

NASA Astrophysics Data System (ADS)

Bouquiere, J. P.

1992-06-01

This high resolution and low temperature study, at 15 K, of the vitamin B 12 coenzyme ( C72H100N18O17PCo) was undertaken to confirm and clarify the water networks identified at 279 K by Savage [1]. Details of the data collection and refinement of the low temperature structure are described, a comparison of the coenzyme molecule structures at 15 and 279 K is made, and that of solvent structures outlined.

Coenzymes, Viruses and the RNA World

NASA Astrophysics Data System (ADS)

Reyes-Prieto, F.; Hernández-Morales, R.; Jácome, R.; Becerra, A.; Lazcano, A.

2017-07-01

Bioinformatic search for homologous sequences involved in ribonucleotidyl-coenzyme biosynthesis has shown that they are absent in RNA viral genomes, indicating that RNA viruses may not be direct holdovers from an ancient RNA/protein world.

A case of mitochondrial encephalomyopathy associated with a muscle coenzyme Q10 deficiency.

PubMed

Boitier, E; Degoul, F; Desguerre, I; Charpentier, C; François, D; Ponsot, G; Diry, M; Rustin, P; Marsac, C

1998-01-01

We report severe coenzyme Q10 deficiency of muscle in a 4-year-old boy presenting with progressive muscle weakness, seizures, cerebellar syndrome, and a raised cerebro-spinal fluid lactate concentration. State-3 respiratory rates of muscle mitochondria with glutamate, pyruvate, palmitoylcarnitine, and succinate as respiratory substrates were markedly reduced, whereas ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine were oxidized normally. The activities of complexes I, II, III and IV of the electron transport chain were normal, but the activities of complexes I+III and II+III, both systems requiring coenzyme Q10 as an electron carrier, were dramatically decreased. These results suggested a defect in the mitochondrial coenzyme Q10 content. This was confirmed by the direct assessment of coenzyme Q10 level by high-performance liquid chromatography in patient's muscle homogenate and isolated mitochondria, revealing levels of 16% and 6% of the control values, respectively. We did not find any impairment of the respiratory chain either in a lymphoblastoid cell line or in skin cultured fibroblasts from the patient, suggesting that the coenzyme Q10 depletion was tissue-specific. This is a new case of a muscle deficiency of mitochondrial coenzyme Q in a patient suffering from an encephalomyopathy.

Coenzyme Q10 protects ischemic myocardium in an open-chest swine model.

PubMed

Atar, D; Mortensen, S A; Flachs, H; Herzog, W R

1993-01-01

Myocardial stunning, defined as a reversible decrease in contractility after ischemia and reperfusion, may be a manifestation of reperfusion injury caused by free oxygen radical damage. The aim of this study was to test the hypothesis that pretreatment with coenzyme Q10 (ubiquinone), believed to act as a free radical scavenger, reduces myocardial stunning in a porcine model. Twelve swine were randomized to receive either oral supplementation with coenzyme Q10 or placebo for 20 days. A normothermic open-chest model was used with short occlusion (8 min) of the distal left descending coronary artery followed by reperfusion. Regional contractile function was measured with epicardial Doppler crystals in ischemic and nonischemic segments by measuring thickening fraction of the left ventricular wall during systole. Stunning time was defined as the elapsed time of reduced contractility until return to baseline. Coenzyme Q10 concentrations were measured in blood and homogenized myocardial tissue by high performance liquid chromatography. Plasma levels of reduced coenzyme Q10 (ubiquinol) were higher in swine pretreated with the experimental medication as compared to placebo (mean 0.45 mg/l versus 0.11 mg/l, respectively). Myocardial tissue concentrations, however, did not show any changes (mean 0.79 micrograms/mg dry weight versus 0.74 micrograms/mg). Stunning time was significantly reduced in coenzyme Q10 pretreated animals (13.7 +/- 7.7 min versus 32.8 +/- 3.1 min, P < 0.01). In conclusion, chronic pretreatment with coenzyme Q10 protects ischemic myocardium in an open-chest swine model. The beneficial effect of coenzyme Q10 on myocardial stunning may be due to protection from free radical mediated reperfusion injury. This protective effect seems to be generated by a humoral rather than intracellular mechanism.

Coenzyme Q and Mitochondrial Disease

ERIC Educational Resources Information Center

Quinzii, Catarina M.; Hirano, Michio

2010-01-01

Coenzyme Q[subscript 10] (CoQ[subscript 10]) is an essential electron carrier in the mitochondrial respiratory chain and an important antioxidant. Deficiency of CoQ[subscript 10] is a clinically and molecularly heterogeneous syndrome, which, to date, has been found to be autosomal recessive in inheritance and generally responsive to CoQ[subscript…

Potency of pre-post treatment of coenzyme Q10 and melatonin supplement in ameliorating the impaired fatty acid profile in rodent model of autism.

PubMed

El-Ansary, Afaf; Al-Ghamdi, Mashael; Bhat, Ramesa Shafi; Al-Daihan, Sooad; Al-Ayadhi, Laila

2016-01-01

Abnormalities in fatty acid metabolism and membrane fatty acid composition play a part in a wide range of neurodevelopmental and psychiatric disorders. Altered fatty acid homeostasis as a result of insufficient dietary supplementation, genetic defects, the function of enzymes involved in their metabolism, or mitochondrial dysfunction contributes to the development of autism. This study evaluates the association of altered brain lipid composition and neurotoxicity related to autism spectrum disorders in propionic acid (PA)-treated rats. Forty-eight young male western albino rats were used in this study. They were grouped into six equal groups with eight rats in each. The first group received only phosphate buffered saline (control group). The second group received a neurotoxic dose of buffered PA (250 mg/kg body weight/day for 3 consecutive days). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for 1 week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for 1 week prior to PA (protected groups). Methyl esters of fatty acid were extracted with hexane, and the fatty acid composition of the extract was analyzed on a gas chromatography. The obtained data proved that fatty acids are altered in brain tissue of PA-treated rats. All saturated fatty acids were increased while all unsaturated fatty acids were significantly decreased in the PA-treated group and relatively ameliorated in the pre-post melatonin and coenzyme Q groups. Melatonin and coenzyme Q were effective in restoring normal level of most of the impaired fatty acids in PA-intoxicated rats which could help suggest both as supplements to ameliorate the autistic features induced in rat pups.

Enhancing the Activity of the DLPFC with tDCS Alters Risk Preference without Changing Interpersonal Trust

PubMed Central

Zheng, Haoli; Wang, Siqi; Guo, Wenmin; Chen, Shu; Luo, Jun; Ye, Hang; Huang, Daqiang

2017-01-01

Interpersonal trust plays an essential role in economic interactions and social development. Extensive behavioral experiments have examined the nature of trust, particularly the question of whether trusting decisions are connected to risk preferences or risk attitudes. Various laboratory observations have been reported regarding the difference between trust and risk, and neural imaging studies have demonstrated that the right dorsolateral prefrontal cortex (rDLPFC) is more activated when individuals decide to trust other human beings compared with individuals decide to invest in a non-social risk condition. Moreover, the rDLPFC has been found to exhibit an intimate relationship with risk preference in previous neuroscience studies. However, the causal relationship between the rDLPFC and trust has rarely been revealed. Whether modulating the excitability of the rDLPFC, which shares roles in both trust and risk decisions, alters the trust or risk preference of participants remains unknown. In the present study, we aimed to provide evidence of a direct link between the neural and behavioral results through the application of transcranial direct current stimulation (tDCS) over the rDLPFC. We found that activating the rDLPFC altered the risk preferences of our participants, whereas no such significant effect over interpersonal trust was observed. Our findings indicate that enhancing the excitability of the rDLPFC using tDCS leads to more conservative decision-makings in a risk game, and this effect is specific to non-social risk rather than social-related trust. PMID:28232785

A possible prebiotic synthesis of pantetheine, a precursor to coenzyme A.

PubMed

Keefe, A D; Newton, G L; Miller, S L

1995-02-23

The involvement of coenzyme A in many enzyme reactions suggests that it acted in this capacity very early in the development of life on Earth. Particularly relevant in this regard is its role in the activation of amino acids and hydroxy acids in the biosynthesis of some peptide antibiotics--a mechanism of peptide synthesis that forms the basis for the proposal that a thioester world could have preceded the RNA world. The components of coenzyme A have been shown to be probable prebiotic compounds: beta-alanine, pantoyl lactone and cysteamine and possibly adenosine. We show here that the pantetheine moiety of coenzyme A (which also occurs in a number of enzymes) can be synthesized in yields of several per cent by heating pantoyl lactone, beta-alanine and cysteamine at temperatures as low as 40 degrees C. These components are extremely soluble and so would have been preferentially concentrated in evaporating bodies of water, for example on beaches and at lagoon margins. Our results show that amide bonds can be formed at temperatures as low as 40 degrees C, and provide circumstantial support for the suggestion that pantetheine and coenzyme A were important in the earliest metabolic systems.

A possible prebiotic synthesis of pantetheine, a precursor to coenzyme A

NASA Technical Reports Server (NTRS)

Keefe, A. D.; Newton, G. L.; Miller, S. L.

1995-01-01

The involvement of coenzyme A in many enzyme reactions suggests that it acted in this capacity very early in the development of life on Earth. Particularly relevant in this regard is its role in the activation of amino acids and hydroxy acids in the biosynthesis of some peptide antibiotics--a mechanism of peptide synthesis that forms the basis for the proposal that a thioester world could have preceded the RNA world. The components of coenzyme A have been shown to be probable prebiotic compounds: beta-alanine, pantoyl lactone and cysteamine and possibly adenosine. We show here that the pantetheine moiety of coenzyme A (which also occurs in a number of enzymes) can be synthesized in yields of several per cent by heating pantoyl lactone, beta-alanine and cysteamine at temperatures as low as 40 degrees C. These components are extremely soluble and so would have been preferentially concentrated in evaporating bodies of water, for example on beaches and at lagoon margins. Our results show that amide bonds can be formed at temperatures as low as 40 degrees C, and provide circumstantial support for the suggestion that pantetheine and coenzyme A were important in the earliest metabolic systems.

Gene encoding acetyl-coenzyme A carboxylase

DOEpatents

Roessler, Paul G.; Ohlrogge, John B.

1996-01-01

A DNA encoding an acetyl-coenzyme A carboxylase (ACCase) from a photosynthetic organism and functional derivatives thereof which are resistant to inhibition from certain herbicides. This gene can be placed in organisms to increase their fatty acid content or to render them resistant to certain herbicides.

Structural Insight into Methyl-Coenzyme M Reductase Chemistry using Coenzyme B Analogues†,‡

PubMed Central

Cedervall, Peder E.; Dey, Mishtu; Pearson, Arwen R.; Ragsdale, Stephen W.; Wilmot, Carrie M.

2011-01-01

Methyl-coenzyme M reductase (MCR) catalyzes the final and rate-limiting step in methane biogenesis; the reduction of methyl-coenzyme M (methyl-SCoM) by coenzyme B (CoBSH) to methane and a heterodisulfide (CoBS-SCoM). Crystallographic studies show that the active site is deeply buried within the enzyme, and contains a highly reduced nickel-tetrapyrrole, coenzyme F430. Methyl-SCoM must enter the active site prior to CoBSH, as species derived from analogues of methyl-SCoM are always observed bound to the F430 nickel in the deepest part of the 30 Å long substrate channel that leads from the protein surface to the active site. The seven-carbon mercaptoalkanoyl chain of CoBSH binds within a 16 Å predominantly hydrophobic part of the channel close to F430, with the CoBSH thiolate lying closest to the nickel at a distance of 8.8 Å. It has previously been suggested that binding of CoBSH initiates catalysis by inducing a conformational change that moves methyl-SCoM closer to the nickel promoting cleavage of the C-S bond of methyl-SCoM. In order to better understand the structural role of CoBSH early in the MCR mechanism, we have determined crystal structures of MCR in complex with four different CoBSH analogues; pentanoyl-, hexanoyl-, octanoyl- and nonanoyl- derivatives of CoBSH (CoB5SH, CoB6SH, CoB8SH and CoB9SH respectively). The data presented here reveal that the shorter CoB5SH mercaptoalkanoyl chain overlays with that of CoBSH, but terminates two units short of the CoBSH thiolate position. In contrast, the mercaptoalkanoyl chain of CoB6SH adopts a different conformation, such that its thiolate is coincident with the position of the CoBSH thiolate. This is consistent with the observation that CoB6SH is a slow substrate. A labile water in the substrate channel was found to be a sensitive indicator for the presence of CoBSH and HSCoM. The longer CoB8SH and CoB9SH analogues can be accommodated in the active site through exclusion of this water. These analogues react with

Gene encoding acetyl-coenzyme A carboxylase

DOEpatents

Roessler, P.G.; Ohlrogge, J.B.

1996-09-24

A DNA encoding an acetyl-coenzyme A carboxylase (ACCase) from a photosynthetic organism and functional derivatives are disclosed which are resistant to inhibition from certain herbicides. This gene can be placed in organisms to increase their fatty acid content or to render them resistant to certain herbicides. 5 figs.

Alteration of the coenzyme A biosynthetic pathway in neurodegeneration with brain iron accumulation syndromes.

PubMed

Venco, Paola; Dusi, Sabrina; Valletta, Lorella; Tiranti, Valeria

2014-08-01

NBIA (neurodegeneration with brain iron accumulation) comprises a heterogeneous group of neurodegenerative diseases having as a common denominator, iron overload in specific brain areas, mainly basal ganglia and globus pallidus. In the past decade a bunch of disease genes have been identified, but NBIA pathomechanisms are still not completely clear. PKAN (pantothenate kinase-associated neurodegeneration), an autosomal recessive disorder with progressive impairment of movement, vision and cognition, is the most common form of NBIA. It is caused by mutations in the PANK2 (pantothenate kinase 2) gene, coding for a mitochondrial enzyme that phosphorylates vitamin B5 in the first reaction of the CoA (coenzyme A) biosynthetic pathway. A distinct form of NBIA, denominated CoPAN (CoA synthase protein-associated neurodegeneration), is caused by mutations in the CoASY (CoA synthase) gene coding for a bifunctional mitochondrial enzyme, which catalyses the final steps of CoA biosynthesis. These two inborn errors of CoA metabolism further support the concept that dysfunctions in CoA synthesis may play a crucial role in the pathogenesis of NBIA.

Concentrations in beef and lamb of taurine, carnosine, coenzyme Q(10), and creatine.

PubMed

Purchas, R W; Rutherfurd, S M; Pearce, P D; Vather, R; Wilkinson, B H P

2004-03-01

Levels of taurine, carnosine, coenzyme Q(10), and creatine were measured in beef liver and several muscles of beef and lamb and in cooked and uncooked meat. The amino acid taurine has numerous biological functions, the dipeptide carnosine is a buffer as well as an antioxidant, coenzyme Q(10) is also an antioxidant present within mitochondria, and creatine along with creatine phosphate is involved with energy metabolism in muscle. Large differences were shown for all compounds between beef cheek muscle (predominantly red fibres) and beef semitendinosus muscle (mainly white fibres), with cheek muscle containing 9.9 times as much taurine, and 3.2 times as much coenzyme Q(10), but only 65% as much creatine and 9% as much carnosine. Levels in lamb relative to beef semitendinosus muscles were higher for taurine but slightly lower for carnosine, coenzyme Q(10) and creatine. Values for all the compounds varied significantly between eight lamb muscles, possibly due in part to differences in the proportion of muscle fibre types. Slow cooking (90 min at 70 °C) of lamb longissimus and semimembranosus muscles led to significant reductions in the content of taurine, carnosine, and creatine (P<0.001), but a slight increase in coenzyme Q(10). There was also a four-fold increase in creatinine, presumably due to its formation from creatine. It is concluded that biologically, and possibly nutritionally, significant levels of taurine, carnosine, coenzyme Q(10), and creatine are present in beef and lamb, but that these levels vary between muscles, between animals, and with cooking.

Coenzyme Q10 plus Multivitamin Treatment Prevents Cisplatin Ototoxicity in Rats

PubMed Central

Astolfi, Laura; Simoni, Edi; Valente, Filippo; Ghiselli, Sara; Hatzopoulos, Stavros; Chicca, Milvia; Martini, Alessandro

2016-01-01

Cisplatin (Cpt) is known to induce a high level of oxidative stress, resulting in an increase of reactive oxygen species damaging the inner ear and causing hearing loss at high frequencies. Studies on animal models show that antioxidants may lower Cpt-induced ototoxicity. The aim of this study is to evaluate the ototoxic effects of two different protocols of Cpt administration in a Sprague-Dawley rat model, and to test in the same model the synergic protective effects of a solution of coenzyme Q10 terclatrate and Acuval 400®, a multivitamin supplement containing antioxidant agents and minerals (Acu-Qter). The Cpt was administered intraperitoneally in a single dose (14 mg/kg) or in three daily doses (4.6 mg/kg/day) to rats orally treated or untreated with Acu-Qter for 5 days. The auditory function was assessed by measuring auditory brainstem responses from 2 to 32 kHz at day 0 and 5 days after treatment. Similar hearing threshold and body weight alterations were observed in both Cpt administration protocols, but mortality reduced to zero when Cpt was administered in three daily doses. The Acu-Qter treatment was able to prevent and completely neutralize ototoxicity in rats treated with three daily Cpt doses, supporting the synergic protective effects of coenzyme Q terclatrate and Acuval 400® against Cpt-induced oxidative stress. The administration protocol involving three Cpt doses is more similar to common human chemotherapy protocols, therefore it appears more useful for long-term preclinical studies on ototoxicity prevention. PMID:27632426

Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

PubMed Central

González-Alonso, Adrián; Ramírez-Tortosa, César L.; Varela-López, Alfonso; Roche, Enrique; Arribas, María I.; Ramírez-Tortosa, M. Carmen; Giampieri, Francesca; Ochoa, Julio J.; Quiles, José L.

2015-01-01

An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources. PMID:26426013

76 FR 42729 - Certain Coenzyme Q10 Products and Methods of Making Same; Notice of Institution of Investigation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-19

... INTERNATIONAL TRADE COMMISSION [Inv. No. 337-TA-790] Certain Coenzyme Q10 Products and Methods of... United States after importation of certain coenzyme Q10 products and methods of making same by reason of... after importation of certain coenzyme Q10 products and methods of making same that infringe one or more...

Alterations of sucrose preference after Roux-en-Y gastric bypass.

PubMed

Bueter, M; Miras, A D; Chichger, H; Fenske, W; Ghatei, M A; Bloom, S R; Unwin, R J; Lutz, T A; Spector, A C; le Roux, C W

2011-10-24

Roux-en-Y gastric bypass (gastric bypass) patients reportedly have changes in perception and consumption of sweet-tasting foods. This study aimed to further investigate alterations in sweet food intake in rats and sucrose detection in humans after gastric bypass. Wistar rats were randomized to gastric bypass or sham-operations and preference for sucrose (sweet), sodium chloride (salty), citric acid (sour) and quinine hydrochloride (bitter) was assessed with standard two-bottle intake tests (vs. water). Intestinal T1R2 and T1R3 expression and plasma levels of glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) were measured. Furthermore, obese patients and normal weight controls were tested for sucrose taste detection thresholds pre- and postoperatively. Visual analogue scales measuring hedonic perception were used to determine the sucrose concentration considered by patients and controls as "just about right" pre- and postoperatively. Gastric bypass reduced the sucrose intake relative to water in rats (p<0.001). Preoperative sucrose exposure reduced this effect. Preference or aversion for compounds representative of other taste qualities in naïve rats remained unaffected. Intestinal T1R2 and T1R3 expression was significantly decreased in the alimentary limb while plasma levels of GLP-1 and PYY were elevated after bypass in rats (p=0.01). Bypass patients showed increased taste sensitivity to low sucrose concentrations compared with controls (p<0.05), but both groups considered the same sucrose concentration as "just about right" postoperatively. In conclusion, gastric bypass reduces sucrose intake relative to water in sucrose-naïve rats, but preoperative sucrose experience attenuates this effect. Changes in sucrose taste detection do not predict hedonic taste ratings of sucrose in bypass patients which remain unchanged. Thus, factors other than the unconditional affective value of the taste may also play a role in determining food preferences after gastric bypass

Myocardial dysfunction in mitochondrial diabetes treated with Coenzyme Q10.

PubMed

Salles, João Eduardo; Moisés, Valdir A; Almeida, Dirceu R; Chacra, Antonio R; Moisés, Regina S

2006-04-01

Maternally-inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. Although some previous articles have reported that this mutation may be a cause of cardiomyopathy in diabetes, the degree of cardiac involvement and a specific treatment has not been established. Here, we reported a case of a patient with MIDD who developed congestive heart failure and the therapeutic usefulness of Coenzyme Q10 (CoQ10). In our patient, after the introduction of Coenzyme Q10 150 mg/day, there was a gradual improvement on left ventricular function evaluated by echocardiography. The fractional shortening (FS) and ejection fraction (EF) increased from 26 to 34% and from 49 to 64%, respectively. No side effects were noted. Three months after CoQ10 discontinuation, the parameters of systolic function evaluated by echocardiography decreased, suggesting that CoQ10 had a beneficial effect. Identification of diabetes and cardiomyopathy due to mitochondrial gene mutation may have therapeutic implications and Coenzyme Q10 is a possible adjunctive treatment in such patients.

Comparative bioavailability of two novel coenzyme Q10 preparations in humans.

PubMed

Joshi, S S; Sawant, S V; Shedge, A; Halpner, A D

2003-01-01

To determine the absorptive properties of 2 novel coenzyme Q10 preparations, a fast-melting tablet and an effervescent tablet, compared with currently available formulations. In the first trial, the absorptive properties of 4 different coenzyme Q10 preparations (fast-melting, effervescent, soft gelatin, and powder-filled hard shell) were studied in a randomized, single-dose, crossover study. Twenty-four male subjects were given a 60 mg dose of coenzyme Q10 and plasma coenzyme Q10 was measured over the next 12 hours. Pharmacokinetic properties including area under the curve (AUC), maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax) and elimination half-life (t 1/2) were measured. In a separate single-dose study, the absorptive characteristics of a different coenzyme Q10 soft gel (Q-Gel) were studied in 6 male subjects. Area under the curve (microg/ml x h) for the fast-melting and effervescent formulations, while marginally greater, was not significantly different when compared to the soft gelatin and powder-filled preparations, 5.4 +/- 1.04 (110%) and 5.5 +/- 0.589 (112%) versus 5.0 +/- 0.859 (102%) and 4.9 +/- 0.812 (100%), respectively. Cmax for the 2 novel formulations was also not statistically different from the soft gelatin or powder-filled preparations, 0.87 +/- 0.14 and 0.86 +/- 0.074 versus 0.70 +/- 0.010 and 0.81 +/- 0.159 (microg/ml). Tmax however, was significantly shorter for the fast-melting and effervescent formulations compared with the soft gel and powder-filled forms, 1.3 +/- 0.348 and 2.0 +/- 0.552 versus 3.7 +/- 0.702 and 4.1 +/- 0.993 (h), respectively. The results of the second trial were similar to those of the powder-filled and soft gel formulations from the first study. The novel fast-melting and effervescent formulations provide a more rapid delivery of CoQ10 to the blood while exhibiting a similar AUC compared with current formulations. The potential clinical significance of this finding should be further

[Regulation of the expression of coenzyme Q-synthesis complex during ageing].

PubMed

Campos-Silva, Carmen; Reyes-Torres, Iván; Rivera, Maximiliano; Meza-Torres, Catherine; Hernández-Camacho, Juan Diego; Rodríguez-Bies, Elisabet; Navas, Plácido; López-Lluch, Guillermo

Coenzyme Q is an essential component in the activity of the mitochondrial electron transport chain. Its synthesis involves, at least, a complex of ten different proteins. In this study, an attempt is made to determine the evolution of the expression of the genes involved in coenzyme Q synthesis during mouse ageing. The messenger RNA (mRNA) of different organs, such as brain, liver, kidney and skeletal muscle from young (8 months), mature (18 months), and old (24 months) mice was extracted by using Trizol and was then analysed by real time PCR (qPCR) using specific primers for all the known components of the coenzyme Q-synthesis complex (COQ genes). Liver showed the highest age-dependent changes in mRNA levels of the different components of Q-synthesis complex, affecting the extent of the variation as well as the significance of the change. In most of the cases, mRNA levels of the different components were higher in mature animals compared to young and old animals. When mRNAs of young and old animals were compared, only minor reductions of mRNA levels were found. Kidney showed a pattern similar to that found in liver as regards the changes in expression, although with lower increases in mature animals than those observed in the liver. Brain and skeletal muscle showed low variations, with muscle being the tissue with less changes, although a pattern similar to that found in liver and kidney was found, with slight increases in mature animals. The results of this study indicate that ageing is an important factor affecting COQ gene expression, but its effect depends on the organ, and that mature animals show higher levels of mRNA than young and old animals. Taken into consideration the importance of coenzyme Q in cell metabolism and ageing, a more detailed study is needed to understand the gene regulation of the coenzyme Q-synthesis mechanisms during ageing. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Extrafloral nectar content alters foraging preferences of a predatory ant

PubMed Central

Wilder, Shawn M.; Eubanks, Micky D.

2010-01-01

We tested whether the carbohydrate and amino acid content of extrafloral nectar affected prey choice by a predatory ant. Fire ants, Solenopsis invicta, were provided with artificial nectar that varied in the presence of carbohydrates and amino acids and were then provided with two prey items that differed in nutritional content, female and male crickets. Colonies of fire ants provided with carbohydrate supplements consumed less of the female crickets and frequently did not consume the high-lipid ovaries of female crickets. Colonies of fire ants provided with amino acid supplements consumed less of the male crickets. While a number of studies have shown that the presence of extrafloral nectar or honeydew can affect ant foraging activity, these results suggest that the nutritional composition of extrafloral nectar is also important and can affect subsequent prey choice by predatory ants. Our results suggest that, by altering the composition of extrafloral nectar, plants could manipulate the prey preferences of ants foraging on them. PMID:19864270

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes.

PubMed

Alkholy, Usama M; Abdalmonem, Nermin; Zaki, Ahmed; Elkoumi, Mohamed A; Hashim, Mustafa I Abu; Basset, Maha A A; Salah, Hossam E

2018-02-07

The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=-0.31; p=0.022) and the duration of type 1 diabetes (r=-0.35, p=0.012). Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Prevention of coronary atherosclerosis by the use of combination therapy with antioxidant coenzyme Q10 and statins.

PubMed

Chapidze, G; Kapanadze, S; Dolidze, N; Bachutashvili, Z; Latsabidze, N

2005-01-01

The goal of the present research was to assess the efficacy of combination treatment with antioxidant coenzyme Q10 and simvastatin as well as coenzyme Q10 without statin therapy in order to prevent coronary atherosclerosis. 42 outpatients were divided into 2 groups: receiving coenzyme Q10 (Hasco-Lek, Poland) 60mg daily and its combination with simvastatin (zocor, vasilip) 10mg daily for an 8-week period. The treatment with coenzyme Q10 demonstrated its potential independent role in positive modification of oxidative stress, antiatherogenic fraction of lipid profile, atherogenic ratio, platelet aggregability. Taking into consideration the obtained results the study supports the use of coenzyme Q10 in combination with statins. Suggested attractive approach may result in complete correction of dislipidemia, reverse of endothelial dysfunction, reduce degree of oxidative stress and platelet aggregability. Consequently such a combination may be beneficial in preventing of further development of atherosclerosis in native coronary arteries as well as in bypass grafts in all coronary heart disease patients with or without myocardial revascularization.

Incubation temperature alters thermal preference and response to heat stress of broiler chickens along the rearing phase.

PubMed

Morita, V S; Almeida, V R; Matos Junior, J B; Vicentini, T I; van den Brand, H; Boleli, I C

2016-08-01

The current study aimed to investigate whether embryonic temperature manipulation may alter thermal preference throughout the rearing phase of broiler chickens and how this manipulation may affect response to thermal challenge, metabolism, growth rate and feed intake rate. Eggs were exposed to a constant incubation temperature [machine temperatures: 36°C (Low), 37.5°C (Control), and 39°C (High); eggshell temperature of 37.4 ± 0.08°C, 37.8 ± 0.15°C, and 38.8 ± 0.33°C, respectively] from d 13 till hatching. Low treatment chickens showed lower plasma T3 and GH levels at d 1 of age and lower T3 level at d 42 of age compared to the Control treatment. Preferred ambient, rectal temperature, T4 level, growth rate, food intake rate, and response to thermal challenge were not altered in these chickens. On the other hand, High-treatment chickens exhibited high preferred ambient temperature and rectal temperature during the first 2 wk post-hatch, lower plasma T3 level at d 21 and 42 and a delayed increase in respiratory movement in response to thermal challenge compared to the Control treatment. However, chickens subjected to the Control and High treatments did not differ in T4 and GH level and performance. We conclude that exposure to high temperature during late embryonic development has long-lasting effects on the thermoregulatory system of broiler chickens by affecting the heat tolerance of these chickens. Moreover, the preferred ambient temperature of the chickens from heat-treated eggs correspond to those recommended for the strain under study, whereas for the cold-treated and control-chickens it was 1°C below, indicating that incubation temperature might have consequences on the ambient temperature chickens require during the rearing phase. © 2016 Poultry Science Association Inc.

Effects of various vitamins and coenzymes Q on reactions involving alpha-hydroxyl-containing radicals.

PubMed

Shadyro, Oleg I; Sosnovskaya, Anna A; Edimecheva, Irina P; Grintsevich, Ivan B; Lagutin, Petr Yu; Alekseev, Aleksei V; Kazem, Kamel

2005-07-01

Effects of vitamins B, C, E, K and P, as well as coenzymes Q, on formation of final products of radiation-induced free-radical transformations of ethanol, ethylene glycol, alpha-methylglycoside and glucose in aqueous solutions were studied. Based on the obtained results, it can be concluded that there are substances among vitamins and coenzymes that effectively interact with alpha-hydroxyl-containing radicals. In the presence of these substances, recombination reactions of alpha-hydroxyalkyl radicals and fragmentation of alpha-hydroxy-beta-substituted organic radicals are suppressed. It has been established that the observed effects are due to the ability of the vitamins and coenzymes under study to either oxidize alpha-hydroxyl-containing radicals yielding the respective carbonyl compounds or reduce them into the initial molecules.

Effects of stress on human mating preferences: stressed individuals prefer dissimilar mates

PubMed Central

Lass-Hennemann, Johanna; Deuter, Christian E.; Kuehl, Linn K.; Schulz, André; Blumenthal, Terry D.; Schachinger, Hartmut

2010-01-01

Although humans usually prefer mates that resemble themselves, mating preferences can vary with context. Stress has been shown to alter mating preferences in animals, but the effects of stress on human mating preferences are unknown. Here, we investigated whether stress alters men's preference for self-resembling mates. Participants first underwent a cold-pressor test (stress induction) or a control procedure. Then, participants viewed either neutral pictures or pictures of erotic female nudes whose facial characteristics were computer-modified to resemble either the participant or another participant, or were not modified, while startle eyeblink responses were elicited by noise probes. Erotic pictures were rated as being pleasant, and reduced startle magnitude compared with neutral pictures. In the control group, startle magnitude was smaller during foreground presentation of photographs of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to self-resembling mates. In the stress group, startle magnitude was larger during foreground presentation of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to dissimilar mates. Our findings show that stress affects human mating preferences: unstressed individuals showed the expected preference for similar mates, but stressed individuals seem to prefer dissimilar mates. PMID:20219732

Virus Infection of Plants Alters Pollinator Preference: A Payback for Susceptible Hosts?

PubMed Central

Davey, Matthew P.; Bruce, Toby J. A.; Caulfield, John C.; Furzer, Oliver J.; Reed, Alison; Robinson, Sophie I.; Miller, Elizabeth; Davis, Christopher N.; Pickett, John A.; Whitney, Heather M.; Glover, Beverley J.; Carr, John P.

2016-01-01

Plant volatiles play important roles in attraction of certain pollinators and in host location by herbivorous insects. Virus infection induces changes in plant volatile emission profiles, and this can make plants more attractive to insect herbivores, such as aphids, that act as viral vectors. However, it is unknown if virus-induced alterations in volatile production affect plant-pollinator interactions. We found that volatiles emitted by cucumber mosaic virus (CMV)-infected tomato (Solanum lycopersicum) and Arabidopsis thaliana plants altered the foraging behaviour of bumblebees (Bombus terrestris). Virus-induced quantitative and qualitative changes in blends of volatile organic compounds emitted by tomato plants were identified by gas chromatography-coupled mass spectrometry. Experiments with a CMV mutant unable to express the 2b RNA silencing suppressor protein and with Arabidopsis silencing mutants implicate microRNAs in regulating emission of pollinator-perceivable volatiles. In tomato, CMV infection made plants emit volatiles attractive to bumblebees. Bumblebees pollinate tomato by ‘buzzing’ (sonicating) the flowers, which releases pollen and enhances self-fertilization and seed production as well as pollen export. Without buzz-pollination, CMV infection decreased seed yield, but when flowers of mock-inoculated and CMV-infected plants were buzz-pollinated, the increased seed yield for CMV-infected plants was similar to that for mock-inoculated plants. Increased pollinator preference can potentially increase plant reproductive success in two ways: i) as female parents, by increasing the probability that ovules are fertilized; ii) as male parents, by increasing pollen export. Mathematical modeling suggested that over a wide range of conditions in the wild, these increases to the number of offspring of infected susceptible plants resulting from increased pollinator preference could outweigh underlying strong selection pressures favoring pathogen resistance

A randomized controlled trial of coenzyme Q10 for fatigue in the late-onset sequelae of poliomyelitis.

PubMed

Peel, Margaret M; Cooke, Marie; Lewis-Peel, Helen J; Lea, Rodney A; Moyle, Wendy

2015-12-01

To determine if coenzyme Q(10) alleviates fatigue in the late-onset sequelae of poliomyelitis. Parallel-group, randomized, placebo-controlled trial. Coenzyme Q(10) has been shown to boost muscle energy metabolism in post-polio subjects but it does not promote muscle strength, endurance or function in polio survivors with post-poliomyelitis syndrome. However, the collective increased energy metabolism might contribute to a reduction in post-polio fatigue. Polio survivors from the Australian post-polio networks in Queensland and New South Wales who attribute a moderate to high level of fatigue to their diagnosed late-onset sequelae of poliomyelitis. Those with fatigue-associated comorbidities of diabetes, anaemia, hypothyroidism and fibromyalgia were excluded. Participants were assigned (1:1), with stratification of those who use energy-saving mobility aids, to receive 100 mg coenzyme Q(10) or matching placebo daily for 60 days. Participants and investigators were blinded to group allocation. Fatigue was assessed by the Multidimensional Assessment of Fatigue as the primary outcome and the Fatigue Severity Scale as secondary outcome. Of 103 participants, 54 were assigned to receive coenzyme Q(10) and 49 to receive the placebo. The difference in the mean score reductions between the two groups was not statistically significant for either fatigue measure. Oral supplementation with coenzyme Q(10) was safe and well-tolerated. A daily dose of 100 mg coenzyme Q(10) for 60 days does not alleviate the fatigue of the late-onset sequelae of poliomyelitis. The registration number for the clinical trial is ACTRN 12612000552886. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cocaine decreases saccharin preference without altering sweet taste sensitivity.

PubMed

Roebber, Jennifer K; Izenwasser, Sari; Chaudhari, Nirupa

2015-06-01

In rodents, saccharin consumption is suppressed when the sweet taste stimulus is paired with moderate doses of cocaine. Several hypotheses have been used to explain the seemingly contradictory effect of decreased consumption of a normally preferred substance following a highly rewarding drug. A common theme across these hypotheses is that saccharin is interpreted as less rewarding after cocaine pairing. We considered the alternative possibility that suppression is caused not by a change in reward circuitry, but rather by a change in taste detection, for instance by altering the afferent taste response and decreasing sensitivity to sweet taste stimuli. To evaluate this possibility, we measured saccharin taste sensitivity of mice before and after a standard cocaine-pairing paradigm. We measured taste sensitivity using a brief-access lickometer equipped with multiple concentrations of saccharin solution and established concentration-response curves before and after saccharin-cocaine pairing. Our results indicate that the EC50 for saccharin was unaltered following pairing. Instead, the avidity of licking saccharin, an indicator of motivation, was depressed. Latency to first-lick, a negative indicator of motivation, was also dramatically increased. Thus, our findings are consistent with the interpretation that saccharin-cocaine pairing results in devaluing of the sweet taste reward. Copyright © 2015 Elsevier Inc. All rights reserved.

Validation of CoaBC as a Bactericidal Target in the Coenzyme A Pathway of Mycobacterium tuberculosis.

PubMed

Evans, Joanna C; Trujillo, Carolina; Wang, Zhe; Eoh, Hyungjin; Ehrt, Sabine; Schnappinger, Dirk; Boshoff, Helena I M; Rhee, Kyu Y; Barry, Clifton E; Mizrahi, Valerie

2016-12-09

Mycobacterium tuberculosis relies on its own ability to biosynthesize coenzyme A to meet the needs of the myriad enzymatic reactions that depend on this cofactor for activity. As such, the essential pantothenate and coenzyme A biosynthesis pathways have attracted attention as targets for tuberculosis drug development. To identify the optimal step for coenzyme A pathway disruption in M. tuberculosis, we constructed and characterized a panel of conditional knockdown mutants in coenzyme A pathway genes. Here, we report that silencing of coaBC was bactericidal in vitro, whereas silencing of panB, panC, or coaE was bacteriostatic over the same time course. Silencing of coaBC was likewise bactericidal in vivo, whether initiated at infection or during either the acute or chronic stages of infection, confirming that CoaBC is required for M. tuberculosis to grow and persist in mice and arguing against significant CoaBC bypass via transport and assimilation of host-derived pantetheine in this animal model. These results provide convincing genetic validation of CoaBC as a new bactericidal drug target.

In vitro methanol production from methyl coenzyme M using the Methanosarcina barkeri MtaABC protein complex.

PubMed

Dong, Ming; Gonzalez, Tara D; Klems, Meghan M; Steinberg, Lisa M; Chen, Wilfred; Papoutsakis, Eleftherios T; Bahnson, Brian J

2017-09-01

Methanol:coenzyme M methyltransferase is an enzyme complex composed of three subunits, MtaA, MtaB, and MtaC, found in methanogenic archaea and is needed for their growth on methanol ultimately producing methane. MtaABC catalyzes the energetically favorable methyl transfer from methanol to coenzyme M to form methyl coenzyme M. Here we demonstrate that this important reaction for possible production of methanol from the anaerobic oxidation of methane can be reversed in vitro. To this effect, we have expressed and purified the Methanosarcina barkeri MtaABC enzyme, and developed an in vitro functional assay that demonstrates MtaABC can catalyze the energetically unfavorable (ΔG° = 27 kJ/mol) reverse reaction starting from methyl coenzyme M and generating methanol as a product. Demonstration of an in vitro ability of MtaABC to produce methanol may ultimately enable the anaerobic oxidation of methane to produce methanol and from methanol alternative fuel or fuel-precursor molecules. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1243-1249, 2017. © 2017 American Institute of Chemical Engineers.

Interaction of Metabolic Stress with Chronic Mild Stress in Altering Brain Cytokines and Sucrose Preference

PubMed Central

Remus, Jennifer L.; Stewart, Luke T.; Camp, Robert M.; Novak, Colleen M.; Johnson, John D.

2015-01-01

There is growing evidence that metabolic stressors increase an organism’s risk of depression. Chronic mild stress is a popular animal model of depression and several serendipitous findings have suggested that food deprivation prior to sucrose testing in this model is necessary to observe anhedonic behaviors. Here, we directly tested this hypothesis by exposing animals to chronic mild stress and used an overnight two bottle sucrose test (food ad libitum) on day 5 and 10, then food and water deprive animals overnight and tested their sucrose consumption and preference in a 1h sucrose test the following morning. Approximately 65% of stressed animals consumed sucrose and showed a sucrose preference similar to non-stressed controls in an overnight sucrose test, while 35% showed a decrease in sucrose intake and preference. Following overnight food and water deprivation the previously ‘resilient’ animals showed a significant decrease in sucrose preference and greatly reduced sucrose intake. In addition, we evaluated whether the onset of anhedonia following food and water deprivation corresponds to alterations in corticosterone, epinephrine, circulating glucose, or interleukin-1 beta expression in limbic brain areas. While all stressed animals showed adrenal hypertrophy and elevated circulating epinephrine, only stressed animals that were food deprived were hypoglycemic compared to food deprived controls. Additionally, food and water deprivation significantly increased hippocampus IL-1β while food and water deprivation only increased hypothalamus IL-1β in stress susceptible animals. These data demonstrate that metabolic stress of food and water deprivation interacts with chronic stressor exposure to induce physiological and anhedonic responses. PMID:25914924

Metal plasmon-coupled fluorescence imaging and label free coenzyme detection in cells

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

Zhang, Jian, E-mail: jian@cfs.bioment.umaryland.edu; Fu, Yi; Li, Ge

2012-08-31

Highlights: Black-Right-Pointing-Pointer Metal nanoparticle for fluorescence cell imaging. Black-Right-Pointing-Pointer Non-invasive emission detection of coenzyme in cell on time-resolved confocal microscope. Black-Right-Pointing-Pointer Near-field interaction of flavin adenine dinucleotide with silver substrate. Black-Right-Pointing-Pointer Isolation of emissions by coenzymes from cellular autofluorescence on fluorescence cell imaging. -- Abstract: Flavin adenine dinucleotide (FAD) is a key metabolite in cellular energy conversion. Flavin can also bind with some enzymes in the metabolic pathway and the binding sites may be changed due to the disease progression. Thus, there is interest on studying its expression level, distribution, and redox state within the cells. FAD is naturally fluorescent,more » but it has a modest extinction coefficient and quantum yield. Hence the intrinsic emission from FAD is generally too weak to be isolated distinctly from the cellular backgrounds in fluorescence cell imaging. In this article, the metal nanostructures on the glass coverslips were used as substrates to measure FAD in cells. Particulate silver films were fabricated with an optical resonance near the absorption and the emission wavelengths of FAD which can lead to efficient coupling interactions. As a result, the emission intensity and quantum yield by FAD were greatly increased and the lifetime was dramatically shortened resulting in less interference from the longer lived cellular background. This feature may overcome the technical limits that hinder the direct observation of intrinsically fluorescent coenzymes in the cells by fluorescence microscopy. Fluorescence cell imaging on the metallic particle substrates may provide a non-invasive strategy for collecting the information of coenzymes in cells.« less

Coenzyme Q{sub 10} and alpha-tocopherol protect against amitriptyline toxicity

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

Cordero, Mario D.; Dpto. Citologia e Histologia Normal y Patologica, Facultad de Medicina. Universidad de Sevilla. 41009 Sevilla; Moreno-Fernandez, Ana Maria

Since amitriptyline is a very frequently prescribed antidepressant drug, it is not surprising that amitriptyline toxicity is relatively common. Amitriptyline toxic systemic effects include cardiovascular, autonomous nervous, and central nervous systems. To understand the mechanisms of amitriptyline toxicity we studied the cytotoxic effects of amitriptyline treatment on cultured primary human fibroblasts and zebrafish embryos, and the protective role of coenzyme Q{sub 10} and alpha-tocopherol, two membrane antioxidants. We found that amitriptyline treatment induced oxidative stress and mitochondrial dysfunction in primary human fibroblasts. Mitochondrial dysfunction in amitriptyline treatment was characterized by reduced expression levels of mitochondrial proteins and coenzyme Q{sub 10},more » decreased NADH:cytochrome c reductase activity, and a drop in mitochondrial membrane potential. Moreover, and as a consequence of these toxic effects, amitriptyline treatment induced a significant increase in apoptotic cell death activating mitochondrial permeability transition. Coenzyme Q{sub 10} and alpha-tocopherol supplementation attenuated ROS production, lipid peroxidation, mitochondrial dysfunction, and cell death, suggesting that oxidative stress affecting cell membrane components is involved in amitriptyline cytotoxicity. Furthermore, amitriptyline-dependent toxicity and antioxidant protection were also evaluated in zebrafish embryos, a well established vertebrate model to study developmental toxicity. Amitriptyline significantly increased embryonic cell death and apoptosis rate, and both antioxidants provided a significant protection against amitriptyline embryotoxicity.« less

Acyl Coenzyme A Thioesterase 7 Regulates Neuronal Fatty Acid Metabolism To Prevent Neurotoxicity

PubMed Central

Ellis, Jessica M.; Wong, G. William

2013-01-01

Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7N−/−, revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7N−/− mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7N−/− mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity. PMID:23459938

Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity.

PubMed

Ellis, Jessica M; Wong, G William; Wolfgang, Michael J

2013-05-01

Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7(N-/-), revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7(N-/-) mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7(N-/-) mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity.

LC/MS/MS analysis of α-tocopherol and coenzyme Q10 content in lyophilized royal jelly, beebread and drone homogenate.

PubMed

Hryniewicka, Marta; Karpinska, Agnieszka; Kijewska, Marta; Turkowicz, Monika Joanna; Karpinska, Joanna

2016-11-01

This study shows the results of application liquid chromatography-tandem mass spectrometry (LC/MS/MS) for assay of the content of α-tocopherol and coenzyme Q 10 in bee products of animal origin, i.e. royal jelly, beebread and drone homogenate. The biological matrix was removed using extraction with n-hexane. It was found that drone homogenate is a rich source of coenzyme Q 10 . It contains only 8 ± 1 µg/g of α-tocopherol and 20 ± 2 µg/g of coenzyme Q 10 . The contents of assayed compounds in royal jelly were 16 ± 3 and 8 ± 0.2 µg/g of α-tocopherol and coenzyme Q 10 , respectively. Beebread appeared to be the richest of α-tocopherol. Its level was 80 ± 30 µg/g, while the level of coenzyme Q 10 was only 11.5 ± 0.3 µg/g. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study.

PubMed

Tuncer, Ahmet Ali; Bozkurt, Mehmet Fatih; Koken, Tulay; Dogan, Nurhan; Pektaş, Mine Kanat; Baskin Embleton, Didem

2016-01-01

Objective. This study aims to evaluate whether alpha-lipoic acid and/or coenzyme Q10 can protect the prepubertal ovarian tissue from ischemia-reperfusion injury in an experimental rat model of ovarian torsion. Materials and Methods. Forty-two female preadolescent Wistar-Albino rats were divided into 6 equal groups randomly. The sham group had laparotomy without torsion; the other groups had torsion/detorsion procedure. After undergoing torsion, group 2 received saline, group 3 received olive oil, group 4 received alpha-lipoic acid, group 5 received coenzyme Q10, and group 6 received both alpha-lipoic acid and coenzyme Q10 orally. The oxidant-antioxidant statuses of these groups were compared using biochemical measurement of oxidized/reduced glutathione, glutathione peroxidase and malondialdehyde, pathological evaluation of damage and apoptosis within the ovarian tissue, and immunohistochemical assessment of nitric oxide synthase. Results. The left ovaries of the alpha-lipoic acid + coenzyme Q10 group had significantly lower apoptosis scores and significantly higher nitric oxide synthase content than the left ovaries of the control groups. The alpha-lipoic acid + coenzyme Q10 group had significantly higher glutathione peroxidase levels and serum malondialdehyde concentrations than the sham group. Conclusions. The combination of alpha-lipoic acid and coenzyme Q10 has beneficial effects on oxidative stress induced by ischemia-reperfusion injury related to ovarian torsion.

Effects of L-carnitine and coenzyme q10 on impaired spermatogenesis caused by isoproterenol in male rats.

PubMed

Ghanbarzadeh, S; Garjani, A; Ziaee, M; Khorrami, A

2014-09-01

Nowadays, cardiovascular diseases and male infertility are two big health problems in industrial countries.The aim of the present study was to investigate the protective role of coenzyme Q10 and L-Carnitine pretreatment in the impaired spermatogenesis caused by isoproterenol (ISO) in male rats.Thirty-two male Wistar rats were allocated in 4 groups. ISO was injected for 2 consecutive days (100 mg/kg) in ISO treated groups. Before ISO administration, pretreatment with Coenzyme Q10 (10 mg/kg/day) and L-Carnitine (350 mg/kg/day) were conducted for 20 consecutive days. Sex hormones level, malondialdehyde (MDA) and total antioxidant concentration as well as testis, epididymis and seminal vesicle weight were investigated.Increase in the concentration of MDA and decrease in total antioxidant level was observed following ISO administration. Accordingly, the sperm viability as well as testis, epididymis and seminal vesicle weights were decreased. In the case of sex hormones, the testosterone and LH levels were decreased and the concentration of FSH was increased. Pretreatment with L-carnitine and Coenzyme Q10 significantly decreased the MDA level and increased total antioxidant, LH and testosterone levels. Pretreatment with L-carnitine and Coenzyme Q10 also improved semen parameters and organs weight which were impaired by ISO administration.L-carnitine and Coenzyme Q10 pretreatment could protect spermatogenesis in male rats with ISO administration. © Georg Thieme Verlag KG Stuttgart · New York.

Coenzyme Q10 Supplementation Decreases Statin-Related Mild-to-Moderate Muscle Symptoms: A Randomized Clinical Study

PubMed Central

Skarlovnik, Ajda; Janić, Miodrag; Lunder, Mojca; Turk, Martina; Šabovič, Mišo

2014-01-01

Background Statin use is frequently associated with muscle-related symptoms. Coenzyme Q10 supplementation has yielded conflicting results in decreasing statin myopathy. Herein, we tested whether coenzyme Q10 supplementation could decrease statin-associated muscular pain in a specific group of patients with mild-to-moderate muscle symptoms. Material/Methods Fifty patients treated with statins and reporting muscle pain were recruited. The Q10 group (n=25) received coenzyme Q10 supplementation over a period of 30 days (50 mg twice daily), and the control group (n=25) received placebo. The Brief Pain Inventory (BPI) questionnaire was used and blood testing was performed at inclusion in the study and after 30 days of supplementation. Results The intensity of muscle pain, measured as the Pain Severity Score (PSS), in the Q10 group was reduced from 3.9±0.4 to 2.9±0.4 (P<0.001). The Pain Interference Score (PIS) after Q10 supplementation was reduced from 4.0±0.4 to 2.6±0.4 (P<0.001). In the placebo group, PSS and PIS did not change. Coenzyme Q10 supplementation decreased statin-related muscle symptoms in 75% of patients. The relative values of PSS and PIS significantly decreased (−33.1% and −40.3%, respectively) in the Q10 group compared to placebo group (both P<0.05). From baseline, no differences in liver and muscle enzymes or cholesterol values were found. Conclusions The present results show that coenzyme Q10 supplementation (50 mg twice daily) effectively reduced statin-related mild-to-moderate muscular symptoms, causing lower interference of statin-related muscular symptoms with daily activities. PMID:25375075

Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study.

PubMed

Skarlovnik, Ajda; Janić, Miodrag; Lunder, Mojca; Turk, Martina; Šabovič, Mišo

2014-11-06

Statin use is frequently associated with muscle-related symptoms. Coenzyme Q10 supplementation has yielded conflicting results in decreasing statin myopathy. Herein, we tested whether coenzyme Q10 supplementation could decrease statin-associated muscular pain in a specific group of patients with mild-to-moderate muscle symptoms. Fifty patients treated with statins and reporting muscle pain were recruited. The Q10 group (n=25) received coenzyme Q10 supplementation over a period of 30 days (50 mg twice daily), and the control group (n=25) received placebo. The Brief Pain Inventory (BPI) questionnaire was used and blood testing was performed at inclusion in the study and after 30 days of supplementation. The intensity of muscle pain, measured as the Pain Severity Score (PSS), in the Q10 group was reduced from 3.9±0.4 to 2.9±0.4 (P<0.001). The Pain Interference Score (PIS) after Q10 supplementation was reduced from 4.0±0.4 to 2.6±0.4 (P<0.001). In the placebo group, PSS and PIS did not change. Coenzyme Q10 supplementation decreased statin-related muscle symptoms in 75% of patients. The relative values of PSS and PIS significantly decreased (-33.1% and -40.3%, respectively) in the Q10 group compared to placebo group (both P<0.05). From baseline, no differences in liver and muscle enzymes or cholesterol values were found. The present results show that coenzyme Q10 supplementation (50 mg twice daily) effectively reduced statin-related mild-to-moderate muscular symptoms, causing lower interference of statin-related muscular symptoms with daily activities.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects.

PubMed

Zaki, Moushira E; El-Bassyouni, Hala T; Tosson, Angie M S; Youness, Eman; Hussein, Jihan

Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p=0.002), while coenzyme Q10 was significantly decreased (p=0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Balneotherapy and coenzyme Q10 in clinical and experimental medicine.

PubMed

Gvozdjakova, Anna; Kucharska, Jarmila; Sykora, L'ubomir; Singh, Ram B

2014-01-01

Balneotherapy or Spa therapy is used in neurological, cardiovascular, musculoskeletal, dermatological and gynecological diseases, in infertility as well as in metabolic disturbances. Beneficial effects of balneotherapy at the metabolic level is not fully understood. Authors have documented enhancement of antioxidants concentrations (coenzyme Q10- CoQ(10-OX) and alpha-tocopherol) of women with gynecological diseases by treatment with natural mineral water (Spa Lucky balneotherapy, Slovakia). In an experiment with rats, drinking of Spa Lucky mineral water decreased oxidative stress and enhanced concentrations of antioxidants CoQ(9-OX), CoQ(10-OX) in the myocardium, and alpha-tocopherol in uterus, ovaries and myocardium. Drinking of Spa Lucky water by rats stimulated myocardial mitochondrial respiration and energy production, and diminished skeletal muscle mitochondrial function. Simultaneous ingestion of coenzyme Q10 with drinking spa water returned mitochondrial parameters to the values of the control group. This pilot study helps explain the role of antioxidants, oxidative stress and mitochondrial energy production in beneficial effects of Spa Lucky balneotherapy.

Effects of α-Glycerophosphate and of Palmityl-Coenzyme A on Lipid Synthesis in Yeast Extracts

PubMed Central

White, David; Klein, Harold P.

1966-01-01

White, David (Ames Research Center, Moffett Field, Calif.), and Harold P. Klein. Effects of α-glycerophosphate and of palmityl-coenzyme A on lipid synthesis in yeast extracts. J. Bacteriol. 91:1218–1223. 1966.—The incorporation of acetate into fatty acids, but not into nonsaponifiable lipids, was stimulated by α-glycerophosphate in a supernatant fraction of Saccharomyces cerevisiae, obtained after centrifugation at 86,000 × g for 60 min. There was a pronounced effect at concentrations below 2 mm, but at concentrations above 5 mm α-glycerophosphate was relatively less stimulatory. α-Glycerophosphate markedly increased the percentage of esterified fatty acids among the products, and the formation of both saturated and unsaturated fatty acids was stimulated. Palmityl-coenzyme A inhibited fatty acid synthesis, affecting the formation of unsaturated acids more severely than saturated acids. In the presence of sufficient α-glycerophosphate to alleviate these inhibitions, palmityl-coenzyme A still reduced the formation of certain unsaturated fatty acids. PMID:5929752

Thermodynamics of various F420 coenzyme models as sources of electrons, hydride ions, hydrogen atoms and protons in acetonitrile.

PubMed

Xia, Ke; Shen, Guang-Bin; Zhu, Xiao-Qing

2015-06-14

32 F420 coenzyme models with alkylation of the three different N atoms (N1, N3 and N10) in the core structure (XFH(-)) were designed and synthesized and the thermodynamic driving forces (defined in terms of the molar enthalpy changes or the standard redox potentials in this work) of the 32 XFH(-) releasing hydride ions, hydrogen atoms and electrons, the thermodynamic driving forces of the 32 XFH˙ releasing protons and hydrogen atoms and the thermodynamic driving forces of XF(-)˙ releasing electrons in acetonitrile were determined using titration calorimetry and electrochemical methods. The effects of the methyl group at N1, N3 and N10 and a negative charge on N1 and N10 atoms on the six thermodynamic driving forces of the F420 coenzyme models and their related reaction intermediates were examined; the results show that seating arrangements of the methyl group and the negative charge have remarkably different effects on the thermodynamic properties of the F420 coenzyme models and their related reaction intermediates. The effects of the substituents at C7 and C8 on the six thermodynamic driving forces of the F420 coenzyme models and their related reaction intermediates were also examined; the results show that the substituents at C7 and C8 have good Hammett linear free energy relationships with the six thermodynamic parameters. Meanwhile, a reasonable determination of possible reactions between members of the F420 family and NADH family in vivo was given according to a thermodynamic analysis platform constructed using the elementary step thermodynamic parameter of F420 coenzyme model 2FH(-) and NADH model MNAH releasing hydride ions in acetonitrile. The information disclosed in this work can not only fill a gap in the chemical thermodynamics of F420 coenzyme models as a class of very important organic sources of electrons, hydride ions, hydrogen atoms and protons, but also strongly promote the fast development of the chemistry and applications of F420 coenzyme.

Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals

PubMed Central

Atanassov, Ilian; Kuznetsova, Irina; Hinze, Yvonne; Mourier, Arnaud; Filipovska, Aleksandra

2017-01-01

Dysfunction of the oxidative phosphorylation (OXPHOS) system is a major cause of human disease and the cellular consequences are highly complex. Here, we present comparative analyses of mitochondrial proteomes, cellular transcriptomes and targeted metabolomics of five knockout mouse strains deficient in essential factors required for mitochondrial DNA gene expression, leading to OXPHOS dysfunction. Moreover, we describe sequential protein changes during post-natal development and progressive OXPHOS dysfunction in time course analyses in control mice and a middle lifespan knockout, respectively. Very unexpectedly, we identify a new response pathway to OXPHOS dysfunction in which the intra-mitochondrial synthesis of coenzyme Q (ubiquinone, Q) and Q levels are profoundly decreased, pointing towards novel possibilities for therapy. Our extensive omics analyses provide a high-quality resource of altered gene expression patterns under severe OXPHOS deficiency comparing several mouse models, that will deepen our understanding, open avenues for research and provide an important reference for diagnosis and treatment. PMID:29132502

Compound Heterozygous Inheritance of Mutations in Coenzyme Q8A Results in Autosomal Recessive Cerebellar Ataxia and Coenzyme Q10 Deficiency in a Female Sib-Pair.

PubMed

Jacobsen, Jessie C; Whitford, Whitney; Swan, Brendan; Taylor, Juliet; Love, Donald R; Hill, Rosamund; Molyneux, Sarah; George, Peter M; Mackay, Richard; Robertson, Stephen P; Snell, Russell G; Lehnert, Klaus

2017-11-21

Autosomal recessive ataxias are characterised by a fundamental loss in coordination of gait with associated atrophy of the cerebellum. There is significant clinical and genetic heterogeneity amongst inherited ataxias; however, an early molecular diagnosis is essential with low-risk treatments available for some of these conditions. We describe two female siblings who presented early in life with unsteady gait and cerebellar atrophy. Whole exome sequencing revealed compound heterozygous inheritance of two pathogenic mutations (p.Leu277Pro, c.1506+1G>A) in the coenzyme Q8A gene (COQ8A), a gene central to biosynthesis of coenzyme Q (CoQ). The paternally derived p.Leu277Pro mutation is predicted to disrupt a conserved motif in the substrate-binding pocket of the protein, resulting in inhibition of CoQ 10 production. The maternal c.1506+1G>A mutation destroys a canonical splice donor site in exon 12 affecting transcript processing and subsequent protein translation. Mutations in this gene can result in primary coenzyme Q 10 deficiency type 4, which is characterized by childhood onset of cerebellar ataxia and exercise intolerance, both of which were observed in this sib-pair. Muscle biopsies revealed unequivocally low levels of CoQ 10, and the siblings were subsequently established on a therapeutic dose of CoQ 10 with distinct clinical evidence of improvement after 1 year of treatment. This case emphasises the importance of an early and accurate molecular diagnosis for suspected inherited ataxias, particularly given the availability of approved treatments for some subtypes.

Functional contribution of coenzyme specificity-determining sites of 7α-hydroxysteroid dehydrogenase from Clostridium absonum.

PubMed

Lou, Deshuai; Wang, Yue; Tan, Jun; Zhu, Liancai; Ji, Shunlin; Wang, Bochu

2017-10-01

Studies of the molecular determinants of coenzyme specificity help to reveal the structure-function relationship of enzymes, especially with regards to coenzyme specificity-determining sites (CSDSs) that usually mediate complex interactions. NADP(H)-dependent 7α-hydroxysteroid dehydrogenase from Clostridium absonum (CA 7α-HSDH), a member of the short-chain dehydrogenase/reductase superfamily (SDRs), possesses positively charged CSDSs that mainly contain T15, R16, R38, and R194, forming complicated polar interactions with the adenosine ribose C2 phosphate group of NADP(H). The R38 residue is crucial for coenzyme anchoring, but the influence of the other residues on coenzyme utilization is still not clear. Hence, we performed alanine scanning mutagenesis and molecular dynamic (MD) simulations. The results suggest that the natural CSDSs have the greatest NADP(H)-binding affinity, but not the best activity (k cat ) toward NADP + . Compared with the wild type and other mutants, the mutant R194A showed the highest catalytic efficiency (k cat /K m ), which was more than three-times that of the wild type. MD simulation and kinetics analysis suggested that the importance of the CSDSs of CA 7α-HSDH should be in accordance with the following order R38>T15>R16>R194, and S39 may have a supporting role in NADP(H) anchoring for mutants R16A/T194A and T15A/R16A/T194A. Copyright © 2017. Published by Elsevier Ltd.

Coenzyme Q10: A New Treatment for Hemorrhagic Shock

DTIC Science & Technology

2014-10-29

SUBJECT TERMS hemorrhagic shock, ubiquinol, Coenzyme Q10, patient outcome 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...o leo& to tboOigllll failure. The < Iota fur AlM •1 ha"’ boon ._...runym.,..,; •• ted in p=en~atlons and publiobed tn Expu""’""" P/u<llology. Tho

The effect of coenzyme Q10 in statin myopathy.

PubMed

Zlatohlavek, Lukas; Vrablik, Michal; Grauova, Barbora; Motykova, Eva; Ceska, Richard

2012-01-01

Statins significantly reduce CV morbidity and mortality. Unfortunately, one of the side effects of statins is myopathy, for which statins cannot be administered in sufficient doses or administered at all. The aim of this study was to demonstrate the effect of coenzyme Q10 in patients with statin myopathy. Twenty eight patients aged 60.6±10.7 years were monitored (18 women and 10 men) and treated with different types and doses of statin. Muscle weakness and pain was monitored using a scale of one to ten, on which patients expressed the degree of their inconvenience. Examination of muscle problems was performed prior to administration of CQ10 and after 3 and 6 months of dosing. Statistical analysis was performed using Friedman test, Annova and Students t-test. Pain decreased on average by 53.8% (p<0.0001), muscle weakness by 44.4% (p<0.0001). The CQ10 levels were increased by more than 194% (from 0,903 μg/ml to 2.66 μg/ml; p<0.0001). After a six-month administration of coenzyme Q10, muscle pain and sensitivity statistically significantly decreased.

Coq6 Is Responsible for the C4-deamination Reaction in Coenzyme Q Biosynthesis in Saccharomyces cerevisiae*

PubMed Central

Ozeir, Mohammad; Pelosi, Ludovic; Ismail, Alexandre; Mellot-Draznieks, Caroline; Fontecave, Marc; Pierrel, Fabien

2015-01-01

The yeast Saccharomyces cerevisiae is able to use para-aminobenzoic acid (pABA) in addition to 4-hydroxybenzoic acid as a precursor of coenzyme Q, a redox lipid essential to the function of the mitochondrial respiratory chain. The biosynthesis of coenzyme Q from pABA requires a deamination reaction at position C4 of the benzene ring to substitute the amino group with an hydroxyl group. We show here that the FAD-dependent monooxygenase Coq6, which is known to hydroxylate position C5, also deaminates position C4 in a reaction implicating molecular oxygen, as demonstrated with labeling experiments. We identify mutations in Coq6 that abrogate the C4-deamination activity, whereas preserving the C5-hydroxylation activity. Several results support that the deletion of Coq9 impacts Coq6, thus explaining the C4-deamination defect observed in Δcoq9 cells. The vast majority of flavin monooxygenases catalyze hydroxylation reactions on a single position of their substrate. Coq6 is thus a rare example of a flavin monooxygenase that is able to act on two different carbon atoms of its C4-aminated substrate, allowing its deamination and ultimately its conversion into coenzyme Q by the other proteins constituting the coenzyme Q biosynthetic pathway. PMID:26260787

Lip line preference for variant face types.

PubMed

Anwar, Nabila; Fida, Mubassar

2012-06-01

To determine the effect of altered lip line on attractiveness and to find preferred lip line for vertical face types in both genders. Cross-sectional analytical study. The Aga Khan University Hospital, Karachi, from May to July 2009. Photographs of two selected subjects were altered to produce three face types for the same individual with the aim of keeping the frame of the smile constant. Lip line was then altered for both the subjects as: both dentitions visible, upper incisors visible, upper incisors and 2 mm gum and 4 mm gum visible. The pictures were rated by different professionals for attractiveness. Descriptive statistics for the raters and multiple factor ANOVA was used to find the most attractive lip line. The total number of raters was 100 with the mean age of 30.3 ± 8 years. The alterations in the smile parameters produced statistically significant difference in the attractiveness of faces, whereas the perception difference was found to be insignificant amongst raters of different professions. Preferred lip line was the one showing only the upper incisors in dolico and mesofacial male and female genders whereas 2 mm gum show was preferred in brachyfacial subjects. The variability in lip line showed significant difference in the perceived attractiveness. Preferred lip lines as the one showing only the upper incisors in dolico and mesofacial male and female genders whereas 2 mm gum show was preferred in brachyfacial subjects.

Changing Less-Preferred Duties to More-Preferred: A Potential Strategy for Improving Supervisor Work Enjoyment

ERIC Educational Resources Information Center

Green, Carolyn W.; Reid, Dennis H.; Passante, Susan; Canipe, Vicki

2008-01-01

We evaluated a strategy for making highly nonpreferred work duties more preferred as a potential means of enhancing work enjoyment among supervisors in a human service setting. Repeated preference ratings and rankings were completed by 4 supervisors during baseline to identify their most disliked work tasks. These tasks were then altered by…

Coenzyme Q 10 improves lactic acidosis, strokelike episodes, and epilepsy in a patient with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes).

PubMed

Berbel-Garcia, Angel; Barbera-Farre, Jose Ramon; Etessam, Jesús Porta; Salio, Antonio Martínez; Cabello, Ana; Gutierrez-Rivas, Eduardo; Campos, Yolanda

2004-01-01

Mitochondrial encephalomyopathies encompass a group of disorders that have impaired oxidative metabolism in skeletal muscles and central nervous system. Many compounds have been used in clinical trials on mitochondrial diseases, but the outcomes have been variable. It remains controversial whether treatment of mitochondrial diseases with coenzyme Q 10 is effective. This paper describes a case of mitochondrial myopathy, encephalopathy, lactic acidosis, strokelike episodes, and exercise intolerance successfully treated with coenzyme Q 10. Efficacy of this therapy in this patient is correlated to control of lactic acidosis and serum creatine kinase levels. Disappointingly, larger studies with coenzyme Q 10 failed to demonstrate a clear beneficial effect on the entire study population with regard to clinical improvement or several parameters of the oxidative metabolism. They suggest that the use of coenzyme Q in treatment of mitochondrial diseases should be confined to protocols. There is a confounding variation in phenotype and genotype, and the natural history of the disorders in individual patients is not accurately predictable. The unpredictable a priori efficacy of therapy suggests that a long-term trial of oral coenzyme Q may be warranted.

Coenzyme Q10 protects renal proximal tubule cells against nicotine-induced apoptosis through induction of p66shc-dependent antioxidant responses.

PubMed

Arany, Istvan; Carter, Anthony; Hall, Samuel; Fulop, Tibor; Dixit, Mehul

2017-02-01

Chronic nicotine exposure (via smoking, E-cigarettes) increases oxidative stress in the kidney that sensitizes it to additional injury in experimental models and in the renal patient. The pro-apoptotic p66 shc protein-via serine36 phosphorylation that facilitates its mitochondrial translocation and therein cytochrome c binding-generates oxidative stress that leads to injury of renal proximal tubule cells during chronic nicotine exposure. Coenzyme Q10-a clinically safe antioxidant-has been used against nicotine/smoke extract-associated oxidative stress in various non-renal cells. This study explored the anti-oxidant/anti-apoptotic effect of Coenzyme Q10 on nicotine-induced oxidative stress and its impact on p66shc in cultured rat renal proximal tubule cells (NRK52E). We studied the anti-oxidant effect of 10 µM Coenzyme Q10 using various mutants of the p66shc gene and also determined the induction of selected anti-oxidant entities (antioxidant response element, promoter of the manganese superoxide dismutase gene) in reporter luciferase assay during oxidative stress induced by 200 µM nicotine. Our studies revealed that Coenzyme Q10 strongly inhibits nicotine-mediated production of reactive oxygen species and consequent apoptosis that requires serine36 phosphorylation but not mitochondrial translocation/cytochrome c binding of p66 shc . While both nicotine and Coenzyme Q10 stimulates the p66shc promoter, only nicotine exposure results in mitochondrial translocation of p66 shc . In contrast, the Coenzyme Q10-stimulated and non-mitochondrial p66 shc activates the anti-oxidant manganese superoxide dismutase promoter via the antioxidant response elements and hence, rescues cells from nicotine-induced oxidative stress and consequent apoptosis.

Adolescent social defeat increases adult amphetamine conditioned place preference and alters D2 dopamine receptor expression

PubMed Central

Burke, Andrew R.; Watt, Michael J.; Forster, Gina L.

2011-01-01

Components of the brain’s dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. Rats exposed to repeated social defeat in adolescence (P35–P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70). In contrast, rats experiencing foot-shock during the same developmental period exhibited amphetamine CPP levels similar to non-stressed controls. Our previous experiments suggested adolescent defeat alters dopamine activity in the mesocorticolimbic system. Furthermore, dopamine receptors have been implicated in the expression of amphetamine CPP. Therefore, we hypothesized that alteration to dopamine receptor expression in the mesocorticolimbic system may be associated with to heightened amphetamine CPP of adult rats exposed to adolescence defeat. We measured D1 and D2 dopamine receptor protein content in the medial prefrontal cortex, nucleus accumbens (NAc) and dorsal striatum following either adolescent social defeat or foot-shock stress and then adult amphetamine CPP. In controls, amphetamine CPP training reduced D2 receptor protein content in the NAc core. However, this down-regulation of NAc core D2 receptors was blocked by exposure to social defeat but not foot-shock stress in adolescence. These results suggest social defeat stress in adolescence alters the manner in which later amphetamine exposure down-regulates D2 receptors. Furthermore, persistent alterations to adult D2 receptor expression and amphetamine responses may depend on the type of stress experienced in adolescence. PMID:21933700

Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

PubMed

Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

2016-07-01

Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring. © 2015 Society for the Study of Addiction.

Heterologous Expression of Bacterial Epoxyalkane:Coenzyme M Transferase and Inducible Coenzyme M Biosynthesis in Xanthobacter Strain Py2 and Rhodococcus rhodochrous B276

PubMed Central

Krum, Jonathan G.; Ensign, Scott A.

2000-01-01

Coenzyme M (CoM) (2-mercaptoethanesulfonic acid) biosynthesis is shown to be coordinately regulated with the expression of the enzymes of alkene and epoxide metabolism in the propylene-oxidizing bacteria Xanthobacter strain Py2 and Rhodococcus rhodochrous strain B276. These results provide the first evidence for the involvement of CoM in propylene metabolism by R. rhodochrous and demonstrate for the first time the inducible nature of eubacterial CoM biosynthesis. PMID:10762269

Donor-Acceptor Distance Sampling Enhances the Performance of "Better than Nature" Nicotinamide Coenzyme Biomimetics.

PubMed

Geddes, Alexander; Paul, Caroline E; Hay, Sam; Hollmann, Frank; Scrutton, Nigel S

2016-09-07

Understanding the mechanisms of enzymatic hydride transfer with nicotinamide coenzyme biomimetics (NCBs) is critical to enhancing the performance of nicotinamide coenzyme-dependent biocatalysts. Here the temperature dependence of kinetic isotope effects (KIEs) for hydride transfer between "better than nature" NCBs and several ene reductase biocatalysts is used to indicate transfer by quantum mechanical tunneling. A strong correlation between rate constants and temperature dependence of the KIE (ΔΔH(⧧)) for H/D transfer implies that faster reactions with NCBs are associated with enhanced donor-acceptor distance sampling. Our analysis provides the first mechanistic insight into how NCBs can outperform their natural counterparts and emphasizes the need to optimize donor-acceptor distance sampling to obtain high catalytic performance from H-transfer enzymes.

Young children's preferences for listening rates.

PubMed

Leeper, H A; Thomas, C L

1978-12-01

A paired-comparison paradigm was utilized to determine the preferences of 20 young children for listening rate for prose speech. An electronic expansion/compression technique yielded nine rates of speech ranging from 100 wpm to 200 wpm, with intervals of 25 wpm. The results indicated that the children most preferred a listening rate of 200 wpm and least preferred a rate of 100 wpm. Comparisons of the present findings with preference rates of older, post-adolescent children and adults are discussed. Direction for further research with temporal alteration and linguistic constraints on the message are considered.

Biochemistry of Mitochondrial Coenzyme Q Biosynthesis.

PubMed

Stefely, Jonathan A; Pagliarini, David J

2017-10-01

Coenzyme Q (CoQ, ubiquinone) is a redox-active lipid produced across all domains of life that functions in electron transport and oxidative phosphorylation and whose deficiency causes human diseases. Yet, CoQ biosynthesis has not been fully defined in any organism. Several proteins with unclear molecular functions facilitate CoQ biosynthesis through unknown means, and multiple steps in the pathway are catalyzed by currently unidentified enzymes. Here we highlight recent progress toward filling these knowledge gaps through both traditional biochemistry and cutting-edge 'omics' approaches. To help fill the remaining gaps, we present questions framed by the recently discovered CoQ biosynthetic complex and by putative biophysical barriers. Mapping CoQ biosynthesis, metabolism, and transport pathways has great potential to enhance treatment of numerous human diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of Pyridine Carboxylic Acids in CM2 Carbonaceous Chondrites: Potential Precursor Molecules for Ancient Coenzymes

NASA Technical Reports Server (NTRS)

Smith, Karen E.; Callahan, Michael P.; Gerakines, Perry A.; Dworkin, Jason P.; House, Christopher H.

2014-01-01

The distribution and abundances of pyridine carboxylic acids (including nicotinic acid) in eight CM2 carbonaceous chondrites (ALH 85013, DOM 03183, DOM 08003, EET 96016, LAP 02333, LAP 02336, LEW 85311, and WIS 91600) were investigated by liquid chromatography coupled to UV detection and high resolution Orbitrap mass spectrometry. We find that pyridine monocarboxylic acids are prevalent in CM2-type chondrites and their abundance negatively correlates with the degree of pre-terrestrial aqueous alteration that the meteorite parent body experienced. We lso report the first detection of pyridine dicarboxylic acids in carbonaceous chondrites. Additionally, we carried out laboratory studies of proton-irradiated pyridine in carbon dioxide-rich ices (a 1:1 mixture) to serve as a model of the interstellar ice chemistry that may have led to the synthesis of pyridine carboxylic acids. Analysis of the irradiated ice residue shows that a comparable suite of pyridine mono- and dicarboxylic acids was produced, although aqueous alteration may still play a role in the synthesis (and ultimate yield) of these compounds in carbonaceous meteorites. Nicotinic acid is a precursor to nicotinamide adenine dinucleotide, a likely ancient molecule used in cellular metabolism in all of life, and its common occurrence in CM2 chondrites may indicate that meteorites may have been a source of molecules for the emergence of more complex coenzymes on the early Earth.

Investigation of Pyridine Carboxylic Acids in CM2 Carbonaceous Chondrites: Potential Precursor Molecules for Ancient Coenzymes

NASA Technical Reports Server (NTRS)

Smith, Karen E.; Callahan, Michael P.; Gerakines, Perry A.; Dworkin, Jason P.; House, Christopher H.

2014-01-01

The distribution and abundances of pyridine carboxylic acids (including nicotinic acid) in eight CM2 carbonaceous chondrites (ALH 85013, DOM 03183, DOM 08003, EET 96016, LAP 02333, LAP 02336, LEW 85311, and WIS 91600) were investigated by liquid chromatography coupled to UV detection and high resolution Orbitrap mass spectrometry. We find that pyridine monocarboxylic acids are prevalent in CM2-type chondrites and their abundance negatively correlates with the degree of pre-terrestrial aqueous alteration that the meteorite parent body experienced. We also report the first detection of pyridine dicarboxylic acids in carbonaceous chondrites. Additionally, we carried out laboratory studies of proton-irradiated pyridine in carbon dioxide-rich ices (a 1:1 mixture) to serve as a model of the interstellar ice chemistry that may have led to the synthesis of pyridine carboxylic acids. Analysis of the irradiated ice residue shows that a comparable suite of pyridine mono- and dicarboxylic acids was produced, although aqueous alteration may still play a role in the synthesis (and ultimate yield) of these compounds in carbonaceous meteorites. Nicotinic acid is a precursor to nicotinamide adenine dinucleotide, a likely ancient molecule used in cellular metabolism in all of life, and its common occurrence in CM2 chondrites may indicate that meteorites may have been a source of molecules for the emergence of more complex coenzymes on the early Earth.

Nano-encapsulation of coenzyme Q10 using octenyl succinic anhydride modified starch

USDA-ARS?s Scientific Manuscript database

Octenyl succinic anhydride modified starch (OSA-ST) was used to encapsulate Coenzyme Q10 (CoQ10). CoQ10 was dissolved in rice bran oil (RBO), and incorporated into an aqueous OSA-ST solution. High pressure homogenization (HPH) of the mixture was conducted at 170 MPa for 5-6 cycles. The resulting ...

Combined atorvastatin and coenzyme Q10 improve the left ventricular function in isoproterenol-induced heart failure in rat.

PubMed

Garjani, Alireza; Andalib, Sina; Biabani, Sajjad; Soraya, Hamid; Doustar, Yousef; Garjani, Afagh; Maleki-Dizaji, Nasrin

2011-09-01

The effect of atorvastatin on cardiac remodeling, function, and homodynamic parameters in isoproterenol-induced heart failure was evaluated in the present study. A subcutaneous injection of isoproterenol (5mg/kg/day) for 10 days was used for the induction of heart failure. Isoproterenol administration produced intensive myocardial necrosis and fibrosis with a significant decrease in the arterial pressure indices, heart rate, contractility (LVdP/dt(max)) and relaxation (LVdP/dt(min)), but an increase in the left ventricular end-diastolic pressure. Rats were randomly assigned to control, treatment with only atorvastatin, and treatment with atorvastatin plus coenzyme Q10. Histopathological analysis showed a marked attenuation of myocyte necrosis and interstitial fibrosis in all atorvastatin treated groups (P<0.001). A low dose of atorvastatin (5mg/kg/day) significantly improved the left ventricular systolic pressure, contractility and relaxation (P<0.01). On the contrary, a high dose of atorvastatin (20mg/kg/day) worsened the isoproterenol-induced left ventricular dysfunction by a further reduction of LVdP/dt(max) from +2780 ± 94 to +1588 ± 248 (mmHg/s; P<0.01) and LVdP/dt(min) from -2007 ± 190 to -2939 ± 291 (mmHg/s; P<0.05). Co-administration of coenzyme Q10 with atorvastatin reversed the hemodynamic depression and the left ventricular dysfunction to a high level (P<0.001). There was a lower level of LVEDPs in the atorvastatin+coenzyme Q10 treated groups (3 ± 1 and 4 ± 1.4 versus 8 ± 3.5 and 14 ± 3.6 mmHg, respectively), thereby suggesting improvement in the myocardial stiffness by the combined coenzyme Q10 and atorvastatin treatment. The atorvastatin therapy attenuated myocardial necrosis and fibrosis in isoproterenol-induced heart failure. However, a high dose of the drug considerably worsened the left ventricular dysfunction and hemodynamic depression, which was reversed by coenzyme Q10 co-administration. Copyright © 2011 Elsevier B.V. All rights

Observational Effects on the Preferences of Children with Autism

ERIC Educational Resources Information Center

Leaf, Justin B.; Oppenheim-Leaf, Misty L.; Leaf, Ronald; Courtemanche, Andrea B.; Taubman, Mitchell; McEachin, John; Sheldon, Jan B.; Sherman, James A.

2012-01-01

Children with an autism spectrum disorder (ASD) may play with limited objects or toys, making it difficult for teachers to identify reinforcers to use in teaching new skills. The goal of this study was to alter children's preferences from highly preferred toys to toys that were originally less preferred using an observational pairing procedure.…

Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

PubMed Central

Ates, Orhan; Bilen, Habip; Keles, Sadullah; Alp, H. Hakan; Keleş, Mevlüt Sait; Yıldırım, Kenan; Öndaş, Osman; Pınar, L. Can; Civelekler, Mustafa; Baykal, Orhan

2013-01-01

AIM To determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration. METHODS Patients with type 2 diabetes and PDRP were determined to be the case group (n=50). The control group was consist of healthy individuals (n=50). Plasma CoQ10 and malondialdehyde (MDA) levels were measured in both groups. RESULTS Ubiquinone-10 (Coenzyme Q10) levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively. CONCLUSION The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy. PMID:24195048

Ethanol production from xylose by recombinant Saccharomyces cerevisiae expressing protein-engineered NADH-preferring xylose reductase from Pichia stipitis.

PubMed

Watanabe, Seiya; Abu Saleh, Ahmed; Pack, Seung Pil; Annaluru, Narayana; Kodaki, Tsutomu; Makino, Keisuke

2007-09-01

A recombinant Saccharomyces cerevisiae strain transformed with xylose reductase (XR) and xylitol dehydrogenase (XDH) genes from Pichia stipitis (PsXR and PsXDH, respectively) has the ability to convert xylose to ethanol together with the unfavourable excretion of xylitol, which may be due to intercellular redox imbalance caused by the different coenzyme specificity between NADPH-preferring XR and NAD(+)-dependent XDH. In this study, we focused on the effect(s) of mutated NADH-preferring PsXR in fermentation. The R276H and K270R/N272D mutants were improved 52- and 146-fold, respectively, in the ratio of NADH/NADPH in catalytic efficiency [(k(cat)/K(m) with NADH)/(k(cat)/K(m) with NADPH)] compared with the wild-type (WT), which was due to decrease of k(cat) with NADPH in the R276H mutant and increase of K(m) with NADPH in the K270R/N272D mutant. Furthermore, R276H mutation led to significant thermostabilization in PsXR. The most positive effect on xylose fermentation to ethanol was found by using the Y-R276H strain, expressing PsXR R276H mutant and PsXDH WT: 20 % increase of ethanol production and 52 % decrease of xylitol excretion, compared with the Y-WT strain expressing PsXR WT and PsXDH WT. Measurement of intracellular coenzyme concentrations suggested that maintenance of the of NADPH/NADP(+) and NADH/NAD(+) ratios is important for efficient ethanol fermentation from xylose by recombinant S. cerevisiae.

EEG and ERP profiles in the high alcohol preferring (HAP) and low alcohol preferring (LAP) mice: relationship to ethanol preference.

PubMed

Slawecki, Craig J; Grahame, Nicholas J; Roth, Jennifer; Katner, Simon N; Ehlers, C L

2003-01-31

Neurophysiological measures, such as decreased P300 amplitude and altered EEG alpha activity, have been associated with increased alcoholism risk. The purpose of the present study was to extend the assessment of the neurophysiological indices associated with alcohol consumption to a recently developed mouse model of high ethanol consumption, the first replicate line of high alcohol preferring (HAP-1) and low alcohol preferring (LAP-1) mice. Male HAP-1, LAP-1, and HS mice from the Institute for Behavioral Genetics at the University of Colorado Health Science Center (i.e., HS/Ibg mice) were implanted with cortical electrodes. EEG activity, and event related potentials (ERPs) were then examined. Following electrophysiological assessment, ethanol preference was assessed to examine the relationship between neurophysiological indices and ethanol consumption. EEG analyses revealed that HAPs and HS/Ibgs had greater peak frequency in the 2-4-Hz band and lower peak frequency in the 6-8- and 1-50-Hz bands of the cortical EEG compared to LAPs. Compared to HAPs, LAPs and HS/Ibgs had decreased peak EEG frequency in the 8-16-Hz band. Decreased parietal cortical power from 8 to 50 Hz was associated with high initial ethanol preference in HAP mice. In regards to ERPs, P1 amplitude was greater in HAPs compared to both LAPs and HS/Ibgs and the P3 latency in LAPs was decreased compared to both HAPs and HS/Ibgs. As expected, HAPs consumed more ethanol and had higher ethanol preference than LAPs and HS/Ibgs. There were no significant differences in ethanol intake or preference between HS/Ibgs and LAPs. These data indicate that selective breeding of the HAP and LAP lines has resulted in the divergence of EEG and ERP phenotypes. The differences observed suggest that increased cortical P1 amplitude and altered cortical EEG activity in the 8-50-Hz frequency range may be neurophysiological 'risk factors' associated with high ethanol consumption in mice. Decreased P3 latency in LAPs compared

Nuclear-cytoplasmic localization of acetyl coenzyme A synthetase-1 in the rat brain

PubMed Central

Ariyannur, Prasanth S.; Moffett, John R.; Madhavarao, Chikkathur N; Arun, Peethambaran; Vishnu, Nisha; Jacobowitz, David M.; Hallows, William C.; Denu, John M.; Namboodiri, Aryan M.A.

2011-01-01

Acetyl coenzyme A synthetase 1 (AceCS1) catalyzes the synthesis of acetyl coenzyme A from acetate and coenzyme A, and is thought to play diverse roles ranging from fatty acid synthesis to gene regulation. Using an affinity purified antibody generated against an 18-mer peptide sequence of AceCS1, and a polyclonal antibody directed against recombinant AceCS1 protein, we examined the expression of AceCS1 in the rat brain. AceCS1 immunoreactivity in the adult rat brain was present predominantly in cell nuclei, with only light to moderate cytoplasmic staining in some neurons, axons and oligodendrocytes. Some non-neuronal cell nuclei were very strongly immunoreactive, including those of some oligodendrocytes, whereas neuronal nuclei ranged from unstained to moderately stained. Both antibodies stained some neuronal cell bodies and axons, especially in the hindbrain. AceCS1 immunoreactivity was stronger and more widespread in the brains of 18 day old rats than in adults, with increased expression in oligodendrocytes and neurons, including cortical pyramidal cells. Expression of AceCS1 was substantially upregulated in neurons throughout the brain after controlled cortical impact injury. The strong AceCS1 expression observed in the nuclei of CNS cells during brain development and after injury is consistent with a role in nuclear histone acetylation and therefore the regulation of chromatin structure and gene expression. The cytoplasmic staining observed in some oligodendrocytes, especially during postnatal brain development, suggests an additional role in CNS lipid synthesis and myelination. Neuronal and axonal localization implicates AceCS1 in cytoplasmic acetylation reactions in some neurons. PMID:20533355

Oxalyl-Coenzyme A Reduction to Glyoxylate Is the Preferred Route of Oxalate Assimilation in Methylobacterium extorquens AM1

PubMed Central

Schneider, Kathrin; Skovran, Elizabeth

2012-01-01

Oxalate catabolism is conducted by phylogenetically diverse organisms, including Methylobacterium extorquens AM1. Here, we investigate the central metabolism of this alphaproteobacterium during growth on oxalate by using proteomics, mutant characterization, and 13C-labeling experiments. Our results confirm that energy conservation proceeds as previously described for M. extorquens AM1 and other characterized oxalotrophic bacteria via oxalyl-coenzyme A (oxalyl-CoA) decarboxylase and formyl-CoA transferase and subsequent oxidation to carbon dioxide via formate dehydrogenase. However, in contrast to other oxalate-degrading organisms, the assimilation of this carbon compound in M. extorquens AM1 occurs via the operation of a variant of the serine cycle as follows: oxalyl-CoA reduction to glyoxylate and conversion to glycine and its condensation with methylene-tetrahydrofolate derived from formate, resulting in the formation of C3 units. The recently discovered ethylmalonyl-CoA pathway operates during growth on oxalate but is nevertheless dispensable, indicating that oxalyl-CoA reductase is sufficient to provide the glyoxylate required for biosynthesis. Analysis of an oxalyl-CoA synthetase- and oxalyl-CoA-reductase-deficient double mutant revealed an alternative, although less efficient, strategy for oxalate assimilation via one-carbon intermediates. The alternative process consists of formate assimilation via the tetrahydrofolate pathway to fuel the serine cycle, and the ethylmalonyl-CoA pathway is used for glyoxylate regeneration. Our results support the notion that M. extorquens AM1 has a plastic central metabolism featuring multiple assimilation routes for C1 and C2 substrates, which may contribute to the rapid adaptation of this organism to new substrates and the eventual coconsumption of substrates under environmental conditions. PMID:22493020

Melatonin administration alters nicotine preference consumption via signaling through high-affinity melatonin receptors.

PubMed

Horton, William J; Gissel, Hannah J; Saboy, Jennifer E; Wright, Kenneth P; Stitzel, Jerry A

2015-07-01

While it is known that tobacco use varies across the 24-h day, the time-of-day effects are poorly understood. Findings from several previous studies indicate a potential role for melatonin in these time-of-day effects; however, the specific underlying mechanisms have not been well characterized. Understanding of these mechanisms may lead to potential novel smoking cessation treatments. The objective of this study is examine the role of melatonin and melatonin receptors in nicotine free-choice consumption A two-bottle oral nicotine choice paradigm was utilized with melatonin supplementation in melatonin-deficient mice (C57BL/6J) or without melatonin supplementation in mice proficient at melatonin synthesis (C3H/Ibg) compared to melatonin-proficient mice lacking both or one of the high-affinity melatonin receptors (MT1 and MT2; double-null mutant DM, or MT1 or MT2). Preference for bitter and sweet tastants also was assessed in wild-type and MT1 and MT2 DM mice. Finally, home cage locomotor monitoring was performed to determine the effect of melatonin administration on activity patterns. Supplemental melatonin in drinking water significantly reduced free-choice nicotine consumption in C57BL/6J mice, which do not produce endogenous melatonin, while not altering activity patterns. Independently, genetic deletion of both MT1 and MT2 receptors in a melatonin-proficient mouse strain (C3H) resulted in significantly more nicotine consumption than controls. However, single genetic deletion of either the MT1 or MT2 receptor alone did not result in increased nicotine consumption. Deletion of MT1 and MT2 did not impact taste preference. This study demonstrates that nicotine consumption can be affected by exogenous or endogenous melatonin and requires at least one of the high-affinity melatonin receptors. The fact that expression of either the MT1 or MT2 melatonin receptor is sufficient to maintain lower nicotine consumption suggests functional overlap and potential mechanistic

Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis

PubMed Central

Mkrtchyan, Garik; Aleshin, Vasily; Parkhomenko, Yulia; Kaehne, Thilo; Luigi Di Salvo, Martino; Parroni, Alessia; Contestabile, Roberto; Vovk, Andrey; Bettendorff, Lucien; Bunik, Victoria

2015-01-01

Thiamin (vitamin B1) is a pharmacological agent boosting central metabolism through the action of the coenzyme thiamin diphosphate (ThDP). However, positive effects, including improved cognition, of high thiamin doses in neurodegeneration may be observed without increased ThDP or ThDP-dependent enzymes in brain. Here, we determine protein partners and metabolic pathways where thiamin acts beyond its coenzyme role. Malate dehydrogenase, glutamate dehydrogenase and pyridoxal kinase were identified as abundant proteins binding to thiamin- or thiazolium-modified sorbents. Kinetic studies, supported by structural analysis, revealed allosteric regulation of these proteins by thiamin and/or its derivatives. Thiamin triphosphate and adenylated thiamin triphosphate activate glutamate dehydrogenase. Thiamin and ThDP regulate malate dehydrogenase isoforms and pyridoxal kinase. Thiamin regulation of enzymes related to malate-aspartate shuttle may impact on malate/citrate exchange, responsible for exporting acetyl residues from mitochondria. Indeed, bioinformatic analyses found an association between thiamin- and thiazolium-binding proteins and the term acetylation. Our interdisciplinary study shows that thiamin is not only a coenzyme for acetyl-CoA production, but also an allosteric regulator of acetyl-CoA metabolism including regulatory acetylation of proteins and acetylcholine biosynthesis. Moreover, thiamin action in neurodegeneration may also involve neurodegeneration-related 14-3-3, DJ-1 and β-amyloid precursor proteins identified among the thiamin- and/or thiazolium-binding proteins. PMID:26212886

Fermentation of 1,2-Propanediol and 1,2-Ethanediol by Some Genera of Enterobacteriaceae, Involving Coenzyme B12-Dependent Diol Dehydratase

PubMed Central

Toraya, Tetsuo; Honda, Susumu; Fukui, Saburo

1979-01-01

Klebsiella pneumoniae (Aerobacter aerogenes) ATCC 8724 was able to grow anaerobically on 1,2-propanediol and 1,2-ethanediol as carbon and energy sources. Whole cells of the bacterium grown anaerobically on 1,2-propanediol or on glycerol catalyzed conversion of 1,2-diols and aldehydes to the corresponding acids and alcohols. Glucose-grown cells also converted aldehydes, but not 1,2-diols, to acids and alcohols. The presence of activities of coenzyme B12-dependent diol dehydratase, alcohol dehydrogenase, coenzyme-A-dependent aldehyde dehydrogenase, phosphotransacetylase, and acetate kinase was demonstrated with crude extracts of 1,2-propanediol-grown cells. The dependence of the levels of these enzymes on growth substrates, together with cofactor requirements in in vitro conversion of these substrates, indicates that 1,2-diols are fermented to the corresponding acids and alcohols via aldehydes, acyl-coenzyme A, and acyl phosphates. This metabolic pathway for 1,2-diol fermentation was also suggested in some other genera of Enterobacteriaceae which were able to grow anaerobically on 1,2-propanediol. When the bacteria were cultivated in a 1,2-propanediol medium not supplemented with cobalt ion, the coenzyme B12-dependent conversion of 1,2-diols to aldehydes was the rate-limiting step in this fermentation. This was because the intracellular concentration of coenzyme B12 was very low in the cells grown in cobalt-deficient medium, since the apoprotein of diol dehydratase was markedly induced in the cells grown in the 1,2-propanediol medium. Better cell yields were obtained when the bacteria were grown anaerobically on 1,2-propanediol. Evidence is presented that aerobically grown cells have a different metabolic pathway for utilizing 1,2-propanediol. PMID:378959

Octopamine influences honey bee foraging preference.

PubMed

Giray, Tugrul; Galindo-Cardona, Alberto; Oskay, Devrim

2007-07-01

Colony condition and differences in individual preferences influence forage type collected by bees. Physiological bases for the changing preferences of individual foragers are just beginning to be examined. Recently, for honey bees octopamine is shown to influence age at onset of foraging and probability of dance for rewards. However, octopamine has not been causally linked with foraging preference in the field. We tested the hypothesis that changes in octopamine may alter forage type (preference hypothesis). We treated identified foragers orally with octopamine or its immediate precursor, tyramine, or sucrose syrup (control). Octopamine-treated foragers switched type of material collected; control bees did not. Tyramine group results were not different from the control group. In addition, sugar concentrations of nectar collected by foragers after octopamine treatment were lower than before treatment, indicating change in preference. In contrast, before and after nectar concentrations for bees in the control group were similar. These results, taken together, support the preference hypothesis.

[The isozymes of stearil-coenzymeA-desaturase and insulin activity in the light of phylogenetic theory of pathology. Oleic fatty acid and realization of biologic functions of trophology and locomotion].

PubMed

2013-11-01

The formation of function of isozymes of stearil-coenzymeA-desaturases occured at the different stages of phylogeny under realization of biologic function of trophology (stearil-coenzymeA-desaturase 1) and biologic function of locomotion, insulin system (stearil-coenzymeA-desaturase 2) billions years later. The stearil-coenzymeA-desaturase 1 transforms in C 18:1 oleic fatty acid only exogenous C 16:0 palmitinic saturated fatty acid. The stearil-coenzymeA-desaturase 2 transforms only endogenic palmitinic saturated fatty acid, synthesized form glucose. The biologic role of insulin is in energy support of biologic function of locomotion. Insulin through expressing stearil-coenzymeA-desaturase 2 transforms energetically non-optimal palmitinic variation of metabolism of substrates into highly effective oleic variation for cells' groundwork of energy (saturated fatty acid and mono fatty acid). The surplus of palmitinic saturated fatty acid in food is enabled in pathogenesis of resistance to insulin and derangement of synthesis of hormone by beta-cells of islets. The resistance to insulin and diabetes mellitus are primarily the derangement of metabolism of saturated fatty acids with mono fatty acids, energy problems of organism and only afterwards the derangement of metabolism of carbohydrates. It is desirable to restrict food intake of exogenous palmitinic saturated fatty acid. The reasons are low expression of independent of insulin stearil-coenzymeA-desaturase 2, marked lipotoxicity of polar form of palmitinic saturated fatty acid and synthesis of non-optimal palmitinic triglycerides instead of physiologic and more energetically more effective oleic triglycerides.

Arachidonic acid alters tomato HMG expression and fruit growth and induces 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent lycopene accumulation

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

Rodriguez-Concepcion, M.; Gruissem, W.

Regulation of isoprenoid end-product synthesis required for normal growth and development in plants is not well understood. To investigate the extent to which specific genes for the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) are involved in end-product regulation, the authors manipulated expression of the HMG1 and HMG2 genes in tomato (Lycopersicon esculentum) fruit using arachidonic acid (AA). In developing young fruit AA blocked fruit growth, inhibited HMG1, and activated HMG2 expression. These results are consistent with other reports indicating that HMG1 expression is closely correlated with growth processes requiring phytosterol production. In mature-green fruit AA strongly induced the expression ofmore » HMG2, PSY1 (the gene for phytoene synthase), and lycopene accumulation before the normal onset of carotenoid synthesis and ripening. The induction of lycopene synthesis was not blocked by inhibition of HMGR activity using mevinolin, suggesting that cytoplasmic HMGR is not required for carotenoid synthesis. Their results are consistent with the function of an alternative plastid isoprenoid pathway (the Rohmer pathway) that appears to direct the production of carotenoids during tomato fruit ripening.« less

Diurnal lighting patterns and habitat alter opsin expression and colour preferences in a killifish

PubMed Central

Johnson, Ashley M.; Stanis, Shannon; Fuller, Rebecca C.

2013-01-01

Spatial variation in lighting environments frequently leads to population variation in colour patterns, colour preferences and visual systems. Yet lighting conditions also vary diurnally, and many aspects of visual systems and behaviour vary over this time scale. Here, we use the bluefin killifish (Lucania goodei) to compare how diurnal variation and habitat variation (clear versus tannin-stained water) affect opsin expression and the preference to peck at different-coloured objects. Opsin expression was generally lowest at midnight and dawn, and highest at midday and dusk, and this diurnal variation was many times greater than variation between habitats. Pecking preference was affected by both diurnal and habitat variation but did not correlate with opsin expression. Rather, pecking preference matched lighting conditions, with higher preferences for blue at noon and for red at dawn/dusk, when these wavelengths are comparatively scarce. Similarly, blue pecking preference was higher in tannin-stained water where blue wavelengths are reduced. In conclusion, L. goodei exhibits strong diurnal cycles of opsin expression, but these are not tightly correlated with light intensity or colour. Temporally variable pecking preferences probably result from lighting environment rather than from opsin production. These results may have implications for the colour pattern diversity observed in these fish. PMID:23698009

Taste preference changes throughout different life stages in male rats

PubMed Central

Yamamoto, Takashi; Ueda, Katsura; Nakatsuka, Michiko; Kumabe, Shunji; Inui, Tadashi; Iwai, Yasutomo

2017-01-01

Taste preference, a key component of food choice, changes with aging. However, it remains unclear how this occurs. To determine differences in taste preference between rats in different life stages, we examined the consumption of taste solutions and water using a two-bottle test. Male Sprague-Dawley rats of different ages were used: juvenile (3–6 weeks), young adult (8–11 weeks), adult (17–20 weeks), middle-aged (34–37 weeks), and old-aged (69–72 weeks). The intakes of the high and low concentration solutions presented simultaneously were measured. We observed that the old-aged group had lower preference ratios for 0.3 M sucrose and 0.1 M MSG in comparison with other groups. The preference ratio for 0.03 mM QHCl was higher in the middle-aged group than in the three younger groups and higher in the old-aged group than the juvenile group. The taste preferences for HCl and NaCl did not significantly differ among the age groups. The old-aged group tended to prefer high concentrations of sucrose, QHCl, NaCl, and MSG to low concentrations, indicating age-related decline in taste sensitivity. We also aimed to investigate differences between life stages in the electrophysiological responses of the chorda tympani nerve, one of the peripheral gustatory nerves, to taste stimuli. The electrophysiological recordings showed that aging did not alter the function of the chorda tympani nerve. This study showed that aging induced alterations in taste preference. It is likely that these alterations are a result of functional changes in other peripheral taste nerves, the gastrointestinal system, or the central nervous system. PMID:28742813

Mechanism of α-Glycerophosphate Regulation of Acetyl-Coenzyme A Carboxylase of Saccharomyces cerevisiae

PubMed Central

Rasmussen, Roberta K.; Klein, Harold P.

1968-01-01

The mechanism proposed for the activation of animal acetyl-coenzyme A (CoA) carboxylase by α-glycerophosphate, namely, the removal of inhibitory palmityl-CoA via glyceride synthesis, is not the only possible one in the yeast system because extracts exhibiting marked stimulation of acetyl-CoA carboxylase activity by α-glyerophosphate show a lack of acyl-CoA compounds. PMID:5643049

Nanoencapsulation of coenzyme Q10 and vitamin E acetate protects against UVB radiation-induced skin injury in mice.

PubMed

Pegoraro, Natháli S; Barbieri, Allanna V; Camponogara, Camila; Mattiazzi, Juliane; Brum, Evelyne S; Marchiori, Marila C L; Oliveira, Sara M; Cruz, Letícia

2017-02-01

This study aimed to investigate the feasibility of producing semisolid formulations based on nanocapsule suspensions containing the association of the coenzyme Q10 and vitamin E acetate by adding gellan gum (2%) to the suspensions. Furthermore, we studied their application as an alternative for the treatment of inflammation induced by ultraviolet B (UVB) radiation. For this, an animal model of injury induced by UVB-radiation was employed. All semisolids presented pH close to 5.5, drug content above 95% and mean diameter on the nanometric range, after redispersion in water. Besides, the semisolids presented non-Newtonian flow with pseudoplastic behavior and suitable spreadability factor values. The results also showed that the semisolid containing coenzyme Q10-loaded nanocapsules with higher vitamin E acetate concentration reduced in 73±8% the UVB radiation-induced ear edema. Moreover, all formulations tested were able to reduce inflammation parameters evaluated through MPO activity and histological procedure on injured tissue and the semisolids containing the nanoencapsulated coenzyme Q10 reduced oxidative parameters assessment through the non-protein thiols levels and lipid peroxidation. This way, the semisolids based on nanocapsules may be considered a promising approach for the treatment and prevention of skin inflammation diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Coenzyme Q10 Therapy

PubMed Central

Garrido-Maraver, Juan; Cordero, Mario D.; Oropesa-Ávila, Manuel; Fernández Vega, Alejandro; de la Mata, Mario; Delgado Pavón, Ana; de Miguel, Manuel; Pérez Calero, Carmen; Villanueva Paz, Marina; Cotán, David; Sánchez-Alcázar, José A.

2014-01-01

For a number of years, coenzyme Q10 (CoQ10) was known for its key role in mitochondrial bioenergetics; later studies demonstrated its presence in other subcellular fractions and in blood plasma, and extensively investigated its antioxidant role. These 2 functions constitute the basis for supporting the clinical use of CoQ10. Also, at the inner mitochondrial membrane level, CoQ10 is recognized as an obligatory cofactor for the function of uncoupling proteins and a modulator of the mitochondrial transition pore. Furthermore, recent data indicate that CoQ10 affects the expression of genes involved in human cell signaling, metabolism and transport, and some of the effects of CoQ10 supplementation may be due to this property. CoQ10 deficiencies are due to autosomal recessive mutations, mitochondrial diseases, aging-related oxidative stress and carcinogenesis processes, and also statin treatment. Many neurodegenerative disorders, diabetes, cancer, and muscular and cardiovascular diseases have been associated with low CoQ10 levels as well as different ataxias and encephalomyopathies. CoQ10 treatment does not cause serious adverse effects in humans and new formulations have been developed that increase CoQ10 absorption and tissue distribution. Oral administration of CoQ10 is a frequent antioxidant strategy in many diseases that may provide a significant symptomatic benefit. PMID:25126052

Menstrual cycle phase alters women's sexual preferences for composers of more complex music.

PubMed

Charlton, Benjamin D

2014-06-07

Over 140 years ago Charles Darwin first argued that birdsong and human music, having no clear survival benefit, were obvious candidates for sexual selection. Whereas the first contention is now universally accepted, his theory that music is a product of sexual selection through mate choice has largely been neglected. Here, I provide the first, to my knowledge, empirical support for the sexual selection hypothesis of music evolution by showing that women have sexual preferences during peak conception times for men that are able to create more complex music. Two-alternative forced-choice experiments revealed that woman only preferred composers of more complex music as short-term sexual partners when conception risk was highest. No preferences were displayed when women chose which composer they would prefer as a long-term partner in a committed relationship, and control experiments failed to reveal an effect of conception risk on women's preferences for visual artists. These results suggest that women may acquire genetic benefits for offspring by selecting musicians able to create more complex music as sexual partners, and provide compelling support for Darwin's assertion 'that musical notes and rhythm were first acquired by the male or female progenitors of mankind for the sake of charming the opposite sex'.

Methyl-coenzyme M reductase from methanogenic archaea: isotope effects on label exchange and ethane formation with the homologous substrate ethyl-coenzyme M.

PubMed

Scheller, Silvan; Goenrich, Meike; Thauer, Rudolf K; Jaun, Bernhard

2013-10-09

Ethyl-coenzyme M (CH3CH2-S-CH2CH2-SO3(-), Et-S-CoM) serves as a homologous substrate for the enzyme methyl-coenzyme M reductase (MCR) resulting in the product ethane instead of methane. The catalytic reaction proceeds via an intermediate that already contains all six C-H bonds of the product. Because product release occurs after a second, rate-limiting step, many cycles of intermediate formation and reconversion to substrate occur before a substantial amount of ethane is released. In deuterated buffer, the intermediate becomes labeled, and C-H activation in the back reaction rapidly leads to labeled Et-S-CoM, which enables intermediate formation to be detected. Here, we present a comprehensive analysis of this pre-equilibrium. (2)H- and (13)C-labeled isotopologues of Et-S-CoM were used as the substrates, and the time course of each isotopologue was followed by NMR spectroscopy. A kinetic simulation including kinetic isotope effects allowed determination of the primary and α- and β-secondary isotope effects for intermediate formation and for the C-H/C-D bond activation in the ethane-containing intermediate. The values obtained are in accordance with those found for the native substrate Me-S-CoM (see preceding publication, Scheller, S.; Goenrich, M.; Thauer, R. K.; Jaun, B. J. Am. Chem. Soc. 2013, 135, DOI: 10.1021/ja406485z) and thus imply the same catalytic mechanism for both substrates. The experiment by Floss and co-workers, demonstrating a net inversion of configuration to chiral ethane with CH3CDT-S-CoM as the substrate, is compatible with the observed rapid isotope exchange if the isotope effects measured here are taken into account.

Probing Reversible Chemistry in Coenzyme B12-Dependent Ethanolamine Ammonia Lyase with Kinetic Isotope Effects

PubMed Central

Jones, Alex R; Rentergent, Julius; Scrutton, Nigel S; Hay, Sam

2015-01-01

Coenzyme B12-dependent enzymes such as ethanolamine ammonia lyase have remarkable catalytic power and some unique properties that enable detailed analysis of the reaction chemistry and associated dynamics. By selectively deuterating the substrate (ethanolamine) and/or the β-carbon of the 5′-deoxyadenosyl moiety of the intrinsic coenzyme B12, it was possible to experimentally probe both the forward and reverse hydrogen atom transfers between the 5′-deoxyadenosyl radical and substrate during single-turnover stopped-flow measurements. These data are interpreted within the context of a kinetic model where the 5′-deoxyadenosyl radical intermediate may be quasi-stable and rearrangement of the substrate radical is essentially irreversible. Global fitting of these data allows estimation of the intrinsic rate constants associated with CoC homolysis and initial H-abstraction steps. In contrast to previous stopped-flow studies, the apparent kinetic isotope effects are found to be relatively small. PMID:25950663

The Local Dinucleotide Preference of APOBEC3G Can Be Altered from 5′-CC to 5′-TC by a Single Amino Acid Substitution

PubMed Central

Rathore, Anurag; Carpenter, Michael A; Demir, Özlem; Ikeda, Terumasa; Li, Ming; Shaban, Nadine; Law, Emily K.; Anokhin, Dmitry; Brown, William L.; Amaro, Rommie E.; Harris, Reuben S.

2013-01-01

APOBEC3A and APOBEC3G are DNA cytosine deaminases with biological functions in foreign DNA and retrovirus restriction, respectively. APOBEC3A has an intrinsic preference for cytosine preceded by thymine (5′-TC) in single-stranded DNA substrates, whereas APOBEC3G prefers the target cytosine to be preceded by another cytosine (5′-CC). To determine the amino acids responsible for these strong dinucleotide preferences, we analyzed a series of chimeras in which putative DNA binding loop regions of APOBEC3G were replaced with the corresponding regions from APOBEC3A. Loop 3 replacement enhanced APOBEC3G catalytic activity but did not alter its intrinsic 5′-CC dinucleotide substrate preference. Loop 7 replacement caused APOBEC3G to become APOBEC3A-like and strongly prefer 5′-TC substrates. Simultaneous loop 3/7 replacement resulted in a hyperactive APOBEC3G variant that also preferred 5′-TC dinucleotides. Single amino acid exchanges revealed D317 as a critical determinant of dinucleotide substrate specificity. Multi-copy explicitly solvated all-atom molecular dynamics simulations suggested a model in which D317 acts as a helix-capping residue by constraining the mobility of loop 7, forming a novel binding pocket that favorably accommodates cytosine. All catalytically active APOBEC3G variants, regardless of dinucleotide preference, retained HIV-1 restriction activity. These data support a model in which the loop 7 region governs the selection of local dinucleotide substrates for deamination but is unlikely to be part of the higher level targeting mechanisms that direct these enzymes to biological substrates such as HIV-1 cDNA. PMID:23938202

The implications of choice: prescribing generic or preferred pharmaceuticals improves medication adherence for chronic conditions.

PubMed

Shrank, William H; Hoang, Tuyen; Ettner, Susan L; Glassman, Peter A; Nair, Kavita; DeLapp, Dee; Dirstine, June; Avorn, Jerry; Asch, Steven M

2006-02-13

A large proportion of Americans are enrolled in 3-tier pharmacy benefit plans. We studied whether patients enrolled in such plans who receive generic or preferred brand-name agents when initiating chronic therapy were more adherent to treatment than those who received nonpreferred brand-name medications. We analyzed pharmacy claims filled between October 1, 2001, and October 1, 2003, from a large health plan for 6 classes of chronic medications: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, calcium channel blockers, oral contraceptives, orally inhaled corticosteroids, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors. We measured adherence as the proportion of days covered (PDC) in each drug class during the first year of therapy. We evaluated how the formulary status of the initial prescription (generic, preferred, or nonpreferred) influenced PDC and adequate adherence, defined as PDC greater than 80%, over the subsequent year. A total of 7532 new prescriptions were filled in 1 of the classes evaluated: 1747 (23.2%) for nonpreferred medications, 4376 (58.1%) for preferred drugs, and 1409 (18.7%) for generic drugs. After controlling for patient sociodemographic characteristics and drug class, PDC was 12.6% greater for patients initiated on generic medications vs nonpreferred medications (58.8% vs 52.2%; P<.001). The PDC was 8.8% greater for patients initiated on preferred vs nonpreferred medications (56.8% vs 52.2%; P<.001). Patients initiated on generic and preferred medications had 62% and 30% greater odds, respectively, of achieving adequate adherence compared with those who received nonpreferred medications. In 3-tier pharmacy benefit plans, prescribing generic or preferred medications within a therapeutic class is associated with improvements in adherence to therapy.

Endogenous Formation of Preferences: Choices Systematically Change Willingness-to-Pay for Goods

ERIC Educational Resources Information Center

Voigt, Katharina; Murawski, Carsten; Bode, Stefan

2017-01-01

Standard decision theory assumes that choices result from stable preferences. This position has been challenged by claims that the act of choosing between goods may alter preferences. To test this claim, we investigated in three experiments whether choices between equally valued snack food items can systematically shape preferences. We directly…

Relative bioavailability and antioxidant potential of two coenzyme q10 preparations.

PubMed

Kurowska, Elzbieta M; Dresser, George; Deutsch, Luisa; Bassoo, Errol; Freeman, David J

2003-01-01

Coenzyme Q10 (CoQ10) is synthesized by the human body and found in certain foods. Daily supplementation of CoQ10 could protect against heart disease but the bioavailability of CoQ10 supplements depends on the formulation taken. We compared the bioavailability and antioxidant properties of two commercial CoQ10 formulations, a commercial grade CoQ10 powder (commercial grade CoQ) and a new BT-CoQ10 BIO-TRANSFORMED (BT-CoQ10) obtained by fermentation of a soy-based, CoQ10-rich media with baker's yeast. Eleven healthy individuals participated in a randomized two-way crossover trial, with a 3-week washout period. Capsules containing 300 mg of either BT-CoQ10 or commercial grade CoQ10 were given daily for 1 week and multiple blood samples were taken for CoQ10, glutathione and glutathione peroxidase (GPx) determination. In 3 subjects, baseline plasma CoQ10 levels were lower prior to BT than prior to commercial grade CoQ treatment. In the remaining participants, ingestion of BT vs. commercial grade CoQ significantly increased maximum plasma CoQ10 concentration (+126%, p = 0.04) and tended to increase CoQ10 area under the curve from 0 to 24 h (+160%, p = 0.07). One week of treatment with each formulation increased plasma CoQ10 but did not alter plasma glutathione or GPx activity. The enhanced bioavailability of the BT product might be due to its predominantly reduced, hydrophilic membrane-complex form. Copyright 2003 S. Karger AG, Basel

Light-dependent gene regulation by a coenzyme B12-based photoreceptor

PubMed Central

Ortiz-Guerrero, Juan Manuel; Polanco, María Carmen; Murillo, Francisco J.; Padmanabhan, S.; Elías-Arnanz, Montserrat

2011-01-01

Cobalamin (B12) typically functions as an enzyme cofactor but can also regulate gene expression via RNA-based riboswitches. B12-directed gene regulatory mechanisms via protein factors have, however, remained elusive. Recently, we reported down-regulation of a light-inducible promoter in the bacterium Myxococcus xanthus by two paralogous transcriptional repressors, of which one, CarH, but not the other, CarA, absolutely requires B12 for activity even though both have a canonical B12-binding motif. Unanswered were what underlies this striking difference, what is the specific cobalamin used, and how it acts. Here, we show that coenzyme B12 (5′-deoxyadenosylcobalamin, AdoB12), specifically dictates CarH function in the dark and on exposure to light. In the dark, AdoB12-binding to the autonomous domain containing the B12-binding motif foments repressor oligomerization, enhances operator binding, and blocks transcription. Light, at various wavelengths at which AdoB12 absorbs, dismantles active repressor oligomers by photolysing the bound AdoB12 and weakens repressor–operator binding to allow transcription. By contrast, AdoB12 alters neither CarA oligomerization nor operator binding, thus accounting for its B12-independent activity. Our findings unveil a functional facet of AdoB12 whereby it serves as the chromophore of a unique photoreceptor protein class acting in light-dependent gene regulation. The prevalence of similar proteins of unknown function in microbial genomes suggests that this distinct B12-based molecular mechanism for photoregulation may be widespread in bacteria. PMID:21502508

Hepatic Concentration and Distribution of Coenzyme A and Carnitine during a Streptococcus pneumoniae Infection in the Rat: Possible Implications on Fatty Acid Metabolism and Ketogenesis

DTIC Science & Technology

1981-01-09

subcellular distribution of carnitine and coenzyme A (CoA). Compared to fasted control ILJ rats, fasted-infected rats have a decreased ketogenic capacity...decreased ketogenic capacity that is associated with an accumulation of total hepatic carnitine and a decrease in total hepatic coenzyme A. The...cholesterol. IiA .Ii INTRODUCTION Rats infected with Streptococcus pneumoniae have a decreased hep-tic ketogenic capacity which is associated with an

[Effect of phlebodium decumanum and coenzyme Q10 on sports performance in professional volleyball players].

PubMed

García Verazaluce, Juan José; Vargas Corzo, María Del Carmen; Aguilar Cordero, María José; Ocaña Peinado, Francisco; Sarmiento Ramírez, Álvaro; Guisado Barrilao, Rafael

2014-10-03

Physical training programmes are based on provoking transitory states of fatigue in order to induce super compensation by the biological systems involved in the activity, in order to improve the athlete's medium-long term performance. The administration of nutritional supplements with antioxidant and immunomodulatory properties, such as Phlebodium decumanum and coenzyme Q10, can be a very advantageous means of achieving recovery from the inflammation and tissue damage caused by the stress of prolonged, intense exercise. An experimental, longitudinal, double- blind experiment was conducted, with three randomised groups obtained from a sample of 30 male volleyball players (aged 22-32 years) at the University of Granada, with a high level of training (17 hours a week during the 6 months preceding the study). The effects were then evaluated of a month-long physical training programme, common to all the study groups, associated with the simultaneous administration of the following nutritional supplements: Phlebodium decumanum (4 capsules of 400 mg/capsule, daily), Experimental Group 1; Phlebodium decumanum (same dose and schedule as Group 1) plus coenzyme Q10 (4 capsules of 30 mg/ capsule, daily), Experimental Group 2; a placebo substance, Control Group. The following dependent blood variables were examined to assess the effects of the intervention on the basal immune and endocrine-metabolic profile: cortisol and interleukin-6, both related to the axis of exercise-induced stress; and lactic acid and ammonium, related essentially to the anaerobic metabolism of energy. All the study groups presented favourable adaptive changes with respect to the endocrine-metabolic and immune profile, as reflected by a significant decrease in the post-test concentrations of cortisol, interleukin 6, lactic acid and ammonium, compared to the values recorded before the physical activity with/without nutritional supplement, per protocol. The groups that achieved the most favourable profile

Coenzyme Q10 and statins: biochemical and clinical implications.

PubMed

Littarru, Gian Paolo; Langsjoen, Peter

2007-06-01

Statins are drugs of known and undisputed efficacy in the treatment of hypercholesterolemia, usually well tolerated by most patients. In some cases treatment with statins produces skeletal muscle complaints, and/or mild serum CK elevation; the incidence of rhabdomyolysis is very low. As a result of the common biosynthetic pathway Coenzyme Q (ubiquinone) and dolichol levels are also affected, to a certain degree, by the treatment with these HMG-CoA reductase inhibitors. Plasma levels of CoQ10 are lowered in the course of statin treatment. This could be related to the fact that statins lower plasma LDL levels, and CoQ10 is mainly transported by LDL, but a decrease is also found in platelets and in lymphocytes of statin treated patients, therefore it could truly depend on inhibition of CoQ10 synthesis. There are also some indications that statin treatment affects muscle ubiquinone levels, although it is not yet clear to which extent this depends on some effect on mitochondrial biogenesis. Some papers indicate that CoQ10 depletion during statin therapy might be associated with subclinical cardiomyopathy and this situation is reversed upon CoQ10 treatment. We can reasonably hypothesize that in some conditions where other CoQ10 depleting situations exist treatment with statins may seriously impair plasma and possible tissue levels of coenzyme Q10. While waiting for a large scale clinical trial where patients treated with statins are also monitored for their CoQ10 status, with a group also being given CoQ10, physicians should be aware of this drug-nutrient interaction and be vigilant to the possibility that statin drugs may, in some cases, impair skeletal muscle and myocardial bioenergetics.

Social and physical environment alter cocaine conditioned place preference and dopaminergic markers in adolescent male rats.

PubMed

Zakharova, E; Miller, J; Unterwald, E; Wade, D; Izenwasser, S

2009-10-20

This study was done to determine whether social and environmental factors alter cocaine reward and proteins implicated in mediating drug reward in rats during early adolescence. On postnatal day (PND) 23, rats were housed under conditions where both social (number of rats per cage) and environmental (availability of toys) factors were manipulated. Socially isolated rats were housed alone impoverished with no toys (II) or enriched with toys (IE). Social rats were housed two rats/cage with no toys (SI2) or with toys (SE2), or three/cage with (SE3) or without (SI3) toys. On PND 43, cocaine conditioned place preference (CPP) sessions began with the post-test done on PND 47. Cocaine CPP was established in response to 5 or 10 mg/kg cocaine in II rats, and CPP was decreased with the addition of cage mates or toys. No CPP was seen to any dose in SI3 or SE3 rats. Enriched housing (SE3) increased dopamine transporter (DAT) protein in the nucleus accumbens compared to II. There also were differential effects of cocaine on tyrosine hydroxylase and DAT depending on housing, with both increased by cocaine in II but not SE3 rats. DARPP-32 was unchanged by housing or cocaine, while phospho-Thr(34)-DARPP-32 was increased by cocaine treatment across conditions. Thus, both social and environmental enrichment decrease cocaine CPP during adolescence and different housing alters proteins that regulate dopaminergic neurotransmission in a manner that may account for the observed differences in cocaine-induced reward.

MeaA, a Putative Coenzyme B12-Dependent Mutase, Provides Methylmalonyl Coenzyme A for Monensin Biosynthesis in Streptomyces cinnamonensis

PubMed Central

Zhang, Weiwen; Reynolds, Kevin A.

2001-01-01

The ratio of the major monensin analogs produced by Streptomyces cinnamonensis is dependent upon the relative levels of the biosynthetic precursors methylmalonyl-coenzyme A (CoA) (monensin A and monensin B) and ethylmalonyl-CoA (monensin A). The meaA gene of this organism was cloned and sequenced and was shown to encode a putative 74-kDa protein with significant amino acid sequence identity to methylmalonyl-CoA mutase (MCM) (40%) and isobutyryl-CoA mutase (ICM) large subunit (36%) and small subunit (52%) from the same organism. The predicted C terminus of MeaA contains structural features highly conserved in all coenzyme B12-dependent mutases. Plasmid-based expression of meaA from the ermE∗ promoter in the S. cinnamonensis C730.1 strain resulted in a decreased ratio of monensin A to monensin B, from 1:1 to 1:3. Conversely, this ratio increased to 4:1 in a meaA mutant, S. cinnamonensis WM2 (generated from the C730.1 strain by insertional inactivation of meaA by using the erythromycin resistance gene). In both of these experiments, the overall monensin titers were not significantly affected. Monensin titers, however, did decrease over 90% in an S. cinnamonensis WD2 strain (an icm meaA mutant). Monensin titers in the WD2 strain were restored to at least wild-type levels by plasmid-based expression of the meaA gene or the Amycolatopsis mediterranei mutAB genes (encoding MCM). In contrast, growth of the WD2 strain in the presence of 0.8 M valine led only to a partial restoration (<25%) of monensin titers. These results demonstrate that the meaA gene product is significantly involved in methylmalonyl-CoA production in S. cinnamonensis and that under the tested conditions the presence of both MeaA and ICM is crucial for monensin production in the WD2 strain. These results also indicate that valine degradation, implicated in providing methylmalonyl-CoA precursors for many polyketide biosynthetic processes, does not do so to a significant degree for monensin biosynthesis

Overexpression of a BAHD Acyltransferase, OsAt10, Alters Rice Cell Wall Hydroxycinnamic Acid Content and Saccharification1[C][W][OA

PubMed Central

Bartley, Laura E.; Peck, Matthew L.; Kim, Sung-Ryul; Ebert, Berit; Manisseri, Chithra; Chiniquy, Dawn M.; Sykes, Robert; Gao, Lingfang; Rautengarten, Carsten; Vega-Sánchez, Miguel E.; Benke, Peter I.; Canlas, Patrick E.; Cao, Peijian; Brewer, Susan; Lin, Fan; Smith, Whitney L.; Zhang, Xiaohan; Keasling, Jay D.; Jentoff, Rolf E.; Foster, Steven B.; Zhou, Jizhong; Ziebell, Angela; An, Gynheung; Scheller, Henrik V.; Ronald, Pamela C.

2013-01-01

Grass cell wall properties influence food, feed, and biofuel feedstock usage efficiency. The glucuronoarabinoxylan of grass cell walls is esterified with the phenylpropanoid-derived hydroxycinnamic acids ferulic acid (FA) and para-coumaric acid (p-CA). Feruloyl esters undergo oxidative coupling with neighboring phenylpropanoids on glucuronoarabinoxylan and lignin. Examination of rice (Oryza sativa) mutants in a grass-expanded and -diverged clade of BAHD acyl-coenzyme A-utilizing transferases identified four mutants with altered cell wall FA or p-CA contents. Here, we report on the effects of overexpressing one of these genes, OsAt10 (LOC_Os06g39390), in rice. An activation-tagged line, OsAT10-D1, shows a 60% reduction in matrix polysaccharide-bound FA and an approximately 300% increase in p-CA in young leaf tissue but no discernible phenotypic alterations in vegetative development, lignin content, or lignin composition. Two additional independent OsAt10 overexpression lines show similar changes in FA and p-CA content. Cell wall fractionation and liquid chromatography-mass spectrometry experiments isolate the cell wall alterations in the mutant to ester conjugates of a five-carbon sugar with p-CA and FA. These results suggest that OsAT10 is a p-coumaroyl coenzyme A transferase involved in glucuronoarabinoxylan modification. Biomass from OsAT10-D1 exhibits a 20% to 40% increase in saccharification yield depending on the assay. Thus, OsAt10 is an attractive target for improving grass cell wall quality for fuel and animal feed. PMID:23391577

Predator crypsis enhances behaviourally mediated indirect effects on plants by altering bumblebee foraging preferences

PubMed Central

Ings, Thomas C.; Chittka, Lars

2009-01-01

Predators of pollinators can influence pollination services and plant fitness via both consumptive (reducing pollinator density) and non-consumptive (altering pollinator behaviour) effects. However, a better knowledge of the mechanisms underlying behaviourally mediated indirect effects of predators is necessary to properly understand their role in community dynamics. We used the tripartite relationship between bumblebees, predatory crab spiders and flowers to ask whether behaviourally mediated effects are localized to flowers harbouring predators, or whether bees extend their avoidance to entire plant species. In a tightly controlled laboratory environment, bumblebees (Bombus terrestris) were exposed to a random mixture of equally rewarding yellow and white artificial flowers, but foraging on yellow flowers was very risky: bees had a 25 per cent chance of receiving a simulated predation attempt by ‘robotic’ crab spiders. As bees learnt to avoid ‘dangerous’ flowers, their foraging preferences changed and they began to visit fewer yellow flowers than expected by chance. Bees avoided spider-free yellow flowers as well as dangerous yellow flowers when spiders were more difficult to detect (the colour of yellow spiders was indistinguishable from that of yellow flowers). Therefore, this interaction between bee learning and predator crypsis could lead flower species harbouring cryptic predators to suffer from reduced reproductive success. PMID:19324797

Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals

PubMed Central

Sun, Jiao; Wang, Fan; Sui, Yue; She, Zhennan; Zhai, Wenjun; Wang, Chunling; Deng, Yihui

2012-01-01

In this paper work, four naked nanocrystals (size range 80–700 nm) were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q10 nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q10 increased as particle size decreased. The bioavailability of coenzyme Q10 after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC0–48 was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold. PMID:23166438

Biochemical and molecular characterization of the isocitrate dehydrogenase with dual coenzyme specificity from the obligate methylotroph Methylobacillus Flagellatus.

PubMed

Romkina, Anastasia Y; Kiriukhin, Michael Y

2017-01-01

The isocitrate dehydrogenase (MfIDH) with unique double coenzyme specificity from Methylobacillus flagellatus was purified and characterized, and its gene was cloned and overexpressed in E. coli as a fused protein. This enzyme is homodimeric,-with a subunit molecular mass of 45 kDa and a specific activity of 182 U mg -1 with NAD+ and 63 U mg -1 with NADP+. The MfIDH activity was dependent on divalent cations and Mn2+ enhanced the activity the most effectively. MfIDH exhibited a cofactor-dependent pH-activity profile. The optimum pH values were 8.5 (NAD+) and 6.0 (NADP+).The Km values for NAD+ and NADP+ were 113 μM and 184 μM respectively, while the Km values for DL-isocitrate were 9.0 μM (NAD+), 8.0 μM (NADP+). The MfIDH specificity (kcat/Km) was only 5-times higher for NAD+ than for NADP+. The purified MfIDH displayed maximal activity at 60°C. Heat-inactivation studies showed that the MfIDH was remarkably thermostable, retaining full activity at 50°C and losting ca. 50% of its activity after one hour of incubation at 75°C. The enzyme was insensitive to the presence of intermediate metabolites, with the exception of 2 mM ATP, which caused 50% inhibition of NADP+-linked activity. The indispensability of the N6 amino group of NAD(P)+ in its binding to MfIDH was demonstrated. MfIDH showed high sequence similarity with bacterial NAD(P)+-dependent type I isocitrate dehydrogenases (IDHs) rather than with eukaryotic NAD+-dependent IDHs. The unique double coenzyme specificity of MfIDH potentially resulted from the Lys340, Ile341 and Ala347 residues in the coenzyme-binding site of the enzyme. The discovery of a type I IDH with double coenzyme specificity elucidates the evolution of this subfamily IDHs and may provide fundamental information for engineering enzymes with desired properties.

Denys-Drash syndrome associated WT1 glutamine 369 mutants have altered sequence-preferences and altered responses to epigenetic modifications

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

Hashimoto, Hideharu; Zhang, Xing; Zheng, Yu

Mutations in human zinc-finger transcription factor WT1 result in abnormal development of the kidneys and genitalia and an array of pediatric problems including nephropathy, blastoma, gonadal dysgenesis and genital discordance. Several overlapping phenotypes are associated with WT1 mutations, including Wilms tumors, Denys-Drash syndrome (DDS), Frasier syndrome (FS) and WAGR syndrome (Wilms tumor, aniridia, genitourinary malformations, and mental retardation). These conditions vary in severity from individual to individual; they can be fatal in early childhood, or relatively benign into adulthood. DDS mutations cluster predominantly in zinc fingers (ZF) 2 and 3 at the C-terminus of WT1, which together with ZF4 determinemore » the sequence-specificity of DNA binding. We examined three DDS associated mutations in ZF2 of human WT1 where the normal glutamine at position 369 is replaced by arginine (Q369R), lysine (Q369K) or histidine (Q369H). These mutations alter the sequence-specificity of ZF2, we find, changing its affinity for certain bases and certain epigenetic forms of cytosine. X-ray crystallography of the DNA binding domains of normal WT1, Q369R and Q369H in complex with preferred sequences revealed the molecular interactions responsible for these affinity changes. DDS is inherited in an autosomal dominant fashion, implying a gain of function by mutant WT1 proteins. This gain, we speculate, might derive from the ability of the mutant proteins to sequester WT1 into unproductive oligomers, or to erroneously bind to variant target sequences.« less

The Effect of Coenzyme Q10 Supplementation on Circulating Levels of Novel Adipokine Adipolin/CTRP12 in Overweight and Obese Patients with Type 2 Diabetes.

PubMed

Mehrdadi, P; Kolahdouz Mohammadi, R; Alipoor, E; Eshraghian, M R; Esteghamati, A; Hosseinzadeh-Attar, M J

2017-03-01

Background: Adipolin, the novel adipokine that is proposed to be reduced in diabetes, obesity and inflammation, may improve glycemic control. It is known that coenzyme Q10 could improve insulin sensitivity. The aim of the current study was to investigate the effect of Q10 supplementation on adipolin concentration and glucose metabolism in overweight and obese diabetic patients. Material & Methods: Sixty four patients with type 2 diabetes and 25alterations were observed in FBS, fasting insulin and HOMA-IR within or between Q10 and placebo groups. Conclusions: Coenzyme Q10 reduced HbA1c considerably in overweight and obese patients with diabetes, although interestingly adipolin levels declined simultaneously. In this study, Q10 modulated glucose homeostasis, which was expected to be mediated by increasing adipolin. The similar mechanisms of action of Q10 and adipolin may justify lowering effect of Q10 on adipolin. In addition, the possible anti-adipogenic effect of Q10 might explain the significant reduction in weight and waist circumference and hence the adipolin decrease. Further studies are required to evaluate the precise role of adipolin in glucose metabolism as well as the probable effects of coenzyme Q10 on adipose tissue and adipokines. © Georg Thieme Verlag KG Stuttgart · New York.

Coenzyme Q10 deficiencies in neuromuscular diseases.

PubMed

Artuch, Rafael; Salviati, Leonardo; Jackson, Sandra; Hirano, Michio; Navas, Plácido

2009-01-01

Coenzyme Q (CoQ) is an essential component of the respiratory chain but also participates in other mitochondrial functions such as regulation of the transition pore and uncoupling proteins. Furthermore, this compound is a specific substrate for enzymes of the fatty acids beta-oxidation pathway and pyrimidine nucleotide biosynthesis. Furthermore, CoQ is an antioxidant that acts in all cellular membranes and lipoproteins. A complex of at least ten nuclear (COQ) genes encoded proteins synthesizes CoQ but its regulation is unknown. Since 1989, a growing number of patients with multisystemic mitochondrial disorders and neuromuscular disorders showing deficiencies of CoQ have been identified. CoQ deficiency caused by mutation(s) in any of the COQ genes is designated primary deficiency. Other patients have displayed other genetic defects independent on the CoQ biosynthesis pathway, and are considered to have secondary deficiencies. This review updates the clinical and molecular aspects of both types of CoQ deficiencies and proposes new approaches to understanding their molecular bases.

Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice

PubMed Central

Karanth, Santhosh; Tran, Vy My; Kuberan, Balagurunathan; Schlegel, Amnon

2013-01-01

SUMMARY Lipid disorders pose therapeutic challenges. Previously we discovered that mutation of the hepatocyte β-hydroxybutyrate transporter Slc16a6a in zebrafish causes hepatic steatosis during fasting, marked by increased hepatic triacylglycerol, but not cholesterol. This selective diversion of trapped ketogenic carbon atoms is surprising because acetate and acetoacetate can exit mitochondria and can be incorporated into both fatty acids and cholesterol in normal hepatocytes. To elucidate the mechanism of this selective diversion of carbon atoms to fatty acids, we fed wild-type and slc16a6a mutant animals high-protein ketogenic diets. We find that slc16a6a mutants have decreased activity of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr), despite increased Hmgcr protein abundance and relative incorporation of mevalonate into cholesterol. These observations suggest the presence of an endogenous Hmgcr inhibitor. We took a candidate approach to identify such inhibitors. First, we found that mutant livers accumulate multiple polyunsaturated fatty acids (PUFAs) and PUFA-CoAs, and we showed that human HMGCR is inhibited by PUFA-CoAs in vitro. Second, we injected mice with an ethyl ester of the PUFA eicosapentaenoic acid and observed an acute decrease in hepatic Hmgcr activity, without alteration in Hmgcr protein abundance. These results elucidate a mechanism for PUFA-mediated cholesterol lowering through direct inhibition of Hmgcr. PMID:24057001

Characterization of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme of human small intestine.

PubMed

Hiramine, Yasushi; Tanabe, Toshizumi

2011-06-01

Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme plays a significant role in dietary triacylglycerol (TAG) absorption in the small intestine. However, the characteristics of human intestinal DGAT enzyme have not been examined in detail. The aim of our study was to characterize the human intestinal DGAT enzyme by examining acyl-CoA specificity, temperature dependency, and selectivity for 1,2-diacylglycerol (DAG) or 1,3-DAG. We detected DGAT activity of human intestinal microsome and found that the acyl-CoA specificity and temperature dependency of intestinal DGAT coincided with those of recombinant human DGAT1. To elucidate the selectivity of human intestinal DGAT to 1,2-DAG or 1,3-DAG, we conducted acyl-coenzyme A:monoacylglycerol acyltransferase assays using 1- or 2-monoacylglycerol (MAG) as substrates. When 2-MAG was used as acyl acceptor, both 1,2-DAG and TAG were generated; however, when 1-MAG was used, 1,3-DAG was predominantly observed and little TAG was detected. These findings suggest that human small intestinal DGAT, which is mainly encoded by DGAT1, utilizes 1,2-DAG as the substrate to form TAG. This study will contribute to understand the lipid absorption profile in the small intestine.

Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis

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

Stefely, Jonathan A.; Reidenbach, Andrew G.; Ulbrich, Arne

The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. In this paper, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flipsmore » this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Finally, our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.« less

Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis

DOE PAGES

Stefely, Jonathan A.; Reidenbach, Andrew G.; Ulbrich, Arne; ...

2014-12-11

The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. In this paper, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flipsmore » this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Finally, our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.« less

Primary Coenzyme Q Deficiency in Pdss2 Mutant Mice Causes Isolated Renal Disease

PubMed Central

Haase, Volker H.; King, Rhonda; Polyak, Erzsebet; Selak, Mary; Yudkoff, Marc; Hancock, Wayne W.; Meade, Ray; Saiki, Ryoichi; Lunceford, Adam L.; Clarke, Catherine F.; Gasser, David L.

2008-01-01

Coenzyme Q (CoQ) is an essential electron carrier in the respiratory chain whose deficiency has been implicated in a wide variety of human mitochondrial disease manifestations. Its multi-step biosynthesis involves production of polyisoprenoid diphosphate in a reaction that requires the enzymes be encoded by PDSS1 and PDSS2. Homozygous mutations in either of these genes, in humans, lead to severe neuromuscular disease, with nephrotic syndrome seen in PDSS2 deficiency. We now show that a presumed autoimmune kidney disease in mice with the missense Pdss2kd/kd genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2kd/kd mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2loxP/loxP knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes. Liver-conditional B6.Alb/cre,Pdss2loxP/loxP knockout mice have no overt disease despite demonstration that their livers have undetectable CoQ9 levels, impaired respiratory capacity, and significantly altered intermediary metabolism as evidenced by transcriptional profiling and amino acid quantitation. These data suggest that disease manifestations of CoQ deficiency relate to tissue-specific respiratory capacity thresholds, with glomerular podocytes displaying the greatest sensitivity to Pdss2 impairment. PMID:18437205

Looking for a similar partner: host plants shape mating preferences of herbivorous insects by altering their contact pheromones.

PubMed

Geiselhardt, Sven; Otte, Tobias; Hilker, Monika

2012-09-01

The role of phenotypical plasticity in ecological speciation and the evolution of sexual isolation remains largely unknown. We investigated whether or not divergent host plant use in an herbivorous insect causes assortative mating by phenotypically altering traits involved in mate recognition. We found that males of the mustard leaf beetle Phaedon cochleariae preferred to mate with females that were reared on the same plant species to females provided with a different plant species, based on divergent cuticular hydrocarbon profiles that serve as contact pheromones. The cuticular hydrocarbon phenotypes of the beetles were host plant specific and changed within 2 weeks after a shift to a novel host plant species. We suggest that plant-induced phenotypic divergence in mate recognition cues may act as an early barrier to gene flow between herbivorous insect populations on alternative host species, preceding genetic divergence and thus, promoting ecological speciation. © 2012 Blackwell Publishing Ltd/CNRS.

Function of Coenzyme F420 in Aerobic Catabolism of 2,4,6-Trinitrophenol and 2,4-Dinitrophenol by Nocardioides simplex FJ2-1A

PubMed Central

Ebert, Sybille; Rieger, Paul-Gerhard; Knackmuss, Hans-Joachim

1999-01-01

2,4,6-Trinitrophenol (picric acid) and 2,4-dinitrophenol were readily biodegraded by the strain Nocardioides simplex FJ2-1A. Aerobic bacterial degradation of these π-electron-deficient aromatic compounds is initiated by hydrogenation at the aromatic ring. A two-component enzyme system was identified which catalyzes hydride transfer to picric acid and 2,4-dinitrophenol. Enzymatic activity was dependent on NADPH and coenzyme F420. The latter could be replaced by an authentic preparation of coenzyme F420 from Methanobacterium thermoautotrophicum. One of the protein components functions as a NADPH-dependent F420 reductase. A second component is a hydride transferase which transfers hydride from reduced coenzyme F420 to the aromatic system of the nitrophenols. The N-terminal sequence of the F420 reductase showed high homology with an F420-dependent NADP reductase found in archaea. In contrast, no N-terminal similarity to any known protein was found for the hydride-transferring enzyme. PMID:10217752

In vitro effects of zinc, D-aspartic acid, and coenzyme-Q10 on sperm function.

PubMed

Giacone, Filippo; Condorelli, Rosita A; Mongioì, Laura M; Bullara, Valentina; La Vignera, Sandro; Calogero, Aldo E

2017-05-01

Reactive oxygen species favor reproductive processes at low concentrations, but damage spermatozoa and decrease their fertilizing capacity at high concentrations. During infection and/or inflammation of the accessory sex glands reactive oxygen species overproduction may occur which, in turn, may negatively impact on sperm motility, sperm DNA fragmentation, and lipid peroxidation. A number of nutraceutical formulations containing antioxidant molecules have been developed to counteract the deleterious effects of the oxidative stress. A recent formulation containing zinc, D-aspartic acid, and coenzyme-Q10 is present in the pharmaceutical market. Based on these premises, the aim of the present study was to evaluate the effects of this combination on spermatozoa in vitro. The study was conducted on 24 men (32.2 ± 5.5 years): 12 normozoospermic men and 12 asthenozoospermic patients. Spermatozoa from each sample were divided into two control aliquots (aliquot A and B) and an aliquot incubated with zinc, D-aspartic acid, and coenzyme-Q10 (aliquot C). After 3 h of incubation, the following parameters were evaluated: progressive motility, number of spermatozoa with progressive motility recovered after swim-up, lipid peroxidation, and DNA fragmentation. Incubation with zinc, D-aspartic acid, and coenzyme-Q10 maintained sperm motility in normozoospermic men (37.7 ± 1.2 % vs. 35.8 ± 2.3 % at time zero) and improved it significantly in asthenozoospermic patients (26.5 ± 1.9 % vs. 18.8 ± 2.0 % at time zero) (p < 0.01). This resulted in a significantly higher (p < 0.01) number of spermatozoa with progressive motility recovered after swim-up in both normozospermic men (4.1 ± 0.9 vs. 3.3 ± 1.0 millions) and asthenozooseprmic patients (3.2 ± 0.8 vs. 1.6 ± 0.5 millions). Finally, a statistically significant lower sperm lipid peroxidation was found after incubation with zinc, D-aspartic acid, and coenzyme-Q10 (p < 0

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial.

PubMed

Dai, Yuk-Ling; Luk, Ting-Hin; Yiu, Kai-Hang; Wang, Mei; Yip, Pandora M C; Lee, Stephen W L; Li, Sheung-Wai; Tam, Sidney; Fong, Bonnie; Lau, Chu-Pak; Siu, Chung-Wah; Tse, Hung-Fat

2011-06-01

Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 μg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047). In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Biosynthesis of coenzyme Q in eukaryotes.

PubMed

Kawamukai, Makoto

2016-01-01

Coenzyme Q (CoQ) is a component of the electron transport chain that participates in aerobic cellular respiration to produce ATP. In addition, CoQ acts as an electron acceptor in several enzymatic reactions involving oxidation-reduction. Biosynthesis of CoQ has been investigated mainly in Escherichia coli and Saccharomyces cerevisiae, and the findings have been extended to various higher organisms, including plants and humans. Analyses in yeast have contributed greatly to current understanding of human diseases related to CoQ biosynthesis. To date, human genetic disorders related to mutations in eight COQ biosynthetic genes have been reported. In addition, the crystal structures of a number of proteins involved in CoQ synthesis have been solved, including those of IspB, UbiA, UbiD, UbiX, UbiI, Alr8543 (Coq4 homolog), Coq5, ADCK3, and COQ9. Over the last decade, knowledge of CoQ biosynthesis has accumulated, and striking advances in related human genetic disorders and the crystal structure of proteins required for CoQ synthesis have been made. This review focuses on the biosynthesis of CoQ in eukaryotes, with some comparisons to the process in prokaryotes.

Novel HPLC-UV Method for Simultaneous Determination of Fat-soluble Vitamins and Coenzyme Q10 in Medicines and Supplements.

PubMed

Temova-Rakuša, Žane; Srečnik, Eva; Roškar, Robert

2017-09-01

A precise, accurate and rapid HPLC-UV method for simultaneous determination of fat-soluble vitamins (vitamin D3, E-acetate, K1, β-carotene, A-palmitate) and coenzyme Q10 was developed and validated according to ICH guidelines. Optimal chromatographic separation of the analytes in minimal analysis time (8 min) was achieved on a Luna C18 150 × 4.6 mm column using a mixture of acetonitrile, tetrahydrofuran and water (50:45:5, v/v/v). The described reversed phase HPLC method is the first published for quantification of these five fat-soluble vitamins and coenzyme Q10 within a single chromatographic run. The method was further applied for quantification of the analytes in selected liquid and solid dosage forms, registered as nutritional supplements and prescription medicines, which confirmed its suitability for routine analysis.

Attenuating GABAA Receptor Signaling in Dopamine Neurons Selectively Enhances Reward Learning and Alters Risk Preference in Mice

PubMed Central

Parker, Jones G.; Wanat, Matthew J.; Soden, Marta E.; Ahmad, Kinza; Zweifel, Larry S.; Bamford, Nigel S.; Palmiter, Richard D.

2011-01-01

Phasic dopamine transmission encodes the value of reward-predictive stimuli and influences both learning and decision-making. Altered dopamine signaling is associated with psychiatric conditions characterized by risky choices such as pathological gambling. These observations highlight the importance of understanding how dopamine neuron activity is modulated. While excitatory drive onto dopamine neurons is critical for generating phasic dopamine responses, emerging evidence suggests that inhibitory signaling also modulates these responses. To address the functional importance of inhibitory signaling in dopamine neurons, we generated mice lacking the β3 subunit of the GABAA receptor specifically in dopamine neurons (β3-KO mice) and examined their behavior in tasks that assessed appetitive learning, aversive learning, and risk preference. Dopamine neurons in midbrain slices from β3-KO mice exhibited attenuated GABA-evoked inhibitory post-synaptic currents. Furthermore, electrical stimulation of excitatory afferents to dopamine neurons elicited more dopamine release in the nucleus accumbens of β3-KO mice as measured by fast-scan cyclic voltammetry. β3-KO mice were more active than controls when given morphine, which correlated with potential compensatory upregulation of GABAergic tone onto dopamine neurons. β3-KO mice learned faster in two food-reinforced learning paradigms, but extinguished their learned behavior normally. Enhanced learning was specific for appetitive tasks, as aversive learning was unaffected in β3-KO mice. Finally, we found that β3-KO mice had enhanced risk preference in a probabilistic selection task that required mice to choose between a small certain reward and a larger uncertain reward. Collectively, these findings identify a selective role for GABAA signaling in dopamine neurons in appetitive learning and decision-making. PMID:22114279

Cuprizone Intoxication Induces Cell Intrinsic Alterations in Oligodendrocyte Metabolism Independent of Copper Chelation.

PubMed

Taraboletti, Alexandra; Walker, Tia; Avila, Robin; Huang, He; Caporoso, Joel; Manandhar, Erendra; Leeper, Thomas C; Modarelli, David A; Medicetty, Satish; Shriver, Leah P

2017-03-14

Cuprizone intoxication is a common animal model used to test myelin regenerative therapies for the treatment of diseases such as multiple sclerosis. Mice fed this copper chelator develop reversible, region-specific oligodendrocyte loss and demyelination. While the cellular changes influencing the demyelinating process have been explored in this model, there is no consensus about the biochemical mechanisms of toxicity in oligodendrocytes and about whether this damage arises from the chelation of copper in vivo. Here we have identified an oligodendroglial cell line that displays sensitivity to cuprizone toxicity and performed global metabolomic profiling to determine biochemical pathways altered by this treatment. We link these changes with alterations in brain metabolism in mice fed cuprizone for 2 and 6 weeks. We find that cuprizone induces widespread changes in one-carbon and amino acid metabolism as well as alterations in small molecules that are important for energy generation. We used mass spectrometry to examine chemical interactions that are important for copper chelation and toxicity. Our results indicate that cuprizone induces global perturbations in cellular metabolism that may be independent of its copper chelating ability and potentially related to its interactions with pyridoxal 5'-phosphate, a coenzyme essential for amino acid metabolism.

Critical assessment of various techniques for the extraction of carotenoids and co-enzyme Q10 from the Thraustochytrid strain ONC-T18.

PubMed

Armenta, Roberto E; Burja, Adam; Radianingtyas, Helia; Barrow, Colin J

2006-12-27

A variety of techniques for extracting carotenoids from the marine Thraustochytrium sp. ONC-T18 was compared. Specifically, the organic solvents acetone, ethyl acetate, and petroleum ether were tested, along with direct and indirect ultrasonic assisted extraction (probe vs bath) methods. Techniques that used petroleum ether/acetone/water (15:75:10, v/v/v) with 3 h of agitation, or 5 min in an ultrasonic bath, produced the highest extraction yields of total carotenoids (29-30.5 microg g-1). Concentrations up to 11.5 microg g-1 of canthaxanthin and 17.5 microg g-1 of beta;-carotene were detected in extracts stored for 6 weeks. Astaxanthin and echinenone were also detected as minor compounds. Extracts with and without antioxidants showed similar carotenoid concentration profiles. However, total carotenoid concentrations were approximately 8% higher when antioxidants were used. Finally, an easy-to-perform and inexpensive method to detect co-enzymes in ONC-T18 was also developed using silica gel TLC plates. Five percent methanol in toluene as a mobile phase consistently eluted co-enzyme Q10 standards and could separate the co-enzyme fractions present in ONC-T18.

Individual lifetime pollen and nectar foraging preferences in bumble bees

NASA Astrophysics Data System (ADS)

Hagbery, Jessica; Nieh, James C.

2012-10-01

Foraging specialization plays an important role in the ability of social insects to efficiently allocate labor. However, relatively little is known about the degree to which individual bumble bees specialize on collecting nectar or pollen, when such preferences manifest, and if individuals can alter their foraging preferences in response to changes in the colony workforce. Using Bombus impatiens, we monitored all foraging visits made by every bee in multiple colonies and showed that individual foragers exhibit consistent lifetime foraging preferences. Based upon the distribution of foraging preferences, we defined three forager types (pollen specialists, nectar specialists, and generalists). In unmanipulated colonies, 16-36 % of individuals specialized (≥90 % of visits) on nectar or pollen only. On its first day of foraging, an individual's foraging choices (nectar only, pollen only, or nectar and pollen) significantly predicted its lifetime foraging preferences. Foragers that only collected pollen on their first day of foraging made 1.61- to 1.67-fold more lifetime pollen foraging visits (as a proportion of total trips) than foragers that only collected nectar on their first foraging day. Foragers were significantly larger than bees that stayed only in the nest. We also determined the effect of removing pollen specialists at early (brood present) or later (brood absent) stages in colony life. These results suggest that generalists can alter their foraging preferences in response to the loss of a small subset of foragers. Thus, bumble bees exhibit individual lifetime foraging preferences that are established early in life, but generalists may be able to adapt to colony needs.

The Value of Coenzyme Q10 Determination in Mitochondrial Patients

PubMed Central

Yubero, Delia; Allen, George; Artuch, Rafael; Montero, Raquel

2017-01-01

Coenzyme Q10 (CoQ) is a lipid that is ubiquitously synthesized in tissues and has a key role in mitochondrial oxidative phosphorylation. Its biochemical determination provides insight into the CoQ status of tissues and may detect CoQ deficiency that can result from either an inherited primary deficiency of CoQ metabolism or may be secondary to different genetic and environmental conditions. Rapid identification of CoQ deficiency can also allow potentially beneficial treatment to be initiated as early as possible. CoQ may be measured in different specimens, including plasma, blood mononuclear cells, platelets, urine, muscle, and cultured skin fibroblasts. Blood and urinary CoQ also have good utility for CoQ treatment monitoring. PMID:28338638

The use of coenzyme Q0 as a template in the development of a molecularly imprinted polymer for the selective recognition of coenzyme Q10.

PubMed

Contin, Mario; Flor, Sabrina; Martinefski, Manuela; Lucangioli, Silvia; Tripodi, Valeria

2014-01-07

In this work, a novel molecularly imprinted polymer (MIP) for use as a solid phase extraction sorbent was developed for the determination of coenzyme Q10 (CoQ10) in liver extract. CoQ10 is an essential cofactor in mitochondrial oxidative phosphorylation and a powerful antioxidant agent found in low concentrations in biological samples. This fact and its high hydrophobicity make the analysis of CoQ10 technically challenging. Accordingly, a MIP was synthesised using coenzyme Q0 as the template, methacrylic acid as the functional monomer, acetonitrile as the porogen, ethylene glycol dimethacrylate as the crosslinker and benzoyl peroxide as the initiator. Various parameters affecting the polymer preparation and extraction efficiency were evaluated. Morphological characterisation of the MIP and its proper comparison with C18 as a sorbent in solid phase extraction were performed. The optimal conditions for the molecularly imprinted solid phase extraction (MISPE) consisted of 400 μL of sample mixed with 30 mg of MIP and 600 μL of water to reach the optimum solution loading. The loading was followed by a washing step consisting of 1 mL of a 1-propanol solution (1-propanol:water, 30:70,v/v) and elution with 1 mL of 1-propanol. After clean-up, the CoQ10 in the samples was analysed by high performance liquid chromatography. The extraction recoveries were higher than 73.7% with good precision (3.6-8.3%). The limits of detection and quantification were 2.4 and 7.5 μg g(-1), respectively, and a linear range between 7.5 and 150 μg g(-1) of tissue was achieved. The new MISPE procedure provided a successful clean-up for the determination of CoQ10 in a complex matrix. Copyright © 2013 Elsevier B.V. All rights reserved.

Regulation of 4CL, encoding 4-coumarate: coenzyme A ligase, expression in kenaf under diverse stress conditions

USDA-ARS?s Scientific Manuscript database

We cloned the full length 4CL ortholog encoding 4-coumarate: coenzymeA ligase from kenaf (Hibiscus cannabiuns) using degenerate primers and RACE (rapid amplification of cDNA ends) systems. The 4CL is a key regulatory enzyme of the phenylpropanoid pathway that regulates the activation of cinnamic ac...

Does the contraceptive pill alter mate choice in humans?

PubMed

Alvergne, Alexandra; Lummaa, Virpi

2010-03-01

Female and male mate choice preferences in humans both vary according to the menstrual cycle. Women prefer more masculine, symmetrical and genetically unrelated men during ovulation compared with other phases of their cycle, and recent evidence suggests that men prefer ovulating women to others. Such monthly shifts in mate preference have been suggested to bring evolutionary benefits in terms of reproductive success. New evidence is now emerging that taking the oral contraceptive pill might significantly alter both female and male mate choice by removing the mid-cycle change in preferences. Here, we review support for such conclusions and speculate on the consequences of pill-induced choice of otherwise less-preferred partners for relationship satisfaction, durability and, ultimately, reproductive outcomes.

Natural selection on thermal preference, critical thermal maxima and locomotor performance.

PubMed

Gilbert, Anthony L; Miles, Donald B

2017-08-16

Climate change is resulting in a radical transformation of the thermal quality of habitats across the globe. Whereas species have altered their distributions to cope with changing environments, the evidence for adaptation in response to rising temperatures is limited. However, to determine the potential of adaptation in response to thermal variation, we need estimates of the magnitude and direction of natural selection on traits that are assumed to increase persistence in warmer environments. Most inferences regarding physiological adaptation are based on interspecific analyses, and those of selection on thermal traits are scarce. Here, we estimate natural selection on major thermal traits used to assess the vulnerability of ectothermic organisms to altered thermal niches. We detected significant directional selection favouring lizards with higher thermal preferences and faster sprint performance at their optimal temperature. Our analyses also revealed correlational selection between thermal preference and critical thermal maxima, where individuals that preferred warmer body temperatures with cooler critical thermal maxima were favoured by selection. Recent published estimates of heritability for thermal traits suggest that, in concert with the strong selective pressures we demonstrate here, evolutionary adaptation may promote long-term persistence of ectotherms in altered thermal environments. © 2017 The Author(s).

Cognitive Fatigue Destabilizes Economic Decision Making Preferences and Strategies.

PubMed

Mullette-Gillman, O'Dhaniel A; Leong, Ruth L F; Kurnianingsih, Yoanna A

2015-01-01

It is common for individuals to engage in taxing cognitive activity for prolonged periods of time, resulting in cognitive fatigue that has the potential to produce significant effects in behaviour and decision making. We sought to examine whether cognitive fatigue modulates economic decision making. We employed a between-subject manipulation design, inducing fatigue through 60 to 90 minutes of taxing cognitive engagement against a control group that watched relaxing videos for a matched period of time. Both before and after the manipulation, participants engaged in two economic decision making tasks (one for gains and one for losses). The analyses focused on two areas of economic decision making--preferences and choice strategies. Uncertainty preferences (risk and ambiguity) were quantified as premium values, defined as the degree and direction in which participants alter the valuation of the gamble in comparison to the certain option. The strategies that each participant engaged in were quantified through a choice strategy metric, which contrasts the degree to which choice behaviour relies upon available satisficing or maximizing information. We separately examined these metrics for alterations within both the gains and losses domains, through the two choice tasks. The fatigue manipulation resulted in significantly greater levels of reported subjective fatigue, with correspondingly higher levels of reported effort during the cognitively taxing activity. Cognitive fatigue did not alter uncertainty preferences (risk or ambiguity) or informational strategies, in either the gains or losses domains. Rather, cognitive fatigue resulted in greater test-retest variability across most of our economic measures. These results indicate that cognitive fatigue destabilizes economic decision making, resulting in inconsistent preferences and informational strategies that may significantly reduce decision quality.

Cognitive Fatigue Destabilizes Economic Decision Making Preferences and Strategies

PubMed Central

Mullette-Gillman, O’Dhaniel A.; Leong, Ruth L. F.; Kurnianingsih, Yoanna A.

2015-01-01

Objective It is common for individuals to engage in taxing cognitive activity for prolonged periods of time, resulting in cognitive fatigue that has the potential to produce significant effects in behaviour and decision making. We sought to examine whether cognitive fatigue modulates economic decision making. Methods We employed a between-subject manipulation design, inducing fatigue through 60 to 90 minutes of taxing cognitive engagement against a control group that watched relaxing videos for a matched period of time. Both before and after the manipulation, participants engaged in two economic decision making tasks (one for gains and one for losses). The analyses focused on two areas of economic decision making—preferences and choice strategies. Uncertainty preferences (risk and ambiguity) were quantified as premium values, defined as the degree and direction in which participants alter the valuation of the gamble in comparison to the certain option. The strategies that each participant engaged in were quantified through a choice strategy metric, which contrasts the degree to which choice behaviour relies upon available satisficing or maximizing information. We separately examined these metrics for alterations within both the gains and losses domains, through the two choice tasks. Results The fatigue manipulation resulted in significantly greater levels of reported subjective fatigue, with correspondingly higher levels of reported effort during the cognitively taxing activity. Cognitive fatigue did not alter uncertainty preferences (risk or ambiguity) or informational strategies, in either the gains or losses domains. Rather, cognitive fatigue resulted in greater test-retest variability across most of our economic measures. These results indicate that cognitive fatigue destabilizes economic decision making, resulting in inconsistent preferences and informational strategies that may significantly reduce decision quality. PMID:26230404

Cloning, Baeyer-Villiger Biooxidations, and Structures of the Camphor Pathway 2-Oxo-Δ3-4,5,5-Trimethylcyclopentenylacetyl-Coenzyme A Monooxygenase of Pseudomonas putida ATCC 17453

PubMed Central

Leisch, Hannes; Shi, Rong; Grosse, Stephan; Morley, Krista; Bergeron, Hélène; Cygler, Miroslaw; Iwaki, Hiroaki; Hasegawa, Yoshie

2012-01-01

A dimeric Baeyer-Villiger monooxygenase (BVMO) catalyzing the lactonization of 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-coenzyme A (CoA), a key intermediate in the metabolism of camphor by Pseudomonas putida ATCC 17453, had been initially characterized in 1983 by Ougham and coworkers (H. J. Ougham, D. G. Taylor, and P. W. Trudgill, J. Bacteriol. 153:140–152, 1983). Here we cloned and overexpressed the 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-CoA monooxygenase (OTEMO) in Escherichia coli and determined its three-dimensional structure with bound flavin adenine dinucleotide (FAD) at a 1.95-Å resolution as well as with bound FAD and NADP+ at a 2.0-Å resolution. OTEMO represents the first homodimeric type 1 BVMO structure bound to FAD/NADP+. A comparison of several crystal forms of OTEMO bound to FAD and NADP+ revealed a conformational plasticity of several loop regions, some of which have been implicated in contributing to the substrate specificity profile of structurally related BVMOs. Substrate specificity studies confirmed that the 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetic acid coenzyme A ester is preferred over the free acid. However, the catalytic efficiency (kcat/Km) favors 2-n-hexyl cyclopentanone (4.3 × 105 M−1 s−1) as a substrate, although its affinity (Km = 32 μM) was lower than that of the CoA-activated substrate (Km = 18 μM). In whole-cell biotransformation experiments, OTEMO showed a unique enantiocomplementarity to the action of the prototypical cyclohexanone monooxygenase (CHMO) and appeared to be particularly useful for the oxidation of 4-substituted cyclohexanones. Overall, this work extends our understanding of the molecular structure and mechanistic complexity of the type 1 family of BVMOs and expands the catalytic repertoire of one of its original members. PMID:22267661

Enzymic Dehalogenation of 4-Chlorobenzoyl Coenzyme A in Acinetobacter sp. Strain 4-CB1

PubMed Central

Copley, Shelley D.; Crooks, Gwen P.

1992-01-01

4-Chlorobenzoate degradation in cell extracts of Acinetobacter sp. strain 4-CB1 occurs by initial synthesis of 4-chlorobenzoyl coenzyme A (4-chlorobenzoyl CoA) from 4-chlorobenzoate, CoA, and ATP. 4-Chlorobenzoyl CoA is dehalogenated to 4-hydroxybenzoyl CoA. Following the dehalogenation reaction, 4-hydroxybenzoyl CoA is hydrolyzed to 4-hydroxybenzoate and CoA. Possible roles for the CoA moiety in the dehalogenation reaction are discussed. PMID:16348702

A Novel, Ecologically Relevant, Highly Preferred, and Non-invasive Means of Oral Substance Administration for Rodents

PubMed Central

Sobolewski, Marissa; Allen, Joshua L.; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A.

2017-01-01

Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of

A novel, ecologically relevant, highly preferred, and non-invasive means of oral substance administration for rodents.

PubMed

Sobolewski, Marissa; Allen, Joshua L; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A

2016-01-01

Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of

Influence of branding on preference-based decision making.

PubMed

Philiastides, Marios G; Ratcliff, Roger

2013-07-01

Branding has become one of the most important determinants of consumer choices. Intriguingly, the psychological mechanisms of how branding influences decision making remain elusive. In the research reported here, we used a preference-based decision-making task and computational modeling to identify which internal components of processing are affected by branding. We found that a process of noisy temporal integration of subjective value information can model preference-based choices reliably and that branding biases are explained by changes in the rate of the integration process itself. This result suggests that branding information and subjective preference are integrated into a single source of evidence in the decision-making process, thereby altering choice behavior.

Effects of coenzyme Q10 supplementation on activities of selected antioxidative enzymes and lipid peroxidation in hypertensive patients treated with indapamide. A pilot study.

PubMed

Kędziora-Kornatowska, Kornelia; Czuczejko, Jolanta; Motyl, Jadwiga; Szewczyk-Golec, Karolina; Kozakiewicz, Mariusz; Pawluk, Hanna; Kędziora, Józef; Błaszczak, Robert; Banach, Maciej; Rysz, Jacek

2010-08-30

An increase in oxidative stress is strongly documented in hypertensive patients. In blood vessels, oxidative stress increases the production of superoxide anion (O(2) (•-)) that reacts with nitric oxide (NO) and impairs the ability of endothelium to relax. Many reports indicate a beneficial effect of coenzyme Q10 (CoQ) in hypertension. Coenzyme Q10 therapy may lower O(2) (•-) and thus decrease the complications associated with hypertension. The aim of our study was to evaluate the effects of CoQ supplementation on antioxidative enzyme activities and lipid peroxidation in elderly hypertensive patients. We determined the activities of superoxide dismutase (SOD-1) and glutathione peroxidase (GSH-Px) and the concentration of malondialdehyde (MDA) in erythrocytes of 27 elderly (mean age 72.5 ±6.1 year) hypertensive patients treated with indapamide at baseline and after 12 weeks of CoQ supplementation (60 mg twice a day) in comparison with 30 healthy elderly volunteers (mean age 76.8 ±8.5 year). Decrease of SOD-1 (p < 0.001) and insignificant reduction of GSH-Px activities and increase of MDA (p < 0.001) level were observed in hypertensive patients in comparison to healthy volunteers before supplementation. Coenzyme Q10 administration resulted in a significant increase only in SOD-1 activity (p < 0.001). The present study indicates that CoQ improves the most important component of the antioxidant defence system - SOD-1, which is responsible for O(2) (•-) scavenging. Coenzyme Q10 may be used as an additional therapeutic agent for prophylaxis and treatment of hypertension in elderly patients.

Predator-induced changes of female mating preferences: innate and experiential effects

PubMed Central

2011-01-01

Background In many species males face a higher predation risk than females because males display elaborate traits that evolved under sexual selection, which may attract not only females but also predators. Females are, therefore, predicted to avoid such conspicuous males under predation risk. The present study was designed to investigate predator-induced changes of female mating preferences in Atlantic mollies (Poecilia mexicana). Males of this species show a pronounced polymorphism in body size and coloration, and females prefer large, colorful males in the absence of predators. Results In dichotomous choice tests predator-naïve (lab-reared) females altered their initial preference for larger males in the presence of the cichlid Cichlasoma salvini, a natural predator of P. mexicana, and preferred small males instead. This effect was considerably weaker when females were confronted visually with the non-piscivorous cichlid Vieja bifasciata or the introduced non-piscivorous Nile tilapia (Oreochromis niloticus). In contrast, predator experienced (wild-caught) females did not respond to the same extent to the presence of a predator, most likely due to a learned ability to evaluate their predators' motivation to prey. Conclusions Our study highlights that (a) predatory fish can have a profound influence on the expression of mating preferences of their prey (thus potentially affecting the strength of sexual selection), and females may alter their mate choice behavior strategically to reduce their own exposure to predators. (b) Prey species can evolve visual predator recognition mechanisms and alter their mate choice only when a natural predator is present. (c) Finally, experiential effects can play an important role, and prey species may learn to evaluate the motivational state of their predators. PMID:21726456

Bioenergetic Effects of Mitochondrial-Targeted Coenzyme Q Analogs in Endothelial Cells

PubMed Central

Fink, Brian D.; Herlein, Judith A.; Yorek, Mark A.; Fenner, Amanda M.; Kerns, Robert J.

2012-01-01

Mitochondrial-targeted analogs of coenzyme Q (CoQ) are under development to reduce oxidative damage induced by a variety of disease states. However, there is a need to understand the bioenergetic effects of these agents and whether or not these effects are related to redox properties, including their known pro-oxidant effects. We examined the bioenergetic effects of two mitochondrial-targeted CoQ analogs in their quinol forms, mitoquinol (MitoQ) and plastoquinonyl-decyl-triphenylphosphonium (SkQ1), in bovine aortic endothelial cells. We used an extracellular oxygen and proton flux analyzer to assess mitochondrial action at the intact-cell level. Both agents, in dose-dependent fashion, reduced the oxygen consumption rate (OCR) directed at ATP turnover (OCRATP) (IC50 values of 189 ± 13 nM for MitoQ and 181 ± 7 for SKQ1; difference not significant) while not affecting or mildly increasing basal oxygen consumption. Both compounds increased extracellular acidification in the basal state consistent with enhanced glycolysis. Both compounds enhanced mitochondrial superoxide production assessed by using mitochondrial-targeted dihydroethidium, and both increased H2O2 production from mitochondria of cells treated before isolation of the organelles. The manganese superoxide dismutase mimetic manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin did not alter or actually enhanced the actions of the targeted CoQ analogs to reduce OCRATP. In contrast, N-acetylcysteine mitigated this effect of MitoQ and SkQ1. In summary, our data demonstrate the important bioenergetic effects of targeted CoQ analogs. Moreover, these effects are mediated, at least in part, through superoxide production but depend on conversion to H2O2. These bioenergetic and redox actions need to be considered as these compounds are developed for therapeutic purposes. PMID:22661629

Bioenergetic effects of mitochondrial-targeted coenzyme Q analogs in endothelial cells.

PubMed

Fink, Brian D; Herlein, Judith A; Yorek, Mark A; Fenner, Amanda M; Kerns, Robert J; Sivitz, William I

2012-09-01

Mitochondrial-targeted analogs of coenzyme Q (CoQ) are under development to reduce oxidative damage induced by a variety of disease states. However, there is a need to understand the bioenergetic effects of these agents and whether or not these effects are related to redox properties, including their known pro-oxidant effects. We examined the bioenergetic effects of two mitochondrial-targeted CoQ analogs in their quinol forms, mitoquinol (MitoQ) and plastoquinonyl-decyl-triphenylphosphonium (SkQ1), in bovine aortic endothelial cells. We used an extracellular oxygen and proton flux analyzer to assess mitochondrial action at the intact-cell level. Both agents, in dose-dependent fashion, reduced the oxygen consumption rate (OCR) directed at ATP turnover (OCR(ATP)) (IC₅₀ values of 189 ± 13 nM for MitoQ and 181 ± 7 for SKQ1; difference not significant) while not affecting or mildly increasing basal oxygen consumption. Both compounds increased extracellular acidification in the basal state consistent with enhanced glycolysis. Both compounds enhanced mitochondrial superoxide production assessed by using mitochondrial-targeted dihydroethidium, and both increased H₂O₂ production from mitochondria of cells treated before isolation of the organelles. The manganese superoxide dismutase mimetic manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin did not alter or actually enhanced the actions of the targeted CoQ analogs to reduce OCR(ATP). In contrast, N-acetylcysteine mitigated this effect of MitoQ and SkQ1. In summary, our data demonstrate the important bioenergetic effects of targeted CoQ analogs. Moreover, these effects are mediated, at least in part, through superoxide production but depend on conversion to H₂O₂. These bioenergetic and redox actions need to be considered as these compounds are developed for therapeutic purposes.

Coenzyme Q(10) , endothelial function, and cardiovascular disease.

PubMed

Littarru, Gian Paolo; Tiano, Luca; Belardinelli, Romualdo; Watts, Gerald F

2011-01-01

Since the time a precise role of coenzyme Q(10) (CoQ(10) ) in myocardial bioenergetics was established, the involvement of CoQ in the pathophysiology of heart failure was hypothesized. This provided the rationale for numerous clinical trials of CoQ(10) as adjunctive treatment for heart failure. A mild hypotensive effect of CoQ was reported in the early years of clinical use of this compound. We review early human and animal studies on the vascular effects of CoQ. We then focus on endothelial dysfunction in type 2 diabetes and the possible impact on this condition of antioxidants and nutritional supplements, and in particular the therapeutic effects of CoQ. The effect of CoQ(10) on endothelial dysfunction in ischemic heart disease is also reviewed together with recent data highlighting that treatment with CoQ(10) increases extracellular SOD activity. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

Pyridine Nucleotide Complexes with Bacillus anthracis Coenzyme A-Disulfide Reductase: A Structural Analysis of Dual NAD(P)H Specificity

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

Wallen,J.; Paige, C.; Mallett, T.

2008-01-01

We have recently reported that CoASH is the major low-molecular weight thiol in Bacillus anthracis, and we have now characterized the kinetic and redox properties of the B. anthracis coenzyme A-disulfide reductase (CoADR, BACoADR) and determined the crystal structure at 2.30 Angstroms resolution. While the Staphylococcus aureus and Borrelia burgdorferi CoADRs exhibit strong preferences for NADPH and NADH, respectively, B. anthracis CoADR can use either pyridine nucleotide equally well. Sequence elements within the respective NAD(P)H-binding motifs correctly reflect the preferences for S. aureus and Bo. burgdorferi CoADRs, but leave questions as to how BACoADR can interact with both pyridine nucleotides.more » The structures of the NADH and NADPH complexes at ca. 2.3 Angstroms resolution reveal that a loop consisting of residues Glu180-Thr187 becomes ordered and changes conformation on NAD(P)H binding. NADH and NADPH interact with nearly identical conformations of this loop; the latter interaction, however, involves a novel binding mode in which the 2'-phosphate of NADPH points out toward solvent. In addition, the NAD(P)H-reduced BACoADR structures provide the first view of the reduced form (Cys42-SH/CoASH) of the Cys42-SSCoA redox center. The Cys42-SH side chain adopts a new conformation in which the conserved Tyr367'-OH and Tyr425'-OH interact with the nascent thiol(ate) on the flavin si-face. Kinetic data with Y367F, Y425F, and Y367, 425F BACoADR mutants indicate that Tyr425' is the primary proton donor in catalysis, with Tyr367' functioning as a cryptic alternate donor in the absence of Tyr425'.« less

Coenzyme Q as an antiadipogenic factor.

PubMed

Bour, Sandy; Carmona, Maria-Carmen; Galinier, Anne; Caspar-Bauguil, Sylvie; Van Gaal, Luc; Staels, Bart; Pénicaud, Luc; Casteilla, Louis

2011-02-01

Coenzyme Q (CoQ) is not only the single antioxidant synthesized in humans but also an obligatory element of mitochondrial functions. We have previously reported CoQ deficiency in white adipose tissue of ob/ob mice. We sought to determine (i) whether this deficit exists in all species and its relevance in human obesity and (ii) to what extent CoQ could be involved in adipocyte differentiation. Here we identified in rodents as well as in humans a specific very strong nonlinear negative correlation between CoQ content in subcutaneous adipose tissue and obesity indexes. This striking correlation reveals a threshold value similar in both species. This relative deficit in CoQ content in adipose tissue rapidly took place during the time course of high-fat-diet-induced obesity in mice. Adipocyte differentiation was assessed in vitro using the preadipocyte 3T3-F442A cell line. When CoQ synthesis was inhibited by a pharmacological approach using chlorobenzoic acid, this strongly triggered adipose differentiation. In contrast, adipogenesis was strongly inhibited when a long-term increase in CoQ content was obtained by overexpressing human 4-hydroxy benzoate acid polyprenyltransferase gene. Altogether, these data suggest that a strict level of CoQ remains essential for adipocyte differentiation, and its impairment is associated with obesity.

Microbes and masculinity: Does exposure to pathogenic cues alter women's preferences for male facial masculinity and beardedness?

PubMed

McIntosh, Toneya L; Lee, Anthony J; Sidari, Morgan J; Stower, Rebecca E; Sherlock, James M; Dixson, Barnaby J W

2017-01-01

Women's preferences for men's androgen dependent secondary sexual traits are proposed to be phenotypically plastic in response to exposure to pathogens and pathogen disgust. While previous studies report that masculinity in facial shape is more attractive to women who have recently been exposed to pathogenic cues and who are high in self-reported pathogen disgust, facial hair may reduce male attractiveness under conditions of high pathogens as beards are a possible breeding ground for disease carrying ectoparasites. In the present study, we test whether women's preferences for beardedness and facial masculinity vary due to exposure to different pathogenic cues. Participants (N = 688, mean age + 1SD = 31.94 years, SD = 6.69, range = 18-67) rated the attractiveness of facial composite stimuli of men when they were clean-shaven or fully bearded. These stimuli were also manipulated in order to vary sexual dimorphism by ±50%. Ratings were conducted before and after exposure to one of four experimental treatments in which participants were primed to either high pathogens (e.g. infected cuts), ectoparasites (e.g. body lice), a mixture of pathogens and ectoparasites, or a control condition (e.g. innocuous liquids). Participants then completed the three-domain disgust scale measuring attitudes to moral, sexual and pathogen disgust. We predicted that women would prefer facial masculinity following exposure to pathogenic cues, but would show reduced preferences for facial hair following exposure to ectoparasites. Women preferred full beards over clean-shaven faces and masculinised over feminised faces. However, none of the experimental treatments influenced the direction of preferences for facial masculinity or beardedness. We also found no association between women's self-reported pathogen disgust and their preferences for facial masculinity. However, there was a weak positive association between moral disgust scores and preferences for facial masculinity, which might

Design, optimization and characterization of coenzyme Q10- and D-panthenyl triacetate-loaded liposomes

PubMed Central

Çelik, Burak; Sağıroğlu, Ali Asram; Özdemir, Samet

2017-01-01

Coenzyme Q10 (CoQ10) is a lipid-soluble molecule found naturally in many eukaryotic cells and is essential for electron transport chain and energy generation in mitochondria. D-Panthenyl triacetate (PTA) is an oil-soluble derivative of D-panthenol, which is essential for coenzyme A synthesis in the epithelium. Liposomal formulations that encapsulate both ingredients were prepared and optimized by applying response surface methodology for increased stability and skin penetration. The optimum formulation comprised 4.17 mg CoQ10, 4.22 mg PTA and 13.95 mg cholesterol per 100 mg of soy phosphatidylcholine. The encapsulation efficiency of the optimized formulation for CoQ10 and PTA was found to be 90.89%±3.61% and 87.84%±4.61%, respectively. Narrow size distribution was achieved with an average size of 161.6±3.6 nm, while a spherical and uniform shape was confirmed via scanning electron microscopy and transmission electron microscopy images. Cumulative release of 90.93% for PTA and 24.41% for CoQ10 was achieved after 24 hours of in vitro release study in sink conditions. Physical stability tests indicated that the optimized liposomes were suitable for storage at 4°C for at least 60 days. The results suggest that the optimized liposomal formulation would be a promising delivery system for both ingredients in various topical applications. PMID:28744121

Cross-Fostering of Male Mice Subtly Affects Female Olfactory Preferences

PubMed Central

Liu, Ying-Juan; Zhang, Yao-Hua; Li, Lai-Fu; Du, Rui-Qing; Zhang, Jin-Hua; Zhang, Jian-Xu

2016-01-01

The maternal environment has been shown to influence female olfactory preferences through early chemosensory experience. However, little is known about the influence of the maternal environment on chemosignals. In this study, we used two inbred mouse strains, C57BL/6 (C57) and BALB/c (BALB), and explored whether adoption could alter male chemosignals and thus influence female olfactory preferences. In Experiment 1, C57 pups were placed with BALB dams. Adult BALB females then served as the subjects in binary choice tests between paired male urine odours (BALB vs. C57, BALB vs. adopted C57 and C57 vs. adopted C57). In Experiment 2, BALB pups were placed with C57 dams, and C57 females served as the subjects in binary choice tests between paired male urine odours (C57 vs. BALB, C57 vs. adopted BALB, and BALB vs. adopted BALB). In both experiments, we found that females preferred the urine of males from different genetic backgrounds, suggesting that female olfactory preferences may be driven by genetic compatibility. Cross-fostering had subtle effects on female olfactory preferences. Although the females showed no preference between the urine odours of adopted and non-adopted males of the other strain, the BALB females preferred the urine odour of BALB males to that of adopted C57 males, whereas the C57 females showed no preference between the urine odour of C57 and adopted BALB males. Using gas chromatography-mass spectrometry (GC-MS) and stepwise discriminant analysis, we found that the ratios of volatile chemicals from urine and preputial gland secretions were altered in the fostered male mice; these changes may have resulted in the behavioural changes observed in the females. Overall, the results suggest that female mice prefer urine odours from males with different genetic backgrounds; this preference may be driven by genetic compatibility. The early maternal environment influences the chemosignals of males and thus may influence the olfactory preferences of

Acetyl Coenzyme A Stimulates RNA Polymerase II Transcription and Promoter Binding by Transcription Factor IID in the Absence of Histones

PubMed Central

Galasinski, Shelly K.; Lively, Tricia N.; Grebe de Barron, Alexandra; Goodrich, James A.

2000-01-01

Protein acetylation has emerged as a means of controlling levels of mRNA synthesis in eukaryotic cells. Here we report that acetyl coenzyme A (acetyl-CoA) stimulates RNA polymerase II transcription in vitro in the absence of histones. The effect of acetyl-CoA on basal and activated transcription was studied in a human RNA polymerase II transcription system reconstituted from recombinant and highly purified transcription factors. Both basal and activated transcription were stimulated by the addition of acetyl-CoA to transcription reaction mixtures. By varying the concentrations of general transcription factors in the reaction mixtures, we found that acetyl-CoA decreased the concentration of TFIID required to observe transcription. Electrophoretic mobility shift assays and DNase I footprinting revealed that acetyl-CoA increased the affinity of the general transcription factor TFIID for promoter DNA in a TBP-associated factor (TAF)-dependent manner. Interestingly, acetyl-CoA also caused a conformational change in the TFIID-TFIIA-promoter complex as assessed by DNase I footprinting. These results show that acetyl-CoA alters the DNA binding activity of TFIID and indicate that this biologically important cofactor functions at multiple levels to control gene expression. PMID:10688640

Acetyl coenzyme A stimulates RNA polymerase II transcription and promoter binding by transcription factor IID in the absence of histones.

PubMed

Galasinski, S K; Lively, T N; Grebe De Barron, A; Goodrich, J A

2000-03-01

Protein acetylation has emerged as a means of controlling levels of mRNA synthesis in eukaryotic cells. Here we report that acetyl coenzyme A (acetyl-CoA) stimulates RNA polymerase II transcription in vitro in the absence of histones. The effect of acetyl-CoA on basal and activated transcription was studied in a human RNA polymerase II transcription system reconstituted from recombinant and highly purified transcription factors. Both basal and activated transcription were stimulated by the addition of acetyl-CoA to transcription reaction mixtures. By varying the concentrations of general transcription factors in the reaction mixtures, we found that acetyl-CoA decreased the concentration of TFIID required to observe transcription. Electrophoretic mobility shift assays and DNase I footprinting revealed that acetyl-CoA increased the affinity of the general transcription factor TFIID for promoter DNA in a TBP-associated factor (TAF)-dependent manner. Interestingly, acetyl-CoA also caused a conformational change in the TFIID-TFIIA-promoter complex as assessed by DNase I footprinting. These results show that acetyl-CoA alters the DNA binding activity of TFIID and indicate that this biologically important cofactor functions at multiple levels to control gene expression.

Awareness of identity alteration and diagnostic preference between borderline personality disorder and dissociative disorders.

PubMed

Sar, Vedat; Alioğlu, Firdevs; Akyuz, Gamze; Tayakısı, Emre; Öğülmüş, Ezgi F; Sönmez, Doğuş

2017-01-01

This study inquires into identity alteration among college students and its relationship to borderline personality disorder (BPD) and/or dissociative disorders (DDs). Steinberg Identity Alteration Questionnaire (SIAQ), Childhood Trauma Questionnaire (CTQ), and self-report screening tool of the BPD section of the Structured Clinical Interview for DSM-IV (SCID-BPD) were administered to 1301 college students. Participants who fit the diagnostic criteria of BPD (n = 80) according to the clinician-administered SCID-BPD and 111 non-BPD controls were evaluated using the Structured Clinical Interview for DSM-IV DDs (SCID-D) by two psychiatrists blind to the group membership and scale scores. Test-retest evaluations and internal consistency analyses suggested that SIAQ was a reliable instrument. Of the participants, 11.3% reported a SIAQ score 25 or above alongside some impairment. SIAQ scores differentiated participants who fit the diagnostic criteria for a DD from those who did not. While self-report identity alteration was correlated with all childhood trauma types, clinician-assessed identity alteration was correlated with childhood sexual abuse only. Those who fit criteria for both disorders had the highest identity alteration scores in self-report and clinician-assessment. Although both syndromes had significant effect on self-report identity alteration total scores, in contrast to DD, BPD did not have an effect on the clinician-administered evaluation. An impression of personality disorder rather than a DD may seem more likely when identity alteration remains subtle in clinical assessment, notwithstanding its presence in self-report. Lack of recognition of identity alteration may lead to overdiagnosis of BPD among individuals who have a DD.

Neural correlates of cognitive dissonance and choice-induced preference change

PubMed Central

Izuma, Keise; Matsumoto, Madoka; Murayama, Kou; Samejima, Kazuyuki; Sadato, Norihiro; Matsumoto, Kenji

2010-01-01

According to many modern economic theories, actions simply reflect an individual's preferences, whereas a psychological phenomenon called “cognitive dissonance” claims that actions can also create preference. Cognitive dissonance theory states that after making a difficult choice between two equally preferred items, the act of rejecting a favorite item induces an uncomfortable feeling (cognitive dissonance), which in turn motivates individuals to change their preferences to match their prior decision (i.e., reducing preference for rejected items). Recently, however, Chen and Risen [Chen K, Risen J (2010) J Pers Soc Psychol 99:573–594] pointed out a serious methodological problem, which casts a doubt on the very existence of this choice-induced preference change as studied over the past 50 y. Here, using a proper control condition and two measures of preferences (self-report and brain activity), we found that the mere act of making a choice can change self-report preference as well as its neural representation (i.e., striatum activity), thus providing strong evidence for choice-induced preference change. Furthermore, our data indicate that the anterior cingulate cortex and dorsolateral prefrontal cortex tracked the degree of cognitive dissonance on a trial-by-trial basis. Our findings provide important insights into the neural basis of how actions can alter an individual's preferences. PMID:21135218

Neural correlates of cognitive dissonance and choice-induced preference change.

PubMed

Izuma, Keise; Matsumoto, Madoka; Murayama, Kou; Samejima, Kazuyuki; Sadato, Norihiro; Matsumoto, Kenji

2010-12-21

According to many modern economic theories, actions simply reflect an individual's preferences, whereas a psychological phenomenon called "cognitive dissonance" claims that actions can also create preference. Cognitive dissonance theory states that after making a difficult choice between two equally preferred items, the act of rejecting a favorite item induces an uncomfortable feeling (cognitive dissonance), which in turn motivates individuals to change their preferences to match their prior decision (i.e., reducing preference for rejected items). Recently, however, Chen and Risen [Chen K, Risen J (2010) J Pers Soc Psychol 99:573-594] pointed out a serious methodological problem, which casts a doubt on the very existence of this choice-induced preference change as studied over the past 50 y. Here, using a proper control condition and two measures of preferences (self-report and brain activity), we found that the mere act of making a choice can change self-report preference as well as its neural representation (i.e., striatum activity), thus providing strong evidence for choice-induced preference change. Furthermore, our data indicate that the anterior cingulate cortex and dorsolateral prefrontal cortex tracked the degree of cognitive dissonance on a trial-by-trial basis. Our findings provide important insights into the neural basis of how actions can alter an individual's preferences.

Relative fluid novelty differentially alters the time course of limited-access ethanol and water intake in selectively bred high-alcohol-preferring mice.

PubMed

Linsenbardt, David N; Boehm, Stephen L

2015-04-01

The influence of previous alcohol (ethanol [EtOH])-drinking experience on increasing the rate and amount of future EtOH consumption might be a genetically regulated phenomenon critical to the development and maintenance of repeated excessive EtOH abuse. We have recently found evidence supporting this view, wherein inbred C57BL/6J (B6) mice develop progressive increases in the rate of binge EtOH consumption over repeated drinking-in-the-dark (DID) EtOH access sessions (i.e., "front loading"). The primary goal of this study was to evaluate identical parameters in high-alcohol-preferring (HAP) mice to determine whether similar temporal alterations in limited-access EtOH drinking develop in a population selected for high EtOH preference/intake under continuous (24-hour) access conditions. Using specialized volumetric drinking devices, HAP mice received 14 daily 2-hour DID EtOH or water access sessions. A subset of these mice was then given 1 day access to the opposite assigned fluid on day 15. Home cage locomotor activity was recorded concomitantly on each day of these studies. The possibility of behavioral/metabolic tolerance was evaluated on day 16 using experimenter-administered EtOH. The amount of EtOH consumed within the first 15 minutes of access increased markedly over days. However, in contrast to previous observations in B6 mice, EtOH front loading was also observed on day 15 in mice that only had previous DID experience with water. Furthermore, a decrease in the amount of water consumed within the first 15 minutes of access compared to animals given repeated water access was observed on day 15 in mice with 14 previous days of EtOH access. These data further illustrate the complexity and importance of the temporal aspects of limited-access EtOH consumption and suggest that previous procedural/fluid experience in HAP mice selectively alters the time course of EtOH and water consumption. Copyright © 2015 by the Research Society on Alcoholism.

Relative Fluid Novelty Differentially Alters the Time Course of Limited-Access Ethanol and Water Intake in Selectively Bred High Alcohol Preferring Mice

PubMed Central

Linsenbardt, David N.; Boehm, Stephen L.

2015-01-01

Background The influence of previous alcohol (ethanol) drinking experience on increasing the rate and amount of future ethanol consumption might be a genetically-regulated phenomenon critical to the development and maintenance of repeated excessive ethanol abuse. We have recently found evidence supporting this view, wherein inbred C57BL/6J (B6) mice develop progressive increases in the rate of binge-ethanol consumption over repeated Drinking-in-the-Dark (DID) ethanol access sessions (i.e. ‘front-loading’). The primary goal of the present study was to evaluate identical parameters in High Alcohol Preferring (HAP) mice to determine if similar temporal alterations in limited-access ethanol drinking develop in a population selected for high ethanol preference/intake under continuous (24hr) access conditions. Methods Using specialized volumetric drinking devices, HAP mice received 14 daily 2 hour DID ethanol or water access sessions. A subset of these mice was then given one day access to the opposite assigned fluid on day 15. Home cage locomotor activity was recorded concomitantly on each day of these studies. The possibility of behavioral/metabolic tolerance was evaluated on day 16 using experimenter administered ethanol. Results The amount of ethanol consumed within the first 15 minutes of access increased markedly over days. However, in contrast to previous observations in B6 mice, ethanol front-loading was also observed on day 15 in mice that only had previous DID experience with water. Furthermore, a decrease in the amount of water consumed within the first 15 minutes of access compared to animals given repeated water access was observed on day 15 in mice with 14 previous days of ethanol access. Conclusions These data further illustrate the complexity and importance of the temporal aspects of limited-access ethanol consumption, and suggest that previous procedural/fluid experience in HAP mice selectively alters the time course of ethanol and water consumption

A new role for coenzyme F420 in aflatoxin reduction by soil mycobacteria.

PubMed

Graham, David E

2010-11-01

Hepatotoxic aflatoxins have found a worthy adversary in two new families of bacterial oxidoreductases. These enzymes use the reduced coenzyme F420 to initiate the degradation of furanocoumarin compounds, including the major mycotoxin products of Aspergillus flavus. Along with pyridoxal 5'-phosphate synthases and aryl nitroreductases, these proteins form a large and versatile superfamily of flavin and deazaflavin-dependent oxidoreductases. F420-dependent members of this family appear to share a common mechanism of hydride transfer from the reduced, low-potential deazaflavin to the electron-deficient ring systems of their substrates. © 2010 Blackwell Publishing Ltd.

Involvement of tristetraprolin in transcriptional activation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase by insulin

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

Ness, Gene C., E-mail: gness@hsc.usf.edu; Edelman, Jeffrey L.; Brooks, Patricia A.

2012-03-30

Highlights: Black-Right-Pointing-Pointer siRNAs to tristetraprolin blocks transcription of HMGR in vivo in rat liver. Black-Right-Pointing-Pointer siRNAs to tristetraprolin inhibits insulin activation of HMGR transcription. Black-Right-Pointing-Pointer Insulin acts to rapidly increase tristetraprolin in liver nuclear extracts. -- Abstract: Several AU-rich RNA binding element (ARE) proteins were investigated for their possible effects on transcription of hepatic 3-hydroxy-3-methyglutaryl coenzyme A reductase (HMGR) in normal rats. Using in vivo electroporation, four different siRNAs to each ARE protein were introduced together with HMGR promoter (-325 to +20) luciferase construct and compared to saline controls. All four siRNAs to tristetraprolin (TTP) completely eliminated transcription from themore » HMGR promoter construct. Since insulin acts to rapidly increase hepatic HMGR transcription, the effect of TTP siRNA on induction by insulin was tested. The 3-fold stimulation by insulin was eliminated by this treatment. In comparison, siRNA to AU RNA binding protein/enoyl coenzyme A hydratase (AUH) had no effect. These findings indicate a role for TTP in the insulin-mediated activation of hepatic HMGR transcription.« less

Restoring de novo Coenzyme Q biosynthesis in Caenorhabditis elegans coq-3 mutants yields profound rescue compared to exogenous Coenzyme Q supplementation

PubMed Central

Gomez, Fernando; Saiki, Ryoichi; Chin, Randall; Srinivasan, Chandra; Clarke, Catherine F.

2012-01-01

Coenzyme Q (ubiquinone or Q) is an essential lipid component of the mitochondrial electron transport chain. In Caenorhabditis elegans Q biosynthesis involves at least nine steps, including the hydroxylation of the hydroquinone ring by CLK-1 and two O-methylation steps mediated by COQ-3. We characterize two C. elegans coq-3 deletion mutants, and show that while each has defects in Q synthesis, their phenotypes are distinct. First generation homozygous coq-3(ok506) mutants are fertile when fed the standard lab diet of Q-replete OP50 E. coli, but their second generation homozygous progeny do not reproduce. In contrast, the coq-3(qm188) deletion mutant remains sterile when fed Q-replete OP50. Quantitative PCR analyses suggest that the longer qm188 deletion may alter expression of the flanking nuo-3 and gdi-1 genes, located 5′ and 3′, respectively of coq-3 within an operon. We surmise that variable expression of nuo-3, a subunit of complex I, or of gdi-1, a guanine nucleotide dissociation inhibitor, may act in combination with defects in Q biosynthesis to produce a more severe phenotype. The phenotypes of both coq-3 mutants are more drastic as compared to the C. elegans clk-1 mutants. When fed OP50, clk-1 mutants reproduce for many generations, but show reduced fertility, slow behaviors, and enhanced life span. The coq-3 and clk-1 mutants all show arrested development and are sterile when fed the Q-deficient E. coli strain GD1 (harboring a mutation in the ubiG gene). However, unlike clk-1 mutant worms, neither coq-3 mutant strain responded to dietary supplementation with purified exogenous Q10. Here we show that the Q9 content can be determined in lipid extracts from just 200 individual worms, enabling the determination of Q content in the coq-3 mutants unable to reproduce. An extra-chromosomal array expressing wild-type C. elegans coq-3 rescued fertility of both coq-3 mutants and partially restored steady-state levels of COQ-3 polypeptide and Q9 content, indicating

Restoring de novo coenzyme Q biosynthesis in Caenorhabditis elegans coq-3 mutants yields profound rescue compared to exogenous coenzyme Q supplementation.

PubMed

Gomez, Fernando; Saiki, Ryoichi; Chin, Randall; Srinivasan, Chandra; Clarke, Catherine F

2012-09-10

Coenzyme Q (ubiquinone or Q) is an essential lipid component of the mitochondrial electron transport chain. In Caenorhabditis elegans Q biosynthesis involves at least nine steps, including the hydroxylation of the hydroquinone ring by CLK-1 and two O-methylation steps mediated by COQ-3. We characterize two C. elegans coq-3 deletion mutants, and show that while each has defects in Q synthesis, their phenotypes are distinct. First generation homozygous coq-3(ok506) mutants are fertile when fed the standard lab diet of Q-replete OP50 Escherichia coli, but their second generation homozygous progeny does not reproduce. In contrast, the coq-3(qm188) deletion mutant remains sterile when fed Q-replete OP50. Quantitative PCR analyses suggest that the longer qm188 deletion may alter expression of the flanking nuo-3 and gdi-1 genes, located 5' and 3', respectively of coq-3 within an operon. We surmise that variable expression of nuo-3, a subunit of complex I, or of gdi-1, a guanine nucleotide dissociation inhibitor, may act in combination with defects in Q biosynthesis to produce a more severe phenotype. The phenotypes of both coq-3 mutants are more drastic as compared to the C. elegans clk-1 mutants. When fed OP50, clk-1 mutants reproduce for many generations, but show reduced fertility, slow behaviors, and enhanced life span. The coq-3 and clk-1 mutants all show arrested development and are sterile when fed the Q-deficient E. coli strain GD1 (harboring a mutation in the ubiG gene). However, unlike clk-1 mutant worms, neither coq-3 mutant strain responded to dietary supplementation with purified exogenous Q(10). Here we show that the Q(9) content can be determined in lipid extracts from just 200 individual worms, enabling the determination of Q content in the coq-3 mutants unable to reproduce. An extra-chromosomal array expressing wild-type C. elegans coq-3 rescued fertility of both coq-3 mutants and partially restored steady-state levels of COQ-3 polypeptide and Q(9

Do Food Preferences Change After Bariatric Surgery?

PubMed

Gero, Daniel; Steinert, Robert E; le Roux, Carel W; Bueter, Marco

2017-09-01

Insights into physiological mechanisms responsible for weight loss after bariatric surgery (BS) have challenged the traditional view that mechanical restriction and caloric malabsorption are major drivers of weight loss and health benefits after BS. Altered diet selection with an increased postoperative preference for low-sugar and low-fat food has also been implicated as a potential mechanism beyond mere reduction of calorie intake. However, the empirical support for this phenomenon is not uniform and evidence is largely based on indirect measurements, such as self-reported food intake data, which are prone to inaccuracy due to their subjective character. Most studies indicate that patients not only reduce their caloric intake after BS, but also show a reduced preference of food with high sugar and high fat content. So far, standard behavioral tests to directly measure changes in food intake behavior after BS have been mainly used in animal models. It remains unclear whether there are fundamental shifts in the palatability of high-fat and sugary foods after BS or simply a decrease in the appetitive drive to ingest them. Studies of appetitive behavior in humans after BS have produced equivocal results. Learning processes may play a role as changes in diet selection seem to progress with time after surgery. So far, direct measures of altered food selection in humans after BS are rare and the durability of altered food selection as well as the role of learning remains elusive.

Microbes and masculinity: Does exposure to pathogenic cues alter women’s preferences for male facial masculinity and beardedness?

PubMed Central

McIntosh, Toneya L.; Lee, Anthony J.; Sidari, Morgan J.; Stower, Rebecca E.; Sherlock, James M.

2017-01-01

Women’s preferences for men’s androgen dependent secondary sexual traits are proposed to be phenotypically plastic in response to exposure to pathogens and pathogen disgust. While previous studies report that masculinity in facial shape is more attractive to women who have recently been exposed to pathogenic cues and who are high in self-reported pathogen disgust, facial hair may reduce male attractiveness under conditions of high pathogens as beards are a possible breeding ground for disease carrying ectoparasites. In the present study, we test whether women’s preferences for beardedness and facial masculinity vary due to exposure to different pathogenic cues. Participants (N = 688, mean age + 1SD = 31.94 years, SD = 6.69, range = 18–67) rated the attractiveness of facial composite stimuli of men when they were clean-shaven or fully bearded. These stimuli were also manipulated in order to vary sexual dimorphism by ±50%. Ratings were conducted before and after exposure to one of four experimental treatments in which participants were primed to either high pathogens (e.g. infected cuts), ectoparasites (e.g. body lice), a mixture of pathogens and ectoparasites, or a control condition (e.g. innocuous liquids). Participants then completed the three-domain disgust scale measuring attitudes to moral, sexual and pathogen disgust. We predicted that women would prefer facial masculinity following exposure to pathogenic cues, but would show reduced preferences for facial hair following exposure to ectoparasites. Women preferred full beards over clean-shaven faces and masculinised over feminised faces. However, none of the experimental treatments influenced the direction of preferences for facial masculinity or beardedness. We also found no association between women’s self-reported pathogen disgust and their preferences for facial masculinity. However, there was a weak positive association between moral disgust scores and preferences for facial masculinity, which

Higher salt preference in heart failure patients.

PubMed

de Souza, Juli Thomaz; Matsubara, Luiz S; Menani, José Vanderlei; Matsubara, Beatriz B; Johnson, Alan Kim; De Gobbi, Juliana Irani Fratucci

2012-02-01

Heart failure (HF) is a complex syndrome that involves changes in behavioral, neural and endocrine regulatory systems. Dietary salt restriction along with pharmacotherapy is considered an essential component in the effective management of symptomatic HF patients. However, it is well recognized that HF patients typically have great difficulty in restricting sodium intake. We hypothesized that under HF altered activity in systems that normally function to regulate body fluid and cardiovascular homeostasis could produce an increased preference for the taste of salt. Therefore, this study was conducted to evaluate the perceived palatability (defined as salt preference) of food with different concentrations of added salt in compensated chronically medicated HF patients and comparable control subjects. Healthy volunteers (n=25) and medicated, clinically stable HF patients (n=38, NYHA functional class II or III) were interviewed and given an evaluation to assess their preferences for different amounts of saltiness. Three salt concentrations (0.58, 0.82, and 1.16 g/100 g) of bean soup were presented to the subjects. Salt preference for each concentration was quantified using an adjective scale (unpleasant, fair or delicious). Healthy volunteers preferred the soup with medium salt concentration (p=0.042), HF patients disliked the low concentration (p<0.001) and preferred the high concentration of salted bean soup (p<0.001). When compared to healthy volunteers, HF patients demonstrated a significantly greater preference for the soup with a high salt concentration (p=0.038). It is concluded that medicated, compensated patients under chronic treatment for HF have an increased preference for salt. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structural Basis of the Induced-Fit Mechanism of 1,4-Dihydroxy-2-Naphthoyl Coenzyme A Synthase from the Crotonase Fold Superfamily

PubMed Central

Li, Jie; Li, Yan; Jiang, Ming; Zhou, Jiahai; Guo, Zhihong

2013-01-01

1, 4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase is a typical crotonase fold enzyme with an implicated role of conformational changes in catalysis. We have identified these conformational changes by determining the structures of its Escherichia coli and Synechocystis sp. PCC6803 orthologues in complex with a product analog. The structural changes include the folding of an active-site loop into a β-hairpin and significant reorientation of a helix at the carboxy terminus. Interestingly, a new interface is formed between the ordered loop and the reoriented helix, both of which also form additional interactions with the coenzyme A moiety of the ligand. Site-directed mutation of the amino acid residues involved in these ligand-induced interactions significantly diminishes the enzyme activity. These results suggest a catalytically essential induced-fit that is likely initiated by the enzyme-ligand interactions at the active site. PMID:23658663

NADPH-dependent coenzyme Q reductase is the main enzyme responsible for the reduction of non-mitochondrial CoQ in cells.

PubMed

Takahashi, Takayuki; Okuno, Masaaki; Okamoto, Tadashi; Kishi, Takeo

2008-01-01

We purified an NADPH-dependent coenzyme Q reductase (NADPH-CoQ reductase) in rat liver cytosol and compared its enzymatic properties with those of the other CoQ10 reductases such as NADPH: quinone acceptor oxidoreductase 1 (NQO1), lipoamide dehydrogenase, thioredoxine reductase and glutathione reductase. NADPH-CoQ reductase was the only enzyme that preferred NADPH to NADH as an electron donor and was also different from the other CoQ10 reductases in the sensitivities to its inhibitors and stimulators. Especially, Zn2+ was the most powerful inhibitor for NADPH-CoQ reductase, but CoQ10 reduction by the other CoQ10 reductases could not be inhibited by Zn2+. Furthermore, the reduction of the CoQ9 incorporated into HeLa cells was also inhibited by Zn2+ in the presence of pyrithione, a zinc ionophore. Moreover, NQO1 gene silencing in HeLa cells by transfection of a small interfering RNA resulted in lowering of both the NQO1 protein level and the NQO1 activity by about 75%. However, this transfection did not affect the NADPH-CoQ reductase activity and the reduction of CoQ9 incorporated into the cells. These results suggest that the NADPH-CoQ reductase located in cytosol may be the main enzyme responsible for the reduction of non-mitochondrial CoQ in cells.

Physiological importance of the heterodisulfide of coenzyme M and 7-mercaptoheptanoylthreonine phosphate in the reduction of carbon dioxide to methane in Methanobacterium

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

Bobik, T.A.; Wolfe, R.S.

1988-01-01

The heterodisulfide of the two coenzymes 2-mercaptoethanesulfonic acid (coenzyme M, HS-CoM) and N-(7-mercaptoheptanoyl)threonine O/sup 3/-phosphate (HS-HTP) increased the rate of CO/sub 2/ reduction to methane by cell extracts 42-fold. The stimulation resulted from activation of the initial step of methanogenesis, the production of formylmethanofuran from methanofuran and CO/sub 2/. These results establish a role for this heterodisulfide (CoM-S-S-HTP) in the reduction of CO/sub 2/ to formylmethanofuran. Evidence indicates that CoM-S-S-HTP is the labile intermediate that accounts for the coupling of the reduction of 2-(methylthio)ethanesulfonic acid by the methylreductase to formylmethanofuran biosynthesis, the RPG effect. The heterodisulfide was found to bemore » labile in cell extracts due to enzyme-catalyzed reduction and possibly thiol-disulfide exchange.« less

Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated with high-dose simvastatin: A possible role in statin-induced hepatotoxicity?

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

Tavintharan, S.; Ong, C.N.; Jeyaseelan, K.

2007-09-01

Lowering of low-density lipoprotein cholesterol is well achieved by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). Statins inhibit the conversion of HMG-CoA to mevalonate, a precursor for cholesterol and coenzyme Q10 (CoQ{sub 10}). In HepG2 cells, simvastatin decreased mitochondrial CoQ{sub 10} levels, and at higher concentrations was associated with a moderately higher degree of cell death, increased DNA oxidative damage and a reduction in ATP synthesis. Supplementation of CoQ{sub 10}, reduced cell death and DNA oxidative stress, and increased ATP synthesis. It is suggested that CoQ{sub 10} deficiency plays an important role in statin-induced hepatopathy, and that CoQ{sub 10} supplementation protectsmore » HepG2 cells from this complication.« less

Antiplasmodial dihetarylthioethers target the coenzyme A synthesis pathway in Plasmodium falciparum erythrocytic stages.

PubMed

Weidner, Thomas; Lucantoni, Leonardo; Nasereddin, Abed; Preu, Lutz; Jones, Peter G; Dzikowski, Ron; Avery, Vicky M; Kunick, Conrad

2017-05-15

Malaria is a widespread infectious disease that threatens a large proportion of the population in tropical and subtropical areas. Given the emerging resistance against the current standard anti-malaria chemotherapeutics, the development of alternative drugs is urgently needed. New anti-malarials representing chemotypes unrelated to currently used drugs have an increased potential for displaying novel mechanisms of action and thus exhibit low risk of cross-resistance against established drugs. Phenotypic screening of a small library (32 kinase-inhibitor analogs) against Plasmodium falciparum NF54-luc asexual erythrocytic stage parasites identified a diarylthioether structurally unrelated to registered drugs. Hit expansion led to a series in which the most potent congener displayed nanomolar antiparasitic activity (IC 50  = 39 nM, 3D7 strain). Structure-activity relationship analysis revealed a thieno[2,3-d]pyrimidine on one side of the thioether linkage as a prerequisite for antiplasmodial activity. Within the series, the oxazole derivative KuWei173 showed high potency (IC 50  = 75 nM; 3D7 strain), good solubility in aqueous solvents (1.33 mM), and >100-fold selectivity toward human cell lines. Rescue experiments identified inhibition of the plasmodial coenzyme A synthesis as a possible mode of action for this compound class. The class of antiplasmodial bishetarylthioethers reported here has been shown to interfere with plasmodial coenzyme A synthesis, a mechanism of action not yet exploited for registered anti-malarial drugs. The oxazole congener KuWei173 displays double-digit nanomolar antiplasmodial activity, selectivity against human cell lines, high drug likeness, and thus represents a promising chemical starting point for further drug development.

TD-DFT Insight into Photodissociation of Co-C Bond in Coenzyme B12

NASA Astrophysics Data System (ADS)

Kozlowski, Pawel; Liu, Hui; Kornobis, Karina; Lodowski, Piotr; Jaworska, Maria

2013-12-01

Coenzyme B12 (AdoCbl) is one of the most biologically active forms of vitamin B12, and continues to be a topic of active research interest. The mechanism of Co-C bond cleavage in AdoCbl, and the corresponding enzymatic reactions are however, not well understood at the molecular level. In this work, time-dependent density functional theory (TD-DFT) has been applied to investigate the photodissociation of coenzyme B12. To reduce computational cost, while retaining the major spectroscopic features of AdoCbl, a truncated model based on ribosylcobalamin (RibCbl) was used to simulate Co-C photodissociation. Equilibrium geometries of RibCbl were obtained by optimization at the DFT/BP86/TZVP level of theory, and low-lying excited states were calculated by TD-DFT using the same functional and basis set. The calculated singlet states, and absorption spectra were simulated in both the gas phase, and water, using the polarizable continuum model (PCM). Both spectra were in reasonable agreement with experimental data, and potential energy curves based on vertical excitations were plotted to explore the nature of Co-C bond dissociation. It was found that a repulsive 3(σCo-C → σ*Co-C) triplet state became dissociative at large Co-C bond distance, similar to a previous observation for methylcobalamin (MeCbl). Furthermore, potential energy surfaces (PESs) obtained as a function of both Co-CRib and Co-NIm distances, identify the S1 state as a key intermediate generated during photoexcitation of RibCbl, attributed to a mixture of a MLCT (metal-to-ligand charge transfer) and a σ bonding-ligand charge transfer (SBLCT) states.

Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration.

PubMed

Fišar, Z; Hroudová, J; Singh, N; Kopřivová, A; Macečková, D

2016-01-01

Some therapeutic and/or adverse effects of drugs may be related to their effects on mitochondrial function. The effects of simvastatin, resveratrol, coenzyme Q10, acetylcysteine, and acetylcarnitine on Complex I-, Complex II-, or Complex IV-linked respiratory rate were determined in isolated brain mitochondria. The protective effects of these biologically active compounds on the calcium-induced decrease of the respiratory rate were also studied. We observed a significant inhibitory effect of simvastatin on mitochondrial respiration (IC50 = 24.0 μM for Complex I-linked respiration, IC50 = 31.3 μM for Complex II-linked respiration, and IC50 = 42.9 μM for Complex IV-linked respiration); the inhibitory effect of resveratrol was found at very high concentrations (IC50 = 162 μM for Complex I-linked respiration, IC50 = 564 μM for Complex II-linked respiration, and IC50 = 1454 μM for Complex IV-linked respiration). Concentrations required for effective simvastatin- or resveratrol-induced inhibition of mitochondrial respiration were found much higher than concentrations achieved under standard dosing of these drugs. Acetylcysteine and acetylcarnitine did not affect the oxygen consumption rate of mitochondria. Coenzyme Q10 induced an increase of Complex I-linked respiration. The increase of free calcium ions induced partial inhibition of the Complex I+II-linked mitochondrial respiration, and all tested drugs counteracted this inhibition. None of the tested drugs showed mitochondrial toxicity (characterized by respiratory rate inhibition) at drug concentrations achieved at therapeutic drug intake. Resveratrol, simvastatin, and acetylcarnitine had the greatest neuroprotective potential (characterized by protective effects against calcium-induced reduction of the respiratory rate).

A combination of coenzyme Q10, feverfew and magnesium for migraine prophylaxis: a prospective observational study.

PubMed

Guilbot, Angèle; Bangratz, Marie; Ait Abdellah, Samira; Lucas, Christian

2017-08-30

Feverfew (Tanacetum parthenium L.), magnesium and coenzyme Q10 are frequently used for migraine prophylaxis. Supplementation with a fixed combination of these three agents (Antemig®, PiLeJe) was investigated in an observational study. Adult patients suffering from migraine according to the criteria of the International Headache Society were enrolled by general practitioners (≥2 migraine attacks during previous month; exclusion of chronic migraine and medication overuse) and after a one-month baseline phase, supplemented with one tablet of 100 mg feverfew, 100 mg coenzyme Q10 and 112.5 mg magnesium per day for 3 months. Supplementation significantly reduced the number of days with migraine headache during third month of supplementation compared to baseline phase (1.3 days ±1.5 versus 4.9 days ±2.6, p < 0.0001; n = 68 intention to treat; primary criterion). The decrease was progressive over the period of supplementation and significant from first month (1st month: -2.5 days ±3.1, p < 0.0001; 2nd month: -3 days ±2.8, p < 0.0001). The proportion of patients with a reduction of at least 50% in the number of days with migraine headache was 75% (51/68) after 3 months, with a progressive increase over the period of supplementation (63.2% [43/68] after 1 month and 70.6% [48/68] after 2 months). The proportion of patients with anxiety and depressive symptoms (Hospital Anxiety and Depression Scale) decreased between baseline phase and third month of supplementation from 61.9% (39/63 patients with information available) to 35% (21/60) for depression and from 52.4% (33/63) to 30% (18/60) for anxiety. An improvement of quality of life (Qualité de Vie et Migraine questionnaire) was also observed. The combination was well tolerated. Results suggest that the proprietary supplement containing feverfew, coenzyme Q10 and magnesium assessed could be beneficial and safe for the prevention of migraine in adult patients and merits further study. Clinical

Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes.

PubMed

Cox, Pete J; Kirk, Tom; Ashmore, Tom; Willerton, Kristof; Evans, Rhys; Smith, Alan; Murray, Andrew J; Stubbs, Brianna; West, James; McLure, Stewart W; King, M Todd; Dodd, Michael S; Holloway, Cameron; Neubauer, Stefan; Drawer, Scott; Veech, Richard L; Griffin, Julian L; Clarke, Kieran

2016-08-09

Ketosis, the metabolic response to energy crisis, is a mechanism to sustain life by altering oxidative fuel selection. Often overlooked for its metabolic potential, ketosis is poorly understood outside of starvation or diabetic crisis. Thus, we studied the biochemical advantages of ketosis in humans using a ketone ester-based form of nutrition without the unwanted milieu of endogenous ketone body production by caloric or carbohydrate restriction. In five separate studies of 39 high-performance athletes, we show how this unique metabolic state improves physical endurance by altering fuel competition for oxidative respiration. Ketosis decreased muscle glycolysis and plasma lactate concentrations, while providing an alternative substrate for oxidative phosphorylation. Ketosis increased intramuscular triacylglycerol oxidation during exercise, even in the presence of normal muscle glycogen, co-ingested carbohydrate and elevated insulin. These findings may hold clues to greater human potential and a better understanding of fuel metabolism in health and disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Downregulation of monocytic differentiation via modulation of CD147 by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

PubMed

Sasidhar, Manda V; Chevooru, Sai Krishnaveni; Eickelberg, Oliver; Hartung, Hans-Peter; Neuhaus, Oliver

2017-01-01

CD147 is an activation induced glycoprotein that promotes the secretion and activation of matrix metalloproteinases (MMPs) and is upregulated during the differentiation of macrophages. Interestingly, some of the molecular functions of CD147 rely on its glycosylation status: the highly glycosylated forms of CD147 induce MMPs whereas the lowly glycosylated forms inhibit MMP activation. Statins are hydroxy-methylglutaryl coenzyme A reductase inhibitors that block the synthesis of mevalonate, thereby inhibiting all mevalonate-dependent pathways, including isoprenylation, N-glycosylation and cholesterol synthesis. In this study, we investigated the role of statins in the inhibition of macrophage differentiation and the associated process of MMP secretion through modulation of CD147. We observed that differentiation of the human monocytic cell line THP-1 to a macrophage phenotype led to upregulation of CD147 and CD14 and that this effect was inhibited by statins. At the molecular level, statins altered CD147 expression, structure and function by inhibiting isoprenylation and N-glycosylation. In addition, statins induced a shift of CD147 from its highly glycosylated form to its lowly glycosylated form. This shift in N-glycosylation status was accompanied by a decrease in the production and functional activity of MMP-2 and MMP-9. In conclusion, these findings describe a novel molecular mechanism of immune regulation by statins, making them interesting candidates for autoimmune disease therapy.

Regeneration of Nicotinamide Coenzymes: Principles and Applications for the Synthesis of Chiral Compounds

NASA Astrophysics Data System (ADS)

Weckbecker, Andrea; Gröger, Harald; Hummel, Werner

Dehydrogenases which depend on nicotinamide coenzymes are of increasing interest for the preparation of chiral compounds, either by reduction of a prochiral precursor or by oxidative resolution of their racemate. The regeneration of oxidized and reduced nicotinamide cofactors is a very crucial step because the use of these cofactors in stoichiometric amounts is too expensive for application. There are several possibilities to regenerate nicotinamide cofactors: established methods such as formate/formate dehydrogenase (FDH) for the regeneration of NADH, recently developed electrochemical methods based on new mediator structures, or the application of gene cloning methods for the construction of "designed" cells by heterologous expression of appropriate genes.

Amphetamine-induced place preference in humans

PubMed Central

Childs, Emma L.; de Wit, Harriet

2009-01-01

Background The conditioned place preference procedure is a widely used animal model of rewarding drug effects that, to date, has not been tested in humans. In this study, we sought to demonstrate that humans, like non-humans, would exhibit a preference for a place previously associated with amphetamine. Further, we investigated the relationship between conditioned place preference and the mood-altering effects of the drug. Methods Thirty-one healthy individuals participated in a five-session procedure during which they experienced the effects of d-amphetamine (20mg) or placebo on two occasions in two distinctive environments (sessions 1 to 4). One group of subjects (paired group, N=19) received amphetamine consistently in one room and placebo in another room, while a second group (unpaired group, N=12) received amphetamine and placebo without regard to the rooms. During the sessions, participants completed questionnaires to rate their mood. On the fifth session, they rated their preference for the two rooms. Results Individuals in the paired group rated their liking of the amphetamine-paired room significantly higher than the placebo-associated room, while there was no difference between ratings of the two rooms for individuals in the unpaired group. In the paired group, drug liking ratings during the conditioning sessions positively predicted preference for the drug-associated room, whereas reports of amphetamine-induced anxiety and dysphoria negatively predicted room liking scores. Conclusions This study demonstrates that humans, like non-humans, prefer a place associated with amphetamine administration. These findings support the idea that subjective responses to a drug contribute to its ability to establish place conditioning. PMID:19111278

Bioinspired Design of Alcohol Dehydrogenase@nano TiO₂ Microreactors for Sustainable Cycling of NAD⁺/NADH Coenzyme.

PubMed

Lin, Sen; Sun, Shiyong; Wang, Ke; Shen, Kexuan; Ma, Biaobiao; Ren, Yuquan; Fan, Xiaoyu

2018-02-24

The bioinspired design and construction of enzyme@capsule microreactors with specific cell-like functionality has generated tremendous interest in recent years. Inspired by their fascinating complexity, scientists have endeavored to understand the essential aspects of a natural cell and create biomimicking microreactors so as to immobilize enzymes within the hierarchical structure of a microcapsule. In this study, simultaneous encapsulation of alcohol dehydrogenase (ADH) was achieved during the preparation of microcapsules by the Pickering emulsion method using amphiphilic modified TiO₂ nanoparticles (NPs) as building blocks for assembling the photocatalytic microcapsule membrane. The ADH@TiO₂ NP microreactors exhibited dual catalytic functions, i.e., spatially confined enzymatic catalysis and the membrane-associated photocatalytic oxidation under visible light. The sustainable cycling of nicotinamide adenine dinucleotide (NAD) coenzyme between NADH and NAD⁺ was realized by enzymatic regeneration of NADH from NAD⁺ reduction, and was provided in a form that enabled further photocatalytic oxidation to NAD⁺ under visible light. This bioinspired ADH@TiO₂ NP microreactor allowed the linking of a semiconductor mineral-based inorganic photosystem to enzymatic reactions. This is a first step toward the realization of sustainable biological cycling of NAD⁺/NADH coenzyme in synthetic functional microsystems operating under visible light irradiation.

Effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver.

PubMed

Lankin, V Z; Ivanova, M V; Konovalova, G G; Tikhaze, A K; Kaminnyi, A I; Kukharchuk, V V

2007-04-01

We studied the effects of two inhibitors of beta-hydroxy-beta-methylglutaryl coenzyme A reductase, simvastatin and lovastatin, on the lag phase of ascorbate-dependent lipid oxidation in rat liver. Oxidizability of liver biological membranes significantly increased in intact animals and rats with induced hypercholesterolemia after peroral administration of these statins. The lag phase of ascorbate-dependent lipid oxidation in liver biomembranes decreased by 2.1 times in hypercholesterolemic rats. In animals of the lovastatin group this parameter decreased by 4.4 times compared to the control. In intact rats receiving simvastatin, the lag phase of oxidation in biomembranes from the liver decreased practically by 2 times. At the same time, in animals receiving simvastatin in combination with antioxidant vitamins (vitamins E and C, provitamin A) and selenium, the period of induction of oxidation increased by 3.3 times. Our results indicate that beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors produce a prooxidant effect on the liver, which can be prevented by administration of antioxidant agents.

Agmatine attenuates methamphetamine-induced conditioned place preference in rats.

PubMed

Thorn, David A; Winter, Jerrold C; Li, Jun-Xu

2012-04-05

The polyamine agmatine modulates a variety of behavioral effects including the abuse-related effects of opioids and has been proposed as a potential medication candidate for the treatment of opioid abuse. However, little is known of the effects of agmatine on the abuse-related effects of other drugs of abuse. This study examined the effects of agmatine on the rewarding effects of methamphetamine in rats using a conditioned place preference paradigm. Methamphetamine (0.1-1.0mg/kg) dose-dependently increased the time spent in methamphetamine-paired side (place preference). Agmatine, at doses that did not produce place preference or aversion (10-32mg/kg), significantly decreased the development of methamphetamine-induced place preference when agmatine was administered in combination with methamphetamine during place conditioning. Agmatine also significantly decreased the expression of methamphetamine-induced place preference when an acute injection of agmatine was given immediately before test session. These doses of agmatine do not alter the motor activity in rats, suggesting that the observed attenuation of methamphetamine-induced place preference was not due to general behavioral disruption. Together, these data suggests that agmatine attenuates the rewarding effects of methamphetamine and may be able to modulate the abuse liability of methamphetamine. Copyright © 2012 Elsevier B.V. All rights reserved.

A Computational Tale of Two Enzymes: Glycerol Dehydration With or Without B12.

PubMed

Kovačević, Borislav; Barić, Danijela; Babic, Darko; Bilić, Luka; Hanževački, Marko; Sandala, Gregory M; Radom, Leo; Smith, David M

2018-06-12

We present a series of QM/MM calculations aimed at understanding the mechanism of the biological dehydration of glycerol. Strikingly and unusually, this process is catalyzed by two different radical enzymes, one of which is a coenzyme-B 12 - dependent enzyme and the other which is a coenzyme-B 12 - independent enzyme. We show that glycerol dehydration in the presence of the coenzyme-B 12 -dependent enzyme proceeds via a 1,2-OH shift, which benefits from a significant catalytic reduction in the barrier. In contrast, the same reaction in the presence of the coenzyme-B 12 -independent enzyme is unlikely to involve the 1,2-OH shift; instead, a strong preference for direct loss of water from a radical intermediate is indicated. We show that this preference and, ultimately the evolution of such enzymes, is strongly linked with the reactivities of the species responsible for abstracting a hydrogen atom from the substrate. It appears that the hydrogen re-abstraction step involving the product-related radical is fundamental to the mechanistic preference. The unconventional 1,2-OH shift seems to be required to generate a product-related radical of sufficient reactivity to cleave the relatively inactive C-H bond arising from the B 12 cofactor. In the absence of B 12 , it is the relatively weak S-H bond of a cysteine residue that must be homolyzed. Such a transformation is much less demanding and its inclusion apparently enables a simpler overall dehydration mechanism.

Relative Preference and Localized Food Affect Predator Space Use and Consumption of Incidental Prey.

PubMed

Schartel, Tyler E; Schauber, Eric M

2016-01-01

Abundant, localized foods can concentrate predators and their foraging efforts, thus altering both the spatial distribution of predation risk and predator preferences for prey that are encountered incidentally. However, few investigations have quantified the spatial scale over which localized foods affect predator foraging behavior and consumption of incidental prey. In spring 2010, we experimentally tested how point-source foods altered how generalist predators (white-footed mice, Peromyscus leucopus) utilized space and depredated two incidental prey items: almonds (Prunus dulcis; highly profitable) and maple seeds (Acer saccharum; less profitable). We estimated mouse population densities with trapping webs, quantified mouse consumption rates of these incidental prey items, and measured local mouse activity with track plates. We predicted that 1) mouse activity would be elevated near full feeders, but depressed at intermediate distances from the feeder, 2) consumption of both incidental prey would be high near feeders providing less-preferred food and, 3) consumption of incidental prey would be contingent on predator preference for prey relative to feeders providing more-preferred food. Mouse densities increased significantly from pre- to post-experiment. Mean mouse activity was unexpectedly greatest in control treatments, particularly <15 m from the control (empty) feeder. Feeders with highly preferred food (sunflower seeds) created localized refuges for incidental prey at intermediate distances (15 to 25m) from the feeder. Feeders with less-preferred food (corn) generated localized high risk for highly preferred almonds <10 m of the feeder. Our findings highlight the contingent but predictable effects of locally abundant food on risk experienced by incidental prey, which can be positive or negative depending on both spatial proximity and relative preference.

Relative Preference and Localized Food Affect Predator Space Use and Consumption of Incidental Prey

PubMed Central

Schartel, Tyler E.; Schauber, Eric M.

2016-01-01

Abundant, localized foods can concentrate predators and their foraging efforts, thus altering both the spatial distribution of predation risk and predator preferences for prey that are encountered incidentally. However, few investigations have quantified the spatial scale over which localized foods affect predator foraging behavior and consumption of incidental prey. In spring 2010, we experimentally tested how point-source foods altered how generalist predators (white-footed mice, Peromyscus leucopus) utilized space and depredated two incidental prey items: almonds (Prunus dulcis; highly profitable) and maple seeds (Acer saccharum; less profitable). We estimated mouse population densities with trapping webs, quantified mouse consumption rates of these incidental prey items, and measured local mouse activity with track plates. We predicted that 1) mouse activity would be elevated near full feeders, but depressed at intermediate distances from the feeder, 2) consumption of both incidental prey would be high near feeders providing less-preferred food and, 3) consumption of incidental prey would be contingent on predator preference for prey relative to feeders providing more-preferred food. Mouse densities increased significantly from pre- to post-experiment. Mean mouse activity was unexpectedly greatest in control treatments, particularly <15 m from the control (empty) feeder. Feeders with highly preferred food (sunflower seeds) created localized refuges for incidental prey at intermediate distances (15 to 25m) from the feeder. Feeders with less-preferred food (corn) generated localized high risk for highly preferred almonds <10 m of the feeder. Our findings highlight the contingent but predictable effects of locally abundant food on risk experienced by incidental prey, which can be positive or negative depending on both spatial proximity and relative preference. PMID:26978659

Alterations to mitochondrial fatty-acid use in skeletal muscle after chronic exposure to hypoxia depend on metabolic phenotype.

PubMed

Malgoyre, Alexandra; Chabert, Clovis; Tonini, Julia; Koulmann, Nathalie; Bigard, Xavier; Sanchez, Hervé

2017-03-01

We investigated the effects of chronic hypoxia on the maximal use of and sensitivity of mitochondria to different substrates in rat slow-oxidative (soleus, SOL) and fast-glycolytic (extensor digitorum longus, EDL) muscles. We studied mitochondrial respiration in situ in permeabilized myofibers, using pyruvate, octanoate, palmitoyl-carnitine (PC), or palmitoyl-coenzyme A (PCoA). The hypophagia induced by hypoxia may also alter metabolism. Therefore, we used a group of pair-fed rats (reproducing the same caloric restriction, as observed in hypoxic animals), in addition to the normoxic control fed ad libitum. The resting respiratory exchange ratio decreased after 21 days of exposure to hypobaric hypoxia (simulated elevation of 5,500 m). The respiration supported by pyruvate and octanoate were unaffected. In contrast, the maximal oxidative respiratory rate for PCoA, the transport of which depends on carnitine palmitoyltransferase 1 (CPT-1), decreased in the rapid-glycolytic EDL and increased in the slow-oxidative SOL, although hypoxia improved affinity for this substrate in both muscle types. PC and PCoA were oxidized similarly in normoxic EDL, whereas chronic hypoxia limited transport at the CPT-1 step in this muscle. The effects of hypoxia were mediated by caloric restriction in the SOL and by hypoxia itself in the EDL. We conclude that improvements in mitochondrial affinity for PCoA, a physiological long-chain fatty acid, would facilitate fatty-acid use at rest after chronic hypoxia independently of quantitative alterations of mitochondria. Conversely, decreasing the maximal oxidation of PCoA in fast-glycolytic muscles would limit fatty-acid use during exercise. NEW & NOTEWORTHY Affinity for low concentrations of long-chain fatty acids (LCFA) in mitochondria skeletal muscles increases after chronic hypoxia. Combined with a lower respiratory exchange ratio, this suggests facility for fatty acid utilization at rest. This fuel preference is related to caloric

MicroCommentary: A New Role for Coenzyme F420 in Aflatoxin Reduction by Soil Mycobacteria

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

Graham, David E

Hepatotoxic aflatoxins have found a worthy adversary in two new families of bacterial oxidoreductases. These enzymes use the reduced coenzyme F420 to initiate the degradation of furanocoumarin compounds, including the major mycotoxin products of Aspergillus flavus. Along with pyridoxalamine 5 -phosphate oxidases and aryl nitroreductases, these proteins form a large and versatile superfamily of flavin and deazaflavin-dependent oxidoreductases. F420-dependent members of this family appear to share a common mechanism of hydride transfer from the reduced deazaflavin to the electron-deficient ring systems of their substrates.

Nonhuman primates prefer slow tempos but dislike music overall.

PubMed

McDermott, Josh; Hauser, Marc D

2007-09-01

Human adults generally find fast tempos more arousing than slow tempos, with tempo frequently manipulated in music to alter tension and emotion. We used a previously published method [McDermott, J., & Hauser, M. (2004). Are consonant intervals music to their ears? Spontaneous acoustic preferences in a nonhuman primate. Cognition, 94(2), B11-B21] to test cotton-top tamarins and common marmosets, two new-World primates, for their spontaneous responses to stimuli that varied systematically with respect to tempo. Across several experiments, we found that both tamarins and marmosets preferred slow tempos to fast. It is possible that the observed preferences were due to arousal, and that this effect is homologous to the human response to tempo. In other respects, however, these two monkey species showed striking differences compared to humans. Specifically, when presented with a choice between slow tempo musical stimuli, including lullabies, and silence, tamarins and marmosets preferred silence whereas humans, when similarly tested, preferred music. Thus despite the possibility of homologous mechanisms for tempo perception in human and nonhuman primates, there appear to be motivational ties to music that are uniquely human.

Glutamatergic transmission in the central nucleus of the amygdala is selectively altered in Marchigian Sardinian alcohol-preferring rats: alcohol and CRF effects

PubMed Central

Herman, Melissa A.; Varodayan, Florence P.; Oleata, Christopher S.; Luu, George; Kirson, Dean; Heilig, Markus; Ciccocioppo, Roberto; Roberto, Marisa

2015-01-01

The CRF system of the central nucleus of the amygdala (CeA) is important for the processing of anxiety, stress, and effects of acute and chronic ethanol. We previously reported that ethanol decreases evoked glutamate transmission in the CeA of Sprague Dawley rats and that ethanol dependence alters glutamate release in the CeA. Here, we examined the effects of ethanol, CRF and a CRF1 receptor antagonist on spontaneous and evoked glutamatergic transmission in CeA neurons from Wistar and Marchigian Sardinian Preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and characterized by heightened activity of the CRF1 system. Basal spontaneous and evoked glutamate transmission in CeA neurons from msP rats was increased compared to Wistar rats. Ethanol had divergent effects, either increasing or decreasing spontaneous glutamate release in the CeA of Wistar rats. This bidirectional effect was retained in msP rats, but the magnitude of the ethanol-induced increase in glutamate release was significantly smaller. The inhibitory effect of ethanol on evoked glutamatergic transmission was similar in both strains. CRF also either increased or decreased spontaneous glutamate release in CeA neurons of Wistar rats, however, in msP rats CRF only increased glutamate release. The inhibitory effect of CRF on evoked glutamatergic transmission was also lost in neurons from msP rats. A CRF1 antagonist produced only minor effects on spontaneous glutamate transmission, which were consistent across strains, and no effects on evoked glutamate transmission. These results demonstrate that the genetically altered CRF system of msP rats results in alterations in spontaneous and stimulated glutamate signaling in the CeA that may contribute to both the anxiety and drinking behavioral phenotypes. PMID:26519902

The Impact of Coenzyme Q[subscript10] Supplement on the Indicators of Muscle Damage in Young Male Skiing Athletes

ERIC Educational Resources Information Center

Demirci, Nevzat

2015-01-01

This study was conducted in order to know the impact of coenzyme Q[subscript 10] (CoQ[subscript 10]) supplement on the muscle damage and total oxidant (TOS) enzyme levels of young skiing athletes during exercise. 15 male athletes were used for two weeks in the study. The athletes were divided into three groups: the control group and two subject…

Improved Xylitol Production from D-Arabitol by Enhancing the Coenzyme Regeneration Efficiency of the Pentose Phosphate Pathway in Gluconobacter oxydans.

PubMed

Li, Sha; Zhang, Jinliang; Xu, Hong; Feng, Xiaohai

2016-02-10

Gluconobacter oxydans is used to produce xylitol from D-arabitol. This study aims to improve xylitol production by increasing the coenzyme regeneration efficiency of the pentose phosphate pathway in G. oxydans. Glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) were overexpressed in G. oxydans. Real-time PCR and enzyme activity assays revealed that G6PDH/6PGDH activity and coenzyme regeneration efficiency increased in the recombinant G. oxydans strains. Approximately 29.3 g/L xylitol was obtained, with a yield of 73.2%, from 40 g/L d-arabitol in the batch biotransformation with the G. oxydans PZ strain. Moreover, the xylitol productivity (0.62 g/L/h) was 3.26-fold of the wild type strain (0.19 g/L/h). In repetitive batch biotransformation, the G. oxydans PZ cells were used for five cycles without incurring a significant loss in productivity. These results indicate that the recombinant G. oxydans PZ strain is economically feasible for xylitol production in industrial bioconversion.

Factors affecting the palmitoyl-coenzyme A desaturase of Saccharomyces cerevisiae

NASA Technical Reports Server (NTRS)

Klein, H. P.; Volkmann, C. M.

1975-01-01

The activity and stability of the palmitoyl-coenzyme A (CoA) desaturase complex of Saccharomyces cerevisiae was influenced by several factors. Cells, grown nonaerobically and then incubated with glucose, either in air or under N2, showed a marked increase in desaturase activity. Cycloheximide, added during such incubations, prevented the increase in activity, suggesting de novo synthesis. The stability of the desaturase from cells grown nonaerobically was affected by subsequent treatment of the cells; enzyme from freshly harvested cells, or from cells that were then shaken under nitrogen, readily lost activity upon washing or during density gradient analysis, whereas aerated cells, in the presence or absence of glucose, yielded stable enzyme preparations. The loss of activity in nonaerobic preparations could be reversed by adding soluble supernatant from these homogenates and could be prevented by growing the cells in the presence of palmitoleic acid and ergosterol, but not with several other lipids tested.

Current state of coenzyme Q(10) production and its applications.

PubMed

Jeya, Marimuthu; Moon, Hee-Jung; Lee, Jeong-Lim; Kim, In-Won; Lee, Jung-Kul

2010-02-01

Coenzyme Q(10) (CoQ(10)), an obligatory cofactor in the aerobic respiratory electron transfer for energy generation, is formed from the conjugation of a benzoquinone ring with a hydrophobic isoprenoid chain. CoQ(10) is now used as a nutritional supplement because of its antioxidant properties and is beneficial in the treatment of several human diseases when administered orally. Bioprocesses have been developed for the commercial production of CoQ(10) because of its increased demand, and these bioprocesses depend on microbes that produce high levels of CoQ(10) naturally. However, as knowledge of the biosynthetic enzymes and the regulatory mechanisms modulating CoQ(10) production increases, approaches arise for the genetic engineering of CoQ(10) production in Escherichia coli and Agrobacterium tumefaciens. This review focused on approaches for CoQ(10) production, strategies used to engineer CoQ(10) production in microbes, and potential applications of CoQ(10).

Plasma levels of coenzyme Q10 in children with hyperthyroidism.

PubMed

Menke, Thomas; Niklowitz, Petra; Reinehr, Thomas; de Sousa, Gideon John; Andler, Werner

2004-01-01

In hyperthyroidism, increased oxygen consumption and free radical production in the stimulated respiratory chain leads to oxidative stress. Apart from its antioxidative function, coenzyme Q10 (CoQ10) is involved in electron transport in the respiratory chain. The aim of this study was to determine whether there is a correlation between an increased respiratory chain activity and the state of CoQ10 in children with hyperthyroidism. The CoQ10 plasma concentration was measured by high-performance liquid chromatography in 12 children with hyperthyroidism before and after treatment. In the hyperthyroid state, the plasma level of CoQ10 was significantly decreased in comparison with the level in the euthyroid state. The correction of the hyperthyroid state resulted in a normalization of the CoQ10 level. Plasma CoQ10 deficiency appears to be related to the stimulated respiratory chain activity in children with hyperthyroidism. Copyright 2004 S. Karger AG, Basel

Critical period for acoustic preference in mice

PubMed Central

Yang, Eun-Jin; Lin, Eric W.; Hensch, Takao K.

2012-01-01

Preference behaviors are often established during early life, but the underlying neural circuit mechanisms remain unknown. Adapting a unique nesting behavior assay, we confirmed a “critical period” for developing music preference in C57BL/6 mice. Early music exposure between postnatal days 15 and 24 reversed their innate bias for silent shelter, which typically could not be altered in adulthood. Instead, exposing adult mice treated acutely with valproic acid or carrying a targeted deletion of the Nogo receptor (NgR−/−) unmasked a strong plasticity of preference consistent with a reopening of the critical period as seen in other systems. Imaging of cFos expression revealed a prominent neuronal activation in response to the exposed music in the prelimbic and infralimbic medial prefrontal cortex only under conditions of open plasticity. Neither behavioral changes nor selective medial prefrontal cortex activation was observed in response to pure tone exposure, indicating a music-specific effect. Open-field center crossings were increased concomitant with shifts in music preference, suggesting a potential anxiolytic effect. Thus, music may offer both a unique window into the emotional state of mice and a potentially efficient assay for molecular “brakes” on critical period plasticity common to sensory and higher order brain areas. PMID:23045690

Critical period for acoustic preference in mice.

PubMed

Yang, Eun-Jin; Lin, Eric W; Hensch, Takao K

2012-10-16

Preference behaviors are often established during early life, but the underlying neural circuit mechanisms remain unknown. Adapting a unique nesting behavior assay, we confirmed a "critical period" for developing music preference in C57BL/6 mice. Early music exposure between postnatal days 15 and 24 reversed their innate bias for silent shelter, which typically could not be altered in adulthood. Instead, exposing adult mice treated acutely with valproic acid or carrying a targeted deletion of the Nogo receptor (NgR(-/-)) unmasked a strong plasticity of preference consistent with a reopening of the critical period as seen in other systems. Imaging of cFos expression revealed a prominent neuronal activation in response to the exposed music in the prelimbic and infralimbic medial prefrontal cortex only under conditions of open plasticity. Neither behavioral changes nor selective medial prefrontal cortex activation was observed in response to pure tone exposure, indicating a music-specific effect. Open-field center crossings were increased concomitant with shifts in music preference, suggesting a potential anxiolytic effect. Thus, music may offer both a unique window into the emotional state of mice and a potentially efficient assay for molecular "brakes" on critical period plasticity common to sensory and higher order brain areas.

Changes in taste preference after colorectal surgery: A longitudinal study.

PubMed

Welchman, Sophie; Hiotis, Perryhan; Pengelly, Steven; Hughes, Georgina; Halford, Jason; Christiansen, Paul; Lewis, Stephen

2015-10-01

Nutrition is a key component of surgical enhanced recovery programmes. However, alterations in food preferences are often reported as reasons for patients not eating in the early postoperative period. We hypothesised that taste preferences are altered in the early postoperative period and this dysgeusia affects patients' food choices during this critical time. This is a longitudinal study looking at taste preferences of patients recovering from surgery. Patients undergoing colonic resections were recruited. Using visual analogue scales participants completed a questionnaire, taste tests and preference scoring of food images for the 6 groups of taste (bitter, salty, savoury, sour, spicy and sweet) preoperatively and on postoperative days 1-3. Patients were also offered snacks postoperatively, which represented foods from the six groups and consumption was measured. Differences from baseline were assessed using the Friedman's and Wilcoxon tests. 31 patients were studied. In the immediate postoperative period participants reported deterioration in their sense of taste (p ≤ 0.001), increased nausea (p < 0.001) and hunger (p = 0.03). Sweet, savoury and spicy tastes were the most popular during the perioperative period. However, only palatability for salty taste increased (p = 0.001) following surgery. The highest rated images were for savoury food with only the ratings for salty food increasing after surgery (p < 0.05). These findings concurred with the sweet, savoury and salty snacks being the most consumed foods in the postoperative period. Bitter, sour and spicy foods were the least frequently consumed. This is the first study to investigate postsurgical patients' food preferences. A consistent change in all the individual tastes with the exception of salty in the postoperative period was observed. The most desirable tastes were for savoury and sweet, reflecting patients' preoperative preferences. An improved understanding of taste may improve the resumption of

Oral contraceptive use in women changes preferences for male facial masculinity and is associated with partner facial masculinity.

PubMed

Little, Anthony C; Burriss, Robert P; Petrie, Marion; Jones, Benedict C; Roberts, S Craig

2013-09-01

Millions of women use hormonal contraception and it has been suggested that such use may alter mate preferences. To examine the impact of oral contraceptive (pill) use on preferences, we tested for within-subject changes in preferences for masculine faces in women initiating pill use. Between two sessions, initiation of pill use significantly decreased women's preferences for male facial masculinity but did not influence preferences for same-sex faces. To test whether altered preference during pill use influences actual partner choice, we examined facial characteristics in 170 age-matched male partners of women who reported having either been using or not using the pill when the partnership was formed. Both facial measurements and perceptual judgements demonstrated that partners of women who used the pill during mate choice have less masculine faces than partners of women who did not use hormonal contraception at this time. Our data (A) provide the first experimental evidence that initiation of pill use in women causes changes in facial preferences and (B) documents downstream effects of these changes on real-life partner selection. Given that hormonal contraceptive use is widespread, effects of pill use on the processes of partner formation have important implications for relationship stability and may have other biologically relevant consequences. Copyright © 2013 Elsevier Ltd. All rights reserved.

Nonhuman Primates Prefer Slow Tempos but Dislike Music Overall

ERIC Educational Resources Information Center

McDermott, Josh; Hauser, Marc D.

2007-01-01

Human adults generally find fast tempos more arousing than slow tempos, with tempo frequently manipulated in music to alter tension and emotion. We used a previously published method [McDermott, J., & Hauser, M. (2004). Are consonant intervals music to their ears? Spontaneous acoustic preferences in a nonhuman primate. Cognition, 94(2), B11-B21]…

Pharmacokinetic Interactions between Nelfinavir and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Atorvastatin and Simvastatin

PubMed Central

Hsyu, Poe-Hirr; Schultz-Smith, Melissa D.; Lillibridge, James H.; Lewis, Ronald H.; Kerr, Bradley M.

2001-01-01

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are effective agents in lowering cholesterol and triglycerides and are being used by human immunodeficiency virus-positive patients to treat the lipid elevation that may be associated with antiretroviral therapy. Many HMG-CoA reductase inhibitors and protease inhibitors are metabolized by the same cytochrome P450 enzyme 3A4 (CYP3A4). In addition, many protease inhibitors are potent inhibitors of CYP3A4. Therefore, coadministration of these two classes of drugs may cause significant drug interactions. This open-label, multiple-dose study was performed to determine the interactions between nelfinavir, a protease inhibitor, and two HMG-CoA reductase inhibitors, atorvastatin and simvastatin, in healthy volunteers. Thirty-two healthy subjects received either atorvastatin calcium (10 mg once a day) or simvastatin (20 mg once a day) for the first 14 days of the study. Nelfinavir (1,250 mg twice a day) was added on days 15 to 28. Pharmacokinetic assessment was performed on days 14 and 28. The study drugs were well tolerated. Nelfinavir increased the steady-state area under the plasma concentration-time curve during one dosing period (AUCτ) of atorvastatin 74% and the maximum concentration (Cmax) of atorvastatin 122% and increased the AUCτ of simvastatin 505% and the Cmax of simvastatin 517%. Neither atorvastatin nor simvastatin appeared to alter the pharmacokinetics of nelfinavir. It is recommended that coadministration of simvastatin with nelfinavir should be avoided, whereas atorvastatin should be used with nelfinavir with caution. PMID:11709322

Studies on the "Aerobic" Acetyl-Coenzyme A Synthetase of Saccharomyces Cerevisiae: Purification, Crystallization, and Physical Properties of the Enzyme

NASA Technical Reports Server (NTRS)

Satyanarayana, T.; Klein, Harold P.

1976-01-01

A procedure for the purification of a stable acetyl-coenzyme A synthetase (ACS) from aerobic cells of Saccharomyces cerevisiae is presented. The steps include differential centrifugation, solubilization of the bound enzyme from the crude mitochondrial fraction, ammonium sulfate fractionation, crystallization to constant specific activity from ammonium sulfate solutions followed by Bio-Gel A-1.5 m column chromatography. The resulting enzyme preparation is homogeneous as judged by chromatography on Bio-Gel columns, QAE-Sephadex A-50 anion exchange columns, analytical ultracentrifugal studies, and polyacrylamide gel electrophoresis. Sedimentation velocity runs revealed a single symmetric peak with an s(sub (20,w)) value of 10.6. The molecular weight of the native enzyme, as determined by gel filtration and analytical ultracentrifugation, is 250,000 +/- 500. In polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, the molecular weight of the single polypeptide chain is 83,000 +/- 500. The purified enzyme is inhibited by palmityl-coenzyme A with a Hill interaction coefficient, n, of 2.88. These studies indicate that the ACS of aerobic Saccharomyces cerevisiae is composed of three subunits of identical or nearly identical size.

Subliminal smells can guide social preferences.

PubMed

Li, Wen; Moallem, Isabel; Paller, Ken A; Gottfried, Jay A

2007-12-01

It is widely accepted that unconscious processes can modulate judgments and behavior, but do such influences affect one's daily interactions with other people? Given that olfactory information has relatively direct access to cortical and subcortical emotional circuits, we tested whether the affective content of subliminal odors alters social preferences. Participants rated the likeability of neutral faces after smelling pleasant, neutral, or unpleasant odors delivered below detection thresholds. Odor affect significantly shifted likeability ratings only for those participants lacking conscious awareness of the smells, as verified by chance-level trial-by-trial performance on an odor-detection task. Across participants, the magnitude of this priming effect decreased as sensitivity for odor detection increased. In contrast, heart rate responses tracked odor valence independently of odor awareness. These results indicate that social preferences are subject to influences from odors that escape awareness, whereas the availability of conscious odor information may disrupt such effects.

Early life exposure to a high fat diet promotes long-term changes in dietary preferences and central reward signaling.

PubMed

Teegarden, S L; Scott, A N; Bale, T L

2009-09-15

Overweight and obesity in the United States continues to grow at epidemic rates in large part due to the overconsumption of calorically-dense palatable foods. Identification of factors influencing long-term macronutrient preferences may elucidate points of prevention and behavioral modification. In our current study, we examined the adult macronutrient preferences of mice acutely exposed to a high fat diet during the third postnatal week. We hypothesized that the consumption of a high fat diet during early life would alter the programming of central pathways important in adult dietary preferences. As adults, the early-exposed mice displayed a significant preference for a diet high in fat compared to controls. This effect was not due to diet familiarity as mice exposed to a novel high carbohydrate diet during this same early period failed to show differences in macronutrient preferences as adults. The increased intake of high fat diet in early exposed mice was specific to dietary preferences as no changes were detected for total caloric intake or caloric efficiency. Mechanistically, mice exposed to a high fat diet during early life exhibited significant alterations in biochemical markers of dopamine signaling in the nucleus accumbens, including changes in levels of phospho-dopamine and cyclic AMP-regulated phosphoprotein, molecular weight 32 kDa (DARPP-32) threonine-75, DeltaFosB, and cyclin-dependent kinase 5. These results support our hypothesis that even brief early life exposure to calorically-dense palatable diets alters long-term programming of central mechanisms important in dietary preferences and reward. These changes may underlie the passive overconsumption of high fat foods contributing to the increasing body mass in the western world.

Coenzyme Q10 protects hair cells against aminoglycoside.

PubMed

Sugahara, Kazuma; Hirose, Yoshinobu; Mikuriya, Takefumi; Hashimoto, Makoto; Kanagawa, Eiju; Hara, Hirotaka; Shimogori, Hiroaki; Yamashita, Hiroshi

2014-01-01

It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10) is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group). In the neomycin group, utricles were cultured with neomycin (1 mM) to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30-0.3 µM). Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.

Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.

PubMed

Alehagen, Urban; Johansson, Peter; Aaseth, Jan; Alexander, Jan; Brismar, Kerstin

2017-01-01

Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P>0.0001), IGF-1 SD score (F = 29; P<0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of

Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency.

PubMed

Di Giovanni, S; Mirabella, M; Spinazzola, A; Crociani, P; Silvestri, G; Broccolini, A; Tonali, P; Di Mauro, S; Servidei, S

2001-08-14

Two brothers with myopathic coenzyme Q10 (CoQ10) deficiency responded dramatically to CoQ10 supplementation. Muscle biopsies before therapy showed ragged-red fibers, lipid storage, and complex I + III and II + III deficiency. Approximately 30% of myofibers had multiple features of apoptosis. After 8 months of treatment, excessive lipid storage resolved, CoQ10 level normalized, mitochondrial enzymes increased, and proportion of fibers with TUNEL-positive nuclei decreased to 10%. The authors conclude that muscle CoQ10 deficiency can be corrected by supplementation of CoQ10, which appears to stimulate mitochondrial proliferation and to prevent apoptosis.

Patient preference to use a questionnaire varies according to attributes.

PubMed

Kim, Na Yae; Richardson, Lyndsay; He, Weilin; Jones, Glenn

2011-08-01

Health care professionals may assume questionnaires are burdensome to patients, and this limits their use in clinical settings and promotes simplification. However, patient adherence may improve by optimizing questionnaire attributes and contexts. This cross-sectional survey used Contingent Valuation methods to directly elicit patient preference for conventional monitoring of symptoms, versus adding a tool to monitoring. Under explicit consideration was the 10-question Edmonton Symptom Assessment System (ESAS). In the questionnaire, attributes of ESAS were sequentially altered to try and force preference reversal. A separate group of participants completed both questionnaire and interviews to explore questionnaire reliability, and extend validity. Overall, 24 of 43 participants preferred using ESAS. Most important attributes to preference were frequency, specificity, and complexity. Where preference is initially against ESAS, it may reverse by simplifying the tool and its administrative processes. Interviews in 10 additional participants supported reproducibility and validity of the questionnaire method. Preference for using tools increases when tools are made relevant and used more appropriately. Questionnaires completed by patients as screening tools or aids to communication may be under-utilized. Optimization of ESAS and similar tools may be guided by empirical findings, including those obtained from Contingent Valuation methodologies. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Reproductive ambition predicts partnered, but not unpartnered, women's preferences for masculine men.

PubMed

Watkins, Christopher D

2012-08-01

Changing circumstances alter the costs and benefits of choosing different mates and are thought to be reflected in women's mate preferences. Indeed, several lines of reasoning, and some prior studies, suggest that individual differences in women's preferences for cues of men's underlying health will be more apparent among partnered women than among unpartnered women. The current study shows that preferences for male faces with masculine shape cues, characteristics that are thought to signal men's underlying health, are positively correlated with partnered, but not unpartnered, women's reported reproductive ambition (i.e., their desire to become pregnant). These findings (1) present new evidence for systematic variation in women's mating strategies, (2) suggest that partnership status may be important for potentially adaptive variation in women's mate preferences, and (3) suggest that reproductive ambition may influence women's mate preferences. Alternative explanations for these findings, focusing on the possible effects of a range of variables that may be correlated with reproductive ambition in partnered women and influence their masculinity preferences, are also discussed. ©2011 The British Psychological Society.

Altered small intestinal absorptive enzyme activities in leptin-deficient obese mice: influence of bowel resection.

PubMed

Kiely, James M; Noh, Jae H; Svatek, Carol L; Pitt, Henry A; Swartz-Basile, Deborah A

2006-07-01

Residual bowel increases absorption after massive small bowel resection. Leptin affects intestinal adaptation, carbohydrate, peptide, and lipid handling. Sucrase, peptidase, and acyl coenzyme A:monoacylglycerol acyltransferase (MGAT) are involved in carbohydrate, protein, and lipid absorption. We hypothesized that leptin-deficient obese mice would have altered absorptive enzymes compared with controls before and after small bowel resection. Sucrase, peptidase (aminopeptidase N [ApN], dipeptidyl peptidase IV [DPPIV]), and MGAT activities were determined from lean control (C57BL/6J, n = 16) and leptin-deficient (Lep(ob), n = 16) mice small bowel before and after 50% resection. Ileal sucrase activity was greater in obese mice before and after resection. Jejunal ApN and DPPIV activities were lower for obese mice before resection; ileal ApN activity was unaltered after resection for both strains. Resection increased DPPIV activity in both strains. Jejunal MGAT in obese mice decreased postresection. In both strains, ileal MGAT activity decreased after resection, and obese mice had greater activity in remnant ileum. After small bowel resection, leptin-deficient mice have increased sucrase activity and diminished ileal ApN, DPPIV, and MGAT activity compared with controls. Therefore, we conclude that leptin deficiency alters intestinal enzyme activity in unresected animals and after small bowel resection. Altered handling of carbohydrate, protein, and lipid may contribute to obesity and diabetes in leptin-deficient mice.

Arecoline Alters Taste Bud Cell Morphology, Reduces Body Weight, and Induces Behavioral Preference Changes in Gustatory Discrimination in C57BL/6 Mice.

PubMed

Peng, Wei-Hau; Chau, Yat-Pang; Lu, Kuo-Shyan; Kung, Hsiu-Ni

2016-01-01

Arecoline, a major alkaloid in areca nuts, is involved in the pathogenesis of oral diseases. Mammalian taste buds are the structural unit for detecting taste stimuli in the oral cavity. The effects of arecoline on taste bud morphology are poorly understood. Arecoline was injected intraperitoneally (IP) into C57BL/6 mice twice daily for 1-4 weeks. After arecoline treatment, the vallate papillae were processed for electron microscopy and immunohistochemistry analysis of taste receptor proteins (T1R2, T1R3, T1R1, and T2R) and taste associated proteins (α-gustducin, PLCβ2, and SNAP25). Body weight, food intake and water consumption were recorded. A 2-bottle preference test was also performed. The results demonstrated that 1) arecoline treatment didn't change the number and size of the taste buds or taste bud cells, 2) electron microscopy revealed the change of organelles and the accumulation of autophagosomes in type II cells, 3) immunohistochemistry demonstrated a decrease of taste receptor T1R2- and T1R3-expressing cells, 4) the body weight and food intake were markedly reduced, and 5) the sweet preference behavior was reduced. We concluded that the long-term injection of arecoline alters the morphology of type II taste bud cells, retards the growth of mice, and affects discrimination competencies for sweet tastants. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Soy protein supports cardiovascular health by downregulating hydroxymethylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein-2 and increasing antioxidant enzyme activity in rats with dextran sodium sulfate-induced mild systemic inflammation.

PubMed

Marsh, Tanya G; Straub, Rachel K; Villalobos, Fatima; Hong, Mee Young

2011-12-01

Animal and human studies have indicated that the presence of soy in the diet improves cardiovascular health. Inflammation plays a pivotal role in the progression of cardiovascular disease (CVD). However, little is known about how dextran sodium sulfate (DSS)-induced systemic inflammation impacts overall heart health and, correspondingly, how soy protein modulates risk of CVD development in DSS-induced systemic inflammation. We hypothesized that soy protein-fed rats would have a lower risk of CVD by beneficial alteration of gene expression involving lipid metabolism and antioxidant capacity in DSS-induced systemic inflammation. Forty Sprague-Dawley rats were divided into 4 groups: casein, casein + DSS, soy protein, and soy protein + DSS. After 26 days, inflammation was induced in one group from each diet by incorporating 3% DSS in drinking water for 48 hours. Soy protein-fed rats had lower final body weights (P = .010), epididymal fat weights (P = .049), total cholesterol (P < .001), and low-density lipoprotein cholesterol (P < .001). In regard to gene expression, soy protein-fed rats had lower sterol regulatory element-binding protein-2 (P = .032) and hydroxymethylglutaryl-coenzyme A reductase (P = .028) levels and higher low-density lipoprotein receptor levels (P = .036). Antioxidant enzyme activity of superoxide dismutase and catalase was higher among the soy protein groups (P = .037 and P = .002, respectively). These results suggest that soy protein positively influences cardiovascular health by regulating serum lipids through modified expression of sterol regulatory element-binding protein-2 and its downstream genes (ie, hydroxymethylglutaryl-coenzyme A reductase and low-density lipoprotein receptor) and by promoting the antioxidant enzyme activity of superoxide dismutase and catalase. Copyright © 2011 Elsevier Inc. All rights reserved.

Slot Machine Preferences of Pathological and Recreational Gamblers Are Verbally Constructed

ERIC Educational Resources Information Center

Dixon, Mark R.; Bihler, Holly L.; Nastally, Becky L.

2011-01-01

The current study attempted to alter preferences for concurrently available slot machines of equal payout through the development of equivalence classes and subsequent transfers of functions. Participants rated stimuli consisting of words thought to be associated with having a gambling problem (e.g., "desperation" and "debt"), words associated…

Fine tuning of coenzyme specificity in family 2 aldo-keto reductases revealed by crystal structures of the Lys-274 → Arg mutant of Candida tenuis xylose reductase (AKR2B5) bound to NAD + and NADP +

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

Leitgeb, Stefan; Petschacher, Barbara; Wilson, David K.

2005-01-11

Aldo-keto reductases of family 2 employ single site replacement Lys → Arg to switch their cosubstrate preference from NADPH to NADH. X-ray crystal structures of Lys-274 → Arg mutant of Candida tenuis xylose reductase (AKR2B5) bound to NAD + and NADP + were determined at a resolution of 2.4 and 2.3 Å, respectively. Due to steric conflicts in the NADP +-bound form, the arginine side chain must rotate away from the position of the original lysine side chain, thereby disrupting a network of direct and water-mediated interactions between Glu-227, Lys-274 and the cofactor 2'-phosphate and 3'-hydroxy groups. Because anchoring contactsmore » of its Glu-227 are lost, the coenzyme-enfolding loop that becomes ordered upon binding of NAD(P) + in the wild-type remains partly disordered in the NADP +-bound mutant. The results delineate a catalytic reaction profile for the mutant in comparison to wild-type.« less

Flavor preferences conditioned by oral monosodium glutamate in mice.

PubMed

Ackroff, Karen; Sclafani, Anthony

2013-11-01

The prototypic umami substance monosodium glutamate (MSG) reinforces preferences for its own flavor, as well as preferences for flavors associated with it, by conditioning processes. Mice of 3 inbred strains (C57BL/6J (B6), 129P3/J, and FVB/NJ) and 2 taste-knockout (KO) groups derived from the B6 lineage were initially indifferent to 200mM MSG, but this evaluation was altered by forced exposure to MSG. B6 and KO mice acquired an MSG preference, 129 mice remained indifferent, and FVB mice avoided MSG. The shifts in preference imply a postoral basis for MSG effects, suggesting that it could produce preferences for associated flavors. New mice were trained with a conditioned stimulus (CS+) flavor mixed in 200mM MSG and a CS- flavor in water. Similar to the parent B6 strain, mice missing the T1r3 element of an umami receptor or the downstream signaling component Trpm5 learned to prefer the CS+ flavor and subsequently showed similar preferences for MSG in an ascending concentration series. Consistent with their responses to forced exposure, the 129 strain did not acquire a significant CS+ preference, and the FVB strain avoided the CS+ flavor. The 129 and FVB strains showed little attraction in the ascending MSG concentration series. Together, these data indicate that the postoral effects of MSG can modulate responses to its own and MSG-paired flavors. The basis for strain differences in the responses to MSG is not certain, but the taste-signaling elements T1r3 and Trpm5, which are also present in the gut, are not required for mediation of this flavor learning.

Thermophilic Coenzyme B12-Dependent Acyl Coenzyme A (CoA) Mutase from Kyrpidia tusciae DSM 2912 Preferentially Catalyzes Isomerization of (R)-3-Hydroxybutyryl-CoA and 2-Hydroxyisobutyryl-CoA.

PubMed

Weichler, Maria-Teresa; Kurteva-Yaneva, Nadya; Przybylski, Denise; Schuster, Judith; Müller, Roland H; Harms, Hauke; Rohwerder, Thore

2015-07-01

The recent discovery of a coenzyme B12-dependent acyl-coenzyme A (acyl-CoA) mutase isomerizing 3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA in the mesophilic bacterium Aquincola tertiaricarbonis L108 (N. Yaneva, J. Schuster, F. Schäfer, V. Lede, D. Przybylski, T. Paproth, H. Harms, R. H. Müller, and T. Rohwerder, J Biol Chem 287:15502-15511, 2012, http://dx.doi.org/10.1074/jbc.M111.314690) could pave the way for a complete biosynthesis route to the building block chemical 2-hydroxyisobutyric acid from renewable carbon. However, the enzyme catalyzes only the conversion of the stereoisomer (S)-3-hydroxybutyryl-CoA at reasonable rates, which seriously hampers an efficient combination of mutase and well-established bacterial poly-(R)-3-hydroxybutyrate (PHB) overflow metabolism. Here, we characterize a new 2-hydroxyisobutyryl-CoA mutase found in the thermophilic knallgas bacterium Kyrpidia tusciae DSM 2912. Reconstituted mutase subunits revealed highest activity at 55°C. Surprisingly, already at 30°C, isomerization of (R)-3-hydroxybutyryl-CoA was about 7,000 times more efficient than with the mutase from strain L108. The most striking structural difference between the two mutases, likely determining stereospecificity, is a replacement of active-site residue Asp found in strain L108 at position 117 with Val in the enzyme from strain DSM 2912, resulting in a reversed polarity at this binding site. Overall sequence comparison indicates that both enzymes descended from different prokaryotic thermophilic methylmalonyl-CoA mutases. Concomitant expression of PHB enzymes delivering (R)-3-hydroxybutyryl-CoA (beta-ketothiolase PhaA and acetoacetyl-CoA reductase PhaB from Cupriavidus necator) with the new mutase in Escherichia coli JM109 and BL21 strains incubated on gluconic acid at 37°C led to the production of 2-hydroxyisobutyric acid at maximal titers of 0.7 mM. Measures to improve production in E. coli, such as coexpression of the chaperone MeaH and repression of

High degree of efficacy in the treatment of cyclic vomiting syndrome with combined co-enzyme Q10, L-carnitine and amitriptyline, a case series

PubMed Central

2011-01-01

Background Cyclic vomiting syndrome (CVS), defined by recurrent stereotypical episodes of nausea and vomiting, is a relatively-common disabling and historically difficult-to-treat condition associated with migraine headache and mitochondrial dysfunction. Limited data suggests that the anti-migraine therapies amitriptyline and cyproheptadine, and the mitochondrial-targeted cofactors co-enzyme Q10 and L-carnitine, have efficacy in episode prophylaxis. Methods A retrospective chart review of 42 patients seen by one clinician that met established CVS diagnostic criteria revealed 30 cases with available outcome data. Participants were treated on a loose protocol consisting of fasting avoidance, co-enzyme Q10 and L-carnitine, with the addition of amitriptyline (or cyproheptadine in those < 5 years) in refractory cases. Blood level monitoring of the therapeutic agents featured prominently in management. Results Vomiting episodes resolved in 23 cases, and improved by > 75% and > 50% in three and one additional case respectively. Among the three treatment failures, two could not tolerate amitriptyline (as was also the case in the child with only > 50% efficacy) and one had multiple congenital gastrointestinal anomalies. Excluding the latter case, substantial efficacy (> 75% response) was 26/29 at the start of treatment, and 26/26 in those able to tolerate the regiment, including high dosages of amitriptyline. Conclusion Our data suggest that a protocol consisting of mitochondrial-targeted cofactors (co-enzyme Q10 and L-carnitine) plus amitriptyline (or possibly cyproheptadine in preschoolers) coupled with blood level monitoring is highly effective in the prevention of vomiting episodes. PMID:21846334

Naloxone treatment alters gene expression in the mesolimbic reward system in 'junk food' exposed offspring in a sex-specific manner but does not affect food preferences in adulthood.

PubMed

Gugusheff, J R; Ong, Z Y; Muhlhausler, B S

2014-06-22

We have previously reported that the opioid receptor blocker, naloxone, is less effective in reducing palatable food intake in offspring exposed to a maternal cafeteria diet during the perinatal period, implicating a desensitization of the central opioid pathway in the programming of food preferences. The present study aimed to investigate the effect of a maternal cafeteria diet and naloxone treatment on the development of the mesolimbic reward pathway and food choices in adulthood. We measured mRNA expression of key components of the reward pathway (mu-opioid receptor, proenkephalin, tyrosine hydroxylase, D1 and D2 receptors and the dopamine active transporter (DAT)) in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of the offspring of control and cafeteria fed (JF) dams at weaning and after a 10-day naloxone treatment post-weaning and determined food preferences in adulthood in the remaining offspring. Naloxone treatment decreased the expression of DAT by 8.2 fold in female control offspring but increased it by 4.3 fold in female offspring of JF dams relative to the saline-injected reference groups. Proenkephalin mRNA expression was higher in the NAc of female JF offspring compared to controls, independent of naloxone treatment (P<0.05). There was no effect of naloxone treatment on food preferences in adulthood in either control or JF offspring. These data indicate that prenatal exposure to a cafeteria diet alters the impact of opioid signaling blockade in the early post-weaning period on gene expression in the central reward pathway in a sex specific manner, but that these changes in gene expression do not appear to have any persistent impact on food preferences in adulthood. Copyright © 2014 Elsevier Inc. All rights reserved.

Methyl-coenzyme M reductase A as an indicator to estimate methane production from dairy cows.

PubMed

Aguinaga Casañas, M A; Rangkasenee, N; Krattenmacher, N; Thaller, G; Metges, C C; Kuhla, B

2015-06-01

The evaluation of greenhouse gas mitigation strategies requires the quantitative assessment of individual methane production. Because methane measurement in respiration chambers is highly accurate, but also comprises various disadvantages such as limited capacity and high costs, the establishment of an indicator for estimating methane production of individual ruminants would provide an alternative to direct methane measurement. Methyl-coenzyme M reductase is involved in methanogenesis and the subunit α of methyl-coenzyme M reductase is encoded by the mcrA gene of rumen archaea. We therefore examined the relationship between methane emissions of Holstein dairy cows measured in respiration chambers with 2 different diets (high- and medium-concentrate diet) and the mcrA DNA and mcrA cDNA abundance determined from corresponding rumen fluid samples. Whole-body methane production per kilogram of dry matter intake and mcrA DNA normalized to the abundance of the rrs gene coding for 16S rRNA correlated significantly when using qmcrA primers. Use of qmcrA primers also revealed linear correlation between mcrA DNA copy number and methane yield. Regression analyses based on normalized mcrA cDNA abundances revealed no significant linear correlation with methane production per kilogram of dry matter intake. Furthermore, the correlations between normalized mcrA DNA abundance and the rumen fluid concentration of acetic and isobutyric acid were positive, whereas the correlations with propionic and lactic acid were negative. These data suggest that the mcrA DNA approach based on qmcrA primers could potentially be a molecular proxy for methane yield after further refinement. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Primary coenzyme Q10 (CoQ 10) deficiencies and related nephropathies.

PubMed

Ozaltin, Fatih

2014-06-01

Oxidative phosphorylation (OXPHOS) is a metabolic pathway that uses energy released by the oxidation of nutrients to generate adenosine triphosphate (ATP). Coenzyme Q10 (CoQ10), also known as ubiquinone, plays an essential role in the human body not only by generating ATP in the mitochondrial respiratory chain but also by providing protection from reactive oxygen species (ROS) and functioning in the activation of many mitochondrial dehydrogenases and enzymes required in pyrimidine nucleoside biosynthesis. The presentations of primary CoQ10 deficiencies caused by genetic mutations are very heterogeneous. The phenotypes related to energy depletion or ROS production may depend on the content of CoQ10 in the cell, which is determined by the severity of the mutation. Primary CoQ10 deficiency is unique among mitochondrial disorders because early supplementation with CoQ10 can prevent the onset of neurological and renal manifestations. In this review I summarize primary CoQ10 deficiencies caused by various genetic abnormalities, emphasizing its nephropathic form.

Cardioprotective Effect of Coenzyme Q10 on Apoptotic Myocardial Cell Death by Regulation of Bcl-2 Gene Expression

PubMed Central

Khan, Najam Ali; Abid, M.; Ahmad, Aftab; Abuzinadah, Mohammed F.; Basheikh, Mohammed; Kishore, Kamal

2017-01-01

Objectives: To investigate the effect of coenzyme Q10 (CoQ10) on apoptotic myocardial cell death in rat model of heart ischemia and reperfusion I/R injury. Materials and Methods: Eighteen rats (200–250 g) were divided into three groups of 6 rats in each. Group I (sham-operated control group): this is the control group. The animals received the surgical procedure without IR injury or any drug treatment. Group II (I/R group): ischemia was accomplished by the occlusion of coronary artery for 30 min followed by reperfusion for 45 min and Group-III (Coenzyme Q10 treated group): Treated with CoQ10 at a dose of 1 mg/kg, postoperative for 7 days before induction of IR injury. Results: The study revealed that pretreatment with CoQ10 has shown protective effect on apoptotic rat heart and agreed with earlier reports that CoQ10 significantly protects from oxidative stress and cytopathological changes caused by cardiac ischemia followed by reperfusion and attenuated decrease of antioxidant enzymes. Nitric oxide production in the heart of ischemic rats was significantly increased by the pretreatment with CoQ10 in comparison with IR group. Conclusions: CoQ10 protects against cardiac apoptosis induced by IR injury by significantly decreasing the apoptotic DNA and regulating the expression of Bcl-2 gene. PMID:29081620

Structural analysis, plastid localization, and expression of the biotin carboxylase subunit of acetyl-coenzyme A carboxylase from tobacco.

PubMed

Shorrosh, B S; Roesler, K R; Shintani, D; van de Loo, F J; Ohlrogge, J B

1995-06-01

Acetyl-coenzyme A carboxylase (ACCase, EC 6.4.1.2) catalyzes the synthesis of malonyl-coenzyme A, which is utilized in the plastid for de novo fatty acid synthesis and outside the plastid for a variety of reactions, including the synthesis of very long chain fatty acids and flavonoids. Recent evidence for both multifunctional and multisubunit ACCase isozymes in dicot plants has been obtained. We describe here the isolation of a tobacco (Nicotiana tabacum L. cv bright yellow 2 [NT1]) cDNA clone (E3) that encodes a 58.4-kD protein that shares 80% sequence similarity and 65% identity with the Anabaena biotin carboxylase subunit of ACCase. Similar to other biotin carboxylase subunits of acetyl-CoA carboxylase, the E3-encoded protein contains a putative ATP-binding motif but lacks a biotin-binding site (methionine-lysine-methionine or methionine-lysine-leucine). The deduced protein sequence contains a putative transit peptide whose function was confirmed by its ability to direct in vitro chloroplast uptake. The subcellular localization of this biotin carboxylase has also been confirmed to be plastidial by western blot analysis of pea (Pisum sativum), alfalfa (Medicago sativa L.), and castor (Ricinus communis L.) plastid preparations. Northern blot analysis indicates that the plastid biotin carboxylase transcripts are expressed at severalfold higher levels in castor seeds than in leaves.

Structural analysis, plastid localization, and expression of the biotin carboxylase subunit of acetyl-coenzyme A carboxylase from tobacco.

PubMed Central

Shorrosh, B S; Roesler, K R; Shintani, D; van de Loo, F J; Ohlrogge, J B

1995-01-01

Acetyl-coenzyme A carboxylase (ACCase, EC 6.4.1.2) catalyzes the synthesis of malonyl-coenzyme A, which is utilized in the plastid for de novo fatty acid synthesis and outside the plastid for a variety of reactions, including the synthesis of very long chain fatty acids and flavonoids. Recent evidence for both multifunctional and multisubunit ACCase isozymes in dicot plants has been obtained. We describe here the isolation of a tobacco (Nicotiana tabacum L. cv bright yellow 2 [NT1]) cDNA clone (E3) that encodes a 58.4-kD protein that shares 80% sequence similarity and 65% identity with the Anabaena biotin carboxylase subunit of ACCase. Similar to other biotin carboxylase subunits of acetyl-CoA carboxylase, the E3-encoded protein contains a putative ATP-binding motif but lacks a biotin-binding site (methionine-lysine-methionine or methionine-lysine-leucine). The deduced protein sequence contains a putative transit peptide whose function was confirmed by its ability to direct in vitro chloroplast uptake. The subcellular localization of this biotin carboxylase has also been confirmed to be plastidial by western blot analysis of pea (Pisum sativum), alfalfa (Medicago sativa L.), and castor (Ricinus communis L.) plastid preparations. Northern blot analysis indicates that the plastid biotin carboxylase transcripts are expressed at severalfold higher levels in castor seeds than in leaves. PMID:7610168

Biochemistry of methyl-coenzyme M reductase: the nickel metalloenzyme that catalyzes the final step in synthesis and the first step in anaerobic oxidation of the greenhouse gas methane.

PubMed

Ragsdale, Stephen W

2014-01-01

Methane, the major component of natural gas, has been in use in human civilization since ancient times as a source of fuel and light. Methanogens are responsible for synthesis of most of the methane found on Earth. The enzyme responsible for catalyzing the chemical step of methanogenesis is methyl-coenzyme M reductase (MCR), a nickel enzyme that contains a tetrapyrrole cofactor called coenzyme F430, which can traverse the Ni(I), (II), and (III) oxidation states. MCR and methanogens are also involved in anaerobic methane oxidation. This review describes structural, kinetic, and computational studies aimed at elucidating the mechanism of MCR. Such studies are expected to impact the many ramifications of methane in our society and environment, including energy production and greenhouse gas warming.

[Coenzyme Q10 enhances the expression of Bcl-2 and inhibits the expressions of Bax and GSK-3β in the hippocampus of rats exposed to ischemia/reperfusion injury].

PubMed

Tian, Shuang; Wang, Di; Li, Xiaodong; Tang, Jianjie; Han, Guang; Dai, Yongyi

2013-07-01

To investigate the effects of coenzyme Q10 pretreatment on the expressions of Bcl-2, Bax and glycogen synthase kinase-3β (GSK-3β) in rats suffering from ischemia/reperfusion injury. Thirty-six adult male SD rats were randomly assigned into 3 groups: sham-operated group (sham), ischemia/reperfusion group (I/R) and coenzyme Q10 preconditioning group (Q10). Focal cerebral ischemia/reperfusion models were established in experimental rats by blocking middle cerebral artery with suture. Histological changes of hippocampal neurons were observed by HE staining. The expressions of Bcl-2, Bax and GSK-3β were detected by immunohistochemistry and Western blotting. Immunohistochemistry showed that the percentage of Bcl-2 positive cells increased in the hippocampus, while the percentages of Bax and GSK-3β positive cells decreased in Q10 group compared with I/R group. Western blotting revealed that the expression level of Bcl-2 was higher and the expression levels of Bax and GSK-3β were lower in Q10 group than in I/R group. There were significant differences between the two groups (P<0.05). Coenzyme Q10 promoted the expression of Bcl-2 and suppressed the expressions of Bax and GSK-3β in the hippocampus of rats exposed to cerebral ischemia/reperfusion.

Aesthetic breast shape preferences among plastic surgeons.

PubMed

Broer, Peter Niclas; Juran, Sabrina; Walker, Marc E; Ng, Reuben; Weichman, Katie; Tanna, Neil; Liu, Yuen-Jong; Shah, Ajul; Patel, Anup; Persing, John A; Thomson, James Grant

2015-06-01

There has been little discussion in the plastic surgery literature regarding breast shape preferences among plastic surgeons, despite strong evidence that such aesthetic preferences are influenced by multiple factors. Much effort has been focused on delineating the objective criteria by which an "attractive" breast might be defined. This study aimed at providing a better understanding of the presence and significance of differences in personal aesthetic perception, and how these relate to a plastic surgeon's demographic, ethnic, and cultural background, as well as practice type (academic vs private). An interactive online survey was designed. Modifiable ranges of upper pole fullness and areola size were achieved via digital alteration, enabling participants to interactively change the shape of a model's breasts. The questionnaire was translated into multiple languages and sent to plastic surgeons worldwide. Demographic data were also collected. Analysis of variance was used to elucidate plastic surgeon's breast shape preferences in respect to sex and age, geographic and ethnic background, as well as practice type. The authors gathered 614 responses from 29 different countries. Significant differences regarding preferences for upper pole fullness, areola size in the natural breast, and areola size in the augmented breast were identified across surgeons from the different countries. Further, significant relationships regarding breast shape preferences were distilled between the age and sex of the surgeon, as well as the practice type. No differences were found in respect to the surgeons' self-reported ethnic background. Country of residence, age, and practice type significantly impact breast shape preferences of plastic surgeons. These findings have implications for both patients seeking and surgeons performing cosmetic and reconstructive breast surgery. In an increasingly global environment, cultural differences and international variability must be considered when

Cold temperature preference in bacterially infected Drosophila melanogaster improves survival but is remarkably suboptimal.

PubMed

Fedorka, Kenneth M; Kutch, Ian C; Collins, Louisa; Musto, Edward

Altering one's temperature preference (e.g. behavioral fever or behavioral chill) is a common immune defense among ectotherms that is likely to be evolutionarily conserved. However, the temperature chosen by an infected host may not be optimal for pathogen defense, causing preference to be inefficient. Here we examined the efficiency of temperature preference in Drosophila melanogaster infected with an LD 50 of the gram negative bacteria Pseudomonas aeruginosa. To this end, we estimated the host's uninfected and infected temperature preferences as well as their optimal survival temperature. We found that flies decreased their preference from 26.3°C to 25.2°C when infected, and this preference was stable over 48h. Furthermore, the decrease in temperature preference was associated with an increased chance of surviving the infection. Nevertheless, the infected temperature preference did not coincide with the optimum temperature for infection survival, which lies at or below 21.4°C. These data suggest that the behavioral response to P. aeruginosa infection is considerably inefficient, and the mechanisms that may account for this pattern are discussed. Future studies of infected temperature preferences should document its efficiency, as this understudied aspect of behavioral immunity can provide important insight into preference evolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lingual CD36 and nutritional status differentially regulate fat preference in obesity-prone and obesity-resistant rats.

PubMed

Douglas Braymer, H; Zachary, Hannah; Schreiber, Allyson L; Primeaux, Stefany D

2017-05-15

Lingual fatty acid receptors (i.e. CD36) mediate the orosensory perception of fat/fatty acids and may contribute to the susceptibility to develop obesity. The current study tested the hypothesis that fat/fatty acid preference in obesity-prone (OP, Osborne-Mendel) and obesity-resistant (OR, S5B/Pl) rats is mediated by nutritional status and lingual CD36. To determine if nutritional status affected linoleic acid (LA) preference in OP and OR rats, rats were either fasted overnight or fed a high fat diet (60% kcal from fat). In OR rats, fasting increased the preference for higher concentrations of LA (1.0%), while consumption of a high fat diet decreased LA preference. In OP rats, fasting increased the preference for lower concentrations of LA (0.25%), however high fat diet consumption did not alter LA preference. To determine if lingual CD36 mediated the effects of an overnight fast on LA preference, the expression of lingual CD36 mRNA was assessed and the effect of lingual application of CD36 siRNA on LA preference was determined. Fasting increased lingual CD36 mRNA expression in OR rats, but failed to alter lingual CD36 mRNA in OP rats. Following an overnight fast, application of lingual CD36 siRNA led to a decrease in LA preference in OR, but not OP rats. Lingual application of CD36 siRNA was also used to determine if lingual CD36 mediated the intake and preference for a high fat diet in OP and OR rats. CD36 siRNA decreased the preference and intake of high fat diet in OR rats, but not OP rats. The results from this study suggest that the dysregulation of lingual CD36 in OP rats is a potential factor leading to increased fat intake and fat preference and an enhanced susceptibility to develop obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

Lingual CD36 and nutritional status differentially regulate fat preference in obesity-prone and obesity-resistant rats

PubMed Central

Braymer, H. Douglas; Zachary, Hannah; Schreiber, Allyson L.; Primeaux, Stefany D.

2017-01-01

Lingual fatty acid receptors (i.e. CD36) mediate the orosensory perception of fat/fatty acids and may contribute to the susceptibility to develop obesity. The current study tested the hypothesis that fat/fatty acid preference in obesity-prone (OP, Osborne-Mendel) and obesity-resistant (OR, S5B/Pl) rats is mediated by nutritional status and lingual CD36. To determine if nutritional status affected linoleic acid (LA) preference in OP and OR rats, rats were either fasted overnight or fed a high fat diet (60% kcal from fat). In OR rats, fasting increased the preference for higher concentrations of LA (1.0%), while consumption of a high fat diet decreased LA preference. In OP rats, fasting increased the preference for lower concentrations of LA (0.25%), however high fat diet consumption did not alter LA preference. To determine if lingual CD36 mediated the effects of an overnight fast on LA preference, the expression of lingual CD36 mRNA was assessed and the effect of lingual application of CD36 siRNA on LA preference was determined. Fasting increased lingual CD36 mRNA expression in OR rats, but failed to alter lingual CD36 mRNA in OP rats. Following an overnight fast, application of lingual CD36 siRNA led to a decrease in LA preference in OR, but not OP rats. Lingual application of CD36 siRNA was also used to determine if lingual CD36 mediated the intake and preference for a high fat diet in OP and OR rats. CD36 siRNA decreased the preference and intake of high fat diet in OR rats, but not OP rats. The results from this study suggest that the dysregulation of lingual CD36 in OP rats is a potential factor leading to increased fat intake and fat preference and an enhanced susceptibility to develop obesity. PMID:28302572

Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens

PubMed Central

Johansson, Peter; Aaseth, Jan; Alexander, Jan; Brismar, Kerstin

2017-01-01

Background Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P>0.0001), IGF-1 SD score (F = 29; P<0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Conclusion Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex

Coenzyme Q supplementation in pulmonary arterial hypertension

PubMed Central

Sharp, Jacqueline; Farha, Samar; Park, Margaret M.; Comhair, Suzy A.; Lundgrin, Erika L.; Tang, W.H. Wilson; Bongard, Robert D.; Merker, Marilyn P.; Erzurum, Serpil C.

2014-01-01

Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH). Because coenzyme Q (CoQ) is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8) in comparison to healthy controls (N=7), at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW) decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement. PMID:25180165

Invertebrate Models for Coenzyme Q10 Deficiency

PubMed Central

Fernández-Ayala, Daniel J.M.; Jiménez-Gancedo, Sandra; Guerra, Ignacio; Navas, Plácido

2014-01-01

The human syndrome of coenzyme Q (CoQ) deficiency is a heterogeneous mitochondrial disease characterized by a diminution of CoQ content in cells and tissues that affects all the electron transport processes CoQ is responsible for, like the electron transference in mitochondria for respiration and ATP production and the antioxidant capacity that it exerts in membranes and lipoproteins. Supplementation with external CoQ is the main attempt to address these pathologies, but quite variable results have been obtained ranging from little response to a dramatic recovery. Here, we present the importance of modeling human CoQ deficiencies in animal models to understand the genetics and the pathology of this disease, although the election of an organism is crucial and can sometimes be controversial. Bacteria and yeast harboring mutations that lead to CoQ deficiency are unable to grow if they have to respire but develop without any problems on media with fermentable carbon sources. The complete lack of CoQ in mammals causes embryonic lethality, whereas other mutations produce tissue-specific diseases as in humans. However, working with transgenic mammals is time and cost intensive, with no assurance of obtaining results. Caenorhabditis elegans and Drosophila melanogaster have been used for years as organisms to study embryonic development, biogenesis, degenerative pathologies, and aging because of the genetic facilities and the speed of working with these animal models. In this review, we summarize several attempts to model reliable human CoQ deficiencies in invertebrates, focusing on mutant phenotypes pretty similar to those observed in human patients. PMID:25126050

Calcium binding and transport by coenzyme Q.

PubMed

Bogeski, Ivan; Gulaboski, Rubin; Kappl, Reinhard; Mirceski, Valentin; Stefova, Marina; Petreska, Jasmina; Hoth, Markus

2011-06-22

Coenzyme Q10 (CoQ10) is one of the essential components of the mitochondrial electron-transport chain (ETC) with the primary function to transfer electrons along and protons across the inner mitochondrial membrane (IMM). The concomitant proton gradient across the IMM is essential for the process of oxidative phosphorylation and consequently ATP production. Cytochrome P450 (CYP450) monoxygenase enzymes are known to induce structural changes in a variety of compounds and are expressed in the IMM. However, it is unknown if CYP450 interacts with CoQ10 and how such an interaction would affect mitochondrial function. Using voltammetry, UV-vis spectrometry, electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), fluorescence microscopy and high performance liquid chromatography-mass spectrometry (HPLC-MS), we show that both CoQ10 and its analogue CoQ1, when exposed to CYP450 or alkaline media, undergo structural changes through a complex reaction pathway and form quinone structures with distinct properties. Hereby, one or both methoxy groups at positions 2 and 3 on the quinone ring are replaced by hydroxyl groups in a time-dependent manner. In comparison with the native forms, the electrochemically reduced forms of the new hydroxylated CoQs have higher antioxidative potential and are also now able to bind and transport Ca(2+) across artificial biomimetic membranes. Our results open new perspectives on the physiological importance of CoQ10 and its analogues, not only as electron and proton transporters, but also as potential regulators of mitochondrial Ca(2+) and redox homeostasis.

Coenzyme Q10 and vitamin E deficiency in Friedreich's ataxia: predictor of efficacy of vitamin E and coenzyme Q10 therapy.

PubMed

Cooper, J M; Korlipara, L V P; Hart, P E; Bradley, J L; Schapira, A H V

2008-12-01

A pilot study of high dose coenzyme Q(10) (CoQ(10))/vitamin E therapy in Friedreich's ataxia (FRDA) patients resulted in significant clinical improvements in most patients. This study investigated the potential for this treatment to modify clinical progression in FRDA in a randomized double blind trial. Fifty FRDA patients were randomly divided into high or low dose CoQ(10)/ vitamin E groups. The change in International Co-operative Ataxia Ratings Scale (ICARS) was assessed over 2 years as the primary end-point. A post hoc analysis was made using cross-sectional data. At baseline serum CoQ(10) and vitamin E levels were significantly decreased in the FRDA patients (P < 0.001). During the trial CoQ(10) and vitamin E levels significantly increased in both groups (P < 0.01). The primary and secondary end-points were not significantly different between the therapy groups. When compared to cross-sectional data 49% of all patients demonstrated improved ICARS scores. This responder group had significantly lower baseline serum CoQ(10) levels. A high proportion of FRDA patients have a decreased serum CoQ(10) level which was the best predictor of a positive clinical response to CoQ(10)/vitamin E therapy. Low and high dose CoQ(10)/vitamin E therapies were equally effective in improving ICARS scores.

The role of coenzyme Q-10 in aging: a follow-up study on life-long oral supplementation Q-10 in rats.

PubMed

Lönnrot, K; Metsä-Ketelä, T; Alho, H

1995-01-01

The essential role of coenzyme Q--ubiquinone--in biological energy transduction is well established. Reduced Q--ubiquinol--has also been shown to act as an antioxidant and to decrease the action of free radicals, which in turn could cause damage to structural lipids or proteins. The accumulation of lipopigments during aging in several peripheral organs and in the nervous system is considered to be related to the peroxidation of unsaturated fatty acids. An age-related decline of Q-10 has been suggested to occur in man and rats. In this study we followed the effects of life-long oral supplementation of coenzyme Q-10 on the development and life-span and pigment accumulation in peripheral tissues and the nervous system of laboratory rats. The Q-10 supplemented group showed a significant increase in Q-10 in plasma and liver, while it was unchanged in other tissues. There was no significant difference between the two groups in the development and mortality of the animals. No differences were observed in lipopigment accumulation. Our results indicate that in rats, life-long supplementation of Q-10 has no beneficial effects on life-span or pigment accumulation.

Structural Characterization of a Human-Type Corrinoid Adenosyltransferase Confirms That Coenzyme B[subscript 12] Is Synthesized through a Four-Coordinate Intermediate

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

St. Maurice, Martin; Mera, Paola; Park, Kiyoung

ATP:cob(I)alamin adenosyltransferases (ACAs) catalyze the transfer of the 5{prime}-deoxyadenosyl moiety from ATP to the upper axial ligand position of cobalamin in the synthesis of coenzyme B{sub 12}. For the ACA-catalyzed reaction to proceed, cob(II)alamin must be reduced to cob(I)alamin in the enzyme active site. This reduction is facilitated through the generation of a four-coordinate cob(II)alamin intermediate on the enzyme. We have determined the high-resolution crystal structure of a human-type ACA from Lactobacillus reuteri with a four-coordinate cob(II)alamin bound in the enzyme active site and with the product, adenosylcobalamin, partially occupied in the active site. The assembled structures represent snapshots ofmore » the steps in the ACA-catalyzed formation of the cobalt-carbon bond of coenzyme B{sub 12}. The structures define the corrinoid binding site and provide visual evidence for a base-off, four-coordinate cob(II)alamin intermediate. The complete structural description of ACA-mediated catalysis reveals the molecular features of four-coordinate cob(II)alamin stabilization and provides additional insights into the molecular basis for dysfunction in human patients suffering from methylmalonic aciduria.« less

Kinematics of preferred and non-preferred handballing in Australian football.

PubMed

Parrington, Lucy; Ball, Kevin; MacMahon, Clare

2015-01-01

In Australian football (AF), handballing proficiently with both the preferred and non-preferred arm is important at elite levels; yet, little information is available for handballing on the non-preferred arm. This study compared preferred and non-preferred arm handballing techniques. Optotrak Certus (100 Hz) collected three-dimensional data for 19 elite AF players performing handballs with the preferred and non-preferred arms. Position data, range of motion (ROM), and linear and angular velocities were collected and compared between preferred and non-preferred arms using dependent t-tests. The preferred arm exhibited significantly greater forearm and humerus ROM and angular velocity and significantly greater shoulder angular velocity at ball contact compared to the non-preferred arm. In addition, the preferred arm produced a significantly greater range of lateral bend and maximum lower-trunk speed, maximum strike-side hip speed and hand speed at ball contact than the non-preferred arm. The non-preferred arm exhibited a significantly greater shoulder angle and lower- and upper-trunk orientation angle, but significantly lower support-elbow angle, trunk ROM, and trunk rotation velocity compared to the preferred arm. Reduced ROM and angular velocities found in non-preferred arm handballs indicates a reduction in the degrees of freedom and a less developed skill. Findings have implication for development of handballing on the non-preferred arm.

Shifts in Food Preferences After Bariatric Surgery: Observational Reports and Proposed Mechanisms.

PubMed

Kapoor, Natasha; Al-Najim, Werd; le Roux, Carel W; Docherty, Neil G

2017-09-01

Bariatric surgery is currently the most effective treatment for obesity. Roux-en-Y gastric bypass (RYGB) is the most commonly performed bariatric procedure and results in long-term weight loss. Alterations in food preference and choices may contribute to the long-term benefits of RYGB. This manuscript reviews the available literature documenting changes in food preference in both humans and experimental animals after RYGB and discusses the current theory on the underlying mechanisms involved. Obesity is associated with an increased preference for sweet and high-fat foods, and the most consistent evidence has been the shift away from these calorie-dense foods in both animal and human studies after RYGB. Self-reporting is the most common method used to record food preferences in humans, while more direct approaches have been used in animal work. This methodological heterogeneity may give rise to inconsistent findings. Future studies in humans should focus on direct measures to permit corroboration of mechanistic insights gained from animal studies.

Cloning and expression of clostridium acetobutylicum ATCC 824 acetoacetyl-coenzyme A:acetate/butyrate:coenzyme A-transferase in Escherichia coli

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

Cary, J.W.; Petersen, D.J.; Bennett, G.N.

1990-06-01

Coenzyme A (CoA)-transferase (acetoacetyl-CoA:acetate/butyrate:CoA-transferase (butyrate-acetoacetate CoA-transferase) (EC 2.8.3.9)) of Clostridium acetobutylicum ATCC 824 is an important enzyme in the metabolic shift between the acid-producing and solvent-forming states of this organism. The genes encoding the two subunits of this enzyme have been cloned and subsequent subcloning experiments established the position of the structural genes for CoA-transferase. Complementation of Escherichia coli ato mutants with the recombinant plasmid pCoAT4 (pUC19 carrying a 1.8-kilobase insert of C. acetobutylicum DNA encoding CoA-transferase activity) enabled the transformants to grow on butyrate as a sole carbon source. Despite the ability of CoA-transferase to complement the ato defectmore » in E. coli mutants, Southern blot and Western blot (immunoblot) analyses showed showed that neither the C. acetobutylicum genes encoding CoA-transferase nor the enzyme itself shared any apparent homology with its E. coli counterpart. Polypeptides of M{sub r} of the purified CoA-transferase subunits were observed by Western blot and maxicell analysis of whole-cell extracts of E.coli harboring pCoAT4. The proximity and orientation of the genes suggest that the genes encoding the two subunits of CoA-transferase may form an operon similar to that found in E. coli. In the plasmid, however, transcription appears to be primarily from the lac promoter of the vector.« less

Respiratory-induced coenzyme Q biosynthesis is regulated by a phosphorylation cycle of Cat5p/Coq7p.

PubMed

Martín-Montalvo, Alejandro; González-Mariscal, Isabel; Padilla, Sergio; Ballesteros, Manuel; Brautigan, David L; Navas, Plácido; Santos-Ocaña, Carlos

2011-11-15

CoQ(6) (coenzyme Q(6)) biosynthesis in yeast is a well-regulated process that requires the final conversion of the late intermediate DMQ(6) (demethoxy-CoQ(6)) into CoQ(6) in order to support respiratory metabolism in yeast. The gene CAT5/COQ7 encodes the Cat5/Coq7 protein that catalyses the hydroxylation step of DMQ(6) conversion into CoQ(6). In the present study, we demonstrated that yeast Coq7 recombinant protein purified in bacteria can be phosphorylated in vitro using commercial PKA (protein kinase A) or PKC (protein kinase C) at the predicted amino acids Ser(20), Ser(28) and Thr(32). The total absence of phosphorylation in a Coq7p version containing alanine instead of these phospho-amino acids, the high extent of phosphorylation produced and the saturated conditions maintained in the phosphorylation assay indicate that probably no other putative amino acids are phosphorylated in Coq7p. Results from in vitro assays have been corroborated using phosphorylation assays performed in purified mitochondria without external or commercial kinases. Coq7p remains phosphorylated in fermentative conditions and becomes dephosphorylated when respiratory metabolism is induced. The substitution of phosphorylated residues to alanine dramatically increases CoQ(6) levels (256%). Conversely, substitution with negatively charged residues decreases CoQ(6) content (57%). These modifications produced in Coq7p also alter the ratio between DMQ(6) and CoQ(6) itself, indicating that the Coq7p phosphorylation state is a regulatory mechanism for CoQ(6) synthesis.

The reaction mechanism of methyl-coenzyme M reductase: How an enzyme enforces strict binding order

DOE PAGES

Wongnate, Thanyaporn; Ragsdale, Stephen W.

2015-02-17

Methyl-coenzyme M reductase (MCR) is a nickel tetrahydrocorphinoid (coenzyme F430) containing enzyme involved in the biological synthesis and anaerobic oxidation of methane. MCR catalyzes the conversion of methyl-2-mercaptoethanesulfonate (methyl-SCoM) and N-7-mercaptoheptanoylthreonine phosphate (CoB 7SH) to CH 4 and the mixed disulfide CoBS-SCoM. In this study, the reaction of MCR from Methanothermobacter marburgensis, with its native substrates was investigated using static binding, chemical quench, and stopped-flow techniques. Rate constants were measured for each step in this strictly ordered ternary complex catalytic mechanism. Surprisingly, in the absence of the other substrate, MCR can bind either substrate; however, only one binary complex (MCR·methyl-SCoM)more » is productive whereas the other (MCR·CoB 7SH) is inhibitory. Moreover, the kinetic data demonstrate that binding of methyl-SCoM to the inhibitory MCR·CoB 7SH complex is highly disfavored ( Kd = 56 mM). However, binding of CoB 7SH to the productive MCR·methyl-SCoM complex to form the active ternary complex (CoB 7SH·MCR(Ni I)·CH 3SCoM) is highly favored ( Kd = 79 μM). Only then can the chemical reaction occur ( kobs = 20 s -1 at 25 °C), leading to rapid formation and dissociation of CH 4 leaving the binary product complex (MCR(Ni II)·CoB 7S -·SCoM), which undergoes electron transfer to regenerate Ni(I) and the final product CoBS-SCoM. In conclusion, this first rapid kinetics study of MCR with its natural substrates describes how an enzyme can enforce a strictly ordered ternary complex mechanism and serves as a template for identification of the reaction intermediates.« less

Exposure to activity-based anorexia impairs contextual learning in weight-restored rats without affecting spatial learning, taste, anxiety, or dietary-fat preference.

PubMed

Boersma, Gretha J; Treesukosol, Yada; Cordner, Zachary A; Kastelein, Anneke; Choi, Pique; Moran, Timothy H; Tamashiro, Kellie L

2016-02-01

Relapse rates are high amongst cases of anorexia nervosa (AN) suggesting that some alterations induced by AN may remain after weight restoration. To study the consequences of AN without confounds of environmental variability, a rodent model of activity-based anorexia (ABA) can be employed. We hypothesized that exposure to ABA during adolescence may have long-term consequences in taste function, cognition, and anxiety-like behavior after weight restoration. To test this hypothesis, we exposed adolescent female rats to ABA (1.5 h food access, combined with voluntary running wheel access) and compared their behavior to that of control rats after weight restoration was achieved. The rats were tested for learning/memory, anxiety, food preference, and taste in a set of behavioral tests performed during the light period. Our data show that ABA exposure leads to reduced performance during the novel object recognition task, a test for contextual learning, without altering performance in the novel place recognition task or the Barnes maze, both tasks that test spatial learning. Furthermore, we do not observe alterations in unconditioned lick responses to sucrose nor quinine (described by humans as "sweet" and "bitter," respectively). Nor Do we find alterations in anxiety-like behavior during an elevated plus maze or an open field test. Finally, preference for a diet high in fat is not altered. Overall, our data suggest that ABA exposure during adolescence impairs contextual learning in adulthood without altering spatial leaning, taste, anxiety, or fat preference. © 2015 Wiley Periodicals, Inc.

Frugivory by Brown Marmorated Stink Bug (Hemiptera: Pentatomidae) Alters Blueberry Fruit Chemistry and Preference by Conspecifics.

PubMed

Zhou, Yucheng; Giusti, M Monica; Parker, Joyce; Salamanca, Jordano; Rodriguez-Saona, Cesar

2016-10-01

The brown marmorated stink bug, Halyomorpha halys (Stål), is an invasive pest from Asia that feeds on many agricultural crops in the United States, including blueberries. Yet, the effects of H. halys feeding on fruit chemistry and induced resistance to insects remain unknown. Here we hypothesized that frugivory by H. halys changes fruit chemical composition, which in turn affects insect feeding behavior. In field experiments, blueberry fruit was either mechanically injured or injured by 0 (control), 2, 5, or 10 H. halys Total soluble solids (°Brix) and anthocyanin and phenolic content in injured and uninjured fruits, as well as their effects on feeding behavior by conspecifics, were measured subsequently in the laboratory. Results showed lower °Brix values in injured fruit as compared with uninjured fruit. Fruit injured by 2 and 5 H. halys also had 32 and 20% higher total phenolics, respectively, than the uninjured controls. The proportions of the anthocyanins derived from delphinidin, cyanidin, and petunidin increased, whereas those from malvidin decreased, in fruit after mechanical wounding and frugivory by H. halys In dual-choice tests, H. halys fed more often on uninjured fruit than those previously injured by conspecifics. These results show that frugivory by H. halys reduces the amounts of soluble solids, alters anthocyanin ratios, and increases levels of phenolics, and, as a result, injured fruits were a less preferred food source for conspecifics. To our knowledge, this is the first study to investigate the effects of frugivory on fruit chemistry and induced fruit resistance against a fruit-eating herbivore. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Magel2 knockout mice manifest altered social phenotypes and a deficit in preference for social novelty.

PubMed

Fountain, M D; Tao, H; Chen, C-A; Yin, J; Schaaf, C P

2017-07-01

MAGEL2 is one of five protein-coding, maternally imprinted, paternally expressed genes in the Prader-Willi syndrome (PWS)-critical domain on chromosome 15q11-q13. Truncating pathogenic variants of MAGEL2 cause Schaaf-Yang syndrome (SHFYNG) (OMIM #615547), a neurodevelopmental disorder related to PWS. Affected individuals manifest a spectrum of neurocognitive and behavioral phenotypes, including intellectual disability and autism spectrum disorder (ASD). Magel2 knockout mice carrying a maternally inherited, imprinted wild-type (WT) allele and a paternally inherited Magel2-lacZ knock-in allele, which abolishes endogenous Magel2 gene function, exhibit several features reminiscent of the human Prader-Willi phenotypes, including neonatal growth retardation, excessive weight gain after weaning and increased adiposity in adulthood. They were shown to have altered circadian rhythm, reduced motor activity and reduced fertility. An extensive assessment for autism-like behaviors in this mouse model was warranted, because of the high prevalence of ASD in human patients. The behavior of Magel2 knockout mice and their WT littermates were assayed via open field, elevated plus maze, tube, three-chamber and partition tests. Our studies confirm decreased horizontal activity of male and female mice and increased vertical activity of females, in the open field. Both sexes spent more time in the open arm of the elevated plus maze, suggestive of reductions in anxiety. Both sexes displayed a lack of preference for social novelty, via a lack of discrimination between known and novel partners in the partition test. The in-depth investigation of behavioral profiles caused by Magel2 loss-of-function helps to elucidate the etiology of behavioral phenotypes both for SHFYNG and PWS in general. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

LsrF, a coenzyme A-dependent thiolase, catalyzes the terminal step in processing the quorum sensing signal autoinducer-2

PubMed Central

Marques, João C.; Oh, Il Kyu; Ly, Daniel C.; Lamosa, Pedro; Ventura, M. Rita; Miller, Stephen T.; Xavier, Karina B.

2014-01-01

The quorum sensing signal autoinducer-2 (AI-2) regulates important bacterial behaviors, including biofilm formation and the production of virulence factors. Some bacteria, such as Escherichia coli, can quench the AI-2 signal produced by a variety of species present in the environment, and thus can influence AI-2–dependent bacterial behaviors. This process involves uptake of AI-2 via the Lsr transporter, followed by phosphorylation and consequent intracellular sequestration. Here we determine the metabolic fate of intracellular AI-2 by characterizing LsrF, the terminal protein in the Lsr AI-2 processing pathway. We identify the substrates of LsrF as 3-hydroxy-2,4-pentadione-5-phosphate (P-HPD, an isomer of AI-2-phosphate) and coenzyme A, determine the crystal structure of an LsrF catalytic mutant bound to P-HPD, and identify the reaction products. We show that LsrF catalyzes the transfer of an acetyl group from P-HPD to coenzyme A yielding dihydroxyacetone phosphate and acetyl-CoA, two key central metabolites. We further propose that LsrF, despite strong structural homology to aldolases, acts as a thiolase, an activity previously undescribed for this family of enzymes. With this work, we have fully characterized the biological pathway for AI-2 processing in E. coli, a pathway that can be used to quench AI-2 and control quorum-sensing–regulated bacterial behaviors. PMID:25225400

The influence of labeling the vegetable content of snack food on children's taste preferences: a pilot study.

PubMed

Pope, Lizzy; Wolf, Randi L

2012-01-01

This pilot study examined whether informing children of the presence of vegetables in select snack food items alters taste preference. A random sample of 68 elementary and middle school children tasted identical pairs of 3 snack food items containing vegetables. In each pair, 1 sample's label included the food's vegetable (eg, broccoli gingerbread spice cake), and 1 sample's label did not (eg, gingerbread spice cake). Participants reported whether the samples tasted the same, or whether they preferred one sample. Frequency of vegetable consumption was also assessed. Taste preferences did not differ for the labeled versus the unlabeled sample of zucchini chocolate chip bread, χ(2) (2, n = 68) = 3.21, P = .20 or broccoli gingerbread spice cake χ(2) (2, n = 68) = 2.15, P = .34. However, students preferred the unlabeled cookies (ie, chocolate chip cookies) over the vegetable-labeled version (ie, chickpea chocolate chip cookies), χ(2) = (2, n = 68) 9.21, P = .01. Chickpeas were consumed less frequently (81% had not tried in past year) as compared to zucchini and broccoli. Informing children of the presence of vegetables hidden within snack food may or may not alter taste preference and may depend on the frequency of prior exposure to the vegetable. Copyright © 2012 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

NAD Kinases: Metabolic Targets Controlling Redox Co-enzymes and Reducing Power Partitioning in Plant Stress and Development

PubMed Central

Li, Bin-Bin; Wang, Xiang; Tai, Li; Ma, Tian-Tian; Shalmani, Abdullah; Liu, Wen-Ting; Li, Wen-Qiang; Chen, Kun-Ming

2018-01-01

NAD(H) and NADP(H) are essential co-enzymes which dominantly control a number of fundamental biological processes by acting as reducing power and maintaining the intracellular redox balance of all life kingdoms. As the only enzymes that catalyze NAD(H) and ATP to synthesize NADP(H), NAD Kinases (NADKs) participate in many essential metabolic reactions, redox sensitive regulation, photosynthetic performance and also reactive oxygen species (ROS) homeostasis of cells and therefore, play crucial roles in both development and stress responses of plants. NADKs are highly conserved enzymes in amino acid sequences but have multiple subcellular localization and diverse functions. They may function as monomers, dimers or multimers in cells but the enzymatic properties in plants are not well elucidated yet. The activity of plant NADK is regulated by calcium/calmodulin and plays crucial roles in photosynthesis and redox co-enzyme control. NADK genes are expressed in almost all tissues and developmental stages of plants with specificity for different members. Their transcripts can be greatly stimulated by a number of environmental factors such as pathogenic attack, irritant applications and abiotic stress treatments. Using transgenic approaches, several studies have shown that NADKs are involved in chlorophyll synthesis, photosynthetic efficiency, oxidative stress protection, hormone metabolism and signaling regulation, and therefore contribute to the growth regulation and stress tolerance of plants. In this review, the enzymatic properties and functional mechanisms of plant NADKs are thoroughly investigated based on literature and databases. The results obtained here are greatly advantageous for further exploration of NADK function in plants. PMID:29662499

Coenzyme Q10 in Cardiovascular and Metabolic Diseases: Current State of the Problem.

PubMed

Zozina, Vladlena I; Covantev, Serghei; Goroshko, Olga A; Krasnykh, Liudmila M; Kukes, Vladimir G

2018-04-15

The burden of cardiovascular and metabolic diseases is increasing with every year. Although the management of these conditions has improved greatly over the years it is still far from perfect. With all of this in mind, there is a need for new methods of prophylaxis and treatment. Coenzyme Q10 (CoQ10) is an essential compound of the human body. There is growing evidence that CoQ10 is tightly linked to cardiometabolic disorders. Its supplementation can be useful in a variety of chronic and acute disorders. This review analyses the role of CoQ10 in hypertension, ischemic heart disease, myocardial infarction, heart failure, viral myocarditis, cardiomyopathies, cardiac toxicity, dyslipidemia, obesity, type 2 diabetes mellitus, metabolic syndrome, cardiac procedures and resuscitation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Coenzyme Q10 Supplementation in Aging and Disease

PubMed Central

Hernández-Camacho, Juan D.; Bernier, Michel; López-Lluch, Guillermo; Navas, Plácido

2018-01-01

Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and an antioxidant in plasma membranes and lipoproteins. It is endogenously produced in all cells by a highly regulated pathway that involves a mitochondrial multiprotein complex. Defects in either the structural and/or regulatory components of CoQ complex or in non-CoQ biosynthetic mitochondrial proteins can result in a decrease in CoQ concentration and/or an increase in oxidative stress. Besides CoQ10 deficiency syndrome and aging, there are chronic diseases in which lower levels of CoQ10 are detected in tissues and organs providing the hypothesis that CoQ10 supplementation could alleviate aging symptoms and/or retard the onset of these diseases. Here, we review the current knowledge of CoQ10 biosynthesis and primary CoQ10 deficiency syndrome, and have collected published results from clinical trials based on CoQ10 supplementation. There is evidence that supplementation positively affects mitochondrial deficiency syndrome and the symptoms of aging based mainly on improvements in bioenergetics. Cardiovascular disease and inflammation are alleviated by the antioxidant effect of CoQ10. There is a need for further studies and clinical trials involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ10 treatment in metabolic syndrome and diabetes, neurodegenerative disorders, kidney diseases, and human fertility. PMID:29459830

Coenzyme Q10 inhibits the release of glutamate in rat cerebrocortical nerve terminals by suppression of voltage-dependent calcium influx and mitogen-activated protein kinase signaling pathway.

PubMed

Chang, Yi; Huang, Shu-Kuei; Wang, Su-Jane

2012-12-05

This study investigates the effects and possible mechanism of coenzyme Q10 (CoQ10) on endogenous glutamate release in the cerebral cortex nerve terminals of rats. CoQ10 inhibited the release of glutamate evoked by the K+ channel blocker 4-aminopyridine (4-AP). CoQ10 reduced the depolarization-induced increase in cytosolic [Ca2+]c but did not alter the 4-AP-mediated depolarization. The effect of CoQ10 on evoked glutamate release was abolished by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) Ca2+ channels and mitogen-activated protein kinase kinase (MEK). In addition, CoQ10 decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, a major presynaptic substrate for ERK. Moreover, the inhibition of glutamate release by CoQ10 was strongly attenuated in mice without synapsin I. These results suggest that CoQ10 inhibits glutamate release from cortical synaptosomes in rats through the suppression of the presynaptic voltage-dependent Ca2+ entry and ERK/synapsin I signaling pathway.

Decreased hepatic contents of coenzyme A molecular species in mice after subchronic mild social defeat stress.

PubMed

Kubota, Yoshifumi; Goto, Tatsuhiko; Hagiya, Yuki; Chohnan, Shigeru; Toyoda, Atsushi

2016-01-01

Social stress may precipitate psychiatric disorders such as depression, which is related to the occurrence of the metabolic syndrome, including obesity and type 2 diabetes. We have evaluated the effects of social stress on central and peripheral metabolism using a model of depression in mice. In the present study, we focused on coenzyme A (CoA) molecular species [i.e. non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA] which play important roles in numerous metabolic pathways, and we analyzed changes in expression of these molecules in the hypothalamus and liver of adult male mice (C57BL/6J) subjected to 10 days of subchronic mild social defeat stress (sCSDS) with ICR mice as aggressors. Mice (n = 12) exposed to showed hyperphagia- and polydipsia-like symptoms and increased body weight gain compared with control mice which were not affected by exposure to ICR mice (n = 12). To elucidate the underlying metabolic features in the sCSDS model, acetyl-CoA, malonyl-CoA and CoASH tissue levels were analyzed using the acyl-CoA cycling method. The levels of hypothalamic malonyl-CoA, which decreases feeding behavior, were not influenced by sCSDS. However, sCSDS reduced levels of acetyl-CoA, malonyl-CoA and total CoA (sum of the three CoA molecular species) in the liver. Hence, hyperphagia-like symptoms in sCSDS mice evidently occurred independently of hypothalamic malonyl-CoA, but might consequently lead to down-regulation of hepatic CoA via altered expression of nudix hydrolase 7. Future studies should investigate the molecular mechanism(s) underlying the down-regulation of liver CoA pools in sCSDS mice.

The radical mechanism of biological methane synthesis by methyl-coenzyme M reductase

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

Wongnate, T.; Sliwa, D.; Ginovska, B.

2016-05-19

Methyl-coenzyme M reductase (MCR), the rate-limiting enzyme in methanogenesis and anaerobic methane oxidation, is responsible for the production of over one billion tons of methane per year. The mechanism of methane synthesis is unknown, with the two leading proposals involving either a methyl-nickel(III) (Mechanism I) or methyl radical/Ni(II)-thiolate (Mechanism II) intermediate(s). When the reaction between the active Ni(I) enzyme with substrates was studied by transient kinetic, spectroscopic and computational methods, formation of an EPR-silent Ni(II)-thiolate intermediate was positively identified by magnetic circular dichroism spectroscopy. There was no evidence for an EPR-active methyl-Ni(III) species. Temperature-dependent transient kinetic studies revealed that themore » activation energy for the initial catalytic step closely matched the value computed by density functional theory for Mechanism II. Thus, our results demonstrate that biological methane synthesis occurs by generation of a methyl radical.« less

Bioavailability enhancement of coenzyme Q10: an extensive review of patents.

PubMed

Beg, Sarwar; Javed, Shamama; Kohli, Kanchan

2010-11-01

Coenzyme Q10 (CoQ10) is a major antioxidant principle found in human body which plays a vital role in maintaining several biochemical pathways of body. It acts as a potential mediator in transferring electrons in oxidoreductive reactions of electron transport chain. Chemically, it is a basic quinone containing moiety having a large and high molecular weight structure. Deficiency of this in body leads to several potential disorders like dysfunctions in cellular energetics, neurological degeneration, higher oxidative stress induced damage, breast cancer etc. The high molecular weight and lipophilicity of CoQ10 makes it poorly water soluble and consequently leads to low systemic availability. Several advancements have been made to enhance the bioavailability of CoQ10 using various approaches like size reduction, solubility enhancement (by solid dispersion, prodrug, complexation, ionization) and use of novel drug carriers such as liposomes, microspheres, nanoparticles, nanoemulsions and self-emulsifying system. The primary objective of the present review is to assemble patents representing the various approaches used for enhancement of CoQ10 bioavailability.

Amitriptyline down-regulates coenzyme Q10 biosynthesis in lung cancer cells.

PubMed

Ortiz, Tamara; Villanueva-Paz, Marina; Díaz-Parrado, Eduardo; Illanes, Matilde; Fernández-Rodríguez, Ana; Sánchez-Alcázar, José A; de Miguel, Manuel

2017-02-15

Amitriptyline, a tricyclic antidepressant, has been proposed as an antitumoral drug in oxidative therapy. Its pro-apoptotic effects, mediated by high reactive oxygen species generation, have been already described. In this study we analysed the effect of amitriptyline on the biosynthesis of coenzyme Q 10 (CoQ), an essential component for electron transport and a potent membrane antioxidant involved in redox signaling. We treated H460 cells, a non-small-cell lung cancer cell line, with amitriptyline and we analysed CoQ levels by HPLC and CoQ biosynthesis rate, as well as the enzymes involved in CoQ biosynthesis by real-time PCR and Western blot. Amitriptyline treatment induced a dose-dependent decrease in CoQ levels in tumor cells. CoQ decreased levels were associated with down-regulation of the expression of COQ4 gene, as well as decreased Coq4 and Coq6 protein levels. Our findings suggest that the effect of amitriptyline on CoQ biosynthesis highlights the potential of this drug for antitumoral oxidative therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Circadian preferences, oxidative stress and inflammatory cytokines in bipolar disorder: A community study.

PubMed

Mondin, Thaise Campos; de Azevedo Cardoso, Taiane; Moreira, Fernanda Pedrotti; Wiener, Carolina; Oses, Jean Pierre; de Mattos Souza, Luciano Dias; Jansen, Karen; da Silva Magalhães, Pedro Vieira; Kapczinski, Flávio; da Silva, Ricardo Azevedo

2016-12-15

To assess circadian preference among a community sample of people with bipolar disorder, major depression and without any mood disorders. Secondly, we investigated the association of circadian preference with cytokines interleukin-6 (IL-6), interleukin-10 (IL-10) and, tumor necrosis factor alpha (TNF-α) and oxidative stress assessed by thiobarbituric acid reactive substances (TBARS), uric acid and Protein Carbonyl Content (PCC). A cross-sectional study nested in a population-based sample. Caseness was confirmed with the Structured Clinical Interview for DSM-IV. A sample of 215 participants, in whom we measured circadian preferences, IL-6, IL-10, TNF-α, TBARS, uric acid, PCC. Biological rhythms were evaluated using the Biological Interview of Assessment in Neuropsychiatry. Bipolar group presented a higher alteration in biological rhythms (40.40±9.78) when compared with the major depression group (36.35±9.18) and control group (27.61±6.89) p<0.001. Subjects with bipolar disorder who were active at night and had a day/night cycle reverse showed decreased levels of IL-6 (t, 44=2.096; p=0.042), (t, 44=2.213; p=0.032), respectively. In the bipolar disorder group subjects who presented day/night cycle reverse had lower TBARS levels (t, 41=2.612; p=0.013). TNF-α were decreased in subjects more active at night with bipolar disorder. Lower serum levels of IL-6, TNF-α and TBARS were associated with evening preference in bipolar disorder group. These findings suggest that chronotype may alter the levels of interleukins and oxidative stress levels in bipolar and healthy subjects. A better understanding of the role of circadian preferences in levels of interleukins and oxidative stress are needed. Copyright © 2016 Elsevier B.V. All rights reserved.

Paraquat induces oxidative stress, neuronal loss in substantia nigra region and parkinsonism in adult rats: neuroprotection and amelioration of symptoms by water-soluble formulation of coenzyme Q10.

PubMed

Somayajulu-Niţu, Mallika; Sandhu, Jagdeep K; Cohen, Jerome; Sikorska, Marianna; Sridhar, T S; Matei, Anca; Borowy-Borowski, Henryk; Pandey, Siyaram

2009-07-27

Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod) evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

Paraquat induces oxidative stress, neuronal loss in substantia nigra region and Parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of Coenzyme Q10

PubMed Central

Somayajulu-Niţu, Mallika; Sandhu, Jagdeep K; Cohen, Jerome; Sikorska, Marianna; Sridhar, TS; Matei, Anca; Borowy-Borowski, Henryk; Pandey, Siyaram

2009-01-01

Background Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. Results Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod) evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. Conclusion Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of Parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses. PMID:19635141

The Vocational Preference Inventory Scores and Environmental Preferences

ERIC Educational Resources Information Center

Kunce, Joseph T.; Kappes, Bruno Maurice

1976-01-01

This study investigated the relationship between vocational interest measured by the Vocational Preference Inventory (VPI) and preferences of 175 undergraduates for structured or unstructured environments. Males having clear-cut preferences for structured situations had significantly higher Realistic-Conventional scores than those without…

Effects of acute corticosterone treatment on partner preferences in male and female zebra finches (Taeniopygia guttata).

PubMed

LaPlante, Kimberly A; Huremovic, Enida; Tomaszycki, Michelle L

2014-04-01

Stress alters physiology and behavior across species. Most research on the effects of stress on behavior uses chronic stressors, and most are correlational. The effects of acute stressors on physiology and behavior have been mixed. Here, we use zebra finches, a highly gregarious species that forms long-term pair bonds, to test the effects of an acute corticosterone (CORT) on opposite-sex partner preferences over a same-sex individual or a group (the latter is a highly appealing option). We had two competing hypotheses. First, we predicted that acute CORT would alter preferences for the opposite sex bird in both conditions in both sexes. However, since there is a sex difference in the effects of CORT on partner preferences in voles, these effects may be more pronounced in males than in females. To test our hypotheses, we administered 2 doses of CORT (10μg and 20μg) or vehicle (control) using a repeated measures design. In the male vs. female test, there was a significant Sex by Treatment interaction, such that in males, 10μg CORT increased preferences for a female over the male compared to when these same males were treated with saline at baseline. There were no effects of treatment in females. In the opposite-sex vs. group condition, there was an overall effect of Treatment, such that the 10μg dose increased preference for the opposite-sex individual over both saline treatments, regardless of sex. These findings further our understanding of the effects of an acute stressor on sexual partner preferences. Copyright © 2014 Elsevier Inc. All rights reserved.

Purification of a Jojoba Embryo Fatty Acyl-Coenzyme A Reductase and Expression of Its cDNA in High Erucic Acid Rapeseed

PubMed Central

Metz, James G.; Pollard, Michael R.; Anderson, Lana; Hayes, Thomas R.; Lassner, Michael W.

2000-01-01

The jojoba (Simmondsia chinensis) plant produces esters of long-chain alcohols and fatty acids (waxes) as a seed lipid energy reserve. This is in contrast to the triglycerides found in seeds of other plants. We purified an alcohol-forming fatty acyl-coenzyme A reductase (FAR) from developing embryos and cloned the cDNA encoding the enzyme. Expression of a cDNA in Escherichia coli confers FAR activity upon those cells and results in the accumulation of fatty alcohols. The FAR sequence shows significant homology to an Arabidopsis protein of unknown function that is essential for pollen development. When the jojoba FAR cDNA is expressed in embryos of Brassica napus, long-chain alcohols can be detected in transmethylated seed oils. Resynthesis of the gene to reduce its A plus T content resulted in increased levels of alcohol production. In addition to free alcohols, novel wax esters were detected in the transgenic seed oils. In vitro assays revealed that B. napus embryos have an endogenous fatty acyl-coenzyme A: fatty alcohol acyl-transferase activity that could account for this wax synthesis. Thus, introduction of a single cDNA into B. napus results in a redirection of a portion of seed oil synthesis from triglycerides to waxes. PMID:10712526

Purification of a jojoba embryo fatty acyl-coenzyme A reductase and expression of its cDNA in high erucic acid rapeseed.

PubMed

Metz, J G; Pollard, M R; Anderson, L; Hayes, T R; Lassner, M W

2000-03-01

The jojoba (Simmondsia chinensis) plant produces esters of long-chain alcohols and fatty acids (waxes) as a seed lipid energy reserve. This is in contrast to the triglycerides found in seeds of other plants. We purified an alcohol-forming fatty acyl-coenzyme A reductase (FAR) from developing embryos and cloned the cDNA encoding the enzyme. Expression of a cDNA in Escherichia coli confers FAR activity upon those cells and results in the accumulation of fatty alcohols. The FAR sequence shows significant homology to an Arabidopsis protein of unknown function that is essential for pollen development. When the jojoba FAR cDNA is expressed in embryos of Brassica napus, long-chain alcohols can be detected in transmethylated seed oils. Resynthesis of the gene to reduce its A plus T content resulted in increased levels of alcohol production. In addition to free alcohols, novel wax esters were detected in the transgenic seed oils. In vitro assays revealed that B. napus embryos have an endogenous fatty acyl-coenzyme A: fatty alcohol acyl-transferase activity that could account for this wax synthesis. Thus, introduction of a single cDNA into B. napus results in a redirection of a portion of seed oil synthesis from triglycerides to waxes.

Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: Impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish

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

Biery, B.J.; Stein, D.E.; Goodman, S.I.

The structure of the human glutaryl coenzyme A dehydrogenase (GCD) gene was determined to contain 11 exons and to span {approximately}7 kb. Fibroblast DNA from 64 unrelated glutaric academia type I (GA1) patients was screened for mutations by PCR amplification and analysis of SSCP. Fragments with altered electrophoretic mobility were subcloned and sequenced to detect mutations that caused GA1. This report describes the structure of the GCD gene, as well as point mutations and polymorphisms found in 7 of its 11 exons. Several mutations were found in more than one patient, but no one prevalent mutation was detected in themore » general population. As expected from pedigree analysis, a single mutant allele causes GA1 in the Old Order Amish of Lancaster County, Pennsylvania. Several mutations have been expressed in Escherichia coli, and all produce diminished enzyme activity. Reduced activity in GCD encoded by the A421V mutation in the Amish may be due to impaired association of enzyme subunits. 13 refs., 5 figs., 3 tabs.« less

Nutritional status alters saccharin intake and sweet receptor mRNA expression in rat taste buds.

PubMed

Chen, Ke; Yan, Jianqun; Suo, Yi; Li, Jinrong; Wang, Qian; Lv, Bo

2010-04-14

Sweet taste usually signifies the presence of caloric food. It is commonly accepted that a close association exists among sweet taste perception, preference, and nutritional status. However, the mechanisms involved remain unknown. To investigate whether nutritional status affects the preference for palatable solutions and alters sweet taste receptor gene expression in rats, we measured saccharin intake and preference using a two-bottle preference test, and changes in body weight, plasma leptin levels, and gene expression for the sweet taste receptor in taste buds in high-fat diet-induced obese rats and chronically diet-restricted rats. We found that the consumption and preference ratios for 0.01 and 0.04 M saccharin were significantly lower in the high-fat diet-induced obese rats than in the normal diet rats, while the serum leptin levels were markedly increased in obese rats. Consistent with the changes in saccharin intake, the gene expression level of the sweet taste receptor T1R3 was significantly decreased in the high-fat diet-induced obese rats compared with the control rats. By contrast, the chronically diet-restricted rats showed remarkably enhanced consumption and preference for 0.04 M saccharin. The serum leptin concentration was decreased, and the gene expression of the leptin receptor was markedly increased in the taste buds. In conclusion, our results suggest that nutritional status alters saccharin preference and the expression of T1R3 in taste buds. These processes may be involved in the mechanisms underlying the modulation of peripheral sweet taste sensitivity, in which leptin plays a role. Copyright 2010 Elsevier B.V. All rights reserved.

Preference for and learning of amino acids in larval Drosophila

PubMed Central

Kudow, Nana; Miura, Daisuke; Schleyer, Michael; Toshima, Naoko; Gerber, Bertram

2017-01-01

ABSTRACT Relative to other nutrients, less is known about how animals sense amino acids and how behaviour is organized accordingly. This is a significant gap in our knowledge because amino acids are required for protein synthesis − and hence for life as we know it. Choosing Drosophila larvae as a case study, we provide the first systematic analysis of both the preference behaviour for, and the learning of, all 20 canonical amino acids in Drosophila. We report that preference for individual amino acids differs according to the kind of amino acid, both in first-instar and in third-instar larvae. Our data suggest that this preference profile changes across larval instars, and that starvation during the third instar also alters this profile. Only aspartic acid turns out to be robustly attractive across all our experiments. The essentiality of amino acids does not appear to be a determinant of preference. Interestingly, although amino acids thus differ in their innate attractiveness, we find that all amino acids are equally rewarding. Similar discrepancies between innate attractiveness and reinforcing effect have previously been reported for other tastants, including sugars, bitter substances and salt. The present analyses will facilitate the ongoing search for the receptors, sensory neurons, and internal, homeostatic amino acid sensors in Drosophila. PMID:28193602

Volatile Ester Formation in Roses. Identification of an Acetyl-Coenzyme A. Geraniol/Citronellol Acetyltransferase in Developing Rose Petals1

PubMed Central

Shalit, Moshe; Guterman, Inna; Volpin, Hanne; Bar, Einat; Tamari, Tal; Menda, Naama; Adam, Zach; Zamir, Dani; Vainstein, Alexander; Weiss, David; Pichersky, Eran; Lewinsohn, Efraim

2003-01-01

The aroma of roses (Rosa hybrida) is due to more than 400 volatile compounds including terpenes, esters, and phenolic derivatives. 2-Phenylethyl acetate, cis-3-hexenyl acetate, geranyl acetate, and citronellyl acetate were identified as the main volatile esters emitted by the flowers of the scented rose var. “Fragrant Cloud.” Cell-free extracts of petals acetylated several alcohols, utilizing acetyl-coenzyme A, to produce the corresponding acetate esters. Screening for genes similar to known plant alcohol acetyltransferases in a rose expressed sequence tag database yielded a cDNA (RhAAT1) encoding a protein with high similarity to several members of the BAHD family of acyltransferases. This cDNA was functionally expressed in Escherichia coli, and its gene product displayed acetyl-coenzyme A:geraniol acetyltransferase enzymatic activity in vitro. The RhAAT1 protein accepted other alcohols such as citronellol and 1-octanol as substrates, but 2-phenylethyl alcohol and cis-3-hexen-1-ol were poor substrates, suggesting that additional acetyltransferases are present in rose petals. The RhAAT1 protein is a polypeptide of 458 amino acids, with a calculated molecular mass of 51.8 kD, pI of 5.45, and is active as a monomer. The RhAAT1 gene was expressed exclusively in floral tissue with maximum transcript levels occurring at stage 4 of flower development, where scent emission is at its peak. PMID:12692346

Colony-level variation in pollen collection and foraging preferences among wild-caught bumble bees (Hymenoptera: Apidae).

PubMed

Saifuddin, Mustafa; Jha, Shalene

2014-04-01

Given that many pollinators have exhibited dramatic declines related to habitat destruction, an improved understanding of pollinator resource collection across human-altered landscapes is essential to conservation efforts. Despite the importance of bumble bees (Bombus spp.) as global pollinators, little is known regarding how pollen collection patterns vary between individuals, colonies, and landscapes. In this study, Vosnesensky bumble bees (Bombus vosnesenskii Radoszkowski) were collected from a range of human-altered and natural landscapes in northern California. Extensive vegetation surveys and Geographic Information System (GIS)-based habitat classifications were conducted at each site, bees were genotyped to identify colony mates, and pollen loads were examined to identify visited plants. In contrast to predictions based on strong competitive interactions, pollen load composition was significantly more similar for bees captured in a shared study region compared with bees throughout the research area but was not significantly more similar for colony mates. Preference analyses revealed that pollen loads were not composed of the most abundant plant species per study region. The majority of ranked pollen preference lists were significantly correlated for pairwise comparisons of colony mates and individuals within a study region, whereas the majority of pairwise comparisons of ranked pollen preference lists between individuals located at separate study regions were uncorrelated. Results suggest that pollen load composition and foraging preferences are similar for bees throughout a shared landscape regardless of colony membership. The importance of native plant species in pollen collection is illustrated through preference analyses, and we suggest prioritization of specific rare native plant species for enhanced bumble bee pollen collection.

Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.

PubMed

Alehagen, Urban; Johansson, Peter; Aaseth, Jan; Alexander, Jan; Wågsäter, Dick

2017-01-01

Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation. Out of the 443 healthy elderly participants that were given supplementation with 200 μg Se/day as organic selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4 years, 25 participants from each group were randomized and evaluated regarding levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR analysis were performed. Volcano- and principal component analyses (PCA)-plots were used to illustrate the differences in microRNA expression between the intervention, and the placebo groups. Serum selenium concentrations were measured before intervention. On average 145 different microRNAs out of 172 were detected per sample. In the PCA plots two clusters could be identified indicating significant difference in microRNA expression between the two groups. The pre-treatment expression of the microRNAs did not differ between active treatment and the placebo groups. When comparing the post-treatment microRNAs in the active and the placebo groups, 70 microRNAs exhibited significant differences in expression, also after adjustment for multiple measurements. For the 20 microRNAs with the greatest difference in expression the difference was up to more than 4 fold and with a P-value that were less than 4.4e-8. Significant differences were found in expression of more than 100 different microRNAs with up to 4 fold differences as a result of the intervention of selenium and coenzyme Q10 combined. The changes in microRNA could be a part of

Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens

PubMed Central

Johansson, Peter; Aaseth, Jan; Alexander, Jan; Wågsäter, Dick

2017-01-01

Background Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation. Methods Out of the 443 healthy elderly participants that were given supplementation with 200 μg Se/day as organic selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4 years, 25 participants from each group were randomized and evaluated regarding levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR analysis were performed. Volcano- and principal component analyses (PCA)–plots were used to illustrate the differences in microRNA expression between the intervention, and the placebo groups. Serum selenium concentrations were measured before intervention. Findings On average 145 different microRNAs out of 172 were detected per sample. In the PCA plots two clusters could be identified indicating significant difference in microRNA expression between the two groups. The pre-treatment expression of the microRNAs did not differ between active treatment and the placebo groups. When comparing the post-treatment microRNAs in the active and the placebo groups, 70 microRNAs exhibited significant differences in expression, also after adjustment for multiple measurements. For the 20 microRNAs with the greatest difference in expression the difference was up to more than 4 fold and with a P-value that were less than 4.4e-8. Conclusions Significant differences were found in expression of more than 100 different microRNAs with up to 4 fold differences as a result of the intervention of selenium and coenzyme Q10 combined. The

Coenzyme Q biosynthesis in health and disease.

PubMed

Acosta, Manuel Jesús; Vazquez Fonseca, Luis; Desbats, Maria Andrea; Cerqua, Cristina; Zordan, Roberta; Trevisson, Eva; Salviati, Leonardo

2016-08-01

Coenzyme Q (CoQ, or ubiquinone) is a remarkable lipid that plays an essential role in mitochondria as an electron shuttle between complexes I and II of the respiratory chain, and complex III. It is also a cofactor of other dehydrogenases, a modulator of the permeability transition pore and an essential antioxidant. CoQ is synthesized in mitochondria by a set of at least 12 proteins that form a multiprotein complex. The exact composition of this complex is still unclear. Most of the genes involved in CoQ biosynthesis (COQ genes) have been studied in yeast and have mammalian orthologues. Some of them encode enzymes involved in the modification of the quinone ring of CoQ, but for others the precise function is unknown. Two genes appear to have a regulatory role: COQ8 (and its human counterparts ADCK3 and ADCK4) encodes a putative kinase, while PTC7 encodes a phosphatase required for the activation of Coq7. Mutations in human COQ genes cause primary CoQ(10) deficiency, a clinically heterogeneous mitochondrial disorder with onset from birth to the seventh decade, and with clinical manifestation ranging from fatal multisystem disorders, to isolated encephalopathy or nephropathy. The pathogenesis of CoQ(10) deficiency involves deficient ATP production and excessive ROS formation, but possibly other aspects of CoQ(10) function are implicated. CoQ(10) deficiency is unique among mitochondrial disorders since an effective treatment is available. Many patients respond to oral CoQ(10) supplementation. Nevertheless, treatment is still problematic because of the low bioavailability of the compound, and novel pharmacological approaches are currently being investigated. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. Copyright © 2016. Published by Elsevier B.V.

Comparing preference assessments: selection- versus duration-based preference assessment procedures.

PubMed

Kodak, Tiffany; Fisher, Wayne W; Kelley, Michael E; Kisamore, April

2009-01-01

In the current investigation, the results of a selection- and a duration-based preference assessment procedure were compared. A Multiple Stimulus With Replacement (MSW) preference assessment [Windsor, J., Piché, L. M., & Locke, P. A. (1994). Preference testing: A comparison of two presentation methods. Research in Developmental Disabilities, 15, 439-455] and a variation of a Free-Operant (FO) preference assessment procedure [Roane, H. S., Vollmer, T. R., Ringdahl, J. E., & Marcus, B. A. (1998). Evaluation of a brief stimulus preference assessment. Journal of Applied Behavior Analysis, 31, 605-620] were conducted with four participants. A reinforcer assessment was conducted to determine which preference assessment procedure identified the item that produced the highest rates of responding. The items identified as most highly preferred were different across preference assessment procedures for all participants. Results of the reinforcer assessment showed that the MSW identified the item that functioned as the most effective reinforcer for two participants.

Postprandial antioxidant effect of the Mediterranean diet supplemented with coenzyme Q10 in elderly men and women.

PubMed

Yubero-Serrano, Elena M; Delgado-Casado, Nieves; Delgado-Lista, Javier; Perez-Martinez, Pablo; Tasset-Cuevas, Inmaculada; Santos-Gonzalez, Monica; Caballero, Javier; Garcia-Rios, Antonio; Marin, Carmen; Gutierrez-Mariscal, Francisco M; Fuentes, Francisco; Villalba, Jose M; Tunez, Isaac; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

2011-12-01

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial cellular oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) lowers postprandial oxidative stress in an elderly population. In this randomized crossover study, 20 participants were assigned to receive three isocaloric diets for periods of 4 week each: (1) Mediterranean diet supplemented with CoQ (Med+CoQ diet), (2) Mediterranean diet (Med diet), and (3) saturated fatty acid-rich diet (SFA diet). After a 12-h fast, the volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. CoQ, lipid peroxides (LPO), oxidized low-density lipoprotein (oxLDL), protein carbonyl (PC), total nitrite, nitrotyrosine plasma levels, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and ischemic reactive hyperaemia (IRH) were determined. Med diet produced a lower postprandial GPx activity and a lower decrease in total nitrite level compared to the SFA diet. Med and Med+CoQ diets induced a higher postprandial increase in IRH and a lower postprandial LPO, oxLDL, and nitrotyrosine plasma levels than the SFA diet. Moreover, the Med+CoQ diet produced a lower postprandial decrease in total nitrite and a greater decrease in PC levels compared to the other two diets and lower SOD, CAT, and GPx activities than the SFA diet.In conclusion, Med diet reduces postprandial oxidative stress by reducing processes of cellular oxidation and increases the action of the antioxidant system in elderly persons and the administration of CoQ further improves this redox balance.

Effects of stress on women's preference for male facial masculinity and their endocrine correlates.

PubMed

Ditzen, Beate; Palm-Fischbacher, Simona; Gossweiler, Lara; Stucky, Livia; Ehlert, Ulrike

2017-08-01

Women's preferences for masculinity in men's faces seem to vary across the menstrual cycle and are assumed to be strongest around ovulation. A number of hormones have been proposed to underlie these subtle cyclic shifts. Furthermore, mating preferences are context-dependent, and stress has been found to alter mate choice, both in animals and humans. Currently, the effects of stress on women's preference for masculinity remain unknown. To examine the hormonal basis and the impact of stress on facial masculinity preference, we tested for within-subject changes in 52 healthy young women who underwent the Trier Social Stress Test (TSST) and the placebo-TSST in randomized order in the late follicular and mid-luteal phases of their menstrual cycle. Menstrual cycle phase and hormone levels were confirmed using estradiol, testosterone, progesterone, and cortisol analyses from saliva. Results show that women were more likely to be attracted to masculine-faced men right before ovulation than in the mid-luteal phase. Estradiol modulated this masculinity preference with high estradiol levels being related to stronger masculinity preference. When stressed however, women experienced a decrease in male facial masculinity preference. In line with these findings, the higher the cortisol increase to stress, the less were masculine faces preferred to more feminine faces. Mate choice is a central component of reproduction. The present results provide information about the effects of stress and hormonal influences on mate preferences in women. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selected biomarkers as predictive tools in testing efficacy of melatonin and coenzyme Q on propionic acid - induced neurotoxicity in rodent model of autism

PubMed Central

2014-01-01

Background Exposures to environmental toxins are now thought to contribute to the development of autism spectrum disorder. Propionic acid (PA) found as a metabolic product of gut bacteria has been reported to mimic/mediate the neurotoxic effects of autism. Results from animal studies may guide investigations on human populations toward identifying environmental contaminants that produce or drugs that protect from neurotoxicity. Forty-eight young male Western Albino rats were used in the present study. They were grouped into six equal groups 8 rats each. The first group received a neurotoxic dose of buffered PA (250 mg/Kg body weight/day for 3 consecutive days). The second group received only phosphate buffered saline (control group). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for one week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for one week prior to PA (protected groups). Heat shock protein70 (Hsp70), Gamma amino-butyric acid (GABA), serotonin, dopamine, oxytocin and interferon γ-inducible protein 16 together with Comet DNA assay were measured in brain tissues of the six studied groups. Results The obtained data showed that PA caused multiple signs of brain toxicity revealed in depletion of GABA, serotonin, and dopamine, are which important neurotransmitters that reflect brain function, interferon γ-inducible protein 16 and oxytocin. A high significant increase in tail length, tail DNA% damage and tail moment was reported indicating the genotoxic effect of PA. Administration of melatonin or coenzyme Q showed both protective and therapeutic effects on PA–treated rats demonstrated in a remarkable amelioration of most of the measured parameters. Conclusion In conclusion, melatonin and coenzyme Q have potential protective and restorative effects against PA-induced brain injury

Selected biomarkers as predictive tools in testing efficacy of melatonin and coenzyme Q on propionic acid - induced neurotoxicity in rodent model of autism.

PubMed

Al-Ghamdi, Mashael; Al-Ayadhi, Laila; El-Ansary, Afaf

2014-02-25

Exposures to environmental toxins are now thought to contribute to the development of autism spectrum disorder. Propionic acid (PA) found as a metabolic product of gut bacteria has been reported to mimic/mediate the neurotoxic effects of autism. Results from animal studies may guide investigations on human populations toward identifying environmental contaminants that produce or drugs that protect from neurotoxicity. Forty-eight young male Western Albino rats were used in the present study. They were grouped into six equal groups 8 rats each. The first group received a neurotoxic dose of buffered PA (250 mg/Kg body weight/day for 3 consecutive days). The second group received only phosphate buffered saline (control group). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for one week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for one week prior to PA (protected groups). Heat shock protein70 (Hsp70), Gamma amino-butyric acid (GABA), serotonin, dopamine, oxytocin and interferon γ-inducible protein 16 together with Comet DNA assay were measured in brain tissues of the six studied groups. The obtained data showed that PA caused multiple signs of brain toxicity revealed in depletion of GABA, serotonin, and dopamine, are which important neurotransmitters that reflect brain function, interferon γ-inducible protein 16 and oxytocin. A high significant increase in tail length, tail DNA% damage and tail moment was reported indicating the genotoxic effect of PA. Administration of melatonin or coenzyme Q showed both protective and therapeutic effects on PA-treated rats demonstrated in a remarkable amelioration of most of the measured parameters. In conclusion, melatonin and coenzyme Q have potential protective and restorative effects against PA-induced brain injury, confirmed by improvement in

Preference for sex of child: a research update.

PubMed

Hammer, M; Mcferran, J

1988-12-01

This study was undertaken in order to determine if various cultural influences since the time of the 1970 Hammer study have significantly altered the view in our society today in regard to the disadvantage of the female role. The study involved asking 558 subjects to fill out a 1-page questionnaire that asked: 1) If you knew for sure that you could have only 1 child, would you prefer that child to be a boy or a girl? and 2) If it were possible for you to be reborn and you could have your choice, would you prefer to return as a male or as a female? Each question also asked for the respondent's reasons for responding as he or she did. In comparing the results of the 1970 study, what seems to be clear is that the perceived female role disadvantage appears to be significantly diminishing in our society, at least as far as most females are concerned. This is especially evident in unmarried college females, for whom there has been a rather dramatic change since 1970. In 1970, this group significantly preferred a male child, whereas in 1986 they significantly preferred a female child. The fact that these females significantly prefer to be reborn as a female rather than a male suggests that the perception by this group of the diminishing of the female role disadvantage is quite substantial. The results for the other groups are much less clear. The clear changes that have taken place since 1970 in regard to female role disadvantage lend more support to the Adlerian view over the Freudian view that such roles are more culturally than anatomically determined, and are therefore amenable to continuous change.

Sex preferences among mothers delivering at Patan Hospital.

PubMed

Chhetri, U D; Ansari, I; Bandary, S; Adhikari, N

2011-01-01

High sex ratios at birth (SRB) are seen in China, Taiwan, South Korea, parts of India and Vietnam. The imbalance is the result of son preference, accentuated by declining fertility. Prenatal sex determination and female feticides are common in many countries. It is reflected in sex ratio To determine reasons for the preferences for different sex; to find out whether there is altered sex ratio at birth and to find out whether female feticide are common among women who had abortion. It is a prospective study. Women who had previous history of abortion and had delivered at Patan Hospital in the year 2066 were interviewed as per questionnaires. Among 560 women with total live births of 965, (462 male and 503 female) during their life time the overall sex ratio was 92 male per 100 female birth; total abortions were 663. Preferences for male were 10%, female 15.4% and either was for 74%. The reason for male preference was to continue family lineage, to bring honor, old age security, and performing funeral rites while the reasons for daughter preferences were that they understand mothers pain, help in household work. The sex ratio of the babies born during the study period was 113 male per 100 female births. The Sex ratio at birth from 1st to 6th deliveries was 61, 79, 101, 210, 286 and 1100 male per 100 female birth respectively. Prenatal sex selection was 8% (by USG) but none had sex selected abortion. Sex ratio of those delivered during the study period was skewed (136 boys per 100 girls) towards male. There was shift in SRB in 4th and subsequent pregnancies in favor of boys. As the male sex ratio increased the number of induced abortion decreased in subsequent pregnancies.

Coenzyme Q biosynthesis and its role in the respiratory chain structure.

PubMed

Alcázar-Fabra, María; Navas, Plácido; Brea-Calvo, Gloria

2016-08-01

Coenzyme Q (CoQ) is a unique electron carrier in the mitochondrial respiratory chain, which is synthesized on-site by a nuclear encoded multiprotein complex. CoQ receives electrons from different redox pathways, mainly NADH and FADH2 from tricarboxylic acid pathway, dihydroorotate dehydrogenase, electron transfer flavoprotein dehydrogenase and glycerol-3-phosphate dehydrogenase that support key aspects of the metabolism. Here we explore some lines of evidence supporting the idea of the interaction of CoQ with the respiratory chain complexes, contributing to their superassembly, including respirasome, and its role in reactive oxygen species production in the mitochondrial inner membrane. We also review the current knowledge about the involvement of mitochondrial genome defects and electron transfer flavoprotein dehydrogenase mutations in the induction of secondary CoQ deficiency. This mechanism would imply specific interactions coupling CoQ itself or the CoQ-biosynthetic apparatus with the respiratory chain components. These interactions would regulate mitochondrial CoQ steady-state levels and function. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. Copyright © 2016 Elsevier B.V. All rights reserved.

The 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductases

PubMed Central

Friesen, Jon A; Rodwell, Victor W

2004-01-01

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyzes the conversion of HMG-CoA to mevalonate, a four-electron oxidoreduction that is the rate-limiting step in the synthesis of cholesterol and other isoprenoids. The enzyme is found in eukaryotes and prokaryotes; and phylogenetic analysis has revealed two classes of HMG-CoA reductase, the Class I enzymes of eukaryotes and some archaea and the Class II enzymes of eubacteria and certain other archaea. Three-dimensional structures of the catalytic domain of HMG-CoA reductases from humans and from the bacterium Pseudomonas mevalonii, in conjunction with site-directed mutagenesis studies, have revealed details of the mechanism of catalysis. The reaction catalyzed by human HMG-CoA reductase is a target for anti-hypercholesterolemic drugs (statins), which are intended to lower cholesterol levels in serum. Eukaryotic forms of the enzyme are anchored to the endoplasmic reticulum, whereas the prokaryotic enzymes are soluble. Probably because of its critical role in cellular cholesterol homeostasis, mammalian HMG-CoA reductase is extensively regulated at the transcriptional, translational, and post-translational levels. PMID:15535874

Effect of Diet on Preference and Intake of Sucrose in Obese Prone and Resistant Rats

PubMed Central

Duca, Frank A.; Swartz, Timothy D.; Covasa, Mihai

2014-01-01

Increased orosensory stimulation from palatable diets and decreased feedback from gut signals have been proposed as contributing factors to obesity development. Whether altered taste functions associated with obesity are common traits or acquired deficits to environmental factors, such as a high-energy (HE)-diet, however, is not clear. To address this, we examined preference and sensitivity of increasing concentrations of sucrose solutions in rats prone (OP) and resistant (OR) to obesity during chow and HE feeding and measured lingual gene expression of the sweet taste receptor T1R3. When chow-fed, OP rats exhibited reduced preference and acceptance of dilute sucrose solutions, sham-fed less sucrose compared to OR rats, and had reduced lingual T1R3 gene expression. HE-feeding abrogated differences in sucrose preference and intake and lingual T1R3 expression between phenotypes. Despite similar sucrose intakes however, OP rats consumed significantly more total calories during 48-h two-bottle testing compared to OR rats. The results demonstrate that OP rats have an innate deficit for sweet taste detection, as illustrated by a reduction in sensitivity to sweets and reduced T1R3 gene expression; however their hyperphagia and subsequent obesity during HE-feeding is most likely not due to altered consumption of sweets. PMID:25329959

Socially transmitted mate preferences in a monogamous bird: a non-genetic mechanism of sexual selection.

PubMed

Swaddle, John P; Cathey, Mark G; Correll, Maureen; Hodkinson, Brendan P

2005-05-22

There is increasing evidence that animals can acquire mate preferences through the use of public information, notably by observing (and copying) the mate preferences of others in the population. If females acquire preferences through social mechanisms, sexual selection could act very rapidly to spread the preference and drive elaboration of the preferred trait(s). Although there are reports of 'mate-choice copying' in polygynous species, there is no clear evidence for this process in monogamous species. Here, we investigated whether adult female zebra finches Taeniopygia guttata can socially acquire sexual preferences for individual males and, in a separate study, for a generalized trait (coloured leg bands) of males. In both studies, test females observed males in two simultaneous conditions: a ('chosen') mixed-sex situation in which a male was paired with a (model) female, and a ('unchosen') same-sex situation in which a male was paired with another male. In the first experiment, after two weeks of females observing males, test females significantly preferred individual males who had been paired with another female (i.e. chosen males). In the second experiment, test females significantly preferred novel males that were wearing the same leg band colour as the apparently chosen males. Our findings are consistent with the conclusion that female zebra finches' mate preferences are altered by public information. Our study implies that mate preferences can spread rapidly through populations by social mechanisms, affecting the strength of sexual selection in a monogamous species.

Reducing preference reversals: The role of preference imprecision and nontransparent methods.

PubMed

Pinto-Prades, José Luis; Sánchez-Martínez, Fernando Ignacio; Abellán-Perpiñán, José María; Martínez-Pérez, Jorge E

2018-05-16

Preferences elicited with matching and choice usually diverge (as characterised by preference reversals), violating a basic rationality requirement, namely, procedure invariance. We report the results of an experiment that shows that preference reversals between matching (Standard Gamble in our case) and choice are reduced when the matching task is conducted using nontransparent methods. Our results suggest that techniques based on nontransparent methods are less influenced by biases (i.e., compatibility effects) than transparent methods. We also observe that imprecision of preferences influences the degree of preference reversals. The preference reversal phenomenon is less strong in subjects with more precise preferences. Copyright © 2018 John Wiley & Sons, Ltd.

Isolation and characterization of cDNAs encoding wheat 3-hydroxy-3-methylglutaryl coenzyme A reductase.

PubMed Central

Aoyagi, K; Beyou, A; Moon, K; Fang, L; Ulrich, T

1993-01-01

The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR, EC 1.1.1.34) is a key enzyme in the isoprenoid biosynthetic pathway. We have isolated partial cDNAs from wheat (Triticum aestivum) using the polymerase chain reaction. Comparison of deduced amino acid sequences of these cDNAs shows that they represent a small family of genes that share a high degree of sequence homology among themselves as well as among genes from other organisms including tomato, Arabidopsis, hamster, human, Drosophila, and yeast. Southern blot analysis reveals the presence of at least four genes. Our results concerning the tissue-specific expression as well as developmental regulation of these HMGR cDNAs highlight the important role of this enzyme in the growth and development of wheat. PMID:8108513

Kinematic comparison of the preferred and non-preferred foot punt kick.

PubMed

Ball, Kevin A

2011-11-01

Kicking with the non-preferred leg is important in Australian Football and becoming important in the rugby codes. The aim of this study was to examine differences between preferred and non-preferred leg kicking in the drop punt kick. Seventeen elite Australian Football players performed kicks with the preferred and non-preferred leg. Optotrak Certus collected kinematic data of the kick leg and pelvis (200 Hz) from kick leg toe-off until ball contact. Foot speed, knee and shank angular velocity at ball contact, and pelvis range of motion were significantly larger for the preferred leg (P < 0.05). In contrast, hip and thigh angular velocity at ball contact and hip range of motion were significantly larger for the non-preferred leg. This indicates different movement patterns, with preferred-leg kicks making greater use of the pelvis, knee, and shank while non-preferred leg kicks rely relatively more on the hip and thigh (P < 0.05). Reasons for this difference might be due to locking degrees of freedom or sub-optimal sequencing in the non-preferred leg. The thigh-knee continuum identified by Ball ( 2008 ) was also evident in this study. Findings have implications for training non-preferred leg kicking for performance and injury prevention.

An invasive plant alters pollinator-mediated phenotypic selection on a native congener.

PubMed

Beans, Carolyn M; Roach, Deborah A

2015-01-01

• Recent studies suggest that invasive plants compete reproductively with native plants by reducing the quantity or quality of pollinator visits. Although these studies have revealed ecological consequences of pollinator-mediated competition between invasive and native plants, the evolutionary outcomes of these interactions remain largely unexplored.• We studied the ecological and evolutionary impact of pollinator-mediated competition with an invasive jewelweed, Impatiens glandulifera, on a co-occurring native congener, I. capensis. Using a pollinator choice experiment, a hand pollination experiment, and a selection analysis, we addressed the following questions: (1) Do native pollinators show preference for the invasive or native jewelweed, and do they move between the two species? (2) Does invasive jewelweed pollen inhibit seed production in the native plant? (3) Does the invasive jewelweed alter phenotypic selection on the native plant's floral traits?• The pollinator choice experiment showed that pollinators strongly preferred the invasive jewelweed. The hand pollination experiment demonstrated that invasive pollen inhibited seed production in the native plant. The selection analysis showed that the presence of the invasive jewelweed altered phenotypic selection on corolla height in the native plant.• Invasive plants have the potential to alter phenotypic selection on floral traits in native plant populations. If native plants can evolve in response to this altered selection pressure, the evolution of floral traits may play an important role in permitting long-term coexistence of native and invasive plants. © 2015 Botanical Society of America, Inc.

How Are Preferences Revealed?

PubMed Central

Beshears, John; Choi, James J.; Laibson, David; Madrian, Brigitte C.

2009-01-01

Revealed preferences are tastes that rationalize an economic agent’s observed actions. Normative preferences represent the agent’s actual interests. It sometimes makes sense to assume that revealed preferences are identical to normative preferences. But there are many cases where this assumption is violated. We identify five factors that increase the likelihood of a disparity between revealed preferences and normative preferences: passive choice, complexity, limited personal experience, third-party marketing, and intertemporal choice. We then discuss six approaches that jointly contribute to the identification of normative preferences: structural estimation, active decisions, asymptotic choice, aggregated revealed preferences, reported preferences, and informed preferences. Each of these approaches uses consumer behavior to infer some property of normative preferences without equating revealed and normative preferences. We illustrate these issues with evidence from savings and investment outcomes. PMID:24761048

Transitivity of Preferences

ERIC Educational Resources Information Center

Regenwetter, Michel; Dana, Jason; Davis-Stober, Clintin P.

2011-01-01

Transitivity of preferences is a fundamental principle shared by most major contemporary rational, prescriptive, and descriptive models of decision making. To have transitive preferences, a person, group, or society that prefers choice option "x" to "y" and "y" to "z" must prefer "x" to…

Neural coding underlying the cue preference for celestial orientation

PubMed Central

el Jundi, Basil; Warrant, Eric J.; Byrne, Marcus J.; Khaldy, Lana; Baird, Emily; Smolka, Jochen; Dacke, Marie

2015-01-01

Diurnal and nocturnal African dung beetles use celestial cues, such as the sun, the moon, and the polarization pattern, to roll dung balls along straight paths across the savanna. Although nocturnal beetles move in the same manner through the same environment as their diurnal relatives, they do so when light conditions are at least 1 million-fold dimmer. Here, we show, for the first time to our knowledge, that the celestial cue preference differs between nocturnal and diurnal beetles in a manner that reflects their contrasting visual ecologies. We also demonstrate how these cue preferences are reflected in the activity of compass neurons in the brain. At night, polarized skylight is the dominant orientation cue for nocturnal beetles. However, if we coerce them to roll during the day, they instead use a celestial body (the sun) as their primary orientation cue. Diurnal beetles, however, persist in using a celestial body for their compass, day or night. Compass neurons in the central complex of diurnal beetles are tuned only to the sun, whereas the same neurons in the nocturnal species switch exclusively to polarized light at lunar light intensities. Thus, these neurons encode the preferences for particular celestial cues and alter their weighting according to ambient light conditions. This flexible encoding of celestial cue preferences relative to the prevailing visual scenery provides a simple, yet effective, mechanism for enabling visual orientation at any light intensity. PMID:26305929

Neural coding underlying the cue preference for celestial orientation.

PubMed

el Jundi, Basil; Warrant, Eric J; Byrne, Marcus J; Khaldy, Lana; Baird, Emily; Smolka, Jochen; Dacke, Marie

2015-09-08

Diurnal and nocturnal African dung beetles use celestial cues, such as the sun, the moon, and the polarization pattern, to roll dung balls along straight paths across the savanna. Although nocturnal beetles move in the same manner through the same environment as their diurnal relatives, they do so when light conditions are at least 1 million-fold dimmer. Here, we show, for the first time to our knowledge, that the celestial cue preference differs between nocturnal and diurnal beetles in a manner that reflects their contrasting visual ecologies. We also demonstrate how these cue preferences are reflected in the activity of compass neurons in the brain. At night, polarized skylight is the dominant orientation cue for nocturnal beetles. However, if we coerce them to roll during the day, they instead use a celestial body (the sun) as their primary orientation cue. Diurnal beetles, however, persist in using a celestial body for their compass, day or night. Compass neurons in the central complex of diurnal beetles are tuned only to the sun, whereas the same neurons in the nocturnal species switch exclusively to polarized light at lunar light intensities. Thus, these neurons encode the preferences for particular celestial cues and alter their weighting according to ambient light conditions. This flexible encoding of celestial cue preferences relative to the prevailing visual scenery provides a simple, yet effective, mechanism for enabling visual orientation at any light intensity.

Haploinsufficiency of COQ4 causes coenzyme Q10 deficiency.

PubMed

Salviati, Leonardo; Trevisson, Eva; Rodriguez Hernandez, Maria Angeles; Casarin, Alberto; Pertegato, Vanessa; Doimo, Mara; Cassina, Matteo; Agosto, Caterina; Desbats, Maria Andrea; Sartori, Geppo; Sacconi, Sabrina; Memo, Luigi; Zuffardi, Orsetta; Artuch, Rafael; Quinzii, Catarina; Dimauro, Salvatore; Hirano, Michio; Santos-Ocaña, Carlos; Navas, Plácido

2012-03-01

COQ4 encodes a protein that organises the multienzyme complex for the synthesis of coenzyme Q(10) (CoQ(10)). A 3.9 Mb deletion of chromosome 9q34.13 was identified in a 3-year-old boy with mental retardation, encephalomyopathy and dysmorphic features. Because the deletion encompassed COQ4, the patient was screened for CoQ(10) deficiency. A complete molecular and biochemical characterisation of the patient's fibroblasts and of a yeast model were performed. The study found reduced COQ4 expression (48% of controls), CoQ(10) content and biosynthetic rate (44% and 43% of controls), and activities of respiratory chain complex II+III. Cells displayed a growth defect that was corrected by the addition of CoQ(10) to the culture medium. Knockdown of COQ4 in HeLa cells also resulted in a reduction of CoQ(10.) Diploid yeast haploinsufficient for COQ4 displayed similar CoQ deficiency. Haploinsufficency of other genes involved in CoQ(10) biosynthesis does not cause CoQ deficiency, underscoring the critical role of COQ4. Oral CoQ(10) supplementation resulted in a significant improvement of neuromuscular symptoms, which reappeared after supplementation was temporarily discontinued. Mutations of COQ4 should be searched for in patients with CoQ(10) deficiency and encephalomyopathy; patients with genomic rearrangements involving COQ4 should be screened for CoQ(10) deficiency, as they could benefit from supplementation.

Production of stable isotope-labeled acyl-coenzyme A thioesters by yeast stable isotope labeling by essential nutrients in cell culture

PubMed Central

Snyder, Nathaniel W.; Tombline, Gregory; Worth, Andrew J.; Parry, Robert C.; Silvers, Jacob A.; Gillespie, Kevin P.; Basu, Sankha S.; Millen, Jonathan; Goldfarb, David S.; Blair, Ian A.

2015-01-01

Acyl-coenzyme A (CoA) thioesters are key metabolites in numerous anabolic and catabolic pathways, including fatty acid biosynthesis and β-oxidation, the Krebs cycle, and cholesterol and isoprenoid biosynthesis. Stable isotope dilution-based methodology is the gold standard for quantitative analyses by mass spectrometry. However, chemical synthesis of families of stable isotope labeled metabolites such as acyl-coenzyme A thioesters is impractical. Previously, we biosynthetically generated a library of stable isotope internal standard analogs of acyl-CoA thioesters by exploiting the essential requirement in mammals and insects for pantothenic acid (vitamin B5) as a metabolic precursor for the CoA backbone. By replacing pantothenic acid in the cell media with commercially available [13C3 15N1]-pantothenic acid, mammalian cells exclusively incorporated [13C3 15N1]-pantothenate into the biosynthesis of acyl-CoA and acyl-CoA thioesters. We have now developed a much more efficient method for generating stable isotope labeled CoA and acyl-CoAs from [13C3 15N1]-pantothenate using Stable Isotope Labeling by Essential nutrients in Cell culture (SILEC) in Pan6 deficient yeast cells. Efficiency and consistency of labeling were also increased, likely due to the stringently defined and reproducible conditions used for yeast culture. The yeast SILEC method greatly enhances the ease of use and accessibility of labeled CoA thioesters and also provides proof-of-concept for generating other labeled metabolites in yeast mutants. PMID:25572876

Evidence for co-operativity in coenzyme binding to tetrameric Sulfolobus solfataricus alcohol dehydrogenase and its structural basis: fluorescence, kinetic and structural studies of the wild-type enzyme and non-co-operative N249Y mutant

PubMed Central

2005-01-01

The interaction of coenzyme with thermostable homotetrameric NAD(H)-dependent alcohol dehydrogenase from the thermoacidophilic sulphur-dependent crenarchaeon Sulfolobus solfataricus (SsADH) and its N249Y (Asn-249→Tyr) mutant was studied using the high fluorescence sensitivity of its tryptophan residues Trp-95 and Trp-117 to the binding of coenzyme moieties. Fluorescence quenching studies performed at 25 °C show that SsADH exhibits linearity in the NAD(H) binding [the Hill coefficient (h)∼1) at pH 9.8 and at moderate ionic strength, in addition to positive co-operativity (h=2.0–2.4) at pH 7.8 and 6.8, and at pH 9.8 in the presence of salt. Furthermore, NADH binding is positively co-operative below 20 °C (h∼3) and negatively co-operative at 40–50 °C (h∼0.7), as determined at moderate ionic strength and pH 9.8. Steady-state kinetic measurements show that SsADH displays standard Michaelis–Menten kinetics between 35 and 45 °C, but exhibits positive and negative co-operativity for NADH oxidation below (h=3.3 at 20 °C) and above (h=0.7 at 70–80 °C) this range of temperatures respectively. However, N249Y SsADH displays non-co-operative behaviour in coenzyme binding under the same experimental conditions used for the wild-type enzyme. In loop 270–275 of the coenzyme domain and segments at the interface of dimer A–B, analyses of the wild-type and mutant SsADH structures identified the structural elements involved in the intersubunit communication and suggested a possible structural basis for co-operativity. This is the first report of co-operativity in a tetrameric ADH and of temperature-induced co-operativity in a thermophilic enzyme. PMID:15651978

Evidence for co-operativity in coenzyme binding to tetrameric Sulfolobus solfataricus alcohol dehydrogenase and its structural basis: fluorescence, kinetic and structural studies of the wild-type enzyme and non-co-operative N249Y mutant.

PubMed

Giordano, Antonietta; Febbraio, Ferdinando; Russo, Consiglia; Rossi, Mosè; Raia, Carlo A

2005-06-01

The interaction of coenzyme with thermostable homotetrameric NAD(H)-dependent alcohol dehydrogenase from the thermoacidophilic sulphur-dependent crenarchaeon Sulfolobus solfataricus (SsADH) and its N249Y (Asn-249-->Tyr) mutant was studied using the high fluorescence sensitivity of its tryptophan residues Trp-95 and Trp-117 to the binding of coenzyme moieties. Fluorescence quenching studies performed at 25 degrees C show that SsADH exhibits linearity in the NAD(H) binding [the Hill coefficient (h) approximately 1) at pH 9.8 and at moderate ionic strength, in addition to positive co-operativity (h=2.0-2.4) at pH 7.8 and 6.8, and at pH 9.8 in the presence of salt. Furthermore, NADH binding is positively co-operative below 20 degrees C (h approximately 3) and negatively co-operative at 40-50 degrees C (h approximately 0.7), as determined at moderate ionic strength and pH 9.8. Steady-state kinetic measurements show that SsADH displays standard Michaelis-Menten kinetics between 35 and 45 degrees C, but exhibits positive and negative co-operativity for NADH oxidation below (h=3.3 at 20 degrees C) and above (h=0.7 at 70-80 degrees C) this range of temperatures respectively. However, N249Y SsADH displays non-co-operative behaviour in coenzyme binding under the same experimental conditions used for the wild-type enzyme. In loop 270-275 of the coenzyme domain and segments at the interface of dimer A-B, analyses of the wild-type and mutant SsADH structures identified the structural elements involved in the intersubunit communication and suggested a possible structural basis for co-operativity. This is the first report of co-operativity in a tetrameric ADH and of temperature-induced co-operativity in a thermophilic enzyme.

Nicotinic Acid Metabolism, V. A Cobamide Coenzyme-Dependent Conversion of α-Methyleneglutaric Acid to Dimethylmaleic Acid

PubMed Central

Kung, H. F.; Cederbaum, S.; Tsai, L.; Stadtman, T. C.

1970-01-01

A new B12-coenzyme-dependent isomerization, catalyzed by extracts of a nicotinate-fermenting clostridium, results in the conversion of α-methyleneglutaric acid to dimethylmaleic acid. These two acids are intermediates in the multistep anaerobic process wherein nicotinate is converted, ultimately, to one mole each of propionate, acetate, carbon dioxide, and ammonia. Dimethylmaleic acid reacts in its anhydride form with 2,4-dinitrophenylhydrazine to form N-2′,4′-dinitrophenyl-anilino-3,4-dimethylmaleimide. The characteristic reddish color exhibited by the latter derivative in alkaline solution serves as a convenient quantitative assay for dimethylmaleic acid. Comparison of the 2,4-dinitrophenylhydrazine derivatives of the product of the enzymic reaction and of synthetic dimethylmaleic anhydride showed them to be identical in every respect. PMID:5266166

Differential Substrate Specificity and Kinetic Behavior of Escherichia coli YfdW and Oxalobacter formigenes Formyl Coenzyme A Transferase▿ †

PubMed Central

Toyota, Cory G.; Berthold, Catrine L.; Gruez, Arnaud; Jónsson, Stefán; Lindqvist, Ylva; Cambillau, Christian; Richards, Nigel G. J.

2008-01-01

The yfdXWUVE operon appears to encode proteins that enhance the ability of Escherichia coli MG1655 to survive under acidic conditions. Although the molecular mechanisms underlying this phenotypic behavior remain to be elucidated, findings from structural genomic studies have shown that the structure of YfdW, the protein encoded by the yfdW gene, is homologous to that of the enzyme that mediates oxalate catabolism in the obligate anaerobe Oxalobacter formigenes, O. formigenes formyl coenzyme A transferase (FRC). We now report the first detailed examination of the steady-state kinetic behavior and substrate specificity of recombinant, wild-type YfdW. Our studies confirm that YfdW is a formyl coenzyme A (formyl-CoA) transferase, and YfdW appears to be more stringent than the corresponding enzyme (FRC) in Oxalobacter in employing formyl-CoA and oxalate as substrates. We also report the effects of replacing Trp-48 in the FRC active site with the glutamine residue that occupies an equivalent position in the E. coli protein. The results of these experiments show that Trp-48 precludes oxalate binding to a site that mediates substrate inhibition for YfdW. In addition, the replacement of Trp-48 by Gln-48 yields an FRC variant for which oxalate-dependent substrate inhibition is modified to resemble that seen for YfdW. Our findings illustrate the utility of structural homology in assigning enzyme function and raise the question of whether oxalate catabolism takes place in E. coli upon the up-regulation of the yfdXWUVE operon under acidic conditions. PMID:18245280

Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly.

PubMed

Alehagen, Urban; Aaseth, Jan; Alexander, Jan; Johansson, Peter

2018-01-01

Selenium and coenzyme Q10 are both necessary for optimal cell function in the body. The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases. Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed. The main publication reported reduced cardiovascular mortality as a result of the intervention. In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function. From a rural municipality in Sweden, four hundred forty-three healthy elderly individuals were included. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results, mortality was registered. After 12 years a significantly reduced CV mortality could be seen in those supplemented with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active treatment group, and 38.7% in the placebo group. A multivariate Cox regression analysis demonstrated a reduced CV mortality risk in the active treatment group (HR: 0.59; 95%CI 0.42-0.81; P = 0.001). In those with ischemic heart disease, diabetes, hypertension and impaired functional capacity we demonstrated a significantly reduced CV mortality risk. This is a 12-year follow-up of a group of healthy elderly participants that were supplemented with selenium and coenzyme Q10 for four years. Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity. The results thus validate the results obtained in the 10-year evaluation. The protective action was not confined to the intervention period, but

Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia.

PubMed

Tóth, Štefan; Šajty, Matej; Pekárová, Tímea; Mughees, Adil; Štefanič, Peter; Katz, Matan; Spišáková, Katarína; Pella, Jozef; Pella, Daniel

2017-07-26

Statins represent a group of drugs that are currently indicated in the primary and secondary prevention of cardiovascular events. Their administration can be associated with side effects and the insufficient reduction of triacylglyceride (TAG) levels. This study aimed to assess the effect of the triple combination of statins with omega-3 fatty acids and coenzyme Q10 (CoQ10) on parameters associated with atherogenesis and statin side effects. In this pilot randomized double-blind trial, 105 subjects who met the criteria of combined dislipidemia and elevated TAG levels were randomly divided into three groups. In the control group, unaltered statin therapy was indicated. In the second and third groups, omega-3 PUFA 2.52 g/day (Zennix fa Pleuran) and omega-3 PUFA 2.52 g+CoQ10 200 mg/day (Pharma Nord ApS) were added, res//. At the end of the 3-month period (±1 week), all patients were evaluated. Significant reduction of hepatic enzymes activity, systolic blood preasure, inflammatory markers and TAG levels were detected in both groups in comparison to the control group. Activity of SOD and GPx increased significantly after additive therapy. Coenzyme Q10 addition significantly reduced most of the abovementioned parameters (systolic blood preasure, total cholesterol, LDL, hsCRP, IL-6, SOD) in comparison with the statin+omega-3 PUFA group. The intensity of statin adverse effects were significantly reduced in the group with the addition of CoQ10. The results of this pilot study suggest the possible beneficial effects of triple combination on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.

Coenzyme Q10 Ameliorates Trimethyltin Chloride Neurotoxicity in Experimental Model of Injury in Dentate Gyrus of Hippocampus: A Histopathological and Behavioral Study

PubMed Central

Sakhaie, Mohammad Hassan; Soleimani, Mansoureh; Pirhajati, Vahid; Soleimani Asl, Sara; Madjd, Zahra; Mehdizadeh, Mehdi

2016-01-01

Background Coenzyme Q10 has antioxidative and free radical scavenging effects. CoQ10 supplementation is known to have neuroprotective effects in some neurodegenerative diseases, such as Parkinson’s disease and Huntington’s disease. Objectives The aim of this study was to evaluate both histopathologic and behavioral whether Coenzyme Q10 is protective against trimethyltin chloride (TMT) induced hippocampal damage. Materials and Methods This was an experimental study. Thirty-six Balb/c mice were divided into four groups, as follows: 1) control group; 2) sham group of mice that received a 100 µL intraperitoneal injection (IP) of sesame oil; 3) TMT group of mice that received a single 2.5 mg/kg/day IP injection of TMT; and 4) TMT + CoQ10 group of mice that received a 10 mg/kg IP injection of CoQ10. Body weight and Morris water maze (MWM) responses were investigated. In addition, the dentate gyrus neurons of the hippocampus were evaluated histopathologically by light and electron microscopes. Results This study revealed that the body weight scale was found to be significantly higher in the CoQ10 group (21.39 ± 2.70), compared to the TMT group (19.39 ± 2.74) (P < 0.05). In the TMT group, the animals showed body a weight loss that was significantly lower than that of the control group (22.33 ± 3.06) (P < 0.05). Our results showed that CoQ10 provided protection against MWM deficits. Furthermore, TMT impaired the ability of mice to locate the hidden platform, compared to the control group (P < 0.05). Microscopic studies showed that TMT caused histopathological changes in the dentate gyrus and increased the number of necrotic neurons (476 ± 78.51), compared to the control group (208 ± 40.84) (P < 0.001). But, CoQ10 significantly attenuated (31 9 ± 60.08) the density of necrotic neurons compared to TMT (P < 0.05). Conclusions The results of the present study indicate that Coenzyme Q10 diminished neuronal necrosis and improved learning memory. Part of its beneficial

Systematic Analysis of the 4-Coumarate:Coenzyme A Ligase (4CL) Related Genes and Expression Profiling during Fruit Development in the Chinese Pear.

PubMed

Cao, Yunpeng; Han, Yahui; Li, Dahui; Lin, Yi; Cai, Yongping

2016-10-19

In plants, 4-coumarate:coenzyme A ligases (4CLs), comprising some of the adenylate-forming enzymes, are key enzymes involved in regulating lignin metabolism and the biosynthesis of flavonoids and other secondary metabolites. Although several 4CL-related proteins were shown to play roles in secondary metabolism, no comprehensive study on 4CL-related genes in the pear and other Rosaceae species has been reported. In this study, we identified 4CL-related genes in the apple, peach, yangmei, and pear genomes using DNATOOLS software and inferred their evolutionary relationships using phylogenetic analysis, collinearity analysis, conserved motif analysis, and structure analysis. A total of 149 4CL-related genes in four Rosaceous species (pear, apple, peach, and yangmei) were identified, with 30 members in the pear. We explored the functions of several 4CL and acyl-coenzyme A synthetase (ACS) genes during the development of pear fruit by quantitative real-time PCR (qRT-PCR). We found that duplication events had occurred in the 30 4CL-related genes in the pear. These duplicated 4CL-related genes are distributed unevenly across all pear chromosomes except chromosomes 4, 8, 11, and 12. The results of this study provide a basis for further investigation of both the functions and evolutionary history of 4CL-related genes.

A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy.

PubMed

Taylor, Beth A; Lorson, Lindsay; White, C Michael; Thompson, Paul D

2015-02-01

Coenzyme Q10 (CoQ10) supplementation is the most popular therapy for statin myalgia among both physicians and patients despite limited and conflicting evidence of its efficacy. This study examined the effect of coenzyme Q10 (CoQ10) supplementation on simvastatin-associated muscle pain, muscle strength and aerobic performance in patients with confirmed statin myalgia. Statin myalgia was confirmed in 120 patients with prior symptoms of statin myalgia using an 8-week randomized, double-blind crossover trial of simvastatin 20 mg/d and placebo. Forty-one subjects developed muscle pain with simvastatin but not with placebo and were randomized to simvastatin 20 mg/d combined with CoQ10 (600 mg/d ubiquinol) or placebo for 8 weeks. Muscle pain (Brief Pain Inventory [BPI]), time to pain onset, arm and leg muscle strength, and maximal oxygen uptake (VO2max) were measured before and after each treatment. Serum CoQ10 increased from 1.3 ± 0.4 to 5.2 ± 2.3 mcg/mL with simvastatin and CoQ10, but did not increase with simvastatin and placebo (1.3 ± 0.3 to 0.8 ± 0.2) (p < 0.05). BPI pain severity and interference scores increased with simvastatin therapy (both p < 0.01), irrespective of CoQ10 assignment (p = 0.53 and 0.56). There were no changes in muscle strength or VO2max with simvastatin with or without CoQ10 (all p > 0.10). Marginally more subjects reported pain with CoQ10 (14 of 20 vs 7 of 18; p = 0.05). There was no difference in time to pain onset in the CoQ10 (3.0 ± 2.0 weeks) vs. placebo (2.4 ± 2.1 wks) groups (p = 0.55). A similar lack of CoQ10 effect was observed in 24 subjects who were then crossed over to the alternative treatment. Only 36% of patients complaining of statin myalgia develop symptoms during a randomized, double-blind crossover of statin vs placebo. CoQ10 supplementation does not reduce muscle pain in patients with statin myalgia. Trial RegistrationNCT01140308; www.clinicaltrials.gov. Copyright © 2014 Elsevier Ireland Ltd

Structural and functional characterization of a new recombinant histidine-tagged acyl coenzyme A binding protein (ACBP) from mouse

PubMed Central

Petrescu, Anca D.; Huang, Huan; Hostetler, Heather A.; Schroeder, Friedhelm; Kier, Ann B.

2008-01-01

Acyl-coenzyme A binding protein (ACBP) has been proposed to transport fatty acyl-CoAs intracellularly, facilitating their metabolism. In this study, a new mouse recombinant ACBP was produced by insertion of a histidine (his) tag at the C-terminus to allow efficient purification by Ni-affinity chromatography. The his-tag was inserted at the C-terminus since ACBP is a small molecular size (10 kDa) protein whose structure and activity are sensitive to amino acid substitutions in the N-terminus. The his tag had no or little effect on ACBP structure or ligand binding affinity and specificity. His-ACBP bound the naturally-occurring fluorescent cis-parinaroyl-CoA with very high affinity (Kd=2.15 nM), but exhibited no affinity for non-esterified cis-parinaric acid. To determine if the presence of the C-terminal his tag altered ACBP interactions with other proteins, direct binding to hepatocyte nuclear factor 4α (HNF-4α), a nuclear receptor regulating transcription of genes involved in lipid metabolism, was examined. His-ACBP and HNF-4α were labeled with Cy5 and Cy3, respectively, and direct interaction was determined by a novel fluorescence resonance energy transfer (FRET) binding assay. FRET analysis showed that his-ACBP directly interacted with HNF-4α (intermolecular distance of 73 Å) at high affinity (Kd=64-111 nM) similar to native ACBP. The his-tag also had no effect on ACBPs ability to interact with and stimulate microsomal enzymes utilizing or forming fatty acyl CoA. Thus, C-terminal his-tagged-ACBP maintained very similar structural and functional features of the untagged native protein and can be used in further in vitro experiments that require pure recombinant ACBP. PMID:18178100

Parallel circuits control temperature preference in Drosophila during ageing.

PubMed

Shih, Hsiang-Wen; Wu, Chia-Lin; Chang, Sue-Wei; Liu, Tsung-Ho; Lai, Jason Sih-Yu; Fu, Tsai-Feng; Fu, Chien-Chung; Chiang, Ann-Shyn

2015-07-16

The detection of environmental temperature and regulation of body temperature are integral determinants of behaviour for all animals. These functions become less efficient in aged animals, particularly during exposure to cold environments, yet the cellular and molecular mechanisms are not well understood. Here, we identify an age-related change in the temperature preference of adult fruit flies that results from a shift in the relative contributions of two parallel mushroom body (MB) circuits—the β'- and β-systems. The β'-circuit primarily controls cold avoidance through dopamine signalling in young flies, whereas the β-circuit increasingly contributes to cold avoidance as adult flies age. Elevating dopamine levels in β'-afferent neurons of aged flies restores cold sensitivity, suggesting that the alteration of cold avoidance behaviour with ageing is functionally reversible. These results provide a framework for investigating how molecules and individual neural circuits modulate homeostatic alterations during the course of senescence.

MSG intake and preference in mice are influenced by prior testing experience.

PubMed

Ackroff, Karen; Weintraub, Rachel; Sclafani, Anthony

2012-09-10

Monosodium glutamate (MSG), the prototypical umami substance, is used as a flavor enhancer in many foods, but when presented alone is often only weakly attractive. Yet with experience mice will develop strong preferences for MSG solution over water. The present experiments explored the conditions that change indifference to preference for MSG. C57BL/6J mice were given a series of 2-day two-bottle tests with water vs. an ascending series of MSG concentrations (0.1-450 mM) to assess preference and intake. Naive mice were indifferent to all concentrations, but following forced one-bottle exposure to 300 mM MSG they preferred most concentrations and consumed more MSG. Exposure to 100mM MSG also increased subsequent MSG preference but not intake. Experience with other nutritive solutions (8% sucrose, 8% Polycose, 8% casein hydrolysate, and isocaloric 3.5% soybean oil emulsion) also enhanced subsequent MSG preference and intake. Polycose and sucrose experience were almost as effective as MSG experience. However, not all sapid solutions were effective; 0.8% sucralose and 10mM MSG exposure did not alter subsequent MSG preference. The generality of the preexposure effect was tested by offering an ascending series (0.1-100 mM) of inosine monophosphate (IMP), another umami substance; initial indifference was converted to preference after forced exposure to 300 mM MSG. Together these results suggest that a combination of oral and post-oral effects may be responsible for the experience effect, with MSG itself the most potent stimulus. A final experiment revealed that MSG preference in naïve mice is enhanced by presenting the MSG and water drinking spouts far apart rather than side by side. Thus the preferences for umami solutions in mice are subject to influence from prior tastant experience as well spout position, which should be taken into account when studying acceptance of taste solutions in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Coenzyme Q deficiency causes impairment of the sulfide oxidation pathway.

PubMed

Ziosi, Marcello; Di Meo, Ivano; Kleiner, Giulio; Gao, Xing-Huang; Barca, Emanuele; Sanchez-Quintero, Maria J; Tadesse, Saba; Jiang, Hongfeng; Qiao, Changhong; Rodenburg, Richard J; Scalais, Emmanuel; Schuelke, Markus; Willard, Belinda; Hatzoglou, Maria; Tiranti, Valeria; Quinzii, Catarina M

2017-01-01

Coenzyme Q (CoQ) is an electron acceptor for sulfide-quinone reductase (SQR), the first enzyme of the hydrogen sulfide oxidation pathway. Here, we show that lack of CoQ in human skin fibroblasts causes impairment of hydrogen sulfide oxidation, proportional to the residual levels of CoQ. Biochemical and molecular abnormalities are rescued by CoQ supplementation in vitro and recapitulated by pharmacological inhibition of CoQ biosynthesis in skin fibroblasts and ADCK3 depletion in HeLa cells. Kidneys of Pdss2 kd/kd mice, which only have ~15% residual CoQ concentrations and are clinically affected, showed (i) reduced protein levels of SQR and downstream enzymes, (ii) accumulation of hydrogen sulfides, and (iii) glutathione depletion. These abnormalities were not present in brain, which maintains ~30% residual CoQ and is clinically unaffected. In Pdss2 kd/kd mice, we also observed low levels of plasma and urine thiosulfate and increased blood C4-C6 acylcarnitines. We propose that impairment of the sulfide oxidation pathway induced by decreased levels of CoQ causes accumulation of sulfides and consequent inhibition of short-chain acyl-CoA dehydrogenase and glutathione depletion, which contributes to increased oxidative stress and kidney failure. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Adaptation, Acceptance and Adaptive Preferences in Health and Capability Well-Being Measurement Amongst Those Approaching End of Life.

PubMed

Coast, Joanna; Bailey, Cara; Orlando, Rosanna; Armour, Kathy; Perry, Rachel; Jones, Louise; Kinghorn, Philip

2018-05-09

Adaptive preferences occur when people subconsciously alter their views to account for the possibilities available to them. Adaptive preferences may be problematic where these views are used in resource allocation decisions because they may lead to underestimation of the true benefits of providing services. This research explored the nature and extent of both adaptation (changing to better suit the context) and adaptive preferences (altering preferences in response to restricted options) in individuals approaching the end of life (EoL). Qualitative data from 'thinkaloud' interviews with 33 hospice patients, 22 close persons and 17 health professionals were used alongside their responses to three health/well-being measures for use in resource allocation decisions: EQ-5D-5L (health status); ICECAP-A (adult capability); and ICECAP-SCM (Supportive Care Measure; EoL capability). Constant comparative analysis combined a focus on both verbalised perceptions across the three groups and responses to the measures. Data collection took place between October 2012 and February 2014. Informants spoke clearly about how patients had adapted their lives in response to symptoms associated with their terminal condition. It was often seen as a positive choice to accept their state and adapt in this way but, at the same time, most patients were fully aware of the health and capability losses that they had faced. Self-assessments of health and capability generally appeared to reflect the pre-adaptation state, although there were exceptions. Despite adapting to their conditions, the reference group for individuals approaching EoL largely remained a healthy, capable population, and most did not show evidence of adaptive preferences.

Acute ethanol does not always affect delay discounting in rats selected to prefer or avoid ethanol.

PubMed

Wilhelm, Clare J; Mitchell, Suzanne H

2012-01-01

The purpose of this study was to determine whether animals predisposed to prefer alcohol possess an altered acute response to alcohol on a delay discounting task relative to animals predisposed to avoid alcohol. We used rats selected to prefer or avoid alcohol to assess whether genotype moderates changes in delay discounting induced by acute ethanol exposure. Selectively bred rat lines of Sardinian alcohol-preferring (sP; n = 8) and non-preferring (sNP; n = 8) rats, and alko alcohol (AA, n = 8) and alko non-alcohol (ANA, n = 8) rats were trained in an adjusting amount task to assess delay discounting. There were no significant effects of line on baseline discounting; however, both lines of alcohol-preferring rats exhibit slowed reaction times. Acute ethanol (0, 0.25, 0.5 g/kg) treatment also had no effect on delay discounting in any of the selectively bred rat lines. Our data indicate that in these lines of animals, alcohol preference or avoidance has no impact on delay discounting following acute ethanol exposure. It is possible that other genetic models or lines may be differentially affected by alcohol and exhibit qualitatively and quantitatively different responses in delay discounting tasks.

Reductive, Coenzyme A-Mediated Pathway for 3-Chlorobenzoate Degradation in the Phototrophic Bacterium Rhodopseudomonas palustris

PubMed Central

Egland, Paul G.; Gibson, Jane; Harwood, Caroline S.

2001-01-01

We isolated a strain of Rhodopseudomonas palustris (RCB100) by selective enrichment in light on 3-chlorobenzoate to investigate the steps that it uses to accomplish anaerobic dechlorination. Analyses of metabolite pools as well as enzyme assays suggest that R. palustris grows on 3-chlorobenzoate by (i) converting it to 3-chlorobenzoyl coenzyme A (3-chlorobenzoyl–CoA), (ii) reductively dehalogenating 3-chlorobenzoyl–CoA to benzoyl-CoA, and (iii) degrading benzoyl-CoA to acetyl-CoA and carbon dioxide. R. palustris uses 3-chlorobenzoate only as a carbon source and thus incorporates the acetyl-CoA that is produced into cell material. The reductive dechlorination route used by R. palustris for 3-chlorobenzoate degradation differs from those previously described in that a CoA thioester, rather than an unmodified aromatic acid, is the substrate for complete dehalogenation. PMID:11229940

Factors Influencing Parents' Preferences and Parents' Perceptions of Child Preferences of Picturebooks

PubMed Central

Wagner, Laura

2017-01-01

This study examined factors influencing parents' preferences and their perceptions of their children's preferences for picturebooks. First, a content analysis was conducted on a set of picturebooks (N = 87) drawn from the sample described in Wagner (2013); Then, parents (N = 149) rated the books and several content properties were examined for their ability to predict parents' preferences and their perception of their children's preferences. The initial content analysis found correlated clusters of disparate measures of complexity (linguistic, cognitive, narrative) and identified a distinctive sub-genre of modern books featuring female protagonists. The experimental preference analysis found that parents' own preferences were most influenced by the books' age and status; parents' perceptions of their children's preferences were influenced by gender, with parents perceiving their sons (but not daughters) as dis-preferring books with female protagnoists. In addition, influences of the child's reading ability and the linguistic complexity of the book on preferences suggested a sensitivity to the cultural practice of joint book-reading. PMID:28919869

Weight loss decreases self-reported appetite and alters food preferences in overweight and obese adults: Observational data from the DiOGenes study.

PubMed

Andriessen, Charlotte; Christensen, Pia; Vestergaard Nielsen, Lone; Ritz, Christian; Astrup, Arne; Meinert Larsen, Thomas; Martinez, J Alfredo; Saris, Wim H M; van Baak, Marleen A; Papadaki, Angeliki; Kunesova, Marie; Jebb, Susan; Blundell, John; Lawton, Clare; Raben, Anne

2018-06-01

People with obesity often struggle to maintain their weight loss after a weight loss period. Furthermore, the effect of weight loss on appetite and food preferences remains unclear. Hence this study investigated the effect of weight loss on subjective appetite and food preferences in healthy, overweight and obese volunteers. A subgroup of adult participants (n = 123) from the Diet Obesity and Genes (DiOGenes) study (subgroup A) was recruited from across six European countries. Participants lost ≥8% of initial body weight during an 8-week low calorie diet (LCD). Subjective appetite and food preferences were measured before and after the LCD, in response to a standardized meal test, using visual analogue rating scales (VAS) and the Leeds Food Choice Questionnaire (FCQ). After the LCD, participants reported increased fullness (p < 0.05), decreased desire to eat (p < 0.05) and decreased prospective consumption (p < 0.05) after consuming the test meal. An interaction effect (visit x time) was found for hunger ratings (p < 0.05). Area under the curve (AUC) for hunger, desire to eat and prospective consumption was decreased by 18.1%, 20.2% and 21.1% respectively whereas AUC for fullness increased by 13.9%. Preference for low-energy products measured by the Food Preference Checklist (FPC) decreased by 1.9% before the test meal and by 13.5% after the test meal (p < 0.05). High-carbohydrate and high-fat preference decreased by 11.4% and 16.2% before the test meal and by 17.4% and 22.7% after the meal (p < 0.05). No other effects were observed. These results suggest that LCD induced weight loss decreases the appetite perceptions of overweight volunteers whilst decreasing their preference for high-fat-, high-carbohydrate-, and low-energy products. Copyright © 2018 Elsevier Ltd. All rights reserved.

Can Molecular Hippocampal Alterations Explain Behavioral ...

EPA Pesticide Factsheets

Studies in both humans and animals have shown that prenatal stress can alter cognitive function and other neurological behaviors in adult offspring. One possible underlying mechanism for this may lie with alterations in hippocampal gene expression. The present study examined genotypical outcomes in adult male and female offspring of rats exposed to variable stress during pregnancy. Dams (n=15/treatment) were subjected to several non-chemical stressors including intermittent noise, light, crowding, restraint, and altered circadian lighting, from gestational day (GD) 13 to 20. Tail blood was drawn on GD 12, 16 and 20 to verify a stress response. Corticosterone levels were not different between the stressed and non-stressed dams on GD12 but was significantly increased in stressed dams on GD 16 and 20 compared to controls. Dams gave birth on GD22 (postnatal day or PND 0). Several behavioral tests were used to assess the cognitive and behavioral phenotype of the offspring from PND 49 through 86, including the Morris water maze and novel object recognition. Male and female stressed offspring showed reduced reversal learning on the Morris water maze and stressed females did not show a significant preference for the novel object (57 ± 8%) while control females did (71 ± 3%). This indicates altered cognition in prenatally stressed offspring. On PND 91-92, offspring were necropsied and hippocampal tissue was collected. Genotypic outcomes of prenatal stress w

Near-future carbon dioxide levels alter fish behaviour by interfering with neurotransmitter function

NASA Astrophysics Data System (ADS)

Nilsson, Göran E.; Dixson, Danielle L.; Domenici, Paolo; McCormick, Mark I.; Sørensen, Christina; Watson, Sue-Ann; Munday, Philip L.

2012-03-01

Predicted future CO2 levels have been found to alter sensory responses and behaviour of marine fishes. Changes include increased boldness and activity, loss of behavioural lateralization, altered auditory preferences and impaired olfactory function. Impaired olfactory function makes larval fish attracted to odours they normally avoid, including ones from predators and unfavourable habitats. These behavioural alterations have significant effects on mortality that may have far-reaching implications for population replenishment, community structure and ecosystem function. However, the underlying mechanism linking high CO2 to these diverse responses has been unknown. Here we show that abnormal olfactory preferences and loss of behavioural lateralization exhibited by two species of larval coral reef fish exposed to high CO2 can be rapidly and effectively reversed by treatment with an antagonist of the GABA-A receptor. GABA-A is a major neurotransmitter receptor in the vertebrate brain. Thus, our results indicate that high CO2 interferes with neurotransmitter function, a hitherto unrecognized threat to marine populations and ecosystems. Given the ubiquity and conserved function of GABA-A receptors, we predict that rising CO2 levels could cause sensory and behavioural impairment in a wide range of marine species, especially those that tightly control their acid-base balance through regulatory changes in HCO3- and Cl- levels.

Wheel running reduces high-fat diet intake, preference and mu-opioid agonist stimulated intake

PubMed Central

Liang, Nu-Chu; Bello, Nicholas T.; Moran, Timothy H.

2015-01-01

The ranges of mechanisms by which exercise affects energy balance remain unclear. One potential mechanism may be that exercise reduces intake and preference for highly palatable, energy dense fatty foods. The current study used a rodent wheel running model to determine whether and how physical activity affects HF diet intake/preference and reward signaling. Experiment 1 examined whether wheel running affected the ability of intracerebroventricular (ICV) µ opioid receptor agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO) to increase HF diet intake. Experiment 2 examined the effects of wheel running on the intake of and preference for a previously preferred HF diet. We also assessed the effects of wheel running and diet choice on mesolimbic dopaminergic and opioidergic gene expression. Experiment 1 revealed that wheel running decreased the ability of ICV DAMGO administration to stimulate HF diet intake. Experiment 2 showed that wheel running suppressed weight gain and reduced intake and preference for a previously preferred HF diet. Furthermore, the mesolimbic gene expression profile of wheel running rats was different from that of their sedentary paired-fed controls but similar to that of sedentary rats with large HF diet consumption. These data suggest that alterations in preference for palatable, energy dense foods play a role in the effects of exercise on energy homeostasis. The gene expression results also suggest that the hedonic effects of exercise may substitute for food reward to limit food intake and suppress weight gain. PMID:25668514

Synthesis of fruity ethyl esters by acyl coenzyme A: alcohol acyltransferase and reverse esterase activities in Oenococcus oeni and Lactobacillus plantarum.

PubMed

Costello, P J; Siebert, T E; Solomon, M R; Bartowsky, E J

2013-03-01

To assess the abilities of commercial wine lactic acid bacteria (LAB) to synthesize potentially flavour active fatty acid ethyl esters and determine mechanisms involved in their production. Oenococcus oeni AWRI B551 produced significant levels of ethyl hexanoate and ethyl octanoate following growth in an ethanolic test medium, and ester formation generally increased with increasing pH (4.5 > 3.5), anaerobiosis and precursor supplementation. Cell-free extracts of commercial O. oeni strains and Lactobacillus plantarum AWRI B740 were also tested for ester-synthesizing capabilities in a phosphate buffer via: (i) acyl coenzyme A: alcohol acyltransferase (AcoAAAT) activity and (ii) reverse esterase activity. For both ester-synthesizing activities, strain-dependent variation was observed, with AcoAAAT activity generally greater than reverse esterase. Reverse esterase in O. oeni AWRI B551 also esterified 1-propanol to produce propyl octanoate, and deuterated substrates ([(2)H(6)]ethanol and [(2)H(15)]octanoic acid) to produce the fully deuterated ester, [(2)H(5)]ethyl [(2)H(15)]octanoate. Wine LAB exhibit ethyl ester-synthesizing capability and possess two different ester-synthesizing activities, one of which is associated with an acyl coenzyme A: alcohol acyltransferase. This study demonstrates that wine LAB exhibit enzyme activities that can augment the ethyl ester content of wine. This knowledge will facilitate greater control over the impacts of malolactic fermentation on the fruity sensory properties and quality of wine. © 2012 Australian Wine Research Institute © 2012 The Society for Applied Microbiology.

The effect of coenzyme Q10 included by γ-cyclodextrin on the growth of fission yeast studied by microscope Raman spectroscopy

NASA Astrophysics Data System (ADS)

Nishida, Tatsuro; Kaino, Tomohiro; Ikarashi, Ryo; Nakata, Daisuke; Terao, Keiji; Ando, Masahiro; Hamaguchi, Hiro-o.; Kawamukai, Makoto; Yamamoto, Tatsuyuki

2013-09-01

The inclusion complex of coenzyme Q10 (CoQ10) by γ-cyclodextrin (γ-CD), CoQ10-CD complex, was recently developed. The addition of the CoQ10-CD complex recovered the growth of a fission yeast mutant strain, Δdps1, which otherwise cannot grow well due to the lack of coenzyme Q producing ability. However, the oxygen consumption rate of this strain was not restored by the addition of the CoQ10-CD complex. The addition of two other anti-oxidative reagents, glutathione and ascorbic acid, also recovered the growth of the Δdps1 strain as well. These results indicated that the recovery of the growth of Δdps1 was brought about by the anti-oxidative property of CoQ10. The intensity of Raman spectra of Δdps1 at 1602 cm-1, which is prominently observed for the wild type of the fission yeast, was compared between before and after addition of the CoQ10-CD complex. The signal was very weakly observed for Δdps1 and did not increase in intensity by the addition of the CoQ10-CD complex. These results suggested the recovery of the growth of Δdps1 was brought about not by the restoration of respiration function of Δdps1 but by the anti-oxidative property of CoQ10 to result in the decrease in the oxidative stress.

Recurrent Ventricular Tachycardia in Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency.

PubMed

Bala, P; Ferdinandusse, S; Olpin, S E; Chetcuti, P; Morris, A A M

2016-01-01

We report a baby with medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency who presented on day 2 with poor feeding and lethargy. She was floppy with hypoglycaemia (1.8 mmol/l) and hyperammonaemia (182 μmol/l). Despite correction of these and a continuous intravenous infusion of glucose at 4.5-6.2 mg/kg/min, she developed generalised tonic clonic seizures on day 3. She also suffered two episodes of pulseless ventricular tachycardia, from which she was resuscitated successfully. Unfortunately, she died on day 5, following a third episode of pulseless ventricular tachycardia. Arrhythmias are generally thought to be rarer in MCAD deficiency than in disorders of long-chain fatty acid oxidation. This is, however, the sixth report of ventricular tachyarrhythmias in MCAD deficiency. Five of these involved neonates and it may be that patients with MCAD deficiency are particularly prone to ventricular arrhythmias in the newborn period. Three of the patients (including ours) had normal blood glucose concentrations at the time of the arrhythmias and had been receiving intravenous glucose for many hours. These cases suggest that arrhythmias can be induced by medium-chain acylcarnitines or other metabolites accumulating in MCAD deficiency. Ventricular tachyarrhythmias can occur in MCAD deficiency, especially in neonates.

Preparation of coenzyme Q10 liposomes using supercritical anti-solvent technique.

PubMed

Xia, Fei; Jin, Heyang; Zhao, Yaping; Guo, Xinqiu

2012-01-01

Coenzyme Q(10) (CoQ(10)) proliposomes were prepared using the supercritical anti-solvent (SAS) technique to encapsulate CoQ(10). The mixture of cholesterol and soya bean phosphatidylcholine (PC) was chosen as wall materials. The effects of operation conditions (temperature, pressure and components) on the recovery of CoQ(10) and the CoQ(10) loading in CoQ(10) proliposomes were studied. At the optimum conditions of pressure of 8.0 MPa, temperature of 35°C, the weight ratio of 1/10 between CoQ(10) and PC, and the weight ratio of 1/3 between cholesterol and PC, the CoQ(10) loading reached 8.92%. CoQ(10) liposomes were obtained by hydrating CoQ(10) proliposomes and the entrapment efficiency of CoQ(10) reached 82.28%. The morphologies of CoQ(10) proliposomes were characterized by scanning electron microscope, and their solid states were characterized by X-ray diffractometer. The structures of CoQ(10) liposomes were characterized by transmission electron microscope. The particle size distribution of CoQ(10) liposomes was determined by dynamic light scattering instrument. The results indicate that CoQ(10) liposomes with particle sizes about 50 nm can be easily obtained from hydrating CoQ(10) proliposomes prepared by SAS technique.

Trichostatin A (TSA) facilitates formation of partner preference in male prairie voles (Microtus ochrogaster).

PubMed

Duclot, F; Wang, H; Youssef, C; Liu, Y; Wang, Z; Kabbaj, M

2016-05-01

In the socially monogamous prairie voles (Microtus ochrogaster), the development of a social bonding is indicated by the formation of partner preference, which involves a variety of environmental and neurochemical factors and brain structures. In a most recent study in female prairie voles, we found that treatment with the histone deacetylase inhibitor trichostatin A (TSA) facilitates the formation of partner preference through up-regulation of oxytocin receptor (OTR) and vasopressin V1a receptor (V1aR) genes expression in the nucleus accumbens (NAcc). In the present study, we tested the hypothesis that TSA treatment also facilitates partner preference formation and alters OTR and V1aR genes expression in the NAcc in male prairie voles. We thus observed that central injection of TSA dose-dependently promoted the formation of partner preference in the absence of mating in male prairie voles. Interestingly, TSA treatment up-regulated OTR, but not V1aR, gene expression in the NAcc similarly as they were affected by mating - an essential process for naturally occurring partner preference. These data, together with others, not only indicate the involvement of epigenetic events but also the potential role of NAcc oxytocin in the regulation of partner preference in both male and female prairie voles. Copyright © 2016 Elsevier Inc. All rights reserved.

Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells

PubMed Central

Tsuchiya, Yugo; Peak-Chew, Sew Yeu; Newell, Clare; Miller-Aidoo, Sheritta; Mangal, Sriyash; Zhyvoloup, Alexander; Bakovic´, Jovana; Malanchuk, Oksana; Pereira, Gonçalo C.; Kotiadis, Vassilios; Szabadkai, Gyorgy; Duchen, Michael R.; Campbell, Mark; Cuenca, Sergio Rodriguez; Vidal-Puig, Antonio; James, Andrew M.; Murphy, Michael P.; Filonenko, Valeriy; Skehel, Mark

2017-01-01

Coenzyme A (CoA) is an obligatory cofactor in all branches of life. CoA and its derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. Abnormal biosynthesis and homeostasis of CoA and its derivatives have been associated with various human pathologies, including cancer, diabetes and neurodegeneration. Using an anti-CoA monoclonal antibody and mass spectrometry, we identified a wide range of cellular proteins which are modified by covalent attachment of CoA to cysteine thiols (CoAlation). We show that protein CoAlation is a reversible post-translational modification that is induced in mammalian cells and tissues by oxidising agents and metabolic stress. Many key cellular enzymes were found to be CoAlated in vitro and in vivo in ways that modified their activities. Our study reveals that protein CoAlation is a widespread post-translational modification which may play an important role in redox regulation under physiological and pathophysiological conditions. PMID:28341808

Modeling of process parameters for enhanced production of coenzyme Q10 from Rhodotorula glutinis.

PubMed

Balakumaran, Palanisamy Athiyaman; Meenakshisundaram, Sankaranarayanan

2015-01-01

Coenzyme Q10 (CoQ10) plays an indispensable role in ATP generation through oxidative phosphorylation and helps in scavenging superoxides generated during electron transfer reactions. It finds extensive applications specifically related to oxidative damage and metabolic dysfunctions. This article reports the use of a statistical approach to optimize the concentration of key variables for the enhanced production of CoQ10 by Rhodotorula glutinis in a lab-scale fermenter. The culture conditions that promote optimum growth and CoQ10 production were optimized and the interaction of significant variables para-hydroxybenzoic acid (PHB, 819.34 mg/L) and soybean oil (7.78% [v/v]) was studied using response surface methodology (RSM). CoQ10 production increased considerably from 10 mg/L (in control) to 39.2 mg/L in batch mode with RSM-optimized precursor concentration. In the fed-batch mode, PHB and soybean oil feeding strategy enhanced CoQ10 production to 78.2 mg/L.

Self-Love or Other-Love? Explicit Other-Preference but Implicit Self-Preference

PubMed Central

Gebauer, Jochen E.; Göritz, Anja S.; Hofmann, Wilhelm; Sedikides, Constantine

2012-01-01

Do humans prefer the self even over their favorite other person? This question has pervaded philosophy and social-behavioral sciences. Psychology’s distinction between explicit and implicit preferences calls for a two-tiered solution. Our evolutionarily-based Dissociative Self-Preference Model offers two hypotheses. Other-preferences prevail at an explicit level, because they convey caring for others, which strengthens interpersonal bonds–a major evolutionary advantage. Self-preferences, however, prevail at an implicit level, because they facilitate self-serving automatic behavior, which favors the self in life-or-die situations–also a major evolutionary advantage. We examined the data of 1,519 participants, who completed an explicit measure and one of five implicit measures of preferences for self versus favorite other. The results were consistent with the Dissociative Self-Preference Model. Explicitly, participants preferred their favorite other over the self. Implicitly, however, they preferred the self over their favorite other (be it their child, romantic partner, or best friend). Results are discussed in relation to evolutionary theorizing on self-deception. PMID:22848605

Fractionating choice: A study on reward discrimination, preference and relative valuation in the rat (Rattus norvegicus)

PubMed Central

Ricker, Joshua M.; Hatch, Justin D.; Powers, Daniel D.; Cromwell, Howard C.

2016-01-01

Choice behavior combines discrimination between distinctive outcomes, preference for specific outcomes and relative valuation of comparable outcomes. Previous work has focused on one component (i.e., preference) disregarding other influential processes that might provide a more complete understanding. Animal models of choice have been explored primarily utilizing extensive training, limited freedom for multiple decisions and sparse behavioral measures constrained to a single phase of motivated action. The present study used a paradigm that combines different elements of previous methods with the goal to distinguish among components of choice and explore how well components match predictions based on risk-sensitive foraging strategies. In order to analyze discrimination and relative valuation, it was necessary to have an option that shifted and an option that remained constant. Shifting outcomes among weeks included a change in single-option outcome (0 to 1 to 2 pellets) or a change in mixed-option outcome (0 or 5 to 0 or 3 to 0 or 1 pellets). Constant outcomes among weeks were also mixedoption (0 or 3 pellets) or single-option (1 pellet). Shifting single-option outcomes among weeks led to better discrimination, more robust preference and significant incentive contrast effects for the alternative outcome. Shifting multi-options altered choice components and led to dissociations among discrimination, preference, and reduced contrast effects. During extinction, all components were impacted with the greatest deficits during the shifting mixed-option outcome sessions. Results suggest choice behavior can be optimized for one component but suboptimal for others depending upon the complexity of alterations in outcome value between options. PMID:27078079

Rapid activation by 3,5,3'-L-triiodothyronine of adenosine 5'-monophosphate-activated protein kinase/acetyl-coenzyme a carboxylase and akt/protein kinase B signaling pathways: relation to changes in fuel metabolism and myosin heavy-chain protein content in rat gastrocnemius muscle in vivo.

PubMed

de Lange, Pieter; Senese, Rosalba; Cioffi, Federica; Moreno, Maria; Lombardi, Assunta; Silvestri, Elena; Goglia, Fernando; Lanni, Antonia

2008-12-01

T3 stimulates metabolic rate in many tissues and induces changes in fuel use. The pathways by which T3 induces metabolic/structural changes related to altered fuel use in skeletal muscle have not been fully clarified. Gastrocnemius muscle (isolated at different time points after a single injection of T3 into hypothyroid rats), displayed rapid inductions of AMP-activated protein kinase (AMPK) phosphorylation (threonine 172; within 6 h) and acetyl-coenzyme A carboxylase phosphorylation (serine 79; within 12 h). As a consequence, increases occurred in mitochondrial fatty acid oxidation and carnitine palmitoyl transferase activity. Concomitantly, T3 stimulated signaling toward increased glycolysis through a rapid increase in Akt/protein kinase B (serine 473) phosphorylation (within 6 h) and a directly related increase in the activity of phosphofructokinase. The kinase specificity of the above effects was verified by treatment with inhibitors of AMPK and Akt activity (compound C and wortmannin, respectively). In contrast, glucose transporter 4 translocation to the membrane (activated by T3 within 6 h) was maintained when either AMPK or Akt activity was inhibited. The metabolic changes were accompanied by a decline in myosin heavy-chain Ib protein [causing a shift toward the fast-twitch (glycolytic) phenotype]. The increases in AMPK and acetyl-coenzyme A carboxylase phosphorylation were transient events, both levels declining from 12 h after the T3 injection, but Akt phosphorylation remained elevated until at least 48h after the injection. These data show that in skeletal muscle, T3 stimulates both fatty acid and glucose metabolism through rapid activations of the associated signaling pathways involving AMPK and Akt/protein kinase B.

U2AF1 mutations alter splice site recognition in hematological malignancies.

PubMed

Ilagan, Janine O; Ramakrishnan, Aravind; Hayes, Brian; Murphy, Michele E; Zebari, Ahmad S; Bradley, Philip; Bradley, Robert K

2015-01-01

Whole-exome sequencing studies have identified common mutations affecting genes encoding components of the RNA splicing machinery in hematological malignancies. Here, we sought to determine how mutations affecting the 3' splice site recognition factor U2AF1 alter its normal role in RNA splicing. We find that U2AF1 mutations influence the similarity of splicing programs in leukemias, but do not give rise to widespread splicing failure. U2AF1 mutations cause differential splicing of hundreds of genes, affecting biological pathways such as DNA methylation (DNMT3B), X chromosome inactivation (H2AFY), the DNA damage response (ATR, FANCA), and apoptosis (CASP8). We show that U2AF1 mutations alter the preferred 3' splice site motif in patients, in cell culture, and in vitro. Mutations affecting the first and second zinc fingers give rise to different alterations in splice site preference and largely distinct downstream splicing programs. These allele-specific effects are consistent with a computationally predicted model of U2AF1 in complex with RNA. Our findings suggest that U2AF1 mutations contribute to pathogenesis by causing quantitative changes in splicing that affect diverse cellular pathways, and give insight into the normal function of U2AF1's zinc finger domains. © 2015 Ilagan et al.; Published by Cold Spring Harbor Laboratory Press.

CINRG pilot trial of coenzyme Q10 in steroid-treated Duchenne muscular dystrophy.

PubMed

Spurney, Christopher F; Rocha, Carolina Tesi; Henricson, Erik; Florence, Julaine; Mayhew, Jill; Gorni, Ksenija; Pasquali, Livia; Pestronk, Alan; Martin, Gerard R; Hu, Fengming; Nie, Lei; Connolly, Anne M; Escolar, Diana M

2011-08-01

Corticosteroid treatment slows disease progression and is the standard of care for Duchenne muscular dystrophy (DMD). Coenzyme Q10 (CoQ10) is a potent antioxidant that may improve function in dystrophin-deficient muscle. We performed an open-label, "add-on" pilot study of CoQ10 in thirteen 5-10-year-old DMD patients on steroids. The primary outcome measure was the total quantitative muscle testing (QMT) score. Twelve of 16 children (mean age 8.03 ± 1.64 years) completed the trial. Target serum levels of CoQ10 (≥2.5 μg/ml) were shown to be subject- and administration-dependent. Nine of 12 subjects showed an increase in total QMT score. Overall, CoQ10 treatment resulted in an 8.5% increase in muscle strength (P = 0.03). Addition of CoQ10 to prednisone therapy in DMD patients resulted in an increase in muscle strength. These results warrant a larger, controlled trial of CoQ10 in DMD. Copyright © 2011 Wiley Periodicals, Inc.

Acute ethanol administration affects zebrafish preference for a biologically inspired robot.

PubMed

Spinello, Chiara; Macrì, Simone; Porfiri, Maurizio

2013-08-01

Preclinical animal models constitute a cornerstone against which the reward processes involved in drug addiction are often studied and dissected. While rodents have traditionally represented the species of choice, a growing body of literature indicates that zebrafish are emerging as a valuable model organism. Specifically, several studies demonstrate that the effects of ethanol at the level of emotional- and cognitive-related domains can be reliably investigated using zebrafish. The rapidly evolving nature of these efforts allows substantial room for the development of novel experimental paradigms suited to this freshwater species. The field of ethorobotics may prove particularly beneficial, due to its ability to convey fully controllable and easily reproducible experimental tools. In this study, we addressed the possibility of using a biologically inspired robot to investigate the emotionally related properties of ethanol in a preference task in zebrafish. To this aim, we evaluated wild-type zebrafish preference toward a robotic stimulus and addressed whether ethanol administration (0.25% and 1.00% ethanol/water concentration) may alter such preferences. In accordance with our previous studies, we observed that zebrafish exhibit a natural attraction toward the robot. Additionally, in agreement with our predictions, we showed that ethanol administration abolishes such preferences. This work is the first to demonstrate that robotic stimuli can be used in zebrafish to investigate the reward-related properties of alcohol. Copyright © 2013 Elsevier Inc. All rights reserved.

Parallel circuits control temperature preference in Drosophila during ageing

PubMed Central

Shih, Hsiang-Wen; Wu, Chia-Lin; Chang, Sue-Wei; Liu, Tsung-Ho; Sih-Yu Lai, Jason; Fu, Tsai-Feng; Fu, Chien-Chung; Chiang, Ann-Shyn

2015-01-01

The detection of environmental temperature and regulation of body temperature are integral determinants of behaviour for all animals. These functions become less efficient in aged animals, particularly during exposure to cold environments, yet the cellular and molecular mechanisms are not well understood. Here, we identify an age-related change in the temperature preference of adult fruit flies that results from a shift in the relative contributions of two parallel mushroom body (MB) circuits—the β′- and β-systems. The β′-circuit primarily controls cold avoidance through dopamine signalling in young flies, whereas the β-circuit increasingly contributes to cold avoidance as adult flies age. Elevating dopamine levels in β′-afferent neurons of aged flies restores cold sensitivity, suggesting that the alteration of cold avoidance behaviour with ageing is functionally reversible. These results provide a framework for investigating how molecules and individual neural circuits modulate homeostatic alterations during the course of senescence. PMID:26178754

Changes in taste preference and steps taken after sleep curtailment.

PubMed

Smith, Shannon L; Ludy, Mary-Jon; Tucker, Robin M

2016-09-01

A substantial proportion of the population does not achieve the recommended amount of sleep. Previous work demonstrates that sleep alterations perturb energy balance by disrupting appetite hormones, increasing energy intake, and decreasing physical activity. This study explored the influence of sleep duration on taste perception as well as effects on dietary intake and physical activity. Participants (n=24 habitual short sleepers and n=27 habitual long sleepers, 82.4% female, 88.2% white, 25.2±7.7years) completed two randomized taste visits; one following short sleep duration (≤7h) and one following long sleep duration (>7h). Taste perception measures included sweet and salt detection thresholds (ascending 3-alternative, forced-choice method), as well as sweet preference (Monell 2-series, forced-choice, paired-comparison, tracking method). Steps and sleep were tracked via FitBit, an activity monitoring device. Dietary intake was assessed using 24-hour recalls and analyzed using Nutritionist Pro. Habitual long-sleepers had a higher sweet taste preference (p=0.042) and took fewer steps (p=0.036) following sleep curtailment compared to the night where they slept >7h but did not experience changes in dietary intake or detection thresholds. Habitual short-sleepers did not experience changes in taste perception, activity, or dietary intake following sleep alteration. Habitual long-sleepers may be at greater risk of gaining weight when typical sleep patterns are disrupted. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of the additives on clouding behavior and thermodynamics of coenzyme Q10-Kolliphor HS15 micelle aqueous solutions

NASA Astrophysics Data System (ADS)

Hu, Li; Zhang, Jing; Zhu, Chao; Pan, Hong-chun; Liu, Hong

2017-11-01

Herein we investigate the effect of different additives (electrolytes, amino acids, PEG, and sugars) on the cloud points (CP) of coenzyme Q10 (CoQ10) - Kolliphor HS15 (HS15) micelle aqueous solutions. The CP values were decreased with the increase of electrolytes and sugars, following: CPAl3+ < CPMg2+ < CPCa2+ < CPNa+ < CPK+ < CPNH4+; CPdisaccharide < CPmonosaccharide. The presences of Arginine and Tryptophan significantly increased the CP; while the other amino acids reduced the CP. A depression of CP for CoQ10-HS15 micelle solution with PEG was molecular weight of PEG dependent. The significant thermodynamic parameters were also evaluated and discussed.

Preference and avoidance pH of brook trout Salvelinus fontinalis and brown trout Salmo trutta exposed to different holding pH.

PubMed

Fost, B A; Ferreri, C P

2015-08-01

The goal of this study was to determine if short-term exposure of brook trout Salvelinus fontinalis and brown trout Salmo trutta to a lower pH than found in their source stream results in a shift in preference or avoidance pH. The lack of a shift in preference or avoidance pH of adult S. fontinalis and S. trutta suggests that these species can be held at a pH different from the source waterbody for a short period of time without altering preference or avoidance pH behaviour. © 2015 The Fisheries Society of the British Isles.

Reduction of coenzyme q10 content: a possible effect of isoproterenol on heart failure and myocardial infarction in rat.

PubMed

Khorrami, A; Garjani, A; Ghanbarzadeh, S; Andalib, S

2014-04-01

Myocardial infarction (MI) was induced by subcutaneous injection of isoproterenol (ISO) to investigate the effect of ISO on Coenzyme Q10 (CoQ10) content of myocardium and subsequent effects on lipid peroxidation, electrocardiogram pattern and hemodynamic parameters of the rat's heart.36 male Wistar rats were divided randomly into 6 groups. To induce heart failure (HF) and MI, 10 and 100 mg/kg of ISO was administered subcutaneously for 10 and 2 consecutive days, respectively. The effects of ISO on myocardium CoQ10 content, concentration of malondialdehyde, ECG pattern and hemodynamic parameters of heart were analyzed.ISO-treated rats showed significant alteration in heart hemodynamic parameters such as reduction of left-ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, besides increase of left ventricular end-diastolic pressure. Significant depletion of heart CoQ10 content (from 4.57 and 4.55 µg/100 mg tissue in control groups to 2.85 and 2.89 µg/100 mg tissue in ISO-induced HF and MI groups respectively) and increase in tissue levels of malondialdehyde (47.1 and 53.8 nmol/100 mg tissue in ISO-induced HF and MI groups, respectively) were also observed in ISO-treated animals compared with the normal animals (17.4 and 18.8 nmol/100 mg tissue in control groups, respectively). Additionally CoQ10 improved ISO effects on hemodynamic parameters and ECG pattern in ISO-induced HF and myocardial injury.The present findings have demonstrated that the cardiotoxic effects of ISO such as oxidative damage and hemodynamic declination might be related to depletion of CoQ10 concentration. © Georg Thieme Verlag KG Stuttgart · New York.

Postprandial antioxidant gene expression is modified by Mediterranean diet supplemented with coenzyme Q(10) in elderly men and women.

PubMed

Yubero-Serrano, Elena M; Gonzalez-Guardia, Lorena; Rangel-Zuñiga, Oriol; Delgado-Casado, Nieves; Delgado-Lista, Javier; Perez-Martinez, Pablo; Garcia-Rios, Antonio; Caballero, Javier; Marin, Carmen; Gutierrez-Mariscal, Francisco M; Tinahones, Francisco J; Villalba, Jose M; Tunez, Isaac; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

2013-02-01

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial gene expression and protein levels involved in oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) improves this situation in an elderly population. Twenty participants were randomized to receive three isocaloric diets each for 4 weeks: Mediterranean diet supplemented with CoQ (Med + CoQ diet), Mediterranean diet (Med diet), saturated fatty acid-rich diet (SFA diet). After 12-h fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Nrf2, p22(phox) and p47(phox), superoxide dismutase 1 and 2 (SOD1 and SOD2), glutathione peroxidase 1 (GPx1), thiorredoxin reductase (TrxR) gene expression and Kelch-like ECH associating protein 1 (Keap-1) and citoplasmic and nuclear Nrf2 protein levels were determined. Med and Med + CoQ diets induced lower Nrf2, p22(phox), p47(phox), SOD1, SOD2 and TrxR gene expression and higher cytoplasmic Nrf2 and Keap-1 protein levels compared to the SFA diet. Moreover, Med + CoQ diet produced lower postprandial Nrf2 gene expression and lower nuclear Nrf2 protein levels compared to the other diets and lower GPx1 gene expression than the SFA diet. Our results support the antioxidant effect of a Med diet and that exogenous CoQ supplementation has a protective effects against free radical overgeneration through the lowering of postprandial oxidative stress modifying the postprandial antioxidant protein levels and reducing the postprandial expression of antioxidant genes in peripheral blood mononuclear cells.

Systematic Analysis of the 4-Coumarate:Coenzyme A Ligase (4CL) Related Genes and Expression Profiling during Fruit Development in the Chinese Pear

PubMed Central

Cao, Yunpeng; Han, Yahui; Li, Dahui; Lin, Yi; Cai, Yongping

2016-01-01

In plants, 4-coumarate:coenzyme A ligases (4CLs), comprising some of the adenylate-forming enzymes, are key enzymes involved in regulating lignin metabolism and the biosynthesis of flavonoids and other secondary metabolites. Although several 4CL-related proteins were shown to play roles in secondary metabolism, no comprehensive study on 4CL-related genes in the pear and other Rosaceae species has been reported. In this study, we identified 4CL-related genes in the apple, peach, yangmei, and pear genomes using DNATOOLS software and inferred their evolutionary relationships using phylogenetic analysis, collinearity analysis, conserved motif analysis, and structure analysis. A total of 149 4CL-related genes in four Rosaceous species (pear, apple, peach, and yangmei) were identified, with 30 members in the pear. We explored the functions of several 4CL and acyl-coenzyme A synthetase (ACS) genes during the development of pear fruit by quantitative real-time PCR (qRT-PCR). We found that duplication events had occurred in the 30 4CL-related genes in the pear. These duplicated 4CL-related genes are distributed unevenly across all pear chromosomes except chromosomes 4, 8, 11, and 12. The results of this study provide a basis for further investigation of both the functions and evolutionary history of 4CL-related genes. PMID:27775579

Happy faces are preferred regardless of familiarity--sad faces are preferred only when familiar.

PubMed

Liao, Hsin-I; Shimojo, Shinsuke; Yeh, Su-Ling

2013-06-01

Familiarity leads to preference (e.g., the mere exposure effect), yet it remains unknown whether it is objective familiarity, that is, repetitive exposure, or subjective familiarity that contributes to preference. In addition, it is unexplored whether and how different emotions influence familiarity-related preference. The authors investigated whether happy or sad faces are preferred or perceived as more familiar and whether this subjective familiarity judgment correlates with preference for different emotional faces. An emotional face--happy or sad--was paired with a neutral face, and participants rated the relative preference and familiarity of each of the paired faces. For preference judgment, happy faces were preferred and sad faces were less preferred, compared with neutral faces. For familiarity judgment, happy faces did not show any bias, but sad faces were perceived as less familiar than neutral faces. Item-by-item correlational analyses show preference for sad faces--but not happy faces--positively correlate with familiarity. These results suggest a direct link between positive emotion and preference, and argue at least partly against a common cause for familiarity and preference. Instead, facial expression of different emotional valence modulates the link between familiarity and preference.

Stress during Adolescence Alters Palatable Food Consumption in a Context-Dependent Manner.

PubMed

Handy, Christine; Yanaga, Stephanie; Reiss, Avery; Zona, Nicole; Robinson, Emily; Saxton, Katherine B

2016-01-01

Food consumption and preferences may be shaped by exposure to stressful environments during sensitive periods in development, and even small changes in consumption can have important effects on long term health. Adolescence is increasingly recognized as a sensitive period, in which adverse experiences can alter development, but the specific programming effects that may occur during adolescence remain incompletely understood. The current study seeks to explore the effects of stress during late adolescence on consumption of a palatable, high-fat, high-sugar food in adulthood-under basal conditions, as well following acute stress. Male Long-Evans rats were exposed to a regimen of variable stress for seven days in late adolescence (PND 45-51). During the stress regimen, stressed animals gained significantly less weight than control animals, but weight in adulthood was unaffected by adolescent stress. Palatable food consumption differed between experimental groups, and the direction of effect depended on context; stressed rats ate significantly more palatable food than controls upon first exposure, but ate less following an acute stressor. Leptin levels and exploratory behaviors did not differ between stressed and non-stressed groups, suggesting that other factors regulate preference for a palatable food. Altered food consumption following adolescent stress suggests that rats remain sensitive to stress during late adolescence, and that adult feeding behavior may be affected by previous adverse experiences. Such programming effects highlight adolescence as a period of plasticity, with the potential to shape long term food consumption patterns and preferences.

Stress during Adolescence Alters Palatable Food Consumption in a Context-Dependent Manner

PubMed Central

Handy, Christine; Yanaga, Stephanie; Reiss, Avery; Zona, Nicole; Robinson, Emily; Saxton, Katherine B.

2016-01-01

Food consumption and preferences may be shaped by exposure to stressful environments during sensitive periods in development, and even small changes in consumption can have important effects on long term health. Adolescence is increasingly recognized as a sensitive period, in which adverse experiences can alter development, but the specific programming effects that may occur during adolescence remain incompletely understood. The current study seeks to explore the effects of stress during late adolescence on consumption of a palatable, high-fat, high-sugar food in adulthood—under basal conditions, as well following acute stress. Male Long-Evans rats were exposed to a regimen of variable stress for seven days in late adolescence (PND 45–51). During the stress regimen, stressed animals gained significantly less weight than control animals, but weight in adulthood was unaffected by adolescent stress. Palatable food consumption differed between experimental groups, and the direction of effect depended on context; stressed rats ate significantly more palatable food than controls upon first exposure, but ate less following an acute stressor. Leptin levels and exploratory behaviors did not differ between stressed and non-stressed groups, suggesting that other factors regulate preference for a palatable food. Altered food consumption following adolescent stress suggests that rats remain sensitive to stress during late adolescence, and that adult feeding behavior may be affected by previous adverse experiences. Such programming effects highlight adolescence as a period of plasticity, with the potential to shape long term food consumption patterns and preferences. PMID:26872268

Bees prefer foods containing neonicotinoid pesticides

NASA Astrophysics Data System (ADS)

Kessler, Sébastien C.; Tiedeken, Erin Jo; Simcock, Kerry L.; Derveau, Sophie; Mitchell, Jessica; Softley, Samantha; Stout, Jane C.; Wright, Geraldine A.

2015-05-01

The impact of neonicotinoid insecticides on insect pollinators is highly controversial. Sublethal concentrations alter the behaviour of social bees and reduce survival of entire colonies. However, critics argue that the reported negative effects only arise from neonicotinoid concentrations that are greater than those found in the nectar and pollen of pesticide-treated plants. Furthermore, it has been suggested that bees could choose to forage on other available flowers and hence avoid or dilute exposure. Here, using a two-choice feeding assay, we show that the honeybee, Apis mellifera, and the buff-tailed bumblebee, Bombus terrestris, do not avoid nectar-relevant concentrations of three of the most commonly used neonicotinoids, imidacloprid (IMD), thiamethoxam (TMX), and clothianidin (CLO), in food. Moreover, bees of both species prefer to eat more of sucrose solutions laced with IMD or TMX than sucrose alone. Stimulation with IMD, TMX and CLO neither elicited spiking responses from gustatory neurons in the bees' mouthparts, nor inhibited the responses of sucrose-sensitive neurons. Our data indicate that bees cannot taste neonicotinoids and are not repelled by them. Instead, bees preferred solutions containing IMD or TMX, even though the consumption of these pesticides caused them to eat less food overall. This work shows that bees cannot control their exposure to neonicotinoids in food and implies that treating flowering crops with IMD and TMX presents a sizeable hazard to foraging bees.

Bees prefer foods containing neonicotinoid pesticides.

PubMed

Kessler, Sébastien; Tiedeken, Erin Jo; Simcock, Kerry L; Derveau, Sophie; Mitchell, Jessica; Softley, Samantha; Stout, Jane C; Wright, Geraldine A

2015-05-07

The impact of neonicotinoid insecticides on insect pollinators is highly controversial. Sublethal concentrations alter the behaviour of social bees and reduce survival of entire colonies. However, critics argue that the reported negative effects only arise from neonicotinoid concentrations that are greater than those found in the nectar and pollen of pesticide-treated plants. Furthermore, it has been suggested that bees could choose to forage on other available flowers and hence avoid or dilute exposure. Here, using a two-choice feeding assay, we show that the honeybee, Apis mellifera, and the buff-tailed bumblebee, Bombus terrestris, do not avoid nectar-relevant concentrations of three of the most commonly used neonicotinoids, imidacloprid (IMD), thiamethoxam (TMX), and clothianidin (CLO), in food. Moreover, bees of both species prefer to eat more of sucrose solutions laced with IMD or TMX than sucrose alone. Stimulation with IMD, TMX and CLO neither elicited spiking responses from gustatory neurons in the bees' mouthparts, nor inhibited the responses of sucrose-sensitive neurons. Our data indicate that bees cannot taste neonicotinoids and are not repelled by them. Instead, bees preferred solutions containing IMD or TMX, even though the consumption of these pesticides caused them to eat less food overall. This work shows that bees cannot control their exposure to neonicotinoids in food and implies that treating flowering crops with IMD and TMX presents a sizeable hazard to foraging bees.

Alteration of cell cycle progression by Sindbis virus infection

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

Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa

We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Veromore » cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.« less

Altered Sense of Humor in Dementia

PubMed Central

Clark, Camilla N.; Nicholas, Jennifer M.; Gordon, Elizabeth; Golden, Hannah L.; Cohen, Miriam H.; Woodward, Felix J.; Macpherson, Kirsty; Slattery, Catherine F.; Mummery, Catherine J.; Schott, Jonathan M.; Rohrer, Jonathan D.; Warren, Jason D.

2015-01-01

Sense of humor is potentially relevant to social functioning in dementias, but has been little studied in these diseases. We designed a semi-structured informant questionnaire to assess humor behavior and preferences in patients with behavioral variant frontotemporal dementia (bvFTD; n = 15), semantic dementia (SD; n = 7), progressive nonfluent aphasia (PNFA; n = 10), and Alzheimer’s disease (AD; n = 16) versus healthy age-matched individuals (n = 21). Altered (including frankly inappropriate) humor responses were significantly more frequent in bvFTD and SD (all patients) than PNFA or AD (around 40% of patients). All patient groups liked satirical and absurdist comedy significantly less than did healthy controls. This pattern was reported premorbidly for satirical comedy in bvFTD, PNFA, and AD. Liking for slapstick comedy did not differ between groups. Altered sense of humor is particularly salient in bvFTD and SD, but also frequent in AD and PNFA. Humor may be a sensitive probe of social cognitive impairment in dementia, with diagnostic, biomarker and social implications. PMID:26444779

Acetyl-coenzyme A synthetase 2 is a nuclear protein required for replicative longevity in Saccharomyces cerevisiae

PubMed Central

Falcón, Alaric A.; Chen, Shaoping; Wood, Michael S.

2013-01-01

Acs2p is one of two acetyl-coenzyme A synthetases in Saccharomyces cerevisiae. We have prepared and characterized a monoclonal antibody specific for Acs2p and find that Acs2p is localized primarily to the nucleus, including the nucleolus, with a minor amount in the cytosol. We find that Acs2p is required for replicative longevity: an acs2Δ strain has a reduced replicative life span compared to wild-type and acs1Δ strains. Furthermore, replicatively aged acs2Δ cells contain elevated levels of extrachromosomal rDNA circles, and silencing at the rDNA locus is impaired in an acs2Δ strain. These findings indicate that Acs2p-mediated synthesis of acetyl-CoA in the nucleus functions to promote rDNA silencing and replicative longevity in yeast. PMID:19618123

Young women's preferences for market work: responses to marital events.

PubMed

Spitze, G D; Waite, L J

1981-01-01

A causal model of changes in women's longrun tastes for paid employment was developed. It is based on the premise that women have a certain preference for market versus home work at the beginning of a year and that during the year some women experience a marital event, which may be a 1st marriage, a 1st birth, or the breakup of an existing marriage. This marital event may then cause some of the women experiencing it to revise their relative tastes for employment and work in the home. It is argued that changes in the level of such resources as time and money and changes in feelings of personal fulfillment that occur as a result of marriage, 1st birth, or divorce are responsible for alterations in market work preferences. Data from the National Longitudinal Survey of Young Women were used to examine how women's relative preference for market work and home work are affected by the transitions of 1st marriage, marital dissolution, and 1st birth. This survey includes yearly data on over 5000 young women over a recent 5 year period. Personal interviews were conducted with a national probability sample of the noninstitutionalized female population age 14-24 in 1968, with yearly reinterviews through 1973. The impact of a 1st marriage during a year on preference for market work at the end of that year was consistently negative from ages 14 through 23. The likelihood that a young woman prefers market to home work at age 35 decreases from 10-20 percentage points upon 1st marriage. Women who first marry beyond age 24 experience no change in preferences for labor force participation. The positive impact of marital dissolution on a young woman's preference for labor force participation was substantial--between 18 and 29 percentage points--and tended to be higher the later it occurred. The experience of marital dissolution causes women to need to prepare for work. The results suggest that it also increases their desire to work. A 1st birth had no immediate impact but was followed

A new double coupling system: synthesis of citronellyl acetate via transacetylation to citronellol from acetyl coenzyme A produced from glucose and free fatty acids.

PubMed

Oda, S; Ohta, H

2001-08-01

A double coupling system, which couples metabolism of glucose and transacetylation, is a unique procedure for the production of acetic esters. In the novel coupling system described in this article, acetyl coenzyme A (acetyl-CoA) was supplied via metabolism of both glucose and exogenous saturated fatty acids. While short and middle chain fatty acids having C4-8 were very biotoxic, myristic acid (C14) was effectively used as a source of acetyl-CoA.

Oxidoreductases Involved in Cell Carbon Synthesis of Methanobacterium thermoautotrophicum

PubMed Central

Zeikus, J. G.; Fuchs, G.; Kenealy, W.; Thauer, R. K.

1977-01-01

Cell-free extracts of Methanobacterium thermoautotrophicum were found to contain high activities of the following oxidoreductases (at 60°C): pyruvate dehydrogenase (coenzyme A acetylating), 275 nmol/min per mg of protein; α-ketoglutarate dehydrogenase (coenzyme A acylating), 100 nmol/min per mg; fumarate reductase, 360 nmol/min per mg; malate dehydrogenase, 240 nmol/min per mg; and glyceraldehyde-3-phosphate dehydrogenase, 100 nmol/min per mg. The kinetic properties (apparent Vmax and KM values), pH optimum, temperature dependence of the rate, and specificity for electron acceptors/donors of the different oxidoreductases were examined. Pyruvate dehydrogenase and α-ketoglutarate dehydrogenase were shown to be two separate enzymes specific for factor 420 rather than for nicotinamide adenine dinucleotide (NAD), NADP, or ferredoxin as the electron acceptor. Both activities catalyzed the reduction of methyl viologen with the respective α-ketoacid and a coenzyme A-dependent exchange between the carboxyl group of the α-ketoacid and CO2. The data indicate that the two enzymes are similar to pyruvate synthase and α-ketoglutarate synthase, respectively. Fumarate reductase was found in the soluble cell fraction. This enzyme activity coupled with reduced benzyl viologen as the electron donor, but reduced factor 420, NADH, or NADPH was not effective. The cells did not contain menaquinone, thus excluding this compound as the physiological electron donor for fumarate reduction. NAD was the preferred coenzyme for malate dehydrogenase, whereas NADP was preferred for glyceraldehyde-3-phosphate dehydrogenase. The organism also possessed a factor 420-dependent hydrogenase and a factor 420-linked NADP reductase. The involvement of the described oxidoreductases in cell carbon synthesis is discussed. PMID:914779

Risk Preference and Diagnosticity.

ERIC Educational Resources Information Center

Rocklin, Thomas

Researchers have suggested two models of risk preference to account for subjects' preference for tasks of moderate difficulty. The affective model proposes that pride of success and shame of failure are responsible for the observed preference. The cognitive model suggests preference for tasks of moderate difficulty because they are the most…

The evidence basis for coenzyme Q therapy in oxidative phosphorylation disease.

PubMed

Haas, Richard H

2007-06-01

The evidence supporting a treatment benefit for coenzyme Q10 (CoQ10) in primary mitochondrial disease (mitochondrial disease) whilst positive is limited. Mitochondrial disease in this context is defined as genetic disease causing an impairment in mitochondrial oxidative phosphorylation (OXPHOS). There are no treatment trials achieving the highest Level I evidence designation. Reasons for this include the relative rarity of mitochondrial disease, the heterogeneity of mitochondrial disease, the natural cofactor status and easy 'over the counter availability' of CoQ10 all of which make funding for the necessary large blinded clinical trials unlikely. At this time the best evidence for efficacy comes from controlled trials in common cardiovascular and neurodegenerative diseases with mitochondrial and OXPHOS dysfunction the etiology of which is most likely multifactorial with environmental factors playing on a background of genetic predisposition. There remain questions about dosing, bioavailability, tissue penetration and intracellular distribution of orally administered CoQ10, a compound which is endogenously produced within the mitochondria of all cells. In some mitochondrial diseases and other commoner disorders such as cardiac disease and Parkinson's disease low mitochondrial or tissue levels of CoQ10 have been demonstrated providing an obvious rationale for supplementation. This paper discusses the current state of the evidence supporting the use of CoQ10 in mitochondrial disease.

Improving coenzyme Q8 production in Escherichia coli employing multiple strategies.

PubMed

Xu, Wen; Yang, Shuiyun; Zhao, Junchao; Su, Tingting; Zhao, Liangrui; Liu, Jiankang

2014-08-01

Coenzyme Q (CoQ) is a medically valuable compound and a high yielding strain for CoQ will have several benefits for the industrial production of CoQ. To increase the CoQ(8) content of E. coli, we blocked the pathway for the synthesis of menaquinone by deleting the menA gene. The blocking of menaquinone pathway increased the CoQ(8) content by 81 % in E. coli (ΔmenA). To study the CoQ producing potential of E. coli, we employed previous known increasing strategies for systematic metabolic engineering. These include the supplementation with substrate precursors and the co-expression of rate-limiting genes. The co-expression of dxs-ubiA and the supplementation with substrate precursors such as pyruvate (PYR) and parahydroxybenzoic acid (pHBA) increased the content of CoQ(8) in E. coli (ΔmenA) by 125 and 59 %, respectively. Moreover, a 180 % increase in the CoQ(8) content in E. coli (ΔmenA) was realized by the combination of the co-expression of dxs-ubiA and the supplementation with PYR and pHBA. All in all, CoQ(8) content in E. coli increased 4.06 times by blocking the menaquinone pathway, dxs-ubiA co-expression and the addition of sodium pyruvate and parahydroxybenzoic acid to the medium. Results suggested a synergistic effect among different metabolic engineering strategies.

Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for beta-lactam acetylation.

PubMed

He, Hongzhen; Ding, Yi; Bartlam, Mark; Sun, Fei; Le, Yi; Qin, Xincheng; Tang, Hong; Zhang, Rongguang; Joachimiak, Andrzej; Liu, Jinyuan; Zhao, Nanming; Rao, Zihe

2003-01-31

Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55A resolution. The binary complex forms a characteristic "V" shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also report that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.

Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death

PubMed Central

WU, JIANG; JI, FANG; DI, WEN; CHEN, HONGDUO; WAN, YINSHENG

2011-01-01

Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the treatment of a variety of human diseases, including diabetes, obesity and cancer. Mounting evidence suggests that the inhibition of ACC induced of cancer cell apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3 cancer cells has yet to be addressed. This study investigated the cytotoxic mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was found to markedly enhance ACC phosphorylation, whereas AMP-activated protein kinase (AMPK) activator AICAR was found to marginally enhance ACC phosphorylation. Taken together, the data showed ACC is a potential novel molecular target of Taxol. Additionally, ACC inhibition partially contributed to the cytotoxic effect of Taxol in ovarian cancer cells. PMID:22866118

Activation of acetyl-coenzyme A carboxylase is involved in Taxol-induced ovarian cancer cell death.

PubMed

Wu, Jiang; Ji, Fang; DI, Wen; Chen, Hongduo; Wan, Yinsheng

2011-05-01

Acetyl-coenzyme A carboxylase (ACC) is an attractive target for research into the treatment of a variety of human diseases, including diabetes, obesity and cancer. Mounting evidence suggests that the inhibition of ACC induced of cancer cell apoptosis. However, whether the inhibition of ACC regulates apoptosis in CaOV3 cancer cells has yet to be addressed. This study investigated the cytotoxic mechanism of action of ACC inhibition. Results showed that 5-(tetradecyloxy)-2-furoic acid (TOFA), an ACC inhibitor, enhanced Taxol-induced CaOV3 human ovarian cancer cell apoptosis. Notably, when TOFA was administered as a monotherapy, it induced CaOV3 cell apoptosis. Pre-treatment with the EGFR inhibitor PD153035 was found to markedly enhance ACC phosphorylation, whereas AMP-activated protein kinase (AMPK) activator AICAR was found to marginally enhance ACC phosphorylation. Taken together, the data showed ACC is a potential novel molecular target of Taxol. Additionally, ACC inhibition partially contributed to the cytotoxic effect of Taxol in ovarian cancer cells.

Topical Coenzyme Q10 demonstrates mitochondrial-mediated neuroprotection in a rodent model of ocular hypertension.

PubMed

Davis, Benjamin Michael; Tian, Kailin; Pahlitzsch, Milena; Brenton, Jonathan; Ravindran, Nivedita; Butt, Gibran; Malaguarnera, Giulia; Normando, Eduardo M; Guo, Li; Cordeiro, M Francesca

2017-09-01

Coenzyme Q10 (CoQ10) is a mitochondrial-targeted antioxidant with known neuroprotective activity. Its ocular effects when co-solubilised with α-tocopherol polyethylene glycol succinate (TPGS) were evaluated. In vitro studies confirmed that CoQ10 was significantly protective in different retinal ganglion cell (RGC) models. In vivo studies in Adult Dark Agouti (DA) rats with unilateral surgically-induced ocular hypertension (OHT) treated with either CoQ10/TPGS micelles or TPGS vehicle twice daily for three weeks were performed, following which retinal cell health was assessed in vivo using DARC (Detection of Apoptotic Retinal Cells) and post-mortem with Brn3a histological assessment on whole retinal mounts. CoQ10/TPGS showed a significant neuroprotective effect compared to control with DARC (p<0.05) and Brn3 (p<0.01). Topical CoQ10 appears an effective therapy preventing RGC apoptosis and loss in glaucoma-related models. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Women's Contraceptive Preference-Use Mismatch

PubMed Central

He, Katherine; Dalton, Vanessa K.; Zochowski, Melissa K.

2017-01-01

Abstract Background: Family planning research has not adequately addressed women's preferences for different contraceptive methods and whether women's contraceptive experiences match their preferences. Methods: Data were drawn from the Women's Healthcare Experiences and Preferences Study, an Internet survey of 1,078 women aged 18–55 randomly sampled from a national probability panel. Survey items assessed women's preferences for contraceptive methods, match between methods preferred and used, and perceived reasons for mismatch. We estimated predictors of contraceptive preference with multinomial logistic regression models. Results: Among women at risk for pregnancy who responded with their preferred method (n = 363), hormonal methods (non-LARC [long-acting reversible contraception]) were the most preferred method (34%), followed by no method (23%) and LARC (18%). Sociodemographic differences in contraception method preferences were noted (p-values <0.05), generally with minority, married, and older women having higher rates of preferring less effective methods, compared to their counterparts. Thirty-six percent of women reported preference-use mismatch, with the majority preferring more effective methods than those they were using. Rates of match between preferred and usual methods were highest for LARC (76%), hormonal (non-LARC) (65%), and no method (65%). The most common reasons for mismatch were cost/insurance (41%), lack of perceived/actual need (34%), and method-specific preference concerns (19%). Conclusion: While preference for effective contraception was common among this sample of women, we found substantial mismatch between preferred and usual methods, notably among women of lower socioeconomic status and women using less effective methods. Findings may have implications for patient-centered contraceptive interventions. PMID:27710196

Mild clinical manifestation and unusual recovery upon coenzyme Q₁₀ treatment in the first Chinese Leigh syndrome pedigree with mutation m.10197 G>A.

PubMed

Chen, Zhiting; Zhao, Zhenhua; Ye, Qinyong; Chen, Ying; Pan, Xiaodong; Sun, Bin; Huang, Huapin; Zheng, An

2015-03-01

The Leigh syndrome (LS), characterized by psychomotor retardation, seizures, nystagmus, ophthalmoparesis, optic atrophy, ataxia, dystonia, or respiratory failure, is one of the most severe mitochondrial diseases. In the majority of cases, the disease is fatal and patients die before age 5. Mutation m.10197 G>A was found to relate to the severe phenotype of the Leigh syndrome. Here, we describe the first Chinese Leigh syndrome pedigree with this mutation. The proband had the characteristic brain lesions of the Leigh syndrome and presented a decrease in exercise tolerance and mild face paralysis. Sequencing the NADH dehydrogenase, subunit 3 (ND3) gene in the pedigree, revealed that the proband, as well as her unaffected brother, have a high mutant load in the ND3 gene, compared to their mother. Following one‑year treatment with the coenzyme Q10, an obvious improvement in clinical features was observed by magnetic resonance imaging (MRI) in the proband. Our study and previous reports highlight the variability of phenotypic expression of the m.10197 G>A mutation, and suggest that pathogenesis of the syndrome may be affected by a number of factors. This is the first report on successful treatment of an LS patient carrying the mutation m.10197 G>A with the coenzyme Q10, indicating that Q10 may attenuate the mitochondrial dysfunctions caused by the m.10197 G>A mutation.

Preferred and Actual Relative Height among Homosexual Male Partners Vary with Preferred Dominance and Sex Role

PubMed Central

Valentova, Jaroslava Varella; Stulp, Gert; Třebický, Vít; Havlíček, Jan

2014-01-01

Previous research has shown repeatedly that human stature influences mate preferences and mate choice in heterosexuals. In general, it has been shown that tall men and average height women are most preferred by the opposite sex, and that both sexes prefer to be in a relationship where the man is taller than the woman. However, little is known about such partner preferences in homosexual individuals. Based on an online survey of a large sample of non-heterosexual men (N = 541), we found that the majority of men prefer a partner slightly taller than themselves. However, these preferences were dependent on the participant’s own height, such that taller men preferred shorter partners, whereas shorter men preferred taller partners. We also examined whether height preferences predicted the preference for dominance and the adoption of particular sexual roles within a couple. Although a large proportion of men preferred to be in an egalitarian relationship with respect to preferred dominance (although not with respect to preferred sexual role), men that preferred a more dominant and more “active” sexual role preferred shorter partners, whereas those that preferred a more submissive and more “passive” sexual role preferred taller partners. Our results indicate that preferences for relative height in homosexual men are modulated by own height, preferred dominance and sex role, and do not simply resemble those of heterosexual women or men. PMID:24466136

Preferred and actual relative height among homosexual male partners vary with preferred dominance and sex role.

PubMed

Valentova, Jaroslava Varella; Stulp, Gert; Třebický, Vít; Havlíček, Jan

2014-01-01

Previous research has shown repeatedly that human stature influences mate preferences and mate choice in heterosexuals. In general, it has been shown that tall men and average height women are most preferred by the opposite sex, and that both sexes prefer to be in a relationship where the man is taller than the woman. However, little is known about such partner preferences in homosexual individuals. Based on an online survey of a large sample of non-heterosexual men (N = 541), we found that the majority of men prefer a partner slightly taller than themselves. However, these preferences were dependent on the participant's own height, such that taller men preferred shorter partners, whereas shorter men preferred taller partners. We also examined whether height preferences predicted the preference for dominance and the adoption of particular sexual roles within a couple. Although a large proportion of men preferred to be in an egalitarian relationship with respect to preferred dominance (although not with respect to preferred sexual role), men that preferred a more dominant and more "active" sexual role preferred shorter partners, whereas those that preferred a more submissive and more "passive" sexual role preferred taller partners. Our results indicate that preferences for relative height in homosexual men are modulated by own height, preferred dominance and sex role, and do not simply resemble those of heterosexual women or men.

Gastric bypass surgery alters behavioral and neural taste functions for sweet taste in obese rats.

PubMed

Hajnal, Andras; Kovacs, Peter; Ahmed, Tamer; Meirelles, Katia; Lynch, Christopher J; Cooney, Robert N

2010-10-01

Roux-en-Y gastric bypass surgery (GBS) is the most effective treatment for morbid obesity. GBS is a restrictive malabsorptive procedure, but many patients also report altered taste preferences. This study investigated the effects of GBS or a sham operation (SH) on body weight, glucose tolerance, and behavioral and neuronal taste functions in the obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats lacking CCK-1 receptors and lean controls (LETO). OLETF-GBS rats lost body weight (-26%) and demonstrated improved glucose tolerance. They also expressed a reduction in 24-h two-bottle preference for sucrose (0.3 and 1.0 M) and decreased 10-s lick responses for sucrose (0.3 through 1.5 M) compared with OLETF-SH or LETO-GBS. A similar effect was noted for other sweet compounds but not for salty, sour, or bitter tastants. In lean rats, GBS did not alter responses to any stimulus tested. Extracellular recordings from 170 taste-responsive neurons of the pontine parabrachial nucleus revealed a rightward shift in concentration responses to oral sucrose in obese compared with lean rats (OLETF-SH vs. LETO-SH): overall increased response magnitudes (above 0.9 M), and maximum responses occurring at higher concentrations (+0.46 M). These effects were reversed by GBS, and neural responses in OLETF-GBS were statistically not different from those in any LETO groups. These findings confirm obesity-related alterations in taste functions and demonstrate the ability of GBS to alleviate these impairments. Furthermore, the beneficial effects of GBS appear to be independent of CCK-1 receptor signaling. An understanding of the underlying mechanisms for reduced preferences for sweet taste could help in developing less invasive treatments for obesity.

Costly learning: preference for familiar food persists despite negative impact on survival.

PubMed

Costa, Thaiany M; Hebets, Eileen A; Melo, Diogo; Willemart, Rodrigo H

2016-07-01

Animals often rely on events in their environment that provide information (i.e. experience) to alter their future decision-making in ways that are presumed to be beneficial. Such experience-based learning, however, does not always lead to adaptive decision-making. In this study, we use the omnivorous harvestman Heteromitobates discolor to explore the role of past diet on subsequent food choice and survival. We first tested whether a short-term homogeneous diet (rotten crickets, fresh crickets or dog food) influenced subsequent food choice (rotten cricket versus fresh cricket). We next examine the impact of diet on survival. We found that following experience with a homogeneous cricket diet, adult harvestmen displayed a learned preference for familiar food, regardless of whether it was rotten or fresh crickets; individuals experiencing dog food were equally likely to choose rotten versus fresh crickets. We additionally found that individuals that ate rotten crickets suffered shorter survival than those that ate fresh crickets. Together, our results suggest that the diet an individual experiences can lead to maladaptive food preferences-preferences that ultimately result in reduced longevity. © 2016 The Author(s).

Roles of the redox-active disulfide and histidine residues forming a catalytic dyad in reactions catalyzed by 2-ketopropyl coenzyme M oxidoreductase/carboxylase.

PubMed

Kofoed, Melissa A; Wampler, David A; Pandey, Arti S; Peters, John W; Ensign, Scott A

2011-09-01

NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC), an atypical member of the disulfide oxidoreductase (DSOR) family of enzymes, catalyzes the reductive cleavage and carboxylation of 2-ketopropyl-coenzyme M [2-(2-ketopropylthio)ethanesulfonate; 2-KPC] to form acetoacetate and coenzyme M (CoM) in the bacterial pathway of propylene metabolism. Structural studies of 2-KPCC from Xanthobacter autotrophicus strain Py2 have revealed a distinctive active-site architecture that includes a putative catalytic triad consisting of two histidine residues that are hydrogen bonded to an ordered water molecule proposed to stabilize enolacetone formed from dithiol-mediated 2-KPC thioether bond cleavage. Site-directed mutants of 2-KPCC were constructed to test the tenets of the mechanism proposed from studies of the native enzyme. Mutagenesis of the interchange thiol of 2-KPCC (C82A) abolished all redox-dependent reactions of 2-KPCC (2-KPC carboxylation or protonation). The air-oxidized C82A mutant, as well as wild-type 2-KPCC, exhibited the characteristic charge transfer absorbance seen in site-directed variants of other DSOR enzymes but with a pK(a) value for C87 (8.8) four units higher (i.e., four orders of magnitude less acidic) than that for the flavin thiol of canonical DSOR enzymes. The same higher pK(a) value was observed in native 2-KPCC when the interchange thiol was alkylated by the CoM analog 2-bromoethanesulfonate. Mutagenesis of the flavin thiol (C87A) also resulted in an inactive enzyme for steady-state redox-dependent reactions, but this variant catalyzed a single-turnover reaction producing a 0.8:1 ratio of product to enzyme. Mutagenesis of the histidine proximal to the ordered water (H137A) led to nearly complete loss of redox-dependent 2-KPCC reactions, while mutagenesis of the distal histidine (H84A) reduced these activities by 58 to 76%. A redox-independent reaction of 2-KPCC (acetoacetate decarboxylation) was not decreased for any of the

Local population density and group composition influence the signal-preference relationship in Enchenopa treehoppers (Hemiptera: Membracidae).

PubMed

Fowler-Finn, K D; Cruz, D C; Rodríguez, R L

2017-01-01

Many animals exhibit social plasticity - changes in phenotype or behaviour in response to experience with conspecifics that change how evolutionary processes like sexual selection play out. Here, we asked whether social plasticity arising from variation in local population density in male advertisement signals and female mate preferences influences the form of sexual selection. We manipulated local density and determined whether this changed how the distribution of male signals overlapped with female preferences - the signal preference relationship. We specifically look at the shape of female mate preference functions, which, when compared to signal distributions, provide hypotheses about the form of sexual selection. We used Enchenopa binotata treehoppers, a group of plant-feeding insects that exhibit natural variation in local densities across individual host plants, populations, species and years. We measured male signal frequency and female preference functions across the density treatments. We found that male signals varied across local social groups, but not according to local density. By contrast, female preferences varied with local density - favouring higher signal frequencies in denser environments. Thus, local density changes the signal-preference relationship and, consequently, the expected form of sexual selection. We found no influence of sex ratio on the signal-preference relationship. Our findings suggest that plasticity arising from variation in local group density and composition can alter the form of sexual selection with potentially important consequences both for the maintenance of variation and for speciation. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Preformed {beta}-amyloid fibrils are destabilized by coenzyme Q{sub 10} in vitro

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

Ono, Kenjiro; Hasegawa, Kazuhiro; Naiki, Hironobu

2005-04-29

Inhibition of the formation of {beta}-amyloid fibrils (fA{beta}), as well as the destabilization of preformed fA{beta} in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenol, myricetin (Myr), inhibit fA{beta} formation from A{beta} and destabilize preformed fA{beta} in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of coenzyme Q{sub 10} (CoQ{sub 10}) on the formation, extension, and destabilization of fA{beta} at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of CoQ{submore » 10} with NDGA and Myr. CoQ{sub 10} dose-dependently inhibited fA{beta} formation from amyloid {beta}-peptide (A{beta}), as well as their extension. Moreover, it destabilized preformed fA{beta}s. The anti-amyloidogenic effects of CoQ{sub 10} were slightly weaker than those of NDGA and Myr. CoQ{sub 10} could be a key molecule for the development of therapeutics for AD.« less

Coenzyme Q10 protects neural stem cells against hypoxia by enhancing survival signals.

PubMed

Park, Jinse; Park, Hyun-Hee; Choi, Hojin; Kim, Young Seo; Yu, Hyun-Jeung; Lee, Kyu-Yong; Lee, Young Joo; Kim, Seung Hyun; Koh, Seong-Ho

2012-10-10

Recanalization and secondary prevention are the main therapeutic strategies for acute ischemic stroke. Neuroprotective therapies have also been investigated despite unsuccessful clinical results. Coenzyme Q10 (CoQ10), which is an essential cofactor for electron transport in mitochondria, is known to have an antioxidant effect. We investigated the protective effects of CoQ10 against hypoxia in neural stem cells (NSCs). We measured cell viability and levels of intracellular signaling proteins after treatment with several concentrations of CoQ10 under hypoxia-reperfusion. CoQ10 protected NSCs against hypoxia-reperfusion in a concentration-dependent manner by reducing growth inhibition and inhibiting free radical formation. It increased the expression of a number of survival-related proteins such as phosphorylated Akt (pAkt), phosphorylated glycogen synthase kinase 3-β (pGSK3-β), and B-cell lymphoma 2 (Bcl-2) in NSCs injured by hypoxia-reperfusion and reduced the expression of death-related proteins such as cleaved caspase-3. We conclude that CoQ10 has effects against hypoxia-reperfusion induced damage to NSCs by enhancing survival signals and decreasing death signals. Copyright © 2012 Elsevier B.V. All rights reserved.

Explaining tolerance for bitterness in chocolate ice cream using solid chocolate preferences

PubMed Central

Harwood, Meriel L.; Loquasto, Joseph R.; Roberts, Robert F.; Ziegler, Gregory R.; Hayes, John E.

2016-01-01

Chocolate ice cream is commonly formulated with higher sugar levels than nonchocolate flavors to compensate for the inherent bitterness of cocoa. Bitterness, however, is an integral part of the complex flavor of chocolate. In light of the global obesity epidemic, many consumers and health professionals are concerned about the levels of added sugars in foods. Once a strategy for balancing undesirable bitterness and health concerns regarding added sugars has been developed, the task becomes determining whether that product will be acceptable to the consumer. Thus, the purpose of this research was to manipulate the bitterness of chocolate ice cream to examine how this influences consumer preferences. The main goal of this study was to estimate group rejection thresholds for bitterness in chocolate ice cream, and to see if solid chocolate preferences (dark vs. milk) generalized to ice cream. A food-safe bitter ingredient, sucrose octaacetate, was added to chocolate ice cream to alter bitterness without disturbing other the sensory qualities of the ice cream samples, including texture. Untrained chocolate ice cream consumers participated in a large-scale sensory test by indicating their preferences for blinded pairs of unspiked and spiked samples, where the spiked sample had increasing levels of the added bitterant. As anticipated, the group containing individuals who prefer milk chocolate had a much lower tolerance for bitterness in their chocolate ice cream compared with the group of individuals who prefer dark chocolate; indeed, the dark chocolate group tolerated almost twice as much added bitterant in the ice cream before indicating a significant preference for the unspiked (control) ice cream. This work demonstrates the successful application of the rejection threshold method to a complex dairy food. Estimating rejection thresholds could prove to be an effective tool for determining acceptable formulations or quality limits when considering attributes that become

Oviposition preference of cabbage white butterflies in the framework of costs and benefits of interspecific herbivore associations

PubMed Central

Shiojiri, Kaori; Sabelis, Maurice; Takabayashi, Junji

2015-01-01

When deciding where to oviposit, herbivorous insects consider: (i) the plant’s value as a food source, (ii) the risks of competing with con- and heterospecific herbivores, and (iii) the risks of parasitism and predation on the host plant. The presence of con- and/or heterospecific competitors would further affect the oviposition preference, because the preceding herbivores induce direct/indirect defences in plants against forthcoming herbivores, and thereby alter oviposition decisions. In previous studies, the abovementioned factors have not been studied in an integrative manner. We performed here a case study of this by assessing the oviposition preferences of a small white butterfly, Pieris rapae, for plants occupied by combinations of conspecific larvae, heterospecific larvae (Plutella xylostella), specialist parasitoids of Pi. rapae (Cotesia glomerata) and generalist predators (ants). We previously reported that the females showed equal preference for Pl. xylostella-infested and uninfested plants. Here, we showed that Pi. rapae females preferred uninfested plants to conspecific-infested ones, and Pl. xylostella-infested plants to Pi. rapae-infested ones. We discuss these oviposition preferences of Pi. rapae females in the framework of costs and benefits of interspecific herbivore associations from the above point of view. PMID:27019738

The Influence of Labeling the Vegetable Content of Snack Food on Children's Taste Preferences: A Pilot Study

ERIC Educational Resources Information Center

Pope, Lizzy; Wolf, Randi L.

2012-01-01

Objective: This pilot study examined whether informing children of the presence of vegetables in select snack food items alters taste preference. Methods: A random sample of 68 elementary and middle school children tasted identical pairs of 3 snack food items containing vegetables. In each pair, 1 sample's label included the food's vegetable (eg,…

Nutritional programming of coenzyme Q: potential for prevention and intervention?

PubMed

Tarry-Adkins, Jane L; Fernandez-Twinn, Denise S; Chen, Jian-Hua; Hargreaves, Iain P; Martin-Gronert, Malgorzata S; McConnell, Josie M; Ozanne, Susan E

2014-12-01

Low birth weight and rapid postnatal growth increases risk of cardiovascular-disease (CVD); however, underlying mechanisms are poorly understood. Previously, we demonstrated that rats exposed to a low-protein diet in utero that underwent postnatal catch-up growth (recuperated) have a programmed deficit in cardiac coenzyme Q (CoQ) that was associated with accelerated cardiac aging. It is unknown whether this deficit occurs in all tissues, including those that are clinically accessible. We investigated whether aortic and white blood cell (WBC) CoQ is programmed by suboptimal early nutrition and whether postweaning dietary supplementation with CoQ could prevent programmed accelerated aging. Recuperated male rats had reduced aortic CoQ [22 d (35±8.4%; P<0.05); 12 m (53±8.8%; P<0.05)], accelerated aortic telomere shortening (P<0.01), increased DNA damage (79±13% increase in nei-endonucleaseVIII-like-1), increased oxidative stress (458±67% increase in NAPDH-oxidase-4; P<0.001), and decreased mitochondrial complex II-III activity (P<0.05). Postweaning dietary supplementation with CoQ prevented these detrimental programming effects. Recuperated WBCs also had reduced CoQ (74±5.8%; P<0.05). Notably, WBC CoQ levels correlated with aortic telomere-length (P<0.0001) suggesting its potential as a diagnostic marker of vascular aging. We conclude that early intervention with CoQ in at-risk individuals may be a cost-effective and safe way of reducing the global burden of CVDs. © FASEB.

Precision breeding for RNAi suppression of a major 4-coumarate:coenzyme A ligase gene improves cell wall saccharification from field grown sugarcane.

PubMed

Jung, Je Hyeong; Kannan, Baskaran; Dermawan, Hugo; Moxley, Geoffrey W; Altpeter, Fredy

2016-11-01

Sugarcane (Saccharum spp. hybrids) is a major feedstock for commercial bioethanol production. The recent integration of conversion technologies that utilize lignocellulosic sugarcane residues as well as sucrose from stem internodes has elevated bioethanol yields. RNAi suppression of lignin biosynthetic enzymes is a successful strategy to improve the saccharification of lignocellulosic biomass. 4-coumarate:coenzyme A ligase (4CL) is a key enzyme in the biosynthesis of phenylpropanoid metabolites, such as lignin and flavonoids. Identifying a major 4CL involved in lignin biosynthesis among multiple isoforms with functional divergence is key to manipulate lignin biosynthesis. In this study, two full length 4CL genes (Sh4CL1 and Sh4CL2) were isolated and characterized in sugarcane. Phylogenetic, expression and RNA interference (RNAi) analysis confirmed that Sh4CL1 is a major lignin biosynthetic gene. An intragenic precision breeding strategy may facilitate the regulatory approval of the genetically improved events and was used for RNAi suppression of Sh4CL1. Both, the RNAi inducing cassette and the expression cassette for the mutated ALS selection marker consisted entirely of DNA sequences from sugarcane or the sexually compatible species Sorghum bicolor. Field grown sugarcane with intragenic RNAi suppression of Sh4CL1 resulted in reduction of the total lignin content by up to 16.5 % along with altered monolignol ratios without reduction in biomass yield. Mature, field grown, intragenic sugarcane events displayed 52-76 % improved saccharification efficiency of lignocellulosic biomass compared to wild type (WT) controls. This demonstrates for the first time that an intragenic approach can add significant value to lignocellulosic feedstocks for biofuel and biochemical production.

Fatty Acid Synthesis in Pea Root Plastids Is Inhibited by the Action of Long-Chain Acyl- Coenzyme As on Metabolite Transporters1

PubMed Central

Fox, Simon R.; Rawsthorne, Stephen; Hills, Matthew J.

2001-01-01

The uptake in vitro of glucose (Glc)-6-phosphate (Glc-6-P) into plastids from the roots of 10- to 14-d-old pea (Pisum sativum L. cv Puget) plants was inhibited by oleoyl-coenzyme A (CoA) concentrations in the low micromolar range (1–2 μm). The IC50 (the concentration of inhibitor that reduces enzyme activity by 50%) for the inhibition of Glc-6-P uptake was approximately 750 nm; inhibition was reversed by recombinant rapeseed (Brassica napus) acyl-CoA binding protein. In the presence of ATP (3 mm) and CoASH (coenzyme A; 0.3 mm), Glc-6-P uptake was inhibited by 60%, due to long-chain acyl-CoA synthesis, presumably from endogenous sources of fatty acids present in the preparations. Addition of oleoyl-CoA (1 μm) decreased carbon flux from Glc-6-P into the synthesis of starch and through the oxidative pentose phosphate (OPP) pathway by up to 73% and 40%, respectively. The incorporation of carbon from Glc-6-P into fatty acids was not detected under any conditions. Oleoyl-CoA inhibited the incorporation of acetate into fatty acids by 67%, a decrease similar to that when ATP was excluded from incubations. The oleoyl-CoA-dependent inhibition of fatty acid synthesis was attributable to a direct inhibition of the adenine nucleotide translocator by oleoyl-CoA, which indirectly reduced fatty acid synthesis by ATP deprivation. The Glc-6-P-dependent stimulation of acetate incorporation into fatty acids was reversed by the addition of oleoyl-CoA. PMID:11457976

Relations among Spontaneous Preferences, Familiarized Preferences, and Novelty Effects: Measurements with Forced-Choice Techniques

ERIC Educational Resources Information Center

Civan, Andrea; Teller, Davida Y.; Palmer, John

2005-01-01

We here describe a discrete trial, forced-choice, combined spontaneous preference and novelty preference technique. In this technique, spontaneous preferences and familiarized (postfamiliarization) preferences are measured with the same stimulus pairs under closely parallel conditions. A variety of systematic stimulus variations were used in…

Bees prefer foods containing neonicotinoid pesticides

PubMed Central

Simcock, Kerry L.; Derveau, Sophie; Mitchell, Jessica; Softley, Samantha; Stout, Jane C.; Wright, Geraldine A.

2015-01-01

The impact of neonicotinoid insecticides on insect pollinators is highly controversial. Sublethal concentrations alter the behaviour of social bees and reduce survival of entire colonies1-3. However, critics argue that the reported negative effects only arise from neonicotinoid concentrations that are greater than those found in the nectar and pollen of pesticide-treated plants4. Furthermore, it has been suggested that bees could choose to forage on other available flowers and hence avoid or dilute exposure4,5. Here, using a two-choice feeding assay, we show that the honeybee, Apis mellifera, and the buff-tailed bumblebee, Bombus terrestris, do not avoid nectar-relevant concentrations of three of the most commonly-used neonicotinoids, imidacloprid (IMD), thiamethoxam (TMX), and clothianidin (CLO) in food. Moreover, bees of both species prefer to eat more of sucrose solutions laced with IMD or TMX than sucrose alone. Stimulation with IMD, TMX, and CLO neither elicited spiking responses from gustatory neurons in the bees’ mouthparts nor inhibited the responses of sucrose-sensitive neurons. Our data indicate that bees cannot taste neonicotinoids and are not repelled by them. Instead, bees preferred solutions containing IMD or TMX even though the consumption of these pesticides caused them to eat less food overall. This work shows that bees cannot control their exposure to neonicotinoids in food and implies that treating flowering crops with IMD and TMX presents a significant hazard to foraging bees. PMID:25901684

Etiologies of altered mental status in patients with presumed ethanol intoxication.

PubMed

Martel, Marc L; Klein, Lauren R; Lichtenheld, Andrew J; Kerandi, Allan M; Driver, Brian E; Cole, Jon B

2018-06-01

Altered mental status is a commonly evaluated problem in the ED. Ethanol intoxication is common, and prehospital history may bias emergency physicians to suspect this as the cause of altered mental status. Quantitative ethanol measurement can rapidly confirm the diagnosis, or if negative, prompt further evaluation. Our objective was to identify the etiologies of altered mental status in ED patients initially presumed to be intoxicated with ethanol but found to have negative quantitative ethanol levels. This was a 5-year (2012-2016) electronic medical record review of ED patients presenting with altered mental status. Patients were included if they presented with presumed ethanol intoxication and had an initial ethanol concentration of zero. Etiologies of altered mental status were categorized into medical, traumatic, psychiatric, and drug-related causes. 29,322 patients presented during the study period with presumed alcohol intoxication, 1875 patients had negative ethanol levels. The etiology of altered mental status was due to illicit substances in 1337 patients (71%), psychiatric causes in 354 patients (19%), medical causes in 166 patients (9%) and trauma in 18 patients (1%). A total of 179 patients (10%) were admitted to the hospital; 19 patients (1%) to the ICU. The presumptive diagnosis of ethanol intoxication in patients presenting to the ED with altered mental status was inaccurate in 5% of patients. The etiology of altered mental status was serious and required hospitalization in 10% of the cohort. Rapid assessment of quantitative ethanol levels should be performed, breathalyzers may be preferred over serum testing. Copyright © 2018 Elsevier Inc. All rights reserved.

Color preferences are not universal.

PubMed

Taylor, Chloe; Clifford, Alexandra; Franklin, Anna

2013-11-01

Claims of universality pervade color preference research. It has been argued that there are universal preferences for some colors over others (e.g., Eysenck, 1941), universal sex differences (e.g., Hurlbert & Ling, 2007), and universal mechanisms or dimensions that govern these preferences (e.g., Palmer & Schloss, 2010). However, there have been surprisingly few cross-cultural investigations of color preference and none from nonindustrialized societies that are relatively free from the common influence of global consumer culture. Here, we compare the color preferences of British adults to those of Himba adults who belong to a nonindustrialized culture in rural Namibia. British and Himba color preferences are found to share few characteristics, and Himba color preferences display none of the so-called "universal" patterns or sex differences. Several significant predictors of color preference are identified, such as cone-contrast between stimulus and background (Hurlbert & Ling, 2007), the valence of color-associated objects (Palmer & Schloss, 2010), and the colorfulness of the color. However, the relationship of these predictors to color preference was strikingly different for the two cultures. No one model of color preference is able to account for both British and Himba color preferences. We suggest that not only do patterns of color preference vary across individuals and groups but the underlying mechanisms and dimensions of color preference vary as well. The findings have implications for broader debate on the extent to which our perception and experience of color is culturally relative or universally constrained. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for {beta}-lactam acetylation.

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

He, H.; Ding, Y.; Bartlam, M.

2003-01-31

Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55 {angstrom} resolution. The binary complex forms a characteristic 'V' shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also reportmore » that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.« less

Metabolic State Alters Economic Decision Making under Risk in Humans

PubMed Central

Drew, Megan E.; Batterham, Rachel L.; Dolan, Raymond J.

2010-01-01

Background Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity

Preference assessments in the zoo: Keeper and staff predictions of enrichment preferences across species.

PubMed

Mehrkam, Lindsay R; Dorey, Nicole R

2015-01-01

Environmental enrichment is widely used in the management of zoo animals, and is an essential strategy for increasing the behavioral welfare of these populations. It may be difficult, however, to identify potentially effective enrichment strategies that are also cost-effective and readily available. An animal's preference for a potential enrichment item may be a reliable predictor of whether that individual will reliably interact with that item, and subsequently enable staff to evaluate the effects of that enrichment strategy. The aim of the present study was to assess the utility of preference assessments for identifying potential enrichment items across six different species--each representing a different taxonomic group. In addition, we evaluated the agreement between zoo personnel's predictions of animals' enrichment preferences and stimuli selected via a preference assessment. Five out of six species (nine out of 11 individuals) exhibited clear, systematic preferences for specific stimuli. Similarities in enrichment preferences were observed among all individuals of primates, whereas individuals within ungulate and avian species displayed individual differences in enrichment preferences. Overall, zoo personnel, regardless of experience level, were significantly more accurate at predicting least-preferred stimuli than most-preferred stimuli across species, and tended to make the same predictions for all individuals within a species. Preference assessments may therefore be a useful, efficient husbandry strategy for identifying viable enrichment items at both the individual and species levels. © 2015 Wiley Periodicals, Inc.

Assessing Women's Preferences and Preference Modeling for Breast Reconstruction Decision-Making.

PubMed

Sun, Clement S; Cantor, Scott B; Reece, Gregory P; Crosby, Melissa A; Fingeret, Michelle C; Markey, Mia K

2014-03-01

Women considering breast reconstruction must make challenging trade-offs amongst issues that often conflict. It may be useful to quantify possible outcomes using a single summary measure to aid a breast cancer patient in choosing a form of breast reconstruction. In this study, we used multiattribute utility theory to combine multiple objectives to yield a summary value using nine different preference models. We elicited the preferences of 36 women, aged 32 or older with no history of breast cancer, for the patient-reported outcome measures of breast satisfaction, psychosocial well-being, chest well-being, abdominal well-being, and sexual wellbeing as measured by the BREAST-Q in addition to time lost to reconstruction and out-of-pocket cost. Participants ranked hypothetical breast reconstruction outcomes. We examined each multiattribute utility preference model and assessed how often each model agreed with participants' rankings. The median amount of time required to assess preferences was 34 minutes. Agreement among the nine preference models with the participants ranged from 75.9% to 78.9%. None of the preference models performed significantly worse than the best performing risk averse multiplicative model. We hypothesize an average theoretical agreement of 94.6% for this model if participant error is included. There was a statistically significant positive correlation with more unequal distribution of weight given to the seven attributes. We recommend the risk averse multiplicative model for modeling the preferences of patients considering different forms of breast reconstruction because it agreed most often with the participants in this study.

Altering the spectrum of immunoglobulin V gene somatic hypermutation by modifying the active site of AID.

PubMed

Wang, Meng; Rada, Cristina; Neuberger, Michael S

2010-01-18

High-affinity antibodies are generated by somatic hypermutation with nucleotide substitutions introduced into the IgV in a semirandom fashion, but with intrinsic mutational hotspots strategically located to optimize antibody affinity maturation. The process is dependent on activation-induced deaminase (AID), an enzyme that can deaminate deoxycytidine in DNA in vitro, where its activity is sensitive to the identity of the 5'-flanking nucleotide. As a critical test of whether such DNA deamination activity underpins antibody diversification and to gain insight into the extent to which the antibody mutation spectrum is dependent on the intrinsic substrate specificity of AID, we investigated whether it is possible to change the IgV mutation spectrum by altering AID's active site such that it prefers a pyrimidine (rather than a purine) flanking the targeted deoxycytidine. Consistent with the DNA deamination mechanism, B cells expressing the modified AID proteins yield altered IgV mutation spectra (exhibiting a purine-->pyrimidine shift in flanking nucleotide preference) and altered hotspots. However, AID-catalyzed deamination of IgV targets in vitro does not yield the same degree of hotspot dominance to that observed in vivo, indicating the importance of features beyond AID's active site and DNA local sequence environment in determining in vivo hotspot dominance.

Taste preference and psychopathology.

PubMed

Aguayo, G A; Vaillant, M T; Arendt, C; Bachim, S; Pull, C B

2012-01-01

Excessive food intake has been linked to many factors including taste preference and the presence of psychopathology. The purpose of this study was to investigate the association between sweet and salty taste preference and psychopathology in patients with severe obesity. A consecutive series of patients applying for bariatric surgery was recruited for the study. Taste preference was self-reported. Psychopathology was assessed using the revised version of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). 190 patients were included in the study. In comparison with patients who had salty taste preference, patients with sweet taste preference had significantly higher elevations on the depression (OD: 4.090, p = 0.010) and the hysteria (OD: 2.951, p = 0.026) clinical scales of the MMPI-2. The results suggest the presence of an association between taste preference and psychopathology. The findings may be of interest for clinicians who are involved in the treatment of obesity. In particular, they may wish to pay increased attention to patients with sweet taste preference or who have a strong attraction for both sweet and salty foods, in order to detect psychopathology and to adapt the treatment.

Effects of aeration on formation and localization of the acetyl coenzyme A synthetases of Saccharomyces cerevisiae

NASA Technical Reports Server (NTRS)

Klein, H. P.; Jahnke, L.

1979-01-01

Previous studies on the yeast Saccharomyces cerevisiae have shown that two different forms of the enzyme acetyl coenzyme A synthetase (ACS) are present, depending on the conditions under which the cells are grown. The paper evaluates the usefulness of a method designed to assay both synthetases simultaneously in yeast homogenates. The data presented confirm the possibility of simultaneous detection and estimation of the amount of both ACSs of S. cerevisiae in crude homogenates of this strain, making possible the study of physiological factors involved in the formation of these isoenzymes. One important factor for specifying which of the two enzymes is found in these yeast cells is the presence or absence of oxygen in their environment. Aeration not only affects the ratio of the two ACSs but also appears to affect the cellular distribution of these enzymes. Most of the data presented suggest the possibility that the nonaerobic ACS may serve as a precursor to the aerobic form.

c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

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

Ledee, Dolena; Smith, Lincoln; Bruce, Margaret

Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated workingmore » hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.« less

c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

DOE PAGES

Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; ...

2015-08-12

Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated workingmore » hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.« less

c-Myc Alters Substrate Utilization and O-GlcNAc Protein Posttranslational Modifications without Altering Cardiac Function during Early Aortic Constriction

PubMed Central

Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.

2015-01-01

Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC) and non-transgenic littermates (Cont-TAC) were subjected to transverse aortic constriction (TAC; n = 7/group). Additional groups underwent sham surgery (Cont-Sham and MycKO-Sham, n = 5 per group). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes. PMID:26266538

Oligosaccharide Substrate Preferences of Human Extracellular Sulfatase Sulf2 Using Liquid Chromatography-Mass Spectrometry Based Glycomics Approaches

PubMed Central

Huang, Yu; Mao, Yang; Buczek-Thomas, Jo Ann; Nugent, Matthew A.; Zaia, Joseph

2014-01-01

Sulfs are extracellular endosulfatases that selectively remove the 6-O-sulfate groups from cell surface heparan sulfate (HS) chain. By altering the sulfation at these particular sites, Sulfs function to remodel HS chains. As a result of the remodeling activity, HSulf2 regulates a multitude of cell-signaling events that depend on interactions between proteins and HS. Previous efforts to characterize the substrate specificity of human Sulfs (HSulfs) focused on the analysis of HS disaccharides and synthetic repeating units. In this study, we characterized the substrate preferences of human HSulf2 using HS oligosaccharides with various lengths and sulfation degrees from several naturally occurring HS sources by applying liquid chromatography mass spectrometry based glycomics methods. The results showed that HSulf2 preferentially digests highly sulfated HS oligosaccharides with zero acetyl groups and this preference is length dependent. In terms of length of oligosaccharides, HSulf2 digestion induced more sulfation decrease on DP6 (DP: degree of polymerization) compared to DP2, DP4 and DP8. In addition, the HSulf2 preferentially digests the oligosaccharide domain located at the non-reducing end (NRE) of the HS and heparin chain. In addition, the HSulf2 digestion products were altered only for specific isomers. HSulf2 treated NRE oligosaccharides also showed greater decrease in cell proliferation than those from internal domains of the HS chain. After further chromatographic separation, we identified the three most preferred unsaturated hexasaccharide for HSulf2. PMID:25127119

Hormones of choice: the neuroendocrinology of partner preference in animals.

PubMed

Henley, C L; Nunez, A A; Clemens, L G

2011-04-01

Partner preference behavior can be viewed as the outcome of a set of hierarchical choices made by an individual in anticipation of mating. The first choice involves approaching a conspecific verses an individual of another species. As a rule, a conspecific is picked as a mating partner, but early life experiences can alter that outcome. Within a species, an animal then has the choice between a member of the same sex or the opposite sex. The final choice is for a specific individual. This review will focus on the middle choice, the decision to mate with either a male or a female. Available data from rats, mice, and ferrets point to the importance of perinatal exposure to steroid hormones in the development of partner preferences, as well as the importance of activational effects in adulthood. However, the particular effects of this hormone exposure show species differences in both the specific steroid hormone responsible for the organization of behavior and the developmental period when it has its effect. Where these hormones have an effect in the brain is mostly unknown, but regions involved in olfaction and sexual behavior, as well as sexually dimorphic regions, seem to play a role. One limitation of the literature base is that many mate or 'partner preference studies' rely on preference for a specific stimulus (usually olfaction) but do not include an analysis of the relation, if any, that stimulus has to the choice of a particular sexual partner. A second limitation has been the almost total lack of attention to the type of behavior that is shown by the choosing animal once a 'partner' has been chosen, specifically, if the individual plays a mating role typical of its own sex or the opposite sex. Additional paradigms that address these questions are needed for better understanding of partner preferences in rodents. Copyright © 2011 Elsevier Inc. All rights reserved.

Phylogenetic and genomic analysis of Methanomassiliicoccales in wetlands and animal intestinal tracts reveals clade-specific habitat preferences.

PubMed

Söllinger, Andrea; Schwab, Clarissa; Weinmaier, Thomas; Loy, Alexander; Tveit, Alexander T; Schleper, Christa; Urich, Tim

2016-01-01

Methanogenic Thermoplasmata of the novel order Methanomassiliicoccales were recently discovered in human and animal gastro-intestinal tracts (GITs). However, their distribution in other methanogenic environments has not been addressed systematically. Here, we surveyed Methanomassiliicoccales presence in wetland soils, a globally important source of methane emissions to the atmosphere, and in the GITs of different animals by PCR targeting their 16S rRNA and methyl:coenzyme M reductase (α-subunit) genes. We detected Methanomassiliicoccales in all 16 peat soils investigated, indicating their wide distribution in these habitats. Additionally, we detected their genes in various animal faeces. Methanomassiliicoccales were subdivided in two broad phylogenetic clades designated 'environmental' and 'GIT' clades based on differential, although non-exclusive, habitat preferences of their members. A well-supported cluster within the environmental clade comprised more than 80% of all wetland 16S rRNA gene sequences. Metagenome assembly from bovine rumen fluid enrichments resulted in two almost complete genomes of both Methanomassiliicoccales clades. Comparative genomics revealed that members of the environmental clade contain larger genomes and a higher number of genes encoding anti-oxidative enzymes than animal GIT clade representatives. This study highlights the wide distribution of Methanomassiliicoccales in wetlands, which suggests that they contribute to methane emissions from these climate-relevant ecosystems. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Classification and characterization of Japanese consumers' beef preferences by external preference mapping.

PubMed

Sasaki, Keisuke; Ooi, Motoki; Nagura, Naoto; Motoyama, Michiyo; Narita, Takumi; Oe, Mika; Nakajima, Ikuyo; Hagi, Tatsuro; Ojima, Koichi; Kobayashi, Miho; Nomura, Masaru; Muroya, Susumu; Hayashi, Takeshi; Akama, Kyoko; Fujikawa, Akira; Hokiyama, Hironao; Kobayashi, Kuniyuki; Nishimura, Takanori

2017-08-01

Over the past few decades, beef producers in Japan have improved marbling in their beef products. It was recently reported that marbling is not well correlated with palatability as rated by Japanese consumers. This study sought to identify the consumer segments in Japan that prefer sensory characteristics of beef other than high marbling. Three Wagyu beef, one Holstein beef and two lean imported beef longissimus samples were subjected to a descriptive sensory test, physicochemical analysis and a consumer (n = 307) preference test. According to consumer classification and external preference mapping, four consumer segments were identified as 'gradual high-fat likers', 'moderate-fat and distinctive taste likers', 'Wagyu likers' and 'distinctive texture likers'. Although the major trend of Japanese consumers' beef preference was 'marbling liking', 16.9% of the consumers preferred beef samples that had moderate marbling and distinctive taste. The consumers' attitudes expressed in a questionnaire survey were in good agreement with the preference for marbling among the 'moderate-fat and distinctive taste likers'. These results indicate that moderately marbled beef is a potent category in the Japanese beef market. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Fetal Nicotine Exposure Increases Preference for Nicotine Odor in Early Postnatal and Adolescent, but Not Adult, Rats

PubMed Central

Mantella, Nicole M.; Kent, Paul F.; Youngentob, Steven L.

2013-01-01

Human studies demonstrate a four-fold increased possibility of smoking in the children of mothers who smoked during pregnancy. Nicotine is the active addictive component in tobacco-related products, crossing the placenta and contaminating the amniotic fluid. It is known that chemosensory experience in the womb can influence postnatal odor-guided preference behaviors for an exposure stimulus. By means of behavioral and neurophysiologic approaches, we examined whether fetal nicotine exposure, using mini-osmotic pumps, altered the response to nicotine odor in early postnatal (P17), adolescent (P35) and adult (P90) progeny. Compared with controls, fetal exposed rats displayed an altered innate response to nicotine odor that was evident at P17, declined in magnitude by P35 and was absent at P90 - these effects were specific to nicotine odor. The behavioral effect in P17 rats occurred in conjunction with a tuned olfactory mucosal response to nicotine odor along with an untoward consequence on the epithelial response to other stimuli – these P17 neural effects were absent in P35 and P90 animals. The absence of an altered neural effect at P35 suggests that central mechanisms, such as nicotine-induced modifications of the olfactory bulb, bring about the altered behavioral response to nicotine odor. Together, these findings provide insights into how fetal nicotine exposure influences the behavioral preference and responsiveness to the drug later in life. Moreover, they add to a growing literature demonstrating chemosensory mechanisms by which patterns of maternal drug use can be conveyed to offspring, thereby enhancing postnatal vulnerability for subsequent use and abuse. PMID:24358374

Electroconvulsive seizures (ECS) do not prevent LPS-induced behavioral alterations and microglial activation.

PubMed

van Buel, E M; Bosker, F J; van Drunen, J; Strijker, J; Douwenga, W; Klein, H C; Eisel, U L M

2015-12-12

Long-term neuroimmune activation is a common finding in major depressive disorder (MDD). Literature suggests a dual effect of electroconvulsive therapy (ECT), a highly effective treatment strategy for MDD, on neuroimmune parameters: while ECT acutely increases inflammatory parameters, such as serum levels of pro-inflammatory cytokines, there is evidence to suggest that repeated ECT sessions eventually result in downregulation of the inflammatory response. We hypothesized that this might be due to ECT-induced attenuation of microglial activity upon inflammatory stimuli in the brain. Adult male C57Bl/6J mice received a series of ten electroconvulsive seizures (ECS) or sham shocks, followed by an intracerebroventricular (i.c.v.) lipopolysaccharide (LPS) or phosphate-buffered saline (PBS) injection. Brains were extracted and immunohistochemically stained for the microglial marker ionized calcium-binding adaptor molecule 1 (Iba1). In addition, a sucrose preference test and an open-field test were performed to quantify behavioral alterations. LPS induced a short-term reduction in sucrose preference, which normalized within 3 days. In addition, LPS reduced the distance walked in the open field and induced alterations in grooming and rearing behavior. ECS did not affect any of these parameters. Phenotypical analysis of microglia demonstrated an LPS-induced increase in microglial activity ranging from 84 to 213 % in different hippocampal regions (CA3 213 %; CA1 84 %; dentate gyrus 131 %; and hilus 123 %). ECS-induced alterations in microglial activity were insignificant, ranging from -2.6 to 14.3 % in PBS-injected mice and from -20.2 to 6.6 % in LPS-injected mice. We were unable to demonstrate an effect of ECS on LPS-induced microglial activity or behavioral alterations.

Protein CoAlation and antioxidant function of Coenzyme A in prokaryotic cells.

PubMed

Tsuchiya, Yugo; Zhyvoloup, Alexander; Bakovic, Jovana; Thomas, Naam; Yi Kun Yu, Bess; Das, Sayoni; Orengo, Christine; Newell, Clare; Ward, John; Saladino, Giorgio; Comitani, Federico; Gervasio, Francesco L; Malanchuk, Oksana M; Khoruzhenko, Antonina I; Filonenko, Valeriy; Peak-Chew, Sew Yeu; Skehel, Mark; Gout, Ivan

2018-04-06

In all living organisms, Coenzyme A (CoA) is an essential cofactor with a unique design allowing it to function as an acyl group carrier and a carbonyl-activating group in diverse biochemical reactions. It is synthesized in a highly conserved process in prokaryotes and eukaryotes that requires pantothenic acid (vitamin B5), cysteine and ATP. CoA and its thioester derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. A novel unconventional function of CoA in redox regulation has been recently discovered in mammalian cells and termed protein CoAlation. Here, we report for the first time that protein CoAlation occurs at a background level in exponentially growing bacteria and is strongly induced in response to oxidizing agents and metabolic stress. Over 12% of S. aureus gene products were shown to be CoAlated in response to diamide-induced stress . In vitro CoAlation of S. aureus glyceraldehyde-3-phosphate dehydrogenase (SaGAPDH) was found to inhibit its enzymatic activity and to protect the catalytic cysteine 151 from overoxidation by hydrogen peroxide (H 2 O 2 ). These findings suggest that in exponentially growing bacteria CoA functions to generate metabolically active thioesters, while it also has the potential to act as a low molecular weight antioxidant in response to oxidative and metabolic stress. ©2018 The Author(s).

Getting a Handle on the Role of Coenzyme M in Alkene Metabolism

PubMed Central

Krishnakumar, Arathi M.; Sliwa, Darius; Endrizzi, James A.; Boyd, Eric S.; Ensign, Scott A.; Peters, John W.

2008-01-01

Summary: Coenzyme M (2-mercaptoethanesulfonate; CoM) is one of several atypical cofactors discovered in methanogenic archaea which participate in the biological reduction of CO2 to methane. Elegantly simple, CoM, so named for its role as a methyl carrier in all methanogenic archaea, is the smallest known organic cofactor. It was thought that this cofactor was used exclusively in methanogenesis until it was recently discovered that CoM is a key cofactor in the pathway of propylene metabolism in the gram-negative soil microorganism Xanthobacter autotrophicus Py2. A four-step pathway requiring CoM converts propylene and CO2 to acetoacetate, which feeds into central metabolism. In this process, CoM is used to activate and convert highly electrophilic epoxypropane, formed from propylene epoxidation, into a nucleophilic species that undergoes carboxylation. The unique properties of CoM provide a chemical handle for orienting compounds for site-specific redox chemistry and stereospecific catalysis. The three-dimensional structures of several of the enzymes in the pathway of propylene metabolism in defined states have been determined, providing significant insights into both the enzyme mechanisms and the role of CoM in this pathway. These studies provide the structural basis for understanding the efficacy of CoM as a handle to direct organic substrate transformations at the active sites of enzymes. PMID:18772284

Plasticity of preferred body temperatures as means of coping with climate change?

PubMed Central

Gvoždík, Lumír

2012-01-01

Thermoregulatory behaviour represents an important component of ectotherm non-genetic adaptive capacity that mitigates the impact of ongoing climate change. The buffering role of behavioural thermoregulation has been attributed solely to the ability to maintain near optimal body temperature for sufficiently extended periods under altered thermal conditions. The widespread occurrence of plastic modification of target temperatures that an ectotherm aims to achieve (preferred body temperatures) has been largely overlooked. I argue that plasticity of target temperatures may significantly contribute to an ectotherm's adaptive capacity. Its contribution to population persistence depends on both the effectiveness of acute thermoregulatory adjustments (reactivity) in buffering selection pressures in a changing thermal environment, and the total costs of thermoregulation (i.e. reactivity and plasticity) in a given environment. The direction and magnitude of plastic shifts in preferred body temperatures can be incorporated into mechanistic models, to improve predictions of the impact of global climate change on ectotherm populations. PMID:22072284

Plasticity of preferred body temperatures as means of coping with climate change?

PubMed

Gvozdík, Lumír

2012-04-23

Thermoregulatory behaviour represents an important component of ectotherm non-genetic adaptive capacity that mitigates the impact of ongoing climate change. The buffering role of behavioural thermoregulation has been attributed solely to the ability to maintain near optimal body temperature for sufficiently extended periods under altered thermal conditions. The widespread occurrence of plastic modification of target temperatures that an ectotherm aims to achieve (preferred body temperatures) has been largely overlooked. I argue that plasticity of target temperatures may significantly contribute to an ectotherm's adaptive capacity. Its contribution to population persistence depends on both the effectiveness of acute thermoregulatory adjustments (reactivity) in buffering selection pressures in a changing thermal environment, and the total costs of thermoregulation (i.e. reactivity and plasticity) in a given environment. The direction and magnitude of plastic shifts in preferred body temperatures can be incorporated into mechanistic models, to improve predictions of the impact of global climate change on ectotherm populations.

The Role of Symbiont Genetic Distance and Potential Adaptability in Host Preference Towards Pseudonocardia Symbionts in Acromyrmex Leaf-Cutting Ants

PubMed Central

Poulsen, Michael; Maynard, Janielle; Roland, Damien L; Currie, Cameron R

2011-01-01

Fungus-growing ants display symbiont preference in behavioral assays, both towards the fungus they cultivate for food and Actinobacteria they maintain on their cuticle for antibiotic production against parasites. These Actinobacteria, genus Pseudonocardia Henssen (Pseudonocardiacea: Actinomycetales), help defend the ants' fungal mutualist from specialized parasites. In Acromyrmex Mayr (Hymenoptera: Formicidae) leaf-cutting ants, individual colonies maintain either a single or a few strains of Pseudonocardia, and the symbiont is primarily vertically transmitted between generations by colony-founding queens. A recent report found that Acromyrmex workers are able to differentiate between their native Pseudonocardia strain and non-native strains isolated from sympatric or allopatric Acromyrmex species, and show preference for their native strain. Here we explore worker preference when presented with two non-native strains, elucidating the role of genetic distance on preference between strains and Pseudonocardia origin. Our findings suggest that ants tend to prefer bacteria more closely related to their native bacterium and that genetic similarity is probably more important than whether symbionts are ant-associated or free-living. Preliminary findings suggest that when continued exposure to a novel Pseudonocardia strain occurs, ant symbiont preference is potentially adaptable, with colonies apparently being able to alter symbiont preference over time. These findings are discussed in relation to the role of adaptive recognition, potential ecological flexibility in symbiont preference, and more broadly, in relation to self versus non-self recognition. PMID:22225537

Reduction of ascites mortality in broilers by coenzyme Q10.

PubMed

Geng, A L; Guo, Y M; Yang, Y

2004-09-01

Effects of coenzyme Q10 (CoQ10) supplementation on growth performance and ascites were studied in broilers. One hundred eighty 1-d-old Arbor Acre male broiler chicks were randomly allocated into 3 groups with 6 replicates each. From d 8, the diets were supplemented with CoQ10 at levels of 0, 20, and 40 mg/kg, respectively. From d 15 to 21, all the chicks were exposed to low ambient temperature (15 to 18 degrees C) to induce ascites. Average feed intake, BW gain, and feed conversion ratio of the broilers during 0 to 3 wk, 3 to 6 wk, and 0 to 6 wk were measured. The results showed that there were no influences observed on broilers' growth performance, but the mortality due to ascites was reduced by CoQ10 supplementation (P < or = 0.05). Erythrocyte osmotic fragility (EOF) was significantly decreased by 40 mg/kg CoQ10 compared with the control, but no significant changes were observed on blood packed cell volume (PCV) among the treatments. Pulmonary arterial diastolic pressure was significantly decreased on d 36, but no significant changes were observed on right ventricular pressure (RVP), pulmonary arterial systolic pressure, and the maximum change ratio of right intraventricular pressure (+/- dp/ dtmax). Ascites heart index (AHI) was significantly decreased by 40 mg/kg CoQ10 supplementation (P < or = 0.05). The results of this study suggested that CoQ10 has a beneficial effect in reducing ascites mortality in broilers, and 40 mg/kg CoQ10 seems to be more effective than 20 mg/ kg CoQ10.

Optimizing conservation practices in watersheds: Do community preferences matter?

NASA Astrophysics Data System (ADS)

Piemonti, Adriana D.; Babbar-Sebens, Meghna; Jane Luzar, E.

2013-10-01

This paper focuses on investigating (a) how landowner tenure and attitudes of farming communities affect the preference of individual conservation practices in agricultural watersheds, (b) how spatial distribution of landowner tenure affects the spatial optimization of conservation practices on a watershed scale, and (c) how the different attitudes and preferences of stakeholders can modify the effectiveness of alternatives obtained via classic optimization approaches that do not include the influence of existing social attitudes in a watershed during the search process. Results show that for Eagle Creek Watershed in central Indiana, USA, the most optimal alternatives (i.e., highest benefits for minimum economic costs) are for a scenario when the watershed consists of landowners who operate as farmers on their own land. When a different land-tenure scenario was used for the watershed (e.g., share renters and cash renters), the optimized alternatives had similar nitrate reduction benefits and sediment reduction benefits, but at higher economic costs. Our experiments also demonstrated that social attitudes can lead to alteration of optimized alternatives found via typical optimization approaches. For example, when certain practices were rejected by landowner operators whose attitudes toward practices were driven by economic profits, removal of these practices from the optimized alternatives led to a setback of nitrates reduction by 2-50%, peak flow reductions by 11-98 %, and sediments reduction by 20-77%. In conclusion, this study reveals the potential loss in optimality of optimized alternatives possible, when socioeconomic data on farmer preferences and land tenure are not incorporated within watershed optimization investigations.

Loss of Bone Mineral Density Associated with Age in Male Rats Fed on Sunflower Oil Is Avoided by Virgin Olive Oil Intake or Coenzyme Q Supplementation

PubMed Central

Ochoa, Julio J.; Llamas-Elvira, José M.; López-Frías, Magdalena

2017-01-01

The role of dietary fat unsaturation and the supplementation of coenzyme Q have been evaluated in relation to bone health. Male Wistar rats were maintained for 6 or 24 months on two diets varying in the fat source, namely virgin olive oil, rich in monounsaturated fatty acids, or sunflower oil, rich in n-6 polyunsaturated fatty acids. Both dietary fats were supplemented or not with coenzyme Q10 (CoQ10). Bone mineral density (BMD) was evaluated in the femur. Serum levels of osteocalcin, osteopontin, receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), adrenocorticotropin (ACTH) and parathyroid hormone (PTH), as well as urinary F2-isoprostanes were measured. Aged animals fed on virgin olive oil showed higher BMD than those fed on sunflower oil. In addition, CoQ10 prevented the age-related decline in BMD in animals fed on sunflower oil. Urinary F2-isoprostanes analysis showed that sunflower oil led to the highest oxidative status in old animals, which was avoided by supplementation with CoQ10. In conclusion, lifelong feeding on virgin olive oil or the supplementation of sunflower oil on CoQ10 prevented, at least in part mediated by a low oxidative stress status, the age-related decrease in BMD found in sunflower oil fed animals. PMID:28661441

Multi-omic Mitoprotease Profiling Defines a Role for Oct1p in Coenzyme Q Production.

PubMed

Veling, Mike T; Reidenbach, Andrew G; Freiberger, Elyse C; Kwiecien, Nicholas W; Hutchins, Paul D; Drahnak, Michael J; Jochem, Adam; Ulbrich, Arne; Rush, Matthew J P; Russell, Jason D; Coon, Joshua J; Pagliarini, David J

2017-12-07

Mitoproteases are becoming recognized as key regulators of diverse mitochondrial functions, although their direct substrates are often difficult to discern. Through multi-omic profiling of diverse Saccharomyces cerevisiae mitoprotease deletion strains, we predicted numerous associations between mitoproteases and distinct mitochondrial processes. These include a strong association between the mitochondrial matrix octapeptidase Oct1p and coenzyme Q (CoQ) biosynthesis-a pathway essential for mitochondrial respiration. Through Edman sequencing and in vitro and in vivo biochemistry, we demonstrated that Oct1p directly processes the N terminus of the CoQ-related methyltransferase, Coq5p, which markedly improves its stability. A single mutation to the Oct1p recognition motif in Coq5p disrupted its processing in vivo, leading to CoQ deficiency and respiratory incompetence. This work defines the Oct1p processing of Coq5p as an essential post-translational event for proper CoQ production. Additionally, our data visualization tool enables efficient exploration of mitoprotease profiles that can serve as the basis for future mechanistic investigations. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhancement of solubility and dissolution of coenzyme Q10 using solid dispersion formulation.

PubMed

Nepal, Pushp R; Han, Hyo-Kyung; Choi, Hoo-Kyun

2010-01-04

This study aimed to develop a stable solid dispersion of Coenzyme Q(10) (CoQ(10)) with high aqueous solubility and dissolution rate. Among various carriers screened, poloxamer 407 was most effective to form a superior solid dispersion of CoQ(10) having significantly enhanced solubility. Particularly, solid dispersion of CoQ(10) with poloxamer 407 in the weight ratio of 1:5 prepared by melting method enhanced the solubility of CoQ(10) to the greatest extent. However, it exhibited poor stability and hence Aerosil 200 (colloidal silicon dioxide) was incorporated into the solid dispersion as an adsorbent to inhibit the recrystallization process. The solid dispersion of CoQ(10), poloxamer 407 and Aerosil 200 in the weight ratio of 1:5:6 exhibited improved stability with no significant change in solubility during the 1-month stability test. Moreover, the solid dispersion formulation containing Aerosil 200 significantly enhanced the extent of drug release (approx. 75% release) as well as the dissolution rate of CoQ(10). In conclusion, the present study has developed the stable solid dispersion formulation of CoQ(10) with poloxamer 407 and Aerosil 200 for the enhanced solubility and dissolution of CoQ(10), which could also offer some additional advantages including ease of preparation, good flowability and cost-effectiveness.

Clinical, biochemical and molecular aspects of cerebellar ataxia and Coenzyme Q10 deficiency.

PubMed

Montero, Raquel; Pineda, Mercé; Aracil, Asun; Vilaseca, Maria-Antonia; Briones, Paz; Sánchez-Alcázar, José-Antonio; Navas, Plácido; Artuch, Rafael

2007-01-01

Coenzyme Q(10) (CoQ) deficiency is an autosomal recessive disorder presenting five phenotypes: a myopathic form, a severe infantile neurological syndrome associated with nephritic syndrome, an ataxic variant, Leigh syndrome and a pure myopathic form. The third is the most common phenotype related with CoQ deficiency and it will be the focus of this review. This new syndrome presents muscle CoQ deficiency associated with cerebellar ataxia and cerebellar atrophy as the main neurological signs. Biochemically, the hallmark of CoQ deficiency syndrome is a decreased CoQ concentration in muscle and/or fibroblasts. There is no molecular evidence of the enzyme or gene involved in primary CoQ deficiencies associated with cerebellar ataxia, although recently a family has been reported with mutations at COQ2 gene who present a distinct phenotype. Patients with primary CoQ deficiency may benefit from CoQ supplementation, although the clinical response to this therapy varies even among patients with similar phenotypes. Some present an excellent response to CoQ while others show only a partial improvement of some symptoms and signs. CoQ deficiency is the mitochondrial encephalomyopathy with the best clinical response to CoQ supplementation, highlighting the importance of an early identification of this disorder.

The Regulation of Coenzyme Q Biosynthesis in Eukaryotic Cells: All That Yeast Can Tell Us

PubMed Central

González-Mariscal, Isabel; García-Testón, Elena; Padilla, Sergio; Martín-Montalvo, Alejandro; Pomares Viciana, Teresa; Vazquez-Fonseca, Luis; Gandolfo Domínguez, Pablo; Santos-Ocaña, Carlos

2014-01-01

Coenzyme Q (CoQ) is a mitochondrial lipid, which functions mainly as an electron carrier from complex I or II to complex III at the mitochondrial inner membrane, and also as antioxidant in cell membranes. CoQ is needed as electron acceptor in β-oxidation of fatty acids and pyridine nucleotide biosynthesis, and it is responsible for opening the mitochondrial permeability transition pore. The yeast model has been very useful to analyze the synthesis of CoQ, and therefore, most of the knowledge about its regulation was obtained from the Saccharomyces cerevisiae model. CoQ biosynthesis is regulated to support 2 processes: the bioenergetic metabolism and the antioxidant defense. Alterations of the carbon source in yeast, or in nutrient availability in yeasts or mammalian cells, upregulate genes encoding proteins involved in CoQ synthesis. Oxidative stress, generated by chemical or physical agents or by serum deprivation, modifies specifically the expression of some COQ genes by means of stress transcription factors such as Msn2/4p, Yap1p or Hsf1p. In general, the induction of COQ gene expression produced by metabolic changes or stress is modulated downstream by other regulatory mechanisms such as the protein import to mitochondria, the assembly of a multi-enzymatic complex composed by Coq proteins and also the existence of a phosphorylation cycle that regulates the last steps of CoQ biosynthesis. The CoQ biosynthetic complex assembly starts with the production of a nucleating lipid such as HHB by the action of the Coq2 protein. Then, the Coq4 protein recognizes the precursor HHB acting as the nucleus of the complex. The activity of Coq8p, probably as kinase, allows the formation of an initial pre-complex containing all Coq proteins with the exception of Coq7p. This pre-complex leads to the synthesis of 5-demethoxy-Q6 (DMQ6), the Coq7p substrate. When de novo CoQ biosynthesis is required, Coq7p becomes dephosphorylated by the action of Ptc7p increasing the synthesis

Coenzyme Q plays opposing roles on bacteria/fungi and viruses in Drosophila innate immunity.

PubMed

Cheng, W; Song, C; Anjum, K M; Chen, M; Li, D; Zhou, H; Wang, W; Chen, J

2011-08-01

Coenzyme Q (CoQ or ubiquinone) is a lipid-soluble component of virtually all types of cell membranes and has been shown to play multiple metabolic functions. Several clinical diseases including encephalomyopathy, cerebellar ataxia and isolated myopathy were shown to be associated with CoQ deficiency. However, the role of CoQ in immunity has not been defined. In the present study, we showed that flies defective in CoQ biosynthetic gene coq2 were more susceptible to bacterial and fungal infections, while were more resistant to viruses. We found that Drosophila contained both CoQ9 and CoQ10, and food supplement of CoQ10 could partially rescue the impaired immune functions of coq2 mutants. Surprisingly, wild-type flies fed CoQ10 became more susceptible to viral infection, which suggested that extra caution should be taken when using CoQ10 as a food supplement. We further showed that CoQ was essential for normal induction of anti-microbial peptides and amplification of viruses. Our work determined CoQ content in Drosophila and described its function in immunity for the first time. © 2011 Blackwell Publishing Ltd.

Heightened sour preferences during childhood.

PubMed

Liem, Djin Gie; Mennella, Julie A

2003-02-01

Basic research has revealed that the chemical sensory world of children is different from that of adults, as evidenced by their heightened preferences for sweet and salty tastes. However, little is known about the ontogeny of sour taste preferences, despite the growing market of extreme sour candies. The present study investigated whether the level of sourness most preferred in a food matrix and the ability to discriminate differences in sour intensity differed between 5- to 9-year-old children and their mothers, by using a rank-by-elimination procedure embedded in the context of a game. Mothers also completed a variety of questionnaires and children were asked several questions to assess whether children's temperament and food preferences and habits related to sour preferences. The results indicated that, although every mother and all but two of the children (92%) were able to rank the gelatins from most to least sour, more than one-third (35%) of the children, but virtually none of the adults, preferred the high levels of sour taste (0.25 M citric acid) in gelatin. Those children who preferred the extreme sour tastes were significantly less food neophobic (P < 0.05) and tended to experience a greater variety of fruits when compared with the remaining children (P = 0.11). Moreover, the children's preference for sour tastes generalized to other foods, such as candies and lemons, as reported by both children and mothers. These findings are the first experimental evidence to demonstrate that sour taste preferences are heightened during childhood and that such preferences are related to children's food habits and preferences. Further research is needed to unfold the relationship between the level of sour taste preferred and the actual consumption of sour-tasting foods and flavors in children.

Heightened Sour Preferences During Childhood

PubMed Central

Liem, Djin Gie; Mennella, Julie A.

2009-01-01

Basic research has revealed that the chemical sensory world of children is different from that of adults, as evidenced by their heightened preferences for sweet and salty tastes. However, little is known about the ontogeny of sour taste preferences, despite the growing market of extreme sour candies. The present study investigated whether the level of sourness most preferred in a food matrix and the ability to discriminate differences in sour intensity differed between 5- to 9-year-old children and their mothers, by using a rank-by-elimination procedure embedded in the context of a game. Mothers also completed a variety of questionnaires and children were asked several questions to assess whether children’s temperament and food preferences and habits related to sour preferences. The results indicated that, although every mother and all but two of the children (92%) were able to rank the gelatins from most to least sour, more than one-third (35%) of the children, but virtually none of the adults, preferred the high levels of sour taste (0.25 M citric acid) in gelatin. Those children who preferred the extreme sour tastes were significantly less food neophobic (P < 0.05) and tended to experience a greater variety of fruits when compared with the remaining children (P = 0.11). Moreover, the children’s preference for sour tastes generalized to other foods, such as candies and lemons, as reported by both children and mothers. These findings are the first experimental evidence to demonstrate that sour taste preferences are heightened during childhood and that such preferences are related to children’s food habits and preferences. Further research is needed to unfold the relationship between the level of sour taste preferred and the actual consumption of sour-tasting foods and flavors in children. PMID:12588738

Great apes prefer cooked food.

PubMed

Wobber, Victoria; Hare, Brian; Wrangham, Richard

2008-08-01

The cooking hypothesis proposes that a diet of cooked food was responsible for diverse morphological and behavioral changes in human evolution. However, it does not predict whether a preference for cooked food evolved before or after the control of fire. This question is important because the greater the preference shown by a raw-food-eating hominid for the properties present in cooked food, the more easily cooking should have been adopted following the control of fire. Here we use great apes to model food preferences by Paleolithic hominids. We conducted preference tests with various plant and animal foods to determine whether great apes prefer food items raw or cooked. We found that several populations of captive apes tended to prefer their food cooked, though with important exceptions. These results suggest that Paleolithic hominids would likewise have spontaneously preferred cooked food to raw, exapting a pre-existing preference for high-quality, easily chewed foods onto these cooked items. The results, therefore, challenge the hypothesis that the control of fire preceded cooking by a significant period.

Order effect in a study on US voters’ preferences: quantum framework representation of the observables

NASA Astrophysics Data System (ADS)

Khrennikova, Polina

2014-12-01

The US political system in the recent years has been mainly formed by a Divided Government, which is regarded as a consequence of ‘non-separability’ of voters’ preferences. The non- separability phenomenon emerges as a result of strong correlations that the voters establish between their preferences for the Congress and the White House contests. We investigate with help of the empirical data from the Smith et al (1999 J. Polit. Sci. 43 737-764) study what implications the upcoming information (encoded in the observables- questions) has on the non- separability emergence. We show that the informational context of the questions alters the preference frequencies that cannot be captured in a classical probabilistic framework. We attribute the changes to the incompatibility of observables C and P, which correspond to questions being asked. We embed our data in a quantum framework and model the voters’ mental state evolution as it is impacted by the operators, to show the non-commutativity of the transition probabilities as a result of the question order effect.

The role of individual time preferences in health behaviors among hypertensive adults: a pilot study.

PubMed

Axon, R Neal; Bradford, W David; Egan, Brent M

2009-01-01

An economic framework incorporating patients' time-value preferences may help explain individual variation in preventive health behaviors. We conducted a pilot study to examine the relationship between health discount rates and preventive health practices. A group of 422 hypertensive individuals were assessed by written survey regarding their actual or likely preventive health behaviors, and they were posed a series of time preference questions. Regression methods that account for the interval nature of the time preference responses were used to estimate individual respondents' discount rates. Dichotomous regression analyses (using probit models) adjusted for gender, age, race, income, and health status revealed mean health discount rates of 0.438 or (43.8%) per year (standard deviation [SD], 0.07). Analyses adjusted for age, gender, race, income level, insurance status, and health status indicated that a 1% increase in discount rate increased the likelihood respondents would not check their BP by 3.5% (P = .003), not alter diet and exercise habits by 0.6% (P = .004), and not follow doctors' treatment plans by 1.6% (P = .05). Compared to the four lowest quintiles, patients in the highest quintile of discount rates (annualized discount rates between 50% and 57.2%) tended to have lower likelihood of ever checking blood pressure (BP) at home (42.5% vs. 47.6%; P = .36), of not using their physician's office for sick care (16.5% vs. 27.6%; P = .01), and of not altering their diet and exercise habits in response to a diagnosis of hypertension (6.8% vs. 12.4%; P = .07). These preliminary data indicate that the degree to which individuals discount the future has a significant impact on their health behaviors.

Assessing Women’s Preferences and Preference Modeling for Breast Reconstruction Decision Making

PubMed Central

Sun, Clement S.; Cantor, Scott B.; Reece, Gregory P.; Crosby, Melissa A.; Fingeret, Michelle C.

2014-01-01

Background: Women considering breast reconstruction must make challenging trade-offs among issues that often conflict. It may be useful to quantify possible outcomes using a single summary measure to aid a breast cancer patient in choosing a form of breast reconstruction. Methods: In this study, we used multiattribute utility theory to combine multiple objectives to yield a summary value using 9 different preference models. We elicited the preferences of 36 women, aged 32 or older with no history of breast cancer, for the patient-reported outcome measures of breast satisfaction, psychosocial well-being, chest well-being, abdominal well-being, and sexual well-being as measured by the BREAST-Q in addition to time lost to reconstruction and out-of-pocket cost. Participants ranked hypothetical breast reconstruction outcomes. We examined each multiattribute utility preference model and assessed how often each model agreed with participants’ rankings. Results: The median amount of time required to assess preferences was 34 minutes. Agreement among the 9 preference models with the participants ranged from 75.9% to 78.9%. None of the preference models performed significantly worse than the best-performing risk-averse multiplicative model. We hypothesize an average theoretical agreement of 94.6% for this model if participant error is included. There was a statistically significant positive correlation with more unequal distribution of weight given to the 7 attributes. Conclusions: We recommend the risk-averse multiplicative model for modeling the preferences of patients considering different forms of breast reconstruction because it agreed most often with the participants in this study. PMID:25105083

Nucleus accumbens mu opioid receptors regulate context-specific social preferences in the juvenile rat.

PubMed

Smith, Caroline J W; Wilkins, Kevin B; Li, Sara; Tulimieri, Maxwell T; Veenema, Alexa H

2018-03-01

The μ opioid receptor (MOR) in the nucleus accumbens (NAc) is involved in assigning pleasurable, or hedonic value to rewarding stimuli. Importantly, the hedonic value of a given rewarding stimulus likely depends on an individual's current motivational state. Here, we examined the involvement of MORs in the motivation to interact with a novel or a familiar (cage mate) conspecific in juvenile rats. First, we demonstrated that the selective MOR antagonist CTAP administered into the NAc reduces social novelty preference of juvenile males, by decreasing the interaction time with the novel conspecific and increasing the interaction time with the cage mate. Next, we found that a 3-h separation period from the cage mate reduces social novelty preference in both juvenile males and females, which was primarily driven by an increase in interaction time with the cage mate. Last, we showed that MOR agonism (intracerebroventricularly or in the NAc) restored social novelty preference in juvenile males that did not show social novelty preference following social isolation. Taken together, these data support a model in which endogenous MOR activation in the NAc facilitates the relative hedonic value of novel over familiar social stimuli. Our results may implicate the MOR in neuropsychiatric disorders characterized by altered social motivation, such as major depression and autism spectrum disorder. Copyright © 2017 Elsevier Ltd. All rights reserved.

Explaining tolerance for bitterness in chocolate ice cream using solid chocolate preferences.

PubMed

Harwood, Meriel L; Loquasto, Joseph R; Roberts, Robert F; Ziegler, Gregory R; Hayes, John E

2013-08-01

Chocolate ice cream is commonly formulated with higher sugar levels than nonchocolate flavors to compensate for the inherent bitterness of cocoa. Bitterness, however, is an integral part of the complex flavor of chocolate. In light of the global obesity epidemic, many consumers and health professionals are concerned about the levels of added sugars in foods. Once a strategy for balancing undesirable bitterness and health concerns regarding added sugars has been developed, the task becomes determining whether that product will be acceptable to the consumer. Thus, the purpose of this research was to manipulate the bitterness of chocolate ice cream to examine how this influences consumer preferences. The main goal of this study was to estimate group rejection thresholds for bitterness in chocolate ice cream, and to see if solid chocolate preferences (dark vs. milk) generalized to ice cream. A food-safe bitter ingredient, sucrose octaacetate, was added to chocolate ice cream to alter bitterness without disturbing other the sensory qualities of the ice cream samples, including texture. Untrained chocolate ice cream consumers participated in a large-scale sensory test by indicating their preferences for blinded pairs of unspiked and spiked samples, where the spiked sample had increasing levels of the added bitterant. As anticipated, the group containing individuals who prefer milk chocolate had a much lower tolerance for bitterness in their chocolate ice cream compared with the group of individuals who prefer dark chocolate; indeed, the dark chocolate group tolerated almost twice as much added bitterant in the ice cream before indicating a significant preference for the unspiked (control) ice cream. This work demonstrates the successful application of the rejection threshold method to a complex dairy food. Estimating rejection thresholds could prove to be an effective tool for determining acceptable formulations or quality limits when considering attributes that become

Behavioral contagion during learning about another agent’s risk-preferences acts on the neural representation of decision-risk

PubMed Central

Suzuki, Shinsuke; Jensen, Emily L. S.; Bossaerts, Peter; O’Doherty, John P.

2016-01-01

Our attitude toward risk plays a crucial role in influencing our everyday decision-making. Despite its importance, little is known about how human risk-preference can be modulated by observing risky behavior in other agents at either the behavioral or the neural level. Using fMRI combined with computational modeling of behavioral data, we show that human risk-preference can be systematically altered by the act of observing and learning from others’ risk-related decisions. The contagion is driven specifically by brain regions involved in the assessment of risk: the behavioral shift is implemented via a neural representation of risk in the caudate nucleus, whereas the representations of other decision-related variables such as expected value are not affected. Furthermore, we uncover neural computations underlying learning about others’ risk-preferences and describe how these signals interact with the neural representation of risk in the caudate. Updating of the belief about others’ preferences is associated with neural activity in the dorsolateral prefrontal cortex (dlPFC). Functional coupling between the dlPFC and the caudate correlates with the degree of susceptibility to the contagion effect, suggesting that a frontal–subcortical loop, the so-called dorsolateral prefrontal–striatal circuit, underlies the modulation of risk-preference. Taken together, these findings provide a mechanistic account for how observation of others’ risky behavior can modulate an individual’s own risk-preference. PMID:27001826

Comparison of species composition and richness of fish assemblages in altered and unaltered littoral habitats

USGS Publications Warehouse

Poe, T.P.; Hatcher, C.O.; Brown, C.L.; Schloesser, D.W.

1986-01-01

Species composition and richness of fish assemblages in altered and unaltered littoral habitats in Lake St. Clair, Michigan, differed between areas. A percid-cyprinid-cyprinodontid assemblage dominated in the unaltered area, Muscamoot Bay, which has a natural shoreline (with almost no alteration due to dredging or bulkheading), high water quality, and high species richness of aquatic macrophytes. A centrarchid assemblage dominated in the altered area, Belvidere Bay, which has a bulkheaded shoreline, many dredged areas, reduced water quality due to inputs of nutrients from a nearby river, and relatively low species richness of aquatic macrophytes. Habitat factors, species richness and abundance of aquatic macrophytes, had the most influence on fish community structure in both areas. The percid-cyprinid-cyprinodontid assemblage was significantly correlated with six species of macrophytes whereas the centrarchid assemblage was significantly correlated with only four. These patterns suggest that preference for diverse habitats was higher, and tolerance to habitat alteration lower, in percid-cyprinid-cyprinodontid assemblages than in centrarchid assemblages.

Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

PubMed

Roy, Abhro Jyoti; Stanely Mainzen Prince, P

2013-10-01

The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

Color preference in red-green dichromats.

PubMed

Álvaro, Leticia; Moreira, Humberto; Lillo, Julio; Franklin, Anna

2015-07-28

Around 2% of males have red-green dichromacy, which is a genetic disorder of color vision where one type of cone photoreceptor is missing. Here we investigate the color preferences of dichromats. We aim (i) to establish whether the systematic and reliable color preferences of normal trichromatic observers (e.g., preference maximum at blue, minimum at yellow-green) are affected by dichromacy and (ii) to test theories of color preference with a dichromatic sample. Dichromat and normal trichromat observers named and rated how much they liked saturated, light, dark, and focal colors twice. Trichromats had the expected pattern of preference. Dichromats had a reliable pattern of preference that was different to trichromats, with a preference maximum rather than minimum at yellow and a much weaker preference for blue than trichromats. Color preference was more affected in observers who lacked the cone type sensitive to long wavelengths (protanopes) than in those who lacked the cone type sensitive to medium wavelengths (deuteranopes). Trichromats' preferences were summarized effectively in terms of cone-contrast between color and background, and yellow-blue cone-contrast could account for dichromats' pattern of preference, with some evidence for residual red-green activity in deuteranopes' preference. Dichromats' color naming also could account for their color preferences, with colors named more accurately and quickly being more preferred. This relationship between color naming and preference also was present for trichromat males but not females. Overall, the findings provide novel evidence on how dichromats experience color, advance the understanding of why humans like some colors more than others, and have implications for general theories of aesthetics.

Color preference in red–green dichromats

PubMed Central

Álvaro, Leticia; Moreira, Humberto; Lillo, Julio; Franklin, Anna

2015-01-01

Around 2% of males have red–green dichromacy, which is a genetic disorder of color vision where one type of cone photoreceptor is missing. Here we investigate the color preferences of dichromats. We aim (i) to establish whether the systematic and reliable color preferences of normal trichromatic observers (e.g., preference maximum at blue, minimum at yellow-green) are affected by dichromacy and (ii) to test theories of color preference with a dichromatic sample. Dichromat and normal trichromat observers named and rated how much they liked saturated, light, dark, and focal colors twice. Trichromats had the expected pattern of preference. Dichromats had a reliable pattern of preference that was different to trichromats, with a preference maximum rather than minimum at yellow and a much weaker preference for blue than trichromats. Color preference was more affected in observers who lacked the cone type sensitive to long wavelengths (protanopes) than in those who lacked the cone type sensitive to medium wavelengths (deuteranopes). Trichromats’ preferences were summarized effectively in terms of cone-contrast between color and background, and yellow-blue cone-contrast could account for dichromats’ pattern of preference, with some evidence for residual red–green activity in deuteranopes’ preference. Dichromats’ color naming also could account for their color preferences, with colors named more accurately and quickly being more preferred. This relationship between color naming and preference also was present for trichromat males but not females. Overall, the findings provide novel evidence on how dichromats experience color, advance the understanding of why humans like some colors more than others, and have implications for general theories of aesthetics. PMID:26170287

Tears or Fears? Comparing Gender Stereotypes about Movie Preferences to Actual Preferences.

PubMed

Wühr, Peter; Lange, Benjamin P; Schwarz, Sascha

2017-01-01

This study investigated the accuracy of gender-specific stereotypes about movie-genre preferences for 17 genres. In Study 1, female and male participants rated the extent to which 17 movie genres are preferred by women or men. In Study 2, another sample of female and male participants rated their own preference for each genre. There were three notable results. First, Study 1 revealed the existence of gender stereotypes for the majority of genres (i.e., for 15 of 17 genres). Second, Study 2 revealed the existence of actual gender differences in preferences for the majority of genres (i.e., for 11 of 17 genres). Third, in order to assess the accuracy of gender stereotypes on movie preferences, we compared the results of both studies and found that the majority of gender stereotypes were accurate in direction, but inaccurate in size. In particular, the stereotypes overestimated actual gender differences for the majority of movie genres (i.e., 10 of 17). Practical and theoretical implications of these findings are discussed.

Tears or Fears? Comparing Gender Stereotypes about Movie Preferences to Actual Preferences

PubMed Central

Wühr, Peter; Lange, Benjamin P.; Schwarz, Sascha

2017-01-01

This study investigated the accuracy of gender-specific stereotypes about movie-genre preferences for 17 genres. In Study 1, female and male participants rated the extent to which 17 movie genres are preferred by women or men. In Study 2, another sample of female and male participants rated their own preference for each genre. There were three notable results. First, Study 1 revealed the existence of gender stereotypes for the majority of genres (i.e., for 15 of 17 genres). Second, Study 2 revealed the existence of actual gender differences in preferences for the majority of genres (i.e., for 11 of 17 genres). Third, in order to assess the accuracy of gender stereotypes on movie preferences, we compared the results of both studies and found that the majority of gender stereotypes were accurate in direction, but inaccurate in size. In particular, the stereotypes overestimated actual gender differences for the majority of movie genres (i.e., 10 of 17). Practical and theoretical implications of these findings are discussed. PMID:28392774

Beverage intake preference and bowel preparation laxative taste preference for colonoscopy

PubMed Central

Laiyemo, Adeyinka O; Burnside, Clinton; Laiyemo, Maryam A; Kwagyan, John; Williams, Carla D; Idowu, Kolapo A; Ashktorab, Hassan; Kibreab, Angesom; Scott, Victor F; Sanderson, Andrew K

2015-01-01

AIM: To examine whether non-alcoholic beverage intake preferences can guide polyethylene glycol (PEG)-based bowel laxative preparation selection for patients. METHODS: We conducted eight public taste test sessions using commercially procured (A) unflavored PEG, (B) citrus flavored PEG and (C) PEG with ascorbate (Moviprep). We collected characteristics of volunteers including their beverage intake preferences. The volunteers tasted the laxatives in randomly assigned orders and ranked the laxatives as 1st, 2nd, and 3rd based on their taste preferences. Our primary outcome is the number of 1st place rankings for each preparation. RESULTS: A total of 777 volunteers completed the study. Unflavored PEG was ranked as 1st by 70 (9.0%), flavored PEG by 534 (68.7%) and PEG with ascorbate by 173 (22.3%) volunteers. Demographic, lifestyle characteristics and beverage intake patterns for coffee, tea, and carbonated drinks did not predict PEG-based laxative preference. CONCLUSION: Beverage intake pattern was not a useful guide for PEG-based laxative preference. It is important to develop more tolerable and affordable bowel preparation laxatives for colonoscopy. Also, patients should taste their PEG solution with and without flavoring before flavoring the entire gallon as this may give them more opportunity to pick a pattern that may be more tolerable. PMID:26261736

Beverage intake preference and bowel preparation laxative taste preference for colonoscopy.

PubMed

Laiyemo, Adeyinka O; Burnside, Clinton; Laiyemo, Maryam A; Kwagyan, John; Williams, Carla D; Idowu, Kolapo A; Ashktorab, Hassan; Kibreab, Angesom; Scott, Victor F; Sanderson, Andrew K

2015-08-06

To examine whether non-alcoholic beverage intake preferences can guide polyethylene glycol (PEG)-based bowel laxative preparation selection for patients. We conducted eight public taste test sessions using commercially procured (A) unflavored PEG, (B) citrus flavored PEG and (C) PEG with ascorbate (Moviprep). We collected characteristics of volunteers including their beverage intake preferences. The volunteers tasted the laxatives in randomly assigned orders and ranked the laxatives as 1(st), 2(nd), and 3(rd) based on their taste preferences. Our primary outcome is the number of 1(st) place rankings for each preparation. A total of 777 volunteers completed the study. Unflavored PEG was ranked as 1(st) by 70 (9.0%), flavored PEG by 534 (68.7%) and PEG with ascorbate by 173 (22.3%) volunteers. Demographic, lifestyle characteristics and beverage intake patterns for coffee, tea, and carbonated drinks did not predict PEG-based laxative preference. Beverage intake pattern was not a useful guide for PEG-based laxative preference. It is important to develop more tolerable and affordable bowel preparation laxatives for colonoscopy. Also, patients should taste their PEG solution with and without flavoring before flavoring the entire gallon as this may give them more opportunity to pick a pattern that may be more tolerable.

The Food Environment, Preference, and Experience Modulate the Effects of Exendin-4 on Food Intake and Reward.

PubMed

Mella, Ricardo; Schmidt, Camila B; Romagnoli, Pierre-Paul; Teske, Jennifer A; Perez-Leighton, Claudio

2017-11-01

The obesogenic food environment facilitates access to multiple palatable foods. Exendin-4 (EX4) is a glucagon-like peptide 1 receptor (GLP1R) agonist that inhibits food intake and has been proposed as an obesity therapy. This study tested whether the composition of the food environment and experience with palatable foods modulate the effects of EX4 on food intake and reward. Mice fed a cafeteria (CAF) or control diet were tested for the anorectic effects of EX4 when simultaneously offered foods of varying individual preference and in a conditioned place preference (CPP) test for chocolate. Plasma glucagon-like peptide 1 (GLP1) and hypothalamic GLP1R mRNA were analyzed post mortem. Mice fed a CAF diet developed individual food preference patterns. Offering mice either novel or highly preferred foods decreased the potency of EX4 to inhibit food intake compared to low preference foods or chow. Compared to the control diet, CAF diet intake blocked the decrease in chocolate CPP caused by EX4 and decreased the expression of hypothalamic GLP1R mRNA without altering the plasma GLP1 concentration. The composition of the food environment, food preference, and experience modulate the ability of EX4 to inhibit food intake and reward. These data highlight the significance of modeling the complexity of the human food environment in preclinical obesity studies. © 2017 The Obesity Society.

Carbon and Nitrogen Provisions Alter the Metabolic Flux in Developing Soybean Embryos1[W][OA

PubMed Central

Allen, Doug K.; Young, Jamey D.

2013-01-01

Soybean (Glycine max) seeds store significant amounts of their biomass as protein, levels of which reflect the carbon and nitrogen received by the developing embryo. The relationship between carbon and nitrogen supply during filling and seed composition was examined through a series of embryo-culturing experiments. Three distinct ratios of carbon to nitrogen supply were further explored through metabolic flux analysis. Labeling experiments utilizing [U-13C5]glutamine, [U-13C4]asparagine, and [1,2-13C2]glucose were performed to assess embryo metabolism under altered feeding conditions and to create corresponding flux maps. Additionally, [U-14C12]sucrose, [U-14C6]glucose, [U-14C5]glutamine, and [U-14C4]asparagine were used to monitor differences in carbon allocation. The analyses revealed that: (1) protein concentration as a percentage of total soybean embryo biomass coincided with the carbon-to-nitrogen ratio; (2) altered nitrogen supply did not dramatically impact relative amino acid or storage protein subunit profiles; and (3) glutamine supply contributed 10% to 23% of the carbon for biomass production, including 9% to 19% of carbon to fatty acid biosynthesis and 32% to 46% of carbon to amino acids. Seed metabolism accommodated different levels of protein biosynthesis while maintaining a consistent rate of dry weight accumulation. Flux through ATP-citrate lyase, combined with malic enzyme activity, contributed significantly to acetyl-coenzyme A production. These fluxes changed with plastidic pyruvate kinase to maintain a supply of pyruvate for amino and fatty acids. The flux maps were independently validated by nitrogen balancing and highlight the robustness of primary metabolism. PMID:23314943

Negotiating treatment preferences: Physicians' formulations of patients' stance.

PubMed

Landmark, Anne Marie Dalby; Svennevig, Jan; Gulbrandsen, Pål

2016-01-01

Eliciting patients' values and treatment preferences is an essential element in models of shared decision making, yet few studies have investigated the interactional realizations of how physicians do this in authentic encounters. Drawing on video-recorded encounters from Norwegian secondary care, the present study uses the fine-grained empirical methodology of conversation analysis (CA) to identify one conversational practice physicians use, namely, formulations of patients' stance, in which physicians summarize or paraphrase their understanding of the patient's stance towards treatment. The purpose of this study is twofold: (1) to explore what objectives formulations of patients' stance achieve while negotiating treatment and (2) to discuss these objectives in relation to core requirements in shared decision making. Our analysis demonstrates that formulating the patient's stance is a practice physicians use in order to elicit, check, and establish patients' attitudes towards treatment. This practice is in line with general recommendations for making shared decisions, such as exploring and checking patients' preferences and values. However, the formulations may function as a device for doing more than merely checking and establishing common ground and bringing up patients' preferences and views: Accompanied by subtle deprecating expressions, they work to delegitimize the patients' stances and indirectly convey the physicians' opposing stance. Once established, these positions can be used as a basis for challenging and potentially altering the patient's attitude towards the decision, thereby making it more congruent with the physician's view. Therefore, in addition to bringing up patients' views towards treatment, we argue that physicians may use formulations of patients' stance as a resource for directing the patient towards decisions that are congruent with the physician's stance in situations with potential disagreement, whilst (ostensibly) avoiding a more

In the Eye of the Beholder: Owner Preferences for Variations in Cats' Appearances with Specific Focus on Skull Morphology.

PubMed

Farnworth, Mark J; Packer, Rowena M A; Sordo, Lorena; Chen, Ruoning; Caney, Sarah M A; Gunn-Moore, Danièlle A

2018-02-20

Changes in the popularity of cat breeds are largely driven by human perceptions of, and selection for, phenotypic traits including skull morphology. The popularity of breeds with altered skull shapes appears to be increasing, and owner preferences are an important part of this dynamic. This study sought to establish how and why a range of phenotypic attributes, including skull shape, affect preferences shown by cat owners. Two questionnaires were distributed on-line to cat owners who were asked to rate preferences for pictures of cats on a 0-10 scale. Veterinarian consensus established the skull types of the cats pictured (i.e., level of brachycephaly (BC) or dolichocephaly (DC)). Preferences were then explored relative to cat skull type, coat and eye color, and coat length. Generalized estimating equations identified relationships between physical characteristics and respondent ratings. Further sub-analyses explored effects of respondents' occupation, location and previous cat ownership on rating scores. Overall, cats with extreme changes in skull morphology (both BC and DC) were significantly less preferred than mesocephalic cats. Green eyes, ginger coat color and medium length coat were most preferred. Current owners of a BC or DC pure bred cat showed significantly greater preference for cats with similar features and significantly lower preference for the opposite extreme. Respondents from Asia were significantly more likely to prefer both BC and DC cats as compared to respondents from other locations. Finally, those in an animal care profession, as compared to other professions, provided a significantly lower preference rating for BC cats but not for DC cats. This work, despite the acknowledged limitations, provides preliminary evidence that preferences for cat breeds, and their associated skull morphologies, are driven by both cultural and experiential parameters. This information may allow for better targeting of educational materials concerning cat breeds.

Prefer feeling bad? Subcultural differences in emotional preferences between Han Chinese and Mongolian Chinese.

PubMed

Deng, Xinmei; Cheng, Chen; Chow, Hiu Mei; Ding, Xuechen

2018-03-01

As a multi-ethnic country that is comprised of diverse cultural systems, there has been little research on the subcultural differences in emotional preferences in China. Also, little attention has been paid to examine how explicit and implicit attitudes towards emotions influence emotional preferences interactively. In this study, we manipulated explicit attitudes towards emotions among Han (N = 62) and Mongolian Chinese individuals (N = 70). We assessed participants' implicit attitudes towards emotions to explore their contributions to emotional preferences. (a) Han Chinese had lower preferences for pleasant emotions than Mongolian Chinese after inducing contra-hedonic attitudes towards emotions, and (b) after priming contra-hedonic attitudes towards emotions, the more Han Chinese participants evaluated pleasant emotions as negative implicitly, the less they preferred to engage in pleasant emotional activities. These findings contribute to the growing literature of subcultural differences and demonstrate that explicit and implicit attitudes towards emotions interactively influence individuals' emotional preferences between different subculture groups. © 2018 International Union of Psychological Science.

Cushing's syndrome mutant PKA L205R exhibits altered substrate specificity

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

Lubner, Joshua M.; Dodge-Kafka, Kimberly L.; Carlson, Cathrine R.

The PKA L205R hotspot mutation has been implicated in Cushing's syndrome through hyperactive gain-of-function PKA signaling; however, its influence on substrate specificity has not been investigated. Here, we employ the Proteomic Peptide Library (ProPeL) approach to create high-resolution models for PKA WT and PKA L205R substrate specificity. We reveal that the L205R mutation reduces canonical hydrophobic preference at the substrate P + 1 position, and increases acidic preference in downstream positions. Using these models, we designed peptide substrates that exhibit altered selectivity for specific PKA variants, and demonstrate the feasibility of selective PKA L205R loss-of-function signaling. Through these results, wemore » suggest that substrate rewiring may contribute to Cushing's syndrome disease etiology, and introduce a powerful new paradigm for investigating mutation-induced kinase substrate rewiring in human disease.« less

Cushing's syndrome mutant PKA L205R exhibits altered substrate specificity

DOE PAGES

Lubner, Joshua M.; Dodge-Kafka, Kimberly L.; Carlson, Cathrine R.; ...

2017-02-01

The PKA L205R hotspot mutation has been implicated in Cushing's syndrome through hyperactive gain-of-function PKA signaling; however, its influence on substrate specificity has not been investigated. Here, we employ the Proteomic Peptide Library (ProPeL) approach to create high-resolution models for PKA WT and PKA L205R substrate specificity. We reveal that the L205R mutation reduces canonical hydrophobic preference at the substrate P + 1 position, and increases acidic preference in downstream positions. Using these models, we designed peptide substrates that exhibit altered selectivity for specific PKA variants, and demonstrate the feasibility of selective PKA L205R loss-of-function signaling. Through these results, wemore » suggest that substrate rewiring may contribute to Cushing's syndrome disease etiology, and introduce a powerful new paradigm for investigating mutation-induced kinase substrate rewiring in human disease.« less

Impaired decision making in oppositional defiant disorder related to altered psychophysiological responses to reinforcement.

PubMed

Luman, Marjolein; Sergeant, Joseph A; Knol, Dirk L; Oosterlaan, Jaap

2010-08-15

When making decisions, children with oppositional defiant disorder (ODD) are thought to focus on reward and ignore penalty. This is suggested to be associated with a state of low psychophysiological arousal. This study investigates decision making in 18 children with oppositional defiant disorder and 24 typically developing control subjects. Children were required to choose between three alternatives that carried either frequent small rewards and occasional small penalties (advantageous), frequent large rewards and increasing penalties (seductive), or frequent small rewards and increasing penalties (disadvantageous). Penalties in the seductive and disadvantageous alternatives increased either in frequency or magnitude in two conditions. Heart rate (HR) and skin conductance responses to reinforcement were obtained. In the magnitude condition, children with ODD showed an increased preference for the seductive alternative (carrying large rewards); this was not observed in the frequency condition. Children with ODD, compared with typically developing children, displayed greater HR reactivity to reward (more HR deceleration) and smaller HR reactivity to penalty. Correlation analyses showed that decreased HR responses to penalty were related to an increased preference for large rewards. No group differences were observed in skin conductance responses to reward or penalty. The findings suggest that an increased preference for large rewards in children with ODD is related to a reduced cardiac reactivity to aversive stimuli. This confirms notions of impaired decision making and altered reinforcement sensitivity in children with ODD and adds to the literature linking altered autonomic control to antisocial behavior. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in C57BL/6J mice

PubMed Central

Blednov, Yuri A.; Benavidez, Jillian M.; Black, Mendy; Harris, R. Adron

2014-01-01

Some anti-inflammatory medications reduce alcohol consumption in rodent models. Inhibition of phosphodiesterases (PDE) increases cAMP and reduces inflammatory signaling. Rolipram, an inhibitor of PDE4, markedly reduced ethanol intake and preference in mice and reduced ethanol seeking and consumption in alcohol-preferring fawn-hooded rats (Hu et al., 2011; Wen et al., 2012). To determine if these effects were specific for PDE4, we compared nine PDE inhibitors with different subtype selectivity: propentofylline (nonspecific), vinpocetine (PDE1), olprinone, milrinone (PDE3), zaprinast (PDE5), rolipram, mesopram, piclamilast, and CDP840 (PDE4). Alcohol intake was measured in C57BL/6J male mice using 24-h two-bottle choice and two-bottle choice with limited (3-h) access to alcohol. Only the selective PDE4 inhibitors reduced ethanol intake and preference in the 24-h two-bottle choice test. For rolipram, piclamilast, and CDP840, this effect was observed after the first 6 h but not after the next 18 h. Mesopram, however, produced a long-lasting reduction of ethanol intake and preference. In the limited access test, rolipram, piclamilast, and mesopram reduced ethanol consumption and total fluid intake and did not change preference for ethanol, whereas CDP840 reduced both consumption and preference without altering total fluid intake. Our results provide novel evidence for a selective role of PDE4 in regulating ethanol drinking in mice. We suggest that inhibition of PDE4 may be an unexplored target for medication development to reduce excessive alcohol consumption. PMID:24904269

When "altering brain function" becomes "mind control".

PubMed

Koivuniemi, Andrew; Otto, Kevin

2014-01-01

Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control.

Topical treatment with coenzyme Q10-containing formulas improves skin's Q10 level and provides antioxidative effects.

PubMed

Knott, Anja; Achterberg, Volker; Smuda, Christoph; Mielke, Heiko; Sperling, Gabi; Dunckelmann, Katja; Vogelsang, Alexandra; Krüger, Andrea; Schwengler, Helge; Behtash, Mojgan; Kristof, Sonja; Diekmann, Heike; Eisenberg, Tanya; Berroth, Andreas; Hildebrand, Janosch; Siegner, Ralf; Winnefeld, Marc; Teuber, Frank; Fey, Sven; Möbius, Janne; Retzer, Dana; Burkhardt, Thorsten; Lüttke, Juliane; Blatt, Thomas

2015-01-01

Ubiquinone (coenzyme Q10, Q10) represents an endogenously synthesized lipid-soluble antioxidant which is crucial for cellular energy production but is diminished with age and under the influence of external stress factors in human skin. Here, it is shown that topical Q10 treatment is beneficial with regard to effective Q10 replenishment, augmentation of cellular energy metabolism, and antioxidant effects. Application of Q10-containing formulas significantly increased the levels of this quinone on the skin surface. In the deeper layers of the epidermis the ubiquinone level was significantly augmented indicating effective supplementation. Concurrent elevation of ubiquinol levels suggested metabolic transformation of ubiquinone resulting from increased energy metabolism. Incubation of cultured human keratinocytes with Q10 concentrations equivalent to treated skin showed a significant augmentation of energy metabolism. Moreover, the results demonstrated that stressed skin benefits from the topical Q10 treatment by reduction of free radicals and an increase in antioxidant capacity. © 2015 International Union of Biochemistry and Molecular Biology.

Do Italian women prefer cesarean section? Results from a survey on mode of delivery preferences

PubMed Central

2013-01-01

Background About 20 million cesareans occur each year in the world and rates have steadily increased in almost all middle- and high-income countries over the last decades. Maternal request is often argued as one of the key forces driving this increase. Italy has the highest cesarean rate of Europe, yet there are no national surveys on the views of Italian women about their preferences on route of delivery. This study aimed to assess Italian women´s preference for mode of delivery, as well as reasons and factors associated with this preference, in a nationally representative sample of women. Methods This cross sectional survey was conducted between December 2010-March 2011. An anonymous structured questionnaire asked participants what was their preferred mode of delivery and explored the reasons for this preference by assessing their agreement to a series of statements. Participants were also asked to what extent their preference was influenced by a series of possible sources. The 1st phase of the study was carried out among readers of a popular Italian women´s magazine (Io Donna). In a 2nd phase, the study was complemented by a structured telephone interview. Results A total of 1000 Italian women participated in the survey and 80% declared they would prefer to deliver vaginally if they could opt. The preference for vaginal delivery was significantly higher among older (84.7%), more educated (87.6%), multiparous women (82.3%) and especially among those without any previous cesareans (94.2%). The main reasons for preferring a vaginal delivery were not wanting to be separated from the baby during the first hours of life, a shorter hospital stay and a faster postpartum recovery. The main reasons for preferring a cesarean were fear of pain, convenience to schedule the delivery and because it was perceived as being less traumatic for the baby. The source which most influenced the preference of these Italian women was their obstetrician, followed by friends or relatives

Estimation of methanogen biomass via quantitation of coenzyme M

USGS Publications Warehouse

Elias, Dwayne A.; Krumholz, Lee R.; Tanner, Ralph S.; Suflita, Joseph M.

1999-01-01

Determination of the role of methanogenic bacteria in an anaerobic ecosystem often requires quantitation of the organisms. Because of the extreme oxygen sensitivity of these organisms and the inherent limitations of cultural techniques, an accurate biomass value is very difficult to obtain. We standardized a simple method for estimating methanogen biomass in a variety of environmental matrices. In this procedure we used the thiol biomarker coenzyme M (CoM) (2-mercaptoethanesulfonic acid), which is known to be present in all methanogenic bacteria. A high-performance liquid chromatography-based method for detecting thiols in pore water (A. Vairavamurthy and M. Mopper, Anal. Chim. Acta 78:363–370, 1990) was modified in order to quantify CoM in pure cultures, sediments, and sewage water samples. The identity of the CoM derivative was verified by using liquid chromatography-mass spectroscopy. The assay was linear for CoM amounts ranging from 2 to 2,000 pmol, and the detection limit was 2 pmol of CoM/ml of sample. CoM was not adsorbed to sediments. The methanogens tested contained an average of 19.5 nmol of CoM/mg of protein and 0.39 ± 0.07 fmol of CoM/cell. Environmental samples contained an average of 0.41 ± 0.17 fmol/cell based on most-probable-number estimates. CoM was extracted by using 1% tri-(N)-butylphosphine in isopropanol. More than 90% of the CoM was recovered from pure cultures and environmental samples. We observed no interference from sediments in the CoM recovery process, and the method could be completed aerobically within 3 h. Freezing sediment samples resulted in 46 to 83% decreases in the amounts of detectable CoM, whereas freezing had no effect on the amounts of CoM determined in pure cultures. The method described here provides a quick and relatively simple way to estimate methanogenic biomass.

Therapeutic Potential of Co-enzyme Q10 in Retinal Diseases.

PubMed

Zhang, Xun; Tohari, Ali Mohammad; Marcheggiani, Fabio; Zhou, Xinzhi; Reilly, James; Tiano, Luca; Shu, Xinhua

2017-01-01

Coenzyme Q10 (CoQ10) plays a critical role in mitochondrial oxidative phosphorylation by serving as an electron carrier in the respiratory electron transport chain. CoQ10 also functions as a lipid-soluble antioxidant by protecting lipids, proteins and DNA damaged by oxidative stress. CoQ10 deficiency has been associated with a number of human diseases in which CoQ10 supplementation therapy has been effective in slowing or reversing pathological changes. Oxidative stress is a major contributory factor in the process of retinal degeneration. The related literature was reviewed through searching PubMed using keywords: CoQ10, CoQ10 and oxidative stress, CoQ10 and retinal degeneration. The functions of CoQ10 were summarized and its use in the treatment of age-related macular degeneration and glaucoma highlighted. The therapeutic potential of CoQ10 for other retinal diseases was also discussed. CoQ10 has been applied in different types of neurodegeneration. CoQ10 is detectable in retina and declines with ageing. Early studies showed treatment of CoQ10 improved visual function in patients with age-related macular degeneration. In glaucomatous models, CoQ10 exposure protected ganglion cell death from environmental stress; in glaucoma patients, CoQ10 treatment demonstrated beneficial effects on function of inner retina and enhancement of visual cortical response. Since oxidative stress also plays a critical role in the pathogenesis of diabetic retinopathy and retinitis pigmentosa, CoQ10 is a therapeutic target for both conditions. A wide range of evidence supports a role of CoQ10 in retinal diseases through inhibiting production of reactive oxygen species and protecting neuroretinal cells from oxidative damage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Calorie restriction inhibits relapse behaviour and preference for alcohol within a two-bottle free choice paradigm in the alcohol preferring (iP) rat.

PubMed

Guccione, Lisa; Djouma, Elvan; Penman, Jim; Paolini, Antonio G

2013-02-17

Among its many beneficial effects, calorie restriction (CR) has also been found to reduce anxiety related behavior in the rodent. With heightened levels of stress and anxiety implicated as a key precipitating factor of relapse and alcohol addiction, it was found that a 25% CR in addition to inducing anxiolytic effects also had the capacity to reduce intake of alcohol and inhibit relapse within a model of operant self-administration. The aim of this study was to investigate if a 25% CR would also display similar effects in a two-bottle free choice paradigm, whereby 24 h ad libitum access to both 10% ethanol and water is provided. All animals were initially tested on the elevated plus maze (EPM) and open field test prior to commencing the two-bottle free choice paradigm. Differences between control and CR25% animals demonstrated the anxiolytic effects of CR, with the CR25% group displaying greater percentage of open arm/total arm duration and open arm/total arm entries in the EPM. During the acquisition phase of the two-bottle free choice paradigm, CR25% animals showed a reduced intake of 10% ethanol in ml/kg, in comparison to the control group. Whilst control animals displayed a strong preference for 10% ethanol, the CR25% group consumed both 10% ethanol and water equally with no differences found in total fluid intake between groups. Similarly this was also the case following forced deprivation. In addition to reduced intake and lack of preference for 10% ethanol, CR 25% animals unlike controls failed to display a typical alcohol deprivation effect following abstinence. Taken collectively the results of this study suggest that CR may act as a protective factor against addiction and relapse in the alcohol preferring (iP) rat. In addition, given CR25% animals did not display a preference for 10% ethanol, results also suggest that CR may be altering the hedonic impact of ethanol within this group. Copyright © 2012 Elsevier Inc. All rights reserved.

Difference in plantar pressure between the preferred and non‐preferred feet in four soccer‐related movements

PubMed Central

Wong, Pui‐lam; Chamari, Karim; Chaouachi, Anis; De Wei Mao; Wisløff, Ulrik; Hong, Youlian

2007-01-01

Objective and participants The present study measured the difference in plantar pressure between the preferred and non‐preferred foot in four soccer‐related movements in 15 male university soccer players (mean (SD) age 20.9 (1.3) years, mean (SD) height 173 (4) cm and mean (SD) weight 61.7 (3.6) kg). Design To record plantar pressure distribution, players randomly wore three types of soccer shoes (classical 6‐stud and 12‐stud, and specially designed 12‐stud) embedded with an insole pressure recorder device with 99 sensors, divided into 10 areas for analysis. Plantar pressure was recorded in five successful trials in each of the four soccer‐related movements: running (at 3.3 m/s), sideward cutting, 45° cutting and landing from a vertical jump. Results Plantar pressures of the preferred and non‐preferred foot were different in 115 of 120 comparisons. The overall plantar pressure of the preferred foot was higher than that of the non‐preferred foot. Specifically, in each of the four movements, higher pressure was found in the preferred foot during the take‐off phase, whereas this was found in the non‐preferred foot during the landing phase. This would suggest a tendency of the preferred foot for higher motion force and of the non‐preferred foot for a greater role in body stabilisation. Conclusions The data indicate that the preferred and non‐preferred foot should be treated independently with regard to strength/power training to avoid unnecessary injuries. Different shoes/insoles and different muscular strengthening programmes are thus suggested for each of the soccer player's feet. PMID:17138639

Network science and the effects of music preference on functional brain connectivity: from Beethoven to Eminem.

PubMed

Wilkins, R W; Hodges, D A; Laurienti, P J; Steen, M; Burdette, J H

2014-08-28

Most people choose to listen to music that they prefer or 'like' such as classical, country or rock. Previous research has focused on how different characteristics of music (i.e., classical versus country) affect the brain. Yet, when listening to preferred music--regardless of the type--people report they often experience personal thoughts and memories. To date, understanding how this occurs in the brain has remained elusive. Using network science methods, we evaluated differences in functional brain connectivity when individuals listened to complete songs. We show that a circuit important for internally-focused thoughts, known as the default mode network, was most connected when listening to preferred music. We also show that listening to a favorite song alters the connectivity between auditory brain areas and the hippocampus, a region responsible for memory and social emotion consolidation. Given that musical preferences are uniquely individualized phenomena and that music can vary in acoustic complexity and the presence or absence of lyrics, the consistency of our results was unexpected. These findings may explain why comparable emotional and mental states can be experienced by people listening to music that differs as widely as Beethoven and Eminem. The neurobiological and neurorehabilitation implications of these results are discussed.

Network Science and the Effects of Music Preference on Functional Brain Connectivity: From Beethoven to Eminem

PubMed Central

Wilkins, R. W.; Hodges, D. A.; Laurienti, P. J.; Steen, M.; Burdette, J. H.

2014-01-01

Most people choose to listen to music that they prefer or ‘like’ such as classical, country or rock. Previous research has focused on how different characteristics of music (i.e., classical versus country) affect the brain. Yet, when listening to preferred music—regardless of the type—people report they often experience personal thoughts and memories. To date, understanding how this occurs in the brain has remained elusive. Using network science methods, we evaluated differences in functional brain connectivity when individuals listened to complete songs. We show that a circuit important for internally-focused thoughts, known as the default mode network, was most connected when listening to preferred music. We also show that listening to a favorite song alters the connectivity between auditory brain areas and the hippocampus, a region responsible for memory and social emotion consolidation. Given that musical preferences are uniquely individualized phenomena and that music can vary in acoustic complexity and the presence or absence of lyrics, the consistency of our results was unexpected. These findings may explain why comparable emotional and mental states can be experienced by people listening to music that differs as widely as Beethoven and Eminem. The neurobiological and neurorehabilitation implications of these results are discussed. PMID:25167363

Preferences for Pink and Blue: The Development of Color Preferences as a Distinct Gender-Typed Behavior in Toddlers.

PubMed

Wong, Wang I; Hines, Melissa

2015-07-01

Many gender differences are thought to result from interactions between inborn factors and sociocognitive processes that occur after birth. There is controversy, however, over the causes of gender-typed preferences for the colors pink and blue, with some viewing these preferences as arising solely from sociocognitive processes of gender development. We evaluated preferences for gender-typed colors, and compared them to gender-typed toy and activity preferences in 126 toddlers on two occasions separated by 6-8 months (at Time 1, M = 29 months; range 20-40). Color preferences were assessed using color cards and neutral toys in gender-typed colors. Gender-typed toy and activity preferences were assessed using a parent-report questionnaire, the Preschool Activities Inventory. Color preferences were also assessed for the toddlers' parents using color cards. A gender difference in color preferences was present between 2 and 3 years of age and strengthened near the third birthday, at which time it was large (d > 1). In contrast to their parents, toddlers' gender-typed color preferences were stronger and unstable. Gender-typed color preferences also appeared to establish later and were less stable than gender-typed toy and activity preferences. Gender-typed color preferences were largely uncorrelated with gender-typed toy and activity preferences. These results suggest that the factors influencing gender-typed color preferences and gender-typed toy and activity preferences differ in some respects. Our findings suggest that sociocognitive influences and play with gender-typed toys that happen to be made in gender-typed colors contribute to toddlers' gender-typed color preferences.

Monosodium glutamate-associated alterations in open field, anxiety-related and conditioned place preference behaviours in mice.

PubMed

Onaolapo, Olakunle James; Aremu, Olaleye Samuel; Onaolapo, Adejoke Yetunde

2017-07-01

The present study investigated changes in behaviour associated with oral monosodium glutamate (a flavouring agent), using the open field, elevated plus maze and conditioned place preference (CPP) paradigms, respectively. Mice were assigned to two groups for CPP [monosodium glutamate (MSG)-naïve (n = 40) and MSG-pretreated (n = 40)] and two groups for open field (OF) and elevated plus maze (EPM) tests [n = 40 each], respectively. Animals in respective groups were then divided into four subgroups (n = 10) (vehicle or MSG (80, 160 and 320 mg/kg)). MSG-naïve mice were observed in the CPP box in three phases (pre-conditioning, conditioning and post-conditioning). Mice were conditioned to MSG or an equivalent volume of saline. The MSG pretreatment group received vehicle or respective doses of MSG daily for 21 days, prior to conditioning. Mice in the OF or EPM groups received vehicle or doses of MSG (orally) for 21 days, at 10 ml/kg. Open field or EPM behaviours were assessed on days 1 and 21. At the end of the experiments, mice in the OF groups were sacrificed and brain homogenates used to assay glutamate and glutamine. Results showed that administration of MSG was associated with a decrease in rearing, dose-related mixed horizontal locomotor, grooming and anxiety-related response and an increase in brain glutamate/glutamine levels. Following exposure to the CPP paradigm, MSG-naïve and MSG-pretreated mice both showed 'drug-paired' chamber preference. The study concluded that MSG (at the administered doses) was associated with changes in open field activities, anxiety-related behaviours and brain glutamate/glutamine levels; its ingestion also probably leads to a stimulation of the brain reward system.

Greater shrub dominance alters breeding habitat and food resources for migratory songbirds in Alaskan arctic tundra.

PubMed

Boelman, Natalie T; Gough, Laura; Wingfield, John; Goetz, Scott; Asmus, Ashley; Chmura, Helen E; Krause, Jesse S; Perez, Jonathan H; Sweet, Shannan K; Guay, Kevin C

2015-04-01

Climate warming is affecting the Arctic in multiple ways, including via increased dominance of deciduous shrubs. Although many studies have focused on how this vegetation shift is altering nutrient cycling and energy balance, few have explicitly considered effects on tundra fauna, such as the millions of migratory songbirds that breed in northern regions every year. To understand how increasing deciduous shrub dominance may alter breeding songbird habitat, we quantified vegetation and arthropod community characteristics in both graminoid and shrub dominated tundra. We combined measurements of preferred nest site characteristics for Lapland longspurs (Calcarius lapponicus) and Gambel's White-crowned sparrows (Zonotrichia leucophrys gambelii) with modeled predictions for the distribution of plant community types in the Alaskan arctic foothills region for the year 2050. Lapland longspur nests were found in sedge-dominated tussock tundra where shrub height does not exceed 20 cm, whereas White-crowned sparrows nested only under shrubs between 20 cm and 1 m in height, with no preference for shrub species. Shrub canopies had higher canopy-dwelling arthropod availability (i.e. small flies and spiders) but lower ground-dwelling arthropod availability (i.e. large spiders and beetles). Since flies are the birds' preferred prey, increasing shrubs may result in a net enhancement in preferred prey availability. Acknowledging the coarse resolution of existing tundra vegetation models, we predict that by 2050 there will be a northward shift in current White-crowned sparrow habitat range and a 20-60% increase in their preferred habitat extent, while Lapland longspur habitat extent will be equivalently reduced. Our findings can be used to make first approximations of future habitat change for species with similar nesting requirements. However, we contend that as exemplified by this study's findings, existing tundra modeling tools cannot yet simulate the fine-scale habitat

Establishing alighting preferences and species transmission differences for Pea seed-borne mosaic virus aphid vectors.

PubMed

Congdon, B S; Coutts, B A; Renton, M; Flematti, G R; Jones, R A C

2017-09-15

representing a range of compound groups (such as aldehydes, ketones and esters) were found in the headspaces of PSbMV-infected than of mock-inoculated pea or faba bean plants. This indicates PSbMV induces physiological changes in these hosts which manifest as altered volatile emissions. These alterations could be responsible for the differences in alighting preferences. Information from this study enhances understanding of virus-vector relationships in the PSbMV-pea and faba bean pathosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

Regulation of Substrate Oxidation Preferences in Muscle by the Peptide Hormone Adropin

PubMed Central

Gao, Su; McMillan, Ryan P.; Jacas, Jordi; Zhu, Qingzhang; Li, Xuesen; Kumar, Ganesh K.; Casals, Núria; Hegardt, Fausto G.; Robbins, Paul D.; Lopaschuk, Gary D.; Hulver, Matthew W.

2014-01-01

Rigorous control of substrate oxidation by humoral factors is essential for maintaining metabolic homeostasis. During feeding and fasting cycles, carbohydrates and fatty acids are the two primary substrates in oxidative metabolism. Here, we report a novel role for the peptide hormone adropin in regulating substrate oxidation preferences. Plasma levels of adropin increase with feeding and decrease upon fasting. A comparison of whole-body substrate preference and skeletal muscle substrate oxidation in adropin knockout and transgenic mice suggests adropin promotes carbohydrate oxidation over fat oxidation. In muscle, adropin activates pyruvate dehydrogenase (PDH), which is rate limiting for glucose oxidation and suppresses carnitine palmitoyltransferase-1B (CPT-1B), a key enzyme in fatty acid oxidation. Adropin downregulates PDH kinase-4 (PDK4) that inhibits PDH, thereby increasing PDH activity. The molecular mechanisms of adropin’s effects involve acetylation (suggesting inhibition) of the transcriptional coactivator PGC-1α, downregulating expression of Cpt1b and Pdk4. Increased PGC-1α acetylation by adropin may be mediated by inhibiting Sirtuin-1 (SIRT1), a PGC-1α deacetylase. Altered SIRT1 and PGC-1α activity appear to mediate aspects of adropin’s metabolic actions in muscle. Similar outcomes were observed in fasted mice treated with synthetic adropin. Together, these results suggest a role for adropin in regulating muscle substrate preference under various nutritional states. PMID:24848071

Tobacco brand preference among Mexican adolescents.

PubMed

West, Joshua H; Hall, P Cougar; Page, Randy M; Trinidad, Dennis R; Lindsay, Gordon B

2012-01-01

Advertising plays a major role in smoking behavior and forming brand preferences. Additionally, the most advertised tobacco brands have also been the most preferred. Maintaining brand loyalty in Latin America remains a priority for the tobacco industry. The purpose of this study was to explore tobacco brand preference trends from 2003 to 2006, and explore marketing and advertising factors that might be associated with these trends. Data for this study came from Mexican adolescents residing in cities that participated in the Global Youth Tobacco Survey in both 2003 and 2006 and reported smoking either Marlboro or Camel cigarettes in the past 30 days. Respondents reported the brand name of their preferred cigarette during the past 30 days. Multivariate regression analysis was used to determine differences by brand preference and exposure to tobacco marketing and advertising, which was assessed using six items. In 2003, most adolescents preferred Marlboro. By 2006, older boys preferred Camel cigarettes to Marlboro, while girls' preference for Camel was similar to their preference for Marlboro. Adolescents that preferred Camel cigarettes in 2003 also reported greater exposure to tobacco marketing and advertising. Findings indicate that there are ongoing shifts in youth brand preference in Mexico, and that these shifts might be related to marketing and advertising practices. There is an ongoing need for monitoring marketing and advertising practices in an effort to protect adolescents from tobacco company exploits.

Social preferences of future physicians

PubMed Central

Li, Jing; Dow, William H.

2017-01-01

We measure the social preferences of a sample of US medical students and compare their preferences with those of the general population sampled in the American Life Panel (ALP). We also compare the medical students with a subsample of highly educated, wealthy ALP subjects as well as elite law school students and undergraduate students. We further associate the heterogeneity in social preferences within medical students to the tier ranking of their medical schools and their expected specialty choice. Our experimental design allows us to rigorously distinguish altruism from preferences regarding equality–efficiency tradeoffs and accurately measure both at the individual level rather than pooling data or assuming homogeneity across subjects. This is particularly informative, because the subjects in our sample display widely heterogeneous social preferences in terms of both their altruism and equality–efficiency tradeoffs. We find that medical students are substantially less altruistic and more efficiency focused than the average American. Furthermore, medical students attending the top-ranked medical schools are less altruistic than those attending lower-ranked schools. We further show that the social preferences of those attending top-ranked medical schools are statistically indistinguishable from the preferences of a sample of elite law school students. The key limitation of this study is that our experimental measures of social preferences have not yet been externally validated against actual physician practice behaviors. Pending this future research, we probed the predictive validity of our experimental measures of social preferences by showing that the medical students choosing higher-paying medical specialties are less altruistic than those choosing lower-paying specialties. PMID:29146826

Endogenous nociceptin modulates diet preference independent of motivation and reward.

PubMed

Koizumi, Miwako; Cagniard, Barbara; Murphy, Niall P

2009-04-20

Previous studies show that the opioid peptide nociceptin stimulates food intake. Here, we studied nociceptin receptor knockout (NOP KO) mice in various behavioral paradigms designed to differentiate psychological and physiological loci at which endogenous nociceptin might control feeding. When presented a choice under food restriction, NOP KO mice displayed reduced preference for high sucrose diet, but lower intake of high fat diet under no-choice conditions. These responses were absent under ad libitum feeding conditions. Conditioned place preference to high fat diet under food-deprived conditions was unaltered in NOP KO mice, suggesting no difference in reward responses. Furthermore, operant food self-administration under a variety of conditions showed no genotype-dependent differences, suggesting no differences in the motivational properties of food. Taste reactivity to sucrose was unchanged in NOP KO mice, though NOP KO mice had altered aversive reactions to quinine solutions under ad libitum feeding, suggesting minor differences in the affective impact of palatable and unpalatable tastants. Although NOP KO mice re-fed following food-deprivation showed normal increases in plasma glucose and insulin, multidimensional scaling analysis showed that the relationship between these measures, body weight and plasma leptin was substantially disrupted in NOP KO, particularly in fasted mice. Additionally, the typical positive relationship between body weight and plasma leptin was considerably weaker in NOP KO mice. Together, these findings suggest that endogenous nociceptin differentially modulates diet preference depending on macronutrient content and homeostatic state, independently of the motivating, rewarding or orosensory properties of food, but may involve metabolic or postingestive processes.

Identification of Bacillus subtilis men mutants which lack O-succinylbenzoyl-coenzyme A synthetase and dihydroxynaphthoate synthase.

PubMed Central

Meganathan, R; Bentley, R; Taber, H

1981-01-01

Menaquinone (vitamin K2)-deficient mutants of Bacillus subtilis, whose growth requirement is satisfied by 1,4-dihydroxy-2-naphthoic acid but not by o-succinylbenzoic acid (OSB), have been analyzed for enzymatic defects. Complementation analysis of cell-free extracts of the mutants revealed that there are two groups, as already indicated by genetic analysis. The missing enzyme in each group was identified by complementation of the cell-free extracts with o-succinylbenzoyl-coenzyme A (CoA) synthetase and dihydroxynaphthoate synthase extracted from Mycobacterium phlei. Mutants found to lack dihydroxynaphthoate synthase, and which therefore complement with dihydroxynaphthoate synthase of M. phlei, were designated as menB; those lacking o-succinylbenzoyl-CoA synthetase, and therefore complementing with o-succinylbenzoyl-CoA synthetase, were designated as menE. The menB mutants RB413 (men-325) and RB415 (men-329), when incubated with [2,3-14C2]OSB, produced only the spirodilactone form of OSB in a reaction that was CoA and adenosine 5'-triphosphate dependent. PMID:6780515

Post-translational thioamidation of methyl-coenzyme M reductase, a key enzyme in methanogenic and methanotrophic Archaea

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

Nayak, Dipti D.; Mahanta, Nilkamal; Mitchell, Douglas A.

Methyl-coenzyme M reductase (MCR), found in strictly anaerobic methanogenic and methanotrophic archaea, catalyzes the reversible production and consumption of the potent greenhouse gas methane. The α subunit of MCR (McrA) contains several unusual post-translational modifications, including a rare thioamidation of glycine. Based on the presumed function of homologous genes involved in the biosynthesis of thioviridamide, a thioamide-containing natural product, we hypothesized that the archaeal tfuA and ycaO genes would be responsible for post-translational installation of thioglycine into McrA. Mass spectrometric characterization of McrA from the methanogenic archaeon Methanosarcina acetivorans lacking tfuA and/or ycaO revealed the presence of glycine, rather thanmore » thioglycine, supporting this hypothesis. Phenotypic characterization of the ∆ycaO-tfuA mutant revealed a severe growth rate defect on substrates with low free energy yields and at elevated temperatures (39°C - 45°C). Our analyses support a role for thioglycine in stabilizing the protein secondary structure near the active site.« less

Post-translational thioamidation of methyl-coenzyme M reductase, a key enzyme in methanogenic and methanotrophic Archaea

DOE PAGES

Nayak, Dipti D.; Mahanta, Nilkamal; Mitchell, Douglas A.; ...

2017-09-07

Methyl-coenzyme M reductase (MCR), found in strictly anaerobic methanogenic and methanotrophic archaea, catalyzes the reversible production and consumption of the potent greenhouse gas methane. The α subunit of MCR (McrA) contains several unusual post-translational modifications, including a rare thioamidation of glycine. Based on the presumed function of homologous genes involved in the biosynthesis of thioviridamide, a thioamide-containing natural product, we hypothesized that the archaeal tfuA and ycaO genes would be responsible for post-translational installation of thioglycine into McrA. Mass spectrometric characterization of McrA from the methanogenic archaeon Methanosarcina acetivorans lacking tfuA and/or ycaO revealed the presence of glycine, rather thanmore » thioglycine, supporting this hypothesis. Phenotypic characterization of the ∆ycaO-tfuA mutant revealed a severe growth rate defect on substrates with low free energy yields and at elevated temperatures (39°C - 45°C). Our analyses support a role for thioglycine in stabilizing the protein secondary structure near the active site.« less

Alterations of reward mechanisms in bulbectomised rats.

PubMed

Grecksch, Gisela; Becker, Axel

2015-06-01

The positive association between alcoholism and depression is a common clinical observation. We investigated the relationship between depression and reward mechanisms using a validated animal model for depressive-like behaviour, the olfactory bulbectomy in rats. The effects of bilateral olfactory bulbectomy on reward mechanisms were studied in two different experimental paradigms - the voluntary self-administration of ethanol and the conditioned place preference to alcohol injection and compared to the effects of ethanol on locomotor activity and body core temperature. The voluntary ethanol intake was increased significantly in bulbectomised rats in a drinking experiment and also after a period of abstinence. Conditioned place preference (CPP) was induced in all animals. However, bulbectomised rats needed a higher dose of alcohol to produce CPP. The sedative effect of ethanol on locomotor activity was reduced in bulbectomised animals. Measurement of body temperature revealed a dose-dependent hypothermic effect of ethanol in both groups. These results suggest that the reward mechanisms may be altered in this animal model as a common phenomenon associated with depression. Furthermore, they support the hypothesis that the addictive and/or rewarding properties of some drugs of abuse may be modified in depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Temporal Constraint Reasoning With Preferences

NASA Technical Reports Server (NTRS)

Khatib, Lina; Morris, Paul; Morris, Robert; Rossi, Francesca

2001-01-01

A number of reasoning problems involving the manipulation of temporal information can naturally be viewed as implicitly inducing an ordering of potential local decisions involving time (specifically, associated with durations or orderings of events) on the basis of preferences. For example. a pair of events might be constrained to occur in a certain order, and, in addition. it might be preferable that the delay between them be as large, or as small, as possible. This paper explores problems in which a set of temporal constraints is specified, where each constraint is associated with preference criteria for making local decisions about the events involved in the constraint, and a reasoner must infer a complete solution to the problem such that, to the extent possible, these local preferences are met in the best way. A constraint framework for reasoning about time is generalized to allow for preferences over event distances and durations, and we study the complexity of solving problems in the resulting formalism. It is shown that while in general such problems are NP-hard, some restrictions on the shape of the preference functions, and on the structure of the preference set, can be enforced to achieve tractability. In these cases, a simple generalization of a single-source shortest path algorithm can be used to compute a globally preferred solution in polynomial time.

Preferences for cardiopulmonary resuscitation.

PubMed

Puopolo, A L; Kennard, M J; Mallatratt, L; Follen, M A; Desbiens, N A; Conners, A F; Califf, R; Walzer, J; Soukup, J; Davis, R B; Phillips, R S

1997-01-01

To examine nurse-patient communication about preferences for cardiopulmonary resuscitation (CPR). Prospective cohort. Sampled were patients and nurses caring for patients enrolled in SUPPORT (1989-91), a multicenter study of seriously-ill hospitalized adults at four U.S. hospitals. Information about patient preferences was obtained by interviews with patients and their designated surrogates. For selected patients, nurses were interviewed prospectively about their understanding of patients' preferences and whether they discussed these preferences with their patients. Nurse demographic information was obtained by questionnaire. Additional patient data were obtained by interview and chart review. Logistic regression was used to identify independent correlates of nurse-patient communication and nurses' understanding of patients' preferences. For 1,763 study patients, 1,427 nurse interviews (response rate 81%) were obtained. The median age of interviewed nurses was 29 years; 96% were women, 68% had a bachelor's or master's degree, and 62% had worked for 5 years or more as a nurse. Nurses reported discussions about CPR with 13% of their patients, and these discussions were more likely if the nurse thought the patient did not want CPR (adjusted odds ratio [AOR] 2.68; 95% CI 1.84 to 3.90), if the nurse had spent more time with the patient (AOR 1.05; 95% CI 1.02 to 1.08) per 5 additional days, if the patient had metastatic cancer (AOR 3.56; 95% CI 1.86 to 6.78), or if the patient was in an intensive care unit at the time of study entry (AOR 2.08; 95% CI 1.26 to 3.42). Diagnosis and study site were also associated with nurses' reports of discussions with patients. Of 551 patients with available data, 58% (n = 317) wanted CPR and 30% (n = 164) did not. Nurses understood patients' CPR preferences correctly for 74% of the patients. Nurses were more likely to understand patients' preferences to forego CPR if the patient was 75 years of age or older (AOR 6.6; 95% CI 2.0 to 22

Psychiatric patients' preferences and experiences in clinical decision-making: examining concordance and correlates of patients' preferences.

PubMed

De las Cuevas, Carlos; Peñate, Wenceslao; de Rivera, Luis

2014-08-01

To assess the concordance between patients' preferred role in clinical decision-making and the role they usually experience in their psychiatric consultations and to analyze the influence of socio-demographic, clinical and personality characteristics on patients' preferences. 677 consecutive psychiatric outpatients were invited to participate in a cross-sectional survey and 507 accepted. Patients completed Control Preference Scale twice consecutively before consultation, one for their preferences of participation and another for the style they usually experienced until then, and locus of control and self-efficacy scales. Sixty-three percent of psychiatric outpatients preferred a collaborative role in decision-making, 35% preferred a passive role and only a 2% an active one. A low concordance for preferred and experienced participation in medical decision-making was registered, with more than a half of patients wanting a more active role than they actually had. Age and doctors' health locus of control orientation were found to be the best correlates for participation preferences, while age and gender were for experienced. Psychiatric diagnoses registered significant differences in patients' preferences of participation but no concerning experiences. The limited concordance between preferred and experienced roles in psychiatric patients is indicative that clinicians need to raise their sensitivity regarding patient's participation. The assessment of patient's attribution style should be useful for psychiatrist to set objectives and priority in the communication with their patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

13 CFR 120.411 - Preferences.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Preferences. 120.411 Section 120.411 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Lenders Participation Criteria § 120.411 Preferences. An agreement to participate under the Act may not establish any Preferences...

13 CFR 120.411 - Preferences.

Code of Federal Regulations, 2010 CFR