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Sample records for acute tryptophan depletion

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

    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'

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

    Crockett, Molly; Clark, Luke; Roiser, Jonathan; Robinson, Oliver; Cools, Roshan; Chase, Henry; Den Ouden, Hanneke; Apergis-Schoute, Annemieke; Campbell-Meiklejohn, Daniel; Seymour, Ben; Sahakian, Barbara; Rogers, Robert; Robbins, Trevor

    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...

  3. The effect of acute tryptophan depletion on emotional distraction and subsequent memory

    Wang, Lihong; Mullette-Gillman, O’Dhaniel A.; Gadde, Kishore M; Kuhn, Cynthia M.; McCarthy, Gregory; Huettel, Scott A.

    2009-01-01

    Serotonin is a key neurotransmitter involved in emotional regulation and memory. A number of studies using acute tryptophan depletion (ATD) in healthy subjects have shown that a temporary serotonin reduction both induces a negative emotional bias and impairs long-term memory. However, little is known about the specific effects of ATD on emotional memory. Using functional magnetic resonance imaging (fMRI), we investigated the effect of ATD on negative memory and executive function in healthy v...

  4. Cognition following acute tryptophan depletion : Difference between first-degree relatives of bipolar disorder patients and matched healthy control volunteers

    Sobczak, S; Riedel, W J; Booij, I; Aan Het Rot, M; Deutz, N E P; Honig, A

    2002-01-01

    BACKGROUND: Serotonergic circuits have been proposed to mediate cognitive processes, particularly learning and memory. Cognitive impairment is often seen in bipolar disorders in relation to a possible lowered serotonergic turnover. METHODS: We investigated the effects of acute tryptophan depletion (

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

    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 ...... effects of CP-Trp compared to CP+Trp were observed. The transient increase in plasma Trp after CP+Trp may impair comparison to the CP-Trp and we therefore recommend in future studies to use a smaller dose of Trp supplement to the CP mixture....

  6. Effects of acute tryptophan depletion on executive function in healthy male volunteers

    Young Allan H

    2003-08-01

    Full Text Available Abstract Background Neurocognitive impairment is frequently described in a number of psychiatric disorders and may be a direct consequence of serotonergic dysfunction. As impairments in executive functions are some of the most frequently described, the purpose of this study was to examine the performance of normal volunteers on a range of executive tasks following a transient reduction of central serotonin (5-HT levels using the method of acute tryptophan depletion (ATD. Methods Fifteen healthy male subjects participated in a within-subject, double-blind, counterbalanced crossover study. ATD was induced by ingestion of a 100 g amino-acid drink. Executive function was evaluated using the Wisconsin Card Sorting Test, Stroop, Verbal Fluency and Trail Making. Visual analogue scales were administered to assess mood. Results Plasma free and total tryptophan concentrations were significantly reduced by the depleting drink (P P = 0.027, with no effect on subjective ratings of mood. Interaction effects between drink and the order of drink administration were observed on most neurocognitive tests. Conclusions The improvement in simple motor speed/ attention following ATD is in keeping with the ascribed role of 5-HT in the cortex, however performance on tests of executive function is not robustly altered. The presence of interaction effects on most tasks suggests that subtle changes may occur but are masked, possibly by simple learning effects, in the context of a crossover design. This has implications for the design of future studies, particularly those examining executive functions.

  7. Acute tryptophan depletion potentiates 3,4-methylenedioxymethamphetamine-induced cerebrovascular hyperperfusion in adult male Wistar rats.

    van Donkelaar, Eva L; Kelly, Paul A T; Dawson, Neil; Blokland, Arjan; Prickaerts, Jos; Steinbusch, Harry W M; Ferrington, Linda

    2010-05-15

    The serotonergic (5-hydroxytryptamine; 5-HT) dysfunction found in depression may affect not only brain function (mood) but also cerebrovascular control. Similar, but possibly occult, disturbances may also be induced by 3,4-methylenedioxymethamphetamine-induced neurotoxicity (MDMA, or "ecstasy"). Acute tryptophan depletion (ATD) is widely used to identify vulnerability to depression, and we hypothesized that repeated MDMA administration would increase the sensitivity of rats to this acute serotonergic challenge. In this study, male Wistar rats were injected with MDMA (20 mg kg(-1), twice daily for 4 days) and challenged 3 weeks later with ATD, induced by intragastric administration of a nutritional mixture with tryptophan (TRP) removed. Cerebral metabolism (CMRG) and blood flow (CBF) were measured in parallel groups of animals following ATD by using quantitative [(14)C]2-deoxyglucose and [(14)C]iodoantipyrine autoradiographic techniques, respectively. A significant reduction in paroxetine binding to 5-HT transporter sites in MDMA-treated rats indicated 5HT terminal depletion, whereas the plasma TRP/sum large neutral amino acids ratio was reduced by 40% following ATD. Under all experimental conditions, the normal close correlation between CBF and metabolic demand was maintained. However, a global analysis of all brain regions revealed a significant decrease in the overall ratio of CBF to CMRG after ATD in control animals, whereas a higher ratio was observed after ATD in the MDMA-treated group. This increase in blood flow relative to cerebral metabolism suggests an ATD-induced loss of cerebrovascular tone in MDMA-treated animals that could have pathophysiological consequences and might conceivably contribute to the behavioral dysfunction of depression. PMID:19998482

  8. 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

    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.

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

    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.

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

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

    2013-01-01

    neural correlates of inhibition using intravenous citalopram and acute tryptophan depletion during functional magnetic resonance imaging. We adapted the NoGo paradigm to isolate effects on inhibition per se as opposed to other aspects of the NoGo paradigm. Successful NoGo inhibition was associated with...... greater activation of the right IFG compared to control trials with alternative responses, indicating that the IFG is activated with inhibition in NoGo trials rather than other aspects of invoked cognitive control. Activation of the left IFG during NoGo trials was greater with citalopram than acute...

  11. 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

    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.

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

    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

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

    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

  14. Tryptophan depletion in depressed patients occurs independent of kynurenine pathway activation.

    Hughes, Martina M; Carballedo, Angela; McLoughlin, Declan M; Amico, Francesco; Harkin, Andrew; Frodl, Thomas; Connor, Thomas J

    2012-08-01

    The kynurenine pathway (KP) and its rate-limiting tryptophan degrading enzyme indolamine 2,3-dioxygenase (IDO) have been implicated in the pathogenesis of depression. IDO expression is driven by inflammatory cytokines, and has been suggested as the link between inflammation and a serotonergic deficit in depression. Studies also indicate that inflammatory cytokines upregulate the serotonin transporter (SERT), representing another mechanism by which inflammation could influence serotonin availability. Here we examined circulating concentrations of inflammatory cytokines (IFN-γ, TNF-α, IL-1β, IL-6), and the acute phase protein CRP alongside plasma tryptophan, kynurenine, kynurenic acid (KYNA) and 3-hydroxyanthranilic acid (3-HAA) concentrations, and whole blood mRNA expression of IDO, kynurenine aminotransferases (KAT I and II), kynurenine-3-monooxygenase (KMO), kynureninase and SERT in patients with major depressive disorder (MDD) compared with age and sex-matched controls. Whilst no changes in TNF-α or IL-1β were observed, plasma concentrations of IL-6, IFN-γ and CRP were increased in the depressed cohort. Despite this inflammatory phenotype, IDO expression or plasma kynurenine were not significantly different between MDD patients and controls. In addition, there was no difference between controls and depressives in concentrations of KYNA and 3-HAA, or in expression of enzymes KAT, KMO or kynureninase that drive their production. Nonetheless, a depletion in tryptophan was evident in depressed patients and was correlated with HAM-D scores. In addition, we failed to observe any difference in SERT mRNA expression in the blood cells from patients with MDD relative to controls. These data support the idea that a mild inflammatory signature is evident in MDD and is accompanied by reduced circulating tryptophan concentrations. However, we found no indication of KP activation in the depressed cohort suggesting that an alternative mechanism mediates the depletion of

  15. Tryptophan

    Tryptophan is an amino acid needed for normal growth in infants and for nitrogen balance in adults. ... The body uses tryptophan to help make niacin and serotonin. Serotonin is thought to produce healthy sleep and a stable mood. In order ...

  16. Effects of acute paroxetine administration on tryptophan metabolism and disposition in the rat.

    Badawy, A. A.; Morgan, C. J.

    1991-01-01

    1 The effects of acute oral administration of paroxetine on tryptophan metabolism and disposition were examined in the rat. 2 Basal liver tryptophan pyrrolase activity was inhibited by paroxetine in vitro and after oral administration. Maximum inhibition was caused by a 1 mg kg-1 dose. 3 Paroxetine administration also inhibited pyrrolase activity that had previously been enhanced by hormonal induction by cortisol or cofactor activation by haematin. The cortisol induction of the enzyme was, ho...

  17. The association of the kynurenine pathway of tryptophan metabolism with acute brain dysfunction during critical illness*

    Adams Wilson, Jessica R.; Morandi, Alessandro; Girard, Timothy D.; Thompson, Jennifer L.; Boomershine, Chad S.; Shintani, Ayumi K.; Ely, E. Wesley; Pandharipande, Pratik P.

    2013-01-01

    Objectives Plasma tryptophan levels are associated with delirium in critically ill patients. Although tryptophan has been linked to the pathogenesis of other neurocognitive diseases through metabolism to neurotoxins via the kynurenine pathway, a role for kynurenine pathway activity in intensive care unit brain dysfunction (delirium and coma) remains unknown. This study examined the association between kynurenine pathway activity as determined by plasma kynurenine concentrations and kynurenine/tryptophan ratios and presence or absence of acute brain dysfunction (defined as delirium/coma-free days) in intensive care unit patients. Design, Setting, and Patients This was a prospective cohort study that utilized patient data and blood samples from the Maximizing Efficacy of Targeted Sedation and Reducing Neurologic Dysfunction trial, which compared sedation with dexmedetomidine vs. lorazepam in mechanically ventilated patients. Measurements and Main Results Baseline plasma kynurenine and tryptophan concentrations were measured using high-performance liquid chromatography with or without tandem mass spectrometry. Delirium was assessed daily using the Confusion Assessment Method for the Intensive Care Unit. Linear regression examined associations between kynurenine pathway activity and delirium/coma-free days after adjusting for sedative exposure, age, and severity of illness. Among 84 patients studied, median age was 60 yrs and Acute Physiology and Chronic Health Evaluation II score was 28.5. Elevated plasma kynurenine and kynurenine/tryptophan ratio were both independently associated with significantly fewer delirium/coma-free days (i.e., fewer days without acute brain dysfunction). Specifically, patients with plasma kynurenine or kynurenine/tryptophan ratios at the 75th percentile of our population had an average of 1.8 (95% confidence interval 0.6–3.1) and 2.1 (95% confidence interval 1.0–3.2) fewer delirium/coma-free days than those patients with values at the 25

  18. Sub-chronic dietary tryptophan depletion--an animal model of depression with improved face and good construct validity.

    Franklin, M; Bermudez, I; Murck, H; Singewald, N; Gaburro, S

    2012-02-01

    Sub-chronic tryptophan depletion (SCTD) is proposed as an animal model for depression. Aims were to test the hypothesis and optimise the time of SCTD-induced depression-related behaviour and associated biochemical changes. Sprague Dawley rats were treated with a low tryptophan (TRP) containing diet for 0, 7 or 14 days. Peripheral and central neurochemical markers were measured. SCTD-induced depression-related behaviour was assessed by the forced swim test (FST). Model sensitivity to antidepressants was tested by concomitant treatment with paroxetine. SCTD-induced significant reductions in weight gain and measures of peripheral and central TRP. Corticosterone, aldosterone and kynurenine (K), increased whilst kynurenic acid (KA), an NMDA antagonist decreased. 5-HT(2) receptor binding Bmax was enhanced but was reversed by paroxetine. Corticosterone and aldosterone were significantly negatively-correlated to weight gain. SCTD increased floating time and reduced swimming time in the FST but were reversed by paroxetine. Aldosterone was increased at 7 and 14 days, whereas other changes maximised at 14 days. Aldosterone may be an early marker or causal link for depression development. Increased corticosterone and brain tissue 5-HT-receptor density may be correlates of depressive behaviour. Consequential increases in NMDA signalling through increased K/KA ratios suggest the model may be useful for testing novel antidepressants. PMID:22074993

  19. Plasmakonzentrationen von Prolaktin, Cortisol, Thyreotropin, Trijodthyronin und Thyroxin bei Schlafentzug-Respondern unter Tryptophan-Depletion im Rahmen einer endogenen Depression

    Sasse, Jörg

    2000-01-01

    Zielbereiche der vorliegenden Arbeit stellten sowohl die Analysen zur Auswirkung eines Schlafentzuges (SE) unter Tryptophan-Depletion (TD) auf die hormonellen Parameter Prolaktin (PRL), Cortisol, Thyreotropin (TSH), Trijodthyronin (T3) und Thyroxin (T4) als auch die daraus resultierenden Rückschlüsse im Hinblick auf eine Verzahnung dieser Parameter nicht nur mit der depressiven Symptomatik sondern auch mit den SE-Wirkmechanismen dar. Zur Untersuchung dieser bislang im Rahmen der biologische...

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

    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.

  1. Studies on the application of tryptophan metabolites as indicators of acute radiation damage and their modification

    It has been the aim of the investigations to continue earlier studies on the amplication of tryptophan metabolites as biochemical indicators after irradiation. These metabolites are of interest as they apparently indicate radiation effects in contrast to other metabolites like taurine and deoxycytidine in a dose range which leads to acute radiation sickness with the consequence of death. This assumption has been confirmed by the results of these studies. Measurements in the urine of rats demonstrate that the excretion of kynurenic acid and of xanthurenic acid as well as especially the ratio of kynurenic acid/anthranilic acid increases considerably in those animals which die some days later. The excretion of the surviving anilic acid increases considerably in those animals which die some days later. The excretion of the surviving animals is characteristical different. This abnormal excretion is induced by changes of specific, hepatic enzyme activities. The investigations have shown that the effects on the enzyme activities apppear not only after X-rays irradiation but also after neutrons. The studies, which have been performed with human material on the NAD-metabolism, demonstrate that with respect to the enzyme activities in the spleen as well as to the urinary excretion the same or similar effects, which have been found with animal experiments, can be expected. (orig.) 891 MG/orig. 892 CKA

  2. Depletion of mucosal substance P in acute otitis media

    Cayé-Thomasen, Per; Schmidt, Peter Thelin; Hermansson, Ann; Holst, Jens Juul; Thomsen, Jens

    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...... fiber release of SP. MATERIAL AND METHODS: To investigate possible release of SP in the middle ear mucosa during AOM, we used a well-established rat model of AOM caused by Streptococcus pneumoniae. Following tissue extraction on Days 1, 3 and 6 post-inoculation, the mucosal concentration of SP was...... measured using a radioimmunoassay. RESULTS: Compared to sham-inoculated control ears, the concentration of SP was significantly reduced on Day 1 and even further reduced on Day 3, whereas partial replenishment was found on Day 6. CONCLUSION: SP seems to be depleted in the rat middle ear mucosa in the...

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

    O'Hara, Caitlin Beth; Keyes, Alexandra; Renwick, Bethany Gwen; Leyton, Marco; Campbell, Iain Cameron; Schmidt, Ulrike Hermine

    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 progressiv...

  4. Mechanism of decline in rat brain 5-hydroxytryptamine after induction of liver tryptophan pyrrolase by hydrocortisone: roles of tryptophan catabolism and kynurenine synthesis

    Young, Simon N.

    1981-01-01

    1 Two mechanisms have been proposed to explain the decline in brain tryptophan and 5-hydroxytryptamine (5-HT) after administration of hydrocortisone and the subsequent induction of liver pyrrolase. These are depletion of tryptophan by high rates of tryptophan catabolism and inhibition of tryptophan uptake by elevated levels of the tryptophan catabolite, kynurenine.

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

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

    2014-01-01

    L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS-directed anti-leukaemia therapy. The...

  6. The protective effect of L-tryptophan versus alpha lipoic acid against L-arginine-induced experimental acute pancreatitis in albino rats

    Lamia M. Farghaly* , Nagwan A. Sabak ** and Naglaa A. El-sherbeny

    2007-03-01

    Full Text Available Aim of the study: This study was conducted to investigate the possible protective effects of L- treptophan "a precursor of melatonin" and alpha lipoic acid against L- arginine-induced experimental acute pancreatitis in albino rats. Methods: Fourty adult male albino rats (200- 250g were randomized into 4 groups (n= 10. Group I, the control group was given 0.9% saline intraperitoneally (i.p. Group II, was given 500 mg/100g L-arginine (i.p as a single dose to induce acute pancreatitis. Group III: was given 250mg/kg L-tryptophan (i.p 30 min prior to L- arginine injection. Group IV: was given 50mg/kg alpha lipioc acid(i.p 30 min prior to L-arginine. Before scarifice, blood samples were obtained from all groups to assay serum amylase and interleukin 6. Animals were sacrificed after 6 hours. For the histopathological study, pancreatic tissue was prepared for histological (H&E, PAS histochemical ( Tween stain for lipases and immunohistochemical ( Bax stain for apoptosis techniques. Both qualitative and quantitative analyses were done to assess the degree of acinar cells affection Results: It was revealed that serum amylase and interleukin 6 in group II rose rapidly. Microscopically, severe acinar cells degeneration, interstitial edema, diffuse bleeding and inflammatory infiltration were demonstrated. These changes were markedly improved with the administration of both L- tryptophan and alpha lipoic acid. Conclusion: It was concluded that both L- tryptophan & alpha lipoic acid reduced the effects of L-arginine-induced acute pancreatitis with better protection achieved by L-tryptophan administration.

  7. Chlamydia exploit the mammalian tryptophan-depletion defense strategy as a counter-defensive cue to trigger a survival state of persistence

    Bonner, Carol A; Byrne, Gerald I.; Jensen, Roy A.

    2014-01-01

    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 Chl...

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

    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....

  9. INDOLEAMINE 2,3-DIOXYGENASE INDUCES EXPRESSION OF A NOVEL TRYPTOPHAN TRANSPORTER IN MOUSE AND HUMAN TUMOR CELLS1

    Silk, Jonathan D.; Lakhal, Samira; Laynes, Robert; Vallius, Laura; Karydis, Ioannis; Marcea, Cornelius; Boyd, C. A. Richard; Cerundolo, Vincenzo

    2011-01-01

    Indoleamine 2,3 dioxygenase (IDO) is the rate-limiting enzyme in the kynurenine pathway, catabolizing tryptophan to kynurenine. Tryptophan depletion by IDO expressing tumors is a common mechanism of immune evasion inducing regulatory T cells and inhibiting effector T cells. As mammalian cells cannot synthesize tryptophan, it remains unclear how IDO positive tumor cells overcome the detrimental effects of local tryptophan depletion.

  10. Tryptophan depletion and formation of alpha-aminoadipic and gamma-glutamic semialdehydes in porcine burger patties with added phenolic-rich fruit extracts.

    Ganhão, Rui; Morcuende, David; Estévez, Mario

    2010-03-24

    The effect of added fruit extracts on the oxidation of muscle proteins in porcine burger patties subjected to cooking and chill storage was studied. Extracts from arbutus berries (Arbutus unedo L., AU), common hawthorns (Crataegus monogyna L., CM), dog roses (Rosa canina L., RC), and elm-leaf blackberries (Rubus ulmifolius Schott, RU) were prepared, characterized, added to burger patties (3% of total weight), and evaluated as inhibitors of protein oxidation. Negative (no added extract, C) and positive control (added quercetin, 230 mg/kg, Q) groups were also included in the design. Protein oxidation was assessed by means of tryptophan loss using fluorescence spectroscopy (FS) and formation of the specific protein carbonyls alpha-aminoadipic (AAS) and gamma-glutamic semialdehyde (GGS) using liquid chromatography and mass spectroscopy (LC-MS). Both advanced methodologies (FS and LC-MS) were found to be reliable and specific protein oxidation measurements that allow us to gain chemical insight into protein oxidation. The mechanisms likely involved in the oxidative reactions affecting proteins during cooking and storage of burger patties are profusely discussed. Phenolic-rich fruit extracts protected tryptophan residues against oxidation and inhibited the formation of both semialdehydes in burger patties during cooking and subsequent chill storage. In general, RC, RU, and AU were the most effective inhibitors of protein oxidation, with this effect being more intense than that of pure polyphenols like quercetin. These fruit extracts could be considered functional ingredients as their antioxidant actions contribute to the enhancement of the nutritional value of the meat products. PMID:20170109

  11. The brain is a target organ after acute exposure to depleted uranium

    The health effects of depleted uranium (DU) are mainly caused by its chemical toxicity. Although the kidneys are the main target organs for uranium toxicity, uranium can also reach the brain. In this paper, the central effects of acute exposure to DU were studied in relation to health parameters and the sleep-wake cycle of adult rats. Animals were injected intraperitoneally with 144 ± 10 μg DU kg-1 as nitrate. Three days after injection, the amounts of uranium in the kidneys represented 2.6 μg of DU g-1 of tissue, considered as a sub-nephrotoxic dosage. The central effect of uranium could be seen through a decrease in food intake as early as the first day after exposure and shorter paradoxical sleep 3 days after acute DU exposure (-18% of controls). With a lower dosage of DU (70 ± 8 μg DU kg-1), no significant effect was observed on the sleep-wake cycle. The present study intends to illustrate the fact that the brain is a target organ, as are the kidneys, after acute exposure to a moderate dosage of DU. The mechanisms by which uranium causes these early neurophysiological perturbations shall be discussed

  12. Effects of maternal L-tryptophan depletion and corticosterone administration on neurobehavioral adjustments in mouse dams and their adolescent and adult daughters.

    Zoratto, Francesca; Berry, Alessandra; Anzidei, Francesca; Fiore, Marco; Alleva, Enrico; Laviola, Giovanni; Macrì, Simone

    2011-08-01

    Major depressive disorder (MDD), a pathology characterized by mood and neurovegetative disturbances, depends on a multi-factorial contribution of individual predisposition (e.g., diminished serotonergic transmission) and environmental factors (e.g., neonatal abuse or neglect). Despite its female-biased prevalence, MDD basic research has mainly focused on male rodents. Most of present models of depression are also devalued due to the fact that they typically address only one of the aforementioned pathogenetic factors. In this paper we first describe the basic principles behind mouse model development and evaluation and then articulate that current models of depression are intrinsically devalued due to poor construct and/or external validity. We then report a first attempt to overcome this limitation through the design of a mouse model in which the genetic and the environmental components of early risk factors for depression are mimicked together. Environmental stress is mimicked through the supplementation of corticosterone in the maternal drinking water while biological predisposition is mimicked through maternal access to an L-tryptophan (the serotonin precursor) deficient diet during the first week of lactation. CD1 dams and their offspring exposed to the L-tryptophan deficient diet (T) and to corticosterone (80mg/l; C) were compared to animal facility reared (AFR) subjects. T and C mice served as intermediate reference groups. Adolescent TC offspring, compared to AFR mice, showed decreased time spent floating in the forced-swim test and increased time spent in the open sectors of an elevated 0-maze. Adult TC offspring showed reduced preference for novelty, decreased breakpoints in the progressive ratio operant procedure and major alterations in central BDNF levels and altered HPA regulation. The route of administration and the possibility to control the independent variables predisposing to depressive-like symptoms disclose novel avenues towards the development

  13. Acute cholesterol depletion leads to net loss of the organic osmolyte taurine in Ehrlich Lettré tumor cells

    Villumsen, Kasper Rømer; Duelund, Lars; Lambert, Ian Henry

    2010-01-01

    reveals that cholesterol depletion increases TauT's affinity toward taurine but reduces its maximal transport capacity. Cholesterol depletion has no impact on TauT regulation by protein kinases A and C. Phospholipase A2 activity, which is required for the activation of volume-sensitive organic anion......In mammalian cells, the organic osmolyte taurine is accumulated by the Na-dependent taurine transporter TauT and released though the volume- and DIDS-sensitive organic anion channel. Incubating Ehrlich Lettré tumor cells with methyl-ß-cyclodextrin (5 mM, 1 h) reduces the total cholesterol pool to...... channel (VSOAC), is increased under isotonic and hypotonic conditions following cholesterol depletion, whereas taurine release under hypotonic conditions is reduced following cholesterol depletion. Hence, acute cholesterol depletion of Ehrlich Lettré cells leads to reduced TauT and VSOAC activities and at...

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

    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. PMID:26808920

  15. Glutathione depletion and acute exercise increase O-GlcNAc protein modification in rat skeletal muscle.

    Peternelj, Tina Tinkara; Marsh, Susan A; Strobel, Natalie A; Matsumoto, Aya; Briskey, David; Dalbo, Vincent J; Tucker, Patrick S; Coombes, Jeff S

    2015-02-01

    Post-translational modification of intracellular proteins with O-linked β-N-acetylglucosamine (O-GlcNAc) profoundly affects protein structure, function, and metabolism. Although many skeletal muscle proteins are O-GlcNAcylated, the modification has not been extensively studied in this tissue, especially in the context of exercise. This study investigated the effects of glutathione depletion and acute exercise on O-GlcNAc protein modification in rat skeletal muscle. Diethyl maleate (DEM) was used to deplete intracellular glutathione and rats were subjected to a treadmill run. White gastrocnemius and soleus muscles were analyzed for glutathione status, O-GlcNAc and O-GlcNAc transferase (OGT) protein levels, and mRNA expression of OGT, O-GlcNAcase and glutamine:fructose-6-phosphate amidotransferase. DEM and exercise both reduced intracellular glutathione and increased O-GlcNAc. DEM upregulated OGT protein expression. The effects of the interventions were significant 4 h after exercise (P exercise. PMID:25416863

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

    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.

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

    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. PMID:26808920

  18. Chlamydia exploit the mammalian tryptophan-depletion defense strategy as a counter-defensive cue to trigger a survival state of persistence.

    Bonner, Carol A; Byrne, Gerald I; Jensen, Roy A

    2014-01-01

    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 (SAM), 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 (Pmp's). 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. Study on decorporating and detoxicating acute depleted uranium poison with some flavonoids

    In order to investigate decorporating and detoxicating acute depleted uranium poison of flavonoids, the decorporation effect of flavonoids with catechol group, chelating agent of catechols amino carboxylic acid type (8102) and dimethyl sulfoxide (DMSO) were studied under DU exposure and Wistar rats as animal model. In 3d later after injecting DU with dose of 20 mg/kg and then injecting flavonoids with dose of 10 mg/kg in abdomen, the mortality, uranium contents, kidney function and pathological observation of kidney were investigated. It has been found that nearly 20% mortality occurs both in the T2 and in T1 groups meanwhile 30% mortality occurs in the control group. But death has not been observed in 8102 group. The concentration of excreted urine uranium increases and the level of serum uranium decreases when T2 used. The retention of uranium in kidney with T2 group also increases. Large reducing of urea nitrogen and creatinine in serum has been observed in 8102 and F1 groups, and reducing of creatinine has also been observed in F2, T1 and T2 groups. The serious injury of kidney has not been observed in T2 group. The protection efficiency can be listed as T2> 8102>T1>F1>QU. It has been revealed that flavonoid T2 is the most effective protector from the damage and poison of DU. (authors)

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

    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.

  1. L -Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications

    Richard, Dawn M.; Dawes, Michael A.; Mathias, Charles W.; Ashley Acheson; Nathalie Hill-Kapturczak; Dougherty, Donald M.

    2009-01-01

    An essential component of the human diet, L-tryptophan is critical in a number of metabolic functions and has been widely used in numerous research and clinical trials. This review provides a brief overview of the role of L-tryptophan in protein synthesis and a number of other metabolic functions. With emphasis on L-tryptophan’s role in synthesis of brain serotonin, details are provided on the research uses of L-tryptophan, particularly L-tryptophan depletion, and on clinical trials that have...

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

    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.

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

    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.

  4. L-tryptophan

    ... brain and serious side effects including heart problems, shivering and anxiety could occur. Do not take L- ... and cause serious side effects including heart problems, shivering, and anxiety. Do not take L-tryptophan if ...

  5. 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.

    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.

  6. High doses of vitamin B6 in the rat are associated with inhibition of hepatic tryptophan metabolism and increased uptake of tryptophan into the brain

    Bender, D.A.; Totoe, L.

    1984-09-01

    Acute administration of vitamin B6 to rats (10 mg/kg body weight) led to reduced urinary excretion of N1-methyl nicotinamide and methyl pyridone carboxamide, indicating inhibition of the oxidative metabolism of tryptophan. There was a considerable reduction in the production of 14CO2 from (ring-2-14C)tryptophan, and a significant inhibition of hepatic tryptophan oxygenase when measured in liver homogenates, together with an increase in the concentration of tryptophan in plasma. There was an increase in both the concentration of tryptophan in the brain and the uptake into the brain of peripherally administered (3H)tryptophan, accompanied by a small increase in the rate of synthesis of 5-hydroxytryptamine in the brain. It is suggested that this increase in the uptake of tryptophan into the brain following a relatively large dose of vitamin B6 may explain the beneficial action of the vitamin in some cases of depressive illness.

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

    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.

  8. Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis.

    Wang, Guohao; Liu, Xudong; Gaertig, Marta A; Li, Shihua; Li, Xiao-Jiang

    2016-03-22

    The Huntington's disease (HD) protein, huntingtin (HTT), is essential for early development. Because suppressing the expression of mutantHTTis an important approach to treat the disease, we must first understand the normal function of Htt in adults versus younger animals. Using inducibleHttknockout mice, we found thatHttdepletion does not lead to adult neurodegeneration or animal death at >4 mo of age, which was also verified by selectively depletingHttin neurons. On the other hand, young Htt KO mice die at 2 mo of age of acute pancreatitis due to the degeneration of pancreatic acinar cells. Importantly, Htt interacts with the trypsin inhibitor, serine protease inhibitor Kazal-type 3 (Spink3), to inhibit activation of digestive enzymes in acinar cells in young mice, and transgenicHTTcan rescue the early death of Htt KO mice. These findings point out age- and cell type-dependent vital functions of Htt and the safety of knocking down neuronal Htt expression in adult brains as a treatment. PMID:26951659

  9. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications

    Richard, Dawn M.; Dawes, Michael A.; Mathias, Charles W.; Acheson, Ashley; Hill-Kapturczak, Nathalie; Dougherty, Donald M.

    2009-01-01

    An essential component of the human diet, L-tryptophan is critical in a number of metabolic functions and has been widely used in numerous research and clinical trials. This review provides a brief overview of the role of L-tryptophan in protein synthesis and a number of other metabolic functions. With emphasis on L-tryptophan’s role in synthesis of brain serotonin, details are provided on the research uses of L-tryptophan, particularly L-tryptophan depletion, and on clinical trials that have...

  10. The protective effect of L-tryptophan versus alpha lipoic acid against L-arginine-induced experimental acute pancreatitis in albino rats

    Lamia M. Farghaly* , Nagwan A. Sabak ** and Naglaa A. El-sherbeny

    2007-01-01

    Aim of the study: This study was conducted to investigate the possible protective effects of L- treptophan "a precursor of melatonin" and alpha lipoic acid against L- arginine-induced experimental acute pancreatitis in albino rats. Methods: Fourty adult male albino rats (200- 250g) were randomized into 4 groups (n= 10). Group I, the control group was given 0.9% saline intraperitoneally (i.p). Group II, was given 500 mg/100g L-arginine (i.p) as a single dose to induce acute pancreatitis. Group...

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

    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.

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

    Jenkins, Trisha A; Nguyen, Jason C D; Polglaze, Kate E; Bertrand, Paul P

    2016-01-01

    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. PMID:26805875

  13. Rotational spectrum of tryptophan

    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.

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

    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

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

    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 pAKTThr308 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

  16. Tryptophan Metabolism in Allergic Disorders.

    Gostner, Johanna M; Becker, Katrin; Kofler, Heinz; Strasser, Barbara; Fuchs, Dietmar

    2016-01-01

    Allergic diseases such as asthma and rhinitis, as well the early phase of atopic dermatitis, are characterized by a Th2-skewed immune environment. Th2-type cytokines are upregulated in allergic inflammation, whereas there is downregulation of the Th1-type immune response and related cytokines, such as interferon-x03B3; (IFN-x03B3;). The latter is a strong inducer of indoleamine 2,3-dioxygenase-1 (IDO-1), which degrades the essential amino acid tryptophan, as part of an antiproliferative strategy of immunocompetent cells to halt the growth of infected and malignant cells, and also of T cells - an immunoregulatory intervention to avoid overactivation of the immune system. Raised serum tryptophan concentrations have been reported in patients with pollen allergy compared to healthy blood donors. Moreover, higher baseline tryptophan concentrations have been associated with a poor response to specific immunotherapy. It has been shown that the increase in tryptophan concentrations in patients with pollen allergy only exists outside the pollen season, and not during the season. Interestingly, there is only a minor alteration of the kynurenine to tryptophan ratio (Kyn/Trp, an index of tryptophan breakdown). The reason for the higher tryptophan concentrations in patients with pollen allergy outside the season remains a matter of discussion. To this regard, the specific interaction of nitric oxide (NO∙) with the tryptophan-degrading enzyme IDO-1 could be important, because an enhanced formation of NO∙ has been reported in patients with asthma and allergic rhinitis. Importantly, NO∙ suppresses the activity of the heme enzyme IDO-1, which could explain the higher tryptophan levels. Thus, inhibitors of inducible NO∙ synthase should be reconsidered as candidates for antiallergic therapy out of season that may abrogate the arrest of IDO-1 by decreasing the production of NO∙. Considering its association with the pathophysiology of atopic disease, tryptophan metabolism may

  17. Traditional reactive carbonyl scavengers do not prevent the carbonylation of brain proteins induced by acute glutathione depletion

    Zheng, J; Bizzozero, O. A.

    2010-01-01

    This study investigated the effect of reactive carbonyl species (RCS)-trapping agents on the formation of protein carbonyls during depletion of brain glutathione (GSH). To this end, rat brain slices were incubated with the GSH-depletor diethyl maleate in the absence or presence of chemically different RCS scavengers (hydralazine, methoxylamine, aminoguanidine, pyridoxamine, carnosine, taurine and z-histidine hydrazide). Despite their strong reactivity towards the most common RCS, none of the ...

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

    Bandeira, Luana Graziella; Bortolot, Beatriz Salari; Cecatto, Matheus Jorand; Monte-Alto-Costa, Andréa; Romana-Souza, Bruna

    2015-01-01

    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 e...

  19. TRYPTOPHAN PROMOTES CHARITABLE DONATING

    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.

  20. Deuteration of tryptophan and perlolyrine

    Deuterated tryptophan was prepared by simple exchange reactions in DC1 or D2O solution. The yield and abundance of deuterated tryptophan obtained from using DC1 as the deuterium solute was 92% and 98.5% respectively, whereas that by using D2O was 95% and 96.2% respectively. Deuterated perlolyrine was synthesized starting from deuterated tryptophan via acid-catalyzed ring-closure, aromatization and hydrolysis, with a yield of 11.6% and abundance of about 95%. The labelled perlolyrine was suitable for studying drug metabolism

  1. Tryptophan auxotrophs of Rhizobium japonicum.

    Wells, S E; Kuykendall, L D

    1983-01-01

    Eleven tryptophan-requiring mutants of Rhizobium japonicum I-110 ARS were isolated after nitrous acid mutagenesis and fell into five groups based on characterization by supplementation with intermediates and enzyme assays.

  2. Traditional reactive carbonyl scavengers do not prevent the carbonylation of brain proteins induced by acute glutathione depletion.

    Zheng, J; Bizzozero, O A

    2010-03-01

    This study investigated the effect of reactive carbonyl species (RCS)-trapping agents on the formation of protein carbonyls during depletion of brain glutathione (GSH). To this end, rat brain slices were incubated with the GSH-depletor diethyl maleate in the absence or presence of chemically different RCS scavengers (hydralazine, methoxylamine, aminoguanidine, pyridoxamine, carnosine, taurine and z-histidine hydrazide). Despite their strong reactivity towards the most common RCS, none of the scavengers tested, with the exception of hydralazine, prevented protein carbonylation. These findings suggest that the majority of protein-associated carbonyl groups in this oxidative stress paradigm do not derive from stable lipid peroxidation products like malondialdehyde (MDA), acrolein and 4-hydroxynonenal (4-HNE). This conclusion was confirmed by the observation that the amount of MDA-, acrolein- and 4-HNE-protein adducts does not increase upon GSH depletion. Additional studies revealed that the efficacy of hydralazine at preventing carbonylation was due to its ability to reduce oxidative stress, most likely by inhibiting mitochondrial production of superoxide and/or by scavenging lipid free radicals. PMID:20001647

  3. Tryptophan Research in Panic Disorder

    Eduard Maron; Jakov Shlik; Nutt, David J

    2008-01-01

    A considerable body of evidence suggests the involvement of serotonin neurotransmission in the pathogenesis of panic disorder. Research on pathways and functions of tryptophan, an essential amino acid converted into serotonin, may advance our understanding of serotonergic actions in panic disorder and related phenomena. The investigative approaches in this field include manipulations of tryptophan availability as well as genetic association and functional brain imaging studies. In this review...

  4. Enhanced Surfactant Adsorption via Polymer Depletion Forces: A Simple Model for Reversing Surfactant Inhibition in Acute Respiratory Distress Syndrome

    Stenger, Patrick C.; Zasadzinski, Joseph A.

    2006-01-01

    Lung surfactant adsorption to an air-water interface is strongly inhibited by an energy barrier imposed by the competitive adsorption of albumin and other surface-active serum proteins that are present in the lung during acute respiratory distress syndrome. This reduction in surfactant adsorption results in an increased surface tension in the lung and an increase in the work of breathing. The reduction in surfactant adsorption is quantitatively described using a variation of the classical Smo...

  5. Developing novel therapeutic strategies for acute lung injury and infection-peripheral blood monocyte depletion and prophylactic antimicrobial therapy

    Dhaliwal, Kanwaldeep

    2013-01-01

    BACKGROUND Acute lung injury (ALI) and nosocomial pneumonia are major causes of morbidity and mortality. There are 200,000 cases per year of ALI in the US with a mortality of 40%. On the intensive care unit (ICU), ALI accounts for over 40% of all ventilated patients at any one time. Despite this huge burden on healthcare and the relatively high prevalence, no therapies currently exist in clinical practice that attenuate the condition. The pathophysiology and aetiology of ALI is...

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

    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

  7. Metabolism of an oral tryptophan load. I: Effects of dose and pretreatment with tryptophan.

    Green, A. R.; Aronson, J K; Curzon, G; Woods, H F

    1980-01-01

    1 The metabolism of three oral doses of L-tryptophan (50, 25 and 10 mg/kg) in healthy young males has been investigated. 2 There was a linear relationship between both peak and area under curve of the total plasma tryptophan concentrations whilst the relationship between these parameters and plasma free tryptophan was hyperbolic. 3 Before the tryptophan load about 85% of plasma tryptophan was bound to albumin. As plasma tryptophan concentrations increased there was a hyperbolic increase in fr...

  8. Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury

    Looney, Mark R.; Nguyen, John X.; Hu, Yongmei; Van Ziffle, Jessica A.; Lowell, Clifford A.; Matthay, Michael A

    2009-01-01

    Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality in the US. Previously, we established an immune-mediated TRALI mouse model, wherein mice with cognate antigen were challenged with MHC class I mAb. In this study, when mice housed in a rodent, specific pathogen–free barrier room were challenged with MHC I mAb, there was significant protection from TRALI compared with nonbarrier mice. Priming mice with LPS restored lung injury with mAb challe...

  9. Tryptophan supplementation and the response to unfairness in healthy volunteers

    Hilal eCerit

    2015-07-01

    Full Text Available Experimental manipulation of serotonin (5-HT availability has been shown to modulate social behavior. For instance, serotonin depletion increased the rejection rates of unfair offers in the Ultimatum Game (UG, whereas a single dose of the serotonin reuptake inhibitor (citalopram decreased rejection rates. These effects were observed immediately after the manipulation. The aim of this study was to investigate the effect of prolonged Tryptophan (TRP supplementation on UG performance in healthy individuals. A randomized double-blind placebo-controlled design was used. Healthy volunteers (N=47 completed the UG before and after a 6-day intervention of TRP (2.8 g/day or placebo. Impulsivity was measured with a Go-Stop task. The overall analyses showed that TRP supplementation had no significant effect on UG scores, but the direction of the effect was opposite from expectations. Because repeated performance of the UG may lead to unwanted learning effects or strategical changes, additional analyses were conducted in which participants (N=7 who accepted all offers on the second measurement were excluded. These analyses revealed that the TRP-group rejected very unfair offers more often than the placebo group. The groups did not differ on impulsivity. Increasing serotonin through TRP supplements increased the rejection of very unfair offers. The direction of our findings is inconsistent with earlier studies that showed that increasing 5-HT availability results in less rejection of unfair offers. The current findings thus importantly suggest that effects of acute vs. prolonged enhancement of 5-HT availability may differ. Also, the outcomes show that the UG is a complex task and participants’ decisions may depend on context, e.g., prior experience with the task.

  10. T-cell depleted haploidentical three loci mismatched bone-marrow and peripheral blood stem cell transplantation in acute leukaemia patients

    Objectives: Allogeneic bone-marrow transplantation (BMT) is an established treatment for many haematological malignancies. Unfortunately, most patients lack an HLA geno typically identical sibling and require an alternative donor, such as an HLA-haploidentical mismatched related donor, an HLA phenotypically matched or partially mismatched unrelated donor or an HLA-similar cord blood stem cell donor. However, these types of BMT increase the risk of graft-versus-host disease (GvHD), graft failure, delayed immuno reconstitution and fatal infection that observed after a sibling matched donor. Many centers are exploring the possibility of using donors other than matched sibling. Our approach has been to employ T-cell depleted mismatched haploidentical familial donor BMT to solve the problem of GvHD, a highly immuno- and myelo-suppressive conditioning regimen to reduce the incidence of graft failure and relapse, a graft inoculum plus G-CSF donor mobilized peripheral blood stem cells (PBSC) to overcome the host-versus-graft barrier. Patients and methods: Thirty-six patients (25 male, 11 female; median age 22 years, range 2-51) were treated with an allogeneic T-depleted haploidentical three loci mismatched bone-marrow and G-CSF mobilized PBSC transplantation from a familiar donor (18 siblings, 17 parents and 1 cousin) between March 1993 and June 1995. All had high-risk or advanced stage acute myeloid (12) or acute lymphoid (24) leukaemia; 18 were in haematological complete remission (CR) and 18 in chemo resistant relapse. Patients were conditioned with 8 Gy single dose TBI administered on day -5 at an instantaneous dose-rate of 13.4-31.7 cGy/min/midplane and average of 6.7-12.12 cGy/min/midplane. Shields were used to reduce the lung dose to 7 Gy in the first 23 cases and to 6 Gy in the last 13. 10 mg/Kg thiotepa were administered on day -4, 5 mg/Kg rabbit ATG from day -4 to day -1, 60 or 50 mg/Kg/cyclophosphamide on days -3 and -2. Bone-marrow and PBSC were infused on day

  11. The Toxicity of Depleted Uranium

    Wayne Briner

    2010-01-01

    Depleted uranium (DU) is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a c...

  12. Nutritional Aspect of Tryptophan Metabolism

    Tsutomu Fukuwatari; Katsumi Shibata

    2013-01-01

    Mammals, including humans, can synthesize the vitamin nicotinamide from tryptophan in the liver. The resultant nicotinamide is distributed to non-hepatic tissues. We have studied the effects of changes in tryptophan–nicotinamide metabolism on niacin nutritional status. The liver plays a critical role in nicotinamide supply. Animal studies showed that the tryptophan–nicotinamide pathway is affected by physiological conditions, the presence of disease, nutrients, hormones, and chemicals. Human ...

  13. Autoxidation of tryptophan in aqueous solutions

    LJUBICA R. JOSIMOVIC; IVANA A. JANKOVIC

    2001-01-01

    Autoxidation of tryptophan was investigated in aqueous solutions by the gamma radiolytic technique. The oxygen uptake and formation of peroxide materials was followed as a function of pH, dose rate and concentration of tryptophan. The results obtained indicate that TrpH(OH)OO. radicals react with tryptophan by adduct formation thus propagating autoxidation. The chain propagation length (CPL) for a 2·102 mol dm3 tryptophan solution at pH 9.5 and a dose rate 0.01 Gy s1 was estimated to be ~ 5.8...

  14. 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

    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.

  15. Inhibition of tryptophan - pyrrolase activity and elevation of brain tryptophan concentration by fluoxetine in rats

    Objective: To investigate in-vitro as well as in-vivo effects of various doses of fluoxetine (SSRI) on tryptophan metabolism in rates. Results: In in-vitro (10 - 1000 mM) as well in-vivo (0.5 - 30 mg/kg body wt.) studies, fluoxetine showed a statistically significant inhibition of rat liver tryptophan pyrrolase (tryptophan-2,3-dioxygenase; EC 1.13.11.11) activity. Significant increases were noted at 10 and 30 mg/kg doses in brain, serum (total and free) and liver L-tryptophan concentrations. Similarly, serum non-esterified free fatty acids showed a significant increase at both doses. There was no effect on serum glucose and albumin concentrations. Conclusion: It is suggested that major mechanism of action of fluoxetine is that of elevating brain tryptophan concentration and hence 5-HT synthesis by increasing the availability of circulating tryptophan to the brain secondarily to inhibition of major tryptophan degrading enzyme, hepatic tryptophan pyrrolase. It is assumed that fluoxetine inhibits the binding of apoenzyme form of tryptophan pyrrolase with its cofactor haem. The results are discussed in relation to possible involvement of disturbed hepatic tryptophan metabolism in depressive illness. (author)

  16. The Toxicity of Depleted Uranium

    Wayne Briner

    2010-01-01

    Full Text Available Depleted uranium (DU is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed.

  17. Serotonin release varies with brain tryptophan levels

    Schaechter, Judith D.; Wurtman, Richard J.

    1990-01-01

    This study examines directly the effects on serotonin release of varying brain tryptophan levels within the physiologic range. It also addresses possible interactions between tryptophan availability and the frequency of membrane depolarization in controlling serotonin release. We demonstrate that reducing tryptophan levels in rat hypothalamic slices (by superfusing them with medium supplemented with 100 microM leucine) decreases tissue serotonin levels as well as both the spontaneous and the electrically-evoked serotonin release. Conversely, elevating tissue tryptophan levels (by superfusing slices with medium supplemented with 2 microM tryptophan) increases both the tissue serotonin levels and the serotonin release. Serotonin release was found to be affected independently by the tryptophan availability and the frequency of electrical field-stimulation (1-5 Hz), since increasing both variables produced nearly additive increases in release. These observations demonstrate for the first time that both precursor-dependent elevations and reductions in brain serotonin levels produce proportionate changes in serotonin release, and that the magnitude of the tryptophan effect is unrelated to neuronal firing frequency. The data support the hypothesis that serotonin release is proportionate to intracellular serotonin levels.

  18. Volume-independent reductions in glomerular filtration rate in acute chloride-depletion alkalosis in the rat. Evidence for mediation by tubuloglomerular feedback.

    Galla, J. H.; Bonduris, D N; Sanders, P W; Luke, R. G.

    1984-01-01

    We have recently described reduced superficial nephron glomerular filtration rate (SNGFR) in chloride-depletion alkalosis (CDA) without volume depletion. To elucidate the mechanism of this phenomenon, we studied three degrees of increasing severity of CDA (groups CDA-1, 2, and 3) produced by one or two peritoneal dialyses against 0.15 M NaHCO3 and electrolyte infusions of different Cl and HCO3 content in Sprague-Dawley rats; control rats (CON) were dialyzed against and infused with Ringers-HC...

  19. Tryptophan protection of phage from ultraviolet irradiation

    Bacteriophage SP02c12 and its isolated DNA were irradiated at 254 nm in tryptophan solutions. At a concentration of 10 mM, the amino acid exerted a protective effect on intact virus. The magnitude of this effect depended upon the length of time elapsed between mixing and irradiation. No protection was observed for solutions irradiated immediately after mixing. Tryptophan did not have a significant effect on UV sensitivity of the isolated viral DNA. No covalent crosslinking of tryptophan to DNA was observed. (author)

  20. l-Tryptophan Production by Achromobacter liquidum

    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, 6...

  1. Stable isotope labeled L-tryptophan

    Stable isotope labeled L-tryptophan is an application of nucleus technology in amino acids. Progresses in stable isotope labeled L-tryptophan in recent years are reviewed.. In the respect of synthesis, in addition to the methods of organic synthesis and isotope exchange, the microbial technology which has the advantage of U-label and construct has been used widely. In the respect of applications, stable isotope labeled L-tryptophan as trace has been used widely in yields of medicine, biology and chemistry et al. Along with the development of protein engineering, molecular biology and peptide drugs, they will have a fine future. (authors)

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

    David P. Hamilton; Stephen Craig Cary; Frode Rise; Miles, Christopher O.; Jonathan Puddick; Susanna A. Wood; Michèle R. Prinsep; Wilkins, Alistair L.

    2013-01-01

    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 chromatogr...

  3. Identity determinants of E. coli tryptophan tRNA.

    Himeno, H; T. Hasegawa; Asahara, H; Tamura, K.; Shimizu, M

    1991-01-01

    The first base pair of the acceptor stem A1-U72 and the discriminator base G73, as well as the anticodon nucleotides, characterize the tryptophan tRNA in E. coli. To determine the contribution of these nucleotides to the tryptophan acceptor activity, various transcripts of E. coli tryptophan tRNA mutants were constructed. Substitutions of the discriminator base G73, which is conserved within prokaryotic tryptophan tRNAs, impaired aminoacylation with tryptophan. Substitutions of other purine-p...

  4. Depleted uranium

    Full text: The Director General of the International Atomic Energy Agency (IAEA), Mohamed ElBaradei, issued today the following statement: The IAEA has been involved in United Nations efforts relating to the impact of the use of depleted uranium (DU) ammunition in Kosovo. It has supported the United Nations Environment Programme (UNEP) in the assessment which it is making, at the request of the Secretary-General, of that impact. In this connection, in November 2000, Agency experts participated in a UNEP-led fact-finding mission in Kosovo. DU is only slightly radioactive, being about 40% as radioactive as natural uranium. Chemically and physically, DU behaves in the same way as natural uranium. The chemical toxicity is normally the dominant factor for human health. However, it is necessary to carefully assess the impact of DU in the special circumstances in which it was used, e.g. to determine whether it was inhaled or ingested or whether fragments came into close contact with individuals. It is therefore essential, before an authoritative conclusion can be reached, that a detailed survey of the territory in which DU was used and of the people who came in contact with the depleted uranium in any form be carried out. In the meantime it would be prudent, as recommended by the leader of the November UNEP mission, to adopt precautionary measures. Depending on the results of the survey further measures may be necessary. The Agency, within its statutory responsibilities and on the basis of internationally accepted radiation safety standards, will continue to co-operate with other organizations, in particular WHO and UNEP, with a view to carrying out a comprehensive assessment. Co-operation by and additional information from NATO will be prerequisites. The experience gained from such an assessment could be useful for similar studies that may be carried out elsewhere in the Balkans or in the Gulf. (author)

  5. Regulation of tryptophan genes in Rhizobium leguminosarum.

    Holmgren, E; I. P. Crawford

    1982-01-01

    Twelve tryptophan auxotrophs of Rhizobium leguminosarum were characterized biochemically. They were grown in complex and minimal media with several carbon sources, in both limiting and excess tryptophan. Missing enzyme activities allowed assignment of all mutant to the trpE, trpD, trpB, or trpA gene, confirming earlier results with the same mutants (Johnston et al., Mol. Gen. Genet. 165:323-330, 1978). In regulatory experiments, only the first enzyme of the pathway, anthranilate synthase, res...

  6. 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

    Crespo, Elena; Lucia, Marc; Cruzado, Josep M.; Luque, Sergio; Melilli, Edoardo; Manonelles, Anna; Lloberas, Nuria; Torras, Joan; Grinyó, Josep M.; Bestard, Oriol

    2015-01-01

    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 therapy. PMID:25689405

  7. Tryptophan auxotrophs were obtained by random transposon insertions in the Methanococcus maripaludis tryptophan operon.

    Porat, Iris; Whitman, William B

    2009-08-01

    Methanococcus maripaludis is an anaerobic, methane-producing archaeon that utilizes H(2) or formate for the reduction of CO(2) to methane. Tryptophan auxotrophs were constructed by in vitro insertions of the Tn5 transposon into the tryptophan operon, followed by transformation into M. maripaludis. This method could serve for rapid insertions into large cloned DNA regions. PMID:19566682

  8. Tryptophan auxotrophs were obtained by random transposon insertions in the Methanonococcus maripaludis tryptophan operon

    Porat, Iris; Whitman, William B.

    2009-01-01

    Methanococcus maripaludis is an anaerobic, methane-producing archaeon that utilizes H2 or formate for the reduction of CO2 to methane. Tryptophan auxotrophs were constructed by in vitro insertions of the Tn5 transposon into the tryptophan operon, followed by transformation into M. maripaludis. This method could serve for rapid insertions into large cloned DNA regions.

  9. Model reactions concerning the effects of gamma rays on tryptophan and peptides containing tryptophan

    The stability of heterocyclic reactive amino acid tryptophan (TRP) against the effects of gamma rays was examined in an aqueous medium. When doses in the range between 5 and 56 kGray were tested, the disintegration of tryptophan was seen toshow linear increases that were consistent with the intensity of irradiation. The radiolysis products obtained were condensed by means of high pressure liquid chromatography and subsequently determined using a method, in which gas chromatogr aphy was combined with mass spectroscope techniques. Irradiation was found to be the melanins of indole. The effects of the primary structure of peptides on the radiosensitivity of tryptophan are still open to discussion, as is the role of the neighbourhood groups in dipeptides and tripeptides that contain tryptophan. A systematic analysis of radiolysis products of tryptophan may provide valuable information on the development of mutagenic and carcinogenic radiolysis products during the irradiation of food products. (JH)

  10. Radiation induced decomposition of tryptophan in the presence of oxygen

    Tryptophan decomposition in oxygenated aqueous solutions in neutral media was investigated by gamma and pulsed electron irradiation. By using pulse radiolysis it was found that 27% of tryptophan OH-adducts eliminate water. Tryptophan neutral radical, Trp, thus formed reacts rapidly with O2-.. The remaining tryptophan OH-adducts react with oxygen to give peroxy radicals which may eliminate O2-., produce N-formylkynurenine and disproportionate yielding organic peroxides. Peroxy radicals derived from tryptophan H-adducts regenerate tryptophan by the elimination of HO2., and recombine with TrpH(OH)OO. radicals producing organic peroxides. (author)

  11. Tryptophan-Restriction Diets Help to Maintain L-Tryptophan Homeostasis in Tryptophan 2,3-Dioxygenase Knockout Mice

    Akihiro Maeta; Tsutomu Fukuwatari; Hiroshi Funakoshi; Toshikazu Nakamura; Katsumi Shibata

    2013-01-01

    We hypothesized that the requirements of essential nutrients are dependent upon catabolic abilities. Mice lacking L-tryptophan 2,3-dioxygenase (TDO) are available. The body concentration of L-tryptophan (L-Trp) has been reported to be higher in TDO-deficient mice than in wild-type (WT) mice. We examined the requirement of an appropriate L-Trp level for TDO-deficient mice using several biomarkers. TDO-deficient mice were fed a 10% amino-acid mixture diet containing 0.06%, 0.08%, and 0.17% L-Tr...

  12. Tryptophan metabolism in vitamin B6-deficient mice

    Bender, D A; Njagi, E. N.; Danielian, P. S.

    1990-01-01

    Vitamin B6 deficiency was induced in mice by maintenance for 4 weeks on a vitamin B6-free diet. Tryptophan metabolism was assessed by determining the urinary excretion of tryptophan metabolites, the metabolism of [14C]tryptophan in vivo and the formation of tryptophan and niacin metabolites by isolated hepatocytes. The vitamin B6-deficient animals excreted more xanthurenic acid and 3-hydroxykynurenine, and less of the niacin metabolites N1-methyl nicotinamide and methyl-2-pyridone-4-carboxami...

  13. Eosinophilic fasciitis associated with L-tryptophan ingestion.

    Hamilton, M. E.

    1991-01-01

    A 62 year old woman taking L-tryptophan developed eosinophilic fasciitis shortly after starting an exercise class. She received prednisone without benefit but improved after azathioprine treatment was started and L-tryptophan was discontinued. As products containing L-tryptophan have recently been implicated in development of the eosinophilia-myalgia syndrome it is suggested that the use of L-tryptophan might have contributed to the development of eosinophilic fasciitis in this patient. Simil...

  14. Tryptophan biosynthesis in the marine luminous bacterium Vibrio harveyi.

    Bieger, C D; I. P. Crawford

    1983-01-01

    Tryptophan biosynthetic enzyme levels in wild-type Vibrio harveyi and a number of tryptophan auxotrophs of this species were coordinately regulated over a 100-fold range of specific activities. The tryptophan analog indoleacrylic acid evoked substantial derepression of the enzymes in wild-type cells. Even higher enzyme levels were attained in auxotrophs starved for tryptophan, regardless of the location of the block in the pathway. A derepressed mutant selected by resistance to 5-fluorotrypto...

  15. Destruction of tryptophan during the aerobic oxidation of sulfite ions

    Tryptophan was rapidly destroyed aerobically in the presence of Mn2+ and sulfite. The rate of destruction was greatly increased when horseradish peroxidase was added. The optimal pH for the reaction was 8.0. The destruction of tryptophan was dependent on the aerobic oxidation of sulfite. Superoxide dismutase inhibited sulfite oxidation and thus inhibited the tryptophan destruction. Tracer studies using 14C indicate that tryptophan is converted into at least 4 products

  16. Complete remission of VZV reactivation treated with valganciclovir in a patient with total lymphocyte depletion and acute kidney injury after allogeneic bone marrow transplantation.

    Maximova, Natalia; Antonio, Pizzol; Marilena, Granzotto; Rovere, Francesca; Tamaro, Paolo

    2015-01-01

    Varicella zoster virus (VZV), a threat for hematopoietic stem cell transplantation (HSCT) recipients, is still one of the most common viral pathogens that affect these patients with a reported incidence ranging between 17% and 50% in the post transplantation period. Valganciclovir (V-GCV), a valine ester pro-drug of GCV orally administrable, has recently shown great activity against CMV infections, but there are no reports of its clinical efficacy against VZV. We here report a case history of a patient with positive serologic test for VZV, who underwent allogeneic HSCT and developed an atypical varicella-like illness. First-line therapy with foscarnet had to be discontinued due rapid development of renal impairment (creatinine: 2.60 mg/dL, urea: 130.6 mg/dL) and therefore was switched to V-GCV. The renal impairment and skin lesions of the patient fully recovered after few days of therapy, even though the patient had complete lymphocyte depletion. This is the first case of a patient with chickenpox-like illness treated successfully with V-GCV. PMID:25131855

  17. Similarity in the acute cytotoxic response of mammalian cells to mercury (II) and x-rays: DNA damage and glutathione depletion

    Pronounced strand breakage of DNA analyzed elution techniques was produced in intact Chinese hamster ovary cells by 25 μM HgCl2 within 1 hr or 100 μM HgCl2 within 15 min. HgCl2-induced strand breakage was directly proportional to concentration up to 100 μM and to time within 1 hr. Levels of reduced glutathione decreased following HgCl2 in parallel with the induction of DNA strand breakage. Evidence is presented that this rapid and pronounced induction of DNA strand breaks and other cytotoxic responses following acute exposure to HgCl2 resembles the cellular effects of X-rays

  18. Requirement of young pigs for apparent ileal digestible tryptophan

    Schutte, J.B.; Verstraten, A.J.M.A.; Lenis, N.P.; Jong, de, P.; Diepen, van, C.A.

    1995-01-01

    In 5 growth trials with a total of 420 pigs, tryptophan requirements from 20 to 40 kg liveweight were estimated. L-Tryptophan 0, 0.15, 0.30, 0.45 and 0.60 g/kg was added to a basal diet containing tapioca, barley and maize, with CP 162 g/kg and tryptophan 1.65 g/kg. The control diet was supplemented with lysine, methionine plus cystine, threonine, isoleucine, valine and histidine to assure that only tryptophan was limiting pig performance. Diets were freely given as pellets. Total tryptophan ...

  19. Haploidentical Transplantation Without In Vitro T-Cell Depletion Results in Outcomes Equivalent to Those of Contemporaneous Matched Sibling and Unrelated Donor Transplantation for Acute Leukemia.

    Yu, Sijian; Fan, Qian; Sun, Jing; Fan, Zhiping; Zhang, Yu; Jiang, Qianli; Huang, Fen; Xuan, Li; Dai, Min; Zhou, Hongsheng; Liu, Hui; Liu, Qi-Fa

    2016-03-01

    The aim of the study is to determine whether HLA-haploidentical-related donor (HRD) transplant can achieve equivalent outcomes and have stronger GVL compared to HLA-matched sibling donor (MSD) and HLA-matched unrelated donor (MUD) transplants.A total of 355 consecutive patients with acute leukemia undergoing allogeneic transplant at our single institute between March 2008 and March 2014 were enrolled in this retrospective investigation.Of the 355 patients, 96 cases received HRD, 153 MSD, and 106 MUD transplants. HRD transplant was associated with higher incidences of grade II to IV aGVHD (40.6%) compared with MSD (23.5%, P = 0.002) and MUD transplants (34.0%, P = 0.049), whereas incidences of grade III to IV aGVHD (11.4%, 7.8%, 10.5%, respectively; P = 0.590) and cGVHD (29.5%, 24.0%, 29.5%, respectively; P = 0.538) did not differ among 3 groups. Five-year relapse rates were 19.2%, 26.8%, and 23.0% in 3 groups, respectively (P = 0.419). However, of 206 high-risk patients, the relapse rate in HRD transplant was lower than in MSD transplant (23.8% vs 41.9%, P = 0.026). Multivariate analysis showed that HRD had beneficial impact on relapse (for MSD: P = 0.006). Five-year transplant-related mortality was lower in MSD transplant compared with those in HRD (17.3% vs 26.4%, P = 0.041) and MUD transplants (17.3% vs 24.1%, P = 0.037). Five-year overall survival were 60.4%, 64.6%, and 61.0%, respectively, in HRD, MSD, and MUD groups (P = 0.371); 5-year disease-free survival were 59.6%, 58.8%, and 54.9%, respectively (P = 0.423).Our results suggest that HRD transplant results in outcomes equivalent to MSD and MUD transplants. HRD might carry a superior GVL effect compared to MSD for high-risk patients. PMID:26986108

  20. Electron-impact-induced tryptophan molecule fragmentation

    In our investigation, we have studied the interactions of low-energy (<70 eV) electrons with tryptophan molecule belonging to the essential amino acids in order to probe the intrinsic properties of the molecule and trace its change(s) under the electron impact. The fragmentation of a gas-phase tryptophan molecule by low-energy electrons was studied both experimentally and theoretically. Various positively charged fragments were observed and analyzed. A special attention was paid to the energy characteristics of the ionic fragment yield. The geometrical parameters of the initial molecule rearrangement were also analyzed. The fragmentation observed was due to either a simple bond cleavage or more complex reactions involving molecular rearrangements

  1. Expression, Purification and Characterisation of Tryptophan Hydroxylases

    Windahl, Michael Skovbo

    2007-01-01

    og co-substratet tetrahydrobiopterin spalter dioxygen (O2) så det ene oxygen-atom indsættes i aminosyren tryptophan. Der findes to forskellige former af TPH: TPH-1 findes flere forskellige steder i kroppen, mens TPH-2 findes i hjernen hvor det har afgørende betydning for mængden af serotonin i...... tetrahydro-biopterin og O2. Denne opdagelse er meget vigtig for udvikling af lægemidler, som individuelt kan regulere TPH-1s eller TPH-2s enzymaktivitet. Desuden er det vist, at tryptophan binder til TPH før tetrahydrobiopterin og O2. Den 3-dimensionelle struktur af TPH-1 er bestemt ved brug af...

  2. Purification and Characterization of Tryptophan Hydroxylase

    Haahr, Lærke Tvedebrink; Christensen, Hans Erik Mølager

    2012-01-01

    Denne afhandling omhandler oprensning og karakterisering af jern enzymet tryptophanhydroxylase (TPH). TPH eksisterer i to isoformer, TPH1 og TPH2. Hver isoform består af 3 strukturelt forskellige domæner: det regulatoriske, det katalytiske og det tetrameriserende domæne. TPH katalyserer omdannelsen af tryptophan til 5-hydroxytryptophan, hvilket er det hastighedsbestemmende trin i biosyntesen af serotonin. Serotonin er en vigtig neurotransmitter, som er involveret i en række psykiske sygdommme...

  3. Tryptophan structure and dynamics using GROMOS

    The desire to use tryptophan as a fluorescent probe to study protein motion has motivated studies on tryptophan in aqueous solution. Tryptophan's biexponential fluorescence decay in solution has given rise to models which account for this behavior by postulating the existence of rotamers about the C/sub α/-C/sub β/ bond. These models require that the rotamers do not interconvert during the fluorescence lifetime; this assumption has not been verified. Further, there are certain peculiarities in assigning particular fluorescence lifetimes to these rotamers on the basis of proximity of the charged quenching groups. To address these issues the authors have used energy minimization and classical molecular dynamics as bases for transition rate and population estimates. These suggest that the C/sub β/-C/sub γ/ dihedral (chi/sub 2/) determines the fluorescence lifetime for equilibrating groups of C/sub α/-C/sub β/ rotamers. The energy minimization was similar to that already reported in the literature, but with GROMOS charges (for tryptophan in solution) and GROMOS interaction potentials. A potential surface for the energies of chi/sub 1/,chi/sub 2/ conformations was generated by constraining the dihedrals and minimizing the potential energy of the remaining degrees of freedom. Energy barriers between conformers range from about 3 kcal/mol to about 8 kcal/mol. The smaller barriers correspond to chi/sub 1/ rotations. Seven 100-psec classical dynamics trajectories were calculated for the system coupled to a heat bath with a time constant of 0.1 psec (solvent molecules are not explicityly included)

  4. DEPLETED URANIUM TECHNICAL WORK

    The Depleted Uranium Technical Work is designed to convey available information and knowledge about depleted uranium to EPA Remedial Project Managers, On-Scene Coordinators, contractors, and other Agency managers involved with the remediation of sites contaminated with this mater...

  5. 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 Metabolites123

    Rios-Avila, Luisa; Nijhout, H Frederik; Reed, Michael C.; SITREN, HARRY S.; Gregory, Jesse F.

    2013-01-01

    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 enz...

  6. Tryptophan availability modulates serotonin release from rat hypothalamic slices

    Schaechter, Judith D.; Wurtman, Richard J.

    1989-01-01

    The relationship between the tryptophan availability and serononin release from rat hypothalamus was investigated using a new in vitro technique for estimating rates at which endogenous serotonin is released spontaneously or upon electrical depolarization from hypothalamic slices superfused with a solution containing various amounts of tryptophan. It was found that the spontaneous, as well as electrically induced, release of serotonin from the brain slices exhibited a dose-dependent relationship with the tryptophan concentration of the superfusion medium.

  7. Tryptophan-Degrading Enzymes in Tumoral Immune Resistance

    van Baren, Nicolas; Van den Eynde, Benoît J

    2015-01-01

    Tryptophan is required for T lymphocyte effector functions. Its degradation is one of the mechanisms selected by tumors to resist immune destruction. Two enzymes, tryptophan-2,3-dioxygenase and indoleamine 2,3-dioxygenase 1, control tryptophan degradation through the kynurenine pathway. A third protein, indoleamine 2,3-dioxygenase 2, was identified more recently. All three enzymes were reported to be expressed in tumors, and are candidate targets for pharmacological inhibition aimed at restor...

  8. Radiolysis of aqueous-ethanolic solution of tryptophan

    The effect of ethanol on radiation stability of tryptophan during γ-irradiation of its aqueous solutions was investigated. In comparison with radiation losses of tryptophan irradiated in pure water, the losses in aqueous-ethanolic solutions are considerably higher and they increase with increasing ethanol concentration. Basic radiation products of tryptophan formed on irradiation of its aqueous-ethanolic solutions in consequence of the reaction of tryptophan with acetaldehyde as the main product of radiolysis of ethanol were followed by paper electrophoresis. (author)

  9. Gamma-radiolysis of aqueous solutions of tryptophan

    The nature of stable radiolytic products of tryptophan was investigated under different experimental conditions. Solutions of various tryptophan concentrations (10-2-10-4 mol dm-3) at pH 2 and 6.6 were analysed by paper and thin layer chromatography. In deaerated neutral solutions six products, which appeared to be invariant of initial tryptophan concentration, were observed. Chromatograms developed from deaerated solution at pH 2 revealed only one spot. In N2O-saturated solutions four products whose relative concentrations depended on the initial tryptophan concentration were observed. (author)

  10. Effect of tryptophan administration on tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in human lumbar and cisternal cerebrospinal fluid.

    Young, S N; Gauthier, S.

    1981-01-01

    Tryptophan 5-hydroxyindoleacetic acid and indoleacetic acid were measured in cerebrospinal fluid taken during pneumoencephalography from patients, some of whom took a 3 g or 6 g tryptophan load at various times before. Measurements were made on both lumbar and cisternal cerebrospinal fluid and the results showed similarities between indoleamine metabolism in human brain and spinal cord. Our data suggested that (1) the blood-brain barrier active transport system for tryptophan is not far from ...

  11. Metabolism of an oral tryptophan load. II: Effect of pretreatment with the putative tryptophan pyrrolase inhibitors nicotinamide or allopurinol.

    Green, A. R.; Aronson, J K; Curzon, G; Woods, H F

    1980-01-01

    1 The effect of seven days administration of either allopurinol (300 mg daily) or nicotinamide (500 mg twice daily) on the metabolism of an oral L-tryptophan load (50 mg/kg) has been investigated. 2 Administration of either drug failed to alter the plasma total or free tryptophan or plasma kynurenine curve. Nor was the urinary excretion of tryptophan, kynurenine, 5-hydroxyindoleacetic acid or indole acetic acid influenced. 3 Allopurinol pretreatment did increase the volume of distribution of ...

  12. Depleted Uranium Management

    The paper considers radiological and toxic impact of the depleted uranium on the human health. Radiological influence of depleted uranium is less for 60 % than natural uranium due to the decreasing of short-lived isotopes uranium-234 and uranium-235 after enrichment. The formation of radioactive aerosols and their impact on the human are mentioned. Use of the depleted uranium weapons has also a chemical effect on intake due to possible carcinogenic influence on kidney. Uranium-236 in the substance of the depleted uranium is determined. The fact of beta-radiation formation in the uranium-238 decay is regarded. This effect practically is the same for both depleted and natural uranium. Importance of toxicity of depleted uranium, as the heavier chemical substance, has a considerable contribution to the population health. The paper analyzes risks regarding the use of the depleted uranium weapons. There is international opposition against using weapons with depleted uranium. Resolution on effects of the use of armaments and ammunitions containing depleted uranium was five times supported by the United Nations (USA, United Kingdom, France and Israel did not support). The decision for banning of depleted uranium weapons was supported by the European Parliament

  13. Chemical Modification of Tryptophan Residues in Pullulanase

    2005-01-01

    Tryptophan(Trp)residues in pullulanase have been chemically modified with N-bromossuccinimide(NBS). The results of ultraviolet spectra indicated that there are 18 Trp residues in pullulanase and nine of them are located on the surface of the enzyme. Three of these Trp residues are none-essential residues which showed the fastest reaction speed by Zhou's plot. Two of the seven relative faster reacting residues are essential for the activity of the enzyme. The other eight are none-reactive residues with lowest reaction speed.

  14. One-step of tryptophan attenuator inactivation and promoter swapping to improve the production of L-tryptophan in Escherichia coli

    Gu Pengfei; Yang Fan; Kang Junhua; Wang Qian; Qi Qingsheng

    2012-01-01

    Abstract Background L-tryptophan is an aromatic amino acid widely used in the food, chemical and pharmaceutical industries. In Escherichia coli, L-tryptophan is synthesized from phosphoenolpyruvate and erythrose 4-phosphate by enzymes in the shikimate pathway and L-tryptophan branch pathway, while L-serine and phosphoribosylpyrophosphate are also involved in L-tryptophan synthesis. In order to construct a microbial strain for efficient L-tryptophan production from glucose, we developed a one ...

  15. Characterisation of the tryptophan synthase alpha subunit in maize

    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.

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

    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. π-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 10-3 mol L-1, the limiting molecular area of lecithin increased from 110.5 to 138.5 A2, but the collapse pressure of the monolayer decreased from 47.6 to 42.3 mN m-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 106 Ω and 3.573 x 10-8 F to 1.391 x 106 Ω and 3.340 x 10-8 F when the concentration of tryptophan increased from 0 to 2 x 10-3 mol L-1. Correspondingly, the breakdown voltage of s-BLM decreased from 2.51 to 1.72 V.

  17. Depleted uranium in Japan

    In Japan, depleted uranium ammunition is regarded as nuclear weapons and meets with fierce opposition. The fact that US Marines mistakenly fired bullets containing depleted uranium on an island off Okinawa during training exercises in December 1995 and January 1996, also contributes. The overall situation in this area in Japan is outlined. (P.A.)

  18. Management of depleted uranium

    Large stocks of depleted uranium have arisen as a result of enrichment operations, especially in the United States and the Russian Federation. Countries with depleted uranium stocks are interested in assessing strategies for the use and management of depleted uranium. The choice of strategy depends on several factors, including government and business policy, alternative uses available, the economic value of the material, regulatory aspects and disposal options, and international market developments in the nuclear fuel cycle. This report presents the results of a depleted uranium study conducted by an expert group organised jointly by the OECD Nuclear Energy Agency and the International Atomic Energy Agency. It contains information on current inventories of depleted uranium, potential future arisings, long term management alternatives, peaceful use options and country programmes. In addition, it explores ideas for international collaboration and identifies key issues for governments and policy makers to consider. (authors)

  19. Water Depletion Threatens Agriculture

    Brauman, K. A.; Richter, B. D.; Postel, S.; Floerke, M.; Malsy, M.

    2014-12-01

    Irrigated agriculture is the human activity that has by far the largest impact on water, constituting 85% of global water consumption and 67% of global water withdrawals. Much of this water use occurs in places where water depletion, the ratio of water consumption to water availability, exceeds 75% for at least one month of the year. Although only 17% of global watershed area experiences depletion at this level or more, nearly 30% of total cropland and 60% of irrigated cropland are found in these depleted watersheds. Staple crops are particularly at risk, with 75% of global irrigated wheat production and 65% of irrigated maize production found in watersheds that are at least seasonally depleted. Of importance to textile production, 75% of cotton production occurs in the same watersheds. For crop production in depleted watersheds, we find that one half to two-thirds of production occurs in watersheds that have not just seasonal but annual water shortages, suggesting that re-distributing water supply over the course of the year cannot be an effective solution to shortage. We explore the degree to which irrigated production in depleted watersheds reflects limitations in supply, a byproduct of the need for irrigation in perennially or seasonally dry landscapes, and identify heavy irrigation consumption that leads to watershed depletion in more humid climates. For watersheds that are not depleted, we evaluate the potential impact of an increase in irrigated production. Finally, we evaluate the benefits of irrigated agriculture in depleted and non-depleted watersheds, quantifying the fraction of irrigated production going to food production, animal feed, and biofuels.

  20. Increased Tryptophan Catabolism is Associated with Increased Frequency of CD161+Tc17/MAIT Cells, and Lower CD4+ T cell Count in HIV-1 infected Patients on cART after Two Years of Follow-up

    Gaardbo, Julie Christine; Trøseid, Marius; Stiksrud, Birgitte;

    2015-01-01

    BACKGROUND: HIV infection is associated with increased ratio between kynurenine and tryptophan (KTR) in plasma, increased microbial translocation, expansion of Tregs and depletion of Tc17/mucosa associated invariant T cells (MAIT) cells. The association between these parameters and the impact of ...

  1. Photochemical hydrogen-deuterium exchange reaction of tryptophan: the role in nonradiative decay of singlet tryptophan

    The mechanism of nonradiative decay of singlet excited tryptophan (Trp) in aqueous solution was investigated by a highly selective photosubstitution of the C-4 hydrogen of Trp with deuterium of solvent D2O. It was concluded that intramolecular proton transfer from the α-ammonia group giving rise to formation of a protonated species plays an important role in the nonradiative decay of singlet Trp at neutral pH. 11 references, 1 figure

  2. The azide radical and its reaction with tryptophan and tyrosine

    Azide radicals react with azide ions according to N3 + N3- N6-, K = 0.33 dm3 mol-1. The species N6- has an absorption maximum at 645 nm epsilon = 6600 dm3 mol-1 cm-1. The reaction between the azide radical and ferrocyanide at an azide concentration of 0.05 mol dm-3 is independent of ionic strength, showing that N3 is the reacting form of the radical. From the reduction potentials of the azide radical and tryptophan, azide radicals can react with tryptophan by electron transfer. Reaction of azide radicals with tyrosine can also proceed by electron transfer. Whereas the formation of the tryptophan radical cation can be demonstrated in the reaction of Br2- with tryptophan, its formation could not be observed directly in the reaction of N3 with tryptophan because the azide ion deprotonates the tryptophan radical cation at high concentrations of azide. Reactions are proposed to account for observations made in previous pulse radiolysis studies of solutions containing azide and tryptophan or tyrosine. (author)

  3. Modelling the evolution of the archaeal tryptophan synthase

    Merkl Rainer

    2007-01-01

    Abstract Background Microorganisms and plants are able to produce tryptophan. Enzymes catalysing the last seven steps of tryptophan biosynthesis are encoded in the canonical trp operon. Among the trp genes are most frequently trpA and trpB, which code for the alpha and beta subunit of tryptophan synthase. In several prokaryotic genomes, two variants of trpB (named trpB1 or trpB2) occur in different combinations. The evolutionary history of these trpB genes is under debate. Results In order to...

  4. Lattice Raman scattering in gamma-irradiated tryptophan crystals

    The character of change in lattice Raman spectra of aromatic aminoacid crystals-D-tryptophan - under the effect of gamma radiation has been traced. The choice of aromatic aminoacid as object for investigation is related to assumed high sensitivity of tryptophan crystal structure to the effect of short-wave irradiation due to the presence of a great number of protons in it, which interect intensively with gamma quanta. Considerable change in lattice Raman spectrum of D-tryptophan crystals under the effect of small doses of gamma irradiation has been revealed

  5. Radiation induced decomposition of tryptophan in deaerated aqueous solutions

    The effect of absorbed dose on the decomposition of tryptophan under gamma irradiation has been investigated. Neutral deaerated and N2O saturated solutions of various tryptophan concentrations were analysed. In both cases the decomposition yield of tryptophan decreases as irradiation dose increases. From the observed dependence initial yields G0(-Trp) = 3.35 and 4.75 were estimated for deaerated and N2O saturated solutions respectively. Estimated initial yields are in good agreement with values calculated according to the reaction scheme proposed. (author)

  6. A conserved suppressor mutation in a tryptophan auxotroph results in dysregulation of Pseudomonas quinolone signal synthesis.

    Knoten, Claire A; Wells, Greg; Coleman, James P; Pesci, Everett C

    2014-07-01

    Pseudomonas aeruginosa is a common nosocomial pathogen that relies on three cell-to-cell signals to regulate multiple virulence factors. The Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4-quinolone) is one of these signals, and it is known to be important for P. aeruginosa pathogenesis. PQS is synthesized in a multistep reaction that condenses anthranilate and a fatty acid. In P. aeruginosa, anthranilate is produced via the kynurenine pathway and two separate anthranilate synthases, TrpEG and PhnAB, the latter of which is important for PQS synthesis. Others have previously shown that a P. aeruginosa tryptophan auxotroph could grow on tryptophan-depleted medium with a frequency of 10(-5) to 10(-6). These revertants produced more pyocyanin and had increased levels of phnA transcript. In this study, we constructed similar tryptophan auxotroph revertants and found that the reversion resulted from a synonymous G-to-A nucleotide mutation within pqsC. This change resulted in increased pyocyanin and decreased PQS, along with an increase in the level of the pqsD, pqsE, and phnAB transcripts. Reporter fusion and reverse transcriptase PCR studies indicated that a novel transcript containing pqsD, pqsE, and phnAB occurs in these revertants, and quantitative real-time PCR experiments suggested that the same transcript appears in the wild-type strain under nutrient-limiting conditions. These results imply that the PQS biosynthetic operon can produce an internal transcript that increases anthranilate production and greatly elevates the expression of the PQS signal response protein PqsE. This suggests a novel mechanism to ensure the production of both anthranilate and PQS-controlled virulence factors. PMID:24748618

  7. Uses of depleted uranium

    The depleted uranium is that in which percentage of uranium-235 fission executable is less than 0.2% or 0.3%. It is usually caused by the process of reprocessing the nuclear fuel burning, and also mixed with some other radioactive elements such as uranium 236, 238 and plutonium 239. The good features of the depleted uranium are its high density, low price and easily mined. So, the specifications for depleted uranium make it one of the best materials in case you need to have objects small in size, but quite heavy regarding its size. Uses of deplet ed uranium were relatively increased in domestic industrial uses as well as some uses in nuclear industry in the last few years. So it has increased uses in many areas of military and peaceful means such as: in balancing the giant air crafts, ships and missiles and in the manufacture of some types of concrete with severe hardness. (author)

  8. Molecular Mechanism of Tryptophan-Dependent Transcriptional Regulation in Chlamydia trachomatis

    Akers, Johnny C.; Tan, Ming

    2006-01-01

    Tryptophan is an essential amino acid that is required for normal development in Chlamydia species, and tryptophan metabolism has been implicated in chlamydial persistence and tissue tropism. The ability to synthesize tryptophan is not universal among the Chlamydiaceae, but species that have a predicted tryptophan biosynthetic pathway also encode an ortholog of TrpR, a regulator of tryptophan metabolism in many gram-negative bacteria. We show that in Chlamydia trachomatis serovar D, TrpR regu...

  9. A Jerte Valley Cherry-Based Product as a Supply of Tryptophan

    Paredes, Sergio D.; Carmen Barriga; Juan. I Maynar-Mariño; Javier Cubero; Antonio F. Toribio-Delgado; Javier Espino; María Garrido; Rodríguez, Ana B.

    2012-01-01

    L-Tryptophan (tryptophan) is an essential amino acid in humans. It has important roles as a precursor of different bioactive compounds. Based on previous studies in which tryptophan has been shown to be present in fresh cherries, the aim of the present work was to analyze the tryptophan content of a Jerte Valley cherry-based product. A previously optimized method of analysis of tryptophan was used, ie, high-performance liquid chromatography with fluorescence detection (HPLC/FL). As expected, ...

  10. Tryptophan Properties in Fluorescence and Functional Stability of Plasminogen Activator Inhibitor 1

    Verheyden, Stefan; Sillen, Alain; Gils, Ann; Paul J Declerck; Engelborghs, Yves

    2003-01-01

    Plasminogen activator inhibitor 1 harbors four tryptophan residues at positions 86, 139, 175, and 262. To investigate the contribution of each tryptophan residue to the total fluorescence and to reveal the mutual interactions of the tryptophan residues and interactions with the other amino acids, 15 mutants in which tryptophan residues have been replaced by phenylalanines were constructed, purified, and characterized. Conformational distribution analysis revealed that the tryptophan mutants h...

  11. Molecular mechanism of tryptophan-dependent transcriptional regulation in Chlamydia trachomatis

    Akers, Johnny C.; Tan, Ming

    2006-01-01

    Tryptophan is an essential amino acid that is required for normal development in Chlamydia species, and tryptophan metabolism has been implicated in chlamydial persistence and tissue tropism. The ability to synthesize tryptophan is not universal among the Chlamydiaceae, but species that have a predicted tryptophan biosynthetic pathway also encode an ortholog of TrpR, a regulator of tryptophan metabolism in many gram-negative bacteria. We show that in Chlamydia trachomatis serovar D, TrpR regu...

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

    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. Depleted uranium during the Kosovo war

    Using the depleted uranium (DU) in the war and civil aims is considered. There are characterized the head parts of projectiles (drifts) from DU, used during Balkan wars, are described. The uranium isotope activity and exposure dose rates from β, γ and photon radiation of the drifts are investigated. The content of uranium and plutonium isotopes in the soil samples are measured. It is concluded that DU cannot exercise the acute influence on the health of military man and civil population

  14. Tryptophan and ATTO 590: Mutual Fluorescence Quenching and Exciplex Formation

    Bhattacharjee, Ujjal [Ames Laboratory; Beck, Christie [Ames Laboratory; Winter, Arthur [Iowa State University; Wells, Carson [Iowa State University; Petrich, Jacob W [Ames Laboratory

    2014-07-24

    Investigation of fluorescence quenching of probes, such as ATTO dyes, is becoming an increasingly important topic owing to the use of these dyes in super-resolution microscopies and in single-molecule studies. Photoinduced electron transfer is their most important nonradiative pathway. Because of the increasing frequency of the use of ATTO and related dyes to investigate biological systems, studies are presented for inter- and intramolecular quenching of ATTO 590 with tryptophan. In order to examine intramolecular quenching, an ATTO 590–tryptophan conjugate was synthesized. It was determined that tryptophan is efficiently quenching ATTO 590 fluorescence by excited-state charge transfer and two charge transfer complexes are forming. In addition, it was discovered that an exciplex (whose lifetime is 5.6 ns) can be formed between tryptophan and ATTO 590, and it is suggested that the possibility of such exciplex formation should be taken into account when protein fluorescence is monitored in a system tagged with ATTO dyes.

  15. Inhibition of tryptophan pyrrolase activity in restraint female rats following medroxyproge-sterone administration

    To determine the effects of Medroxyprogesterone (hormonal contraceptive) in restraint stressed female rats in relation to tryptophan metabolism. Female Albino Wistar rats (150-200 gm body wt) were selected and divided into four groups (n=5 in each group). Rats were injected intraperitoneally either vehicle or Medroxyprogesterone (25mg/kg/ml) and were immediately subjected to 2 hours restraint stress while respective controls remained in their home cages. In restraint stress group, hepatic holo and total tryptophan pyrrolase activities were increased. Liver tryptophan, total serum tryptophan and albumin concentration were decreased. Brain tryptophan, 5HT and 5HIAA concentrations were increased. Medroxyprogesterone administration in unrestraint rats inhibited holo, total and apo enzyme activities with increases in liver tryptophan concentrations. Effect of restraint stress following Medroxyprogesterone administration when compared with drug injected unrestrained group showed increase in holo and total tryptophan pyrrolase activities with decrease in liver tryptophan concentrations. Brain tryptophan, 5HT and 5HIAA levels were increased. Results when compared with vehicle injected stressed-rats showed that total and apo tryptophan pyrrolase activities were decreased. Liver tryptophan, serum tryptophan and albumin concentrations were increased but brain tryptophan metabolism was not effected. It is concluded that Medroxyprogesterone inhibits stress induce increases in peripheral tryptophan metabolism and increases plasma tryptophan. Although stress induced increases in brain indoles were not effected by the drug at two hours, further studies on time course effects of this drug will be needed to explore its possible anxiolytic effects. (author)

  16. Kernel modifications and tryptophan content in QPM segregating generations

    -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. Conformational Effects on Tryptophan Fluorescence in Cyclic Hexapeptides

    Pan, Chia-Pin; Barkley, Mary D.

    2004-01-01

    The peptide bond quenches tryptophan fluorescence by excited-state electron transfer, which probably accounts for most of the variation in fluorescence intensity of peptides and proteins. A series of seven peptides was designed with a single tryptophan, identical amino acid composition, and peptide bond as the only known quenching group. The solution structure and side-chain χ1 rotamer populations of the peptides were determined by one-dimensional and two-dimensional 1H-NMR. All peptides have...

  18. Tryptophan rotamer distributions in amphipathic peptides at a lipid surface.

    Clayton, A H; Sawyer, W. H.

    1999-01-01

    The fluorescence decay of tryptophan is a sensitive indicator of its local environment within a peptide or protein. We describe the use of frequency domain fluorescence spectroscopy to determine the conformational and environmental changes associated with the interaction of single tryptophan amphipathic peptides with a phospholipid surface. The five 18-residue peptides studied are based on a class A amphipathic peptide known to associate with lipid bilayers. The peptides contain a single tryp...

  19. Role of Tryptophan Residues in Gramicidin Channel Organization and Function

    Chattopadhyay, Amitabha; RAWAT, SATINDER S.; Greathouse, Denise V.; Kelkar, Devaki A.; Koeppe, Roger E.

    2008-01-01

    The linear peptide gramicidin forms prototypical ion channels specific for monovalent cations and has been used extensively to study the organization, dynamics, and function of membrane-spanning channels. The tryptophan residues in gramicidin channels are crucial for maintaining the structure and function of the channel. We explored the structural basis for the reduction in channel conductance in the case of single-tryptophan analogs of gramicidin with three Trp → hydrophobic substitutions us...

  20. Digestible tryptophan:lysine ratio for laying hens

    Matheus Ramalho de Lima

    2012-10-01

    Full Text Available The objective of this study was to evaluate the requirement of digestible tryptophan for white laying hens in the production stage fed diets of different digestible tryptophan:digestible lysine ratios, as well as animal performance and histological alterations in their reproductive and digestive systems. A total of 280 white laying hens at 29 weeks of age were distributed in a completely randomized design with five treatments and seven replications with eight birds in each. The treatments consisted of a base feed, formulated with corn, soybean meal and corn gluten meal, and supplemented with the synthetic amino acids L-lysine, DL-methionine, L-threonine, L-isoleucine, L-arginine, and L-valine, so as to meet the nutritional requirements for laying hens, except for digestible tryptophan. The basal diet was supplemented with 0.00; 0.017; 0.035; 0.052; and 0.069 g/kg of L-tryptophan in substitution for corn starch with the objective of reaching the levels of 0.151; 0.167; 0.183; 0.199; and 0.215 g/kg of digestible tryptophan in the feed. For the ratio between digestible amino acids and lysine, the recommendation of Brazilian Tables for Poultry and Swine was followed, except for the digestible tryptophan:digestible lysine ratios, which were 19, 21, 23, 25 and 27 for each treatment. The variation in the digestible tryptophan:digestible lysine ratio promoted changes in performance and in the histological characteristics, improving the results. The digestible tryptophan:digestible lysine ratio of 24.5% in the feed of white laying hens in production stage promotes better animal performance and histological results.

  1. Stabilization of lignin peroxidases in white rot fungi by tryptophan.

    Collins, P. J.; Field, J. A.; Teunissen, P; Dobson, A D

    1997-01-01

    Supplementation of various cultures of white rot fungi with tryptophan was found to have a large stimulatory effect on lignin peroxidase activity levels. This enhancement was greater than that observed in the presence of the lignin peroxidase recycling agent veratryl alcohol. Using reverse transcription-PCR, we found that tryptophan does not act to induce lignin peroxidase expression at the level of gene transcription. Instead, the activity enhancement observed is likely to result from the pr...

  2. Tryptophan Transport in Human Fibroblast Cells—A Functional Characterization

    Vumma Ravi; Johansson Jessica; Lewander Tommy; Venizelos Nikolaos

    2011-01-01

    There are indications that serotonergic neurotransmission is disturbed in several psychiatric disorders. One explanation may be disturbed transport of tryptophan (precursor for serotonin synthesis) across cell membranes. Human fibroblast cells offer an advantageous model to study the transport of amino acids across cell membranes, since they are easy to propagate and the environmental factors can be controlled. The aim of this study was to functionally characterize tryptophan transport and to...

  3. Synthesis of [α-15N]-dl-tryptophan

    [α-15N]-dl-tryptophan was synthesized by the use of Al-Ni alloy catalytic hydrogenation from 15N-glycine via several steps. The overall yield of the final product was 46.9% and the abundance of 15N was about 93%. The physicochemical properties of the synthetic compound obtained were the same as those of the standard tryptophan. Its structure were confirmed by the elemental analyses, MS, UV and paper chromatography

  4. Regulation of tryptophan operon expression in the archaeon Methanothermobacter thermautotrophicus.

    Xie, Yunwei; Reeve, John N

    2005-09-01

    Conserved trp genes encode enzymes that catalyze tryptophan biosynthesis in all three biological domains, and studies of their expression in Bacteria and eukaryotes have revealed a variety of different regulatory mechanisms. The results reported here provide the first detailed description of an archaeal trp gene regulatory system. We have established that the trpEGCFBAD operon in Methanothermobacter thermautotrophicus is transcribed divergently from a gene (designated trpY) that encodes a tryptophan-sensitive transcription regulator. TrpY binds to TRP box sequences (consensus, TGTACA) located in the overlapping promoter regions between trpY and trpE, inhibiting trpY transcription in the absence of tryptophan and both trpY and trpEGCFBAD transcription in the presence of tryptophan. TrpY apparently inhibits trpY transcription by blocking RNA polymerase access to the site of trpY transcription initiation and represses trpEGCFBAD transcription by preventing TATA box binding protein (TBP) binding to the TATA box sequence. Given that residue 2 (W2) is the only tryptophan in TrpY and in TrpY homologues in other Euryarchaea and that there is only one tryptophan codon in the entire trpEGCFBAD operon (trpB encodes W175), expression of the trp operon may also be regulated in vivo by the supply of charged tRNA(Trp) available to translate the second codon of the trpY mRNA. PMID:16159776

  5. Complexity in regulation of tryptophan biosynthesis in Bacillus subtilis.

    Gollnick, Paul; Babitzke, Paul; Antson, Alfred; Yanofsky, Charles

    2005-01-01

    Bacillus subtilis uses novel regulatory mechanisms in controlling expression of its genes of tryptophan synthesis and transport. These mechanisms respond to changes in the intracellular concentrations of free tryptophan and uncharged tRNA(Trp). The major B. subtilis protein that regulates tryptophan biosynthesis is the tryptophan-activated RNA-binding attenuation protein, TRAP. TRAP is a ring-shaped molecule composed of 11 identical subunits. Active TRAP binds to unique RNA segments containing multiple trinucleotide (NAG) repeats. Binding regulates both transcription termination and translation in the trp operon, and translation of other coding regions relevant to tryptophan metabolism. When there is a deficiency of charged tRNA(Trp), B. subtilis forms an anti-TRAP protein, AT. AT antagonizes TRAP function, thereby increasing expression of all the genes regulated by TRAP. Thus B. subtilis and Escherichia coli respond to identical regulatory signals, tryptophan and uncharged tRNA(Trp), yet they employ different mechanisms in regulating trp gene expression. PMID:16285852

  6. Carbon dots from tryptophan doped glucose for peroxynitrite sensing

    Simões, Eliana F.C. [CIQ-UP, Grupo de Ciências Biológicas e Bioanalíticas, Faculdade de Farmácia da Universidade de Coimbra, Pólo das Ciências da Saúde, 3000-548 Coimbra (Portugal); CIQ-UP, Departamento de Química, Faculdade de Ciências da Universidade do Porto, R. Campo Alegre 687, 4169-007 Porto (Portugal); Esteves da Silva, Joaquim C.G. [CIQ-UP, Departamento de Química, Faculdade de Ciências da Universidade do Porto, R. Campo Alegre 687, 4169-007 Porto (Portugal); Leitão, João M.M., E-mail: jleitao@ff.uc.pt [CIQ-UP, Grupo de Ciências Biológicas e Bioanalíticas, Faculdade de Farmácia da Universidade de Coimbra, Pólo das Ciências da Saúde, 3000-548 Coimbra (Portugal)

    2014-12-10

    Highlights: • Synthesis of tryptophan doped carbon dots. • Experimental design optimization of the tryptophan doped carbon dots synthesis. • Fluorescence sensing of peroxynitrite by tryptophan doped carbon dots. • Peroxynitrite quantification in serum samples by tryptophan doped carbon dots. - Abstract: Tryptophan doped carbon dots (Trp-CD) were microwave synthesized. The optimum conditions of synthesizing of the Trp-CD were established by response surface multivariate optimization methodologies and were the following: 2.5 g of glucose and 300 mg of tryptophan diluted in 15 mL of water exposed for 5 min to a microwave radiation of 700 W. Trp-CD have an average size of 20 nm, were fluorescent with a quantum yield of 12.4% and the presence of peroxynitrite anion (ONOO{sup −}) provokes quenching of the fluorescence. The evaluated analytical methodology for ONOO{sup −} detection shows a linear response range from 5 to 25 μM with a limit of detection of 1.5 μM and quantification of 4.9 μM. The capability of the ONOO{sup −} quantification was evaluated in standard solutions and in fortified serum samples.

  7. Carbon dots from tryptophan doped glucose for peroxynitrite sensing

    Highlights: • Synthesis of tryptophan doped carbon dots. • Experimental design optimization of the tryptophan doped carbon dots synthesis. • Fluorescence sensing of peroxynitrite by tryptophan doped carbon dots. • Peroxynitrite quantification in serum samples by tryptophan doped carbon dots. - Abstract: Tryptophan doped carbon dots (Trp-CD) were microwave synthesized. The optimum conditions of synthesizing of the Trp-CD were established by response surface multivariate optimization methodologies and were the following: 2.5 g of glucose and 300 mg of tryptophan diluted in 15 mL of water exposed for 5 min to a microwave radiation of 700 W. Trp-CD have an average size of 20 nm, were fluorescent with a quantum yield of 12.4% and the presence of peroxynitrite anion (ONOO−) provokes quenching of the fluorescence. The evaluated analytical methodology for ONOO− detection shows a linear response range from 5 to 25 μM with a limit of detection of 1.5 μM and quantification of 4.9 μM. The capability of the ONOO− quantification was evaluated in standard solutions and in fortified serum samples

  8. Synthesis of [3-14C]-L-tryptophan and 5'-hydroxy-[3-14C]-L-tryptophan

    The synthesis of selectively labeled [3-14C]-L-tryptophan and its derivative 5'-hydroxy-[3-14C]-L-tryptophan using chemical and multienzymatic methods is reported. The key intermediate for this synthesis, 3-14C]-DL-alanine was obtained from 14CH3I as a result of its condensation with N- (diphenylmethylene)glycine tert-butyl ester. Next, the mixture containing [3-14C]-DL-alanine, indole or 5-hydroxyindole has been converted to [3-14C]-L-tryptophan or 5'-hydroxy-[3-14C]-L-tryptophan, respectively, in a one-pot multienzymatic reaction using four enzymes: -amino acid oxidase, catalase, glutamic-pyruvic transaminase and tryptophanase. (author)

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

    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.

  10. Antarctic ozone depletion

    Antarctic ozone depletion is most severe during the southern hemisphere spring, when the local reduction in the column amount may be as much as 50 percent. The extent to which this ozone poor air contributes to the observed global ozone loss is a matter of debate, but there is some evidence that fragments of the 'ozone hole' can reach lower latitudes following its breakup in summer. Satellite data show the seasonal evolution of the ozone hole. A new dimension has been added to Antarctic ozone depletion with the advent of large volcanic eruptions such as that from Mount Pinatubo in 1991. (author). 5 refs., 1 fig

  11. Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies

    Introduction: Tryptophan oxidation via the kynurenine pathway is an important mechanism of tumoral immunoresistance. Increased tryptophan metabolism via the serotonin pathway has been linked to malignant progression in breast cancer. In this study, we combined quantitative positron emission tomography (PET) with tumor immunohistochemistry to analyze tryptophan transport and metabolism in breast cancer. Methods: Dynamic α-[11C]methyl-L-tryptophan (AMT) PET was performed in nine women with stage II–IV breast cancer. PET tracer kinetic modeling was performed in all tumors. Expression of L-type amino acid transporter 1 (LAT1), indoleamine 2,3-dioxygenase (IDO; the initial and rate-limiting enzyme of the kynurenine pathway) and tryptophan hydroxylase 1 (TPH1; the initial enzyme of the serotonin pathway) was assessed by immunostaining of resected tumor specimens. Results: Tumor AMT uptake peaked at 5–20 min postinjection in seven tumors; the other two cases showed protracted tracer accumulation. Tumor standardized uptake values (SUVs) varied widely (2.6–9.8) and showed a strong positive correlation with volume of distribution values derived from kinetic analysis (P < .01). Invasive ductal carcinomas (n = 6) showed particularly high AMT SUVs (range, 4.7–9.8). Moderate to strong immunostaining for LAT1, IDO and TPH1 was detected in most tumor cells. Conclusions: Breast cancers show differential tryptophan kinetics on dynamic PET. SUVs measured 5–20 min postinjection reflect reasonably the tracer's volume of distribution. Further studies are warranted to determine if in vivo AMT accumulation in these tumors is related to tryptophan metabolism via the kynurenine and serotonin pathways.

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

    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.

  13. Willpower depletion and framing effects

    de Haan, Thomas; van Veldhuizen, Roel

    2013-01-01

    We investigate whether depleting people's cognitive resources (or willpower) affects the degree to which they are susceptible to framing effects. Recent research in social psychology and economics has suggested that willpower is a resource that can be temporarily depleted and that a depleted level of willpower is associated with self-control problems in a variety of contexts. In this study, we extend the willpower depletion paradigm to framing effects and argue that willpower depletion should...

  14. Further investigation on the radiosynthesis of α-[11C]methyl-tryptophan

    Improved procedures for the radiosynthesis of α-[11C]-methyl-tryptophan and α-[11C]methyl-tryptophan methyl ester were studied. Following α-deprotonation of tryptophan methyl ester benzaldimine with LDA, 60 - 80% of no carrier added [11C]iodomethane was incorporated in 5 minutes at 27 - 30 oC. After HPLC purification, radiochemically pure α-[11C]methyl-tryptophan or its methyl ester was produced with minimum chemical contamination form tryptophan. The [11C]methyl-tryptophan synthesized, however, was found to be a racemate. (Author)

  15. One-step of tryptophan attenuator inactivation and promoter swapping to improve the production of L-tryptophan in Escherichia coli

    Gu Pengfei

    2012-03-01

    Full Text Available Abstract Background L-tryptophan is an aromatic amino acid widely used in the food, chemical and pharmaceutical industries. In Escherichia coli, L-tryptophan is synthesized from phosphoenolpyruvate and erythrose 4-phosphate by enzymes in the shikimate pathway and L-tryptophan branch pathway, while L-serine and phosphoribosylpyrophosphate are also involved in L-tryptophan synthesis. In order to construct a microbial strain for efficient L-tryptophan production from glucose, we developed a one step tryptophan attenuator inactivation and promoter swapping strategy for metabolic flux optimization after a base strain was obtained by overexpressing the tktA, mutated trpE and aroG genes and inactivating a series of competitive steps. Results The engineered E. coli GPT1002 with tryptophan attenuator inactivation and tryptophan operon promoter substitution exhibited 1.67 ~ 9.29 times higher transcription of tryptophan operon genes than the control GPT1001. In addition, this strain accumulated 1.70 g l-1 L-tryptophan after 36 h batch cultivation in 300-mL shake flask. Bioreactor fermentation experiments showed that GPT1002 could produce 10.15 g l-1 L-tryptophan in 48 h. Conclusions The one step inactivating and promoter swapping is an efficient method for metabolic engineering. This method can also be applied in other bacteria.

  16. Surface geometry of tryptophan adsorbed on gold colloidal nanoparticles

    Hussain, Shafqat; Pang, Yoonsoo

    2015-09-01

    Two distinct surface-enhanced Raman (SER) spectra of tryptophan depending on the surface adsorption geometry were obtained by using colloidal gold nanoparticles reduced by borohydride and citrate ions. According to the vibrational assignments based on DFT simulations, the SER spectra of tryptamine and 3-indolepropionic acid, and the pH dependence of tryptophan SER spectrum, we found that some indole ring vibrations are very sensitive to the surface adsorption geometry of the molecules. With citrate-reduced gold colloids, tryptophan and related molecules mainly adsorb via the protonated amine group while maintaining a perpendicular geometry of the indole ring to the surface. However, a flat geometry of the indole ring to the surface is preferred on the borohydride-reduced gold colloids where the surface adsorption occurs mainly through the indole ring π electrons. By comparing our results with previous reports on the SER spectra of tryptophan on various silver and gold surfaces, we propose a general adsorption model of tryptophan on metal nanosurfaces.

  17. Kinetics of oxidation of tryptophan by sodium hypochlorite

    The oxidation of tryptophan to 3-indoleacetaldehyde with sodium hypochlorite was investigated with 14C labelled DL-tryptophan. The reaction was performed under pseudo first order conditions. From the pH dependence of the reaction it was concluded that only the unprotonated tryptophan is converted to the aldehyde. The activation energy is 35 +- 2.2 (SE) kJ x mol-1 as derived from the Arrhenius plot. Variing the pH between 8.5 and 11.0 and the temperature in the range from 298 K to 318 K did not alter the selectivity of the reaction as confirmed by TLC of the product (purity >= 90%). A possible reaction mechanism is proposed. (orig.)

  18. Intrinsic Depletion or Not

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

    in between he polymer cushion and bulk water the layer was attributed to water of reduced density and was called "depletion layer".  Impurities or preparative artefacts were excluded as its origin. Later on, the formation of nanobubbles from this vapour-like water phase was initiated by tipping the......  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...... carrier and biomimetic membranes deposited thereupon and exposed to bulk water. While monitoring the sequential build-up of the sandwiched composite structure by continuous neutron reflectivity experiments the formation of an unexpected additional layer was detected (1). Located at the polystyrene surface...

  19. Depletion of intense fields

    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.

  20. Ozone depletion by hydrofluorocarbons

    Hurwitz, Margaret M.; Fleming, Eric L.; Newman, Paul A.; Li, Feng; Mlawer, Eli; Cady-Pereira, Karen; Bailey, Roshelle

    2015-10-01

    Atmospheric concentrations of hydrofluorocarbons (HFCs) are projected to increase considerably in the coming decades. Chemistry climate model simulations forced by current projections show that HFCs will impact the global atmosphere increasingly through 2050. As strong radiative forcers, HFCs increase tropospheric and stratospheric temperatures, thereby enhancing ozone-destroying catalytic cycles and modifying the atmospheric circulation. These changes lead to a weak depletion of stratospheric ozone. Simulations with the NASA Goddard Space Flight Center 2-D model show that HFC-125 is the most important contributor to HFC-related atmospheric change in 2050; its effects are comparable to the combined impacts of HFC-23, HFC-32, HFC-134a, and HFC-143a. Incorporating the interactions between chemistry, radiation, and dynamics, ozone depletion potentials (ODPs) for HFCs range from 0.39 × 10-3 to 30.0 × 10-3, approximately 100 times larger than previous ODP estimates which were based solely on chemical effects.

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

    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

  2. Tryptophan Hydroxylase 2 Gene Polymorphism in Anxiety and Depressive Disorder in Kashmiri Population

    Mushtaq, Raheel; Shoib, Sheikh; Shah, Tabindah; Mushtaq, Sahil

    2014-01-01

    Background: The gene of tryptophan hydroxylase is widely recognized as a major candidate gene in many psychiatric disorders. However, no study has been done which investigates tryptophan hydroxylase 2 gene polymorphism in anxiety and depressive disorders in Kashmiri population (India).

  3. Capital expenditure and depletion

    In the future, the increase in oil demand will be covered for the most part by non conventional oils, but conventional sources will continue to represent a preponderant share of the world oil supply. Their depletion represents a complex challenge involving technological, economic and political factors. At the same time, there is reason for concern about the decrease in exploration budgets at the major oil companies. (author)

  4. Incorporation of tryptophan analogues into the lantibiotic nisin.

    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. PMID:26872656

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

    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

  6. Dynamic behavior in mathematical models of the tryptophan operon

    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.

  7. Alleviation of hysteria in laying hens with dietary tryptophan.

    Laycock, S. R.; Ball, R O

    1990-01-01

    A commercial layer breeder flock that was suffering from hysteria was fed a diet containing 5 grams tryptophan/kg for six days. The incidence of episodes of hysteria declined from five times/hour on day 0 to once/hour on day 6 and none on day 8. Feed consumption increased from 107 g to 145 g/hen/day and egg production increased 23% during the six day feeding period. The tryptophan concentration in plasma doubled (from 95.6 to 188.2 mumol/mL). Plasma phenylalanine and tyrosine also increased. ...

  8. Subtle stereoconformational change of tryptophanase provoking D-tryptophan activity

    It has been found in this investigation that the stereospecificity of enzyme is full of flexibility and that tryptophanase has an activity also toward D-tryptophan in ammonium phosphate solution at high concentration as L-tryptophan. This fact may show that D-amino acids have physiologically significant activity. It is considered that the appearance of such the activity is related to a stereoconformational change of tryptophanase. This was investigated by the measurement of circular dichroism and fluorescence spectra. Furthermore the change of steric structure was also examined on the denaturated tryptophanase inactivated by gamma irradiation. (M.H.)

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

    Jonas, A J; Butler, I J

    1989-01-01

    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 concentr...

  10. Enhancement of rat brain metabolism of a tryptophan load by chronic ethanol administration

    1980-01-01

    We have previously shown that chronic ethanol administration enhances brain 5-hydroxytryptamine synthesis by increasing the availability of circulating tryptophan to the brain secondary to the decreased liver tryptophan pyrrolase activity. We now find that ethanol enhances the brain metabolism of a tryptophan load by the same mechanism. The results are discussed in relation to ethanol preference and the need for further clinical work on the effects of alcoholism on tryptophan metabolism.

  11. Ozone-depleting Substances (ODS)

    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...

  12. Linear mapping of tryptophan residues in Vesiculovirus M and N proteins by partial chemical cleavage.

    Brown, E.; Prevec, L.

    1982-01-01

    Nonlimit chemical cleavage at tryptophan residues of protein labeled at the amino terminus afforded a simple procedure for generating specific fragments and for mapping tryptophan positions. A comparison of the matrix (M) and nucleocapsid (N) proteins of four members of the Vesiculovirus group by this procedure suggests considerable conservation of tryptophan number and location in the four serotypes examined.

  13. Depleted uranium management alternatives

    This report evaluates two management alternatives for Department of Energy depleted uranium: continued storage as uranium hexafluoride, and conversion to uranium metal and fabrication to shielding for spent nuclear fuel containers. The results will be used to compare the costs with other alternatives, such as disposal. Cost estimates for the continued storage alternative are based on a life-cycle of 27 years through the year 2020. Cost estimates for the recycle alternative are based on existing conversion process costs and Capital costs for fabricating the containers. Additionally, the recycle alternative accounts for costs associated with intermediate product resale and secondary waste disposal for materials generated during the conversion process

  14. Stratospheric ozone depletion

    The amount of stratospheric ozone and the reduction of the ozone layer vary according to seasons and latitudes. At present total and vertical ozone is monitored over all Austria. The mean monthly ozone levels between 1994 and 2000 are presented. Data on stratospheric ozone and UV-B radiation are published daily on the home page http: www.lebesministerium.at. The use of ozone depleting substances such as chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs) is provided. Besides, the national measures taken to reduce their use. Figs. 2, Tables 2. (nevyjel)

  15. Tryptophan as a link between psychopathology and somatic states

    Russo, Sascha; Kema, Ido P; Fokkema, M Rebecca; Boon, Jim C; Willemse, Pax H B; de Vries, Elisabeth G E; den Boer, Johannes A; Korf, Jakob

    2003-01-01

    OBJECTIVE: Several somatic illnesses are associated with psychiatric comorbidity. Evidence is provided that availability of the essential amino acid tryptophan, which is the precursor of serotonin, may cause this phenomenon. METHODS: We performed a database search to find relevant articles published

  16. Electron-transfer reactions of tryptophan and tyrosine derivatives

    Oxidation of tryptophan, tyrosine, and derivatives by oxidizing radicals was studied by pulse radiolysis in aqueous solutions at 20 0C. Rate constants for the oxidation of tryptophan derivatives with .N3 and Br2-. radicals vary from 8 x 108 to 4.8 and 109 M-1 s-1 and oxidation goes to completion; no pH dependence was observed. Oxidation rate constants for tyrosine derivatives increase upon deprotonation of the phenolic residue at higher pH. Redox potentials for the indolyl and phenoxyl radicals were derived from the measured equilibrium constants by using p-methoxyphenol (E/sub 7.5/ = 0.6 and E13 = 0.4 V), bisulfite (E3 = 0.84 V), and guanosine (E7 = 0.91 V) redox couples as reference systems. Redox potentials of tryptophan derivatives were found to be in dependent on the nature of the side chain and higher than the redox potentials of tryptophan derivatives. Electron transfer from tyrosine to tryptophyl radical was found to be slow in neutral media and is suggested to proceed via multiple steps, one of which is proton transfer from tyrosine to tryptophyl radical followed by electron transfer. 26 references, 2 figures, 4 tables

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

    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…

  18. Comparison of fractal dimension and Shannon entropy in myocytes from rats treated with histidine-tryptophan-glutamate and histidine-tryptophan cetoglutarate

    de Oliveira, Marcos Aurélio Barboza; Brandi, Antônio Carlos; dos Santos, Carlos Alberto; Botelho, Paulo Henrique Husseni; Cortez, José Luís Lasso; de Godoy, Moacir Fernandes; Braile, Domingo Marcolino

    2014-01-01

    Introduction Solutions that cause elective cardiac arrest are constantly evolving, but the ideal compound has not yet been found. The authors compare a new cardioplegic solution with histidine-tryptophan-glutamate (Group 2) and other one with histidine-tryptophan-cetoglutarate (Group 1) in a model of isolated rat heart. Objective To quantify the fractal dimension and Shannon entropy in rat myocytes subjected to cardioplegia solution using histidine-tryptophan with glutamate in an experimental...

  19. Decomposition of protein tryptophan fluorescence spectra into log-normal components. III. Correlation between fluorescence and microenvironment parameters of individual tryptophan residues.

    Reshetnyak, Y K; Koshevnik, Y; Burstein, E A

    2001-01-01

    In our previous paper (Reshetnyak, Ya. K., and E. A. Burstein. 2001. Biophys. J. 81:1710-1734) we confirmed the existence of five statistically discrete classes of emitting tryptophan fluorophores in proteins. The differences in fluorescence properties of tryptophan residues of these five classes reflect differences in interactions of excited states of tryptophan fluorophores with their microenvironment in proteins. Here we present a system of describing physical and structural parameters of ...

  20. 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

    Crespo, Elena; Lucia, Marc; Cruzado, Josep M.; Luque, Sergio; Melilli, Edoardo; Manonelles, Anna; Lloberas, Nuria; Torras, Joan; Grinyó, Josep M.; Bestard, Oriol

    2015-01-01

    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, p...

  1. The stimulus-induced release of 5-hydroxytryptamine and tryptophan from superfused rat brain synaptosomes

    The synthesis of 5-hydroxytryptamine (5-HT) from 3H-tryptophan in rat forebrain synaptosomes was studied. Synaptosomes which had been preincubated with 3H-tryptophan were perfused with Krebs solution and the release of tryptophan, 5-HT and 5-hydroxyindoleactic acid (5-HIAA) was determined. K+ depolarization induced a Ca2+ -dependent release of 5-HT and tryptophan but had no effect on 5-HIAA efflux. This finding suggests that the release of tryptophan is unlikely to be a non-specific effect of depolarization. (Author)

  2. L-Tryptophan prevents Escherichia coli biofilm formation and triggers biofilm degradation.

    Shimazaki, Junji; Furukawa, Soichi; Ogihara, Hirokazu; Morinaga, Yasushi

    2012-03-23

    The effect of deletion of trp operon and tna operon on the Escherichia coli biofilm formation was investigated in order to elucidate the role of L-tryptophan metabolism in biofilm formation. trp operon deletion mutants ΔtrpC, ΔtrpD and ΔtrpE deficient in L-tryptophan biosynthesis showed higher biofilm formation. In addition, ΔtnaC with increased L-tryptophan degradation activity showed higher biofilm formation. On the contrary, ΔtnaA deletion mutant which lost L-tryptophan degradation activity showed low biofilm formation. From these results, it was suggested that decrease of intracellular L-tryptophan level induced biofilm formation and increase of L-tryptophan repressed biofilm formation. So the effect of the addition of L-tryptophan to the medium on the E. coli biofilm formation was investigated. L-Tryptophan addition at starting culture decreased biofilm formation and furthermore L-tryptophan addition after 16 h culture induced the degradation of preformed biofilm. From the above results, it was suggested that maintenance of high intracellular L-tryptophan concentration prevents E. coli biofilm formation and elevation of intracellular L-tryptophan concentration triggers degradation of matured biofilm. PMID:22386992

  3. Depleted uranium: Metabolic disruptor?

    The presence of uranium in the environment can lead to long-term contamination of the food chain and of water intended for human consumption and thus raises many questions about the scientific and societal consequences of this exposure on population health. Although the biological effects of chronic low-level exposure are poorly understood, results of various recent studies show that contamination by depleted uranium (DU) induces subtle but significant biological effects at the molecular level in organs including the brain, liver, kidneys and testicles. For the first time, it has been demonstrated that DU induces effects on several metabolic pathways, including those metabolizing vitamin D, cholesterol, steroid hormones, acetylcholine and xenobiotics. This evidence strongly suggests that DU might well interfere with many metabolic pathways. It might thus contribute, together with other man-made substances in the environment, to increased health risks in some regions. (authors)

  4. Riddle of depleted uranium

    Depleted Uranium (DU) is the waste product of uranium enrichment from the manufacturing of fuel rods for nuclear reactors in nuclear power plants and nuclear power ships. DU may also results from the reprocessing of spent nuclear reactor fuel. Potentially DU has both chemical and radiological toxicity with two important targets organs being the kidney and the lungs. DU is made into a metal and, due to its availability, low price, high specific weight, density and melting point as well as its pyrophoricity; it has a wide range of civilian and military applications. Due to the use of DU over the recent years, there appeared in some press on health hazards that are alleged to be due to DU. In these paper properties, applications, potential environmental and health effects of DU are briefly reviewed

  5. Depleted zinc: Properties, application, production

    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.

  6. Elementary processes during collisions of ions with tryptophan molecules

    Afrosimov, V. V.; Basalaev, A. A.; Kuz'michev, V. V.; Panov, M. N.; Smirnov, O. V.

    2016-03-01

    The relative cross sections of elementary processes occurring in single collisions of tryptophan molecules in the gaseous phase with He2+ ions with energy 4 keV/u are measured using time-of-flight mass spectrometry for studying the mechanism of radiation damage of amino acid molecules. The fragmentation channels for intermediate singly and doubly charged tryptophan molecular ions formed during one-electron capture, two-electron capture, and electron capture with ionization are investigated. Significant difference is observed in the mass spectra of fragmentation of intermediate doubly charged ions formed during the capture with ionization and double capture, which is associated with different energies of excitation of {C11H12N2O2}2+* ions.

  7. Investigation of Fragmentation of Tryptophan Nitrogen Radical Cation

    Piatkivskyi, Andrii; Happ, Marshall; Lau, Justin Kai-Chi; Siu, K. W. Michael; Hopkinson, Alan C.; Ryzhov, Victor

    2015-08-01

    This work describes investigation of the fragmentation mechanism of tryptophan N-indolyl radical cation, H3N+-TrpN• ( m/ z 204) studied via DFT calculations and several gas-phase experimental techniques. The main fragment ion at m/ z 131, shown to be a mixture of up to four isomers including 3-methylindole (3MI) π-radical cation, was found to undergo further loss of an H atom to yield one of the two isomeric m/ z 130 ions. 3-Methylindole radical cation generated independently (via CID of [CuII(terpy)3MI]•2+) displayed gas-phase reactivity partially similar to that of the m/ z 131 fragment, further confirming our proposed mechanism. CID of deuterated tryptophan N-indolyl radical cation ( m/ z 208) suggested that up to six H atoms are involved in the pathway to formation of the m/ z 131 ion, consistent with hydrogen atom scrambling during CID of protonated Trp.

  8. Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans

    Lionella Palego; Laura Betti; Alessandra Rossi; Gino Giannaccini

    2016-01-01

    L-Tryptophan is the unique protein amino acid (AA) bearing an indole ring: its biotransformation in living organisms contributes either to keeping this chemical group in cells and tissues or to breaking it, by generating in both cases a variety of bioactive molecules. Investigations on the biology of Trp highlight the pleiotropic effects of its small derivatives on homeostasis processes. In addition to protein turn-over, in humans the pathways of Trp indole derivatives cover the synthesis of ...

  9. Aromatic amine dehydrogenase, a second tryptophan tryptophylquinone enzyme.

    Govindaraj, S; Eisenstein, E.; Jones, L. H.; Sanders-Loehr, J; Chistoserdov, A Y; Davidson, V L; Edwards, S. L.

    1994-01-01

    Aromatic amine dehydrogenase (AADH) catalyzes the oxidative deamination of aromatic amines including tyramine and dopamine. AADH is structurally similar to methylamine dehydrogenase (MADH) and possesses the same tryptophan tryptophylquinone (TTQ) prosthetic group. AADH exhibits an alpha 2 beta 2 structure with subunit molecular weights of 39,000 and 18,000 and with a quinone covalently attached to each beta subunit. Neither subunit cross-reacted immunologically with antibodies to the correspo...

  10. Gramicidin tryptophans mediate formamidinium-induced channel stabilization.

    Seoh, S A; Busath, D

    1995-01-01

    Compared with alkali metal cations, formamidinium ions stabilize the gramicidin A channel molecule in monoolein bilayers (Seoh and Busath, 1993a). A similar effect is observed with N-acetyl gramicidin channel molecules in spite of the modified forces at the dimeric junction (Seoh and Busath, 1993b). Here we use electrophysiological measurements with tryptophan-to-phenylalanine-substituted gramicidin analogs to show that the formamidinium-induced channel molecule stabilization is eliminated wh...

  11. Regulation of Tryptophan Operon Expression in the Archaeon Methanothermobacter thermautotrophicus

    Xie, Yunwei; Reeve, John N.

    2005-01-01

    Conserved trp genes encode enzymes that catalyze tryptophan biosynthesis in all three biological domains, and studies of their expression in Bacteria and eukaryotes have revealed a variety of different regulatory mechanisms. The results reported here provide the first detailed description of an archaeal trp gene regulatory system. We have established that the trpEGCFBAD operon in Methanothermobacter thermautotrophicus is transcribed divergently from a gene (designated trpY) that encodes a try...

  12. Immunochemical characterization of brain and pineal tryptophan hydroxylase.

    Chung, Y. I.; Park, D. H.; Kim, M.; Baker, H; Joh, T H

    2001-01-01

    Recombinant mouse tryptophan hydroxylase (TPH) was expressed in Escherichia coli, using a bacterial expression vector and has been purified to homogeneity by sonication followed by Sepharose 4B column chromatography and native slab gel electrophoresis. This purified enzymatically active TPH protein was used for production of a specific antiserum. This antiserum identified the predicted TPH band (molecular weight, 54 kDa) on Western blot of crude extracts from the rat and mouse dorsal raphe, a...

  13. Separation of tryptophan enantiomers with molecularly imprinted polypyrrole electrode column

    2010-01-01

    In this study,we have fabricated molecularly imprinted polypyrrole(PPy) packed electrode columns and investigated their effects on separation of tryptophan(Trp) enantiomers by using potential control.The results indicate that the imprinted PPy electrode columns could efficiently enhance the L-Trp uptake and separate Trp enantiomers effectively,implying the great potential for the enantioselective recognition of other amino acids enantiomers.

  14. Tryptophan-abhängige Pigmentsynthese bei Brandpilzen

    Mayer, Peter Karl

    2007-01-01

    Im Jahre 1998 konnten MAYSER ET AL. erstmals nachweisen, dass die Aminosäure L-Tryptophan bei dem Brandpilz Malassezia furfur eine Pigmentbildung induziert. Die entstandenen Pigmente und Fluorochrome werden mit dem Krankheitsbild der Pityriasis versicolor in Verbindung gebracht. Im Gegensatz zu Malassezia furfur sind Brandpilze obligate Pflanzenparasiten. Aufgrund der phylogenetischen Klassifikation von Malassezia furfur als Brandpilz wurden insgesamt 27 Brandpilze auf Pigmentbildung untersuc...

  15. Structural Insights into Regioselectivity in the Enzymatic Chlorination of Tryptophan

    Zhu, Xiaofeng; De Laurentis, Walter; Leang, Khim; Herrmann, Julia; Ihlefeld, Katja; van Pée, Karl-Heinz; Naismith, James H.

    2009-01-01

    The regioselectively controlled introduction of chlorine into organic molecules is an important biological and chemical process. This importance derives from the observation that many pharmaceutically active natural products contain a chlorine atom. Flavin-dependent halogenases are one of the principal enzyme families responsible for regioselective halogenation of natural products. Structural studies of two flavin-dependent tryptophan 7-halogenases (PrnA and RebH) have generated important ins...

  16. Tryptophan-Containing Cyclic Dipeptides Studied by Optical Activity

    Hudecová, Jana; Horníček, Jan; Šebestík, Jaroslav; Buděšínský, Miloš; Bouř, Petr

    Oxford : Diamond, 2011. s. 20-20. [CD 2011. The International Conference on Chiroptical Spectroscopy /13./. 24.07.2011-28.07.2011, Oxford] R&D Projects: GA MŠk(CZ) LH11033; GA ČR GAP208/11/0105 Grant ostatní: AV ČR(CZ) M200550902; UK CZ(CZ) 126310 Institutional research plan: CEZ:AV0Z40550506 Keywords : cyclic dipeptides * ROA * DFT calculations * tryptophan e Subject RIV: CF - Physical ; Theoretical Chemistry

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

    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.

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

    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.

  19. Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders.

    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.

  20. L-Tryptophan L-tryptophanium bromide: Anhydrous and monohydrate

    Ghazaryan, V. V.; Giester, G.; Fleck, M.; Petrosyan, A. M.

    2015-12-01

    L-Tryptophan L-tryptophanium bromide (I) and L-tryptophan L-tryptophanium bromide monohydrate (II) are new salts with (A⋯A+) type dimeric cation. The salt (I) crystallizes in the monoclinic system (space group P21, Z = 2) and is isostructural with respective chloride (V.V. Ghazaryan et al., Spectrochim. Acta A 136(2015) 743-750), while the salt (II) was obtained previously (T. Takigawa et al., Bull. Chem. Soc. Jap. 39(1966) 2369-2378) and described as hemyhydrate without structure determination. The salt (II) crystallizes in orthorhombic system (space group P212121, Z = 4). The dimeric cations in (I) and (II) are formed by O-H⋯O hydrogen bonds with the O⋯O distances equal to 2.538(3) Å and 2.481(3) Å respectively. The infrared and Raman spectra of the crystals are studied and compared with the spectra of L-tryptophan L-tryptophanium chloride and L-tryptophanium bromide.

  1. Depletable resources and the economy.

    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

  2. Stratospheric ozone depletion.

    Rowland, F Sherwood

    2006-05-29

    Solar ultraviolet radiation creates an ozone layer in the atmosphere which in turn completely absorbs the most energetic fraction of this radiation. This process both warms the air, creating the stratosphere between 15 and 50 km altitude, and protects the biological activities at the Earth's surface from this damaging radiation. In the last half-century, the chemical mechanisms operating within the ozone layer have been shown to include very efficient catalytic chain reactions involving the chemical species HO, HO2, NO, NO2, Cl and ClO. The NOX and ClOX chains involve the emission at Earth's surface of stable molecules in very low concentration (N2O, CCl2F2, CCl3F, etc.) which wander in the atmosphere for as long as a century before absorbing ultraviolet radiation and decomposing to create NO and Cl in the middle of the stratospheric ozone layer. The growing emissions of synthetic chlorofluorocarbon molecules cause a significant diminution in the ozone content of the stratosphere, with the result that more solar ultraviolet-B radiation (290-320 nm wavelength) reaches the surface. This ozone loss occurs in the temperate zone latitudes in all seasons, and especially drastically since the early 1980s in the south polar springtime-the 'Antarctic ozone hole'. The chemical reactions causing this ozone depletion are primarily based on atomic Cl and ClO, the product of its reaction with ozone. The further manufacture of chlorofluorocarbons has been banned by the 1992 revisions of the 1987 Montreal Protocol of the United Nations. Atmospheric measurements have confirmed that the Protocol has been very successful in reducing further emissions of these molecules. Recovery of the stratosphere to the ozone conditions of the 1950s will occur slowly over the rest of the twenty-first century because of the long lifetime of the precursor molecules. PMID:16627294

  3. Adenosine triphosphate-pyrophosphate isotopic exchange reaction: a tool for determination of tryptophan

    Quantitative determination of tryptophan at the picomole level is described, using the ATP-[32P]PPi isotopic exchange reaction catalyzed by tryptophanyl-tRNA synthetase. Sensitivity limits of 500 fmol were obtained. The presence of other amino acids at a 1000-fold excess over tryptophan did not interfere significantly with the quantitative determination of tryptophan. The specificity of the reaction was checked using five tryptophan analogs. These analogs did not prevent the determination of tryptophan when present in the same concentration range as tryptophan. When sensitive determination of a single amino acid is needed, the ATP-[32P]PPi exchange reaction catalyzed by aminoacyl-tRNA synthetases is suggested as a general method and as an alternative to HPLC procedures

  4. Tryptophan fluorescence quenching by alkaline earth metal cations in deionized bacteriorhodopsin.

    Wang, G; Wang, A J; Hu, K S

    2000-12-01

    Tryptophan quenching by the addition of alkaline earth metal cations to deionized bacteriorhodopsin suspensions was determined. The results show that the addition of cation primarily quenches fluorescence from surface tryptophan residues. The quenched intensity exhibits a 1/R dependence, where R is the ionic radius of the corresponding metal ion. This observation results from a stronger energy transfer coupling between the tryptophan and the retinal. The membrane curvature may be involved as a result of cations motion and correlated conformational changes. PMID:11332888

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

    Yanofsky, C; Horn, V.; Gollnick, P

    1991-01-01

    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 leve...

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

    Marzieh Dehghan Shasaltaneh; Zahra Moosavi-Nejad; Sara Gharavi; Jamshid Fooladi

    2013-01-01

    Background and Objectives 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. Materials and Methods 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....

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

    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

  8. Decreased tryptophan and increased kynurenine levels in mastocytosis associated with digestive symptoms.

    Georgin-Lavialle, Sophie; Launay, Jean-Marie; Côté, Francine; Soucié, Erinn; Soria, Angèle; Damaj, Gandhi; Moura, Daniela Silva; Canioni, Danielle; Hanssens, Katia; Chandesris, Marie-Olivia; Barète, Stéphane; Dubreuil, Patrice; Lortholary, Olivier; Hermine, Olivier; Sokol, Harry

    2016-01-01

    The main metabolism pathway of tryptophan is protein formation, but it can also be metabolized into serotonin and kynurenine. Indoleamine 2,3-dioxygenase (IDO) is the enzyme that catalyzes the degradation of tryptophan into kynurenine. Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in various tissues with 57% of patients having gastrointestinal involvement. We studied tryptophan metabolism in mastocytosis patients displaying or not gastrointestinal features an...

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

    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.

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

    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.

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

    Bellina, Bruno; Merthe, Daniel J.; Kresin, Vitaly V.

    2015-03-01

    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 ṡ ṡ ṡ 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.

  12. Studies on the mechanism by which tryptophan efflux from isolated synaptosomes is stimulated by depolarization.

    Collard, K. J.; Wilkinson, L S; Lewis, D J

    1988-01-01

    1. The efflux and influx of tryptophan across the synaptosomal plasma membrane has been studied under a variety of experimental conditions, in order to examine the mechanism by which depolarization enhances the efflux of tryptophan from superfused synaptosomes. 2. Efflux of [3H]-tryptophan from preloaded superfused synaptosomes was found to be enhanced by K+ depolarization in a Ca2+ and dose-dependent manner. In contrast, [3H]-phenylalanine efflux was only poorly stimulated by depolarization ...

  13. Arabidopsis cytochrome P450 cyp83B1 mutations activate the tryptophan biosynthetic pathway.

    Smolen, Gromoslaw; Bender, Judith

    2002-01-01

    In plants, the tryptophan biosynthetic pathway provides a number of important secondary metabolites including the growth regulator indole-3-acetic acid (IAA) and indole glucosinolate defense compounds. Genes encoding tryptophan pathway enzymes are transcriptionally induced by a variety of stress signals, presumably to increase the production of both tryptophan and secondary metabolites during defense responses. To understand the mechanism of transcriptional induction, we isolated altered tryp...

  14. Radiolysis of aqueous oxygen-free solutions of tryptophan at various pH values

    Gamma radiolysis of 10 sup(-2)M aqueous oxygen-free tryptophan solutions irradiated at various pH values and in a Nsub(2)O atmosphere was investigated. The values of the radiation losses of tryptophan and the yields of NHsub(3) were determined. Using HPLC with an electrochemical detector, the formation of hydroxylated radiation products of tryptophan was followed. The effect of pH on the radiolysis course is discussed. (author)

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

    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. PMID:2472426

  16. UV radiation-induced photochemical damage of tryptophan in peptides, proteins and ocular lenses

    These studies were undertaken to investigate the possible involvement of the amino acid tryptophan in the near-ultraviolet radiation-induced photochemical alteration of peptides and proteins and the role tryptophan photolysis plays in ocular lens damage. Sample irradiations were performed to determine if tryptophan photolysis occurs with radiation in the UV-A region in comparison to photolysis induced by wavelengths in the normal absorption band of the amino acid (UV-B). Photolysis studies were carried out on free tryptophan and two dipeptides, tryptophyglycine and glycyltryptophan, in aqueous solutions at different pH values in the range 4.5-10.0 under aerated or anaerobic conditions. Rates of photolysis of these 290 nm-irradiated compounds, detected by observing tryptophan fluorescence intensity loss during irradiation, were compared and significant differences were observed for each compound which varied with pH and oxygen environment. Another series of experiments examined the photolysis of tryptophan residues in lens proteins in whole rat lenses induced by 290 nm and 298 nm dye laser radiation. Tryptophan residue photolysis was, once again, monitored by loss in tryptophan fluorescence intensity. A relationship was derived between tryptophan loss and photoproduct buildup during irradiation

  17. Mechanisms of elevation of rat brain tryptophan concentration by various doses of salicylate.

    Badawy, A. A.

    1982-01-01

    1 The roles of inhibition of liver tryptophan pyrrolase activity and of displacement of tryptophan from its binding sites on serum proteins have been investigated in relation to the increase in rat brain tryptophan concentration after administration of various doses of sodium salicylate. 2 The elevation of brain tryptophan concentration by sodium salicylate (0.5 mg/kg) was caused by inhibition of liver pyrrolase activity, whereas that by doses of the drug of 50 mg/kg and above was achieved ma...

  18. The disposition of intravenous L-tryptophan in healthy subjects and in patients with liver disease.

    Rössle, M; Herz, R; Mullen, K D; Jones, D b

    1986-01-01

    The disposition of free and of total tryptophan following an intravenous load of 1.5 g of L-tryptophan was evaluated in eight patients with non-cirrhotic liver disease, 40 patients with cirrhosis of the liver (21 Child's A, 15 Child's B, 4 Child's C) and in 14 healthy subjects. Cirrhosis affected disposition of tryptophan by (a) decreasing the clearance of both free and total tryptophan by 64% (P less than 0.001) and 34% (P less than 0.01), respectively, (b) by increasing the apparent volume ...

  19. Testing fully depleted CCD

    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.

  20. Probing the role of tryptophan-derived secondary metabolism in defense responses against Bipolaris oryzae infection in rice leaves by a suicide substrate of tryptophan decarboxylase.

    Ishihara, Atsushi; Nakao, Takahito; Mashimo, Yuko; Murai, Masatoshi; Ichimaru, Naoya; Tanaka, Chihiro; Nakajima, Hiromitsu; Wakasa, Kyo; Miyagawa, Hisashi

    2011-01-01

    Tryptophan-derived secondary metabolites, including serotonin and its hydroxycinnamic acid amides, markedly accumulate in rice leaves in response to pathogen attack. These compounds have been implicated in the physical defense system against pathogen invasion by being deposited in cell walls. Serotonin is biosynthesized from tryptophan via tryptamine, and tryptophan decarboxylase (TDC) catalyzes the first committed reaction. In this study, (S)-α-(fluoromethyl)tryptophan (S-αFMT) was utilized to investigate the effects of the inhibition of TDC on the defense responses of rice leaves. S-αFMT, enantiospecifically synthesized from L-tryptophan, effectively inhibited TDC activity extracted from rice leaves infected by Bipolaris oryzae. The inhibition rate increased dependently on the incubation time, indicating that S-αFMT served as a suicide substrate. Treatment of rice seedlings with S-αFMT suppressed accumulation of serotonin, tryptamine, and hydroxycinnamic acid amides of serotonin in a dose-dependent manner in B. oryzae-inoculated leaves. The lesions formed on seedlings treated with S-αFMT lacked deposition of brown materials, and those leaves were severely damaged in comparison with leaves without S-αFMT treatment. Administrating tryptamine to S-αFMT-treated leaves restored accumulation of tryptophan-derived secondary metabolites as well as deposition of brown material. In addition, tryptamine administration reduced damage caused by fungal infection. Accordingly, the accumulation of tryptophan-derived secondary metabolites was suggested to be part of the effective defense mechanism of rice. PMID:21112065

  1. 13C-tryptophan breath test detects increased catabolic turnover of tryptophan along the kynurenine pathway in patients with major depressive disorder

    Toshiya Teraishi; Hiroaki Hori; Daimei Sasayama; Junko Matsuo; Shintaro Ogawa; Miho Ota; Kotaro Hattori; Masahiro Kajiwara; Teruhiko Higuchi; Hiroshi Kunugi

    2015-01-01

    Altered tryptophan–kynurenine (KYN) metabolism has been implicated in major depressive disorder (MDD). The l-[1-13C]tryptophan breath test (13C-TBT) is a noninvasive, stable-isotope tracer method in which exhaled 13CO2 is attributable to tryptophan catabolism via the KYN pathway. We included 18 patients with MDD (DSM-IV) and 24 age- and sex-matched controls. 13C-tryptophan (150 mg) was orally administered and the 13CO2/12CO2 ratio in the breath was monitored for 180 min. The cumulative recove...

  2. Depletable resources and the economy.

    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, time preference and efficiency.For the steady state, three variants are distinguished; the stationary state, the physical steady state and the state of steady growth. It is concluded that the so-call...

  3. Gallium uptake in tryptophan-related pulmonary disease

    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

  4. Species and Cell Types Difference in Tryptophan Metabolism

    Yuki Murakami; Kuniaki Saito

    2013-01-01

    L-Tryptophan (L-TRP) is a nutritionally essential amino acid and the kynurenine (KYN) pathway is the major route of L-TRP catabolism. Besides being synthesized for proteins, L-TRP and its metabolites have critical roles for the functions of nervous and immune systems. Many researches show that optimal amounts of L-TRP in diets depend on species, developmental stages, environmental factors and health status. We have shown that KYN pathway-related enzyme activities vary among species, tissue an...

  5. Identification of Two Novel Modifications at Tryptophan Residues

    Zheng, Shuzhen; Zhang, Kai; Tian, Shanshan; He, Xiwen; Zhang, Yukui

    2015-08-01

    Protein post-translational modifications (PTMs) play important roles in cellular physiology. Mass spectrometry (MS) has been developed into a powerful tool to identify all possible protein modifications. Herein, we describe our efforts to deduce the structures of two unknown modifications at tryptophan (Trp) residues (W + 92 Da and W + 108 Da). The two modifications were further confirmed by aligning the MS/MS fragmentation of synthetic peptide with in-vivo peptide identified. Finally, the mimic experiment elucidated how two Trp modifications occur. This study, therefore, expands current knowledge of Trp modifications.

  6. Macrophage Depletion in Hypertensive Rats Accelerates Development of Cardiomyopathy

    Zandbergen, H.R.; Sharma, U.C.; S. Gupta; Verjans, J.W.H.; Borne, van den, J.J.G.C.; S Pokharel; Brakel, T.; Duijvestijn, A; Rooijen, van, J.; Maessen, J.G.; Reutelingsperger, C.P.M.; Pinto, Y.; Narula, J.; Hofstra, L

    2009-01-01

    Inflammation contributes to the process of ventricular remodeling after acute myocardial injury. To investigate the role of macrophages in the chronic process of cardiac remodeling, they were selectively depleted by intravenous administration of liposomal clodronate in heart failure-prone hypertensive Ren-2 rats from the age of 7 until 13 weeks. plain liposomes were used for comparison. Liposomal clodronate treatment reduced the number of blood monocytes and decreased the number of macrophage...

  7. Direct observation of resonance tryptophan-to-chromophore energy transfer in visible fluorescent proteins

    Visser, NV; Borst, JW; Hink, MA; van Hoek, A; Visser, AJWG

    2005-01-01

    Visible fluorescent proteins from Aequorea victoria contain next to the fluorophoric group a single tryptophan residue. Both molecules form a single donor-acceptor pair for resonance energy transfer (RET) within the protein. Time-resolved fluorescence experiments using tryptophan excitation have sho

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

    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. Photophysics of tryptophan in H2O, D2O, and in nonaqueous solvents

    The fluorescence properties of tryptophan in water and deuterated water have been examined. Tryptophan molecules exhibit three distinct fluorescence lifetimes in water which become longer in deuterated water; the two shorter lifetimes are present below the pK of the amino group and the long lifetime appears as the pH is raised through this pK. The steady-state quenching of tryptophan fluorescence by hydrogen ion in the region of pH less than 3 shows a definite wavelength effect, consistent with less-pronounced quenching of the subnanosecond component whose emission maximum is at 330 nm. The Stern-Volmer plots show a marked curvature in the direction of decreasing Stern-Volmer constant as [H3O+] increases. Deuterium ion also quenches tryptophan fluorescence at low pD. A kinetic scheme is proposed which reproduces both the steady-state and lifetime quenching results. Tryptophan in methanol or ethanol exhibits three fluorescence lifetimes; the relative percentage of the long component vs. the intermediate component can be varied by the addition of triethylamine or acid. In dimethyl sulfoxide, tryptophan and tryptophan deuterated at the amino and ring nirogen positions show identical behavior, both having the same decay parameters. These results are discussed in light of the theories which have recently been proposed to account for the several components in tryptophan fluorescence decay. Solvent interaction is suggested to play a critical role

  10. Tritium kinetic isotope effects on enzymatic decomposition of L-tryptophan

    The tritium kinetic isotope effect on position 2 has been determined in the reaction of decomposition of L-tryptophan, L-Trp, catalyzed by enzyme TPase, (EC 4.1.99.1). The numerical values of isotope effects in the course of reaction were obtained by the competitive method using [1-14C]-L-tryptophan as internal radiometric standard. (author)

  11. Regioselective Nitration of Nα,N1-Bis(trifluoroacetyl)-L-Tryptophan Methyl Ester: Efficient Synthesis of 2-Nitro and 6-Nitro-N-Trifluoroacetyl-L-Tryptophan Methyl Ester

    Osborne, Andrew S.; Som, Phanneth; Metcalf, Jessica L.; Phillips, Robert S.

    2008-01-01

    Nitration of Nα,N1-bis(trifluoroacetyl)-L-tryptophan methyl ester with HNO3 in acetic anhydride at 0° C provides Nα-trifluoroacetyl-2-nitro-L-tryptophan methyl ester in 67% yield, whereas nitration in trifluoroacetic acid at 0° C gives Nα-trifluoroacetyl-6-nitro-L-tryptophan methyl ester in 69% yield.

  12. Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans.

    Palego, Lionella; Betti, Laura; Rossi, Alessandra; Giannaccini, Gino

    2016-01-01

    L-Tryptophan is the unique protein amino acid (AA) bearing an indole ring: its biotransformation in living organisms contributes either to keeping this chemical group in cells and tissues or to breaking it, by generating in both cases a variety of bioactive molecules. Investigations on the biology of Trp highlight the pleiotropic effects of its small derivatives on homeostasis processes. In addition to protein turn-over, in humans the pathways of Trp indole derivatives cover the synthesis of the neurotransmitter/hormone serotonin (5-HT), the pineal gland melatonin (MLT), and the trace amine tryptamine. The breakdown of the Trp indole ring defines instead the "kynurenine shunt" which produces cell-response adapters as L-kynurenine, kynurenic and quinolinic acids, or the coenzyme nicotinamide adenine dinucleotide (NAD(+)). This review aims therefore at tracing a "map" of the main molecular effectors in human tryptophan (Trp) research, starting from the chemistry of this AA, dealing then with its biosphere distribution and nutritional value for humans, also focusing on some proteins responsible for its tissue-dependent uptake and biotransformation. We will thus underscore the role of Trp biochemistry in the pathogenesis of human complex diseases/syndromes primarily involving the gut, neuroimmunoendocrine/stress responses, and the CNS, supporting the use of -Omics approaches in this field. PMID:26881063

  13. Tryptophan autofluorescence imaging of neoplasms of the human colon

    Banerjee, Bhaskar; Renkoski, Timothy; Graves, Logan R.; Rial, Nathaniel S.; Tsikitis, Vassiliki Liana; Nfonsom, Valentine; Pugh, Judith; Tiwari, Piyush; Gavini, Hemanth; Utzinger, Urs

    2012-01-01

    Detection of flat neoplasia is a major challenge in colorectal cancer screening, as missed lesions can lead to the development of an unexpected `incident' cancer prior to the subsequent endoscopy. The use of a tryptophan-related autofluorescence has been reported to be increased in murine intestinal dysplasia. The emission spectra of cells isolated from human adenocarcinoma and normal mucosa of the colon were studied and showed markedly greater emission intensity from cancerous cells compared to cells obtained from the surrounding normal mucosa. A proto-type multispectral imaging system optimized for ultraviolet macroscopic imaging of tissue was used to obtain autofluorescence images of surgical specimens of colonic neoplasms and normal mucosa after resection. Fluorescence images did not display the expected greater emission from the tumor as compared to the normal mucosa, most probably due to increased optical absorption and scattering in the tumors. Increased fluorescence intensity in neoplasms was observed however, once fluorescence images were corrected using reflectance images. Tryptophan fluorescence alone may be useful in differentiating normal and cancerous cells, while in tissues its autofluorescence image divided by green reflectance may be useful in displaying neoplasms.

  14. Acetate binding induces fluorescence enhancement in tryptophan ligands

    Deka, Arup K.; Sarma, Rupam J., E-mail: rjs@gauhati.ac.in

    2014-03-15

    The anion coordination properties of bis-tryptophan dicarboxamide ligands 1–3 were investigated using fluorescence and {sup 1}H NMR spectroscopy. It was observed that the coordination of acetate anions to these ligands produced emissions at 381 nm with gradual enhancement of fluorescence. In comparison, fluoride produced minor enhancement, the addition of chloride, bromide and nitrate anions caused quenching of ligand fluorescence. {sup 1}H NMR studies revealed that the ligands coordinated to the acetate anions through the indole and amide NH groups. -- Highlights: • We have synthesized and characterized three tryptophan-based diamide ligands 1–3. • We have reported new polymorph of ligand 1 (Crystal structure) in this article. • The role of intramolecular hydrogen bonding (1 vs. 2) in anion binding was investigated. • We were able to identify the role amide/indole NH in anion binding using {sup 1}H NMR. • On the basis of {sup 1}H NMR, we have established role of aromatic CH–anion interactions during anion complexation.

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

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

    2008-01-01

    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...... 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 the...... iron and the tryptophan Cζ3 atom that is hydroxylated. The binding of tryptophan and maybe the imidazole has caused the structural changes in the catalytic domain compared to the structure of the human TPH1 without tryptophan. The structure of chicken TPH1 is more compact, and the loops of residues Leu...

  16. The effect of ionizing radiation on tryptophan fluorescence of thymocyte and erythrocyte plasma membranes

    The effect of γ-radiation on tryptophan fluorescence of thymocyte and erythrocyte plasma membrane preparations was studied. The intensity of tryptophan fluorescence decreased after applying radiation doses up to 15 Gy. The radiosensitivity of thymocyte membranes appeared to be higher than that of the erythrocyte ghosts. Tryptophan radiolysis did not significantly contribute to the effects of radiation. The fraction of tryptophan residues accessible for quenching by I- decreased from 0.87 in the untreated membranes to 0.63 and 0.49 in membranes after doses of 10 and 250 Gy, respectively. The effective quenching constant and the tryptophan fluorescence polarization increased after irradiation. The mechanisms producing these radiation-induced changes are discussed. (author)

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

    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. TRYPTOPHAN: EFFECTS ON NEUTOTRANSMITTERS, BEHAVIOR, MEAT QUALITY, AND THE RESULTS OF CURRENT REQUIREMENT STUDIES IN NURSERY PIGS

    Tryptophan is one of most interesting and complex amino acids. The lack of sensitive methods for tryptophan determination in proteins and biological fluids, low content in common feedstuffs, low product availability, high cost of crystalline tryptophan, and the high degree of variability associated...

  19. Nonlinear lower hybrid wave depletion

    Two numerical ray tracing codes with focusing are used to compute lower hybrid daughter wave amplification by quasi-mode parametric decay. The first code, LHPUMP provides a numerical pump model on a grid. This model is used by a second code, LHFQM which computes daughter wave amplification inside the pump extent and follows the rays until their energy is absorbed by the plasma. An analytic model is then used to estimate pump depletion based on the numerical results. Results for PLT indicate strong pump depletion at the plasma edge at high density operation for the 800 Mhz wave frequency, but weak depletion for the 2.45 Ghz experiment. This is proposed to be the mechanism responsible for the high density limit for current drive as well as for the difficulty to heat ions

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

    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.

  1. The effect of pH on the aerobic and anaerobic photolysis of tryptophan and some tryptophan-containing dipeptides

    Rates of photolysis, quantum yields of fluorescence, and fluorescence emission maxima for the dipeptides glycyltryptophan (Gly-Trp) and tryptophylglycine (Trp-Gly) and for free tryptophan (Trp) were determined under both degassed and aerated conditions in the pH range 4.5-10.0. The photolyses were performed at 250C using 290 nm radiation from a 1000 W xenon lamp. Photolysis rates were determined by monitoring tryptophan fluorescence loss with time. It was found that Trp-Gly and free Trp showed similar behavior in that their fluorescence quantum yields and photolysis rates increased significantly above neutral pH. In contrast, the Gly-Trp fluorescence yield was smaller than that of Trp or Trp-Gly, showing no significant increase at high pH and the photolysis rate for Gly-Trp decreased with increasing pH. In comparing aerated to degassed samples, degassing had a far greater effect on the photolysis rates of Trp and Trp-Gly than on the photolysis rate of Gly-Trp especially at higher pH. But, degassing did not change the relative fluorescence quantum yields or fluorescence emission maxima of any of the three compounds. Possible mechanisms for photolysis under various experimental conditions were examined in light of the data. (author)

  2. Ventilatory adaptation to hypoxia occurs in serotonin-depleted rats.

    Olson, E B

    1987-08-01

    To test the hypothesis that serotonin mediated respiratory activity is involved in ventilatory adaptation to hypoxia, rats were treated with parachlorophenylalanine (PCPA), a potent, long-acting inhibitor of tryptophan hydroxylase, the rate-limiting enzyme in the biosynthesis of serotonin. In normoxia, a single, intraperitoneal injection of 300 mg PCPA/kg body weight decreased the Paco2 from a control level at 39.1 +/- 0.6 Torr (mean +/- 95% confidence limits) to 34.0 +/- 0.6 Torr measured during a period from 1 to 48 h following PCPA treatment. This PCPA-produced hyperventilation corresponds to an increase of 3.7 +/- 0.5 in the VA (BTPS)/Vco2 (STPD) ratio. Hyperventilation during ventilatory adaptation to hypoxia (PIO2 approximately equal to 90 Torr) was superimposed in an additive fashion on the underlying hyperventilation due to PCPA pretreatment. Specifically, PCPA pretreatment caused an average 3.5 +/- 1.2 increase in the VA/VCO2 ratio determined in acute (1 h) hypoxia, chronic (24 h) hypoxia and acute return to normoxia following chronic hypoxia. Since ventilatory adaptation to hypoxia occurred in rats treated with PCPA, the prolonged, serotonin mediated respiratory activity described by Millhorn et al. (1980b) is probably not important in ventilatory acclimatization to - or deacclimatization from - hypoxia. PMID:2957766

  3. Modelling the evolution of the archaeal tryptophan synthase

    Merkl Rainer

    2007-04-01

    Full Text Available Abstract Background Microorganisms and plants are able to produce tryptophan. Enzymes catalysing the last seven steps of tryptophan biosynthesis are encoded in the canonical trp operon. Among the trp genes are most frequently trpA and trpB, which code for the alpha and beta subunit of tryptophan synthase. In several prokaryotic genomes, two variants of trpB (named trpB1 or trpB2 occur in different combinations. The evolutionary history of these trpB genes is under debate. Results In order to study the evolution of trp genes, completely sequenced archaeal and bacterial genomes containing trpB were analysed. Phylogenetic trees indicated that TrpB sequences constitute four distinct groups; their composition is in agreement with the location of respective genes. The first group consisted exclusively of trpB1 genes most of which belonged to trp operons. Groups two to four contained trpB2 genes. The largest group (trpB2_o contained trpB2 genes all located outside of operons. Most of these genes originated from species possessing an operon-based trpB1 in addition. Groups three and four pertain to trpB2 genes of those genomes containing exclusively one or two trpB2 genes, but no trpB1. One group (trpB2_i consisted of trpB2 genes located inside, the other (trpB2_a of trpB2 genes located outside the trp operon. TrpA and TrpB form a heterodimer and cooperate biochemically. In order to characterise trpB variants and stages of TrpA/TrpB cooperation in silico, several approaches were combined. Phylogenetic trees were constructed for all trp genes; their structure was assessed via bootstrapping. Alternative models of trpB evolution were evaluated with parsimony arguments. The four groups of trpB variants were correlated with archaeal speciation. Several stages of TrpA/TrpB cooperation were identified and trpB variants were characterised. Most plausibly, trpB2 represents the predecessor of the modern trpB gene, and trpB1 evolved in an ancestral bacterium

  4. Substitutions of Thr30 provide mechanistic insight into tryptophan-mediated activation of TRAP binding to RNA

    Payal, Vandana; Gollnick, Paul

    2006-01-01

    TRAP is an 11 subunit RNA binding protein that regulates expression of genes involved in tryptophan biosynthesis and transport in Bacillus subtilis. TRAP is activated to bind RNA by binding up to 11 molecules of l-tryptophan in pockets formed by adjacent subunits. The precise mechanism by which tryptophan binding activates TRAP is not known. Thr30 is in the tryptophan binding pocket. A TRAP mutant in which Thr30 is substituted with Val (T30V) does not bind tryptophan but binds RNA constitutiv...

  5. DOPAMINE DEPLETION SLOWS RETINAL TRANSMISSION

    In male hooded rats, depletion of norepinephrine and dopamine by a-methyl-paratyrosine (AMT) significantly increased the latencies of early peaks in flash-evoked potentials recorded from the visual cortex, lateral geniculate nucleus, and optic tract. These effects were not produc...

  6. Was the Chlamydial Adaptative Strategy to Tryptophan Starvation an Early Determinant of Plastid Endosymbiosis?

    Cenci, Ugo; Ducatez, Mathieu; Kadouche, Derifa; Colleoni, Christophe; Ball, Steven G

    2016-01-01

    Chlamydiales were recently proposed to have sheltered the future cyanobacterial ancestor of plastids in a common inclusion. The intracellular pathogens are thought to have donated those critical transporters that triggered the efflux of photosynthetic carbon and the consequent onset of symbiosis. Chlamydiales are also suspected to have encoded glycogen metabolism TTS (Type Three Secretion) effectors responsible for photosynthetic carbon assimilation in the eukaryotic cytosol. We now review the reasons underlying other chlamydial lateral gene transfers evidenced in the descendants of plastid endosymbiosis. In particular we show that half of the genes encoding enzymes of tryptophan synthesis in Archaeplastida are of chlamydial origin. Tryptophan concentration is an essential cue triggering two alternative modes of replication in Chlamydiales. In addition, sophisticated tryptophan starvation mechanisms are known to act as antibacterial defenses in animal hosts. We propose that Chlamydiales have donated their tryptophan operon to the emerging plastid to ensure increased synthesis of tryptophan by the plastid ancestor. This would have allowed massive expression of the tryptophan rich chlamydial transporters responsible for symbiosis. It would also have allowed possible export of this valuable amino-acid in the inclusion of the tryptophan hungry pathogens. Free-living single cell cyanobacteria are devoid of proteins able to transport this amino-acid. We therefore investigated the phylogeny of the Tyr/Trp transporters homologous to E. coli TyrP/Mre and found yet another LGT from Chlamydiales to Archaeplastida thereby considerably strengthening our proposal. PMID:27446814

  7. Role for tryptophan in regulation of protein synthesis in porcine muscle

    Experiments were conducted to determine the effect of varying concentrations of dietary tryptophan on growth rate and protein synthesis in edible muscle tissues of growing swine. A total of 45 immature swine (initial weight approximately 24 kg) were fed corn-gelatin diets containing 0.5 (n = 8), 0.8 (n = 10), 1.3 (n = 10), 1.5 (n = 7) or 2.0 (n = 10) g tryptophan/kg diet for 35 d. Animals fed 0.5 and 0.8 g tryptophan/kg grew more slowly, consumed less feed and had a lower efficiency of feed utilization than animals fed higher concentrations of tryptophan. Thirty similar animals were used in a second experiment. Diets containing 0.5, 0.8, 1.0, 1.5 or 2.0 g tryptophan/kg diet (n = 6) were fed for 14 d, after which all animals were killed and samples were taken of longissimus dorsi, triceps brachii and biceps femoris. Protein synthetic activity was determined by monitoring the incorporation of [14C]phenylalanine into protein in vitro. There was no significant difference in synthetic activity between different muscle types. There was no effect of diet on the activity of the muscle soluble protein fraction. The activity of the muscle ribosomal fraction, however, was positively correlated with increasing concentrations of dietary tryptophan. It was concluded that tryptophan has the potential to regulate muscle protein synthesis in a manner beyond serving simply as a component of protein

  8. Functional roles of Tryptophan residues in diketoreductase from Acinetobacter baylyi

    Yan Huang1, Zhuo Lu1, Min Ma1, Nan Liu1 & Yijun Chen1,2,*

    2012-08-01

    Full Text Available Diketoreductase (DKR from Acinetobacter baylyi contains twotryptophan residues at positions 149 and 222. Trp-149 andTrp-222 are located along the entry path of substrate into activesite and at the dimer interface of DKR, respectively. Single anddouble substitutions of these positions were generated to probethe roles of tryptophan residues. After replacing Trp with Alaand Phe, biochemical and biophysical characteristics of themutants were thoroughly investigated. Enzyme activity andsubstrate binding affinity of W149A and W149F wereremarkably decreased, suggesting that Trp-149 regulates theposition of substrate at the binding site. Meanwhile, enzymeactivity of W222F was increased by 1.7-fold while W222A wascompletely inactive. In addition to lower thermostability ofTrp-222 mutants, molecular modeling of the mutants revealedthat Trp-222 is vital to protein folding and dimerization of theenzyme.

  9. Doxycycline induced photodamage to human neutrophils and tryptophan

    Neutrophil function were studied following irradiation (340-380 nm) of the cells in the presence of 22 μM 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 D2O, 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 D2O and nearly abolished in the presence of 0.25 mM NaN3, 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. (author)

  10. Doxycycline induced photodamage to human neutrophils and tryptophan

    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.

  11. The combined depletion of monoamines alters the effectiveness of subthalamic deep brain stimulation.

    Faggiani, Emilie; Delaville, Claire; Benazzouz, Abdelhamid

    2015-10-01

    Non-motor symptoms of Parkinson's disease are under-studied and therefore not well treated. Here, we investigated the role of combined depletions of dopamine, norepinephrine and/or serotonin in the manifestation of motor and non-motor deficits in the rat. Then, we studied the impact of these depletions on the efficacy of deep brain stimulation of the subthalamic nucleus (STN-DBS). We performed selective depletions of dopamine, norepinephrine and serotonin, and the behavioral effects of different combined depletions were investigated using the open field, the elevated plus maze and the forced swim test. Bilateral dopamine depletion alone induced locomotor deficits associated with anxiety and mild "depressive-like" behaviors. Although additional depletions of norepinephrine and/or serotonin did not potentiate locomotor and anxiety disorders, combined depletions of the three monoamines dramatically exacerbated "depressive-like" behavior. STN-DBS markedly reversed locomotor deficits and anxiety behavior in animals with bilateral dopamine depletion alone. However, these improvements were reduced or lost by the additional depletion of norepinephrine and/or serotonin, indicating that the depletion of these monoamines may interfere with the antiparkinsonian efficacy of STN-DBS. Furthermore, our results showed that acute STN-DBS improved "depressive-like" disorder in animals with bilateral depletion of dopamine and also in animals with combined depletions of the three monoamines, which induced severe immobility in the forced swim test. Our data highlight the key role of monoamine depletions in the pathophysiology of anxiety and depressive-like disorders and provide the first evidence of their negative consequences on the efficacy of STN-DBS upon the motor and anxiety disorders in the context of Parkinson's disease. PMID:26206409

  12. Effect of gamma irradiation on methionine and tryptophan content in soya protein products

    Effect of gamma irradiation on the content of methionine and tryptophan in soya protein products were investigated. Irradiation with doses of 1, 3 and 5 kGy caused significant (p = 0.05) decrease of methionine contents. Parallel with the decrease in methionine also the relative quality of proteins is lowered. Tryptophan content were significantly reduced (p = 0.05) at irradiation doses of 3 and 5 kGy. The relative decrease of methionine and tryptophan contents are significantly correlated (p = 0.05) with relative increase in amount of products by the irradiation induced oxidation of lipids; correlation coefficients were 0.576 and 0.715

  13. The role of tryptophan in the photochemical crosslinking of peptides and proteins

    Irradiation of wool and several other proteins in the presence of 14C-labelled tryptophan results in the covalent binding of radioactive material to the protein. This result is consistent with the claim that irradiation of proteins introduces crosslinks involving tryptophan residues. Radiolabelling techniques have been used to study the products of irradiation of the tripeptide, Ala-14C-Trp-Val. Some of these products are polymeric - further evidence for the involvement of tryptophan in crosslinking reactions. Most of the yellow material produced during irradiation in air is polymeric. (orig.)

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

    Windahl, Michael Skovbo; Boesen, Jane; Karlsen, Pernille Efferbach; Christensen, Hans Erik Mølager

    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......, purified and the kinetic properties have been studied and are compared. Substrate inhibition by tryptophan is observed for isoform 1 but not for isoform 2. Large differences are observed in the K m,tetrahydrobiopterin values for the two isoforms, being >10 times larger for isoform 1 compared to isoform 2....

  15. Arabidopsis thaliana auxotrophs reveal a tryptophan-independent biosynthetic pathway for indole-3-acetic acid.

    Normanly, J; Cohen, J D; Fink, G. R.

    1993-01-01

    We used tryptophan auxotrophs of the dicot Arabidopsis thaliana (wall cress) to determine whether tryptophan has the capacity to serve as a precursor to the auxin, indole-3-acetic acid (IAA). Quantitative gas chromatography-selected ion monitoring-mass spectrometry (GC-SIM-MS) revealed that the trp2-1 mutant, which is defective in the conversion of indole to tryptophan, accumulated amide- and ester-linked IAA at levels 38-fold and 19-fold, respectively, above those of the wild type. Tryptopha...

  16. The influence of tryptophan on gluconeogenesis in the perfused liver of irradiated rats

    The liver isolated at different times after exposure to 7 Gy radiation responded in a different way to the effect of tryptophan (0.75 g/l) used as a gluconeogenesis inhibitor. While 24 h after irradiation of the addition of tryptophan inhibited gluconeogenesis from circulating exogenous amino acids, in 3 days, on the contrary, gluconeogenesis in the liver of donors was enhanced. It is suggested that these effects of tryptophan are associated with different functional status of the liver during the postirradiation observation period

  17. Radiation induced modification of tryptophan and tyrosine residues in flavocytochrome b2 in dilute aqueous solution

    Steady state gamma irradiation of an aqueous solution of flavocytochrome b2 under different conditions led to modification of tryptophan and tyrosine residues. These aromatic amino acid residues were more susceptible to the attack by OH radicals than H atoms. Unchanged quantum yield values for tryptophan and tyrosine residues and unchanged tryptophan excited state lifetime in the irradiated enzyme suggests that irradiation results in breakage of some non-covalent bonds disrupting the peptide framework partially. It is justified by the circular dichroic studies for the irradiated enzyme which shows a reduced helicity but no evolution towards any other structures.

  18. [Biomedical and economic consequences of stratosphere ozone depletion].

    Strzhizhovskiĭ, A D

    1998-01-01

    Information on possible human health-changes associated with stratosphere ozone depletion and amplification factor (% increase of the stick rate by 1% decrease of ozone) values for acute (erythema, keratitis, cataract, immunosuppression) and chronic (skin cancer, cataract) effects of natural UV-radiation was analysed. Amplification factor (AF) values for acute UV-effects increase with degree of ozone depletion. For degrees less than 12.5% they are independent of latitude and equal to 1.9 for erythema, 1.3-1.5 for keratitis, 1.7-2.3 for cataract and 0.9-1.1 for immunosuppression. AF values for incidence of non-melanoma skin cancer are independent of age, higher in males than females, and higher for squamous cell carcinoma, than for basal cell carcinoma. Their optimal estimations for whites equal to 2.7 for basal cell and 4.6 for squamous cell carcinoma. AF values for incidence of cutaneous malignant melanoma range between 1 and 2, for melanoma mortality--between 0.3 and 2. AF values for incidence of cataract range between 0.3 and 1.2 with optimal estimations between 0.6 and 0.8. Prognosis of non-melanoma skin cancer and cataract incidences, melanoma mortality and economic loss for different scenarios of stratosphere ozone depletion are presented. PMID:9633627

  19. Brain kinetics of 11 C-labelled L-tryptophan and 5-hydroxy-L-tryptophan in the Rhesus monkey. A study using positron emission tomography

    5-hydroxy-L-tryptophan labelled with 11 C is introduced as a tracer for the vivo assessment of brain serotonin synthesis in the Rhesus monkey using positron emission tomography, PET. Increasing radioactivities were seen in the striatal area in contrast to that seen in other brain regions. Following 11 C-labelled L-tryptophan an even spread of brain radioactivity was seen. This selective increase most probably results from the decarboxylation of tracer and retention of formed products since no striatal increase of radioactivity was seen when 5-hydroxy-L-tryptophan labelled with 11 C in the carboxy-position was administered. Furthermore, pretreatment of the monkey with a centrally active decarboxylase inhibitor (NSD 1015, 10 mg/kg) did not lead to increased striatal radioactivities after the administration of 5-hydroxy-(β-11 C)-L-tryptophan. The selective utilization of the radiotracer in the striatal area increased with a rate constant calculated to be 0.0055 ± 0.0015 min-1 (n=5) using the surrounding brain as reference area. A non-significant influence of radiolabelled metabolites to the rate constants measured was shown after pretreatment of the monkeys with selective and non-selective monoamine oxidase inhibitors, respectively. These results may give a basis for the use of the new tracer 5-hydroxy-(β-11 C)-L-tryptophan in PET-studies of brain serotonin metabolism in health and disease. (authors)

  20. Biogenic amines and acute thermal stress in the rat

    Williams, B. A.; Moberg, G. P.

    1975-01-01

    A study is summarized which demonstrates that depletion of the biogenic amines 5-hydroxytryptamine (5-HT) or norepinephrine (NE) alters the normal thermoregulatory responses to acute temperature stress. Specifically, NE depletion caused a significant depression in equilibrium rectal temperature at 22 C and a greater depression in rectal temperature than controls in response to cold (6 C) stress; NE depletion also resulted in a significantly higher rectal temperature response to acute heat (38 C) stress. Depletion of 5-HT had less severe effects. It remains unclear whether the primary site of action of these agents is central or peripheral.

  1. Civil use of depleted uranium

    In this paper the civilian exploitation of depleted uranium is briefly reviewed. Different scenarios relevant to its use are discussed in terms of radiation exposure for workers and the general public. The case of the aircraft accident which occurred in Amsterdam in 1992 involving a fire, is discussed in terms of the radiological exposure to bystanders. All information given has been obtained on the basis of an extensive literature search and are not based on measurements performed at the Institute for Transuranium Elements

  2. Ozone Depletion from Nearby Supernovae

    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...

  3. Ozone Depletion from Nearby Supernovae

    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.

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

    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

  5. Linoleic acid, thymine, and tryptophan radiosensitization by protoporphyrin in presence of oxygene

    Sensitizing effect induced by protoporphyrin, an active molecule in photooxidation is studied. Studied substances are tryptophan, thymine, linoleic acid, each component representing one of the great groups of biological components, nucleic acid, proteins, lipids

  6. Changes in the tryptophan fluorescence in gamma-irradiated human haemoglobin

    The effect of gamma-radiation on human haemoglobin was studied by means of fluorescence spectroscopy. Irradiation with doses in the range of 0-2.4 Mrad led to an increase in fluorescence intensity, and a red shift of the fluorescence maximum. Such spectral changes should be attributed mainly to a more polar environment of tryptophan residues in irradiation haemoglobin caused by protein unfolding and to a concomitant increase in separation between tryptophan residues and haem groups. Differences in fluorescence intensity but not spectral distribution between control and irradiated samples denatured in guanidinium hydrochloride indicate a radiation-induced decrease in tryptophan content. Fluorescence quenching by caesium ions was observed in irradiated haemoglobin but not in native haemoglobin. The Stern-Volmer constant calculated for caesium quenching indicates tht the fraction of tryptophan residues accessible to the quencher increases after irradiation. (author)

  7. Synthesis of enantiomerically pure α-[14C]methyl-L-tryptophan

    A practical method for the preparation of large amounts of enantiomerically pure α-[14C]methyl-L-tryptophan using the enzymatic resolution of the corresponding D,L-methyl ester is reported. The radiolabelled α-methyl group was introduced using the α-methylation of the lithium enolate of the Schiff base of L-tryptophan methyl ester. Hydrolysis of the Schiff base with 1 N HCl provided the D,L-methyl ester of α-[14C]methyl tryptophan. Enantioselective enzymatic hydrolysis of the L-methyl ester by α-chymotrypsin gave the enantiometrically pure α-[14C]methyl-L-tryptophan. The overall yield of this preparation was 33%. (author)

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

    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.

  9. Effect of disordered hemes on energy transfer rates between tryptophans and heme in myoglobin.

    Gryczynski, Z.; Fronticelli, C; Tenenholz, T; Bucci, E

    1993-01-01

    Our recent linear dichroism study of heme transitions (Gryczynski, Z., E. Bucci, and J. Kusba. 1993. Photochem. Photobiology. in press) indicate that heme cannot be considered a planar oscillator when it acts as an acceptor of radiationless excitation energy transfer from tryptophan. The linear nature of the heme absorption transition moment in the near-UV region implies a strong dependence of the transfer rate factors on the relative angular position of the heme and tryptophan, i.e., on the ...

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

    Strasser, Barbara; Geiger, Daniela; Schauer, Markus; Gatterer, Hannes; Burtscher, Martin; Fuchs, Dietmar

    2016-01-01

    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 increased immune

  11. Post-epidemic eosinophilia myalgia syndrome associated with L-Tryptophan

    Allen, Jeffrey A; Peterson, Alicia; Sufit, Robert; Hinchcliff, Monique E.; Mahoney, J. Matthew; Wood, Tammara A.; Miller, Frederick W; Whitfield, Michael L.; Varga, John

    2011-01-01

    Eosinophilia–myalgia syndrome (EMS) is characterized by subacute onset of myalgias and peripheral eosinophilia, followed by chronic neuropathy and skin induration. An epidemic of EMS in 1989 was linked to L-tryptophan consumption originating from a single source. Following the Food and Drug Administration (FDA) ban on the sale of L-tryptophan, the incidence of EMS declined rapidly. Moreover, no new cases have been published since the FDA ban was lifted in 2005. We report the clinical, histopa...

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

    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 association of sleep quality and insomnia with dietary intake of tryptophan and niacin

    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. Materials and methods: A survey on past week's dietary intake (food frequency questionnaire)was completed by N = 509 Dutch university students (20.8 years old). The SLEEP-50 questionnaire subscale on in...

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

    Barbara Strasser; Daniela Geiger; Markus Schauer; Hannes Gatterer; Martin Burtscher; Dietmar Fuchs

    2016-01-01

    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 immun...

  15. Using tryptophan fluorescence to measure the stability of membrane proteins folded in liposomes

    Moon, C. Preston; Fleming, Karen G.

    2011-01-01

    Accurate measurements of the thermodynamic stability of folded membrane proteins require methods for monitoring their conformation that are free of experimental artifacts. For tryptophan fluorescence emission experiments with membrane proteins folded into liposomes, there are two significant sources of artifacts: the first is light scattering by the liposomes; the second is the nonlinear relationship of some tryptophan spectral parameters with changes in protein conformation. Both of these so...

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

    Zhou, Jia

    2010-01-01

    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 + in...

  17. Changes of intermediary taurine and tryptophan metabolism after combined radiation-thermal injury

    The dynamics of changes of the taurine and tryptophane concentration in blood serum of rats has been studied during 30 days after 3b degree burn of 15% of body surface after total even exposure to radiation in doses of 3 and 6 Gy, and after combined radiation thermal injury. Combined radiation-thermal injury was found to be characterized by reduced concentration of taurine but an increase of the tryptophane level from the second-third day after the injury

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

    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

  19. Issues in Stratospheric Ozone Depletion.

    Lloyd, Steven Andrew

    Following the announcement of the discovery of the Antarctic ozone hole in 1985 there have arisen a multitude of questions pertaining to the nature and consequences of polar ozone depletion. This thesis addresses several of these specific questions, using both computer models of chemical kinetics and the Earth's radiation field as well as laboratory kinetic experiments. A coupled chemical kinetic-radiative numerical model was developed to assist in the analysis of in situ field measurements of several radical and neutral species in the polar and mid-latitude lower stratosphere. Modeling was used in the analysis of enhanced polar ClO, mid-latitude diurnal variation of ClO, and simultaneous measurements of OH, HO_2, H_2 O and O_3. Most importantly, such modeling was instrumental in establishing the link between the observed ClO and BrO concentrations in the Antarctic polar vortex and the observed rate of ozone depletion. The principal medical concern of stratospheric ozone depletion is that ozone loss will lead to the enhancement of ground-level UV-B radiation. Global ozone climatology (40^circS to 50^ circN latitude) was incorporated into a radiation field model to calculate the biologically accumulated dosage (BAD) of UV-B radiation, integrated over days, months, and years. The slope of the annual BAD as a function of latitude was found to correspond to epidemiological data for non-melanoma skin cancers for 30^circ -50^circN. Various ozone loss scenarios were investigated. It was found that a small ozone loss in the tropics can provide as much additional biologically effective UV-B as a much larger ozone loss at higher latitudes. Also, for ozone depletions of > 5%, the BAD of UV-B increases exponentially with decreasing ozone levels. An important key player in determining whether polar ozone depletion can propagate into the populated mid-latitudes is chlorine nitrate, ClONO_2 . As yet this molecule is only indirectly accounted for in computer models and field

  20. Room temperature phosphorescence study on the structural flexibility of single tryptophan containing proteins

    Kowalska-Baron, Agnieszka; Gałęcki, Krystian; Wysocki, Stanisław

    2015-01-01

    In this study, we have undertaken efforts to find correlation between phosphorescence lifetimes of single tryptophan containing proteins and some structural indicators of protein flexibility/rigidity, such as the degree of tryptophan burial or its exposure to solvent, protein secondary and tertiary structure of the region of localization of tryptophan as well as B factors for tryptophan residue and its immediate surroundings. Bearing in mind that, apart from effective local viscosity of the protein/solvent matrix, the other factor that concur in determining room temperature tryptophan phosphorescence (RTTP) lifetime in proteins is the extent of intramolecular quenching by His, Cys, Tyr and Trp side chains, the crystallographic structures derived from the Brookhaven Protein Data Bank were also analyzed concentrating on the presence of potentially quenching amino acid side chains in the close proximity of the indole chromophore. The obtained results indicated that, in most cases, the phosphorescence lifetimes of tryptophan containing proteins studied tend to correlate with the above mentioned structural indicators of protein rigidity/flexibility. This correlation is expected to provide guidelines for the future development of phosphorescence lifetime-based method for the prediction of structural flexibility of proteins, which is directly linked to their biological function.

  1. Role of decreased Plasma Tryptophan in memory deficits observed in Type-I diabetes

    Objective: To investigate the relationship between plasma tryptophan and the occurrence of memory dysfunctions in male and female type 1 diabetics. Methods: The case-control study was conducted at two urban healthcare facilities in Karachi from January to June 2009, and comprised 100 diabetic subjects of among whom were 50 men and 50 women. The controls were also similar in number and gender. A questionnaire was used to evaluate the memory impairment in the subjects. Plasma tryptophan was determined by high performance liquid chromatography with ultra-violet method. Students t-test was used to analyse tryptophan data. Results: There was considerable memory impairment in the cases (n=40) compared to the controls (n=5). Results also showed a significant (p<0.01) decrease in plasma tryptophan levels in both male and female diabetic patients. Conclusions: Diabetic subjects exhibited occurrence of memory impairment with concomitant decline in plasma tryptophan levels. The findings indicate that decreased brain uptake of tryptophan and lowered brain 5-hydroxytryptamine levels may be responsible for the memory deficits seen in diabetics. (author)

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

    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.

  3. Evaluating the efficacy of tryptophan fluorescence and absorbance as a selection tool for identifying protein crystals

    The effectiveness of using ultraviolet microscopes to illuminate protein crystals in high throughput screens is evaluated. The environment of individual tryptophans in known protein structures and the effectiveness of four commercial robotic UV microscopes to illuminate tryptophan-containing protein crystals by either tryptophan fluorescence (epi-illumination) or absorbance (transmission) are evaluated. In agreement with other studies, tryptophan residues are found on average to be largely buried in protein structures (with ∼84% of their surface area buried) and to be surrounded by partially polar microenvironments (with ∼43% of their surface area covered by polar residues), which suggests an inherent degree of fluorescence signal quenching. In bacterial genomes, up to one-third (∼18.5% on average) of open reading frames are deficient in tryptophan. In the laboratory, because of the attenuation of UV light by the media commonly used in sitting-drop and hanging-drop crystallization trials, it was often necessary to simplify the light path by manually removing or inverting the supporting media. Prolonged exposure (minutes) to UV light precipitates some protein samples. The absorbance spectra of many commercially available media in crystallization trials are presented. The advantages of using tryptophan absorbance over fluorescence for characterizing crystals are discussed

  4. Ab initio study on electron excitation and electron transfer in tryptophan-tyrosine system

    In this article, ab initio calculation has been performed to evaluate the transition energy of electronic excitation in tryptophan and tyrosine by using semiempirical molecular orbital method AM1 and complete active space self-consistent field method. The solvent effect has been considered by means of the conductor-like screening model. After geometric optimizations of isolated tryptophan and tyrosine, and their corresponding radicals and cations, reaction heat of these electron transfer reactions have been obtained by the means of complete active space self-consistent field method. The transition energies from the ground state, respectively, to the lowest excited state and to the lowest triplet state of these two amino acids are also calculated and compared with the experimentally observed values. The ionization potential and electron affinity are also calculated for tryptophan and tyrosine employing Koopmans' theorem and ab initio calculation. Compared with the experimental measurements, the theoretical results are found satisfactory. Theoretical results give good explanations on the experimental phenomena that N3· can preferably oxide the side chain of tryptophan residue and then the electron transfer from tyrosine residue to tryptophan residue follows in peptides involving tryptophan and tyrosine

  5. Acute Bronchitis

    ... of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your cough ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when people ...

  6. Protective Effect of Melatonin on Acute Pancreatitis

    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.

  7. The Case of Ozone Depletion

    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.

  8. The effect of tryptophan on UV-induced DNA photodamage.

    Oladepo, Sulayman A; Loppnow, Glen R

    2010-01-01

    Trp-DNA adducts resulting from UV irradiation of pyrimidine bases and nucleotides in the presence of tryptophan (Trp) have been the subject of previous research. However, the relative yield of the adducts compared with the UV screening effect of Trp has not been previously considered. To determine whether Trp-DNA adduct formation or absorption "screening" by Trp is the predominant process when DNA solutions are irradiated with UV light in the presence of Trp, we irradiated Trp-containing DNA oligonucleotide solutions with UVC light and incubated aliquots of those solutions with molecular beacons (MBs) to detect the damage. We observed a rapid decay of fluorescence of the MBs for pure DNA solutions, thereby indicating damage. However, in the presence of Trp, the fluorescence decay is prolonged, with time constants that increase exponentially with Trp concentration. The results are discussed in terms of a beneficial in vivo cellular protection rather than harmful adduct formation and suggest a net sacrificial absorption of UV light by Trp which actually protects the DNA from UV damage. PMID:20492563

  9. Antitumour agents as inhibitors of tryptophan 2,3-dioxygenase

    Pantouris, Georgios; Mowat, Christopher G., E-mail: C.G.Mowat@ed.ac.uk

    2014-01-03

    Highlights: •∼2800 National Cancer Institute USA compounds have been screened as potential inhibitors of TDO and/or IDO. •Seven compounds with anti-tumour properties have been identified as potent inhibitors. •NSC 36398 (taxifolin, dihydroquercetin) is selective for TDO with a K{sub i} of 16 M. •This may help further our understanding of the role of TDO in cancer. -- Abstract: The involvement of tryptophan 2,3-dioxygenase (TDO) in cancer biology has recently been described, with the enzyme playing an immunomodulatory role, suppressing antitumour immune responses and promoting tumour cell survival and proliferation. This finding reinforces the need for specific inhibitors of TDO that may potentially be developed for therapeutic use. In this work we have screened ∼2800 compounds from the library of the National Cancer Institute USA and identified seven potent inhibitors of TDO with inhibition constants in the nanomolar or low micromolar range. All seven have antitumour properties, killing various cancer cell lines. For comparison, the inhibition potencies of these compounds were tested against IDO and their inhibition constants are reported. Interestingly, this work reveals that NSC 36398 (dihydroquercetin, taxifolin), with an in vitro inhibition constant of ∼16 μM, is the first TDO-selective inhibitor reported.

  10. Uranium, depleted uranium, biological effects

    Physicists, chemists and biologists at the CEA are developing scientific programs on the properties and uses of ionizing radiation. Since the CEA was created in 1945, a great deal of research has been carried out on the properties of natural, enriched and depleted uranium in cooperation with university laboratories and CNRS. There is a great deal of available data about uranium; thousands of analyses have been published in international reviews over more than 40 years. This presentation on uranium is a very brief summary of all these studies. (author)

  11. Determination of deuterium-labeled tryptophan in proteins by means of high-performance liquid chromatography and thermospray mass spectrometry

    In order to develop direct methods for determining the extent of metabolic incorporation of isotopically labeled amino acids into a protein, the determination of deuterated tryptophan in [2H5]tryptophan-bacteriorhodopsin was investigated. The isotopically modified protein was subjected to alkaline hydrolysis. After phenyl isothiocyanate derivatization of the hydrolysate, the mixture was separated by reversed-phase liquid chromatography. Field desorption mass spectrometry and thermospray mass spectrometry were investigated for their ability to determine the ratio between [2H5]tryptophan and total tryptophan in the collected fractions. In order to check the procedure a set of known tryptophan/[2H5]tryptophan mixtures were passed through the same derivatization, HPLC separation, and lyophilization procedure as used for the biological samples

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

    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. Photoinduced Intramolecular Tryptophan Oxidation and Excited-State Behavior of [Re(L-AA)(CO)3(r-diimine)] þ (L = Pyridine or Imidazole, AA = Tryptophan, Tyrosine, Phenylalanine)

    Blanco-Rodríguez, A. M.; Towrie, M.; Sýkora, Jan; Záliš, Stanislav; Vlček Jr., Antonín

    2011-01-01

    Roč. 50, č. 13 (2011), s. 6122-6134. ISSN 0020-1669 R&D Projects: GA MŠk(CZ) LD11082 Institutional research plan: CEZ:AV0Z40400503 Keywords : tryptophan * tyrosine * phenylalanine Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.601, year: 2011

  14. l-Tryptophan Radical Cation Electron Spin Resonance Studies: Connecting Solution-derived Hyperfine Coupling Constants with Protein Spectral Interpretations

    Connor, Henry D.; Sturgeon, Bradley E.; Mottley, Carolyn; Sipe, Herbert J.; Mason, Ronald P.

    2008-01-01

    Fast-flow electron spin resonance (ESR) spectroscopy has been used to detect a free radical formed from the reaction of l-tryptophan with Ce4+ in an acidic aqueous environment. Computer simulations of the ESR spectra from l-tryptophan and several isotopically modified forms strongly support the conclusion that the l-tryptophan radical cation has been detected by ESR for the first time. The hyperfine coupling constants (HFCs) determined from the well-resolved isotropic ESR spectra support expe...

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

    Juan Zhou; Qiao Chen; Li-lan Wang; Yong-hua Wang; Ying-zi Fu

    2011-01-01

    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 tha...

  16. Effect of dialysis on plasma and CSF tryptophan and CSF 5-hydroxyindoleacetic acid in advanced renal disease.

    Sullivan, P A; Murnaghan, D; Callaghan, N; Kantamaneni, B D; Curzon, G

    1980-01-01

    Patients with uraemic encephalopathy were previously found to have low total tryptophan (bound plus free), but high free tryptophan concentrations in the plasma and high CSF tryptophan concentrations. The 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid was also raised in the CSF. A study of the effect of dialysis treatment on these substances in chronic uraemic patients with and without dialysis dementia is described. After an episode of dialysis the patients without dialysis dement...

  17. The photophysics and photochemistry of the near-UV absorbing amino acids-I. Tryptophan and its simple derivatives

    The photophysics and photochemistry of tryptophan and its simple derivatives is comprehensively reviewed with special emphasis on excitation by near-UV radiation. Topics explicitly discussed include the origins of large Stokes shifts in the fluorescence spectra, photoionization, the puzzle of multiple tryptophan fluorescence decay time, photochemical reactions in the presence and absence of oxygen, and the possible mechanisms of these reactions. A separate section reviews the photosensitizing properties of N-formylkynurenine, an important photooxidation product of tryptophan. (author)

  18. Synthesis of (2R,S)-[2-2H] and [2,3-2H] tryptophan

    α-Deuterated tryptophan was prepared either by exchange of the α-hydrogen of tryptophan or by hydrolysis and decarboxylation of ethyl 2-formamido-2-carbethoxy-3-indole propionate, followed by treatment with CH3COO2H. α,β-dideuterated tryptophan was in turn synthetized from ethyl-α-acetamido-indole-3-acrylate, by catalytic deuteration (2H2/Pd-C) and alkaline hydrolysis (NaO2H/2H2O). (author)

  19. Biomedical consequences of ozone depletion

    Coohill, Thomas P.

    1994-07-01

    It is widely agreed that a portion of the earth's protective stratospheric ozone layer is being depleted. The major effect of this ozone loss will be an increase in the amount of ultraviolet radiation (UV reaching the biosphere. This increase will be completely contained within the UVB (290nm - 320nm). It is imperative that assessments be made of the effects of this additional UVB on living organisms. This requires a detailed knowledge of the UVB photobiology of these life forms. One analytical technique to aid in the approximations is the construction of UV action spectra for such important biological end-points as human skin cancer, cataracts, immune suppression; plant photosynthesis and crop yields; and aquatic organism responses to UVB, especially the phytoplankton. Combining these action spectra with the known solar spectrum (and estimates for various ozone depletion scenarios) can give rise to a series of effectiveness spectra for these parameters. This manuscript gives a first approximation, rough estimate, for the effectiveness spectra for some of these bioresponses, and a series of crude temporary values for how a 10% ozone loss would affect the above end-points. These are not intended to masquerade as final answers, but rather, to serve as beginning attempts for a process which should be continually refined. It is hoped that these estimates will be of some limited use to agencies, such as government and industry, that have to plan now for changes in human activities that might alter future atmospheric chemistry in a beneficial manner.

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

    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.

  1. Monomerization of pyrimidine dimers in DNA by tryptophan-containing peptides: wavelength dependence

    Tryptophan-containing peptides and proteins can sensitize the monomerization of pyrimidine dimers in ultraviolet-irradiated DNA; photoreactivating enzymes catalyze the light-induced monomerization of pyrimidine dimers in DNA. It has recently been proposed that a variety of tryptophan-containing proteins and peptides might be confused with true photoreactivating enzymes both in vivo and in vitro. We have thus characterized the wavelengths required for the tryptophan-sensitized dimer monomerization to determine if this process is distinguishable from true enzymatic photoreactivation. We find that 313-nm radiation can monomerize pyrimidine dimers in DNA in the presence of the peptide lysyl-tryptophyl-lysine; however, 334- 365-, and 405-nm radiation are ineffective for fluences up to 1 MJ/m2. In contrast, each of these wavelengths is capable of monomerizing dimers in the presence of photoreactivating enzymes. Indeed, 334 and 365 nm are always more effective than 313-nm radiation in the case of true enzymatic photoreactivation. The inability of wavelengths other than those near 300 nm to drive the tryptophan-mediated reaction efficiently is consistent with recently reported spectroscopic experiments. The extreme differences in the wavelength specificities for true enzymatic photoreactivation and tryptophan-sensitized monomerization mean that it is easy to differentiate experimentally between the two phenomena. Consideration of the spectral distributions of conventional sources of photoreactivating light indicate that it is extremely unlikely that any of them could contain significant intensities of the wavelengths required for efficient tryptophan-sensitized monomerization of pyrimidine dimers. We thus conclude that tryptophan-sensitized monomerization cannot account for the disappearance of pyrimidine dimers from DNA in cells or cell extracts exposed to photoreactivating light

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

    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

  3. Depleted Argon from Underground Sources

    Argon is a strong scintillator and an ideal target for Dark Matter detection; however 39Ar contamination in atmospheric argon from cosmic ray interactions limits the size of liquid argon dark matter detectors due to pile-up. Argon from deep underground is depleted in 39Ar due to the cosmic ray shielding of the earth. In Cortez, Colorado, a CO2 well has been discovered to contain approximately 600 ppm of argon as a contamination in the CO2. We first concentrate the argon locally to 3% in an Ar, N2, and He mixture, from the CO2 through chromatographic gas separation, and then the N2 and He will be removed by continuous distillation to purify the argon. We have collected 26 kg of argon from the CO2 facility and a cryogenic distillation column is under construction at Fermilab to further purify the argon.

  4. Depleted uranium disposal options evaluation

    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

  5. Depleted uranium. Nuclear related problems

    Depleted uranium (DU) has found a military application in Golf War, in Bosnia and in Yugoslavia (Kosovo). In military sense it was very efficient. But the fact that some parts of that ammunition are manufactured from depleted uranium, low level radioactive waste, implies other aspects of this application like radiological, ecological, jurist, ethical and psychological. The subject of this paper is just physical aspect. There are several problems concerning this aspect: production of DU, total amount of DU in the world, 235U/238U relation, radioactivity of DU, measurements, and presence of other radionuclides like plutonium. DU is by product of nuclear technology and represents low-level nuclear waste. Therefore it should be stored. Total amount of DU in the world is about one million tons with an annual increase of 30 000 t. The content of 235U in DU can vary in the range 0.16-0.3%. The total radioactivity of DU is a consequence of 7 radionuclides and amounts 39.42 Bq/mg. This include alpha, beta and gamma radioactivity. Because of characteristics of this radioactivity it is difficult to prospect the terrain except at the site of action. During the impact of DU rods four types of DU particles could be produced: whole penetrators, penetrator parts, big aerosols (>10 μm) and small aerosols (<10 μm). Most of these particles fall locally, although some of them could be find several tens of kilometers away. All these problems have been discussed in this paper. (author)

  6. SRP scientific meeting: depleted uranium

    The meeting was organised by the SRP to review current research and discuss the use, dispersion into the environment and radiological impact of depleted uranium (DU) by the UK and US in recent military conflicts. In addition to other presentations, there were two short presentations by T Cabianca and P Danesi of the IAEA concerning investigations into the DU legacy in Kuwait and the IAEA contribution to environmental contamination assessments of DU in Kosovo. In Kuwait the on-going study is limited to an assessment of the potential radiological consequences of DU residues in three types of site: open desert where DU was fired, farmland where DU was fired and DU storage facilities. The Kuwaiti government has also requested the IAEA to formulate a structured approach to deal with remediating such sites and disposing of the resulting material. In Kosovo the study investigated sand and soil samples from areas where DU had been fired. DU particulates were found in sizes up to 40 μm, but generally much smaller, typically about 5 μm, with 5% less than 1.5 μm in size. These particles were found to contain 90% DU and 1% Ti. Plutonium was also detected, but this was attributed to the 1960s bomb testing programme. This was an informative, well attended meeting that stimulated varied debate between delegates. It revealed that there is still much to learn concerning the effects of depleted uranium in the human body and highlighted the limitations of conventional dose estimates made using ICRP models. A balance must be struck between the operational requirements of the armed forces and acceptable levels of environmental contamination arising from any conflict they are involved in. Most importantly, as a scientific consensus is developed, a clear and consistent approach to providing key information to the public should be adopted, to build confidence in the radiation protection profession

  7. The improved L-tryptophan production in recombinant Escherichia coli by expressing the polyhydroxybutyrate synthesis pathway.

    Gu, Pengfei; Kang, Junhua; Yang, Fan; Wang, Qian; Liang, Quanfeng; Qi, Qingsheng

    2013-05-01

    Polyhydroxybutyrate (PHB), the best known polyhydroxyalkanoates (PHA) has been believed to change intracellular metabolic flow and oxidation/reduction state, as well as enhance stress resistance of the host. In this study, a PHB biosynthesis pathway, which contains phaCAB operon genes from Ralstonia eutropha, was introduced into an L-tryptophan producing Escherichia coli strain GPT1002. The expression of the PHB biosynthesis genes resulted in PHB accumulation inside the cells and improved the L-tryptophan production. Quantitative real-time PCR analysis showed that the transcription of tryptophan operon genes in GPT2000 increased by 1.9 to 4.3 times compared with the control, indicating that PHB biosynthesis in engineered E. coli changed the physiological state of the host. Xylose was added into the medium as co-substrate to enhance the precursor supply for PHB biosynthesis. The addition of xylose improved both extracellular L-tryptophan production and intracellular PHB accumulation. Moreover, we obtained 14.4 g l(-1) L-tryptophan production and 9.7 % PHB (w/w) accumulation in GPT2000 via fed-batch cultivation. PMID:23321909

  8. The photolysis of tryptophan with 337.1 nm laser radiation

    Aqueous solutions of L-tryptophan were photolyzed by exposure to 337.1 nm radiation from a pulsed nitrogen laser. These data were compared with results for the 290 nm conventional-source photolysis of tryptophan. The loss of Trp was observed to be first order for 290 nm photolysis but of mixed order for 337.1 nm photolysis. Five photolysis products including N-formylkynurenine, kynurenine, tryptamine and two unknown products were detected. The tryptophan-containing peptides N-acetyl-tryptophanamide (NATA) and tryptophylglycine (Trp-Gly) were also observed to photolyze upon 337.1 nm laser radiation demonstrating that this phenomenon is not restricted to free tryptophan monomer. A number of experiments were performed in an effort to determine the mechanism of photolysis at this wavelength. It is concluded that this photolysis results either from a very weak absorption tail extending to 337.1 nm in tryptophan itself or from a reaction involving an impurity sensitizer which absorbs the 337.1 nm radiation. (author)

  9. Thermodynamics of tryptophan-mediated activation of the trp RNA-binding attenuation protein.

    McElroy, Craig A; Manfredo, Amanda; Gollnick, Paul; Foster, Mark P

    2006-06-27

    The trp RNA-binding attenuation protein (TRAP) functions in many bacilli to control the expression of the tryptophan biosynthesis genes. Transcription of the trp operon is controlled by TRAP through an attenuation mechanism, in which competition between two alternative secondary-structural elements in the 5' leader sequence of the nascent mRNA is influenced by tryptophan-dependent binding of TRAP to the RNA. Previously, NMR studies of the undecamer (11-mer) suggested that tryptophan-dependent control of RNA binding by TRAP is accomplished through ligand-induced changes in protein dynamics. We now present further insights into this ligand-coupled event from hydrogen/deuterium (H/D) exchange analysis, differential scanning calorimetry (DSC), and isothermal titration calorimetry (ITC). Scanning calorimetry showed tryptophan dissociation to be independent of global protein unfolding, while analysis of the temperature dependence of the binding enthalpy by ITC revealed a negative heat capacity change larger than expected from surface burial, a hallmark of binding-coupled processes. Analysis of this excess heat capacity change using parameters derived from protein folding studies corresponds to the ordering of 17-24 residues per monomer of TRAP upon tryptophan binding. This result is in agreement with qualitative analysis of residue-specific broadening observed in TROSY NMR spectra of the 91 kDa oligomer. Implications for the mechanism of ligand-mediated TRAP activation through a shift in a preexisting conformational equilibrium and an induced-fit conformational change are discussed. PMID:16784236

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

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

    2013-10-15

    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 26.5μM) and trachelogenin (IC50 of 57.4μM) showed higher activity than matairesinol (IC50 >200μM) 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, anticancer and antidepressant properties of C. tinctorius lignans might relate to their suppressive influence on tryptophan breakdown. PMID:23867649

  11. Induction of cytochrome P-450 1A2 by oxidized tryptophan in Hepa lclc7 cells.

    Sindhu, R K; Mitsuhashi, M; Kikkawa, Y

    2000-03-01

    Recent studies from this laboratory have demonstrated that L-tryptophan, after oxidation either by UV-irradiation or ozone, induces aryl hydrocarbon receptor (AhR) activation and binding of the liganded AhR complex to its specific DNA recognition site, thereby initiating transcription of the cytochrome P-450 1a1 (Cyp1a1) gene with concomitant increase of CYP1A1 protein and 7-ethoxyresorufin O-deethylase activity in wild-type mouse hepatoma cells, Hepa lclc7 (Hepa-1), in culture. Temporary inhibition of protein synthesis by cycloheximide resulted in superinduction of oxidized tryptophan-inducible CYP1A1 mRNA, protein, and 7-ethoxyresorufin O-deethylase activity in Hepa-1 cells. In the present communication, the results obtained by immunoblot analyses with monoclonal CYP1A1/1A2 antibody (NIH 1-7-1) demonstrate that both UV- or ozone-oxidized tryptophan also induce CYP1A2 protein in Hepa-1 cells. CYP1A2 mRNA, detected by reverse transcription-polymerase chain reaction, was markedly induced in the UV- or ozone-oxidized tryptophan-treated cells. Temporary inhibition of protein synthesis by cycloheximide further induced oxidized tryptophan-inducible CYP1A2 mRNA as well as the protein in Hepa-1 cells. This is the first report demonstrating the induction of CYP1A2 mRNA and protein in Hepa-1 cells. PMID:10688617

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

    Ajdarzadeh, Ahmad; Consani, Cristina; Bräm, Olivier; Tortschanoff, Andreas; Cannizzo, Andrea [Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratoire de Spectroscopie Ultrarapide, ISIC, Station 6, FSB, CH-1015 Lausanne (Switzerland); Chergui, Majed, E-mail: Majed.chergui@epfl.ch [Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratoire de Spectroscopie Ultrarapide, ISIC, Station 6, FSB, CH-1015 Lausanne (Switzerland)

    2013-08-30

    Highlights: ► We report ultrafast UV studies of tryptophan in water. ► We compared UV transient absorption, photon echo, transient grating and ultrafast fluorescence. ► The results are consistent between these techniques, suggesting avenues for 2D coherent UV spectroscopies. - Abstract: 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.

  13. The stability of free and bound tryptophan against irradiation and oxidizing agents

    Experiments were conducted to test the stability of free and bound tryptophan against irradiation and oxidizing agents. The decrease of fluorescence at 352 +- 4 nm after activation at 289 nm was taken as a criterium of measurement in experiments with free tryptophan. The source for irradiation was the lamp of the spectrofluorometer, a 150 Watt Xenon high pressure lamp. Free tryptophan was not stable when irradiated in the near UV range at pH values between 4 and 10.8, it was destroyed quickly. Additional experiments were conducted with the weak oxidation agent N-Bromosuccinimide (NBS) in alkaline aqueous solutions (pH 11). When there was a fivefold excess of NBS, tryptophan was destroyed completely and faster than by photooxidation. Soybean protein was oxidized with FeCl3, formaldehyde, and H2O2. Thirty-two% of tryptophan were destroyed with a 0,5% FeCl3 solution, 43% with 1% FeCl3 solution, 0% with 5% formaldehyde solution, 43% with 10% formaldehyde solution, and 87% with 5% H2O2 solution. With the exception of FeCl3, only a small amount of soybean protein dissolved during the oxidation. (orig.)

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

    Highlights: ► We report ultrafast UV studies of tryptophan in water. ► We compared UV transient absorption, photon echo, transient grating and ultrafast fluorescence. ► The results are consistent between these techniques, suggesting avenues for 2D coherent UV spectroscopies. - Abstract: 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

  15. Acute Modulation of Sugar Transport in Brain Capillary Endothelial Cell Cultures during Activation of the Metabolic Stress Pathway*

    Cura, Anthony J.; Carruthers, Anthony

    2010-01-01

    GLUT1-catalyzed equilibrative sugar transport across the mammalian blood-brain barrier is stimulated during acute and chronic metabolic stress; however, the mechanism of acute transport regulation is unknown. We have examined acute sugar transport regulation in the murine brain microvasculature endothelial cell line bEnd.3. Acute cellular metabolic stress was induced by glucose depletion, by potassium cyanide, or by carbonyl cyanide p-trifluoromethoxyphenylhydrazone, which reduce or deplete i...

  16. Clodronate treatment significantly depletes macrophages in chickens

    Kameka, Amber M.; Haddadi, Siamak; Jamaldeen, Fathima Jesreen; Moinul, Prima; He, Xiao T.; Nawazdeen, Fathima Hafsa P.; Bonfield, Stephan; Sharif, Shayan; van Rooijen, Nico; Abdul-Careem, Mohamed Faizal

    2014-01-01

    Macrophages function as phagocytes and antigen-presenting cells in the body. As has been demonstrated in mammals, administration of clodronate [dichloromethylene bisphosphonate (Cl2MBP)] encapsulated liposomes results in depletion of macrophages. Although this compound has been used in chickens, its effectiveness in depleting macrophages has yet to be fully determined. Here, we show that a single administration of clodronate liposomes to chickens results in a significant depletion of macropha...

  17. Repulsive depletion interactions in colloid polymer mixtures

    Rudhardt, Daniel; Bechinger, Clemens; Leiderer, Paul

    1999-01-01

    Depletion forces in colloidal systems are known to be entirely attractive, as long as the background of macromolecules is small enough that an ideal gas approach is valid. At higher densities, however, structural correlation effects of the macromolecules which lead to additional repulsive parts in the depletion interaction, have to be taken into account. We have measured the depletion interaction between a single polystyrene sphere and a wall in the presence of non-ionic polymer coils. Althou...

  18. Assessment of the depletion capability in MPACT

    The objective of the paper is to develop and demonstrate the depletion capability with pin resolved transport using the MPACT code. The first section of the paper provides a description of the depletion methodology and the algorithm used to solve the depletion equations in MPACT. A separate depletion library for MPACT is used based on the ORIGEN-S library to provide the basic decay constants and fission yields, as well as the 3-group cross-sections which are used for the isotopes not contained in the MPACT multi-group library. The cross sections for the depletion transmutation matrix were collapsed using the transport flux solution in MPACT based on either the 47 group HELIOS library based on ENDF-VI or a 56 group ORNL library based on ENDF-VII. The second section of this paper then describes the numerical verification of the depletion algorithm using two sets of benchmarks. The first is the JAERI LWR lattice benchmark which had participants from most of the lattice depletion codes currently used in the international nuclear community and the second benchmark is based on data from spent fuel of the Takahama-3 reactor. The results show that MPACT is generally in good agreement with the results of the other benchmark participants as well as the experimental data. Finally, a full core 2D model of CASL AMA benchmark was depleted based on the central plane of the Watts Bar reactor core which demonstrates the whole core depletion capability of MPACT. (author)

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

    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.

  20. Dosimetry of D- and L-enantiomers of 11C-labeled tryptophan and valine

    The authors have previously reported the radiation dosimetry of 11C-labeled DL-tryptophan and DL-valine, as well as clinical pancreatic imaging studies with these agents. Because of significant uptake in both normal pancreas and in pancreatic tumors (thought to be due to the presence of the D-enantiomer), differential diagnosis of pancreatic carcinoma was not feasible. High-performance liquid chromatographic (HPLC) methods were developed for rapid resolution of 11C-labeled DL-tryptophan and DL-valine. Radiation dose estimates to the various organs in man were calculated for the D- and L-enantiomers of 11C-labeled tryptophan and valine, based on tissue distribution data in rats. The dose estimates were sufficiently low that 20-mCi doses of each of the enantiomeric amino acids were approved by the FDA for intravenous administration to humans. 21 references, 3 tables

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

    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.

  2. Dosimetry of D- and L-enantiomers of 11C-labeled tryptophan and valine

    We have previously reported the radiation dosimetry of 11C-labeled DL-tryptophan and DL-valine, as well as clinical pancreatic imaging studies with these agents. Because of significant uptake in both normal pancreas and in pancreatic tumors (thought to be due to the presence of the D-enantiomer), differential diagnosis of pancreatic carcinoma was not feasible. High-performance liquid chromatographic (HPLC) methods were developed for rapid resolution of 11C-labeled DL-tryptophan and DL-valine. Radiation dose estimates to the various organs in man were calculated for the D- and L-enantiomers of 11C-labeled tryptophan and valine, based on tissue distribution data in rats. The dose estimates were sufficiently low that 20-mCi doses of each of the enantiomeric amino acids were approved by the FDA for intravenous administration to humans. 21 refs., 3 tabs

  3. GPR142 Controls Tryptophan-Induced Insulin and Incretin Hormone Secretion to Improve Glucose Metabolism

    Efanov, Alexander M.; Fang, Xiankang; Beavers, Lisa S.; Wang, Xuesong; Wang, Jingru; Gonzalez Valcarcel, Isabel C.; Ma, Tianwei

    2016-01-01

    GPR142, a putative amino acid receptor, is expressed in pancreatic islets and the gastrointestinal tract, but the ligand affinity and physiological role of this receptor remain obscure. In this study, we show that in addition to L-Tryptophan, GPR142 signaling is also activated by L-Phenylalanine but not by other naturally occurring amino acids. Furthermore, we show that Tryptophan and a synthetic GPR142 agonist increase insulin and incretin hormones and improve glucose disposal in mice in a GPR142-dependent manner. In contrast, Phenylalanine improves in vivo glucose disposal independently of GPR142. Noteworthy, refeeding-induced elevations in insulin and glucose-dependent insulinotropic polypeptide are blunted in Gpr142 null mice. In conclusion, these findings demonstrate GPR142 is a Tryptophan receptor critically required for insulin and incretin hormone regulation and suggest GPR142 agonists may be effective therapies that leverage amino acid sensing pathways for the treatment of type 2 diabetes. PMID:27322810

  4. Decreased tryptophan and increased kynurenine levels in mastocytosis associated with digestive symptoms.

    Georgin-Lavialle, S; Launay, J-M; Côté, F; Soucié, E; Soria, A; Damaj, G; Moura, D S; Canioni, D; Hanssens, K; Chandesris, M-O; Barète, S; Dubreuil, P; Lortholary, O; Hermine, O; Sokol, H

    2016-03-01

    The main metabolism pathway of tryptophan is protein formation, but it can also be metabolized into serotonin and kynurenine. Indoleamine 2,3-dioxygenase (IDO) is the enzyme that catalyzes the degradation of tryptophan into kynurenine. Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in various tissues with 57% of patients having gastrointestinal involvement. We studied tryptophan metabolism in mastocytosis patients displaying or not gastrointestinal features and healthy subjects (n = 26 in each group). Mastocytosis patients with digestive symptoms displayed significantly increased kynurenine level and IDO activity as compared to healthy controls and mastocytosis patients without digestive symptoms. This could be linked to mast cell-mediated digestive inflammation among patients with mastocytosis. This work is the first focusing on kynurenine pathway in a mast cell disease and could help to understand the pathogenesis of digestive features in mastocytosis as well as in other mast cell-mediated diseases. PMID:26841279

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

    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.

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

    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.

  7. The radiolysis of tryptophan and leucine with P-32 beta-radiation

    The paper extends earlier experiments on the radiolysis of DL-tryptophan using P-32 beta-radiation to longer reaction times, observing complete destruction of tryptophan by secondary, nonradiolytic processes. In addition DL-leucine is irradiated with P-32 beta-irradiation at -196 C, leading to radiolyses to the extents of about 20-30%, but observing no concomitant asymmetric bias. The complete absence of asymmetric bias in the present and earlier (Bonner et al., 1979) radiolyses of aqueous tryptophan at -25 C and the present radiolyses of water-free leucine at -196 C using P-32 beta-radiation and its accompanying bremsstrahlung leave it an open question whether or not the Vester-Ulbricht beta-decay/bremsstrahlung mechanism for the origin of optical activity is a viable one

  8. Synthesis of no-carrier-added alpha-[11C]methyl-L-tryptophan

    Described here is a synthesis of no-carrier-added alpha-[11C]methyl-L-tryptophan based on alkylation with 11CH3I of an anion generated by reacting the Schiff base of L-tryptophan methyl ester with di-isopropylamine. The synthesis requires approximately 30 min after the end of 11CO2 collection and gives alpha-[11C]methyl-L-tryptophan in a 20-25% radiochemical yield calculated at the end of the synthesis and without correction for radioactive decay. The specific activity of the final radiopharmaceutical, measured at the end of the synthesis, was around 2000 Ci/mmol. Data confirming the stereospecificity of the synthesis are also presented

  9. The radiolysis of tryptophan and leucine with P-32 beta-radiation

    Blair, N. E.; Bonner, W. A.

    1980-01-01

    The paper extends earlier experiments on the radiolysis of DL-tryptophan using P-32 beta-radiation to longer reaction times, observing complete destruction of tryptophan by secondary, nonradiolytic processes. In addition DL-leucine is irradiated with P-32 beta-irradiation at -196 C, leading to radiolyses to the extents of about 20-30%, but observing no concomitant asymmetric bias. The complete absence of asymmetric bias in the present and earlier (Bonner et al., 1979) radiolyses of aqueous tryptophan at -25 C and the present radiolyses of water-free leucine at -196 C using P-32 beta-radiation and its accompanying bremsstrahlung leave it an open question whether or not the Vester-Ulbricht beta-decay/bremsstrahlung mechanism for the origin of optical activity is a viable one.

  10. Two-stages of chiral selectivity in the molecular self-assembly of tryptophan

    Guisinger, Nathan

    Both chirality and molecular assembly are essential and key components to life. In this study we explore the molecular assembly of the amino acid tryptophan (both L- and D- chiralities) on Cu(111). Our investigation utilizes low temperature scanning tunneling microscopy to observe resulting assemblies at the molecular scale. We find that depositing a racemic mixture of both L- and D- tryptophan results in the assembly of basic 6 molecule ``Lego'' structures that are enantiopure. These enantiopure ``Legos'' further assemble into 1-dimensional chains one block at a time. These resulting chains are also enantiopure with chiral selectivity occurring at two stages of assembly. Utilizing scanning tunneling spectroscopy we are able to probe the electronic structure of the chiral Legos that give insight into the root of the observed selectivity. Two-stages of chiral selectivity in the molecular self-assembly of tryptophan.

  11. Kinetics and energetics of one-electron-transfer reactions involving tryptophan neutral and cation radicals

    Reversible one-electron-transfer reactions involving the tryptophan cation and neutral radicals were investigated by pulse radiolysis. The one-electron-reduction potential of the neutral tryptophan radical at pH 7 was determined to be E7 = 1.01 ± 0.03 V by using the bis(1,4,7-triazacyclononane)nickel(III/II) redox couple with E = 0.95 V as a standard. The value obtained with promethazine (E = 0.89 V) as a standard at pH 6 was E6 = 1.11 V. From these measurements, a mean value E7 = 1.03 V results, in agreement with some earlier determinations (1.05 and 1.08 V) obtained in experiments with inorganic redox standards. The kinetics and energetics of the reactions of the tryptophan neutral and cation radicals with selected electron donors were also investigated

  12. The effects of tritium on embryo development: the embryotoxic effects of [3H]tryptophan

    The effects of tritiated amino acids on the development of the early mouse embryo in vitro are described. [3H]tryptophan was extremely toxic, compared with [3H]glutamic acid, and inhibited growth of the two-cell embryo to the blastocyst stage. The LD50 values for the two amino acids were, respectively, 1 and 296 kBq/ml of medium. The two-cell embryo was more sensitive to the irradiation from incorporated [3H]tryptophan than any later stage of development. It was shown that [3H]tryptophan is selectively incorporated into two chromosomal proteins in the two-cell embryo, and that those proteins were stage-specific markers of development. (author)

  13. Structure and biosynthesis of a macrocyclic peptide containing an unprecedented lysine-to-tryptophan crosslink

    Schramma, Kelsey R.; Bushin, Leah B.; Seyedsayamdost, Mohammad R.

    2015-05-01

    Streptococcal bacteria use peptide signals as a means of intraspecies communication. These peptides can contain unusual post-translational modifications, providing opportunities for expanding our understanding of nature's chemical and biosynthetic repertoires. Here, we have combined tools from natural products discovery and mechanistic enzymology to elucidate the structure and biosynthesis of streptide, a streptococcal macrocyclic peptide. We show that streptide bears an unprecedented post-translational modification involving a covalent linkage between two unactivated carbons within the side chains of lysine and tryptophan. The biosynthesis of streptide was addressed by genetic and biochemical studies. The former implicated a new SPASM-domain-containing radical SAM enzyme StrB, while the latter revealed that StrB contains two [4Fe-4S] clusters and installs the unusual lysine-to-tryptophan crosslink in a single step. By intramolecularly stitching together the side chains of lysine and tryptophan, StrB provides a new route for biosynthesizing macrocyclic peptides.

  14. Acute Pancreatitis and Pregnancy

    ... Acute Pancreatitis > Acute Pancreatitis and Pregnancy test Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...

  15. Randomised clinical trial on the effect of a single oral administration of l-tryptophan, at three dose rates, on reaction speed, plasma concentration and haemolysis in horses.

    Noble, Glenys K; Li, Xiuhua; Zhang, Dagong; Sillence, Martin N

    2016-07-01

    Tryptophan (TRP) is marketed as a calmative for horses despite reservations about its efficacy. The aim of this study was to measure the effect of oral TRP administration on the reaction speed of horses. Sixty mature horses were used in a two stage randomised, blind, cross-over study, receiving a placebo and an oral dose of TRP (30, 60 or 120 mg/kg body weight), before undergoing a reaction speed test. Blood samples were taken up to 96 h after TRP administration, to identify signs of acute haemolytic anaemia. Plasma TRP concentrations were increased (P horses when startled. There was no evidence of alterations in clinical pathology parameters in 432 blood samples. While the safety of these doses of TRP can be confirmed, there was no evidence to suggest that a single dose of TRP is an effective calmative for horses. PMID:27240921

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

    Breum, Leif; Rasmussen, Michael H; Hilsted, Jannik; Fernstrom, John D

    2003-01-01

    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......, serotonin function may also be low. Plasma tryptophan concentrations and ratios have been measured only at single time points in obese subjects; it is not known whether low values for these 2 variables persist throughout a 24-h period. OBJECTIVE: Our objective was to determine whether plasma tryptophan...... concentrations and ratios in obese subjects are lower than those in normal-weight subjects throughout a 24-h period and whether they increase when body weight is reduced. DESIGN: Plasma tryptophan concentrations and ratios were examined in obese subjects before and after weight loss and in nonobese control...

  17. Pigment production on L-tryptophan medium by Cryptococcus gattii and Cryptococcus neoformans.

    Stuart Chaskes

    Full Text Available In recent years strains previously grouped within Cryptococcus neoformans have been divided into two species C. neoformans and C. gattii, with Cryptococcus neoformans comprising serotypes A, D, and AD and C. gattii comprising serotypes B and C. Cryptococcus neoformans have also been subdivided into two varieties C. neoformans var. grubii, serotype A, and C. neoformans var. neoformans, serotype D. We analyzed the growth and pigment production characteristics of 139 strains of Cryptococcus spp. in L-tryptophan containing media. Nearly all strains of Cryptococcus, including each variety and serotype tested produced a pink water-soluble pigment (molecular weight of 535.2 Da from L-tryptophan. Consequently, the partial separation of the species was based on whether the pink pigment was secreted into the medium (extracellular or retained as an intracellular pigment. On L-tryptophan medium C. neoformans var. grubii and serotype AD produced a pink extracellular pigment. In contrast, for C. gattii, the pink pigment was localized intracellularly and masked by heavy production of brown pigments. Pigment production by C. neoformans var. neoformans was variable with some strains producing the pink extracellular pigment and others retained the pink pigment intracellularly. The pink intracellular pigment produced by strains of C. neoformans var. neoformans was masked by production of brown pigments. Cryptococcus laccase mutants failed to produce pigments from L-tryptophan. This is the first report that the enzyme laccase is involved in tryptophan metabolism. Prior to this report Cryptococcus laccase produced melanin or melanin like-pigments from heterocyclic compounds that contained ortho or para diphenols, diaminobenzenes and aminophenol compounds. The pigments produced from L-tryptophan were not melanin.

  18. Tryptophan inhibits Proteus vulgaris TnaC leader peptide elongation, activating tna operon expression.

    Cruz-Vera, Luis R; Yang, Rui; Yanofsky, Charles

    2009-11-01

    Expression of the tna operon of Escherichia coli and of Proteus vulgaris is induced by L-tryptophan. In E. coli, tryptophan action is dependent on the presence of several critical residues (underlined) in the newly synthesized TnaC leader peptide, WFNIDXXL/IXXXXP. These residues are conserved in TnaC of P. vulgaris and of other bacterial species. TnaC of P. vulgaris has one additional feature, distinguishing it from TnaC of E. coli; it contains two C-terminal lysine residues following the conserved proline residue. In the present study, we investigated L-tryptophan induction of the P. vulgaris tna operon, transferred on a plasmid into E. coli. Induction was shown to be L-tryptophan dependent; however, the range of induction was less than that observed for the E. coli tna operon. We compared the genetic organization of both operons and predicted similar folding patterns for their respective leader mRNA segments. However, additional analyses revealed that L-tryptophan action in the P. vulgaris tna operon involves inhibition of TnaC elongation, following addition of proline, rather than inhibition of leader peptide termination. Our findings also establish that the conserved residues in TnaC of P. vulgaris are essential for L-tryptophan induction, and for inhibition of peptide elongation. TnaC synthesis is thus an excellent model system for studies of regulation of both peptide termination and peptide elongation, and for studies of ribosome recognition of the features of a nascent peptide. PMID:19767424

  19. New insights into tryptophan and its metabolites in the regulation of bone metabolism.

    Michalowska, M; Znorko, B; Kaminski, T; Oksztulska-Kolanek, E; Pawlak, D

    2015-12-01

    Osteoporosis, a debilitating disease caused by an imbalance between the action of osteoblasts and osteoclasts, is becoming an increasing problem in today's aging population. Although many advances in this field have addressed certain aspects of disease progression and pain management, new approaches to treatment are required. This review focuses on the influence of tryptophan, its metabolites and their influence on bone remodeling. Tryptophan is a precursor to serotonin, melatonin, kynurenines and niacin. Changes of tryptophan levels were noticed in bone metabolic diseases. Moreover, some works indicate that tryptophan plays a role in osteoblastic differentiation. Serotonin can exert different effects on bones, which depend on site of serotonin synthesis. Gut-derived serotonin inhibits bone formation, whereas brain-derived serotonin enhances bone formation and decreases bone resorption. Melatonin, increased differentiation of human mesenchymal stem cells into the osteoblastic cell lineage. Results of melatonin action on bone are anabolic and antiresorptive. Activation of the second tryptophan metabolic pathway, the kynurenine pathway, is associated with osteoblastogenesis and can be implicated in the occurrence of bone diseases. Oxidation products like kynurenine stopped proliferation of bone marrow mesenchymal stem cells. This may result in inhibition of osteoblastic proliferation and differentiation. Kynurenic acid acts as an antagonist at glutamate receptors, which are expressed on osteoclasts. Quinolinic acid activates N-methyl-D-aspartate receptors. 3-hydroxyanthranilic acid exhibits pro-oxidant and antioxidant activity. Decreased concentration of 3-hydroxyanthranilic acid can be one of the causes of osteoporosis. 3-hydroxykynurenine reduced the viability of osteoblast-like cells. Picolinic acid exerted osteogenic effect in vitro. Kynurenine derivatives exert various effects on bones. Discovery of the exact mechanism of action of tryptophan metabolites on

  20. The pH-Dependent Stucture and Properties of Au and Ag Nanoparticles Produced by Tryptophan Reduction.

    Mukha, Iuliia; Vityuk, Nadiia; Severynovska, Olga; Eremenko, Anna; Smirnova, Nataliia

    2016-12-01

    In the work, an attempt was made to combine different experimental conditions to obtain stable gold and silver nanoparticles in the presence of amino acid tryptophan. The pH-dependent properties of gold and silver nanoparticles were studied. UV/visible spectroscopy and laser desorption/ionization mass spectrometry data confirm kynurenine pathway for tryptophan conversion in such systems. PMID:26909781

  1. The pH-Dependent Stucture and Properties of Au and Ag Nanoparticles Produced by Tryptophan Reduction

    Mukha, Iuliia; Vityuk, Nadiia; Severynovska, Olga; Eremenko, Anna; Smirnova, Nataliia

    2016-02-01

    In the work, an attempt was made to combine different experimental conditions to obtain stable gold and silver nanoparticles in the presence of amino acid tryptophan. The pH-dependent properties of gold and silver nanoparticles were studied. UV/visible spectroscopy and laser desorption/ionization mass spectrometry data confirm kynurenine pathway for tryptophan conversion in such systems.

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

    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. PMID:26307347

  3. The pharmacokinetics of L-tryptophan following its intravenous and oral administration.

    Green, A. R.; Aronson, J K; Cowen, P J

    1985-01-01

    The pharmacokinetics of L-tryptophan (5 g and 7.5 g) have been studied after its intravenous administration to healthy subjects and the results compared with those obtained after oral administration (0.7 g-3.5 g). In order to do this, we have re-analysed previously published data relating to oral administration. The data obtained following the oral administration of L-tryptophan suggest that the total body clearance and apparent volume of distribution are saturable. The pharmacokinetics of tr...

  4. Comparison of tryptophan biosynthetic operon regulation in different Gram-positive bacterial species.

    Gutiérrez-Preciado, Ana; Yanofsky, Charles; Merino, Enrique

    2007-09-01

    The tryptophan biosynthetic operon has been widely used as a model system for studying transcription regulation. In Bacillus subtilis, the trp operon is primarily regulated by a tryptophan-activated RNA-binding protein, TRAP. Here we show that in many other Gram-positive species the trp operon is regulated differently, by tRNA(Trp) sensing by the RNA-based T-box mechanism, with T-boxes arranged in tandem. Our analyses reveal an apparent relationship between trp operon organization and the specific regulatory mechanism(s) used. PMID:17555843

  5. Neuartige Tryptophan-Synthasen aus Hyperthermophilen: Charakterisierung der Enzyme aus Sulfolobus solfataricus

    Leopoldseder, Sonja

    2006-01-01

    In der vorliegenden Arbeit wurde die Tryptophan Synthase aus Sulfolobus solfataricus strukturell und funktionell untersucht. Zu diesem Zweck wurden die Operon-ständigen Gene strpA und strpB2a, sowie das nicht Operon-ständige strpB2b getrennt in Escherichia coli exprimiert, die Genprodukte gereinigt und charakterisiert. sTrpB2a und sTrpB2b katalysieren mit vergleichbar hoher Effizienz die Synthese von Tryptophan aus Serin und Indol. Während sTrpB2b nicht mit sTrpA interagiert, bilden sTrpB2a ...

  6. Effects of oestrogen administration on vitamin B6 and tryptophan metabolism in the rat

    Bender, D A; Tagoe, C. E.; Vale, J. A.

    1982-01-01

    1. In order to assess the effects of oestrogens on the metabolism of tryptophan and vitamin B6, ovariectomized rats have been maintained on diets providing known amounts of tryptophan, nicotinamide and vitamin B6. They received oestrone sulphate, 210 micrograms/kg body-wt per d, either incorporated in the diet for 8 weeks, or by daily intraperitoneal injection for periods of 1-3 d. 2. Oestrone sulphate administration caused a slight reduction in the concentration of pyridoxal phosphate in pla...

  7. Tryptophan fluorescence of erythrocyte ghosts after irradiation and unitiation of lipid peroxidation by Fe2+

    It was shown that under the effect of Fe2+ - initiated lipid peroxidation and ionizing radiation tryptophan fluorescence parameters (i.e. intensity and polarization) were subjected to similar changes. Shortly (15 min) after irradiation no changes were observed in the level of products reacting with thiobarbituric acid. It is concluded that the process and products of lipid peroxidation do not markedly contribute to the postirradiation alteration of tryptophan fluorescence. At the same time additional postirradiation damages to proteins can be attributed to activation of lipid peroxidation

  8. Effect of fed-batch on synthesis of 15N-L-tryptophan from precursor fermentation

    Using Candida utilis AS60 as 15N-L-tryptophan producing strain, the influence by different feeding modes of glucose, 15N-(NH4)2SO4 and 15N-anthranilic acid was studied. The results of these experiments show that the yield of 15N-L-tryptophan was 3.073 g/L by addition of 50 g/L of glucose, 2.1 g/L of 15N-(NH4)2SO4 and 1.5 g/L of 15N-anthranilic acid after 36 h of fermentation. (authors)

  9. Beneficial Uses of Depleted Uranium

    Naturally occurring uranium contains 0.71 wt% 235U. In order for the uranium to be useful in most fission reactors, it must be enriched the concentration of the fissile isotope 235U must be increased. Depleted uranium (DU) is a co-product of the processing of natural uranium to produce enriched uranium, and DU has a 235U concentration of less than 0.71 wt%. In the United States, essentially all of the DU inventory is in the chemical form of uranium hexafluoride (UF6) and is stored in large cylinders above ground. If this co-product material were to be declared surplus, converted to a stable oxide form, and disposed, the costs are estimated to be several billion dollars. Only small amounts of DU have at this time been beneficially reused. The U.S. Department of Energy (DOE) has begun the Beneficial Uses of DU Project to identify large-scale uses of DU and encourage its reuse for the primary purpose of potentially reducing the cost and expediting the disposition of the DU inventory. This paper discusses the inventory of DU and its rate of increase; DU disposition options; beneficial use options; a preliminary cost analysis; and major technical, institutional, and regulatory issues to be resolved

  10. Ozone depletion potentials of halocarbons

    The concept of ozone depletion potential (ODP) is widely used in the evaluation of numerous halocarbons and of their replacements for effects on ozone, but the methods, model assumptions and conditions of ODP calculation have not been analyzed adequately. In this paper, a model study of effects on ozone after the instantaneous releases of various amounts of CH3CCl3 and of CHF2Cl(HCFC-22) in the several conditions of the background atmosphere are presented, aimed to understand the main connections of ODP values with the methods of their calculations. To facilitate the ODP computation in numerous versions for long after the releases, the above rather short-lived gases have been used. The variation of released gas global mass from 1 Mt to 1 Gt leads to ODP value increase atmosphere. The same variations are analyzed for the CFC-free atmosphere of 1960s conditions for the anthropogenically loaded atmosphere in the 21st century according to the known IPCC- A scenario (business as usual). Recommendations of proper ways of ODP calculations are proposed for practically important cases

  11. Plutonium in depleted uranium penetrators

    Depleted Uranium (DU) penetrators used in the recent Balkan conflicts have been found to be contaminated with trace amounts of transuranic materials such as plutonium. This contamination is usually a consequence of DU fabrication being carried out in facilities also using uranium recycled from spent military and civilian nuclear reactor fuel. Specific activities of 239+240 Plutonium generally in the range 1 to 12 Bq/kg have been found to be present in DU penetrators recovered from the attack sites of the 1999 NATO bombardment of Kosovo. A DU penetrator recovered from a May 1999 attack site at Bratoselce in southern Serbia and analysed by University College Dublin was found to contain 43.7 +/- 1.9 Bq/kg of 239+240 Plutonium. This analysis is described. An account is also given of the general population radiation dose implications arising from both the DU itself and from the presence of plutonium in the penetrators. According to current dosimetric models, in all scenarios considered likely ,the dose from the plutonium is estimated to be much smaller than that due to the uranium isotopes present in the penetrators. (author)

  12. Optimization of L-Tryptophan Biosynthesis From L-Serine of Processed Iranian Beet and Cane Molasses and Indole by Induced Escherichia coli ATCC 11303 Cells

    Sadeghiyan-Rizi, Tahereh; Fooladi, Jamshid; Momhed Heravi, Majid; Sadrai, Sima

    2014-01-01

    Background: L-tryptophan is an important ingredient in medicines, especially in neuromedicines such as antidepressants. Many commercial processes employ various microorganisms with high tryptophan synthase activity to produce L-tryptophan from indole and L-serine, but these processes are very costly due to the costs of precursors, especially L-serine. Objectives: For this reason, we studied the ability to use processed Iranian cane and beet molasses as L-serine sources for L-tryptophan produc...

  13. Bronchitis - acute

    ... sharing features on this page, please enable JavaScript. Acute bronchitis is swelling and inflammation in the main passages ... present only for a short time. Causes When acute bronchitis occurs, it almost always comes after having a ...

  14. Bronchitis - acute

    Acute bronchitis is swelling and inflammation in the main passages that carry air to the lungs. The swelling narrows ... makes it harder to breathe. Another symptom of bronchitis is a cough. Acute means the symptoms have ...

  15. Acute Bronchitis

    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 ...

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

    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......) 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...

  17. Acute pancreatitis

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    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 ingest...

  18. Acute pancreatitis

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    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....

  19. The Chemistry and Toxicology of Depleted Uranium

    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.

  20. Depletion sensitivity predicts unhealthy snack purchases

    Salmon, Stefanie J.; Adriaanse, Marieke A.; 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 we

  1. Depletion sensitivity predicts unhealthy snack purchases

    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

  2. Tritium transport vessel using depleted uranium

    Heung, L.K.

    1995-01-01

    A tritium transport vessel using depleted uranium was tested in the laboratory using deuterium and protium. The vessel contains 0.5 kg of depleted uranium and can hold up to 18 grams of tritium. The conditions for activation, tritium loading and tritium unloading were defined. The safety aspects that included air-ingress, tritium diffusion, temperature and pressure potentials were evaluated.

  3. Oil depletion and terms of trade

    Irimia-Vladu, Marina; Thompson, Henry

    2007-01-01

    A model of the international oil market model with optimal depletion and offer curves suggests importers face a backward bending offer curve. An oil tariff would then raise oil imports and lower the price of oil including the tariff. Simulations of price and extraction paths for the coming century provide insight into the future of oil depletion and terms of trade.

  4. L-tryptophan synthesis from 14C-anthranilic acid in plants with high and low tryptophan content

    The biosynthesis of L-tryptophan (L-trp) from anthranilic acid-14C (AA-14C) in undamaged organs of the seedlings of kohlrabi and peas, with high L-trp content and maize plants, with low L-trp content was compared. As for maize the experiments were carried out with normal and opaque-2 phenotypes, both with the seedlings and with the ripening kernels. AA-14C is metabolized in the plants to L-trp pool and to glycosyl esters of AA. In maize seedlings L-trp-14C is synthesized relatively less than in kohlrabi and in pea. The de novo formation of L-trp-14C is stopped earlier in maize than in kohlrabi. The level of free L-trp-14C is relatively low in maize in comparison with kohlrabi and peas. In spite of this the formation of L-trp-14C from AA-14C is sufficient in maize to incorporate L-trp both into the proteins and into a secondary metabolite that is not yet defined. At the period of seedlings the incorporation in maize of L-trp into the proteins is comparable with that in kohlrabi, and it is maximum in pea. Maize, at the stage of germination, thus forms proteins rich in L-trp. The formation of free L-trp is approximately ten times lower in ripening kernels and in the leaves adjacent to the ear and it further decreases in the course of the ripening of the kernels. Although the activity of the biosynthesis of the AA-14C→L-trp-14C pathway is relatively lower in maize than in kohlrabi and peas, this pathway is most responsible for the differences in the content of L-trp in these plants. Neither amitrol nor histidine affected the biosynthesis of L-trp in kohlrabi; the interaction of the biosynthetic pathways of L-trp and histidine known in microorganisms is thus not important in a higher plant. (author)

  5. Deuterium - depleted water. Achievements and perspectives

    Deuterium - depleted water represents water that has an isotopic content lower than 145 ppm D/(D+H) which is the natural isotopic content of water. The research conducted at ICSI Ramnicu Valcea, regarding deuterium - depleted water were completed by the following patents: - technique and installation for deuterium - depleted water production; - distilled water with low deuterium content; - technique and installation for the production of distilled water with low deuterium content; - mineralized water with low deuterium content and technique to produce it. The gold and silver medals won at international salons for inventions confirmed the novelty of these inventions. Knowing that deuterium content of water has a big influence on living organisms, beginning with 1996, the ICSI Ramnicu Valcea, deuterium - depleted water producer, co-operated with Romanian specialized institutes for biological effects' evaluation of deuterium - depleted water. The role of natural deuterium in living organisms was examined by using deuterium - depleted water instead of natural water. These investigations led to the following conclusions: 1. deuterium - depleted water caused a tendency towards the increase of the basal tone, accompanied by the intensification of the vasoconstrictor effects of phenylefrine, noradrenaline and angiotensin; the increase of the basal tone and vascular reactivity produced by the deuterium - depleted water persists after the removal of the vascular endothelium; -2. animals treated with deuterium - depleted water showed an increase of the resistance both to sublethal and to lethal gamma radiation doses, suggesting a radioprotective action by the stimulation of non-specific immune defence mechanism; 3, deuterium - depleted water stimulates immune defence reactions, represented by the opsonic, bactericidal and phagocyte capacity of the immune system, together with increase in the numbers of polymorphonuclear neutrophils; 4. investigations regarding artificial

  6. Specification for the VERA Depletion Benchmark Suite

    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.

  7. High Sensitivity Surface Enhanced Raman Scattering Detection of Tryptophan

    Kandakkathara, Archana

    Raman spectroscopy has the capability of providing detailed information about molecular structure, but the extremely small cross section of Raman scattering prevents this technique from applications requiring high sensitivity. Surface enhanced Raman scattering (SERS) on the other hand provides strongly increased Raman signal from molecules attached to metallic nanostructures. SERS is thus a promising technique for high sensitivity analytical applications. One particular area of interest is the application of such techniques for the analysis of the composition of biological cells. However, there are issues which have to be addressed in order to make SERS a reliable technique such as the optimization of conditions for any given analyte, understanding the kinetic processes of binding of the target molecules to the nanostructures and understanding the evolution and coagulation of the nanostructures, in the case of colloidal solutions. The latter processes introduce a delay time for the observation of maximum enhancement factors which must be taken into account for any given implementation of SERS. In the present thesis the goal was to develop very sensitive SERS techniques for the measurement of biomolecules of interest for analysis of the contents of cells. The techniques explored could be eventually be applicable to microfluidic systems with the ultimate goal of analyzing the molecular constituents of single cells. SERS study of different amino acids and organic dyes were performed during the course of this thesis. A high sensitivity detection system based on SERS has been developed and spectrum from tryptophan (Trp) amino acid at very low concentration (10-8 M) has been detected. The concentration at which good quality SERS spectra could be detected from Trp is 4 orders of magnitude smaller than that previously reported in literature. It has shown that at such low concentrations the SERS spectra of Trp are qualitatively distinct from the spectra commonly reported in

  8. Acute pancreatitis

    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.

  9. Acute pancreatitis

    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. Synthesis of Ruthenium Xanthate Complex and Its Electrocatalytic Activity for Tryptophan Oxidation

    WU Fang-hui; CHEN Le; CHU Xiang-feng; WEI Xian-wen

    2013-01-01

    A new ruthenium complex containing bidentate xanthate ligands was synthesized in a good yield.This complex was characterized by elemental analysis,proton nuclear magnetic resonance(1H NMR),Fourier transform infrared(FTIR) and UV-Vis spectroscopies.The cyclic voltammetry of the complex revealed one quasi-redox wave centered at Ru(Ⅲ)/Ru(Ⅱ) couple,indicating its catalytic potential.So the preparation of a glass carbon electrode modified with ruthenium xanthate complex and its electrocatalytic activity toward the oxidation of tryptophan(Trp)were also studied.The experimental results show that the modified electrode had excellent electrocatalytic activity for the oxidation of tryptophan.Moreover,under the optimized conditions,the oxidation peak current was proportional to tryptophan concentration in a range of 2.5× 10-7 to 5.0× 10-5 mol/L with a correlation coefficient of 0.9928 and a detection limit of 8.3 × 10-8 mol/L(S/N=3).Using the proposed method,tryptophan was successfully determined in pharmaceutical samples with standard addition method.

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

    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 demonst...

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

    Strasser, Barbara; Geiger, Daniela; Schauer, Markus; Gatterer, Hannes; Burtscher, Martin; Fuchs, Dietmar

    2016-01-01

    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 (pcognitive processes. PMID:27124720

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

    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 exhibit only minor shifts. In this work, we show that phasor approaches can substantially simplify tryptophan fluorescence analysis. To demonstrate this, we re-analyse previously recorded datasets of the denaturant (guanidinium hydrochloride, GuHCl) induced unfolding of a single-tryptophan-containing variant of apoflavodoxin from Azotobacter vinelandii. For three methods—(1) time-resolved fluorescence, (2) time-resolved fluorescence anisotropy and (3) steady-state fluorescence spectroscopy—we show that the phasor analysis can readily identify the presence of a folding intermediate. Moreover, the fractional contributions of protein states at various stages of unfolding and the values of the free energy difference of the unfolding process (ΔGUN0) are obtained. The outcomes are compared to the global analysis results published previously. (paper)

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

    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.

  15. Wirkung von Transaminaseinhibitoren auf die Tryptophan-abhängige Pigmentbildung von Malassezia furfur

    Vöhrs, Inga Susanne Gabriele

    2010-01-01

    Die vorliegende Arbeit untersucht die Wirkung von Transaminaseinhibitoren auf die Pigmentbildung von Malassezia furfur. Das Phänomen der Pigmentbildung von Malassezia furfur durch Verstoffwechselung der Aminosäure Tryptophan, wenn diese als alleinige Stickstoffquelle vorhanden ist, wurde 1998 erstmalig beschrieben (Mayser 1998). Diese Pigmente können verschiedene klinische Ausprägungen der Pityriasis versicolor verursac...

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

    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.

  17. Copper-Catalyzed Diastereoselective Arylation of Tryptophan Derivatives: Total Synthesis of (+)-Naseseazines A and B

    Kieffer, Madeleine E.; Chuang, Kangway V.; Reisman, Sarah E.

    2013-01-01

    A copper-catalyzed arylation of tryptophan derivatives is reported. The reaction proceeds with high site- and diastereoselectivity to provide aryl pyrroloindoline products in one step from simple starting materials. The utility of this transformation is highlighted in the five-step syntheses of the natural products (+)-naseseazine A and B.

  18. Reprint of 'pH tuning of Nafion for selective detection of tryptophan'

    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.

  19. pH tuning of Nafion for selective detection of tryptophan

    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.

  20. Interfacial Tryptophan Residues: A Role for the Cation-{pi} Effect?

    Petersen, Frederic Nicolas Rønne; Jensen, Morten Ø.; Helix Nielsen, Claus

    2005-01-01

    the interaction between the nitrogen moiety of lipid molecule headgroups and the pi-electron distribution of gramicidin (gA) tryptophan residues (W(9), W(11), W(13), and W(15)) using molecular dynamics (MD) simulations of gA embedded in two hydrated lipid bilayers composed of 1-palmitoyl-2...

  1. pH tuning of Nafion for selective detection of tryptophan

    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. Internal energies of ion-sputtered neutral tryptophan and thymine molecules determined by vacuum ultraviolet photoionization.

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

    2010-05-01

    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 Bi(3)(+) indicates that the ion-sputtered parent molecules have approximately 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 Bi(3)(+) 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. PMID:20353160

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

    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.

  4. Problem-solving test: Attenuation: a mechanism to regulate bacterial tryptophan biosynthesis.

    Szeberényi, József

    2010-11-01

    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. PMID:21567872

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

    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.)

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

    Bader, Arjen N.; Visser, Nina V.; van Amerongen, Herbert; Visser, Antonie J. W. G.

    2014-12-01

    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 exhibit only minor shifts. In this work, we show that phasor approaches can substantially simplify tryptophan fluorescence analysis. To demonstrate this, we re-analyse previously recorded datasets of the denaturant (guanidinium hydrochloride, GuHCl) induced unfolding of a single-tryptophan-containing variant of apoflavodoxin from Azotobacter vinelandii. For three methods—(1) time-resolved fluorescence, (2) time-resolved fluorescence anisotropy and (3) steady-state fluorescence spectroscopy—we show that the phasor analysis can readily identify the presence of a folding intermediate. Moreover, the fractional contributions of protein states at various stages of unfolding and the values of the free energy difference of the unfolding process ≤ft(Δ G\\text{UN}0\\right) are obtained. The outcomes are compared to the global analysis results published previously.

  7. Study of interaction between tryptophan, tyrosine, and phenylalanine separately with silver nanoparticles by fluorescence quenching method

    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 (ΔH, ΔS, and ΔG) 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. (authors)

  8. Reprint of 'pH tuning of Nafion for selective detection of tryptophan'

    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.

  9. Quenching of Tryptophan Fluorescence in Unfolded Cytochrome "c": A Biophysics Experiment for Physical Chemistry Students

    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…

  10. Nucleotides that are essential but not conserved; a sufficient L-tryptophan site in RNA

    Majerfeld, I.; Chocholoušová, Jana; Malaiya, V.; Widmann, J.; McDonald, D.; Reeder, J.; Iyer, M.; Illangasekare, M.; Yarus, M.; Knight, R.

    2010-01-01

    Roč. 16, č. 10 (2010), s. 1915-1924. ISSN 1355-8382 R&D Projects: GA MŠk ME09019 Institutional research plan: CEZ:AV0Z40550506 Keywords : SELEX * molecular modeling * aptamer * evolution * tryptophan Subject RIV: CC - Organic Chemistry Impact factor: 6.051, year: 2010

  11. Study of Interaction Between Tryptophan, Tyrosine, and Phenylalanine Separately with Silver Nanoparticles by Fluorescence Quenching Method

    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.

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

    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...

  13. Tryptophan biosynthesis in stramenopiles: eukaryotic winners in the diatom complex chloroplast

    Jiroutová, Kateřina; Horák, Aleš; Bowler, C.; Oborník, Miroslav

    2007-01-01

    Roč. 65, č. 5 (2007), s. 496-511. ISSN 0022-2844 R&D Projects: GA AV ČR IAA500220502 Institutional research plan: CEZ:AV0Z60220518 Keywords : tryptophan synthesis * mosaic origin * diatom * Oomycetes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.234, year: 2007

  14. Fluorescence imaging of tryptophan and collagen cross-links to evaluate wound closure ex vivo

    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.

  15. Energetics of Photoinduced Charge Migration within the Tryptophan Tetrad of an Animal (6-4) Photolyase.

    Cailliez, Fabien; Müller, Pavel; Firmino, Thiago; Pernot, Pascal; de la Lande, Aurélien

    2016-02-17

    Cryptochromes and photolyases are flavoproteins that undergo cascades of electron/hole transfers after excitation of the flavin cofactor. It was recently discovered that animal (6-4) photolyases, as well as animal cryptochromes, feature a chain of four tryptophan residues, while other members of the family contain merely a tryptophan triad. Transient absorption spectroscopy measurements on Xenopus laevis (6-4) photolyase have shown that the fourth residue is effectively involved in photoreduction but at the same time could not unequivocally ascertain the final redox state of this residue. In this article, polarizable molecular dynamics simulations and constrained density functional theory calculations are carried out to reveal the energetics of charge migration along the tryptophan tetrad. Migration toward the fourth tryptophan is found to be thermodynamically favorable. Electron transfer mechanisms are sought either through an incoherent hopping mechanism or through a multiple sites tunneling process. The Jortner-Bixon formulation of electron transfer (ET) theory is employed to characterize the hopping mechanism. The interplay between electron transfer and relaxation of protein and solvent is analyzed in detail. Our simulations confirm that ET in (6-4) photolyase proceeds out of equilibrium. Multiple site tunneling is modeled with the recently proposed flickering resonance mechanism. Given the position of energy levels and the distribution of electronic coupling values, tunneling over three tryptophan residues may become competitive in some cases, although a hopping mechanism is likely to be the dominant channel. For both reactive channels, computed rates are very sensitive to the starting protein configuration, suggesting that both can take place and eventually be mixed, depending on the state of the system when photoexcitation takes place. PMID:26765169

  16. l-tryptophan and dipeptide derivatives for supercoiled plasmid DNA purification.

    Santos, Tiago; Carvalho, Josué; Corvo, Marta C; Cabrita, Eurico J; Queiroz, J A; Cruz, C

    2016-06-01

    The present study focus on the preparation of chromatography supports for affinity-based chromatography of supercoiled plasmid purification. Three l-tryptophan based supports are prepared through immobilization on epoxy-activated Sepharose and characterized by HR-MAS NMR. The SPR is employed for a fast screening of l-tryptophan derivatives, as potential ligands for the biorecognition of supercoiled isoform, as well as, to establish the suitable experimental conditions for the chromatography. The results reveal that the overall affinity is high (KD=10(-9) and 10(-8)M) and the conditions tested show that the use of HEPES 100mM enables the separation and purification of supercoiled at T=10°C. The STD-NMR is performed to accomplish the epitope mapping of the 5'-mononucleotides bound to l-tryptophan derivatives supports. The data shows that the interactions between the three supports and the 5'-mononucleotides are mainly hydrophobic and π-π stacking. The chromatography experiments are performed with l-tryptophan support and plasmids pVAX-LacZ and pPH600. The supercoiled isoform separation is achieved at T=10°C by decreasing the concentration of (NH4)2SO4 from 2.7 to 0M in HEPES for pVAX-LacZ and 2.65M to 0M in HEPES for pPH600. Overall, l-tryptophan derivatives can be a promising strategy to purify supercoiled for pharmaceutical applications. PMID:26952704

  17. Possible ozone depletions following nuclear explosions

    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.-

  18. Uptake and incorporation of labeled tryptophan isomers into IAA in the jsR1 mutant of Lemna gibba

    Analyses of the IAA-overproducing mutant of Lemna have been initiated in order to study in vivo biosynthesis of IAA. Using radiolabelled tryptophan isomers prepared from commercial sources of 14C-D,L tryptophan by chiral separation kinetics of uptake of L and D tryptophan were determined for sterile cultures of individual jsR1 four-frond colonies. Over a 24 h period, about 50% of the radioactivity from 14C-L-TRP in media, or about 25% from 14C-D-TRP, was found in the plant tissue. Maximal rates of uptake were seen in the first six hors for both isomers. Endogenous levels of tryptophan determined in jsR1 as measures of pool sizes in vivo show 5 to 10 ug/g FW total tryptophan with less than 1% in the D isomer form. Information on uptake and endogenous pool sizes of tryptophan isomers is being used for feeding of stable isotope labeled tryptophan (13C, 14N) to jsR1 at physiological levels. Analyses of incorporation of label into IAA using GC-MS and high resolution mass spectrometry are currently underway

  19. Second harmonic generation from tryptophan-rich short peptides: W(n)K(m) and gramicidin A.

    Duboisset, J; Matar, G; Besson, F; Ficheux, D; Benichou, E; Russier-Antoine, I; Jonin, Ch; Brevet, P F

    2014-09-01

    We report the first hyperpolarizability of a series of tryptophan-rich short peptides with the respective sequence KWK, KWWK, KWWWK, KWWKWWK, where W and K stand for tryptophan and lysine. The measurements were performed with the technique of hyper-Rayleigh scattering in the bulk of an aqueous Tris buffer solution at a pH of 8.5 and a salt concentration of 150 mM at the non-resonant fundamental wavelength of 784 nm. The first hyperpolarizability of the different peptides follows a simple additive model scaling with the number of tryptophan residues contained in the peptide. However, it appears that the first hyperpolarizability response of a single tryptophan residue in the peptide strongly differs from that of an isolated tryptophan. Hence, it is therefore demonstrated that the local environment of the tryptophan residues within the peptide strongly influences its nonlinear optical response. A comparison with the first hyperpolarizability of the natural peptide gramicidin A measured in trifluoroethanol (TFE) further confirms the key role of the local environment on the first hyperpolarizability of tryptophan residues in peptides. PMID:25144248

  20. Effects of tryptophan derivatives and β-carboline alkaloids on radiation- and peroxide-induced transformations of ethanol

    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 O·−2 and HO·2, or on oxidation of α-hydroxyethyl radicals by β-carboline alkaloids. - Highlights: • Tryptophan, 5-hydroxytryptophane and serotonin can reduce or add α-HER. • β-Carboline alkaloids – harmane, harmine, harmaline – can oxidize α-HER. • Tryptophan and its derivatives can reduce oxygen-centered radicals

  1. Mechanism of tryptophan indole-lyase: Insights from pre-steady-state kinetics and substrate and solvent isotope effects

    The pre-steady-state kinetics of the reaction of Escherichia coli tryptophan indole-lyase have been examined with L-tryptophan, 7-aza-DL-tryptophan, and S-benzyl-L-cysteine. L-Tryptophan and 7-aza-DL-tryptophan exhibit three relaxations when the reactions are monitored at 506 nm. With L-tryptophan, α-deuteriation results in an estimated isotope effect of 3.6 on the first phase, while 2H2O produces apparent isotope effects of 2.5 and 2.7 on the second and third phases, respectively. On the basis of the substrate and solvent isotope effects and the effects of aza substitution, these three processes have been assigned to (1) deprotonation of the α-carbon, (2) an enzyme conformational change, and (3) indole tautomerization. In contrast, S-benzyl-L-cysteine exhibits only one catalytically competent relaxation, monitored at 512 nm. The intrinsic isotope effect for the reaction of α-(2H)-S-benzyl-L-cysteine is estimated to be 7.9. α-Proton abstraction is 10 to 100-fold faster than catalytic turnover in these reactions; thus, tautomerization of the indole ring of L-tryptophan may be partially rate-determining. 27 references, 3 figures

  2. Contribution of tryptophan residues to the combining site of a monoclonal anti dinitrophenyl spin-label antibody

    Two Fab fragments of the monoclonal anti dinitrophenyl (DNP) spin-label antibody AN02 were prepared by recombination of specifically deuterated heavy and light chains. In the recombinant H(I)L(II) all the tyrosines and phenylalanines were perdeuterated as were the tryptophan residues of the heavy chain. In the recombinant H(II)L(I) all the tyrosines and phenylalanines were perdeuterated as were the tryptophan residues of the light chain. Saturation of three resonances of H(I)L(II), assigned to tryptophan protons of the light chain, resulted in magnetization transfer to the aromatic proton at position 6 of the DNP ring and to the CH2 protons of the glycines linked to the DNP in a diamagnetic hapten (DNP-DG). Saturation of three resonances of H(II)L(I) assigned to tryptophan protons of the heavy chain resulted in magnetization transfer to the CH2 protons of the glycines in DNP-DG. From the dependence of the magnetization transfer on the irradiation time, the cross relaxation rates between the involved protons were estimated. The inferred distances between these protons of the hapten and certain tryptophan protons are 3-4 A. It is concluded that in the combining site of AN02 there is one tryptophan from the light chain and one tryptophan from the heavy chain that are very near the hapten. When all tyrosines and phenylalanines were perdeuterated and all tryptophan aromatic protons were deuterated except for the protons at positions 2 and 5, titration of the Fab fragments with variable amounts of paramagnetic hapten showed that one proton from the light chain tryptophan is near (less than 7 A) the unpaired electron and that three other protons are significantly closer than 15 A

  3. Structure and Activity of an Aminoacyl-tRNA Synthetase that Charges tRNA with Nitro-Tryptophan

    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.

  4. A Brief Historic Overview of Clinical Disorders Associated with Tryptophan: The Relevance to Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM).

    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). PMID:23032646

  5. Activation of tryptophan biosynthesis by bacillus megaterium through optimization of culture conditions and/or radiation exposure

    For tryptophan biosynthesis by bacillus megaterium, urea containing medium (0.5 g %) without CaCO3 was found to be a more suitable fermentation medium, as it gave good amount extracellular tryptophan (18.33 mg %) by the wild strain of B.megaterium. Similarly, when B. megaterium was exposed to different doses (0.2 up to 8.0 KGy) of gamma radiation and isolates picked from among the survivors, it was found that the highest amount of tryptophan (45.56 mg %) was produced by an isolate from a culture which had been exposed to 7.0 KGy of gamma radiation

  6. Real depletion in nodal diffusion codes

    The fuel depletion is described by more than one hundred fuel isotopes in the advanced lattice codes like HELIOS, but only a few fuel isotopes are accounted for even in the advanced steady-state diffusion codes. The general assumption that the number densities of the majority of the fuel isotopes depend only on the fuel burnup is seriously in error if high burnup is considered. The real depletion conditions in the reactor core differ from the asymptotic ones at the stage of lattice depletion calculations. This study reveals which fuel isotopes should be explicitly accounted for in the diffusion codes in order to predict adequately the real depletion effects in the core. A somewhat strange conclusion is that if the real number densities of the main fissionable isotopes are not explicitly accounted for in the diffusion code, then Sm-149 should not be accounted for either, because the net error in k-inf is smaller (Authors)

  7. Fully Depleted Charge-Coupled Devices

    We have developed fully depleted, back-illuminated CCDs that build upon earlier research and development efforts directed towards technology development of silicon-strip detectors used in high-energy-physics experiments. The CCDs are fabricated on the same type of high-resistivity, float-zone-refined silicon that is used for strip detectors. The use of high-resistivity substrates allows for thick depletion regions, on the order of 200-300 um, with corresponding high detection efficiency for near-infrared and soft x-ray photons. We compare the fully depleted CCD to the p-i-n diode upon which it is based, and describe the use of fully depleted CCDs in astronomical and x-ray imaging applications

  8. Polar stratospheric clouds and ozone depletion

    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.

  9. Depleted UF6 programmatic environmental impact statement

    The US Department of Energy has developed a program for long-term management and use of depleted uranium hexafluoride, a product of the uranium enrichment process. As part of this effort, DOE is preparing a Programmatic Environmental Impact Statement (PEIS) for the depleted UF6 management program. This report duplicates the information available at the web site (http://www.ead.anl.gov/web/newduf6) set up as a repository for the PEIS. Options for the web site include: reviewing recent additions or changes to the web site; learning more about depleted UF6 and the PEIS; browsing the PEIS and related documents, or submitting official comments on the PEIS; downloading all or part of the PEIS documents; and adding or deleting one's name from the depleted UF6 mailing list

  10. Ecological considerations of natural and depleted uranium

    Depleted 238U is a major by-product of the nuclear fuel cycle for which increasing use is being made in counterweights, radiation shielding, and ordnance applications. This paper (1) summarizes the pertinent literature on natural and depleted uranium in the environment, (2) integrates results of a series of ecological studies conducted at Los Alamos Scientific Laboratory (LASL) in New Mexico where 70,000 kg of depleted and natural uranium has been expended to the environment over the past 34 years, and (3) synthesizes the information into an assessment of the ecological consequences of natural and depleted uranium released to the environment by various means. Results of studies of soil, plant, and animal communities exposed to this radiation and chemical environment over a third of a century provide a means of evaluating the behavior and effects of uranium in many contexts

  11. Depleted Uranium and Its Effects on Humans

    Zdeněk Hon

    2015-04-01

    Full Text Available The article summarizes contemporary scientific knowledge of depleted uranium effects on human health due to its use in military conflicts. The discussion covers cases of minimal risk due to external irradiation resulting from the storage and handling of depleted uranium ammunition and, in contrast, important toxicological and radio-toxicological risks of late effects resulting from the inhalation and ingestion of dust particles produced by the burning of the core of the anti-tank ammunition.

  12. Depleted Uranium and Its Effects on Humans

    Zdeněk Hon; Jan Österreicher; Leoš Navrátil

    2015-01-01

    The article summarizes contemporary scientific knowledge of depleted uranium effects on human health due to its use in military conflicts. The discussion covers cases of minimal risk due to external irradiation resulting from the storage and handling of depleted uranium ammunition and, in contrast, important toxicological and radio-toxicological risks of late effects resulting from the inhalation and ingestion of dust particles produced by the burning of the core of the anti-tank ammunition.

  13. Depleted Bulk Heterojunction Colloidal Quantum Dot Photovoltaics

    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.

  14. Radiative characteristics of depleted uranium bomb and it is protection

    Based on the developing process of depleted uranium bombs described in the first part, the radiative characteristics and mechanism of depleted uranium bombs are analyzed emphatically. The deeper discussion on protection of depleted uranium bombs is proceeded

  15. Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke

    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.

  16. Short-chain fluorescent tryptophan tags for on-line detection of functional recombinant proteins

    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

  17. Gender differences in hyperthermia and regional 5-HT and 5-HIAA depletion in the brain following MDMA administration in rats

    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

  18. The different roles of tryptophan transfer RNA in regulating trp operon expression in E. coli versus B. subtilis.

    Yanofsky, Charles

    2004-08-01

    Escherichia coli and Bacillus subtilis use different mechanisms of sensing and responding to tryptophan and uncharged tRNA(Trp) as regulatory signals. In E. coli, tryptophan activates a repressor that binds to the trp promoter- operator, inhibiting transcription initiation. In B. subtilis, tryptophan activates an RNA-binding protein, TRAP, which binds to the trp operon leader RNA, causing transcription termination. In E. coli uncharged tRNA(Trp) accumulation stalls the ribosome attempting translation of tandem Trp codons in the leader-peptide coding region of the operon. This stalling permits the formation of an RNA antiterminator structure, preventing transcription termination. In B. subtilis uncharged tRNA(Trp) accumulation activates transcription and translation of the at operon. AT protein inhibits tryptophan-activated TRAP, thereby preventing TRAP-mediated transcription termination. These differences might reflect the unique organizational features of the respective trp operons and their ancestry. PMID:15262409

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

    Morozzo della Rocca, Blasco; Smith, C I; Tesauro, Cinzia; Desideri, Alessandro; Weightman, P

    The adsorption of a cysteine–tryptophan dipeptide has been monitored at a Au(110)/electrolyte interface using reflection anisotropy spectroscopy. At −0.6 V the dipeptide adsorbed through the formation of Au–S bonds and a link between the NH2 group at the Au surface. As the applied potential was...... changed to + 0.6 V the NH2 group left the surface and the spectra suggest that two dipeptides form a disulphide bridge that binds to the Au surface. This event is accompanied by changes in the orientation of, and possibly interactions between, tryptophan moieties. Returning the applied potential to −0.6 V...... 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...

  20. Reduction of cerebral blood flow in subclinical hepatic encephalopathy and its correlation with plasma-free tryptophan

    Cerebral blood flow (CBF), measured by the noninvasive xenon-133 inhalation method, EEG, and plasma levels of ammonia (NH3) and free tryptophan were determined in 18 hospitalized cirrhotic patients affected with subclinical hepatic encephalopathy, as diagnosed by the Kurtz test. CBF results were significantly lower (p less than 0.001) in the patients' group as compared with a sex- and age-matched normal control population, although seven patients had values in the normal range. NH3 was increased only in six, while free tryptophan was increased in all but two patients. A significant negative correlation (p = 0.02) between CBF and free tryptophan was found, even though it appears to be difficult to interpret. We suggest that CBF impairment in some cirrhotic patients with subclinical hepatic encephalopathy may be related to the systemic metabolic derangement caused by the liver disease; free tryptophan could have some implication in producing CBF reduction

  1. UVB-induced photoperoxidation of lipids of human low and high density lipoproteins. A possible role of tryptophan residues

    Ultraviolet radiation of the UVB region readily destroys tryptophan (Trp) residues of low (LDL) and high (HDL) density lipoproteins. The photooxidation of tryptophan residues is accompanied by peroxidation of low and high density lipoproteins unsaturated fatty acids, as measured by thiobarbituric acid assay. Moreover, low and high density lipoproteins are natural carriers of vitamin E and carotenoids. These two antioxidants are also rapidly bleached by UVB. The UVA radiation promotes neither tryptophan residue destruction nor lipid photoperoxidation. The redox cycling Cu2+ ions considerably increase lipid photoperoxidation. The synergistic action of photo and auto (Cu2+-induced) peroxidation induces marked post-irradiation modifications of apolipoproteins as illustrated by degradation of most tryptophan residues after overnight incubation in the dark of pre-irradiated samples. (author)

  2. 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

    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.

  3. EPRI depletion benchmark calculations using PARAGON

    Highlights: • PARAGON depletion calculations are benchmarked against the EPRI reactivity decrement experiments. • Benchmarks cover a wide range of enrichments, burnups, cooling times, and burnable absorbers, and different depletion and storage conditions. • Results from PARAGON-SCALE scheme are more conservative relative to the benchmark data. • ENDF/B-VII based data reduces the excess conservatism and brings the predictions closer to benchmark reactivity decrement values. - Abstract: In order to conservatively apply burnup credit in spent fuel pool criticality analyses, code validation for both fresh and used fuel is required. Fresh fuel validation is typically done by modeling experiments from the “International Handbook.” A depletion validation can determine a bias and bias uncertainty for the worth of the isotopes not found in the fresh fuel critical experiments. Westinghouse’s burnup credit methodology uses PARAGON™ (Westinghouse 2-D lattice physics code) and its 70-group cross-section library, which have been benchmarked, qualified, and licensed both as a standalone transport code and as a nuclear data source for core design simulations. A bias and bias uncertainty for the worth of depletion isotopes, however, are not available for PARAGON. Instead, the 5% decrement approach for depletion uncertainty is used, as set forth in the Kopp memo. Recently, EPRI developed a set of benchmarks based on a large set of power distribution measurements to ascertain reactivity biases. The depletion reactivity has been used to create 11 benchmark cases for 10, 20, 30, 40, 50, and 60 GWd/MTU and 3 cooling times 100 h, 5 years, and 15 years. These benchmark cases are analyzed with PARAGON and the SCALE package and sensitivity studies are performed using different cross-section libraries based on ENDF/B-VI.3 and ENDF/B-VII data to assess that the 5% decrement approach is conservative for determining depletion uncertainty

  4. Repression is relieved before attenuation in the trp operon of Escherichia coli as tryptophan starvation becomes increasingly severe.

    Yanofsky, C; Kelley, R.L.; Horn, V.

    1984-01-01

    Expression of the tryptophan operon of Escherichia coli is regulated over about a 500- to 600-fold range by the combined action of repression and attenuation. Repression regulates transcription initiation in response to variation in the intracellular concentration of tryptophan. Attenuation regulates transcription termination at a site in the leader region of the operon in response to changes in the extent of charging of tRNATrp. We measured repression independently of attenuation to ascertai...

  5. The tryptophan pathway genes of the Sargasso Sea metagenome: new operon structures and the prevalence of non-operon organization

    Kagan, Juliana; Sharon, Itai; Beja, Oded; Kuhn, Jonathan C

    2008-01-01

    Background The enormous database of microbial DNA generated from the Sargasso Sea metagenome provides a unique opportunity to locate genes participating in different biosynthetic pathways and to attempt to understand the relationship and evolution of those genes. In this article, an analysis of the Sargasso Sea metagenome is made with respect to the seven genes of the tryptophan pathway. Results At least 5% of all the genes that are related to amino acid biosynthesis are tryptophan (trp) gene...

  6. Membrane Organization and Dynamics of ‘Inner Pair’ and ‘Outer Pair’ Tryptophan Residues in Gramicidin Channels

    Haldar, Sourav; Chaudhuri, Arunima; Gu, Hong; Koeppe, Roger E.; Kombrabail, Mamata; Krishnamoorthy, G.; Chattopadhyay, Amitabha

    2012-01-01

    The linear ion channel peptide gramicidin serves as an excellent prototype for monitoring the organization, dynamics and function of membrane-spanning channels. The tryptophan residues in gramicidin channels are crucial for establishing and maintaining the structure and function of the channel in the membrane bilayer. In order to address the basis of differential importance of tryptophan residues in gramicidin channel, we monitored the effects of pairwise substitution of two of the four grami...

  7. Tryptophan Oxidative Metabolism Catalyzed by Geobacillus Stearothermophilus: A Thermophile Isolated from Kuwait Soil Contaminated with Petroleum Hydrocarbons

    Al-Hassan, Jassim M.; Samira Al-Awadi; Sosamma Oommen; Abdulaziz Alkhamis; Mohammad Afzal

    2011-01-01

    Tryptophan metabolism has been extensively studied in humans as well as in soil. Its metabolism takes place mainly through kynurenine pathway yielding hydroxylated, deaminated and many other products of physiological significance. However, tryptophan metabolism has not been studied in an isolated thermophilic bacterium. Geobacillus stearothermophilus is a local thermophile isolated from Kuwait desert soil contaminated with petroleum hydrocarbons. The bacterium grows well at 65 °C in 0.05 M ph...

  8. Tryptophanase-Catalyzed l-Tryptophan Synthesis from d-Serine in the Presence of Diammonium Hydrogen Phosphate

    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. 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

    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 [15N-indole]-labeled tryptophan isomers and incorporation of that label into free indole-3-acetic acid (IAA). Both lines required levels of L-[15N]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-[15N]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. Inhibiting the photosensitized oxidation of anthracene and tryptophan by means of natural antioxidants

    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

  11. Enhanced solid-state electron transport via tryptophan containing peptide networks.

    Amdursky, Nadav

    2013-08-28

    The electrical conductivity via peptide networks was measured using conductive probe atomic force microscopy, where the tryptophan-containing peptide network (composed of Phe-Trp dipeptides) exhibited a superior (5 fold) conductivity in comparison to an all phenylalanine network (composed of Phe-Phe dipeptides). These results are in line with previous spectroscopic measurements exploring intramolecular electron transfer in proteins. Bias-scaling factors (instead of the more commonly used transition voltage spectroscopy method) were calculated for the two peptide networks. These calculations showed substantial differences between the two peptide networks, suggesting different electron transport characteristics. While the factor for the tryptophan-containing network is similar to conjugated molecules with a low electron-tunneling barrier, the one for the all phenylalanine network can be ascribed as an 'intermediate' factor between conjugated and saturated molecules. PMID:23832315

  12. Isolation and Identification of an Antiproliferative Compound from Fructose-Tryptophan Maillard Reaction Products.

    Lee, Sang Hoon; Jeong, Su Jeong; Jang, Gwi Yeong; Kim, Min Young; Hwang, In Guk; Kim, Hyun Young; Woo, Koan Sik; Hwang, Bang Yeon; Song, Jin; Lee, Junsoo; Jeong, Heon Sang

    2016-04-20

    This study was performed to isolate and identify a compound with antiproliferative activity against human stomach cancer cell lines, from fructose-tryptophan Maillard reaction products (MRPs). The MRPs, prepared from a fructose-tryptophan solution heated at 130 °C for 2 h, were fractionated into five solvent fractions: n-hexane, chloroform, ethyl acetate, butanol, and water. The highest antiproliferative activity was found in the chloroform fraction (85.93% at 200 μg/mL), and the active compound from this chloroform fraction was purified by silica gel column chromatography, TLC, and preparative HPLC. The antiproliferative activity (IC50) of the active compound was 42.24 μg/mL, and the active compound was identified as perlolyrine (C16H10N2O2) by (1)H/(13)C NMR, DEPT, HMBC, and LC-ESI-MS. Therefore, this research may be useful in developing perlolyrine as a functional therapeutic agent. PMID:27041128

  13. Enhanced chemiluminescence CdSe quantum dots by histidine and tryptophan

    Hosseini, Morteza; Ganjali, Mohammad Reza; Jarrahi, Afsaneh; Vaezi, Zahra; Mizani, Farhang; Faridbod, Farnoush

    2014-11-01

    The enhancing effect of histidine and tryptophan on chemiluminescence (CL) of CdSe quantum dots (QDs)-H2O2 system was studied. This reaction is based on the catalytic effect of amino acids, causing a significant increase in the light emission, as a result of the reaction of quantum dots (QDs) with hydrogen peroxide. In the optimum conditions, this method was satisfactorily described by linear calibration curve in the range of 0.66-35.5 μM and 0.83-35.1 μM for histidine and tryptophan, respectively. The effect of various parameters such as concentration of CdSe QDs, concentration of H2O2 and concentration of imidazole on the intensity of CL system were studied. The main experimental advantage of the proposed method is it's selective to two amino acids compared with other amino acids.

  14. Optimal performance of the tryptophan operon of E. coli: a stochastic, dynamical, mathematical-modeling approach.

    Salazar-Cavazos, Emanuel; Santillán, Moisés

    2014-02-01

    In this work, we develop a detailed, stochastic, dynamical model for the tryptophan operon of E. coli, and estimate all of the model parameters from reported experimental data. We further employ the model to study the system performance, considering the amount of biochemical noise in the trp level, the system rise time after a nutritional shift, and the amount of repressor molecules necessary to maintain an adequate level of repression, as indicators of the system performance regime. We demonstrate that the level of cooperativity between repressor molecules bound to the first two operators in the trp promoter affects all of the above enlisted performance characteristics. Moreover, the cooperativity level found in the wild-type bacterial strain optimizes a cost-benefit function involving low biochemical noise in the tryptophan level, short rise time after a nutritional shift, and low number of regulatory molecules. PMID:24307084

  15. Molecular basis for the ribosome functioning as an L-tryptophan sensor.

    Bischoff, Lukas; Berninghausen, Otto; Beckmann, Roland

    2014-10-23

    Elevated levels of the free amino acid L-tryptophan (L-Trp) trigger expression of the tryptophanase tnaCAB operon in E. coli. Activation depends on tryptophan-dependent ribosomal stalling during translation of the upstream TnaC peptide. Here, we present a cryoelectron microscopy (cryo-EM) reconstruction at 3.8 Å resolution of a ribosome stalled by the TnaC peptide. Unexpectedly, we observe two L-Trp molecules in the ribosomal exit tunnel coordinated within composite hydrophobic pockets formed by the nascent TnaC peptide and the tunnel wall. As a result, the peptidyl transferase center (PTC) adopts a distinct conformation that precludes productive accommodation of release factor 2 (RF2), thereby inducing translational stalling. Collectively, our results demonstrate how the translating ribosome can act as a small molecule sensor for gene regulation. PMID:25310980

  16. Molecular Basis for the Ribosome Functioning as an L-Tryptophan Sensor

    Lukas Bischoff

    2014-10-01

    Full Text Available Elevated levels of the free amino acid L-tryptophan (L-Trp trigger expression of the tryptophanase tnaCAB operon in E. coli. Activation depends on tryptophan-dependent ribosomal stalling during translation of the upstream TnaC peptide. Here, we present a cryoelectron microscopy (cryo-EM reconstruction at 3.8 Å resolution of a ribosome stalled by the TnaC peptide. Unexpectedly, we observe two L-Trp molecules in the ribosomal exit tunnel coordinated within composite hydrophobic pockets formed by the nascent TnaC peptide and the tunnel wall. As a result, the peptidyl transferase center (PTC adopts a distinct conformation that precludes productive accommodation of release factor 2 (RF2, thereby inducing translational stalling. Collectively, our results demonstrate how the translating ribosome can act as a small molecule sensor for gene regulation.

  17. Tandem transcription and translation regulatory sensing of uncharged tryptophan tRNA.

    Chen, Guangnan; Yanofsky, Charles

    2003-07-11

    The Bacillus subtilis AT (anti-TRAP) protein inhibits the regulatory protein TRAP (trp RNA-binding attenuation protein), thereby eliminating transcription termination in the leader region of the trp operon. Transcription of the AT operon is activated by uncharged tryptophan transfer RNA (tRNATrp). Here we show that translation of AT also is regulated by uncharged tRNATrp. A 10-residue coding region containing three consecutive tryptophan codons is located immediately preceding the AT structural gene. Completion of translation of this coding region inhibits AT synthesis, whereas incomplete translation increases AT production. Tandem sensing of uncharged tRNATrp therefore regulates synthesis of AT, which in turn regulates TRAP's ability to inhibit trp operon expression. PMID:12855807

  18. Molecular analysis of intragenic recombination at the tryptophan synthetase locus in Neurospora crassa

    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.

  19. Semi-automated Synthesis of 1-[18F]fluoroethyl-L-tryptophan

    A novel [18F]fluoro amnio acid analogue 1-[18F]fluoroethyl-L-tryptophan (1-[18F]FETrp) was designed and synthesized. The cold standard 1-[19F]FETrp was synthesized by seven-step reactions, starting from tryptophan. Then fluoro-multifunctional chemistry process control unit (CPCU) was used to synthesize 1-[19F]FETrp by nucleophilic fluorination. 1-[18F]FETrp was synthesized in a two-step semi-automated procedure. The no decay corrected radiochemical yield of 1-[18F]FETrp was 1.5% within 50 min total reaction time. Further experimental work is needed to improve the radiochemical yield, with the hope of attaining a satisfacting new PET imaging agent for differentiating the tumors and inflammation. (authors)

  20. A Structure-Guided Switch in the Regioselectivity of a Tryptophan Halogenase.

    Shepherd, Sarah A; Menon, Binuraj R K; Fisk, Heidi; Struck, Anna-Winona; Levy, Colin; Leys, David; Micklefield, Jason

    2016-05-01

    Flavin-dependent halogenases are potentially useful biocatalysts for the regioselective halogenation of aromatic compounds. Haloaromatic compounds can be utilised in the synthesis and biosynthesis of pharmaceuticals and other valuable products. Here we report the first X-ray crystal structure of a tryptophan 6-halogenase (SttH), which enabled key residues that contribute to the regioselectivity in tryptophan halogenases to be identified. Structure-guided mutagenesis resulted in a triple mutant (L460F/P461E/P462T) that exhibited a complete switch in regioselectivity; with the substrate 3-indolepropionate 75 % 5-chlorination was observed with the mutant in comparison to 90 % 6-chlorination for the wild-type SttH. This is the first clear example of how regiocomplementary halogenases can be created from a single parent enzyme. The biocatalytic repertoire of SttH was also expanded to include a range of indolic and non-indolic substrates. PMID:26840773

  1. Fluorescence quenching interactions of L(-)-tryptophan in dimethyl sulfoxide with trivalent lanthanides

    Excited singlet-triplet crossing of tryptophan in dimethyl sulfoxide is enhanced in the presence of trivalent lanthanide ions, leading to fluorescence quenching and subsequent initial phosphorescence enhancement. The induced system crossing rate constant ksub(isc)sup(ind) ranges from 1.9 x 107 to 1.5 x 108 s-1 at room temperature for the seven lanthanide ions used. A gradual fluorescence quenching accompanies the initial induced system crossing with rate constant ksub(Q)sup(S) ranging from 3 x 108 to 1.4 x 1010 M-1s-1. The value of ksub(Q)sup(S) is proportional to the spectral overlap between the fluorescence of tryptophan and the absorption of the lanthanides. Values of ksub(isc)sup(ind) and ksub(Q)sup(S) are correlated with several parameters of the lanthanides employed. (Auth.)

  2. L-Tryptophan on Cu(111): engineering a molecular labyrinth driven by indole groups

    Yitamben, E. N.; Clayborne, A.; Darling, Seth B.; Guisinger, N. P.

    2015-06-01

    The present article investigates the adsorption and molecular orientation of L-Tryptophan, which is both an essential amino acid important for protein synthesis and of particular interest for the development of chiral molecular electronics and biocompatible processes and devices, on Cu(111) using scanning tunneling microscopy and spectroscopy at 55 K and at room temperature. The arrangement of chemisorbed L-Tryptophan on the copper surface varies with both temperature and surface coverage. At low coverage, small clusters form on the surface irrespective of temperature, while at high coverage an ordered chain structure emerges at room temperature, and a tightly packed structure forms a molecular labyrinth at low temperature. The dominating superstructure of the adsorbates arises from intermolecular hydrogen bonding, and π-bonding interactions between the indole groups of neighboring molecules and the Cu surface.

  3. Depletion sensitivity predicts unhealthy snack purchases.

    Salmon, Stefanie J; Adriaanse, Marieke A; 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 weight on snack purchase behavior were explored. Participants included in the study were instructed to report every snack they bought over the course of one week. The dependent variables were the number of healthy and unhealthy snacks purchased. The results of the present study demonstrate that depletion sensitivity predicts the amount of unhealthy (but not healthy) snacks bought. The more sensitive people are to depletion, the more unhealthy snacks they buy. Moreover, there was some tentative evidence that this relation is more pronounced for people with a weak as opposed to a strong goal to lose weight, suggesting that a strong goal to lose weight may function as a motivational buffer against self-control failures. All in all, these findings provide evidence for the external validity of depletion sensitivity and the relevance of this construct in the domain of eating behavior. PMID:26321417

  4. The New MCNP6 Depletion Capability

    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.

  5. Tryptophan regulates thaxtomin A and indole-3-acetic acid production in Streptomyces scabiei and modifies its interactions with radish seedlings.

    Legault, Geneviève S; Lerat, Sylvain; Nicolas, Philippe; Beaulieu, Carole

    2011-09-01

    The virulence of Streptomyces scabiei, the causal agent of common scab, depends mainly on the production of the toxin thaxtomin A. S. scabiei also produces indole-3-acetic acid (IAA) but the role of this hormone in the interaction between pathogenic streptomycetes and plants has not yet been elucidated. Tryptophan is a biosynthetic precursor of both IAA and thaxtomin A. In this study, the effect of tryptophan on thaxtomin A and IAA production as well as its effect on the transcription of the corresponding biosynthetic genes in S. scabiei has been analyzed. In vitro IAA production depended on the availability of tryptophan. However, addition of this amino acid to the culture medium inhibited the biosynthesis of thaxtomin A. Expression of thaxtomin A biosynthetic genes nos and txtA were strongly repressed in the presence of tryptophan; however, modulation of the expression was not observed for the IAA biosynthetic genes iaaM and iaaH. The effects of an exogenous tryptophan supply on S. scabiei virulence were assessed on radish seedlings. Addition of tryptophan reduced symptoms on inoculated radish roots compared with seedlings grown in the absence of the bacterium, by way of inhibition of thaxtomin A production and increase of IAA biosynthesis. PMID:21521002

  6. The structure of flavin-dependent tryptophan 7-halogenase RebH

    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.

  7. In situ tryptophan-like fluorometers: assessing turbidity and temperature effects for freshwater applications

    Khamis, K.; Sorensen, J. P. R.; Bradley, C.; D. M. Hannah; Lapworth, D.J.; Stevens, R.

    2015-01-01

    Tryptophan-like fluorescence (TLF) is an indicator of human influence on water quality as TLF peaks are associated with the input of labile organic carbon (e.g. sewage or farm waste) and its microbial breakdown. Hence, real-time measurement of TLF could be particularly useful for monitoring water quality at a higher temporal resolution than available hitherto. However, current understanding of TLF quenching/interference is limited for field deployable sensors. We present results from a rigoro...

  8. Rule-based modeling of transcriptional attenuation at the tryptophan operon

    Kuttler, Céline; Lhoussaine, Cédric; Nebut, Mirabelle

    2010-01-01

    International audience Transcriptional attenuation at E.coli's tryptophan operon is a prime example of RNA-mediated gene regulation. In this paper, we present a discrete stochastic model of the fine-grained control of attenuation, based on chemical reactions. Stochastic simulation of our model confirms results that were previously obtained by master or differential equations. Our approach is easier to understand than master equations, although mathematically well founded. It is compact due...

  9. Disturbances of Tryptophan Metabolism and Risk of Depression in HCV Patients Treated with IFN-Alpha

    Oxenkrug, GF; Turski, WA; Zgrajka, W; Weinstock, JV; Ruthazer, R.; P. Summergrad

    2014-01-01

    Depression is a common side-effect of interferon (IFN)-alpha treatment of hepatitis C virus (HCV) infection and melanoma. Disturbances of tryptophan (TRP) metabolism might contribute to development of IFN-alpha–associated depression due to IFN-alpha-induced activation of indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme of TRP–kynurenine (KYN) metabolism. The increased frequency of high producer (T) allele of IFN-gamma (IFNG) (+874) gene, that encodes IFNG production, in depressed pat...

  10. Placental tryptophan metabolism as a potential novel pathway for the developmental origins of mental diseases

    Goeden, Nick; Velasquez, Juan C.; Bonnin, Alexandre

    2013-01-01

    Dysfunction of brain serotonin (5-HT) signaling contributes to the pathophysiology of several psychiatric disorders. However, before 5-HT acts as a neurotransmitter/neuromodulator in the adult brain, increasing evidence suggests that it plays crucial roles in the modulation of essential neurodevelopmental processes. It was recently demonstrated that the placenta synthesizes 5-HT from maternally derived tryptophan during pregnancy. Therefore, genetic and environmental perturbations that affect...

  11. Dynamic Allostery Mediated by a Conserved Tryptophan in the Tec Family Kinases.

    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.

  12. Probing alkali metal–π interactions with the side chain residue of tryptophan

    Hu, Jiaxin; Barbour, Leonard J.; Gokel, George W.

    2002-01-01

    Feeble forces play a significant role in the organization of proteins. These include hydrogen bonding, hydrophobic interactions, salt bridge formation, and steric interactions. The alkali metal cation-π interaction is a force of potentially profound importance but its consideration in biology has been limited by the lack of experimental evidence. Our previous studies of cation–π interactions with Na+ and K+ involved the side arms of tryptophan (indole), tyrosine (phenol),...

  13. Tryptophan PET Imaging of the Kynurenine Pathway in Patient-Derived Xenograft Models of Glioblastoma

    Guastella, Anthony R.; Michelhaugh, Sharon K; Klinger, Neil V.; Kupsky, William J.; Polin, Lisa A.; Muzik, Otto; Juhász, Csaba; Mittal, Sandeep

    2016-01-01

    Increasing evidence demonstrates the immunosuppressive kynurenine pathway’s (KP) role in the pathophysiology of human gliomas. To study the KP in vivo, we used the noninvasive molecular imaging tracer α-[11C]-methyl-l-tryptophan (AMT). The AMT-positron emission tomography (PET) has shown high uptake in high-grade gliomas and predicted survival in patients with recurrent glioblastoma (GBM). We generated patient-derived xenograft (PDX) models from dissociated cells, or tumor fragments, from 5 p...

  14. Molecular dynamics of microbial lipases as determined from their intrinsic tryptophan fluorescence.

    Graupner, M.; Haalck, L; Spener, F.; Lindner, H.; Glatter, O.; Paltauf, F; Hermetter, A

    1999-01-01

    We have studied the intrinsic tryptophan fluorescence of the lipases from Chromobacterium viscosum (CVL), Pseudomonas species (PSL), and Rhizopus oryzae (ROL) in aqueous buffer, zwitterionic detergent micelles, and isopropanol-water mixtures. It was the purpose of this study to obtain information about biophysical properties of the respective enzymes under conditions that modulate enzyme activities and stereoselectivities to a significant extent. According to their decay-associated emission s...

  15. Serum Levels of Tryptophan, 5-Hydroxytryptophan and Serotonin in Patients Affected with Different Forms of Amenorrhea

    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.

  16. Insulin resistance and dysregulation of tryptophan – kynurenine and kynurenine – nicotinamide adenine dinucleotide metabolic pathways

    Oxenkrug, Gregory

    2013-01-01

    Insulin resistance (IR) underlines aging and aging-associated medical (diabetes, obesity, dyslipidemia, hypertension) and psychiatric (depression, cognitive decline) disorders (AAMPD). Molecular mechanisms of IR in genetically or metabolically predisposed individuals remain uncertain. Current review of literature and our data presents the evidences that dysregulation of tryptophan (TRP) – kynurenine (KYN) and KYN – nicotinamide adenine dinucleotide (NAD) metabolic pathways is one of the mecha...

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

    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 i...

  18. L-Tryptophan Production by Auxotrophic and Analogue Resistant Mutants of Aureobacterium flavescens

    Roy, A; S.K. Mukhopadhyay

    2011-01-01

    A number of tyrosine plus phenylalanine double auxotrophic mutants were isolated by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) treatment of a locally isolated strain of Aureobacterium flavescens of which 11A39 and 11A17 were selected on the basis of their tryptophan production in a mineral salt medium over other isolated mutant strains. The mutational block in the aromatic amino acid biosynthetic pathway of the selected double auxotrophs were determined. By controlling pH of the production me...

  19. The Potential Role of Cannabinoids in Modulating Serotonergic Signaling by Their Influence on Tryptophan Metabolism

    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.

  20. Characterization of the putative tryptophan synthase β-subunit from Mycobacterium tuberculosis

    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.

  1. Perturbations of tyrosine metabolism promote the indolepyruvate pathway via tryptophan in host and microbiome.

    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. PMID:25680927

  2. A synergistic effect between cholesterol and tryptophan-flanked transmembrane helices modulates membrane curvature.

    van Duyl, Bianca Y; Meeldijk, Hans; Verkleij, Arie J; Rijkers, Dirk T S; Chupin, Vladimir; de Kruijff, Ben; Killian, J Antoinette

    2005-03-22

    The aim of this study was to gain insight into the structural consequences of hydrophobic mismatch for membrane proteins in lipid bilayers that contain cholesterol. For this purpose, tryptophan-flanked peptides, designed to mimic transmembrane segments of membrane proteins, were incorporated in model membranes of unsaturated phosphatidylcholine bilayers of varying thickness and containing varying amounts of cholesterol. Analysis of the lipid organization by (31)P NMR and cryo-TEM demonstrated the formation of an isotropic phase, most likely representing a cubic phase, which occurred exclusively in mixtures containing lipids with relatively long acyl chains. Formation of this phase was inhibited by incorporation of lysophosphatidylcholine. These results indicate that the isotropic phase is formed as a consequence of negative hydrophobic mismatch and that its formation is related to a negative membrane curvature. When either peptide or cholesterol was omitted from the mixture, isotropic-phase formation did not occur, not even when the concentrations of these compounds were significantly increased. This suggests that formation of the isotropic phase is the result of a synergistic effect between the peptides and cholesterol. Interestingly, isotropic-phase formation was not observed when the tryptophans in the peptide were replaced by either lysines or histidines. We propose a model for the mechanism of this synergistic effect, in which its dependence on the flanking residues is explained by preferential interactions between cholesterol and tryptophan residues. PMID:15766283

  3. Tryptophan PET Imaging of the Kynurenine Pathway in Patient-Derived Xenograft Models of Glioblastoma.

    Guastella, Anthony R; Michelhaugh, Sharon K; Klinger, Neil V; Kupsky, William J; Polin, Lisa A; Muzik, Otto; Juhász, Csaba; Mittal, Sandeep

    2016-01-01

    Increasing evidence demonstrates the immunosuppressive kynurenine pathway's (KP) role in the pathophysiology of human gliomas. To study the KP in vivo, we used the noninvasive molecular imaging tracer α-[(11)C]-methyl-l-tryptophan (AMT). The AMT-positron emission tomography (PET) has shown high uptake in high-grade gliomas and predicted survival in patients with recurrent glioblastoma (GBM). We generated patient-derived xenograft (PDX) models from dissociated cells, or tumor fragments, from 5 patients with GBM. Mice bearing subcutaneous tumors were imaged with AMT-PET, and tumors were analyzed to detect the KP enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, tryptophan 2,3-dioxygenase, kynureninase, and kynurenine 3-monooxygenase. Overall, PET imaging showed robust tumoral AMT uptake in PDX mice with prolonged tracer accumulation over 60 minutes, consistent with AMT trapping seen in humans. Immunostained tumor tissues demonstrated positive detection of multiple KP enzymes. Furthermore, intracranial implantation of GBM cells was performed with imaging at both 9 and 14 days postimplant, with a marked increase in AMT uptake at 14 days and a corresponding high level of tissue immunostaining for KP enzymes. These results indicate that our PDX mouse models recapitulate human GBM, including aberrant tryptophan metabolism, and offer an in vivo system for development of targeted therapeutics for patients with GBM. PMID:27151136

  4. One-electron oxidation of iron(II) complexes of tryptophan and histidine

    Iron(II) complexes of tryptophan and histidine, as models of some metallo-enzymes, have been oxidised by Br2sup(.-) in the pH range 7-11. For the tryptophan complex, the rate of oxidation is controlled by the ligand through the formation of metal-complexed TrpHsup(.+). This species may either undergo intramolecular transfer at rates > 1.7 x 106 s-1 resulting in oxidation of Fesup(II), or may deprotonate at a rate dependent of pH to yield the Fesup(II)-complexed Trpsup(.). The bimolecular rate constants for oxidation of Fesup(II)(aq) and Fesup(II)/tryptophan complexes by both uncomplexed TrpHsup(.+) and Trpsup(.) have also been determined. For histidine complexes, the Fesup(II)-imidazole centre was found to be more reactive than either histidine or Fesup(II)(aq) to Br2sup(.-). Again, oxidation of Fesup(II) is believed to be the likely outcome of the reaction. (author)

  5. Candida glabrata tryptophan-based pigment production via the Ehrlich pathway.

    Brunke, Sascha; Seider, Katja; Almeida, Ricardo Sergio; Heyken, Antje; Fleck, Christian Benjamin; Brock, Matthias; Barz, Dagmar; Rupp, Steffen; Hube, Bernhard

    2010-04-01

    Pigments contribute to the pathogenicity of many fungi, mainly by protecting fungal cells from host defence activities. Here, we have dissected the biosynthetic pathway of a tryptophan-derived pigment of the human pathogen Candida glabrata, identified key genes involved in pigment production and have begun to elucidate the possible biological function of the pigment. Using transcriptional analyses and a transposon insertion library, we have identified genes associated with pigment production. Targeted deletion mutants revealed that the pigment is a by-product of the Ehrlich pathway of tryptophan degradation: a mutant lacking a tryptophan-upregulated aromatic aminotransferase (Aro8) displayed significantly reduced pigmentation and a recombinantly expressed version of this protein was sufficient for pigment production in vitro. Pigment production is tightly regulated as the synthesis is affected by the presence of alternative nitrogen sources, carbon sources, cyclic AMP and oxygen. Growth of C. glabrata on pigment inducing medium leads to an increased resistance to hydrogen peroxide, an effect which was not observed with a mutant defective in pigmentation. Furthermore, pigmented yeast cells had a higher survival rate when exposed to human neutrophils and caused increased damage in a monolayer model of human epithelia, indicating a possible role of pigmentation during interactions with host cells. PMID:20199593

  6. Tryptophan PET Imaging of the Kynurenine Pathway in Patient-Derived Xenograft Models of Glioblastoma

    Guastella, Anthony R.; Michelhaugh, Sharon K.; Klinger, Neil V.; Kupsky, William J.; Polin, Lisa A.; Muzik, Otto; Juhász, Csaba; Mittal, Sandeep

    2016-01-01

    Increasing evidence demonstrates the immunosuppressive kynurenine pathway’s (KP) role in the pathophysiology of human gliomas. To study the KP in vivo, we used the noninvasive molecular imaging tracer α-[11C]-methyl-l-tryptophan (AMT). The AMT-positron emission tomography (PET) has shown high uptake in high-grade gliomas and predicted survival in patients with recurrent glioblastoma (GBM). We generated patient-derived xenograft (PDX) models from dissociated cells, or tumor fragments, from 5 patients with GBM. Mice bearing subcutaneous tumors were imaged with AMT-PET, and tumors were analyzed to detect the KP enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, tryptophan 2,3-dioxygenase, kynureninase, and kynurenine 3-monooxygenase. Overall, PET imaging showed robust tumoral AMT uptake in PDX mice with prolonged tracer accumulation over 60 minutes, consistent with AMT trapping seen in humans. Immunostained tumor tissues demonstrated positive detection of multiple KP enzymes. Furthermore, intracranial implantation of GBM cells was performed with imaging at both 9 and 14 days postimplant, with a marked increase in AMT uptake at 14 days and a corresponding high level of tissue immunostaining for KP enzymes. These results indicate that our PDX mouse models recapitulate human GBM, including aberrant tryptophan metabolism, and offer an in vivo system for development of targeted therapeutics for patients with GBM. PMID:27151136

  7. Ultrafast quenching of tryptophan fluorescence in proteins: Interresidue and intrahelical electron transfer

    Quenching of tryptophan fluorescence in proteins has been critical to the understanding of protein dynamics and enzyme reactions using tryptophan as a molecular optical probe. We report here our systematic examinations of potential quenching residues with more than 40 proteins. With site-directed mutation, we placed tryptophan to desired positions or altered its neighboring residues to screen quenching groups among 20 amino acid residues and of peptide backbones. With femtosecond resolution, we observed the ultrafast quenching dynamics within 100 ps and identified two ultrafast quenching groups, the carbonyl- and sulfur-containing residues. The former is glutamine and glutamate residues and the later is disulfide bond and cysteine residue. The quenching by the peptide-bond carbonyl group as well as other potential residues mostly occurs in longer than 100 ps. These ultrafast quenching dynamics occur at van der Waals distances through intraprotein electron transfer with high directionality. Following optimal molecular orbital overlap, electron jumps from the benzene ring of the indole moiety in a vertical orientation to the LUMO of acceptor quenching residues. Molecular dynamics simulations were invoked to elucidate various correlations of quenching dynamics with separation distances, relative orientations, local fluctuations and reaction heterogeneity. These unique ultrafast quenching pairs, as recently found to extensively occur in high-resolution protein structures, may have significant biological implications

  8. Asymmetric radiosynthesis of α-[11C]methyl-l-tryptophan for PET studies

    Asymmetric radiosynthesis of α-[11C]methyl-l-tryptophan has been achieved using the enantioselective [11C]methylation of the enolate of either 8-(phenylsulfonyl) or 8-acetyl substituted derivatives of dimethyl (2S.3aR, 8aS)-(+)-hexahydropyrrolo[2,3-b]indole-1,2-dicarboxylate. Reaction of the enolates generated by treatment with LDA at -78 deg. C, with [11C]methyl iodide at -78 deg. C gave in 5 min incorporation of the radiolabel of 86% for 8-phenylsulfonyl derivative and 63% for 8-acetyl derivative. The hexahydropyrrolo[2,3-b]indoles were then decyclized to the fully protected α-[11]methyl-l-tryptophan by treatment with trifluoroacetic acid. Removal of all the protecting groups, including the phenylsulfonyl, was achieved by reaction with 10 N NaOH at 210 deg. C in a sealed vial. Neutralization of the alkali with 10 N H2SO4 followed by purification by HPLC gave α-[11C]methyl-l-tryptophan with an overall radiochemical yield of 20% (uncorrected for decay) relative to the amounts of [11C]CH3I from 8-phenylsulfonyl derivative, and 9% (relative to [11C]CH3I; uncorrected for decay) from 8-acetyl derivative in a preparation time of 40 min after [11C]methyl iodide was introduced into the reaction mixture

  9. Acid-induced change in ozone-reactive site in indole ring of tryptophan

    It is well established that ozone as well as oxygen activated by tryptophan 2,3-dioxygenase or indoleamine 2,3-dioxygenase cleave the 2,3-C=C bond of the indole ring of tryptophan to produce N-formylkynurenine. In the present study, however, we found that exposure of tryptophan to aqueous ozone at and below pH 4.5 generated a different compound. The compound was identified as kynurenine by high performance liquid chromatography and mass spectrometry. Exposure of N-formylkynurenine to acidic ozone did not generate a significant amount of kynurenine, indicating that the kynurenine was not produced via N-formylkynurenine. Acidic ozone thus appears to cleave the 1, 2-N-C bond in place of the 2,3-C=C bond of the indole ring, followed by liberation of the 2-C atom. The 1,2-N-C bond and 2,3-C=C bond are likely to undergo changes in their nature of bonding on acidification, enabling ozone to react with the former bond but not with the latter bond.

  10. The modality effect of ego depletion: Auditory task modality reduces ego depletion.

    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. PMID:27241617

  11. Depletion of the nuclear Fermi sea

    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.

  12. Molten-Salt Depleted-Uranium Reactor

    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...

  13. Depleted uranium and the Gulf War syndrome

    Some military personnel involved in the 1991Gulf War have complained of continuing stress-like symptoms for which no obvious cause has been found. These symptoms have at times been attributed to the use of depleted uranium (DU) in shell casings which are believed to have caused toxic effects. Depleted uranium is natural uranium which is depleted in the rarer U-235 isotope. It is a heavy metal and in common with other heavy metals is chemically toxic. It is also slightly radioactive and could give rise to a radiological hazard if dispersed in finely divided form so that it was inhaled. In response to concerns, the possible effects of DU have been extensively studied along with other possible contributors to Gulf War sickness. This article looks at the results of some of the research that has been done on DU. (author)

  14. Ozone depletion and chlorine loading potentials

    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.

  15. Depleted uranium speciation in the Bratoselce soil

    During the air strikes in 1999, about thirteen hundred projectiles with depleted uranium were fired into the Bratoselce, South Serbia. A study providing insight into physical chemical behaviour of depleted uranium originated from dissolved 'material' of projectile penetrators in the contaminated soil have been conducted. Samples were treated according to Tarriers modified procedure of five-step sequential extraction. Suitable choice of solvents for sequential extraction simulated the real conditions in the environment. Fractions are further analysed by alpha spectrometry and atomic absorption spectrometry methods to determine the uranium isotopes and trace or major elements. The results indicated potential substrates for depleted uranium compounds in the investigated environment, with specific soil composition that is essential for prediction of its mobility and bioavailability in certain conditions. (author)

  16. Department of Energy depleted uranium recycle

    With its strategic supply of depleted uranium, the Department of Energy is studying reuse of the material in nuclear radiation shields, military hardware, and commercial applications. the study is expected to warrant a more detailed uranium recycle plan which would include consideration of a demonstration program and a program implementation decision. Such a program, if implemented, would become the largest nuclear material recycle program in the history of the Department of Energy. The bulk of the current inventory of depleted uranium is stored in 14-ton cylinders in the form of solid uranium hexafluoride (UF6). The radioactive 235U content has been reduced to a concentration of 0.2% to 0.4%. Present estimates indicate there are about 55,000 UF6-filled cylinders in inventory and planned operations will provide another 2,500 cylinders of depleted uranium each year. The United States government, under the auspices of the Department of Energy, considers the depleted uranium a highly-refined strategic resource of significant value. A possible utilization of a large portion of the depleted uranium inventory is as radiation shielding for spent reactor fuels and high-level radioactive waste. To this end, the Department of Energy study to-date has included a preliminary technical review to ascertain DOE chemical forms useful for commercial products. The presentation summarized the information including preliminary cost estimates. The status of commercial uranium processing is discussed. With a shrinking market, the number of chemical conversion and fabrication plants is reduced; however, the commercial capability does exist for chemical conversion of the UF6 to the metal form and for the fabrication of uranium radiation shields and other uranium products. Department of Energy facilities no longer possess a capability for depleted uranium chemical conversion

  17. Gammaspectrometric determination of depleted uranium in soil

    Full text: Three years of monitoring the content of natural radionuclides as well as radionuclides of artificial origin in all samples in the south part of the Republic of Serbia and Montenegro indicated that there was widespread, low-level contamination by depleted uranium at this region. High activity of depleted uranium was found in the soil samples taken at the points where the penetrators were found. We used high resolution gamma spectrometry measurements, because of their simplicity and accuracy. Aims of the control were to asses the increase of radioactivity above the natural levels in the immediate and near vicinity of the bomb craters, to asses the corresponding effect of changed natural radioactivity on the health of the population living in these places and finding unexploded depleted uranium bullets. The collected soil samples were cleaned of plants and stones, dried at 105 deg. C - 110 deg. C till constant weight for 24-48 h. After this, the samples were ground, sieved, and measure in cylindrical geometry. Gamma activity was determined by gamma spectrometry measurements using HP Ge detector (ORTEC), with relative efficiency of 25% and energy resolution of 1.85 keV (1332.5 keV 60Co). The analyser system conducts a peak search, energy assignment, quantification and nuclide identification in acquired spectra. Time of measurement varied from 60000 s to 250000 s. Depleted uranium was found in the soil samples from Vranje region and cape Arza (Montenegro). There are four fenced areas in Vranje region (Pljackovica, Bratoselce, Borovac and Reljan) and one in the Montenegro (cape Arza) where we have found depleted uranium penetrators. The 238U and 235U specific activities and their isotopic composition correspond to depleted uranium (238U/235U ratio from 35 to 77). (author)

  18. The Chemistry and Toxicology of Depleted Uranium

    Katz, Sidney A.

    2014-01-01

    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....

  19. Toxicological issues after depleted uranium weapons attacked

    Depleted Uranium (DU) is a byproduct of the uranium enrichment for producing nuclear reactor or nuclear weapon. DU is used in the military as an armor-piercing projectile due to its hardness, strength, and density. A lot of DU weapons were fired in the Gulf War, and bring about critical environmental and internal contamination. Therefore, DU becomes suddenly a hot issue. Some toxicological problems after DU weapons attacked have been reviewed, which include features of internal DU contamination. Hazard of wound contamination and inhalation with insoluble uranium, and other urgent toxicological issues. The healthy effects of implanted with depleted uranium pellets were illustrated in particular

  20. Acute pancreatitis

    ... page: //medlineplus.gov/ency/article/000287.htm Acute pancreatitis To use the sharing features on this page, ... fatty foods after the attack has improved. Outlook (Prognosis) Most cases go away in a week. However, ...

  1. Acute Pericarditis

    ... Sugar Control Helps Fight Diabetic Eye Disease Are 'Workaholics' Prone to OCD, Anxiety? ALL NEWS > Resources First ... cancer, or heart surgery, the fluid is blood. Causes Acute pericarditis usually results from infection or other ...

  2. Effects of B Cell Depletion on Early Mycobacterium tuberculosis Infection in Cynomolgus Macaques.

    Phuah, Jiayao; Wong, Eileen A; Gideon, Hannah P; Maiello, Pauline; Coleman, M Teresa; Hendricks, Matthew R; Ruden, Rachel; Cirrincione, Lauren R; Chan, John; Lin, Philana Ling; Flynn, JoAnne L

    2016-05-01

    Although recent studies in mice have shown that components of B cell and humoral immunity can modulate the immune responses against Mycobacterium tuberculosis, the roles of these components in human and nonhuman primate infections are unknown. The cynomolgus macaque (Macaca fascicularis) model of M. tuberculosis infection closely mirrors the infection outcomes and pathology in human tuberculosis (TB). The present study used rituximab, an anti-CD20 antibody, to deplete B cells in M. tuberculosis-infected macaques to examine the contribution of B cells and humoral immunity to the control of TB in nonhuman primates during the acute phase of infection. While there was no difference in the overall pathology, disease profession, and clinical outcome between the rituximab-treated and untreated macaques in acute infection, analyzing individual granulomas revealed that B cell depletion resulted in altered local T cell and cytokine responses, increased bacterial burden, and lower levels of inflammation. There were elevated frequencies of T cells producing interleukin-2 (IL-2), IL-10, and IL-17 and decreased IL-6 and IL-10 levels within granulomas from B cell-depleted animals. The effects of B cell depletion varied among granulomas in an individual animal, as well as among animals, underscoring the previously reported heterogeneity of local immunologic characteristics of tuberculous granulomas in nonhuman primates. Taken together, our data clearly showed that B cells can modulate the local granulomatous response in M. tuberculosis-infected macaques during acute infection. The impact of these alterations on disease progression and outcome in the chronic phase remains to be determined. PMID:26883591

  3. Acute dyspnea

    Radiodiagnosis is applied to determine the causes of acute dyspnea. Acute dyspnea is shown to aggravate the course of pulmonary diseases (bronchial asthma, obstructive bronchitis, pulmonary edema, throboembolism of pulmonary arteries etc) and cardiovascular diseases (desiseas of myocardium). The main tasks of radiodiagnosis are to determine volume and state of the lungs, localization and type of pulmonary injuries, to verify heart disease and to reveal concomitant complications

  4. Bronchitis (acute)

    Wark, Peter

    2008-01-01

    Acute bronchitis, with transient inflammation of the trachea and major bronchi, affects over 40/1000 adults a year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens.The role of smoking or environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear.A third of people may have longer-term symptoms or recurrence.

  5. CENPA overexpression promotes genome instability in pRb-depleted human cells

    Lentini Laura

    2009-12-01

    Full Text Available Abstract Background Aneuploidy is a hallmark of most human cancers that arises as a consequence of chromosomal instability and it is frequently associated with centrosome amplification. Functional inactivation of the Retinoblastoma protein (pRb has been indicated as a cause promoting chromosomal instability as well centrosome amplification. However, the underlying molecular mechanism still remains to be clarified. Results Here we show that pRb depletion both in wild type and p53 knockout HCT116 cells was associated with the presence of multipolar spindles, anaphase bridges, lagging chromosomes and micronuclei harbouring whole chromosomes. In addition aneuploidy caused by pRb acute loss was not affected by p53 loss. Quantitative real-time RT-PCR showed that pRB depletion altered expression of genes involved in centrosome duplication, kinetochore assembly and in the Spindle Assembly Checkpoint (SAC. However, despite MAD2 up-regulation pRb-depleted cells seemed to have a functional SAC since they arrested in mitosis after treatments with mitotic poisons. Moreover pRb-depleted HCT116 cells showed BRCA1 overexpression that seemed responsible for MAD2 up-regulation. Post-transcriptional silencing of CENPA by RNA interference, resulting in CENP-A protein levels similar to those present in control cells greatly reduced aneuploid cell numbers in pRb-depleted cells. Conclusion Altogether our findings indicate a novel aspect of pRb acute loss that promotes aneuploidy mainly by inducing CENPA overexpression that in turn might induce micronuclei by affecting the correct attachment of spindle microtubules to kinetochores.

  6. Depletion of Cultivatable Gut Microbiota by Broad-Spectrum Antibiotic Pretreatment Worsens Outcome After Murine Stroke

    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

  7. Intersubunit contacts made by tryptophan 120 with biotin are essential for both strong biotin binding and biotin-induced tighter subunit association of streptavidin.

    Sano, T; Cantor, C R

    1995-01-01

    In natural streptavidin, tryptophan 120 of each subunit makes contacts with the biotin bound by an adjacent subunit through the dimer-dimer interface. To understand quantitatively the role of tryptophan 120 and its intersubunit communication in the properties of streptavidin, a streptavidin mutant in which tryptophan 120 is converted to phenylalanine was produced and characterized. The streptavidin mutant forms a tetrameric molecule and binds one biotin per subunit, as does natural streptavid...

  8. Can breakfast tryptophan and vitamin B6 intake and morning exposure to sunlight promote morning-typology in young children aged 2 to 6 years?

    Nakade Miyo; Akimitsu Osami; Wada Kai; Krejci Milada; Noji Teruki; Taniwaki Nozomi; Takeuchi Hitomi; Harada Tetsuo

    2012-01-01

    Abstract This study tried to examine, from epidemiological and physiologic anthropological (Japanese culture on breakfast) points of view, the integrated effects of the amount of tryptophan and vitamin B6 intake and the following exposure to sunlight on the circadian typology and sleep habits in young Japanese children aged 2 to 6 years, using the newly-evaluated calculating system of tryptophan (Tryptophan Index 2009) and vitamin B6 intake (VitaminB6 Index 2009) at breakfast. The positive an...

  9. Application of backtracking algorithm to depletion calculations

    Based on the theory of linear chain method for analytical depletion calculations, the burn-up matrix is decoupled by the divide and conquer strategy and the linear chain with Markov characteristic is formed. The density, activity and decay heat of every nuclide in the chain can be calculated by analytical solutions. Every possible reaction path of the nuclide must be considered during the linear chain establishment process. To confirm the calculation precision and efficiency, the algorithm which can cover all the reaction paths of the nuclide and search the paths automatically according to to problem description and precision restrictions should be sought. Through analysis and comparison of several kinds of searching algorithms, the backtracking algorithm was selected to search and calculate the linear chains using Depth First Search (DFS) method. The depletion program can solve the depletion problem adaptively and with high fidelity. The solution space and time complexity of the program were analyzed. The new developed depletion program was coupled with Monte Carlo program MCMG-II to calculate the benchmark burn-up problem of the first core of China Experimental Fast Reactor (CEFR). The initial verification and validation of the program was performed by the calculation. (author)

  10. Global Warming: Lessons from Ozone Depletion

    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…

  11. Application of backtracking algorithm to depletion calculations

    Based on the theory of linear chain method for analytical depletion calculations, the burnup matrix is decoupled by the divide and conquer strategy and the linear chain with Markov characteristic is formed. The density, activity and decay heat of every nuclide in the chain then can be calculated by analytical solutions. Every possible reaction path of the nuclide must be considered during the linear chain establishment process. To confirm the calculation precision and efficiency, the algorithm which can cover all the reaction paths and search the paths automatically according to the problem description and precision restrictions should be found. Through analysis and comparison of several kinds of searching algorithms, the backtracking algorithm was selected to establish and calculate the linear chains in searching process using depth first search (DFS) method, forming an algorithm which can solve the depletion problem adaptively and with high fidelity. The complexity of the solution space and time was analyzed by taking into account depletion process and the characteristics of the backtracking algorithm. The newly developed depletion program was coupled with Monte Carlo program MCMG-Ⅱ to calculate the benchmark burnup problem of the first core of China Experimental Fast Reactor (CEFR) and the preliminary verification and validation of the program were performed. (authors)

  12. Regulation of Insulin-Like Growth Factor-1 and Growth Hormone Receptor Gene Expression in Weaned Pigs Fed Graded Levels of Dietary Tryptophan

    Jingdong Yin; Xiangshu Piao; Defa Li; Yuhua Ding; Jianjun Xing

    2004-01-01

    Fifty-four, crossbred pigs (Landrace ? Large White ? Pietran) were used in a study to determine the influence of dietary tryptophan on serum IGF-I concentrations as well as IGF-I and growth hormone receptor gene expression in the liver, longissimus dorsi and duodenum of weaned pigs (9.98 + 0.31 kg BW). The pigs were assigned to one of three diets including a low tryptophan (Trp:Lys = 0.11:1.14), a medium tryptophan (Trp:Lys = 0.19:1.13) and a high tryptophan (Trp:Lys = 0.24:1.14) containing d...

  13. Valence-dependent influence of serotonin depletion on model-based choice strategy.

    Worbe, Y; Palminteri, S; Savulich, G; Daw, N D; Fernandez-Egea, E; Robbins, T W; Voon, V

    2016-05-01

    Human decision-making arises from both reflective and reflexive mechanisms, which underpin goal-directed and habitual behavioural control. Computationally, these two systems of behavioural control have been described by different learning algorithms, model-based and model-free learning, respectively. Here, we investigated the effect of diminished serotonin (5-hydroxytryptamine) neurotransmission using dietary tryptophan depletion (TD) in healthy volunteers on the performance of a two-stage decision-making task, which allows discrimination between model-free and model-based behavioural strategies. A novel version of the task was used, which not only examined choice balance for monetary reward but also for punishment (monetary loss). TD impaired goal-directed (model-based) behaviour in the reward condition, but promoted it under punishment. This effect on appetitive and aversive goal-directed behaviour is likely mediated by alteration of the average reward representation produced by TD, which is consistent with previous studies. Overall, the major implication of this study is that serotonin differentially affects goal-directed learning as a function of affective valence. These findings are relevant for a further understanding of psychiatric disorders associated with breakdown of goal-directed behavioural control such as obsessive-compulsive disorders or addictions. PMID:25869808

  14. Acute myelogenous leukemia (AML) - children

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  15. Regular moderate or intense exercise prevents depression-like behavior without change of hippocampal tryptophan content in chronically tryptophan-deficient and stressed mice.

    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.

  16. A worldwide view of groundwater depletion

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

    2010-12-01

    During the last decades, global water demand has increased two-fold due to increasing population, expanding irrigated area and economic development. Globally such demand can be met by surface water availability (i.e., water in rivers, lakes and reservoirs) but regional variations are large and the absence of sufficient rainfall and run-off increasingly encourages the use of groundwater resources, particularly in the (semi-)arid regions of the world. Excessive abstraction for irrigation frequently leads to overexploitation, i.e. if groundwater abstraction exceeds the natural groundwater recharge over extensive areas and prolonged times, persistent groundwater depletion may occur. Observations and various regional studies have revealed that groundwater depletion is a substantial issue in regions such as Northwest India, Northeast Pakistan, Central USA, Northeast China and Iran. Here we provide a global overview of groundwater depletion from the year 1960 to 2000 at a spatial resolution of 0.5 degree by assessing groundwater recharge with the global hydrological model PCR-GLOBWB and subtracting estimates of groundwater abstraction obtained from IGRAC-GGIS database. PCR-GLOBWB was forced by the CRU climate dataset downscaled to daily time steps using ERA40 re-analysis data. PCR-GLOBWB simulates daily global groundwater recharge (0.5 degree) while considering sub-grid variability of each grid cell (e.g., short and tall vegetation, different soil types, fraction of saturated soil). Country statistics of groundwater abstraction were downscaled to 0.5 degree by using water demand (i.e., agriculture, industry and domestic) as a proxy. To limit problems related to increased capture of discharge and increased recharge due to groundwater pumping, we restricted our analysis to sub-humid to arid areas. The uncertainty in the resulting estimates was assessed by a Monte Carlo analysis of 100 realizations of groundwater recharge and 100 realizations of groundwater abstraction

  17. Health and environmental impact of depleted uranium

    Depleted Uranium (DU) is 'nuclear waste' produced from the enrichment process and is mostly made up of 238U and is depleted in the fissionable isotope 235U compared to natural uranium (NU). Depleted uranium has about 60% of the radioactivity of natural uranium. Depleted uranium and natural uranium are identical in terms of the chemical toxicity. Uranium's high density gives depleted uranium shells increased range and penetrative power. This density, combined with uranium's pyrophoric nature, results in a high-energy kinetic weapon that can punch and burn through armour plating. Striking a hard target, depleted uranium munitions create extremely high temperatures. The uranium immediately burns and vaporizes into an aerosol, which is easily diffused in the environment. People can inhale the micro-particles of uranium oxide in an aerosol and absorb them mainly from lung. Depleted uranium has both aspects of radiological toxicity and chemical toxicity. The possible synergistic effect of both kinds of toxicities is also pointed out. Animal and cellular studies have been reported the carcinogenic, neurotoxic, immuno-toxic and some other effects of depleted uranium including the damage on reproductive system and foetus. In addition, the health effects of micro/ nano-particles, similar in size of depleted uranium aerosols produced by uranium weapons, have been reported. Aerosolized DU dust can easily spread over the battlefield spreading over civilian areas, sometimes even crossing international borders. Therefore, not only the military personnel but also the civilians can be exposed. The contamination continues after the cessation of hostilities. Taking these aspects into account, DU weapon is illegal under international humanitarian laws and is considered as one of the inhumane weapons of 'indiscriminate destruction'. The international society is now discussing the prohibition of DU weapons based on 'precautionary principle'. The 1991 Gulf War is reportedly the first

  18. Effect of tryptophan on 2,4-dichlorophenoxyacetic acid toxicity in the nitrogen-fixing-cyanobacterium Nostoc linckia.

    Mishra, A K; Tiwari, D N

    1986-01-01

    The combined effect of a hormone weed killer 2,4-dichlorophenoxyacetic acid (2,4-D) and an amino acid (tryptophan) has been studied on growth and heterocyst differentiation in the cyanobacterium Nostoc linckia. 2.4-D at 100 micrograms/ml stimulated growth and heterocyst frequency in combined nitrogen-free medium while its higher concentrations inhibited both. Tryptophan under similar conditions promoted much growth yield with 3-4 fold enhanced heterocyst frequency than the control. Such heterocysts were immature and showed germination under in situ condition. The concentrations of 2,4-D (100 micrograms/ml) and tryptophan (50 micrograms/ml), stimulatory to growth and heterocyst formation, caused additive effect while herbicide inhibition of nitrogen-fixing growth at higher doses was partially relieved by tryptophan but tryptophan-induced heterocyst frequency was completely suppressed under this condition. The possible role of interaction of these two chemicals on growth and heterocyst formation has been discussed. PMID:3083089

  19. Employing the fluorescence anisotropy and quenching kinetics of tryptophan to hunt for residual structures in denatured proteins

    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.

  20. Metabolic design based on a coupled gene expression-metabolic network model of tryptophan production in Escherichia coli.

    Schmid, Joachim W; Mauch, Klaus; Reuss, Matthias; Gilles, Ernst D; Kremling, Andreas

    2004-10-01

    The presumably high potential of a holistic design approach for complex biochemical reaction networks is exemplified here for the network of tryptophan biosynthesis from glucose, a system whose components have been investigated thoroughly before. A dynamic model that combines the behavior of the trp operon gene expression with the metabolic network of central carbon metabolism and tryptophan biosynthesis is investigated. This model is analyzed in terms of metabolic fluxes, metabolic control, and nonlinear optimization. We compare two models for a wild-type strain and another model for a tryptophan producer. An integrated optimization of the whole network leads to a significant increase in tryptophan production rate for all systems under study. This enhancement is well above the increase that can be achieved by an optimization of subsystems. A constant ratio of control coefficients on tryptophan synthesis rate has been identified for the models regarding or disregarding trp operon expression. Although we found some examples where flux control coefficients even contradict the trends of enzyme activity changes in an optimized profile, flux control can be used as an indication for enzymes that have to be taken into account in optimization. PMID:15491865