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Sample records for acute tryptophan depletion

  1. Effects of Acute Tryptophan Depletion on Three Different Types of Behavioral Impulsivity

    OpenAIRE

    2010-01-01

    Introduction: While central nervous system serotonin has been implicated in a variety of problematic impulsive behaviors, biological manipulation of brain serotonin using acute tryptophan depletion for studying changes in impulsive behavior has received little attention. Methods: Using identical treatment conditions, we examined the effects of reduced serotonin synthesis for each of three matched groups using acute tryptophan depletion. Thirty healthy men and women (ages 18–45) were assigned ...

  2. Evaluation of acute tryptophan depletion and sham depletion with a gelatin-based collagen peptide protein mixture

    DEFF Research Database (Denmark)

    Stenbæk, D S; Einarsdottir, H S; Goregliad-Fjaellingsdal, T

    2016-01-01

    Acute Tryptophan Depletion (ATD) is a dietary method used to modulate central 5-HT to study the effects of temporarily reduced 5-HT synthesis. The aim of this study is to evaluate a novel method of ATD using a gelatin-based collagen peptide (CP) mixture. We administered CP-Trp or CP+Trp mixtures...

  3. Converging evidence for central 5-HT effects in acute tryptophan depletion

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    Crockett, Molly; Clark, Luke; Roiser, Jonathan

    2012-01-01

    Acute tryptophan depletion (ATD), a dietary technique for manipulating brain serotonin (5-HT) function, has advanced our understanding of 5-HT mechanisms in the etiology and treatment of depression and other affective disorders.1 A recent review article in Molecular Psychiatry questioned the vali...

  4. Recognizing emotions in faces : effects of acute tryptophan depletion and bright light

    NARCIS (Netherlands)

    aan het Rot, Marije; Coupland, Nicholas; Boivin, Diane B.; Benkelfat, Chawki; Young, Simon N.

    2010-01-01

    In healthy never-depressed individuals, acute tryptophan depletion (ATD) may selectively decrease the accurate recognition of fearful facial expressions. Here we investigated the perception of facial emotions after ATD in more detail. We also investigated whether bright light, which can reverse ATD'

  5. Acute tryptophan depletion attenuates brain-heart coupling following external feedback

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    Erik M Mueller

    2012-04-01

    Full Text Available External and internal performance feedback triggers neural and visceral modulations such as reactions in the medial prefrontal cortex and insulae or changes of heart period (HP. The functional coupling of neural and cardiac responses following feedback (cortico-cardiac connectivity is not well understood. While linear time-lagged within-subjects correlations of single-trial EEG and HP (cardio-electroencephalographic covariance-tracing, CECT indicate a robust negative coupling of EEG magnitude 300 ms after presentation of an external feedback stimulus with subsequent alterations of heart period (the so-called N300H phenomenon, the neurotransmitter systems underlying feedback-evoked cortico-cardiac connectivity are largely unknown. Because it has been shown that acute tryptophan depletion (ATD, attenuating brain serotonin (5-HT, decreases cardiac but not neural correlates of feedback processing, we hypothesized that 5-HT may be involved in feedback-evoked cortico-cardiac connectivity. In a placebo-controlled double-blind crossover design, twelve healthy participants received a tryptophan-free amino-acid drink at one session and a balanced amino-acid control-drink on another and twice performed a time-estimation task with feedback presented after each trial. N300H magnitude and plasma tryptophan levels were assessed. Results indicated a robust N300H after the control drink, which was significantly attenuated following ATD. Moreover, plasma tryptophan levels during the control session were correlated with N300H amplitude such that individuals with lower tryptophan levels showed reduced N300H. Together, these findings indicate that 5-HT is important for feedback-induced covariation of cortical and cardiac activity. Because individual differences in anxiety have previously been linked to 5-HT, cortico-cardiac coupling and feedback processing, the present findings may be particularly relevant for futures studies linking 5-HT to anxiety.

  6. Reconciling the role of serotonin in behavioral inhibition and aversion: acute tryptophan depletion abolishes punishment-induced inhibition in humans.

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    Crockett, Molly J; Clark, Luke; Robbins, Trevor W

    2009-09-23

    The neuromodulator serotonin has been implicated in a large number of affective and executive functions, but its precise contribution to motivation remains unclear. One influential hypothesis has implicated serotonin in aversive processing; another has proposed a more general role for serotonin in behavioral inhibition. Because behavioral inhibition is a prepotent reaction to aversive outcomes, it has been a challenge to reconcile these two accounts. Here, we show that serotonin is critical for punishment-induced inhibition but not overall motor response inhibition or reporting aversive outcomes. We used acute tryptophan depletion to temporarily lower brain serotonin in healthy human volunteers as they completed a novel task designed to obtain separate measures of motor response inhibition, punishment-induced inhibition, and sensitivity to aversive outcomes. After a placebo treatment, participants were slower to respond under punishment conditions compared with reward conditions. Tryptophan depletion abolished this punishment-induced inhibition without affecting overall motor response inhibition or the ability to adjust response bias in line with punishment contingencies. The magnitude of reduction in punishment-induced inhibition depended on the degree to which tryptophan depletion reduced plasma tryptophan levels. These findings extend and clarify previous research on the role of serotonin in aversive processing and behavioral inhibition and fit with current theorizing on the involvement of serotonin in predicting aversive outcomes.

  7. Studying the effects of dietary body weight-adjusted acute tryptophan depletion on punishment-related behavioral inhibition

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    Tilman J. Gaber

    2015-08-01

    Full Text Available Background: Alterations in serotonergic (5-HT neurotransmission are thought to play a decisive role in affective disorders and impulse control. Objective: This study aims to reproduce and extend previous findings on the effects of acute tryptophan depletion (ATD and subsequently diminished central 5-HT synthesis in a reinforced categorization task using a refined body weight–adjusted depletion protocol. Design: Twenty-four young healthy adults (12 females, mean age [SD]=25.3 [2.1] years were subjected to a double-blind within-subject crossover design. Each subject was administered both an ATD challenge and a balanced amino acid load (BAL in two separate sessions in randomized order. Punishment-related behavioral inhibition was assessed using a forced choice go/no-go task that incorporated a variable payoff schedule. Results: Administration of ATD resulted in significant reductions in TRP measured in peripheral blood samples, indicating reductions of TRP influx across the blood–brain barrier and related brain 5-HT synthesis. Overall accuracy and response time performance were improved after ATD administration. The ability to adjust behavioral responses to aversive outcome magnitudes and behavioral adjustments following error contingent punishment remained intact after decreased brain 5-HT synthesis. A previously observed dissociation effect of ATD on punishment-induced inhibition was not observed. Conclusions: Our results suggest that neurodietary challenges with ATD Moja–De have no detrimental effects on task performance and punishment-related inhibition in healthy adults.

  8. The effects of acute tryptophan depletion on speech and behavioural mimicry in individuals at familial risk for depression.

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    Hogenelst, Koen; Sarampalis, Anastasios; Leander, N Pontus; Müller, Barbara C N; Schoevers, Robert A; aan het Rot, Marije

    2016-03-01

    Major depressive disorder (MDD) has been associated with abnormalities in speech and behavioural mimicry. These abnormalities may contribute to the impairments in interpersonal functioning that are often seen in MDD patients. MDD has also been associated with disturbances in the brain serotonin system, but the extent to which serotonin regulates speech and behavioural mimicry remains unclear. In a randomized, double-blind, crossover study, we induced acute tryptophan depletion (ATD) in individuals with or without a family history of MDD. Five hours afterwards, participants engaged in two behavioural-mimicry experiments in which speech and behaviour were recorded. ATD reduced the time participants waited before speaking, which might indicate increased impulsivity. However, ATD did not significantly alter speech otherwise, nor did it affect mimicry. This suggests that a brief lowering of brain serotonin has limited effects on verbal and non-verbal social behaviour. The null findings may be due to low test sensitivity, but they otherwise suggest that low serotonin has little effect on social interaction quality in never-depressed individuals. It remains possible that recovered MDD patients are more strongly affected. © The Author(s) 2016.

  9. Specificity of the Acute Tryptophan and Tyrosine Plus Phenylalanine Depletion and Loading Tests I. Review of Biochemical Aspects and Poor Specificity of Current Amino Acid Formulations

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    Abdulla A.-B. Badawy

    2010-06-01

    Full Text Available The acute tryptophan or tyrosine plus phenylalanine depletion and loading tests are powerful tools for studying the roles of serotonin, dopamine and noradrenaline in normal subjects and those with behavioural disorders. The current amino acid formulations for these tests, however, are associated with undesirable decreases in ratios of tryptophan or tyrosine plus phenylalanine to competing amino acids resulting in loss of specificity. This could confound biochemical and behavioural findings. Compositions of current formulations are reviewed, the biochemical principles underpinning the tests are revisited and examples of unintended changes in the above ratios and their impact on monoamine function and behaviour will be demonstrated from data in the literature. The presence of excessive amounts of the 3 branched-chain amino acids Leu, Ile and Val is responsible for these unintended decreases and the consequent loss of specificity. Strategies for enhancing the specificity of the different formulations are proposed.

  10. Acute tryptophan depletion increases translational indices of anxiety but not fear: serotonergic modulation of the bed nucleus of the stria terminalis?

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    Robinson, Oliver J; Overstreet, Cassie; Allen, Phillip S; Pine, Daniel S; Grillon, Christian

    2012-07-01

    Serotonin is strongly implicated in the mammalian stress response, but surprisingly little is known about its mode of action. Recent data suggest that serotonin can inhibit aversive responding in humans, but this remains underspecified. In particular, data in rodents suggest that global serotonin depletion may specifically increase long-duration bed nucleus of the stria terminalis (BNST)-mediated aversive responses (ie, anxiety), but not short-duration BNST-independent responses (ie, fear). Here, we extend these findings to humans. In a balanced, placebo-controlled crossover design, healthy volunteers (n=20) received a controlled diet with and without the serotonin precursor tryptophan (acute tryptophan depletion; ATD). Aversive states were indexed by translational acoustic startle measures. Fear and anxiety were operationally defined as the increase in startle reactivity during short- and long-duration threat periods evoked by predictable shock (fear-potentiated startle) and by the context in which the shocks were administered (anxiety-potentiated startle), respectively. ATD significantly increased long-duration anxiety-potentiated startle but had no effect on short-duration fear-potentiated startle. These results suggest that serotonin depletion in humans selectively increases anxiety but not fear. Current translational frameworks support the proposition that ATD thus disinhibits dorsal raphé-originating serotonergic control of corticotropin-releasing hormone-mediated excitation of the BNST. This generates a candidate neuropharmacological mechanism by which depleted serotonin may increase response to sustained threats, alongside clear implications for our understanding of the manifestation and treatment of mood and anxiety disorders.

  11. Simplified dietary acute tryptophan depletion: effects of a novel amino acid mixture on the neurochemistry of C57BL/6J mice

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    Cristina L. Sánchez

    2015-08-01

    Full Text Available Background: Diet and nutrition can impact on the biological processes underpinning neuropsychiatric disorders. Amino acid (AA mixtures lacking a specific neurotransmitter precursor can change the levels of brain serotonin (5-HT or dopamine (DA in the central nervous system. The availability of these substances within the brain is determined by the blood–brain barrier (BBB that restricts the access of peripheral AA into the brain. AA mixtures lacking tryptophan (TRP compete with endogenous TRP for uptake into the brain across the BBB, which in turn leads to a decrease in central nervous 5-HT synthesis. Objective: The present study compared the effects of a simplified acute tryptophan depletion (SATD mixture in mice on blood and brain serotonergic and dopaminergic metabolites to those of a commonly used acute tryptophan depletion mixture (ATD Moja-De and its TRP-balanced control (BAL. Design: The SATD formula is composed of only three large neutral AAs: phenylalanine (PHE, leucine (LEU, and isoleucine (ILE. BAL, ATD Moja-De, or SATD formulas were delivered to adult male C57BL/6J mice by gavage. TRP, monoamines, and their metabolites were quantified in blood and brain regions (hippocampus, frontal cortex, amygdala, caudate putamen, and nucleus accumbens. Results: Both ATD Moja-De and SATD significantly decreased levels of serum and brain TRP, as well as brain 5-HIAA and 5-HT compared with BAL. SATD reduced HVA levels in caudate but did not alter total DA levels or DOPAC. SATD decreased TRP and serotonergic metabolites comparably to ATD Moja-De administration. Conclusion: A simplified and more palatable combination of AAs can manipulate serotonergic function and might be useful to reveal underlying monoamine-related mechanisms contributing to different neuropsychiatric disorders.

  12. Understanding the impact of 5-HTTLPR, antidepressants, and acute tryptophan depletion on brain activation during facial emotion processing: A review of the imaging literature.

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    Raab, Kyeon; Kirsch, Peter; Mier, Daniela

    2016-12-01

    Detecting and evaluating emotional information from facial expressions as a basis for behavioural adaption belong to the core social-cognitive abilities of mankind. Dysfunctions in emotional face processing are observed in several major psychiatric disorders like depression and schizophrenia. In search for psychiatric disease biomarkers using the imaging genetics approach, serotonergic gene polymorphisms have been associated with altered brain circuit activation during emotional face processing. Especially the 5-HTTLPR gene polymorphism has been extensively investigated in association with emotion regulation processes. In this article, imaging genetics literature on emotional face processing, reporting genetic effects of 5-HTTLPR in healthy volunteers is reviewed. Additionally, these results are regarded in relation to pharmacologic challenge (antidepressants, acute tryptophan depletion) imaging studies and discussed in light of recent neurobiological evidence with a focus on serotonin (5-HT1A, 5-HT2C, 5-HT2A) receptor findings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Serotonergic function, substance craving, and psychopathology in detoxified alcohol-addicted males undergoing tryptophan depletion.

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    Wedekind, Dirk; Herchenhein, Thomas; Kirchhainer, Julia; Bandelow, Borwin; Falkai, Peter; Engel, Kirsten; Malchow, Berend; Havemann-Reinecke, Ursula

    2010-12-01

    Alcohol addiction is associated with alterations of central nervous dopaminergic and serotonergic functions. Acute tryptophan depletion has not yet been applied in detoxified alcohol-addicted patients in order to investigate its impact on psychopathology, psychoneuroendocrinology, and substance craving behaviour. 25 alcohol-addicted males randomly either received a tryptophan-free or tryptophan-containing amino acid drink and 7 days later the respective other drink. Anxiety, depression, and craving were assessed before and 5 h after the drink. Tryptophan, 5-HIAA, dopamine, norepinephrine, epinephrine, and HVA in serum were measured before and after both treatments. Nocturnal urinary cortisol measurements and genotyping for the HTTLPR polymorphism of the SLC6A4 gene were performed. Tryptophan depletion resulted in a significant reduction of total and free serum tryptophan while the tryptophan-rich drink increased serum levels. Both treatments caused a significant increase of serum serotonin levels, however, serum 5-HIAA was decreased after depletion but increased after sham depletion. Dopamine and norepinephrine were elevated after tryptophan depletion and sham. Depletion increased depression scores (MADRS), while the full amino acid drink improved state and trait anxiety ratings (STAI) and substance craving. Urinary cortisol excretion was not affected by both treatments. Patients with the ll genotype of the serotonin transporter gene displayed lower baseline tryptophan levels compared to patients with the heterozygous genotype. Results suggest an impaired serotonergic function in alcohol-addicted males.

  14. Specificity of the Acute Tryptophan and Tyrosine Plus Phenylalanine Depletion and Loading Tests Part II: Normalisation of the Tryptophan and the Tyrosine Plus Phenylalanine to Competing Amino Acid Ratios in a New Control Formulation

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    Abdulla A.-B. Badawy

    2010-06-01

    Full Text Available Current formulations for acute tryptophan (Trp or tyrosine (Tyr plus phenylalanine (Phe depletion and loading cause undesirable decreases in ratios of Trp or Tyr + Phe to competing amino acids (CAA, thus undermining the specificities of these tests. Branched-chain amino acids (BCAA cause these unintended decreases, and lowering their content in a new balanced control formulation in the present study led to normalization of all ratios. Four groups (n = 12 each of adults each received one of four 50 g control formulations, with 0% (traditional, 20%, 30%, or 40% less of the BCAA. The free and total [Trp]/[CAA] and [Phe + Tyr]/[BCAA + Trp] ratios all decreased significantly during the first 5 h following the traditional formulation, but were fully normalized by the formulation containing 40% less of the BCAA. We recommend the latter as a balanced control formulation and propose adjustments in the depletion and loading formulations to enhance their specificities for 5-HT and the catecholamines.

  15. The effects of acute tryptophan depletion on reactive aggression in adults with attention-deficit/hyperactivity disorder (ADHD and healthy controls.

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    Marco Zimmermann

    Full Text Available BACKGROUND: The neurotransmitter serotonin (5-HT has been linked to the underlying neurobiology of aggressive behavior, particularly with evidence from studies in animals and humans. However, the underlying neurobiology of aggression remains unclear in the context of attention-deficit/hyperactivity disorder (ADHD, a disorder known to be associated with aggression and impulsivity. We investigated the effects of acute tryptophan depletion (ATD, and the resulting diminished central nervous serotonergic neurotransmission, on reactive aggression in healthy controls and adults with ADHD. METHODOLOGY/PRINCIPAL FINDINGS: Twenty male patients with ADHD and twenty healthy male controls were subjected to ATD with an amino acid (AA beverage that lacked tryptophan (TRP, the physiological precursor of 5-HT and a TRP-balanced AA beverage (BAL in a double-blind, within-subject crossover-study over two study days. We assessed reactive aggression 3.25 hours after ATD/BAL intake using a point-subtraction aggression game (PSAG in which participants played for points against a fictitious opponent. Point subtraction was taken as a measure for reactive aggression. Lowered rates of reactive aggression were found in the ADHD group under ATD after low provocation (LP, with controls showing the opposite effect. In patients with ADHD, trait-impulsivity was negatively correlated with the ATD effect on reactive aggression after LP. Statistical power was limited due to large standard deviations observed in the data on point subtraction, which may limit the use of this particular paradigm in adults with ADHD. CONCLUSIONS/SIGNIFICANCE: Together with previous findings, the data provide preliminary evidence of an inverse association between trait-impulsivity and the ATD effect on reactive aggression after LP (as assessed by the PSAG in patients with ADHD and that this relationship can be found in both adolescents and adults. Because of limited statistical power larger sample

  16. Effects of acute tryptophan depletion on brain serotonin function and concentrations of dopamine and norepinephrine in C57BL/6J and BALB/cJ mice.

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    Caroline Sarah Biskup

    Full Text Available Acute tryptophan depletion (ATD is a method of lowering brain serotonin (5-HT. Administration of large neutral amino acids (LNAA limits the transport of endogenous tryptophan (TRP across the blood brain barrier by competition with other LNAAs and subsequently decreases serotonergic neurotransmission. A recent discussion on the specificity and efficacy of the ATD paradigm for inhibition of central nervous 5-HT has arisen. Moreover, side effects such as vomiting and nausea after intake of amino acids (AA still limit its use. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols. It has been used in preliminary clinical studies but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model. We tested ATD Moja-De (TRP- in two strains of mice: C57BL/6J, and BALB/cJ, which are reported to have impaired 5-HT synthesis and a more anxious phenotype relative to other strains of mice. ATD Moja-De lowered brain TRP, significantly decreased 5-HT synthesis as indexed by 5-HTP levels after decarboxlyase inhibition, and lowered 5-HT and 5-HIAA in both strains of mice, however more so in C57BL/6J than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A balanced (TRP+ control mixture did not raise 5-HT or 5-HIAA. The present findings suggest that ATD Moja-De effectively and specifically suppresses central serotonergic function. These results also demonstrate a strain-specific effect of ATD Moja-De on anxiety-like behavior.

  17. Effects of Acute Tryptophan Depletion on Brain Serotonin Function and Concentrations of Dopamine and Norepinephrine in C57BL/6J and BALB/cJ Mice

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    Biskup, Caroline Sarah; Sánchez, Cristina L.; Arrant, Andrew; Van Swearingen, Amanda E. D.; Kuhn, Cynthia; Zepf, Florian Daniel

    2012-01-01

    Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT). Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the blood brain barrier by competition with other LNAAs and subsequently decreases serotonergic neurotransmission. A recent discussion on the specificity and efficacy of the ATD paradigm for inhibition of central nervous 5-HT has arisen. Moreover, side effects such as vomiting and nausea after intake of amino acids (AA) still limit its use. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols. It has been used in preliminary clinical studies but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model. We tested ATD Moja-De (TRP−) in two strains of mice: C57BL/6J, and BALB/cJ, which are reported to have impaired 5-HT synthesis and a more anxious phenotype relative to other strains of mice. ATD Moja-De lowered brain TRP, significantly decreased 5-HT synthesis as indexed by 5-HTP levels after decarboxlyase inhibition, and lowered 5-HT and 5-HIAA in both strains of mice, however more so in C57BL/6J than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A balanced (TRP+) control mixture did not raise 5-HT or 5-HIAA. The present findings suggest that ATD Moja-De effectively and specifically suppresses central serotonergic function. These results also demonstrate a strain- specific effect of ATD Moja-De on anxiety-like behavior. PMID:22629305

  18. L-Tryptophan depletion bioreactor, a possible cancer therapy

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    Rolf Bambauer

    2015-04-01

    Full Text Available The cancer therapeutic strategies knownto date are not adequate for all cancer patients. Most of them are followed by a high rate of side effects and complications. The L-tryptophan depletion bioreactor is described as a possible new method of cancer therapy. L-tryptophan is an essential amino acid which has been recognized as an important cancer nutrient and its removal can lead to destruction of the tumour. Normal human cells or tumor cells cannot synthesize L-tryptophan and therefore tumor resistance is unlikely to develop. L-tryptophan is also a constituent for different bio-molecules such as Serotonin, Melatonin, and is needed for other synthesis processes in the cell growth. L-tryptophan degrading enzymes with 3 iso-enzymes called tryptophan side chain oxydase (TSO I, II, III were isolated. The 3 iso-enzymes can be differentiated by tryptic digestion. They have different molecular weights with different effectivenesses. All the TSO enzymes have heme that can catalyze essentially similar reactions involving L-tryptophan as a substrate. The most effective TSO is the type TSO III. A column which contained TSO as a bioreactor was integrated in a plasmapheresis unit and tested it in different animals. In sheep and rabbits L-tryptophan depletion in plasma was shown at 95% and 100% rates respectively by a single pass through the bioreactor. The results in immune supprimized rats with tumors were impressive, too. In 20 different tumor cell lines there were different efficacies. Brest cancer and medulloblastoma showed the greatest efficacy of L-tryptophan degrading. The gene technology of TSO production from Pseudomonas is associated with formation of endotoxins. This disadvantage can be prevented by different washing procedures or by using fungal sources for the TSO production. TSO III is developed to treat cancer diseases successfully, and has low side effects. A combination of L-tryptophan depletion with all available cancer therapies is

  19. The effects of tryptophan depletion on impulsivity and mood in healthy men and women

    OpenAIRE

    Walderhaug, Espen

    2007-01-01

    Reduced serotonergic neurotransmission contributes to the pathophysiology of mood disorders, and the majority of modern antidepressants block the serotonin reuptake in the brain. It is also known that people with major depressive disorder are frequently found to have impaired impulse control, and that impulsivity is associated with serotonin. In two separate studies with healthy participants using different designs and a technique called acute tryptophan depletion, which decreases seroton...

  20. Serotonin 2A Receptors, Citalopram and Tryptophan-Depletion

    DEFF Research Database (Denmark)

    Macoveanu, Julian; Hornboll, Bettina; Elliott, Rebecca;

    2013-01-01

    in serotonergic regulation of response inhibition. In 24 healthy adults, we used (18)F-altanserin positron emission tomography to assess cerebral 5-HT(2A) receptors, which have been related to impulsivity. We then investigated the impact of two acute manipulations of brain serotonin levels on behavioral...

  1. Effects of dietary tryptophan and phenylalanine–tyrosine depletion on phasic alertness in healthy adults – A pilot study

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    Hildebrand, Patricia; Königschulte, Werner; Gaber, Tilman Jakob; Bubenzer-Busch, Sarah; Helmbold, Katrin; Biskup, Caroline Sarah; Langen, Karl-Josef; Fink, Gereon Rudolf; Zepf, Florian Daniel

    2015-01-01

    Background The synthesis of the neurotransmitters serotonin (5-HT) and dopamine (DA) in the brain can be directly altered by dietary manipulation of their relevant precursor amino acids (AA). There is evidence that altered serotonergic and dopaminergic neurotransmission are both associated with impaired attentional control. Specifically, phasic alertness is one specific aspect of attention that has been linked to changes in 5-HT and DA availability in different neurocircuitries related to attentional processes. The present study investigated the impact of short-term reductions in central nervous system 5-HT and DA synthesis, which was achieved by dietary depletion of the relevant precursor AA, on phasic alertness in healthy adult volunteers; body weight–adapted dietary tryptophan and phenylalanine–tyrosine depletion (PTD) techniques were used. Methods The study employed a double-blind between-subject design. Fifty healthy male and female subjects were allocated to three groups in a randomized and counterbalanced manner and received three different dietary challenge conditions: acute tryptophan depletion (ATD, for the depletion of 5-HT; N=16), PTD (for the depletion of DA; N=17), and a balanced AA load (BAL; N=17), which served as a control condition. Three hours after challenge intake (ATD/PTD/BAL), phasic alertness was assessed using a standardized test battery for attentional performance (TAP). Blood samples for AA level analyses were obtained at baseline and 360 min after the challenge intake. Results Overall, there were no significant differences in phasic alertness for the different challenge conditions. Regarding PTD administration, a positive correlation between the reaction times and the DA-related depletion magnitude was detected via the lower plasma tyrosine levels and the slow reaction times of the first run of the task. In contrast, higher tryptophan concentrations were associated with slower reaction times in the fourth run of the task in the same

  2. Effects of dietary tryptophan and phenylalanine–tyrosine depletion on phasic alertness in healthy adults – A pilot study

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    Patricia Hildebrand

    2015-04-01

    Full Text Available Background: The synthesis of the neurotransmitters serotonin (5-HT and dopamine (DA in the brain can be directly altered by dietary manipulation of their relevant precursor amino acids (AA. There is evidence that altered serotonergic and dopaminergic neurotransmission are both associated with impaired attentional control. Specifically, phasic alertness is one specific aspect of attention that has been linked to changes in 5-HT and DA availability in different neurocircuitries related to attentional processes. The present study investigated the impact of short-term reductions in central nervous system 5-HT and DA synthesis, which was achieved by dietary depletion of the relevant precursor AA, on phasic alertness in healthy adult volunteers; body weight–adapted dietary tryptophan and phenylalanine–tyrosine depletion (PTD techniques were used. Methods: The study employed a double-blind between-subject design. Fifty healthy male and female subjects were allocated to three groups in a randomized and counterbalanced manner and received three different dietary challenge conditions: acute tryptophan depletion (ATD, for the depletion of 5-HT; N=16, PTD (for the depletion of DA; N=17, and a balanced AA load (BAL; N=17, which served as a control condition. Three hours after challenge intake (ATD/PTD/BAL, phasic alertness was assessed using a standardized test battery for attentional performance (TAP. Blood samples for AA level analyses were obtained at baseline and 360 min after the challenge intake. Results: Overall, there were no significant differences in phasic alertness for the different challenge conditions. Regarding PTD administration, a positive correlation between the reaction times and the DA-related depletion magnitude was detected via the lower plasma tyrosine levels and the slow reaction times of the first run of the task. In contrast, higher tryptophan concentrations were associated with slower reaction times in the fourth run of the

  3. Standardization of formulations for the acute amino acid depletion and loading tests.

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    Badawy, Abdulla A-B; Dougherty, Donald M

    2015-04-01

    The acute tryptophan depletion and loading and the acute tyrosine plus phenylalanine depletion tests are powerful tools for studying the roles of cerebral monoamines in behaviour and symptoms related to various disorders. The tests use either amino acid mixtures or proteins. Current amino acid mixtures lack specificity in humans, but not in rodents, because of the faster disposal of branched-chain amino acids (BCAAs) by the latter. The high content of BCAA (30-60%) is responsible for the poor specificity in humans and we recommend, in a 50g dose, a control formulation with a lowered BCAA content (18%) as a common control for the above tests. With protein-based formulations, α-lactalbumin is specific for acute tryptophan loading, whereas gelatine is only partially effective for acute tryptophan depletion. We recommend the use of the whey protein fraction glycomacropeptide as an alternative protein. Its BCAA content is ideal for specificity and the absence of tryptophan, tyrosine and phenylalanine render it suitable as a template for seven formulations (separate and combined depletion or loading and a truly balanced control). We invite the research community to participate in standardization of the depletion and loading methodologies by using our recommended amino acid formulation and developing those based on glycomacropeptide.

  4. Acute serotonin depletion releases motivated inhibition of response vigour.

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    den Ouden, Hanneke E M; Swart, Jennifer C; Schmidt, Kristin; Fekkes, Durk; Geurts, Dirk E M; Cools, Roshan

    2015-04-01

    The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas, however, has been mixed. In the current study, we aimed to investigate the role of serotonin (5HT) in behavioural vigour as a function of incentive motivation. We employed dietary acute tryptophan depletion (ATD) to lower the 5HT precursor tryptophan during the performance of a speeded visual discrimination task. Feedback valence and feedback probability were manipulated independently and cued prior to target onset. On feedback trials, fast correct responses led to either reward or avoidance of punishment, while slow or incorrect responses led to reward omission or punishment. We show that behavioural responding is inhibited under high incentive motivation (i.e. high-feedback probability) at baseline 5HT levels and that lowering these leads to behavioural disinhibition, while leaving accuracy unaffected. Surprisingly, there were no differential effects of motivational valence, with 5HT depletion releasing behavioural inhibition under both appetitive and aversive motivation. Our findings extend current theories on the role of 5HT in behavioural inhibition by showing that reductions in serotonin lead to increased behavioural vigour only if there is a motivational drive to inhibit behaviour at baseline.

  5. Dietary tryptophan depletion in humans using a simplified two amino acid formula – a pilot study

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    Maike Linden

    2016-12-01

    Full Text Available Background: Acute tryptophan depletion (ATD is a well-established dietary method in translational brain research used to briefly lower central nervous serotonin (5-hydroxytryptamine (5-HT synthesis. A simplified two amino acid ATD formula (ATDPHE/LEU was developed while reducing the overall amount of amino acids (AAs, with the objective of administration especially in children and adolescents in future studies. Objective: This study investigated tryptophan (TRP influx rates across the blood-brain barrier (BBB after dietary ATDPHE/LEU administration relative to the ATD Moja-De protocol that has been established for use in children and adolescents. Design: Seventy-two healthy adults (50% females were randomized into four groups and administered ATD Moja-De, its TRP-balanced control condition (BAL, ATDPHE/LEU, or its respective control mixture (BALPHE/LEU in a counterbalanced, double-blind, between-subjects design. Blood samples were collected at baseline and at hourly intervals for 6 h after AA intake. Questionnaires about mood, taste, and challenge tolerance were completed at fixed time points. Results: Both challenge mixtures significantly reduced central nervous TRP influx as calculated by Michaelis–Menten kinetics relative to baseline and the respective control conditions with only mild and comparable side effects. A greater decline in TRP influx over the BBB after ATDPHE/LEU administration when compared with ATD Moja-De was detected without group effects for taste, challenge tolerance, and mood. There was unintended initial short increase in plasma TRP concentrations observed after ATDPHE/LEU intake, and a possible redistribution between free and protein-bound TRP triggered by protein synthesis stimulated by the ingested AAs may account for this finding. Moreover, a decline in TRP influx after BALPHE/LEU administration over a 6-h period was observed, and the large amount of PHE in the BALPHE/LEU mixture may be a possible explanation for

  6. In vitro rescue of genital strains of Chlamydia trachomatis from interferon-γ and tryptophan depletion with indole-positive, but not indole-negative Prevotella spp.

    Science.gov (United States)

    Ziklo, Noa; Huston, Wilhelmina M; Taing, Kuong; Katouli, Mohammad; Timms, Peter

    2016-12-03

    The natural course of sexually transmitted infections caused by Chlamydia trachomatis varies between individuals. In addition to parasite and host effects, the vaginal microbiota might play a key role in the outcome of C. trachomatis infections. Interferon-gamma (IFN-γ), known for its anti-chlamydial properties, activates the expression of indoleamine 2,3-dioxygenase (IDO1) in epithelial cells, an enzyme that catabolizes the amino acid L- tryptophan into N-formylkynurenine, depleting the host cell's pool of tryptophan. Although C. trachomatis is a tryptophan auxotroph, urogenital strains (but not ocular strains) have been shown in vitro to have the ability to produce tryptophan from indole using the tryptophan synthase (trpBA) gene. It has been suggested that indole producing bacteria from the vaginal microbiota could influence the outcome of Chlamydia infection. We used two in vitro models (treatment with IFN-γ or direct limitation of tryptophan), to study the effects of direct rescue by the addition of exogenous indole, or by the addition of culture supernatant from indole-positive versus indole-negative Prevotella strains, on the growth and infectivity of C. trachomatis. We found that only supernatants from the indole-positive strains, P. intermedia and P. nigrescens, were able to rescue tryptophan-starved C. trachomatis. In addition, we analyzed vaginal secretion samples to determine physiological indole concentrations. In spite of the complexity of vaginal secretions, we demonstrated that for some vaginal specimens with higher indole levels, there was a link to higher recovery of the Chlamydia under tryptophan-starved conditions, lending preliminary support to the critical role of the IFN-γ-tryptophan-indole axis in vivo. Our data provide evidence for the ability of both exogenous indole as well as supernatant from indole producing bacteria such as Prevotella, to rescue genital C. trachomatis from tryptophan starvation. This adds weight to the hypothesis

  7. Intake of tryptophan-enriched whey protein acutely enhances recall of positive loaded words in patients with multiple sclerosis

    NARCIS (Netherlands)

    Lieben, Cindy K; Blokland, Arjan; Deutz, Nicolaas E; Jansen, Willemijn; Han, Gang; Hupperts, Raymond M

    2017-01-01

    BACKGROUND & AIMS: Multiple sclerosis (MS) has physiological and/or immunological characteristics that diminish serotonin metabolism, a neurotransmitter associated with affective and cognitive functions. The aim was examine the acute and dose-dependent effects of a dietary tryptophan (TRP) enrichmen

  8. The Association between Baseline Subjective Anxiety Rating and Changes in Cardiac Autonomic Nervous Activity in Response to Tryptophan Depletion in Healthy Volunteers.

    Science.gov (United States)

    Hsiao, Chih Yin; Tsai, Hsin Chun; Chi, Mei Hung; Chen, Kao Chin; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang

    2016-05-01

    The aim of this study was to investigate the influence of serotonin on anxiety and autonomic nervous system (ANS) function; the correlation between subjective anxiety rating and changes of ANS function following tryptophan depletion (TD) in healthy volunteers was examined. Twenty-eight healthy participants, consisting of 15 females and 13 males, with an average age of 33.3 years, were recruited.Baseline Chinese Symptom Checklist-90-Revised and ANS function measurements were taken. TD was carried out on the testing day, and participants provided blood samples right before and 5 hours after TD. ANS function, somatic symptoms, and Visual Analogue Scales (VASs) were determined after TD. Wilcoxon signed rank test and Spearman ρ correlation were adapted for analyses of the results.The TD procedure reduced total and free plasma tryptophan effectively. After TD, the sympathetic nervous activity increased and parasympathetic nervous activity decreased. Baseline anxiety ratings positively correlated with post-TD changes in sympathetic nervous activity, VAS ratings, and physical symptoms. However, a negative correlation with post-TD changes in parasympathetic nervous activity was found.The change in ANS function after TD was associated with the severity of anxiety in healthy volunteers. This supports the fact that the effect of anxiety on heart rate variability is related to serotonin vulnerability. Furthermore, it also shows that the subjective anxiety rating has a biological basis related to serotonin.

  9. Acute hyponatremia after cardioplegia by histidine-tryptophane-ketoglutarate – a retrospective study

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    Lindner Gregor

    2012-06-01

    Full Text Available Abstract Background Hyponatremia is the most common electrolyte disorder in hospitalized patients and is known to be associated with increased mortality. The administration of antegrade single-shot, up to two liters, histidine-tryptophane-ketoglutarate (HTK solution for adequate electromechanical cardiac arrest and myocardial preservation during minimally invasive aortic valve replacement (MIAVR is a standard procedure. We aimed to determine the impact of HTK infusion on electrolyte and acid–base balance. Methods In this retrospective analysis we reviewed data on patient characteristics, type of surgery, arterial blood gas analysis during surgery and intra-/postoperative laboratory results of patients receiving surgery for MIAVR at a large tertiary care university hospital. Results A total of 25 patients were included in the study. All patients were normonatremic at start of surgery. All patients developed hyponatremia after administration of HTK solution with a significant drop of serum sodium of 15 mmol/L (p  Conclusions Acute hyponatremia during cardioplegia with HTK solution is isotonic and should probably not be corrected without presence of hypotonicity as confirmed by measurement of serum osmolality.

  10. Serotonin and cognitive flexibility: Neuroimaging studies into the effect of acute tryptophan depletion in heathy volunteers

    NARCIS (Netherlands)

    E.A.T. Evers (Elisabeth); F.M. van der Veen (Frederik); D. Fekkes (Durk); J. Jolles (Jellemer)

    2007-01-01

    textabstractCognitive flexibility is the ability to adjust behavior to changes in the environment or task conditions. Previous research suggested that serotonin (5-HT) is involved in cognitive flexibility. Disturbed 5-HT functioning in animals, psychiatric patients and healthy volunteers leads to mo

  11. Serotonin and cognitive flexibility: Neuroimaging studies into the effect of acute tryptophan depletion in heathy volunteers

    NARCIS (Netherlands)

    E.A.T. Evers (Elisabeth); F.M. van der Veen (Frederik); D. Fekkes (Durk); J. Jolles (Jellemer)

    2007-01-01

    textabstractCognitive flexibility is the ability to adjust behavior to changes in the environment or task conditions. Previous research suggested that serotonin (5-HT) is involved in cognitive flexibility. Disturbed 5-HT functioning in animals, psychiatric patients and healthy volunteers leads to

  12. Tryptophan-free diet: a new means for rapidly decreasing brain tryptophan content and serotonin synthesis.

    Science.gov (United States)

    Gessa, G L; Biggio, G; Fadda, F; Corsini, G U; Tagliamonte, A

    1975-01-01

    Changes in the synthesis rate of brain serotonin are positively correlated with changes in the concentration of brain tryptophan, indicating that the concentration of tryptophan in the whole brain reflects that at sites of serotonin synthesis. In turn, the concentration of brain tryptophan is positively correlated with that of free serum tryptophan (tryptophan is the only amino acid bound to serum proteins) and negatively to that of other amino acids competing with tryptophan for the same transport from blood to brain. Consistently, experiments in rats have shown that treatments which increase free tryptophan in serum (in respect to competing amino acids) also increase brain tryptophan and serotonin turnover. Conversely, the ingestion of diets containing all amino acids except tryptophan cause a dramatic fall in free serum tryptophan and a parallel decline in brain tryptophan and serotonin synthesis. In man the administration of an amino acid mixture lacking trytophan produces a marked depletion in serum tryptophan concentration.

  13. Depletion of mucosal substance P in acute otitis media

    DEFF Research Database (Denmark)

    Cayé-Thomasen, Per; Schmidt, Peter Thelin; Hermansson, Ann

    2004-01-01

    OBJECTIVE: The neuropeptide substance P (SP) is an inducer of neurogenic inflammation and bone resorption in the middle ear. Resorption of the bone tissue structures surrounding the middle ear cavity is a distinct feature of the initial stage of acute otitis media (AOM), which may be due to nerve...

  14. The effects of acute tryptophan depletion on speech and behavioural mimicry in individuals at familial risk for depression

    NARCIS (Netherlands)

    Hogenelst, K.; Sarampalis, A.; Leander, N.P.; Müller, B.C.N.; Schoevers, R.A.; Rot, M. aan het

    2016-01-01

    Major depressive disorder (MDD) has been associated with abnormalities in speech and behavioural mimicry. These abnormalities may contribute to the impairments in interpersonal functioning that are often seen in MDD patients. MDD has also been associated with disturbances in the brain serotonin syst

  15. The effects of acute tryptophan depletion on speech and behavioural mimicry in individuals at familial risk for depression

    NARCIS (Netherlands)

    Hogenelst, Koen; Sarampalis, Anastasios; Leander, N. Pontus; Müller, Barbara C.N.; Schoevers, Robert A.; aan het Rot, Marije

    2016-01-01

    Major depressive disorder (MDD) has been associated with abnormalities in speech and behavioural mimicry. These abnormalities may contribute to the impairments in interpersonal functioning that are often seen in MDD patients. MDD has also been associated with disturbances in the brain serotonin syst

  16. Acute MUS81 depletion leads to replication fork slowing and a constitutive DNA damage response

    DEFF Research Database (Denmark)

    Xing, Meichun; Wang, Xiaohui; Palmai-Pallag, Timea;

    2015-01-01

    The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We...... have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found that MUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damage response that ultimately activates cellular senescence. Moreover, we show that MUS81...... is required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replication following replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity....

  17. Age moderates the effect of acute dopamine depletion on passive avoidance learning.

    Science.gov (United States)

    Kelm, Mary Katherine; Boettiger, Charlotte Ann

    2015-04-01

    Despite extensive links between reinforcement-based learning and dopamine (DA), studies to date have not found consistent effects of acute DA reduction on reinforcement learning in both men and women. Here, we tested the effects of reducing DA on reward- and punishment-based learning using the deterministic passive avoidance learning (PAL) task. We tested 16 (5 female) adults (ages 22-40) in a randomized, cross-over design to determine whether reducing global DA by administering an amino acid beverage deficient in the DA precursors, phenylalanine and tyrosine (P/T[-]), would affect PAL task performance. We found that P/T[-] beverage effects on PAL performance were modulated by age. Specifically, we found that P/T depletion significantly improved learning from punishment with increasing participant age. Participants committed 1.49 fewer passive avoidance errors per additional year of age (95% CI, -0.71 - -2.27, r=-0.74, p=0.001). Moreover, P/T depletion improved learning from punishment in adults (ages 26-40) while it impaired learning from punishment in emerging adults (ages 22-25). We observed similar, but non-significant trends in learning from reward. While there was no overall effect of P/T-depletion on reaction time (RT), there was a relationship between the effect of P/T depletion on PAL performance and RT; those who responded more slowly on the P/T[-] beverage also made more errors on the P/T[-] beverage. When P/T-depletion slowed RT after a correct response, there was a worsening of PAL task performance; there was no similar relationship for the RT after an incorrect response and PAL task performance. Moreover, among emerging adults, changes in mood on the P/T[-] beverage negatively correlated with learning from reward on the P/T[-] beverage. Together, we found that both reward- and punishment-based learning are sensitive to central catecholamine levels, and that these effects of acute DA reduction vary with age. Copyright © 2015 Elsevier Inc. All rights

  18. Chlamydia Exploit the Mammalian Tryptophan-Depletion Defense Strategy as a Counter-Defensive Cue to Trigger a Survival State of Persistence.

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    Carol A Bonner

    2014-02-01

    Full Text Available We previously proposed that in Chlamydiaceae rapid vegetative growth and a quiescent state of survival (persistence depend upon alternative protein translational profiles dictated by host tryptophan (Trp availability. These alternative profiles correspond, respectively, with a set of chlamydial proteins having higher-than-predicted contents of Trp (Up-Trp selection, or with another set exhibiting lower-than-predicted contents of Trp (Down-Trp selection. A comparative evaluation of Chlamydiaceae proteomes for Trp content has now been extended to a number of other taxon families within the Chlamydiales Order. At the Order level, elevated Trp content occurs for transporters of nucleotides, S-adenosylmethionine, dicarboxylate substrates, and Trp itself. For Trp and nucleotide transporters, this is even more pronounced in other chlamydiae families (Parachlamydiaceae, Waddliaceae, and Simkaniaceae due to extensive paralog expansion. This suggests that intracellular Trp availability served as an ancient survival cue for enhancement or restraint of chlamydial metabolism in the common Chlamydiales ancestor. The Chlamydiaceae Family further strengthened Up-Trp selection for proteins that function in cell division, lipopolysaccharide biosynthesis, and methyltransferase reactions. Some proteins that exhibit Up-Trp selection are uniquely present in the Chlamydiaceae, e.g., cytotoxin and the paralog families of polymorphic membrane proteins. A striking instance of Down-Trp selection in the Chlamydiaceae is the chorismate biosynthesis pathway and the connecting menaquinone pathway. The newly recognized 1,4-dihydroxy-6-napthoate pathway of menaquinone biosynthesis operates in Chlamydiaceae, whereas the classic 2-napthoate pathway is used in the other Chlamydiales families. Because of the extreme Down-Trp selection, it would appear that menaquinone biosynthesis is particularly important to the integrity of the persistent state maintained under conditions of

  19. Dopamine and food reward: effects of acute tyrosine/phenylalanine depletion on appetite.

    Science.gov (United States)

    Hardman, Charlotte A; Herbert, Vanessa M B; Brunstrom, Jeffrey M; Munafò, Marcus R; Rogers, Peter J

    2012-03-20

    It has been suggested that obese individuals over-eat in order to compensate for deficits in the dopaminergic reward system. The current study used acute tyrosine/phenylalanine depletion (ATPD) to investigate the effect of reduced dopamine function on appetite and the reward value of food in healthy volunteers. The compensatory-eating hypothesis would predict an increase in the reward value and consumption of food following depletion by this method. In a double-blind, counterbalanced, crossover study, 17 male participants (mean age=29.2 (SEM=2.7) years; mean body mass index=24.4 (SEM=0.6) kg/m(2)) were administered with a tyrosine/phenylalanine-free mixture (TYR/PHE-free; depletion condition) and a balanced amino acid mixture (BAL; control). Plasma amino acid levels were measured at baseline and peak depletion (300 min). Appetite, willingness to pay for food, liking, desired portion size and ad libitum food intake were also assessed. The TYR/PHE-free mixture was associated with significant decreases in tyrosine, phenylalanine, and the ratio of tyrosine+phenylalanine to the other large neutral amino acids (all p<.001). There were no effects on our measures of willingness to pay for food or liking. However, in the TYR/PHE-free condition, participants reported significantly lower levels of hunger following a fixed-test meal relative to the BAL condition. In conclusion, we found no evidence for compensatory eating following ATPD. Our results also provide support for the role of dopamine in motivational components of eating.

  20. RNAi mediated acute depletion of Retinoblastoma protein (pRb promotes aneuploidy in human primary cells via micronuclei formation

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    Iovino Flora

    2009-11-01

    Full Text Available Abstract Background Changes in chromosome number or structure as well as supernumerary centrosomes and multipolar mitoses are commonly observed in human tumors. Thus, centrosome amplification and mitotic checkpoint dysfunctions are believed possible causes of chromosomal instability. The Retinoblastoma tumor suppressor (RB participates in the regulation of synchrony between DNA synthesis and centrosome duplication and it is involved in transcription regulation of some mitotic genes. Primary human fibroblasts were transfected transiently with short interfering RNA (siRNA specific for human pRb to investigate the effects of pRb acute loss on chromosomal stability. Results Acutely pRb-depleted fibroblasts showed altered expression of genes necessary for cell cycle progression, centrosome homeostasis, kinetochore and mitotic checkpoint proteins. Despite altered expression of genes involved in the Spindle Assembly Checkpoint (SAC the checkpoint seemed to function properly in pRb-depleted fibroblasts. In particular AURORA-A and PLK1 overexpression suggested that these two genes might have a role in the observed genomic instability. However, when they were post-transcriptionally silenced in pRb-depleted fibroblasts we did not observe reduction in the number of aneuploid cells. This finding suggests that overexpression of these two genes did not contribute to genomic instability triggered by RB acute loss although it affected cell proliferation. Acutely pRb-depleted human fibroblasts showed the presence of micronuclei containing whole chromosomes besides the presence of supernumerary centrosomes and aneuploidy. Conclusion Here we show for the first time that RB acute loss triggers centrosome amplification and aneuploidy in human primary fibroblasts. Altogether, our results suggest that pRb-depleted primary human fibroblasts possess an intact spindle checkpoint and that micronuclei, likely caused by mis-attached kinetochores that in turn trigger

  1. Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-Infection in the Absence of Viral Suppression

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N.; Kazer, Samuel W.; Mjösberg, Jenny

    2016-01-01

    Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-on ILCs remains unknown. We found that human blood...... ILCs were severely depleted during acute viremic HIV-infection and that ILC numbers did not recover after resolution of peak viremia. ILC numbers were preserved by antiretroviral therapy (ART), but only if initiated during acute infection. Transcriptional profiling during the acute phase revealed...... mechanistic link between acute HIV-infection, lymphoid tissue breakdown, and persistent immune dysfunction....

  2. The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa.

    Science.gov (United States)

    O'Hara, Caitlin B; Keyes, Alexandra; Renwick, Bethany; Leyton, Marco; Campbell, Iain C; Schmidt, Ulrike

    2016-01-01

    This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN), specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15) were recruited. The acute phenylalanine/tyrosine depletion (APTD) method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressive ratio (PR) exercise breakpoint task. Both groups worked for the opportunity to exercise, and, at baseline, PR breakpoint scores were higher in AN REC than HC. Compared to values on the experimental control session, APTD did not decrease PR breakpoint scores in AN REC, but significantly decreased scores in HC. These data show that women recovered from AN are more motivated to exercise than HC, although in both groups, activity is more reinforcing than inactivity. Importantly, decreasing dopamine does not reduce the motivation to exercise in people recovered from AN, but in contrast, does so in HC. It is proposed that in AN, drive to exercise develops into a behaviour that is largely independent of dopamine mediated reward processes and becomes dependent on cortico-striatal neurocircuitry that regulates automated, habit- or compulsive-like behaviours. These data strengthen the case for the involvement of reward, learning, habit, and dopaminergic systems in the aetiology of AN.

  3. The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa.

    Directory of Open Access Journals (Sweden)

    Caitlin B O'Hara

    Full Text Available This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN, specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17 and healthy controls (HC, n = 15 were recruited. The acute phenylalanine/tyrosine depletion (APTD method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressive ratio (PR exercise breakpoint task. Both groups worked for the opportunity to exercise, and, at baseline, PR breakpoint scores were higher in AN REC than HC. Compared to values on the experimental control session, APTD did not decrease PR breakpoint scores in AN REC, but significantly decreased scores in HC. These data show that women recovered from AN are more motivated to exercise than HC, although in both groups, activity is more reinforcing than inactivity. Importantly, decreasing dopamine does not reduce the motivation to exercise in people recovered from AN, but in contrast, does so in HC. It is proposed that in AN, drive to exercise develops into a behaviour that is largely independent of dopamine mediated reward processes and becomes dependent on cortico-striatal neurocircuitry that regulates automated, habit- or compulsive-like behaviours. These data strengthen the case for the involvement of reward, learning, habit, and dopaminergic systems in the aetiology of AN.

  4. Role of sodium depletion in acute antidiuretic effect of bendroflumethiazide in rats with nephrogenic diabetes insipidus.

    Science.gov (United States)

    Janjua, N R; Jonassen, T E; Langhoff, S; Thomsen, K; Christensen, S

    2001-10-01

    The mechanisms underlying the acute antidiuretic response to bendroflumethiazide (BFTZ; 0.25 mg/h for 3 h) in rats with nephrogenic diabetes insipidus (NDI) was investigated. NDI was induced in conscious chronically instrumented female Wistar rats either by chronic lithium administration (40-60 mmol Li/kg of diet for 4 weeks) or by acute infusion of V2 antagonist OPC-31260 (0.2 mg/h). Renal clearance experiments were performed in conscious rats instrumented with permanent catheters. During experiments total body water content was held constant by i.v. replacement of urine production (V) with 150 mM glucose. One group in addition received i.v. replacement of urinary sodium losses. In both models of NDI, BFTZ-induced antidiuresis was associated with a decrease in the delivery of tubular fluid to the distal nephron, as measured by lithium clearance (C(Li)). Both the antidiuresis and the decrease in C(Li) could be prevented by sodium replacement. BFTZ did not affect distal water handling as measured by V/C(Li). BFTZ did not induce antidiuresis in normal rats with water diuresis. It is concluded that in rats with NDI, thiazide-induced antidiuresis can be entirely explained by a fall in distal delivery of tubular fluid related to sodium depletion. This contrasts the response in rats with central diabetes insipidus, where thiazides in addition increase distal water reabsorption.

  5. Depletion of CD25+ cells during acute toxoplasmosis does not significantly increase mortality in Swiss OF1 mice

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    Haroon Akbar

    2012-03-01

    Full Text Available The interleukin (IL-2R alpha chain (CD25 is expressed on regulatory T cells (Treg, which constitute more than 85% of the CD25+ T cell population in a naïve mouse. CD25 is also expressed on effector T cells in mice suffering from an acute infection by the obligate intracellular protozoan parasite, Toxoplasma gondii. Lethal toxoplasmosis is accompanied by a significant loss of Treg in mice naturally susceptible to toxoplasmosis. The present study was done to explore the role of Treg cells using an anti-CD25 antibody-mediated depletion in mice naturally resistant to toxoplasmosis. Although a significant decrease in the percentage of Treg cells was observed following anti-CD25 monoclonal antibody injections, the depletion of CD25+ cells during acute toxoplasmosis did not significantly increase the mortality of Swiss OF1 mice and no significant difference was observed in the brain parasitic load between the mice in the depleted-infected and isotype-infected groups. We found no significant difference between the titres of total IgG in the sera of the mice from the two groups in the chronic phase. However, CD25+ cells depletion was followed by significantly higher levels of IL-12 in the serum of depleted mice than in that of mice injected with the isotype control antibody.

  6. Lycopene Pretreatment Ameliorates Acute Ethanol Induced NAD+ Depletion in Human Astroglial Cells

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    Jade Guest

    2015-01-01

    Full Text Available Excessive alcohol consumption is associated with reduced brain volume and cognition. While the mechanisms by which ethanol induces these deleterious effects in vivo are varied most are associated with increased inflammatory and oxidative processes. In order to further characterise the effect of acute ethanol exposure on oxidative damage and NAD+ levels in the brain, human U251 astroglioma cells were exposed to physiologically relevant doses of ethanol (11 mM, 22 mM, 65 mM, and 100 mM for ≤ 30 minutes. Ethanol exposure resulted in a dose dependent increase in both ROS and poly(ADP-ribose polymer production. Significant decreases in total NAD(H and sirtuin 1 activity were also observed at concentrations ≥ 22 mM. Similar to U251 cells, exposure to ethanol (≥22 mM decreased levels of NAD(H in primary human astrocytes. NAD(H depletion in primary astrocytes was prevented by pretreatment with 1 μM of lycopene for 3.5 hours. Unexpectedly, in U251 cells lycopene treatment at concentrations ≥ 5 μM resulted in significant reductions in [NAD(H]. This study suggests that exposure of the brain to alcohol at commonly observed blood concentrations may cause transitory oxidative damage which may be at least partly ameliorated by lycopene.

  7. Neutrophil depletion-but not prevention of Kupffer cell activation-decreases the severity of cerulein-induced acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Catherine M Pastor; Alain Vonlaufen; Fabianna Georgi; Antoine Hadengue; Philippe Morel; Jean-Louis Frossard

    2006-01-01

    AIM: To determine whether neutrophil depletion and Kupffer cell inhibition might combine their protective effects to decrease the severity of acute pancreatitis.METHODS: Mice had cerulein administration to induce acute pancreatitis and were pretreated with either anti-mouse neutrophil serum or gadolinium chloride (GdCl3) to prevent Kupffer cell activation, or both treatments. Injury was assessed in pancreas and lungs.Myeloperoxidases (MPO) assessed neutrophil infiltration.Interleukin-6 (IL-6) and IL-10 were measured in serum,pancreas, lungs and liver.RESULTS: In mice with acute pancreatitis, neutrophil depletion reduced the severity of pancreatitis and pancreatitis-associated lung injury. Kupffer cell inactivation by GdCl3 had less protective effect, although IL-6 and IL-10 concentrations were significantly decreased. The protective treatment brought by neutrophil depletion was not enhanced by Kupffer cell inactivation and both treatments did not combine their protective effects.CONCLUSION: Our results confirm the role of activated neutrophils in aggravating organ injury in acute pancreatitis while the role of Kupffer cell activation is less obvious.

  8. CD97 antibody depletes granulocytes in mice under conditions of acute inflammation via a Fc receptor-dependent mechanism.

    Science.gov (United States)

    Veninga, Henrike; de Groot, Dorien M; McCloskey, Natalie; Owens, Bronwyn M; Dessing, Mark C; Verbeek, J Sjef; Nourshargh, Sussan; van Eenennaam, Hans; Boots, Annemieke M; Hamann, Jörg

    2011-03-01

    Antibodies to the pan-leukocyte adhesion-GPCR CD97 efficiently block neutrophil recruitment in mice, thereby reducing antibacterial host defense, inflammatory disease, and hematopoietic stem cell mobilization. Here, we investigated the working mechanism of the CD97 antibody 1B2. Applying sterile models of inflammation, intravital microscopy, and mice deficient for the CD97L CD55, the complement component C3, or the FcR common γ-chain, we show that 1B2 acts in vivo independent of ligand-binding interference by depleting PMN granulocytes in bone marrow and blood. Granulocyte depletion with 1B2 involved FcR but not complement activation and was associated with increased serum levels of TNF and other proinflammatory cytokines. Notably, depletion of granulocytes by CD97 antibody required acute inflammation, suggesting a mechanism of conditional, antibody-mediated granulocytopenia.

  9. Acute dyskerin depletion triggers cellular senescence and renders osteosarcoma cells resistant to genotoxic stress-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Ping; Mobasher, Maral E.; Alawi, Faizan, E-mail: falawi@upenn.edu

    2014-04-18

    Highlights: • Dyskerin depletion triggers cellular senescence in U2OS osteosarcoma cells. • Dyskerin-depleted cells are resistant to apoptosis induced by genotoxic stress. • Chromatin relaxation sensitizes dyskerin-depleted cells to apoptosis. - Abstract: Dyskerin is a conserved, nucleolar RNA-binding protein implicated in an increasing array of fundamental cellular processes. Germline mutation in the dyskerin gene (DKC1) is the cause of X-linked dyskeratosis congenita (DC). Conversely, wild-type dyskerin is overexpressed in sporadic cancers, and high-levels may be associated with poor prognosis. It was previously reported that acute loss of dyskerin function via siRNA-mediated depletion slowed the proliferation of transformed cell lines. However, the mechanisms remained unclear. Using human U2OS osteosarcoma cells, we show that siRNA-mediated dyskerin depletion induced cellular senescence as evidenced by proliferative arrest, senescence-associated heterochromatinization and a senescence-associated molecular profile. Senescence can render cells resistant to apoptosis. Conversely, chromatin relaxation can reverse the repressive effects of senescence-associated heterochromatinization on apoptosis. To this end, genotoxic stress-induced apoptosis was suppressed in dyskerin-depleted cells. In contrast, agents that induce chromatin relaxation, including histone deacetylase inhibitors and the DNA intercalator chloroquine, sensitized dyskerin-depleted cells to apoptosis. Dyskerin is a core component of the telomerase complex and plays an important role in telomere homeostasis. Defective telomere maintenance resulting in premature senescence is thought to primarily underlie the pathogenesis of X-linked DC. Since U2OS cells are telomerase-negative, this leads us to conclude that loss of dyskerin function can also induce cellular senescence via mechanisms independent of telomere shortening.

  10. Decrease in circulating tryptophan availability to the brain after acute ethanol consumption by normal volunteers: implications for alcohol-induced aggressive behaviour and depression.

    Science.gov (United States)

    Badawy, A A; Morgan, C J; Lovett, J W; Bradley, D M; Thomas, R

    1995-10-01

    Acute ethanol consumption by fasting male volunteers decreases circulating trytophan (Trp) concentration and availability to the brain as determined by the ratio of (Trp) to the sum of its five competitors ([Trp]/[CAA]ratio). These effects of alcohol are specific to Trp, because levels of the 5 competitors are not increased. The decrease in circulating (Trp) is not associated with altered binding to albumin and may therefore be due to enhancement of hepatic Trp pyrrolase activity. It is suggested that, under these conditions brain serotonin synthesis is likely to be impaired and that, as a consequence, a possible strong depletion of brain serotonin in susceptible individuals may induce aggressive behaviour after alcohol consumption. The possible implications of these findings in the relationship between alcohol and depression are also briefly discussed.

  11. Experimental depletion of CD8+ cells in acutely SIVagm-Infected African Green Monkeys results in increased viral replication

    Directory of Open Access Journals (Sweden)

    Apetrei Cristian

    2010-05-01

    Full Text Available Abstract Background In vivo CD8+ cell depletions in pathogenic SIV infections identified a key role for cellular immunity in controlling viral load (VL and disease progression. However, similar studies gave discordant results in chronically-infected SMs, leading some authors to propose that in natural hosts, SIV replication is independent of cellular immunity. To assess the role of cellular immune responses in the control of SIV replication in natural hosts, we investigated the impact of CD8+ cell depletion during acute SIV infection in AGMs. Results Nine AGMs were infected with SIVagm.sab and were followed up to day 225 p.i. Four were intravenously infused with the cM-T807 antibody on days 0 (50 mg/kg, 6, and 13 (10 mg/kg, respectively post infection (p.i.. CD8+ cells were depleted for up to 28 days p.i. in peripheral blood and LNs in all treated AGMs. Partial CD8+ T cell depletion occurred in the intestine. SIVagm VLs peaked at similar levels in both groups (107-108 RNA copies/ml. However, while VLs were controlled in undepleted AGMs, reaching set-point levels (104-105 RNA copies/ml by day 28 p.i., high VLs (>106 RNA copies/ml were maintained by day 21 p.i. in CD8-depleted AGMs. By day 42 p.i., VLs were comparable between the two groups. The levels of immune activation and proliferation remained elevated up to day 72 p.i. in CD8-depleted AGMs and returned to preinfection levels in controls by day 28 p.i. None of the CD8-depleted animals progressed to AIDS. Conclusion CD8+ cells are responsible for a partial control of postacute viral replication in SIVagm.sab-infected AGMs. In contrast to macaques, the SIVagm-infected AGMs are able to control viral replication after recovery of the CD8+ T cells and avoid disease progression.

  12. Acute depletion of plasma glutamine increases leucine oxidation in prednisone-treated humans.

    Science.gov (United States)

    To determine whether depletion in plasma glutamine worsens the catabolic response to corticosteroids, seven healthy volunteers received oral prednisone for 6 days on two separate occasions, at least 2 weeks apart, and in random order. On the sixth day of each treatment course, they received 5 h intr...

  13. Early acute depletion of lymphocytes in calicivirus-infected adult rabbits.

    Science.gov (United States)

    Marques, Raquel M; Costa-E-Silva, António; Aguas, Artur P; Teixeira, Luzia; Ferreira, Paula G

    2010-12-01

    Rabbit Haemorrhagic Disease (RHD) is a lethal infection caused by calicivirus that kills 90% of the infected adult rabbits within 3 days. The calicivirus replicates in the liver and causes a fulminant hepatitis. Most studies on the pathology of RHD have been focused on the fulminant liver disease. This may not be the only mechanism in the pathogenesis of RHD: calicivirus infection may also induce leukopenia in the infected adult rabbits. We show now by flow cytometry analysis that the calicivirus induces an early decrease in B and T cells, in both spleen and liver. The depletion of B and T cells was associated with apoptosis labelled by annexin V. These changes occurred in rabbits before they showed enzymatic evidence of liver damage and persisted after liver transaminase values were very high. We conclude that depletion of lymphocytes caused by the calicivirus infection precedes or attends liver damage. The relative contribution of this lymphocyte depletion for the pathogenesis of the fatal calicivirus infection of rabbits remains to be investigated.

  14. Tryptophan catabolizing enzymes – party of three

    Directory of Open Access Journals (Sweden)

    Helen J Ball

    2014-10-01

    Full Text Available Indoleamine 2,3-dioxygenase (IDO and tryptophan 2,3-dioxygenase (TDO are tryptophan-degrading enzymes that have independently evolved to catalyze the first step in tryptophan catabolism via the kynurenine pathway. The depletion of tryptophan and formation of kynurenine pathway metabolites modulates the activity of the mammalian immune, reproductive and central nervous systems. IDO and TDO enzymes can have overlapping or distinct functions depending on their expression patterns. The expression of TDO and IDO enzymes in mammals differs not only by tissue/cellular localization but also by their induction by distinct stimuli. To add to the complexity, these genes also have undergone duplications in some organisms leading to multiple isoforms of IDO or TDO. For example, many vertebrates, including all mammals, have acquired two IDO genes via gene duplication, although the IDO1-like gene has been lost in some lower vertebrate lineages. Gene duplications can allow the homologs to diverge and acquire different properties to the original gene. There is evidence for IDO enzymes having differing enzymatic characteristics, signaling properties and biological functions. This review analyses the evolutionary convergence of IDO and TDO enzymes as tryptophan-catabolizing enzymes and the divergent evolution of IDO homologs to generate an enzyme family with diverse characteristics not possessed by TDO enzymes, with an emphasis on the immune system.

  15. IL4I1 Is a Novel Regulator of M2 Macrophage Polarization That Can Inhibit T Cell Activation via L-Tryptophan and Arginine Depletion and IL-10 Production.

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    Yinpu Yue

    Full Text Available Interleukin 4-induced gene-1 (IL4I1 was initially described as an early IL-4-inducible gene in B cells. IL4I1 protein can inhibit T cell proliferation by releasing its enzymatic catabolite, H2O2, and this effect is associated with transient down-regulation of T cell CD3 receptor-zeta (TCRζ expression. Herein, we show that IL4I1 contributes to the regulation of macrophage programming. We found that expression of IL4I1 increased during bone marrow-derived macrophage (BMDM differentiation, expression of IL4I1 is much higher in primary macrophages than monocytes, and IL4I1 expression in BMDMs could be induced by Th1 and Th2 cytokines in two different patterns. Gene expression analysis revealed that overexpression of IL4I1 drove the expression of M2 markers (Fizz1, Arg1, YM-1, MR and inhibited the expression of M1-associated cytokines. Conversely, knockdown of IL4I1 by siRNA resulted in opposite effects, and also attenuated STAT-3 and STAT-6 phosphorylation. Furthermore, IL4I1 produced by macrophages catalyzed L-tryptophan degradation, while levo-1-methyl-tryptophan (L-1-MT, but not dextro-1-methyl-tryptophan, partially rescued IL4I1-dependent inhibition of T cell activation. Other inhibitors, such as diphenylene iodonium (DPI, an anti-IL-10Rα blocking antibody, and a nitric oxide synthase inhibitor, NG-monomethyl-L-arginine, also had this effect. Overall, our findings indicate that IL4I1 promotes an enhanced M2 functional phenotype, which is most likely associated with the phosphorylation of STAT-6 and STAT-3. Moreover, DPI, L-1-MT, NG-monomethyl-L-arginine, and anti-IL-10Rα blocking antibody were all found to be effective IL4I1 inhibitors in vitro.

  16. L-tryptophan

    Science.gov (United States)

    ... has been linked to over 1500 reports of eosinophilia-myalgia syndrome (EMS) and 37 deaths. EMS is ... breast-feeding. A white blood cell disorder called eosinophilia: L-tryptophan might make this condition worse. L- ...

  17. Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Henriksen, Louise T; Nersting, Jacob; Raja, Raheel A;

    2014-01-01

    . The objective of this study was to describe CSF asparagine depletion during 30 weeks of pegylated asparaginase therapy, 1000 iu/m(2) i.m. every second week, and to correlate CSF asparagine concentration with serum L-asparaginase enzyme activity. Danish children (1-17 years) with ALL, treated according...... asparagine concentration decreased from a pre-treatment level of 5·3 μmol/l to median levels ≤1·5 μmol/l. However, only 4/31 patients (five samples) had CSF asparagine concentrations below the limit of detection (0·1 μmol/l). In 11 patients, 24 paired same day serum and CSF samples were obtained. A decrease...

  18. Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Zhenzhou, E-mail: jiangcpu@yahoo.com.cn; Bao, Qingli, E-mail: bao_ql@126.com; Sun, Lixin, E-mail: slxcpu@126.com; Huang, Xin, E-mail: huangxinhx66@sohu.com; Wang, Tao, E-mail: wangtao1331@126.com; Zhang, Shuang, E-mail: cat921@sina.com; Li, Han, E-mail: hapo1101@163.com; Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn

    2013-01-15

    This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

  19. Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion.

    Directory of Open Access Journals (Sweden)

    Craig P Motbey

    Full Text Available Mephedrone (4-methylmethcathinone, MMC is a popular recreational drug, yet its potential harms are yet to be fully established. The current study examined the impact of single or repeated MMC exposure on various neurochemical and behavioral measures in rats. In Experiment 1 male adolescent Wistar rats received single or repeated (once a day for 10 days injections of MMC (30 mg/kg or the comparator drug methamphetamine (METH, 2.5 mg/kg. Both MMC and METH caused robust hyperactivity in the 1 h following injection although this effect did not tend to sensitize with repeated treatment. Striatal dopamine (DA levels were increased 1 h following either METH or MMC while striatal and hippocampal serotonin (5-HT levels were decreased 1 h following MMC but not METH. MMC caused greater increases in 5-HT metabolism and greater reductions in DA metabolism in rats that had been previously exposed to MMC. Autoradiographic analysis showed no signs of neuroinflammation ([(125I]CLINDE ligand used as a marker for translocator protein (TSPO expression with repeated exposure to either MMC or METH. In Experiment 2, rats received repeated MMC (7.5, 15 or 30 mg/kg once a day for 10 days and were examined for residual behavioral effects following treatment. Repeated high (30 mg/kg dose MMC produced impaired novel object recognition 5 weeks after drug treatment. However, no residual changes in 5-HT or DA tissue levels were observed at 7 weeks post-treatment. Overall these results show that MMC causes acute but not lasting changes in DA and 5-HT tissue concentrations. MMC can also cause long-term memory impairment. Future studies of cognitive function in MMC users are clearly warranted.

  20. The effect of acute tyrosine phenylalanine depletion on emotion-based decision-making in healthy adults.

    Science.gov (United States)

    Vrshek-Schallhorn, Suzanne; Wahlstrom, Dustin; White, Tonya; Luciana, Monica

    2013-04-01

    Despite interest in dopamine's role in emotion-based decision-making, few reports of the effects of dopamine manipulations are available in this area in humans. This study investigates dopamine's role in emotion-based decision-making through a common measure of this construct, the Iowa Gambling Task (IGT), using Acute Tyrosine Phenylalanine Depletion (ATPD). In a between-subjects design, 40 healthy adults were randomized to receive either an ATPD beverage or a balanced amino acid beverage (a control) prior to completing the IGT, as well as pre- and post-manipulation blood draws for the neurohormone prolactin. Together with conventional IGT performance metrics, choice selections and response latencies were examined separately for good and bad choices before and after several key punishment events. Changes in response latencies were also used to predict total task performance. Prolactin levels increased significantly in the ATPD group but not in the control group. However, no significant group differences in performance metrics were detected, nor were there sex differences in outcome measures. However, the balanced group's bad deck latencies speeded up across the task, while the ATPD group's latencies remained adaptively hesitant. Additionally, modulation of latencies to the bad decks predicted total score for the ATPD group only. One interpretation is that ATPD subtly attenuated reward salience and altered the approach by which individuals achieved successful performance, without resulting in frank group differences in task performance.

  1. Tryptophan oxygenation: mechanistic considerations.

    Science.gov (United States)

    Naismith, James H

    2012-06-01

    From a protein structural viewpoint, tryptophan is often considered an inert structural amino acid, playing a role as a hydrophobic anchor in membrane proteins or as part of the hydrophobic core of soluble proteins. However, tryptophan is the only polyaromatic amino acid and, from a chemical viewpoint, possesses unique reactivity owing to the electron-richness of the indole system. This reactivity is seen in the area of natural products and metabolites which have exquisite modifications of the indole ring system. Enzymes have evolved multiple strategies to break or modify the indole ring; one particular class is the IDO/TDO (indoleamine/tryptophan dioxygenase) superfamily. A new member of this family, PrnB, on the surface catalyses a very different reaction, but actually shares much of the early chemistry with the tryptophan dioxygenases. Studies on PrnB have contributed to our understanding of the wider superfamily. In the present mini-review, recent developments in our understanding of how the TDO class of enzymes use activated molecular oxygen to break the indole ring are discussed.

  2. Indoleamine 2,3-dioxygenase depletes tryptophan, activates general control non-derepressible 2 kinase and down-regulates key enzymes involved in fatty acid synthesis in primary human CD4+ T cells.

    Science.gov (United States)

    Eleftheriadis, Theodoros; Pissas, Georgios; Antoniadi, Georgia; Liakopoulos, Vassilios; Stefanidis, Ioannis

    2015-10-01

    Indoleamine 2,3-dioxygenase (IDO) is expressed in antigen-presenting cells and exerts immunosuppressive effects on CD4(+) T cells. One mechanism is through the inhibition of aerobic glycolysis. Another prerequisite for T-cell proliferation and differentiation into effector cells is increased fatty acid (FA) synthesis. The effect of IDO on enzymes involved in FA synthesis was evaluated in primary human cells both in mixed lymphocyte reactions in the presence or not of the IDO inhibitor 1-dl-methyl-tryptophan, and in stimulated CD4(+) T cells in the presence or not of the general control non-derepressible 2 (GCN2) kinase activator tryptophanol (TRP). IDO or TRP inhibited cell proliferation. By assessing the level of GCN2 kinase or mammalian target of rapamycin complex 1 substrates along with a kynurenine free system we showed that IDO exerts its effect mainly through activation of GCN2 kinase. IDO or TRP down-regulated ATP-citrate lyase and acetyl coenzyme A carboxylase 1, key enzymes involved in FA synthesis. Also, IDO or TRP altered the expression of enzymes that control the availability of carbon atoms for FA synthesis, such as lactate dehydrogenase-A, pyruvate dehydrogenase, glutaminase 1 and glutaminase 2, in a way that inhibits FA synthesis. In conclusion, IDO through GCN2 kinase activation inhibits CD4(+) T-cell proliferation and down-regulates key enzymes that directly or indirectly promote FA synthesis, a prerequisite for CD4(+) T-cell proliferation and differentiation into effector cell lineages. © 2015 John Wiley & Sons Ltd.

  3. Rotational spectrum of tryptophan

    Energy Technology Data Exchange (ETDEWEB)

    Sanz, M. Eugenia, E-mail: maria.sanz@kcl.ac.uk; Cabezas, Carlos, E-mail: ccabezas@qf.uva.es; Mata, Santiago, E-mail: santiago.mata@uva.es; Alonso, Josè L., E-mail: jlalonso@qf.uva.es [Grupo de Espectroscopia Molecular (GEM), Edificio Quifima, Laboratorios de Espectroscopia y Bioespectroscopia, Unidad Asociada CSIC, Parque Científico Uva, Universidad de Valladolid, 47011 Valladolid (Spain)

    2014-05-28

    The rotational spectrum of the natural amino acid tryptophan has been observed for the first time using a combination of laser ablation, molecular beams, and Fourier transform microwave spectroscopy. Independent analysis of the rotational spectra of individual conformers has conducted to a definitive identification of two different conformers of tryptophan, with one of the observed conformers never reported before. The analysis of the {sup 14}N nuclear quadrupole coupling constants is of particular significance since it allows discrimination between structures, thus providing structural information on the orientation of the amino group. Both observed conformers are stabilized by an O–H···N hydrogen bond in the side chain and a N–H···π interaction forming a chain that reinforce the strength of hydrogen bonds through cooperative effects.

  4. Rotational Spectrum of Tryptophan

    Science.gov (United States)

    Sanz, M. Eugenia; Cabezas, Carlos; Mata, Santiago; Alonso, José L.

    2014-06-01

    The rotational spectrum of the natural amino acid tryptophan has been observed using a recently constructed LA-MB-FTMW spectrometer, specifically designed to optimize the detection of heavier molecules at a lower frequency range. Independent analyses of the rotational spectra of individual conformers have conducted to a definitive identification of two different conformers of tryptophan, with one of the observed conformers never reported before. The experimental values of the 14N nuclear quadrupole coupling constants have been found capital in the discrimination of the conformers. Both observed conformers are stabilized by a O-H\\cdotsN hydrogen bond in the side chain and a N-H\\cdotsπ interaction forming a chain that reinforces the strength of hydrogen bonds through cooperative effects.

  5. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

    Directory of Open Access Journals (Sweden)

    Trisha A. Jenkins

    2016-01-01

    Full Text Available The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis.

  6. Dopamine and pain sensitivity: neither sulpiride nor acute phenylalanine and tyrosine depletion have effects on thermal pain sensations in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Susanne Becker

    Full Text Available Based on animal studies and some indirect clinical evidence, dopamine has been suggested to have anti-nociceptive effects. Here, we investigated directly the effects of increased and decreased availability of extracellular dopamine on pain perception in healthy volunteers. In Study 1, participants ingested, in separate sessions, a placebo and a low dose of the centrally acting D2-receptor antagonist sulpiride, intended to increase synaptic dopamine via predominant pre-synaptic blockade. No effects were seen on thermal pain thresholds, tolerance, or temporal summation. Study 2 used the acute phenylalanine and tyrosine depletion (APTD method to transiently decrease dopamine availability. In one session participants ingested a mixture that depletes the dopamine amino acid precursors, phenylalanine and tyrosine. In the other session they ingested a nutritionally balanced control mixture. APTD led to a small mood-lowering response following aversive thermal stimulation, but had no effects on the perception of cold, warm, or pain stimuli. In both studies the experimental manipulation of dopaminergic neurotransmission was successful as indicated by manipulation checks. The results contradict proposals that dopamine has direct anti-nociceptive effects in acute experimental pain. Based on dopamine's well-known role in reward processing, we hypothesize that also in the context of pain, dopamine acts on stimulus salience and might play a role in the initiation of avoidance behavior rather than having direct antinociceptive effects in acute experimental pain.

  7. Dopamine and pain sensitivity: neither sulpiride nor acute phenylalanine and tyrosine depletion have effects on thermal pain sensations in healthy volunteers.

    Science.gov (United States)

    Becker, Susanne; Ceko, Marta; Louis-Foster, Mytsumi; Elfassy, Nathaniel M; Leyton, Marco; Shir, Yoram; Schweinhardt, Petra

    2013-01-01

    Based on animal studies and some indirect clinical evidence, dopamine has been suggested to have anti-nociceptive effects. Here, we investigated directly the effects of increased and decreased availability of extracellular dopamine on pain perception in healthy volunteers. In Study 1, participants ingested, in separate sessions, a placebo and a low dose of the centrally acting D2-receptor antagonist sulpiride, intended to increase synaptic dopamine via predominant pre-synaptic blockade. No effects were seen on thermal pain thresholds, tolerance, or temporal summation. Study 2 used the acute phenylalanine and tyrosine depletion (APTD) method to transiently decrease dopamine availability. In one session participants ingested a mixture that depletes the dopamine amino acid precursors, phenylalanine and tyrosine. In the other session they ingested a nutritionally balanced control mixture. APTD led to a small mood-lowering response following aversive thermal stimulation, but had no effects on the perception of cold, warm, or pain stimuli. In both studies the experimental manipulation of dopaminergic neurotransmission was successful as indicated by manipulation checks. The results contradict proposals that dopamine has direct anti-nociceptive effects in acute experimental pain. Based on dopamine's well-known role in reward processing, we hypothesize that also in the context of pain, dopamine acts on stimulus salience and might play a role in the initiation of avoidance behavior rather than having direct antinociceptive effects in acute experimental pain.

  8. Effects of acute tyrosine/phenylalanine depletion on the selective processing of smoking-related cues and the relative value of cigarettes in smokers.

    Science.gov (United States)

    Hitsman, Brian; MacKillop, James; Lingford-Hughes, Anne; Williams, Tim M; Ahmad, Faheem; Adams, Sally; Nutt, David J; Munafò, Marcus R

    2008-03-01

    Acute tyrosine/phenylalanine depletion (ATPD) is a validated neurobiological challenge that results in reduced dopaminergic neurotransmission, allowing examination of the effects of a hypodopaminergic state on craving-related processes. We studied 16 nonabstaining smokers (>10 cigarettes/day; 9 males; age 20-33 years) to whom was administered a tyrosine/phenylalanine-free mixture (TYR/PHE-free) and a balanced amino acid mixture (BAL) in a double-blind, counterbalanced, crossover design. Subjective cigarette craving, attentional bias to smoking-related word cues, relative value of cigarettes, negative mood, and expired carbon monoxide (CO) levels were measured at various timepoints through 300 min. Participants smoked at hourly intervals to prevent acute nicotine withdrawal during testing. The TYR/PHE-free mixture, as compared to the BAL mixture, was associated with a greater increase in CO levels from baseline (p = 0.01). Adjusting for the potential confounding influence of between-condition differences in CO levels across time, TYR/PHE-free mixture was associated with increased demand for cigarettes (p = 0.01) and decreased attentional bias toward smoking-related words (p = 0.003). There were no significant differences between conditions in either subjective craving or depressed or anxious mood (p values > 0.05). Among nonabstaining daily smokers, acute dopaminergic depletion via ATPD may influence smoking behavior and indices of smoking-related motivation, such as attentional bias to smoking cues and relative cigarette value, which are not readily captured by subjective craving.

  9. Acute effects of breakfasts containing alpha-lactalbumin, or gelatin with or without added tryptophan, on hunger, 'satiety' hormones and amino acid profiles.

    Science.gov (United States)

    Nieuwenhuizen, Arie G; Hochstenbach-Waelen, Ananda; Veldhorst, Margriet A B; Westerterp, Klaas R; Engelen, Mariëlle P K J; Brummer, Robert-Jan M; Deutz, Nicolaas E P; Westerterp-Plantenga, Margriet S

    2009-06-01

    Proteins are the most satiating macronutrients. Tryptophan (TRP) may contribute to the satiating effect, as it serves as a precursor for the anorexigenic neurotransmitter serotonin. To address the role of TRP in the satiating properties of dietary protein, we compared three different breakfasts, containing either alpha-lactalbumin (high in TRP), gelatin (low in TRP) or gelatin with added TRP (gelatin+TRP, high in TRP), on appetite. Twenty-four subjects (22-29 kg/m2; aged 19-37 years) received a subject-specific breakfast at t = 0 with 10, 55 and 35 % energy from protein, carbohydrate and fat respectively in a randomised, single-blind design. Hunger, glucagon-like peptide (GLP)-1, ghrelin, amino acid concentrations and energy intake during a subsequent lunch were determined. Suppression of hunger was stronger 240 min after the breakfast with alpha-lactalbumin compared with gelatin and gelatin+TRP. Total plasma amino acid concentrations were lower with alpha-lactalbumin compared with gelatin with or without TRP (from t = 180-240 min). TRP concentrations were higher after alpha-lactalbumin than after gelatin with or without TRP from t = 0-100 min, whereas from t = 100-240 min, TRP concentrations were lower after gelatin than after alpha-lactalbumin and gelatin+TRP. The plasma ratio of TRP to other large neutral amino acids (LNAA) was, only at t = 100 min, lower after gelatin+TRP than after the other breakfasts. Plasma amino acid responses, TRP concentrations and TRP:LNAA ratios were not correlated with hunger. GLP-1 and ghrelin concentrations were similar for all diets. Energy intake during a subsequent lunch was similar for all diets. Summarised, an alpha-lactalbumin breakfast suppresses hunger more than a gelatin or gelatin+TRP breakfast. This cannot be explained by (possible) differences found in TRP concentrations and TRP:LNAA ratios in the breakfasts and in plasma, as well as in circulating total amino acids, GLP-1 and ghrelin.

  10. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    Energy Technology Data Exchange (ETDEWEB)

    Madden, Jill A. [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Hoyer, Patricia B. [Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States); Devine, Patrick J. [INRS—Institut Armand-Frappier Research Centre, University of Quebec, Laval, QC H7V 1B7 (Canada); Keating, Aileen F., E-mail: akeating@iastate.edu [Department of Animal Science, Iowa State University, Ames, IA 50011 (United States); Department of Physiology, University of Arizona, Tucson, AZ 85724 (United States)

    2014-05-01

    Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKT{sup Thr308} protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

  11. TRYPTOPHAN PROMOTES CHARITABLE DONATING

    Directory of Open Access Journals (Sweden)

    Laura eSteenbergen

    2014-12-01

    Full Text Available The link between serotonin (5-HT and one of the most important elements of prosocial behavior, charity, has remained largely uninvestigated. In the present study, we tested whether charitable donating can be promoted by administering the food supplement L-Tryptophan (TRP, the biochemical precursor of 5-HT. Participants were compared with respect to the amount of money they donated when given the opportunity to make a charitable donation. As expected, compared to a neutral placebo, TRP appears to increase the participants’ willingness to donate money to a charity. This result supports the idea that the food we eat may act as a cognitive enhancer modulating the way we think and perceive the world and others.

  12. Exogenous Tryptophan Promotes Cutaneous Wound Healing of Chronically Stressed Mice through Inhibition of TNF-α and IDO Activation.

    Directory of Open Access Journals (Sweden)

    Luana Graziella Bandeira

    Full Text Available Stress prolongs the inflammatory response compromising the dermal reconstruction and wound closure. Acute stress-induced inflammation increases indoleamine 2, 3-dioxygenase-stimulated tryptophan catabolism. To investigate the role of indoleamine 2, 3-dioxygenase expression and tryptophan administration in adverse effects of stress on cutaneous wound healing, mice were submitted to chronic restraint stress and treated with tryptophan daily until euthanasia. Excisional lesions were created on each mouse and 5 or 7 days later, the lesions were analyzed. In addition, murine skin fibroblasts were exposed to elevated epinephrine levels plus tryptophan, and fibroblast activity was evaluated. Tryptophan administration reversed the reduction of the plasma tryptophan levels and the increase in the plasma normetanephrine levels induced by stress 5 and 7 days after wounding. Five days after wounding, stress-induced increase in the protein levels of tumor necrosis factor-α and indoleamine 2, 3-dioxygenase, and this was inhibited by tryptophan. Stress-induced increase in the lipid peroxidation and the amount of the neutrophils, macrophages and T cells number was reversed by tryptophan 5 days after wounding. Tryptophan administration inhibited the reduction of myofibroblast density, collagen deposition, re-epithelialization and wound contraction induced by stress 5 days after wounding. In dermal fibroblast culture, the tryptophan administration increased the cell migration and AKT phosphorylation in cells treated with high epinephrine levels. In conclusion, tryptophan-induced reduction of inflammatory response and indoleamine 2, 3-dioxygenase expression may have accelerated cutaneous wound healing of chronically stressed mice.

  13. Transient depletion of T cells with high LFA-1 expression from peripheral circulation during acute Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G; Abdulhadi, N H

    1991-01-01

    Acute P. falciparum malaria is associated with loss of in vitro T cell responsiveness to antigenic stimulation, and with high plasma levels of soluble interleukin 2 receptor (IL 2R). In the present study peripheral T cells from acute P. falciparum malaria patients from a malaria-endemic area......-bound IL 2R (CD25) and ICAM-1 (CD54) did not reveal in vivo activated T cells in the peripheral blood of the patients. Taken together, these data suggest that circulating T cells recognizing parasite antigens are temporarily withdrawn from peripheral circulation during P. falciparum malaria....

  14. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia.

    Science.gov (United States)

    Zhou, Qing; Bucher, Christoph; Munger, Meghan E; Highfill, Steven L; Tolar, Jakub; Munn, David H; Levine, Bruce L; Riddle, Megan; June, Carl H; Vallera, Daniel A; Weigel, Brenda J; Blazar, Bruce R

    2009-10-29

    Tumor-induced immune suppression can permit tumor cells to escape host immune resistance. To elucidate host factors contributing to the poor response of adoptively transferred tumor-reactive cytotoxic T lymphocytes (CTLs), we used a systemic model of murine acute myeloid leukemia (AML). AML progression resulted in a progressive regulatory T-cell (Treg) accumulation in disease sites. The adoptive transfer of in vitro-generated, potently lytic anti-AML-reactive CTLs failed to reduce disease burden or extend survival. Compared with non-AML-bearing hosts, transferred CTLs had reduced proliferation in AML sites of metastases. Treg depletion by a brief course of interleukin-2 diphtheria toxin (IL-2DT) transiently reduced AML disease burden but did not permit long-term survival. In contrast, IL-2DT prevented anti-AML CTL hypoproliferation, increased the number of transferred CTLs at AML disease sites, reduced AML tumor burden, and resulted in long-term survivors that sustained an anti-AML memory response. These data demonstrated that Tregs present at AML disease sites suppress adoptively transferred CTL proliferation, limiting their in vivo expansion, and Treg depletion before CTL transfer can result in therapeutic efficacy in settings of substantial pre-existing tumor burden in which antitumor reactive CTL infusion alone has proven ineffective.

  15. The Effects of Acute Dopamine Precursor Depletion on the Cognitive Control Functions of Performance Monitoring and Conflict Processing: An Event-Related Potential (ERP) Study

    Science.gov (United States)

    Primosch, Mark; Leyton, Marco; Steffensen, Scott C.

    2015-01-01

    Studies using medications and psychiatric populations implicate dopamine in cognitive control and performance monitoring processes. However, side effects associated with medication or studying psychiatric groups may confound the relationship between dopamine and cognitive control. To circumvent such possibilities, we utilized a randomized, double-blind, placebo-controlled, within-subjects design wherein participants were administered a nutritionally-balanced amino acid mixture (BAL) and an amino acid mixture deficient in the dopamine precursors tyrosine (TYR) and phenylalanine (PHE) on two separate occasions. Order of sessions was randomly assigned. Cognitive control and performance monitoring were assessed using response times (RT), error rates, the N450, an event-related potential (ERP) index of conflict monitoring, the conflict slow potential (conflict SP), an ERP index of conflict resolution, and the error-related negativity (ERN) and error positivity (Pe), ERPs associated with performance monitoring. Participants were twelve males who completed a Stroop color-word task while ERPs were collected four hours following acute PHE and TYR depletion (APTD) or balanced (BAL) mixture ingestion in two separate sessions. N450 and conflict SP ERP amplitudes significantly differentiated congruent from incongruent trials, but did not differ as a function of APTD or BAL mixture ingestion. Similarly, ERN and Pe amplitudes showed significant differences between error and correct trials that were not different between APTD and BAL conditions. Findings indicate that acute dopamine precursor depletion does not significantly alter cognitive control and performance monitoring ERPs. Current results do not preclude the role of dopamine in these processes, but suggest that multiple methods for dopamine-related hypothesis testing are needed. PMID:26492082

  16. Persistence of HCV in Acutely-Infected Patients Depletes C24-Ceramide and Upregulates Sphingosine and Sphinganine Serum Levels

    Science.gov (United States)

    Grammatikos, Georgios; Dietz, Julia; Ferreiros, Nerea; Koch, Alexander; Dultz, Georg; Bon, Dimitra; Karakasiliotis, Ioannis; Lutz, Thomas; Knecht, Gaby; Gute, Peter; Herrmann, Eva; Zeuzem, Stefan; Mavromara, Penelope; Sarrazin, Christoph; Pfeilschifter, Josef

    2016-01-01

    Hepatitis C virus (HCV) substantially affects lipid metabolism, and remodeling of sphingolipids appears to be essential for HCV persistence in vitro. The aim of the current study is the evaluation of serum sphingolipid variations during acute HCV infection. We enrolled prospectively 60 consecutive patients with acute HCV infection, most of them already infected with human immunodeficiency virus (HIV), and serum was collected at the time of diagnosis and longitudinally over a six-month period until initiation of antiviral therapy or confirmed spontaneous clearance. Quantification of serum sphingolipids was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Spontaneous clearance was observed in 11 out of 60 patients (18.3%), a sustained viral response (SVR) in 43 out of 45 patients (95.5%) receiving an antiviral treatment after follow-up, whereas persistence of HCV occurred in six out of 60 patients (10%). C24-ceramide (C24-Cer)-levels increased at follow-up in patients with spontaneous HCV eradication (p < 0.01), as compared to baseline. Sphingosine and sphinganine values were significantly upregulated in patients unable to clear HCV over time compared to patients with spontaneous clearance of HCV infection on follow-up (p = 0.013 and 0.006, respectively). In summary, the persistence of HCV after acute infection induces a downregulation of C24Cer and a simultaneous elevation of serum sphingosine and sphinganine concentrations. PMID:27304952

  17. L-tryptophan in depression.

    Science.gov (United States)

    Farkas, T; Dunner, D L; Fieve, R R

    1976-06-01

    L-tryptophan, the amino acid precursor of serotonin, was administered to 16 depressive patients in a double-blind study of its potential antidepressant efficacy. Antidepressant responses were observed in one of ten unipolar patients and in three of six bipolar patients. These results are discussed in the context of possible interactions of amines with electrolyte systems in the etiology of affective illness.

  18. Tryptophan metabolism and immunogenetics in major depression: a role for interferon-γ gene.

    Science.gov (United States)

    Myint, Aye Mu; Bondy, Brigitta; Baghai, Thomas C; Eser, Daniela; Nothdurfter, Caroline; Schüle, Cornelius; Zill, Peter; Müller, Norbert; Rupprecht, Rainer; Schwarz, Markus J

    2013-07-01

    The tryptophan metabolism and immune activation play a role in pathophysiology of major depressive disorders. The pro-inflammatory cytokine interferon-γ transcriptionally induces the indoleamine 2,3-dioxygenase enzyme that degrades the tryptophan and thus induces serotonin depletion. The polymorphism of certain cytokine genes was reported to be associated with major depression. We investigated the association between interferon-γ (IFNγ) gene CA repeat polymorphism, the profile of serotonin and tryptophan pathway metabolites and clinical parameters in 125 depressed patients and 93 healthy controls. Compared to controls, serum tryptophan and 5-hydroxyindoleacetic acid (5HIAA) concentrations in the patients were significantly lower and serum kynurenine concentrations were significantly higher at baseline (p<0.0001). The presence of IFNγ CA repeat allele 2 homozygous has significant association with higher kynurenine concentrations in controls (F=4.47, p=0.038) as well as in patients (F=3.79, p=0.045). The existence of interferon-γ CA repeat allele 2 (homo- or heterozygous) showed significant association with increase of tryptophan breakdown over time during the study period (F=6.0, p=0.019). The results indicated the association between IFNγ CA repeat allele 2, tryptophan metabolism and the effect of medication.

  19. The Role of Placental Tryptophan Catabolism

    Science.gov (United States)

    Sedlmayr, Peter; Blaschitz, Astrid; Stocker, Roland

    2014-01-01

    This review discusses the mechanisms and consequences of degradation of tryptophan (Trp) in the placenta, focusing mainly on the role of indoleamine 2,3-dioxygenase-1 (IDO1), one of three enzymes catalyzing the first step of the kynurenine pathway of Trp degradation. IDO1 has been implicated in regulation of feto-maternal tolerance in the mouse. Local depletion of Trp and/or the presence of metabolites of the kynurenine pathway mediate immunoregulation and exert antimicrobial functions. In addition to the decidual glandular epithelium, IDO1 is localized in the vascular endothelium of the villous chorion and also in the endothelium of spiral arteries of the decidua. Possible consequences of IDO1-mediated catabolism of Trp in the endothelium encompass antimicrobial activity and immunosuppression, as well as relaxation of the placental vasotonus, thereby contributing to placental perfusion and growth of both placenta and fetus. It remains to be evaluated whether other enzymes mediating Trp oxidation, such as indoleamine 2,3-dioxygenase-2, Trp 2,3-dioxygenase, and Trp hydroxylase-1 are of relevance to the biology of the placenta. PMID:24904580

  20. Parallel variation of ventricular CSF tryptophan and free serum tryptophan in man.

    Science.gov (United States)

    Young, S N; Lal, S; Feldmuller, F; Sourkes, T L; Ford, R M; Kiely, M; Martin, J B

    1976-01-01

    Tryptophan was measured in the ventricular CSE and serum and the neutral amino acids leucine, isoleucine, valine, phenylalanine, and tyrosine were measured in the serum of two cases with ventricular drains. Samples were taken every two hours for 24 hours in one case and for 16 hours in the other. The CSF tryptophan was correlated significantly with the free--that is, non-albumin-bound--serum tryptophan but not with the total serum tryptophan. CSF tryptophan was not correlated significantly with the ratio of free serum tryptophan to the sum of the neutral amino acids. These data suggest that, in man, brain tryptophan concentrations are influenced by the free and not the total serum tryptophan and that physiological variations of the neutral amino acids do not appreciably influence the concentration of brain trytophan.

  1. Acute inhalation toxicity evaluation of a 93:7 mixture of perfluoro-2-butene and 1-bromopropane, a replacement candidate for ozone depleting substances. Interim report, July--August 1997

    Energy Technology Data Exchange (ETDEWEB)

    Feldmann, M.L.; Leahy, H.F.; Vinegar, A.

    1997-10-01

    The DoD requires the development of toxicity profiles for chemical substitute candidates proposed to replace ozone depleting substances such as chloro- and fluorocarbons and halons. A 93:7 mixture of perfluoro-2-butene and 1-bromopropane was identified as a possible replacement candidate for ozone-depleting fire extinguishants. An acute inhalation toxicity test utilizing male and female Fischer 344 rats was performed on this test material. No deaths occurred in any of the rats exposed to 5.3 mg/L of the 93:7 perfluoro-2-butene and 1-bromopropane mixture. Body weights of male and female rats during the subsequent 14-day observation period were unaffected by treatment. The test material did not produce acute toxicity via the inhalation route.

  2. Effects of serotonin depletion on punishment processing in the orbitofrontal and anterior cingulate cortices of healthy women.

    Science.gov (United States)

    Helmbold, K; Zvyagintsev, M; Dahmen, B; Bubenzer-Busch, S; Gaber, T J; Crockett, M J; Klasen, M; Sánchez, C L; Eisert, A; Konrad, K; Habel, U; Herpertz-Dahlmann, B; Zepf, F D

    2015-06-01

    Diminished synthesis of the neurotransmitter serotonin (5-HT) has been linked to disrupted impulse control in aversive contexts. However, the neural correlates underlying a serotonergic modulation of female impulsivity remain unclear. The present study investigated punishment-induced inhibition in healthy young women. Eighteen healthy female subjects (aged 20-31) participated in a double-blinded, counterbalanced, placebo-controlled, within subjects, repeated measures study. They were assessed on two randomly assigned occasions that were controlled for menstrual cycle phase. In a randomized order, one day, acute tryptophan depletion (ATD) was used to reduce 5-HT synthesis in the brain. On the other day, participants received a tryptophan-balanced amino acid load (BAL) as a control condition. Three hours after administration of ATD/BAL, neural activity was recorded during a modified Go/No-Go task implementing reward or punishment processes using functional magnetic resonance imaging (fMRI). Neural activation during No-Go trials in punishment conditions after BAL versus ATD administration correlated positively with the magnitude of central 5-HT depletion in the ventral and subgenual anterior cingulate cortices (ACC). Furthermore, neural activation in the medial orbitofrontal cortex (mOFC) and the dorsal ACC correlated positively with trait impulsivity. The results indicate reduced neural sensitivity to punishment after short-term depletion of 5-HT in brain areas related to emotion regulation (subgenual ACC) increasing with depletion magnitude and in brain areas related to appraisal and expression of emotions (mOFC and dorsal ACC), increasing with trait impulsivity. This suggests a serotonergic modulation of neural circuits related to emotion regulation, impulsive behavior, and punishment processing in females.

  3. l-Tryptophan Production by Achromobacter liquidum

    Science.gov (United States)

    Ujimaru, Toshihiko; Kakimoto, Toshio; Chibata, Ichiro

    1983-01-01

    Conditions for the production of tryptophanase from Achromobacter liquidum and for the conversion of l-serine and indole to l-tryptophan were studied. The enzyme could be produced in amounts as great as 0.750 U/ml (degradation) and 0.294 U/ml (synthesis) by shaking cultures at 30°C in a medium containing dextrin, yeast extract, l-tryptophan, and l-glutamic acid. l-Tryptophan was produced most efficiently by shaking the cells at 37°C in a reaction mixture containing 60 mg of l-serine per ml, 60 mg of indole per ml, and 0.5 mM pyridoxal phosphate. After 3 days, 96 mg of l-tryptophan per ml was formed, and l-tryptophan was easily isolated to 85.4% yield by concentration of the reaction mixture. PMID:16346331

  4. Posttranslational isoprenylation of tryptophan in bacteria

    Science.gov (United States)

    Sugita, Tomotoshi; Abe, Ikuro

    2017-01-01

    Posttranslational isoprenylation is generally recognized as a universal modification of the cysteine residues in peptides and the thiol groups of proteins in eukaryotes. In contrast, the Bacillus quorum sensing peptide pheromone, the ComX pheromone, possesses a posttranslationally modified tryptophan residue, and the tryptophan residue is isoprenylated with either a geranyl or farnesyl group at the gamma position to form a tricyclic skeleton that bears a newly formed pyrrolidine, similar to proline. The post-translational dimethylallylation of two tryptophan residues of a cyclic peptide, kawaguchipeptin A, from cyanobacteria has also been reported. Interestingly, the modified tryptophan residues of kawaguchipeptin A have the same scaffold as that of the ComX pheromones, but with the opposite stereochemistry. This review highlights the biosynthetic pathways and posttranslational isoprenylation of tryptophan. In particular, recent studies on peptide modifying enzymes are discussed.

  5. Serotonin Depletion Does not Modify the Short-Term Brain Hypometabolism and Hippocampal Neurodegeneration Induced by the Lithium-Pilocarpine Model of Status Epilepticus in Rats.

    Science.gov (United States)

    García-García, Luis; Shiha, Ahmed Anis; Bascuñana, Pablo; de Cristóbal, Javier; Fernández de la Rosa, Rubén; Delgado, Mercedes; Pozo, Miguel A

    2016-05-01

    It has been reported that fluoxetine, a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, has neuroprotective properties in the lithium-pilocarpine model of status epilepticus (SE) in rats. The aim of the present study was to investigate the effect of 5-HT depletion by short-term administration of p-chlorophenylalanine (PCPA), a specific tryptophan hydroxylase inhibitor, on the brain hypometabolism and neurodegeneration induced in the acute phase of this SE model. Our results show that 5-HT depletion did modify neither the brain basal metabolic activity nor the lithium-pilocarpine-induced hypometabolism when evaluated 3 days after the insult. In addition, hippocampal neurodegeneration and astrogliosis triggered by lithium-pilocarpine were not exacerbated by PCPA treatment. These findings point out that in the early latent phase of epileptogenesis, non-5-HT-mediated actions may contribute, at least in some extent, to the neuroprotective effects of fluoxetine in this model of SE.

  6. Distinct Patterns of Tryptophan Maintenance in Tissues during Kynurenine Pathway Activation in Simian Immunodeficiency Virus-Infected Macaques

    Directory of Open Access Journals (Sweden)

    Julia L Drewes

    2016-12-01

    Full Text Available Induction of the kynurenine pathway (KP of tryptophan catabolism has been proposed to contribute to T cell dysfunction during human/simian immunodeficiency virus (HIV/SIV infection via depletion of local tryptophan levels and production of immunomodulatory KP metabolites. However, while changes in tryptophan and KP metabolites have been observed in plasma, their levels in lymphoid tissues and levels of enzymes downstream of indoleamine 2,3-dioxygenase (IDO1 have been relatively unexplored. We used our SIV-infected pigtailed macaque model to analyze longitudinal changes in KP metabolites and enzymes by gas chromatography/mass spectrometry and NanoString nCounter gene expression analysis, respectively, in spleen and blood compared to changes previously established in brain and CSF. We found that tryptophan levels were remarkably stable in tissue sites despite robust depletion in the circulating plasma and CSF. We also demonstrated that intracellular tryptophan reserves were maintained in cultured cells even in the presence of depleted extracellular tryptophan levels. Kynurenine, 3-hydroxykynurenine, quinolinic acid, and the KP enzymes all displayed highly divergent patterns in the sites examined, though IDO1 expression always correlated with local kynurenine/tryptophan ratios. Finally, we demonstrated by FACS that myeloid dendritic cells (mDCs and cells of monocytic lineage were the highest producers of IDO1 in chronically infected spleens. Overall our study reveals insights into the tissue-specific regulation of KP enzymes and metabolites and, in particular, highlights the multiple mechanisms by which cells and tissues seek to prevent TRP starvation during inflammation.

  7. Insuficiência respiratória aguda como manifestação da síndrome de eosinofilia-mialgia associada à ingestão de L-triptofano Acute respiratory failure as a manifestation of eosinophilia-myalgia syndrome associated with L-tryptophan intake

    Directory of Open Access Journals (Sweden)

    Tiago de Araujo Guerra Grangeia

    2007-12-01

    Full Text Available A síndrome da eosinofilia-mialgia foi descrita em 1989 em pacientes que apresentavam mialgia progressiva e incapacitante e eosinofilia sérica, nos líquidos e secreções. A maioria dos pacientes relatava uso prévio de L-triptofano. Sintomas respiratórios são relatados em até 80% dos casos, eventualmente como manifestação única. O tratamento inclui suspensão da droga e corticoterapia. Relatamos o caso de uma mulher de 61 anos com insuficiência respiratória aguda após uso de L-triptofano, hidroxitriptofano e outras drogas. A paciente apresentava eosinofilia no sangue, lavado broncoalveolar e derrame pleural. Após a suspensão da medicação e corticoterapia, houve melhora clínica e radiológica em poucos dias.Eosinophilia-myalgia syndrome was described in 1989 in patients who presented progressive and incapacitating myalgia and eosinophilia in blood, fluids and secretions. Most patients report previous L-tryptophan intake. Respiratory manifestations are found in up to 80% of the cases, occasionally as the only manifestation. Treatment includes drug discontinuation and administration of corticosteroids. Here, we describe the case of a 61-year-old female admitted with acute respiratory failure after using L-tryptophan, hydroxytryptophan and other drugs. The patient presented eosinophilia, together with elevated eosinophil counts in the bronchoalveolar lavage and pleural effusion. After discontinuation of the drugs previously used, corticosteroids were administered, resulting in clinical and radiological improvement within just a few days.

  8. Structural Characterization of New Microcystins Containing Tryptophan and Oxidized Tryptophan Residues

    Directory of Open Access Journals (Sweden)

    David P. Hamilton

    2013-08-01

    Full Text Available Microcystins are cyclic peptides produced by cyanobacteria, which can be harmful to humans and animals when ingested. Eight of the (more than 90 microcystin variants presently characterized, contain the amino acid tryptophan. The well-researched oxidation products of tryptophan; kynurenine, oxindolylalanine, and N-formylkynurenine, have been previously identified in intact polypeptides but microcystin congeners containing oxidized tryptophan moieties have not been reported. Liquid chromatography-tandem mass spectrometric analysis of an extract of Microcystis CAWBG11 led to the tentative identification of two new tryptophan-containing microcystins (MC‑WAba and MC-WL, as well as eight other microcystin analogs containing kynurenine, oxindolylalanine and N‑formylkynurenine (Nfk. Investigation of one of these congeners (MC‑NfkA by nuclear magnetic resonance spectroscopy was used to verify the presence of Nfk in the microcystin. Liquid chromatography-mass spectrometry analysis of a tryptophan oxidation experiment demonstrated that tryptophan-containing microcystins could be converted into oxidized tryptophan analogs and that low levels of oxidized tryptophan congeners were present intracellularly in CAWBG11. MC-NfkR and MC-LNfk were detected in standards of MC-WR and MC-LW, indicating that care during storage of tryptophan-containing microcystins is required.

  9. Partial depletion of CD4(+)CD25(+)Foxp3(+) T regulatory cells significantly increases morbidity during acute phase Toxoplasma gondii infection in resistant BALB/c mice.

    Science.gov (United States)

    Morampudi, Vijay; De Craeye, Stephane; Le Moine, Alain; Detienne, Sophie; Braun, M Y; D'Souza, Sushila

    2011-04-01

    CD4(+)CD25(+)Foxp3(+) T regulatory (Treg) cells, are known to regulate responses to infectious agents. Here we compared disease progression in BALB/c and C57BL/6(B6) mice infected perorally with Toxoplasma gondii for 7 days and examined the affect of partial depletion of Treg cells in these mice. BALB/c mice were seen to be resistant to peroral infection whereas B6 mice were susceptible in terms of mortality. Although the depletion of Treg cells before infection had no effect on the survival of B6 or BALB/c mice, it resulted in increased parasite burdens in BALB/c mice, especially in the lamina propria, but not in B6 mice. Pro-inflammatory cytokines were also increased in Treg cells depleted BALB/c mice as compared to B6 mice. In addition Treg cell depleted BALB/c mice displayed increased ileal histopathology compared to their non-treated counterparts. These findings provide evidence for the contribution of Treg cells, in the resistance of BALB/c mice against peroral T. gondii infection.

  10. The impact of chronic GVHD on survival of Patients with acute myeloid leukemia after non-T-cell depleted HLA-identical sibling peripheral blood stem cells transplantation

    Directory of Open Access Journals (Sweden)

    farhad Shahsavar

    2012-06-01

    Conclusion: These data indicate that the occurrence of cGVHD is an important predictor of outcome of non-T-cell depleted HLA-identical sibling allogeneic PBSCT, in those AML patients who develope cGVHD have a high chance of survival.

  11. Mechanism of Inhibition of Novel Tryptophan Hydroxylase Inhibitors Revealed by Co-crystal Structures and Kinetic Analysis.

    Science.gov (United States)

    Cianchetta, Giovanni; Stouch, Terry; Yu, Wangsheng; Shi, Zhi-Cai; Tari, Leslie W; Swanson, Ronald V; Hunter, Michael J; Hoffman, Isaac D; Liu, Qingyun

    2010-04-14

    Trytophan Hydroxylase Type I (TPH1), most abundantly expressed in the gastrointestinal tract, initiates the synthesis of serotonin by catalyzing hydroxylation of tryptophan in the presence of biopterin and oxygen. We have previously described three series of novel, periphery-specific TPH1 inhibitors that selectively deplete serotonin in the gastrointestinal tract. We have now determined co-crystal structures of TPH1 with three of these inhibitors at high resolution. Analysis of the structural data showed that each of the three inhibitors fills the tryptophan binding pocket of TPH1 without reaching into the binding site of the cofactor pterin, and induces major conformational changes of the enzyme. The enzyme-inhibitor complexes assume a compact conformation that is similar to the one in tryptophan complex. Kinetic analysis showed that all three inhibitors are competitive versus the substrate tryptophan, consistent with the structural data that the compounds occupy the tryptophan binding site. On the other hand, all three inhibitors appear to be uncompetitive versus the cofactor 6-methyltetrahydropterin, which is not only consistent with the structural data but also indicate that the hydroxylation reaction follows an ordered binding mechanism in which a productive complex is formed only if tryptophan binds only after pterin, similar to the kinetic mechanisms of tyrosine and phenylalanine hydroxylase.

  12. Tetrahydro-beta-carboline-3-carboxylic acids and contaminants of L-tryptophan.

    Science.gov (United States)

    Adachi, J; Asano, M; Ueno, Y

    2000-06-09

    Methods for the separation, identification, and quantitative assay of contaminants of L-tryptophan implicated in eosinophilia-myalgia syndrome (EMS) are described. Propylsulfonic acid (PRS), benzenesulfonic acid (SCX), and octyl-derivatized silica (C8) bonded-phase cartridges were used for the separation; LC-MS and GC-MS for identification; and HPLC-UV-fluorescence detection for quantitative analyses of norharman, harman, tetrahydro-beta-carboline-3-carboxylic acid (TCCA), 1-methyltetrahydro-beta-carboline-3-carboxylic acid (MTCA), 1,1'-ethylidenbis(tryptophan) (EBT), and 3-(phenylamino)alanine (PAA). The tissue distribution, excretion, and metabolism of these contaminants of L-tryptophan associated with EMS after acute and chronic dosage regimens are described. Considerable amounts of EBT were observed in the large intestine of rats administered EBT, showing a transfer without decomposition in gastric fluid. In addition, MTCA was detected in the blood and urine as well as the organs of rats treated with EBT, suggesting MTCA as a major metabolite of EBT. PAA accumulated markedly in the brain, among the organs of rats, after both acute and chronic administration of PAA, while MTCA accumulated in the kidneys of rats after chronic dosage of MTCA. Ethanol and/or acetaldehyde-induced formation of MTCA, as well as tryptophan-induced formation of TCCA, occurred endogenously in man and animals.

  13. Pre-transplant donor-specific T-cell alloreactivity is strongly associated with early acute cellular rejection in kidney transplant recipients not receiving T-cell depleting induction therapy.

    Directory of Open Access Journals (Sweden)

    Elena Crespo

    Full Text Available Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90, to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67. We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction

  14. Antidepressant-like activity of sildenafil following acute and subchronic treatment in the forced swim test in mice: effects of restraint stress and monoamine depletion.

    Science.gov (United States)

    Socała, Katarzyna; Nieoczym, Dorota; Pieróg, Mateusz; Szuster-Ciesielska, Agnieszka; Wyska, Elżbieta; Wlaź, Piotr

    2016-10-01

    Sildenafil is a highly effective oral agent for the treatment of erectile dysfunction of multiple etiologies. Although in clinical practice sildenafil is often used in depressed patients, its influence on the pathophysiology of depression remains unclear. The aim of the present study was to evaluate the antidepressant-like activity following acute and subchronic treatment with sildenafil in naïve mice as well as in mice with reserpine- and restraint stress-induced depressive-like behavior. Since corticosterone is released in response to acute stress, we also aimed to assess the influence of sildenafil on serum corticosterone level in non-stressed and stressed animals. The antidepressant activity of sildenafil was assessed in the forced swim test. Corticosterone serum level was determined by using ELISA method, while brain and serum sildenafil level via HPLC method. Sildenafil administered acutely exerted an antidepressant-like effect. Subchronic (14 days) administration of sildenafil resulted only in a weak antidepressant-like effect when evaluated 24 h after the last dose. Acute but not subchronic sildenafil administration reversed the reserpine- and stress-induced immobility in the forced swim test. The lack of effects of sildenafil after subchronic treatment could have been related to its complete elimination from the brain within 24 h from the last injection. Interestingly, acute administration of sildenafil produced a marked increase in serum corticosterone level in both non-stressed and stressed animals. Sildenafil exerts differential effects in the forced swim test after acute and subchronic administration. Further studies on the antidepressant activity of sildenafil are required.

  15. Acute hypotension associated with intraoperative cell salvage using a leukocyte depletion filter during management of obstetric hemorrhage due to amniotic fluid embolism.

    Science.gov (United States)

    Rogers, William Kirke; Wernimont, Sarah A; Kumar, Girish C; Bennett, Eliza; Chestnut, David H

    2013-08-01

    Amniotic fluid embolism (AFE) is a rare but catastrophic obstetric complication that can lead to profound coagulopathy and hemorrhage. The role of cell salvage and recombinant human Factor VIIa (rFVIIa) administration in such cases remains unclear. We present a case of AFE and describe our experience with the use of cell salvage and rFVIIa administration during the resuscitation. Cell salvage and transfusion through a leukocyte depletion filter was attempted after the diagnosis of AFE was made, but the attempted transfusion was immediately followed by hypotension and a worsening of hemodynamics. rFVIIa, on the contrary, was used with clinical improvement in coagulopathy and without apparent adverse thrombotic effect.

  16. Rotational Spectra of Phenylalanine, Tirosine and Tryptophan

    Science.gov (United States)

    Mata, S.; Perez, C.; Sanz, M. E.; Blanco, S.; López, J. C.; Alonso, J. L.

    2009-06-01

    The rotational spectra of the aromatic natural amino acids phenylalanine, tyrosine and tryptophan have been investigated by Laser Ablation Molecular Beam Fourier transform Microwave Spectroscopy LA-MB-FTMW. The spectra of two rotamers of phenylalanine have been detected in the supersonic expansion. Both forms are stabilized by a chain of intramolecular hydrogen bonds O-H\\cdotsN-H\\cdots{π}, being the carboxylic group incis configuration. One conformer of tyrosine, which only differs from phenylalanine in a -OH group inpara position, has been also characterized. Preliminary results on the rotational spectrum of tryptophan are presented.

  17. Tryptophan distribution in yeast hexokinase isoenzyme B

    Energy Technology Data Exchange (ETDEWEB)

    Kramp, D.C.; Feldman, I.

    1978-01-01

    Titrations of the quenching of the tryptophan fluorescence of yeast hexokinase isoenzyme B by Cs/sup +/, I/sup -/ and glucose as quenchers, singly and in various combinations, have been performed at pH 5.5, 8.3, and 10.1 at 20/sup 0/C. The iodide and glucose titrations at pH 8.3 indicated that the four tryptophan residues of the monomer subunit can be classified as: (1) a highly accessible surface tryptophan (Trp-S/sub 1/); (2) a surface tryptophan (Trp-S/sub 2/) with restricted accessibility (possibly in a crevice); (3) a glucose-quenchable cleft tryptophan (Trp-G); and (4) a buried tryptophan (Trp-B) in the hydrophobic interior. The Stern-Volmer constants, k/sub I/, calculated for iodide quenching of the two surface residues at pH 8.3 are 22 and 3.3 M/sup -1/. The k/sub I/ value of Trp-G at this pH is iodide dependent, increasing from 1.2 to 1.4 M/sup -1/ as the iodide concentration increases from 0.1 to 0.65 M, probably because of iodide-induced alteration of the cleft structure. An iodide concentration above 0.65 M quenches Trp-B detectably, demonstrating that a high iodide concentration produces a large structural change in the isoenzyme. The percentages of the total 350 nm emission attributable to the individual tryptophan residues at pH 8.3 are 9, 22, 28, and 41%, for Trp-S/sub 1/, Trp-S/sub 2/, Trp-G, and Trp-B, respectively. At pH 5.5 even a low iodide concentration causes some quenching of Trp-B, especially in presence of saturating glucose. Glucose increases the iodide quenchability at this pH. At pH 10.1 glucose does not quench the tryptophan emission, and it does not influence the iodide-quenching action. However, at this high pH the k/sub 1/ of Trp-S/sub 1/ is reduced to the point where it is not resolvable from the k/sub I/ values of Trp-S/sub 2/ and Trp-G, even though the sum of the fractional fluorescence contributions of these three residues is the same as at pH 8.3.

  18. Utilization of superoxide anion by indoleamine oxygenase-catalyzed tryptophan and indoleamine oxidation.

    Science.gov (United States)

    Hayaishi, O

    1996-01-01

    The following is our current working hypothesis concerning the biological significance of IDO induction. When tissues are invaded by virus, bacteria, or parasites, leukocytes and lymphocytes will accumulate at the site and interferon will be produced by these cells in the inflammatory loci. The interferon thus produced is released and interacts with the cell surface to trigger IDO induction in the same or other types of cells. As a consequence of inflammation, superoxide anion is liberated and serves as a substrate for IDO. Although it is possible that some trytophan metabolites may activate the immune system or act as bacteriostatic agents, available evidence does not support this hypothesis. We therefore tentatively conclude that tryptophan is degraded by IDO and depleted, whereby the growth of viruses, bacteria and certain parasites is inhibited, because tryptophan is the least available and therefore most important essential amino acid for their growth.

  19. Tryptic digestion of the human erythrocyte glucose transporter: effects on ligand binding and tryptophan fluorescence.

    Science.gov (United States)

    May, J M; Qu, Z C; Beechem, J M

    1993-09-21

    The conformation of the human erythrocyte glucose transport protein has been shown to determine its susceptibility to enzymatic cleavage on a large cytoplasmic loop. We took the converse approach and investigated the effects of tryptic digestion on the conformational structure of this protein. Exhaustive tryptic digestion of protein-depleted erythrocyte ghosts decreased the affinity of the residual transporter for cytochalasin B by 3-fold but did not affect the total number of binding sites. Tryptic digestion also increased the affinity of the residual transporter for D-glucose and inward-binding sugar phenyl beta-D-glucopyranoside but decreased that for the outward-binding 4,6-O-ethylidene glucose. These results suggest that tryptic cleavage stabilized the remaining transporter in an inward-facing conformation, but one with decreased affinity for cytochalasin B. The steady-state fluorescence emission scan of the purified reconstituted glucose transport protein was unaffected by tryptic digestion. Addition of increasing concentrations of potassium iodide resulted in linear Stern-Volmer plots, which were also unaffected by prior tryptic digestion. The tryptophan oxidant N-bromosuccinimide was investigated to provide a more sensitive measure of tryptophan environment. This agent irreversibly inhibited 3-O-methylglucose transport in intact erythrocytes and cytochalasin B binding in protein-depleted ghosts, with a half-maximal effect observed for each activity at about 0.3-0.4 nM. Treatment of purified glucose transport protein with N-bromosuccinimide resulted in a time-dependent quench of tryptophan fluorescence, which was resolved into two components by nonlinear regression using global analysis. Tryptic digestion retarded the rate of oxidation of the more slowly reacting class of tryptophans. (ABSTRACT TRUNCATED AT 250 WORDS)

  20. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia

    OpenAIRE

    Zhou, Qing; Bucher, Christoph; Munger, Meghan E.; Highfill, Steven L.; Tolar, Jakub; Munn, David H.; Levine, Bruce L.; Riddle, Megan; June, Carl H.; Vallera, Daniel A.; Weigel, Brenda J.; Blazar, Bruce R.

    2009-01-01

    Tumor-induced immune suppression can permit tumor cells to escape host immune resistance. To elucidate host factors contributing to the poor response of adoptively transferred tumor-reactive cytotoxic T lymphocytes (CTLs), we used a systemic model of murine acute myeloid leukemia (AML). AML progression resulted in a progressive regulatory T-cell (Treg) accumulation in disease sites. The adoptive transfer of in vitro–generated, potently lytic anti–AML-reactive CTLs failed to reduce disease bur...

  1. Improving therapeutics in anorexia nervosa with tryptophan.

    Science.gov (United States)

    Haleem, Darakhshan Jabeen

    2017-06-01

    A growing body of evidence suggests that our diet is an important contributing factor in the development, management and prevention of a number of psychiatric illnesses. Tryptophan, an essential amino acid, is the sole precursor of neurotransmitter 5-hydroxytryptamine (5-HT; serotonin). Administration of tryptophan can boost serotonin neurotransmission to produce therapeutically important effects in serotonin deficiency disorders. Anorexia nervosa (AN) an eating disorder associated with high levels of psychiatric comorbidity including psychosis, hyperactivity, depression and anxiety has highest lethality of all psychiatric illnesses. Evidence suggests that excessive dieting and food restriction can decrease brain tryptophan and serotonin in AN patients to precipitate depression, psychosis and hyperactivity. There are currently no FDA approved pharmacological treatments available for AN patients; antidepressants and antipsychotics, largely used to treat associated psychiatric comorbidities are also not very effective. The aim of this non-systematic review article is to evaluate and document a potential importance of tryptophan supplementation in improving therapeutics in AN patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Tryptophan-induced eosinophilia-myalgia syndrome.

    OpenAIRE

    Criswell, L A; Sack, K. E.

    1990-01-01

    Eight patients who became ill while taking tryptophan had myalgia, fatigue, rash, fever, edema, alopecia, arthralgias, diminished joint motion, skin tightening, muscle cramping, and distal paresthesias. Three had shortness of breath, and one had pulmonary hypertension. Laboratory abnormalities included peripheral eosinophilia, leukocytosis, thrombocytosis, raised erythrocyte sedimentation rate, and elevated serum levels of aldolase, lactate dehydrogenase, and liver enzymes. Of 4 chest radiogr...

  3. Origin of tryptophan fluorescence lifetimes. Part 2: fluorescence lifetimes origin of tryptophan in proteins.

    Science.gov (United States)

    Albani, J R

    2014-01-01

    Fluorescence intensity decays of L-tryptophan in proteins dissolved in pH 7 buffer, in ethanol and in 6 M guanidine pH 7.8 and in lyophilized proteins were measured. In all protein conditions, three lifetimes were obtained along the emission spectrum (310-410 nm). The two shortest lifetimes are in the same range of those obtained for L-Trp in water or in ethanol. Thus, these two lifetimes originate from specific two sub-structures existing in the excited state and are inherent to the tryptophan structure independently of the surrounding environment (amino acids residues, solvent, etc.) In proteins, the third lifetime originates from the interactions that are occurring between tryptophan residues and neighboring amino acids. Populations of these lifetimes are independent of the excitation wavelength and thus originate from pre-defined sub structures existing in the excited state and put into evidence after tryptophan excitation. Fluorescence decay studies of different tripeptides having a tryptophan residue in second position show that the best analysis is obtained with two fluorescence lifetimes. Consequently, this result seems to exclude the possibility that peptide bond induces the third fluorescence lifetimes. Indole dissolved in water and/or in ethanol emits with two fluorescence lifetimes that are completely different from those observed for L-Trp. Absence of the third lifetime in ethanol demonstrates that indole behaves differently when compared to tryptophan. Thus, it seems not adequate to attribute fluorescence lifetime or fluorescence properties of tryptophan to indole ring and to compare tryptophan fluorescence properties in proteins to molecules having close structures such as NATA which fluoresces with one lifetime.

  4. Origin of tryptophan fluorescence lifetimes part 1. Fluorescence lifetimes origin of tryptophan free in solution.

    Science.gov (United States)

    Albani, J R

    2014-01-01

    Fluorescence intensity decays of L-tryptophan free in polar, hydrophobic and mixture of polar-hydrophobic solvents were recorded along the emission spectrum (310-410 nm). Analysis of the data show that emission of tryptophan occurs with two lifetimes in 100% polar and hydrophobic environments. The values of the two lifetimes are not the same in both environments while their populations (pre-exponentials values) are identical. Fluorescence lifetimes and pre-exponentials values do not change with the excitation wavelength and thus are independent of excitation energy. Our results indicate that tryptophan emission occurs from two specific sub-structures existing in the excited state. These sub-structures differ from those present in the ground states and characterize an internal property and/or organization of the tryptophan structure in the excited state. By sub-substructure, we mean here tryptophan backbone and its electronic cloud. In ethanol, three fluorescence lifetimes were measured; two lifetimes are very close to those observed in water (0.4-0.5 ns and 2-4 ns). Presence of a third lifetime for tryptophan in ethanol results from the interaction of both hydrophobic and hydrophilic dipoles or chemical functions of ethanol with the fluorophore.

  5. Reduced-Intensity Conditioning Combined with (188)Rhenium Radioimmunotherapy before Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients with Acute Myeloid Leukemia: The Role of In Vivo T Cell Depletion.

    Science.gov (United States)

    Schneider, Sebastian; Strumpf, Annette; Schetelig, Johannes; Wunderlich, Gerd; Ehninger, Gerhard; Kotzerke, Jörg; Bornhäuser, Martin

    2015-10-01

    The combination of reduced-intensity conditioning, (188)rhenium anti-CD66 radioimmunotherapy, and in vivo T cell depletion was successfully applied in elderly patients with acute myeloid leukemia or myelodysplastic syndrome. Within a prospective phase II protocol, we investigated whether a dose reduction of alemtuzumab (from 75 mg to 50 mg MabCampath) would improve leukemia-free survival by reducing the incidence of relapse. Fifty-eight patients (median age, 67 years; range, 54 to 76) received radioimmunotherapy followed by fludarabine 150 mg/m(2) and busulfan 8 mg/kg combined with either 75 mg (n = 26) or 50 mg (n = 32) alemtuzumab. Although we observed a trend towards a shorter duration of neutropenia in the 50 mg group (median, 19 versus 21 days; P = .07), the time from transplantation to neutrophil and platelet engraftment as well as the overall incidence of engraftment did not differ. The incidence of severe acute graft-versus-host disease tended to be higher after the lower alemtuzumab dose (17% versus 4%; P = .15). No significant differences in the cumulative incidences of relapse (38% versus 35%; P = .81) or nonrelapse mortality (46% versus 27%; P = .31) were observed. Accordingly, disease-free and overall survival were not significantly different between groups. Although the feasibility of radioimmunotherapy plus reduced-intensity conditioning could be demonstrated in elderly patients, the dose reduction of alemtuzumab had no positive impact on overall outcome.

  6. Acute infection with bovine viral diarrhea virus of low or high virulence leads to depletion and redistribution of WC1(+) γδ T cells in lymphoid tissues of beef calves.

    Science.gov (United States)

    Palomares, Roberto A; Sakamoto, Kaori; Walz, Heather L; Brock, Kenny V; Hurley, David J

    2015-10-15

    The objective of this study was to determine the abundance and distribution of γδ T lymphocytes in lymphoid tissue during acute infection with high (HV) or low virulence (LV) non-cytopathic bovine viral diarrhea virus (BVDV) in beef calves. This study was performed using tissue samples from a previous experiment in which thirty beef calves were randomly assigned to 1 of 3 groups: LV [n=10; animals inoculated intranasally (IN) with LV BVDV-1a (strain SD-1)], HV [n=10; animals inoculated IN with HV BVDV-2 (strain 1373)], and control (n=10; animals inoculated with cell culture medium). On day 5 post inoculation, animals were euthanized, and samples from spleen and mesenteric lymph nodes (MLN) were collected to assess the abundance of WC1(+) γδ T cells. A higher proportion of calves challenged with BVDV showed signs of apoptosis and cytophagy in MLN and spleen samples compared to the control group. A significantly lower number of γδ T cells was observed in spleen and MLN from calves in HV and LV groups than in the control calves (P<0.05). In conclusion, acute infection with HV or LV BVDV resulted in depletion of WC1(+) γδ T cells in mucosal and systemic lymphoid tissues at five days after challenge in beef calves. This reduction in γδ T cells in the studied lymphoid tissues could be also due to lymphocyte trafficking to other tissues.

  7. Purification and Characterization of Tryptophan Hydroxylase

    DEFF Research Database (Denmark)

    Haahr, Lærke Tvedebrink

    This thesis deals with the purification and characterization of the iron-containing enzyme tryptophan hydroxylase (TPH). TPH exists in two isoforms, called TPH1 and TPH2. Each isoform consists of threestructural distinct domains: the regulatory, the catalytic and the tetramerization domain. TPH...... of this project was to developpurification methods for full-length TPH1 and TPH2 as well as to characterize purified TPH variants. A successful purification method for full-length human TPH1 (hTPH1) was developed, which resulted in pure, active and stable protein. The method includes affinity-purification using....... The crystallization procedure for the catalytic domain of gallus gallus TPH1 (cgTPH1) was optimized to faster crystal growth by addition of tryptophan and incubation at room temperature. Crystals without imidazole in the crystallization conditions could be obtained. The solved structures were however of poor quality...

  8. Synthesis of constrained analogues of tryptophan

    Directory of Open Access Journals (Sweden)

    Elisabetta Rossi

    2015-10-01

    Full Text Available A Lewis acid-catalysed diastereoselective [4 + 2] cycloaddition of vinylindoles and methyl 2-acetamidoacrylate, leading to methyl 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate derivatives, is described. Treatment of the obtained cycloadducts under hydrolytic conditions results in the preparation of a small library of compounds bearing the free amino acid function at C-3 and pertaining to the class of constrained tryptophan analogues.

  9. Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease.

    Science.gov (United States)

    Romani, Luigina; Fallarino, Francesca; De Luca, Antonella; Montagnoli, Claudia; D'Angelo, Carmen; Zelante, Teresa; Vacca, Carmine; Bistoni, Francesco; Fioretti, Maria C; Grohmann, Ursula; Segal, Brahm H; Puccetti, Paolo

    2008-01-10

    Half a century ago, chronic granulomatous disease (CGD) was first described as a disease fatally affecting the ability of children to survive infections. Various milestone discoveries have since been made, from an insufficient ability of patients' leucocytes to kill microbes to the underlying genetic abnormalities. In this inherited disorder, phagocytes lack NADPH oxidase activity and do not generate reactive oxygen species, most notably superoxide anion, causing recurrent bacterial and fungal infections. Patients with CGD also suffer from chronic inflammatory conditions, most prominently granuloma formation in hollow viscera. The precise mechanisms of the increased microbial pathogenicity have been unclear, and more so the reasons for the exaggerated inflammatory response. Here we show that a superoxide-dependent step in tryptophan metabolism along the kynurenine pathway is blocked in CGD mice with lethal pulmonary aspergillosis, leading to unrestrained Vgamma1(+) gammadelta T-cell reactivity, dominant production of interleukin (IL)-17, defective regulatory T-cell activity and acute inflammatory lung injury. Although beneficial effects are induced by IL-17 neutralization or gammadelta T-cell contraction, complete cure and reversal of the hyperinflammatory phenotype are achieved by replacement therapy with a natural kynurenine distal to the blockade in the pathway. Effective therapy, which includes co-administration of recombinant interferon-gamma (IFN-gamma), restores production of downstream immunoactive metabolites and enables the emergence of regulatory Vgamma4(+) gammadelta and Foxp3(+) alphabeta T cells. Therefore, paradoxically, the lack of reactive oxygen species contributes to the hyperinflammatory phenotype associated with NADPH oxidase deficiencies, through a dysfunctional kynurenine pathway of tryptophan catabolism. Yet, this condition can be reverted by reactivating the pathway downstream of the superoxide-dependent step.

  10. Dietary tryptophan intake and suicide rate in industrialized nations.

    Science.gov (United States)

    Voracek, Martin; Tran, Ulrich S

    2007-03-01

    The objective of this study was to assess the ecological association of dietary tryptophan intake and suicide rates across industrialized nations. Tryptophan, an essential amino acid, is the rate-limiting precursor of serotonin biosynthesis. The serotonergic system has been strongly implicated in the neurobiology of suicide. Contemporary male and female suicide rates for the general population (42 countries) and the elderly (38 countries) were correlated with national estimates of dietary tryptophan intake. Measures of tryptophan intake were significantly negatively associated to national suicide rates. Controlling for national affluence, total alcohol consumption and happiness levels slightly attenuated these associations, but left all of them negative. The effect is an ecological (group-level) finding. Estimated per capita tryptophan supply is only a proxy for actual consumption. Developed nations ranking high in dietary tryptophan intake rank low in suicide rates, independent of national wealth, alcohol intake and happiness.

  11. Tryptophan and kynurenine determination in human hair by liquid chromatography.

    Science.gov (United States)

    Dario, Michelli F; Freire, Thamires Batello; Pinto, Claudinéia Aparecida Sales de Oliveira; Prado, María Segunda Aurora; Baby, André R; Velasco, Maria Valéria R

    2017-09-18

    Tryptophan, an amino acid found in hair proteinaceous structure is used as a marker of hair photodegradation. Also, protein loss caused by several chemical/physical treatments can be inferred by tryptophan quantification. Kynurenine is a photo-oxidation product of tryptophan, expected to be detected when hair is exposed mainly to UVB (290-320nm) radiation range. Tryptophan from hair is usually quantified directly as a solid or after alkaline hydrolysis, spectrofluorimetrically. However, these types of measure are not sufficiently specific and present several interfering substances. Thus, this work aimed to propose a quantification method for both tryptophan and kynurenine in hair samples, after alkali hydrolysis process, by using high-performance liquid chromatography (HPLC) with fluorimetric and UV detection. The tryptophan and kynurenine quantification method was developed and validated. Black, white, bleached and dyed (blond and auburn) hair tresses were used in this study. Tryptophan and kynurenine were separated within ∼9min by HPLC. Both black and white virgin hair samples presented similar concentrations of tryptophan, while bleaching caused a reduction in the tryptophan content as well as dyeing process. Unexpectedly, UV/vis radiation did not promote significantly the conversion of tryptophan into its photo-oxidation product and consequently, kynurenine was not detected. Thus, this works presented an acceptable method for quantification of tryptophan and its photooxidation metabolite kynurenine in hair samples. Also, the results indicated that bleaching and dyeing processes promoted protein/amino acids loss but tryptophan is not extensively degraded in human hair by solar radiation. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Plasma L-Tryptophan Levels, Subjective Sleepiness and Daytime Sleep.

    Science.gov (United States)

    1980-09-01

    hydroxylase enzyme at the first step in the serotonin synthetic pathway is not saturated (Friedman et al, 1972). The availability of the amino acid...changes in rats after parachloro- phenylalanine (PCPA). Wyatt’s work (Wyatt et al, 1970) showing 1-tryptophan effects on sleep in subjects pretreated with...tryptophan hydroxylase in midbrain of the rat. Science 166: 1274-76. Brezinova, V., Loudon, J., and Oswald, I. 1972. Tryptophan and sleep. Lancet 2: 1086-87

  13. The High-Risk Human Papillomavirus E6 Oncogene Exacerbates the Negative Effect of Tryptophan Starvation on the Development of Chlamydia trachomatis

    Science.gov (United States)

    Sherchand, Shardulendra P.; Ibana, Joyce A.; Zea, Arnold H.; Quayle, Alison J.; Aiyar, Ashok

    2016-01-01

    Chlamydia trachomatis is an obligate intracellular pathogen that requires specific essential nutrients from the host cell, one of which is the amino acid tryptophan. In this context interferon gamma (IFNγ) is the major host protective cytokine against chlamydial infections because it induces the expression of the host enzyme, indoleamine 2,3-dioxygenase 1, that degrades tryptophan, thereby restricting bacterial replication. The mechanism by which IFNγ acts has been dissected in vitro using epithelial cell-lines such as HeLa, HEp-2, or the primary-like endocervical cell-line A2EN. All these cell-lines express the high-risk human papillomavirus oncogenes E6 & E7. While screening cell-lines to identify those suitable for C. trachomatis co-infections with other genital pathogens, we unexpectedly found that tryptophan starvation did not completely block chlamydial development in cell-lines that were HR-HPV negative, such as C33A and 293. Therefore, we tested the hypothesis that HR-HPV oncogenes modulate the effect of tryptophan starvation on chlamydial development by comparing chlamydial development in HeLa and C33A cell-lines that were both derived from cervical carcinomas. Our results indicate that during tryptophan depletion, unlike HeLa, C33A cells generate sufficient intracellular tryptophan via proteasomal activity to permit C. trachomatis replication. By generating stable derivatives of C33A that expressed HPV16 E6, E7 or E6 & E7, we found that E6 expression alone was sufficient to convert C33A cells to behave like HeLa during tryptophan starvation. The reduced tryptophan levels in HeLa cells have a biological consequence; akin to the previously described effect of IFNγ, tryptophan starvation protects C. trachomatis from clearance by doxycycline in HeLa but not C33A cells. Curiously, when compared to the known Homo sapiens proteome, the representation of tryptophan in the HR-HPV E6 & E6AP degradome is substantially lower, possibly providing a mechanism that

  14. Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study

    NARCIS (Netherlands)

    The, G.K.H.; Verkes, R.J.; Fekkes, D.; Bleijenberg, G.; Meer, J.W. van der; Buitelaar, J.K.

    2014-01-01

    BACKGROUND: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare.A somatic explanation for the fatigue is lacking. There is clinical and experimental evidence

  15. Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study

    NARCIS (Netherlands)

    G.K.H. The (Gerard K.H.); R.J. Verkes (Robbert); D. Fekkes (Durk); G. Bleijenberg (G.); J.W.M. van der Meer (Jos); J.K. Buitelaar (Jan)

    2014-01-01

    textabstractBackground: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare. A somatic explanation for the fatigue is lacking. There is clinical and experimen

  16. Intrinsic Depletion or Not

    DEFF Research Database (Denmark)

    Klösgen, Beate; Bruun, Sara; Hansen, Søren;

      The presence of a depletion layer of water along extended hydrophobic interfaces, and a possibly related formation of nanobubbles, is an ongoing discussion. The phenomenon was initially reported when we, years ago, chose thick films (~300-400Å) of polystyrene as cushions between a crystalline...... giving rise to depletion layers, and the mechanisms and border conditions that control their presence and extension require still clarification. Recently, careful systematic reflectivity experiments were re-done on the same system. No depletion layers were found, and it was conjectured that the whole...

  17. Development of Bacillus subtilis mutants to produce tryptophan in pigs

    DEFF Research Database (Denmark)

    Bjerre, Karin; Cantor, Mette D.; Nørgaard, Jan Værum

    2017-01-01

    Objectives To generate tryptophan-overproducing Bacillus subtilis strains for in situ use in pigs, to reduce the feed cost for farmers and nitrogen pollution. Results A novel concept has been investigated—to generate B. subtilis strains able to produce tryptophan (Trp) in situ in pigs. Mutagenesis...

  18. Tryptophan analogues. 1. Synthesis and antihypertensive activity of positional isomers.

    Science.gov (United States)

    Safdy, M E; Kurchacova, E; Schut, R N; Vidrio, H; Hong, E

    1982-06-01

    A series of tryptophan analogues having the carboxyl function at the beta-position was synthesized and tested for antihypertensive activity. The 5-methoxy analogue 46 exhibited antihypertensive activity in the rat via the oral route and was much more potent than the normal tryptophan analogue. The methyl ester was found to be a critical structural feature for activity.

  19. 2-Methyl-L-tryptophan is a substrate of tryptophanase.

    Science.gov (United States)

    Faleev, N G; Gogoleva, O I; Dementieva, I S; Zakomirdina, L N; Belikov, V M

    1995-04-01

    Tryptophanase was generally considered to be inactive towards tryptophan derivatives substituted at 2-position of the indole ring. We have shown that cells containing tryptophanase catalyze the formation of 2-methyl-L-tryptophan from 2-methylindole and L-serine, and from 2-methylindole, pyruvate and ammonium ion. The kinetics of pyruvate formation from 2-methyl-L-tryptophan and its alpha-deuterated analogue catalyzed by homogeneous tryptophanase were examined. The primary deuterium isotope effect (kH/kD = 4.0) as well as the absorption spectrum of tryptophanase complex with 2-methyl-L-tryptophan indicate that the rate of enzymatic reaction of 2-methyl-L-tryptophan is in a considerable degree determined by the stage of removal of alpha-proton.

  20. Addressing Ozone Layer Depletion

    Science.gov (United States)

    Access information on EPA's efforts to address ozone layer depletion through regulations, collaborations with stakeholders, international treaties, partnerships with the private sector, and enforcement actions under Title VI of the Clean Air Act.

  1. Characterisation of the tryptophan synthase alpha subunit in maize

    Directory of Open Access Journals (Sweden)

    Gierl Alfons

    2008-04-01

    Full Text Available Abstract Background In bacteria, such as Salmonella typhimurium, tryptophan is synthesized from indole-3-glycerole phosphate (IGP by a tryptophan synthase αββα heterotetramer. Plants have evolved multiple α (TSA and β (TSB homologs, which have probably diverged in biological function and their ability of subunit interaction. There is some evidence for a tryptophan synthase (TS complex in Arabidopsis. On the other hand maize (Zea mays expresses the TSA-homologs BX1 and IGL that efficiently cleave IGP, independent of interaction with TSB. Results In order to clarify, how tryptophan is synthesized in maize, two TSA homologs, hitherto uncharacterized ZmTSA and ZmTSAlike, were functionally analyzed. ZmTSA is localized in plastids, the major site of tryptophan biosynthesis in plants. It catalyzes the tryptophan synthase α-reaction (cleavage of IGP, and forms a tryptophan synthase complex with ZmTSB1 in vitro. The catalytic efficiency of the α-reaction is strongly enhanced upon complex formation. A 160 kD tryptophan synthase complex was partially purified from maize leaves and ZmTSA was identified as native α-subunit of this complex by mass spectrometry. ZmTSAlike, for which no in vitro activity was detected, is localized in the cytosol. ZmTSAlike, BX1, and IGL were not detectable in the native tryptophan synthase complex in leaves. Conclusion It was demonstrated in vivo and in vitro that maize forms a tryptophan synthase complex and ZmTSA functions as α-subunit in this complex.

  2. Destabilization of artificial biomembrane induced by the penetration of tryptophan

    Energy Technology Data Exchange (ETDEWEB)

    Chen Liuhua [Department of Chemistry, Tongji University, Shanghai 200092 (China); Gan Lihua, E-mail: ganlh@tongji.edu.cn [Department of Chemistry, Tongji University, Shanghai 200092 (China); Liu Mingxian; Fan Rong; Xu Zijie; Hao Zhixian; Chen Longwu [Department of Chemistry, Tongji University, Shanghai 200092 (China)

    2011-03-15

    The effect of tryptophan on the membrane stability was studied by using three artificial biological membranes including liposome, Langmuir monolayer and solid supported bilayer lipid membrane (s-BLM) as models. All the results indicate that the penetration of tryptophan can destabilize different artificial biological membranes. The diameter of liposome and the leakage of calcein from liposome increased with the increase of tryptophan concentration because the penetration of tryptophan was beneficial for dehydrating the polar head groups of lipids and the formation of fusion intermediates. {pi}-A isotherms of lecithin on the subphase of tryptophan solution further confirm that tryptophan can penetrate into lipid monolayer and reduce the stability of lipid monolayer. When the concentration of tryptophan increased from 0 to 2 x 10{sup -3} mol L{sup -1}, the limiting molecular area of lecithin increased from 110.5 to 138.5 A{sup 2}, but the collapse pressure of the monolayer decreased from 47.6 to 42.3 mN m{sup -1}, indicating the destabilization of lipid monolayer caused by the penetration of tryptophan. The resistance spectra of s-BLM demonstrate that the existence of tryptophan leads to the formation of some defects in s-BLM and the destabilization of s-BLM. The values of electron-transfer resistance and double layer capacitance respectively decreased from 5.765 x 10{sup 6} {Omega} and 3.573 x 10{sup -8} F to 1.391 x 10{sup 6} {Omega} and 3.340 x 10{sup -8} F when the concentration of tryptophan increased from 0 to 2 x 10{sup -3} mol L{sup -1}. Correspondingly, the breakdown voltage of s-BLM decreased from 2.51 to 1.72 V.

  3. Tryptophan and tryptophan-like substances in cloud water: Occurrence and photochemical fate

    Science.gov (United States)

    Bianco, Angelica; Passananti, Monica; Deguillaume, Laurent; Mailhot, Gilles; Brigante, Marcello

    2016-07-01

    This work investigates the occurrence and photochemical behaviour of tryptophan (TRP) in the cloud aqueous phase. The concentrations of tryptophan, TRYptophan LIke Substances (TRYLIS) and HUmic LIke Substances (HULIS) in real cloud water, collected between October 2013 and November 2014 at the top of the puy de Dôme station, were determined using the Excitation-Emission-Matrix (EEM) technique. The amount of free and complexed tryptophan (TRP) up to 10-7 M in cloud aqueous phase was quantified by HPLC-UV-fluorescence analysis, and its photoreactivity under sun-simulated conditions was investigated in synthetic water samples mimicking cloud aqueous phase compositions (oceanic and continental origins). TRP undergoes direct photolysis, and its degradation is enhanced in the presence of naturally occurring species able to photo-generate hydroxyl radicals (HOrad). The polychromatic quantum yield of TRP (ϕ290-340 nm TRP) is estimated to be 8.37 × 10-4 between 290 and 340 nm, corresponding to the degradation rate (RTRPd) of 1.29 × 10-11 M s-1 under our irradiation conditions. The degradation is accelerated up to 3.65 × 10-10 and 8.26 × 10-10 M s-1 in synthetic oceanic and continental cloud water samples doped with 100 μM hydrogen peroxide, respectively. Hydroxyl radical-mediated transformation leads to the generation of different functionalized and oxidized products, as well as small carboxylic acids, such as formate and acetate. Moreover, fluorescent signals of irradiated solutions indicate the formation of HULIS.

  4. A mathematical model of tryptophan metabolism via the kynurenine pathway provides insights into the effects of vitamin B-6 deficiency, tryptophan loading, and induction of tryptophan 2,3-dioxygenase on tryptophan metabolites.

    Science.gov (United States)

    Rios-Avila, Luisa; Nijhout, H Frederik; Reed, Michael C; Sitren, Harry S; Gregory, Jesse F

    2013-09-01

    Vitamin B-6 deficiency is associated with impaired tryptophan metabolism because of the coenzyme role of pyridoxal 5'-phosphate (PLP) for kynureninase and kynurenine aminotransferase. To investigate the underlying mechanism, we developed a mathematical model of tryptophan metabolism via the kynurenine pathway. The model includes mammalian data on enzyme kinetics and tryptophan transport from the intestinal lumen to liver, muscle, and brain. Regulatory mechanisms and inhibition of relevant enzymes were included. We simulated the effects of graded reduction in cellular PLP concentration, tryptophan loads and induction of tryptophan 2,3-dioxygenase (TDO) on metabolite profiles and urinary excretion. The model predictions matched experimental data and provided clarification of the response of metabolites in various extents of vitamin B-6 deficiency. We found that moderate deficiency yielded increased 3-hydroxykynurenine and a decrease in kynurenic acid and anthranilic acid. More severe deficiency also yielded an increase in kynurenine and xanthurenic acid and more pronounced effects on the other metabolites. Tryptophan load simulations with and without vitamin B-6 deficiency showed altered metabolite concentrations consistent with published data. Induction of TDO caused an increase in all metabolites, and TDO induction together with a simulated vitamin B-6 deficiency, as has been reported in oral contraceptive users, yielded increases in kynurenine, 3-hydroxykynurenine, and xanthurenic acid and decreases in kynurenic acid and anthranilic acid. These results show that the model successfully simulated tryptophan metabolism via the kynurenine pathway and can be used to complement experimental investigations.

  5. Tryptophan degradation and neopterin levels in treated rheumatoid arthritis patients.

    Science.gov (United States)

    Ozkan, Yesim; Mete, Guray; Sepici-Dincel, Aylin; Sepici, Vesile; Simsek, Bolkan

    2012-01-01

    Increased kynurenine/tryptophan-reflects trytophan degradation-and neopterin levels have been regarded as a biochemical marker of cell-mediated immune response and inflammation. This study was designed to evaluate the usefulness of tryptophan degradation and neopterin levels in active rheumatoid arthritis patients under therapy. In this case-control study, kynurenine and tryptophan levels were determined by HPLC; neopterin and tumor necrosis factor-α levels were measured with ELISA in 32 active rheumatoid arthritis patients and 20 healthy controls. Although mean values of tryptophan, kynurenine, ratio of kynurenine to tryptophan, neopterin, and tumor necrosis factor-α levels did not show statistically significant differences between patient and control groups, neopterin levels correlated positively with kynurenine (r = 0.582, p < 0.02), kynurenine/tryptophan (r = 0.486, p < 0.05), erythrocyte sedimentation rate (r = 0.472, p < 0.05) and RF (r = 0.478, p < 0.05) in the rheumatoid arthritis group. CRP levels of the patient group correlated with kynurenine levels (r = 0.524, p < 0.03). Determination of tryptophan degradation and neopterin levels in chronic inflammatory disease may provide a better understanding of progression of the disease.

  6. Exploring the mechanism of tryptophan 2,3-dioxygenase

    Science.gov (United States)

    Thackray, Sarah J.; Mowat, Christopher G.; Chapman, Stephen K.

    2008-01-01

    The haem proteins TDO (tryptophan 2,3-dioxygenase) and IDO (indoleamine 2,3-dioxygenase) are specific and powerful oxidation catalysts that insert one molecule of dioxygen into L-tryptophan in the first and rate-limiting step in the kynurenine pathway. Recent crystallographic and biochemical analyses of TDO and IDO have greatly aided our understanding of the mechanisms employed by these enzymes in the binding and activation of dioxygen and tryptophan. In the present paper, we briefly discuss the function, structure and possible catalytic mechanism of these enzymes. PMID:19021508

  7. Metabolism and serum levels of tryptophan in senile cataract patients.

    Science.gov (United States)

    Costa, C; Angi, M R; De Carli, M; Vanzan, S; Allegri, G

    1982-03-30

    In order to clarify the role of tryptophan in the patogenesis of senile cataract, we have studied the serum total and free levels of tryptophan in cataract patients as compared with age and sex-matched controls, and the urinary excretion of 10 metabolites after oral load of the amino acid. This excretion increases in the cataract group both as total per cent and as kynurenine. No difference has been found in the free and total serum tryptophan between normal subjects and cataract patients. A possible role of the kynurenines in the pathogenesis of senile cataract is suggested.

  8. Intrinsic Depletion or Not

    DEFF Research Database (Denmark)

    Klösgen, Beate; Bruun, Sara; Hansen, Søren;

    with an AFM (2).    The intuitive explanation for the depletion based on "hydrophobic mismatch" between the obviously hydrophilic bulk phase of water next to the hydrophobic polymer. It would thus be an intrinsic property of all interfaces between non-matching materials. The detailed physical interaction path......  The presence of a depletion layer of water along extended hydrophobic interfaces, and a possibly related formation of nanobubbles, is an ongoing discussion. The phenomenon was initially reported when we, years ago, chose thick films (~300-400Å) of polystyrene as cushions between a crystalline...

  9. Shear-affected depletion interaction

    NARCIS (Netherlands)

    July, C.; Kleshchanok, D.; Lang, P.R.

    2012-01-01

    We investigate the influence of flow fields on the strength of the depletion interaction caused by disc-shaped depletants. At low mass concentration of discs, it is possible to continuously decrease the depth of the depletion potential by increasing the applied shear rate until the depletion force i

  10. protein, tryptophan and lysine contents in quality protien maize ...

    African Journals Online (AJOL)

    owner

    for human nutrition recommended by Food and Agriculture Organization in ... METHODS: The protein, tryptophan and lysine contents of improved ... This study revealed the fact that genetic factor influences the protein, ... Ethiop J Health Sci.

  11. Micro-environmental influences on the fluorescence of tryptophan

    Science.gov (United States)

    Sun, Feng; Zong, Wansong; Liu, Rutao; Chai, Jun; Liu, Ying

    2010-07-01

    The fluorescence characteristics of protein molecules are mainly due to their tryptophan (Trp), tyrosine (Tyr) and phenylalanine (Phe) residues, among which tryptophan is the most important. Studying the influence of the micro-environment on tryptophan fluorescence can give us direct and convincing evidence for changes of protein structure and function. In this paper, fluorescence spectroscopy was used to evaluate the changes of tryptophan fluorescence under a variety of micro-environmental conditions (temperature, pH, polarity, presence of surfactants and oxidants) and the mechanisms responsible. This study not only presents more direct evidence to explain how and why the protein fluorescence spectra change, but also provides a new method for analyzing the effect of environmental changes on protein function.

  12. Tryptophan rich diet as a new approach to study the serotoninergic enteropancreatic axis.

    OpenAIRE

    Goke, B.; Richter, G; Keim, V; Arnold, R

    1987-01-01

    The influence of a tryptophan enriched diet (L-tryptophan added as 1% of total diet), fed over 10 days, on the rat duodenum and pancreas was studied by immunohistology, measurements of serotonin and tryptophan tissue concentrations by HPLC, and incubations of pancreatic lobules. Ingestion of a tryptophan enriched diet resulted in increased contents of tryptophan and serotonin in the duodenum that was not accompanied by a significant change of the serotonin cell density. Neither basal nor CCK-...

  13. Tryptophan degradation in women with breast cancer: a pilot study

    Directory of Open Access Journals (Sweden)

    Schubert Christine M

    2011-05-01

    Full Text Available Abstract Background Altered tryptophan metabolism and indoleamine 2,3-dioxygenase activity are linked to cancer development and progression. In addition, these biological factors have been associated with the development and severity of neuropsychiatric syndromes, including major depressive disorder. However, this biological mechanism associated with both poor disease outcomes and adverse neuropsychiatric symptoms has received little attention in women with breast cancer. Therefore, a pilot study was undertaken to compare levels of tryptophan and other proteins involved in tryptophan degradation in women with breast cancer to women without cancer, and secondarily, to examine levels in women with breast caner over the course of chemotherapy. Findings Blood samples were collected from women with a recent diagnosis of breast cancer (n = 33 before their first cycle of chemotherapy and after their last cycle of chemotherapy. The comparison group (n = 24 provided a blood sample prior to breast biopsy. Plasma concentrations of tryptophan, kynurenine, and tyrosine were determined. The kynurenine to tryptophan ratio (KYN/TRP was used to estimate indoleamine 2,3-dioxygenase activity. On average, the women with breast cancer had lower levels of tryptophan, elevated levels of kynurenine and tyrosine and an increased KYN/TRP ratio compared to women without breast cancer. There was a statistically significant difference between the two groups in the KYN/TRP ratio (p = 0.036, which remained elevated in women with breast cancer throughout the treatment trajectory. Conclusions The findings of this pilot study suggest that increased tryptophan degradation may occur in women with early-stage breast cancer. Given the multifactorial consequences of increased tryptophan degradation in cancer outcomes and neuropsychiatric symptom manifestation, this biological mechanism deserves broader attention in women with breast cancer.

  14. Plasma tryptophan concentration in depressive illness and mania.

    Science.gov (United States)

    Peet, M; Moody, J P; Worrall, E P; Walker, P; Naylor, G J

    1976-03-01

    Total and free plasma trytophan levels were measured in depressive and manic patients before and after recovery. No change was found in total or free plasma trytophan concentration on recovery from depressive illness. Free plasma tryptophan levels were higher in recovered manics than in active manics, and a group of four manic patients tested before and after recovery showed a significant increase in free plasma tryptophan concentration on recovery.

  15. Efficient Asymmetric Synthesis of Tryptophan Analogues Having Useful Photophysical Properties

    Science.gov (United States)

    Talukder, Poulami; Chen, Shengxi; Arce, Pablo M.

    2014-01-01

    Two new fluorescent probes of protein structure and dynamics have been prepared by concise asymmetric syntheses using the Schöllkopf chiral auxiliary. The site-specific incorporation of one probe into dihydrofolate reductase is reported. The utility of these tryptophan derivatives lies in their absorption and emission maxima which differ from those of tryptophan, as well as in their large Stokes shifts and high molar absorptivities. PMID:24392870

  16. Kernel modifications and tryptophan content in QPM segregating generations

    Directory of Open Access Journals (Sweden)

    -Ignjatović-Micić Dragana

    2010-01-01

    Full Text Available Maize has poor nutritional value due to deficiency of two essential amino acids - tryptophan and lysine. Although recessive opaque2 (o2 mutation significantly increases their content in the endosperm, incorporation of opaque2 into high yielding cultivars was not commercially successful, because of its numerous agronomic and processing problems due to soft endosperm. Quality protein maize - QPM has lately been introduced as opaque2 maize with improved endosperm hardness and improved agronomic traits, but mostly within tropical and subtropical germplasm. The ongoing breeding project at MRI includes improvement of MRI opaque2 lines and conversion of standard lines to QPM germplasm. The main selection steps in QPM breeding involve assessing kernel modifications and tryptophan level in each generation. Herein, we present the results of the analysis for these traits on F3 and BC1F1 generations of QPM x opaque2, opaque2 x QPM and standard lines x QPM crosses. The results showed that the majority the genotypes had kernel types 2 and 3 (good modifications. The whole grain tryptophan content in F3 and BC1F1 genotypes of crosses between QPM and opaque2 germplasm was at the quality protein level, with a few exceptions. All BC1F1 genotypes of standard lines x QPM had tryptophan content in the range of normal maize, while majority of F3 genotypes had tryptophan content at level of QPM. The progeny (with increased tryptophan levels of QPM and opaque2 crosses had significantly higher tryptophan content compared to the progeny of crosses between standard and QPM lines - 0.098 to 0.114 and 0.080, respectively. All genotypes that had poorly modified kernels and/or low tryptophan content will be discarded from further breeding.

  17. Utilization of DL- and L-tryptophan in young pigs

    NARCIS (Netherlands)

    Schutte, J.B.; Van Weerden, E.J.; Koch, F.

    1988-01-01

    Two trials involving young pigs (total numbers 288 and 400, respectively) were performed to compare the biological activity of Dl- and L-tryptophan under restricted (trial 1) and ad libitum (trial 2) feeding conditions. In trial 1, three additions of Dl-tryptophan (0·3, 0·6 and 0·9 g/kg) and two

  18. Flavin-dependent Tryptophan Halogenases and Their Use in Formation of Novel Tryptophan Derived Compounds

    Institute of Scientific and Technical Information of China (English)

    CHEN Xian-Ping; HUANG Mei-Fa; WANG Bin

    2008-01-01

    Ravin-dependent halogenases are now known to play a significant role in the introduction of chloride and bro- mide into activated organic molecules. Herein a new strategy was reported to formate monodechloroaminopyrrolni-trin derivative 3-(2-amino-4-chlorophenyl)pyrrole, which is a key intermediate for the analysis and mutagenesis of pyrrolnitrin biosynthesis, by combinatorial biosynthesis using regioselective tryptophan halogenases. The successful production in Pseudomonas, with combinatorial cultivating method, demonstrates the feasibility of the new ap-proach to modify and analyze these important secondary metabolite pathways.

  19. Differential effects of L-tryptophan and L-leucine administration on brain resting state functional networks and plasma hormone levels

    Science.gov (United States)

    Zanchi, Davide; Meyer-Gerspach, Anne Christin; Suenderhauf, Claudia; Janach, Katharina; le Roux, Carel W.; Haller, Sven; Drewe, Jürgen; Beglinger, Christoph; Wölnerhanssen, Bettina K.; Borgwardt, Stefan

    2016-01-01

    Depending on their protein content, single meals can rapidly influence the uptake of amino acids into the brain and thereby modify brain functions. The current study investigates the effects of two different amino acids on the human gut-brain system, using a multimodal approach, integrating physiological and neuroimaging data. In a randomized, placebo-controlled trial, L-tryptophan, L-leucine, glucose and water were administered directly into the gut of 20 healthy subjects. Functional MRI (fMRI) in a resting state paradigm (RS), combined with the assessment of insulin and glucose blood concentration, was performed before and after treatment. Independent component analysis with dual regression technique was applied to RS-fMRI data. Results were corrected for multiple comparisons. In comparison to glucose and water, L-tryptophan consistently modifies the connectivity of the cingulate cortex in the default mode network, of the insula in the saliency network and of the sensory cortex in the somatosensory network. L-leucine has lesser effects on these functional networks. L-tryptophan and L-leucine also modified plasma insulin concentration. Finally, significant correlations were found between brain modifications after L-tryptophan administration and insulin plasma levels. This study shows that acute L-tryptophan and L-leucine intake directly influence the brain networks underpinning the food-reward system and appetite regulation. PMID:27760995

  20. The tryptophan aminotransferase Tam1 catalyses the single biosynthetic step for tryptophan-dependent pigment synthesis in Ustilago maydis.

    Science.gov (United States)

    Zuther, Katja; Mayser, Peter; Hettwer, Ursula; Wu, Wenying; Spiteller, Peter; Kindler, Bernhard L J; Karlovsky, Petr; Basse, Christoph W; Schirawski, Jan

    2008-04-01

    Tryptophan is a precursor for many biologically active secondary metabolites. We have investigated the origin of indole pigments first described in the pityriasis versicolor-associated fungus Malassezia furfur. Some of the identified indole pigments have properties potentially explaining characteristics of the disease. As M. furfur is not amenable to genetic manipulation, we used Ustilago maydis to investigate the pathway leading to pigment production from tryptophan. We show by high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance analysis that the compounds produced by U. maydis include those putatively involved in the etiology of pityriasis versicolor. Using a reverse genetics approach, we demonstrate that the tryptophan aminotransferase Tam1 catalyses pigment biosynthesis by conversion of tryptophan into indolepyruvate. A forward genetics approach led to the identification of mutants incapable of producing the pigments. These mutants were affected in the sir1 gene, presumably encoding a sulphite reductase. In vitro experiments with purified Tam1 showed that 2-oxo 4-methylthio butanoate serves as a substrate linking tryptophan deamination to sulphur metabolism. We provide the first direct evidence that these indole pigments form spontaneously from indolepyruvate and tryptophan without any enzymatic activity. This suggests that compounds with a proposed function in M. furfur-associated disease consist of indolepyruvate-derived spontaneously generated metabolic by-products.

  1. Depletion of intense fields

    CERN Document Server

    Seipt, D; Marklund, M; Bulanov, S S

    2016-01-01

    The interaction of charged particles and photons with intense electromagnetic fields gives rise to multi-photon Compton and Breit-Wheeler processes. These are usually described in the framework of the external field approximation, where the electromagnetic field is assumed to have infinite energy. However, the multi-photon nature of these processes implies the absorption of a significant number of photons, which scales as the external field amplitude cubed. As a result, the interaction of a highly charged electron bunch with an intense laser pulse can lead to significant depletion of the laser pulse energy, thus rendering the external field approximation invalid. We provide relevant estimates for this depletion and find it to become important in the interaction between fields of amplitude $a_0 \\sim 10^3$ and electron bunches with charges of the order of nC.

  2. Learning about ozone depletion

    Energy Technology Data Exchange (ETDEWEB)

    Crutzen, J. P. [Department of Atmospheric Chemistry, Max Planck Institute for Chemistry, Mainz, Germany; Oppenheimer M. [Woodrow Wilson School of Public and International Affairs, Department of Geosciences, Princeton University, Princeton, NJ (United States)

    2008-07-15

    Stratospheric ozone depletion has been much studied as a case history in the interaction between environmental science and environmental policy. The positive influence of science on policy is often underscored, but here we review the photochemistry of ozone in order to illustrate how scientific learning has the potential to mislead policy makers. The latter may occur particularly in circumstances where limited observations are combined with simplified models of a complex system, such as may generally occur in the global change arena. Even for the well-studied case of ozone depletion, further research is needed on the dynamics of scientific learning, particularly the scientific assessment process, and how assessments influence the development of public policy.

  3. Depletion of Intense Fields

    Science.gov (United States)

    Seipt, D.; Heinzl, T.; Marklund, M.; Bulanov, S. S.

    2017-04-01

    The interaction of charged particles and photons with intense electromagnetic fields gives rise to multiphoton Compton and Breit-Wheeler processes. These are usually described in the framework of the external field approximation, where the electromagnetic field is assumed to have infinite energy. However, the multiphoton nature of these processes implies the absorption of a significant number of photons, which scales as the external field amplitude cubed. As a result, the interaction of a highly charged electron bunch with an intense laser pulse can lead to significant depletion of the laser pulse energy, thus rendering the external field approximation invalid. We provide relevant estimates for this depletion and find it to become important in the interaction between fields of amplitude a0˜1 03 and electron bunches with charges of the order of 10 nC.

  4. Kynurenine pathway in psychosis: evidence of increased tryptophan degradation.

    LENUS (Irish Health Repository)

    Barry, Sandra

    2009-05-01

    The kynurenine pathway of tryptophan degradation may serve to integrate disparate abnormalities heretofore identified in research aiming to elucidate the complex aetiopathogenesis of psychotic disorders. Post-mortem brain tissue studies have reported elevated kynurenine and kynurenic acid in the frontal cortex and upregulation of the first step of the pathway in the anterior cingulate cortex of individuals with schizophrenia. In this study, we examined kynurenine pathway activity by measuring tryptophan breakdown, a number of pathway metabolites and interferon gamma (IFN-gamma), which is the preferential activator of the first-step enzyme, indoleamine dioxygenase (IDO), in the plasma of patients with major psychotic disorder. Plasma tryptophan, kynurenine pathway metabolites were measured using high-performance liquid chromatography (HPLC) in 34 patients with a diagnosis on the psychotic spectrum (schizophrenia or schizoaffective disorder) and in 36 healthy control subjects. IFN-gamma was measured using enzyme-linked immunosorbent assay (ELISA). The mean tryptophan breakdown index (kynurenine\\/tryptophan) was significantly higher in the patient group compared with controls (P < 0.05). IFN-gamma measures did not differ between groups (P = 0.23). No relationship was found between measures of psychopathology, symptom severity and activity in the first step in the pathway. A modest correlation was established between the tryptophan breakdown index and illness duration. These results provide evidence for kynurenine pathway upregulation, specifically involving the first enzymatic step, in patients with major psychotic disorder. Increased tryptophan degradation in psychoses may have potential consequences for the treatment of these disorders by informing the development of novel therapeutic compounds.

  5. Decreased tryptophan metabolism in patients with autism spectrum disorders

    Science.gov (United States)

    2013-01-01

    Background Autism spectrum disorders (ASDs) are relatively common neurodevelopmental conditions whose biological basis has been incompletely determined. Several biochemical markers have been associated with ASDs, but there is still no laboratory test for these conditions. Methods We analyzed the metabolic profile of lymphoblastoid cell lines from 137 patients with neurodevelopmental disorders with or without ASDs and 78 normal individuals, using Biolog Phenotype MicroArrays. Results Metabolic profiling of lymphoblastoid cells revealed that the 87 patients with ASD as a clinical feature, as compared to the 78 controls, exhibited on average reduced generation of NADH when tryptophan was the sole energy source. The results correlated with the behavioral traits associated with either syndromal or non-syndromal autism, independent of the genetic background of the individual. The low level of NADH generation in the presence of tryptophan was not observed in cell lines from non-ASD patients with intellectual disability, schizophrenia or conditions exhibiting several similarities with syndromal autism except for the behavioral traits. Analysis of a previous small gene expression study found abnormal levels for some genes involved in tryptophan metabolic pathways in 10 patients. Conclusions Tryptophan is a precursor of important compounds, such as serotonin, quinolinic acid, and kynurenic acid, which are involved in neurodevelopment and synaptogenesis. In addition, quinolinic acid is the structural precursor of NAD+, a critical energy carrier in mitochondria. Also, the serotonin branch of the tryptophan metabolic pathway generates NADH. Lastly, the levels of quinolinic and kynurenic acid are strongly influenced by the activity of the immune system. Therefore, decreased tryptophan metabolism may alter brain development, neuroimmune activity and mitochondrial function. Our finding of decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and

  6. Ozone-depleting Substances (ODS)

    Data.gov (United States)

    U.S. Environmental Protection Agency — This site includes all of the ozone-depleting substances (ODS) recognized by the Montreal Protocol. The data include ozone depletion potentials (ODP), global warming...

  7. Indole-3-Acetic Acid Biosynthesis in the Mutant Maize orange pericarp, a Tryptophan Auxotroph.

    Science.gov (United States)

    Wright, A D; Sampson, M B; Neuffer, M G; Michalczuk, L; Slovin, J P; Cohen, J D

    1991-11-15

    The maize mutant orange pericarp is a tryptophan auxotroph, which results from mutation of two unlinked loci of tryptophan synthase B. This mutant was used to test the hypothesis that tryptophan is the precursor to the plant hormone indole-3-acetic acid (IAA). Total IAA in aseptically grown mutant seedlings was 50 times greater than in normal seedlings. In mutant seedlings grown on media containing stable isotopelabeled precursors, IAA was more enriched than was tryptophan. No incorporation of label into IAA from tryptophan could be detected. These results establish that IAA can be produced de novo without tryptophan as an intermediate.

  8. Determination of tryptophan and tryptophan metabolites in grape must and wine.

    Science.gov (United States)

    Hoenicke, K; Simat, T J; Steinhart, H; Christoph, N; Köhler, H J; Schwab, A

    1999-01-01

    Tryptophan (Trp) and its metabolites, especially indole-3-acetic acid (IAA), are considered as potential precursors of 2-aminoacetophenone (AAP), an aroma compound which causes the "untypical aging off-flavor" (UTA) in Vitis vinifera white wines. In this study RP-HPLC with fluorescence detection was used for the qualitative and quantitative analysis of Trp and Trp-metabolites in 39 grapes, 22 grape musts and 16 wines, to which different viticultural conditions (ripeness, pruning, strip of leaves, soil condition) have been applied. A sensitive and selective determination was achieved after solid phase extraction using an anion exchange material. Only traces of Trp-metabolites could be determined in the examined grapes and grape musts, but their amounts increased significantly during fermentation, whereas the amount of Trp decreased. Different viticultural measures, besides the time of grape harvest, showed no significant influences on the amount of Trp and Trp-metabolites.

  9. Incorporation of tryptophan analogues into the lantibiotic nisin.

    Science.gov (United States)

    Zhou, Liang; Shao, Jinfeng; Li, Qian; van Heel, Auke J; de Vries, Marcel P; Broos, Jaap; Kuipers, Oscar P

    2016-05-01

    Lantibiotics are posttranslationally modified peptides with efficient inhibitory activity against various Gram-positive bacteria. In addition to the original modifications, incorporation of non-canonical amino acids can render new properties and functions to lantibiotics. Nisin is the most studied lantibiotic and contains no tryptophan residues. In this study, a system was constructed to incorporate tryptophan analogues into nisin, which included the modification machinery (NisBTC) and the overexpression of tryptophanyl-tRNA synthetase (TrpRS). Tryptophan and three different tryptophan analogues (5-fluoroTrp (5FW), 5-hydroxyTrp (5HW) and 5-methylTrp (5MeW)) were successfully incorporated at four different positions of nisin (I1W, I4W, M17W and V32W). The incorporation efficiency of tryptophan analogues into mutants I1W, M17W and V32W was over 97 %, while the mutant I4W showed relatively low incorporation efficiency (69-93 %). The variants with 5FW showed relatively higher production yield, while 5MeW-containing variants showed the lowest yield. The dehydration efficiency of serines or threonines was affected by the tryptophan mutants of I4W and V32W. The affinity of the peptides for the cation-ion exchange and reverse phase chromatography columns was significantly reduced when 5HW was incorporated. The antimicrobial activity of IIW and its 5FW analogue both decreased two times compared to that of nisin, while that of its 5HW analogue decreased four times. The 5FW analogue of I4W also showed two times decreased activity than nisin. However, the mutant M17W and its 5HW analogue both showed 32 times reduced activity relative to that of nisin.

  10. Maintenance valine, isoleucine, and tryptophan requirements for poultry.

    Science.gov (United States)

    de Lima, M B; Sakomura, N K; Dorigam, J C P; da Silva, E P; Ferreira, N T; Fernandes, J B K

    2016-04-01

    Poultry maintenance requirements for valine, isoleucine, and tryptophan were measured by nitrogen balance using different unit systems. The nitrogen balance trial lasted 5 d with 48 h of fasting (with roosters receiving only water+sucrose) and the last 72 h for feeding and excreta collection. Forty grams of each diet first-limiting in valine, isoleucine, or tryptophan was fed by tube each day (3 d) to give a range of intakes from 0 to 101, 0 to 119, and 0 to 34 mg/kg BW d of valine, isoleucine, and tryptophan, respectively. A nitrogen-free diet containing energy, vitamins, and minerals, meeting the rooster requirements, was offered ad libitum during these three d. To confirm that the amino acids studied were limiting, a treatment was added with a control diet formulated by adding 0.24 g/kg of L-valine, 0.21 g/kg of L-isoleucine, and 0.10 g/kg of L-tryptophan to the diets with lower amino acid level. Excreta were collected during the last 3 d of the balance period and the nitrogen content of the excreta was analyzed. For each amino acid, a linear regression between nitrogen retention (NR) and amino acid intake was performed. The equations from linear regression were: NR=-98.6 (±10.1)+2.4 (±0.2)×Val, NR=-46.9 (±7.1)+2.3 (±0.1)×Ile, NR=-39.5 (±7.7)+7.3 (±0.4)×Trp; where Val, Ile, and Trp are the intakes of valine, isoleucine, and tryptophan in mg/kg body weight per d, respectively. The valine, isoleucine, and tryptophan required to maintain the body at zero NR were calculated to be 41, 20, and 5 mg/kg body weight per d, respectively. For the system unit mg per kg of metabolic weight, the intake of valine, isoleucine, and tryptophan was 59, 32, and 9, respectively. Considering the degree of maturity of the animal and body protein content (BPm (0.73)×u), the amounts of valine, isoleucine, and tryptophan required for maintenance were calculated to be 247, 134, and 37 mg per unit of maintenance protein (BPm (0.73)×u) per d. Maintenance requirement is more

  11. Heme-containing dioxygenases involved in tryptophan oxidation.

    Science.gov (United States)

    Millett, Elizabeth S; Efimov, Igor; Basran, Jaswir; Handa, Sandeep; Mowat, Christopher G; Raven, Emma Lloyd

    2012-04-01

    Heme iron is often used in biology for activation of oxygen. The mechanisms of oxygen activation by heme-containing monooxygenases (the cytochrome P450s) are well known, and involve formation of a Compound I species, but information on the heme-containing dioxygenase enzymes involved in tryptophan oxidation lags far behind. In this review, we gather together information emerging recently from structural, mechanistic, spectroscopic, and computational approaches on the heme dioxygenase enzymes involved in tryptophan oxidation. We explore the subtleties that differentiate various heme enzymes from each other, and use this to piece together a developing picture for oxygen activation in this particular class of heme-containing dioxygenases.

  12. Dynamic behavior in mathematical models of the tryptophan operon

    Science.gov (United States)

    Santillán, Moisés; Mackey, Michael C.

    2001-03-01

    This paper surveys the general theory of operon regulation as first formulated by Goodwin and Griffith, and then goes on to consider in detail models of regulation of tryptophan production by Bliss, Sinha, and Santillán and Mackey, and the interrelationships between them. We further give a linear stability analysis of the Santillán and Mackey model for wild type E. coli as well as three different mutant strains that have been previously studied in the literature. This stability analysis indicates that the tryptophan production systems should be stable, which is in accord with our numerical results.

  13. Role of brain tryptophan and serotonin in secondary anorexia.

    Science.gov (United States)

    Rossi-Fanelli, Filippo; Laviano, Alessandro

    2003-01-01

    Anorexia and reduced energy intake contribute to worsen the prognosis of patients suffering from a number of chronic diseases, by promoting skeletal muscle wasting, leading to the development of malnutrition and eventually cachexia. The pathogenesis of cancer anorexia is still matter of debate. Many possible mediators, including hormones, peptides, and neurotransmitters, appear to be involved. However, consistent animal and clinical data suggest that brain tryptophan and serotonin may represent a common final pathway shared by many contributing factors. Supporting this hypothesis, recent data showed that the manipulation of brain tryptophan availability ameliorates anorexia and food intake in cancer patients.

  14. Phasor approaches simplify the analysis of tryptophan fluorescence data in protein denaturation studies

    NARCIS (Netherlands)

    Bader, A.N.; Visser, N.V.; Amerongen, van H.; Visser, A.J.W.G.

    2014-01-01

    The intrinsic fluorescence of tryptophan is frequently used to investigate the structure of proteins. The analysis of tryptophan fluorescence data is challenging: fluorescence (anisotropy) decays typically have multiple lifetime (correlation time) components and fluorescence spectra are broad and ex

  15. Metabolomic profiling of permethrin-treated Drosophila melanogaster identifies a role for tryptophan catabolism in insecticide survival.

    Science.gov (United States)

    Brinzer, Robert A; Henderson, Louise; Marchiondo, Alan A; Woods, Debra J; Davies, Shireen A; Dow, Julian A T

    2015-12-01

    Insecticides and associated synergists are rapidly losing efficacy in target insect pest populations making the discovery of alternatives a priority. To discover novel targets for permethrin synergists, metabolomics was performed on permethrin-treated Drosophila melanogaster. Changes were observed in several metabolic pathways including those for amino acids, glycogen, glycolysis, energy, nitrogen, NAD(+), purine, pyrimidine, lipids and carnitine. Markers for acidosis, ammonia stress, oxidative stress and detoxification responses were also observed. Many of these changes had not been previously characterized after permethrin exposure. From the altered pathways, tryptophan catabolism was selected for further investigation. The knockdown of some tryptophan catabolism genes (vermilion, cinnabar and CG6950) in the whole fly and in specific tissues including fat body, midgut and Malpighian tubules using targeted RNAi resulted in altered survival phenotypes against acute topical permethrin exposure. The knockdown of vermilion, cinnabar and CG6950 in the whole fly also altered survival phenotypes against chronic oral permethrin, fenvalerate, DDT, chlorpyriphos and hydramethylnon exposure. Thus tryptophan catabolism has a previously uncharacterized role in defence against insecticides, and shows that metabolomics is a powerful tool for target identification in pesticide research.

  16. Ozone Depletion by Hydrofluorocarbons

    Science.gov (United States)

    Hurwitz, M.; Fleming, E. L.; Newman, P. A.; Li, F.; Mlawer, E. J.; Cady-Pereira, K. E.; Bailey, R.

    2015-12-01

    Hydrofluorocarbons (HFCs) are second-generation replacements for the chlorofluorocarbons (CFCs), halons and other substances that caused the 'ozone hole'. Atmospheric concentrations of HFCs are projected to increase dramatically in the coming decades. Coupled chemistry-climate simulations forced by these projections show that HFCs will impact the global atmosphere in 2050. As strong radiative forcers, HFCs modulate atmospheric temperature, thereby changing ozone-destroying catalytic cycles and enhancing the stratospheric circulation. These changes lead to a weak depletion of stratospheric ozone. Sensitivity simulations with the NASA Goddard Space Flight Center (GSFC) 2D model show that HFC-125 is the most important contributor to atmospheric change in 2050, as compared with HFC-23, HFC-32, HFC-134a and HFC-143a. Incorporating the interactions between chemistry, radiation and dynamics, for a likely 2050 climate, ozone depletion potentials (ODPs) for HFCs range from 4.3x10-4 to 3.5x10-2; previously HFCs were assumed to have negligible ODPs since these species lack chlorine or bromine atoms. The ozone impacts of HFCs are further investigated with the Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM). The GEOSCCM is a three-dimensional, fully coupled ocean-atmosphere model with interactive stratospheric chemistry. Sensitivity simulations in which CO2, CFC-11 and HCFC-22 are enhanced individually are used as proxies for the atmospheric response to the HFC concentrations expected by the mid-21st century. Sensitivity simulations provide quantitative estimates of the impacts of these greenhouse gases on global total ozone, and can be used to assess their effects on the recovery of Antarctic ozone.

  17. Improved survival of acute lymphoblastic leukemia patients of HLA-A3/11 absent for donor KIR3DL2 after non-T-cell depleted HLA-identical sibling hematopoietic stem cells transplantation

    Directory of Open Access Journals (Sweden)

    farhad shahsavar

    2011-08-01

    Conclusion: These data indicate that the absence of HLA class I ligand in the recipient for donor-inhibitory KIR can be a prognostic factor for transplantation outcomes in non-T-cell depleted HLA-identical sibling hematopoietic stem-cell transplantation and that the lack of HLA-A3/11 for donor KIR3DL2 can contribute to improved survival for patients with ALL.

  18. Physiological studies of tryptophan transport and tryptophanase operon induction in Escherichia coli.

    Science.gov (United States)

    Yanofsky, C; Horn, V; Gollnick, P

    1991-10-01

    Escherichia coli forms three permeases that can transport the amino acid tryptophan: Mtr, AroP, and TnaB. The structural genes for these permeases reside in separate operons that are subject to different mechanisms of regulation. We have exploited the fact that the tryptophanase (tna) operon is induced by tryptophan to infer how tryptophan transport is influenced by the growth medium and by mutations that inactivate each of the permease proteins. In an acid-hydrolyzed casein medium, high levels of tryptophan are ordinarily required to obtain maximum tna operon induction. High levels are necessary because much of the added tryptophan is degraded by tryptophanase. An alternate inducer that is poorly cleaved by tryptophanase, 1-methyltryptophan, induces efficiently at low concentrations in both tna+ strains and tna mutants. In an acid-hydrolyzed casein medium, the TnaB permease is most critical for tryptophan uptake; i.e., only mutations in tnaB reduce tryptophanase induction. However, when 1-methyltryptophan replaces tryptophan as the inducer in this medium, mutations in both mtr and tnaB are required to prevent maximum induction. In this medium, AroP does not contribute to tryptophan uptake. However, in a medium lacking phenylalanine and tyrosine the AroP permease is active in tryptophan transport; under these conditions it is necessary to inactivate the three permeases to eliminate tna operon induction. The Mtr permease is principally responsible for transporting indole, the degradation product of tryptophan produced by tryptophanase action. The TnaB permease is essential for growth on tryptophan as the sole carbon source. When cells with high levels of tryptophanase are transferred to tryptophan-free growth medium, the expression of the tryptophan (trp) operon is elevated. This observation suggests that the tryptophanase present in these cells degrades some of the synthesized tryptophan, thereby creating a mild tryptophan deficiency. Our studies assign roles to

  19. The tryptophan requirements of pullets in the early production stage

    African Journals Online (AJOL)

    cost of 1 kg tryptophan is 20 times the marginal value of 1 kg egg. Under the same ... centration of the diet influence food consumption, the daily amount of amino ..... time spent on correspondence, consultation and analysing the data is highly ...

  20. An immunosuppressive tryptophan-derived alkaloid from Lepidagathis cristata.

    Science.gov (United States)

    Ravikanth, V; Niranjan Reddy, V L; Ramesh, P; Prabhakar Rao, T; Diwan, P V; Khar, A; Venkateswarlu, Y

    2001-12-01

    An immunosuppressive, tryptophan-derived alkaloid cristatin A (1), and two known compounds, cycloartenol and stigmasta-5,11(12)-diene-3 beta-ol, were isolated from the whole plant Lepidagathis cristata Willd. The structures of the isolates were established by interpretation of their spectral data.

  1. Dimeric Complexes of Tryptophan with M2+ Metal Ions

    NARCIS (Netherlands)

    Dunbar, R. C.; Steill, J. D.; Polfer, N. C.; Oomens, J.

    2009-01-01

    IRMPD spectroscopy using the FELIX free electron laser and a Fourier transform ICR mass spectrometer was used to characterize the structures of electrosprayed dimer complexes M(2+)Trp(2) of tryptophan with a series of eight doubly charged metal ions, including alkaline earths Ca, Sr, and Ba, and tra

  2. Preliminary study: voluntary food intake in dogs during tryptophan supplementation.

    Science.gov (United States)

    Fragua, Víctor; González-Ortiz, Gemma; Villaverde, Cecilia; Hervera, Marta; Mariotti, Valentina Maria; Manteca, Xavier; Baucells, María Dolores

    2011-10-01

    Tryptophan, a precursor of important molecules such as serotonin, melatonin and niacin, is an essential amino acid for dogs. In pigs, tryptophan supplementation has been shown to induce a significant increase in food intake. The aim of the present study was to assess whether long-term tryptophan supplementation increases voluntary food intake in dogs and to observe whether this was accompanied by a change in serum ghrelin. In the present study, sixteen adult Beagle dogs were used, with four male and four female dogs fed diets supplemented with tryptophan (1 g/dog per d) during 81 d (Trp) and four male and four female dogs that were not supplemented (control). A voluntary food intake test was performed during 5 d following the supplementation period. The Trp group tended to show a higher food intake during the voluntary food intake test (58.0 (SE 5.37) v. 77.5 (SE 3.65) g/kg metabolic weight per d; P = 0.074). No significant differences were found for serum ghrelin concentrations.

  3. Association between Tryptophan Hydroxylase 2 Gene Polymorphism and Completed Suicide

    Science.gov (United States)

    Fudalej, Sylwia; Ilgen, Mark; Fudalej, Marcin; Kostrzewa, Grazyna; Barry, Kristen; Wojnar, Marcin; Krajewski, Pawel; Blow, Frederic; Ploski, Rafal

    2010-01-01

    The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…

  4. Depleted zinc: Properties, application, production.

    Science.gov (United States)

    Borisevich, V D; Pavlov, A V; Okhotina, I A

    2009-01-01

    The addition of ZnO, depleted in the Zn-64 isotope, to the water of boiling water nuclear reactors lessens the accumulation of Co-60 on the reactor interior surfaces, reduces radioactive wastes and increases the reactor service-life because of the inhibitory action of zinc on inter-granular stress corrosion cracking. To the same effect depleted zinc in the form of acetate dihydrate is used in pressurized water reactors. Gas centrifuge isotope separation method is applied for production of depleted zinc on the industrial scale. More than 20 years of depleted zinc application history demonstrates its benefits for reduction of NPP personnel radiation exposure and combating construction materials corrosion.

  5. Redox Properties of Tryptophan Metabolism and the Concept of Tryptophan Use in Pregnancy

    Science.gov (United States)

    Xu, Kang; Liu, Hongnan; Bai, Miaomiao; Gao, Jing; Wu, Xin; Yin, Yulong

    2017-01-01

    During pregnancy, tryptophan (Trp) is required for several purposes, and Trp metabolism varies over time in the mother and fetus. Increased oxidative stress (OS) with high metabolic, energy and oxygen demands during normal pregnancy or in pregnancy-associated disorders has been reported. Taking the antioxidant properties of Trp and its metabolites into consideration, we made four hypotheses. First, the use of Trp and its metabolites is optional based on their antioxidant properties during pregnancy. Second, dynamic Trp metabolism is an accommodation mechanism in response to OS. Third, regulation of Trp metabolism could be used to control/attenuate OS according to variations in Trp metabolism during pregnancy. Fourth, OS-mediated injury could be alleviated by regulation of Trp metabolism in pregnancy-associated disorders. Future studies in normal/abnormal pregnancies and in associated disorders should include measurements of free Trp, total Trp, Trp metabolites, and activities of Trp-degrading enzymes in plasma. Abnormal pregnancies and some associated disorders may be associated with disordered Trp metabolism related to OS. Mounting evidence suggests that the investigation of the use of Trp and its metabolites in pregnancy will be meanful. PMID:28737706

  6. Inhibition of Escherichia coli tryptophan indole-lyase by tryptophan homologues.

    Science.gov (United States)

    Do, Quang T; Nguyen, Giang T; Celis, Victor; Phillips, Robert S

    2014-10-15

    We have designed, synthesized and evaluated homotryptophan analogues as possible mechanism-based inhibitors for Escherichia coli tryptophan indole-lyase (tryptophanase, TIL, E.C. 4.1.99.1). As a quinonoid structure is an intermediate in the reaction mechanism of TIL, we anticipated that homologation of the physiological substrate, L-Trp would provide analogues resembling the transition state for β-elimination, and potentially inhibit TIL. Our results demonstrate that L-homotryptophan (1a) is a moderate competitive inhibitor of TIL, with Ki=67 μM, whereas L-bishomotryptophan (1b) displays more potent inhibition, with Ki=4.7 μM. Pre-steady-state kinetics indicated the formation of an external aldimine and quinonoid with 1a, but only the formation of an external aldimine for 1b, suggesting differences in the inhibition mechanism. These results demonstrate that formation of a quinonoid complex is not required for strong inhibition. In addition, the Trp analogues were evaluated as inhibitors of Salmonella typhimurium Trp synthase. Our results indicate that compound 1b is at least 25-fold more selective toward TIL than Trp synthase. We report that compound 1b is comparable to the most potent inhibitor previously reported, while displaying high selectivity for TIL. Thus, 1b is a potential lead for the development of novel antibacterials.

  7. Ego depletion impairs implicit learning.

    Science.gov (United States)

    Thompson, Kelsey R; Sanchez, Daniel J; Wesley, Abigail H; Reber, Paul J

    2014-01-01

    Implicit skill learning occurs incidentally and without conscious awareness of what is learned. However, the rate and effectiveness of learning may still be affected by decreased availability of central processing resources. Dual-task experiments have generally found impairments in implicit learning, however, these studies have also shown that certain characteristics of the secondary task (e.g., timing) can complicate the interpretation of these results. To avoid this problem, the current experiments used a novel method to impose resource constraints prior to engaging in skill learning. Ego depletion theory states that humans possess a limited store of cognitive resources that, when depleted, results in deficits in self-regulation and cognitive control. In a first experiment, we used a standard ego depletion manipulation prior to performance of the Serial Interception Sequence Learning (SISL) task. Depleted participants exhibited poorer test performance than did non-depleted controls, indicating that reducing available executive resources may adversely affect implicit sequence learning, expression of sequence knowledge, or both. In a second experiment, depletion was administered either prior to or after training. Participants who reported higher levels of depletion before or after training again showed less sequence-specific knowledge on the post-training assessment. However, the results did not allow for clear separation of ego depletion effects on learning versus subsequent sequence-specific performance. These results indicate that performance on an implicitly learned sequence can be impaired by a reduction in executive resources, in spite of learning taking place outside of awareness and without conscious intent.

  8. Depletable resources and the economy.

    NARCIS (Netherlands)

    Heijman, W.J.M.

    1991-01-01

    The subject of this thesis is the depletion of scarce resources. The main question to be answered is how to avoid future resource crises. After dealing with the complex relation between nature and economics, three important concepts in relation with resource depletion are discussed: steady state, ti

  9. Serotonergic neurotransmission and lapses of attention in children and adolescents with attention deficit hyperactivity disorder: availability of tryptophan influences attentional performance.

    Science.gov (United States)

    Zepf, Florian D; Gaber, Tilman J; Baurmann, David; Bubenzer, Sarah; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Stadler, Christina; Poustka, Fritz; Wöckel, Lars

    2010-08-01

    Deficiencies in serotonergic (5-HT) neurotransmission have frequently been linked to altered attention and memory processes. With attention deficit hyperactivity disorder (ADHD) being associated with impaired attention and working memory, this study investigated the effects of a diminished 5-HT turnover achieved by rapid tryptophan depletion (RTD) on attentional performance in children and adolescents with ADHD. Twenty-two male patients with ADHD (aged 9-15 yr) received the RTD procedure Moja-De and a tryptophan (Trp)-balanced placebo (Pla) in a randomized, double-blind, within-subject crossover design on two separate study days. Lapses of attention (LA) and phasic alertness (PA) were assessed within the test battery for attentional performance under depleted and sham-depleted conditions 120 (T1), 220 (T2) and 300 (T3) min after intake of RTD/Pla. At T1 there was a significant main effect for RTD, indicating more LA under intake of a Trp-balanced Pla compared to diminished 5-HT neurotransmission. For T2/T3 there were no such effects. PA was not affected by the factors RTD/Pla and time. Interactions of 5-HT with other neurotransmitters as possible underlying neurochemical processes could be subject to further investigations involving healthy controls as regards altered attentional performance in children and adolescents.

  10. Consumption of peptide-included and free tryptophan induced by peroxyl radicals: A kinetic study.

    Science.gov (United States)

    Fuentes, E; López-Alarcón, C

    2014-10-01

    It is well-known that tryptophan residues are efficiently oxidized by peroxyl radicals, generating kynurenine, and N-formyl kynurenine as well as hydroperoxide derivatives as products. In the present work we studied the kinetic of such reaction employing free and peptide-included tryptophan. Two azocompounds were used to produce peroxyl radicals: AAPH (2,2'-Azobis(2-methylpropionamidine) dihydrochloride) and ABCVA (4,4'-Azobis(4-cyanovaleric acid)), which generate cationic and anionic peroxyl radicals, respectively. Tryptophan consumption was assessed by fluorescence spectroscopy and the reactions were carried out in phosphate buffer (75mM, pH 7.4) at 45°C. Only a slight effect of the peroxyl radical charge was evidenced on the consumption of free tryptophan and the dipeptide Gly-Trp. Employing AAPH as peroxyl radical source, at low free tryptophan concentrations (1-10µM) near 0.3 mol of tryptophan were consumed per each mol of peroxyl radicals introduced into the system. However, at high free tryptophan concentrations (100µM-1mM) such stoichiometry increased in a tryptophan concentration-way. At 1mM three moles of tryptophan were consumed per mol of AAPH-derived peroxyl radicals, evidencing the presence of chain reactions. A similar behavior was observed when di and tri-peptides (Gly-Trp, Trp-Gly, Gly-Trp-Gly, Trp-Ala, Ala-Trp-Ala) were studied. Nonetheless, at low initial concentration (5µM), the initial consumption rate of tryptophan included in the peptides was two times higher than free tryptophan. In contrast, at high concentration (1mM) free and peptide-included tryptophan showed similar initial consumption rates. These results could be explained considering a disproportionation process of tryptophanyl radicals at low free tryptophan concentrations, a process that would be inhibited when tryptophan is included in peptides.

  11. Testing fully depleted CCD

    Science.gov (United States)

    Casas, Ricard; Cardiel-Sas, Laia; Castander, Francisco J.; Jiménez, Jorge; de Vicente, Juan

    2014-08-01

    The focal plane of the PAU camera is composed of eighteen 2K x 4K CCDs. These devices, plus four spares, were provided by the Japanese company Hamamatsu Photonics K.K. with type no. S10892-04(X). These detectors are 200 μm thick fully depleted and back illuminated with an n-type silicon base. They have been built with a specific coating to be sensitive in the range from 300 to 1,100 nm. Their square pixel size is 15 μm. The read-out system consists of a Monsoon controller (NOAO) and the panVIEW software package. The deafualt CCD read-out speed is 133 kpixel/s. This is the value used in the calibration process. Before installing these devices in the camera focal plane, they were characterized using the facilities of the ICE (CSIC- IEEC) and IFAE in the UAB Campus in Bellaterra (Barcelona, Catalonia, Spain). The basic tests performed for all CCDs were to obtain the photon transfer curve (PTC), the charge transfer efficiency (CTE) using X-rays and the EPER method, linearity, read-out noise, dark current, persistence, cosmetics and quantum efficiency. The X-rays images were also used for the analysis of the charge diffusion for different substrate voltages (VSUB). Regarding the cosmetics, and in addition to white and dark pixels, some patterns were also found. The first one, which appears in all devices, is the presence of half circles in the external edges. The origin of this pattern can be related to the assembly process. A second one appears in the dark images, and shows bright arcs connecting corners along the vertical axis of the CCD. This feature appears in all CCDs exactly in the same position so our guess is that the pattern is due to electrical fields. Finally, and just in two devices, there is a spot with wavelength dependence whose origin could be the result of a defectous coating process.

  12. Opposing Biological Functions of Tryptophan Catabolizing Enzymes During Intracellular Infection

    Science.gov (United States)

    Divanovic, Senad; Sawtell, Nancy M.; Trompette, Aurelien; Warning, Jamie I.; Dias, Alexandra; Cooper, Andrea M.; Yap, George S.; Arditi, Moshe; Shimada, Kenichi; DuHadaway, James B.; Prendergast, George C.; Basaraba, Randall J.; Mellor, Andrew L.; Munn, David H.; Aliberti, Julio

    2012-01-01

    Recent studies have underscored physiological and pathophysiological roles for the tryptophan-degrading enzyme indolamine 2,3-dioxygenase (IDO) in immune counterregulation. However, IDO was first recognized as an antimicrobial effector, restricting tryptophan availability to Toxoplasma gondii and other pathogens in vitro. The biological relevance of these findings came under question when infectious phenotypes were not forthcoming in IDO-deficient mice. The recent discovery of an IDO homolog, IDO-2, suggested that the issue deserved reexamination. IDO inhibition during murine toxoplasmosis led to 100% mortality, with increased parasite burdens and no evident effects on the immune response. Similar studies revealed a counterregulatory role for IDO during leishmaniasis (restraining effector immune responses and parasite clearance), and no evident role for IDO in herpes simplex virus type 1 (HSV-1) infection. Thus, IDO plays biologically important roles in the host response to diverse intracellular infections, but the dominant nature of this role—antimicrobial or immunoregulatory—is pathogen-specific. PMID:21990421

  13. Archetypal tryptophan-rich antimicrobial peptides: properties and applications.

    Science.gov (United States)

    Shagaghi, Nadin; Palombo, Enzo A; Clayton, Andrew H A; Bhave, Mrinal

    2016-02-01

    Drug-resistant microorganisms ('superbugs') present a serious challenge to the success of antimicrobial treatments. Subsequently, there is a crucial need for novel bio-control agents. Many antimicrobial peptides (AMPs) show a broad-spectrum activity against bacteria, fungi or viruses and are strong candidates to complement or substitute current antimicrobial agents. Some AMPs are also effective against protozoa or cancer cells. The tryptophan (Trp)-rich peptides (TRPs) are a subset of AMPs that display potent antimicrobial activity, credited to the unique biochemical properties of tryptophan that allow it to insert into biological membranes. Further, many Trp-rich AMPs cross bacterial membranes without compromising their integrity and act intracellularly, suggesting interactions with nucleic acids and enzymes. In this work, we overview some archetypal TRPs derived from natural sources, i.e., indolicidin, tritrpticin and lactoferricin, summarising their biochemical properties, structures, antimicrobial activities, mechanistic studies and potential applications.

  14. Structure and Mechanistic Implications of a Tryptophan Synthase Quinonoid Intermediate

    Energy Technology Data Exchange (ETDEWEB)

    Barends,T.; Domratcheva, T.; Kulik, V.; Blumenstein, L.; Niks, D.; Dunn, M.; Schlichting, I.

    2008-01-01

    Quinonoid intermediates play a key role in the catalytic mechanism of pyridoxal 5'-phosphate (PLP)-dependent enzymes. Whereas structures of other PLP-bound reaction intermediates have been determined, a high-quality structure of a quinonoid species has not been reported. We present the crystal structure of the indoline quinonoid intermediate of tryptophan synthase (see figure) and discuss its implications for the enzymatic mechanism and allosteric regulation.

  15. Tryptophan requirements of growing pigs: a dose response study

    NARCIS (Netherlands)

    Vinyeta, E.; Bikker, P.; Corrent, E.; Rovers, M.

    2010-01-01

    A total of 144 pigs were divided into four dietary treatment groups with increasing tryptophan:lysine ratios (apparent ileal digestible (AID) Trp:Lys 0:14, 0:17, 0:20 and 0:23 and standardized ileal digestible (SID) Trp:Lys 0:15, 0:18, 0:21 and 0:24) for 6 weeks. There were 6 replicates with 6

  16. Kinetics of L-tryptophan in depressive patients: a possible correlation between the plasma concentrations of L-tryptophan and some psychiatric rating scales.

    Science.gov (United States)

    Hoes, M J; Loeffen, T; Vree, T B

    1981-01-01

    The plasma concentration and flux of L-tryptophan are abnormal in primary depressive patients, according to the literature. The plasma concentrations of L-tryptophan over a 6-h period after ingestion of 5 g L-tryptophan were investigated and did not differ significantly between depressive patients and controls during the absorption, distribution, and elimination phases. There was no correlation between the plasma concentrations with anxiety or depression scores, or with the excretion in urine of 17-hydroxycorticosteroids and xanthurenic acid during the 24 h after L-tryptophan. Treatment with either 125 mg pyridoxine (three times daily with meals) and L-tryptophan (3 g at 10 PM) or with maprotiline (100 mg at 10 PM) had no influence on the plasma concentrations of L-tryptophan after 2 or 4 weeks of treatment. This excludes L-tryptophan deficiency as a pathogenic factor of depression in the patients studied. No kinetic differences could be demonstrated in the depressive patients, making differences in body compartments or flux of L-tryptophan unlikely to be of pathogenic importance to depression.

  17. 5-Hydroxytryptophan, a major product of tryptophan degradation, is essential for optimal replication of human parainfluenza virus.

    Science.gov (United States)

    Rabbani, M A G; Barik, Sailen

    2017-03-01

    Interferon (IFN) exerts its antiviral effect by inducing a large family of cellular genes, named interferon (IFN)-stimulated genes (ISGs). An intriguing member of this family is indoleamine 2,3-dioxygenase (IDO), which catalyzes the first and rate-limiting step of the main branch of tryptophan (Trp) degradation, the kynurenine pathway. We recently showed that IDO strongly inhibits human parainfluenza virus type 3 (PIV3), a significant respiratory pathogen. Here, we show that 5-hydoxytryptophan (5-HTP), the first product of an alternative branch of Trp degradation and a serotonin precursor, is essential to protect virus growth against IDO in cell culture. We also show that the apparent antiviral effect of IDO on PIV3 is not due to the generation of the kynurenine pathway metabolites, but rather due to the depletion of intracellular Trp by IDO, as a result of which this rare amino acid becomes unavailable for the alternative, proviral 5-HTP pathway.

  18. Concurrent quantification of tryptophan and its major metabolites

    Science.gov (United States)

    Lesniak, Wojciech G.; Jyoti, Amar; Mishra, Manoj K.; Louissaint, Nicolette; Romero, Roberto; Chugani, Diane C.; Kannan, Sujatha; Kannan, Rangaramanujam M.

    2014-01-01

    An imbalance in tryptophan (TRP) metabolites is associated with several neurological and inflammatory disorders. Therefore, analytical methods allowing for simultaneous quantification of TRP and its major metabolites would be highly desirable, and may be valuable as potential biomarkers. We have developed a HPLC method for concurrent quantitative determination of tryptophan, serotonin, 5-hydroxyindoleacetic acid, kynurenine, and kynurenic acid in tissue and fluids. The method utilizes the intrinsic spectroscopic properties of TRP and its metabolites that enable UV absorbance and fluorescence detection by HPLC, without additional labeling. The origin of the peaks related to analytes of interest was confirmed by UV–Vis spectral patterns using a PDA detector and mass spectrometry. The developed methods were validated in rabbit fetal brain and amniotic fluid at gestational day 29. Results are in excellent agreement with those reported in the literature for the same regions. This method allows for rapid quantification of tryptophan and four of its major metabolites concurrently. A change in the relative ratios of these metabolites can provide important insights in predicting the presence and progression of neuroinflammation in disorders such as cerebral palsy, autism, multiple sclerosis, Alzheimer disease, and schizophrenia. PMID:24036037

  19. Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders.

    Science.gov (United States)

    Ravikumar, A; Deepadevi, K V; Arun, P; Manojkumar, V; Kurup, P A

    2000-09-01

    Catabolism of tryptophan and tyrosine in relation to the isoprenoid pathway was studied in neurological and psychiatric disorders. The concentration of trytophan, quinolinic acid, kynurenic acid, serotonin and 5-hydroxyindoleacetic acid was found to be higher in the plasma of patients with all these disorders; while that of tyrosine, dopamine, epinephrine and norepinephrine was lower. There was increase in free fatty acids and decrease in albumin (factors modulating tryptophan transport) in the plasma of these patients. Concentration of digoxin, a modulator of amino acid transport, and the activity of HMG CoA reductase, which synthesizes digoxin, were higher in these patients; while RBC membrane Na+-K+ ATPase activity showed a decrease. Concentration of plasma ubiquinone (part of which is synthesised from tyrosine) and magnesium was also lower in these patients. No morphine could be detected in the plasma of these patients except in MS. On the other hand, strychnine and nicotine were detectable. These results indicate hypercatabolism of tryptophan and hypocatabolism of tyrosine in these disorders, which could be a consequence of the modulating effect of hypothalamic digoxin on amino acid transport.

  20. Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders.

    Directory of Open Access Journals (Sweden)

    Ravikumar A

    2000-07-01

    Full Text Available Catabolism of tryptophan and tyrosine in relation to the isoprenoid pathway was studied in neurological and psychiatric disorders. The concentration of trytophan, quinolinic acid, kynurenic acid, serotonin and 5-hydroxyindoleacetic acid was found to be higher in the plasma of patients with all these disorders; while that of tyrosine, dopamine, epinephrine and norepinephrine was lower. There was increase in free fatty acids and decrease in albumin (factors modulating tryptophan transport in the plasma of these patients. Concentration of digoxin, a modulator of amino acid transport, and the activity of HMG CoA reductase, which synthesizes digoxin, were higher in these patients; while RBC membrane Na+-K+ ATPase activity showed a decrease. Concentration of plasma ubiquinone (part of which is synthesised from tyrosine and magnesium was also lower in these patients. No morphine could be detected in the plasma of these patients except in MS. On the other hand, strychnine and nicotine were detectable. These results indicate hypercatabolism of tryptophan and hypocatabolism of tyrosine in these disorders, which could be a consequence of the modulating effect of hypothalamic digoxin on amino acid transport.

  1. Comparison of tryptophan interactions to free and grafted BSA protein.

    Science.gov (United States)

    Garnier, F; Randon, J; Rocca, J L

    2000-04-28

    The binding of d- and l-tryptophan molecules to bovine serum albumin (BSA) protein has been studied using liquid chromatography and ultrafiltration in the pH range from 7 to 11. A hydrophobic interaction between tryptophan and BSA has been observed at pH 7.0 on BSA grafted chromatographic column. However, this interaction is negligible at higher pH for which the interaction to the stereospecific site was predominant. For both grafted and free proteins, the complexation mechanism was a competitive binding of d- and l-enantiomers on a single site. The apparent complexation constants for both d- and l-tryptophan show a maximum in the pH range 9-10. The variations of the apparent complexation constants versus pH were the result of the protonation of both the amino acid and a single site of the protein assuming that the complexation occurs between the zwitter-ionic amino acid form and the unprotonated BSA site. The apparent pK(BSA) is slightly shifted from 8.3 for grafted BSA protein to 9.4 for free BSA protein. This shift is presumably as a result of the different protein conformation.

  2. Tryptophan synthase of Phaeophyceae originated from the secondary host nucleus

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yalan; CHI Shan; WU Shuangxiu; LIU Cui; YU Jun; WANG Xumin; CHEN Shengping; LIU Tao

    2014-01-01

    Tryptophan synthase (TS, EC 4.2.1.20) catalyzes the last two steps of L-tryptophan biosynthesis. In pro-karyotes, tryptophan synthase is a multi-enzyme complex, and it consists ofαandβsubunit which forms anα-ββ-αcomplex. In fungi and diatoms, TS is a bifunctional enzyme. Because of the limited genomic and transcriptomic data of algae, there are few studies on TS evolution of algae. Here we analyzed the data of the 1000 Plants Project (1KP), and focused on red algae and brown algae. We found out that the TS of Phaeophy-ceae were fusion genes, which probably originated from the secondary host nucleus, and that the TS of Rho-dophyta contained two genes, TSA and TSB, which both display a possible cyanobacterial origin at the time of primary endosymbiosis. In addition, there were two types of TSB genes (TSB1 and TSB2). Through the multiple sequence alignment of TSB proteins, we found several residues conserved in TSB1 but variable in TSB2 which connect withαsubunit. The phenomenon may suggest that the TSB2 sequences of Rhodophyta cannot form stable complex with TSA.

  3. Tyrosine, phenylalanine, and tryptophan in gastroesophageal malignancy: a systematic review.

    Science.gov (United States)

    Wiggins, Tom; Kumar, Sacheen; Markar, Sheraz R; Antonowicz, Stefan; Hanna, George B

    2015-01-01

    Gastroesophageal cancer has a rapidly increasing incidence worldwide and reliable biomarkers are urgently required to facilitate earlier diagnosis and improve survival. The aromatic amino acids tyrosine, phenylalanine, and tryptophan represent potential biomarkers and their relation to gastroesophageal cancer will be evaluated in this review. An electronic literature search was performed to identify all published research relating to the measurement of tyrosine, phenylalanine, or tryptophan in the biofluids or tissues of patients with gastroesophageal cancer. Sixteen studies were included in this systematic review. Six studies investigated serum concentrations, which all found decreased concentrations of these aromatic amino acids, except one study that found increased phenylalanine. Five studies reported increased concentrations within gastric content of these patients and two reported increased urinary concentrations. Tissue concentrations of these aromatic amino acids were increased in three studies. Tyrosine, phenylalanine, and tryptophan represent potential biomarkers of gastroesophageal cancer, and further research is necessary to definitively establish the mechanism responsible for altered concentrations of these compounds in patients with gastroesophageal cancer.

  4. Nanosensor detection of an immunoregulatory tryptophan influx/kynurenine efflux cycle.

    Science.gov (United States)

    Kaper, Thijs; Looger, Loren L; Takanaga, Hitomi; Platten, Michael; Steinman, Lawrence; Frommer, Wolf B

    2007-10-01

    Mammalian cells rely on cellular uptake of the essential amino acid tryptophan. Tryptophan sequestration by up-regulation of the key enzyme for tryptophan degradation, indoleamine 2,3-dioxygenase (IDO), e.g., in cancer and inflammation, is thought to suppress the immune response via T cell starvation. Additionally, the excreted tryptophan catabolites (kynurenines) induce apoptosis of lymphocytes. Whereas tryptophan transport systems have been identified, the molecular nature of kynurenine export remains unknown. To measure cytosolic tryptophan steady-state levels and flux in real time, we developed genetically encoded fluorescence resonance energy transfer nanosensors (FLIPW). The transport properties detected by FLIPW in KB cells, a human oral cancer cell line, and COS-7 cells implicate LAT1, a transporter that is present in proliferative tissues like cancer, in tryptophan uptake. Importantly, we found that this transport system mediates tryptophan/kynurenine exchange. The tryptophan influx/kynurenine efflux cycle couples tryptophan starvation to elevation of kynurenine serum levels, providing a two-pronged induction of apoptosis in neighboring cells. The strict coupling protects cells that overproduce IDO from kynurenine accumulation. Consequently, this mechanism may contribute to immunosuppression involved in autoimmunity and tumor immune escape.

  5. Nanosensor detection of an immunoregulatory tryptophan influx/kynurenine efflux cycle.

    Directory of Open Access Journals (Sweden)

    Thijs Kaper

    2007-10-01

    Full Text Available Mammalian cells rely on cellular uptake of the essential amino acid tryptophan. Tryptophan sequestration by up-regulation of the key enzyme for tryptophan degradation, indoleamine 2,3-dioxygenase (IDO, e.g., in cancer and inflammation, is thought to suppress the immune response via T cell starvation. Additionally, the excreted tryptophan catabolites (kynurenines induce apoptosis of lymphocytes. Whereas tryptophan transport systems have been identified, the molecular nature of kynurenine export remains unknown. To measure cytosolic tryptophan steady-state levels and flux in real time, we developed genetically encoded fluorescence resonance energy transfer nanosensors (FLIPW. The transport properties detected by FLIPW in KB cells, a human oral cancer cell line, and COS-7 cells implicate LAT1, a transporter that is present in proliferative tissues like cancer, in tryptophan uptake. Importantly, we found that this transport system mediates tryptophan/kynurenine exchange. The tryptophan influx/kynurenine efflux cycle couples tryptophan starvation to elevation of kynurenine serum levels, providing a two-pronged induction of apoptosis in neighboring cells. The strict coupling protects cells that overproduce IDO from kynurenine accumulation. Consequently, this mechanism may contribute to immunosuppression involved in autoimmunity and tumor immune escape.

  6. Crystal Structure and Mechanism of Tryptophan 2,3-Dioxygenase, a Heme Enzyme Involved in Tryptophan Catabolism and in Quinolinate Biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang,Y.; Kang, S.; Mukherjee, T.; Bale, S.; Crane, B.; Begley, T.; Ealick, S.

    2007-01-01

    The structure of tryptophan 2,3-dioxygenase (TDO) from Ralstonia metallidurans was determined at 2.4 {angstrom}. TDO catalyzes the irreversible oxidation of L-tryptophan to N-formyl kynurenine, which is the initial step in tryptophan catabolism. TDO is a heme-containing enzyme and is highly specific for its substrate L-tryptophan. The structure is a tetramer with a heme cofactor bound at each active site. The monomeric fold, as well as the heme binding site, is similar to that of the large domain of indoleamine 2,3-dioxygenase, an enzyme that catalyzes the same reaction except with a broader substrate tolerance. Modeling of the putative (S)-tryptophan hydroperoxide intermediate into the active site, as well as substrate analogue and mutagenesis studies, are consistent with a Criegee mechanism for the reaction.

  7. "When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect.

    Science.gov (United States)

    Salmon, Stefanie J; Adriaanse, Marieke A; De Vet, Emely; Fennis, Bob M; De Ridder, Denise T D

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion.

  8. Tryptophan and its metabolite concentrations in human plasma and breast milk during the perinatal period.

    Directory of Open Access Journals (Sweden)

    Kamimura,Shigehito

    1991-04-01

    Full Text Available Concentrations of tryptophan (free and protein bound and its metabolites in plasma of maternal vein at delivery, umbilical vein, umbilical artery, neonatal vein and breast milk were determined by high performance liquid chromatography. The plasma levels of tryptophan and most of its metabolites in umbilical vein and artery were significantly higher than those in maternal vein. The concentration of total tryptophan in plasma of neonatal vein showed marked decrease at 24 h after birth in comparison with that at birth, but the total kynurenine concentration was not decreased in plasma of neonatal vein. The colostrum contained a high level of total tryptophan. There were high ratios of free to total tryptophan in colostrum, transitional and mature milk. In the blood, ratios of free to total of tryptophan and kynurenine were kept at constant level throughout the perinatal period.

  9. Fatigue in patients with lung cancer is related with accelerated tryptophan breakdown.

    Directory of Open Access Journals (Sweden)

    Katharina Kurz

    Full Text Available BACKGROUND: Patients with cancer often suffer from fatigue and decreased quality of life which might be related to the breakdown of essential amino acid tryptophan. METHODS: In 50 patients with lung cancer we examined fatigue and the deterioration of quality of life in patients using the Functional Assessment of Cancer Therapy Anemia (FACT-An and -Fatigue (FACT-F subscales of FACT-General and the Mental adjustment to Cancer (MAC questionnaires. Results were compared with tryptophan breakdown as well as serum concentrations of immune activation markers. RESULTS: Scores of psychological tests correlated significantly with tryptophan breakdown and with circulatory markers of inflammation. However, immune activation and tryptophan breakdown were not related to MAC scores. CONCLUSIONS: Tryptophan breakdown relates with fatigue and impaired quality of life in patients with lung cancer, while declining tryptophan levels are not associated with patients'coping strategies.

  10. Electrochemical properties of tyrosine phenoxy and tryptophan indolyl radicals in peptides and amino acid analogues

    Energy Technology Data Exchange (ETDEWEB)

    DeFelippis, M.R.; Murthy, C.P.; Klapper, M.H. (Ohio State Univ., Columbus (United States)); Broitman, F.; Weinraub, D.; Faraggi, M. (Nuclear Research Centre-Negev, Beer Sheva (Israel))

    1991-04-18

    Reported here are the redox potentials of the tyrosine phenoxy (tyrO{sup {sm bullet}}) and tryptophan indolyl (trp{sup {sm bullet}}) radicals in peptides containing tyrosine or tryptophan residues. These were determined with pulse radiolysis, and the electrochemical techniques of cyclic voltammetry and differential pulse polarography. The pulse radiolytic and electrochemical methods yield comparable results. There are small differences (relative to the free amino acid) in redox potentials among the different tryptophan and tyrosine containing peptides; in the case of tryptophan these changes may correlate with the position of amino acid in the peptide. The authors also present the redox potentials of some tyrosine and tryptophan derivatives and the acid/base properties of the tryptophan radical cation, when both free and peptide bound.

  11. Depleting depletion: Polymer swelling in poor solvent mixtures

    Science.gov (United States)

    Mukherji, Debashish; Marques, Carlos; Stuehn, Torsten; Kremer, Kurt

    A polymer collapses in a solvent when the solvent particles dislike monomers more than the repulsion between monomers. This leads to an effective attraction between monomers, also referred to as depletion induced attraction. This attraction is the key factor behind standard polymer collapse in poor solvents. Strikingly, even if a polymer exhibits poor solvent condition in two different solvents, it can also swell in mixtures of these two poor solvents. This collapse-swelling-collapse scenario is displayed by poly(methyl methacrylate) (PMMA) in aqueous alcohol. Using molecular dynamics simulations of a thermodynamically consistent generic model and theoretical arguments, we unveil the microscopic origin of this phenomenon. Our analysis suggests that a subtle interplay of the bulk solution properties and the local depletion forces reduces depletion effects, thus dictating polymer swelling in poor solvent mixtures.

  12. Proton transfer in histidine-tryptophan heterodimers embedded in helium droplets

    Energy Technology Data Exchange (ETDEWEB)

    Bellina, Bruno; Merthe, Daniel J.; Kresin, Vitaly V. [Department of Physics and Astronomy, University of Southern California, Los Angeles, California 90089-0484 (United States)

    2015-03-21

    We used cold helium droplets as nano-scale reactors to form and ionize, by electron bombardment and charge transfer, aromatic amino acid heterodimers of histidine with tryptophan, methyl-tryptophan, and indole. The molecular interaction occurring through an N–H ⋅ ⋅ ⋅ N hydrogen bond leads to a proton transfer from the indole group of tryptophan to the imidazole group of histidine in a radical cationic environment.

  13. Reaction pathway of tryptophanase-catalyzed L-tryptophan synthesis from D-serine

    OpenAIRE

    Shimada, Akihiko; Ozaki, Haruka; Saito, Takeshi; Fujii, Noriko

    2011-01-01

    Tryptophanase, L-tryptophan indole-lyase with extremely absolute stereospecificity, can change the stereospecificity in concentrated diammonium hydrogenphosphate solution. While tryptophanase is not inert to d-serine in the absence of diammonium hydrogenphosphate, it can undergo L-tryptophan synthesis from d-serine along with indole in the presence of it. It has been well known that tryptophanase synthesizes L-tryptophan from l-serine through a β-substitution mechanism of the ping-pong type. ...

  14. Proton transfer in histidine-tryptophan heterodimers embedded in helium droplets

    CERN Document Server

    Bellina, Bruno; Kresin, Vitaly V

    2015-01-01

    We used cold helium droplets as nano-scale reactors to form and ionize, by electron bombardment and charge transfer, aromatic amino acid heterodimers of histidine with tryptophan, methyl-tryptophan, and indole. The molecular interaction occurring through an N-H...N hydrogen bond leads to a proton transfer from the indole group of tryptophan to the imidazole group of histidine in a radical cationic environment.

  15. Circumvention of defective neutral amino acid transport in Hartnup disease using tryptophan ethyl ester.

    Science.gov (United States)

    Jonas, A J; Butler, I J

    1989-07-01

    Tryptophan ethyl ester, a lipid-soluble tryptophan derivative, was used to bypass defective gastrointestinal neutral amino acid transport in a child with Hartnup disease. The child's baseline tryptophan concentrations in serum (20 +/- 6 microM) and cerebrospinal fluid (1.0 +/- 0.2 microM) were persistently less than 50% of normal values. Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, was also less than 50% of normal (21 +/- 2 ng/ml). Serum tryptophan concentrations increased only modestly and briefly after an oral challenge with 200 mg/kg of oral L-tryptophan, reflecting the absorptive defect. An oral challenge with 200 mg/kg of tryptophan ethyl ester resulted in a prompt increase in serum tryptophan to a peak of 555 microM. Sustained treatment with 20 mg/kg q6h resulted in normalization of serum (66 +/- 15 microM) and cerebrospinal fluid tryptophan concentrations (mean = 2.3 microM). Cerebrospinal fluid 5-HIAA increased to more normal concentrations (mean = 33 ng/ml). No toxicity was observed over an 8-mo period of treatment, chronic diarrhea resolved, and body weight, which had remained unchanged for 7 mo before ester therapy, increased by approximately 26%. We concluded that tryptophan ethyl ester is effective at circumventing defective gastrointestinal neutral amino acid transport and may be useful in the treatment of Hartnup disease.

  16. Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour.

    Science.gov (United States)

    Desbonnet, Lieve; Clarke, Gerard; Traplin, Alexander; O'Sullivan, Orla; Crispie, Fiona; Moloney, Rachel D; Cotter, Paul D; Dinan, Timothy G; Cryan, John F

    2015-08-01

    There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may

  17. Rotational Mixing and Lithium Depletion

    CERN Document Server

    Pinsonneault, M H

    2010-01-01

    I review basic observational features in Population I stars which strongly implicate rotation as a mixing agent; these include dispersion at fixed temperature in coeval populations and main sequence lithium depletion for a range of masses at a rate which decays with time. New developments related to the possible suppression of mixing at late ages, close binary mergers and their lithium signature, and an alternate origin for dispersion in young cool stars tied to radius anomalies observed in active young stars are discussed. I highlight uncertainties in models of Population II lithium depletion and dispersion related to the treatment of angular momentum loss. Finally, the origins of rotation are tied to conditions in the pre-main sequence, and there is thus some evidence that enviroment and planet formation could impact stellar rotational properties. This may be related to recent observational evidence for cluster to cluster variations in lithium depletion and a connection between the presence of planets and s...

  18. Charge depletion in organic heterojunction

    Science.gov (United States)

    Ng, T. W.; Lo, M. F.; Lee, S. T.; Lee, C. S.

    2012-03-01

    Until now two types of organic-organic heterojunction (OHJ) have been observed in P-N junctions formed between undoped-organic semiconductors. Charge-transfers across OHJs are either negligible or showing electron transfer from P-type to N-type materials, leading to charges accumulation near the interface. Here, we observed that junction of 4,4',4''-tris(2-methylphenyl-phenylamino)triphenylamine (m-MTDATA)/bathocuproine (BCP) show the third-behavior. Electrons in BCP (N-type) transfer to m-MTDATA (P-type), leading to depletion of mobile majority carriers near the junction. While "depletion junctions" are typical in inorganic semiconductors, there are no reports in undoped-OHJ. Formation mechanism of depletion OHJs and fundamental differences between inorganic and organic HJs are discussed.

  19. Dendritic biomimicry: microenvironmental hydrogen-bonding effects on tryptophan fluorescence.

    Science.gov (United States)

    Koenig, S; Müller, L; Smith, D K

    2001-03-02

    Two series of dendritically modified tryptophan derivatives have been synthesised and their emission spectra measured in a range of different solvents. This paper presents the syntheses of these novel dendritic structures and discusses their emission spectra in terms of both solvent and dendritic effects. In the first series of dendrimers, the NH group of the indole ring is available for hydrogen bonding, whilst in the second series, the indole NH group has been converted to NMe. Direct comparison of the emission wavelengths of analogous NH and NMe derivatives indicates the importance of the Kamlet-Taft solvent beta3 parameter, which reflects the ability of the solvent to accept a hydrogen bond from the NH group, an effect not possible for the NMe series of dendrimers. For the NH dendrimers, the attachment of a dendritic shell to the tryptophan subunit leads to a red shift in emission wavelength. This dendritic effect only operates in non-hydrogen-bonding solvents. For the NMe dendrimers, however, the attachment of a dendritic shell has no effect on the emission spectra of the indole ring. This proves the importance of hydrogen bonding between the branched shell and the indole NH group in causing the dendritic effect. This is the first time a dendritic effect has been unambiguously assigned to individual hydrogen-bonding interactions and indicates that such intramolecular interactions are important in dendrimers, just as they are in proteins. Furthermore, this paper sheds light on the use of tryptophan residues as a probe of the microenvironment within proteins--in particular, it stresses the importance of hydrogen bonds formed by the indole NH group.

  20. Quantification of tryptophan in plasma by high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Renata Romanholi Pinhati

    2012-01-01

    Full Text Available A simple, rapid and selective method using high-performance liquid chromatography with ultraviolet detection (267 nm was applied for the determination of tryptophan in plasma. Separation was carried out on a C18 column (150 x 4.6 mm internal diameter in 6 min. The mobile phase consisted of 5 mM the sodium acetate and acetonitrile (92:8, v/v. The method was shown to be precise and accurate, and good recovery of analyte was achieved, characterizing the method as efficient and reliable for use in laboratory analysis.

  1. Serotonin synthesis rate and the tryptophan hydroxylase-2

    DEFF Research Database (Denmark)

    Furmark, Tomas; Marteinsdottir, Ina; Frick, Andreas

    2016-01-01

    emission tomography and 5-hydroxy-L-[β -(11)C]tryptophan, [(11)C]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G......-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [(11)C]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder...

  2. Gallium uptake in tryptophan-related pulmonary disease

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S.M.; Park, C.H.; Intenzo, C.M.; Patel, R. (Thomas Jefferson Univ. Hospital, Philadelphia, PA (USA))

    1991-02-01

    We describe a patient who developed fever, fatigue, muscle weakness, dyspnea, skin rash, and eosinophilia after taking high doses of tryptophan for insomnia for two years. A gallium-67 scan revealed diffuse increased uptake in the lung and no abnormal uptake in the muscular distribution. Bronchoscopy and biopsy confirmed inflammatory reactions with infiltration by eosinophils, mast cells, and lymphocytes. CT scan showed an interstitial alveolar pattern without fibrosis. EMG demonstrated diffuse myopathy. Muscle biopsy from the right thigh showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations.

  3. Impact of mineral resource depletion

    CSIR Research Space (South Africa)

    Brent, AC

    2006-09-01

    Full Text Available In a letter to the editor, the authors comment on BA Steen's article on "Abiotic Resource Depletion: different perceptions of the problem with mineral deposits" published in the special issue of the International Journal of Life Cycle Assessment...

  4. Global depletion of groundwater resources

    NARCIS (Netherlands)

    Wada, Y.; Beek, L.P.H. van; van Kempen, C.M.; Reckman, J.W.T.M.; Vasak, S.; Bierkens, M.F.P.

    2010-01-01

    In regions with frequent water stress and large aquifer systems groundwater is often used as an additional water source. If groundwater abstraction exceeds the natural groundwater recharge for extensive areas and long times, overexploitation or persistent groundwater depletion occurs. Here we provid

  5. Tryptophan tryptophylquinone biosynthesis: a radical approach to posttranslational modification.

    Science.gov (United States)

    Davidson, Victor L; Liu, Aimin

    2012-11-01

    Protein-derived cofactors are formed by irreversible covalent posttranslational modification of amino acid residues. An example is tryptophan tryptophylquinone (TTQ) found in the enzyme methylamine dehydrogenase (MADH). TTQ biosynthesis requires the cross-linking of the indole rings of two Trp residues and the insertion of two oxygen atoms onto adjacent carbons of one of the indole rings. The diheme enzyme MauG catalyzes the completion of TTQ within a precursor protein of MADH. The preMADH substrate contains a single hydroxyl group on one of the tryptophans and no crosslink. MauG catalyzes a six-electron oxidation that completes TTQ assembly and generates fully active MADH. These oxidation reactions proceed via a high valent bis-Fe(IV) state in which one heme is present as Fe(IV)=O and the other is Fe(IV) with both axial heme ligands provided by amino acid side chains. The crystal structure of MauG in complex with preMADH revealed that catalysis does not involve direct contact between the hemes of MauG and the protein substrate. Rather it is accomplished through long-range electron transfer, which presumably generates radical intermediates. Kinetic, spectrophotometric, and site-directed mutagenesis studies are beginning to elucidate how the MauG protein controls the reactivity of the hemes and mediates the long range electron/radical transfer required for catalysis. This article is part of a Special Issue entitled: Radical SAM enzymes and Radical Enzymology.

  6. Synthesis and Characterization of Gold Nanoparticles by Tryptophane

    Directory of Open Access Journals (Sweden)

    Azim Akbarzadeh

    2009-01-01

    Full Text Available Problem statement: Preparation and synthesis of gold nanoparticles with small size and suitable stability is very important and applicable particularly in medicine. In this study, we have prepared gold nanoparticles by chemical reduction method employing L-Tryptophane as a reducing agent for ionic gold. Approach: The gold nanoparticles are the most employed amongst the different metallic nanoparticles in the fields of nanomedicine and nanobiotechnology. Therefore, the employed method should provide suitable particle size, shape and particle distribution in order to obtain nanoparticles of high activity and efficiency indicating the importance of the technique. In this study, HAuCl4 .3H2O, L-Tryptophane and polyethyleneglycol (PEG were used to produce AuCl-4 ions. They were acted as pre-material, reducing and stabilizing agents respectively. Results: The size, distribution and formation of gold nanoparticles were confirmed by Transmission Electron Microscopy (TEM indicating the diameter of gold nanoparticles at the range of 10-25 nm and UV spectroscopy. The formed nanoparticles showed the highest absorption at 518 nm. Conclusion: The gold nanoparticles were stable in PEG1000. Since these nanoparticles have suitable size distribution they can be considered as a suitable candidate to be employed in nanomedicine and nanobiotechnology.

  7. 实验性急性肺损伤部分液体通气效应与剂量的关系%Dose-response relationship of partial liquid ventilation in surfactant depletion induced by acute lung injury

    Institute of Scientific and Technical Information of China (English)

    孙婵; 王仲红; 彭雪梅; 邹鹏

    2003-01-01

    目的:对肺灌洗诱导的急性肺损伤家兔实施不同剂量氟碳(perfluorocarbon, PFC)的部分液体通气(partial liquid ventilation, PLV),观察其疗效及剂量-效应关系.方法:14只成年健康家兔,麻醉后经气管导管用生理盐水反复肺内灌洗,直至动脉氧分压(PaO2)<13.33 kPa (100 mmHg)达1 h,记录肺气体交换、血液动力学及呼吸动力各参数作为肺损伤(acute lung injury, ALI)基础值.随机分为PLV组及对照组,对照组以呼吸机行常规机械通气,不给予任何治疗措施;PLV组动物于ALI后每30 min气管内灌入PFC(FC 3280,3 M,德国)6 mL*kg-1共3次,总量为18 mL*kg-1.以上述呼吸参数行机械通气.最后一次灌注后继续行机械通气3 h,每小时记录各参数次.结果:PLV组PaO2及动脉血氧饱和度(HbO2)在灌注第一个剂量的PFC后即显著改善,并与剂量呈相关性;PaCO2在灌注第一个PFC剂量后较ALI时显著降低,但并不随剂量的增加而继续降低.结论:以氟碳为媒介的部分液体通气可明显改善肺灌洗诱导的急性肺损伤家兔的肺氧合,并呈剂量相关性,同时呼吸动力的改善与剂量无关.

  8. The association of sleep quality and insomnia with dietary intake of tryptophan and niacin

    NARCIS (Netherlands)

    Verster, J.; Fernstrand, A.; Bury, D.; Roth, T.; Garssen, J.

    2015-01-01

    Introduction: Dietary intake of tryptophan and niacin have been related to sleep. However, the sleep-promoting effects of these nutrients are still under investigation. The aim of the current study was to examine the relationship between daily dietary intake of tryptophan and niacin and sleep. Mater

  9. Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation

    NARCIS (Netherlands)

    van der Goot, Annemieke T.; Zhu, Wentao; Vazquez-Manrique, Rafael P.; Seinstra, Renee I.; Dettmer, Katja; Michels, Helen; Farina, Francesca; Krijnen, Jasper; Melki, Ronald; Buijsman, Rogier C.; Silva, Mariana Ruiz; Thijssen, Karen L.; Kema, Ido P.; Neri, Christian; Oefner, Peter J.; Nollen, Ellen A. A.

    2012-01-01

    Toxicity of aggregation-prone proteins is thought to play an important role in aging and age-related neurological diseases like Parkinson and Alzheimer's diseases. Here, we identify tryptophan 2,3-dioxygenase (tdo-2), the first enzyme in the kynurenine pathway of tryptophan degradation, as a metabol

  10. Expression, purification and enzymatic characterization of the catalytic domains of human tryptophan hydroxylase isoforms

    DEFF Research Database (Denmark)

    Windahl, Michael Skovbo; Boesen, Jane; Karlsen, Pernille Efferbach;

    2009-01-01

    Tryptophan hydroxylase exists in two isoforms: Isoform 1 catalyses the first and rate-limiting step in the synthesis of serotonin in the peripheral parts of the body while isoform 2 catalyses this step in the brain. The catalytic domains of human tryptophan hydroxylase 1 and 2 have been expressed...

  11. Tryptophan content for monitoring breast cancer cell aggressiveness by native fluorescence spectroscopy

    Science.gov (United States)

    Zhang, Lin; Pu, Yang; Xue, Jianpeng; Pratavieira, Sebastião.; Xu, Baogang; Achilefu, Samuel; Alfano, R. R.

    2014-03-01

    This study shows tryptophan as the key native marker in cells to determine the level of aggressive cancer in breast cell lines using native fluorescence spectroscopy. An algorithm based on the ratio of tryptophan fluorescence intensity at 340 nm to intensity at 460 nm is associated with aggressiveness of the cancer cells. The higher the ratio is, the more aggressive the tumor towards metastasis.

  12. Self-assembling tryptophan-based designer peptides as intracellular delivery vehicles.

    Science.gov (United States)

    Bhardwaj, Ishanki; Jha, Divya; Admane, Prasad; Panda, Amulya K; Haridas, V

    2016-01-15

    A series of tryptophan-based peptides W1a, b-W4a, b, with diverse architectures were designed and synthesized. These tryptophan containing peptides can self-assemble to spherical particle. This self-assembled system was demonstrated to encapsulate rhodamine B and penetrate the cell membrane.

  13. Chiral Discrimination of Tryptophan Enantiomers via (1R, 2R-2-Amino-1, 2-Diphenyl Ethanol Modified Interface

    Directory of Open Access Journals (Sweden)

    Juan Zhou

    2011-01-01

    Full Text Available The paper reported that a simple chiral selective interface constructed by (1R, 2R-2-amino-1, 2-diphenyl ethanol had been developed to discriminate tryptophan enantiomers. Cyclic voltammetry (CV and electrochemical impedance spectroscopy (EIS were used for the characteristic analysis of the electrode. The results indicated that the interface showed stable and sensitive property to determine the tryptophan enantiomers. Moreover, it exhibited the better stereoselectivity for L-tryptophan than that for D-tryptophan. The discrimination characteristics of the chiral selective interface for discriminating tryptophan enantiomers, including the response time, the effect of tryptophan enantiomers concentration, and the stability, were investigated in detail. In addition, the chiral selective interface was used to determine the enantiomeric composition of L- and D-tryptophan enantiomer mixtures by measuring the relative change of the peak current as well as in pure enantiomeric solutions. These results suggested that the chiral selective interface has the potential for enantiomeric discrimination of tryptophan enantiomers.

  14. Enhancement of stability of L-tryptophan dehydrogenase from Nostoc punctiforme ATCC29133 and its application to L-tryptophan assay.

    Science.gov (United States)

    Matsui, Daisuke; Okazaki, Seiji; Matsuda, Motoki; Asano, Yasuhisa

    2015-02-20

    Microbial NAD(+)-dependent L-tryptophan dehydrogenase (TrpDH, EC1.4.1.19), which catalyzes the reversible oxidative deamination and the reductive amination between L-tryptophan and indole-3-pyruvic acid, was found in the scytonemin biosynthetic pathway of Nostoc punctiforme ATCC29133. The TrpDH exhibited high specificity toward L-tryptophan, but its instability was a drawback for L-tryptophan determination. The mutant enzyme TrpDH L59F/D168G/A234D/I296N with thermal stability was obtained by screening of Escherichia coli transformants harboring various mutant genes, which were generated by error-prone PCR using complementation in an L-tryptophan auxotroph of E. coli. The specific activity and stability of this mutant enzyme were higher than those of the wild type enzyme. We also revealed here that in these four mutation points, the two amino acid residues Asp168 and Ile296 contributed to increase the enzyme stability, and the Leu59, Ala234 residues to increase its specific activity. Growth of the strain harboring the gene of above 4 point mutated enzyme was accelerated by the enhanced performance. In the present study, we demonstrated that TrpDH L59F/D168G/A234D/I296N was available for determination of L-tryptophan in human plasma. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Raman microbeam spectrometer noninvasively measures biomoelcules to monitor the tryptophan metabolic pathway

    Science.gov (United States)

    Michel, Gregory; Bigelow, Alan W.; Harden, Jamie; Krueger, James G.; Gareau, Daniel S.

    2014-03-01

    Toward improving early detection of melanoma by accurate diagnosis and avoidance of unnecessary surgical excisions of common moles, we are developing noninvasive quantitative spectral fingerprinting of protein expression using Raman spectroscopy within confocally gated volumes of tissue. Our first target is the L-tryptophan catabolism pathway, which is unregulated in the tumor micro-environment and inhibits the immune response that usually is tumor suppressive. The tryptophan pathway is therefore worthy of diagnostic measurement and finding the ratio of L-tryptophan to its metabolites may aid a melanoma diagnosis. We report the intensity of the Raman signal from L-tryptophan and quinolinic acid, which are found during different stages of the tryptophan metabolic pathway.

  16. Correlation of tryptophan fluorescence intensity decay parameters with sup 1 H NMR-determined rotamer conformations: (tryptophan sup 2 )oxytocin

    Energy Technology Data Exchange (ETDEWEB)

    Ross, J.B.A.; Schwartz, G.P.; Laws, W.R. (Mount Sinai, New York, NY (United States)); Wyssbrod, H.R.; Porter, R.A. (Univ. of Louisville, KY (United States)); Michaels, C.A. (Swarthmore Coll., PA (United States))

    1992-02-18

    While the fluorescence decay kinetics of tyrosine model compounds can be explained in terms of heterogeneity derived from the three ground-state {chi}{sup 1} rotamers, a similar correlation has yet to be directly observed for a tryptophan residue. In addition, the asymmetric indole ring might also lead to heterogeneity from {chi}{sup 2} rotations. In this paper, the time-resolved and steady-state fluorescence properties of (tryptophan{sup 2})oxytocin at pH 3 are presented and compared with {sup 1}H NMR results. According to the unrestricted analyses of individual fluorescence decay curves taken as a function of emission wavelength-independent decay constants, only three exponential terms are required. In addition, the preexponential weighting factors (amplitudes) have the same relative relationship (weights) as the {sup 1}H NMR-determined {chi}{sup 1} rotamer populations of the indole side chain. {sup 15}N was used in heteronuclear coupling experiments to confirm the rotamer assignments. Inclusion of a linked function restricting the decay amplitudes to the {chi}{sup 1} rotamer populations in the individual decay curve analyses and in the global analysis confirms this correlation. According to qualitative nuclear Overhauser data, there are two {chi}{sup 2} populations.

  17. Rapid reversal by naloxone of the chronic effects of morphine on rat liver and brain tryptophan metabolism.

    OpenAIRE

    Badawy, A. A.; Evans, M.

    1981-01-01

    The chronic morphine-induced inhibition of rat liver tryptophan pyrrolase activity and the resultant increases in tryptophan availability to the brain and brain 5-hydroxytryptamine (5-HT) synthesis are reversed within 10 min after naloxone administration. The possible involvement of hepatic tryptophan metabolism in morphine dependence is briefly discussed.

  18. Ozone Depletion from Nearby Supernovae

    CERN Document Server

    Gehrels, N; Jackman, C H; Cannizzo, J K; Mattson, B J; Chen, W; Gehrels, Neil; Laird, Claude M.; Jackman, Charles H.; Cannizzo, John K.; Mattson, Barbara J.; Chen, Wan

    2003-01-01

    Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time, improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made in theoretical modeling of supernovae and of the resultant gamma-ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma-rays and cosmic rays. We find that for the combined ozone depletion roughly to double the ``biologically active'' UV flux received at the surface of the Earth, the supernova mu...

  19. Ozone Depletion from Nearby Supernovae

    Science.gov (United States)

    Gehrels, Neil; Laird, Claude M.; Jackman, Charles H.; Cannizzo, John K.; Mattson, Barbara J.; Chen, Wan; Bhartia, P. K. (Technical Monitor)

    2002-01-01

    Estimates made in the 1970's indicated that a supernova occurring within tens of parsecs of Earth could have significant effects on the ozone layer. Since that time improved tools for detailed modeling of atmospheric chemistry have been developed to calculate ozone depletion, and advances have been made also in theoretical modeling of supernovae and of the resultant gamma ray spectra. In addition, one now has better knowledge of the occurrence rate of supernovae in the galaxy, and of the spatial distribution of progenitors to core-collapse supernovae. We report here the results of two-dimensional atmospheric model calculations that take as input the spectral energy distribution of a supernova, adopting various distances from Earth and various latitude impact angles. In separate simulations we calculate the ozone depletion due to both gamma rays and cosmic rays. We find that for the combined ozone depletion from these effects roughly to double the 'biologically active' UV flux received at the surface of the Earth, the supernova must occur at approximately or less than 8 parsecs.

  20. Ozone depletion, paradigms, and politics

    Energy Technology Data Exchange (ETDEWEB)

    Iman, R.L.

    1993-10-01

    The destruction of the Earth`s protective ozone layer is a prime environmental concern. Industry has responded to this environmental problem by: implementing conservation techniques to reduce the emission of ozone-depleting chemicals (ODCs); using alternative cleaning solvents that have lower ozone depletion potentials (ODPs); developing new, non-ozone-depleting solvents, such as terpenes; and developing low-residue soldering processes. This paper presents an overview of a joint testing program at Sandia and Motorola to evaluate a low-residue (no-clean) soldering process for printed wiring boards (PWBs). Such processes are in widespread use in commercial applications because they eliminate the cleaning operation. The goal of this testing program was to develop a data base that could be used to support changes in the mil-specs. In addition, a joint task force involving industry and the military has been formed to conduct a follow-up evaluation of low-residue processes that encompass the concerns of the tri-services. The goal of the task force is to gain final approval of the low-residue technology for use in military applications.

  1. Auxin-inducible protein depletion system in fission yeast

    Directory of Open Access Journals (Sweden)

    Kakimoto Tatsuo

    2011-02-01

    Full Text Available Abstract Background Inducible inactivation of a protein is a powerful approach for analysis of its function within cells. Fission yeast is a useful model for studying the fundamental mechanisms such as chromosome maintenance and cell cycle. However, previously published strategies for protein-depletion are successful only for some proteins in some specific conditions and still do not achieve efficient depletion to cause acute phenotypes such as immediate cell cycle arrest. The aim of this work was to construct a useful and powerful protein-depletion system in Shizosaccaromyces pombe. Results We constructed an auxin-inducible degron (AID system, which utilizes auxin-dependent poly-ubiquitination of Aux/IAA proteins by SCFTIR1 in plants, in fission yeast. Although expression of a plant F-box protein, TIR1, decreased Mcm4-aid, a component of the MCM complex essential for DNA replication tagged with Aux/IAA peptide, depletion did not result in an evident growth defect. We successfully improved degradation efficiency of Mcm4-aid by fusion of TIR1 with fission yeast Skp1, a conserved F-box-interacting component of SCF (improved-AID system; i-AID, and the cells showed severe defect in growth. The i-AID system induced degradation of Mcm4-aid in the chromatin-bound MCM complex as well as those in soluble fractions. The i-AID system in conjunction with transcription repression (off-AID system, we achieved more efficient depletion of other proteins including Pol1 and Cdc45, causing early S phase arrest. Conclusion Improvement of the AID system allowed us to construct conditional null mutants of S. pombe. We propose that the off-AID system is the powerful method for in vivo protein-depletion in fission yeast.

  2. Chemical Modification and Fluorescence Spectrum of Tryptophan Residues in Pullulanase

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Tryptophan(Trp) residues in a pullulanase were modified by N-bromosuccinimide(NBS). The results of the Spande method indicate that there are 18 Trp residues in the pullulanase and nine of them are located on the surface of the enzyme. Three of these Trp residues are nonessential residues which show the fastest reaction rate according to the Zou′s plot. Two of the seven relative faster reacting residues are essential for the activity of the enzyme. The other eight are the slowest in the reaction rate or non-reactive residues for the reaction. The fluorescence and circular dichroism(CD) spectra of the pullulanase have been changed after the reaction with NBS. Potassium iodide(KI) and acrylamide also have remarkable influences on the fluorescence spectra of the pullulanase.

  3. Tryptophan, Neurodegeneration and HIV-Associated Neurocognitive Disorder

    Directory of Open Access Journals (Sweden)

    Nicholas W.S. Davies

    2010-06-01

    Full Text Available This review presents an up-to-date assessment of the role of the tryptophan metabolic and catabolic pathways in neurodegenerative disease and HIV-associated neurocognitive disorder. The kynurenine pathway and the effects of each of its enzymes and products are reviewed. The differential expression of the kynurenine pathway in cells within the brain, including inflammatory cells, is explored given the increasing recognition of the importance of inflammation in neurodegenerative disease. An overview of common mechanisms of neurodegeneration is presented before a review and discussion of the evidence for a pathogenetic role of the kynurenine pathway in Alzheimer’s disease, HIV-associated neurocognitive disorder, Huntington’s disease, motor neurone disease, and Parkinson’s disease.

  4. Doxycycline induced photodamage to human neutrophils and tryptophan

    Energy Technology Data Exchange (ETDEWEB)

    Sandberg, S.; Glette, J.; Hopen, G.; Solberg, C.O. (Haukeland Sykehus, Bergen (Norway))

    1984-01-01

    Neutrophil function were studied following irradiation (340-380 nm) of the cells in the presence of 22 ..mu..M doxycycline. At increasing light fluence the locomotion, chemiluminescence and glucose oxidation (by the hexose monophosphate shunt) of the neutrophils steadily decreased. The photodamage increased with increasing preincubation temperature and time and was enhanced in D/sub 2/O, reduced in azide and abolished in anaerobiosis. Superoxide dismutase, catalase or mannitol did not influence the photodamage. Photooxidation of tryptophan in the presence of doxycycline was increased 9-10-fold in D/sub 2/O and nearly abolished in the presence of 0.25 mM NaN/sub 3/, indicating that singlet oxygen is the most important reactive oxygen species in the doxycycline-induced photodamage. The results may explain some of the features of tetracycline-induced photosensitivity and why other authors have obtained diverging results when studying the influence of tetracyclines on neutrophil functions.

  5. Biochemistry of primary headaches: role of tyrosine and tryptophan metabolism.

    Science.gov (United States)

    D'Andrea, G; Cevoli, S; Colavito, D; Leon, A

    2015-05-01

    The pathogenesis of migraine as well as cluster headache (CH) is yet a debated question. In this review, we discuss the possible role of the of tyrosine and tryptophan metabolism in the pathogenesis of these primary headaches. These include the abnormalities in the synthesis of neurotransmitters: high level of DA, low level of NE and very elevated levels of octopamine and synephrine (neuromodulators) in plasma of episodic migraine without aura and CH patients. We hypothesize that the imbalance between the levels of neurotransmitters and elusive amines synthesis is due to a metabolic shift directing tyrosine toward an increased decarboxylase and reduced hydroxylase enzyme activities. The metabolic shift of the tyrosine is favored by a state of neuronal hyperexcitability and a reduced mitochondrial activity present in migraine. In addition we present biochemical studies performed in chronic migraine and chronic tension-type headache patients to verify if the same anomalies of the tyrosine and tryptophan metabolism are present in these primary headaches and, if so, their possible role in the chronicity process of CM and CTTH. The results show that important abnormalities of tyrosine metabolism are present only in CM patients (very high plasma levels of DA, NE and tryptamine). Tryptamine plasma levels were found significantly lower in both CM and CTTH patients. In view of this, we propose that migraine and, possibly, CH attacks derive from neurotransmitter and neuromodulator metabolic abnormalities in a hyperexcitable and hypoenergetic brain that spread from the frontal lobe, downstream, resulting in abnormally activated nuclei of the pain matrix. The low tryptamine plasma levels found in CM and CTTH patients suggest that these two primary chronic headaches are characterized by a common insufficient serotoninergic control of the pain threshold.

  6. Acute oral administration of a tyrosine and phenylalanine-free amino acid mixture reduces exercise capacity in the heat.

    Science.gov (United States)

    Tumilty, Les; Davison, Glen; Beckmann, Manfred; Thatcher, Rhys

    2013-06-01

    Acute tyrosine administration is associated with increased exercise capacity in the heat. To explore whether reduced plasma tyrosine and phenylalanine (tyrosine precursor) is associated with impaired exercise capacity in the heat, eight healthy, moderately trained male volunteers, unacclimated to exercise in the heat, performed two tests in a crossover design separated by at least 7 days. In a randomised, double-blind fashion, subjects ingested 500 mL flavoured, sugar-free water containing amino acids [(TYR-free; isoleucine 15 g, leucine 22.5 g, valine 17.5 g, lysine 17.5 g, methionine 5 g, threonine 10 g, tryptophan 2.5 g)] to lower the ratio of plasma tyrosine plus phenylalanine:amino acids competing for blood-brain barrier uptake (CAA), a key determinant of brain uptake, or a balanced mixture (BAL; TYR-free plus 12.5 g tyrosine and 12.5 g phenylalanine). One hour later, subjects cycled to exhaustion at 63 ± 5 % [Formula: see text]O2peak in 30 °C and 60 % relative humidity. Pre-exercise ratio of plasma tyrosine plus phenylalanine:ΣCAA declined 75 ± 5 % from rest in TYR-free (P 0.05) and thermal sensation (P > 0.05) were similar at exhaustion in both trials. These data indicate that acutely depleting plasma catecholamine precursors:ΣCAA is associated with reduced submaximal exercise capacity in the heat.

  7. Cane molasses as a source of precursors in the bioproduction of tryptophan by Bacillus subtilis.

    Directory of Open Access Journals (Sweden)

    Marzieh Dehghan Shasaltaneh

    2013-09-01

    Full Text Available The essential amino acid L-tryptophan can be produced by a condensation reaction between indole and L-serine, catalyzed by B. subtilis with tryptophan synthase activity. Application of the tryptophan is widespread in the biotechnology domain and is sometimes added to feed products as a food fortifier.The optimum concentration of the Iranian cane molasses was determined by measuring the amount of biomass after growth in 1 to 30 g/mL of molasses. The maximum amount of biomass was obtained in 10 g/mL molasses. Chromatographic methods, TLC and HPLC, were used to assay the amount of tryptophan produced in the presence of precursors of tryptophan production (indole and serine and/or molasses.Our results indicate the importance of the Iranian cane molasses not only as carbon source, but also as a source of precursors for tryptophan production.This report evaluates the potential of cane molasses as an economical source for tryptophan production by B. subtilis, hence eliminating the requirement for additional serine and indole as precursors.

  8. The Case of Ozone Depletion

    Science.gov (United States)

    Lambright, W. Henry

    2005-01-01

    While the National Aeronautics and Space Administration (NASA) is widely perceived as a space agency, since its inception NASA has had a mission dedicated to the home planet. Initially, this mission involved using space to better observe and predict weather and to enable worldwide communication. Meteorological and communication satellites showed the value of space for earthly endeavors in the 1960s. In 1972, NASA launched Landsat, and the era of earth-resource monitoring began. At the same time, in the late 1960s and early 1970s, the environmental movement swept throughout the United States and most industrialized countries. The first Earth Day event took place in 1970, and the government generally began to pay much more attention to issues of environmental quality. Mitigating pollution became an overriding objective for many agencies. NASA's existing mission to observe planet Earth was augmented in these years and directed more toward environmental quality. In the 1980s, NASA sought to plan and establish a new environmental effort that eventuated in the 1990s with the Earth Observing System (EOS). The Agency was able to make its initial mark via atmospheric monitoring, specifically ozone depletion. An important policy stimulus in many respects, ozone depletion spawned the Montreal Protocol of 1987 (the most significant international environmental treaty then in existence). It also was an issue critical to NASA's history that served as a bridge linking NASA's weather and land-resource satellites to NASA s concern for the global changes affecting the home planet. Significantly, as a global environmental problem, ozone depletion underscored the importance of NASA's ability to observe Earth from space. Moreover, the NASA management team's ability to apply large-scale research efforts and mobilize the talents of other agencies and the private sector illuminated its role as a lead agency capable of crossing organizational boundaries as well as the science-policy divide.

  9. Action orientation overcomes the ego depletion effect.

    Science.gov (United States)

    Dang, Junhua; Xiao, Shanshan; Shi, Yucai; Mao, Lihua

    2015-04-01

    It has been consistently demonstrated that initial exertion of self-control had negative influence on people's performance on subsequent self-control tasks. This phenomenon is referred to as the ego depletion effect. Based on action control theory, the current research investigated whether the ego depletion effect could be moderated by individuals' action versus state orientation. Our results showed that only state-oriented individuals exhibited ego depletion. For individuals with action orientation, however, their performance was not influenced by initial exertion of self-control. The beneficial effect of action orientation against ego depletion in our experiment results from its facilitation for adapting to the depleting task.

  10. "When the going gets tough, who keeps going?" Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T D

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  11. "When the going gets tough, who keeps going?" : Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  12. "When the going gets tough, who keeps going?" : Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  13. Physics of Fully Depleted CCDs

    CERN Document Server

    Holland, S E; Kolbe, W F; Lee, J S

    2014-01-01

    In this work we present simple, physics-based models for two effects that have been noted in the fully depleted CCDs that are presently used in the Dark Energy Survey Camera. The first effect is the observation that the point-spread function increases slightly with the signal level. This is explained by considering the effect on charge-carrier diffusion due to the reduction in the magnitude of the channel potential as collected signal charge acts to partially neutralize the fixed charge in the depleted channel. The resulting reduced voltage drop across the carrier drift region decreases the vertical electric field and increases the carrier transit time. The second effect is the observation of low-level, concentric ring patterns seen in uniformly illuminated images. This effect is shown to be most likely due to lateral deflection of charge during the transit of the photogenerated carriers to the potential wells as a result of lateral electric fields. The lateral fields are a result of space charge in the fully...

  14. Acute serotonin depletion releases motivated inhibition of response vigour

    NARCIS (Netherlands)

    Ouden, H.E.M. den; Swart, J.C.; Schmidt, K.; Fekkes, D.; Geurts, D.E.M.; Cools, R.

    2015-01-01

    RATIONALE: The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas,

  15. Acute serotonin depletion releases motivated inhibition of response vigour

    NARCIS (Netherlands)

    Ouden, H.E.M. den; Swart, J.C.; Schmidt, K.; Fekkes, D.; Geurts, D.E.M.; Cools, R.

    2015-01-01

    Rationale The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas,

  16. Acute serotonin depletion releases motivated inhibition of response vigour

    NARCIS (Netherlands)

    Ouden, H.E.M. den; Swart, J.C.; Schmidt, K.; Fekkes, D.; Geurts, D.E.M.; Cools, R.

    2015-01-01

    Rationale The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas,

  17. Acute serotonin depletion releases motivated inhibition of response vigour

    NARCIS (Netherlands)

    Ouden, H.E.M. den; Swart, J.C.; Schmidt, K.; Fekkes, D.; Geurts, D.E.M.; Cools, R.

    2015-01-01

    RATIONALE: The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas,

  18. The 1988 Antarctic ozone depletion - Comparison with previous year depletions

    Science.gov (United States)

    Schoeberl, Mark R.; Stolarski, Richard S.; Krueger, Arlin J.

    1989-01-01

    The 1988 spring Antarctic ozone depletion was observed by TOMS to be substantially smaller than in recent years. The minimum polar total ozone values declined only 15 percent during September 1988, compared to nearly 50 percent during September 1987. At southern midlatitudes, exceptionally high total ozone values were recorded beginning in July 1988. The total integrated southern hemispheric ozone increased rapidly during the Austral spring, approaching 1980 levels during October. The high midlatitude total ozone values were associated with a substantial increase in eddy activity as indicated by the standard deviation in total ozone in the zonal band 30-60 deg S. Mechanisms through which the increased midlatitude eddy activity could disrupt the formation of the Antarctic ozone hole are briefly discussed.

  19. Clinical evaluation of 5-hydroxy-L-tryptophan as an antidepressant drug.

    Science.gov (United States)

    Nakajima, T; Kudo, Y; Kaneko, Z

    1978-01-01

    Effectiveness of 5-hydroxy-L-trytophan as an antidepressant drug was studied with 59 patients with depressive symptoms using Rating Scale for Depression made by Clinico-Psychopharmacology Research Group in Japan for a preparatory step of a double blind clinical study of 5-hydroxy-L-tryptophan treatment of depression. A daily dose of 150--300 mg of 5-hydroxyl-L-tryptophan was administered for three weeks. Favorable responses were observed in 40 patients (67.8%), of whom 13 patients were markedly improved. These effects were noticed in 32 patients (80% of the improved patients) within a week of the treatment. Analysis of General Improvement Rating in the various subtypes of depressive symptoms indicated that endogenous depression and involutional or senile depression were the preferable indication of 5-hydroxy-L-tryptophan loading. The main side effects of 5-hydroxy-L-tryptophan were gastrointestinal disturbances which were minimized by the simultaneous administration of metoclopromide or trihexyphenidyl.

  20. Picosecond Fluorescence Dynamics of Tryptophan and 5-Fluorotryptophan in Monellin : Slow Water-Protein Relaxation Unmasked

    NARCIS (Netherlands)

    Xu, Jianhua; Chen, Binbin; Callis, Patrik Robert; Muiño, Pedro L; Rozeboom, Henriette J; Broos, Jaap; Toptygin, Dmitri; Brand, Ludwig; Knutson, Jay R

    2015-01-01

    Time Dependent Fluorescence Stokes (emission wavelength) Shifts (TDFSS) from tryptophan (Trp) following sub-picosecond excitation are increasingly used to investigate protein dynamics, most recently enabling active research interest into water dynamics near the surface of proteins. Unlike many fluor

  1. Irritability rather than depression during interferon treatment is linked to increased tryptophan catabolism

    NARCIS (Netherlands)

    Russo, S; Kema, IP; Haagsma, EB; Boon, JC; Willemse, PHB; Den Boer, JA; De Vries, EGE; Korf, J

    2005-01-01

    Objective: Treatment with recombinant interferon is associated with high rates of psychiatric comorbidity. We investigated the relation between catabolism of the essential amino acid tryptophan, being rate-limiting of peripheral and cerebral serotonin formation, and psychiatric symptoms in patients

  2. Ultraviolet transient absorption, transient grating and photon echo studies of aqueous tryptophan

    Science.gov (United States)

    Ajdarzadeh, Ahmad; Consani, Cristina; Bräm, Olivier; Tortschanoff, Andreas; Cannizzo, Andrea; Chergui, Majed

    2013-08-01

    We compare UV transient grating (TG) experiments of aqueous tryptophan with transient absorption (TA) and fluorescence up-conversion measurements. The TG and TA signals show a bi-exponential rise with sub-ps and ps time constants, which are consistent with the fluorescence studies. Using experimental data, we provide an equation for the homodyne-detected TG signal, taking into account the sub-100 fs internal conversion of tryptophan after excitation. In addition, we measure a sub-100 fs homogeneous electronic dephasing time for tryptophan in water by the photon echo (PE) technique. These measurements provide a consistent picture of excited state dynamics of aqueous tryptophan that may serve as a basis for coherent 2D-UV spectroscopy of biosystems.

  3. Picosecond Fluorescence Dynamics of Tryptophan and 5-Fluorotryptophan in Monellin : Slow Water-Protein Relaxation Unmasked

    NARCIS (Netherlands)

    Xu, Jianhua; Chen, Binbin; Callis, Patrik Robert; Muiño, Pedro L; Rozeboom, Henriette J; Broos, Jaap; Toptygin, Dmitri; Brand, Ludwig; Knutson, Jay R

    2015-01-01

    Time Dependent Fluorescence Stokes (emission wavelength) Shifts (TDFSS) from tryptophan (Trp) following sub-picosecond excitation are increasingly used to investigate protein dynamics, most recently enabling active research interest into water dynamics near the surface of proteins. Unlike many

  4. Detection of water proximity to tryptophan residues in proteins by single photon radioluminescence.

    Science.gov (United States)

    Bicknese, S; Zimet, D; Park, J; van Hoek, A N; Shohet, S B; Verkman, A S

    1995-05-01

    We recently developed a single photon radioluminescence (SPR) technique to measure submicroscopic distances in biological samples [Bicknese et al., and Shahrokh et al., Biophys. J., 63 (1992) 1256-1279]. SPR arises from the excitation of a fluorophore by the energy deposited from a slowing beta decay electron. The purpose of this study was to detect 3H2O molecules near tryptophan residues in proteins by tryptophan SPR. To detect small SPR signals, a sample compartment with reflective ellipsoidal optics was constructed, and amplified signals from a cooled photomultiplier were resolved by pulse-height analysis. A Monte Carlo calculation was carried out to quantify the relationship between SPR signal and 3H2O-tryptophan proximity. Measurements of tryptophan SPR were made on aqueous tryptophan; dissolved melittin (containing a single tryptophan); native and denatured aldolase; dissolved aldolase, monellin, and human serum albumin; and the integral membrane proteins CHIP28 (containing a putative aqueous pore) and MIP26 using 3H2O or the aqueous-phase probe 3H-3-O-methylglucose (OMG). After subtraction of a Bremsstrahlung background signal, the SPR signal from aqueous tryptophan (cps.microCi-1 mumol-1 +/- SE) was 8.6 +/- 0.2 with 3H2O and 7.8 +/- 0.3 with 3HOMG (n = 8). With 3H2O as donor, the SPR signal (cps.microCi-1 mumol-1) was 9.0 +/- 0.3 for monomeric melittin in low salt (trytophan exposed) and 4.6 +/- 0.8 (n = 9) for tetrameric melittin in high salt (tryptophans buried away from aqueous solution). The ratio of SPR signal obtained for aldolase under denaturing conditions of 8 M urea (fluorophores exposed) versus non-denaturing buffer (fluorophores buried) was 1.53 +/- 0.07 (n = 6). Ratios of SPR signals normalized to fluorescence intensities for monellin, aldolase, and human serum albumin, relative to that for d-tryptophan, were 1.42, 1.09, and 1.04, indicating that the cross-section for excitation of fluorophores in proteins is greater than that for tryptophan in

  5. Impaired reward learning and intact motivation after serotonin depletion in rats.

    Science.gov (United States)

    Izquierdo, Alicia; Carlos, Kathleen; Ostrander, Serena; Rodriguez, Danilo; McCall-Craddolph, Aaron; Yagnik, Gargey; Zhou, Feimeng

    2012-08-01

    Aside from the well-known influence of serotonin (5-hydroxytryptamine, 5-HT) on emotional regulation, more recent investigations have revealed the importance of this monoamine in modulating cognition. Parachlorophenylalanine (PCPA) depletes 5-HT by inhibiting tryptophan hydroxylase, the enzyme required for 5-HT synthesis and, if administered at sufficiently high doses, can result in a depletion of at least 90% of the brain's 5-HT levels. The present study assessed the long-lasting effects of widespread 5-HT depletions on two tasks of cognitive flexibility in Long Evans rats: effort discounting and reversal learning. We assessed performance on these tasks after administration of either 250 or 500 mg/kg PCPA or saline (SAL) on two consecutive days. Consistent with a previous report investigating the role of 5-HT on effort discounting, pretreatment with either dose of PCPA resulted in normal effortful choice: All rats continued to climb tall barriers to obtain large rewards and were not work-averse. Additionally, rats receiving the lower dose of PCPA displayed normal reversal learning. However, despite intact motivation to work for food rewards, rats receiving the largest dose of PCPA were unexpectedly impaired relative to SAL rats on the pretraining stages leading up to reversal learning, ultimately failing to approach and respond to the stimuli associated with reward. High performance liquid chromatography (HPLC) with electrochemical detection confirmed 5-HT, and not dopamine, levels in the ventromedial frontal cortex were correlated with this measure of associative reward learning.

  6. Targeting Tryptophan Catabolism: A Novel Method to Block Triple-Negative Breast Cancer Metastasis

    Science.gov (United States)

    2016-04-01

    on the beginnings of this work in http://www.eurekalert.org/pub_releases/2014-12/uocd-ptd121014. php What do you plan to do during the next reporting...14). The essential amino acid tryptophan is required for protein synthesis and is a precursor for the formation of multiple signaling molecules...including serotonin (15). The majority of tryptophan catabolism occurs via the kynurenine pathway, leading to synthesis of NADþ along with intermediate

  7. Effects of dietary L-tryptophan supplementation on intestinal response to chronic unpredictable stress in broilers.

    Science.gov (United States)

    Yue, Yunshuang; Guo, Yuming; Yang, Ying

    2017-07-01

    Stress has been recognized as a critical risk factor for gastrointestinal diseases in both humans and animals. However, nutritional strategies to attenuate stress-induced intestinal barrier function and underlying mechanisms remain largely unknown. This study tested the hypothesis that L-tryptophan enhanced intestinal barrier function by regulating mucosal serotonin metabolism in chronic unpredictable stress-exposed broilers. One-day-old male broilers (Arbor Acres) were fed a basal diet supplemented with or without L-tryptophan in the absence or presence of chronic unpredictable stress. Feed intake, body weight gain, plasma corticosterone and 5-hydroxytryptamine (5-HT), intestinal permeability, mucosal secretory IgA (sIgA), and mRNA levels for tryptophan hydroxylase 1 (TPH1), IL-1β, IL-6, TNF-α, IL-10, protein abundance for claudin-1, occludin, and ZO-1 were determined. Stress exposure led to elevated plasma corticosterone (P L-tryptophan supplementation. Western blot analysis showed that stress exposure resulted in decreased protein abundance for occludin, claudin-1, and ZO-1, which was attenuated by L-tryptophan. mRNA levels for IL-1β, IL-6, and TNF-α were increased, but those for IL-10 were decreased, in the jejunal tissue of broilers subjected to stress. This effect of stress on cytokine expression was abolished by L-tryptophan treatment. The effects of stress were associated with decreased plasma concentration of 5-HT (P L-Tryptophan supplementation markedly attenuated stress-induced alterations in 5-HT and TPH1 mRNA level in jejunal tissues of broilers. Collectively, these results indicate that L-tryptophan supplementation alleviates chronic unpredictable stress-induced intestinal barrier dysfunction by regulating 5-HT metabolism in broilers.

  8. Flexible Enantioselectivity of Tryptophanase Attributable to Benzene Ring in Heterocyclic Moiety of D-Tryptophan

    OpenAIRE

    Akihiko Shimada; Haruka Ozaki

    2012-01-01

    The invariance principle of enzyme enantioselectivity must be absolute because it is absolutely essential to the homochiral biological world. Most enzymes are strictly enantioselective, and tryptophanase is one of the enzymes with extreme absolute enantioselectivity for L-tryptophan. Contrary to conventional knowledge about the principle, tryptophanase becomes flexible to catalyze D-tryptophan in the presence of diammonium hydrogenphosphate. Since D-amino acids are ordinarily inert or functio...

  9. Studies on the biotin-binding site of avidin. Tryptophan residues involved in the active site.

    OpenAIRE

    Gitlin, G; Bayer, E A; Wilchek, M

    1988-01-01

    Egg-white avidin was modified with the tryptophan-specific reagent 2-hydroxy-5-nitrobenzyl bromide. The complete loss of biotin-binding activity was achieved upon modification of an average of one tryptophan residue per avidin subunit. The identity of the modified residues was determined by isolating the relevant tryptic and chymotryptic peptides from CNBr-cleaved avidin fragments. The results demonstrate that Trp-70 and Trp-110 are modified in approximately equivalent proportions. It is beli...

  10. Effects of Tryptophan Content and Backbone Spacing on the Uptake Efficiency of Cell-Penetrating Peptides

    KAUST Repository

    Rydberg, Hanna A.

    2012-07-10

    Cell-penetrating peptides (CPPs) are able to traverse cellular membranes and deliver macromolecular cargo. Uptake occurs through both endocytotic and nonendocytotic pathways, but the molecular requirements for efficient internalization are not fully understood. Here we investigate how the presence of tryptophans and their position within an oligoarginine influence uptake mechanism and efficiency. Flow cytometry and confocal fluorescence imaging are used to estimate uptake efficiency, intracellular distribution and toxicity in Chinese hamster ovarian cells. Further, membrane leakage and lipid membrane affinity are investigated. The peptides contain eight arginine residues and one to four tryptophans, the tryptophans positioned either at the N-terminus, in the middle, or evenly distributed along the amino acid sequence. Our data show that the intracellular distribution varies among peptides with different tryptophan content and backbone spacing. Uptake efficiency is higher for the peptides with four tryptophans in the middle, or evenly distributed along the peptide sequence, than for the peptide with four tryptophans at the N-terminus. All peptides display low cytotoxicity except for the one with four tryptophans at the N-terminus, which was moderately toxic. This finding is consistent with their inability to induce efficient leakage of dye from lipid vesicles. All peptides have comparable affinities for lipid vesicles, showing that lipid binding is not a decisive parameter for uptake. Our results indicate that tryptophan content and backbone spacing can affect both the CPP uptake efficiency and the CPP uptake mechanism. The low cytotoxicity of these peptides and the possibilities of tuning their uptake mechanism are interesting from a therapeutic point of view. © 2012 American Chemical Society.

  11. Effects of Exhaustive Aerobic Exercise on Tryptophan-Kynurenine Metabolism in Trained Athletes.

    Directory of Open Access Journals (Sweden)

    Barbara Strasser

    Full Text Available Exhaustive exercise can cause a transient depression of immune function. Data indicate significant effects of immune activation cascades on the biochemistry of monoamines and amino acids such as tryptophan. Tryptophan can be metabolized through different pathways, a major route being the kynurenine pathway, which is often systemically up-regulated when the immune response is activated. The present study was undertaken to examine the effect of exhaustive aerobic exercise on biomarkers of immune activation and tryptophan metabolism in trained athletes. After a standardized breakfast 2 h prior to exercise, 33 trained athletes (17 women, 16 men performed an incremental cycle ergometer exercise test at 60 rpm until exhaustion. After a 20 min rest phase, the participants performed a 20 min maximal time-trial on a cycle ergometer (RBM Cyclus 2, Germany. During the test, cyclists were strongly encouraged to choose a maximal pedalling rate that could be maintained for the respective test duration. Serum concentrations of amino acids tryptophan, kynurenine, phenylalanine, and tyrosine were determined by HPLC and immune system biomarker neopterin by ELISA at rest and immediately post exercise. Intense exercise was associated with a strong increase in neopterin concentrations (p<0.001, indicating increased immune activation following intense exercise. Exhaustive exercise significantly reduced tryptophan concentrations by 12% (p<0.001 and increased kynurenine levels by 6% (p = 0.022. Also phenylalanine to tyrosine ratios were lower after exercise as compared with baseline (p<0.001. The kynurenine to tryptophan ratio correlated with neopterin (r = 0.560, p<0.01. Thus, increased tryptophan catabolism by indoleamine 2,3-dioxygenase appears likely. Peak oxygen uptake correlated with baseline tryptophan and kynurenine concentrations (r = 0.562 and r = 0.511, respectively, both p<0.01. Findings demonstrate that exhaustive aerobic exercise is associated with

  12. Syntheses and Self-assembling Behaviors of Pentagonal Conjugates of Tryptophane Zipper-Forming Peptide

    Directory of Open Access Journals (Sweden)

    Nobuo Kimizuka

    2011-08-01

    Full Text Available Pentagonal conjugates of tryptophane zipper-forming peptide (CKTWTWTE with a pentaazacyclopentadecane core (Pentagonal-Gly-Trpzip and Pentagonal-Ala-Trpzip were synthesized and their self-assembling behaviors were investigated in water. Pentagonal-Gly-Trpzip self-assembled into nanofibers with the width of about 5 nm in neutral water (pH 7 via formation of tryptophane zipper, which irreversibly converted to nanoribbons by heating. In contrast, Pentagonal-Ala-Trpzip formed irregular aggregates in water.

  13. The maize auxotrophic mutant orange pericarp is defective in duplicate genes for tryptophan synthase beta.

    Science.gov (United States)

    Wright, A D; Moehlenkamp, C A; Perrot, G H; Neuffer, M G; Cone, K C

    1992-06-01

    orange pericarp (orp) is a seedling lethal mutant of maize caused by mutations in the duplicate unlinked recessive loci orp1 and orp2. Mutant seedlings accumulate two tryptophan precursors, anthranilate and indole, suggesting a block in tryptophan biosynthesis. Results from feeding studies and enzyme assays indicate that the orp mutant is defective in tryptophan synthase beta activity. Thus, orp is one of only a few amino acid auxotrophic mutants to be characterized in plants. Two genes encoding tryptophan synthase beta were isolated from maize and sequenced. Both genes encode polypeptides with high homology to tryptophan synthase beta enzymes from other organisms. The cloned genes were mapped by restriction fragment length polymorphism analysis to approximately the same chromosomal locations as the genetically mapped factors orp1 and orp2. RNA analysis indicates that both genes are expressed in all tissues examined from normal plants. Together, the biochemical, genetic, and molecular data verify the identity of orp1 and orp2 as duplicate structural genes for the beta subunit of tryptophan synthase.

  14. Flexible Enantioselectivity of Tryptophanase Attributable to Benzene Ring in Heterocyclic Moiety of D-Tryptophan

    Directory of Open Access Journals (Sweden)

    Akihiko Shimada

    2012-05-01

    Full Text Available The invariance principle of enzyme enantioselectivity must be absolute because it is absolutely essential to the homochiral biological world. Most enzymes are strictly enantioselective, and tryptophanase is one of the enzymes with extreme absolute enantioselectivity for L-tryptophan. Contrary to conventional knowledge about the principle, tryptophanase becomes flexible to catalyze D-tryptophan in the presence of diammonium hydrogenphosphate. Since D-amino acids are ordinarily inert or function as inhibitors even though they are bound to the active site, the inhibition behavior of D-tryptophan and several inhibitors involved in this process was examined in terms of kinetics to explain the reason for this flexible enantioselectivity in the presence of diammonium hydrogenphosphate. Diammonium hydrogenphosphate gave tryptophanase a small conformational change so that D-tryptophan could work as a substrate. As opposed to other D-amino acids, D-tryptophan is a very bulky amino acid with a benzene ring in its heterocyclic moiety, and so we suggest that this structural feature makes the catalysis of D-tryptophan degradation possible, consequently leading to the flexible enantioselectivity. The present results not only help to understand the mechanism of enzyme enantioselectivity, but also shed light on the origin of homochirality.

  15. L-Tryptophan Production in Escherichia coli Improved by Weakening the Pta-AckA Pathway.

    Science.gov (United States)

    Liu, Lina; Duan, Xuguo; Wu, Jing

    2016-01-01

    Acetate accumulation during the fermentation process of Escherichia coli FB-04, an L-tryptophan production strain, is detrimental to L-tryptophan production. In an initial attempt to reduce acetate formation, the phosphate acetyltransferase gene (pta) from E. coli FB-04 was deleted, forming strain FB-04(Δpta). Unfortunately, FB-04(Δpta) exhibited a growth defect. Therefore, pta was replaced with a pta variant (pta1) from E. coli CCTCC M 2016009, forming strain FB-04(pta1). Pta1 exhibits lower catalytic capacity and substrate affinity than Pta because of a single amino acid substitution (Pro69Leu). FB-04(pta1) lacked the growth defect of FB-04(Δpta) and showed improved fermentation performance. Strain FB-04(pta1) showed a 91% increase in L-tryptophan yield in flask fermentation experiments, while acetate production decreased by 35%, compared with its parent FB-04. Throughout the fed-batch fermentation process, acetate accumulation by FB-04(pta1) was slower than that by FB-04. The final L-tryptophan titer of FB-04(pta1) reached 44.0 g/L, representing a 15% increase over that of FB-04. Metabolomics analysis showed that the pta1 genomic substitution slightly decreased carbon flux through glycolysis and significantly increased carbon fluxes through the pentose phosphate and common aromatic pathways. These results indicate that this strategy enhances L-tryptophan production and decreases acetate accumulation during the L-tryptophan fermentation process.

  16. Liver and brain tryptophan metabolism following hydrocortisone administration to rats and gerbils.

    Science.gov (United States)

    Green, A R; Sourkes, T L; Young, S N

    1975-02-01

    1 Liver tryptophan pyrrolase activity is low in the mongolian gerbil (Meriones unguiculatus) and is not induced by hydrocortisone (5 mg/kg). In contrast, there is measurable activity in the rat liver and this is induced by hydrocortisone. In vivo measurements confirmed the absence of induction in gerbils but suggested that they were able to metabolize tryptophan. However no detectable pyrrolase activity was found in any other tissues either before or after hydrocortisone. 2 In agreement with previous observations hydrocortisone decreased rat brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) 6 h after administration. Brain tryptophan concentrations were also decreased at this time. In contrast, hydrocortisone did not alter gerbil brain 5-HT, 5-HIAA or trytophan. alpha-Methyltryptophan activated hepatic tryptophan pyrrolase and decreased brain 5-HT and 5-HIAA in both animals. 3 Results suggest that the decrease in rat brain 5-HT and 5-HIAA following hydrocortisone may be associated with the rise in liver tryptophan pyrrolase and that the brain amine changes are mediated through the decrease in brain tryptophan concentration.

  17. Flexible enantioselectivity of tryptophanase attributable to benzene ring in heterocyclic moiety of d-tryptophan.

    Science.gov (United States)

    Shimada, Akihiko; Ozaki, Haruka

    2012-01-01

    The invariance principle of enzyme enantioselectivity must be absolute because it is absolutely essential to the homochiral biological world. Most enzymes are strictly enantioselective, and tryptophanase is one of the enzymes with extreme absolute enantioselectivity for L-tryptophan. Contrary to conventional knowledge about the principle, tryptophanase becomes flexible to catalyze D-tryptophan in the presence of diammonium hydrogenphosphate. Since D-amino acids are ordinarily inert or function as inhibitors even though they are bound to the active site, the inhibition behavior of D-tryptophan and several inhibitors involved in this process was examined in terms of kinetics to explain the reason for this flexible enantioselectivity in the presence of diammonium hydrogenphosphate. Diammonium hydrogenphosphate gave tryptophanase a small conformational change so that D-tryptophan could work as a substrate. As opposed to other D-amino acids, D-tryptophan is a very bulky amino acid with a benzene ring in its heterocyclic moiety, and so we suggest that this structural feature makes the catalysis of D-tryptophan degradation possible, consequently leading to the flexible enantioselectivity. The present results not only help to understand the mechanism of enzyme enantioselectivity, but also shed light on the origin of homochirality.

  18. Efficient isotopic tryptophan labeling of membrane proteins by an indole controlled process conduct.

    Science.gov (United States)

    Berger, Christian; Berndt, Sandra; Pichert, Annelie; Theisgen, Stephan; Huster, Daniel

    2013-06-01

    A protocol for the efficient isotopic labeling of large G protein-coupled receptors with tryptophan in Escherichia coli as expression host was developed that sufficiently suppressed the naturally occurring L-tryptophan indole lyase, which cleaves tryptophan into indole, pyruvate, and ammonia resulting in scrambling of the isotopic label in the protein. Indole produced by the tryptophanase is naturally used as messenger for cell-cell communication. Detailed analysis of different process conducts led to the optimal expression strategy, which mimicked cell-cell communication by the addition of indole during expression. Discrete concentrations of indole and (15) N2 -L-tryptophan at dedicated time points in the fermentation drastically increased the isotopic labeling efficiency. Isotope scrambling was only observed in glutamine, asparagine, and arginine side chains but not in the backbone. This strategy allows producing specifically tryptophan labeled membrane proteins at high concentrations avoiding the disadvantages of the often low yields of auxotrophic E. coli strains. In the fermentation process carried out according to this protocol, we produced ∼15 mg of tryptophan labeled neuropeptide Y receptor type 2 per liter medium.

  19. L-Tryptophan's effects on brain chemistry and sleep in cats and rats: a review.

    Science.gov (United States)

    Radulovacki, M

    1982-01-01

    In this review I shall discuss published and unpublished work from my laboratory dealing with L-tryptophan's effects on brain monoamines and sleep in cats and rats. From our work it appears that normal animals may not be suitable subjects for testing sleep-inducing effect of tryptophan since their slow-wave sleep (SWS) latency is relatively short. In polyphasic sleepers like cats, we did not observe tryptophan's hypnotic effect with any dosage used (10, 30 or 135 mg/kg). However, we found small, but statistically significant, sleep-inducing effect of tryptophan (30 mg/kg, IP) in normal rats. We have tried, therefore, to create insomniac cats with long sleep latencies by using methysergide, a serotonin receptor blocker. The results show that in insomniac cats hypnotic effect of tryptophan, a precursor to brain serotonin, was observed. It involved not only reduction of sleep latencies but also an increase in SWS. It seems likely that tryptophan's partial reversal of methysergide's effect in cats occurred via a dual mechanism of serotonergic activation and catecholaminergic deactivation, while its sleep-inducing effect in normal rats may have been due to the attenuation of the activity of brain catecholamines.

  20. Depleted uranium disposal options evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Hertzler, T.J.; Nishimoto, D.D.; Otis, M.D. [Science Applications International Corp., Idaho Falls, ID (United States). Waste Management Technology Div.

    1994-05-01

    The Department of Energy (DOE), Office of Environmental Restoration and Waste Management, has chartered a study to evaluate alternative management strategies for depleted uranium (DU) currently stored throughout the DOE complex. Historically, DU has been maintained as a strategic resource because of uses for DU metal and potential uses for further enrichment or for uranium oxide as breeder reactor blanket fuel. This study has focused on evaluating the disposal options for DU if it were considered a waste. This report is in no way declaring these DU reserves a ``waste,`` but is intended to provide baseline data for comparison with other management options for use of DU. To PICS considered in this report include: Retrievable disposal; permanent disposal; health hazards; radiation toxicity and chemical toxicity.

  1. Tryptophan probes at the α-synuclein and membrane interface

    Science.gov (United States)

    Pfefferkorn, Candace M.; Lee, Jennifer C.

    2010-01-01

    Understanding how environmental factors affect the conformational dynamics of α-synuclein (α-syn) is of great importance because the accumulation and deposit of aggregated α-syn in the brain are intimately connected to Parkinson’s disease etiology. Measurements of steady-state and time-resolved fluorescence of single tryptophan-containing α-syn variants have revealed distinct phospholipid vesicle and micelle interactions at residues 4, 39, 94, and 125. Our circular dichroism (CD) data confirm that Trp mutations do not affect α-syn membrane binding properties (apparent association constant Kaapp∼1×107M−1 for all synucleins) saturating at an estimated lipid-to-protein molar ratio of 380 or approximately 120 proteins covering ~7% of the surface area of an 80 nm diameter vesicle. Fluorophores at positions 4 and 94 are the most sensitive to the lipid bilayer with pronounced spectral blue-shifts (W4: Δλmax ~23 nm; W94: Δλmax ~10 nm) and quantum yield increases (W4, W94: ~3 fold) while W39 and W125 remain primarily water-exposed. Time-resolved fluorescence data show that all sites (except W125) have subpopulations that interact with the membrane. PMID:20229987

  2. Cloning, expression, purification and characterization of tryptophan hydroxylase variants

    DEFF Research Database (Denmark)

    Boesen, Jane

    ). The main goal was to purify full-length hTPH1. Based on earlier results, hTPH1 was purified using detergent in the purification methods. After incubation of the hTPH1 sample with 0.1 % of n-dodecyl-β-D-maltopyranoside (DDM) the protein binds to the anion exchange column and elutes over a large area...... in the anion exchange, indicating that the protein still exists in different oligomer forms. This was also observed in the gel filtration. Variants of both hTPH1 and hTPH2 containing the regulatory domain or parts of it were constructed and tested for expression in Escherichia coli as well as solubility...... was determined and compared with parameters of chTPH2. Large differences were observed between the two isoforms and tryptophan inhibition was observed for chTPH1 but not for chTPH2. Mass spectrometric analysis of chTPH1 shows that the sample contains two species: chTPH1 and another species, which could...

  3. Novel tryptophan metabolic pathways in auxin biosynthesis in silkworm.

    Science.gov (United States)

    Yokoyama, Chiaki; Takei, Mami; Kouzuma, Yoshiaki; Nagata, Shinji; Suzuki, Yoshihito

    2017-08-01

    In the course of our study of the biosynthetic pathway of auxin, a class of phytohormones, in insects, we proposed the biosynthetic pathway tryptophan (Trp)→indole-3-acetaldoxime (IAOx)→indole-3-acetadehyde (IAAld)→indole-3-acetic acid (IAA). In this study, we identified two branches in the metabolic pathways in the silkworm, possibly affecting the efficiency of IAA production: Trp→indole-3-pyruvic acid→indole-3-lactic acid and IAAld→indole-3-ethanol. We also determined the apparent conversion activities (2.05×10(-7)UmL(-1) for Trp→IAA, 1.30×10(-5)UmL(-1) for IAOx→IAA, and 3.91×10(-1)UmL(-1) for IAAld→IAA), which explain why IAOx and IAAld are barely detectable as either endogenous compounds or metabolites of their precursors. The failure to detect IAAld, even in the presence of an inhibitor of the conversion IAAld→IAA, is explained by a switch in the conversion from IAAld→IAA to IAAld→IEtOH. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Hydration of protonated aromatic amino acids: phenylalanine, tryptophan, and tyrosine.

    Science.gov (United States)

    Gao, Bing; Wyttenbach, Thomas; Bowers, Michael T

    2009-04-01

    The first steps of hydration of the protonated aromatic amino acids phenylalanine, tryptophan, and tyrosine were studied experimentally employing a mass spectrometer equipped with a drift cell to examine the sequential addition of individual water molecules in equilibrium experiments and theoretically by a combination of molecular mechanics and electronic structure calculations (B3LYP/6-311++G**) on the three amino acid systems including up to five water molecules. It is found that both the ammonium and carboxyl groups offer good water binding sites with binding energies of the order of 13 kcal/mol for the first water molecule. Subsequent water molecules bind less strongly, in the range of 7-11 kcal/mol for the second through fifth water molecules. The ammonium group is able to host up to three water molecules and the carboxyl group one water molecule before additional water molecules bind either to the amino acid side chain as in tyrosine or to already-bound water in a second solvation shell around the ammonium group. Reasons for the surprisingly high water affinity of the neutral carboxyl group, comparable to that of the charge-carrying ammonium group, are found to be high intrinsic hydrophilicity, favorable charge-dipole alignment, and--for the case of multiply hydrated species--favorable dipole-dipole interaction among water molecules and the lack of alternative fully exposed hydration sites.

  5. Ego depletion increases risk-taking.

    Science.gov (United States)

    Fischer, Peter; Kastenmüller, Andreas; Asal, Kathrin

    2012-01-01

    We investigated how the availability of self-control resources affects risk-taking inclinations and behaviors. We proposed that risk-taking often occurs from suboptimal decision processes and heuristic information processing (e.g., when a smoker suppresses or neglects information about the health risks of smoking). Research revealed that depleted self-regulation resources are associated with reduced intellectual performance and reduced abilities to regulate spontaneous and automatic responses (e.g., control aggressive responses in the face of frustration). The present studies transferred these ideas to the area of risk-taking. We propose that risk-taking is increased when individuals find themselves in a state of reduced cognitive self-control resources (ego-depletion). Four studies supported these ideas. In Study 1, ego-depleted participants reported higher levels of sensation seeking than non-depleted participants. In Study 2, ego-depleted participants showed higher levels of risk-tolerance in critical road traffic situations than non-depleted participants. In Study 3, we ruled out two alternative explanations for these results: neither cognitive load nor feelings of anger mediated the effect of ego-depletion on risk-taking. Finally, Study 4 clarified the underlying psychological process: ego-depleted participants feel more cognitively exhausted than non-depleted participants and thus are more willing to take risks. Discussion focuses on the theoretical and practical implications of these findings.

  6. Tryptophanase-catalyzed L-tryptophan synthesis from D-serine in the presence of diammonium hydrogen phosphate.

    Science.gov (United States)

    Shimada, Akihiko; Ozaki, Haruka; Saito, Takeshi; Noriko, Fujii

    2009-06-01

    Tryptophanase, an enzyme with extreme absolute stereospecificity for optically active stereoisomers, catalyzes the synthesis of l-tryptophan from l-serine and indole through a beta-substitution mechanism of the ping-pong type, and has no activity on d-serine. We previously reported that tryptophanase changed its stereospecificity to degrade d-tryptophan in highly concentrated diammonium hydrogen phosphate, (NH(4))(2)HPO(4) solution. The present study provided the same stereospecific change seen in the d-tryptophan degradation reaction also occurs in tryptophan synthesis from d-serine. Tryptophanase became active to d-serine to synthesize l-tryptophan in the presence of diammonium hydrogen phosphate. This reaction has never been reported before. d-serine seems to undergo beta-replacement via an enzyme-bonded alpha-aminoacylate intermediate to yield l-tryptophan.

  7. Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation

    OpenAIRE

    Campbell, Eric L.; Bruyninckx, Walter J.; Kelly, Caleb J; Louise E. Glover; McNamee, Eóin N.; Bowers, Brittelle E.; Bayless, Amanda J.; Scully, Melanie; Saeedi, Bejan J.; Golden-Mason, Lucy; Ehrentraut, Stefan F.; Curtis, Valerie F; Burgess, Adrianne; Garvey, John F; Sorensen, Amber

    2014-01-01

    Acute intestinal inflammation involves early accumulation of neutrophils (PMN) followed by either resolution or progression to chronic inflammation. Based on recent evidence mucosal metabolism influences disease outcomes, we hypothesized that transmigrating PMN influence the transcriptional profile of the surrounding mucosa. Microarray studies revealed a cohort of hypoxia-responsive genes regulated by PMN-epithelial crosstalk. Transmigrating PMN rapidly depleted microenvironmental O2 sufficie...

  8. From tryptophan to hydroxytryptophan: reflections on a busy life.

    Science.gov (United States)

    Fisher, Hans

    2009-01-01

    Given the very difficult odyssey of my early years, who could have imagined the incredible and successful journey that constituted my life path after age 13? I was born into a Jewish family in Breslau, Germany, right before the rise of Nazism and Hitler's election. After Kristallnacht, when my father was taken to Buchenwald Concentration Camp, we had to leave Germany as soon as possible. The first opportunity came in May of 1939, when we boarded the SS St. Louis bound for Havana, Cuba. Almost all passengers were denied entrance into Cuba, and the ship had to go back to Europe, where I ended up in France. In December of 1939, during World War II, I was fortunate to be able to leave France. This time I made it to Cuba, where my father was already in residence. A year later, my entire family was allowed into the United States. I took advantage of all the educational resources in this land of opportunity. I graduated valedictorian of my high school class and earned a four-year scholarship to Rutgers University, where I obtained a Bachelor of Science degree. I went on to earn a Master's degree from the University of Connecticut and finally a PhD from the University of Illinois. Within two months after graduating from Illinois, I was hired as an assistant professor of nutritional biochemistry at Rutgers, where I enjoyed a most productive research and teaching career. My PhD research involved tryptophan and niacin metabolism in the chick, and upon arrival at Rutgers I continued amino acid studies with the goal of assessing the essential amino acid requirements for egg production. This research was crowned with success and was followed with amino acid requirement studies for maintenance and for growth in rabbits, and ultimately with a reevaluation of requirements in adult humans. An outgrowth of the maintenance requirements led to a series of investigations into the metabolism of histidine, histamine, and carnosine (a histidine-containing dipeptide). Histamine, we found

  9. Investigation of intranodal depletion effects

    Energy Technology Data Exchange (ETDEWEB)

    Forslund, P. E-mail: petri.forslund@se.abb.com; Mueller, E.; Lindahl, S

    2001-02-01

    The modeling of depletion induced intranodal effects on important neutron physical parameters in nodal diffusion theory is addressed. Consideration is given to two situations where these aspects are of particular interest, namely, in mixed oxide cores where strong interaction between uranium and plutonium mixed oxide assemblies occur, and in boiling water reactor cores where significant control rod history effects are encountered. A model based on a low order polynomial representation of intranodal cross-section spatial behaviour is considered. Two approaches for determining the constraints for the polynomial fitting procedure are applied. The first one is a conventional method employing intranodal exposure values, whereas the second model combines intranodal exposure and isotopic inventory information. Numerical studies are performed in order to evaluate the relative merits of the different models. It is demonstrated that pin power predictions are significantly influenced by intranodal effects. It is also found that the combined use of intranodal isotopic inventory and exposure distributions for estimating intranodal cross-section behaviour significantly improves the accuracy in pin powers over the more traditional approach of utilizing exposure distributions only.

  10. Depleted argon from underground sources

    Energy Technology Data Exchange (ETDEWEB)

    Back, H.O.; /Princeton U.; Alton, A.; /Augustana U. Coll.; Calaprice, F.; Galbiati, C.; Goretti, A.; /Princeton U.; Kendziora, C.; /Fermilab; Loer, B.; /Princeton U.; Montanari, D.; /Fermilab; Mosteiro, P.; /Princeton U.; Pordes, S.; /Fermilab

    2011-09-01

    Argon is a powerful scintillator and an excellent medium for detection of ionization. Its high discrimination power against minimum ionization tracks, in favor of selection of nuclear recoils, makes it an attractive medium for direct detection of WIMP dark matter. However, cosmogenic {sup 39}Ar contamination in atmospheric argon limits the size of liquid argon dark matter detectors due to pile-up. The cosmic ray shielding by the earth means that Argon from deep underground is depleted in {sup 39}Ar. In Cortez Colorado a CO{sub 2} well has been discovered to contain approximately 500ppm of argon as a contamination in the CO{sub 2}. In order to produce argon for dark matter detectors we first concentrate the argon locally to 3-5% in an Ar, N{sub 2}, and He mixture, from the CO{sub 2} through chromatographic gas separation. The N{sub 2} and He will be removed by continuous cryogenic distillation in the Cryogenic Distillation Column recently built at Fermilab. In this talk we will discuss the entire extraction and purification process; with emphasis on the recent commissioning and initial performance of the cryogenic distillation column purification.

  11. Plasma Tryptophan and the Kynurenine–Tryptophan Ratio Are Associated with the Acquisition of Statural Growth Deficits and Oral Vaccine Underperformance in Populations with Environmental Enteropathy

    Science.gov (United States)

    Kosek, Margaret N.; Mduma, Estomih; Kosek, Peter S.; Lee, Gwenyth O.; Svensen, Erling; Pan, William K. Y.; Olortegui, Maribel Paredes; Bream, Jay H.; Patil, Crystal; Asayag, Cesar Ramal; Sanchez, Graciela Meza; Caulfield, Laura E.; Gratz, Jean; Yori, Pablo Peñataro

    2016-01-01

    Early childhood enteric infections have adverse impacts on child growth and can inhibit normal mucosal responses to oral vaccines, two critical components of environmental enteropathy. To evaluate the role of indoleamine 2,3-dioxygenase 1 (IDO1) activity and its relationship with these outcomes, we measured tryptophan and the kynurenine–tryptophan ratio (KTR) in two longitudinal birth cohorts with a high prevalence of stunting. Children in rural Peru and Tanzania (N = 494) contributed 1,251 plasma samples at 3, 7, 15, and 24 months of age and monthly anthropometrics from 0 to 36 months of age. Tryptophan concentrations were directly associated with linear growth from 1 to 8 months after biomarker assessment. A 1-SD increase in tryptophan concentration was associated with a gain in length-for-age Z-score (LAZ) of 0.17 over the next 6 months in Peru (95% confidence interval [CI] = 0.11–0.23, P < 0.001) and a gain in LAZ of 0.13 Z-scores in Tanzania (95% CI = 0.03–0.22, P = 0.009). Vaccine responsiveness data were available for Peru only. An increase in kynurenine by 1 μM was associated with a 1.63 (95% CI = 1.13–2.34) increase in the odds of failure to poliovirus type 1, but there was no association with tetanus vaccine response. A KTR of 52 was 76% sensitive and 50% specific in predicting failure of response to serotype 1 of the oral polio vaccine. KTR was associated with systemic markers of inflammation, but also interleukin-10, supporting the association between IDO1 activity and immunotolerance. These results strongly suggest that the activity of IDO1 is implicated in the pathophysiology of environmental enteropathy, and demonstrates the utility of tryptophan and kynurenine as biomarkers for this syndrome, particularly in identifying those at risk for hyporesponsivity to oral vaccines. PMID:27503512

  12. Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party

    Directory of Open Access Journals (Sweden)

    Marie Thérèse Rubio

    2017-01-01

    Full Text Available Abstract Background The impact of the use of anti-thymocyte globulin (ATG in allogeneic stem cell transplantation performed with HLA-identical sibling donors following fludarabine and 4 days intravenous busulfan myeloablative conditioning regimen has been poorly explored. Methods We retrospectively analyzed 566 patients who underwent a first HLA-identical allogeneic stem cell transplantation with this conditioning regimen for acute myeloid leukemia in first complete remission between 2006 and 2013 and compared the outcomes of 145 (25.6% patients who received ATG (ATG group to 421 (74.4% who did not (no-ATG group. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results Patients in the ATG group were older, received more frequently peripheral blood stem cell grafts from older donors, and were transplanted more recently. With a median follow-up of 19 months, patients in the ATG group had reduced 2-year cumulative incidence of chronic graft-versus-host disease (GVHD (31 vs. 52%, p = 0.0002 and of its extensive form (8 vs. 26%, p < 0.0001 but similar relapse incidence (22 vs. 27%, p = 0.23 leading to improved GVHD and relapse-free survival (GRFS (60 vs. 40%, p = 0.0001. In multivariate analyses, the addition of ATG was independently associated with lower chronic GVHD (HR = 0.46, p = 0.0001, improved leukemia-free survival (HR = 0.67, p = 0.027, overall survival (HR = 0.65, p = 0.027, and GRFS (HR = 0.51, p = 4 × 10−5. Recipient age above 50 years was the only other factor associated with worse survivals. Conclusions These results suggest that the use of ATG with fludarabine and 4 days intravenous busulfan followed by HLA-identical sibling donor allogeneic stem cell transplantation for acute myeloid leukemia improves overall transplant outcomes due to reduced incidence of chronic GVHD without increased

  13. Depletion sensitivity predicts unhealthy snack purchases

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; Fennis, Bob M.; Vet, De Emely; Ridder, De Denise T.D.

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose

  14. Depletion sensitivity predicts unhealthy snack purchases

    NARCIS (Netherlands)

    Salmon, Stefanie J.; Adriaanse, Marieke A.|info:eu-repo/dai/nl/304823023; Fennis, Bob M.; De Vet, Emely; De Ridder, Denise T D

    2016-01-01

    The aim of the present research is to examine the relation between depletion sensitivity - a novel construct referring to the speed or ease by which one's self-control resources are drained - and snack purchase behavior. In addition, interactions between depletion sensitivity and the goal to lose

  15. The Chemistry and Toxicology of Depleted Uranium

    Directory of Open Access Journals (Sweden)

    Sidney A. Katz

    2014-03-01

    Full Text Available Natural uranium is comprised of three radioactive isotopes: 238U, 235U, and 234U. Depleted uranium (DU is a byproduct of the processes for the enrichment of the naturally occurring 235U isotope. The world wide stock pile contains some 1½ million tons of depleted uranium. Some of it has been used to dilute weapons grade uranium (~90% 235U down to reactor grade uranium (~5% 235U, and some of it has been used for heavy tank armor and for the fabrication of armor-piercing bullets and missiles. Such weapons were used by the military in the Persian Gulf, the Balkans and elsewhere. The testing of depleted uranium weapons and their use in combat has resulted in environmental contamination and human exposure. Although the chemical and the toxicological behaviors of depleted uranium are essentially the same as those of natural uranium, the respective chemical forms and isotopic compositions in which they usually occur are different. The chemical and radiological toxicity of depleted uranium can injure biological systems. Normal functioning of the kidney, liver, lung, and heart can be adversely affected by depleted uranium intoxication. The focus of this review is on the chemical and toxicological properties of depleted and natural uranium and some of the possible consequences from long term, low dose exposure to depleted uranium in the environment.

  16. High homocysteine induces betaine depletion.

    Science.gov (United States)

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J

    2015-04-28

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI-LC-MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte.

  17. Specification for the VERA Depletion Benchmark Suite

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kang Seog [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-12-17

    CASL-X-2015-1014-000 iii Consortium for Advanced Simulation of LWRs EXECUTIVE SUMMARY The CASL neutronics simulator MPACT is under development for the neutronics and T-H coupled simulation for the pressurized water reactor. MPACT includes the ORIGEN-API and internal depletion module to perform depletion calculations based upon neutron-material reaction and radioactive decay. It is a challenge to validate the depletion capability because of the insufficient measured data. One of the detoured methods to validate it is to perform a code-to-code comparison for benchmark problems. In this study a depletion benchmark suite has been developed and a detailed guideline has been provided to obtain meaningful computational outcomes which can be used in the validation of the MPACT depletion capability.

  18. Microenvironment of tryptophan residues in beta-lactoglobulin derivative polypeptide-sodium dodecyl sulfate complexes.

    Science.gov (United States)

    Imamura, T; Konishi, K

    1992-06-01

    The changes of microenvironment of tryptophan residues in beta-lactoglobulin A and its cyanogen bromide (CNBr) fragments with the binding of sodium dodecyl sulfate (SDS) were studied with measurements of the rates of N-bromosuccinimide (NBS) modification reactions by stopped-flow photometry. Two tryptophan residues of carboxyamidomethylated (RCM) beta-lactoglobulin A in the states of their complexes with SDS were clearly distinguishable by their differences in NBS modification rates. We confirmed by experiments with CNBr fragments containing trytophan residue. The modification rates of Trp 19 in RCM beta-lactoglobulin A-SDS complexes were about 10-fold smaller than those expected for tryptophan residues exposed entirely to the aqueous solvent. The Trp 61 was hardly changed. The change of rate constants for Trp 19 was virtually consistent with those observed when N-acetyl-L-trytophan ethylester was dissolved in SDS micelles. For various species of polypeptide-SDS complexes, all tryptophan residues were reactive to NBS and also, for some of them, the differences in NBS modification rates were observed between tryptophan residues on a common polypeptide chain. These results suggest micellar and heterogeneous bindings of SDS to polypeptides.

  19. Reaction pathway of tryptophanase-catalyzed L-tryptophan synthesis from D-serine.

    Science.gov (United States)

    Shimada, Akihiko; Ozaki, Haruka; Saito, Takeshi; Fujii, Noriko

    2011-11-01

    Tryptophanase, L-tryptophan indole-lyase with extremely absolute stereospecificity, can change the stereospecificity in concentrated diammonium hydrogenphosphate solution. While tryptophanase is not inert to D-serine in the absence of diammonium hydrogenphosphate, it can undergo L-tryptophan synthesis from D-serine along with indole in the presence of it. It has been well known that tryptophanase synthesizes L-tryptophan from L-serine through a β-substitution mechanism of the ping-pong type. However, a metabolic pathway of L-tryptophan synthesis from D-serine has remained unclear. The present study aims to elucidate it. Diammonium hydrogenphosphate plays a role in the emergence of catalytic activity on D-serine. The salt gives tryptophanase a small conformational change, which makes it possible to catalyze D-serine. Tryptophanase-bound D-serine produces L-tryptophan synthesis by β-replacement reaction via the enzyme-bound aminoacrylate intermediate. Our result will be valuable in studying the origin of homochirality.

  20. Lignans from Carthamus tinctorius suppress tryptophan breakdown via indoleamine 2,3-dioxygenase

    Science.gov (United States)

    Kuehnl, Susanne; Schroecksnadel, Sebastian; Temml, Veronika; Gostner, Johanna M.; Schennach, Harald; Schuster, Daniela; Schwaiger, Stefan; Rollinger, Judith M.; Fuchs, Dietmar; Stuppner, Hermann

    2013-01-01

    Seed extracts of Carthamus tinctorius L. (Asteraceae), safflower, have been traditionally used to treat coronary disease, thrombotic disorders, and menstrual problems but also against cancer and depression. A possible effect of C. tinctorius compounds on tryptophan-degrading activity of enzyme indoleamine 2,3-dioxygenase (IDO) could explain many of its activities. To test for an effect of C. tinctorius extracts and isolated compounds on cytokine-induced IDO activity in immunocompetent cells in vitro methanol and ethylacetate seed extracts were prepared from cold pressed seed cakes of C. tinctorius and three lignan derivatives, trachelogenin, arctigenin and matairesinol were isolated. The influence on tryptophan breakdown was investigated in peripheral blood mononuclear cells (PBMCs). Effects were compared to neopterin production in the same cellular assay. Both seed extracts suppressed tryptophan breakdown in stimulated PBMC. The three structurally closely related isolates exerted differing suppressive activity on PBMC: arctigenin (IC50 26.5 μM) and trachelogenin (IC50 of 57.4 μM) showed higher activity than matairesinol (IC50 >200 μM) to inhibit tryptophan breakdown. Effects on neopterin production were similar albeit generally less strong. Data show an immunosuppressive property of compounds which slows down IDO activity. The in vitro results support the view that some of the anti-inflammatory, anti-cancer and antidepressant properties of C. tinctorius lignans might relate to their suppressive influence on tryptophan breakdown. PMID:23867649

  1. Mutagenesis of tryptophan199 suggests that hopping is required for MauG-dependent tryptophan tryptophylquinone biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Tarboush, Nafez Abu; Jensen, Lyndal M.R.; Yukl, Erik T.; Geng, Jiafeng; Liu, Aimin; Wilmot, Carrie M.; Davidson, Victor L. (Central Florida); (GSU); (UMMC); (UMM)

    2011-12-07

    The diheme enzyme MauG catalyzes the posttranslational modification of the precursor protein of methylamine dehydrogenase (preMADH) to complete biosynthesis of its protein-derived tryptophan tryptophylquinone (TTQ) cofactor. Catalysis proceeds through a high valent bis-Fe(IV) redox state and requires long-range electron transfer (ET), as the distance between the modified residues of preMADH and the nearest heme iron of MauG is 19.4 {angstrom}. Trp199 of MauG resides at the MauG-preMADH interface, positioned midway between the residues that are modified and the nearest heme. W199F and W199K mutations did not affect the spectroscopic and redox properties of MauG, or its ability to stabilize the bis-Fe(IV) state. Crystal structures of complexes of W199F/K MauG with preMADH showed no significant perturbation of the MauG-preMADH structure or protein interface. However, neither MauG variant was able to synthesize TTQ from preMADH. In contrast, an ET reaction from diferrous MauG to quinone MADH, which does not require the bis-Fe(IV) intermediate, was minimally affected by the W199F/K mutations. W199F/K MauGs were able to oxidize quinol MADH to form TTQ, the putative final two-electron oxidation of the biosynthetic process, but with k{sub cat}/K{sub m} values approximately 10% that of wild-type MauG. The differential effects of the W199F/K mutations on these three different reactions are explained by a critical role for Trp199 in mediating multistep hopping from preMADH to bis-Fe(IV) MauG during the long-range ET that is required for TTQ biosynthesis.

  2. Tryptophan metabolism in tsetse flies and the consequences of its derangement

    Directory of Open Access Journals (Sweden)

    R. H. Gooding

    1987-01-01

    Full Text Available Literature comparing salmon and wild type Glossina morsitans morsitans and that comparing tan and wild type Glossina palpalis palpalis is reviewed. New information is presented on behaviour and biochemistry of salmon and wild type G. m. morsitans. The eye color mutants result from two lesions in the tryptophan to xanthommatin pathway: lack of tryptophan oxygenase in G. m morsitans and failure to produce or retain xanthommatin in eyes (but not in testes of G. p. palpalis. The salmon allele in G. m. morsitans is pleiotropic and profoundly affects many aspects of fly biology including longevity, reproductive capacity, vision, vectorial capacity and duration of flight, but not circadian rhythms. The tan allele in G. p. palpalis has little effect upon the biology of flies under laboratory conditions, except that tan flies appear less active than normal. Adult tsetse flies metabolize tryptophan to kynurenine which is excreted; fluctuations in activities of the enzymes producing kynurenine suggest this pathway is under metabolic control.

  3. Effect of tryptophan suplementation in quails (Coturnix coturnix japónica

    Directory of Open Access Journals (Sweden)

    Liliana Betancourt López

    2005-05-01

    Full Text Available The behaviour and productive parameters of 288 quails (Coturnix coturnix japonica were studied in a commercial farm. They were supplemented with tryptophan as a precursor of the neurotransmitter serotonin. Levels of 0 (T1, 1,25 mg/day (T2 and 2,5 mg/day (T3. The control group showed a higher number of birds (P<0,05 with an aggressive position before an external stimulus. This study proves that tryphtophan decreases aggression and stabilizes social behaviour. Similarly, the number of birds with moulted backs was higher in the witness group. During the evaluation period a higher egg weight was observed along with improved food conversion and a higher weight gain in the groups supplemented with tryptophan clearly showing the positive effect of tryptophan.

  4. Determination of epristeride by its quenching effect on the fluorescence of L-tryptophan

    Institute of Scientific and Technical Information of China (English)

    Ai-Qin Gong; Xia-Shi Zhu

    2013-01-01

    A rapid, novel spectrofluorimetric method to determine epristeride (EP) in biological fluids and a pharmaceutical formulation was developed, based on the fact that fluorescence intensity of L-tryptophan could be quenched by EP in the medium of pH ¼ 9.0. The various factors influencing fluorescence quenching were discussed. The quenching mechanism was investigated with the quenching type, synchronous fluorescence spectra and quantum efficiency. Under the optimized conditions, fluorescence quenching value (ΔF ¼ FL-tryptophan-FEP-L-tryptophan) showed a good linear relationship with the EP concentration ranging from 0.4 to 12.0μg/mL. The linearity, recovery and limit of detection demonstrated that the proposed method was suitable for EP determination in biological fluids and EP tablets. The method was successfully applied to the analysis of EP in real samples and the obtained results were in good agreement with the results of the official method.

  5. Adsorption of the Enantiomers of Tryptophan on Stationary Phase Bonded with Bovine Serum Albumin

    Institute of Scientific and Technical Information of China (English)

    ZHANG Fengbao; CHENG Ming; LI Shuang; LIU Liang; ZHANG Guoliang

    2006-01-01

    Frontal analysis is frequently applied to measuring single or multi-component adsorption isotherms. In this work, the competitive adsorption isotherm data of two enantiomers of tryptophan were obtained by competitive frontal analysis. The stationary phase in the column was silica-immobilized bovine serum albumin(BSA)by the derivative method, and the mobile phase was a phosphate buffer. These isotherm data were fitted by the competitive Bilangmuir model. This model can account for the behavior of both tryptophan enantiomers and these profiles were found to fit the experimental band profiles(square error is 0.999 6). The parameters obtained were used in numericai calculations to predict the band profiles of the racemic mixtures of tryptophan. The equilibriumdispersive model provides satisfactory prediction, with minor differences between the calculated and the experimental profiles.

  6. The crystal structure of tryptophan hydroxylase with bound amino acid substrate

    DEFF Research Database (Denmark)

    Windahl, Michael Skovbo; Petersen, Charlotte Rode; Christensen, Hans Erik Mølager

    2008-01-01

    124−Asp139 and Ile367−Thr369 close around the active site. Similar structural changes are seen in the catalytic domain of phenylalanine hydroxylase (PAH) upon binding of substrate analogues norleucine and thienylalanine to the PAH·BH4 complex. In fact, the chicken TPH1·Trp·imidazole structure......Tryptophan hydroxylase (TPH) is a mononuclear non-heme iron enzyme, which catalyzes the reaction between tryptophan, O2, and tetrahydrobiopterin (BH4) to produce 5-hydroxytryptophan and 4a-hydroxytetrahydrobiopterin. This is the first and rate-limiting step in the biosynthesis...... of the neurotransmitter and hormone serotonin (5-hydroxytryptamine). We have determined the 1.9 Å resolution crystal structure of the catalytic domain (Δ1−100/Δ415−445) of chicken TPH isoform 1 (TPH1) in complex with the tryptophan substrate and an iron-bound imidazole. This is the first structure of any aromatic amino...

  7. Flow-injection chemiluminescence determination of tryptophan using galangin-potassium permanganate-polyphosphoric acid system

    Institute of Scientific and Technical Information of China (English)

    Hui Chen; Li Li; Min Zhou; Yong Jun Ma

    2008-01-01

    A high sensitive flow-injection chemiluminescence (FI-CL)method for the determination of tryptephan has been developed.The method is based on the chemiluminescence reaction of galangin-potassium perrnanganate-tryptophan in polyphosphoric acid (PPA)media.Under the optimized conditions,tryptophan was determined in the range 0.05-10 μg/mL with the detection limit (30)of 5.0× 10-3 μg/mL.The relative standard deviation (RSD)was 1.0% for 11 replicate determinations of 1.0 μg/mL tryptophan.Three synthetic samples were determined selectively with recoveries in the range from 99.6% to 102.0% in the presence of other amino acids.

  8. Possible ozone depletions following nuclear explosions

    Science.gov (United States)

    Whitten, R. C.; Borucki, W. J.; Turco, R. P.

    1975-01-01

    The degree of depletion of the ozone layer ensuing after delivery of strategic nuclear warheads (5000 and 10,000 Mton) due to production of nitrogen oxides is theoretically assessed. Strong depletions are calculated for 16-km and 26-km altitudes, peaking 1-2 months after detonation and lasting for three years, while a significant depletion at 36 km would peak after one year. Assuming the explosions occur between 30 and 70 deg N, these effects should be much more pronounced in this region than over the Northern Hemisphere as a whole. It is concluded that Hampson's concern on this matter (1974) is well-founded.-

  9. The crystal structure of tryptophan hydroxylase with bound amino acid substrate

    DEFF Research Database (Denmark)

    Windahl, Michael Skovbo; Petersen, Charlotte Rode; Christensen, Hans Erik Mølager

    2008-01-01

    acid hydroxylase with bound natural amino acid substrate. The iron coordination can be described as distorted trigonal bipyramidal coordination with His273, His278, and Glu318 (partially bidentate) and one imidazole as ligands. The tryptophan stacks against Pro269 with a distance of 3.9 Å between...... of the neurotransmitter and hormone serotonin (5-hydroxytryptamine). We have determined the 1.9 Å resolution crystal structure of the catalytic domain (Δ1−100/Δ415−445) of chicken TPH isoform 1 (TPH1) in complex with the tryptophan substrate and an iron-bound imidazole. This is the first structure of any aromatic amino...

  10. Tryptophan-Ethylester, the False (Unveiled) Melatonin Isomer in Red Wine

    Science.gov (United States)

    Iriti, Marcello; Vigentini, Ileana

    2015-01-01

    Among the food plants, the presence of melatonin in grapes (Vitis vinifera L.) deserves particular attention because of the production of wine, an alcoholic beverage of economic relevance and with putative healthy effects. Furthermore, melatonin isomers have been detected in wine too. Recently, one of these isomers has been identified as tryptophan-ethylester, a compound with the same molecular weight of melatonin. In this Commentary, we briefly comment the source(s) of tryptophan-ethylester in wine and the putative nutritional role(s). PMID:25922582

  11. [Nature of tryptophan photooxidation products in lysozyme in the presence of methylene blue].

    Science.gov (United States)

    Churakova, N I; Kravchenko, N A; Serebriakov, E P; Kaverzneva, E D

    1976-05-01

    One out of six trytophan residues in two lysozyme modification, obtained under lysozyme photooxidation in the presence of methylene blue, is found to be oxidized to N'-formylkinurenine (in one modification) and to kinurenine (in the other modification). The transition of one modification into another via detaching of N'-formyl group by soft acid hydrolysis has shown that one and the same tryptophan residue is oxidized in both products, Possible mechanism of tryptophan oxidation to the products mentioned is discu-sed on the basis of the hypothesis on signlet mechanism of lysozyme photooxidation in the presence of methylene blue.

  12. Studies on the biotin-binding site of avidin. Tryptophan residues involved in the active site.

    Science.gov (United States)

    Gitlin, G; Bayer, E A; Wilchek, M

    1988-01-01

    Egg-white avidin was modified with the tryptophan-specific reagent 2-hydroxy-5-nitrobenzyl bromide. The complete loss of biotin-binding activity was achieved upon modification of an average of one tryptophan residue per avidin subunit. The identity of the modified residues was determined by isolating the relevant tryptic and chymotryptic peptides from CNBr-cleaved avidin fragments. The results demonstrate that Trp-70 and Trp-110 are modified in approximately equivalent proportions. It is believed that these residues are located in the active site of avidin and take part in the binding of biotin. PMID:3355517

  13. Studies on the biotin-binding site of avidin. Tryptophan residues involved in the active site.

    Science.gov (United States)

    Gitlin, G; Bayer, E A; Wilchek, M

    1988-02-15

    Egg-white avidin was modified with the tryptophan-specific reagent 2-hydroxy-5-nitrobenzyl bromide. The complete loss of biotin-binding activity was achieved upon modification of an average of one tryptophan residue per avidin subunit. The identity of the modified residues was determined by isolating the relevant tryptic and chymotryptic peptides from CNBr-cleaved avidin fragments. The results demonstrate that Trp-70 and Trp-110 are modified in approximately equivalent proportions. It is believed that these residues are located in the active site of avidin and take part in the binding of biotin.

  14. 6-Nitro-L-tryptophan: a novel spectroscopic probe of trp aporepressor and human serum albumin.

    Science.gov (United States)

    Phillips, R S; Marmorstein, R Q

    1988-04-01

    The binding of 6-nitro-L-tryptophan to trp aporepressor and human serum albumin has been examined by visible difference spectroscopy and circular dichroism. 6-Nitro-L-tryptophan, prepared by nitration of L-tryptophan with nitric acid in glacial acetic acid, exhibits a visible and near-uv absorption spectrum with lambda max at about 330 nm (epsilon = 7 X 10(3) M-1 cm-1) and a shoulder near 380 nm in H2O. In the presence of trp aporepressor, the visible absorption intensity is sharply diminished. Visible difference spectral titration data give KD = 1.27 X 10(-4) M and n = 0.95 per subunit at 25 degrees C. While 6-nitro-L-tryptophan exhibits no significant circular dichroism between 300 and 500 nm, the complex with trp aporepressor exhibits strong circular dichroism signals, with a negative maximum at 386 nm (delta epsilon = -7.5 M-1 cm-1) and a positive maximum at 310 nm (delta epsilon = +6 M-1 cm-1). Circular dichroism titration data give KD = 1.69 X 10(-4) M and n = 0.90 per subunit at 25 degrees C. The KD values determined spectroscopically are in excellent agreement with that determined by equilibrium dialysis, KD = 1.5 X 10(-4) M at 25 degrees C. In the presence of human serum albumin, the spectrum of 6-nitro-L-tryptophan exhibits a blue shift and an increase in absorption intensity; similar changes are observed in solvents of low dielectric contrast such as 80% aqueous dioxane. Visible difference spectral titration data give KD = 8.0 X 10(-5) M and n = 0.95 for human serum albumin. The complex of 6-nitro-L-tryptophan with human serum albumin exhibits a strong positive circular dichroism maximum at 380 nm (delta epsilon = +9.8 M-1 cm-1) with a shoulder at 310-320 nm. Circular dichroism titration data give KD = 6.4 X 10(-5) M and n = 0.83, in good agreement with the visible difference spectral results. Taken together, our results demonstrate the utility of 6-nitro-L-tryptophan as a spectroscopic probe for tryptophan-binding proteins.

  15. Adsorption of the cysteine–tryptophan dipeptide at the Au(110)/liquid interface studied using reflection anisotropy spectroscopy

    DEFF Research Database (Denmark)

    Morozzo della Rocca, Blasco; Smith, C I; Tesauro, Cinzia

    2010-01-01

    failed to re-establish the initial population of Au–S bonds and the changes induced in the region of the spectrum associated with the tryptophan's by the positive potentials were permanent on the time scale of an hour. Subtle changes associated with the tryptophan moieties indicate that the orientation...

  16. Fluorescent differentiation and quantificational detection of free tryptophan in serum within a confined metal-organic tetrahedron.

    Science.gov (United States)

    He, Cheng; Wang, Jian; Wu, Pengyan; Jia, Lingyun; Bai, Ying; Zhang, Zhichao; Duan, Chunying

    2012-12-18

    A metal-organic cerium tetrahedron having size constraints and cooperated interactions within its cavity was used to selectively recognize tryptophan over other natural amino acids and Trp-containing peptides. It was applied in quantificational detection of free tryptophan in serum.

  17. Twenty-four-hour plasma tryptophan concentrations and ratios are below normal in obese subjects and are not normalized by substantial weight reduction

    DEFF Research Database (Denmark)

    Breum, Leif; Rasmussen, Michael H; Hilsted, Jannik

    2003-01-01

    subjects. Blood samples were drawn frequently throughout the 24-h period. An insulin tolerance test was also used to determine whether weight loss altered the ability of insulin to modify plasma concentrations of tryptophan and of the other large neutral amino acids. RESULTS: Plasma tryptophan......BACKGROUND: Plasma tryptophan concentrations and the ratio of tryptophan to other large neutral amino acids (plasma tryptophan ratio) are reportedly low in obese subjects. The plasma tryptophan ratio predicts brain tryptophan uptake and serotonin production. If this ratio is low in obese subjects...... concentrations and ratios in obese subjects were low at all times; these effects persisted after weight reduction. Plasma concentrations of all the large neutral amino acids decreased during insulin infusion in all the groups. CONCLUSIONS: The low 24-h plasma tryptophan ratios in obese and formerly obese...

  18. The tryptophan hydroxylase activation inhibitor, AGN-2979, decreases regional 5-HT synthesis in the rat brain measured with alpha-[14C]methyl-L-tryptophan: an autoradiographic study.

    Science.gov (United States)

    Hasegawa, Shu; Kanemaru, Kazuya; Gittos, Maurice; Diksic, Mirko

    2005-10-15

    Many experimental conditions are stressful for animals. It is well known that stress induces tryptophan hydroxylase (TPH) activation, resulting in increased serotonin (5-HT) synthesis. In our experimental procedure to measure 5-HT synthesis using alpha-[(14)C]methyl-L-tryptophan (alpha-MTrp) autoradiographic method, the hind limbs of animals are restrained using a loose-fitted plaster cast such that the forelimbs of the animal remain free. The objective of the present investigation was to evaluate the changes, if any, in 5-HT synthesis, after injecting these restrained rats with the TPH activation inhibitor AGN-2979. The effect on regional 5-HT synthesis was studied using the alpha-MTrp autoradiographic method. The hypothesis was that the TPH activation inhibitor would reduce 5-HT synthesis, if TPH activation was induced by this restraint. The rats received injection of AGN-2979 (10 mg/kg, i.p.) or distilled water vehicle (1 mL/kg, i.p.) 1 h prior to tracer administration. The free- and total tryptophan concentrations were not significantly different between the treatment and control groups. The results demonstrate that 5-HT synthesis in AGN-2979 treated rats is significantly decreased (-12 to -35%) in both the raphe nuclei and their terminal areas when compared to the control rats. These findings suggest that restrained conditions, such as those used in our experimental protocol, induce TPH activation resulting in an increased 5-HT synthesis throughout the brain. The reduction in 5-HT synthesis in the AGN-2979 group is not related to a change in the plasma tryptophan. Because there was no activation in the pineal body, the structure having a different isoform of TPH, we can propose that it is only the brain TPH that becomes activated with this specific restraint.

  19. Ingestion of branched-chain amino acids and tryptophan during sustained exercise in man: failure to affect performance

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Raaymakers, J S; Saris, W H

    1995-01-01

    tryptophan ingestion caused a 7- to 20-fold increase. Exercise time to exhaustion was not different between treatments (122 +/- 3 min). 3. The data suggest that manipulation of tryptophan supply to the brain either has no additional effect upon serotoninergic activity during prolonged exhaustive exercise......1. An increased uptake of tryptophan in the brain may increase serotoninergic activity and recently has been suggested to be a cause of fatigue during prolonged exercise. The present study, therefore, investigates whether ingestion of tryptophan or the competing branched-chain amino acids (BCAAs......) affect performance. Ten endurance-trained male athletes were studied during cycle exercise at 70-75% maximal power output, while ingesting, ad random and double-blind, drinks that contained 6% sucrose (control) or 6% sucrose supplemented with (1) tryptophan (3 g l-1), (2) a low dose of BCAA (6 g l-1...

  20. Ingestion of branched-chain amino acids and tryptophan during sustained exercise in man: failure to affect performance

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Raaymakers, J S; Saris, W H

    1995-01-01

    1. An increased uptake of tryptophan in the brain may increase serotoninergic activity and recently has been suggested to be a cause of fatigue during prolonged exercise. The present study, therefore, investigates whether ingestion of tryptophan or the competing branched-chain amino acids (BCAAs...... tryptophan ingestion caused a 7- to 20-fold increase. Exercise time to exhaustion was not different between treatments (122 +/- 3 min). 3. The data suggest that manipulation of tryptophan supply to the brain either has no additional effect upon serotoninergic activity during prolonged exhaustive exercise......) or (3) a high dose of BCAA (18 g l-1). 2. These treatments greatly increased the plasma concentration of the respective amino acids. Using the kinetic parameters of transport of human brain capillaries, BCAA supplements were estimated to reduce brain tryptophan uptake at exhaustion by 8-12%, while...

  1. Polar stratospheric clouds and ozone depletion

    Science.gov (United States)

    Toon, Owen B.; Turco, Richard P.

    1991-01-01

    A review is presented of investigations into the correlation between the depletion of ozone and the formation of polar stratospheric clouds (PSCs). Satellite measurements from Nimbus 7 showed that over the years the depletion from austral spring to austral spring has generally worsened. Approximately 70 percent of the ozone above Antarctica, which equals about 3 percent of the earth's ozone, is lost during September and October. Various hypotheses for ozone depletion are discussed including the theory suggesting that chlorine compounds might be responsible for the ozone hole, whereby chlorine enters the atmosphere as a component of chlorofluorocarbons produced by humans. The three types of PSCs, nitric acid trihydrate, slowly cooling water-ice, and rapidly cooling water-ice clouds act as important components of the Antarctic ozone depletion. It is indicated that destruction of the ozone will be more severe each year for the next few decades, leading to a doubling in area of the Antarctic ozone hole.

  2. [Hepatomioneuropathy secondary to mitochondrial DNA depletion].

    Science.gov (United States)

    Blanco-Barca, M O; Gómez-Lado, C; Campos-González, Y; Castro-Gago, M

    2007-04-01

    Mitochondrial DNA depletion (mtDNA) is an highly heterogeneous condition characterized by a decreased number of mtDNA copies. The patient is a 22-month-old girl with generalized hypotonia, marked weakness, respiratory failure, arterial hypertension, hyperlactacidemia, hepatosplenomegaly and mild hypertransaminasemia without hepatic failure neither hypoketotic hypoglycemia. Electromyographic findings were consistent with neuromyopathy and muscle biopsy suggested a neurogenic atrophy. Electron microscopy revealed lipid droplets, subsarcolemmal accumulation of mitochondrias and glycogen granules. Respiratory chain enzime activities were normal. Genetic study in muscle showed mtDNA depletion, and the diagnosis of spinal muscular atrophy caused by survival motoneuron gene deletion was excluded. This case might be a novel phenotype of mtDNA depletion which could be named hepatomioneuropatyc form. A normal result of respiratory chain enzimes in muscle doesn't excluded mtDNA depletion.

  3. Differential degradation of motor deficits during gradual dopamine depletion with 6-hydroxydopamine in mice

    Science.gov (United States)

    Willard, Amanda M.; Bouchard, Rachel S.; Gittis, Aryn H.

    2015-01-01

    Parkinson’s disease (PD) is a movement disorder whose cardinal motor symptoms arise due to the progressive loss of dopamine. Although this dopamine loss typically progresses slowly over time, currently there are very few animal models that enable incremental dopamine depletion over time within the same animal. This type of gradual dopamine depletion model would be useful in studies aimed at the prodromal phase of PD, when dopamine levels are pathologically low but motor symptoms have not yet presented. Utilizing the highly characterized neurotoxin 6-hydroxydopamine (6-OHDA), we have developed a paradigm to gradually deplete dopamine levels in the striatum over a user-defined time course – spanning weeks to months – in C57BL/6 mice. Dopamine depletions were achieved by administration of five low dose injections (0.75 µg) of 6-OHDA through an implanted intracranial bilateral cannula targeting the medial forebrain bundle. Levels of dopamine within the striatum declined linearly with successive injections, quantified using tyrosine hydroxylase immunostaining and high-performance liquid chromatography. Behavioral testing was carried out at each time point to study the onset and progression of motor impairments as a function of dopamine loss over time. We found that spontaneous locomotion, measured in an open field, was robust to loss of dopamine until ~70% of striatal dopamine was lost. Beyond this point, additional dopamine loss caused a sharp decline in motor performance, reaching a final level comparable to that of acutely depleted mice. Similarly, although rearing behavior was more sensitive to dopamine loss and declined linearly as a function of dopamine levels, it eventually declined to levels similar to that seen in acutely depleted mice. In contrast, motor coordination, measured on a vertical pole task, was only moderately impaired in gradually depleted mice, despite severe impairments observed in acutely depleted mice. These results demonstrate the

  4. Depleted bulk heterojunction colloidal quantum dot photovoltaics

    Energy Technology Data Exchange (ETDEWEB)

    Barkhouse, D.A.R. [Department of Electrical and Computer Engineering, University of Toronto, 10 King' s College Road, Toronto, Ontario M5S 3G4 (Canada); IBM Thomas J. Watson Research Center, Kitchawan Road, Yorktown Heights, NY, 10598 (United States); Debnath, Ratan; Kramer, Illan J.; Zhitomirsky, David; Levina, Larissa; Sargent, Edward H. [Department of Electrical and Computer Engineering, University of Toronto, 10 King' s College Road, Toronto, Ontario M5S 3G4 (Canada); Pattantyus-Abraham, Andras G. [Department of Electrical and Computer Engineering, University of Toronto, 10 King' s College Road, Toronto, Ontario M5S 3G4 (Canada); Quantum Solar Power Corporation, 1055 W. Hastings, Ste. 300, Vancouver, BC, V6E 2E9 (Canada); Etgar, Lioz; Graetzel, Michael [Laboratory for Photonics and Interfaces, Institute of Chemical Sciences and Engineering, School of Basic Sciences, Swiss Federal Institute of Technology, CH-1015 Lausanne (Switzerland)

    2011-07-26

    The first solution-processed depleted bulk heterojunction colloidal quantum dot solar cells are presented. The architecture allows for high absorption with full depletion, thereby breaking the photon absorption/carrier extraction compromise inherent in planar devices. A record power conversion of 5.5% under simulated AM 1.5 illumination conditions is reported. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Depleted Bulk Heterojunction Colloidal Quantum Dot Photovoltaics

    KAUST Repository

    Barkhouse, D. Aaron R.

    2011-05-26

    The first solution-processed depleted bulk heterojunction colloidal quantum dot solar cells are presented. The architecture allows for high absorption with full depletion, thereby breaking the photon absorption/carrier extraction compromise inherent in planar devices. A record power conversion of 5.5% under simulated AM 1.5 illumination conditions is reported. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Effects of Riverbed Conductance on Stream Depletion

    Science.gov (United States)

    Lackey, G.; Neupauer, R. M.; Pitlick, J.

    2012-12-01

    In the western United States and other regions of the world where growing population and changing climates are threatening water supplies, accurate modeling of potential human impacts on water resources is becoming more important. Stream depletion, the reduction of surface water flow due to the extraction of groundwater from a hydraulically connected aquifer, is one of the more direct ways that development can alter water availability, degrade water quality and endanger aquatic habitats. These factors have made the accurate modeling of stream depletion an important step in the process of installing groundwater wells in regions that are susceptible to this phenomenon. Proper estimation of stream depletion requires appropriate parameterization of aquifer and streambed hydraulic properties. Although many studies have conducted numerical investigations to determine stream depletion at specific sites, they typically do not measure streambed hydraulic conductivity (Kr), but rather assume a representative value. In this work, we establish a hypothetical model aquifer that is 2000 m by 1600 m and has a meandering stream running through its center. The Kr of the model stream is varied from 1.0x10-9 m s-1 to 1.0x10-2 m s-1 in order to determine the sensitivity of the stream depletion calculations to this parameter. It was found that when Kr is in the lower part of this range, slight changes in K¬r lead to significant impacts on the calculated stream depletion values. We vary Kr along the stream channel according to naturally occurring patterns and demonstrate that alterations of the parameter over a few orders of magnitude can affect the estimated stream depletion caused by a well at a specified location. The numerical simulations show that the mean value of Kr and its spatial variability along the channel should be realistic to develop an accurate model of stream depletion.

  7. A theoretical model of atmospheric ozone depletion

    Science.gov (United States)

    Midya, S. K.; Jana, P. K.; Lahiri, T.

    1994-01-01

    A critical study on different ozone depletion and formation processes has been made and following important results are obtained: (i) From analysis it is shown that O3 concentration will decrease very minutely with time for normal atmosphere when [O], [O2] and UV-radiation remain constant. (ii) An empirical equation is established theoretically between the variation of ozone concentration and time. (iii) Special ozone depletion processes are responsible for the dramatic decrease of O3-concentration at Antarctica.

  8. Digestible tryptophan:digestible lysine ratio in diets for laying hens from 24 to 40 weeks of age

    Directory of Open Access Journals (Sweden)

    Arele Arlindo Calderano

    2012-10-01

    Full Text Available The objective of this study was to determine the ideal digestible tryptophan:digestible lysine ratio in diets for laying hens from 24 to 40 weeks of age. Two hundred and forty Hy-Line W-36 laying hens at 24 weeks of age were distributed in a completely randomized design, with five treatments, eight replicates and six birds per experimental unit. The digestible tryptophan levels in the experimental diets were 1.57; 1.68; 1.79; 1.90 and 2.01 g/kg, providing ratios of digestible tryptophan:digestible lysine of 0.215; 0.230; 0.245; 0.260 and 0.275. The increase in the levels of digestible tryptophan in the diet linearly improved the feed intake, digestible tryptophan intake, digestible lysine intake, egg production, egg mass, feed conversion per egg mass and utilization efficiency of digestible lysine for eggs mass. There were quadratic effects from the digestible tryptophan levels on egg weight. For the efficiency of utilization of digestible lysine for egg mass, there was better adjustment of the data to the LRP model. The level of digestible tryptophan in the diet from which the plateau occurred was 0.184%. This level corresponded to the intake of 142 mg/bird/day of digestible tryptophan and digestible tryptophan:digestible lysine ratio of 0.252. The ideal digestible tryptophan:digestible lysine ratio recommended in diets for laying hens from 24 to 40 weeks of age is 0.252 (25.2%.

  9. Anatomy of Depleted Interplanetary Coronal Mass Ejections

    Science.gov (United States)

    Kocher, M.; Lepri, S. T.; Landi, E.; Zhao, L.; Manchester, W. B., IV

    2017-01-01

    We report a subset of interplanetary coronal mass ejections (ICMEs) containing distinct periods of anomalous heavy-ion charge state composition and peculiar ion thermal properties measured by ACE/SWICS from 1998 to 2011. We label them “depleted ICMEs,” identified by the presence of intervals where C6+/C5+ and O7+/O6+ depart from the direct correlation expected after their freeze-in heights. These anomalous intervals within the depleted ICMEs are referred to as “Depletion Regions.” We find that a depleted ICME would be indistinguishable from all other ICMEs in the absence of the Depletion Region, which has the defining property of significantly low abundances of fully charged species of helium, carbon, oxygen, and nitrogen. Similar anomalies in the slow solar wind were discussed by Zhao et al. We explore two possibilities for the source of the Depletion Region associated with magnetic reconnection in the tail of a CME, using CME simulations of the evolution of two Earth-bound CMEs described by Manchester et al.

  10. Nutritional Stress Induced by Tryptophan-Degrading Enzymes Results in ATF4-Dependent Reprogramming of the Amino Acid Transporter Profile in Tumor Cells

    DEFF Research Database (Denmark)

    Timosenko, Elina; Ghadbane, Hemza; Silk, Jonathan D

    2016-01-01

    Tryptophan degradation is an immune escape strategy shared by many tumors. However, cancer cells' compensatory mechanisms remain unclear. We demonstrate here that a shortage of tryptophan caused by expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) resulted in AT...

  11. Comorbidity between depression and inflammatory bowel disease explained by immune-inflammatory, oxidative, and nitrosative stress; tryptophan catabolite; and gut-brain pathways.

    Science.gov (United States)

    Martin-Subero, Marta; Anderson, George; Kanchanatawan, Buranee; Berk, Michael; Maes, Michael

    2016-04-01

    The nature of depression has recently been reconceptualized, being conceived as the clinical expression of activated immune-inflammatory, oxidative, and nitrosative stress (IO&NS) pathways, including tryptophan catabolite (TRYCAT), autoimmune, and gut-brain pathways. IO&NS pathways are similarly integral to the pathogenesis of inflammatory bowel disease (IBD). The increased depression prevalence in IBD associates with a lower quality of life and increased morbidity in IBD, highlighting the role of depression in modulating the pathophysiology of IBD.This review covers data within such a wider conceptualization that better explains the heightened co-occurrence of IBD and depression. Common IO&NS underpinning between both disorders is evidenced by increased pro-inflammatory cytokine levels, eg, interleukin-1 (IL-1) and tumor necrosis factor-α, IL-6 trans-signalling; Th-1- and Th-17-like responses; neopterin and soluble IL-2 receptor levels; positive acute phase reactants (haptoglobin and C-reactive protein); lowered levels of negative acute phase reactants (albumin, transferrin, zinc) and anti-inflammatory cytokines (IL-10 and transforming growth factor-β); increased O&NS with damage to lipids, proteinsm and DNA; increased production of nitric oxide (NO) and inducible NO synthase; lowered plasma tryptophan but increased TRYCAT levels; autoimmune responses; and increased bacterial translocation. As such, heightened IO&NS processes in depression overlap with the biological underpinnings of IBD, potentially explaining their increased co-occurrence. This supports the perspective that there is a spectrum of IO&NS disorders that includes depression, both as an emergent comorbidity and as a contributor to IO&NS processes. Such a frame of reference has treatment implications for IBD when "comorbid" with depression.

  12. Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants.

    Directory of Open Access Journals (Sweden)

    Katerina V Savelieva

    Full Text Available The neurotransmitter serotonin (5-HT plays an important role in both the peripheral and central nervous systems. The biosynthesis of serotonin is regulated by two rate-limiting enzymes, tryptophan hydroxylase-1 and -2 (TPH1 and TPH2. We used a gene-targeting approach to generate mice with selective and complete elimination of the two known TPH isoforms. This resulted in dramatically reduced central 5-HT levels in Tph2 knockout (TPH2KO and Tph1/Tph2 double knockout (DKO mice; and substantially reduced peripheral 5-HT levels in DKO, but not TPH2KO mice. Therefore, differential expression of the two isoforms of TPH was reflected in corresponding depletion of 5-HT content in the brain and periphery. Surprisingly, despite the prominent and evolutionarily ancient role that 5-HT plays in both vertebrate and invertebrate physiology, none of these mutations resulted in an overt phenotype. TPH2KO and DKO mice were viable and normal in appearance. Behavioral alterations in assays with predictive validity for antidepressants were among the very few phenotypes uncovered. These behavioral changes were subtle in the TPH2KO mice; they were enhanced in the DKO mice. Herein, we confirm findings from prior descriptions of TPH1 knockout mice and present the first reported phenotypic evaluations of Tph2 and Tph1/Tph2 knockout mice. The behavioral effects observed in the TPH2 KO and DKO mice strongly confirm the role of 5-HT and its synthetic enzymes in the etiology and treatment of affective disorders.

  13. The vitamin B6 requirement in oral contraceptive users. II. Assessment by tryptophan metabolites, vitamin B6, and pyridoxic acid levels in urine.

    Science.gov (United States)

    Donald, E A; Bossé, T R

    1979-05-01

    The requirement for vitamin B6 in oral contraceptive users was studied in 8 college-age women who used combined (7) or sequential (1) oral contraceptives. The subjects and 8 controls consumed a basal diet supplemented to result in daily intake of 2.06 mg pyridoxine hydrochloride for 10 days (predepletion) and then containing only .36 mg of vitamin B6 for 32 days. After the depletion period, the diet was supplemented with pyridoxine hydrochloride to increase the intake of B6 to .96, 1.56, and 5.06 mg for 8, 9, and 7 days respectively. Complete 14-hour urine collections were analyzed for xanthurenic acid, kynurenic acids, kynurenine, and 3-hydroxykynurenine after administration of a l load-dose of 2 gm L-trytophan on days 2, 11, 18, 25, 32, 39, 43, 50 , 59, and 66 for the subjects and days 2 and 10 for the controls. Pretryptophan urine was analyzed for vitamin B6. Posttryptophan urine was analyzed for 4-pyridoxic acid. It was found that during the depletion phase the excretion of tryptophan metabolites increased significantly. Excretion dropped significantly upon supplementation with 1.56 or 5.06 mg of vitamin B6, returning values to normal. Levels of vitamin B6 and 4-pyridoxic acid in the urine decreased during depletion to be restored to normal upon supplementation with 1.56 mg/day. Since an intake of 5.0 mg vitamin B6 caused a loss of the vitamin in the urine and all levels were returned to normal with an intake of 1.56 mg, it is suggested that 1.5 mg of vitamin B6 is sufficient to meet the needs of most oral contraceptive users and that there is no significant difference in the vitamin B6 requirement of oral contraceptive users and nonusers.

  14. Central fatigue and nycthemeral change of serum tryptophan and serotonin in the athletic horse

    Directory of Open Access Journals (Sweden)

    Percipalle Maurizio

    2005-04-01

    Full Text Available Abstract Background The serotonergic system is associated with numerous brain functions, including the resetting of the mammalian circadian clock. The synthesis and metabolism of 5-HT in the brain increases in response to exercise and is correlated with high levels of blood-borne tryptophan (TRP. The present investigation was aimed at testing the existence of a daily rhythm of TRP and 5-HT in the blood of athletic horses. Methods Blood samples from 5 Thoroughbred mares were collected at 4-hour intervals for 48 hours (starting at 08:00 hours on day 1 and finishing at 4:00 on day 2 via an intravenous cannula inserted into the jugular vein. Tryptophan and serotonin concentrations were assessed by HPLC. Data analysis was conducted by one-way repeated measures analysis of variance (ANOVA and by the single cosinor method. Results ANOVA showed a highly significant influence of time both on tryptophan and on serotonin, in all horses, on either day, with p values Conclusion The results showed that serotonin and tryptophan blood levels undergo nycthemeral variation with typical evening acrophases. These results enhance the understanding of the athlete horse's chronoperformance and facilitate the establishment of training programs that take into account the nycthemeral pattern of aminoacids deeply involved in the onset of central fatigue.

  15. Cross-linking of lens crystallin proteins induced by tryptophan metabolites and metal ions

    DEFF Research Database (Denmark)

    Tweeddale, Helen J; Hawkins, Clare Louise; Janmie, Joane F

    2016-01-01

    Long-wavelength solar UV radiation is implicated in photodamage to the human eye. The human lens contains multiple tryptophan-derived compounds that have significant absorbance bands in the UVA region (λ 315-400 nm) that act as efficient physical filters for these wavelengths. The concentrations...

  16. Diurnal variation in total plasma tryptophan in controls and in depression.

    Science.gov (United States)

    Candito, M; Souêtre, E; Iordache, A; Pringuey, D; Ardisson, J L; Chambon, P; Darcourt, G

    1990-01-01

    Circadian rhythms of total tryptophan were investigated by assays of hourly blood samples over 25 h. The study population consisted of four endogenously depressed patients investigated in the absence of any treatment and six healthy controls. The abnormalities detected by statistical analyses in untreated depression consisted mainly of amplitude reduction; the phase positions of the depressed patients were similar to those of the controls.

  17. REPLACEMENT OF TRYPTOPHAN RESIDUES IN HALOALKANE DEHALOGENASE REDUCES HALIDE BINDING AND CATALYTIC ACTIVITY

    NARCIS (Netherlands)

    KENNES, C; PRIES, F; KROOSHOF, GH; BOKMA, E; Kingma, Jacob; JANSSEN, DB

    1995-01-01

    Haloalkane dehalogenase catalyzes the hydrolytic cleavage of carbon-halogen bonds in short-chain haloalkanes. Two tryptophan residues of the enzyme (Trp125 and Trp175) form a halide-binding site in the active-site cavity, and were proposed to play a role in catalysis. The function of these residues

  18. A Relay Pathway between Arginine and Tryptophan Metabolism Confers Immunosuppressive Properties on Dendritic Cells

    NARCIS (Netherlands)

    G. Mondanelli (Giada); R. Bianchi (Roberta); M.T. Pallotta (Maria Teresa); C. Orabona (Ciriana); E. Albini (Elisa); A. Iacono (Alberta); M.L. Belladonna (Maria Laura); C. Vacca (Carmine); F. Fallarino (Francesca); A. Macchiarulo (Antonio); S. Ugel (Stefano); V. Bronte (Vincenzo); F. Gevi (Federica); L. Zolla (Lello); A.P. Verhaar (Auke); M.P. Peppelenbosch (Maikel); E.M.C. Mazza (Emilia Maria Cristina); S. Bicciato (Silvio); Y. Laouar (Yasmina); L. Santambrogio (Laura); P. Puccetti (Paolo); C. Volpi (Claudia); U. Grohmann (Ursula)

    2016-01-01

    textabstractArginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunoregulatory enzymes catalyzing the degradation of l-arginine and l-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity

  19. Serum Stabilities of Short Tryptophan-and Arginine-Rich Antimicrobial Peptide Analogs

    NARCIS (Netherlands)

    Nguyen, L.T.; Chau, J.K.; Perry, N.A.; de Boer, L.; Zaat, S.A.J.; Vogel, H.J.

    2010-01-01

    Background: Several short antimicrobial peptides that are rich in tryptophan and arginine residues were designed with a series of simple modifications such as end capping and cyclization. The two sets of hexapeptides are based on the Trp- and Arg-rich primary sequences from the "antimicrobial centre

  20. Molecular docking of bacosides with tryptophan hydroxylase: a model to understand the bacosides mechanism.

    Science.gov (United States)

    Rajathei, David Mary; Preethi, Jayakumar; Singh, Hemant K; Rajan, Koilmani Emmanuvel

    2014-08-01

    Tryptophan hydroxylase (TPH) catalyses l-tryptophan into 5-hydroxy-l-tryptophan, which is the first and rate-limiting step of serotonin (5-HT) biosynthesis. Earlier, we found that TPH2 up-regulated in the hippocampus of postnatal rats after the oral treatment of Bacopa monniera leaf extract containing the active compound bacosides. However, the knowledge about the interactions between bacosides with TPH is limited. In this study, we take advantage of in silico approach to understand the interaction of bacoside-TPH complex using three different docking algorithms such as HexDock, PatchDock and AutoDock. All these three algorithms showed that bacoside A and A3 well fit into the cavity consists of active sites. Further, our analysis revealed that major active compounds bacoside A3 and A interact with different residues of TPH through hydrogen bond. Interestingly, Tyr235, Thr265 and Glu317 are the key residues among them, but none of them are either at tryptophan or BH4 binding region. However, its note worthy to mention that Tyr 235 is a catalytic sensitive residue, Thr265 is present in the flexible loop region and Glu317 is known to interacts with Fe. Interactions with these residues may critically regulate TPH function and thus serotonin synthesis. Our study suggested that the interaction of bacosides (A3/A) with TPH might up-regulate its activity to elevate the biosynthesis of 5-HT, thereby enhances learning and memory formation.

  1. Effect of a B-vitamin on tryptophan metabolism in South African Bantu with pellagra

    Energy Technology Data Exchange (ETDEWEB)

    Hankes, L.V.; Jansen, C.R.; DeBruin, E.P.; Schmaeler, M.

    1983-01-01

    The metabolism of kynurenine, a metabolite in the tryptophan-niacin pathway, before and after vitamin B6 therapy was studied in pellagra patients. The patients given vitamin B6 showed a higher metabolism of L-kynurenine-keto-/sup 14/C than the patients without vitamin B6. (ACR)

  2. Effect of diet on plasma tryptophan and serotonin in trained mares and geldings

    NARCIS (Netherlands)

    Alberghina, D.; Giannetto, C.; Visser, E.K.; Ellis, A.D.

    2010-01-01

    Concentrations of tryptophan (TRP) and serotonin (5-HT) in plasma were measured in 36 moderately trained Dutch warmblood horses after eight weeks on a high fibre (n=18) or high starch (n=18) diet. Samples were taken three hours after feeding, when the horse was at rest, either at 11.00 or 14.00 hour

  3. Lactococcus lactis as expression host for the biosynthetic incorporation of tryptophan analogues into recombinant proteins

    NARCIS (Netherlands)

    El Khattabi, Mohamed; van Roosmalen, Maarten L.; Jager, Dennis; Metselaar, Heidi; Permentier, Hjalmar; Leenhouts, Kees; Broos, Jaap

    2008-01-01

    Incorporation of Trp (tryptophan) analogues into a protein may facilitate its structural analysis by spectroscopic techniques. Development of a biological system for the biosynthetic incorporation of such analogues into proteins is of considerable importance. The Gram-negative Escherichia coli is th

  4. Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

    Directory of Open Access Journals (Sweden)

    Michele Mari

    2014-08-01

    Full Text Available The reaction of 3-substituted indoles with dehydroalanine (Dha derivatives under Lewis acid-mediated conditions has been investigated. The formation of 2-substituted tryptophans is proposed to occur through a selective alkylative dearomatization–cyclization followed by C3- to C2-alkyl migration and rearomatization.

  5. Dietary tryptophan and threonine supply to 28 days old weaned piglets

    DEFF Research Database (Denmark)

    Fernández, José Adalberto; Strathe, Anders Bjerring

    2009-01-01

    The effects of dietary levels of tryptophan (TRP) and threonine (THR) on appetite, growth performance and faecal score were assessed in an experiment with 360 weaned piglets. Littermate male castrates and females (1:1), weaned at 28 days of age, were given free access to feed during 28 days. Six...

  6. The tryptophan kynurenine pathway, neopterin and IL-6 during vulvectomy and abdominal hysterectomy.

    Science.gov (United States)

    Hol, Jaap Willem; Stolker, Robert J; Klimek, Markus; Stronks, Dirk L; Fekkes, Durk

    2014-12-20

    Surgery has wide ranging immunomodulatory properties of which the mechanism is poorly understood. In order to investigate how different types of surgery influence inflammation, we designed a longitudinal observational study investigating two inflammatory profiles of two separate patient groups undergoing gynaecological operations of differing severity. In addition to measuring the well known inflammatory markers neopterin and IL-6, we also determined the kynurenine/tryptophan ratio. This study was a prospective, single center, two-armed observational study involving 28 female patients. Plasma levels of tryptophan, kynurenine, neopterin and IL-6 were determined from samples taken at: 24 hrs pre-operative, prior to induction, ten minutes before the operation was expected to end, and at 24 and 96 hours post operative in patients undergoing abdominal hysterectomy and vulvectomy. There were 15 and 13 patients included in the vulvectomy and abdominal hysterectomy groups, respectively. In this study we show that anesthesia and surgery significantly increases the enzyme activity of indoleamine 2, 3 dioxygenase (IDO) as measured by the kynurenine/tryptophan ratio (P=0.003), while maintaining stable neopterin levels. However, abdominal hysterectomy causes a considerable IL-6 increase (P<0.001). Surgery and associated anesthesia cause a significant tryptophan level decrease while significantly increasing IDO activity. Both types of surgery produce nearly identical neopterin time curve relationships, with no significant change occurring in either group. However, even though neopterin is unaffected by the severity of surgery, IL-6 responded to surgical invasiveness by revealing a significant increase during abdominal hysterectomy.

  7. Tryptophan Content of the Serum Albumin of Normal and of Cadmium-Poisoned Monkeys

    Science.gov (United States)

    Kench, J. E.; Sutherland, Elizabeth M.

    1967-01-01

    In order to characterize further the minialbumins (molecular weight 5,000 to 20,000) found in cadmium-poisoned men and animals, the tryptophan content of albumins found in the serum and urine of cadmium-poisoned monkeys was measured by two methods and compared with that of serum albumin (molecular weight 66,000) of normal animals. Normal serum albumin of the monkey was found to contain 2 residues of trytophan per molecule of the protein, whereas all albumins in the poisoned monkeys, whether of normal size or low-molecular weight, contained less tryptophan, this amino acid being absent entirely in the minialbumins of both serum and urine. Serum albumin of the usual molecular weight (66,000) in the cadmium-poisoned monkeys contained approximately 30% less tryptophan than its normal counterpart in untreated animals. Taken in conjunction with previous observations on the behaviour of minialbumins, which aggregate readily in low-salt media including isotonic saline, it is concluded that approximately 30% of the circulating serum albumin in the poisoned monkeys arose by aggregation of minialbumin molecules. On the basis of the close similarity in amino acid composition, in nearly all other respects, between the various albumins, it is suggested that minialbumin comprises a mixture of peptides derived by fission of the normal albumin molecule along its whole chain length, and that subsequently a peptide containing both tryptophan residues is either deleted metabolically or excluded in the preparation procedures. PMID:4965263

  8. Biotransformation of tryptophan by liquid medium culture of Psilocybe coprophila (Basidiomycetes).

    Science.gov (United States)

    Alarcón, Julio; Foncea, Leyla; Aguila, Sergio; Alderete, Joel B

    2006-01-01

    Chemical reactions performed by fungi have been used as a modern tool in chemistry. In this work, we show the tryptophan biotransformation with Psilocybe coprophila on liquid culture medium. The results prove once more the versatility of fungi in performing a wide range of industrially attractive chemical reactions.

  9. Experimental Evidence and In Silico Identification of Tryptophan Decarboxylase in Citrus Genus

    Directory of Open Access Journals (Sweden)

    Luigi De Masi

    2017-02-01

    Full Text Available Plant tryptophan decarboxylase (TDC converts tryptophan into tryptamine, precursor of indolealkylamine alkaloids. The recent finding of tryptamine metabolites in Citrus plants leads to hypothesize the existence of TDC activity in this genus. Here, we report for the first time that, in Citrus x limon seedlings, deuterium labeled tryptophan is decarboxylated into tryptamine, from which successively deuterated N,N,N-trimethyltryptamine is formed. These results give an evidence of the occurrence of the TDC activity and the successive methylation pathway of the tryptamine produced from the tryptophan decarboxylation. In addition, with the aim to identify the genetic basis for the presence of TDC, we carried out a sequence similarity search for TDC in the Citrus genomes using as a probe the TDC sequence reported for the plant Catharanthus roseus. We analyzed the genomes of both Citrus clementina and Citrus sinensis, available in public database, and identified putative protein sequences of aromatic l-amino acid decarboxylase. Similarly, 42 aromatic l-amino acid decarboxylase sequences from 23 plant species were extracted from public databases. Potential sequence signatures for functional TDC were then identified. With this research, we propose for the first time a putative protein sequence for TDC in the genus Citrus.

  10. Distinct Tryptophan Catabolism and Th17/Treg Balance in HIV Progressors and Elite Controllers

    NARCIS (Netherlands)

    Jenabian, Mohammad-Ali; Patel, Mital; Kema, Ido; Kanagaratham, Cynthia; Radzioch, Danuta; Thebault, Pamela; Lapointe, Rejean; Tremblay, Cecile; Gilmore, Norbert; Ancuta, Petronela; Routy, Jean-Pierre

    2013-01-01

    Tryptophan (Trp) catabolism into immunosuppressive kynurenine (Kyn) by indoleamine 2,3-dioxygenase (IDO) was previously linked to Th17/Treg differentiation and immune activation. Here we examined Trp catabolism and its impact on Th17/Treg balance in uninfected healthy subjects (HS) and a large cohor

  11. Tryptophan hydroxylase is modulated by L-type calcium channels in the rat pineal gland.

    Science.gov (United States)

    Barbosa, Roseli; Scialfa, Julieta Helena; Terra, Ilza Mingarini; Cipolla-Neto, José; Simonneaux, Valérie; Afeche, Solange Castro

    2008-02-27

    Calcium is an important second messenger in the rat pineal gland, as well as cAMP. They both contribute to melatonin synthesis mediated by the three main enzymes of the melatonin synthesis pathway: tryptophan hydroxylase, arylalkylamine N-acetyltransferase and hydroxyindole-O-methyltransferase. The cytosolic calcium is elevated in pinealocytes following alpha(1)-adrenergic stimulation, through IP(3)-and membrane calcium channels activation. Nifedipine, an L-type calcium channel blocker, reduces melatonin synthesis in rat pineal glands in vitro. With the purpose of investigating the mechanisms involved in melatonin synthesis regulation by the L-type calcium channel, we studied the effects of nifedipine on noradrenergic stimulated cultured rat pineal glands. Tryptophan hydroxylase, arylalkylamine N-acetyltransferase and hydroxyindole-O-methyltransferase activities were quantified by radiometric assays and 5-hydroxytryptophan, serotonin, N-acetylserotonin and melatonin contents were quantified by HPLC with electrochemical detection. The data showed that calcium influx blockaded by nifedipine caused a decrease in tryptophan hydroxylase activity, but did not change either arylalkylamine N-acetyltransferase or hydroxyindole-O-methyltransferase activities. Moreover, there was a reduction of 5-hydroxytryptophan, serotonin, N-acetylserotonin and melatonin intracellular content, as well as a reduction of serotonin and melatonin secretion. Thus, it seems that the calcium influx through L-type high voltage-activated calcium channels is essential for the full activation of tryptophan hydroxylase leading to melatonin synthesis in the pineal gland.

  12. Problem-Solving Test: Attenuation--A Mechanism to Regulate Bacterial Tryptophan Biosynthesis

    Science.gov (United States)

    Szeberenyi, Jozsef

    2010-01-01

    Terms to be familiar with before you start to solve the test: tryptophan, transcription unit, operon, "trp" repressor, corepressor, operator, promoter, palindrome, initiation, elongation, and termination of transcription, open reading frame, coupled transcription/translation, chromosome-polysome complex. (Contains 2 figures and 1 footnote.)

  13. PYROLYTIC PRODUCTS FROM TRYPTOPHAN AND GLUTAMIC-ACID ARE POSITIVE IN THE MAMMALIAN SPOT-TEST

    DEFF Research Database (Denmark)

    Jensen, Niels Juul

    1983-01-01

    Pyrolysates of tryptophan (Trp-P-2) and glutamic acid (Glu-P-1) are known mutagens in in vitro short term mutagenicity tests, and have also shown carcinogenic effects in long term animal studies. The present study demonstrates that they also produce mutations in somatic cells. This result...

  14. A novel photocatalytic conversion of Tryptophan to Kynurenine using black light as a light source

    NARCIS (Netherlands)

    Hamdy Mohamed Saad, M.S.; Scott, E.L.; Carr, R.H.; Sanders, J.P.M.

    2012-01-01

    The photocatalytic conversion of an aqueous solution of l-tryptophan (Trp) to kynurenine (KN) was investigated under the illumination of different light sources. Results show that Trp converted to KN with a selectivity of 64% under the illumination of a medium pressure (MP) Hg lamp. KN selectivity w

  15. Internal Energies of Ion-Sputtered Neutral Tryptophan and Thymine Molecules Determined by Vacuum Ultraviolet Photoionization

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jia; Takahashi, Lynelle; Wilson, Kevin R.; Leone, Stephen R.; Ahmed, Musahid

    2010-03-11

    Vacuum ultraviolet photoionization coupled to secondary neutral mass spectrometry (VUV-SNMS) of deposited tryptophan and thymine films are performed at the Chemical Dynamics Beamline. The resulting mass spectra show that while the intensity of the VUV-SNMS signal is lower than the corresponding secondary ion mass spectroscopy (SIMS) signal, the mass spectra are significantly simplified in VUV-SNMS. A detailed examination of tryptophan and thymine neutral molecules sputtered by 25 keV Bi3 + indicates that the ion-sputtered parent molecules have ~;;2.5 eV of internal energy. While this internal energy shifts the appearance energy of the photofragment ions for both tryptophan and thymine, it does not change the characteristic photoionizaton efficiency (PIE) curves of thymine versus photon energy. Further analysis of the mass spectral signals indicate that approximately 80 neutral thymine molecules and 400 tryptophan molecules are sputtered per incident Bi3 + ion. The simplified mass spectra and significant characteristic ion contributions to the VUV-SNMS spectra indicate the potential power of the technique for organic molecule surface analysis.

  16. Stabilization of Tryptophan Hydroxylase 2 by L-Phenylalanine Induced Dimerization

    DEFF Research Database (Denmark)

    Tidemand, Kasper Damgaard; Christensen, Hans Erik Mølager; Hoeck, Niclas;

    2016-01-01

    Tryptophan hydroxylase 2 (TPH2) catalyses the initial and rate-limiting step in the biosynthesis of serotonin, which is associated with a variety of disorders such as depression, obsessive compulsive disorder, and schizophrenia. Full length TPH2 is poorly characterized due to low purification qua...

  17. Quenching of Tryptophan Fluorescence in Unfolded Cytochrome "c": A Biophysics Experiment for Physical Chemistry Students

    Science.gov (United States)

    Schlamadinger, Diana E.; Kats, Dina I.; Kim, Judy E.

    2010-01-01

    Laboratory experiments that focus on protein folding provide excellent opportunities for undergraduate students to learn important topics in the expanding interdisciplinary field of biophysics. Here, we describe the use of Stern-Volmer plots to determine the extent of solvent accessibility of the single tryptophan residue (trp-59) in unfolded and…

  18. Study of Interaction Between Tryptophan, Tyrosine, and Phenylalanine Separately with Silver Nanoparticles by Fluorescence Quenching Method

    Science.gov (United States)

    Roy, S.; Das, T. K.

    2015-09-01

    Using the spectroscopic method, the individual interaction of the three biochemically important amino acids, which are constituents of protein, namely, tryptophan, tyrosine, and phenylalanine with biologically synthesized silver nanoparticles has been investigated. The obtained UV-Vis spectra show the formation of ground-state complexes between tryptophan, tyrosine, and phenylalanine with silver nanoparticles. Silver nanoparticles possess the ability to quench the intrinsic fluorescence of the aforesaid amino acids by a dynamic quenching process. The binding constant, number of binding sites, and corresponding thermodynamic parameters (Δ H, Δ S, and Δ G) based on the interaction system were calculated for 293, 303, and 313 K. In the case of tryptophan and phenylalanine, with increase in temperature, the binding constant K was found to decrease; conversely, it was found to increase with increase in temperature in the case of tyrosine. The thermodynamic results revealed that the binding process was spontaneous; hydrogen bonding and van der Waals interaction were the predominant forces responsible for the complex stabilization in the case of tryptophan and phenylalanine, respectively, whereas in the case of tyrosine, hydrophobic interaction was the sole force conferring stability. Moreover, the Förster non-radiation energy transfer theory has been applied to calculate the average binding distance among the above amino acids and silver nanoparticles. The results show a binding distance of <7 nm, which ensures that energy transfer does occur between the said amino acids and silver nanoparticles.

  19. Melatonin biosynthesis in plants: multiple pathways catalyze tryptophan to melatonin in the cytoplasm or chloroplasts.

    Science.gov (United States)

    Back, Kyoungwhan; Tan, Dun-Xian; Reiter, Russel J

    2016-11-01

    Melatonin is an animal hormone as well as a signaling molecule in plants. It was first identified in plants in 1995, and almost all enzymes responsible for melatonin biosynthesis had already been characterized in these species. Melatonin biosynthesis from tryptophan requires four-step reactions. However, six genes, that is, TDC, TPH, T5H, SNAT, ASMT, and COMT, have been implicated in the synthesis of melatonin in plants, suggesting the presence of multiple pathways. Two major pathways have been proposed based on the enzyme kinetics: One is the tryptophan/tryptamine/serotonin/N-acetylserotonin/melatonin pathway, which may occur under normal growth conditions; the other is the tryptophan/tryptamine/serotonin/5-methoxytryptamine/melatonin pathway, which may occur when plants produce large amounts of serotonin, for example, upon senescence. The melatonin biosynthetic capacity associated with conversion of tryptophan to serotonin is much higher than that associated with conversion of serotonin to melatonin, which yields a low level of melatonin synthesis in plants. Many melatonin intermediates are produced in various subcellular compartments, such as the cytoplasm, endoplasmic reticulum, and chloroplasts, which either facilitates or impedes the subsequent enzymatic steps. Depending on the pathways, the final subcellular sites of melatonin synthesis vary at either the cytoplasm or chloroplasts, which may differentially affect the mode of action of melatonin in plants. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Reprint of 'pH tuning of Nafion for selective detection of tryptophan'

    Energy Technology Data Exchange (ETDEWEB)

    Frith, K.-A. [Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, Grahamstown, 6140 (South Africa); Limson, J.L., E-mail: j.limson@ru.ac.z [Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, Grahamstown, 6140 (South Africa)

    2010-05-30

    Selective and sensitive detection of the amino acid tryptophan is of importance in food processing, pharmaceutical formulations and in biological fluids. Electrochemical methods of detection of tryptophan are hampered by sluggish electron transfer kinetics and in complex matrices through overlapping peaks from interferents. This study examines the potential of the cation exchange membrane Nafion to enhance selectivity and sensitivity of this analyte through a seldom explored feature of this membrane: pH manipulation. A detailed examination of the effect of pH on the selectivity afforded by Nafion as a function of the analyte charge is presented. Selective detection of tryptophan and significant increases in sensitivity of its detection was observed in the presence of melatonin, dopamine and other interferents present in a pharmaceutical formulation through manipulation of the pH of the solution. At pH 3.0 at a Nafion-modified electrode, changes in the protonation of melatonin and tryptophan lowered the anodic potential of the analytes in a non-uniform manner increasing the peak resolution and permitting analyses with detection limits of 1.6 +- 0.1 nM and 1.6 +- 0.2 nM, respectively.

  1. pH tuning of Nafion for selective detection of tryptophan

    Energy Technology Data Exchange (ETDEWEB)

    Frith, K.-A. [Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, Grahamstown, 6140 (South Africa); Limson, J.L. [Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, Grahamstown, 6140 (South Africa)], E-mail: j.limson@ru.ac.za

    2009-05-01

    Selective and sensitive detection of the amino acid tryptophan is of importance in food processing, pharmaceutical formulations and in biological fluids. Electrochemical methods of detection of tryptophan are hampered by sluggish electron transfer kinetics and in complex matrices through overlapping peaks from interferents. This study examines the potential of the cation exchange membrane Nafion to enhance selectivity and sensitivity of this analyte through a seldom explored feature of this membrane: pH manipulation. A detailed examination of the effect of pH on the selectivity afforded by Nafion as a function of the analyte charge is presented. Selective detection of tryptophan and significant increases in sensitivity of its detection was observed in the presence of melatonin, dopamine and other interferents present in a pharmaceutical formulation through manipulation of the pH of the solution. At pH 3.0 at a Nafion-modified electrode, changes in the protonation of melatonin and tryptophan lowered the anodic potential of the analytes in a non-uniform manner increasing the peak resolution and permitting analyses with detection limits of 1.6 {+-} 0.1 nM and 1.6 {+-} 0.2 nM, respectively.

  2. Quantum chemical calculations of tryptophan → heme electron and excitation energy transfer rates in myoglobin.

    Science.gov (United States)

    Suess, Christian J; Hirst, Jonathan D; Besley, Nicholas A

    2017-04-01

    The development of optical multidimensional spectroscopic techniques has opened up new possibilities for the study of biological processes. Recently, ultrafast two-dimensional ultraviolet spectroscopy experiments have determined the rates of tryptophan → heme electron transfer and excitation energy transfer for the two tryptophan residues in myoglobin (Consani et al., Science, 2013, 339, 1586). Here, we show that accurate prediction of these rates can be achieved using Marcus theory in conjunction with time-dependent density functional theory. Key intermediate residues between the donor and acceptor are identified, and in particular the residues Val68 and Ile75 play a critical role in calculations of the electron coupling matrix elements. Our calculations demonstrate how small changes in structure can have a large effect on the rates, and show that the different rates of electron transfer are dictated by the distance between the heme and tryptophan residues, while for excitation energy transfer the orientation of the tryptophan residues relative to the heme is important. © 2017 The Authors Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

  3. New Approach For Prediction Groundwater Depletion

    Science.gov (United States)

    Moustafa, Mahmoud

    2017-01-01

    Current approaches to quantify groundwater depletion involve water balance and satellite gravity. However, the water balance technique includes uncertain estimation of parameters such as evapotranspiration and runoff. The satellite method consumes time and effort. The work reported in this paper proposes using failure theory in a novel way to predict groundwater saturated thickness depletion. An important issue in the failure theory proposed is to determine the failure point (depletion case). The proposed technique uses depth of water as the net result of recharge/discharge processes in the aquifer to calculate remaining saturated thickness resulting from the applied pumping rates in an area to evaluate the groundwater depletion. Two parameters, the Weibull function and Bayes analysis were used to model and analyze collected data from 1962 to 2009. The proposed methodology was tested in a nonrenewable aquifer, with no recharge. Consequently, the continuous decline in water depth has been the main criterion used to estimate the depletion. The value of the proposed approach is to predict the probable effect of the current applied pumping rates on the saturated thickness based on the remaining saturated thickness data. The limitation of the suggested approach is that it assumes the applied management practices are constant during the prediction period. The study predicted that after 300 years there would be an 80% probability of the saturated aquifer which would be expected to be depleted. Lifetime or failure theory can give a simple alternative way to predict the remaining saturated thickness depletion with no time-consuming processes such as the sophisticated software required.

  4. Regulating the balance between the kynurenine and serotonin pathways of tryptophan metabolism.

    Science.gov (United States)

    Li, Yang; Hu, Nan; Yang, Dan; Oxenkrug, Gregory; Yang, Qing

    2017-03-01

    Tryptophan is metabolized along the kynurenine and serotonin pathways, resulting in formation of kynurenine metabolites, neuroactive serotonin and melatonin. Each pathway is critical for maintaining healthy homeostasis. However, the two pathways are extremely unequal in their ability to degrade tryptophan, and little is known about the mechanisms maintaining the balance between them. Here, we demonstrated that in PC12 cells, a change of expression of key genes of one pathway resulted in a change of expression of key genes of the other. Melatonin, the end product of the serotonin pathway, played an important role in tryptophan metabolism by affecting both key enzymes of the two pathways. Melatonin treatment induced the expression of indole-2,3-dioxygenase 1 (IDO1) and enhanced the activity of the IDO1 promoter while decreasing the expression of arylalkylamine N-acetyl transferase. Melatonin treatment up-regulated the expression of forkhead box protein O1 (FoxO1) and enhanced the binding of FoxO1 to the IDO1 promoter. FoxO1 was shown to be a new regulator for IDO1 expression. Melatonin treatment decreased the phosphorylation of FoxO1 by extracellular signal-regulated kinases 1 and 2 and protein kinase B (Akt) and increased the phosphorylation of binding protein 14-3-3 by c-Jun N-terminal kinase (JNK), and thus the complex of FoxO1-14-3-3 in the cytoplasm was disassembled and FoxO1 was relocated to the nucleus to induce IDO1 expression. The JNK signaling pathway played an important role in melatonin-induced IDO1 up-regulation. In conclusion, this study suggests a link between melatonin, JNK, FoxO1 and IDO1 that acts as a potential balance regulator of tryptophan metabolism, and offers a new approach to treat diseases related to dysregulation of tryptophan metabolism. © 2017 Federation of European Biochemical Societies.

  5. Fluorescence imaging of tryptophan and collagen cross-links to evaluate wound closure ex vivo

    Science.gov (United States)

    Wang, Ying; Ortega-Martinez, Antonio; Farinelli, Bill; Anderson, R. R.; Franco, Walfre

    2016-02-01

    Wound size is a key parameter in monitoring healing. Current methods to measure wound size are often subjective, time-consuming and marginally invasive. Recently, we developed a non-invasive, non-contact, fast and simple but robust fluorescence imaging (u-FEI) method to monitor the healing of skin wounds. This method exploits the fluorescence of native molecules to tissue as functional and structural markers. The objective of the present study is to demonstrate the feasibility of using variations in the fluorescence intensity of tryptophan and cross-links of collagen to evaluate proliferation of keratinocyte cells and quantitate size of wound during healing, respectively. Circular dermal wounds were created in ex vivo human skin and cultured in different media. Two serial fluorescence images of tryptophan and collagen cross-links were acquired every two days. Histology and immunohistology were used to validate correlation between fluorescence and epithelialization. Images of collagen cross-links show fluorescence of the exposed dermis and, hence, are a measure of wound area. Images of tryptophan show higher fluorescence intensity of proliferating keratinocytes forming new epithelium, as compared to surrounding keratinocytes not involved in epithelialization. These images are complementary since collagen cross-links report on structure while tryptophan reports on function. HE and immunohistology show that tryptophan fluorescence correlates with newly formed epidermis. We have established a fluorescence imaging method for studying epithelialization processes during wound healing in a skin organ culture model, our approach has the potential to provide a non-invasive, non-contact, quick, objective and direct method for quantitative measurements in wound healing in vivo.

  6. The tryptophan/kynurenine pathway, systemic inflammation, and long-term outcome after kidney transplantation.

    Science.gov (United States)

    de Vries, Laura V; Minović, Isidor; Franssen, Casper F M; van Faassen, Martijn; Sanders, Jan-Stephan F; Berger, Stefan P; Navis, Gerjan; Kema, Ido P; Bakker, Stephan J L

    2017-08-01

    Tryptophan is metabolized along the kynurenine pathway, initially to kynurenine, and subsequently to cytotoxic 3-hydroxykynurenine. There is increasing interest in this pathway because of its proinflammatory nature, and drugs interfering in it have received increasing attention. We aimed to investigate whether serum and urinary parameters of the tryptophan/kynurenine pathway, and particularly cytotoxic 3-hydroxykynurenine, are associated with systemic inflammation and long-term outcome in renal transplant recipients (RTR). Data were collected in outpatient RTR with a functioning graft for >1 yr. Tryptophan, kynurenine, and 3-hydroxykynurenine in serum and urine were measured using LC-MS/MS. A total of 561 RTR (age: 51 ± 12 yr; 56% male) were included at a median of 6.0 (2.6-11.6) yr posttransplantation. Baseline median serum tryptophan was 40.0 (34.5-46.0) µmol/l, serum kynurenine was 1.8 (1.4-2.2) µmol/l, and serum 3-hydroxykynurenine was 42.2 (31.0-61.7) nmol/l. Serum kynurenine and 3-hydroxykynurenine were strongly associated with parameters of systemic inflammation. During follow-up for 7.0 (6.2-7.5) yr, 51 RTR (9%) developed graft failure and 120 RTR (21%) died. Both serum kynurenine and 3-hydroxykynurenine were independently associated with graft failure [HR 1.72 (1.23-2.41), P = 0.002; and HR 2.03 (1.42-2.90), P inflammation and prospectively with adverse long-term outcome after kidney transplantation. Serum 3-hydroxykynurenine may be an interesting biomarker and target for the evaluation of drugs interfering in the tryptophan/kynurenine pathway. Copyright © 2017 the American Physiological Society.

  7. Protective Effect of Melatonin on Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Jolanta Jaworek

    2012-01-01

    Full Text Available Melatonin, a product of the pineal gland, is released from the gut mucosa in response to food ingestion. Specific receptors for melatonin have been detected in many gastrointestinal tissues including the pancreas. Melatonin as well as its precursor, L-tryptophan, attenuates the severity of acute pancreatitis and protects the pancreatic tissue from the damage caused by acute inflammation. The beneficial effect of melatonin on acute pancreatitis, which has been reported in many experimental studies and supported by clinical observations, is related to: (1 enhancement of antioxidant defense of the pancreatic tissue, through direct scavenging of toxic radical oxygen (ROS and nitrogen (RNS species, (2 preservation of the activity of antioxidant enzymes; such as superoxide dismutase (SOD, catalase (CAT, or glutathione peroxidase (GPx, (3 the decline of pro-inflammatory cytokine tumor necrosis α (TNFα production, accompanied by stimulation of an anti-inflammatory IL-10, (4 improvement of pancreatic blood flow and decrease of neutrophil infiltration, (5 reduction of apoptosis and necrosis in the inflamed pancreatic tissue, (6 increased production of chaperon protein (HSP60, and (7 promotion of regenerative process in the pancreas. Conclusion. Endogenous melatonin produced from L-tryptophan could be one of the native mechanisms protecting the pancreas from acute damage and accelerating regeneration of this gland. The beneficial effects of melatonin shown in experimental studies suggest that melatonin ought to be employed in the clinical trials as a supportive therapy in acute pancreatitis and could be used in people at high risk for acute pancreatitis to prevent the development of pancreatic inflammation.

  8. Sub-structures formed in the excited state are responsible for tryptophan residues fluorescence in β-lactoglobulin.

    Science.gov (United States)

    Albani, Jihad-Rene

    2011-07-01

    Origin of tryptophan residues fluorescence in β-lactoglobulin is analyzed. Fluorescence lifetimes and spectra of β-lactoglobulin solution are measured at pH going from 2 to 12 and in 6 M guanidine. Tryptophan residues emit with three lifetimes at all conditions. Two lifetimes (0.4-0.5 ns and 2-4 ns) are in the same range of those measured for tryptophan free in solution. Lifetimes in the denatured states are lower than those measured in the native state. Pre-exponential values are modified with the protein structure. Data are identical to those already obtained for other proteins. Fluorescence lifetimes characterize internal states of the tryptophan residues (Tryptophan sub-structures) independently of the tryptophan environments, the third lifetime results from the interaction that is occurring between the Trp residues and its environment. Pre-exponential values characterize substructures populations. In conclusion, tryptophan mission occurs from substates generated in the excited state. This is in good agreement with the theory we described in recent works.

  9. Groundwater depletion embedded in international food trade

    Science.gov (United States)

    Dalin, Carole; Wada, Yoshihide; Kastner, Thomas; Puma, Michael J.

    2017-03-01

    Recent hydrological modelling and Earth observations have located and quantified alarming rates of groundwater depletion worldwide. This depletion is primarily due to water withdrawals for irrigation, but its connection with the main driver of irrigation, global food consumption, has not yet been explored. Here we show that approximately eleven per cent of non-renewable groundwater use for irrigation is embedded in international food trade, of which two-thirds are exported by Pakistan, the USA and India alone. Our quantification of groundwater depletion embedded in the world’s food trade is based on a combination of global, crop-specific estimates of non-renewable groundwater abstraction and international food trade data. A vast majority of the world’s population lives in countries sourcing nearly all their staple crop imports from partners who deplete groundwater to produce these crops, highlighting risks for global food and water security. Some countries, such as the USA, Mexico, Iran and China, are particularly exposed to these risks because they both produce and import food irrigated from rapidly depleting aquifers. Our results could help to improve the sustainability of global food production and groundwater resource management by identifying priority regions and agricultural products at risk as well as the end consumers of these products.

  10. The New MCNP6 Depletion Capability

    Energy Technology Data Exchange (ETDEWEB)

    Fensin, Michael Lorne [Los Alamos National Laboratory; James, Michael R. [Los Alamos National Laboratory; Hendricks, John S. [Los Alamos National Laboratory; Goorley, John T. [Los Alamos National Laboratory

    2012-06-19

    The first MCNP based inline Monte Carlo depletion capability was officially released from the Radiation Safety Information and Computational Center as MCNPX 2.6.0. Both the MCNP5 and MCNPX codes have historically provided a successful combinatorial geometry based, continuous energy, Monte Carlo radiation transport solution for advanced reactor modeling and simulation. However, due to separate development pathways, useful simulation capabilities were dispersed between both codes and not unified in a single technology. MCNP6, the next evolution in the MCNP suite of codes, now combines the capability of both simulation tools, as well as providing new advanced technology, in a single radiation transport code. We describe here the new capabilities of the MCNP6 depletion code dating from the official RSICC release MCNPX 2.6.0, reported previously, to the now current state of MCNP6. NEA/OECD benchmark results are also reported. The MCNP6 depletion capability enhancements beyond MCNPX 2.6.0 reported here include: (1) new performance enhancing parallel architecture that implements both shared and distributed memory constructs; (2) enhanced memory management that maximizes calculation fidelity; and (3) improved burnup physics for better nuclide prediction. MCNP6 depletion enables complete, relatively easy-to-use depletion calculations in a single Monte Carlo code. The enhancements described here help provide a powerful capability as well as dictate a path forward for future development to improve the usefulness of the technology.

  11. Melatonin and its precursor, L-tryptophan: influence on pancreatic amylase secretion in vivo and in vitro.

    Science.gov (United States)

    Jaworek, Jolanta; Nawrot, Katarzyna; Konturek, Stanisław J; Leja-Szpak, Anna; Thor, Piotr; Pawlik, Wiesław W

    2004-04-01

    Melatonin, considered as a main pineal product, may be also synthetized in the gastrointestinal tract from L-tryptophan. Melatonin has been recently shown to affect insulin release and its receptors have been characterized in the pancreas however, the effects of melatonin on the pancreatic enzyme secretion have not been examined. The aim of this study was to investigate the effects of melatonin or L-tryptophan on amylase secretion in vivo in anaesthetized rats with pancreato-biliary fistulas, and in vitro using isolated pancreatic acini. Melatonin (1, 5 or 25 mg/kg) or L-tryptophan (10, 50 or 250 mg/kg) given to the rats as a intraperitoneal (i.p.) bolus injection produced significant and dose-dependent increases in pancreatic amylase secretion under basal conditions or following stimulation of enzyme secretion by diversion of bile-pancreatic juice. This was accompanied by a dose-dependent rise in melatonin plasma level. Stimulation of pancreatic enzyme secretion caused by melatonin or L-tryptophan was completely abolished by vagotomy, deactivation of sensory nerves with capsaicin or pretreatment with CCK1 receptor antagonists (tarazepide or L-364,718). Pretreatment with luzindole, an antagonist of melatonin MT(2) receptor failed to affect melatonin- or L-tryptophan-induced amylase secretion. Administration of melatonin (1, 5 or 25 mg/kg i.p.) or L-tryptophan (10, 50 or 250 mg/kg i.p.) to the rats resulted in the dose-dependent increase of cholecystokinin (CCK) plasma immunoreactivity. Enzyme secretion from isolated pancreatic acini was not significantly affected by melatonin or L-tryptophan used at doses of 10(-8) -10(-5) M. We conclude that exogenous melatonin, as well as that produced endogenously from L-tryptophan, stimulates pancreatic enzyme secretion in vivo while increasing CCK release. Stimulatory effect of melatonin or L-tryptophan on the exocrine pancreas involves vagal sensory nerves and the CCK release by these substances.

  12. Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan.

    Science.gov (United States)

    Pfefferkorn, E R

    1984-01-01

    Treatment of human fibroblasts with human recombinant gamma interferon blocked the growth of Toxoplasma gondii, an obligate intracellular protozoan parasite. Growth of the parasite was measured by a plaque assay 7 days after infection or by the incorporation of [3H]uracil 1 or 2 days after infection. The antitoxoplasma activity induced in the host cells by gamma interferon was strongly dependent upon the tryptophan concentration of the medium. Progressively higher minimal inhibitory concentrations of gamma interferon were observed as the tryptophan concentration in the culture medium was increased. Treatment with gamma interferon did not make the cells impermeable to tryptophan. The kinetics of [3H]tryptophan uptake into the acid-soluble pools of control and gamma interferon-treated cultures were identical during the first 48 sec. Thereafter uptake of [3H]tryptophan into the acid-soluble pool of control fibroblasts reached the expected plateau after 96 sec. In contrast, uptake of [3H]tryptophan continued for at least 12 min in the gamma interferon-treated cultures. At that time, the acid-soluble pool of the gamma interferon-treated cultures contained 8 times the radioactivity of the control cultures. This continued accumulation was the result of rapid intracellular degradation of [3H]tryptophan into kynurenine and N-formylkynurenine that leaked slowly from the cells. These two metabolites were also recovered from the medium of cultures treated for 1 or 2 days with gamma interferon. Human recombinant alpha and beta interferons, which have no antitoxoplasma activity, did not induce any detectable degradation of tryptophan. Several hypotheses are presented to explain how the intracellular degradation of tryptophan induced by gamma interferon could restrict the growth of an obligate intracellular parasite. Images PMID:6422465

  13. Ego depletion in visual perception: Ego-depleted viewers experience less ambiguous figure reversal.

    Science.gov (United States)

    Wimmer, Marina C; Stirk, Steven; Hancock, Peter J B

    2017-02-22

    This study examined the effects of ego depletion on ambiguous figure perception. Adults (N = 315) received an ego depletion task and were subsequently tested on their inhibitory control abilities that were indexed by the Stroop task (Experiment 1) and their ability to perceive both interpretations of ambiguous figures that was indexed by reversal (Experiment 2). Ego depletion had a very small effect on reducing inhibitory control (Cohen's d = .15) (Experiment 1). Ego-depleted participants had a tendency to take longer to respond in Stroop trials. In Experiment 2, ego depletion had small to medium effects on the experience of reversal. Ego-depleted viewers tended to take longer to reverse ambiguous figures (duration to first reversal) when naïve of the ambiguity and experienced less reversal both when naïve and informed of the ambiguity. Together, findings suggest that ego depletion has small effects on inhibitory control and small to medium effects on bottom-up and top-down perceptual processes. The depletion of cognitive resources can reduce our visual perceptual experience.

  14. The modality effect of ego depletion: Auditory task modality reduces ego depletion.

    Science.gov (United States)

    Li, Qiong; Wang, Zhenhong

    2016-08-01

    An initial act of self-control that impairs subsequent acts of self-control is called ego depletion. The ego depletion phenomenon has been observed consistently. The modality effect refers to the effect of the presentation modality on the processing of stimuli. The modality effect was also robustly found in a large body of research. However, no study to date has examined the modality effects of ego depletion. This issue was addressed in the current study. In Experiment 1, after all participants completed a handgrip task, one group's participants completed a visual attention regulation task and the other group's participants completed an auditory attention regulation task, and then all participants again completed a handgrip task. The ego depletion phenomenon was observed in both the visual and the auditory attention regulation task. Moreover, participants who completed the visual task performed worse on the handgrip task than participants who completed the auditory task, which indicated that there was high ego depletion in the visual task condition. In Experiment 2, participants completed an initial task that either did or did not deplete self-control resources, and then they completed a second visual or auditory attention control task. The results indicated that depleted participants performed better on the auditory attention control task than the visual attention control task. These findings suggest that altering task modality may reduce ego depletion.

  15. Ozone depletion and chlorine loading potentials

    Science.gov (United States)

    Pyle, John A.; Wuebbles, Donald J.; Solomon, Susan; Zvenigorodsky, Sergei; Connell, Peter; Ko, Malcolm K. W.; Fisher, Donald A.; Stordal, Frode; Weisenstein, Debra

    1991-01-01

    The recognition of the roles of chlorine and bromine compounds in ozone depletion has led to the regulation or their source gases. Some source gases are expected to be more damaging to the ozone layer than others, so that scientific guidance regarding their relative impacts is needed for regulatory purposes. Parameters used for this purpose include the steady-state and time-dependent chlorine loading potential (CLP) and the ozone depletion potential (ODP). Chlorine loading potentials depend upon the estimated value and accuracy of atmospheric lifetimes and are subject to significant (approximately 20-50 percent) uncertainties for many gases. Ozone depletion potentials depend on the same factors, as well as the evaluation of the release of reactive chlorine and bromine from each source gas and corresponding ozone destruction within the stratosphere.

  16. Plasmonic nanoprobes for stimulated emission depletion microscopy

    CERN Document Server

    Cortes, Emiliano; Sinclair, Hugo G; Guldbrand, Stina; Peveler, William J; Davies, Timothy; Parrinello, Simona; Görlitz, Frederik; Dunsby, Chris; Neil, Mark A A; Sivan, Yonatan; Parkin, Ivan P; French, Paul M; Maier, Stefan A

    2016-01-01

    Plasmonic nanoparticles influence the absorption and emission processes of nearby emitters due to local enhancements of the illuminating radiation and the photonic density of states. Here, we use the plasmon resonance of metal nanoparticles in order to enhance the stimulated depletion of excited molecules for super-resolved microscopy. We demonstrate stimulated emission depletion (STED) microscopy with gold nanorods with a long axis of only 26 nm and a width of 8 nm that provide an enhancement of the resolution compared to fluorescent-only probes without plasmonic components irradiated with the same depletion power. These novel nanoparticle-assisted STED probes represent a ~2x10^3 reduction in probe volume compared to previously used nanoparticles and we demonstrate their application to the first plasmon-assisted STED cellular imaging. We also discuss their current limitations.

  17. Molten-Salt Depleted-Uranium Reactor

    CERN Document Server

    Dong, Bao-Guo; Gu, Ji-Yuan

    2015-01-01

    The supercritical, reactor core melting and nuclear fuel leaking accidents have troubled fission reactors for decades, and greatly limit their extensive applications. Now these troubles are still open. Here we first show a possible perfect reactor, Molten-Salt Depleted-Uranium Reactor which is no above accident trouble. We found this reactor could be realized in practical applications in terms of all of the scientific principle, principle of operation, technology, and engineering. Our results demonstrate how these reactors can possess and realize extraordinary excellent characteristics, no prompt critical, long-term safe and stable operation with negative feedback, closed uranium-plutonium cycle chain within the vessel, normal operation only with depleted-uranium, and depleted-uranium high burnup in reality, to realize with fission nuclear energy sufficiently satisfying humanity long-term energy resource needs, as well as thoroughly solve the challenges of nuclear criticality safety, uranium resource insuffic...

  18. Self-regulation, ego depletion, and inhibition.

    Science.gov (United States)

    Baumeister, Roy F

    2014-12-01

    Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it.

  19. Depletion of the nuclear Fermi sea

    CERN Document Server

    Rios, A; Dickhoff, W H

    2009-01-01

    The short-range and tensor components of the bare nucleon-nucleon interaction induce a sizeable depletion of low momenta in the ground state of a nuclear many-body system. The self-consistent Green's function method within the ladder approximation provides an \\textit{ab-initio} description of correlated nuclear systems that accounts properly for these effects. The momentum distribution predicted by this approach is analyzed in detail, with emphasis on the depletion of the lowest momentum state. The temperature, density, and nucleon asymmetry (isospin) dependence of the depletion of the Fermi sea is clarified. A connection is established between the momentum distribution and the time-ordered components of the self-energy, which allows for an improved interpretation of the results. The dependence on the underlying nucleon-nucleon interaction provides quantitative estimates of the importance of short-range and tensor correlations in nuclear systems.

  20. Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke

    Directory of Open Access Journals (Sweden)

    Machado Livia S

    2005-08-01

    Full Text Available Abstract Background While gelatinase (MMP-2 and -9 activity is increased after focal ischemia/reperfusion injury in the brain, the relative contribution of neutrophils to the MMP activity and to the development of hemorrhagic transformation remains unknown. Results Anti-PMN treatment caused successful depletion of neutrophils in treated animals. There was no difference in either infarct volume or hemorrhage between control and PMN depleted animals. While there were significant increases in gelatinase (MMP-2 and MMP-9 expression and activity and edema formation associated with ischemia, neutrophil depletion failed to cause any change. Conclusion The main finding of this study is that, in the absence of circulating neutrophils, MMP-2 and MMP-9 expression and activity are still up-regulated following focal cerebral ischemia. Additionally, neutrophil depletion had no influence on indicators of ischemic brain damage including edema, hemorrhage, and infarct size. These findings indicate that, at least acutely, neutrophils are not a significant contributor of gelatinase activity associated with acute neurovascular damage after stroke.

  1. Structure and Activity of an Aminoacyl-tRNA Synthetase that Charges tRNA with Nitro-Tryptophan

    Energy Technology Data Exchange (ETDEWEB)

    Buddha,M.; Crane, B.

    2005-01-01

    The most divergent of two tryptophanyl tRNA synthetases (TrpRS II) found in Deinococcus radiodurans interacts with a nitric oxide synthase protein that produces 4-nitro-tryptophan (4-NRP). TrpRS II efficiently charges transfer RNATrp with 4-NRP and 5-hydroxy-tryptophan (5-HRP). The crystal structures of TrpRS II bound to tryptophan and 5-HRP reveal residue substitutions that accommodate modified indoles. A class of auxiliary bacterial TrpRSs conserve this capacity to charge tRNA with nonstandard amino acids.

  2. Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms.

    Science.gov (United States)

    Fuchs, D; Möller, A A; Reibnegger, G; Stöckle, E; Werner, E R; Wachter, H

    1990-01-01

    We investigated serum neopterin, tryptophan, and kynurenine concentrations in 23 HIV-1 seropositive patients (Walter Reed Stage 4-6). Ten patients presented with polyneuropathy and three with dementia, one of the patients with dementia also had polyneuropathy and dementia. We found significant associations between lower trytophan concentrations and neurologic/psychiatric symptoms. The negative correlation of tryptophan with kynurenine and neopterin concentrations indicates activity of indoleamine 2,3-dioxygenase (IDO) in patients. IDO can be induced by cytokines such as interferon-gamma and therefore low tryptophan levels may result from chronic immune stimulation in HIV-1 seropositives.

  3. A Brief Historic Overview of Clinical Disorders Associated with Tryptophan: The Relevance to Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM).

    Science.gov (United States)

    Blankfield, Adele

    2012-01-01

    Last century there was a short burst of interest in the tryptophan related disorders of pellagra and related abnormalities that are usually presented in infancy.1,2 Nutritional physiologists recognized that a severe human dietary deficiency of either tryptophan or the B group vitamins could result in central nervous system (CNS) sequelae such as ataxia, cognitive dysfunction and dysphoria, accompanied by skin hyperpigmentation.3,4 The current paper will focus on the emerging role of tryptophan in chronic fatigue syndrome (CFS) and fibromyalgia (FM).

  4. Review of the implications of dietary tryptophan intake in patients with irritable bowel syndrome and psychiatric disorders.

    Science.gov (United States)

    Agazzi, A; De Ponti, F; De Giorgio, R; Candura, S M; Anselmi, L; Cervio, E; Di Nucci, A; Tonini, M

    2003-08-01

    In this review, we address the possible role of the essential amino acid L-tryptophan or its metabolic derivative 5-hydroxytryptophan in the modulation of serotonin (5-hydroxytryptamine) synthesis and thereby in affecting the pathophysiology of central and peripheral nervous system disorders, including depression and irritable bowel syndrome. L-Tryptophan may represent a link between apparently disparate functional disorders and is of interest for general gastroenterologists, neurogastroenterologists, and neurologists. On the basis of estimates showing that approximately 20% of patients with functional bowel disorders seeking care in referral centres have psychiatric comorbidity, we attempt to provide a conceptual framework for defining the possible role of L-tryptophan in this population.

  5. Sensitivity study of control rod depletion coefficients

    OpenAIRE

    Blomberg, Joel

    2015-01-01

    This report investigates the sensitivity of the control rod depletion coefficients, Sg, to different input parameters and how this affects the accumulated 10B depletion, β. Currently the coefficients are generated with PHOENIX4, but the geometries can be more accurately simulated in McScram. McScram is used to calculate Control Rod Worth, which in turn is used to calculate Nuclear End Of Life, and Sg cannot be generated in the current version of McScram. Therefore, it is also analyzed whether...

  6. Short-chain fluorescent tryptophan tags for on-line detection of functional recombinant proteins

    Directory of Open Access Journals (Sweden)

    Siepert Eva-Maria

    2012-09-01

    Full Text Available Abstract Background Conventional fluorescent proteins, such as GFP, its derivatives and flavin mononucleotide based fluorescent proteins (FbFPs are often used as fusion tags for detecting recombinant proteins during cultivation. These reporter tags are state-of-the-art; however, they have some drawbacks, which can make on-line monitoring challenging. It is discussed in the literature that the large molecular size of proteins of the GFP family may stress the host cell metabolism during production. In addition, fluorophore formation of GFP derivatives is oxygen-dependent resulting in a lag-time between expression and fluorescence detection and the maturation of the protein is suppressed under oxygen-limited conditions. On the contrary, FbFPs are also applicable in an oxygen-limited or even anaerobic environment but are still quite large (58% of the size of GFP. Results As an alternative to common fluorescent tags we developed five novel tags based on clustered tryptophan residues, called W-tags. They are only 5-11% of the size of GFP. Based on the property of tryptophan to fluoresce in absence of oxygen it is reasonable to assume that the functionality of our W-tags is also given under anaerobic conditions. We fused these W-tags to a recombinant protein model, the anti-CD30 receptor single-chain fragment variable antibody (scFv Ki-4(scFv and the anti-MucI single-chain fragment variable M12(scFv. During cultivation in Microtiter plates, the overall tryptophan fluorescence intensity of all cultures was measured on-line for monitoring product formation via the different W-tags. After correlation of the scattered light signal representing biomass concentration and tryptophan fluorescence for the uninduced cultures, the fluorescence originating from the biomass was subtracted from the overall tryptophan signal. The resulting signal, thus, represents the product fluorescence of the tagged and untagged antibody fragments. The product fluorescence signal

  7. Acute pancreatitis

    Science.gov (United States)

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... pancreatitis; Pancreas - inflammation Images Digestive system Endocrine glands Pancreatitis, acute - CT scan Pancreatitis - series References Forsmark CE. Pancreatitis. ...

  8. Cystitis - acute

    Science.gov (United States)

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  9. Gender differences in hyperthermia and regional 5-HT and 5-HIAA depletion in the brain following MDMA administration in rats

    NARCIS (Netherlands)

    Wallinga, Alinde E.; Grahlmann, Carolin; Granneman, Ramon A.; Koolhaas, Jaap M.; Buwalda, Bauke

    2011-01-01

    In the present research the role of gender in MDMA-induced hyperthermia and serotonin depletion is studied by injecting male and female male rats with MDMA or saline 3 times (i.p.) with 3 h interval at dosages of 0.3, 1, 3 or 9 mg/kg at an ambient temperature of 25 degrees C. The acute hyperthermia

  10. Contrasts between Antarctic and Arctic ozone depletion.

    Science.gov (United States)

    Solomon, Susan; Portmann, Robert W; Thompson, David W J

    2007-01-09

    This work surveys the depth and character of ozone depletion in the Antarctic and Arctic using available long balloon-borne and ground-based records that cover multiple decades from ground-based sites. Such data reveal changes in the range of ozone values including the extremes observed as polar air passes over the stations. Antarctic ozone observations reveal widespread and massive local depletion in the heart of the ozone "hole" region near 18 km, frequently exceeding 90%. Although some ozone losses are apparent in the Arctic during particular years, the depth of the ozone losses in the Arctic are considerably smaller, and their occurrence is far less frequent. Many Antarctic total integrated column ozone observations in spring since approximately the 1980s show values considerably below those ever observed in earlier decades. For the Arctic, there is evidence of some spring season depletion of total ozone at particular stations, but the changes are much less pronounced compared with the range of past data. Thus, the observations demonstrate that the widespread and deep ozone depletion that characterizes the Antarctic ozone hole is a unique feature on the planet.

  11. Global Warming: Lessons from Ozone Depletion

    Science.gov (United States)

    Hobson, Art

    2010-01-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of…

  12. Global Warming: Lessons from Ozone Depletion

    Science.gov (United States)

    Hobson, Art

    2010-01-01

    My teaching and textbook have always covered many physics-related social issues, including stratospheric ozone depletion and global warming. The ozone saga is an inspiring good-news story that's instructive for solving the similar but bigger problem of global warming. Thus, as soon as students in my physics literacy course at the University of…

  13. “When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

    Science.gov (United States)

    Salmon, Stefanie J.; Adriaanse, Marieke A.; De Vet, Emely; Fennis, Bob M.; De Ridder, Denise T. D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In three studies, we assessed individual differences in depletion sensitivity, and demonstrate that depletion sensitivity moderates ego-depletion effects. The Depletion Sensitivity Scale (DSS) was employed to assess depletion sensitivity. Study 1 employs the DSS to demonstrate that individual differences in sensitivity to ego-depletion exist. Study 2 shows moderate correlations of depletion sensitivity with related self-control concepts, indicating that these scales measure conceptually distinct constructs. Study 3 demonstrates that depletion sensitivity moderates the ego-depletion effect. Specifically, participants who are sensitive to depletion performed worse on a second self-control task, indicating a stronger ego-depletion effect, compared to participants less sensitive to depletion. PMID:25009523

  14. “When the going gets tough, who keeps going?” Depletion sensitivity moderates the ego-depletion effect

    NARCIS (Netherlands)

    Salmon, S.J.; Adriaanse, M.A.; Vet, de E.W.M.L.; Fennis, B.M.; Ridder, de D.T.D.

    2014-01-01

    Self-control relies on a limited resource that can get depleted, a phenomenon that has been labeled ego-depletion. We argue that individuals may differ in their sensitivity to depleting tasks, and that consequently some people deplete their self-control resource at a faster rate than others. In thre

  15. Differences in fluorescence profiles from breast cancer tissues due to changes in relative tryptophan content via energy transfer: tryptophan content correlates with histologic grade and tumor size but not with lymph node metastases

    Science.gov (United States)

    Sordillo, Laura A.; Sordillo, Peter P.; Budansky, Yury; Pu, Yang; Alfano, Robert R.

    2014-12-01

    The correlation between histologic grade, an increasingly important measure of prognosis for patients with breast cancer, and tryptophan levels from tissues of 15 breast carcinoma patients was investigated. Changes in the relative content of key native organic biomolecule tryptophan were seen from the fluorescence spectra of cancerous and paired normal tissues with excitation wavelengths of 280 and 300 nm. Due to a large spectral overlap and matching excitation-emission spectra, fluorescence resonance energy transfer from tryptophan-donor to reduced nicotinamide adenine dinucleotides-acceptor was noted. We used the ratios of fluorescence intensities at their spectral emission peaks, or spectral fingerprint peaks, at 340, 440, and 460 nm. Higher ratios correlated strongly with high histologic grade, while lower-grade tumors had low ratios. Large tumor size also correlated with high ratios, while the number of lymph node metastases, a major factor in staging, was not correlated with tryptophan levels. High histologic grade correlates strongly with increased content of tryptophan in breast cancer tissues and suggests that measurement of tryptophan content may be useful as a part of the evaluation of these patients.

  16. Nutritional Evaluation of Glycated Valine and Tryptophan as a Precursor for Protein Synthesis in Chicken Embryo Myoblasts

    National Research Council Canada - National Science Library

    Makino, Ryosuke; Sugahara, Misaki; Kita, Kazumi

    2015-01-01

    Valine and Tryptophan plays a role of being a precursor for protein synthesis. Glycation is a non-enzymatic reaction causing dehydrating condensation between the carbonyl group of glucose and the α...

  17. Nutritional Evaluation of Glycated Valine and Tryptophan as a Precursor for Protein Synthesis in Chicken Embryo Myoblasts

    National Research Council Canada - National Science Library

    Makino, Ryosuke; Sugahara, Misaki; Kita, Kazumi

    2015-01-01

    Valine and Tryptophan play a role of being a precursor for protein synthesis. Glycation is a non-enzymatic reaction causing dehydrating condensation between the carbonyl group of glucose and the α...

  18. Evening intake of α-lactalbumin increases plasma tryptophan availability and improves morning alertness and brain measures of attention

    NARCIS (Netherlands)

    Markus, C.R.; Jonkman, L.M.; Lammers, J.H.C.M.; Deutz, N.E.P.; Messer, M.H.; Rigtering, N.

    2005-01-01

    Background: Brain serotonin function is thought to promote sleep regulation and cognitive processes, whereas sleep abnormalities and subsequent behavioral decline are often attributed to deficient brain serotonin activity. Brain uptake of the serotonin precursor tryptophan is dependent on nutrients

  19. Complement depletion deteriorates clinical outcomes of severe abdominal sepsis: a conspirator of infection and coagulopathy in crime?

    Directory of Open Access Journals (Sweden)

    Jianan Ren

    Full Text Available BACKGROUND: The complement depletion commonly occurred during sepsis, but it was often underestimated compared with severe infection or coagulation dysfunction. OBJECTIVE: This study was designed to investigate the alteration of complement system in patients with severe abdominal sepsis and evaluate the role of complement depletion in prognosis of such patients. The relationship between complement depletion and infection or coagulopathy was also explored. METHODS: Forty-five patients with severe abdominal sepsis were prospectively conducted among individuals referral to SICU. Currently recommended treatments, such as early goal-directed resuscitation, source control and antibiotics therapy, were performed. Acute physiology and chronic health evaluation II (APACHE II and sepsis related organ failure assessment (SOFA scores were employed to evaluate severity. Plasma levels of C3, C4, CRP, PCT, D-dimer and other parameters were detected within eight times of observation. The 28-day mortality, length of stay, and postoperative complications were compared between complement depletion and non-complement depletion groups. RESULTS: Within the study period, eight (17.8% patients died, five of them suffering from complement depletion. The overall incidence of complement depletion was 64.4%. At admission, mean complement C3 and C4 levels were 0.70 and 0.13 mg/mL, respectively. Using ROC analysis for mortality prediction, the area under the curve of C3 was 0.926 (95% CI, 0.845-0.998, P<0.001, with optimal cutpoint value of 0.578 mg/mL. Complement C3 depletion was shown to be no correlation to severity scores, however, strongly correlated with elevated D-dimer, PCT concentrations and increased postoperative complications. CONCLUSIONS: Complement C3 depletion was found to be connected to poor prognosis in severe abdominal sepsis. This depletion seems to be associated with coagulopathy and aggravated infection during sepsis, which should be paid close

  20. How Depleted is the MORB mantle?

    Science.gov (United States)

    Hofmann, A. W.; Hart, S. R.

    2015-12-01

    Knowledge of the degree of mantle depletion of highly incompatible elements is critically important for assessing Earth's internal heat production and Urey number. Current views of the degree of MORB source depletion are dominated by Salters and Stracke (2004), and Workman and Hart (2005). The first is based on an assessment of average MORB compositions, whereas the second considers trace element data of oceanic peridotites. Both require an independent determination of one absolute concentration, Lu (Salters & Stracke), or Nd (Workman & Hart). Both use parent-daughter ratios Lu/Hf, Sm/Nd, and Rb/Sr calculated from MORB isotopes combined with continental-crust extraction models, as well as "canonical" trace element ratios, to boot-strap the full range of trace element abundances. We show that the single most important factor in determining the ultimate degree of incompatible element depletion in the MORB source lies in the assumptions about the timing of continent extraction, exemplified by continuous extraction versus simple two-stage models. Continued crust extraction generates additional, recent mantle depletion, without affecting the isotopic composition of the residual mantle significantly. Previous emphasis on chemical compositions of MORB and/or peridotites has tended to obscure this. We will explore the effect of different continent extraction models on the degree of U, Th, and K depletion in the MORB source. Given the uncertainties of the two most popular models, the uncertainties of U and Th in DMM are at least ±50%, and this impacts the constraints on the terrestrial Urey ratio. Salters, F.J.M. and Stracke, A., 2004, Geochem. Geophys. Geosyst. 5, Q05004. Workman, R.K. and Hart, S.R., 2005, EPSL 231, 53-72.

  1. Molecular analysis of intragenic recombination at the tryptophan synthetase locus in Neurospora crassa

    Indian Academy of Sciences (India)

    A. Wiest; D. Barchers; M. Eaton; R. Henderson; R. Schnittker; K. Mccluskey

    2013-12-01

    Fifteen different classically generated and mapped mutations at the tryptophan synthetase locus in Neurospora crassa have been characterized to the level of the primary sequence of the gene. This sequence analysis has demonstrated that intragenic recombination is accurate to order mutations within one open reading frame. While classic genetic analysis correctly ordered the mutations, the position of mutations characterized by gene sequence analysis was more accurate. A leaky mutation was found to have a wild-type primary sequence. The presence of unique polymorphisms in the primary sequence of the trp-3 gene from strain 861 confirms that it has a unique history relative to the other strains studied. Most strains that were previously shown to be immunologically nonreactive with antibody preparations raised against tryptophan synthetase protein were shown to have nonsense mutations. This work defines 14 alleles of the N. crassa trp-3 gene.

  2. Tryptophan-Assisted Synthesis Reduces Bimetallic Gold/Silver Nanoparticle Cytotoxicity and Improves Biological Activity

    Directory of Open Access Journals (Sweden)

    Igor O. Shmarakov

    2014-10-01

    Full Text Available Aiming to reduce the potential in vivo hepato-and nephrotoxicity of Ag/Au bimetallic nanoparticles (NPs stabilized by sodium dodecyl sulphate (SDS, an approach involving a simultaneous reduction of silver nitrate and tetrachlorauratic acid using tryptophan (Trp as a reducing/stabilizing agent was applied during NP synthesis. The obtained Ag/Au/Trp NPs (5–15 nm sized were able to form stable aggregates with an average size of 370–450 nm and were potentially less toxic than Ag/Au/SDS in relation to a mouse model system based on clinical biochemical parameters and oxidative damage product estimation. Ag/Au/Trp NPs were shown to exhibit anticancer activity in relation to a Lewis lung carcinoma model. The data generated from the present study support the fact that the use of tryptophan in NP synthesis is effective in attenuating the potential hepatotoxicity and nephrotoxicity of NPs during their in vivo application.

  3. Inhibiting the photosensitized oxidation of anthracene and tryptophan by means of natural antioxidants

    Science.gov (United States)

    Aksenova, N. A.; Vyzhlova, E. N.; Malinovskaya, V. V.; Parfenov, V. V.; Solov'eva, A. B.; Timashev, P. S.

    2013-08-01

    It is shown that model reactions of photosensitized oxidation of anthracene and tryptophan can be used for evaluation and comparison of antioxidant activity of various classes of compounds. Inhibition of the oxidation of substrates in the presence of the familiar antioxidants tocopherol (vitamin E), ascorbic acid (vitamin C), and mixtures of these vitamins with methionine, and in the presence of reputed antioxidants dihydroquercetin and taurine, are considered. It is concluded that all of the above compounds except for taurine have antioxidant properties; i.e., they reduce the rate constants of the photosensitized oxidation of anthracene and tryptophan. It is found that the inhibition of oxidation is associated with the interaction between antioxidants and singlet oxygen. Analysis of the kinetic dependences of the photosensitized oxidation of substrates in the presence of antioxidants reveals that a mixture of vitamins inhibits the process most efficiently, and inhibition occurs at the initial stages due to more active interaction between singlet oxygen and vitamin C

  4. The Effect of Tryptophan on Serotonin-Like Neurons in Duck Cerebellum

    Institute of Scientific and Technical Information of China (English)

    LIU Hua-zhen; TANG Wen-hua; PENG Ke-mei; CHEN Wen-qin; LUO Guan-zhong; WANG Yan; WEI Lan

    2006-01-01

    Healthy Cherry Valley ducks were used in the present study. Different doses of tryptophan were injected intraperitoneallyto them after being fasted 4 h (8:00 a.m.-12:00 a.m.). One hour later, they were deeply anaesthetized and perfused. The cerebellum was removed to make serial paraffin longitudinal sections. The streptavidin-biotin-peroxidase complex (SABC) method was used to study the distribution of serotonin-like neurons in the cerebellum. All films were analysed by using a computer-assisted image analysis system. Serotonin-like neurons are only localized in cerebellar Purkinje cell layer. The optical density averages of serotonin-like neurons in 200 and 100 mg kg-1 group are significantly higher than that of O mg kg-1 group (P<0.01). These results show that serotonin-like neurons are distributed in Purkinje cell layer and that excessive tryptophan can affect the content of serotonin in cerebellum.

  5. Stochastic thermodynamics of a chemical nanomachine: The channeling enzyme tryptophan synthase.

    Science.gov (United States)

    Loutchko, Dimitri; Eisbach, Maximilian; Mikhailov, Alexander S

    2017-01-14

    The enzyme tryptophan synthase is characterized by a complex pattern of allosteric interactions that regulate the catalytic activity of its two subunits and opening or closing of their ligand gates. As a single macromolecule, it implements 13 different reaction steps, with an intermediate product directly channeled from one subunit to another. Based on experimental data, a stochastic model for the operation of tryptophan synthase has been earlier constructed [D. Loutchko, D. Gonze, and A. S. Mikhailov, J. Phys. Chem. B 120, 2179 (2016)]. Here, this model is used to consider stochastic thermodynamics of such a chemical nanomachine. The Gibbs energy landscape of the internal molecular states is determined, the production of entropy and its flow within the enzyme are analyzed, and the information exchange between the subunits resulting from allosteric cross-regulations and channeling is discussed.

  6. Tyrosine- and tryptophan-coated gold nanoparticles inhibit amyloid aggregation of insulin.

    Science.gov (United States)

    Dubey, Kriti; Anand, Bibin G; Badhwar, Rahul; Bagler, Ganesh; Navya, P N; Daima, Hemant Kumar; Kar, Karunakar

    2015-12-01

    Here, we have strategically synthesized stable gold (AuNPs(Tyr), AuNPs(Trp)) and silver (AgNPs(Tyr)) nanoparticles which are surface functionalized with either tyrosine or tryptophan residues and have examined their potential to inhibit amyloid aggregation of insulin. Inhibition of both spontaneous and seed-induced aggregation of insulin was observed in the presence of AuNPs(Tyr), AgNPs(Tyr), and AuNPs(Trp) nanoparticles. These nanoparticles also triggered the disassembly of insulin amyloid fibrils. Surface functionalization of amino acids appears to be important for the inhibition effect since isolated tryptophan and tyrosine molecules did not prevent insulin aggregation. Bioinformatics analysis predicts involvement of tyrosine in H-bonding interactions mediated by its C=O, -NH2, and aromatic moiety. These results offer significant opportunities for developing nanoparticle-based therapeutics against diseases related to protein aggregation.

  7. Identification of a quorum sensing pheromone posttranslationally farnesylated at the internal tryptophan residue from Bacillus subtilis subsp. natto.

    Science.gov (United States)

    Hayashi, Shunsuke; Usami, Syohei; Nakamura, Yuta; Ozaki, Koki; Okada, Masahiro

    2015-01-01

    Bacillus subtilis subsp. natto produces poly-γ-glutamic acid under the control of quorum sensing. We identified ComXnatto pheromone as the quorum-sensing pheromone with an amino acid sequence of Lys-Trp-Pro-Pro-Ile-Glu and the tryptophan residue posttranslationally modified by a farnesyl group. ComXnatto pheromone is unique in the sense that the 5th tryptophan residue from the C-terminal is farnesylated.

  8. Tryptophanase-Catalyzed l-Tryptophan Synthesis from d-Serine in the Presence of Diammonium Hydrogen Phosphate

    OpenAIRE

    Fujii Noriko; Haruka Ozaki; Takeshi Saito; Akihiko Shimada

    2009-01-01

    Tryptophanase, an enzyme with extreme absolute stereospecificity for optically active stereoisomers, catalyzes the synthesis of L-tryptophan from L-serine and indole through a β-substitution mechanism of the ping-pong type, and has no activity on D-serine. We previously reported that tryptophanase changed its stereospecificity to degrade D-tryptophan in highly concentrated diammonium hydrogen phosphate, (NH4)2HPO4 solution. The present study provided the same stereospecific change seen in the...

  9. Indole production by the tryptophanase TnaA in Escherichia coli is determined by the amount of exogenous tryptophan.

    Science.gov (United States)

    Li, Gang; Young, Kevin D

    2013-02-01

    The signalling molecule indole occurs in significant amounts in the mammalian intestinal tract and regulates diverse microbial processes, including bacterial motility, biofilm formation, antibiotic resistance and host cell invasion. In Escherichia coli, the enzyme tryptophanase (TnaA) produces indole from tryptophan, but it is not clear what determines how much indole E. coli can produce and excrete, making it difficult to interpret experiments that investigate the biological effects of indole at high concentrations. Here, we report that the final yield of indole depends directly, and perhaps solely, on the amount of exogenous tryptophan. When supplied with a range of tryptophan concentrations, E. coli converted this amino acid into an equal amount of indole, up to almost 5 mM, an amount well within the range of the highest concentrations so far examined for their physiological effects. Indole production relied heavily on the tryptophan-specific transporter TnaB, even though the alternative transporters AroP and Mtr could import sufficient tryptophan to induce tnaA expression. This TnaB requirement proceeded via tryptophan transport and was not caused by activation of TnaA itself. Bacterial growth was unaffected by the presence of TnaA in the absence of exogenous tryptophan, suggesting that the enzyme does not hydrolyse significant quantities of the internal anabolic amino acid pool. The results imply that E. coli synthesizes TnaA and TnaB mainly, or solely, for the purpose of converting exogenous tryptophan into indole, under conditions and for signalling purposes that remain to be fully elucidated.

  10. Tryptophanase-Catalyzed l-Tryptophan Synthesis from d-Serine in the Presence of Diammonium Hydrogen Phosphate

    OpenAIRE

    Shimada, Akihiko; Ozaki, Haruka; Saito, Takeshi; Fujii, Noriko

    2009-01-01

    Tryptophanase, an enzyme with extreme absolute stereospecificity for optically active stereoisomers, catalyzes the synthesis of l-tryptophan from l-serine and indole through a β-substitution mechanism of the ping-pong type, and has no activity on d-serine. We previously reported that tryptophanase changed its stereospecificity to degrade d-tryptophan in highly concentrated diammonium hydrogen phosphate, (NH4)2HPO4 solution. The present study provided the same stereospecific change seen in the...

  11. Serum Immune System Biomarkers Neopterin and Interleukin-10 Are Strongly Related to Tryptophan Metabolism in Healthy Young Adults.

    Science.gov (United States)

    Deac, Oana M; Mills, James L; Gardiner, Clair M; Shane, Barry; Quinn, Louise; Midttun, Øivind; McCann, Adrian; Meyer, Klaus; Ueland, Per M; Fan, Ruzong; Lu, Zhaohui; Brody, Lawrence C; Molloy, Anne M

    2016-09-01

    Changes in tryptophan metabolism through the vitamin B-6-dependent kynurenine pathway have been linked to activation of the immune system. We hypothesized that blood concentrations of tryptophan and its catabolites were associated with biomarkers relevant to inflammatory processes in healthy noninflamed subjects. Healthy young adults (n = 737) aged 18-28 y without any known diseases or clinical evidence of inflammation provided blood samples for analysis of serum tryptophan/kynurenine metabolites, neopterin, C-reactive protein (CRP), and plasma pyridoxal 5'-phosphate (PLP) with LC-tandem mass spectrometry methodologies. A panel of cytokines was measured in serum by using high-sensitivity ELISA assays. Anthropometric and lifestyle data were collected by questionnaire. Multiple linear regression analysis to determine the effect of measured serum cytokine concentrations as predictors of tryptophan metabolites was performed on inverse normal-rank transformations of the data, adjusted for sex, body mass index, smoking, alcohol intake, and contraceptive use in women. Median serum CRP and neopterin concentrations were well below established clinical cutoffs for inflammation. We observed significant positive associations between serum interleukin-10 (IL-10) and serum kynurenine (P = 0.0002), the kynurenine-to-tryptophan ratio (KTR) (P = 0.003), 3-hydroxykynurenine (P = 0.01), and 3-hydroxyanthranilic acid (P = 0.04). Serum neopterin was positively associated with kynurenine, the KTR (both P < 0.0001), and anthranilic acid (P = 0.004), and was negatively associated with serum tryptophan (P = 0.01) and PLP (P < 0.0001). Serum tumor necrosis factor α was also negatively associated with tryptophan (P < 0.001). In healthy young adults with no apparent inflammatory conditions, serum tryptophan metabolites are significantly associated with key immune system biomarkers. The observed association between IL-10 and kynurenine is unexpected and suggests that kynurenine

  12. The structure of flavin-dependent tryptophan 7-halogenase RebH

    Energy Technology Data Exchange (ETDEWEB)

    Bitto, Eduard; Huang, Yu; Bingman, Craig A.; Singh, Shanteri; Thorson, Jon S.; Phillips, Jr., George N. (UW)

    2010-02-19

    Enzyme catalyzed regio- and stereo-specific halogenations influence the biological activity of a diverse array of therapeutically important natural products, including the antibiotics vancomycin and chloramphenicol as well as the anticancer agents calicheamicin and rebeccamycin. The major class of enzymes responsible for this challenging synthetic reaction, the flavin-dependent halogenases, catalyzes the formation of carbon-halogen bonds using flavin, a halide ion (Cl{sup -}, Br{sup -} or I{sup -}), and O{sub 2}. Recent mechanistic and structural advances achieved with the model flavin-dependent tryptophan 7-halogenases PrnA and RebH have greatly enhanced the level of understanding of this unique reaction. According to these studies, the mechanism for tryptophan halogenation proceeds via FAD(C4a)-OOH activation of a chloride ion into the transient chlorinating species HOCl. The key evidence for the requirement of a transient chlorinating species is the discovery that a {approx}10-{angstrom}-long tunnel separates FAD and tryptophan in the ligand-bound form of PrnA. In a recent compelling study to elucidate the strategy by which RebH controls this highly reactive and indiscriminant oxidant, a Lys79-{var_epsilon}NH-Cl chloramine intermediate was implicated as the actual chlorinating species within RebH and a structural investigation of RebH was reported. Here we report our independent structural analysis of Lechevalieria aerocolonigenes RebH (Uni-Prot accession number Q8KHZ8, 530 amino acids) in its apo-form as well as in a complex with both tryptophan and FAD.

  13. Serum Levels of Tryptophan, 5-Hydroxytryptophan and Serotonin in Patients Affected with Different Forms of Amenorrhea

    Directory of Open Access Journals (Sweden)

    S. Comai

    2010-06-01

    Full Text Available Tryptophan (Trp is present in the serum, partly bound to albumine and in the free form. The unbound portion of circulating tryptophan has the property of crossing the hematoencephalic barrier and being converted within the brain into serotonin (5-HT through the enzymatic processes of hydroxylation and decarboxylation. The serotoninergic system plays an important role in neuroendocrine control of reproductive hormone secretion, and in particular, it may influence GnRH pulsatility, a function essential for reproductive processes. In this study, we analysed serum levels of tryptophan, serotonin and 5-hydroxytryptophan (5-HTP in women with three different forms of amenorrhea: 16 patients were diagnosed with anorexia nervosa, 60 patients with functional hypothalamic amenorrhea, and 14 patients with hyperprolactinemia. Data were compared with those of a group of 25 healthy women. Serum Trp levels were significantly (P ≤ 0.05 lower in the anorexic (11.64 ± 0.53 µg/ml, mean ± S.E. than in the control (12.98 ± 0.37 µg/ml groups. In addition, in the anorexic group a statistical dispersion of Trp values was shown indicating a bimodal data distribution suggesting the existence of two different subgroups of patients. Regarding 5-HTP, an increase of its serum level was observed in all the groups with amenorrhea with the highest value in hyperprolactinemic patients. On the contrary, no statistical differences in serum 5-HT levels among the four analyzed groups were observed. This study shows that women affected by various forms of amenorrhea present an altered metabolism of tryptophan via serotonin and, in particular, markedly high differences are observed between the two subgroups of anorexic patients.

  14. Effect of Tryptophan on the corrosion behavior of low alloy steel in sulfamic acid

    OpenAIRE

    Hesham T.M. Abdel-Fatah; Salah A.M. Rashwan; S.M. Abd El Wahaab; Aliaa A.M. Hassan

    2016-01-01

    Sulfamic acid is widely used in various industrial acid cleaning applications. In the present work, the inhibition effect of Tryptophan (Tryp) on the corrosion of low alloy steel in sulfamic acid solutions at four different temperatures was studied. The investigations involved electrochemical methods (electrochemical impedance spectroscopy; EIS and the new technique electrochemical frequency modulation; EFM) as well as gravimetric measurements. The inhibition efficiency and the apparent activ...

  15. Dynamic Allostery Mediated by a Conserved Tryptophan in the Tec Family Kinases.

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    Nikita Chopra

    2016-03-01

    Full Text Available Bruton's tyrosine kinase (Btk is a Tec family non-receptor tyrosine kinase that plays a critical role in immune signaling and is associated with the immunological disorder X-linked agammaglobulinemia (XLA. Our previous findings showed that the Tec kinases are allosterically activated by the adjacent N-terminal linker. A single tryptophan residue in the N-terminal 17-residue linker mediates allosteric activation, and its mutation to alanine leads to the complete loss of activity. Guided by hydrogen/deuterium exchange mass spectrometry results, we have employed Molecular Dynamics simulations, Principal Component Analysis, Community Analysis and measures of node centrality to understand the details of how a single tryptophan mediates allostery in Btk. A specific tryptophan side chain rotamer promotes the functional dynamic allostery by inducing coordinated motions that spread across the kinase domain. Either a shift in the rotamer population, or a loss of the tryptophan side chain by mutation, drastically changes the coordinated motions and dynamically isolates catalytically important regions of the kinase domain. This work also identifies a new set of residues in the Btk kinase domain with high node centrality values indicating their importance in transmission of dynamics essential for kinase activation. Structurally, these node residues appear in both lobes of the kinase domain. In the N-lobe, high centrality residues wrap around the ATP binding pocket connecting previously described Catalytic-spine residues. In the C-lobe, two high centrality node residues connect the base of the R- and C-spines on the αF-helix. We suggest that the bridging residues that connect the catalytic and regulatory architecture within the kinase domain may be a crucial element in transmitting information about regulatory spine assembly to the catalytic machinery of the catalytic spine and active site.

  16. Uremic anorexia: a consequence of persistently high brain serotonin levels? The tryptophan/serotonin disorder hypothesis.

    Science.gov (United States)

    Aguilera, A; Selgas, R; Codoceo, R; Bajo, A

    2000-01-01

    Anorexia is a frequent part of uremic syndrome, contributing to malnutrition in dialysis patients. Many factors have been suggested as responsible for uremic anorexia. In this paper we formulate a new hypothesis to explain the appetite disorders in dialysis patients: "the tryptophan/serotonin disorder hypothesis." We review current knowledge of normal hunger-satiety cycle control and the disorders described in uremic patients. There are four phases in food intake regulation: (1) the gastric phase, during which food induces satiety through gastric distention and satiety peptide release; (2) the post absorptive phase, during which circulating compounds, including glucose and amino acids, cause satiety by hepatic receptors via the vagus nerve; (3) the hepatic phase, during which adenosine triphosphate (ATP) concentration is the main stimulus inducing hunger or satiety, with cytokines inhibiting ATP production; and (4) the central phase, during which appetite is regulated through peripheral (circulating plasma substances and neurotransmitters) and brain stimuli. Brain serotonin is the final target for peripheral mechanisms controlling appetite. High brain serotonin levels and a lower serotonin/dopamine ratio cause anorexia. Plasma and brain amino acid concentrations are recognized factors involved in neurotransmitter synthesis and appetite control. Tryptophan is the substrate of serotonin synthesis. High plasma levels of anorectics such as tryptophan (plasma and brain), cholecystokinin, tumor necrosis factor alpha, interleukin-1, and leptin, and deficiencies of nitric oxide and neuropeptide Y have been described in uremia; all increase intracerebral serotonin. We suggest that brain serotonin hyperproduction due to a uremic-dependent excess of tryptophan may be the final common pathway involved in the genesis of uremic anorexia. Various methods of ameliorating anorexia by decreasing the central effects of serotonin are proposed.

  17. Complete phenotypic recovery of an Alzheimer's disease model by a quinone-tryptophan hybrid aggregation inhibitor.

    Directory of Open Access Journals (Sweden)

    Roni Scherzer-Attali

    Full Text Available The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic proteins. Here, using in vitro, in vivo and in silico tools we describe the synthesis and functional characterization of a rationally designed inhibitor of the Alzheimer's disease-associated beta-amyloid. This compound, 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp, combines the recognition capacities of both quinone and tryptophan moieties and completely inhibited Abeta oligomerization and fibrillization, as well as the cytotoxic effect of Abeta oligomers towards cultured neuronal cell line. Furthermore, when fed to transgenic Alzheimer's disease Drosophila model it prolonged their life span and completely abolished their defective locomotion. Analysis of the brains of these flies showed a significant reduction in oligomeric species of Abeta while immuno-staining of the 3(rd instar larval brains showed a significant reduction in Abeta accumulation. Computational studies, as well as NMR and CD spectroscopy provide mechanistic insight into the activity of the compound which is most likely mediated by clamping of the aromatic recognition interface in the central segment of Abeta. Our results demonstrate that interfering with the aromatic core of amyloidogenic peptides is a promising approach for inhibiting various pathogenic species associated with amyloidogenic diseases. The compound NQTrp can serve as a lead for developing a new class of disease modifying drugs for Alzheimer's disease.

  18. Enhanced synthesis of 5-hydroxy-l-tryptophan through tetrahydropterin regeneration

    OpenAIRE

    Hara, Ryotaro; Kino, Kuniki

    2013-01-01

    5-Hydroxy-l-tryptophan (5-HTP) is a naturally occurring aromatic amino acid present in the seeds of the African plant Griffonia simplicifolia. Although 5-HTP has therapeutic effects in various symptoms, efficient method of producing 5-HTP has not been established. In this study, we developed a novel cofactor regeneration process to achieve enhanced synthesis of 5-HTP by using modified l-phenylalanine 4-hydroxylase of Chromobacterium violaceum. For the synthesis of 5-HTP using Escherichia coli...

  19. Identification of potential sites for tryptophan oxidation in recombinant antibodies using tert-butylhydroperoxide and quantitative LC-MS.

    Directory of Open Access Journals (Sweden)

    Miriam Hensel

    Full Text Available Amino acid oxidation is known to affect the structure, activity, and rate of degradation of proteins. Methionine oxidation is one of the several chemical degradation pathways for recombinant antibodies. In this study, we have identified for the first time a solvent accessible tryptophan residue (Trp-32 in the complementary-determining region (CDR of a recombinant IgG1 antibody susceptible to oxidation under real-time storage and elevated temperature conditions. The degree of light chain Trp-32 oxidation was found to be higher than the oxidation level of the conserved heavy chain Met-429 and the heavy chain Met-107 of the recombinant IgG1 antibody HER2, which have already been identified as being solvent accessible and sensitive to chemical oxidation. In order to reduce the time for simultaneous identification and functional evaluation of potential methionine and tryptophan oxidation sites, a test system employing tert-butylhydroperoxide (TBHP and quantitative LC-MS was developed. The optimized oxidizing conditions allowed us to specifically oxidize the solvent accessible methionine and tryptophan residues that displayed significant oxidation in the real-time stability and elevated temperature study. The achieved degree of tryptophan oxidation was adequate to identify the functional consequence of the tryptophan oxidation by binding studies. In summary, the here presented approach of employing TBHP as oxidizing reagent combined with quantitative LC-MS and binding studies greatly facilitates the efficient identification and functional evaluation of methionine and tryptophan oxidation sites in the CDR of recombinant antibodies.

  20. Insights into transport mechanism from LeuT engineered to transport tryptophan

    Energy Technology Data Exchange (ETDEWEB)

    Piscitelli, Chayne L.; Gouaux, Eric (Oregon HSU)

    2012-01-10

    LeuT is a bacterial homologue of the neurotransmitter:sodium symporter (NSS) family and, being the only NSS member to have been structurally characterized by X-ray crystallography, is a model protein for studying transporter structure and mechanism. Transport activity in LeuT was hypothesized to require structural transitions between open-to-out and occluded conformations dependent upon protein:ligand binding complementarity. Here, using crystallographic and functional analysis, we show that binding site modification produces changes in both structure and activity that are consistent with complementarity-dependent structural transitions to the occluded state. The mutation I359Q converts the activity of tryptophan from inhibitor to transportable substrate. This mutation changes the local environment of the binding site, inducing the bound tryptophan to adopt a different conformer than in the wild-type complex. Instead of trapping the transporter open, tryptophan binding now allows the formation of an occluded state. Thus, transport activity is correlated to the ability of the ligand to promote the structural transition to the occluded state, a step in the transport cycle that is dependent on protein:ligand complementarity in the central binding site.

  1. The Potential Role of Cannabinoids in Modulating Serotonergic Signaling by Their Influence on Tryptophan Metabolism

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    Dietmar Fuchs

    2010-08-01

    Full Text Available Phytocannabinoids present in Cannabis plants are well known to exert potent anti-inflammatory and immunomodulatory effects. Previously, we have demonstrated that the psychoactive D9-tetrahydrocannabinol (THC and the non-psychotropic cannabidiol (CBD modulate mitogen-induced Th1-type immune responses in peripheral blood mononuclear cells (PBMC. The suppressive effect of both cannabinoids on mitogen-induced tryptophan degradation mediated by indoleamine-2,3-dioxygenase (IDO, suggests an additional mechanism by which antidepressive effects of cannabinoids might be linked to the serotonergic system. Here, we will review the role of tryptophan metabolism in the course of cell mediated immune responses and the relevance of cannabinoids in serotonergic signaling. We conclude that in particular the non-psychotropic CBD might be useful for the treatment of mood disorders in patients with inflammatory diseases, since this cannabinoid seems to be safe and its effects on activation-induced tryptophan degradation by CBD were more potent as compared to THC.

  2. Effect of zinc on the biosynthesis of tryptophan, indol auxins and gibberellins in barely

    Energy Technology Data Exchange (ETDEWEB)

    Masev, N.; Kutacek, M.

    1966-01-01

    The action of zinc on the growth of barley and the biosynthesis of indol compounds and gibberellin-like substances was investigated in a number of concentrations of zinc from doses stimulating growth to toxic doses. The seeds were soaked before sowing in solutions of zinc sulfate (5 x 10/sup -5/ to 5 x 10/sup -1/% Zn), and the plants cultivated for 7 days in water. Lower concentrations of zinc increased both plant growth and the biosynthesis of tryptophan and auxins. At the optimum concentration of 5 x 10/sup -3/% Zn this increase in tryptophan amounted to 241% of the variant without zinc; in substances with an R/sub F/ corresponding to indolyacetic acid, the increase determined by the biological test, was 207% as against the variant without zinc. Higher concentrations of zinc inhibited growth, the tryptophan content was decreased to below that of the control without zinc and the auxin content also fell to below the control values. Zinc also influenced the content of gibberellin-like substances in the plants. At a concentration of 5 x 10/sup -3/% Zn the increase in the growth activity in the gibberellic acid area of the chromatogram was 294% of the variant without zinc. At toxic concentrations of zinc, the content of gibberellin-like substances fell to below that of the controls. The finding that zinc acts simultaneously on the biosynthesis of auxins and gibberellins is also evidence for the common action of growth substances of various chemical types on plant growth.

  3. Negative Impact of Hypoxia on Tryptophan 2,3-Dioxygenase Function

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    Frank Elbers

    2016-01-01

    Full Text Available Tryptophan is an essential amino acid for hosts and pathogens. The liver enzyme tryptophan 2,3-dioxygenase (TDO provokes, by its ability to degrade tryptophan to N-formylkynurenine, the precursor of the immune-relevant kynurenines, direct and indirect antimicrobial and immunoregulatory states. Up to now these TDO-mediated broad-spectrum effector functions have never been observed under hypoxia in vitro, although physiologic oxygen concentrations in liver tissue are low, especially in case of infection. Here we analysed recombinant expressed human TDO and ex vivo murine TDO functions under different oxygen conditions and show that TDO-induced restrictions of clinically relevant pathogens (bacteria, parasites and of T cell proliferation are abrogated under hypoxic conditions. We pinpointed the loss of TDO efficiency to the reduction of TDO activity, since cell survival and TDO protein levels were unaffected. In conclusion, the potent antimicrobial as well as immunoregulatory effects of TDO were substantially impaired under hypoxic conditions that pathophysiologically occur in vivo. This might be detrimental for the appropriate host immune response towards relevant pathogens.

  4. Perturbations of tyrosine metabolism promote the indolepyruvate pathway via tryptophan in host and microbiome.

    Science.gov (United States)

    Gertsman, Ilya; Gangoiti, Jon A; Nyhan, William L; Barshop, Bruce A

    2015-03-01

    The drug nitisinone (NTBC) is used to treat tyrosinemia type I, and more recently has been also used for the treatment of another disorder of tyrosine metabolism, alkaptonuria. While studying the dose effects of NTBC treatment on alkaptonuria, untargeted metabolomics revealed perturbations in a completely separate pathway, that of tryptophan metabolism. Significant elevations in several indolic compounds associated with the indolepyruvate pathway of tryptophan metabolism were present in NTBC-treated patient sera and correlated with elevations of an intermediate of tyrosine metabolism. Indolic compounds of this pathway have long been associated with commensal bacterial and plant metabolism. These exogenous sources of indoles have been more recently implicated in affecting mammalian cell function and disease. We studied the correlation of these indolic compounds in other disorders of tyrosine metabolism including tyrosinemia types I and II as well as transient tyrosinemia, and demonstrated that 4-hydroxyphenylpyruvate (4-HPP) was directly responsible for the promotion of this pathway. We then investigated the regulation of the indolepyruvate pathway and the role of 4-HPP further in both mammalian cells and intestinal microbial cultures. We demonstrated that several of the indolic products, including indolepyruvate and indolelactate, were in fact generated by human cell metabolism, while the downstream indole metabolite, indolecarboxaldehyde, was produced exclusively by microbial cultures of human gut flora. This study describes a symbiotic perturbation in host and microbiome tryptophan metabolism in response to elevations related to defects of tyrosine metabolism and concomitant drug treatment.

  5. Peroxidase catalyzed nitration of tryptophan derivatives. Mechanism, products and comparison with chemical nitrating agents.

    Science.gov (United States)

    Sala, Alberto; Nicolis, Stefania; Roncone, Raffaella; Casella, Luigi; Monzani, Enrico

    2004-07-01

    The enzymatic nitration of tryptophan derivatives by oxidation of nitrite has been studied using lactoperoxidase and horseradish peroxidase, and compared with the chemical nitration produced by nitrogen dioxide and peroxynitrite. HPLC, mass spectra and NMR analysis of the mixture of products clearly show that nitration occurs at position 4-, 6-, 7-, and N1 of the indole ring, and nitrosation at position N1. Kinetic studies performed on peroxidase/NO2-/H2O2 systems showed substrate saturation behavior with all the tryptophan derivatives employed. The rate dependence on nitrite concentration was found to be linear with horseradish peroxidase while it exhibited saturation behavior with lactoperoxidase. The composition of the product mixture depends on the nitrating agent. While the production of 4-nitro, 6-nitro, 7-nitro and N1-nitro derivatives follows a similar trend, indicating that they are formed according to a similar mechanism, the ratio between the N1-nitroso derivative and other derivatives depends markedly on the nitrite concentration when tryptophan modification is performed by the peroxidase/H2O2/nitrite systems. Analysis of the data indicates that at low nitrite concentration the enzymatic reaction occurs through the classical peroxidase cycle. At high nitrite concentration the reaction proceeds through a different intermediate that we assume to be a protein bound peroxynitrite species.

  6. Insights into transport mechanism from LeuT engineered to transport tryptophan.

    Science.gov (United States)

    Piscitelli, Chayne L; Gouaux, Eric

    2012-01-04

    LeuT is a bacterial homologue of the neurotransmitter:sodium symporter (NSS) family and, being the only NSS member to have been structurally characterized by X-ray crystallography, is a model protein for studying transporter structure and mechanism. Transport activity in LeuT was hypothesized to require structural transitions between open-to-out and occluded conformations dependent upon protein:ligand binding complementarity. Here, using crystallographic and functional analysis, we show that binding site modification produces changes in both structure and activity that are consistent with complementarity-dependent structural transitions to the occluded state. The mutation I359Q converts the activity of tryptophan from inhibitor to transportable substrate. This mutation changes the local environment of the binding site, inducing the bound tryptophan to adopt a different conformer than in the wild-type complex. Instead of trapping the transporter open, tryptophan binding now allows the formation of an occluded state. Thus, transport activity is correlated to the ability of the ligand to promote the structural transition to the occluded state, a step in the transport cycle that is dependent on protein:ligand complementarity in the central binding site.

  7. Separation of tryptophan enantiomers by ligand-exchange chromatography with novel chiral ionic liquids ligand.

    Science.gov (United States)

    Qing, Haiqun; Jiang, Xinyu; Yu, Jingang

    2014-03-01

    Chiral ionic liquids (CILs) with amino acids as cations have been applied as novel chiral ligands coordinated with Cu(2+) to separate tryptophan enantiomers in ligand exchange chromatography. Four kinds of amino acid ionic liquids, including [L-Pro][CF3COO], [L-Pro][NO3], [L-Pro]2[SO4], and [L-Phe][CF3COO] were successfully synthesized and used for separation of tryptophan enantiomers. To optimize the separation conditions, [L-Pro][CF3COO] was selected as the model ligand. Some factors influencing the efficiency of chiral separation, such as copper ion concentration, CILs concentration, methanol ratio (methanol/H2O, v/v), and pH, were investigated. The obtained optimal separation conditions were as follows: 8.0 mmol/L Cu(OAc)2, 4.0 mmol/L [L-Pro][CF3COO], and 20% (v/v) methanol at pH 3.6. Under the optimum conditions, acceptable enantioseparation of tryptophan enantiomers could be observed with a resolution of 1.89. The results demonstrate the good applicability of CILs with amino acids as cations for chiral separation. Furthermore, a comparative study was also conducted for exploring the mechanism of the CILs as new ligands in ligand exchange chromatography. © 2014 Wiley Periodicals, Inc.

  8. Characterization of the putative tryptophan synthase β-subunit from Mycobacterium tuberculosis

    Institute of Scientific and Technical Information of China (English)

    Hongbo Shen; Yanping Yang; Feifei Wang; Ying Zhang; Naihao Ye; Shengfeng Xu; Honghai Wang

    2009-01-01

    The increasing emergence of drug-resistant tuberculosis (TB)poses a serious threat to the control of this disease.It is in urgent need to develop new TB drugs.Tryptophan biosynthetic pathway plays an important role in the growth and replication of Mycobacterium tuberculosis(Mtb).The β-subunit of tryptophan synthase(TrpB)catalyzes the last step of the tryptophan biosynthetic pathway,and it might be a potential target for TB drug design.In this study,we overexpressed,purified,and characterized the putative TrpB-encoding gene Rv1612 in Mtb H37Rv.Results showed that Mtb His-TrpB optimal enzymatic activity is at pH 7.8 with 0.15 M Na+or 0.18 M Mg2+ at 37℃.Structure analysis indicated that Mtb TrpB exhibited a typical β/α barrel structure.The amino acid residues believed to interact with the enzyme cofactor pyridoxal-5'-phosphate were predicted by homology modeling and structure alignment.The role of these residues in catalytic activity of the Mtb His-TrpB was confirmed by site-directed mutagenesis.These results provided reassuring structural information for drug design based on TrpB.

  9. Stable isotope labeling, in vivo, of D- and L-tryptophan pools in lemna gibba and the low incorporation of label into indole-3-acetic acid

    Energy Technology Data Exchange (ETDEWEB)

    Baldi, B.G. (Dept. of Agriculture, Beltsville, MD (USA)); Maher, B.R. (Univ. of Maryland, College Park (USA)); Slovin, J.P.; Cohen, J.D. (Dept. of Agriculture, Beltsville, MD (USA) Univ. of Maryland, College Park (USA))

    1991-04-01

    The authors present evidence that the role of tryptophan and other potential intermediates in the pathways that could lead to indole derivatives needs to be reexamined. Two lines of Lemna gibba were tested for uptake of ({sup 15}N-indole)-labeled tryptophan isomers and incorporation of that label into free indole-3-acetic acid (IAA). Both lines required levels of L-({sup 15}N)tryptophan 2 to 3 orders of magnitude over endogenous levels in order to obtain measurable incorporation of label into IAA. Labeled L-tryptophan was extractable from plant tissue after feeding and showed no measurable isomerization into D-tryptophan. D-({sup 15}N)trytophan supplied to Lemna at rates of approximately 400 times excess of endogenous D-tryptophan levels (to yield an isotopic enrichment equal to that which allowed detection of the incorporation of L-tryptophan into IAA), did not result in measurable incorporation of label into free IAA. These results demonstrate that L-tryptophan is a more direct precursor to IAA than the D isomer and suggest (a) that the availability of tryptophan in vivo is not a limiting factor in the biosynthesis of IAA, thus implying that other regulatory mechanisms are in operation and (b) that L-tryptophan also may not be a primary precursor to IAA in plants.

  10. Depletion of Cultivatable Gut Microbiota by Broad-Spectrum Antibiotic Pretreatment Worsens Outcome After Murine Stroke

    Science.gov (United States)

    Winek, Katarzyna; Engel, Odilo; Koduah, Priscilla; Heimesaat, Markus M.; Fischer, André; Bereswill, Stefan; Dames, Claudia; Kershaw, Olivia; Gruber, Achim D.; Curato, Caterina; Oyama, Naoki; Meisel, Christian; Meisel, Andreas

    2016-01-01

    Background and Purpose— Antibiotics disturbing microbiota are often used in treatment of poststroke infections. A bidirectional brain–gut microbiota axis was recently suggested as a modulator of nervous system diseases. We hypothesized that gut microbiota may be an important player in the course of stroke. Methods— We investigated the outcome of focal cerebral ischemia in C57BL/6J mice after an 8-week decontamination with quintuple broad-spectrum antibiotic cocktail. These microbiota-depleted animals were subjected to 60 minutes middle cerebral artery occlusion or sham operation. Infarct volume was measured using magnetic resonance imaging, and mice were monitored clinically throughout the whole experiment. At the end point, tissues were preserved for further analysis, comprising histology and immunologic investigations using flow cytometry. Results— We found significantly decreased survival in the middle cerebral artery occlusion microbiota-depleted mice when the antibiotic cocktail was stopped 3 days before surgery (compared with middle cerebral artery occlusion specific pathogen-free and sham-operated microbiota-depleted mice). Moreover, all microbiota-depleted animals in which antibiotic treatment was terminated developed severe acute colitis. This phenotype was rescued by continuous antibiotic treatment or colonization with specific pathogen-free microbiota before surgery. Further, infarct volumes on day one did not differ between any of the experimental groups. Conclusions— Conventional microbiota ensures intestinal protection in the mouse model of experimental stroke and prevents development of acute and severe colitis in microbiota-depleted mice not given antibiotic protection after cerebral ischemia. Our experiments raise the clinically important question as to whether microbial colonization or specific microbiota are crucial for stroke outcome. PMID:27056982

  11. Acute Bronchitis

    Science.gov (United States)

    ... Smoking also slows down the healing process. Acute bronchitis treatment Most cases of acute bronchitis can be treated at home.Drink fluids, but ... bronchial tree. Your doctor will decide if this treatment is right for you. Living with acute bronchitis Most cases of acute bronchitis go away on ...

  12. Neutron-activation revisited: the depletion and depletion-activation models.

    Science.gov (United States)

    Abdel-Rahman, Wamied; Podgorsak, Ervin B

    2005-02-01

    The growth of a radioactive daughter in neutron activation is commonly described with the saturation model that ignores the consumption of parent nuclei during the radio-activation process. This approach is not valid when radioactive sources with high specific activities are produced or when the particle fluence rates used are very high. Assuming a constant neutron fluence rate throughout the activation target, a neutron-activation model that accounts for the depletion in parent nuclei is introduced. This depletion model is governed by relationships similar to those describing the parent-daughter-granddaughter decay series, and, in contrast to the saturation model, correctly predicts the practical limit of the daughter specific activity, irrespective of the particle fluence rate. Also introduced is a neutron-activation model that in addition to parent depletion accounts for the neutron activation of daughter nuclei in situations where the cross section for this effect is high. The model is referred to as the depletion-activation model and it provides the most realistic description for the daughter specific activity in neutron activation. Three specific neutron activation examples of interest to medical physics are presented: activation of molybdenum-98 into molybdenum-99 described by the saturation model; activation of cobalt-59 into cobalt-60 described by the depletion model; and activation of iridium-191 into iridium-192 described by the depletion-activation model.

  13. C ring may be dispensable for β-carboline: Design, synthesis, and bioactivities evaluation of tryptophan analog derivatives based on the biosynthesis of β-carboline alkaloids.

    Science.gov (United States)

    Huang, Yuanqiong; Liu, Yongxian; Liu, Yuxiu; Song, Hongjian; Wang, Qingmin

    2016-02-01

    According to our previous work and the latest research on the biosynthesis of β-carboline, and using the reverse thinking strategy, tryptophan, the biosynthesis precursor of β-carboline alkaloids, and their derivatives were synthesized, and their biological activities and structure-activity relationships were studied. This bioassay showed that these compounds exhibited good inhibitory activities against tobacco mosaic virus (TMV); especially (S)-2-amino-3-(1H-indol-3-yl)-N-octylpropanamide (4) (63.3±2.1%, 67.1±1.9%, 68.7±1.3%, and 64.5±3.1%, 500μg/mL) exhibited the best antiviral activity both in vitro and in vivo. Compound 4 was chosen for the field trials and the acute oral toxicity test, the results showed that the compound exhibited good anti-TMV activity in the field and low acute oral toxicity. We also found that these compounds showed antifungal activities and insecticidal activities.

  14. Replacements For Ozone-Depleting Foaming Agents

    Science.gov (United States)

    Blevins, Elana; Sharpe, Jon B.

    1995-01-01

    Fluorinated ethers used in place of chlorofluorocarbons and hydrochlorofluorocarbons. Replacement necessary because CFC's and HCFC's found to contribute to depletion of ozone from upper atmosphere, and manufacture and use of them by law phased out in near future. Two fluorinated ethers do not have ozone-depletion potential and used in existing foam-producing equipment, designed to handle liquid blowing agents soluble in chemical ingredients that mixed to make foam. Any polyurethane-based foams and several cellular plastics blown with these fluorinated ethers used in processes as diverse as small batch pours, large sprays, or double-band lamination to make insulation for private homes, commercial buildings, shipping containers, and storage tanks. Fluorinated ethers proved useful as replacements for CFC refrigerants and solvents.

  15. Assessment of Preferred Depleted Uranium Disposal Forms

    Energy Technology Data Exchange (ETDEWEB)

    Croff, A.G.; Hightower, J.R.; Lee, D.W.; Michaels, G.E.; Ranek, N.L.; Trabalka, J.R.

    2000-06-01

    The Department of Energy (DOE) is in the process of converting about 700,000 metric tons (MT) of depleted uranium hexafluoride (DUF6) containing 475,000 MT of depleted uranium (DU) to a stable form more suitable for long-term storage or disposal. Potential conversion forms include the tetrafluoride (DUF4), oxide (DUO2 or DU3O8), or metal. If worthwhile beneficial uses cannot be found for the DU product form, it will be sent to an appropriate site for disposal. The DU products are considered to be low-level waste (LLW) under both DOE orders and Nuclear Regulatory Commission (NRC) regulations. The objective of this study was to assess the acceptability of the potential DU conversion products at potential LLW disposal sites to provide a basis for DOE decisions on the preferred DU product form and a path forward that will ensure reliable and efficient disposal.

  16. Depletion of putative chemosensitive respiratory neurons in the ventral medullary surface in multiple system atrophy.

    Science.gov (United States)

    Benarroch, Eduardo E; Schmeichel, Ann M; Low, Phillip A; Parisi, Joseph E

    2007-02-01

    Multiple system atrophy (MSA) is a disorder that may manifest with reduced respiratory chemosensitivity and central sleep apnoea. Chemosensitive glutamatergic and serotonergic neurons located just beneath the ventral medullary surface, corresponding to the human arcuate nucleus (ArcN), have recently been implicated in control of automatic breathing in response to hypercapnia and hypoxia. We sought to determine whether these neurons were affected in MSA. Medullae were obtained at post-mortem from 11 patients (8 men, 3 women, age 64 +/- 3 years) with neuropathologically confirmed MSA and 11 control subjects (6 men and 5 women, age 66 +/- 4 years). Fifty micrometre sections obtained throughout the medulla were processed for vesicular glutamate transporter-2 (VGLUT-2), tryptophan-hydroxylase (TrOH), glial fibrillary acid protein (GFAP) and alpha-synuclein immunoreactivity. Cell counts, GFAP immunoreactivity and presence of glial cytoplasmic inclusions (GCIs) were assessed in the ArcN. In MSA, compared with controls, there was a marked depletion of ArcN neurons immunoreactive for either VGLUT-2 (74 +/- 21 versus 342 +/- 84 cells/section, P section, P medullary surface in all cases. Our results indicate that there is severe loss of putative chemosensitive glutamatergic and serotonergic neurons as well as marked astrocytic gliosis in the ventral medullary surface in MSA. This may provide a possible morphological basis for impaired respiratory chemosensitivity and central sleep apnoea in this disorder.

  17. Amino acid challenge and depletion techniques in human functional neuroimaging studies: an overview.

    Science.gov (United States)

    Biskup, C S; Gaber, T; Helmbold, K; Bubenzer-Busch, S; Zepf, F D

    2015-04-01

    Imbalances of neurotransmitter systems, particularly serotonin (5-HT) and dopamine (DA), are known to play an essential role in many neuropsychiatric disorders. The transient manipulation of such systems through the alteration of their amino acid precursors is a well-known research tool. Among these methods are alterations of tryptophan, the essential amino acid (AA) precursor of 5-HT, as well as manipulations of tyrosine and phenylalanine, the AA precursors of DA, which can be metabolized into norepinephrine and subsequently into epinephrine. These systems can be loaded by applying a large dose of these AAs or depleted by applying an amino acid mixture lacking the respective AAs serving as precursors. Functional neuroimaging has given insights into differential brain activation patterns and functions depending on the tasks performed, pharmacological treatments or specific disorders. Such research has shed light on the function of many brain areas as well as their interactions. The combination of AA challenge approaches with neuroimaging techniques has been subject of numerous studies. Overall, the studies conducted in this particular field of research have shown that AA challenge techniques are valid and effective research tools that allow the investigation of serotonergic and dopaminergic systems without causing serious side effects or long-term damage to the subjects. In this review, we will present an overview of the results obtained so far and discuss the implications of these findings as well as open questions that remain to be answered.

  18. Ecological and corrosion behavior of depleted uranium

    Directory of Open Access Journals (Sweden)

    Stojanović Mirjana D.

    2015-01-01

    Full Text Available Environmental pollution with radionuclides, particularly uranium and its decay products is a serious global problem. The current scientific studies estimated that the contamination originating from TENORM, caused by nuclear and non-nuclear technologies, has significantly increased natural level of radioactivity in the last thirty years. During the last decades all the more were talking about the "new pollutant" - depleted uranium (DU, which has been used in anti-tank penetrators because of its high density, penetration and pyrophoric properties. It is estimated that during the Gulf War, the war in Bosnia and Yugoslavia and during the invasion of Iraq, 1.4 million missiles with depleted uranium was fired. During the NATO aggression against the ex Yugoslavia in 1999., 112 locations in Kosovo and Metohija, 12 locations in southern Serbia and two locations in Montenegro were bombed. On this occasion, approximately 10 tons of depleted uranium were entered into the environment, mainly on land, where the degree of contamination ranged from 200 Bq / kg to 235 000 Bq/kg, which is up to 1000 times higher than the natural level. Fourteen years ago there was very little information about the behavior of ecological systems damaged by DU penetrators fired. Today, unfortunately, we are increasingly faced with the ―invisible threat" of depleted uranium, which has a strong radioactive and hemotoxic impact on human health. Present paper provides a detailed overview of the current understanding of corrosion and corrosion behavior of DU and environmental factors that control corrosion, together with indicators of environmental impact in order to highlight areas that need further attention in developing remediation programs.

  19. The ultimate disposition of depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    Lemons, T.R. [Uranium Enrichment Organization, Oak Ridge, TN (United States)

    1991-12-31

    Depleted uranium (DU) is produced as a by-product of the uranium enrichment process. Over 340,000 MTU of DU in the form of UF{sub 6} have been accumulated at the US government gaseous diffusion plants and the stockpile continues to grow. An overview of issues and objectives associated with the inventory management and the ultimate disposition of this material is presented.

  20. Effective Depletion Potential of Colloidal Spheres

    Institute of Scientific and Technical Information of China (English)

    LI Wei-Hua; MA Hong-Ru

    2004-01-01

    @@ A new semianalytical method, which is a combination of the density functional theory with Rosenfeld density functional and the Ornstein-Zernike equation, is proposed for the calculation of the effective depletion potentials between a pair of big spheres immersed in a small hard sphere fluid. The calculated results are almost identical to the integral equation method with the Percus-Yevick approximation, and are also in agreement well with the Monte Carlo simulation results.

  1. T4 phage lysozyme: a protein designed for understanding tryptophan photophysics

    Science.gov (United States)

    Hudson, Bruce S.; Harris, Dan

    1990-05-01

    Bacteriophage T4 lysozyme in its wild type form contains three tryptophan residues (at sequence postions 126, 138 and 158). These three residues are in rather different environments in the protein: 126 and 158 are near the protein surface while residue 138 is more buried. T4 lysozyme has been genetically engineered to prepare all possible variants in which one or more of the tryptophan residues have been replaced by tyrosine. The available data supports the hypothesis that this substitution has, at most, a very minor effect on the structure of the protein. The three species with single tryptophan residues have been investigated in detail. The surface location of residue 126 compared to the buried location of residue 138 is reflected in the difference in collisional quenching observed with added potassium iodide. It is found that the spectral and radiative properties of the three proteins are very similar but that their radiationless decay properties are quite distinct. This is apparently due to short-range collisional quenching by neighboring side chains. Comparison with solution quenching measurements permits the identification of the specific quenching groups involved for each tryptophan residue and provides a semi-quantitative rationale for the radiationless decay rate. This collisional quenching interpretation is supported by mutational effects on fluorescence quantum yield. This simple picture of the behavior of these single-tryptophan proteins is clearly revealed in this particular case because of the unambiguous choice of collisional quenching groups. The time dependence of the fluorescence decay of each of these single-tryptophan proteins is quite complex. Several methods of analysis are presented and discussed in terms of their underlying physical basis. Internal collisional quenching, as suggested from the comparative studies, is expected to lead to non-exponential behavior. This is consistent with the observed time dependence. Analysis of the temporal

  2. Barium depletion in hollow cathode emitters

    Energy Technology Data Exchange (ETDEWEB)

    Polk, James E., E-mail: james.e.polk@jpl.nasa.gov; Mikellides, Ioannis G.; Katz, Ira [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, California 91109 (United States); Capece, Angela M. [Graduate Aerospace Laboratories, California Institute of Technology, Pasadena, California 91125 (United States)

    2016-01-14

    Dispenser hollow cathodes rely on a consumable supply of Ba released by BaO-CaO-Al{sub 2}O{sub 3} source material in the pores of a tungsten matrix to maintain a low work function surface. The examination of cathode emitters from long duration tests shows deposits of tungsten at the downstream end that appear to block the flow of Ba from the interior. In addition, a numerical model of Ba transport in the cathode plasma indicates that the Ba partial pressure in the insert may exceed the equilibrium vapor pressure of the dominant Ba-producing reaction, and it was postulated previously that this would suppress Ba loss in the upstream part of the emitter. New measurements of the Ba depletion depth from a cathode insert operated for 8200 h reveal that Ba loss is confined to a narrow region near the downstream end, confirming this hypothesis. The Ba transport model was modified to predict the depletion depth with time. A comparison of the calculated and measured depletion depths gives excellent qualitative agreement, and quantitative agreement was obtained assuming an insert temperature 70 °C lower than measured beginning-of-life values.

  3. Mitochondrial DNA depletion analysis by pseudogene ratioing.

    Science.gov (United States)

    Swerdlow, Russell H; Redpath, Gerard T; Binder, Daniel R; Davis, John N; VandenBerg, Scott R

    2006-01-30

    The mitochondrial DNA (mtDNA) depletion status of rho(0) cell lines is typically assessed by hybridization or polymerase chain reaction (PCR) experiments, in which the failure to hybridize mtDNA or amplify mtDNA using mtDNA-directed primers suggests thorough mitochondrial genome removal. Here, we report the use of an mtDNA pseudogene ratioing technique for the additional confirmation of rho0 status. Total genomic DNA from a U251 human glioma cell line treated with ethidium bromide was amplified using primers designed to anneal either mtDNA or a previously described nuclear DNA-embedded mtDNA pseudogene (mtDNApsi). The resultant PCR product was used to generate plasmid clones. Sixty-two plasmid clones were genotyped, and all arose from mtDNApsi template. These data allowed us to determine with 95% confidence that the resultant mtDNA-depleted cell line contains less than one copy of mtDNA per 10 cells. Unlike previous hybridization or PCR-based analyses of mtDNA depletion, this mtDNApsi ratioing technique does not rely on interpretation of a negative result, and may prove useful as an adjunct for the determination of rho0 status or mtDNA copy number.

  4. 5-Hydroxy-tryptophan for the treatment of L-DOPA-induced dyskinesia in the rat Parkinson's disease model.

    Science.gov (United States)

    Tronci, Elisabetta; Lisci, Carlo; Stancampiano, Roberto; Fidalgo, Camino; Collu, Maria; Devoto, Paola; Carta, Manolo

    2013-12-01

    The serotonin system has recently emerged as an important player in the appearance of L-DOPA-induced dyskinesia (LID) in experimental models of Parkinson's disease, as it provides an unregulated source of L-DOPA-derived dopamine release in the dopamine-depleted striatum. Accordingly, toxin lesion or pharmacological silencing of serotonin neurons suppressed LID in the rat and monkey models of Parkinson's disease. However, 5-HT1 receptor agonists were also found to partially reduce the therapeutic effect of L-DOPA. In this study, we evaluated whether enhancement of the serotonin tone induced by the administration of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) could affect induction and expression of LID, as well as the therapeutic effect of L-DOPA, in 6-OHDA-lesioned rats. Drug naïve and L-DOPA-primed 6-OHDA-lesioned rats were chronically treated with a daily injection of L-DOPA (6 mg/kg plus benserazide, s.c.) alone, or in combination with 5-HTP (24-48 mg/kg, i.p.). The abnormal involuntary movements (AIMs) test, as well as the stepping and the motor activity tests, were performed during the chronic treatments. Results showed that 5-HTP reduced the appearance of LID of about 50% at both tested doses. A partial reduction of the therapeutic effect of L-DOPA was seen with the higher but not with the lower dose of 5-HTP. 5-HTP 24 mg/kg was also able to reduce the expression of dyskinesia in L-DOPA-primed dyskinetic rats, to a similar extent than in L-DOPA-primed rats. Importantly, the antidyskinetic effect of 5-HTP 24 mg/kg does not appear to be due to a competition with L-DOPA for crossing the blood-brain barrier; in fact, similar L-DOPA striatal levels were found in L-DOPA only and L-DOPA plus 5-HTP 24 mg/kg treated animals. These data further confirm the involvement of the serotonin system in the appearance of LID, and suggest that 5-HTP may be useful to counteract the appearance of dyskinesia in Parkinson's disease patients.

  5. Single turnover kinetics of tryptophan hydroxylase: evidence for a new intermediate in the reaction of the aromatic amino acid hydroxylases.

    Science.gov (United States)

    Pavon, Jorge Alex; Eser, Bekir; Huynh, Michaela T; Fitzpatrick, Paul F

    2010-09-07

    Tryptophan hydroxylase (TrpH) uses a non-heme mononuclear iron center to catalyze the tetrahydropterin-dependent hydroxylation of tryptophan to 5-hydroxytryptophan. The reactions of the TrpH.Fe(II), TrpH.Fe(II).tryptophan, TrpH.Fe(II).6MePH(4).tryptophan, and TrpH.Fe(II).6MePH(4).phenylalanine complexes with O(2) were monitored by stopped-flow absorbance spectroscopy and rapid quench methods. The second-order rate constant for the oxidation of TrpH.Fe(II) has a value of 104 M(-1) s(-1) irrespective of the presence of tryptophan. Stopped-flow absorbance analyses of the reaction of the TrpH.Fe(II).6MePH(4).tryptophan complex with oxygen are consistent with the initial step being reversible binding of oxygen, followed by the formation with a rate constant of 65 s(-1) of an intermediate I that has maximal absorbance at 420 nm. The rate constant for decay of I, 4.4 s(-1), matches that for formation of the 4a-hydroxypterin product monitored at 248 nm. Chemical-quench analyses show that 5-hydroxytryptophan forms with a rate constant of 1.3 s(-1) and that overall turnover is limited by a subsequent slow step, presumably product release, with a rate constant of 0.2 s(-1). All of the data with tryptophan as substrate can be described by a five-step mechanism. In contrast, with phenylalanine as substrate, the reaction can be described by three steps: a second-order reaction with oxygen to form I, decay of I as tyrosine forms, and slow product release.

  6. Regular moderate or intense exercise prevents depression-like behavior without change of hippocampal tryptophan content in chronically tryptophan-deficient and stressed mice.

    Directory of Open Access Journals (Sweden)

    Hosung Lee

    Full Text Available Regular exercise has an antidepressant effect in human subjects. Studies using animals have suggested that the antidepressant effect of exercise is attributable to an increase of brain 5-hydroxytryptamine (5-HT; however, the precise mechanism underlying the antidepressant action via exercise is unclear. In contrast, the effect of 5-HT on antidepressant activity has not been clarified, in part because the therapeutic response to antidepressant drugs has a time lag in spite of the rapid increase of brain 5-HT upon administration of these drugs. This study was designed to investigate the contribution of brain 5-HT to the antidepressant effect of exercise. Mice were fed a tryptophan-deficient diet and stressed using chronic unpredictable stress (CUS for 4 weeks with or without the performance of either moderate or intense exercise on a treadmill 3 days per week. The findings demonstrated that the onset of depression-like behavior is attributable not to chronic reduction of 5-HT but to chronic stress. Regular exercise, whether moderate or intense, prevents depression-like behavior with an improvement of adult hippocampal cell proliferation and survival and without the recovery of 5-HT. Concomitantly, the mice that exercised showed increased hippocampal noradrenaline. Regular exercise prevents the impairment of not long-term memory but short-term memory in a 5-HT-reduced state. Together, these findings suggest that: (1 chronic reduction of brain 5-HT may not contribute to the onset of depression-like behavior; (2 regular exercise, whether moderate or intense, prevents the onset of chronic stress-induced depression-like behavior independent of brain 5-HT and dependent on brain adrenaline; and (3 regular exercise prevents chronic tryptophan reduction-induced impairment of not long-term but short-term memory.

  7. Lithium Depletion in Fully Convective Pre-Main Sequence Stars

    CERN Document Server

    Bildsten, L; Matzner, C D; Ushomirsky, G; Bildsten, Lars; Brown, Edward F.; Matzner, Christopher D.; Ushomirsky, Greg

    1996-01-01

    We present an analytic calculation of the thermonuclear depletion of lithium in contracting, fully convective, pre-main sequence stars of mass M 0.08 M_sun) and for constraining the masses of lithium depleted stars.

  8. (JASR) Vol. 12, No. 2, 2012 DEPLETING FOREST RESOURCES OF ...

    African Journals Online (AJOL)

    HP

    undisturbed lands leading to depletion of the forest cover and increase on the sand dunes .... depletion of the ozone layer leading to a rise in global temperature. ... Nigeria has good correlation with greenhouse gas emission which can cause ...

  9. Depletions at Browns Park National Wildlife Refuge [Draft

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Estimated depletion associated with the operation of Spitzie Marsh in Browns Park National Wildlife Refuge. Attached are the methods used to estimate depletion....

  10. Self-regulatory depletion increases emotional reactivity in the amygdala

    National Research Council Canada - National Science Library

    Wagner, Dylan D; Heatherton, Todd F

    2013-01-01

    ... attention control task that required effortful inhibition (depletion group) or not (control group). Compared to the control group, depleted participants showed increased activity in the left amygdala to negative but not to positive or neutral scenes...

  11. Depletion of alveolar macrophages in CD11c diphtheria toxin receptor mice produces an inflammatory response

    Science.gov (United States)

    Roberts, Lydia M; Ledvina, Hannah E; Tuladhar, Shraddha; Rana, Deepa; Steele, Shaun P; Sempowski, Gregory D; Frelinger, Jeffrey A

    2015-01-01

    Alveolar macrophages play a critical role in initiating the immune response to inhaled pathogens and have been shown to be the first cell type infected following intranasal inoculation with several pathogens, including Francisella tularensis. In an attempt to further dissect the role of alveolar macrophages in the immune response to Francisella, we selectively depleted alveolar macrophages using CD11c.DOG mice. CD11c.DOG mice express the diphtheria toxin receptor (DTR) under control of the full CD11c promoter. Because mice do not express DTR, tissue restricted expression of the primate DTR followed by treatment with diphtheria toxin (DT) has been widely used as a tool in immunology to examine the effect of acute depletion of a specific immune subset following normal development. We successfully depleted alveolar macrophages via intranasal administration of DT. However, alveolar macrophage depletion was accompanied by many other changes to the cellular composition and cytokine/chemokine milieu in the lung that potentially impact innate and adaptive immune responses. Importantly, we observed a transient influx of neutrophils in the lung and spleen. Our experience serves as a cautionary note to other researchers using DTR mice given the complex changes that occur following DT treatment that must be taken into account when analyzing data. PMID:26029367

  12. Children's Models of the Ozone Layer and Ozone Depletion.

    Science.gov (United States)

    Christidou, Vasilia; Koulaidis, Vasilis

    1996-01-01

    The views of 40 primary students on ozone and its depletion were recorded through individual, semi-structured interviews. The data analysis resulted in the formation of a limited number of models concerning the distribution and role of ozone in the atmosphere, the depletion process, and the consequences of ozone depletion. Identifies five target…

  13. Children's Models of the Ozone Layer and Ozone Depletion.

    Science.gov (United States)

    Christidou, Vasilia; Koulaidis, Vasilis

    1996-01-01

    The views of 40 primary students on ozone and its depletion were recorded through individual, semi-structured interviews. The data analysis resulted in the formation of a limited number of models concerning the distribution and role of ozone in the atmosphere, the depletion process, and the consequences of ozone depletion. Identifies five target…

  14. 26 CFR 1.642(e)-1 - Depreciation and depletion.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Depreciation and depletion. 1.642(e)-1 Section 1... (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.642(e)-1 Depreciation and depletion. An estate or trust is allowed the deductions for depreciation and depletion, but only to the extent...

  15. A modern depleted uranium manufacturing facility

    Energy Technology Data Exchange (ETDEWEB)

    Zagula, T.A.

    1995-07-01

    The Specific Manufacturing Capabilities (SMC) Project located at the Idaho National Engineering Laboratory (INEL) and operated by Lockheed Martin Idaho Technologies Co. (LMIT) for the Department of Energy (DOE) manufactures depleted uranium for use in the U.S. Army MIA2 Abrams Heavy Tank Armor Program. Since 1986, SMC has fabricated more than 12 million pounds of depleted uranium (DU) products in a multitude of shapes and sizes with varying metallurgical properties while maintaining security, environmental, health and safety requirements. During initial facility design in the early 1980`s, emphasis on employee safety, radiation control and environmental consciousness was gaining momentum throughout the DOE complex. This fact coupled with security and production requirements forced design efforts to focus on incorporating automation, local containment and computerized material accountability at all work stations. The result was a fully automated production facility engineered to manufacture DU armor packages with virtually no human contact while maintaining security, traceability and quality requirements. This hands off approach to handling depleted uranium resulted in minimal radiation exposures and employee injuries. Construction of the manufacturing facility was complete in early 1986 with the first armor package certified in October 1986. Rolling facility construction was completed in 1987 with the first certified plate produced in the fall of 1988. Since 1988 the rolling and manufacturing facilities have delivered more than 2600 armor packages on schedule with 100% final product quality acceptance. During this period there was an annual average of only 2.2 lost time incidents and a single individual maximum radiation exposure of 150 mrem. SMC is an example of designing and operating a facility that meets regulatory requirements with respect to national security, radiation control and personnel safety while achieving production schedules and product quality.

  16. Effects of tryptophan derivatives and β-carboline alkaloids on radiation- and peroxide-induced transformations of ethanol

    Science.gov (United States)

    Sverdlov, R. L.; Brinkevich, S. D.; Shadyro, O. I.

    2014-05-01

    The subject of this study was investigation of interactions of tryptophan and its derivatives, including structurally related β-carboline alkaloids with oxygen- and carbon-centered radicals being formed during radiation- and peroxide-induced transformations of ethanol. It was shown that the above named compounds suppressed recombination and disproportionation reactions of α-hydroxyethyl radicals. The inhibitory effects of tryptophan, 5-hydroxytryptophan and serotonin were mainly realized by means of reduction and addition reactions, while those of β-carboline alkaloids - harmine, harmane and harmaline - were due to oxidation reactions. Melatonin displayed low reactivity towards α-hydroxyethyl radicals. Tryptophan derivatives and β-carboline alkaloids were found to inhibit radiation-induced oxidation of ethanol while being virtually not used up. The low transformation yields of tryptophan, 5-hydroxytryptophan and serotonin, as well as β-carboline alkaloids, indicate their capability of regeneration, which could occur on interaction of tryptophan with О-2 and НО2, or on oxidation of α-hydroxyethyl radicals by β-carboline alkaloids.

  17. Employing the fluorescence anisotropy and quenching kinetics of tryptophan to hunt for residual structures in denatured proteins

    Indian Academy of Sciences (India)

    Satish Kumar; Rajaram Swaminathan

    2007-03-01

    Residual structures in denatured proteins have acquired importance in recent years owing to their role as protein-folding initiation sites. Locating these structures in proteins has proved quite formidable, requiring techniques like NMR. Here in this report, we take advantage of the ubiquitous presence of tryptophan residues in residual structures to hunt for their presence using steady-state fluorescence spectroscopy. The surface accessibility and rotational dynamics of tryptophan in putative residual structures among ten different proteins, namely glucagon, melittin, subtilisin carlsberg, myelin basic protein, ribonuclease T1, human serum albumin, barstar mutant, bovine serum albumin, lysozyme and Trp-Met-Asp-Phe-NH2 peptide, was studied using steady state fluorescence quenching and anisotropy, respectively. Five proteins, namely ribonuclease T1, bovine serum albumin, melittin, barstar and hen egg white lysozyme appear likely to possess tryptophan(s) in hydrophobic clusters based on their reduced bimolecular quenching rates and higher steady-state anisotropy in proportion to their chain length. We also show that the fluorescence emission maximum of tryptophan is insensitive to the presence of residual structures.

  18. An Unusual Case of Colon Perforation Complicating Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Anthony A. Aghenta

    2009-08-01

    Full Text Available Colonic complications of severe acute pancreatitis occur rarely. Although there have been several theories on how pancreatic pseudocysts rupture into the colon, the exact pathogenesis remains unknown. We report an unusual case of pseudocysts complicating severe acute pancreatitis presenting with colonic perforation in a 71-year-old man with a history of chronic mesenteric ischemia. Pressure effects from a giant pseudocyst and intravascular volume depletion with acute insult on chronic mesenteric ischemia are highlighted as possible etiologic factors.

  19. Capstone Depleted Uranium Aerosols: Generation and Characterization

    Energy Technology Data Exchange (ETDEWEB)

    Parkhurst, MaryAnn; Szrom, Fran; Guilmette, Ray; Holmes, Tom; Cheng, Yung-Sung; Kenoyer, Judson L.; Collins, John W.; Sanderson, T. Ellory; Fliszar, Richard W.; Gold, Kenneth; Beckman, John C.; Long, Julie

    2004-10-19

    In a study designed to provide an improved scientific basis for assessing possible health effects from inhaling depleted uranium (DU) aerosols, a series of DU penetrators was fired at an Abrams tank and a Bradley fighting vehicle. A robust sampling system was designed to collect aerosols in this difficult environment and continuously monitor the sampler flow rates. Aerosols collected were analyzed for uranium concentration and particle size distribution as a function of time. They were also analyzed for uranium oxide phases, particle morphology, and dissolution in vitro. The resulting data provide input useful in human health risk assessments.

  20. Heatstroke Pathophysiology: The Energy Depletion Model

    Science.gov (United States)

    1989-06-12

    Pathophysiology: The Energy Depletion Model Roger W. Hubbard, Ph.D., Director Heat Research Division U. S. Army Research Institute of Environmental...Medicine Natick, MA 01760-5007 USA Send correspondence to: Roger W. Hubbard, Ph.D. Director Heat Research Division USARIEM Kansas St Natick, MA 01760...The NaK-Pump. Part B: Celular Asoects J.C. Skou, J.G. Normy, A.B. Maunsback, and M. Esmann (Eds) New York: Alan R. Uss, 1988, pp. 171-194. 54: Lewis

  1. Scientific assessment of ozone depletion: 1991

    Science.gov (United States)

    1991-01-01

    Over the past few years, there have been highly significant advances in the understanding of the impact of human activities on the Earth's stratospheric ozone layer and the influence of changes in chemical composition of the radiative balance of the climate system. Specifically, since the last international scientific review (1989), there have been five major advances: (1) global ozone decreases; (2) polar ozone; (3) ozone and industrial halocarbons; (4) ozone and climate relations; and (5) ozone depletion potentials (ODP's) and global warming potentials (GWP's). These topics and others are discussed.

  2. Correlation between cosmic rays and ozone depletion.

    Science.gov (United States)

    Lu, Q-B

    2009-03-20

    This Letter reports reliable satellite data in the period of 1980-2007 covering two full 11-yr cosmic ray (CR) cycles, clearly showing the correlation between CRs and ozone depletion, especially the polar ozone loss (hole) over Antarctica. The results provide strong evidence of the physical mechanism that the CR-driven electron-induced reaction of halogenated molecules plays the dominant role in causing the ozone hole. Moreover, this mechanism predicts one of the severest ozone losses in 2008-2009 and probably another large hole around 2019-2020, according to the 11-yr CR cycle.

  3. Optical assessment of phytoplankton nutrient depletion

    DEFF Research Database (Denmark)

    Heath, M.R.; Richardson, Katherine; Kiørboe, Thomas

    1990-01-01

    status (carbon/nitrogen ratio) and the absorption ratio that was independent of light and temperature climate. The absorption ratio for nutrient-replete cells was shown to vary between taxonomic groups. However, the inter-specific variation was less than the differences observed between nutrient......-replete and nutrient-depleted cells. The field data suggest that the absorption ratio may be a useful indicator of nutritional status of natural phytoplankton populations, and can be used to augment the interpretation of other data....

  4. The Time of Shipbuilding Order Depletion

    Institute of Scientific and Technical Information of China (English)

    Reporter Xing Dan

    2012-01-01

    In 2012, shipbuilding market is facing even colder weather. Depletion of orders, deals that can only ensure cost recovery ndustry which has already bankruptcy of ship yards one after another are also torturing this had many uncertainties. Some shipbuilding enterprises are trying to survive by cutting off parts of their business, some enterprises are leaving like the horses migrating on the African grassland, only those horses that have fights with crocodiles will reach the fertile land and enjoy the next warm spring. the business. It is survived the fierce

  5. RESERVOIR CAPACITY DEPLETION ON ACCOUNT OF SEDIMENTATION

    Institute of Scientific and Technical Information of China (English)

    Prabhata K.SWAMEE

    2001-01-01

    Capacity depletion is an important information required for planning of multipurpose reservoirs. It is a complex phenomenon involving diverse fields like surface hydrology, sediment transport, varied flow hydraulics and soil consolidation. Proper assessment of capacity reduction is helpful in ascertaining the life of the reservoir and the project benefits for cost/benefit analysis. In this study dimensionally consistent equations for deposition volume and the trap efficiency have been obtained. Methods of obtaining the parameters involved these equations have also been indicated. It was found that there is good agreement with the field data. It is hoped that the equations are useful to design engineer.

  6. Enhanced synthesis of 5-hydroxy-l-tryptophan through tetrahydropterin regeneration.

    Science.gov (United States)

    Hara, Ryotaro; Kino, Kuniki

    2013-12-09

    5-Hydroxy-l-tryptophan (5-HTP) is a naturally occurring aromatic amino acid present in the seeds of the African plant Griffonia simplicifolia. Although 5-HTP has therapeutic effects in various symptoms, efficient method of producing 5-HTP has not been established. In this study, we developed a novel cofactor regeneration process to achieve enhanced synthesis of 5-HTP by using modified l-phenylalanine 4-hydroxylase of Chromobacterium violaceum. For the synthesis of 5-HTP using Escherichia coli whole cell bioconversion, l-tryptophan and 5-HTP degradation by E. coli endogenous catabolic enzymes should be considered. The tryptophanase gene was disrupted using the λ red recombination system, since tryptophanase is postulated as an initial enzyme for the degradation of l-tryptophan and 5-HTP in E. coli. For regeneration of the cofactor pterin, we screened and investigated several key enzymes, including dihydropteridine reductase from E. coli, glucose dehydrogenase from Bacillus subtilis, and pterin-4α-carbinolamine dehydratase from Pseudomonas syringae. Genes encoding these three enzymes were overexpressed in an E. coli tryptophanase-deficient host, resulting in the synthesis of 0.74 mM 5-HTP in the presence of 0.1 mM pterin and the synthesis of 0.07 mM 5-HTP in the absence of regeneration of pterin. These results clearly indicated the successful regeneration of pterin. Following optimization of the reaction conditions, 2.5 mM 5-HTP was synthesized with cofactor regeneration, while 0.8 mM 5-HTP was recovered without cofactor regeneration under the same reaction conditions, suggesting that the principle described here provides a new method for cofactor regeneration.

  7. The Role of Amino Acid Permeases and Tryptophan Biosynthesis in Cryptococcus neoformans Survival.

    Directory of Open Access Journals (Sweden)

    João Daniel Santos Fernandes

    Full Text Available Metabolic diversity is an important factor during microbial adaptation to different environments. Among metabolic processes, amino acid biosynthesis has been demonstrated to be relevant for survival for many microbial pathogens, whereas the association between pathogenesis and amino acid uptake and recycling are less well-established. Cryptococcus neoformans is an opportunistic fungal pathogen with many habitats. As a result, it faces frequent metabolic shifts and challenges during its life cycle. Here we studied the C. neoformans tryptophan biosynthetic pathway and found that the pathway is essential. RNAi indicated that interruptions in the biosynthetic pathway render strains inviable. However, auxotroph complementation can be partially achieved by tryptophan uptake when a non preferred nitrogen source and lower growth temperature are applied, suggesting that amino acid permeases may be the target of nitrogen catabolism repression (NCR. We used bioinformatics to search for amino acid permeases in the C. neoformans and found eight potential global permeases (AAP1 to AAP8. The transcriptional profile of them revealed that they are subjected to regulatory mechanisms which are known to respond to nutritional status in other fungi, such as (i quality of nitrogen (Nitrogen Catabolism Repression, NCR and carbon sources (Carbon Catabolism Repression, CCR, (ii amino acid availability in the extracellular environment (SPS-sensing and (iii nutritional deprivation (Global Amino Acid Control, GAAC. This study shows that C. neoformans has fewer amino acid permeases than other model yeasts, and that these proteins may be subjected to complex regulatory mechanisms. Our data suggest that the C. neoformans tryptophan biosynthetic pathway is an excellent pharmacological target. Furthermore, inhibitors of this pathway cause Cryptococcus growth arrest in vitro.

  8. 'Melatonin isomer' in wine is not an isomer of the melatonin but tryptophan-ethylester.

    Science.gov (United States)

    Gardana, Claudio; Iriti, Marcello; Stuknytė, Milda; De Noni, Ivano; Simonetti, Paolo

    2014-11-01

    Melatonin is a neurohormone, chronobiotic, and antioxidant compound found in wine and deriving directly from grapes and/or synthesized by yeast during alcoholic fermentation. In addition, a melatonin isomer has been detected in different foods, wine among them. The special interest for melatonin isomer related to the fact that it was found in greater quantities than melatonin and probably shares some of its biological properties. Despite this, its chemical structure has not yet been defined; although some researchers hypothesize, it could be melatonin with the ethylacetamide group shifted into position N1. Thus, the aim of our study was to identify the structures of the melatonin isomer. For this purpose, melatonin and melatonin isomer in Syrah wine were separated chromatographically by a sub-2 μm particle column and detected by tandem mass spectrometry. The sample was then purified and concentrated by solid-phase extraction, hydrolyzed with alkali or esterase, and substrates and products quantified by UPLC-MS/MS. Moreover, melatonin, melatonin isomer, and their product ions were evaluated by high-resolution mass spectrometry. The amount of melatonin isomer and melatonin in the wine was 84 ± 4 and 3 ± 0 ng/mL, respectively. In the solutions, containing diluted alkali or esterase, melatonin isomer was hydrolyzed in about 8 min. Correspondingly, tryptophan was detected, and its amount increased and reached the maximum concentration in about 8 min. Melatonin concentration was not affected by diluted alkali or esterase. The fragmentation pattern of melatonin isomer was different from that of melatonin but comparable to that of tryptophan-ethylester. Finally, the so-called melatonin isomer identity was verified by cochromatography with authentic standard of tryptophan-ethylester. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Structural basis for the binding of tryptophan-based motifs by δ-COP.

    Science.gov (United States)

    Suckling, Richard J; Poon, Pak Phi; Travis, Sophie M; Majoul, Irina V; Hughson, Frederick M; Evans, Philip R; Duden, Rainer; Owen, David J

    2015-11-17

    Coatomer consists of two subcomplexes: the membrane-targeting, ADP ribosylation factor 1 (Arf1):GTP-binding βγδζ-COP F-subcomplex, which is related to the adaptor protein (AP) clathrin adaptors, and the cargo-binding αβ'ε-COP B-subcomplex. We present the structure of the C-terminal μ-homology domain of the yeast δ-COP subunit in complex with the WxW motif from its binding partner, the endoplasmic reticulum-localized Dsl1 tether. The motif binds at a site distinct from that used by the homologous AP μ subunits to bind YxxΦ cargo motifs with its two tryptophan residues sitting in compatible pockets. We also show that the Saccharomyces cerevisiae Arf GTPase-activating protein (GAP) homolog Gcs1p uses a related WxxF motif at its extreme C terminus to bind to δ-COP at the same site in the same way. Mutations designed on the basis of the structure in conjunction with isothermal titration calorimetry confirm the mode of binding and show that mammalian δ-COP binds related tryptophan-based motifs such as that from ArfGAP1 in a similar manner. We conclude that δ-COP subunits bind Wxn(1-6)[WF] motifs within unstructured regions of proteins that influence the lifecycle of COPI-coated vesicles; this conclusion is supported by the observation that, in the context of a sensitizing domain deletion in Dsl1p, mutating the tryptophan-based motif-binding site in yeast causes defects in both growth and carboxypeptidase Y trafficking/processing.

  10. Intraprotein electron transfer between tyrosine and tryptophan in DNA photolyase from Anacystis nidulans.

    Science.gov (United States)

    Aubert, C; Mathis, P; Eker, A P; Brettel, K

    1999-05-11

    Light-induced electron transfer reactions leading to the fully reduced, catalytically competent state of the flavin adenine dinucleotide (FAD) cofactor have been studied by flash absorption spectroscopy in DNA photolyase from Anacystis nidulans. The protein, overproduced in Escherichia coli, was devoid of the antenna cofactor, and the FAD chromophore was present in the semireduced form, FADH., which is inactive for DNA repair. We show that after selective excitation of FADH. by a 7-ns laser flash, fully reduced FAD (FADH-) is formed in less than 500 ns by electron abstraction from a tryptophan residue. Subsequently, a tyrosine residue is oxidized by the tryptophanyl radical with t(1)/(2) = 50 microseconds. The amino acid radicals were identified by their characteristic absorption spectra, with maxima at 520 nm for Trp. and 410 nm for TyrO. The newly discovered electron transfer between tyrosine and tryptophan occurred for approximately 40% of the tryptophanyl radicals, whereas 60% decayed by charge recombination with FADH- (t(1)/(2) = 1 ms). The tyrosyl radical can also recombine with FADH- but at a much slower rate (t(1)/(2) = 76 ms) than Trp. In the presence of an external electron donor, however, TyrO. is rereduced efficiently in a bimolecular reaction that leaves FAD in the fully reduced state FADH-. These results show that electron transfer from tyrosine to Trp. is an essential step in the process leading to the active form of photolyase. They provide direct evidence that electron transfer between tyrosine and tryptophan occurs in a native biological reaction.

  11. Extracellular N-acetylaspartate depletion in traumatic brain injury.

    Science.gov (United States)

    Belli, Antonio; Sen, Jon; Petzold, Axel; Russo, Salvatore; Kitchen, Neil; Smith, Martin; Tavazzi, Barbara; Vagnozzi, Roberto; Signoretti, Stefano; Amorini, Angela Maria; Bellia, Francesco; Lazzarino, Giuseppe

    2006-02-01

    N-Acetylaspartate (NAA) is almost exclusively localized in neurons in the adult brain and is present in high concentration in the CNS. It can be measured by proton magnetic resonance spectroscopy and is seen as a marker of neuronal damage and death. NMR spectroscopy and animal models have shown NAA depletion to occur in various types of chronic and acute brain injury. We investigated 19 patients with traumatic brain injury (TBI). Microdialysis was utilized to recover NAA, lactate, pyruvate, glycerol and glutamate, at 12-h intervals. These markers were correlated with survival and a 6-month Glasgow Outcome Score. Eleven patients died and eight survived. A linear mixed model analysis showed a significant effect of outcome and of the interaction between time of injury and outcome on NAA levels (p = 0.009 and p = 0.004, respectively). Overall, extracellular NAA was 34% lower in non-survivors. A significant non-recoverable fall was observed in this group from day 4 onwards, with a concomitant rise in lactate-pyruvate ratio and glycerol. These results suggest that mitochondrial dysfunction is a significant contributor to poor outcome following TBI and propose extracellular NAA as a potential marker for monitoring interventions aimed at preserving mitochondrial function.

  12. Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

    Science.gov (United States)

    Tolnai, Gergely L; Brand, Jonathan P

    2016-01-01

    Summary The selective functionalization of peptides containing only natural amino acids is important for the modification of biomolecules. In particular, the installation of an alkyne as a useful handle for bioconjugation is highly attractive, but the use of a carbon linker is usually required. Herein, we report the gold-catalyzed direct alkynylation of tryptophan in peptides using the hypervalent iodine reagent TIPS-EBX (1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one). The reaction proceeded in 50–78% yield under mild conditions and could be applied to peptides containing other nucleophilic and aromatic amino acids, such as serine, phenylalanine or tyrosine. PMID:27340466

  13. NO-tryptophan: a new small molecule located in the rat brain

    Directory of Open Access Journals (Sweden)

    A. Mangas

    2016-09-01

    Full Text Available A highly specific monoclonal antibody directed against nitric oxide-tryptophan (NO-W with good affinity (10-9 M and specificity was developed. In the rat brain, using an indirect immunoperoxidase technique, cell bodies containing NO-W were exclusively found in the intermediate and dorsal parts of the lateral septal nucleus. No immunoreactive fibres were found in the rat brain. This work reports the first visualization and the morphological characteristics of cell bodies containing NO-W in the mammalian brain. The restricted distribution of NO-W in the rat brain suggests that this molecule could be involved in specific physiological mechanisms. 

  14. NO-tryptophan: a new small molecule located in the rat brain.

    Science.gov (United States)

    Mangas, A; Yajeya, J; González, N; Duleu, S; Geffard, M; Coveñas, R

    2016-09-22

    A highly specific monoclonal antibody directed against nitric oxide-tryptophan (NO-W) with good affinity (10-9 M) and specificity was developed. In the rat brain, using an indirect immunoperoxidase technique, cell bodies containing NO-W were exclusively found in the intermediate and dorsal parts of the lateral septal nucleus. No immunoreactive fibres were found in the rat brain. This work reports the first visualization and the morphological characteristics of cell bodies containing NO-W in the mammalian brain. The restricted distribution of NO-W in the rat brain suggests that this molecule could be involved in specific physiological mechanisms.

  15. Adrenal hormones and increase of liver tyrosine aminotransferase and tryptophan pyrrolase activity after immobilization in rats.

    Science.gov (United States)

    Németh, S; Vigas, M

    1975-06-01

    In adrenomedullectomized rats the postimmobilization increase of liver tyrosine aminotransferase and tryptophan pyrrolase activity was similar as in intact animals, wherease in adrenalectomized rats this response was completely absent. In intact animals a positive correlation between the magnitude of the response of both enzymes and the duration of immobilization and/or the extent of plasma corticosterone increase was observedmit is concluded that the postimmobilization hyperactivity of both enzymes arises exclusively as a consequence of hypercorticosteronaemia, catecholamines and other hormones being without any influence on this response.

  16. Novel Fluorescent Chemosensors Based on Tryptophan Unit for Cu2+ and Fe3+ in Aqueous Solution

    Institute of Scientific and Technical Information of China (English)

    CHENG Peng-fei; XU Kuo-xi; YAO Wen-yong; KONG Hua-jie; KOU Li; MA Xiao-dan; WANG Chao-jie

    2013-01-01

    We reported four fluorescent chemosensors containing tryptophan units.The fluorescence spectrum titration experiments suggest that chemosensors 1,2,3 and 4 are highly selective for Cu2+ and Fe3+ over Li+,Na+,K+,Co2+,Zn2+,Ni2+,Hg2+ and Cr3+ via forming complexes with Cu2+ or Fe3+,which is confirmed by dramatical quench of fluoreseence in aqueous solution at pH 7.4,thus making all the chemosensors suitable for Cu2+ and Fe3+ fluorescent sensors.

  17. Tryptophan 19 residue is the origin of bovine β-lactoglobulin fluorescence.

    Science.gov (United States)

    Albani, Jihad René; Vogelaer, Julie; Bretesche, Loïc; Kmiecik, Daniel

    2014-03-01

    β-Lactoglobulin consists of a single polypeptide of 162 amino acid residues with 2 Trp residues, Trp 19 present in a hydrophobic pocket and Trp 61 present at the surface of the protein near the pocket. This study aimed to characterize the respective contribution of the two Trp residues to the overall fluorescence of the protein. We added for that calcofluor white, an extrinsic fluorophore, which, at high concentration compared to that of the protein, quenches completely emission of hydrophobic Trp residue(s). The study was performed at different pHs by recording fluorescence steady state spectra and measuring fluorescence lifetimes of the Trp-residues using Single Time Photon Counting method. Our results indicate that addition of calcofluor white does not induce a red shift of the tryptophan(s) emission peak (332nm) but only a decrease in the fluorescence intensity. This means that Trp 61 residue does not contribute to the protein emission, tryptophan emission occurs from Trp 19 residue only. Also, excitation spectrum peak position (283nm) of β-lactoglobulin is not modified upon calcofluor white binding. These results mean that structural rearrangements within β-lactoglobulin are not occurring upon calcofluor white binding. Energy transfer between Trp 19 residue and calcofluor white occurs with 100% efficiency, i.e. the two fluorophores are very close one to each other (<5Å). This energy transfer is not Forster type. Fluorescence intensity decay of Trp 19 residue occurs with three lifetimes, equal to 0.48, 1.49 and 4.29ns at pH 2 (monomeric state). Very close values were obtained at the different studied pHs (2-12) and where β-lactoglobulin is at different quaternary structure or present in solution in a mixture of dimers and monomers. Our data are interpreted as the results of emission occurring from different substructures of the tryptophan, reached at the excited state. The populations of these substructures characterized by the pre-exponential parameters

  18. Acute Bronchitis

    Science.gov (United States)

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

  19. Bronchitis - acute

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001087.htm Bronchitis - acute To use the sharing features on this page, please enable JavaScript. Acute bronchitis is swelling and inflamed tissue in the main ...

  20. Simulations and observations of plasma depletion, ion composition, and airglow emissions in two auroral ionospheric depletion experiments

    Science.gov (United States)

    Yau, A. W.; Whalen, B. A.; Harris, F. R.; Gattinger, R. L.; Pongratz, M. B.

    1985-01-01

    Observations of plasma depletion, ion composition modification, and airglow emissions in the Waterhole experiments are presented. The detailed ion chemistry and airglow emission processes related to the ionospheric hole formation in the experiment are examined, and observations are compared with computer simulation results. The latter indicate that the overall depletion rates in different parts of the depletion region are governed by different parameters.

  1. Glutathione Depletion Induces Spermatogonial Cell Autophagy.

    Science.gov (United States)

    Mancilla, Héctor; Maldonado, Rodrigo; Cereceda, Karina; Villarroel-Espíndola, Franz; Montes de Oca, Marco; Angulo, Constanza; Castro, Maite A; Slebe, Juan C; Vera, Juan C; Lavandero, Sergio; Concha, Ilona I

    2015-10-01

    The development and survival of male germ cells depend on the antioxidant capacity of the seminiferous tubule. Glutathione (GSH) plays an important role in the antioxidant defenses of the spermatogenic epithelium. Autophagy can act as a pro-survival response during oxidative stress or nutrient deficiency. In this work, we evaluated whether autophagy is involved in spermatogonia-type germ cell survival during severe GSH deficiency. We showed that the disruption of GSH metabolism with l-buthionine-(S,R)-sulfoximine (BSO) decreased reduced (GSH), oxidized (GSSG) glutathione content, and GSH/GSSG ratio in germ cells, without altering reactive oxygen species production and cell viability, evaluated by 2',7'-dichlorodihydrofluorescein (DCF) fluorescence and exclusion of propidium iodide assays, respectively. Autophagy was assessed by processing the endogenous protein LC3I and observing its sub-cellular distribution. Immunoblot and immunofluorescence analysis showed a consistent increase in LC3II and accumulation of autophagic vesicles under GSH-depletion conditions. This condition did not show changes in the level of phosphorylation of AMP-activated protein kinase (AMPK) or the ATP content. A loss in S-glutathionylated protein pattern was also observed. However, inhibition of autophagy resulted in decreased ATP content and increased caspase-3/7 activity in GSH-depleted germ cells. These findings suggest that GSH deficiency triggers an AMPK-independent induction of autophagy in germ cells as an adaptive stress response. © 2015 Wiley Periodicals, Inc.

  2. Halocarbon ozone depletion and global warming potentials

    Science.gov (United States)

    Cox, Richard A.; Wuebbles, D.; Atkinson, R.; Connell, Peter S.; Dorn, H. P.; Derudder, A.; Derwent, Richard G.; Fehsenfeld, F. C.; Fisher, D.; Isaksen, Ivar S. A.

    1990-01-01

    Concern over the global environmental consequences of fully halogenated chlorofluorocarbons (CFCs) has created a need to determine the potential impacts of other halogenated organic compounds on stratospheric ozone and climate. The CFCs, which do not contain an H atom, are not oxidized or photolyzed in the troposphere. These compounds are transported into the stratosphere where they decompose and can lead to chlorine catalyzed ozone depletion. The hydrochlorofluorocarbons (HCFCs or HFCs), in particular those proposed as substitutes for CFCs, contain at least one hydrogen atom in the molecule, which confers on these compounds a much greater sensitivity toward oxidation by hydroxyl radicals in the troposphere, resulting in much shorter atmospheric lifetimes than CFCs, and consequently lower potential for depleting ozone. The available information is reviewed which relates to the lifetime of these compounds (HCFCs and HFCs) in the troposphere, and up-to-date assessments are reported of the potential relative effects of CFCs, HCFCs, HFCs, and halons on stratospheric ozone and global climate (through 'greenhouse' global warming).

  3. Equatorial airglow depletions induced by thermospheric winds

    Energy Technology Data Exchange (ETDEWEB)

    Meriwether, J.W.; Biondi, M.A.; Anderson, D.N.

    1985-08-01

    Interferometric observations on the 630.0 nm nightglow brightness at the equatorial station at Arequipa, Peru (16.2 S, 71.4 W geographic, 3.2 S dip latitude) have revealed widespread areas of airglow depletion, with reductions in intensity as large as factors of 3 or 4. These depletions correlated closely with large increases of the equatorward (northward) wind and the 630.0 nm kinetic temperature. On occasion, the usually small meridional wind reached a velocity of 100 m/s near 22h LT lasting for 1 to 2 hours. The temperature increases of 100K or more existed only in the poleware (southward) direction. Comparisons with modeling calculations suggest that this effect results from an upward movement of the ionosphere along the inclined magnetic field lines, driven by the equatorward neutral wind. The airglow column integrated emission rate is consequently decreased by the slower rate of formation and subsequent dissociative recombination of molecular oxygen ions within the higher F-layer. We conclude that the transient period of equatorward wind is a result of the passage of the midnight pressure bulge. (Author)

  4. Equatorial airglow depletions induced by thermospheric winds

    Energy Technology Data Exchange (ETDEWEB)

    Meriwether J.W. Jr.; Biondi, M.A.; Anderson, D.N.

    1985-08-01

    Interferometric observations of the 630.0 nm nightglow brightness at the equatorial station of Arequipa. Peru (16.2/sup 0/S, 71.4/sup 0/W geographic, 3.2/sup 0/S dip latitude) have revealed widespread areas of airglow depletion, with reductions in intensity as large as factors of 3 or 4. These depletions correlated closely with large increases of the equatorward (northward) wind and the 630.0 nm kinetic temperature. On occasion, the usually small meridonal wind reached a velocity of 100 m/s near 22/sup h/ LT lasting for 1 or 2 hours. The temperature increases of 10 K or more existed only in the poleward (southward) direction. Comparisons with modeling calculations suggest that this effect results from an upward movement of the ionosphere along the inclined magnetic field lines, driven by the equatorward neutral wind. The airglow column integrated emission rate is consequently decreased by the slower rate of formation and subsequent dissociative recombination of molecular oxygen ions within the higher F-layer. We conclude that the transient period of equatorward wind is a result of the passage of the midnight pressure bulge.

  5. Abundances and Depletions of Interstellar Oxygen

    Science.gov (United States)

    Jensen, A. G.; Rachford, B. L.; Snow, T. P.

    2003-12-01

    We extend previous work on interstellar oxygen abundances with the addition of data from the Far Ultraviolet Spectroscopic Explorer (FUSE). We report on the abundance of interstellar neutral oxygen (OI) for several sightlines, using data from FUSE, the International Spectroscopic Explorer (IUE), and the Hubble Space Telescope (HST). OI column densities are derived by measuring the equivalent widths of several ultraviolet absorption lines, and subsequently fitting those to a curve of growth. The column densities of our best-constrained sightlines show a ratio of O/H that agrees with the current best solar value if dust is considered. We do not see evidence of enhanced depletion of gas-phase oxygen that is systematically variable with respect to the physical parameters of different environments (e.g., reddening or molecular fraction). The column densities of our less well-constrained sightlines show some scatter in O/H, but many agree with the solar value to within errors. We discuss these results in the context of deriving the best methods for determining interstellar abundances, the unresolved question of the best value for O/H in the interstellar medium (ISM), the O/H ratio observed in Galactic stars, and the depletion of gas-phase oxygen onto dust grains. Financial support for this research has been provided by the National Science Foundation GK-12 Program and NASA contract NAS 5-32985.

  6. The Ternary Complex of PrnB (the Second Enzyme in the Pyrrolnitrin Biosynthesis Pathway), Tryptophan, and Cyanide Yields New Mechanistic Insights into the Indolamine Dioxygenase Superfamily*

    Science.gov (United States)

    Zhu, Xiaofeng; van Pée, Karl-Heinz; Naismith, James H.

    2010-01-01

    Pyrrolnitrin (3-chloro-4-(2′-nitro-3′-chlorophenyl)pyrrole) is a broad-spectrum antifungal compound isolated from Pseudomonas pyrrocinia. Four enzymes (PrnA, PrnB, PrnC, and PrnD) are required for pyrrolnitrin biosynthesis from tryptophan. PrnB rearranges the indole ring of 7-Cl-l-tryptophan and eliminates the carboxylate group. PrnB shows robust activity in vivo, but in vitro activity for PrnB under defined conditions remains undetected. The structure of PrnB establishes that the enzyme belongs to the heme b-dependent indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) family. We report the cyanide complex of PrnB and two ternary complexes with both l-tryptophan or 7-Cl-l-tryptophan and cyanide. The latter two complexes are essentially identical and mimic the likely catalytic ternary complex that occurs during turnover. In the cyanide ternary complexes, a loop previously disordered becomes ordered, contributing to the binding of substrates. The conformations of the bound tryptophan substrates are changed from that seen previously in the binary complexes. In l-tryptophan ternary complex, the indole ring now adopts the same orientation as seen in the PrnB binary complexes with other tryptophan substrates. The amide and carboxylate group of the substrate are orientated in a new conformation. Tyr321 and Ser332 play a key role in binding these groups. The structures suggest that catalysis requires an l-configured substrate. Isothermal titration calorimetry data suggest d-tryptophan does not bind after cyanide (or oxygen) coordinates with the distal (or sixth) site of heme. This is the first ternary complex with a tryptophan substrate of a member of the tryptophan dioxygenase superfamily and has mechanistic implications. PMID:20421301

  7. Intrinsic Tryptophan Fluorescence in the Detection and Analysis of Proteins: A Focus on Förster Resonance Energy Transfer Techniques

    Directory of Open Access Journals (Sweden)

    Amar B. T. Ghisaidoobe

    2014-12-01

    Full Text Available F resonance energy transfer (FRET occurs when the distance between a donor fluorophore and an acceptor is within 10 nm, and its application often necessitates fluorescent labeling of biological targets. However, covalent modification of biomolecules can inadvertently give rise to conformational and/or functional changes. This review describes the application of intrinsic protein fluorescence, predominantly derived from tryptophan (\\(\\uplambda_{\\textsc{ex}}\\sim\\ nm, \\(\\uplambda_{\\textsc{em}}\\sim\\ 350 nm, in protein-related research and mainly focuses on label-free FRET techniques. In terms of wavelength and intensity, tryptophan fluorescence is strongly influenced by its (or the proteinlocal environment, which, in addition to fluorescence quenching, has been applied to study protein conformational changes. Intrinsic F resonance energy transfer (iFRET, a recently developed technique, utilizes the intrinsic fluorescence of tryptophan in conjunction with target-specific fluorescent probes as FRET donors and acceptors, respectively, for real time detection of native proteins.

  8. Synchrotron ultraviolet microspectroscopy on rat cortical bone: involvement of tyrosine and tryptophan in the osteocyte and its environment.

    Directory of Open Access Journals (Sweden)

    Stéphane Pallu

    Full Text Available Alcohol induced osteoporosis is characterized by a bone mass decrease and microarchitecture alterations. Having observed an excess in osteocyte apoptosis, we aimed to assess the bone tissue biochemistry, particularly in the osteocyte and its environment. For this purpose, we used a model of alcohol induced osteoporosis in rats. Bone sections of cortical bone were investigated using synchrotron UV-microspectrofluorescence at subcellular resolution. We show that bone present three fluorescence peaks at 305, 333 and 385 nm, respectively corresponding to tyrosine, tryptophan and collagen. We have determined that tyrosine/collagen and tryptophan/collagen ratios were higher in the strong alcohol consumption group. Tryptophan is related to the serotonin metabolism involved in bone formation, while tyrosine is involved in the activity of tyrosine kinases and phosphatases in osteocytes. Our experiment represents the first combined synchrotron UV microspectroscopy analysis of bone tissue with a quantitative biochemical characterization in the osteocyte and surrounding matrix performed separately.

  9. Effects of L-tryptophan, Fructan, and Casein on Reducing Ammonia, Hydrogen Sulfide, and Skatole in Fermented Swine Manure

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    Q. K. Sheng

    2015-08-01

    Full Text Available The effects of daily dietary Bacillus subtilis (Bs, and adding L-tryptophan, fructan, or casein to fecal fermentation broths were investigated as means to reduce the production of noxious gas during manure fermentation caused by ammonia, hydrogen sulfide (H2S, and 3-methylindole (skatole. Eighty swine (50.0±0.5 kg were equally apportioned to an experimental group given Bs in daily feed, or a control group without Bs. After 6 weeks, fresh manure was collected from both groups for fermentation studies using a 3×3 orthogonal array, in which tryptophan, casein, and fructan were added at various concentrations. After fermentation, the ammonia, H2S, L-tryptophan, skatole, and microflora were measured. In both groups, L-tryptophan was the principle additive increasing skatole production, with significant correlation (r = 0.9992. L-tryptophan had no effect on the production of ammonia, H2S, or skatole in animals fed Bs. In both groups, fructan was the principle additive that reduced H2S production (r = 0.9981. Fructan and Bs significantly interacted in H2S production (p = 0.014. Casein was the principle additive affecting the concentration of ammonia, only in the control group. Casein and Bs significantly interacted in ammonia production (p = 0.039. The predominant bacteria were Bacillus spp. CWBI B1434 (26% in the control group, and Streptococcus alactolyticus AF201899 (36% in the experimental group. In summary, daily dietary Bs reduced ammonia production during fecal fermentation. Lessening L-tryptophan and increasing fructan in the fermentation broth reduced skatole and H2S.

  10. Influence of the tryptophan-indole-IFNγ axis on human genital Chlamydia trachomatis infection: role of vaginal co-infections

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    Ashok eAiyar

    2014-06-01

    Full Text Available The natural history of genital Chlamydia trachomatis infections can vary widely; infections can spontaneously resolve but can also last from months to years, potentially progressing to cause significant pathology. The host and bacterial factors underlying this wide variation are not completely understood, but emphasize the bacterium’s capacity to evade/adapt to the genital immune response, and/or exploit local environmental conditions to survive this immune response. IFNγ is considered to be a primary host protective cytokine against endocervical C. trachomatis infections. IFNγ acts by inducing the host enzyme indoleamine 2,3-dioxygenase, which catabolizes tryptophan, thereby depriving the bacterium of this essential amino acid. In vitro studies have revealed that tryptophan deprivation causes Chlamydia to enter a viable but non-infectious growth pattern that is termed a persistent growth form, characterized by a unique morphology and gene expression pattern. Provision of tryptophan can reactivate the bacterium to the normal developmental cycle. There is a significant difference in the capacity of ocular and genital C. trachomatis serovars to counter tryptophan deprivation. The latter uniquely encode a functional tryptophan synthase to synthesize tryptophan via indole salvage, should indole be available in the infection microenvironment. In vitro studies have confirmed the capacity of indole to mitigate the effects of IFNγ; it has been suggested that a perturbed vaginal microbiome may provide a source of indole in vivo. Consistent with this hypothesis, the microbiome associated with bacterial vaginosis includes species that encode a tryptophanase to produce indole. In this review, we discuss the natural history of genital chlamydial infections, morphological and molecular changes imposed by IFNγ on Chlamydia, and finally, the microenvironmental conditions associated with vaginal co-infections that can ameliorate the effects of IFNγ on C

  11. Tryptophan, thiamine and indole-3-acetic acid exchange between Chlorella sorokiniana and the plant growth-promoting bacterium Azospirillum brasilense.

    Science.gov (United States)

    Palacios, Oskar A; Gomez-Anduro, Gracia; Bashan, Yoav; de-Bashan, Luz E

    2016-06-01

    During synthetic mutualistic interactions between the microalga Chlorella sorokiniana and the plant growth-promoting bacterium (PGPB) Azospirillum brasilense, mutual exchange of resources involved in producing and releasing the phytohormone indole-3-acetic acid (IAA) by the bacterium, using tryptophan and thiamine released by the microalga, were measured. Although increased activities of tryptophan synthase in C. sorokiniana and indole pyruvate decarboxylase (IPDC) in A. brasilense were observed, we could not detect tryptophan or IAA in the culture medium when both organisms were co-immobilized. This indicates that no extra tryptophan or IAA is produced, apart from the quantities required to sustain the interaction. Over-expression of the ipdC gene occurs at different incubation times: after 48 h, when A. brasilense was immobilized alone and grown in exudates of C. sorokiniana and at 96 h, when A. brasilense was co-immobilized with the microalga. When A. brasilense was cultured in exudates of C. sorokiniana, increased expression of the ipdC gene, corresponding increase in activity of IPDC encoded by the ipdC gene, and increase in IAA production were measured during the first 48 h of incubation. IAA production and release by A. brasilense was found only when tryptophan and thiamine were present in a synthetic growth medium (SGM). The absence of thiamine in SGM yielded no detectable IAA. In summary, this study demonstrates that C. sorokiniana can exude sufficient tryptophan and thiamine to allow IAA production by a PGPB during their interaction. Thiamine is essential for IAA production by A. brasilense and these three metabolites are part of a communication between the two microorganisms.

  12. Preliminary Study on Cost-Effective L-Tryptophan Production from Indole and L-Serine by E. coli Cells

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    Sadeghiyan-Rizi, Tahereh; Fooladi, Jamshid; Sadrai, Sima

    2016-01-01

    Background: L-tryptophan is used widespread in the pharmaceutical industry. The majority of L-Trp production depends on microbial processes that produce L-tryptophan from indole and L-serine. These processes are very costly due to the costs of precursors, especially L-serine. Use of inexpensive substitutions as the L-serine source of L-tryptophan production enables us to reach a cost-effective process. In this paper, effect of Triton X-100 on L-Trp production and the ability to use Iranian cane molasses as inexpensive L-serine source was investigated. Methods: Escherichia coli (E. coli) ATCC 11303 cells were grown in 10-L fermenter containing minimal medium supplemented with beet molasses as an inexpensive carbon source and indole as tryptophan synthase inducer. Whole cells of stationary phase were used as biocatalyst for L-Trp production. Triton X-100 addition to the production medium as indole reservoir was investigated. Then, cane molasses was used as L-Ser source in L-Trp production medium. Amount of L-Tryptophan and theoretical yield of L-Trp production was determined by HPLC and by a colorimetrically method on the basis of remaining indole assay, respectively. Results: As a result, triton X-100 increased L-Trp production three times. Also, the result showed that 0.68 mM L-Tryptophan was produced in the presence of cane molasses at 37°C for 8 hr. Conclusion: This result showed that cane molasses of Qazvin sugar factory includes significant amounts of L-Ser that makes it a suitable substitution for L-Ser in L-Trp production. Therefore, it has the potential to be used for cost-effective L-Trp production in industrial scale. PMID:27920887

  13. Determination of tryptophan and histidine by adsorptive cathodic stripping voltammetry using H-point standard addition method.

    Science.gov (United States)

    Ensafi, Ali A; Hajian, R

    2006-11-24

    A sequential method is proposed for the determination of tryptophane and histidine by adsorptive cathodic stripping voltammetry using standard addition and H-point standard addition method (HPSAM). The complexes of copper(II) with the amino acids were accumulated onto the surface of a hanging mercury drop electrode for 60s. Then the preconcentrated complexes were reduced by square wave voltammetry and the peak currents were measured. The effect of various parameters such as pH, concentration of copper, accumulation potential, accumulation time and scan rate on the sensitivity were studied by one-at-a time and artificial neural network. Under the optimized conditions, the peak currents at about +0.05 to -0.30 V is proportional to the concentration of tryptophan and histidine over the concentration ranges of 5-220 and 100-1200 nM, respectively. Optimization of the parameters by one-at-a time showed that at accumulation potential of 0.10 V (versus Ag/AgCl reference electrode) the peak current is proportional only to the concentration of tryptophan and histidine does not have any contribution to the current. The optimization results by artificial neural network showed that at accumulation potential of -0.06 V (versus Ag/AgCl) the peak current is proportional to the both concentrations of tryptophan and histidine. Therefore, the method of H-point standard addition has been used for resolving overlap voltamograms for determination of histidine in the present of tryptophane. The method was successfully applied to the determination of tryptophan and histidine in synthetic and real samples.

  14. Tryptophan-2,3-dioxygenase (TDO) inhibition ameliorates neurodegeneration by modulation of kynurenine pathway metabolites

    Science.gov (United States)

    Breda, Carlo; Sathyasaikumar, Korrapati V.; Sograte Idrissi, Shama; Notarangelo, Francesca M.; Estranero, Jasper G.; Moore, Gareth G. L.; Green, Edward W.; Kyriacou, Charalambos P.; Schwarcz, Robert; Giorgini, Flaviano

    2016-01-01

    Metabolites of the kynurenine pathway (KP) of tryptophan (TRP) degradation have been closely linked to the pathogenesis of several neurodegenerative disorders. Recent work has highlighted the therapeutic potential of inhibiting two critical regulatory enzymes in this pathway—kynurenine-3-monooxygenase (KMO) and tryptophan-2,3-dioxygenase (TDO). Much evidence indicates that the efficacy of KMO inhibition arises from normalizing an imbalance between neurotoxic [3-hydroxykynurenine (3-HK); quinolinic acid (QUIN)] and neuroprotective [kynurenic acid (KYNA)] KP metabolites. However, it is not clear if TDO inhibition is protective via a similar mechanism or if this is instead due to increased levels of TRP—the substrate of TDO. Here, we find that increased levels of KYNA relative to 3-HK are likely central to the protection conferred by TDO inhibition in a fruit fly model of Huntington’s disease and that TRP treatment strongly reduces neurodegeneration by shifting KP flux toward KYNA synthesis. In fly models of Alzheimer’s and Parkinson’s disease, we provide genetic evidence that inhibition of TDO or KMO improves locomotor performance and ameliorates shortened life span, as well as reducing neurodegeneration in Alzheimer's model flies. Critically, we find that treatment with a chemical TDO inhibitor is robustly protective in these models. Consequently, our work strongly supports targeting of the KP as a potential treatment strategy for several major neurodegenerative disorders and suggests that alterations in the levels of neuroactive KP metabolites could underlie several therapeutic benefits. PMID:27114543

  15. Imaging C. elegans with thiolated tryptophan-based NIR fluorescent gold nanoclusters

    Energy Technology Data Exchange (ETDEWEB)

    Barman, Apurba Kr. [Indian Institute of Technology Kanpur, Department of Chemistry (India); Chaturbedi, Amaresh; Subramaniam, K. [Indian Institute of Technology Kanpur, Department of Biological Sciences and Bioengineering (India); Verma, Sandeep, E-mail: sverma@iitk.ac.in [Indian Institute of Technology Kanpur, Department of Chemistry (India)

    2013-11-15

    Multidentate, thiolated, tryptophan-containing peptide conjugates were synthesized for the preparation of gold nanoclusters (AuNCs). Precursor Au{sub 11}(PPh{sub 3}){sub 8}Cl{sub 3} was prepared by the reduction of HAuCl{sub 4}, followed by the use of tryptophan-containing peptide conjugates in ligand displacement reactions, to afford near-infrared fluorescent AuNCs. The emission maxima for these newly synthesized AuNCs were ∼715 nm. AuNCs were characterized with the help of UV–Vis, FTIR, fluorescence and MALDI analysis. FTIR spectra showed that the ligands bind to Au atoms through Au–S bonds, while MALDI mass spectra revealed that the clusters consisted of 20–23 Au atoms. Introduction of hydrophilic –COOH groups engendered water solubility to these AuNCs, enabling bioimaging applications. We demonstrate fluorescence imaging of the nematode C. elegans and confirm distribution of these AuNCs in nematode gut with the help of green fluorescent protein co-localization experiments.

  16. Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates

    Science.gov (United States)

    Caldwell, Harlan D.; Wood, Heidi; Crane, Debbie; Bailey, Robin; Jones, Robert B.; Mabey, David; Maclean, Ian; Mohammed, Zeena; Peeling, Rosanna; Roshick, Christine; Schachter, Julius; Solomon, Anthony W.; Stamm, Walter E.; Suchland, Robert J.; Taylor, Lacey; West, Sheila K.; Quinn, Tom C.; Belland, Robert J.; McClarty, Grant

    2003-01-01

    We previously reported that laboratory reference strains of Chlamydia trachomatis differing in infection organotropism correlated with inactivating mutations in the pathogen’s tryptophan synthase (trpBA) genes. Here, we have applied functional genomics to extend this work and find that the paradigm established for reference serovars also applies to clinical isolates — specifically, all ocular trachoma isolates tested have inactivating mutations in the synthase, whereas all genital isolates encode a functional enzyme. Moreover, functional enzyme activity was directly correlated to IFN-γ resistance through an indole rescue mechanism. Hence, a strong selective pressure exists for genital strains to maintain a functional synthase capable of using indole for tryptophan biosynthesis. The fact that ocular serovars (serovar B) isolated from the genital tract were found to possess a functional synthase provided further persuasive evidence of this association. These results argue that there is an important host-parasite relationship between chlamydial genital strains and the human host that determines organotropism of infection and the pathophysiology of disease. We speculate that this relationship involves the production of indole by components of the vaginal microbial flora, allowing chlamydiae to escape IFN-γ–mediated eradication and thus establish persistent infection. PMID:12782678

  17. Jasmonoyl-L-Tryptophan Disrupts IAA Activity through the AUX1 Auxin Permease

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    Paul Staswick

    2017-05-01

    Full Text Available Amide-linked conjugates between tryptophan (Trp and jasmonic (JA or indole-3-acetic (IAA acids interfered with gravitropism and other auxin-dependent activities in Arabidopsis, but the mechanism was unclear. To identify structural features necessary for activity several additional Trp conjugates were synthesized. The phenylacetic acid (PAA conjugate was active, while several others were not. Common features of active conjugates is that they have ring structures that are linked to Trp through an acetic acid side chain, while longer or shorter linkages are inactive or less active. A dominant mutant, called tryptophan conjugate response1-D that is insensitive to JA-Trp, but still sensitive to other active conjugates, was identified and the defect was found to be a substitution of Asn for Asp456 in the C-terminal domain of the IAA cellular permease AUX1. Mutant seedling primary root growth in the absence of added conjugate was 15% less than WT, but otherwise plant phenotype appeared normal. These results suggest that JA-Trp disrupts AUX1 activity, but that endogenous JA-Trp has only a minor role in regulating plant growth. In contrast with IAA- and JA-Trp, which are present at <2 pmole g-1 FW, PAA-Trp was found at about 30 pmole g-1 FW. The latter, or other undiscovered Trp conjugates, may still have important endogenous roles, possibly helping to coordinate other pathways with auxin response.

  18. Au nanoparticles on tryptophan-functionalized graphene for sensitive detection of dopamine

    Energy Technology Data Exchange (ETDEWEB)

    Lian, Qianwen; Luo, Ai; An, Zhenzhen; Li, Zhuang; Guo, Yongyang; Zhang, Dongxia [Key Laboratory of Bioelectrochemistry & Environmental Analysis of Gansu Province, College of Geography and Environment Science, Northwest Normal University, 730070, Lanzhou (China); Xue, Zhonghua [College of Chemistry and Chemical Engineering, Northwest Normal University, 730070, Lanzhou (China); Zhou, Xibin, E-mail: zhouxb@nwnu.edu.cn [Key Laboratory of Bioelectrochemistry & Environmental Analysis of Gansu Province, College of Geography and Environment Science, Northwest Normal University, 730070, Lanzhou (China); Lu, Xiaoquan, E-mail: Luxq@nwnu.edu.cn [College of Chemistry and Chemical Engineering, Northwest Normal University, 730070, Lanzhou (China)

    2015-09-15

    Graphical abstract: - Highlights: • A novel AuNPs/Trp-GR composite was fabricated by directly electrochemical deposition. • The composite exhibited excellent electrocatalytic activity towards DA. • The proposed method was applied to real samples. - Abstract: A novel and uniform gold nanoparticles/tryptophan-functionalized graphene nanocomposite (AuNPs/Trp-GR) has been successfully fabricated by directly electrochemical depositing gold onto the surface of tryptophan-functionalized graphene (Trp-GR). The nanostructure of AuNPs/Trp-GR was characterized by using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). It was demonstrated that Au nanoparticles were well dispersed on the surface of Trp-GR which might attribute to the more binding sites provided by Trp-GR for the formation of Au nanoparticles. The electrocatalytic activity of the AuNPs/Trp-GR towards the dopamine (DA) was systematically investigated using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Under optimum conditions, a wide and valuable linear range (0.5–411 μM), a low detection limit (0.056 μM, S/N = 3), good repeatability and stability were obtained for the determination of DA. Furthermore, the modified electrode was successfully applied to real samples analysis.

  19. Conformational characterization of human eukaryotic initiation factor 2alpha: a single tryptophan protein.

    Science.gov (United States)

    Sreejith, R K; Yadav, Viveka Nand; Varshney, Nishant K; Berwal, Sunil K; Suresh, C G; Gaikwad, Sushama M; Pal, Jayanta K

    2009-12-11

    The alpha-subunit of the human eukaryotic initiation factor 2 (heIF2alpha), a GTP binding protein, plays a major role in the initiation of protein synthesis. During various cytoplasmic stresses, eIF2alpha gets phosphorylated by eIF2alpha-specific kinases resulting in inhibition of protein synthesis. The cloned and over expressed heIF2alpha, a protein with a single tryptophan (trp) residue was examined for its conformational characteristics using steady-state and time-resolved tryptophan fluorescence, circular dichroism (CD) and hydrophobic dye binding. The steady-state fluorescence spectrum, fluorescence lifetimes (tau(1)=1.13ns and tau(2)=4.74ns) and solute quenching studies revealed the presence of trp conformers in hydrophobic and differential polar environment at any given time. Estimation of the alpha-helix and beta-sheet content showed: (i) more compact structure at pH 2.0, (ii) distorted alpha-helix and rearranged beta-sheet in presence of 4M guanidine hydrochloride and (iii) retention of more than 50% ordered structure at 95 degrees C. Hydrophobic dye binding to the protein with loosened tertiary structure was observed at pH 2.0 indicating the existence of a molten globule-like structure. These observations indicate the inherent structural stability of the protein under various denaturing conditions.

  20. Design and synthesis of tryptophan containing dipeptide derivatives as formyl peptide receptor 1 antagonist.

    Science.gov (United States)

    Hwang, Tsong-Long; Hung, Chih-Hao; Hsu, Ching-Yun; Huang, Yin-Ting; Tsai, Yu-Chi; Hsieh, Pei-Wen

    2013-06-14

    Our previous studies identified an Fmoc-(S,R)-tryptophan-containing dipeptide derivative, 1, which selectively inhibited neutrophil elastase release induced by formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) in human neutrophils. In an attempt to improve pharmacological activity, a series of tryptophan-containing dipeptides were synthesized and their pharmacological activities were investigated in human neutrophils. Of these, five compounds 3, 6, 19a, 24a, and 24b exhibited potent and dual inhibitory effects on FMLP-induced superoxide anion (O2˙(-)) generation and neutrophil elastase release in neutrophils with IC50 values of 0.23/0.60, 1.88/2.47, 1.87/3.60, 0.12/0.37, and 1.32/1.03 μM, respectively. Further studies indicated that inhibition of superoxide production in human neutrophils by these dipeptides was associated with the selective inhibition of formyl peptide receptor 1 (FPR1). Furthermore, the results of structure-activity relationship studies concluded that the fragment N-benzoyl-Trp-Phe-OMe (3) was most suitable as a core structure for interaction with FPR1, and may be approved as a lead for the development of new drugs in the treatment of neutrophilic inflammatory diseases. As some of the synthesized compounds exhibited separable conformational isomers, and showed diverse bioactivities, the conformation analysis of these compounds is also discussed herein.

  1. Synthesis of deuterium-labelled halogen derivatives of L-tryptophan catalysed by tryptophanase.

    Science.gov (United States)

    Winnicka, Elżbieta; Szymańska, Jolanta; Kańska, Marianna

    2016-06-01

    The isotopomers of halogen derivatives of l-tryptophan (l-Trp) (4'-F-, 7'-F-, 5'-Cl- and 7'-Br-l-Trp), specifically labelled with deuterium in α-position of the side chain, were obtained by enzymatic coupling of the corresponding halogenated derivatives of indole with S-methyl-l-cysteine in (2)H2O, catalysed by enzyme tryptophanase (EC 4.1.99.1). The positional deuterium enrichment of the resulting tryptophan derivatives was controlled using (1)H NMR. In accordance with the mechanism of the lyase reaction, a 100% deuterium labelling was observed in the α-position; the chemical yields were between 23 and 51%. Furthermore, β-F-l-alanine, synthesized from β-F-pyruvic acid by the l-alanine dehydrogenase reaction, has been tested as a coupling agent to obtain the halogenated deuterium-labelled derivatives of l-Trp. The chemical yield (∼30%) corresponded to that as observed with S-methyl-l-cysteine but the deuterium label was only 63%, probably due to the use of a not completely deuterated incubation medium.

  2. Screening of multicomponent crystals of L-tryptophan with three isomers of pyridinedicarboxylic acids

    Science.gov (United States)

    Das, Babulal

    2016-08-01

    Multicomponent crystallization of L-tryptophan with three different isomers of pyridinedicarboxylic acids, namely, 2,3-pyridinedicarboxylic acid (2,3-PDA), 2,5-pyridinedicarboxylic acid (2,5-PDA) and 2,6-pyridinedicarboxylic acid (2,6-PDA), were screened using conventional solution cocrystallization technique. Whereas the new phases derived from the amino acid with 2,3-PDA or 2,5-PDA were analyzed using powder X-ray diffraction and thermal analysis techniques, the crystalline phase synthesized from 2,6-substituted isomer was further characterized by single crystal X-ray diffraction. Structural analysis revealed that the amino acid exists in the zwitterionic form interacting with the neutral 2,6-PDA by strong intermolecular hydrogen bonding. The components in the co-crystal self-assemble leading to a three dimensional hydrogen bonded closed packed network structure. Isothermal calorimetric titration showed that among the three isomers, 2,6-PDA showed relatively strong binding interaction towards the amino acid in water at 298 K. All the crystals exhibit marginal quenching of fluorescence properties of L-tryptophan in the solid state.

  3. Fluorescent proteins as biosensors by quenching resonance energy transfer from endogenous tryptophan: detection of nitroaromatic explosives.

    Science.gov (United States)

    Gingras, Alexa; Sarette, Joseph; Shawler, Evan; Lee, Taeyoung; Freund, Steve; Holwitt, Eric; Hicks, Barry W

    2013-10-15

    Ensuring domestic safety from terrorist attack is a daunting challenge because of the wide array of chemical agents that must be screened. A panel of purified fluorescent protein isoforms (FPs) was screened for the ability to detect various explosives, explosive simulants, and toxic agents. In addition to their commonly used visible excitation wavelengths, essentially all FPs can be excited by UV light at 280 nm. Ultraviolet illumination excites electrons in endogenous tryptophan (W) residues, which then relax by Förster Resonance Energy Transfer (FRET) to the chromophore of the FP, and thus the FPs emit with their typical visible spectra. Taking advantage of the fact that tryptophan excitation can be quenched by numerous agents, including nitroaromatics like TNT and nitramines like RDX, it is demonstrated that quenching of visible fluorescence from UV illumination of FPs can be used as the basis for detecting these explosives and explosive degradation products. This work provides the foundation for production of an array of genetically-modified FPs for in vitro biosensors capable of rapid, simultaneous, sensitive and selective detection of a wide range of explosive or toxic agents. Published by Elsevier B.V.

  4. Tryptophan-Assisted Synthesis Reduces Bimetallic Gold/Silver Nanoparticle Cytotoxicity and Improves Biological Activity

    Directory of Open Access Journals (Sweden)

    Igor O. Shmarakov

    2014-10-01

    Full Text Available Aiming to reduce the potential in vivo hepato-and neph‐ rotoxicity of Ag/Au bimetallic nanoparticles (NPs stabi‐ lized by sodium dodecyl sulphate (SDS, an approach involving a simultaneous reduction of silver nitrate and tetrachlorauratic acid using tryptophan (Trp as a reduc‐ ing/stabilizing agent was applied during NP synthesis. The obtained Ag/Au/Trp NPs (5-15 nm sized were able to form stable aggregates with an average size of 370-450 nm and were potentially less toxic than Ag/Au/SDS in relation to a mouse model system based on clinical biochemical param‐ eters and oxidative damage product estimation. Ag/Au/Trp NPs were shown to exhibit anticancer activity in relation to a Lewis lung carcinoma model. The data generated from the present study support the fact that the use of tryptophan in NP synthesis is effective in attenuating the potential hepatotoxicity and nephrotoxicity of NPs during their in vivo application.

  5. Quantitative analysis of flavonoids, sugars, phenylalanine and tryptophan in onion scales during storage under ambient conditions.

    Science.gov (United States)

    Sharma, Kavita; Assefa, Awraris D; Ko, Eun Young; Lee, Eul Tai; Park, Se Won

    2015-04-01

    A comprehensive quantitative analysis of flavonoids, sugars, phenylalanine, and tryptophan have been carried out in different onion scales during storage at ambient temperature (20-23 °C) and relative humidity (60-80 %). Depending on the length of storage, dry matter content and composition shows variation inside the onion bulbs. Inner sprouts were observed on longitudinally cut bulbs after 2 months and visible sprouts appeared after 5 months of storage. The bulbs lost 20 to 30 % of their weight at the end of the storage. Higher dry matter content was observed in the inner scales. Significantly high content of quercetin in inner scales and high level of quercetin-3,4'-O-diglucoside and quercetin-4'-O-monoglucoside in outer scales was observed during a 7 months storage. During storage period, high content of fructose and glucose was observed in the middle scales while sucrose was high in the inner scales. There was no particular trend observed within analyzed amino acids. However, the content of phenylalanine was higher than tryptophan.

  6. Novel N-Doped Carbon Dots/β-Cyclodextrin Nanocomposites for Enantioselective Recognition of Tryptophan Enantiomers

    Directory of Open Access Journals (Sweden)

    Qi Xiao

    2016-11-01

    Full Text Available Based on N-doped carbon dots/β-cyclodextrin nanocomposites modified glassy carbon electrodes (N-CDs/β-CD/GCE, an effective electrochemical sensor for enantioselective recognition of tryptophan (Trp enantiomers was developed by differential pulse voltammograms (DPVs. Fluorescent N-CDs were synthesized through a hydrothermal method and characterized by spectroscopic approaches. The N-CDs/β-CD nanocomposites were efficiently electrodeposited on the surface of GCE through C–N bond formation between N-CDs and electrode. The obtained N-CDs/β-CD/GCE was characterized by multispectroscopic and electrochemical methods. Such N-CDs/β-CD/GCE generated a significantly lower Ip and more negative Ep in the presence of l-Trp in DPVs, which was used for the enantioselective recognition of Trp enantiomers. The N-CDs/β-CD nanocomposites showed different binding constants for tryptophan enantiomers, and they further selectively bonded with l-Trp to form inclusion complexes. This N-CDs/β-CD/GCE combined advantages of N-CDs with strong C–N binding ability and β-CD with specific recognition of Trp enantiomers to fabricate a novel sensing platform for enantioselective recognition of Trp enantiomers. This strategy provided the possibility of using a nanostructured sensor to discriminate the chiral molecules in bio-electroanalytical applications.

  7. Ruminal tryptophan-utilizing bacteria degrade ergovaline from tall fescue seed extract.

    Science.gov (United States)

    Harlow, B E; Goodman, J P; Lynn, B C; Flythe, M D; Ji, H; Aiken, G E

    2017-02-01

    The objectives of this study were to evaluate degradation of ergovaline in a tall fescue [ (Schreb.) Darbysh.] seed extract by rumen microbiota ex vivo and to identify specific bacteria capable of ergovaline degradation in vitro. Rumen cell suspensions were prepared by harvesting rumen fluid from fistulated wether goats ( = 3), straining, and differential centrifugation. Suspensions were dispensed into anaerobic tubes with added Trypticase with or without extract (∼10 μg kg ergovaline). Suspensions were incubated for 48 h at 39°C. Samples were collected at 0, 24, and 48 h for ergovaline analysis and enumeration of hyper-ammonia producing (HAB) and tryptophan-utilizing bacteria. Ergovaline values were analyzed by repeated measures using the mixed procedure of SAS. Enumeration data were log transformed for statistical analysis. When suspensions were incubated with extract, 11 to 15% of ergovaline disappearance was observed over 48 h ( = 0.02). After 24 h, suspensions with added extract had 10-fold less HAB than controls ( = 0.04), but treatments were similar by 48 h ( = 1.00). However, after 24 h and 48 h, suspensions with extract had 10-fold more tryptophan-utilizing bacteria ( bacteria tested did not degrade ergovaline. The results of this study indicate which rumen bacteria may play an important role in ergovaline degradation and that microbiological strategies for controlling their activity could have ramifications for fescue toxicosis and other forms of ergotism in ruminants.

  8. Functional and fluorescence analyses of tryptophan residues in H+-pyrophosphatase of Clostridium tetani.

    Science.gov (United States)

    Chen, Yen-Wei; Lee, Ching-Hung; Huang, Yun-Tzu; Pan, Yih-Jiuan; Lin, Shih-Ming; Lo, Yueh-Yu; Lee, Chien-Hsien; Huang, Lin-Kun; Huang, Yu-Fen; Hsu, Yu-Di; Pan, Rong-Long

    2014-04-01

    Homodimeric proton-translocating pyrophosphatase (H+-PPase; EC 3.6.1.1) maintains the cytoplasmic pH homeostasis of many bacteria and higher plants by coupling pyrophosphate (PPi) hydrolysis and proton translocation. H+-PPase accommodates several essential motifs involved in the catalytic mechanism, including the PPi binding motif and Acidic I and II motifs. In this study, 3 intrinsic tryptophan residues, Trp-75, Trp-365, and Trp-602, in H+-PPase from Clostridium tetani were used as internal probes to monitor the local conformational state of the periplasm domain, transmembrane region, and cytoplasmic domain, respectively. Upon binding of the substrate analog Mg-imidodiphosphate (Mg-IDP), local structural changes prevented the modification of tryptophan residues by N-bromosuccinimide (NBS), especially at Trp-602. Following Mg-Pi binding, Trp-75 and Trp-365, but not Trp-602, were slightly protected from structural modifications by NBS. These results reveal the conformation of H+-PPase is distinct in the presence of different ligands. Moreover, analyses of the Stern-Volmer relationship and steady-state fluorescence anisotropy also indicate that the local structure around Trp-602 is more exposed to solvent and varied under different environments. In addition, Trp-602 was identified to be a crucial residue in the H+-PPase that may potentially be involved in stabilizing the structure of the catalytic region by site-directed mutagenesis analysis.

  9. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-01-01

    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  10. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-05-01

    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  11. Cord blood glutathione depletion in preterm infants: correlation with maternal cysteine depletion.

    Directory of Open Access Journals (Sweden)

    Alice Küster

    Full Text Available BACKGROUND: Depletion of blood glutathione (GSH, a key antioxidant, is known to occur in preterm infants. OBJECTIVE: Our aim was to determine: 1 whether GSH depletion is present at the time of birth; and 2 whether it is associated with insufficient availability of cysteine (cys, the limiting GSH precursor, or a decreased capacity to synthesize GSH. METHODOLOGY: Sixteen mothers delivering very low birth weight infants (VLBW, and 16 mothers delivering healthy, full term neonates were enrolled. Immediately after birth, erythrocytes from umbilical vein, umbilical artery, and maternal blood were obtained to assess GSH [GSH] and cysteine [cys] concentrations, and the GSH synthesis rate was determined from the incorporation of labeled cysteine into GSH in isolated erythrocytes ex vivo, measured using gas chromatography mass spectrometry. PRINCIPAL FINDINGS: Compared with mothers delivering at full term, mothers delivering prematurely had markedly lower erythrocyte [GSH] and [cys] and these were significantly depressed in VLBW infants, compared with term neonates. A strong correlation was found between maternal and fetal GSH and cysteine levels. The capacity to synthesize GSH was as high in VLBW as in term infants. CONCLUSION: The current data demonstrate that: 1 GSH depletion is present at the time of birth in VLBW infants; 2 As VLBW neonates possess a fully active capacity to synthesize glutathione, the depletion may arise from inadequate cysteine availability, potentially due to maternal depletion. Further studies would be needed to determine whether maternal-fetal cysteine transfer is decreased in preterm infants, and, if so, whether cysteine supplementation of mothers at risk of delivering prematurely would strengthen antioxidant defense in preterm neonates.

  12. Highly specific ''sensing'' of tryptophan by a luminescent europium(III) complex

    Energy Technology Data Exchange (ETDEWEB)

    Stubenrauch, Jan A.; Mevissen, Christian; Schulte, Marie F.; Bochenek, Steffen; Albrecht, Markus [RWTH Univ. Aachen (Germany). Inst. fuer Organische Chemie; Subramanian, Palani S. [Central Salt and Marine Chemicals, Research Institute (CSRI), Gujarat (India)

    2016-07-01

    The europium(III) complex 1-Cl{sub 3} (S,S-2,2{sup '}-(((1,10-phenanthroline-2,9-diyl)bis(methanylylidene))bis (azanylyliden e))bis(3-methylbutanamide)europiumtrichloride) undergoes, only in the presence of the amino acid tryptophan, a change of emission at 615 nm. In the presence of few equivalents of tryptophan, emission of the europium complex is enhanced while it disappears upon addition of large amounts. This behavior can be assigned to displacement of the sensitizing phenanthroline ligand of 1-Cl{sub 2} x Trp in the latter case.

  13. Mass spectrometric analysis of a UV-cross-linked protein-DNA complex: tryptophans 54 and 88 of E. coli SSB cross-link to DNA

    DEFF Research Database (Denmark)

    Steen, H; Petersen, J; Mann, M

    2001-01-01

    of two different peptide-DNA heteroconjugates was accomplished by matrix-assisted laser desorption/ionization mass spectrometry and allowed assignment of tryptophan-54 and tryptophan-88 as candidate cross-linked residues. Sequencing of those peptide-DNA heteroconjugates by nanoelectrospray quadrupole...

  14. A simple two step procedure for purification of the catalytic domain of chicken tryptophan hydroxylase 1 in a form suitable for crystallization

    DEFF Research Database (Denmark)

    Windahl, Michael Skovbo; Petersen, Charlotte R.; Munch, Astrid;

    2008-01-01

    Tryptophan hydroxylase (TPH) [EC 1.14.16.4] catalyzes the conversion of tryptophan to 5-hydroxytryptophan, which is the first and rate-determining step in the biosynthesis of the neurotransmitter serotonin. We have expressed the catalytic domain of chicken (Gallus gallus) TPH isoform 1 in Escheri...

  15. Plasma corticosteroid dynamics in channel catfish, Ictalurus punctatus (Rafinesque), during and after oxygen depletion

    Science.gov (United States)

    Tomasso J.R., Davis; Parker, N.C.

    1981-01-01

    Plasma corticosteroid concentrations in channel catfish, Ictalurus punctatus, (normally 1.0 ± 0.3 μg/100 ml) increased significantly (to 5.9 ± 1.2μg/100 ml) in response to acute oxygen depletion and then returned to control levels within 30 min after the dissolved oxygen concentration was increased; however, a secondary increase in plasma corticosteroid levels was observed 6 h after exposure. Corticosteroid levels also increased in fish exposed to dissolved oxygen concentration of blue was not effective in preventing interrenal response to low dissolved oxygen. No diurnal plasma corticosteroid rhythm was observed in fish exposed to diurnal chemical rhythms of culture ponds.

  16. Depleted Uranium Penetrators : Hazards and Safety

    Directory of Open Access Journals (Sweden)

    S. S. Rao

    1997-01-01

    Full Text Available The depleted uranium (DU alloy is a state-of-the-art material for kinetic energy penetrators due to its superior ballistic performance. Several countries use DU penetrators in their main battle tanks. There is no gamma radiation hazard to the crew members from stowage of DO rounds. Open air firing can result in environmental contamination and associated hazards due to airborne particles containing essentially U/sub 3/0/sub 8/ and UO/sub 2/. Inhalation of polluted air only through respirators or nose masks and refraining form ingestion of water or food materials from contaminated environment are safety measures for avoiding exposure to uranium and its toxicity. Infusion of sodium bicarbonate helps in urinary excretion of uranium that may have entered the body.

  17. Arctic Ozone Depletion from UARS MLS Measurements

    Science.gov (United States)

    Manney, G. L.

    1995-01-01

    Microwave Limb Sounder (MLS) measurements of ozone during four Arctic winters are compared. The evolution of ozone in the lower stratosphere is related to temperature, chlorine monoxide (also measured by MLS), and the evolution of the polar vortex. Lagrangian transport calculations using winds from the United Kingdom Meteorological Office's Stratosphere-Troposphere Data Assimilation system are used to estimate to what extent the evolution of lower stratospheric ozone is controlled by dynamics. Observations, along with calculations of the expected dynamical behavior, show evidence for chemical ozone depletion throughout most of the Arctic lower stratospheric vortex during the 1992-93 middle and late winter, and during all of the 1994-95 winter that was observed by MLS. Both of these winters were unusually cold and had unusually cold and had unusually strong Arctic polar vortices compared to meteorological data over the past 17 years.

  18. Ozone depletion following future volcanic eruptions

    Science.gov (United States)

    Eric Klobas, J.; Wilmouth, David M.; Weisenstein, Debra K.; Anderson, James G.; Salawitch, Ross J.

    2017-07-01

    While explosive volcanic eruptions cause ozone loss in the current atmosphere due to an enhancement in the availability of reactive chlorine following the stratospheric injection of sulfur, future eruptions are expected to increase total column ozone as halogen loading approaches preindustrial levels. The timing of this shift in the impact of major volcanic eruptions on the thickness of the ozone layer is poorly known. Modeling four possible climate futures, we show that scenarios with the smallest increase in greenhouse gas concentrations lead to the greatest risk to ozone from heterogeneous chemical processing following future eruptions. We also show that the presence in the stratosphere of bromine from natural, very short-lived biogenic compounds is critically important for determining whether future eruptions will lead to ozone depletion. If volcanic eruptions inject hydrogen halides into the stratosphere, an effect not considered in current ozone assessments, potentially profound reductions in column ozone would result.

  19. Kinetic depletion model for pellet ablation

    Energy Technology Data Exchange (ETDEWEB)

    Kuteev, Boris V. [State Technical Univ., St. Petersburg (Russian Federation)

    2001-11-01

    A kinetic model for depletion effect, which determines pellet ablation when the pellet passes a rational magnetic surface, is formulated. The model predicts a moderate decrease of the ablation rate compared with the earlier considered monoenergy versions [1, 2]. For typical T-10 conditions the ablation rate reduces by a reactor of 2.5 when the 1-mm pellet penetrates through the plasma center. A substantial deceleration of pellets -about 15% per centimeter of low shire rational q region; is predicted. Penetration for Low Field Side and High Field Side injections is considered taking into account modification of the electron distribution function by toroidal magnetic field. It is shown that Shafranov shift and toroidal effects yield the penetration length for HFS injection higher by a factor of 1.5. This fact should be taken into account when plasma-shielding effects on penetration are considered. (author)

  20. Anxiety, ego depletion, and sports performance.

    Science.gov (United States)

    Englert, Chris; Bertrams, Alex

    2012-10-01

    In the present article, we analyzed the role of self-control strength and state anxiety in sports performance. We tested the hypothesis that self-control strength and state anxiety interact in predicting sports performance on the basis of two studies, each using a different sports task (Study 1: performance in a basketball free throw task, N = 64; Study 2: performance in a dart task, N = 79). The patterns of results were as expected in both studies: Participants with depleted self-control strength performed worse in the specific tasks as their anxiety increased, whereas there was no significant relation for participants with fully available self-control strength. Furthermore, different degrees of available self-control strength did not predict performance in participants who were low in state anxiety, but did in participants who were high in state anxiety. Thus increasing self-control strength could reduce the negative anxiety effects in sports and improve athletes' performance under pressure.