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Sample records for dual leucine zipper-bearing

  1. Leucine aminopeptidase blood test

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003559.htm Leucine aminopeptidase blood test To use the sharing features on this page, ... Alternative Names Serum leucine aminopeptidase; LAP - serum Images Blood test References Chernecky CC, Berger BJ. Leucine aminopeptidase (LAP) - ...

  2. Surface properties of aqueous amino acid solutions II. Leucine-leucine hydrochloride and leucine-sodium leucinate mixtures.

    Science.gov (United States)

    Matubayasi, Norihiro; Matsuyama, Shohei; Akizuki, Ryosuke

    2005-08-15

    To understand the distinction between the effects of zwitterionic, anionic, and cationic l-leucine upon adsorption and lateral interactions at air/water surface, the surface tensions of aqueous solutions of l-leucine-l-leucine hydrochloride and l-leucine-sodium l-leucinate mixtures were measured as a function of concentration and composition at 25 degrees C. The surface activity decreases in the order l-leucine >l-leucine hydrochloride > sodium l-leucinate. Both l-leucine hydrochloride and sodium l-leucinate form gaseous adsorbed films through the experimentally accessible concentration range, while the adsorbed film of zwitterionic l-leucine shows a transition between gaseous and expanded film.

  3. The leucine-rich repeat structure.

    Science.gov (United States)

    Bella, J; Hindle, K L; McEwan, P A; Lovell, S C

    2008-08-01

    The leucine-rich repeat is a widespread structural motif of 20-30 amino acids with a characteristic repetitive sequence pattern rich in leucines. Leucine-rich repeat domains are built from tandems of two or more repeats and form curved solenoid structures that are particularly suitable for protein-protein interactions. Thousands of protein sequences containing leucine-rich repeats have been identified by automatic annotation methods. Three-dimensional structures of leucine-rich repeat domains determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. As the essential structural principles become well established, the leucine-rich repeat architecture is emerging as an attractive framework for structural prediction and protein engineering. This review presents an update of the current understanding of leucine-rich repeat structure at the primary, secondary, tertiary and quaternary levels and discusses specific examples from recently determined three-dimensional structures.

  4. Hypothalamic leucine metabolism regulates liver glucose production.

    Science.gov (United States)

    Su, Ya; Lam, Tony K T; He, Wu; Pocai, Alessandro; Bryan, Joseph; Aguilar-Bryan, Lydia; Gutiérrez-Juárez, Roger

    2012-01-01

    Amino acids profoundly affect insulin action and glucose metabolism in mammals. Here, we investigated the role of the mediobasal hypothalamus (MBH), a key center involved in nutrient-dependent metabolic regulation. Specifically, we tested the novel hypothesis that the metabolism of leucine within the MBH couples the central sensing of leucine with the control of glucose production by the liver. We performed either central (MBH) or systemic infusions of leucine in Sprague-Dawley male rats during basal pancreatic insulin clamps in combination with various pharmacological and molecular interventions designed to modulate leucine metabolism in the MBH. We also examined the role of hypothalamic ATP-sensitive K(+) channels (K(ATP) channels) in the effects of leucine. Enhancing the metabolism of leucine acutely in the MBH lowered blood glucose through a biochemical network that was insensitive to rapamycin but strictly dependent on the hypothalamic metabolism of leucine to α-ketoisocaproic acid and, further, insensitive to acetyl- and malonyl-CoA. Functional K(ATP) channels were also required. Importantly, molecular attenuation of this central sensing mechanism in rats conferred susceptibility to developing hyperglycemia. We postulate that the metabolic sensing of leucine in the MBH is a previously unrecognized mechanism for the regulation of hepatic glucose production required to maintain glucose homeostasis.

  5. Effects of leucine, isoleucine, or threonine infusion on leucine metabolism in humans

    International Nuclear Information System (INIS)

    Schwenk, W.F.; Haymond, M.W.

    1987-01-01

    Leucine and/or its α-keto acid, α-ketoisocaproate (KIC), have been reported to spare protein in humans. To determine whether specific amino acid infusions affect whole-body protein metabolism as estimated by changes in leucine flux and oxidation, five groups of normal subjects were infused with saline, leucine, isoleucine, or threonine. Independent estimates of leucine metabolism were obtained using simultaneous infusions of [ 3 H]-leucine and α-[ 14 C]ketoisocaproate. Nearly identical results were obtained using either tracer compared with the saline controls. Compared with the saline controls, leucine infusion (1) had no effect on estimated rates of appearance of endogenous leucine, (2) stimulated leucine oxidation, (3) decreased plasma concentrations of other amino acids, and (4) stimulated nonoxidized leucine disappearance in a dose-dependent fashion. In contrast, isoleucine and threonine infusions had no effect on leucine metabolism. Assuming the validity of the isotope model employed, these data suggest that the purported anabolic effect of leucine infusion on whole-body protein metabolism is mediated via stimulation of protein synthesis rather than decreased proteolysis

  6. Leucine metabolism in patients with Hepatic Encephalopathy

    International Nuclear Information System (INIS)

    McGhee, A.S.; Kassouny, M.E.; Matthews, D.E.; Millikan, W.

    1986-01-01

    A primed continuous infusion of [ 15 N, 1- 13 C]leucine was used to determine whether increased oxidation and/or protein synthesis of leucine occurs in patients with cirrhosis. Five controls and patients were equilibrated on a metabolic balance diet [0.6 g protein per kg ideal body weight (IBW)]. An additional four patients were equilibrated in the same manner with the same type of diet with a protein level of 0.75 g per kg IBW. Plasma leucine and breath CO 2 enrichments were measured by mass spectrometry. Protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW. Results indicate that systemic derangements of leucine metabolism are not the cause of Hepatic Encephalopathy

  7. Changes in leucine kinetics during meal absorption: effects of dietary leucine availability

    International Nuclear Information System (INIS)

    Nissen, S.; Haymond, M.W.

    1986-01-01

    Whole-body leucine and α/-ketoisocaproate (KIC) metabolism were estimated in mature dogs fed a complete meal, a meal devoid of branched-chain amino acids, and a meal devoid of all amino acids. Using a constant infusion of [4,5- 3 H]leucine and α-[1- 14 C]ketoisocaproate (KIC), combined with dietary [5,5,5- 2 H 3 ]leucine, the rate of whole-body proteolysis, protein synthesis, leucine oxidation, and interconversion leucine and KIC were estimated along with the rate of leucine absorption. Digestion of the complete meal resulted in a decrease in the rate of endogenous proteolysis, a small increase in the estimated rate of leucine entering protein, and a twofold increase in the rate of leucine oxidation. Ingestion of either the meal devoid of branched-chain amino acids or devoid of all amino acids resulted in a decrease in estimates of whole-body rates of proteolysis and protein synthesis, decreased leucine oxidation, and a decrease in the interconversion of leucine and KIC. The decrease in whole-body proteolysis was closely associated with the rise in plasma insulin concentrations following meal ingestion. Together these data suggest that the transition from tissue metabolism to anabolism is the result, at least in part, of decreased whole-body proteolysis. This meal-related decrease in proteolysis is independent of the dietary amino acid composition or content. In contrast, the rate of protein synthesis was sustained only when the meal complete in all amino acids was provided, indicating an overriding control of protein synthesis by amino acid availability

  8. Leucine uptake and bacteriophage adsorption a Vibrio strain

    International Nuclear Information System (INIS)

    Robb, F.T.; Robb, S.M.; Mothibeli, M.A.; Woods, D.R.

    1982-01-01

    Vibrio mutants with altered leucine transport systems were isolated as part of a study on the physiological characteristics of stationary phase Vibrio cells. The strains are investigated and show that mutants which are defective in leucine uptake are unable to adsorb phage α3a. Elevated leucine transport produces a concomitant increase in the rate of phage adsorption. Phage adsortpion and L-leucine transport experiments indicated that there was a correlation between phage α3a adsorption and leucine uptake. The results suggest that the transport of L-leucine and phage α3 are linked

  9. Role of leucine in hepatic ketogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kulaylat, M.N.; Frexes-Steed, M.; Geer, R.; Williams, P.E.; Abumrad, N.N.

    1988-03-01

    Isolated hepatocyte studies demonstrated that leucine can be a precursor of ketone bodies. In this study we examine the relative contribution of leucine to hepatic ketogenesis in vivo. Three groups of conscious dogs with long-term indwelling catheters in the femoral artery, hepatic vein, and portal vein were studied. Group I (n = 3) animals were fasted overnight for 24 hours, and those in groups II and III (n = 4, each) were fasted for 62 to 68 hours (designated 3-day fast). Groups I and III received intravenous saline solution (0.9%) and served as controls. In group II selective acute insulin deficiency (SAID) was induced by a peripheral intravenous somatostatin (SRIF) infusion and intraportal glucagon (0.55 ng/body weight/min). Net hepatic production (NHP) of ketone bodies (kb) and leucine (leu) was measured by the arteriovenous difference technique. Hepatic conversion of leucine to ketone bodies was measured by continuous infusion of L-U-(/sup 14/C)-leucine and by determination of the appearance of (/sup 14/C)-ketone bodies across the liver. In the group fasted overnight NHPleu was 0.02 +/- 0.01 mumol/kg/min, a value not different from zero. NHPkb was 3.1 +/- 0.1 mumol/kg/min and hepatic conversion of leucine to ketone bodies accounted for 3.5% of NHPkb. Insulin deficiency after 3 day's fasting resulted in a near 70% increase in NHPleu (from basal values of 0.31 +/- 0.1 mumol/kg/min to 0.52 +/- 0.06 mumol/kg/min during SAID, p less than 0.01). NHPkb increased from 11.0 +/- 1.0 to 15.5 mumol/kg/min (p less than 0.05). The rate of leucine conversion to ketone bodies (L-C) increased from 1.1 +/- 0.25 to 2.4 +/- 0.3 mumol/kg/min (p less than 0.01) with SAID.

  10. Role of leucine in hepatic ketogenesis

    International Nuclear Information System (INIS)

    Kulaylat, M.N.; Frexes-Steed, M.; Geer, R.; Williams, P.E.; Abumrad, N.N.

    1988-01-01

    Isolated hepatocyte studies demonstrated that leucine can be a precursor of ketone bodies. In this study we examine the relative contribution of leucine to hepatic ketogenesis in vivo. Three groups of conscious dogs with long-term indwelling catheters in the femoral artery, hepatic vein, and portal vein were studied. Group I (n = 3) animals were fasted overnight for 24 hours, and those in groups II and III (n = 4, each) were fasted for 62 to 68 hours (designated 3-day fast). Groups I and III received intravenous saline solution (0.9%) and served as controls. In group II selective acute insulin deficiency (SAID) was induced by a peripheral intravenous somatostatin (SRIF) infusion and intraportal glucagon (0.55 ng/body weight/min). Net hepatic production (NHP) of ketone bodies (kb) and leucine (leu) was measured by the arteriovenous difference technique. Hepatic conversion of leucine to ketone bodies was measured by continuous infusion of L-U-[ 14 C]-leucine and by determination of the appearance of [ 14 C]-ketone bodies across the liver. In the group fasted overnight NHPleu was 0.02 +/- 0.01 mumol/kg/min, a value not different from zero. NHPkb was 3.1 +/- 0.1 mumol/kg/min and hepatic conversion of leucine to ketone bodies accounted for 3.5% of NHPkb. Insulin deficiency after 3 day's fasting resulted in a near 70% increase in NHPleu (from basal values of 0.31 +/- 0.1 mumol/kg/min to 0.52 +/- 0.06 mumol/kg/min during SAID, p less than 0.01). NHPkb increased from 11.0 +/- 1.0 to 15.5 mumol/kg/min (p less than 0.05). The rate of leucine conversion to ketone bodies (L-C) increased from 1.1 +/- 0.25 to 2.4 +/- 0.3 mumol/kg/min (p less than 0.01) with SAID

  11. Crystal Structure of FadA Adhesin from Fusobacterium nucleatum Reveals a Novel Oligomerization Motif, the Leucine Chain

    Energy Technology Data Exchange (ETDEWEB)

    Nithianantham, Stanley; Xu, Minghua; Yamada, Mitsunori; Ikegami, Akihiko; Shoham, Menachem; Han, Yiping W.; (Case Western)

    2009-04-07

    Many bacterial appendages have filamentous structures, often composed of repeating monomers assembled in a head-to-tail manner. The mechanisms of such linkages vary. We report here a novel protein oligomerization motif identified in the FadA adhesin from the Gram-negative bacterium Fusobacterium nucleatum. The 2.0 {angstrom} crystal structure of the secreted form of FadA (mFadA) reveals two antiparallel {alpha}-helices connected by an intervening 8-residue hairpin loop. Leucine-leucine contacts play a prominent dual intra- and intermolecular role in the structure and function of FadA. First, they comprise the main association between the two helical arms of the monomer; second, they mediate the head-to-tail association of monomers to form the elongated polymers. This leucine-mediated filamentous assembly of FadA molecules constitutes a novel structural motif termed the 'leucine chain.' The essential role of these residues in FadA is corroborated by mutagenesis of selected leucine residues, which leads to the abrogation of oligomerization, filament formation, and binding to host cells.

  12. Protein and leucine metabolism in maple syrup urine disease

    International Nuclear Information System (INIS)

    Thompson, G.N.; Bresson, J.L.; Pacy, P.J.; Bonnefont, J.P.; Walter, J.H.; Leonard, J.V.; Saudubray, J.M.; Halliday, D.

    1990-01-01

    Constant infusions of [13C]leucine and [2H5]phenylalanine were used to trace leucine and protein kinetics, respectively, in seven children with maple syrup urine disease (MSUD) and eleven controls matched for age and dietary protein intake. Despite significant elevations of plasma leucine (mean 351 mumol/l, range 224-477) in MSUD subjects, mean whole body protein synthesis [3.78 +/- 0.42 (SD) g.kg-1. 24 h-1] and catabolism (4.07 +/- 0.46) were similar to control values (3.69 +/- 0.50 and 4.09 +/- 0.50, respectively). The relationship between phenylalanine and leucine fluxes was also similar in MSUD subjects (mean phenylalanine-leucine flux ratio 0.35 +/- 0.07) and previously reported adult controls (0.33 +/- 0.02). Leucine oxidation was undetectable in four of the MSUD subjects and very low in the other three (less than 4 mumol.kg-1.h-1; controls 13-20). These results show that persistent elevation in leucine concentration has no effect on protein synthesis. The marked disturbance in leucine metabolism in MSUD did not alter the relationship between rates of catabolism of protein to phenylalanine and leucine, which provides further support for the validity of the use of a single amino acid to trace whole body protein metabolism. The minimal leucine oxidation in MSUD differs from findings in other inborn metabolic errors and indicates that in patients with classical MSUD there is no significant route of leucine disposal other than through protein synthesis

  13. Small leucine-rich proteoglycans in the aging skeleton

    DEFF Research Database (Denmark)

    Young, M F; Bi, Y; Ameye, L

    2006-01-01

    Small Leucine-Rich Proteoglyans (SLRPs) are major skeletal extracellular matrix (ECM) components that comprise a family of 13 members containing repeats of a leucine-rich motif. To examine SLRP function, we generated mice deficient in one or more member and analyzed them at the tissue, cell and m...

  14. The effect of a dietary leucine excess on the immunoresponsiveness ...

    African Journals Online (AJOL)

    occurred with a leucine-overloaded, balanced diet (18% casein), or with a 4% casein diet supplemented with leucine. Chevalier & Aschkenasy (1977) reported that rats need consume only a small amount of protein in order to maintain an almost normal immunological response, provided that the food consumed is balanced ...

  15. Small leucine-rich proteoglycans in the aging skeleton

    DEFF Research Database (Denmark)

    Young, M F; Bi, Y; Ameye, L

    2006-01-01

    Small Leucine-Rich Proteoglyans (SLRPs) are major skeletal extracellular matrix (ECM) components that comprise a family of 13 members containing repeats of a leucine-rich motif. To examine SLRP function, we generated mice deficient in one or more member and analyzed them at the tissue, cell...

  16. Leucine and valine requirements of the growing germfree chicks

    International Nuclear Information System (INIS)

    Ishibashi, Teru; Kametaka, Masao; Ozaki, Akira; Yamamoto, Tetsuzo; Mitsuoka, Tomotari.

    1977-01-01

    To compare the requirements of leucine and valine of the growing germfree and conventional chicks, 7-day-old chicks were fed a diet with graded levels of leucine or valine for 7 days. Daily gains of body weight of the germfree chicks were greater than those of the conventional chicks when the dietary leucine or valine level was higher than the requirement level. Adversely, daily gains of body weight of the germfree chicks were less than those of the conventional chicks when the dietary leucine or valine level was very low. Leucine and valine requirements for maximum growth, however, was the same and estimated to be 0.95 and 0.78%, repectively, of the diet for both groups. After the feeding test, the chicks were injected with L-leucine- and L-valine-U- 14 C and expired carbon dioxide was collected for 2 and 3 hours, respectively. From the percentage of recovery of 14 C in the expired carbon dioxide, the leucine and valine requirements were found to be 0.80 and 0.53% of the diet for both groups, respectively. Three hours after feeding test, the plasma free valine concentration was estimated in the chicks which was not injected the isotope. The requirement of valine was estimated to be 0.59% for the germfree chicks and 0.54% for the conventional chicks. From the above data, it may be concluded that no difference, or very small if any, is found in the requirements of leucine and valine between the germfree chicks and those of the conventional chicks. (auth.)

  17. Effect of exercise training on leucine oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Hendrix, M.K.; Layman, D.K.

    1986-03-01

    Oxidation of the BCAA leucine is increased during a bout of exhaustive exercise. The purpose of this study was to determine the effects of exercise training on leu oxidation during aerobic exercise. Female Sprague-Dawley rats were fed a commercial diet ad lib and divided into sedentary and two trained groups. Animals were trained to run on a treadmill with a 10/sup 0/ incline at 28 m/min for 5 wks for either 50 or 120 min/day. There were no differences in food intake or body weight. After a 12 hr fast, animals were run for 50 or 120 min and changes in leu catabolism determined by measurement of in vivo leu oxidation and activity of branched chain keto acid dehydrogenase (BCKAD). For measurement of leu oxidation, rats were injected IP with 4 ..mu..Ci 1-/sup 14/C-leu during the last 15 min of exercise, placed in glass metabolic chambers, and /sup 14/CO/sub 2/ collected in 1 N NaOH for 30 min periods. Leu oxidation was increased by 40% after 50 min of exercise and by 79% after 120 min of exercise. Five weeks of training reduced the rate of leu oxidation during an exercise bout. The activity of the BCKAD was not increased in the trained animals after either 50 or 120 min of exercise. These data indicate that the rate of leu oxidation during exercises is dependent on the duration of the exercise and that training will reduce the magnitude of this effect.

  18. Circadian secretion patterns of ß-endorphin and leucine enkephalin

    Directory of Open Access Journals (Sweden)

    E. H. de Wet

    1992-07-01

    Full Text Available ß-endorphin and leucine enkephalin are neuropeptides with potent opioid activity. In a study to investigate the circadian secretion patterns of the above-mentioned, blood samples were collected hourly from 12 healthy males who were subjected to the experiment for 24 hours. Radioimmunoassays were used in the analysis of plasma samples for ß-endorphin and leucine enkephalin. Peak concentrations of ß-endorphin were demonstrated from 08:00-09:00, while peak concentrations of leucine enkephalin occured from 23:00-07:00. Trough concentrations of ß-endorphin occurred from 24:00-05:00, while trough con­centrations of leucine enkephalin were demonstrated from 09:00-12:00. The illustrated circadian secretion pattern for ß-endorphin simulates the well-known circadian rhythm of cortisol. The answer to this may be in the fact that ß-endorphin and corticotropin stem from the same precursor. The illustrated circadian secretion pattern for leucine enkephalin simulates that of melatonin. The reason for this is unclear.

  19. Dual Diagnosis

    Science.gov (United States)

    A person with dual diagnosis has both a mental disorder and an alcohol or drug problem. These conditions occur together frequently. In particular, ... to emotional and mental problems. Someone with a dual diagnosis must treat both conditions. For the treatment ...

  20. Leucine metabolism in cirrhotic patients with hepatic encephalopathy

    International Nuclear Information System (INIS)

    McGhee, A.S.

    1985-01-01

    The purpose of this study was to determine whether increased oxidation of or protein synthesis requiring leucine occurs in cirrhotic patients. Five control subjects and four subjects with cirrhosis were equilibrated on a baseline diet (0.6 g protein per kg ideal body weight [IBW]) with sufficient nonprotein calories to preclude negative nitrogen balance. An additional four patients were equilibrated on the same type of diet with a higher protein level (0.75 g per kg IBW). Control subjects and the patients were then studied during continuous infusion of L-[ 15 N, 1- 13 C] leucine in the fasted state and, in the fed state, with a Propac diet which had the same distribution of energy nutrients as the baseline diets. Plasma levels of L-[ 15 N, 1- 13 C], L-[1- 13 C] and L-[ 15 N] leucine were measured during isotopic steady state by gas chromatography-mass spectrometry and fractional excretion of 13 CO 2 in breath samples were analyzed by isotopic ratio mass spectrometry. During the fasted and fed states leucine metabolism was measured to quantitate rates of nitrogen flux (Q/sub N/), carbon flux (Q/sub c/) and oxidation to carbon dioxide and water (C). From these measured values, proteins breakdown (B), protein synthesis (S), deamination (X 0 ) and reamination (X/sub N/) were calculated. The results showed that protein synthesis and leucine metabolism were identical in controls and patients when both were fed a diet with 0.6 g protein/kg IBW and maintenance level of nonprotein calories. The data also showed that leucine metabolism can be quantitatively and reproducibly measured in subjects with cirrhosis

  1. Dietary leucine requirement of juvenile Japanese seabass ( Lateolabrax japonicus)

    Science.gov (United States)

    Li, Yan; Cheng, Zhenyan; Mai, Kangsen; Ai, Qinghui

    2015-02-01

    A 56-day feeding trial was conducted to examine the dietary leucine requirement of juvenile Japanese seabass in seawater floating net cages (1.5 m × 1.5 m × 2.0 m). Six isonitrogenous (crude protein 40%) and isoenergetic (gross energy 20 kJ g-1) diets were formulated to contain different concentrations of leucine (0.9%, 1.49%, 2.07%, 2.70%, 3.30% and 3.88% of dry matter). Crystalline L-amino acids were supplemented to simulate the whole body amino acid pattern of Japanese seabass except for leucine. Three groups (30 fish individuals each, 8.0 g ± 0.20 g in initial weight) were fed to apparent satiation at 5:00 and 17:30 every day. During the experimental period, the water temperature ranged from 26 to 32δC and salinity from 26 to 30, and the dissolved oxygen was maintained at 7 mg L-1. The results showed that weight gain ( WG), nitrogen retention ( NR), feed efficiency ( FE) and protein efficiency ratio ( PER) were significantly increased when dietary leucine was increased from 0.90% to 2.70% of dry matter, and then declined. WG was the highest when fish were fed D4 containing 2.70% of leucine. No significant differences were observed in body composition among dietary treatments ( P > 0.05). Considering the change of WG, the optimum dietary leucine requirement of juvenile Japanese seabass was either 2.39% of dry matter or 5.68% of dietary protein.

  2. [Preparation of leucine-methyl glutamate-glutamic acid copolymers].

    Science.gov (United States)

    Pan, S; Shi, F; Huang, L; Zhou, Q; Lin, Z; Yi, W

    1997-06-01

    The method for preparing leucine-methyl glutamate-glutamic acid copolymer was studied. In the first place benzyl glutamate and methyl glutamate were synthesized respectively. Then N-carboxy anhydrides (NCA) of leucine, benzyl glutamate or methyl glutamate were prepared in a closed container by phosgene-toluene solution method. After copolymerization the copolymers were debenzylated and demethylated by anhydrous hydrogen bromide. The free carboxyl group mole content in side chains of the copolymer was controlled by various standing periods following bubbling HBr. Analysis of infrared spectrogram and ultraviolet asorbance of copolymers indicated that this procedure resulted in the loss of almost all benzyl groups and some methyl groups.

  3. Quantitative role of splanchnic region in leucine metabolism: L-(1-13C,15N)leucine and substrate balance studies

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Y.M.; Wagner, D.A.; Tredget, E.E.; Walaszewski, J.A.; Burke, J.F.; Young, V.R. (Shriners Burns Institute, MA (USA))

    1990-07-01

    The role of the splanchnic region (Sp) in whole body leucine metabolism was assessed in six chronically catheterized fasting mongrel dogs and in eight dogs during constant enteral feeding of a complete amino acid solution (0.24 g.kg-1.h-1). We used primed continuous intravenous infusions of L-(1-13C,15N)leucine and L-(1-14C)leucine and measurements of arteriovenous isotope and leucine balance across the gut, liver, and Sp. In the fasted condition, 3.5% of arterial leucine supply was oxidized in the Sp, accounting for 13% of total body leucine oxidation, with 10% by liver. With amino acid feeding (1) leucine carbon and nitrogen fluxes and oxidation were increased (P less than 0.01) at the whole body level; (2) the percent of whole body leucine oxidation occurring in the Sp and liver increased (P less than 0.01) to 41 and 27%, respectively; (3) fractional metabolic utilization of leucine delivered to the Sp was reduced (P less than 0.01) from 47 to 35%; (4) the deamination rate of leucine in the gut was increased (P less than 0.05), along with an increased reamination rate of alpha-ketoisocaproic acid in the Sp (P less than 0.05). These findings reveal that the Sp accounts for a small fraction of whole body leucine oxidation during the fasting condition, but it plays a quantitatively important role in total body leucine oxidation during amino acid feeding; the gut and liver play cooperative roles in controlling leucine supply to peripheral tissues.

  4. 21 CFR 862.1460 - Leucine aminopeptidase test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Leucine aminopeptidase test system. 862.1460 Section 862.1460 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  5. Leucine supplementation in the management of protein energy ...

    African Journals Online (AJOL)

    Background: Wasting accounts for 4.7% of all deaths of children under five years of age globally. Currently there is no standard for treatment of moderate wasting in children resulting in high variability of treatment methods and low predictability if recovery outcomes. Leucine, a branched chain amino acid,has recently ...

  6. Kinetics and mechanism of oxidation of L-leucine by alkaline ...

    Indian Academy of Sciences (India)

    The kinetics of oxidation of L-leucine by diperiodatocuprate (III) (DPC) in aqueous alkaline medium at a constant ionic strength of 0.10mol dm-3 was studied spectrophotometrically. The reaction between L-leucine and DPC in alkaline medium exhibits 1:4 stoichiometry (L-leucine: DPC). The reaction is of first order in [DPC] ...

  7. Finding a Leucine in a Haystack: Searching the Proteome for ambigous Leucine-Aspartic Acid motifs

    KAUST Repository

    Arold, Stefan T.

    2016-01-25

    Leucine-aspartic acid (LD) motifs are short helical protein-protein interaction motifs involved in cell motility, survival and communication. LD motif interactions are also implicated in cancer metastasis and are targeted by several viruses. LD motifs are notoriously difficult to detect because sequence pattern searches lead to an excessively high number of false positives. Hence, despite 20 years of research, only six LD motif–containing proteins are known in humans, three of which are close homologues of the paxillin family. To enable the proteome-wide discovery of LD motifs, we developed LD Motif Finder (LDMF), a web tool based on machine learning that combines sequence information with structural predictions to detect LD motifs with high accuracy. LDMF predicted 13 new LD motifs in humans. Using biophysical assays, we experimentally confirmed in vitro interactions for four novel LD motif proteins. Thus, LDMF allows proteome-wide discovery of LD motifs, despite a highly ambiguous sequence pattern. Functional implications will be discussed.

  8. Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Band, Margaret M; Sumukadas, Deepa; Struthers, Allan D; Avenell, Alison; Donnan, Peter T; Kemp, Paul R; Smith, Karen T; Hume, Cheryl L; Hapca, Adrian; Witham, Miles D

    2018-01-04

    Sarcopenia (the age-related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia. Promising preliminary data exist from small studies for both interventions, but neither has yet been tested in adequately powered randomised trials in patients with sarcopenia. Leucine and ACE inhibitors in sarcopenia (LACE) is a multicentre, masked, placebo-controlled, 2 × 2 factorial randomised trial evaluating the efficacy of leucine and perindopril (angiotensin converting enzyme inhibitor (ACEi)) in patients with sarcopenia. The trial will recruit 440 patients from primary and secondary care services across the UK. Male and female patients aged 70 years and over with sarcopenia as defined by the European Working Group on Sarcopenia (based on low total skeletal muscle mass on bioimpedance analysis and either low gait speed or low handgrip strength) will be eligible for participation. Participants will be excluded if they have a contraindication to, or are already taking, an ACEi, angiotensin receptor blocker or leucine. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at all points between baseline and 12 months. Secondary outcomes include appendicular muscle mass measured using dual-energy X-ray absorptiometry, muscle strength, activities of daily living, quality of life, activity using pedometer step counts and falls. Participants, clinical teams, outcomes assessors and trial analysts are masked to treatment allocation. A panel of biomarkers including

  9. Differential effects of leucine and leucine-enriched whey protein on skeletal muscle protein synthesis in aged mice

    NARCIS (Netherlands)

    Dijk, Francina J.; Dijk, van Miriam; Walrand, Stéphane; Loon, van Luc J.C.; Norren, van Klaske; Luiking, Yvette C.

    2018-01-01

    Background & aims: It has been suggested that anabolic resistance, or a blunted protein synthetic response to anabolic stimuli, contributes to the failure of muscle mass maintenance in older adults. The amino acid leucine is one of the most prominent food-related anabolic stimuli. However, data

  10. Leucine kinetics from [2H3]- and [13C]leucine infused simultaneously by gut and vein

    International Nuclear Information System (INIS)

    Hoerr, R.A.; Matthews, D.E.; Bier, D.M.; Young, V.R.

    1991-01-01

    In amino acid tracer kinetic studies of the fed state, ingested amino acid may be taken up during its initial transit through splanchnic tissues and thus not enter the plasma compartment where tracer is infused. To investigate this possibility, adult human subjects received simultaneous intravenous (iv) and intragastric (ig) leucine tracer infusions, first during a postabsorptive (PA) 4-h primed continuous ig infusion of L-[1-13C]-leucine and L-[5,5,5-2H3]leucine iv, followed on a separate day by a fed infusion, in which an ig infusion of a liquid formula was started 2 h before the tracer infusion and continued throughout the tracer study. Subjects were accustomed to a constant experimental diet supplying 1.5 g protein.kg-1.day-1 and 41-45 kcal.kg-1.day-1 for 7 and 12 days before the PA and fed studies, respectively. For the PA study, plasma enrichment for the ig tracer was 3.34 +/- 0.27 (SE) mol + excess and for the iv tracer it was 4.18 +/- 0.10 (P less than 0.02). Enrichments of alpha-keto-isocaproic acid (KIC) were 3.24 +/- 0.16 (ig) and 3.02 +/- 0.14 (iv), respectively [not significant (NS)]. For the fed study, plasma leucine enrichment for the ig tracer was 2.15 +/- 0.14 and for the iv tracer was 2.84 +/- 0.09 (P less than 0.02). KIC enrichments were 2.02 +/- 0.08 (ig) and 2.24 +/- 0.08 (iv), respectively (NS). In the PA study, the ratio of the plasma leucine enrichments for the ig and iv tracers was 0.80 +/- 0.06 and in the fed experiment, 0.76 +/- 0.05, respectively

  11. Leucine kinetics from (2H3)- and ( sup 13 C)leucine infused simultaneously by gut and vein

    Energy Technology Data Exchange (ETDEWEB)

    Hoerr, R.A.; Matthews, D.E.; Bier, D.M.; Young, V.R. (Massachusetts Institute of Technology, Cambridge (USA))

    1991-01-01

    In amino acid tracer kinetic studies of the fed state, ingested amino acid may be taken up during its initial transit through splanchnic tissues and thus not enter the plasma compartment where tracer is infused. To investigate this possibility, adult human subjects received simultaneous intravenous (iv) and intragastric (ig) leucine tracer infusions, first during a postabsorptive (PA) 4-h primed continuous ig infusion of L-(1-13C)-leucine and L-(5,5,5-2H3)leucine iv, followed on a separate day by a fed infusion, in which an ig infusion of a liquid formula was started 2 h before the tracer infusion and continued throughout the tracer study. Subjects were accustomed to a constant experimental diet supplying 1.5 g protein.kg-1.day-1 and 41-45 kcal.kg-1.day-1 for 7 and 12 days before the PA and fed studies, respectively. For the PA study, plasma enrichment for the ig tracer was 3.34 +/- 0.27 (SE) mol + excess and for the iv tracer it was 4.18 +/- 0.10 (P less than 0.02). Enrichments of alpha-keto-isocaproic acid (KIC) were 3.24 +/- 0.16 (ig) and 3.02 +/- 0.14 (iv), respectively (not significant (NS)). For the fed study, plasma leucine enrichment for the ig tracer was 2.15 +/- 0.14 and for the iv tracer was 2.84 +/- 0.09 (P less than 0.02). KIC enrichments were 2.02 +/- 0.08 (ig) and 2.24 +/- 0.08 (iv), respectively (NS). In the PA study, the ratio of the plasma leucine enrichments for the ig and iv tracers was 0.80 +/- 0.06 and in the fed experiment, 0.76 +/- 0.05, respectively.

  12. Can leucine supplementation attenuate muscle atrophy? A literature review

    OpenAIRE

    Amaral, Rafael Bruno; Martins, Carlos Eduardo Carvalho; Lancha Junior, Antonio Herbert; Painelli, Vitor de Salles

    2015-01-01

    Abstract Currently, there has been new expectations in studying strategies with the potential to mitigate the skeletal muscle atrophy that characterizes conditions such as aging, disuse, cancer, and the use of certain medications. Among them, amino acid leucine has received special attention due to its potential to stimulate specific pathways of protein synthesis in skeletal muscle. Due to the wide spread use of this amino acid by the media, several studies have been aimed at investigating th...

  13. Identification and characterization of Paragonimus westermani leucine aminopeptidase.

    Science.gov (United States)

    Song, Su-Min; Park, Joon-Hyung; Kim, Jin; Kim, Suk-Il; Hong, Yeon-Chul; Kong, Hyun-Hee; Chung, Dong-Il

    2008-09-01

    Paragonimus westermani is a tissue-invading trematode parasite that causes inflammatory lung disease as well as systemic infections including cerebral invasion in carnivorous mammals. While aminopeptidases play important roles in trematodes in the catabolism of host hemoglobin, an essential source of nutrient for the parasite, little is known about aminopeptidase in Paragonimus. Presently, we isolated a cDNA encoding a 58 kDa P. westermani leucine aminopeptidase (PwLAP). Deduced amino acid sequence of PwLAP exhibited significant sequence homology with LAP from Schistosoma spp. and Fasciola hepatica. Biochemical analysis of the recombinant PwLAP protein demonstrated preferential substrate specificity for Leu-NHMec and inhibition by EDTA, 1,10-phenanthroline, and bestatin, which are conserved characteristics of the M17 family of leucine aminopeptidase. PwLAP exhibited relatively higher enzyme activity in the presence of Mn2+ compared to Schistosoma mansoni LAP. Based on the biochemical properties and immunohistochemical analysis, PwLAP is concluded to represent a leucine aminopeptidase. The enzyme is most likely responsible for the catabolism of host hemoglobin, and, hence, represents a potential target of Paragonimus chemotherapy.

  14. The Effect of Oral Leucine on Protein Metabolism in Adolescents with Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Wilson ThomasA

    2010-11-01

    Full Text Available Lack of insulin results in a catabolic state in subjects with insulin-dependent diabetes mellitus which is reversed by insulin treatment. Amino acid supply, especially branched chain amino acids such as leucine, enhances protein synthesis in both animal and human studies. This small study was undertaken to assess the acute effect of supplemental leucine on protein metabolism in adolescents with type 1 diabetes. L-[1-13C] Leucine was used to assess whole-body protein metabolism in six adolescent females (16–18 yrs with type 1 diabetes during consumption of a basal diet (containing 58 μmoles leucine/kg/h and the basal diet with supplemental leucine (232 μmoles leucine/kg/h. Net leucine balance was significantly higher with supplemental leucine ( μmoles leucine/kg body weight/hr than with the basal diet (, due to reduced protein degradation ( μmoles leucine/kg body weight/hr compared to the basal diet (, .

  15. Metabolism and acetylation contribute to leucine-mediated inhibition of cardiac glucose uptake.

    Science.gov (United States)

    Renguet, Edith; Ginion, Audrey; Gélinas, Roselle; Bultot, Laurent; Auquier, Julien; Robillard Frayne, Isabelle; Daneault, Caroline; Vanoverschelde, Jean-Louis; Des Rosiers, Christine; Hue, Louis; Horman, Sandrine; Beauloye, Christophe; Bertrand, Luc

    2017-08-01

    High plasma leucine levels strongly correlate with type 2 diabetes. Studies of muscle cells have suggested that leucine alters the insulin response for glucose transport by activating an insulin-negative feedback loop driven by the mammalian target of rapamycin/p70 ribosomal S6 kinase (mTOR/p70S6K) pathway. Here, we examined the molecular mechanism involved in leucine's action on cardiac glucose uptake. Leucine was indeed able to curb glucose uptake after insulin stimulation in both cultured cardiomyocytes and perfused hearts. Although leucine activated mTOR/p70S6K, the mTOR inhibitor rapamycin did not prevent leucine's inhibitory action on glucose uptake, ruling out the contribution of the insulin-negative feedback loop. α-Ketoisocaproate, the first metabolite of leucine catabolism, mimicked leucine's effect on glucose uptake. Incubation of cardiomyocytes with [ 13 C]leucine ascertained its metabolism to ketone bodies (KBs), which had a similar negative impact on insulin-stimulated glucose transport. Both leucine and KBs reduced glucose uptake by affecting translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Finally, we found that leucine elevated the global protein acetylation level. Pharmacological inhibition of lysine acetyltransferases counteracted this increase in protein acetylation and prevented leucine's inhibitory action on both glucose uptake and GLUT4 translocation. Taken together, these results indicate that leucine metabolism into KBs contributes to inhibition of cardiac glucose uptake by hampering the translocation of GLUT4-containing vesicles via acetylation. They offer new insights into the establishment of insulin resistance in the heart. NEW & NOTEWORTHY Catabolism of the branched-chain amino acid leucine into ketone bodies efficiently inhibits cardiac glucose uptake through decreased translocation of glucose transporter 4 to the plasma membrane. Leucine increases protein acetylation. Pharmacological inhibition of acetylation

  16. Comparison of the fates of ingested leucine and ingested 2-ketoisocaproate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Imura, K.; Walser, M. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1990-05-01

    We previously reported that the ratio, R, of 14C to 3H in the leucine of whole body protein, measured 6 h after ingestion of (3H)leucine and (1-14C)2-ketoisocaproate is equal to ratio of the dose of leucine to the dose of 2-ketoisocaproate (KIC) (on a leucine-free diet) required to achieve the same rate of growth. To determine whether R is dependent on the interval between injection and sampling, R was measured at intervals in purified whole body protein after oral injection of these isotopes in groups of rats; it was constant from 1 h onward for 1 wk, averaging 0.64 +/- 0.01 (means +/- SEM). Thus, the extent of incorporation into the leucine of whole body protein of ingested KIC remains close to 64% of the incorporation of ingested leucine administered as such simultaneously, from 1 h onward for at least 1 wk.

  17. L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase

    DEFF Research Database (Denmark)

    Knudsen, P; Kofod, Hans; Lernmark, A

    1983-01-01

    , a cloned rat islet tumor cell line. A twofold increase in islet glutamate dehydrogenase activity was induced by 5 mmol/liter L-leucine OMe, a larger effect than that of L-leucine (P less than 0.02), whereas L-arginine OMe had a small inhibitory effect. We conclude that L-leucine OMe is a potent stimulus...... of insulin secretion and that its effect on the beta-cells may be exerted by activating islet glutamate dehydrogenase....

  18. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    International Nuclear Information System (INIS)

    Ventrucci, Gislaine; Mello, Maria Alice Roston de; Gomes-Marcondes, Maria Cristina Cintra

    2002-01-01

    It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones

  19. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    Directory of Open Access Journals (Sweden)

    de Mello Maria

    2002-04-01

    Full Text Available Abstract Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein: pregnant (N, tumor-bearing (WN, pair-fed rats (Np. Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine: leucine (L, tumor-bearing (WL and pair-fed with leucine (Lp. Non pregnant rats (C, which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

  20. Acetone Formation in the Vibrio Family: a New Pathway for Bacterial Leucine Catabolism

    Science.gov (United States)

    Nemecek-Marshall, Michele; Wojciechowski, Cheryl; Wagner, William P.; Fall, Ray

    1999-01-01

    There is current interest in biological sources of acetone, a volatile organic compound that impacts atmospheric chemistry. Here, we determined that leucine-dependent acetone formation is widespread in the Vibrionaceae. Sixteen Vibrio isolates, two Listonella species, and two Photobacterium angustum isolates produced acetone in the presence of l-leucine. Shewanella isolates produced much less acetone. Growth of Vibrio splendidus and P. angustum in a fermentor with controlled aeration revealed that acetone was produced after a lag in late logarithmic or stationary phase of growth, depending on the medium, and was not derived from acetoacetate by nonenzymatic decarboxylation in the medium. l-Leucine, but not d-leucine, was converted to acetone with a stoichiometry of approximately 0.61 mol of acetone per mol of l-leucine. Testing various potential leucine catabolites as precursors of acetone showed that only α-ketoisocaproate was efficiently converted by whole cells to acetone. Acetone production was blocked by a nitrogen atmosphere but not by electron transport inhibitors, suggesting that an oxygen-dependent reaction is required for leucine catabolism. Metabolic labeling with deuterated (isopropyl-d7)-l-leucine revealed that the isopropyl carbons give rise to acetone with full retention of deuterium in each methyl group. These results suggest the operation of a new catabolic pathway for leucine in vibrios that is distinct from the 3-hydroxy-3-methylglutaryl-coenzyme A pathway seen in pseudomonads. PMID:10601206

  1. The Explicit Determinations Of Dual Plane Curves And Dual Helices In Terms Of Its Dual Curvature And Dual Torsion

    OpenAIRE

    Lee Jae Won; Choi Jin Ho; Jin Dae Ho

    2014-01-01

    In this paper, we give the explicit determinations of dual plane curves, general dual helices and dual slant helices in terms of its dual curvature and dual torsion as a fundamental theory of dual curves in a dual 3-space

  2. Dietary leucine requirement for juvenile large yellow croaker Pseudosciaena crocea (Richardson, 1846)

    Science.gov (United States)

    Li, Yan; Ai, Qinghui; Mai, Kangsen; Xu, Wei; Cheng, Zhenyan; He, Zhigang

    2010-12-01

    Dietary leucine requirement for juvenile large yellow croaker, Pseudosciaena crocea Richardson 1846 (initial body weight 6.0 g ± 0.1 g) was determined using dose-response method. Six isonitogenous (crude protein 43%) and isoenergetic (19 kJ g-1) practical diets containing six levels of leucine (Diets 1-6) ranging from 1.23% to 4.80% (dry matter) were made at about 0.7% increment of leucine. Equal amino acid nitrogen was maintained by replacing leucine with glutamic acid. Triplicate groups of 60 individuals were fed to apparent satiation by hand twice daily (05:00 and 17:30). The water temperature was 26-32°C, salinity 26-30 and dissolved oxygen approximately 7 mg L-1 during the experimental period. Final weight (FW) of large yellow croaker initially increased with increasing level of dietary leucine but then decreased at further higher level of leucine. The highest FW was obtained in fish fed diet with 3.30% Leucine (Diet 4). FW of fish fed the diet with 4.80% Leucine (Diet 6) was significantly lower than those fed Diet 4. However, no significant differences were observed between the other dietary treatments. Feed efficiency (FE) and whole body composition were independent of dietary leucine contents ( P > 0.05). The results indicated that leucine was essential for growth of juvenile large yellow croaker. On the basis of FW, the optimum dietary leucine requirement for juvenile large yellow croaker was estimated to be 2.92% of dry matter (6.79% of dietary protein).

  3. QCD Dual

    DEFF Research Database (Denmark)

    Sannino, Francesco

    2009-01-01

    We uncover a novel solution of the 't Hooft anomaly matching conditions for QCD. Interestingly in the perturbative regime the new gauge theory, if interpreted as a possible QCD dual, predicts the critical number of flavors above which QCD in the nonperturbative regime, develops an infrared stable...

  4. Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes

    Directory of Open Access Journals (Sweden)

    Chunzi Liang

    2014-01-01

    Full Text Available Previous studies from this laboratory demonstrate that dietary leucine protects against high fat diet-induced mitochondrial impairments and stimulates mitochondrial biogenesis and energy partitioning from adipocytes to muscle cells through SIRT1-mediated mechanisms. Moreover, β-hydroxy-β-methyl butyrate (HMB, a metabolite of leucine, has been reported to activate AMPK synergistically with resveratrol in C2C12 myotubes. Therefore, we hypothesize that leucine-induced activation of SIRT1 and AMPK is the central event that links the upregulated mitochondrial biogenesis and fatty acid oxidation in skeletal muscle. Thus, C2C12 myotubes were treated with leucine (0.5 mM, alanine (0.5 mM, valine (0.5 mM, EX527 (SIRT1 inhibitor, 25 μM, and Compound C (AMPK inhibitor, 25 μM alone or in combination to determine the roles of AMPK and SIRT1 in leucine-modulation of energy metabolism. Leucine significantly increased mitochondrial content, mitochondrial biogenesis-related genes expression, fatty acid oxidation, SIRT1 activity and gene expression, and AMPK phosphorylation in C2C12 myotubes compared to the controls, while EX527 and Compound C markedly attenuated these effects. Furthermore, leucine treatment for 24 hours resulted in time-dependent increases in cellular NAD+, SIRT1 activity, and p-AMPK level, with SIRT1 activation preceding that of AMPK, indicating that leucine activation of SIRT1, rather than AMPK, is the primary event.

  5. Kinetics and mechanism of oxidation of L-leucine by alkaline ...

    Indian Academy of Sciences (India)

    forms active sites of enzymes and helps in maintain- ing their proper conformation by keeping them in proper ionic states. So, oxidation of L-leucine may help in understanding some aspects of enzyme kinet- ics. Recent research has discovered that L-leucine acts in a unique way: it can help burn fat without burning muscle.

  6. Glutamate dehydrogenase contributes to leucine sensing in the regulation of autophagy

    NARCIS (Netherlands)

    Lorin, Séverine; Tol, Marc J.; Bauvy, Chantal; Strijland, Anneke; Poüs, Christian; Verhoeven, Arthur J.; Codogno, Patrice; Meijer, Alfred J.

    2013-01-01

    Amino acids, leucine in particular, are known to inhibit autophagy, at least in part by their ability to stimulate MTOR-mediated signaling. Evidence is presented showing that glutamate dehydrogenase, the central enzyme in amino acid catabolism, contributes to leucine sensing in the regulation of

  7. Effect of preeclampsia in the mother on the leucine metabolism in the newborn infant.

    NARCIS (Netherlands)

    Saenz De Pipaon Marcos, M.; Wattimena, D.J.; Beek, R.H. van; Lotgering, F.K.; Sauer, P.J.J.

    2002-01-01

    The leucine turnover in newborn infants is influenced by factors such as nutritional state and corticosteroid treatment. Little is known about maternal factors influencing the leucine turnover in the newborn. In order to approach the effect of preeclampsia in the mother on neonatal protein turnover,

  8. Effect of preeclampsia in the mother on the leucine metabolism in the newborn infant

    NARCIS (Netherlands)

    Marcos, MSD; Wattimena, DJL; Van Beek, RHT; Lotgering, FK; Sauer, PJJ

    2002-01-01

    The leucine turnover in newborn infants is influenced by factors such as nutritional state and corticosteroid treatment. Little is known about maternal factors influencing the leucine turnover in the newborn. In order to approach the effect of preeclampsia in the mother on neonatal protein turnover,

  9. SIRT4 Is a Lysine Deacylase that Controls Leucine Metabolism and Insulin Secretion

    DEFF Research Database (Denmark)

    Anderson, Kristin A; Huynh, Frank K; Fisher-Wellman, Kelsey

    2017-01-01

    in leucine oxidation, and we show a primary role for SIRT4 in controlling this pathway in mice. Furthermore, we find that dysregulated leucine metabolism in SIRT4KO mice leads to elevated basal and stimulated insulin secretion, which progressively develops into glucose intolerance and insulin resistance...

  10. Self Assembly of Poly(ethylene oxide-b-lysine-b-leucine) in Dilute Aqueous Solution

    Science.gov (United States)

    Machado, Craig; Barnes, Brooke; Bentz, Kyle; Savin, Daniel

    In general, the self-assembly of amphiphilic block polymers is dictated by the balance of three thermodynamic parameters. When one or more of the blocks exhibits a specific interaction, this balance can be shifted. In this study, the self-assembly of block polypeptides in dilute aqueous solution is examined via light scattering and transmission electron microscopy (TEM). Triblock polymers of poly(ethylene oxide-b-lysine-b-leucine) (PEO-Lys-Leu) with varying lengths of the poly(leucine) block were synthesized in order to study the effect of poly(leucine) block length on assembly behavior. It was observed that the presence of the leucine block facilitates formation of elongated structures such as nanotubes, hydrogels and hierarchical fractal assemblies. In all cases, radius of gyration (Rg) was greater than the hydrodynamic radius (Rh). A clear increase in size of the aggregates can be seen with increasing degree of polymerization of the poly(leucine) block.

  11. Leucine-based receptor sorting motifs are dependent on the spacing relative to the plasma membrane

    DEFF Research Database (Denmark)

    Geisler, C; Dietrich, J; Nielsen, B L

    1998-01-01

    Many integral membrane proteins contain leucine-based motifs within their cytoplasmic domains that mediate internalization and intracellular sorting. Two types of leucine-based motifs have been identified. One type is dependent on phosphorylation, whereas the other type, which includes an acidic...... amino acid, is constitutively active. In this study, we have investigated how the spacing relative to the plasma membrane affects the function of both types of leucine-based motifs. For phosphorylation-dependent leucine-based motifs, a minimal spacing of 7 residues between the plasma membrane...... and the phospho-acceptor was required for phosphorylation and thereby activation of the motifs. For constitutively active leucine-based motifs, a minimal spacing of 6 residues between the plasma membrane and the acidic residue was required for optimal activity of the motifs. In addition, we found that the acidic...

  12. Leucine improves protein nutritional status and regulates hepatic lipid metabolism in calorie-restricted rats.

    Science.gov (United States)

    Pedroso, João Alfredo B; Nishimura, Luciana Sigueta; de Matos-Neto, Emídio Marques; Donato, Jose; Tirapegui, Julio

    2014-06-01

    Several studies have highlighted the potential of leucine supplementation for the treatment of metabolic diseases including type 2 diabetes and obesity. Caloric restriction is a common approach to improve the health in diabetic and obese subjects. However, very few studies assessed the effects of leucine supplementation in calorie-restricted animals. Rats were subjected to a 30% calorie-restricted diet for 6 weeks to study the effects of leucine supplementation on protein status markers and lipid metabolism. Caloric restriction reduced the body weight. However, increased leucine intake preserved body lean mass and protein mass and improved protein anabolism as indicated by the increased circulating levels of albumin and insulin-like growth factor-1 (IGF-1), and the liver expression of albumin and IGF-1 messenger RNA. Leucine supplementation also increased the circulating levels of interleukin-6 and leptin but did not affect the tumour necrosis factor-α and monocyte chemotactic protein-1 concentrations. Ketone bodies were increased in rats consuming a leucine-rich diet, but we observed no changes in cholesterol or triglycerides concentrations. Caloric restriction reduced the liver expression of peroxisome proliferator activated receptor-α and glucose-6-phosphatase, whereas leucine supplementation increased the liver expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA) reductase and sterol regulatory element-binding transcription factor 1. A leucine-rich diet during caloric restriction preserved whole body protein mass and improved markers of protein anabolism. In addition, leucine modulated the hepatic lipid metabolism. These results indicate that increased leucine intake may be useful in preventing excessive protein waste in conditions of large weight loss. Copyright © 2013 John Wiley & Sons, Ltd.

  13. Dual Entwining Structures and Dual Entwined Modules

    OpenAIRE

    Abuhlail, Jawad Y.

    2003-01-01

    In this note we introduce and investigate the concepts of dual entwining structures and dual entwined modules. This generalizes the concepts of dual Doi-Koppinen structures and dual Doi-Koppinen modules introduced (in the infinite case over rings) by the author is his dissertation.

  14. L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase

    DEFF Research Database (Denmark)

    Knudsen, P; Kofod, Hans; Lernmark, A

    1983-01-01

    Column perifusion of collagenase-isolated mouse pancreatic islets was used to study the dynamics of insulin release in experiments lasting for several hours. The methyl esters of L-leucine and L-arginine were synthesized. Whereas L-arginine methyl ester (L-arginine OMe) had no effect, L-leucine OMe...... stimulated the release of insulin. The effect of L-leucine OMe was maximal at 5 mmol/liter. Whereas the Km for glucose-stimulated insulin release was unaffected by 1 mmol/liter L-leucine OMe, the maximal release of D-glucose was increased by the amino acid derivative that appeared more effective than L-leucine....... L-Leucine OMe was also a potent stimulus of insulin release from the perfused mouse pancreas. In the presence of 10 mmol/liter L-glutamine, 1 mmol/liter L-leucine OMe induced a 50- to 75-fold increase in insulin release. A similar stimulatory effect was also observed in column-perifused RIN 5F cells...

  15. Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

    Directory of Open Access Journals (Sweden)

    Marcelo G. Pereira

    2014-09-01

    Full Text Available This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA. Young male Wistar rats were supplemented with leucine (1.35 g/kg per day; then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA of regenerating myofibers (p > 0.05 from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I and Smad2/3 in regenerating muscles (p < 0.05. Leucine also reduced neonatal myosin heavy chain (MyHC-n (p < 0.05, increased adult MyHC-II expression (p < 0.05 and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05. Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.

  16. Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro.

    Science.gov (United States)

    Martin, Neil R W; Turner, Mark C; Farrington, Robert; Player, Darren J; Lewis, Mark P

    2017-10-01

    The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co-incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly-controlled investigations into nutritional regulation of muscle physiology. © 2017 The Authors. Journal of Cellular Physiology Published by wiley periodicals, Inc.

  17. Effect of burn and first-pass splanchnic leucine extraction on protein kinetics in rats

    International Nuclear Information System (INIS)

    Karlstad, M.D.; DeMichele, S.J.; Istfan, N.; Blackburn, G.L.; Bistrian, B.R.

    1988-01-01

    The effects of burn and first-pass splanchnic leucine extraction (FPE) on protein kinetics and energy expenditure were assessed by measuring O 2 consumption, CO 2 production, nitrogen balance, leucine kinetics, and tissue fractional protein synthetic rates (FSR-%/day) in enterally fed rats. Anesthetized male rats (200 g) were scalded on their dorsum with boiling water (25-30% body surface area) and enterally fed isovolemic diets that provided 60 kcal/day and 2.4 g of amino acids/day for 3 days. Controls were not burned. An intravenous or intragastric infusion of L-[1- 14 C]leucine was used to assess protein kinetics on day 3. FPE was taken as the ratio of intragastric to intravenous plasma leucine specific activity. There was a 69% reduction in cumulative nitrogen balance (P less than 0.001) and a 17-19% increase in leucine oxidation (P less than 0.05) and total energy expenditure (P less than 0.01) in burned rats. A 15% decrease in plasma leucine clearance (P less than 0.05) was accompanied by a 20% increase in plasma [leucine] (P less than 0.01) in burned rats. Burn decreased rectus muscle FSR from 5.0 +/- 0.4 to 3.5 +/- 0.5 (P less than 0.05) and increased liver FSR from 19.0 +/- 0.5 to 39.2 +/- 3.4 (P less than 0.01). First pass extraction of dietary leucine by the splanchnic bed was 8% in controls and 26% in burned rats. Leucine kinetics corrected for FPE showed increased protein degradation with burn that was not evident without FPE correction. This hypermetabolic burn model can be useful in the design of enteral diets that optimize rates of protein synthesis and degradation

  18. Reduction in plasma leucine after sprint exercise is greater in males than in females

    DEFF Research Database (Denmark)

    Esbjörnsson, M; Rooyackers, O; Norman, B

    2012-01-01

    There is a pronounced gender difference in the accumulation of plasma ammonia after sprint exercise. Ammonia is a key intermediate in amino acid metabolism, which implies that gender-related differences in plasma and muscle amino acid concentrations after sprint exercise exist. To study this, thr...... bouts of 30-s sprint exercise were performed by healthy females (n=8) and males (n=6). Blood leucine and muscle leucine were collected over the exercise period. Basal arterial plasma and skeletal muscle leucine were 40% higher in males than females (P...

  19. Radiobiological half-lives for carbon-14 and hydrogen-3 leucine in man

    International Nuclear Information System (INIS)

    Classic, K.L.; Schwenk, W.F.; Haymond, M.W.

    1986-01-01

    In vivo estimates of protein metabolism in many are often made by oral or intravenous administration of leucine or its ∼-ketoacid, ∼-ketoisocaproate, labeled with 14 C or 3 H. Previous estimates of radiation dose from such tracers have been based on the measurement of 14 CO 2 in breath. Using measurements of the decay of 3 H or 14 C leucine from plasma proteins, longer biological half-lives for these compounds were obtained. The estimated total-body radiation absorbed dose is 0.97 mrad/uCi for [1- 14 C]KIC (or [1- 14 C]leucine) and 0.11 mrad/ + Ci for ]4,5- 3 H]leucine (or [ 3 H]KIC). Assuming administered doses of 100 μCi each, the total-body radiation absorbed dose is still well within the limits set by the FDA for Radioactive Drug Research Committees. 12 references, 3 figures, 3 tables

  20. Isovalerianeacidæmi--en sjælden og alvorlig defekt i nedbrydningen af leucin

    DEFF Research Database (Denmark)

    Lund, Ann-Britt Kiholm; Lund, Allan

    2011-01-01

    Isovaleric acidaemia (IVA) is an organic acidemia caused by deficient metabolism of the essential amino acid leucine. We describe the biochemistry, diagnostics, and treatment of IVA, and present the known Danish patients....

  1. Glucocorticoid Induced Leucine Zipper inhibits apoptosis of cardiomyocytes by doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar, David; Strom, Joshua; Chen, Qin M., E-mail: qchen@email.arizona.edu

    2014-04-01

    Doxorubicin (Dox) is an indispensable chemotherapeutic agent for the treatment of various forms of neoplasia such as lung, breast, ovarian, and bladder cancers. Cardiotoxicity is a major concern for patients receiving Dox therapy. Previous work from our laboratory indicated that glucocorticoids (GCs) alleviate Dox-induced apoptosis in cardiomyocytes. Here we have found Glucocorticoid-Induced Leucine Zipper (GILZ) to be a mediator of GC-induced cytoprotection. GILZ was found to be induced in cardiomyocytes by GC treatment. Knocking down of GILZ using siRNA resulted in cancelation of GC-induced cytoprotection against apoptosis by Dox treatment. Overexpressing GILZ by transfection was able to protect cells from apoptosis induced by Dox as measured by caspase activation, Annexin V binding and morphologic changes. Western blot analyses indicate that GILZ overexpression prevented cytochrome c release from mitochondria and cleavage of caspase-3. When bcl-2 family proteins were examined, we found that GILZ overexpression causes induction of the pro-survival protein Bcl-xL. Since siRNA against Bcl-xL reverses GC induced cytoprotection, Bcl-xL induction represents an important event in GILZ-induced cytoprotection. Our data suggest that GILZ functions as a cytoprotective gene in cardiomyocytes. - Highlights: • Corticosteroids act as a cytoprotective agent in cardiomyocytes • Corticosteroids induce GILZ expression in cardiomyocytes • Elevated GILZ results in resistance against apoptosis induced by doxorubicin • GILZ induces Bcl-xL protein without inducing Bcl-xL mRNA.

  2. Structural basis for leucine-induced allosteric activation of glutamate dehydrogenase.

    Science.gov (United States)

    Tomita, Takeo; Kuzuyama, Tomohisa; Nishiyama, Makoto

    2011-10-28

    Glutamate dehydrogenase (GDH) catalyzes reversible conversion between glutamate and 2-oxoglutarate using NAD(P)(H) as a coenzyme. Although mammalian GDH is regulated by GTP through the antenna domain, little is known about the mechanism of allosteric activation by leucine. An extremely thermophilic bacterium, Thermus thermophilus, possesses GDH with a unique subunit configuration composed of two different subunits, GdhA (regulatory subunit) and GdhB (catalytic subunit). T. thermophilus GDH is unique in that the enzyme is subject to allosteric activation by leucine. To elucidate the structural basis for leucine-induced allosteric activation of GDH, we determined the crystal structures of the GdhB-Glu and GdhA-GdhB-Leu complexes at 2.1 and 2.6 Å resolution, respectively. The GdhB-Glu complex is a hexamer that binds 12 glutamate molecules: six molecules are bound at the substrate-binding sites, and the remaining six are bound at subunit interfaces, each composed of three subunits. The GdhA-GdhB-Leu complex is crystallized as a heterohexamer composed of four GdhA subunits and two GdhB subunits. In this complex, six leucine molecules are bound at subunit interfaces identified as glutamate-binding sites in the GdhB-Glu complex. Consistent with the structure, replacement of the amino acid residues of T. thermophilus GDH responsible for leucine binding made T. thermophilus GDH insensitive to leucine. Equivalent amino acid replacement caused a similar loss of sensitivity to leucine in human GDH2, suggesting that human GDH2 also uses the same allosteric site for regulation by leucine.

  3. Isovalerianeacidæmi--en sjælden og alvorlig defekt i nedbrydningen af leucin

    DEFF Research Database (Denmark)

    Lund, Ann-Britt Kiholm; Lund, Allan

    2011-01-01

    Isovaleric acidaemia (IVA) is an organic acidemia caused by deficient metabolism of the essential amino acid leucine. We describe the biochemistry, diagnostics, and treatment of IVA, and present the known Danish patients.......Isovaleric acidaemia (IVA) is an organic acidemia caused by deficient metabolism of the essential amino acid leucine. We describe the biochemistry, diagnostics, and treatment of IVA, and present the known Danish patients....

  4. Some properties of dual and approximate dual of fusion frames

    OpenAIRE

    Arefijamaal, Ali Akbar; Neyshaburi, Fahimeh Arabyani

    2016-01-01

    In this paper we extend the notion of approximate dual to fusion frames and present some approaches to obtain dual and approximate alternate dual fusion frames. Also, we study the stability of dual and approximate alternate dual fusion frames.

  5. Metabolic Mechanism for l-Leucine-Induced Metabolome To Eliminate Streptococcus iniae.

    Science.gov (United States)

    Du, Chao-Chao; Yang, Man-Jun; Li, Min-Yi; Yang, Jun; Peng, Bo; Li, Hui; Peng, Xuan-Xian

    2017-05-05

    Crucial metabolites that modulate hosts' metabolome to eliminate bacterial pathogens have been documented, but the metabolic mechanisms are largely unknown. The present study explores the metabolic mechanism for l-leucine-induced metabolome to eliminate Streptococcus iniae in tilapia. GC-MS-based metabolomics was used to investigate the tilapia liver metabolic profile in the presence of exogenous l-leucine. Thirty-seven metabolites of differential abundance were determined, and 11 metabolic pathways were enriched. Pattern recognition analysis identified serine and proline as crucial metabolites, which are the two metabolites identified in survived tilapias during S. iniae infection, suggesting that the two metabolites play crucial roles in l-leucine-induced elimination of the pathogen by the host. Exogenous l-serine reduces the mortality of tilapias infected by S. iniae, providing a robust proof supporting the conclusion. Furthermore, exogenous l-serine elevates expression of genes IL-1β and IL-8 in tilapia spleen, but not TNFα, CXCR4 and Mx, suggesting that the metabolite promotes a phagocytosis role of macrophages, which is consistent with the finding that l-leucine promotes macrophages to kill both Gram-positive and Gram-negative bacterial pathogens. Therefore, the ability of phagocytosis enhanced by exogenous l-leucine is partly attributed to elevation of l-serine. These results demonstrate a metabolic mechanism by which exogenous l-leucine modulates tilapias' metabolome to enhance innate immunity and eliminate pathogens.

  6. Nutritional efficiency of alpha-ketoisocaproate relative to leucine, assessed isotopically

    Energy Technology Data Exchange (ETDEWEB)

    Kang, C.W.; Walser, M.

    1985-10-01

    The efficiency of alpha-ketoisocaproate as a dietary substitute for leucine was assessed in rats by two techniques: first, the minimal dose of alpha-ketoisocaproate required, as a supplement to a leucine-free diet, to achieve a growth rate as great as animals receiving leucine was found to be between 2.2 and 4.4 times larger. Therefore the nutritional efficiency of alpha-ketoisocaproate lies between 0.23 and 0.46. Second, alpha-(1- UC)-ketoisocaproate and (TH)leucine were administered orally and the ratio of UC/TH incorporated into the leucine of whole-body protein and fibrin was measured. This ratio, divided by the ratio UC/TH injected, was the same in fibrin as in whole-body protein and averaged 0.39. Thus both techniques yield the same value, within the error of measurement, for the relative nutritional efficiency of alpha-ketoisocaproate. The authors also found that alpha-ketoisocaproate feeding at varying dosage did not alter this ratio in whole-body protein, suggesting that neither wide variations in growth rate nor exposure for 10 days to alpha-ketoisocaproate alters the relative rates of utilization (or oxidation) of alpha-ketoisocaproate vs. leucine.

  7. Leucine nutrition in animals and humans: mTOR signaling and beyond.

    Science.gov (United States)

    Li, Fengna; Yin, Yulong; Tan, Bie; Kong, Xiangfeng; Wu, Guoyao

    2011-11-01

    Macronutrients, such as protein or amino acid, not only supply calories but some components may also play as signaling molecules to affect feeding behavior, energy balance, and fuel efficiency. Leucine, a branched-chain amino acid is a good example. After structural roles are satisfied, the ability of leucine to function as signal and oxidative substrate is based on a sufficient intracellular concentration. Therefore, leucine level must be sufficiently high to play the signaling and metabolic roles. Leucine is not only a substrate for protein synthesis of skeletal muscle, but also plays more roles beyond that. Leucine activates signaling factor of mammalian target of rapamycin (mTOR) to promote protein synthesis in skeletal muscle and in adipose tissue. It is also a major regulator of the mTOR sensitive response of food intake to high protein diet. Meanwhile, leucine regulates blood glucose level by promoting gluconeogenesis and aids in the retention of lean mass in a hypocaloric state. It is beneficial to animal nutrition and clinical application and extrapolation to humans.

  8. How to find a leucine in a haystack? Structure, ligand recognition and regulation of leucine-aspartic acid (LD) motifs

    KAUST Repository

    Alam, Tanvir

    2014-05-29

    LD motifs (leucine-aspartic acidmotifs) are short helical protein-protein interaction motifs that have emerged as key players in connecting cell adhesion with cell motility and survival. LD motifs are required for embryogenesis, wound healing and the evolution of multicellularity. LD motifs also play roles in disease, such as in cancer metastasis or viral infection. First described in the paxillin family of scaffolding proteins, LD motifs and similar acidic LXXLL interaction motifs have been discovered in several other proteins, whereas 16 proteins have been reported to contain LDBDs (LD motif-binding domains). Collectively, structural and functional analyses have revealed a surprising multivalency in LD motif interactions and a wide diversity in LDBD architectures. In the present review, we summarize the molecular basis for function, regulation and selectivity of LD motif interactions that has emerged from more than a decade of research. This overview highlights the intricate multi-level regulation and the inherently noisy and heterogeneous nature of signalling through short protein-protein interaction motifs. © 2014 Biochemical Society.

  9. Similar effects of leucine rich and regular dairy products on muscle mass and functions of older polymyalgia rheumatica patients: a randomized crossover trial.

    Science.gov (United States)

    Björkman, M P; Pilvi, T K; Kekkonen, R A; Korpela, R; Tilvis, R S

    2011-06-01

    Leucine-rich milk and whey proteins have been suggested for prevention of age related loss of muscle mass and strength i.e. sarcopenia. The effects of milk protein supplementation and low intensity home based physical exercise on body composition and muscle functions were investigated. A randomized double blind crossover trial. Community dwelling members of Helsinki rheumatoid association. Older people (N=47, mean age 69.5 years) suffering from polymyalgia rheumatica. Patients performed as many stand ups as possible twice a day after which they ingested a regular (Control) or a whey protein enriched dairy product with high leucine content (Test). The 8-week intervention periods were separated by a 4-week wash-out. Body composition was measured by dual x-ray absorptiometry and muscle functions by hand grip strength, force platform countermovement jump performance, chair stand test, and walking speed. The 16-week home-based post-exercise supplementation resulted in a 1.8% increase (p = 0.052) in lower limb muscle mass. Walking speed (+5.3%, p = 0.007) and chair stand test performance (-12.2 %, p products prevent or treat age-associated sarcopenia and whether they are superior to the present commercial milk products.

  10. Aminotransferases and Leucine Aminopeptidase Activity in Blood Plasma of Chickens

    International Nuclear Information System (INIS)

    Kraljevic, P.; Stojevic, Z.; Milinkovic-Tur, S.; Simpraga, M.; Miljanic, S.

    1998-01-01

    It has been reported that irradiation of mammals by gama-rays cause increase of some enzyme activity in their blood plasma (Miller and Gates 1949; Milch and Albaum 1959; Hughes 1958; Miholjcic et al. 1979). In our previous papers (Kraljevic et al., 1982; Kraljevic and Emanovic 1993) it has been shown that activities of some enzymes in the blood plasma of chickens after an intramuscular injection of radioactive isotope 32 P. In this paper an attempt has been made to investigate the influence of gamma-ray irradiation of the whole body of chickens upon activity of some enzymes in their blood plasma. We also wanted to investigate whether the activity of aspartate-aminotransferase (AST), alanine aminotransferase (ALT) and leucine-aminopeptidase (LAP) may serve as an additional test for functional liver damage in chickens caused by gamma-ray. Fifty day old hybrid male chickens of heavy Jata breeds were irradiated by gamma-ray in the dose of 7,23±0,95 Gy. Blood samples were taken from the wing vein on days 1, 3, 5, 7, 9 and 15 after irradiation. Activity of AST, ALT, and LAP in the blood plasma were determined spectrophotometrically using Boehringer Mannheim GmbH optimized kits. At the end of the experiment all birds were sacrificed and, as well as died birds were photomorphologically and histologically investigated. The obtained results showed decrease of activity of all three enzymes during the whole period of investigation, but significant decrease showed only AST and LAP. It seems that both enzymes may serve as additional test for functional liver damage in chickens by external gamma-rays. (author)

  11. Distribution and Evolution of Yersinia Leucine-Rich Repeat Proteins

    Science.gov (United States)

    Hu, Yueming; Huang, He; Hui, Xinjie; Cheng, Xi; White, Aaron P.

    2016-01-01

    Leucine-rich repeat (LRR) proteins are widely distributed in bacteria, playing important roles in various protein-protein interaction processes. In Yersinia, the well-characterized type III secreted effector YopM also belongs to the LRR protein family and is encoded by virulence plasmids. However, little has been known about other LRR members encoded by Yersinia genomes or their evolution. In this study, the Yersinia LRR proteins were comprehensively screened, categorized, and compared. The LRR proteins encoded by chromosomes (LRR1 proteins) appeared to be more similar to each other and different from those encoded by plasmids (LRR2 proteins) with regard to repeat-unit length, amino acid composition profile, and gene expression regulation circuits. LRR1 proteins were also different from LRR2 proteins in that the LRR1 proteins contained an E3 ligase domain (NEL domain) in the C-terminal region or an NEL domain-encoding nucleotide relic in flanking genomic sequences. The LRR1 protein-encoding genes (LRR1 genes) varied dramatically and were categorized into 4 subgroups (a to d), with the LRR1a to -c genes evolving from the same ancestor and LRR1d genes evolving from another ancestor. The consensus and ancestor repeat-unit sequences were inferred for different LRR1 protein subgroups by use of a maximum parsimony modeling strategy. Structural modeling disclosed very similar repeat-unit structures between LRR1 and LRR2 proteins despite the different unit lengths and amino acid compositions. Structural constraints may serve as the driving force to explain the observed mutations in the LRR regions. This study suggests that there may be functional variation and lays the foundation for future experiments investigating the functions of the chromosomally encoded LRR proteins of Yersinia. PMID:27217422

  12. Role and metabolism of free leucine in skeletal muscle in protein sparing action of dietary carbohydrate and fat

    International Nuclear Information System (INIS)

    Nakano, Kiwao; Ishikawa, Tamotsu

    1977-01-01

    Feeding rats with either a carbohydrate meal or a fat meal to the previously fasted rats caused significant decrease in urinary output of urea and total nitrogen. The content of free leucine in skeletal muscle decreased in the rats fed either a carbohydrate meal or a fat meal. Feeding of either a carbohydrate meal or a fat meal stimulated incorporation of L-leucine-1- 14 C into protein fraction of skeletal muscle and reduced its oxidation to 14 CO 2 . These results suggest that the metabolism of leucine is under nutritional regulation and that the decrease in content of free leucine in skeletal muscle might be caused by enhanced reutilization of leucine into protein by the feeding of a carbohydrate meal or a fat meal. The role of free leucine in skeletal muscle as a regulator of protein turnover in the tissue are discussed in relation to the metabolism of this branched chain amino acid. (auth.)

  13. Over-Expression of Cysteine Leucine Rich Protein Is Related to SAG Resistance in Clinical Isolates of Leishmania donovani.

    Science.gov (United States)

    Das, Sanchita; Shah, Priyanka; Tandon, Rati; Yadav, Narendra Kumar; Sahasrabuddhe, Amogh A; Sundar, Shyam; Siddiqi, Mohammad Imran; Dube, Anuradha

    2015-08-01

    Resistance emergence against antileishmanial drugs, particularly Sodium Antimony Gluconate (SAG) has severely hampered the therapeutic strategy against visceral leishmaniasis, the mechanism of resistance being indistinguishable. Cysteine leucine rich protein (CLrP), was recognized as one of the overexpressed proteins in resistant isolates, as observed in differential proteomics between sensitive and resistant isolates of L. donovani. The present study deals with the characterization of CLrP and for its possible connection with SAG resistance. In pursuance of deciphering the role of CLrP in SAG resistance, gene was cloned, over-expressed in E. coli system and thereafter antibody was raised. The expression profile of CLrP and was found to be over-expressed in SAG resistant clinical isolates of L. donovani as compared to SAG sensitive ones when investigated by real-time PCR and western blotting. CLrP has been characterized through bioinformatics, immunoblotting and immunolocalization analysis, which reveals its post-translational modification along with its dual existence in the nucleus as well as in the membrane of the parasite. Further investigation using a ChIP assay confirmed its DNA binding potential. Over-expression of CLrP in sensitive isolate of L. donovani significantly decreased its responsiveness to SAG (SbV and SbIII) and a shift towards the resistant mode was observed. Further, a significant increase in its infectivity in murine macrophages has been observed. The study reports the differential expression of CLrP in SAG sensitive and resistant isolates of L. donovani. Functional intricacy of CLrP increases with dual localization, glycosylation and DNA binding potential of the protein. Further over-expressing CLrP in sensitive isolate of L. donovani shows significantly decreased sensitivity towards SAG and increased infectivity as well, thus assisting the parasite in securing a safe niche. Results indicates the possible contribution of CLrP to antimonial

  14. Reviewing the Effects of l-Leucine Supplementation in the Regulation of Food Intake, Energy Balance, and Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    João A.B. Pedroso

    2015-05-01

    Full Text Available Leucine is a well-known activator of the mammalian target of rapamycin (mTOR. Because mTOR signaling regulates several aspects of metabolism, the potential of leucine as a dietary supplement for treating obesity and diabetes mellitus has been investigated. The objective of the present review was to summarize and discuss the available evidence regarding the mechanisms and the effects of leucine supplementation on the regulation of food intake, energy balance, and glucose homeostasis. Based on the available evidence, we conclude that although central leucine injection decreases food intake, this effect is not well reproduced when leucine is provided as a dietary supplement. Consequently, no robust evidence indicates that oral leucine supplementation significantly affects food intake, although several studies have shown that leucine supplementation may help to decrease body adiposity in specific conditions. However, more studies are necessary to assess the effects of leucine supplementation in already-obese subjects. Finally, although several studies have found that leucine supplementation improves glucose homeostasis, the underlying mechanisms involved in these potential beneficial effects remain unknown and may be partially dependent on weight loss.

  15. Leucine Differentially Regulates Gene-Specific Translation in Mouse Skeletal Muscle.

    Science.gov (United States)

    Drummond, Micah J; Reidy, Paul T; Baird, Lisa M; Dalley, Brian K; Howard, Michael T

    2017-09-01

    Background: Amino acids, especially leucine, are particularly effective in promoting protein synthesis. Leucine is known to increase the rate of protein synthesis in skeletal muscle through the mechanistic target of rapamycin complex 1-dependent, as well as -independent, signaling pathways. However, the overall translation program is poorly defined, and it is unknown how the activation of these pathways differentially controls the translation of specific mRNAs. Objective: Ribosome profiling and RNA sequencing were used to precisely define the translational program activated by an acute oral dose of leucine. Methods: Adult male C57BL/6 mice were deprived of food overnight before the delivery of an acute dose of l-leucine (9.4 mg) ( n = 6) or vehicle ( n = 5) and tissues collected 30 min later. Ribosome footprints and total RNA were isolated and subjected to deep sequencing. Changes in gene-specific mRNA abundance and ribosome occupancy were determined between the leucine-treated and control groups by aligning sequence reads to Reference Sequence database mRNAs and applying statistical features of the Bioconductor package edgeR. Results: Our data revealed mRNA features that confer translational control of skeletal muscle mRNAs in response to an acute dose of leucine. The subset of skeletal muscle mRNAs that are activated consists largely of terminal oligopyrimidine mRNAs (false discovery rate: translation had 5' untranslated regions with increased length. Only the small nuclear RNAs, which are required for ribosome biogenesis, were significantly altered in RNA abundance. The inferred functional translational program activated by dietary leucine includes increased protein synthesis capacity and energy metabolism, upregulation of sarcomere-binding proteins, modulation of circadian rhythm, and suppression of select immune components. Conclusions: These results clarify the translation program acutely stimulated by leucine in mouse skeletal muscle and establish new

  16. Infusion and sampling site effects on two-pool model estimates of leucine metabolism

    International Nuclear Information System (INIS)

    Helland, S.J.; Grisdale-Helland, B.; Nissen, S.

    1988-01-01

    To assess the effect of site of isotope infusion on estimates of leucine metabolism infusions of alpha-[4,5-3H]ketoisocaproate (KIC) and [U- 14 C]leucine were made into the left or right ventricles of sheep and pigs. Blood was sampled from the opposite ventricle. In both species, left ventricular infusions resulted in significantly lower specific radioactivities (SA) of [ 14 C]leucine and [ 3 H]KIC. [ 14 C]KIC SA was found to be insensitive to infusion and sampling sites. [ 14 C]KIC was in addition found to be equal to the SA of [ 14 C]leucine only during the left heart infusions. Therefore, [ 14 C]KIC SA was used as the only estimate for [ 14 C]SA in the equations for the two-pool model. This model eliminated the influence of site of infusion and blood sampling on the estimates for leucine entry and reduced the impact on the estimates for proteolysis and oxidation. This two-pool model could not compensate for the underestimation of transamination reactions occurring during the traditional venous isotope infusion and arterial blood sampling

  17. Endocrine responses and acute mTOR pathway phosphorylation to resistance exercise with leucine and whey

    Directory of Open Access Journals (Sweden)

    MT Lane

    2017-02-01

    Full Text Available Leucine ingestion reportedly activates the mTOR pathway in skeletal muscle, contributing to a hypertrophy response. The purpose of the study was to compare the post-resistance exercise effects of leucine and whey protein supplementation on endocrine responses and muscle mTOR pathway phosphorylation. On visit 1, subjects (X±SD; n=20; age=27.8±2.8yrs provided baseline blood samples for analysis of cortisol, glucose and insulin; a muscle biopsy of the vastus lateralis muscle to assess mTOR signaling pathway phosphorylation; and were tested for maximum strength on the leg press and leg extension exercises. For visits 2 and 3, subjects were randomized in a double-blind crossover design to ingest either leucine and whey protein (10g+10g; supplement or a non-caloric placebo. During these visits, 5 sets of 10 repetitions were performed on both exercises, immediately followed by ingestion of the supplement or placebo. Blood was sampled 30 min post-, and a muscle biopsy 45 min post-exercise. Western blots quantified total and phosphorylated proteins. Insulin increased (α<.05 with supplementation with no change in glucose compared to placebo. Relative phosphorylation of AKT and rpS6 were greater with leucine and whey supplementation compared to placebo. Supplementation of leucine and whey protein immediately after heavy resistance exercise increases anabolic signaling in human skeletal muscle.

  18. Use of the [14C]Leucine Incorporation Technique To Measure Bacterial Production in River Sediments and the Epiphyton

    Science.gov (United States)

    Fischer, Helmut; Pusch, Martin

    1999-01-01

    Bacterial production is a key parameter for the understanding of carbon cycling in aquatic ecosystems, yet it remains difficult to measure in many aquatic habitats. We therefore tested the applicability of the [14C]leucine incorporation technique for the measurement of bulk bacterial production in various habitats of a lowland river ecosystem. To evaluate the method, we determined (i) extraction efficiencies of bacterial protein from the sediments, (ii) substrate saturation of leucine in sediments, the biofilms on aquatic plants (epiphyton), and the pelagic zone, (iii) bacterial activities at different leucine concentrations, (iv) specificity of leucine uptake by bacteria, and (v) the effect of the incubation technique (perfused-core incubation versus slurry incubation) on leucine incorporation into protein. Bacterial protein was best extracted from sediments and precipitated by hot trichloroacetic acid treatment following ultrasonication. For epiphyton, an alkaline-extraction procedure was most efficient. Leucine incorporation saturation occurred at 1 μM in epiphyton and 100 nM in the pelagic zone. Saturation curves in sediments were difficult to model but showed the first level of leucine saturation at 50 μM. Increased uptake at higher leucine concentrations could be partly attributed to eukaryotes. Addition of micromolar concentrations of leucine did not enhance bacterial electron transport activity or DNA replication activity. Similar rates of leucine incorporation into protein calculated for whole sediment cores were observed after slurry and perfused-core incubations, but the rates exhibited strong vertical gradients after the core incubation. We conclude that the leucine incorporation method can measure bacterial production in a wide range of aquatic habitats, including fluvial sediments, if substrate saturation and isotope dilution are determined. PMID:10508068

  19. Impaired intracortical transmission in G2019S leucine rich-repeat kinase Parkinson patients.

    Science.gov (United States)

    Ponzo, Viviana; Di Lorenzo, Francesco; Brusa, Livia; Schirinzi, Tommaso; Battistini, Stefania; Ricci, Claudia; Sambucci, Manolo; Caltagirone, Carlo; Koch, Giacomo

    2017-05-01

    A mutation in leucine-rich repeat kinase 2 is the most common cause of hereditary Parkinson's disease (PD), yet the neural mechanisms and the circuitry potentially involved are poorly understood. We used different transcranial magnetic stimulation protocols to explore in the primary motor cortex the activity of intracortical circuits and cortical plasticity (long-term potentiation) in patients with the G2019S leucine-rich repeat kinase 2 gene mutation when compared with idiopathic PD patients and age-matched healthy subjects. Paired pulse transcranial magnetic stimulation was used to investigate short intracortical inhibition and facilitation and short afferent inhibition. Intermittent theta burst stimulation, a form of repetitive transcranial magnetic stimulation, was used to test long-term potentiation-like cortical plasticity. Leucine-rich repeat kinase 2 and idiopathic PD were tested both in ON and in OFF l-dopa therapy. When compared with idiopathic PD and healthy subjects, leucine-rich repeat kinase 2 PD patients showed a remarkable reduction of short intracortical inhibition in both ON and in OFF l-dopa therapy. This reduction was paralleled by an increase of intracortical facilitation in OFF l-dopa therapy. Leucine-rich repeat kinase 2 PD showed abnormal long-term potentiation-like cortical plasticity in ON l-dopa therapy. The motor cortex in leucine-rich repeat kinase 2 mutated PD patients is strongly disinhibited and hyperexcitable. These abnormalities could be a result of an impairment of inhibitory (gamma-Aminobutyric acid) transmission eventually related to altered neurotransmitter release. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  20. Measurement of L-[1-14C]leucine kinetics in splanchnic and leg tissues in humans. Effect of amino acid infusion

    International Nuclear Information System (INIS)

    Gelfand, R.A.; Glickman, M.G.; Castellino, P.; Louard, R.J.; DeFronzo, R.A.

    1988-01-01

    Although whole-body leucine flux is widely measured to study body protein turnover in humans, the contribution of specific tissues to the total-body measurement remains unknown. By combining the organ-balance technique with the systemic infusion of L-[1-14C]leucine, we quantitated leucine production and disposal by splanchnic and leg tissues and by the whole body, simultaneously, in six normal men before and during amino acid infusion. At steady state, disposal of arterial leucine by splanchnic and leg tissues was calculated from the percent extraction (E) of L-[1-14C]leucine counts: uptake = E x [Leu]a x flow. Tissue release of cold leucine (from protein turnover) into vein was calculated as the difference between leucine uptake and the net tissue leucine balance. In the postabsorptive state, despite substantial (P less than .01) extraction of L-[1-14C]leucine by splanchnic (23 +/- 1%) and leg (18 +/- 2%) tissues, net leucine balance across both tissue beds was small, indicating active simultaneous disposal and production of leucine at nearly equivalent rates. Splanchnic tissues accounted for approximately 50% of the measured total-body leucine flux. During amino acid infusion, the net leucine balance across splanchnic and leg tissues became positive, reflecting not only an increase in leucine uptake but also a marked suppression (by approximately 50%, P less than .02) of cold leucine release. This reduction in splanchnic and leg leucine release was indicated by a sharp decline in whole-body endogenous leucine flux

  1. Synthesis of (S)-leucine-13C3 and its metabolites

    International Nuclear Information System (INIS)

    Yuan, S.S.; Foos, J.

    1981-01-01

    A synthesis for (S)-2-amino-4-methyl- 13 C-pentanoic-2,5- 13 C 2 acid ((S)-leucine- 13 C 3 ) is described. The alkyl chain was constructed by condensing acetone-1,3- 13 C 2 with triethyl phosphonacetate-1- 13 C to form 3-methyl- 13 C-2-butenoic-1,4- 13 C 2 acid (beta-methylcrotonic- 13 C 3 acid) and this was reduced to 3-methyl- 13 C-butanal-1,4- 13 C 2 (isovaleryl aldehyde- 13 C 3 ). Conversion to (S)-leucine- 13 C 3 was accomplished via the Strecker synthesis followed by enzymatic resolution. (author)

  2. Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Kerkhoven, Eduard J.; Kim, Young-Mo; Wei, Siwei

    2017-01-01

    correlation was observed between the responses on the transcript and protein levels. Combination of DGA1 overexpression with nitrogen limitation resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular......, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered...

  3. Dual Diagnosis - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Dual Diagnosis URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Dual Diagnosis - Multiple Languages To use the sharing features ...

  4. Dual Youla parameterization

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik

    2003-01-01

    A different aspect of using the parameterisation of all systems stabilised by a given controller, i.e. the dual Youla parameterisation, is considered. The relation between system change and the dual Youla parameter is derived in explicit form. A number of standard uncertain model descriptions...... are considered and the relation with the dual Youla parameter given. Some applications of the dual Youla parameterisation are considered in connection with the design of controllers and model/performance validation....

  5. DUAL TIMELIKE NORMAL AND DUAL TIMELIKE SPHERICAL CURVES IN DUAL MINKOWSKI SPACE

    OpenAIRE

    ÖNDER, Mehmet

    2009-01-01

    Abstract: In this paper, we give characterizations of dual timelike normal and dual timelike spherical curves in the dual Minkowski 3-space and we show that every dual timelike normal curve is also a dual timelike spherical curve. Keywords: Normal curves, Dual Minkowski 3-Space, Dual Timelike curves. Mathematics Subject Classifications (2000): 53C50, 53C40. DUAL MINKOWSKI UZAYINDA DUAL TIMELIKE NORMAL VE DUAL TIMELIKE KÜRESEL EĞRİLER Özet: Bu çalışmada, dual Minkowski 3-...

  6. Cloning and characterization of an aromatic amino acid and leucine permease of Penicillium chrysogenum

    NARCIS (Netherlands)

    Trip, Hein; Evers, Melchior E.; Konings, Wil N.; Driessen, Arnold J.M.

    2002-01-01

    The gene encoding the amino acid permease ArlP (Aromatic and leucine Permease) was isolated from the filamentous fungus Penicillium chrysogenum after PCR using degenerated oligonucleotides based on conserved regions of fungal amino acid permeases. The cDNA clone was used for expression of the

  7. Kinetics and mechanism of oxidation of L-leucine by alkaline ...

    Indian Academy of Sciences (India)

    J. Chem. Sci. Vol. 124, No. 4, July 2012, pp. 809–819. c Indian Academy of Sciences. Kinetics and mechanism of oxidation of L-leucine by alkaline ... Post Graduate Department of Studies in Chemistry, Karnatak University, Dharwad 580003, India e-mail: ... anism of this drug by DPC, there was a need for under- standing the ...

  8. 3D Printing of Protein Models in an Undergraduate Laboratory: Leucine Zippers

    Science.gov (United States)

    Meyer, Scott C.

    2015-01-01

    An upper-division undergraduate laboratory experiment is described that explores the structure/function relationship of protein domains, namely leucine zippers, through a molecular graphics computer program and physical models fabricated by 3D printing. By generating solvent accessible surfaces and color-coding hydrophobic, basic, and acidic amino…

  9. An EThcD-Based Method for Discrimination of Leucine and Isoleucine Residues in Tryptic Peptides

    Science.gov (United States)

    Zhokhov, Sergey S.; Kovalyov, Sergey V.; Samgina, Tatiana Yu.; Lebedev, Albert T.

    2017-08-01

    An EThcD-based approach for the reliable discrimination of isomeric leucine and isoleucine residues in peptide de novo sequencing procedure has been proposed. A multistage fragmentation of peptide ions was performed with Orbitrap Elite mass spectrometer in electrospray ionization mode. At the first stage, z-ions were produced by ETD or ETcaD fragmentation of doubly or triply charged peptide precursor ions. These primary ions were further fragmented by HCD with broad-band ion isolation, and the resulting w-ions showed different mass for leucine and isoleucine residues. The procedure did not require manual isolation of specific z-ions prior to HCD stage. Forty-three tryptic peptides (3 to 27 residues) obtained by trypsinolysis of human serum albumin (HSA) and gp188 protein were analyzed. To demonstrate a proper solution for radical site migration problem, three non-tryptic peptides were also analyzed. A total of 93 leucine and isoleucine residues were considered and 83 of them were correctly identified. The developed approach can be a reasonable substitution for additional Edman degradation procedure, which is still used in peptide sequencing for leucine and isoleucine discrimination.

  10. Autophagy and leucine promote chronological longevity and respiration proficiency during calorie restriction in yeast.

    Science.gov (United States)

    Aris, John P; Alvers, Ashley L; Ferraiuolo, Roy A; Fishwick, Laura K; Hanvivatpong, Amanda; Hu, Doreen; Kirlew, Christine; Leonard, Michael T; Losin, Kyle J; Marraffini, Michelle; Seo, Arnold Y; Swanberg, Veronica; Westcott, Jennifer L; Wood, Michael S; Leeuwenburgh, Christiaan; Dunn, William A

    2013-10-01

    We have previously shown that autophagy is required for chronological longevity in the budding yeast Saccharomyces cerevisiae. Here we examine the requirements for autophagy during extension of chronological life span (CLS) by calorie restriction (CR). We find that autophagy is upregulated by two CR interventions that extend CLS: water wash CR and low glucose CR. Autophagy is required for full extension of CLS during water wash CR under all growth conditions tested. In contrast, autophagy was not uniformly required for full extension of CLS during low glucose CR, depending on the atg allele and strain genetic background. Leucine status influenced CLS during CR. Eliminating the leucine requirement in yeast strains or adding supplemental leucine to growth media extended CLS during CR. In addition, we observed that both water wash and low glucose CR promote mitochondrial respiration proficiency during aging of autophagy-deficient yeast. In general, the extension of CLS by water wash or low glucose CR was inversely related to respiration deficiency in autophagy-deficient cells. Also, autophagy is required for full extension of CLS under non-CR conditions in buffered media, suggesting that extension of CLS during CR is not solely due to reduced medium acidity. Thus, our findings show that autophagy is: (1) induced by CR, (2) required for full extension of CLS by CR in most cases (depending on atg allele, strain, and leucine availability) and, (3) promotes mitochondrial respiration proficiency during aging under CR conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Lipid-protein interactions. The leucine transport system of Lactococcus lactis.

    NARCIS (Netherlands)

    Veld, Geertruida Elisabeth in 't

    1992-01-01

    In summary, it is concluded, that a functionally reconstituted leucine transport system of L. lactis is affected by bilayer features in the following order of importance: lipid headgroup (H+-bonding) › acyl chain carbon number (thickness) › cholesterol (fluidity) › acyl chain unsaturation (indirect

  12. Catabolism of leucine to branched-chain fatty acids in Staphylococcus xylosus

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Hansen, A M; Lauritsen, F R

    2004-01-01

    Staphylococcus xylosus is an important starter culture in the production of flavours from the branched-chain amino acids leucine, valine and isoleucine in fermented meat products. The sensorially most important flavour compounds are the branched-chain aldehydes and acids derived from...

  13. Gibberellic acid, amino acids (glycine and L-leucine), vitamin B2 ...

    African Journals Online (AJOL)

    SAM

    2014-03-14

    Mar 14, 2014 ... The combined effects of zinc, gibberellic acid, vitamin B2, amino acids (glycine and L-leucine) on pigment production were evaluated in a liquid culture of Monascus purpureus. In this study, response surface design was used to optimize each parameter. The data were analyzed using Minitab 14 software.

  14. Gibberellic acid, amino acids (glycine and L-leucine), vitamin B 2 ...

    African Journals Online (AJOL)

    The combined effects of zinc, gibberellic acid, vitamin B2, amino acids (glycine and L-leucine) on pigment production were evaluated in a liquid culture of Monascus purpureus. In this study, response surface design was used to optimize each parameter. The data were analyzed using Minitab 14 software. Five parameters ...

  15. Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice

    NARCIS (Netherlands)

    Peters, S.J.; Helvoort, van A.; Kegler, D.; Argiles, J.M.; Luiking, Y.C.; Laviano, A.; Bergenhenegouwen, van J.; Deutz, N.E.P.; Haagsman, H.P.; Gorselink, M.; Norren, van K.

    2011-01-01

    Cancer cachexia, which is characterized by muscle wasting, is associated with increased morbidity and mortality. Because muscle protein synthesis may be increased and protein breakdown reduced by leucine supplementation, we used the C26 tumor-bearing cachectic mouse model to assess the effects of

  16. Positive selection in the leucine-rich repeat domain of Gro1 genes in ...

    Indian Academy of Sciences (India)

    Positive selection in the leucine-rich repeat domain of Gro1 genes in. Solanum species. Valentino Ruggieri, Angelina Nunziata and Amalia Barone. J. Genet. 93, 755–765. Rank of templates representing the top ten threading templates used by I-TASSER. Rank. PDB hit. Iden1. Iden2. Cov. Norm. Z-score. 1. 4mn8A. 0.22.

  17. Molecular characterization of the di-leucine-based internalization motif of the T cell receptor

    DEFF Research Database (Denmark)

    Dietrich, J; Hou, X; Wegener, A M

    1996-01-01

    Several cell surface receptors including the T cell receptor (TCR) are phosphorylated and down-regulated following activation of protein kinases. We have recently shown that both phosphorylation of Ser-126 and the presence of the di-leucine sequence Leu-131 and Leu-132 in CD3 gamma are required...

  18. Leucine-protein supplemented recovery feeding enhances subsequent cycling performance in well-trained men.

    Science.gov (United States)

    Thomson, Jasmine S; Ali, Ajmol; Rowlands, David S

    2011-04-01

    The purpose of this study was to determine whether a practical leucine-protein, high-carbohydrate postexercise feeding regimen could improve recovery, as measured by subsequent cycling performance and mechanistic markers, relative to control feeding. In a crossover, 10 male cyclists performed 2- to 2.5-h interval training bouts on 3 consecutive evenings, ingesting either leucine-protein, high-carbohydrate nutrition (0.1/0.4/1.2/0.2 g·kg(-1)·h(-1); leucine, protein, carbohydrate, fat, respectively) or isocaloric control (0.06/1.6/0.2 g·kg(-1)·h(-1); protein, carbohydrate, fat, respectively) nutrition for 1.5 h postexercise. Throughout the experimental period diet was controlled, energy and macronutrient intake balanced, and protein intake clamped at 1.6 g·kg(-1)·day(-1). The alternate supplement was provided the next morning, thereby isolating the postexercise nutrition effect. Following 39 h of recovery, cyclists performed a repeat-sprint performance test. Postexercise leucine-protein ingestion improved mean sprint power by 2.5% (99% confidence limit, ±2.6%; p = 0.013) and reduced perceived overall tiredness during the sprints by 13% (90% confidence limit, ±9.2%), but perceptions of leg tiredness and soreness were unaffected. Before exercise, creatine-kinase concentration was lowered by 19% (90% confidence limits, ±18%), but lactate dehydrogenase and pressure-pain threshold were unaltered. There was a small reduction in anger (25% ± 18%), but other moods were unchanged. Plasma leucine (3-fold) and essential amino acid (47%) concentrations were elevated postexercise. Net nitrogen balance trended mildly negative in both conditions (mean ± SD: leucine-protein, -20 ± 46 mg·kg(-1) per 24 h; control, -25 ± 36 mg·kg(-1) per 24 h). The ingestion of a leucine-protein supplement along with other high-carbohydrate food following intense training on consecutive days enhances subsequent high-intensity endurance performance and may attenuate

  19. Dietary leucine--an environmental modifier of insulin resistance acting on multiple levels of metabolism.

    Directory of Open Access Journals (Sweden)

    Yazmin Macotela

    Full Text Available Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor--leucine--can modify insulin resistance by acting on multiple tissues and at multiple levels of metabolism. Mice were placed on a normal or high fat diet (HFD. Dietary leucine was doubled by addition to the drinking water. mRNA, protein and complete metabolomic profiles were assessed in the major insulin sensitive tissues and serum, and correlated with changes in glucose homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum. Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling without altering food intake or weight gain. Increased dietary leucine was also associated with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest changes in a single environmental/nutrient factor can modify multiple metabolic and signaling pathways and modify HFD induced metabolic syndrome by acting at a systemic level on multiple tissues. These data also suggest that increasing dietary leucine may provide an adjunct in the management of obesity-related insulin resistance.

  20. Supplementing Breakfast with a Vitamin D and Leucine-Enriched Whey Protein Medical Nutrition Drink Enhances Postprandial Muscle Protein Synthesis and Muscle Mass in Healthy Older Men.

    Science.gov (United States)

    Chanet, Audrey; Verlaan, Sjors; Salles, Jérôme; Giraudet, Christophe; Patrac, Véronique; Pidou, Véronique; Pouyet, Corinne; Hafnaoui, Nordine; Blot, Adeline; Cano, Noël; Farigon, Nicolas; Bongers, Anke; Jourdan, Marion; Luiking, Yvette; Walrand, Stéphane; Boirie, Yves

    2017-12-01

    Background: A promising strategy to help older adults preserve or build muscle mass is to optimize muscle anabolism through providing an adequate amount of high-quality protein at each meal. Objective: This "proof of principle" study investigated the acute effect of supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink on postprandial muscle protein synthesis and longer-term effect on muscle mass in healthy older adults. Methods: A randomized, placebo-controlled, double-blind study was conducted in 24 healthy older men [mean ± SD: age 71 ± 4 y; body mass index (in kg/m 2 ) 24.7 ± 2.8] between September 2012 and October 2013 at the Unit of Human Nutrition, University of Auvergne, Clermont-Ferrand, France. Participants received a medical nutrition drink [test group; 21 g leucine-enriched whey protein, 9 g carbohydrates, 3 g fat, 800 IU cholecalciferol (vitamin D 3 ), and 628 kJ] or a noncaloric placebo (control group) before breakfast for 6 wk. Mixed muscle protein fractional synthesis rate (FSR) was measured at week 0 in the basal and postprandial state, after study product intake with a standardized breakfast with the use of l-[ 2 H 5 ]-phenylalanine tracer methodology. The longer-term effect of the medical nutrition drink was evaluated by measurement of appendicular lean mass, representing skeletal muscle mass at weeks 0 and 6, by dual-energy X-ray absorptiometry. Results: Postprandial FSR (0-240 min) was higher in the test group than in the control group [estimate of difference (ED): 0.022%/h; 95% CI: 0.010%/h, 0.035%/h; ANCOVA, P = 0.001]. The test group gained more appendicular lean mass than the control group after 6 wk (ED: 0.37 kg; 95% CI: 0.03, 0.72 kg; ANCOVA, P = 0.035), predominantly as leg lean mass (ED: 0.30 kg; 95% CI: 0.03, 0.57 kg; ANCOVA, P = 0.034). Conclusions: Supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink stimulated postprandial muscle protein

  1. Nano spray-dried pyrazinamide-L-leucine dry powders, physical properties and feasibility used as dry powder aerosols.

    Science.gov (United States)

    Kaewjan, Kanogwan; Srichana, Teerapol

    2016-01-01

    The aim of this study was to investigate the effect of adding L-leucine and using an ethanolic solvent on the physicochemical properties and aerodynamic behavior of nano spray-dried pyrazinamide (PZA)-L-leucine powders. A nano spray dryer was employed to prepare PZA-L-leucine powders. The physicochemical properties were evaluated using a scanning electron microscope (SEM), differential scanning calorimetry and X-ray diffraction. The Andersen cascade impactor was used to evaluate the in vitro aerosolization performance of the sprayed powders. The incorporation of L-leucine at 10% improved the percentage fine particle fraction (%FPF) in all ethanolic solvent formulations by up to nearly twofold (20.0-23.4%) compared to the normal spray-dried PZA of (8.8-13.0%). Changes in the particle density and morphology were also observed. The dense solid particles of PZA were completely converted to bulk hollow particles with a thin shell by increasing the L-leucine content up to 50%. Higher ethanol concentration resulted in larger dimensions of the hollow particle but did not directly affect the aerosolization performance. The co-spray dried PZA with 20% L-leucine in a 10% ethanol feed solvent gave the best aerosolization performance (FPF = 33.0%). The co-spray dried PZA with a suitable L-leucine content using a nano spray drying technique could be applied to formulate the PZA DPI.

  2. Long-term leucine supplementation reduces fat mass gain without changing body protein status of aging rats.

    Science.gov (United States)

    Vianna, Daiana; Resende, Gabriela Fulin Teodoro; Torres-Leal, Francisco Leonardo; Pantaleão, Lucas Carminatti; Donato, Jose; Tirapegui, Julio

    2012-02-01

    Aging is characterized by alterations in body composition such as an increase in body fat and decreases in muscle mass (sarcopenia) and bone density (osteopenia). Leucine supplementation has been shown to acutely stimulate protein synthesis and to decrease body fat. However, the long-term effect of consistent leucine supplementation is not well defined. This study investigated the effect of leucine supplementation during aging. Six-month-old rats were divided into three groups: an adult group (n = 10) euthanized at 6 mo of age, a leucine group (n = 16) that received a diet supplemented with 4% leucine for 40 wk, and a control group (n = 19) that received the control diet for 40 wk. The following parameters were evaluated: body weight, food intake, chemical carcass composition, indicators of acquired chronic diseases, and indicators of protein nutritional status. Body weight and fat were lower in the leucine group after 40 wk of supplementation compared with the control group but still higher than in the adult group. The lipid and glycemic profiles were equally altered in the control and leucine groups because of aging. In addition, leucine supplementation did not affect the changes in protein status parameters associated with aging, such as decreases in body and muscle protein and total serum protein. The results indicate that leucine supplementation attenuates body fat gain during aging but does not affect risk indicators of acquired chronic diseases. Furthermore, supplemented animals did not show signs of a prevention of the decrease in lean mass associated with aging. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Dual Supervised Learning

    OpenAIRE

    Xia, Yingce; Qin, Tao; Chen, Wei; Bian, Jiang; Yu, Nenghai; Liu, Tie-Yan

    2017-01-01

    Many supervised learning tasks are emerged in dual forms, e.g., English-to-French translation vs. French-to-English translation, speech recognition vs. text to speech, and image classification vs. image generation. Two dual tasks have intrinsic connections with each other due to the probabilistic correlation between their models. This connection is, however, not effectively utilized today, since people usually train the models of two dual tasks separately and independently. In this work, we p...

  4. Leucine supplementation improves acquired growth hormone resistance in rats with protein-energy malnutrition.

    Science.gov (United States)

    Gao, Xuejin; Tian, Feng; Wang, Xinying; Zhao, Jie; Wan, Xiao; Zhang, Li; Wu, Chao; Li, Ning; Li, Jieshou

    2015-01-01

    Protein-energy malnutrition (PEM) can lead to growth hormone (GH) resistance. Leucine supplementation diets have been shown to increase protein synthesis in muscles. Our study aimed at investigating if long-term leucine supplementation could modulate GH-insulin-like growth factor (IGF)-1 system function and mammalian target of rapamycin (mTOR)-related signal transduction in skeletal muscles in a rat model of severe malnutrition. Male Sprague-Dawley rats (n = 50; weight, 302 ± 5 g) were divided into 5 treatment groups, including 2 control groups (a normal control group that was fed chow and ad libitum water [CON, n = 10] and a malnourished control group [MC, n = 10] that was fed a 50% chow diet). After undergoing a weight loss stage for 4 weeks, rats received either the chow diet (MC-CON, n = 10), the chow diet supplemented with low-dose leucine (MC-L, n = 10), or the chow diet supplemented with high-dose leucine (MC-H, n = 10) for 2 weeks. The muscle masses of the gastrocnemius, soleus, and extensor digitorum longus were significantly reduced in the MC group. Re-feeding increased muscle mass, especially in the MC-L and MC-H groups. In the MC group, serum IGF-1, IGF-binding protein (IGFBP)-3, and hepatic growth hormone receptor (GHR) levels were significantly decreased and phosphorylation of the downstream anabolic signaling effectors protein kinase B (Akt), mTOR, and ribosomal protein S6 kinase 1 (S6K1) were significantly lower than in other groups. However, serum IGF-1 and IGF binding protein (IGFBP)-3 concentrations and hepatic growth hormone receptor (GHR) levels were significantly higher in the MC-L and MC-H groups than in the MC-CON group, and serum IGFBP-1 levels was significantly reduced in the MC-L and MC-H groups. These changes were consistent with those observed for hepatic mRNA expression levels. Phosphorylation of the downstream anabolic signaling effectors Akt, mTOR, and S6K1 were also significantly higher in the MC-L and MC-H groups than in the MC

  5. Dual Income Taxes

    DEFF Research Database (Denmark)

    Sørensen, Peter Birch

    This paper discusses the principles and practices of dual income taxation in the Nordic countries. The first part of the paper explains the rationale and the historical background for the introduction of the dual income tax and describes the current Nordic tax practices. The second part...... of the paper focuses on the problems of taxing income from small businesses and the issue of corporate-personal tax integration under the dual income tax, considering alternative ways of dealing with these challenges. In the third and final part of the paper, I briefly discuss whether introducing a dual income...

  6. Dual quaternions and dual projective spaces

    Energy Technology Data Exchange (ETDEWEB)

    Ata, Erhan [Department of Mathematics, Dumlupinar University, 43100 Kutahya (Turkey)], E-mail: eata@dumlupinar.edu.tr; Yayli, Yusuf [Department of Mathematics, Ankara University, 06100 Ankara (Turkey)

    2009-05-15

    In this study, dual unitary matrices SU{sub D}(2) were obtained. We correspond to one to one elements of the unit dual sphere S{sub D}{sup 3} with the dual unitary matrices SU{sub D}(2). Thus, we express spherical concepts such as meridians of longitude and parallels of latitude on SU{sub D}(2). The equality SO(R{sup 3}) {approx_equal} S{sup 3}/{l_brace}{+-}1{r_brace} = RP{sup 3} known as the real projective spaces was generalized to the dual projective space and then, the equality SO(D{sup 3}){approx_equal}S{sub D}{sup 3}/{l_brace}{+-}1{r_brace}=DP{sup 3} was acquired. In particular, 2-sphere S{sup 2} was obtained by considering dual parts as zero of S{sub D}{sup 3}. Hence, it was found that Hop fibriation map of S{sup 2} can be used for Twistors in quantum mechanics applications.

  7. Papain-Catalyzed Chemoenzymatic Synthesis of Telechelic Polypeptides Using Bis(Leucine Ethyl Ester) Initiator.

    Science.gov (United States)

    Tsuchiya, Kousuke; Numata, Keiji

    2016-07-01

    In order to construct unique polypeptide architectures, a novel telechelic-type initiator with two leucine ethyl ester units is designed for chemoenzymatic polymerization. Glycine or alanine ethyl ester is chemoenzymatically polymerized using papain in the presence of the initiator, and the propagation occurs at each leucine ethyl ester unit to produce the telechelic polypeptide. The formation of the telechelic polypeptides is confirmed by (1) H NMR and MALDI-TOF mass spectroscopies. It is revealed by AFM observation that long nanofibrils are formed from the telechelic polyalanine, whereas a conventional linear polyalanine with a similar degree of polymerization shows granule-like structures. The telechelic polyglycine and polyalanine show the crystalline structures of Polyglycine II and antiparallel β-sheet, respectively. It is demonstrated that this method to synthesize telechelic-type polypeptides potentially opens up a pathway to construct novel hierarchical structures by self-assembly. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Further observations on incorporation of the 14C-leucine into proteins by freshly secreted milk

    International Nuclear Information System (INIS)

    Singh, L.N.

    1976-01-01

    Using freshly secreted bovine milk, no incorporation of DL (1- 14 C)-leucine was observed in the total milk proteins and acid precipitated casein, when these protein fractions were isolated from skim milk. A significant portion of the radioactivity however, remained associated with the heat coagulable whey proteins and proteose-peptone fractions. This association was shown to be due to non enzymatic physical sequestering of the radioactive amino acid or its metabolites with these proteins. Most of the radioactivity was associated with the cream layer proteins and the cellular fraction. The results obtained using filtered milk, incubated milk and certain antibiotics also indicated that the incorporation of 14 C leucine into proteins by freshly secreted milk may be a purely microbial process and physical sequestering of an amino acids with milk proteins. (author)

  9. Parkinson's Disease: Leucine-Rich Repeat Kinase 2 and Autophagy, Intimate Enemies

    Directory of Open Access Journals (Sweden)

    José M. Bravo-San Pedro

    2012-01-01

    Full Text Available Parkinson's disease is the second common neurodegenerative disorder, after Alzheimer's disease. It is a clinical syndrome characterized by loss of dopamine-generating cells in the substancia nigra, a region of the midbrain. The etiology of Parkinson's disease has long been through to involve both genetic and environmental factors. Mutations in the leucine-rich repeat kinase 2 gene cause late-onset Parkinson's disease with a clinical appearance indistinguishable from Parkinson's disease idiopathic. Autophagy is an intracellular catabolic mechanism whereby a cell recycles or degrades damage proteins and cytoplasmic organelles. This degradative process has been associated with cellular dysfunction in neurodegenerative processes including Parkinson's disease. We discuss the role of leucine-rich repeat kinase 2 in autophagy, and how the deregulations of this degradative mechanism in cells can be implicated in the Parkinson's disease etiology.

  10. Parkinson's disease: leucine-rich repeat kinase 2 and autophagy, intimate enemies.

    Science.gov (United States)

    Bravo-San Pedro, José M; Gómez-Sánchez, Rubén; Pizarro-Estrella, Elisa; Niso-Santano, Mireia; González-Polo, Rosa A; Fuentes Rodríguez, José M

    2012-01-01

    Parkinson's disease is the second common neurodegenerative disorder, after Alzheimer's disease. It is a clinical syndrome characterized by loss of dopamine-generating cells in the substancia nigra, a region of the midbrain. The etiology of Parkinson's disease has long been through to involve both genetic and environmental factors. Mutations in the leucine-rich repeat kinase 2 gene cause late-onset Parkinson's disease with a clinical appearance indistinguishable from Parkinson's disease idiopathic. Autophagy is an intracellular catabolic mechanism whereby a cell recycles or degrades damage proteins and cytoplasmic organelles. This degradative process has been associated with cellular dysfunction in neurodegenerative processes including Parkinson's disease. We discuss the role of leucine-rich repeat kinase 2 in autophagy, and how the deregulations of this degradative mechanism in cells can be implicated in the Parkinson's disease etiology.

  11. Lean body mass change over 6 years is associated with dietary leucine intake in an older Danish population

    DEFF Research Database (Denmark)

    McDonald, Cameron Keith; Ankarfeldt, Mikkel Z.; Capra, Sandra

    2016-01-01

    Higher protein intake, and particularly higher leucine intake, is associated with attenuated loss of lean body mass (LBM) over time in older individuals. Dietary leucine is thought to be a key mediator of anabolism. This study aimed to assess this relationship over 6 years among younger and older...... adult Danes. Dietary leucine intake was assessed at baseline and after 6 years in men and women, aged 35-65 years, participating in the Danish cohort of the WHO-MONICA (Multinational MONItoring of trends and determinants in CArdiovascular disease) study (n 368). Changes in LBM over the 6 years were...... measured by bioelectrical impedance using equations developed for this Danish population. The association between leucine and LBM changes was examined using multivariate linear regression and ANCOVA analyses adjusted for potential confounders. After adjustment for baseline LBM, sex, age, energy intake...

  12. Molecular characterization of the di-leucine-based internalization motif of the T cell receptor

    DEFF Research Database (Denmark)

    Dietrich, J; Hou, X; Wegener, A M

    1996-01-01

    Several cell surface receptors including the T cell receptor (TCR) are phosphorylated and down-regulated following activation of protein kinases. We have recently shown that both phosphorylation of Ser-126 and the presence of the di-leucine sequence Leu-131 and Leu-132 in CD3 gamma are required f...... are important. 2) Recognition of phosphorylated CD3 gamma by molecules involved in receptor internalization. In this process Ser(P)-126, Asp-127, Leu-131, and Leu-132 are important....

  13. Systemic D-Phenylalanine and D-Leucine for Effective Treatment of Pain in the Horse

    OpenAIRE

    McKibbin, L. S.; Cheng, R. S. S.

    1982-01-01

    This study showed that subcutaneous injection of a solution of D-amino acids produced effective analgesia in horses. It is postulated that systemic D-phenylalanine and D-leucine may become one of the safe, effective and nonaddictive drugs for acute and chronic pain treatment. These D-amino acids cause analgesia by presumably preserving brain endorphins. They may bind reversibly to enkephalinases and prevent enzymatic degradation of enkephalins.

  14. Site reactivity in the free radicals induced damage to leucine residues: a theoretical study.

    Science.gov (United States)

    Medina, M E; Galano, A; Alvarez-Idaboy, J R

    2015-02-21

    Several recent computational studies have tried to explain the observed selectivity in radical damage to proteins. In this work we use Density Functional Theory and Transition State Theory including tunnelling corrections, reaction path degeneracy, the effect of diffusion, and the role of free radicals to get further insights into this important topic. The reaction between a leucine derivative and free radicals of biological significance, in aqueous and lipid media, has been investigated. Both thermochemical and kinetic analyses, in both hydrophilic and hydrophobic environments, have been carried out. DPPH, ˙OOH, ˙OOCH3, ˙OOCH2Cl, ˙OOCHCl2 and ˙OOCHCH2 radicals do not react with the target molecule. The reactions are proposed to be kinetically controlled. The leucine gamma site was the most reactive for the reactions with ˙N3, ˙OOCCl3, ˙OCH3, ˙OCH2Cl, and ˙OCHCl2 radicals, with rate constants equal to 1.97 × 10(5), 3.24 × 10(4), 6.68 × 10(5), 5.98 × 10(6) and 8.87 × 10(8) M(-1) s(-1), respectively, in aqueous solution. The ˙Cl, ˙OH and ˙OCCl3 radicals react with leucine at the beta, gamma, and delta positions at rates close to the diffusion limit with the alpha position which is the slowest path and the most thermodynamically favored. The presented results confirm that the Bell-Evans-Polanyi principle does not apply for the reactions between amino acid residues and free radicals. Regarding the influence of the environment on the reactivity of the studied series of free radicals towards leucine residues, it is concluded that hydrophilic media slightly lower the reactivity of the studied radicals, compared to hydrophobic ones, albeit the trends in reactivity are very similar.

  15. Unusual activity pattern of leucine aminopeptidase inhibitors based on phosphorus containing derivatives of methionine and norleucine

    Czech Academy of Sciences Publication Activity Database

    Pícha, Jan; Liboska, Radek; Buděšínský, Miloš; Jiráček, Jiří; Pawelczak, M.; Mucha, A.

    2011-01-01

    Roč. 26, č. 2 (2011), s. 155-161 ISSN 1475-6366 R&D Projects: GA ČR GA203/06/1405; GA MŠk(CZ) LC06077 Institutional research plan: CEZ:AV0Z40550506 Keywords : aminophosphonates * aminophospinates * methionine * norleucine * phosphorus containing dipeptides * cytosolic leucine aminopeptidase * inhibitors Subject RIV: CC - Organic Chemistry Impact factor: 1.617, year: 2011

  16. Les besoins en isoleucine, valine et leucine chez le porcelet entre 7 et 15 kg

    DEFF Research Database (Denmark)

    Assadi Soumeh, Elham; van Milgen, Jaap; Sloth, Niels Morten

    2015-01-01

    La réduction des teneurs en protéines des aliments pour porcelets peut se faire uniquement sous contrôle des apports en acides aminés (AA) indispensables tels que les AA ramifies (AAR) valine (Val), isoleucine (Ile) et leucine (Leu) susceptibles d’être déficitaires et d’altérer les performances de...

  17. Impact of leucine supplementation on exercise training induced anti-cardiac remodeling effect in heart failure mice.

    Science.gov (United States)

    de Moraes, Wilson Max Almeida Monteiro; Melara, Thaís Plasti; de Souza, Pamella Ramona Moraes; Guimarães, Fabiana de Salvi; Bozi, Luiz Henrique Marchesi; Brum, Patricia Chakur; Medeiros, Alessandra

    2015-05-15

    Leucine supplementation potentiates the effects of aerobic exercise training (AET) on skeletal muscle; however, its potential effects associated with AET on cardiac muscle have not been clarified yet. We tested whether leucine supplementation would potentiate the anti-cardiac remodeling effect of AET in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α2A/α2CARKO). Mice were assigned to five groups: wild type mice treated with placebo and sedentary (WT, n = 11), α2A/α2CARKO treated with placebo and sedentary (KO, n = 9), α2A/α2CARKO treated with leucine and sedentary (KOL, n = 11), α2A/α2CARKO treated with placebo and AET (KOT, n = 12) or α2A/α2CARKO treated with leucine and AET (KOLT, n = 12). AET consisted of four weeks on a treadmill with 60 min sessions (six days/week, 60% of maximal speed) and administration by gavage of leucine (1.35 g/kg/day) or placebo (distilled water). The AET significantly improved exercise capacity, fractional shortening and re-established cardiomyocytes' diameter and collagen fraction in KOT. Additionally, AET significantly prevented the proteasome hyperactivity, increased misfolded proteins and HSP27 expression. Isolated leucine supplementation displayed no effect on cardiac function and structure (KOL), however, when associated with AET (KOLT), it increased exercise tolerance to a higher degree than isolated AET (KOT) despite no additional effects on AET induced anti-cardiac remodeling. Our results provide evidence for the modest impact of leucine supplementation on cardiac structure and function in exercised heart failure mice. Leucine supplementation potentiated AET effects on exercise tolerance, which might be related to its recognized impact on skeletal muscle.

  18. Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

    International Nuclear Information System (INIS)

    Ventrucci, Gislaine; Mello, Maria Alice R; Gomes-Marcondes, Maria Cristina C

    2007-01-01

    Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Controversly, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated. Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C – pregnant control, W – tumour-bearing, and P – pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine-rich diet: L – pregnant leucine, WL – tumour-bearing, and PL – pair-fed, which received the same amount of food as ingested by the WL group. The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ~35% for eIF2α and eIF5, ~17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced. The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway

  19. Hypertrophy-Promoting Effects of Leucine Supplementation and Moderate Intensity Aerobic Exercise in Pre-Senescent Mice

    OpenAIRE

    Xia, Zhi; Cholewa, Jason; Zhao, Yan; Yang, Yue-Qin; Shang, Hua-Yu; Guimar?es-Ferreira, Lucas; Naimo, Marshall Alan; Su, Quan-Sheng; Zanchi, Nelo Eidy

    2016-01-01

    Several studies have indicated a positive influence of leucine supplementation and aerobic training on the aging skeletal muscle signaling pathways that control muscle protein balance and muscle remodeling. However, the effect of a combined intervention requires further clarification. Thirteen month old CD-1® mice were subjected to moderate aerobic exercise (45 min swimming per day with 3% body weight workload) and fed a chow diet with 5% leucine or 3.4% alanine for 8 weeks. Serum and plasma ...

  20. N-Acetyl-L-Leucine Accelerates Vestibular Compensation after Unilateral Labyrinthectomy by Action in the Cerebellum and Thalamus

    Science.gov (United States)

    Xiong, Guoming; Potschka, Heidrun; Jahn, Klaus; Bartenstein, Peter; Brandt, Thomas; Dutia, Mayank; Dieterich, Marianne; Strupp, Michael; la Fougère, Christian; Zwergal, Andreas

    2015-01-01

    An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular behavioural testing included measurements of nystagmus, head roll tilt and postural imbalance as well as sequential whole-brain [18F]-FDG-μPET was done before and on days 1,3,7 and 15 after UL. A significant reduction of postural imbalance scores was identified on day 7 in the N-acetyl-DL-leucine (p metabolism (rCGM) by means of μPET revealed that only N-acetyl-L-leucine but not N-acetyl-D-leucine caused a significant increase of rCGM in the vestibulocerebellum and a decrease in the posterolateral thalamus and subthalamic region on days 3 and 7. A similar pattern was found when comparing the effect of N-acetyl-L-leucine on rCGM in an UL-group and a sham UL-group without vestibular damage. In conclusion, N-acetyl-L-leucine improves compensation of postural symptoms after UL in a dose-dependent and specific manner, most likely by activating the vestibulocerebellum and deactivating the posterolateral thalamus. PMID:25803613

  1. Dual gravity and matter

    NARCIS (Netherlands)

    Bergshoeff, Eric A.; Roo, Mees de; Kerstan, Sven F.; Kleinschmidt, Axel; Riccioni, Fabio

    We consider the problem of finding a dual formulation of gravity in the presence of non-trivial matter couplings. In the absence of matter a dual graviton can be introduced only for linearised gravitational interactions. We show that the coupling of linearised gravity to matter poses obstructions to

  2. A Dual Egalitarian Solution

    NARCIS (Netherlands)

    Klijn, F.; Slikker, M.; Tijs, S.H.

    2000-01-01

    In this note we introduce an egalitarian solution, called the dual egalitarian solution, that is the natural counterpart of the egalitarian solution of Dutta and Ray (1989).We prove, among others, that for a convex game the egalitarian solution coincides with the dual egalitarian solution for its

  3. Dual Credit Report

    Science.gov (United States)

    Light, Noreen

    2016-01-01

    In 2015, legislation to improve access to dual-credit programs and to reduce disparities in access and completion--particularly for low income and underrepresented students--was enacted. The new law focused on expanding access to College in the High School but acknowledged issues in other dual-credit programs and reinforced the notion that cost…

  4. The Dual Career Family.

    Science.gov (United States)

    Gurtin, Lee

    1980-01-01

    The dual career couple is forced to make a series of choices and compromises that impact the realms of marriage and career. The dilemmas that confront dual career marriages can be overcome only by compromise, accommodation, and mutual understanding on the part of the individuals involved. A revamping of human resources and recruitment programs is…

  5. Liver functional metabolomics discloses an action of L-leucine against Streptococcus iniae infection in tilapias.

    Science.gov (United States)

    Ma, Yan-Mei; Yang, Man-Jun; Wang, Sanying; Li, Hui; Peng, Xuan-Xian

    2015-08-01

    Streptococcus iniae seriously affects the intensive farming of tilapias. Much work has been conducted on prevention and control of S. iniae infection, but little published information on the metabolic response is available in tilapias against the bacterial infection, and no metabolic modulation way may be adopted to control this disease. The present study used GC/MS based metabolomics to characterize the metabolic profiling of tilapias infected by a lethal dose (LD50) of S. iniae and determined two characteristic metabolomes separately responsible for the survival and dying fishes. A reversal changed metabolite, decreased and increased l-leucine in the dying and survival groups, respectively, was identified as a biomarker which featured the difference between the two metabolomes. More importantly, exogenous l-leucine could be used as a metabolic modulator to elevate survival ability of tilapias infected by S. iniae. These results indicate that tilapias mount metabolic strategies to deal with bacterial infection, which can be regulated by exogenous metabolites such as l-leucine. The present study establishes an alternative way, metabolic modulation, to cope with bacterial infections. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. L-leucine transport in liver of Antarctic fish in vivo at 0 degrees C.

    Science.gov (United States)

    Haschemeyer, A E

    1982-03-01

    Uptake of L-[14C]leucine by liver of an endemic Antarctic fish, Trematomus hansoni, was studied by a single injection technique with [3H]inulin as a reference. Rate constants for leucine influx and efflux and incorporation into liver protein were determined by analysis of isotope distribution in the free and protein-bound compartments of liver and in blood draining the liver at various times after injection. Transport rates were slower than in temperate fish at 20 degrees C, but saturation properties and ability to accumulate leucine in liver were comparable. Kinetic analysis indicated that 30% of uptake at 0 degrees C was due to active transport, similar to that in toadfish at 20 degrees C. This contrasts with the absence of this component in toadfish cooled to 10 degrees C. Average polypeptide chain assembly time was 19 min at 0 degrees C. Transport functions were maintained in fish warmed to 10 degrees C; however, protein synthesis declined at temperatures above 5 degrees C. The results indicate this system is adapted to function at extremely low temperatures in a manner qualitatively similar to organisms adapted to much higher temperatures. Transport and synthetic rates, however, were low, consistent with a normal temperature dependency (Q10 about 2.5) for biological reaction rates.

  7. Hypertrophy-Promoting Effects of Leucine Supplementation and Moderate Intensity Aerobic Exercise in Pre-Senescent Mice

    Directory of Open Access Journals (Sweden)

    Zhi Xia

    2016-05-01

    Full Text Available Several studies have indicated a positive influence of leucine supplementation and aerobic training on the aging skeletal muscle signaling pathways that control muscle protein balance and muscle remodeling. However, the effect of a combined intervention requires further clarification. Thirteen month old CD-1® mice were subjected to moderate aerobic exercise (45 min swimming per day with 3% body weight workload and fed a chow diet with 5% leucine or 3.4% alanine for 8 weeks. Serum and plasma were prepared for glucose, urea nitrogen, insulin and amino acid profile analysis. The white gastrocnemius muscles were used for determination of muscle size and signaling proteins involved in protein synthesis and degradation. The results show that both 8 weeks of leucine supplementation and aerobic training elevated the activity of mTOR (mammalian target of rapamycin and its downstream target p70S6K and 4E-BP1, inhibited the ubiquitin-proteasome system, and increased fiber cross-sectional area (CSA in white gastrocnemius muscle. Moreover, leucine supplementation in combination with exercise demonstrated more significant effects, such as greater CSA, protein content and altered phosphorylation (suggestive of increased activity of protein synthesis signaling proteins, in addition to lower expression of proteins involved in protein degradation compared to leucine or exercise alone. The current study shows moderate aerobic training combined with 5% leucine supplementation has the potential to increase muscle size in fast-twitch skeletal muscle during aging, potentially through increased protein synthesis and decreased protein breakdown.

  8. Hypertrophy-Promoting Effects of Leucine Supplementation and Moderate Intensity Aerobic Exercise in Pre-Senescent Mice.

    Science.gov (United States)

    Xia, Zhi; Cholewa, Jason; Zhao, Yan; Yang, Yue-Qin; Shang, Hua-Yu; Guimarães-Ferreira, Lucas; Naimo, Marshall Alan; Su, Quan-Sheng; Zanchi, Nelo Eidy

    2016-05-02

    Several studies have indicated a positive influence of leucine supplementation and aerobic training on the aging skeletal muscle signaling pathways that control muscle protein balance and muscle remodeling. However, the effect of a combined intervention requires further clarification. Thirteen month old CD-1(®) mice were subjected to moderate aerobic exercise (45 min swimming per day with 3% body weight workload) and fed a chow diet with 5% leucine or 3.4% alanine for 8 weeks. Serum and plasma were prepared for glucose, urea nitrogen, insulin and amino acid profile analysis. The white gastrocnemius muscles were used for determination of muscle size and signaling proteins involved in protein synthesis and degradation. The results show that both 8 weeks of leucine supplementation and aerobic training elevated the activity of mTOR (mammalian target of rapamycin) and its downstream target p70S6K and 4E-BP1, inhibited the ubiquitin-proteasome system, and increased fiber cross-sectional area (CSA) in white gastrocnemius muscle. Moreover, leucine supplementation in combination with exercise demonstrated more significant effects, such as greater CSA, protein content and altered phosphorylation (suggestive of increased activity) of protein synthesis signaling proteins, in addition to lower expression of proteins involved in protein degradation compared to leucine or exercise alone. The current study shows moderate aerobic training combined with 5% leucine supplementation has the potential to increase muscle size in fast-twitch skeletal muscle during aging, potentially through increased protein synthesis and decreased protein breakdown.

  9. Oral leucine supplementation is sensed by the brain but neither reduces food intake nor induces an anorectic pattern of gene expression in the hypothalamus.

    Directory of Open Access Journals (Sweden)

    Thais T Zampieri

    Full Text Available Leucine activates the intracellular mammalian target of the rapamycin (mTOR pathway, and hypothalamic mTOR signaling regulates food intake. Although central infusion of leucine reduces food intake, it is still uncertain whether oral leucine supplementation is able to affect the hypothalamic circuits that control energy balance. We observed increased phosphorylation of p70s6k in the mouse hypothalamus after an acute oral gavage of leucine. We then assessed whether acute oral gavage of leucine induces the activation of neurons in several hypothalamic nuclei and in the brainstem. Leucine did not induce the expression of Fos in hypothalamic nuclei, but it increased the number of Fos-immunoreactive neurons in the area postrema. In addition, oral gavage of leucine acutely increased the 24 h food intake of mice. Nonetheless, chronic leucine supplementation in the drinking water did not change the food intake and the weight gain of ob/ob mice and of wild-type mice consuming a low- or a high-fat diet. We assessed the hypothalamic gene expression and observed that leucine supplementation increased the expression of enzymes (BCAT1, BCAT2 and BCKDK that metabolize branched-chain amino acids. Despite these effects, leucine supplementation did not induce an anorectic pattern of gene expression in the hypothalamus. In conclusion, our data show that the brain is able to sense oral leucine intake. However, the food intake is not modified by chronic oral leucine supplementation. These results question the possible efficacy of leucine supplementation as an appetite suppressant to treat obesity.

  10. Dual Credit/Dual Enrollment and Data Driven Policy Implementation

    Science.gov (United States)

    Lichtenberger, Eric; Witt, M. Allison; Blankenberger, Bob; Franklin, Doug

    2014-01-01

    The use of dual credit has been expanding rapidly. Dual credit is a college course taken by a high school student for which both college and high school credit is given. Previous studies provided limited quantitative evidence that dual credit/dual enrollment is directly connected to positive student outcomes. In this study, predictive statistics…

  11. Dual energy CT

    DEFF Research Database (Denmark)

    Al-Najami, Issam; Drue, Henrik Christian; Steele, Robert

    2017-01-01

    and inaccurate with existing methods. Dual Energy Computed Tomography (DECT) enables qualitative tissue differentiation by simultaneous scanning with different levels of energy. We aimed to assess the feasibility of DECT in quantifying tumor response to neoadjuvant therapy in loco-advanced rectal cancer. METHODS...... to determine the average quantitative parameters; effective-Z, water- and iodine-concentration, Dual Energy Index (DEI), and Dual Energy Ratio (DER). These parameters were compared to the regression in the resection specimen as measured by the pathologist. RESULTS: Changes in the quantitative parameters...

  12. Dual Dynamic Programming - DDP

    International Nuclear Information System (INIS)

    Velasquez Bermudez, Jesus M

    1998-01-01

    Objections are presented to the mathematical formulation of the denominated Dual Dynamic programming-PDD that is the theoretical base of several computational model available for the optimal formulation of interconnected hydrothermal systems

  13. Comparative analysis of leucine transport in temperate fish liver in vivo.

    Science.gov (United States)

    Haschemeyer, A E; Persell, R

    1984-01-01

    The uptake of [14C]leucine in toadfish (Opsanus tau) liver in vivo at 10 degrees C has been studied by a single pulse injection technique. Transport parameters were determined on the basis of the distribution of the amino acid and of [3H]inulin, used as a marker for extracellular space, in liver free and protein-bound fractions and in venous blood draining from the liver. Saturation analysis by the Cornish-Bowden method yielded a maximal uptake of 0.26 mumole, which was similar on a concentration basis to that at 21 degrees C when circulation rate and dilution with blood are taken into account. Isoleucine and phenylalanine competed with leucine uptake at 10 degrees C as at 21 degrees C; additional competitors at 10 degrees C included histidine, methionine and valine. Fish acclimated to 10 degrees C for 2 weeks or more showed a restoration in maximal leucine uptake and disappearance of histidine inhibition. Methionine inhibition was retained. Three transport systems in this species are discussed: 20-20, operating in 20 degrees C-acclimated fish at 20 degrees C; 20-10, in 20 degrees C-acclimated fish at 10 degrees C; and 10-10, in 10 degrees C-acclimated fish at 10 degrees C. The properties of these systems are compared with the 0-0 system of Antarctic fish and with transport systems of mammalian cells. The latter are similar to our non-acclimated system, 20-10, suggesting that the mammalian cell may not be at a state of optimal temperature adaptation.

  14. Accumulation of D- vs. L-isomers of alanine and leucine in rat prostatic adenocarcinoma

    International Nuclear Information System (INIS)

    Conti, P.S.; Schmall, B.; Bigler, R.E.; Zanzonico, P.B.; Kleinert, E.; Whitmore, W.F. Jr.

    1985-01-01

    It has been reported that tumor tissue may accumulate some D-amino acids preferentially over the L-isomers. In order to investigate the potential use of carbon-11 labeled amino acid isomers for in vivo tumor studies with positron emission tomography in patients, the tissue distributions of alanine and leucine, substrates for the A-type and L-type amino acid transport systems, respectively, were studied in Copenhagen rates bearing the Dunning R3327G prostatic adenocarcinoma. The authors have previously reported differences in the accumulation of A-type vs. L-type amino acids in rat prostatic adenocarcinoma and normal tissues. All compounds were labeled with C-14 in the carboxyl position with specific activities of 30.0-56.6 mCi/mmol. Higher levels of C-14 activity (Relative Concentration (RC)=dpm found per gm tissue + dpm inject per gm animal mass) were observed in tumor tissue using D-alanine (0.71) compared to L- (0.21) or DL-alanine (0.27) at 45 min post-injection. While tumor/prostate and tumor/liver ratios were above 2 for all three substrates, tumor/blood and tumor/muscle were above one for only the D-isomer. Comparisons made with D-, L-, and DL-leucine also demonstrated a higher level of RC in tumor tissue with the D-isomer (0.84) vs. the L-(0.66) and DL-leucine (0.63). In this case, however, tumor/blood, tumor/prostate, and tumor/muscle ratios were above one for all three substrates, while tumor/liver ratios were below one. These results support the observation of a preferential accumulation of D-amino acids in tumor tissue over the natural L-isomers. Observed differences in the accumulation of the isomers in normal tissues are discussed

  15. Alteration of substrate specificity of leucine dehydrogenase by site-directed mutagenesis

    OpenAIRE

    片岡, 邦重; Kataoka, Kunishige; Tanizawa, Katsuyuki

    2003-01-01

    The residues L40, A113, V291, and V294, in leucine dehydrogenase (LeuDH), predicted to be involved in recognition of the substrate side chain, have been mutated on the basis of the molecular modeling to mimic the substrate specificities of phenylalanine (PheDH), glutamate (GluDH), and lysine dehydrogenases (LysDH). The A113G and A113G/V291L mutants, imitating the PheDH active site, displayed activities toward -phenylalanine and phenylpyruvate with 1.6 and 7.8% of kcat values of the wild-type ...

  16. Investigations on particle surface characteristics vs. dispersion behaviour of L-leucine coated carrier-free inhalable powders.

    Science.gov (United States)

    Raula, Janne; Thielmann, Frank; Naderi, Majid; Lehto, Vesa-Pekka; Kauppinen, Esko I

    2010-01-29

    Aerosol microparticles of salbutamol sulphate are gas-phase coated with an amino acid L-leucine. Depending of the saturated state of L-leucine, the coating is formed by the surface diffusion of L-leucine molecules within a droplet or by the physical vapour deposition (PVD) of L-leucine or by the combination thereof. The PVD coated particles showed excellent aerosolization characteristics in a carrier-free powder delivery from an inhaler. The aerosolization of the fine powders is compared with surface energy parameters analysed by inverse gas chromatography (IGC). The dispersion testing is conducted by a Inhalation Simulator using a fast inhalation profile with inhalation flow rate of 67 l min(-1). It is found that the powder emission is affected by the morphology, surface roughness (asperity size and density) of the particles and acidity of particle surface. The latter affects the dispersion and dose repeatability of fine powder in a case if L-leucine content is high enough. However, there is no direct correlation between dispersive surface energies and aerosolization performances of the powders. Crucial factors for the improved aerosolization rely weakly on surface acid-base properties but strongly on particle morphology and fine-scale surface roughness. 2009 Elsevier B.V. All rights reserved.

  17. Effect of hyperglucagonemia on whole-body leucine metabolism in immature pigs before and during a meal

    International Nuclear Information System (INIS)

    Ostaszewski, P.; Nissen, S.

    1988-01-01

    Leucine metabolism was measured isotopically in 12 immature female pigs to assess the effect of acute hyperglucagonemia on leucine kinetics in both the fed and fasting states. After an overnight fast, immature pigs were infused with α-[ 3 H]ketoisocaproate and [ 14 C]leucine. After a 2-h equilibration period, an infusion of either saline or 7 pg · kg -1 · min -1 of glucagon was begun, which increased plasma glucagon from ∼140 to ∼640 pg/ml and doubled the insulin concentrations. Two hours later, pigs were fed small meals to which [5,5,5- 2 H 3 ]leucine was added to trace absorption. By subtracting absorption from total leucine flux, an estimate of endogenous proteolysis during the meal was made. In the fasting state, glucagon increased proteolysis and increased oxidation. No significant glucagon-related changes in any other flux parameters occurred in the fasting state. Ingestion of the meals caused oxidation to increase 41% in control animals, whereas in glucagon-infused animals, oxidation increased 84%. Additional, animals infused with glucagon suppressed endogenous proteolysis 43% after the meal compared with 55% decrease in control animals. These data indicate that glucagon stimulates whole-body proteolysis in both the fasting and fed states

  18. Three-dimensional structure of carboxypeptidase T from Thermoactinomyces vulgaris in complex with N-BOC-L-leucine.

    Science.gov (United States)

    Timofeev, V I; Kuznetsov, S A; Akparov, V Kh; Chestukhina, G G; Kuranova, I P

    2013-03-01

    The 3D structure of recombinant bacterial carboxypeptidase T (CPT) in complex with N-BOC-L-leucine was determined at 1.38 Å resolution. Crystals for the X-ray study were grown in microgravity using the counter-diffusion technique. N-BOC-L-leucine and SO4(2-) ion bound in the enzyme active site were localized in the electron density map. Location of the leucine side chain in CPT-N-BOC-L-leucine complex allowed identification of the S1 subsite of the enzyme, and its structure was determined. Superposition of the structures of CPT-N-BOC-L-leucine complex and complexes of pancreatic carboxypeptidases A and B with substrate and inhibitors was carried out, and similarity of the S1 subsites in these three carboxypeptidases was revealed. It was found that SO4(2-) ion occupies the same position in the S1' subsite as the C-terminal carboxy group of the substrate.

  19. Quantitative analysis and prediction of curvature in leucine-rich repeat proteins.

    Science.gov (United States)

    Hindle, K Lauren; Bella, Jordi; Lovell, Simon C

    2009-11-01

    Leucine-rich repeat (LRR) proteins form a large and diverse family. They have a wide range of functions most of which involve the formation of protein-protein interactions. All known LRR structures form curved solenoids, although there is large variation in their curvature. It is this curvature that determines the shape and dimensions of the inner space available for ligand binding. Unfortunately, large-scale parameters such as the overall curvature of a protein domain are extremely difficult to predict. Here, we present a quantitative analysis of determinants of curvature of this family. Individual repeats typically range in length between 20 and 30 residues and have a variety of secondary structures on their convex side. The observed curvature of the LRR domains correlates poorly with the lengths of their individual repeats. We have, therefore, developed a scoring function based on the secondary structure of the convex side of the protein that allows prediction of the overall curvature with a high degree of accuracy. We also demonstrate the effectiveness of this method in selecting a suitable template for comparative modeling. We have developed an automated, quantitative protocol that can be used to predict accurately the curvature of leucine-rich repeat proteins of unknown structure from sequence alone. This protocol is available as an online resource at http://www.bioinf.manchester.ac.uk/curlrr/.

  20. LEUCINE-RICH REPEAT CONTAINING 10 (LRRC10 AND DILATED CARDIOMYOPATHY

    Directory of Open Access Journals (Sweden)

    Matthew J Brody

    2016-08-01

    Full Text Available Leucine-rich repeat containing protein 10 (LRRC10 is a cardiomyocyte-specific member of the Leucine-rich repeat containing (LRRC protein superfamily with critical roles in cardiac function and disease pathogenesis. Recent studies have identified LRRC10 mutations in human idiopathic dilated cardiomyopathy (DCM and Lrrc10 homozygous knockout mice develop DCM, strongly linking LRRC10 to the molecular etiology of DCM. LRRC10 localizes to the dyad region in cardiomyocytes where it can interact with actin and α-actinin at the Z-disc and associate with T-tubule components. Indeed, this region is becoming increasingly recognized as a signaling center in cardiomyocytes, not only for calcium cycling, excitation-contraction coupling, and calcium-sensitive hypertrophic signaling, but also as a nodal signaling hub where the myocyte can sense and respond to mechanical stress. Disruption of a wide range of critical structural and signaling molecules in cardiomyocytes confers susceptibility to cardiomyopathies in addition to the more classically studied mutations in sarcomeric proteins. However, the molecular mechanisms underlying DCM remain unclear. Here, we review what is known about the cardiomyocyte functions of LRRC10, lessons learned about LRRC10 and DCM from the Lrrc10 knockout mouse model, and discuss ongoing efforts to elucidate molecular mechanisms whereby mutation or absence of LRRC10 mediates cardiac disease.

  1. An innovative approach to enhance methane hydrate formation kinetics with leucine for energy storage application

    International Nuclear Information System (INIS)

    Veluswamy, Hari Prakash; Kumar, Asheesh; Kumar, Rajnish; Linga, Praveen

    2017-01-01

    Highlights: • Innovative combinatorial hybrid approach to reduce nucleation stochasticity and enhance hydrate growth. • Methane hydrate growth curves are similar in UTR and STR configurations in presence of leucine. • Amalgamation of stirred (STR) and unstirred (UTR) configuration is demonstrated. • Reliable method for scale up and commercial production of Solidified Natural Gas (SNG). - Abstract: Natural gas storage in clathrate hydrates or solidified natural gas (SNG) offers the safest, cleanest and the most compact mode of storage aided by the relative ease in natural gas (NG) recovery with minimal cost compared to known conventional methods of NG storage. The stochastic nature of hydrate nucleation and the slow kinetics of hydrate growth are major challenges that needs to be addressed on the SNG production side. A deterministic and fast nucleation coupled with rapid crystallization kinetics would empower this beneficial technology for commercial application. We propose a hybrid combinatorial approach of methane hydrate formation utilizing the beneficial aspect of environmentally benign amino acid (leucine) as a kinetic promoter by combining stirred and unstirred reactor operation. This hybrid approach is simple, can easily be implemented and scaled-up to develop an economical SNG technology for efficient storage of natural gas on a large scale. Added benefits include the minimal energy requirement during hydrate growth resulting in overall cost reduction for SNG technology.

  2. Leucine aminopeptidase and transaminase activity of intestine epithelium of chickens fed on gamma-irradiated feed

    International Nuclear Information System (INIS)

    Toncheva, E.; Chotinski, D.

    1987-01-01

    An experiment was conducted with 4 groups of male broilers. From hatching to the age of 49 days the chickens were fed as follows: group 1 (control) - compound feed, group 2 - feed gamma treated at 0.35 Mrad, group 3 - at 0.7 Mrad, and group 4 - at 1.0 Mrad. In a homogenate of jejunum mucosa, isolated from 24 chickens, it was determined the activity of leucine aminopeptidase, glutamic oxalacetic transminase and glutamic pyruvic transminase as well as the content of protein. Data obtained showed that activity of leucine aminopeptidase in the intestinal mucosa decreased at most twofold in chickens receiving feed treated at 0.7 Mrad. Irradiation at 1.0 Mrad also led to a significant lowering of enzime activity; at 0.35 Mrad there was of no impact on the activity of this hydrolase in the jejunal mucosa of chickens fed on such feed. Glutamic oxalacetic transminase activity increased significantly only when treated at 0.7 Mrad. Glutamic pyruvic transminase activity was not effected by the applied gamma ray radiation in this experiment

  3. Preliminary structural studies on the leucine-zipper homology region of the human protein Bap31

    Energy Technology Data Exchange (ETDEWEB)

    Mukasa, Takashi; Santelli, Eugenio [Program on Infectious Diseases, Center for Inflammation and Infectious Diseases, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States); Reed, John C. [Program on Apoptosis, Cancer Center, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States); Pascual, Jaime, E-mail: pascual@burnham.org [Program on Infectious Diseases, Center for Inflammation and Infectious Diseases, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States)

    2007-04-01

    A leucine-zipper with properties as apoptotic regulator in the ER has been crystallized. X-ray data to 2.5 Å resolution were collected, molecular replacement solutions were identified and refinement has been started. B-cell receptor-associated protein 31 (Bap31) is an integral membrane protein located in the endoplasmic reticulum (ER) that participates in the transport and quality control of membrane proteins and plays a role in determining cell sensitivity to ER stress and apoptosis. Its cytoplasmic region contains two target sites for caspase cleavage in certain apoptotic pathways. Here, the subcloning, expression, purification and crystallization of the Homo sapiens Bap31 leucine-zipper C-terminal fragment, which spans residues Gly160–Glu246, are reported. An N-terminally His-tagged protein was overexpressed in Escherichia coli and purified by chromatographic methods. X-ray diffraction data were collected in-house to 2.5 Å resolution. Crystals belong to space group P6{sub 1}22/P6{sub 5}22, with unit-cell parameters a = b = 70.7, c = 80.6 Å. Data analysis indicates the presence of one molecule per asymmetric unit.

  4. MHJ_0461 is a multifunctional leucine aminopeptidase on the surface of Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Jarocki, Veronica M; Santos, Jerran; Tacchi, Jessica L; Raymond, Benjamin B A; Deutscher, Ania T; Jenkins, Cheryl; Padula, Matthew P; Djordjevic, Steven P

    2015-01-01

    Aminopeptidases are part of the arsenal of virulence factors produced by bacterial pathogens that inactivate host immune peptides. Mycoplasma hyopneumoniae is a genome-reduced pathogen of swine that lacks the genetic repertoire to synthesize amino acids and relies on the host for availability of amino acids for growth. M. hyopneumoniae recruits plasmin(ogen) onto its cell surface via the P97 and P102 adhesins and the glutamyl aminopeptidase MHJ_0125. Plasmin plays an important role in regulating the inflammatory response in the lungs of pigs infected with M. hyopneumoniae. We show that recombinant MHJ_0461 (rMHJ_0461) functions as a leucine aminopeptidase (LAP) with broad substrate specificity for leucine, alanine, phenylalanine, methionine and arginine and that MHJ_0461 resides on the surface of M. hyopneumoniae. rMHJ_0461 also binds heparin, plasminogen and foreign DNA. Plasminogen bound to rMHJ_0461 was readily converted to plasmin in the presence of tPA. Computational modelling identified putative DNA and heparin-binding motifs on solvent-exposed sites around a large pore on the LAP hexamer. We conclude that MHJ_0461 is a LAP that moonlights as a multifunctional adhesin on the cell surface of M. hyopneumoniae.

  5. Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica

    Directory of Open Access Journals (Sweden)

    Eduard J. Kerkhoven

    2017-06-01

    Full Text Available The yeast Yarrowia lipolytica is a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis in Y. lipolytica and identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1 with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination of DGA1 overexpression with nitrogen limitation resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor.

  6. Self-dual Hopf quivers

    International Nuclear Information System (INIS)

    Huang Hualin; Li Libin; Ye Yu

    2004-07-01

    We study pointed graded self-dual Hopf algebras with a help of the dual Gabriel theorem for pointed Hopf algebras. Quivers of such Hopf algebras are said to be self-dual. An explicit classification of self-dual Hopf quivers is obtained. We also prove that finite dimensional coradically graded pointed self-dual Hopf algebras are generated by group-like and skew-primitive elements as associative algebras. This partially justifies a conjecture of Andruskiewitsch and Schneider and may help to classify finite dimensional self-dual pointed Hopf algebras

  7. Arginine supplementation modulates pig plasma lipids, but not hepatic fatty acids, depending on dietary protein level with or without leucine.

    Science.gov (United States)

    Madeira, Marta Sofia Morgado Dos Santos; Rolo, Eva Sofia Alves; Pires, Virgínia Maria Rico; Alfaia, Cristina Maria Riscado Pereira Mateus; Coelho, Diogo Francisco Maurício; Lopes, Paula Alexandra Antunes Brás; Martins, Susana Isabel Vargas; Pinto, Rui Manuel Amaro; Prates, José António Mestre

    2017-05-30

    In the present study, the effect of arginine and leucine supplementation, and dietary protein level, were investigated in commercial crossbred pigs to clarify their individual or combined impact on plasma metabolites, hepatic fatty acid composition and mRNA levels of lipid sensitive factors. The experiment was conducted on fifty-four entire male pigs (Duroc × Pietrain × Large White × Landrace crossbred) from 59 to 92 kg of live weight. Each pig was randomly assigned to one of six experimental treatments (n = 9). The treatments followed a 2 × 3 factorial arrangement, providing two levels of arginine supplementation (0 vs. 1%) and three levels of basal diet (normal protein diet, NPD; reduced protein diet, RPD; reduced protein diet with 2% of leucine, RPDL). Significant interactions between arginine supplementation and protein level were observed across plasma lipids. While dietary arginine increased total lipids, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol and triacylglycerols in NPD, the inverse effect was observed in RPD. Overall, dietary treatments had a minor impact on hepatic fatty acid composition. RPD increased 18:1c9 fatty acid while the combination of leucine and RPD reduced 18:0 fatty acid. Arginine supplementation increased the gene expression of FABP1, which contributes for triacylglycerols synthesis without affecting hepatic fatty acids content. RPD, with or without leucine addition, upregulated the lipogenic gene CEBPA but downregulated the fat oxidation gene LPIN1. Arginine supplementation was responsible for a modulated effect on plasma lipids, which is dependent on dietary protein level. It consistently increased lipaemia in NPD, while reducing the correspondent metabolites in RPD. In contrast, arginine had no major impact, neither on hepatic fatty acids content nor on fatty acid composition. Likewise, leucine supplementation of RPD, regardless the presence of arginine, promoted no changes on total fatty acids in

  8. Methodological study on determining endogenous amino acid excretion of broiler chickens by single intravenous injection of 3H-leucine

    International Nuclear Information System (INIS)

    Yao Junhu; Wang Kangning; Yang Feng; Zhou Anguo; Cai Xuelin; Duanmu Dao

    1999-01-01

    Forty broiler chickens (1.5 kg of body weight, BW) were randomly divided into 20 groups. Every fifth group was force-fed a nitrogen-free diet (NFD) or a NFd + 3.20% enzyme hydrolysed casein (EHC) diet or diets with 5% and 20% crude protein (CP) in which soybean meal (sol.) was the sole nitrogen source. 30μCi 3 H-leucine/kg BW was intravenously injected into all birds just after the force-feeding. Venous blood samples were taken at 5 min, 4h, 24h, 36h and 48h after the injection, and the amount of excreta for the whole period of 48h was collected. The amino acids excreted after force-feeding NFD + 3.20% EHC of CP5% diet were theoretically endogenous. The ratios of specific radioactivity (SR) in excreta and the value of definite integral in free plasma from 0 to 48 h after injection of labelled leucine were not different (P > 0.05) when NFD, NFD + 3.20% EHC or CP5% diet was fed. From these results and theoretical analysis, it was suggested that for the birds with CP20% diet, the ratio of SR in endogenous leucine and value of definite integral in free plasma from 0 to 48 h after injection of labelled leucine would be the same as that of the birds with NFD diet, and thus endogenous losses of leucine and other amino acids, by the endogenous amino acid pattern measured with NFD diet, could be estimated for CP20% diet. The endogenous amino acid losses measured by this new technique was 120.50% of those measured by NFD method. It was suggested that single intravenous injection of 3 H-leucine first proposed would be more valuable for determining endogenous amino acid losses, especially when practical nitrogen-containing diet was fed

  9. Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis.

    Science.gov (United States)

    Pasiakos, Stefan M; McClung, Holly L; McClung, James P; Margolis, Lee M; Andersen, Nancy E; Cloutier, Gregory J; Pikosky, Matthew A; Rood, Jennifer C; Fielding, Roger A; Young, Andrew J

    2011-09-01

    The effects of essential amino acid (EAA) supplementation during moderate steady state (ie, endurance) exercise on postexercise skeletal muscle metabolism are not well described, and the potential role of supplemental leucine on muscle protein synthesis (MPS) and associated molecular responses remains to be elucidated. This randomized crossover study examined whether EAA supplementation with 2 different concentrations of leucine affected post-steady state exercise MPS, whole-body protein turnover, and mammalian target of rapamycin 1 (mTORC1) intracellular signaling. Eight adults completed 2 separate bouts of cycle ergometry [60 min, 60% VO(2)peak (peak oxygen uptake)]. Isonitrogenous (10 g EAA) drinks with different leucine contents [leucine-enriched (l)-EAA, 3.5 g leucine; EAA, 1.87 g leucine] were consumed during exercise. MPS and whole-body protein turnover were determined by using primed continuous infusions of [(2)H(5)]phenylalanine and [1-(13)C]leucine. Multiplex and immunoblot analyses were used to quantify mTORC1 signaling. MPS was 33% greater (P < 0.05) after consumption of L-EAA (0.08 ± 0.01%/h) than after consumption of EAA (0.06 ± 0.01%/h). Whole-body protein breakdown and synthesis were lower (P < 0.05) and oxidation was greater (P < 0.05) after consumption of L-EAA than after consumption of EAA. Regardless of dietary treatment, multiplex analysis indicated that Akt and mammalian target of rapamycin phosphorylation were increased (P < 0.05) 30 min after exercise. Immunoblot analysis indicated that phosphorylation of ribosomal protein S6 and extracellular-signal regulated protein kinase increased (P < 0.05) and phosphorylation of eukaryotic elongation factor 2 decreased (P < 0.05) after exercise but was not affected by dietary treatment. These findings suggest that increasing the concentration of leucine in an EAA supplement consumed during steady state exercise elicits a greater MPS response during recovery. This trial is registered at clinicaltrials

  10. Effect of dietary nutrients on ileal endogenous losses of threonine, cysteine, methionine, lysine, leucine and protein in broiler chicks.

    Science.gov (United States)

    Cerrate, S; Vignale, S K; Ekmay, R; England, J; Coon, C

    2018-04-01

    An isotope dose technique was utilized (i) to determine endogenous amino acid (AA) and protein losses and (ii) to propose adjusted values for AA requirements. The endogenous flow rate was calculated from the pool of enrichment in plasma AA, assuming similitude to enrichment of endogenous AA. In experiment 1, chicks were orally administered D4-lysine at 2% of estimated lysine intake from 16 to 24 days to find the isotopic steady state of the atom percent excess (APE) of lysine for plasma and jejunal and ileal digesta. The APE of D4-lysine in plasma, jejunal digesta and ileal digesta reached the isotopic steady state at 5.5, 3.4 and 2.0 days, respectively, by using the broken-line model. It was assumed that the isotopic steady state at 5 days identified for D4-lysine is also representative for the 15N-labeled AA. In experiment 2, chicks were fed diets from 1 to 21 days with increasing levels of fat (6%, 8%, 12%, 13% extract ether), protein (26%, 28.5%, 31% CP) or fiber (14%, 16%, 18% NDF) by adding poultry fat, soybean meal, blended animal protein or barley. Chicks were orally administered 15N-threonine, 15N-cysteine, 15N-methionine, 15N-lysine and 15N-leucine at 2% of estimated daily intake for 5 days from 17 to 21 days of age. Dietary nutrients influenced endogenous losses (EL), where dietary fat stimulated EL of lysine (P=0.06), leucine and protein (P=0.07); dietary protein enhanced EL of leucine and protein; and finally the dietary fiber increased EL of leucine. Dietary nutrients also affected apparent ileal digestibility (AID). Dietary fat increased AID of cysteine but decreased AID of lysine. Dietary protein reduced AID of protein, threonine, lysine and leucine, and similarly dietary fiber decreased AID of protein, threonine, methionine, lysine and leucine. In contrast, dietary fat or protein did not affect real ileal digestibility (RID) of protein and AA except threonine and leucine. The dietary fiber reduced the RID of protein, threonine and leucine. This

  11. Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation

    DEFF Research Database (Denmark)

    Behncken, S N; Billestrup, Nils; Brown, R

    2000-01-01

    Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers of the gro......Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers...

  12. The Plant Leucine-Rich Repeat Receptor-Like Kinase PSY1R from Head to Toe

    DEFF Research Database (Denmark)

    Oehlenschlæger, Christian Berg

    PSY1R belongs to the family of plant leucine-rich repeat receptor-like kinases that play important roles in processes such as growth regulation and plant immunity response. PSY1R was proposed to be the receptor of the plant peptide hormone PSY1 which promotes cell expansion. PSY1R was furthermore...... are conserved among related plant leucine-rich repeat receptor-like kinases whereas Ser951 is unique for PSY1R which suggests that it may serve a specialized function in regulation of PSY1R kinase activity....

  13. Body composition of piglets from sows fed the leucine metabolite β-hydroxy β-methyl butyrate in late gestation

    DEFF Research Database (Denmark)

    Flummer, Christine; Kristensen, Niels Bastian; Theil, Peter Kappel

    2012-01-01

    Supplementation of the leucine metabolite β-hydroxy β-methyl butyrate (HMB) to sows during late gestation or lactation has been shown to improve piglet health, survival, and growth. This study aimed to investigate long-term effects of HMB supplementation to late-gestating sows on body characteris......Supplementation of the leucine metabolite β-hydroxy β-methyl butyrate (HMB) to sows during late gestation or lactation has been shown to improve piglet health, survival, and growth. This study aimed to investigate long-term effects of HMB supplementation to late-gestating sows on body...

  14. Dual phase evolution

    CERN Document Server

    Green, David G; Abbass, Hussein A

    2014-01-01

    This book explains how dual phase evolution operates in all these settings and provides a detailed treatment of the subject. The authors discuss the theoretical foundations for the theory, how it relates to other phase transition phenomena and its advantages in evolutionary computation and complex adaptive systems. The book provides methods and techniques to use this concept for problem solving. Dual phase evolution concerns systems that evolve via repeated phase shifts in the connectivity of their elements. It occurs in vast range of settings, including natural systems (species evolution, landscape ecology, geomorphology), socio-economic systems (social networks) and in artificial systems (annealing, evolutionary computing).

  15. Dual-Mode Combustor

    Science.gov (United States)

    Trefny, Charles J (Inventor); Dippold, Vance F (Inventor)

    2013-01-01

    A new dual-mode ramjet combustor used for operation over a wide flight Mach number range is described. Subsonic combustion mode is usable to lower flight Mach numbers than current dual-mode scramjets. High speed mode is characterized by supersonic combustion in a free-jet that traverses the subsonic combustion chamber to a variable nozzle throat. Although a variable combustor exit aperture is required, the need for fuel staging to accommodate the combustion process is eliminated. Local heating from shock-boundary-layer interactions on combustor walls is also eliminated.

  16. Dual-anticipating, dual and dual-lag synchronization in modulated time-delayed systems

    International Nuclear Information System (INIS)

    Ghosh, Dibakar; Chowdhury, A. Roy

    2010-01-01

    In this Letter, dual synchronization in modulated time delay system using delay feedback controller is proposed. Based on Lyapunov stability theory, we suggest a general method to achieve the dual-anticipating, dual, dual-lag synchronization of time-delayed chaotic systems and we find both its existing and sufficient stability conditions. Numerically it is shown that the dual synchronization is also possible when driving system contain two completely different systems. Effect of parameter mismatch on dual synchronization is also discussed. As an example, numerical simulations for the Mackey-Glass and Ikeda systems are conducted, which is in good agreement with the theoretical analysis.

  17. Dose and Latency Effects of Leucine Supplementation in Modulating Glucose Homeostasis: Opposite Effects in Healthy and Glucocorticoid-Induced Insulin-Resistance States

    Directory of Open Access Journals (Sweden)

    Nelo Eidy Zanchi

    2012-11-01

    Full Text Available Dexamethasone (DEXA is a potent immunosupressant and anti-inflammatory agent whose main side effects are muscle atrophy and insulin resistance in skeletal muscles. In this context, leucine supplementation may represent a way to limit the DEXA side effects. In this study, we have investigated the effects of a low and a high dose of leucine supplementation (via a bolus on glucose homeostasis, muscle mass and muscle strength in energy-restricted and DEXA-treated rats. Since the leucine response may also be linked to the administration of this amino acid, we performed a second set of experiments with leucine given in bolus (via gavage versus leucine given via drinking water. Leucine supplementation was found to produce positive effects (e.g., reduced insulin levels only when administrated in low dosage, both via the bolus or via drinking water. However, under DEXA treatment, leucine administration was found to significantly influence this response, since leucine supplementation via drinking water clearly induced a diabetic state, whereas the same effect was not observed when supplied via the gavage.

  18. SREBP-1 dimerization specificity maps to both the helix-loop-helix and leucine zipper domains: use of a dominant negative

    DEFF Research Database (Denmark)

    Rishi, Vikas; Gal, Jozsef; Krylov, Dmitry

    2004-01-01

    -HLH-ZIP proteins MAX, USF, or MITF, even at 100 molar eq. Chimeric proteins containing the HLH domain of SREBP-1 and the leucine zipper from either MAX, USF, or MITF indicate that both the HLH and leucine zipper regions of SREBP-1 contribute to its dimerization specificity. Transient co-transfection studies...

  19. spinning self-dual particles

    International Nuclear Information System (INIS)

    Gamboa, J.; Rivelles, V.O.

    1989-01-01

    Self-dual particles in two-dimensions are presented. They were obtained from chiral boson particle by square root technique. The propagator of spinning self-dual particle is calculated using the BFV formalism. (M.C.K.)

  20. Dual Symmetry in Gauge Theories

    OpenAIRE

    Koshkarov, A. L.

    1997-01-01

    Continuous dual symmetry in electrodynamics, Yang-Mills theory and gravitation is investigated. Dual invariant which leads to badly nonlinear motion equations is chosen as a Lagrangian of the pure classical dual nonlinear electrodynamics. In a natural manner some dual angle which is determined by the electromagnetic strengths at the point of the time-space appears in the model. Motion equations may well be interpreted as the equations of the standard Maxwell theory with source. Alternative in...

  1. Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise

    DEFF Research Database (Denmark)

    Moberg, Marcus; Apró, William; Ekblom, Björn

    2016-01-01

    Protein synthesis is stimulated by resistance exercise and intake of amino acids, in particular leucine. Moreover, activation of mammalian target of rapamycin complex 1 (mTORC1) signaling by leucine is potentiated by the presence of other essential amino acids (EAA). However, the contribution...... of the branched-chain amino acids (BCAA) to this effect is yet unknown. Here we compare the stimulatory role of leucine, BCAA, and EAA ingestion on anabolic signaling following exercise. Accordingly, eight trained volunteers completed four sessions of resistance exercise during which they ingested either placebo......, leucine, BCAA, or EAA (including the BCAA) in random order. Muscle biopsies were taken at rest, immediately after exercise, and following 90 and 180 min of recovery. Following 90 min of recovery the activity of S6 kinase 1 (S6K1) was greater than at rest in all four trials (PlaceboLeucine

  2. The role of leucine in isoprenoid metabolism. Incorporation of [3-13C]leucine and of [2-3H,4-14C]-β,β-dimethyl-acrylic acid into phytosterols by tissue cultures of Andrographis paniculata

    International Nuclear Information System (INIS)

    Anastasis, P.; Freer, I.; Overton, K.; Rycroft, D.; Singh, S.B.

    1985-01-01

    [3- 13 C]Leucine is incorporated into phytosterols by tissue cultures of Andrographis paniculata by breakdown to acetyl-CoA and its subsequent incorporation via (3S)-3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) and mevalonic acid; [2- 3 H,4- 14 C]-β,β-dimethylacrylic acid also is not incorporated intact. (author)

  3. Immobilazation of aerobic microorganisms on glassy sintered material, illustrated by the example of the production of L leucine using Corynebacterium glutamicum. Immobilisierung von aeroben Mikroorganismen an Glassintermaterial am Beispiel der L-Leucin-Produktion mit Corynebacterium glutamicum

    Energy Technology Data Exchange (ETDEWEB)

    Buechs, J.

    1988-12-01

    The aim of this study was to develop the carrier fixation of aerobic microorganisms on open-pore sintered glass material. The fermentative production of L-leucine from {alpha} cetonic isocaproic acid with Corynebacterium glutamicum was chosen as an example of a microbial process with a high demand of oxygen. (orig.).

  4. Dual Smarandache Curves and Smarandache Ruled Surfaces

    OpenAIRE

    Tanju KAHRAMAN; Mehmet ÖNDER; H. Hüseyin UGURLU

    2013-01-01

    In this paper, by considering dual geodesic trihedron (dual Darboux frame) we define dual Smarandache curves lying fully on dual unit sphere S^2 and corresponding to ruled surfaces. We obtain the relationships between the elements of curvature of dual spherical curve (ruled surface) x(s) and its dual Smarandache curve (Smarandache ruled surface) x1(s) and we give an example for dual Smarandache curves of a dual spherical curve.

  5. The primordial metabolism: an ancestral interconnection between leucine, arginine, and lysine biosynthesis

    Science.gov (United States)

    Fondi, Marco; Brilli, Matteo; Emiliani, Giovanni; Paffetti, Donatella; Fani, Renato

    2007-01-01

    Background It is generally assumed that primordial cells had small genomes with simple genes coding for enzymes able to react with a wide range of chemically related substrates, interconnecting different metabolic routes. New genes coding for enzymes with a narrowed substrate specificity arose by paralogous duplication(s) of ancestral ones and evolutionary divergence. In this way new metabolic pathways were built up by primordial cells. Useful hints to disclose the origin and evolution of ancestral metabolic routes and their interconnections can be obtained by comparing sequences of enzymes involved in the same or different metabolic routes. From this viewpoint, the lysine, arginine, and leucine biosynthetic routes represent very interesting study-models. Some of the lys, arg and leu genes are paralogs; this led to the suggestion that their ancestor genes might interconnect the three pathways. The aim of this work was to trace the evolutionary pathway leading to the appearance of the extant biosynthetic routes and to try to disclose the interrelationships existing between them and other pathways in the early stages of cellular evolution. Results The comparative analysis of the genes involved in the biosynthesis of lysine, leucine, and arginine, their phylogenetic distribution and analysis revealed that the extant metabolic "grids" and their interrelationships might be the outcome of a cascade of duplication of ancestral genes that, according to the patchwork hypothesis, coded for unspecific enzymes able to react with a wide range of substrates. These genes belonged to a single common pathway in which the three biosynthetic routes were highly interconnected between them and also to methionine, threonine, and cell wall biosynthesis. A possible evolutionary model leading to the extant metabolic scenarios was also depicted. Conclusion The whole body of data obtained in this work suggests that primordial cells synthesized leucine, lysine, and arginine through a single

  6. Dual beam vidicon digitizer

    International Nuclear Information System (INIS)

    Evans, T.L.

    1976-01-01

    A vidicon waveform digitizer which can simultaneously digitize two independent signals has been developed. Either transient or repetitive waveforms can be digitized with this system. A dual beam oscilloscope is used as the signal input device. The light from the oscilloscope traces is optically coupled to a television camera, where the signals are temporarily stored prior to digitizing

  7. Towards a Dual Approach

    DEFF Research Database (Denmark)

    Holli, Anne Maria; Harder, Mette Marie Stæhr

    2016-01-01

    Drawing on insights from state feminism and legislative studies on parliamentary committees, this article develops a dual approach for the comparative analysis of committees on gender equality. Empirically, it compares the standing committees on gender equality in Denmark and Finland, two Nordic...

  8. Dual Criteria Decisions

    DEFF Research Database (Denmark)

    Andersen, Steffen; Harrison, Glenn W.; Lau, Morten Igel

    2014-01-01

    The most popular models of decision making use a single criterion to evaluate projects or lotteries. However, decision makers may actually consider multiple criteria when evaluating projects. We consider a dual criteria model from psychology. This model integrates the familiar tradeoffs between...

  9. Dual ionization chamber

    International Nuclear Information System (INIS)

    Mallory, J.; Turlej, Z.

    1981-01-01

    Dual ionization chambers are provided for use with an electronic smoke detector. The chambers are separated by electrically-conductive partition. A single radiation source extends through the partition into both chambers, ionizing the air in each. The mid-point current of the device may be balanced by adjusting the position of the source

  10. Chronic leucine supplementation improves lipid metabolism in C57BL/6J mice fed with a high-fat/cholesterol diet

    Directory of Open Access Journals (Sweden)

    Jun Jiao

    2016-09-01

    Full Text Available Background: Leucine supplementation has been reported to improve lipid metabolism. However, lipid metabolism in adipose tissues and liver has not been extensively studied for leucine supplementation in mice fed with a high-fat/cholesterol diet (HFCD. Design: C57BL/6J mice were fed a chow diet, HFCD, HFCD supplemented with 1.5% leucine (HFCD+1.5% Leu group or 3% leucine (HFCD+3% Leu group for 24 weeks. The body weight, peritoneal adipose weight, total cholesterol (TC, triglyceride in serum and liver, and serum adipokines were analyzed. In addition, expression levels of proteins associated with hepatic lipogenesis, adipocyte lipolysis, and white adipose tissue (WAT browning were determined. Results: Mice in the HFCD group developed obesity and deteriorated lipid metabolism. Compared with HFCD, leucine supplementation lowered weight gain and TC levels in circulation and the liver without changing energy intake. The decrease in body fat was supported by histological examination in the WAT and liver. Furthermore, serum levels of proinflammatory adipokines, such as leptin, IL-6, and tumor necrosis factor-alpha, were significantly decreased by supplemented leucine. At the protein level, leucine potently decreased the hepatic lipogenic enzymes (fatty acid synthase and acetyl-coenzyme A carboxylase and corresponding upstream proteins. In epididymal WAT, the reduced expression levels of two major lipases by HFCD, namely phosphorylated hormone-sensitive lipase and adipose triglyceride lipase, were reversed when leucine was supplemented. Uncoupling protein 1, β3 adrenergic receptors, peroxisome proliferator-activated receptor g coactivator-1α, and fibroblast growth factor 21 were involved in the thermogenic program and WAT browning. Leucine additionally upregulated their protein expression in both WAT and interscapular brown adipose tissue. Conclusion: This study demonstrated that chronic leucine supplementation reduced the body weight and improved the

  11. The effects of adding leucine to pre and postexercise carbohydrate beverages on acute muscle recovery from resistance training.

    Science.gov (United States)

    Stock, Matt S; Young, John C; Golding, Lawrence A; Kruskall, Laura J; Tandy, Richard D; Conway-Klaassen, Janice M; Beck, Travis W

    2010-08-01

    The present study examined the effects of adding leucine to pre and postexercise carbohydrate beverages on selected markers of muscle damage, delayed-onset muscle soreness (DOMS), and squat performance for up to 72 hours after lower-body resistance training. Seventeen resistance trained men (mean +/- SD age 22.9 +/- 2.9 years) and 3 resistance trained women (mean +/- SD age 21.6 +/- 2.6 years) performed 6 sets of squats to fatigue using 75% of the 1 repetition maximum. Each subject consumed a carbohydrate beverage 30 minutes before and immediately after exercise with or without the addition of 22.5 mgxkg (45 mgxkg total) of leucine in a randomized, double-blind fashion. Serum creatine kinase (CK), lactate dehydrogenase (LDH), and DOMS were analyzed immediately before (TIME1), 24 (TIME2), 48 (TIME3), and 72 (TIME4) hours after exercise. The subjects repeated the squat protocol at TIME4 to test recovery. No differences were observed between groups for squat performance, defined as the total number of repetitions performed during 6 sets of squats, for both TIME1 and TIME4. The addition of leucine did not significantly decrease CK and LDH activity or DOMS. These results suggested that adding leucine to carbohydrate beverages did not affect acute muscle recovery and squat performance during both initial testing and during a subsequent exercise bout 72 hours later in resistance trained subjects.

  12. Metabolism of leucine and alanine in growing rats fed the diets with various protein to energy ratios

    International Nuclear Information System (INIS)

    Tanaka, Hideyuki; Yamaguchi, Michio; Kametaka, Masao

    1975-01-01

    In order to clarify the nutritional significance of metabolism of the carbon skeleton of individual amino acids, the metabolic fates of L-leucine-U- 14 C and L-alanine-U- 14 C were investigated in growing rats fed the diets with various protein calories percents (PC%) at 410 kcal of metabolizable energy. The incorporation of 14 C into body protein in 12 hr after the injection of leucine- 14 C was about 73% of the dose in the 0 and 5 PC% groups, though it decreased with increasing the levels of dietary protein from 10 to 30 PC%. The value of 14 C recovery in body protein almost agreed with the net protein utilization (NPU) determined for the whole egg protein in a similar experimental condition. The 14 C recovery in expired CO 2 and body lipid suggested that the carbon skeleton of leucine is well utilized as an energy source when the dietary carbohydrate is extensively replaced by protein. While, the incorporation of 14 C into body protein from alanine- 14 C was less than about 11% of the dose in all the dietary groups, and the majority of 14 C was recovered in expired CO 2 and body lipid in a remarked contrast to leucine. A similar pattern in urinary excretion of 14 C was obtained for these amino acids, and the refracted rise of 14 C from 10 PC% may give an indication for minimum protein requirements. (auth.)

  13. Brucella abortus strain RB51 leucine auxotroph as an environmentally safe vaccine for plasmid maintenance and antigen overexpression.

    Science.gov (United States)

    Rajasekaran, Parthiban; Seleem, Mohamed N; Contreras, Andrea; Purwantini, Endang; Schurig, Gerhardt G; Sriranganathan, Nammalwar; Boyle, Stephen M

    2008-11-01

    To avoid potentiating the spread of an antibiotic resistance marker, a plasmid expressing a leuB gene and a heterologous antigen, green fluorescent protein (GFP), was shown to complement a leucine auxotroph of cattle vaccine strain Brucella abortus RB51, which protected CD1 mice from virulent B. abortus 2308 and elicited GFP antibodies.

  14. Leucine, starch and bicarbonate utilization by specific bacterial groups in surface shelf waters off Galicia (NW Spain).

    Science.gov (United States)

    Teira, E; Hernando-Morales, V; Guerrero-Feijóo, E; Varela, M M

    2017-06-01

    The capability of different bacterial populations to degrade abundant polymers, such as algal-derived polysaccharides, or to utilize preferentially polymers over monomers, remains largely unknown. In this study, microautoradiography was combined with fluorescence in situ hybridization (MAR-FISH) to evaluate the ability of Bacteroidetes, SAR11, Roseobacter spp., Gammaproteobacteria and SAR86 cells to use bicarbonate, leucine and starch under natural light conditions at two locations in shelf surface waters off NW Spain. The percentage of cells incorporating bicarbonate was relatively high (mean 32% ± 4%) and was positively correlated with the intensity of solar radiation. The proportion of cells using starch (mean 56% ± 4%) or leucine (mean 47% ± 4%) was significantly higher than that using bicarbonate. On average, SAR11, Roseobacter spp. and Gammaproteobacteria showed a similarly high percentage of cells using leucine (47%-65% of hybridized cells) than using starch (51%-64% of hybridized cells), while Bacteroidetes and SAR86 cells preferentially used starch (53% of hybridized cells) over leucine (34%-40% of hybridized cells). We suggest that the great percentage of bacteria using starch is related to a high ambient availability of polymers associated to algal cell lysis, which, in turn, weakens the short-term coupling between phytoplankton release and bacterial production. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  15. The Influence of 8 Weeks of Whey-Protein and Leucine Supplementation on Physical and Cognitive Performance

    Science.gov (United States)

    2010-01-01

    as a primarv cause of clecreasecl physiciil ancl cognitive pcrlbnnance ( Romanowski & Grabicc, 1974).’I’ryptophan e tering the cenlr"al nervous ystern...oftihore sailing race. European Journal ofApplied Plrysiolo gy, I 04(5),7 87 I 94. Whey Protein, Leucine, and Performance 417 Romanowski , W., & Grabiec

  16. Divergent effects of endogenous and exogenous glucocorticoid-induced leucine zipper in animal models of inflammation and arthritis

    NARCIS (Netherlands)

    Ngo, Devi; Beaulieu, Elaine; Gu, Ran; Leaney, Alexandra; Santos, Leilani; Fan, Huapeng; Yang, Yuanhang; Kao, Wenping; Xu, Jiake; Escriou, Virginie; Loiler, Scott; Vervoordeldonk, Margriet J.; Morand, Eric F.

    2013-01-01

    Glucocorticoid-induced leucine zipper (GILZ) has effects on inflammatory pathways that suggest it to be a key inhibitory regulator of the immune system, and its expression is exquisitely sensitive to induction by glucocorticoids. We undertook this study to test our hypothesis that GILZ deficiency

  17. Leucine supplementation stimulates protein synthesis and reduces degradation signal activation in muscle of newborn pigs during acute endotoxemia

    Science.gov (United States)

    Sepsis disrupts skeletal muscle proteostasis and mitigates the anabolic response to leucine (Leu) in muscle of mature animals. We have shown that Leu stimulates muscle protein synthesis (PS) in healthy neonatal piglets. To determine if supplemental Leu can stimulate PS and reduce protein degradation...

  18. In vitro conditions for 14C-leucine incorporation into the protein of cultured ovaries of the silkworm, Bombyx mori

    International Nuclear Information System (INIS)

    Miyadai, Toshiaki; Yamashita, Okitsugu

    1980-01-01

    Vitellogenic ovaries of silkworm pupae were incubated in vitro in different media based on the Wyatt's medium to establish an adequate condition for culture of silkworm ovaries. Incorporation of 14 C-leucine into protein fraction was determined to assess the biochemical activity of the ovary. When ovaries were incubated in vitro for a short time by 6 hr, a saturation kinetics of incorporation of the labelled leucine was shown. Sequential substitution of K + ion to Na + ion in the medium had no effect on the incorporation of 14 C-leucine, but Mg 2+ ion appeared to stimulate synthetic activity at more than 10 mM. The activity was not affected at pH range 5.0-7.2. Neither different sugars, nor vitellogenin nor lipoprotein prepared from silkworm haemolymph affected the incorporation of 14 C-leucine, when added into the medium. The synthesis of protein depended upon the developmental stages of the cultured ovaries and was most active in 6-day-old ovary. Ovaries developing in pupal body showed comparable changes in synthetic activity. It is concluded that the chemical composition of the medium does not exert a strict effect on synthetic activity of protein in short-term cultures and the ovaries cultured in vitro maintain the activity comparable with those found in in situ condition. (author)

  19. RAS2/PKA pathway activity is involved in the nitrogen regulation of L-leucine uptake in Saccharomyces cerevisiae.

    Science.gov (United States)

    Sáenz, D A; Chianelli, M S; Stella, C A; Mattoon, J R; Ramos, E H

    1997-03-01

    The aim of the present work is to study the participation of RAS2/PKA signal pathway in the nitrogen regulation of L-leucine transport in yeast cells. The study was performed on Saccharomyces cerevisiae isogenic strains with the normal RAS2 gene, the RAS2val19 mutant and the disrupted ras2::LEU2. These strains bring about different activities of the RAS2/PKA signal pathway, L-(14C)-Amino acid uptake measurements were determined in cells grown in a rich YPD medium with a mixed nitrogen source or in minimal media containing NH4+ or L-proline as the sole nitrogen source. We report herein that in all strains used, even in those grown in a minimal proline medium, the activity of the general amino acid permease (GAP1) was not detected. L-Leucine uptake in these strains is mediated by two kinetically characterized transport systems. Their KT values are of the same order as those of S1 and S2 L-leucine permeases. Mutation in the RAS2 gene alters initial velocities and Jmax values in both high and low affinity L-leucine transport systems. Activation of the RAS2/PKA signalling pathway by the RAS2val19 mutation, blocks the response to a poor nitrogen source whereas inactivation of RAS2 by gene disruption, results in an increase of the same response.

  20. Distinct Plasma Profile of Polar Neutral Amino Acids, Leucine, and Glutamate in Children with Autism Spectrum Disorders

    Science.gov (United States)

    Tirouvanziam, Rabindra; Obukhanych, Tetyana V.; Laval, Julie; Aronov, Pavel A.; Libove, Robin; Banerjee, Arpita Goswami; Parker, Karen J.; O'Hara, Ruth; Herzenberg, Leonard A.; Herzenberg, Leonore A.; Hardan, Antonio Y.

    2012-01-01

    The goal of this investigation was to examine plasma amino acid (AA) levels in children with Autism Spectrum Disorders (ASD, N = 27) and neuro-typically developing controls (N = 20). We observed reduced plasma levels of most polar neutral AA and leucine in children with ASD. This AA profile conferred significant post hoc power for discriminating…

  1. Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs

    Science.gov (United States)

    Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have previously shown that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in...

  2. Determination of proteolytic activity using L-[4,5-3H]leucine-labelled globin as a substrate

    International Nuclear Information System (INIS)

    Maliopoulou, T.B.; Dionyssiou-Asteriou, A.; Loucopoulos, D.

    1980-01-01

    A simple and sensitive method for the assay of proteolytic enzyme activity is described. This is based on the digestion of L-[4,5- 3 H]leucine globin by proteolytic enzymes and radioactivity measurement of the trichloroacetic acid soluble cleavage products. (Auth.)

  3. Valine but not leucine or isoleucine supports neurotransmitter glutamate synthesis during synaptic activity in cultured cerebellar neurons

    DEFF Research Database (Denmark)

    Bak, Lasse Kristoffer; Johansen, Maja L.; Schousboe, Arne

    2012-01-01

    Synthesis of neuronal glutamate from a-ketoglutarate for neurotransmission necessitates an amino group nitrogen donor; however, it is not clear which amino acid(s) serves this role. Thus, the ability of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine, to act as amino...

  4. Short-term variability in bacterial abundance, cell properties, and incorporation of leucine and thymidine in subarctic sea ice

    DEFF Research Database (Denmark)

    Kaartokallio, H.; Søgaard, D.H.; Norman, L.

    2013-01-01

    Sea ice is a biome of immense size and provides a range of habitats for diverse microbial communities, many of which are adapted to living at low temperatures and high salinities in brines. We measured simultaneous incorporation of thymidine (TdR) and leucine (Leu), bacterial cell abundance...

  5. Regulation of MIR165/166 by class II and class III homeodomain leucine zipper proteins establishes leaf polarity

    DEFF Research Database (Denmark)

    Merelo, Paz; Ram, Hathi; Caggiano, Monica Pia

    2016-01-01

    A defining feature of plant leaves is their flattened shape. This shape depends on an antagonism between the genes that specify adaxial (top) and abaxial (bottom) tissue identity; however, the molecular nature of this antagonism remains poorly understood. Class III homeodomain leucine zipper (HD...

  6. The enzymatic degradation and transport of leucine-enkephalin and 4-imidazolidinone enkephalin prodrugs at the blood-brain barrier

    DEFF Research Database (Denmark)

    Lund, L.; Bak, A.; Friis, G.J.

    1998-01-01

    In this study, the stability in and transport across a cell culture model of the blood-brain barrier (BBB) is investigated for leucine-enkephalin (Leu-enkephalin) and four 4-imidazolidinone prodrugs of Leu-enkephalin. The results show that Leu-enkephalin is degraded in the cell culture model...

  7. Biosynthesis of the leucine derived α-, β- and γ-hydroxynitrile glucosides in barley (Hordeum vulgare L.)

    DEFF Research Database (Denmark)

    Knoch, Eva; Motawie, Mohammed Saddik; Olsen, Carl Erik

    2016-01-01

    Barley (Hordeum vulgare L.) produces five leucine-derived hydroxynitrile glucosides (HNGs), of which only epiheterodendrin is a cyanogenic glucoside. The four non-cyanogenic HNGs are the β-HNG epidermin and the γ-HNGs osmaronin, dihydroosmaronin and sutherlandin. By analyzing 247 spring barley...

  8. A novel fluorometric ultramicro determination of serum leucine aminopeptidase using a coumarine derivative.

    Science.gov (United States)

    Saifuku, K; Sekine, T; Namihisa, T; Takahashi, T; Kanaoka, Y

    1978-03-01

    A simple and rapid rate assay of serum leucine aminopeptidase is described, using a novel fluorogenic substrate, 7-L-leucyl-4-methylcoumarinylamide. The reaction is initiated by adding 10 microliter of serum, and the fluorescence development for 1 min due to the 7-amino-4-methylcoumarin liberated at 37 degrees C is followed directly on a recorder. The proposed method is proved to be free from error due to the adsorption of the substrate dye to serum albumin and to be applicable to hyperbilirubinemic sera by simple correction. The values obtained by this method showed good correlation with those obtained by the conventional method of Goldbarg and Rutenberg (Goldbarg, J.A. and Rutenberg, A.M. (1958) Cancer 11, 283-291).

  9. A microsystem to evaluate the synthesis of [3H]leucine labeled proteins by macrophages

    International Nuclear Information System (INIS)

    Varesio, L.; Eva, A.

    1980-01-01

    A method is described for evaluating protein synthesis by adherent MPHI by measuring the incorporation of [ 3 H]leucine into TCA precipitable material. By using guanidine-HCl it was possible to remove completely the radiolabeled proteins from the adherent cells that were cultured in microwells, and retain TCA precipitable material. This procedure enabled the authors to harvest the TCA precipitable proteins with a semiautomatic cell harvester. The guanidine-HCl treatment did not affect the recovery of the radioactive proteins and did not alter the sensitivity of the assay. This method is very simple and rapid and, since it is suitable for processing microcultures, permits detailed studies on the biology of small numbers of MPHI. (Auth.)

  10. Structural basis for the regulation of maternal embryonic leucine zipper kinase.

    Directory of Open Access Journals (Sweden)

    Lu-Sha Cao

    Full Text Available MELK (maternal embryonic leucine zipper kinase, which is a member of the AMPK (AMP-activated protein kinase-related kinase family, plays important roles in diverse cellular processes and has become a promising drug target for certain cancers. However, the regulatory mechanism of MELK remains elusive. Here, we report the crystal structure of a fragment of human MELK that contains the kinase domain and ubiquitin-associated (UBA domain. The UBA domain tightly binds to the back of the kinase domain, which may contribute to the proper conformation and activity of the kinase domain. Interestingly, the activation segment in the kinase domain displays a unique conformation that contains an intramolecular disulfide bond. The structural and biochemical analyses unravel the molecular mechanisms for the autophosphorylation/activation of MELK and the dependence of its catalytic activity on reducing agents. Thus, our results may provide the basis for designing specific MELK inhibitors for cancer treatment.

  11. Leucine-rich repeat-containing synaptic adhesion molecules as organizers of synaptic specificity and diversity.

    Science.gov (United States)

    Schroeder, Anna; de Wit, Joris

    2018-04-09

    The brain harbors billions of neurons that form distinct neural circuits with exquisite specificity. Specific patterns of connectivity between distinct neuronal cell types permit the transfer and computation of information. The molecular correlates that give rise to synaptic specificity are incompletely understood. Recent studies indicate that cell-surface molecules are important determinants of cell type identity and suggest that these are essential players in the specification of synaptic connectivity. Leucine-rich repeat (LRR)-containing adhesion molecules in particular have emerged as key organizers of excitatory and inhibitory synapses. Here, we discuss emerging evidence that LRR proteins regulate the assembly of specific connectivity patterns across neural circuits, and contribute to the diverse structural and functional properties of synapses, two key features that are critical for the proper formation and function of neural circuits.

  12. Heart rate variability in leucine-rich repeat kinase 2-associated Parkinson's disease.

    Science.gov (United States)

    Visanji, Naomi P; Bhudhikanok, Grace S; Mestre, Tiago A; Ghate, Taneera; Udupa, Kaviraj; AlDakheel, Amaal; Connolly, Barbara S; Gasca-Salas, Carmen; Kern, Drew S; Jain, Jennifer; Slow, Elizabeth J; Faust-Socher, Achinoam; Kim, Sam; Azhu Valappil, Ruksana; Kausar, Farah; Rogaeva, Ekaterina; William Langston, J; Tanner, Caroline M; Schüle, Birgitt; Lang, Anthony E; Goldman, Samuel M; Marras, Connie

    2017-04-01

    Heart rate variability is reduced in idiopathic PD, indicating cardiac autonomic dysfunction likely resulting from peripheral autonomic synucleinopathy. Little is known about heart rate variability in leucine-rich repeat kinase 2-associated PD. This study investigated heart rate variability in LRRK2-associated PD. Resting electrocardiograms were obtained from 20 individuals with LRRK2-associated PD, 37 nonmanifesting carriers, 48 related noncarriers, 26 idiopathic PD patients, and 32 controls. Linear regression modelling compared time and frequency domain values, adjusting for age, sex, heart rate, and disease duration. Low-frequency power and the ratio of low-high frequency power were reduced in idiopathic PD versus controls (P Heart rate variability may remain intact in LRRK2-associated PD, adding to a growing literature supporting clinical-pathologic differences between LRRK2-associated and idiopathic PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  13. Dietary leucine--an environmental modifier of insulin resistance acting on multiple levels of metabolism

    DEFF Research Database (Denmark)

    Macotela, Yazmin; Emanuelli, Brice; Bång, Anneli M

    2011-01-01

    Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor--leucine--can modify insulin resistance by acting on multiple tissues...... homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose...... with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest...

  14. L-leucine dietary supplementation modulates muscle protein degradation and increases pro-inflammatory cytokines in tumour-bearing rats.

    Science.gov (United States)

    Cruz, Bread; Oliveira, André; Gomes-Marcondes, Maria Cristina Cintra

    2017-08-01

    Cancer cachexia is characterised by involuntary weight loss associated with systemic inflammation and metabolic changes. Studies aimed at maintaining lean body mass in cachectic tumour-bearing hosts have made important contributions reducing the number of deaths and improving the quality of life. In recent years, leucine has demonstrated effective action in maintaining lean body mass by decreasing muscle protein degradation. Currently, there is a growing need to understand how leucine stimulates protein synthesis and acts protectively in a cachectic organism. Thus, this study aimed to assess the effects of a leucine-rich diet on protein degradation signalling in muscle over the course of tumour growth. Animals were distributed into four experimental groups, which did or did not receive 2×10 6 viable Walker-tumour cells. Some were fed a leucine-rich diet, and the groups were subsequently sacrificed at three different time points of tumour evolution (7th, 14th, and 21st days). Protein degradation signals, as indicated by ubiquitin-proteasome subunits (11S, 19S, and 20S) and pro- and anti-inflammatory cytokines, were analysed in all experimental groups. In tumour-bearing animals without nutritional supplementation (W7, W14, and W21 groups), we observed that the tumour growth promoted a concurrent decrease in muscle protein, a sharp increase in pro-inflammatory cytokines (TNFα, IL-6, and IFNγ), and a progressive increase in proteasome subunits (19S and 20S). Thus, the leucine-supplemented tumour-bearing groups showed improvements in muscle mass and protein content, and in this specific situation, the leucine-rich diet led to an increase on the day in cytokine profile and proteasome subunits mainly on the 14th day, which subsequently had a modulating effect on tumour growth on the 21st day. These results indicate that the presence of leucine in the diet may modulate important aspects of the proteasomal pathway in cancer cachexia and may prevent muscle wasting due to

  15. Copolymers based on N-acryloyl-L-leucine and urea methacrylate with pyridine moieties

    Directory of Open Access Journals (Sweden)

    Buruiana Emil C.

    2016-01-01

    Full Text Available By using free radical polymerization of (N-methacryloyloxyethyl-N′-4-picolyl-urea (MAcPU and N-acryloyl-L-leucine (AcLeu, an optically active copolymer, poly[(N-methacryloyloxyethyl-N′-4-picolyl-urea-co-N-acryloyl-L-leucine], MAcPU-co-AcLeu (1.86:1 molar ratio was prepared and subsequently functionalized at the pyridine-N with (1R/S-(−/+-10-camphorsulfonic acid (R/S-CSA and at carboxyl group with (R-(+-α-ethylbenzylamine (R-EBA or trans-4-stilbene methanol (t-StM. The structures, chemical composition and chiroptical activity of the monomers and the copolymers were characterized by spectral analysis (FTIR, 1H (13C-NMR, 1H,1H-COSY, UV/vis, thermal methods (TGA, DSC, fluorescence spectroscopy, gel permeation chromatography and specific rotation measurements. Influence of the optical activity of monomer and modifier on modified copolymers suggested a good correlation between the experimental data obtained (23[α]589=+12.5° for AcLeu and MAcPU-co-AcLeu, 23[α]589=0°+27.5° for (MAcPU-co-AcLeu-R/S-CSA, 23[α]589=+25° for (MAcPU-co-AcLeu-R-EBA, and 23[α]589 = 0° for (MAcPU-co-AcLeu-St. In addition, the photobehavior of the stilbene copolymer (MAcPU-co-AcLeu-St in film was investigated by UV-vis spectroscopy. The fluorescence quenching of the stilbene species in the presence of aliphatic/aromatic amine in DMF solution was evaluated, more efficiently being 4,4′−dipyridyl (detection limit: 7.2 x 10-6 mol/L.

  16. Metabolism of L-leucine-U-14C in young rats fed excess glycine diets

    International Nuclear Information System (INIS)

    Takeuchi, Hisanao; Tadauchi, Nobuo; Muramatsu, Keiichiro

    1975-01-01

    As reported previously, while the growth-depressing effect of excess glycine was prevented by supplementing L-arginine and L-methionine, the degradation of glycine-U-(SUP 14)C into expired carbon dioxide was not accelerated by the supplement of both amino acids. However, it was found that the incorporation of the isotope into the lipids of livers and carcasses increased in the rats fed the excess glycine diet containing both amino acids. The lipid synthesis utilizing excess glycine may be accelerated by adding both amino acids to the 10% casein diet containing excess glycine. In the present experiment, the metabolic fate of L-leucine-U-(SUP 14)C was studied with the rats fed the excess glycine diet with or without L-arginine and L-methionine. 10% casein (10C), 10% casein diet containing 7% glycine (10C7G), or 10C7G Supplemented with 1.4% L-arginine-HCL and 0.9% L-methionine (10C7GArgMet) was fed to each rat, and the diet suspension containing 4 sup(μ)Ci of L-leucine-U-(SUP 14)C per 100 g of body weight was fed forcibly after 12 hr fast. The radioactivity in expired carbon dioxide, TCA soluble fraction, protein, glycogen, lipids and urine, and the concentration of free amino acids in blood plasma, livers and urine were measured. The body weight gain and food intake of the 10C7G group were much smaller than those of the other groups. The recovery of (SUP 14)C-radioactivity in expired carbon dioxide was much lower in the 10C7GArgMet group than that of the other groups. (Kako, I.)

  17. Synergistic effects of polyphenols and methylxanthines with Leucine on AMPK/Sirtuin-mediated metabolism in muscle cells and adipocytes.

    Directory of Open Access Journals (Sweden)

    Antje Bruckbauer

    Full Text Available The AMPK-Sirt1 pathway is an important regulator of energy metabolism and therefore a potential target for prevention and therapy of metabolic diseases. We recently demonstrated leucine and its metabolite β-hydroxy-β-methylbutyrate (HMB to synergize with low-dose resveratrol (200 nM to activate sirtuin signaling and stimulate energy metabolism. Here we show that leucine exerts a direct effect on Sirt1 kinetics, reducing its Km for NAD(+ by >50% and enabling low doses of resveratrol to further activate the enzyme (p = 0.012. To test which structure elements of resveratrol are necessary for synergy, we assessed potential synergy of structurally similar and dissimilar polyphenols as well as other compounds converging on the same pathways with leucine using fatty acid oxidation (FAO as screening tool. Dose-response curves for FAO were constructed and the highest non-effective dose (typically 1-10 nM was used with either leucine (0.5 mM or HMB (5 µM to treat adipocytes and myotubes for 24 h. Significant synergy was detected for stilbenes with FAO increase in adipocytes by 60-70% (p2000% (p1 µM and exhibited little or no synergy. Thus, the six-carbon ring structure bound to a carboxylic group seems to be a necessary element for leucine/HMB synergy with other stilbenes and hydroxycinnamic acids to stimulate AMPK/Sirt1 dependent FAO; these effects occur at concentrations that produce no independent effects and are readily achievable via oral administration.

  18. A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats

    Directory of Open Access Journals (Sweden)

    Gomes-Marcondes M.C.C.

    2003-01-01

    Full Text Available Cancer cachexia induces host protein wastage but the mechanisms are poorly understood. Branched-chain amino acids play a regulatory role in the modulation of both protein synthesis and degradation in host tissues. Leucine, an important amino acid in skeletal muscle, is higher oxidized in tumor-bearing animals. A leucine-supplemented diet was used to analyze the effects of Walker 256 tumor growth on body composition in young weanling Wistar rats divided into two main dietary groups: normal diet (N, 18% protein and leucine-rich diet (L, 15% protein plus 3% leucine, which were further subdivided into control (N or L or tumor-bearing (W or LW subgroups. After 12 days, the animals were sacrificed and their carcass analyzed. The tumor-bearing groups showed a decrease in body weight and fat content. Lean carcass mass was lower in the W and LW groups (W = 19.9 ± 0.6, LW = 23.1 ± 1.0 g vs N = 29.4 ± 1.3, L = 28.1 ± 1.9 g, P < 0.05. Tumor weight was similar in both tumor-bearing groups fed either diet. Western blot analysis showed that myosin protein content in gastrocnemius muscle was reduced in tumor-bearing animals (W = 0.234 ± 0.033 vs LW = 0.598 ± 0.036, N = 0.623 ± 0.062, L = 0.697 ± 0.065 arbitrary intensity, P < 0.05. Despite accelerated tumor growth, LW animals exhibited a smaller reduction in lean carcass mass and muscle myosin maintenance, suggesting that excess leucine in the diet could counteract, at least in part, the high host protein wasting in weanling tumor-bearing rats.

  19. L-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome.

    Science.gov (United States)

    Xu, Baoshan; Sowa, Nenja; Cardenas, Maria E; Gerton, Jennifer L

    2015-03-15

    Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that RBS was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation. l-leucine stimulation of the mTOR pathway partially rescued translation in human RBS cells and development in zebrafish models of RBS. In this study, we investigate protein translation in zebrafish models of CdLS. Our results show that phosphorylation of RPS6 as well as 4E-binding protein 1 (4EBP1) was reduced in nipbla/b, rad21 and smc3-morphant embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis and rRNA production were decreased in the cohesin morphant embryo cells. l-leucine partly rescued protein synthesis and rRNA production in the cohesin morphants and partially restored phosphorylation of RPS6 and 4EBP1. Concomitantly, l-leucine treatment partially improved cohesinopathy embryo development including the formation of craniofacial cartilage. Interestingly, we observed that alpha-ketoisocaproate (α-KIC), which is a keto derivative of leucine, also partially rescued the development of rad21 and nipbla/b morphants by boosting mTOR-dependent translation. In summary, our results suggest that cohesinopathies are caused in part by defective protein synthesis, and stimulation of the mTOR pathway through l-leucine or its metabolite α-KIC can partially rescue development in zebrafish models for CdLS. © The Author 2014. Published by Oxford University Press.

  20. The leucine zipper domains of the transcription factors GCN4 and c-Jun have ribonuclease activity.

    Directory of Open Access Journals (Sweden)

    Yaroslav Nikolaev

    Full Text Available Basic-region leucine zipper (bZIP proteins are one of the largest transcription factor families that regulate a wide range of cellular functions. Owing to the stability of their coiled coil structure leucine zipper (LZ domains of bZIP factors are widely employed as dimerization motifs in protein engineering studies. In the course of one such study, the X-ray structure of the retro-version of the LZ moiety of yeast transcriptional activator GCN4 suggested that this retro-LZ may have ribonuclease activity. Here we show that not only the retro-LZ but also the authentic LZ of GCN4 has weak but distinct ribonuclease activity. The observed cleavage of RNA is unspecific, it is not suppressed by the ribonuclease A inhibitor RNasin and involves the breakage of 3',5'-phosphodiester bonds with formation of 2',3'-cyclic phosphates as the final products as demonstrated by HPLC/electrospray ionization mass spectrometry. Several mutants of the GCN4 leucine zipper are catalytically inactive, providing important negative controls and unequivocally associating the enzymatic activity with the peptide under study. The leucine zipper moiety of the human factor c-Jun as well as the entire c-Jun protein are also shown to catalyze degradation of RNA. The presented data, which was obtained in the test-tube experiments, adds GCN4 and c-Jun to the pool of proteins with multiple functions (also known as moonlighting proteins. If expressed in vivo, the endoribonuclease activity of these bZIP-containing factors may represent a direct coupling between transcription activation and controlled RNA turnover. As an additional result of this work, the retro-leucine zipper of GCN4 can be added to the list of functional retro-peptides.

  1. Regularity of Dual Gabor Windows

    Directory of Open Access Journals (Sweden)

    Ole Christensen

    2013-01-01

    Full Text Available We present a construction of dual windows associated with Gabor frames with compactly supported windows. The size of the support of the dual windows is comparable to that of the given window. Under certain conditions, we prove that there exist dual windows with higher regularity than the canonical dual window. On the other hand, there are cases where no differentiable dual window exists, even in the overcomplete case. As a special case of our results, we show that there exists a common smooth dual window for an interesting class of Gabor frames. In particular, for any value of K∈ℕ, there is a smooth function h which simultaneously is a dual window for all B-spline generated Gabor frames {EmbTnBN(x/2}m,n∈ℕ for B-splines BN of order N=1,…,2K+1 with a fixed and sufficiently small value of b.

  2. Differential effect of long-term leucine supplementation on skeletal muscle and adipose tissue in old rats: an insulin signaling pathway approach.

    Science.gov (United States)

    Zeanandin, Gilbert; Balage, Michèle; Schneider, Stéphane M; Dupont, Joëlle; Hébuterne, Xavier; Mothe-Satney, Isabelle; Dardevet, Dominique

    2012-04-01

    Leucine acts as a signal nutrient in promoting protein synthesis in skeletal muscle and adipose tissue via mTOR pathway activation, and may be of interest in age-related sarcopenia. However, hyper-activation of mTOR/S6K1 has been suggested to inhibit the first steps of insulin signaling and finally promote insulin resistance. The impact of long-term dietary leucine supplementation on insulin signaling and sensitivity was investigated in old rats (18 months old) fed a 15% protein diet supplemented (LEU group) or not (C group) with 4.5% leucine for 6 months. The resulting effects on muscle and fat were examined. mTOR/S6K1 signaling pathway was not significantly altered in muscle from old rats subjected to long-term dietary leucine excess, whereas it was increased in adipose tissue. Overall glucose tolerance was not changed but insulin-stimulated glucose transport was improved in muscles from leucine-supplemented rats related to improvement in Akt expression and phosphorylation in response to food intake. No change in skeletal muscle mass was observed, whereas perirenal adipose tissue mass accumulated (+45%) in leucine-supplemented rats. A prolonged leucine supplementation in old rats differently modulates mTOR/S6K pathways in muscle and adipose tissue. It does not increase muscle mass but seems to promote hypertrophy and hyperplasia of adipose tissue that did not result in insulin resistance.

  3. Higher Representations Duals

    DEFF Research Database (Denmark)

    Sannino, Francesco

    2010-01-01

    We uncover novel solutions of the 't Hooft anomaly matching conditions for scalarless gauge theories with matter transforming according to higher dimensional representations of the underlying gauge group. We argue that, if the duals exist, they are gauge theories with fermions transforming accord......-Dyson approximation. We use the solutions to gain useful insight on the conformal window of the associated electric theory. A consistent picture emerges corroborating previous results obtained via different analytic methods and in agreement with first principle lattice explorations....

  4. Dual isotope assays

    International Nuclear Information System (INIS)

    Smith, G.F.W.; Stevens, R.A.J.; Jacoby, B.

    1980-01-01

    Dual isotope assays for thyroid function are performed by carrying out a radio-immunoassay for two of thyroxine (T4), tri-iodothyronine (T3), thyroid stimulating hormone (TSH), and thyroxine binding globulin (TBG), by a method wherein a version of one of the thyroid components, preferably T4 or T3 is labelled with Selenium-75 and the version of the other thyroid component is labelled with a different radionuclide, preferably Iodine-125. (author)

  5. Dual-Schemata Model

    Science.gov (United States)

    Taniguchi, Tadahiro; Sawaragi, Tetsuo

    In this paper, a new machine-learning method, called Dual-Schemata model, is presented. Dual-Schemata model is a kind of self-organizational machine learning methods for an autonomous robot interacting with an unknown dynamical environment. This is based on Piaget's Schema model, that is a classical psychological model to explain memory and cognitive development of human beings. Our Dual-Schemata model is developed as a computational model of Piaget's Schema model, especially focusing on sensori-motor developing period. This developmental process is characterized by a couple of two mutually-interacting dynamics; one is a dynamics formed by assimilation and accommodation, and the other dynamics is formed by equilibration and differentiation. By these dynamics schema system enables an agent to act well in a real world. This schema's differentiation process corresponds to a symbol formation process occurring within an autonomous agent when it interacts with an unknown, dynamically changing environment. Experiment results obtained from an autonomous facial robot in which our model is embedded are presented; an autonomous facial robot becomes able to chase a ball moving in various ways without any rewards nor teaching signals from outside. Moreover, emergence of concepts on the target movements within a robot is shown and discussed in terms of fuzzy logics on set-subset inclusive relationships.

  6. The DUAL mission concept

    Science.gov (United States)

    von Ballmoos, Peter; Alvarez, Jose; Barriere, Nicolas; Boggs, Steve; Bykov, Andrei; Del Cura Velayos, Juan Manuel; Frontera, Filippo; Hanlon, Lorraine; Hernanz, Margarita; Hinglais, Emmanuel; Isern, Jordi; Jean, Pierre; Knödlseder, Jürgen; Kuiper, Lucien; Leising, Mark; Pirard, Benoît; Prost, Jean-Pierre; da Silva, Rui; Takahashi, Tadayuki; Tomsick, John; Walter, Roland; Zoglauer, Andreas

    2011-09-01

    DUAL will study the origin and evolution of the elements and explores new frontiers of physics: extreme energies that drive powerful stellar explosions and accelerate particles to macroscopic energies; extreme densities that modify the laws of physics around the most compact objects known; and extreme fields that influence matter in a way that is unknown on Earth. The variability of these extreme objects requires continuous all-sky coverage, while detailed study demands an improvement in sensitivity over previous technologies by at least an order of magnitude. The DUAL payload is composed of an All-Sky Compton Imager (ASCI), and two optical modules, the Laue-Lens Optic (LLO) and the Coded-Mask Optic (CMO). The ASCI serves dual roles simultaneously, both as an optimal focal-plane sensor for deep observations with the optical modules and as a sensitive true all-sky telescope in its own right for all-sky surveys and monitoring. While the optical modules are located on the main satellite, the All-Sky Compton Imager is situated on a deployable structure at a distance of 30 m from the satellite. This configuration not only permits to maintain the less massive payload at the focal distance, it also greatly reduces the spacecraft-induced detector background, and, above all it provides ASCI with a continuous all-sky exposure.

  7. Leucine-induced activation of translational initiation is partly regulated by the branched-chain α-keto acid dehydrogenase complex in C2C12 cells

    International Nuclear Information System (INIS)

    Nakai, Naoya; Shimomura, Yoshiharu; Tamura, Tomohiro; Tamura, Noriko; Hamada, Koichiro; Kawano, Fuminori; Ohira, Yoshinobu

    2006-01-01

    Branched-chain amino acid leucine has been shown to activate the translational regulators through the mammalian target of rapamycin. However, the leucine's effects are self-limiting because leucine promotes its own disposal by an oxidative pathway. The irreversible and rate-limiting step in the leucine oxidation pathway is catalyzed by the branched-chain α-keto acid dehydrogenase (BCKDH) complex. The complex contains E1 (α2β2), E2, and E3 subunits, and its activity is abolished by phosphorylation of the E1α subunit by BCKDH kinase. The relationship between the activity of BCKDH complex and leucine-mediated activation of the protein translation was investigated using the technique of RNA interference. The activity of BCKDH complex in C2C12 cell was modulated by transfection of small interfering RNA (siRNA) for BCKDH E2 subunit or BCKDH kinase. Transfection of siRNAs decreased the mRNA expression and protein amount of corresponding gene. Suppression of either E2 subunit or kinase produced opposite effects on the cell proliferation and the activation of translational regulators by leucine. Suppression of BCKDH kinase for 48 h resulted in decreasing cell proliferation. In contrast, E2 suppression led to increased amount of total cellular protein. The phosphorylation of p70 S6 kinase by leucine was increased in E2-siRNA transfected C2C12 cells, whereas the leucine's effect was diminished in kinase-siRNA transfected cells. These results suggest that the activation of the translational regulators by leucine was partly regulated by the activity of BCKDH complex

  8. The corroboration of the predominant localization of radioactivity on the dimethylallyl pyrophosphate-derived moiety of linalool biosynthesized from radioisotopically labeled leucine by higher plants

    International Nuclear Information System (INIS)

    Tange, Keiji; Okita, Hitoshi; Nakao, Yoshitaka; Hirata, Toshifumi; Suga, Takayuki

    1981-01-01

    The co-feeding experiment of leucine-4,5- 3 H and mevalonic-2- 14 C acid corroborated the preferential localization of radioactivity on the 3,3-dimethylallyl pyrophosphate-derived moiety of linalool in its biosynthesis from radioisotopically labeled leucine by Cinnamomum Camphora Sieb. var. linalooliferum Fujita, in contrast to the predominant location of the activity on its isopentenyl pyrophosphate-derived moiety in the biosynthesis from mevalonic acid. Also, it was established that the imbalance in the localization of radioactivity is not influenced by exogenous administration of leucine or inhibition of isopentenyl pyrophosphate isomerase. (author)

  9. Corroboration of the predominant localization of radioactivity on the dimethylallyl pyrophosphate-derived moiety of linalool biosynthesized from radioisotopically labeled leucine by higher plants

    Energy Technology Data Exchange (ETDEWEB)

    Tange, K.; Okita, H.; Nakao, Y.; Hirata, T.; Suga, T. (Hiroshima Univ. (Japan). Faculty of Science)

    1981-06-01

    The co-feeding experiment of leucine-4,5-/sup 3/H and mevalonic-2-/sup 14/C acid corroborated the preferential localization of radioactivity on the 3,3-dimethylallyl pyrophosphate-derived moiety of linalool in its biosynthesis from radioisotopically labeled leucine by Cinnamomum Camphora Sieb. var. linalooliferum Fujita, in contrast to the predominant location of the activity on its isopentenyl pyrophosphate-derived moiety in the biosynthesis from mevalonic acid. Also, it was established that the imbalance in the localization of radioactivity is not influenced by exogenous administration of leucine or inhibition of isopentenyl pyrophosphate isomerase.

  10. Dual Smarandache Curves of a Timelike Curve lying on Unit dual Lorentzian Sphere

    OpenAIRE

    Kahraman, Tanju; Hüseyin Ugurlu, Hasan

    2016-01-01

    In this paper, we give Darboux approximation for dual Smarandache curves of time like curve on unit dual Lorentzian sphere. Firstly, we define the four types of dual Smarandache curves of a timelike curve lying on dual Lorentzian sphere.

  11. Self-dual electromagnetic fields

    Science.gov (United States)

    Chubykalo, Andrew E.; Espinoza, Augusto; Kosyakov, B. P.

    2010-08-01

    We demonstrate the utility of self-dual fields in electrodynamics. Stable configurations of free electromagnetic fields can be represented as superpositions of standing waves, each possessing zero Poynting vector and zero orbital angular momentum. The standing waves are themselves superpositions of self-dual and anti-self-dual solutions. The idea of self-duality provides additional insights into the geometrical and spectral properties of stable electromagnetic configurations, such as those responsible for the formation of ball lightning.

  12. Cold, Gas-Phase UV and IR Spectroscopy of Protonated Leucine Enkephalin and its Analogues

    Science.gov (United States)

    Burke, Nicole L.; Redwine, James; Dean, Jacob C.; McLuckey, Scott A.; Zwier, Timothy S.

    2014-06-01

    The conformational preferences of peptide backbones and the resulting hydrogen bonding patterns provide critical biochemical information regarding the structure-function relationship of peptides and proteins. The spectroscopic study of cryogenically-cooled peptide ions in a mass spectrometer probes these H-bonding arrangements and provides information regarding the influence of a charge site. Leucine enkephalin, a biologically active endogenous opiod peptide, has been extensively studied as a model peptide in mass spectrometry. This talk will present a study of the UV and IR spectroscopy of protonated leucine enkephalin [YGGFL+H]+ and two of its analogues: the sodiated [YGGFL+Na]+ and C-terminally methyl esterified [YGGFL-OMe+H]+ forms. All experiments were performed in a recently completed multi-stage mass spectrometer outfitted with a cryocooled ion trap. Ions are generated via nano-electrospray ionization and the analyte of interest is isolated in a linear ion trap. The analyte ions are trapped in a 22-pole ion trap held at 5 K by a closed cycle helium cryostat and interrogated via UV and IR lasers. Photofragments are trapped and isolated in a second LIT and mass analyzed. Double-resonance UV and IR methods were used to assign the conformation of [YGGFL+H]+, using the NH/OH stretch, Amide I, and Amide II regions of the infrared spectrum. The assigned structure contains a single backbone conformation at vibrational/rotational temperatures of 10 K held together with multiple H-bonds that self-solvate the NH3+ site. A "proton wire" between the N and C termini reinforces the H-bonding activity of the COO-H group to the F-L peptide bond, whose cleavage results in formation of the b4 ion, which is a prevalent, low-energy fragmentation pathway for [YGGFL+H]+. The reinforced H-bonding network in conjunction with the mobile proton theory may help explain the prevalence of the b4 pathway. In order to elucidate structural changes caused by modifying this H-bonding activity

  13. Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica

    Energy Technology Data Exchange (ETDEWEB)

    Kerkhoven, Eduard J.; Kim, Young-Mo; Wei, Siwei; Nicora, Carrie D.; Fillmore, Thomas L.; Purvine, Samuel O.; Webb-Robertson, Bobbie-Jo; Smith, Richard D.; Baker, Scott E.; Metz, Thomas O.; Nielsen, Jens; Lee, Sang Yup

    2017-06-20

    ABSTRACT

    The yeastYarrowia lipolyticais a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis inY. lipolyticaand identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination ofDGA1overexpression with nitrogen limitation resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor.

    IMPORTANCEThe ubiquitous metabolism of lipids involves refined regulation, and an enriched understanding of this regulation would have wide implications. Various factors can influence lipid metabolism, including the environment and genetics. We demonstrated, using a multi-omics and multifactorial experimental setup, that multiple factors affect lipid accumulation in the yeastYarrowia lipolytica. Using integrative analysis, we identified novel interactions between nutrient restriction and genetic factors

  14. Molecular identification and characterization of leucine aminopeptidase 2, an excretory-secretory product of Clonorchis sinensis.

    Science.gov (United States)

    Deng, Chuanhuan; Sun, Jiufeng; Li, Xuerong; Wang, Lexun; Hu, Xuchu; Wang, Xiaoyun; Chen, Wenjun; Lv, Xiaoli; Liang, Chi; Li, Wenfang; Huang, Yan; Li, Ran; Wu, Zhongdao; Yu, Xinbing; Xu, Jin

    2012-10-01

    Aminopeptidases serve vital roles in metabolism of hormones, neurotransmission, turnover of proteins and immunological regulations. Leucine aminopeptidases catalyze the hydrolysis of amino-acid residues from the N-terminus of proteins and peptides. In the present study, leucine aminopeptidase 2 (LAP2) gene of Clonorchis sinensis (C. sinensis) was isolated and identified from an adult cDNA library of C. sinensis. Recombinant CsLAP2 was expressed and purified in Escherichia coli BL21. The open reading frame of LAP2 contains 1,560 bp equivalent to 519 amino acids, a similarity analysis showed a relatively low homology with Homo sapiens (19.0 %), Trypanosoma cruzi (18.0 %), Mus musculus (19.3 %), and relatively high homology with Schistosoma mansoni (65.6 %). The optimum condition of rCsLAP2 enzyme activity was investigated using a fluorescent substrate of Leu-MCA at 37 °C and pH 7.5. The K (m) and V (max) values of rCsLAP2 were 18.2 μM and 10.7 μM/min, respectively. CsLAP2 gene expression can be detected at the stages of the adult worm, metacercaria, excysted metacercaria and egg of C. sinensis using real-time PCR, no difference was observed at the stages of the adult worm, metacercaria and egg. However, CsLAP2 showed a higher expression level at the stage of excysted metacercaria than the adult worm (3.90-fold), metacercaria (4.60-fold) and egg (4.59-fold). Histochemistry analysis showed that CsLAP2 was located at the tegument and excretory vesicle of metacercaria, and the tegument and intestine of adult worm. The immune response specific to rCsLAP2 was characterized by a mixed response patterns of Th1 and Th2, indicating a compounded humoral and cellular immune response. The combined results from the present study indicate that CsLAP2 was an important antigen exposed to host immune system, and probably implicated as potential role in interaction with host cells in clonorchiasis.

  15. Sequence-structure-function relations of the mosquito leucine-rich repeat immune proteins

    Directory of Open Access Journals (Sweden)

    Povelones Michael

    2010-09-01

    Full Text Available Abstract Background The discovery and characterisation of factors governing innate immune responses in insects has driven the elucidation of many immune system components in mammals and other organisms. Focusing on the immune system responses of the malaria mosquito, Anopheles gambiae, has uncovered an array of components and mechanisms involved in defence against pathogen infections. Two of these immune factors are LRIM1 and APL1C, which are leucine-rich repeat (LRR containing proteins that activate complement-like defence responses against malaria parasites. In addition to their LRR domains, these leucine-rich repeat immune (LRIM proteins share several structural features including signal peptides, patterns of cysteine residues, and coiled-coil domains. Results The identification and characterisation of genes related to LRIM1 and APL1C revealed putatively novel innate immune factors and furthered the understanding of their likely molecular functions. Genomic scans using the shared features of LRIM1 and APL1C identified more than 20 LRIM-like genes exhibiting all or most of their sequence features in each of three disease-vector mosquitoes with sequenced genomes: An. gambiae, Aedes aegypti, and Culex quinquefasciatus. Comparative sequence analyses revealed that this family of mosquito LRIM-like genes is characterised by a variable number of 6 to 14 LRRs of different lengths. The "Long" LRIM subfamily, with 10 or more LRRs, and the "Short" LRIMs, with 6 or 7 LRRs, also share the signal peptide, cysteine residue patterning, and coiled-coil sequence features of LRIM1 and APL1C. The "TM" LRIMs have a predicted C-terminal transmembrane region, and the "Coil-less" LRIMs exhibit the characteristic LRIM sequence signatures but lack the C-terminal coiled-coil domains. Conclusions The evolutionary plasticity of the LRIM LRR domains may provide templates for diverse recognition properties, while their coiled-coil domains could be involved in the formation

  16. Dual symmetry in gauge theories

    International Nuclear Information System (INIS)

    Koshkarov, A.L.

    1997-01-01

    Continuous dual symmetry in electrodynamics, Yang-Mills theory and gravitation is investigated. Dual invariant which leads to badly nonlinear motion equations is chosen as a Lagrangian of the pure classical dual nonlinear electrodynamics. In a natural manner some dual angle which is determined by the electromagnetic strengths at the point of the time-space appears in the model. Motion equations may well be interpreted as the equations of the standard Maxwell theory with source. Alternative interpretation is the quasi-Maxwell linear theory with magnetic charge. Analogous approach is possible in the Yang-Mills theory. In this case the dual-invariant non-Abelian theory motion equations possess the same instanton solutions as the conventional Yang-Mills equations have. An Abelian two-parameter dual group is found to exist in gravitation. Irreducible representations have been obtained: the curvature tensor was expanded into the sum of twice anti-self-dual and self-dual parts. Gravitational instantons are defined as (real )solutions to the usual duality equations. Central symmetry solutions to these equations are obtained. The twice anti-self-dual part of the curvature tensor may be used for introduction of new gravitational equations generalizing Einstein''s equations. However, the theory obtained reduces to the conformal-flat Nordstroem theory

  17. Dual-beam CRT

    International Nuclear Information System (INIS)

    1975-01-01

    A dual-beam cathode-ray tube having a pair of electron guns and associated deflection means disposed side-by-side on each side of a central axis is described. The electron guns are parallel and the deflection means includes beam centering plates and angled horizontal deflection plates to direct the electron beams toward the central axis, precluding the need for a large-diameter tube neck in which the entire gun structures are angled. Bowing control plates are disposed adjacent to the beam centering plates to minimize trace bowing, and an intergun shield is disposed between the horizontal deflection plates to control and correct display pattern geometry distortion

  18. Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation

    DEFF Research Database (Denmark)

    Behncken, S N; Billestrup, Nils; Brown, R

    2000-01-01

    Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers of the gro......Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers...... of the growth hormone receptor (GHR) signaling domain. The entire extracellular domain of the GHR was replaced by the hemagglutinin-tagged zipper sequence of either the c-Fos or c-Jun transcription factor (termed Fos-GHR and Jun-GHR, respectively). Transient transfection of Fos-GHR or Jun-GHR resulted...

  19. The Plant Leucine-Rich Repeat Receptor-Like Kinase PSY1R from Head to Toe

    DEFF Research Database (Denmark)

    Oehlenschlæger, Christian Berg

    PSY1R belongs to the family of plant leucine-rich repeat receptor-like kinases that play important roles in processes such as growth regulation and plant immunity response. PSY1R was proposed to be the receptor of the plant peptide hormone PSY1 which promotes cell expansion. PSY1R was furthermore...... are conserved among related plant leucine-rich repeat receptor-like kinases whereas Ser951 is unique for PSY1R which suggests that it may serve a specialized function in regulation of PSY1R kinase activity....... shown to phosphorylate and regulate the activity of the plasma membrane localized H+-ATPase, AHA2. While the mechanism of PSY1R-mediated AHA2 phosphorylation has previously been studied in detail, little is known about how PSY1R binds PSY1 peptide ligand and how the intracellular PSY1R kinase domain...

  20. Post-transcriptional gene silencing of ribosomal protein S6 kinase 1 restores insulin action in leucine-treated skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, A; Salehzadeh, F; Metayer-Coustard, S

    2009-01-01

    Excessive nutrients, especially amino acids, impair insulin action on glucose metabolism in skeletal muscle. We tested the hypothesis that the branched-chain amino acid leucine reduces acute insulin action in primary myotubes via a negative feedback mechanism involving ribosomal protein S6 kinase 1...... (S6K1). The effect of S6K1 on glucose metabolism was determined by applying RNA interference (siRNA). Leucine (5 mM) reduced glucose uptake and incorporation to glycogen by 13% and 22%, respectively, compared to the scramble siRNA-transfected control at the basal level. Leucine also reduced insulin...... to excessive leucine. In conclusion, S6K1 plays an important role in the regulation of insulin action on glucose metabolism in skeletal muscle....

  1. Impaired Uptake and/or Utilization of Leucine by Saccharomyces cerevisiae Is Suppressed by the SPT15-300 Allele of the TATA-Binding Protein Gene

    DEFF Research Database (Denmark)

    Baerends, RJ; Qiu, Jin-Long; Rasmussen, Simon

    2009-01-01

    us to examine the effect of expression of the SPT15-300 allele in various yeast species of industrial importance. Expression of SPT15-300 in leucine-prototrophic strains of S. cerevisiae, Saccharomyces bayanus, or Saccharomyces pastorianus (lager brewing yeast), however, did not improve tolerance...... to ethanol on complex rich medium (yeast extract-peptone-dextrose). The enhanced growth of the laboratory yeast strain BY4741 expressing the SPT15-300 mutant allele was seen only on defined media with low concentrations of leucine, indicating that the apparent improved growth in the presence of ethanol...... was indeed associated with enhanced uptake and/or utilization of leucine. Reexamination of the microarray data published by Alper and coworkers likewise suggested that expression of genes coding for the leucine permeases, Tat1p and Bap3p, were upregulated in the SPT15-300 mutant, as was expression...

  2. Dual-band dual-polarized array for WLAN applications

    CSIR Research Space (South Africa)

    Steyn, JM

    2009-01-01

    Full Text Available Paper presents a dual-band dual-polarized antenna array design for WLAN applications. Four double-dipole elements are orthogonally interleaved to facilitate operation in both the standard WLAN frequency bands (IEEE 802.11b and IEEE 802.11a...

  3. Postprandial leucine and insulin responses and toxicological effects of a novel whey protein hydrolysate-based supplement in rats

    Directory of Open Access Journals (Sweden)

    Toedebusch Ryan G

    2012-06-01

    Full Text Available Abstract The purpose of this study was: aim 1 compare insulin and leucine serum responses after feeding a novel hydrolyzed whey protein (WPH-based supplement versus a whey protein isolate (WPI in rats during the post-absorptive state, and aim 2 to perform a thorough toxicological analysis on rats that consume different doses of the novel WPH-based supplement over a 30-day period. In male Wistar rats (~250 g, n = 40, serum insulin and leucine concentrations were quantified up to 120 min after one human equivalent dose of a WPI or the WPH-based supplement. In a second cohort of rats (~250 g, n = 20, we examined serum/blood and liver/kidney histopathological markers after 30 days of feeding low (1human equivalent dose, medium (3 doses and high (6 doses amounts of the WPH-based supplement. In aim 1, higher leucine levels existed at 15 min after WPH vs. WPI ingestion (p = 0.04 followed by higher insulin concentrations at 60 min (p = 0.002. In aim 2, liver and kidney histopathology/toxicology markers were not different 30 days after feeding with low, medium, high dose WPH-based supplementation or water only. There were no between-condition differences in body fat or lean mass or circulating clinical chemistry markers following the 30-day feeding intervention in aim 2. In comparison to WPI, acute ingestion of a novel WPH-based supplement resulted in a higher transient leucine response with a sequential increase in insulin. Furthermore, chronic ingestion of the tested whey protein hydrolysate supplement appears safe.

  4. Leucine-enriched essential amino acids attenuate inflammation in rat muscle and enhance muscle repair after eccentric contraction.

    Science.gov (United States)

    Kato, Hiroyuki; Miura, Kyoko; Nakano, Sayako; Suzuki, Katsuya; Bannai, Makoto; Inoue, Yoshiko

    2016-09-01

    Eccentric exercise results in prolonged muscle damage that may lead to muscle dysfunction. Although inflammation is essential to recover from muscle damage, excessive inflammation may also induce secondary damage, and should thus be suppressed. In this study, we investigated the effect of leucine-enriched essential amino acids on muscle inflammation and recovery after eccentric contraction. These amino acids are known to stimulate muscle protein synthesis via mammalian target of rapamycin (mTOR), which, is also considered to alleviate inflammation. Five sets of 10 eccentric contractions were induced by electrical stimulation in the tibialis anterior muscle of male SpragueDawley rats (8-9 weeks old) under anesthesia. Animals received a 1 g/kg dose of a mixture containing 40 % leucine and 60 % other essential amino acids or distilled water once a day throughout the experiment. Muscle dysfunction was assessed based on isometric dorsiflexion torque, while inflammation was evaluated by histochemistry. Gene expression of inflammatory cytokines and myogenic regulatory factors was also measured. We found that leucine-enriched essential amino acids restored full muscle function within 14 days, at which point rats treated with distilled water had not fully recovered. Indeed, muscle function was stronger 3 days after eccentric contraction in rats treated with amino acids than in those treated with distilled water. The amino acid mix also alleviated expression of interleukin-6 and impeded infiltration of inflammatory cells into muscle, but did not suppress expression of myogenic regulatory factors. These results suggest that leucine-enriched amino acids accelerate recovery from muscle damage by preventing excessive inflammation.

  5. The prodromal phase of leucine-rich repeat kinase 2-associated Parkinson disease: Clinical and imaging Studies.

    Science.gov (United States)

    Pont-Sunyer, Claustre; Tolosa, Eduardo; Caspell-Garcia, Chelsea; Coffey, Christopher; Alcalay, Roy N; Chan, Piu; Duda, John E; Facheris, Maurizio; Fernández-Santiago, Rubén; Marek, Kenneth; Lomeña, Francisco; Marras, Connie; Mondragon, Elisabet; Saunders-Pullman, Rachel; Waro, Bjorg

    2017-05-01

    Asymptomatic, nonmanifesting carriers of leucine-rich repeat kinase 2 mutations are at increased risk of developing PD. Clinical and neuroimaging features may be associated with gene carriage and/or may demarcate individuals at greater risk for phenoconversion to PD. To investigate clinical and dopamine transporter single-photon emission computed tomography imaging characteristics of leucine-rich repeat kinase 2 asymptomatic carriers. A total of 342 carriers' and 259 noncarriers' relatives of G2019S leucine-rich repeat kinase 2/PD patients and 39 carriers' and 31 noncarriers' relatives of R1441G leucine-rich repeat kinase 2/PD patients were evaluated. Motor and nonmotor symptoms were assessed using specific scales and questionnaires. Neuroimaging quantitative data were obtained in 81 carriers and compared with 41 noncarriers. G2019S carriers scored higher in motor scores and had lower radioligand uptake compared to noncarriers, but no differences in nonmotor symptoms scores were observed. R1441G carriers scored higher in motor scores, had lower radioligand uptake, and had higher scores in depression, dysautonomia, and Rapid Eye Movements Sleep Behavior Disorder Screening Questionnaire scores, but had better cognition scores than noncarriers. Among G2019S carriers, a group with "mild motor signs" was identified, and was significantly older, with worse olfaction and lower radioligand uptake. G2019S and R1441G carriers differ from their noncarriers' relatives in higher motor scores and slightly lower radioligand uptake. Nonmotor symptoms were mild, and different nonmotor profiles were observed in G2019S carriers compared to R1441G carriers. A group of G2019S carriers with known prodromal features was identified. Longitudinal studies are required to determine whether such individuals are at short-term risk of developing overt parkinsonism. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  6. Obese women on a low energy rice and bean diet: effects of leucine, arginine or glycine supplementation on protein turnover

    Directory of Open Access Journals (Sweden)

    J.S. Marchini

    2001-10-01

    Full Text Available This study examined if leucine, arginine or glycine supplementation in adult obese patients (body mass index of 33 ± 4 kg/m² consuming a Brazilian low energy and protein diet (4.2 MJ/day and 0.6 g protein/kg affects protein and amino acid metabolism. After four weeks adaptation to this diet, each subject received supplements of these amino acids (equivalent to 0.2 g protein kg-1 day-1 in random order. On the seventh day of each amino acid supplementation, a single-dose 15N-glycine study was carried out. There were no significant differences in protein flux, synthesis or breakdown. The protein flux (grams of nitrogen, gN/9 h was 55 ± 24 during the nonsupplemented diet intake and 39 ± 10, 44 ± 22 and 58 ± 35 during the leucine-, glycine- and arginine-supplemented diet intake, respectively; protein synthesis (gN/9 h was 57 ± 24, 36 ± 10, 41 ± 22 and 56 ± 36, respectively; protein breakdown (gN/9 h was 51 ± 24, 34 ± 10, 32 ± 28 and 53 ± 35, respectively; kinetic balance (gN/9 h was 3.2 ± 1.8, 4.1 ± 1.7, 3.4 ± 2.9 and 3.9 ± 1.6. There was no difference in amino acid profiles due to leucine, arginine or glycine supplementation. The present results suggest that 0.6 g/kg of dietary protein is enough to maintain protein turnover in obese women consuming a reduced energy diet and that leucine, arginine or glycine supplementation does not change kinetic balance or protein synthesis.

  7. Fast axonal transport of 3H-leucin-labelled proteins in the unhurt and isolated optical nerve of rats

    International Nuclear Information System (INIS)

    Wagner, H.E.

    1981-01-01

    The distribution of radioactivity of amino acid molecules incorporated in protein after injection of 3 H-Leucin into the right bulb was investigated and determined along optical nerve after 1, 2, and 4 h. A slightly increased radioactivity at the point of entrance of the optical nerves into the optical duct was found. A slightly reduced axon diameter was discussed as a possible cause. The radioactivity brought into the optical nerve via the vascular system was determined by measuring the contralateral optical nerve. In relation to the axonally transported activity, it was low. The speed of the fast axonal transport is 168 mm/d. If the processes ruling the amino acids in the perikaryon are taken into consideration, the transport speed is 240 mm/d. The application of the protein synthesis prohibitor, Cycloheximide, 5 minutes after the injection of Leucinin completely prevented the appearance of axonally transported labelled proteins. When cycloheximide was administered 2 h after Leucin, a significantly loner radioactivity than in the nerve could be determined after another 2 h; i.e. the incorporation of Leucin was not completed yet after 2 h. The profile of active compounds was the same as in the control group. In other experiments, the axonal transport of labelled proteins in isolated optical nerve fibres was tested. If the separation was carried out 2 h after the injection of Leucin an extreme reduction in activity could be determined after 1 or 2 h. The continued distribution of activity after cycloheximide treatment and removal of perikarya in comparison with the control indicate the continuation of the transport, also after separation of the axon from the perikaryon. This means that, during the time of the experiment, the mechanism of the fast axonal transport functions independently of the perikaryon. (orig./MG) [de

  8. Comparative genome analysis reveals an absence of leucine-rich repeat pattern-recognition receptor proteins in the kingdom Fungi.

    OpenAIRE

    Darren M Soanes; Nicholas J Talbot

    2010-01-01

    Background In plants and animals innate immunity is the first line of defence against attack by microbial pathogens. Specific molecular features of bacteria and fungi are recognised by pattern recognition receptors that have extracellular domains containing leucine rich repeats. Recognition of microbes by these receptors induces defence responses that protect hosts against potential microbial attack. Methodology/Principal Findings A survey of genome sequences from 101 species, representing a ...

  9. Effects of resource availability and bacterivory on leucine incorporation in different groups of freshwater bacterioplankton, assessed using microautoradiography

    Czech Academy of Sciences Publication Activity Database

    Horňák, Karel; Jezbera, Jan; Nedoma, Jiří; Gasol, J.M.; Šimek, Karel

    2006-01-01

    Roč. 45, č. 3 (2006), s. 277-289 ISSN 0948-3055 R&D Projects: GA ČR GA206/05/0007 Grant - others:FRVŠ(CZ) 1062/2004 Institutional research plan: CEZ:AV0Z60170517 Keywords : leucin e incorporation * bacterial structure * bacterial function Subject RIV: EH - Ecology, Behaviour Impact factor: 2.209, year: 2006

  10. Small leucine zipper protein functions as a negative regulator of estrogen receptor α in breast cancer.

    Directory of Open Access Journals (Sweden)

    Juyeon Jeong

    Full Text Available The nuclear transcription factor estrogen receptor α (ERα plays a critical role in breast cancer progression. ERα acts as an important growth stimulatory protein in breast cancer and the expression level of ERα is tightly related to the prognosis and treatment of patients. Small leucine zipper protein (sLZIP functions as a transcriptional cofactor by binding to various nuclear receptors, including glucocorticoid receptor, androgen receptor, and peroxisome proliferator-activated receptor γ. However, the role of sLZIP in the regulation of ERα and its involvement in breast cancer progression is unknown. We found that sLZIP binds to ERα and represses the transcriptional activity of ERα in ERα-positive breast cancer cells. sLZIP also suppressed the expression of ERα target genes. sLZIP disrupted the binding of ERα to the estrogen response element of the target gene promoter, resulting in suppression of cell proliferation. sLZIP is a novel co-repressor of ERα, and plays a negative role in ERα-mediated cell proliferation in breast cancer.

  11. Biochemical Properties and Potential Applications of Recombinant Leucine Aminopeptidase from Bacillus kaustophilus CCRC 11223

    Directory of Open Access Journals (Sweden)

    Yonghua Wang

    2011-11-01

    Full Text Available Experiments were carried out to investigate the effects of various factors on the activity and conformation of recombinant leucine aminopeptidase of Bacillus kaustophilus CCRC 11223 (BkLAP and potential utilization of BkLAP in the hydrolysis of anchovy protein. Optimal temperature and pH of BkLAP were 70 °C and 8.0 in potassium-phosphate buffer, respectively, and the activity was strongly stimulated by Ni2+, followed by Mn2+ and Co2+. Conformational studies via circular dichroism spectroscopy indicated that various factors could influence the secondary structure of BkLAP to different extents and further induce the changes in enzymatic activity. The secondary structure of BkLAP was slightly modified by Ni2+ at the concentration of 1×10−4 M, however, significant changes on the secondary structures of the enzyme were observed when Hg2+ was added to the concentration of 1×10−4 M. The potential application of BkLAP was evaluated through combination with the commercial or endogenous enzyme to hydrolysis the anchovy protein. Results showed that combining the BkLAP with other enzymes could significantly increase the degree of hydrolysis and amino acid component of hydrolysate. In this regard, BkLAP is a potential enzyme that can be used in the protein hydrolysate industry.

  12. Cellular pattern formation by SCRAMBLED, a leucine-rich repeat receptor-like kinase in Arabidopsis.

    Science.gov (United States)

    Kwak, Su-Hwan; Schiefelbein, John

    2008-02-01

    The appropriate specification of distinct cell types is important for generating the proper tissues and bodies of multicellular organisms. In the root epidermis of Arabidopsis, cell fate determination is accomplished by a transcriptional regulatory circuit that is influenced by positional signaling. A leucine-rich repeat receptor-like kinase, SCRAMBLED (SCM), has been shown to be responsible for the position-dependent aspect of this epidermal pattern. In a recent report, we find that SCM affects the transcriptional regulatory network by down-regulating the WEREWOLF (WER) MYB gene expression in a set of epidermal cells located in a specific position. We also find that SCM and the SCM-related SRF1 and SRF3 are not required for embryonic epidermal patterning and that SRF1 and SRF3 do not act redundantly with SCM. This suggests that distinct positional signaling mechanisms exist for embryonic and post-embryonic epidermal patterning. In this addendum, we discuss the implications of our recent findings and extend our working model for epidermal cell pattering.

  13. LRRML: a conformational database and an XML description of leucine-rich repeats (LRRs).

    Science.gov (United States)

    Wei, Tiandi; Gong, Jing; Jamitzky, Ferdinand; Heckl, Wolfgang M; Stark, Robert W; Rössle, Shaila C

    2008-11-05

    Leucine-rich repeats (LRRs) are present in more than 6000 proteins. They are found in organisms ranging from viruses to eukaryotes and play an important role in protein-ligand interactions. To date, more than one hundred crystal structures of LRR containing proteins have been determined. This knowledge has increased our ability to use the crystal structures as templates to model LRR proteins with unknown structures. Since the individual three-dimensional LRR structures are not directly available from the established databases and since there are only a few detailed annotations for them, a conformational LRR database useful for homology modeling of LRR proteins is desirable. We developed LRRML, a conformational database and an extensible markup language (XML) description of LRRs. The release 0.2 contains 1261 individual LRR structures, which were identified from 112 PDB structures and annotated manually. An XML structure was defined to exchange and store the LRRs. LRRML provides a source for homology modeling and structural analysis of LRR proteins. In order to demonstrate the capabilities of the database we modeled the mouse Toll-like receptor 3 (TLR3) by multiple templates homology modeling and compared the result with the crystal structure. LRRML is an information source for investigators involved in both theoretical and applied research on LRR proteins. It is available at http://zeus.krist.geo.uni-muenchen.de/~lrrml.

  14. Gender-Associated Impact of Early Leucine Supplementation on Adult Predisposition to Obesity in Rats

    Science.gov (United States)

    López, Nora; Sánchez, Juana; Palou, Andreu; Serra, Francisca

    2018-01-01

    Early nutrition plays an important role in development and may constitute a relevant contributor to the onset of obesity in adulthood. The aim of this study was to evaluate the long-term impact of maternal leucine (Leu) supplementation during lactation on progeny in rats. A chow diet, supplemented with 2% Leu, was supplied during lactation (21 days) and, from weaning onwards, was replaced by a standard chow diet. Then, at adulthood (6 months of age), this was replaced with hypercaloric diets (either with high-fat (HF) or high-carbohydrate (HC) content), for two months, to induce obesity. Female offspring from Leu-supplemented dams showed higher increases in body weight and in body fat (62%) than their respective controls; whereas males were somehow protected (15% less fat than the corresponding controls). This profile in Leu-females was associated with altered neuronal architecture at the paraventricular nucleus (PVN), involving neuropeptide Y (NPY) fibers and impaired expression of neuropeptides and factors of the mTOR signaling pathway in the hypothalamus. Interestingly, leptin and adiponectin expression in adipose tissue at weaning and at the time before the onset of obesity could be defined as early biomarkers of metabolic disturbance, predisposing towards adult obesity under the appropriate environment. PMID:29329236

  15. Glucocorticoid-Induced Leucine Zipper Protein Controls Macropinocytosis in Dendritic Cells.

    Science.gov (United States)

    Calmette, Joseph; Bertrand, Matthieu; Vétillard, Mathias; Ellouze, Mehdi; Flint, Shaun; Nicolas, Valérie; Biola-Vidamment, Armelle; Pallardy, Marc; Morand, Eric; Bachelerie, Françoise; Godot, Véronique; Schlecht-Louf, Géraldine

    2016-12-01

    Ag sampling is a key process in dendritic cell (DC) biology. DCs use constitutive macropinocytosis, receptor-mediated endocytosis, and phagocytosis to capture exogenous Ags for presentation to T cells. We investigated the mechanisms that regulate Ag uptake by DCs in the steady-state and after a short-term LPS exposure in vitro and in vivo. We show that the glucocorticoid-induced leucine zipper protein (GILZ), already known to regulate effector versus regulatory T cell activation by DCs, selectively limits macropinocytosis, but not receptor-mediated phagocytosis, in immature and recently activated DCs. In vivo, the GILZ-mediated inhibition of Ag uptake is restricted to the CD8α + DC subset, which expresses the highest GILZ level among splenic DC subsets. In recently activated DCs, we further establish that GILZ limits p38 MAPK phosphorylation, providing a possible mechanism for GILZ-mediated macropinocytosis control. Finally, our results demonstrate that the modulation of Ag uptake by GILZ does not result in altered Ag presentation to CD4 T cells but impacts the efficiency of cross-presentation to CD8 T cells. Altogether, our results identify GILZ as an endogenous inhibitor of macropinocytosis in DCs, the action of which contributes to the fine-tuning of Ag cross-presentation. Copyright © 2016 by The American Association of Immunologists, Inc.

  16. Role of glucocorticoid-induced leucine zipper (GILZ in inflammatory bone loss.

    Directory of Open Access Journals (Sweden)

    Nianlan Yang

    Full Text Available TNF-α plays a key role in the development of rheumatoid arthritis (RA and inflammatory bone loss. Unfortunately, treatment of RA with anti-inflammatory glucocorticoids (GCs also causes bone loss resulting in osteoporosis. Our previous studies showed that overexpression of glucocorticoid-induced leucine zipper (GILZ, a mediator of GC's anti-inflammatory effect, can enhance osteogenic differentiation in vitro and bone acquisition in vivo. To investigate whether GILZ could antagonize TNF-α-induced arthritic inflammation and protect bone in mice, we generated a TNF-α-GILZ double transgenic mouse line (TNF-GILZ Tg by crossbreeding a TNF-α Tg mouse, which ubiquitously expresses human TNF-α, with a GILZ Tg mouse, which expresses mouse GILZ under the control of a 3.6kb rat type I collagen promoter fragment. Results showed that overexpression of GILZ in bone marrow mesenchymal stem/progenitor cells protected mice from TNF-α-induced inflammatory bone loss and improved bone integrity (TNF-GILZ double Tg vs. TNF-αTg, n = 12-15. However, mesenchymal cell lineage restricted GILZ expression had limited effects on TNF-α-induced arthritic inflammation as indicated by clinical scores and serum levels of inflammatory cytokines and chemokines.

  17. Macrophage migration inhibitory factor inhibits the antiinflammatory effects of glucocorticoids via glucocorticoid-induced leucine zipper.

    Science.gov (United States)

    Fan, Huapeng; Kao, Wenping; Yang, Yuan H; Gu, Ran; Harris, James; Fingerle-Rowson, Günter; Bucala, Richard; Ngo, Devi; Beaulieu, Elaine; Morand, Eric F

    2014-08-01

    Glucocorticoids remain a mainstay in the treatment of rheumatoid arthritis (RA). Dose-dependent adverse effects highlight the need for therapies that regulate glucocorticoid sensitivity to enable dosage reduction. Macrophage migration inhibitory factor (MIF) is a proinflammatory protein that has been implicated in the pathogenesis of RA; it impairs glucocorticoid sensitivity via MAPK phosphatase 1 (MKP-1) inhibition. The intracellular protein glucocorticoid-induced leucine zipper (GILZ) mimics the effects of glucocorticoids in models of RA, but whether it represents a target for the modulation of glucocorticoid sensitivity remains unknown. We undertook this study to investigate whether GILZ is involved in the regulation of glucocorticoid sensitivity by MIF. GILZ expression was studied in the presence and absence of MIF, and the role of GILZ in the MIF-dependent regulation of the glucocorticoid sensitivity mediator MKP-1 was studied at the level of expression and function. GILZ expression was significantly inhibited by endogenous MIF, both basally and during responses to glucocorticoid treatment. The effects of MIF on GILZ were dependent on the expression and Akt-induced nuclear translocation of the transcription factor FoxO3A. GILZ was shown to regulate the expression of MKP-1 and consequent MAPK phosphorylation and cytokine release. MIF exerts its effects on MKP-1 expression and MAPK activity through inhibitory effects on GILZ. These findings suggest a previously unsuspected interaction between MIF and GILZ and identify GILZ as a potential target for the therapeutic regulation of glucocorticoid sensitivity. Copyright © 2014 by the American College of Rheumatology.

  18. Alterations in the Helicoverpa armigera midgut digestive physiology after ingestion of pigeon pea inducible leucine aminopeptidase.

    Directory of Open Access Journals (Sweden)

    Purushottam R Lomate

    Full Text Available Jasmonate inducible plant leucine aminopeptidase (LAP is proposed to serve as direct defense in the insect midgut. However, exact functions of inducible plant LAPs in the insect midgut remain to be estimated. In the present investigation, we report the direct defensive role of pigeon pea inducible LAP in the midgut of Helicoverpa armigera (Lepidoptera: Noctuidae and responses of midgut soluble aminopeptidases and serine proteinases upon LAP ingestion. Larval growth and survival was significantly reduced on the diets supplemented with pigeon pea LAP. Aminopeptidase activities in larvae remain unaltered in presence or absence of inducible LAP in the diet. On the contrary, serine proteinase activities were significantly decreased in the larvae reared on pigeon pea LAP containing diet as compared to larvae fed on diet without LAP. Our data suggest that pigeon pea inducible LAP is responsible for the degradation of midgut serine proteinases upon ingestion. Reduction in the aminopeptidase activity with LpNA in the H. armigera larvae was compensated with an induction of aminopeptidase activity with ApNA. Our findings could be helpful to further dissect the roles of plant inducible LAPs in the direct plant defense against herbivory.

  19. A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice

    Directory of Open Access Journals (Sweden)

    Antje Bruckbauer

    2016-01-01

    Full Text Available Sirt1, AMPK, and eNOS modulate hepatic energy metabolism and inflammation and are key players in the development of NASH. L-leucine, an allosteric Sirt1 activator, synergizes with low doses of metformin or sildenafil on the AMPK-eNOS-Sirt1 pathway to reverse mild NAFLD in preclinical mouse models. Here we tested a possible multicomponent synergy to yield greater therapeutic efficacy in NAFLD/NASH. Liver cells and macrophages or an atherogenic diet induced NASH mouse model was treated with two-way and three-way combinations. The three-way combination Sild-Met-Leu increased hepatic fatty acid oxidation and reduced lipogenic gene expression and inflammatory marker in vitro. In mice, Sild-Met-Leu reduced the diet induced increases of ALT, TGFβ, PAI-1, IL1β, and TNFα, hepatic collagen expression, and nearly completely reversed hepatocyte ballooning and triglyceride accumulation, while all two-way combinations had only modest effects. Therefore, these data provide preclinical evidence for therapeutic efficacy of Sild-Met-Leu in the treatment of NAFLD and NASH.

  20. Proteome-level assessment of origin, prevalence and function of Leucine-Aspartic Acid (LD) motifs

    KAUST Repository

    Alam, Tanvir

    2018-03-11

    Short Linear Motifs (SLiMs) contribute to almost every cellular function by connecting appropriate protein partners. Accurate prediction of SLiMs is difficult due to their shortness and sequence degeneracy. Leucine-aspartic acid (LD) motifs are SLiMs that link paxillin family proteins to factors controlling (cancer) cell adhesion, motility and survival. The existence and importance of LD motifs beyond the paxillin family is poorly understood. To enable a proteome-wide assessment of these motifs, we developed an active-learning based framework that iteratively integrates computational predictions with experimental validation. Our analysis of the human proteome identified a dozen proteins that contain LD motifs, all being involved in cell adhesion and migration, and revealed a new type of inverse LD motif consensus. Our evolutionary analysis suggested that LD motif signalling originated in the common unicellular ancestor of opisthokonts and amoebozoa by co-opting nuclear export sequences. Inter-species comparison revealed a conserved LD signalling core, and reveals the emergence of species-specific adaptive connections, while maintaining a strong functional focus of the LD motif interactome. Collectively, our data elucidate the mechanisms underlying the origin and adaptation of an ancestral SLiM.

  1. Essential Role for an M17 Leucine Aminopeptidase in Encystation of Acanthamoeba castellanii.

    Science.gov (United States)

    Lee, Yu-Ran; Na, Byoung-Kuk; Moon, Eun-Kyung; Song, Su-Min; Joo, So-Young; Kong, Hyun-Hee; Goo, Youn-Kyoung; Chung, Dong-Il; Hong, Yeonchul

    2015-01-01

    Encystation of Acanthamoeba leads to the formation of resilient cysts from vegetative trophozoites. This process is essential for parasite survival under unfavorable conditions such as starvation, low temperatures, and exposure to biocides. During encystation, a massive turnover of intracellular components occurs, and a large number of organelles and proteins are degraded by proteases. Previous studies with specific protease inhibitors have shown that cysteine and serine proteases are involved in encystation of Acanthamoeba, but little is known about the role of metalloproteases in this process. Here, we have biochemically characterized an M17 leucine aminopeptidase of Acanthamoeba castellanii (AcLAP) and analyzed its functional involvement in encystation of the parasite. Recombinant AcLAP shared biochemical properties such as optimal pH, requirement of divalent metal ions for activity, substrate specificity for Leu, and inhibition profile by aminopeptidase inhibitors and metal chelators with other characterized M17 family LAPs. AcLAP was highly expressed at a late stage of encystation and mainly localized in the cytoplasm of A. castellanii. Knockdown of AcLAP using small interfering RNA induced a decrease of LAP activity during encystation, a reduction of mature cyst formation, and the formation of abnormal cyst walls. In summary, these results indicate that AcLAP is a typical M17 family enzyme that plays an essential role during encystation of Acanthamoeba.

  2. Essential Role for an M17 Leucine Aminopeptidase in Encystation of Acanthamoeba castellanii.

    Directory of Open Access Journals (Sweden)

    Yu-Ran Lee

    Full Text Available Encystation of Acanthamoeba leads to the formation of resilient cysts from vegetative trophozoites. This process is essential for parasite survival under unfavorable conditions such as starvation, low temperatures, and exposure to biocides. During encystation, a massive turnover of intracellular components occurs, and a large number of organelles and proteins are degraded by proteases. Previous studies with specific protease inhibitors have shown that cysteine and serine proteases are involved in encystation of Acanthamoeba, but little is known about the role of metalloproteases in this process. Here, we have biochemically characterized an M17 leucine aminopeptidase of Acanthamoeba castellanii (AcLAP and analyzed its functional involvement in encystation of the parasite. Recombinant AcLAP shared biochemical properties such as optimal pH, requirement of divalent metal ions for activity, substrate specificity for Leu, and inhibition profile by aminopeptidase inhibitors and metal chelators with other characterized M17 family LAPs. AcLAP was highly expressed at a late stage of encystation and mainly localized in the cytoplasm of A. castellanii. Knockdown of AcLAP using small interfering RNA induced a decrease of LAP activity during encystation, a reduction of mature cyst formation, and the formation of abnormal cyst walls. In summary, these results indicate that AcLAP is a typical M17 family enzyme that plays an essential role during encystation of Acanthamoeba.

  3. AdpC is a Prevotella intermedia 17 leucine-rich repeat internalin-like protein.

    Science.gov (United States)

    Iyer, Divya; Anaya-Bergman, Cecilia; Jones, Kevin; Yanamandra, Sai; Sengupta, Dipanwita; Miyazaki, Hiroshi; Lewis, Janina P

    2010-06-01

    The oral bacterium Prevotella intermedia attaches to and invades gingival epithelial cells, fibroblasts, and endothelial cells. Several genes encoding proteins that mediate both the adhesion and invasion processes are carried on the genome of this bacterium. Here, we characterized one such protein, AdpC, belonging to the leucine-rich repeat (LRR) protein family. Bioinformatics analysis revealed that this protein shares similarity with the Treponema pallidum LRR (LRR(TP)) family of proteins and contains six LRRs. Despite the absence of a signal peptide, this protein is localized on the bacterial outer membrane, indicating that it is transported through an atypical secretion mechanism. The recombinant form of this protein (rAdpC) was shown to bind fibrinogen. In addition, the heterologous host strain Escherichia coli BL21 expressing rAdpC (V2846) invaded fibroblast NIH 3T3 cells at a 40-fold-higher frequency than control E. coli BL21 cells expressing a sham P. intermedia 17 protein. Although similar results were obtained by using human umbilical vein endothelial cells (HUVECs), only a 3-fold-increased invasion of V2846 into oral epithelial HN4 cells was observed. Thus, AdpC-mediated invasion is cell specific. This work demonstrated that AdpC is an important invasin protein of P. intermedia 17.

  4. AdpC Is a Prevotella intermedia 17 Leucine-Rich Repeat Internalin-Like Protein▿

    Science.gov (United States)

    Iyer, Divya; Anaya-Bergman, Cecilia; Jones, Kevin; Yanamandra, Sai; Sengupta, Dipanwita; Miyazaki, Hiroshi; Lewis, Janina P.

    2010-01-01

    The oral bacterium Prevotella intermedia attaches to and invades gingival epithelial cells, fibroblasts, and endothelial cells. Several genes encoding proteins that mediate both the adhesion and invasion processes are carried on the genome of this bacterium. Here, we characterized one such protein, AdpC, belonging to the leucine-rich repeat (LRR) protein family. Bioinformatics analysis revealed that this protein shares similarity with the Treponema pallidum LRR (LRRTP) family of proteins and contains six LRRs. Despite the absence of a signal peptide, this protein is localized on the bacterial outer membrane, indicating that it is transported through an atypical secretion mechanism. The recombinant form of this protein (rAdpC) was shown to bind fibrinogen. In addition, the heterologous host strain Escherichia coli BL21 expressing rAdpC (V2846) invaded fibroblast NIH 3T3 cells at a 40-fold-higher frequency than control E. coli BL21 cells expressing a sham P. intermedia 17 protein. Although similar results were obtained by using human umbilical vein endothelial cells (HUVECs), only a 3-fold-increased invasion of V2846 into oral epithelial HN4 cells was observed. Thus, AdpC-mediated invasion is cell specific. This work demonstrated that AdpC is an important invasin protein of P. intermedia 17. PMID:20308299

  5. Small Leucine-Rich Proteoglycans in Renal Inflammation: Two Sides of the Coin.

    Science.gov (United States)

    Nastase, Madalina V; Janicova, Andrea; Roedig, Heiko; Hsieh, Louise Tzung-Harn; Wygrecka, Malgorzata; Schaefer, Liliana

    2018-04-01

    It is now well-established that members of the small leucine-rich proteoglycan (SLRP) family act in their soluble form, released proteolytically from the extracellular matrix (ECM), as danger-associated molecular patterns (DAMPs). By interacting with Toll-like receptors (TLRs) and the inflammasome, the two SLRPs, biglycan and decorin, autonomously trigger sterile inflammation. Recent data indicate that these SLRPs, besides their conventional role as pro-inflammatory DAMPs, additionally trigger anti-inflammatory signaling pathways to tightly control inflammation. This is brought about by selective employment of TLRs, their co-receptors, various adaptor molecules, and through crosstalk between SLRP-, reactive oxygen species (ROS)-, and sphingolipid-signaling. In this review, the complexity of SLRP signaling in immune and kidney resident cells and its relevance for renal inflammation is discussed. We propose that the dichotomy in SLRP signaling (pro- and anti-inflammatory) allows for fine-tuning the inflammatory response, which is decisive for the outcome of inflammatory kidney diseases.

  6. Transcriptional control by two leucine-responsive regulatory proteins in Halobacterium salinarum R1

    Directory of Open Access Journals (Sweden)

    Tarasov Valery

    2010-05-01

    Full Text Available Abstract Background Archaea combine bacterial-as well as eukaryotic-like features to regulate cellular processes. Halobacterium salinarum R1 encodes eight leucine-responsive regulatory protein (Lrp-homologues. The function of two of them, Irp (OE3923F and lrpA1 (OE2621R, were analyzed by gene deletion and overexpression, including genome scale impacts using microarrays. Results It was shown that Lrp affects the transcription of multiple target genes, including those encoding enzymes involved in amino acid synthesis, central metabolism, transport processes and other regulators of transcription. In contrast, LrpA1 regulates transcription in a more specific manner. The aspB3 gene, coding for an aspartate transaminase, was repressed by LrpA1 in the presence of L-aspartate. Analytical DNA-affinity chromatography was adapted to high salt, and demonstrated binding of LrpA1 to its own promoter, as well as L-aspartate dependent binding to the aspB3 promoter. Conclusion The gene expression profiles of two archaeal Lrp-homologues report in detail their role in H. salinarum R1. LrpA1 and Lrp show similar functions to those already described in bacteria, but in addition they play a key role in regulatory networks, such as controlling the transcription of other regulators. In a more detailed analysis ligand dependent binding of LrpA1 was demonstrated to its target gene aspB3.

  7. Les besoins en isoleucine, valine et leucine chez le porcelet entre 7 et 15 kg

    DEFF Research Database (Denmark)

    Assadi Soumeh, Elham; van Milgen, Jaap; Sloth, Niels Morten

    2015-01-01

    croissance s’ils sont fournis en deçà du besoin. Des études de métaanalyse révèlent que peu de données de type dose‐réponse sont disponibles chez le porcelet pour l’Ile, notamment avec des aliments exempts de cellules de sang, et la Val (van Milgen et al., 2012, 2013). Par ailleurs, une revue de la......La réduction des teneurs en protéines des aliments pour porcelets peut se faire uniquement sous contrôle des apports en acides aminés (AA) indispensables tels que les AA ramifies (AAR) valine (Val), isoleucine (Ile) et leucine (Leu) susceptibles d’être déficitaires et d’altérer les performances de...... literature révèle que seules deux études permettent d’estimer le besoin en Leu (Gloaguen et al., 2013a). L’objectif de cette étude est de décrire la réponse de porcelets entre 7 et 15 kg de poids vif (PV) à des apports croissants d’Ile, Val et Leu digestible iléale standardisée (DIS) dans trois études dose...

  8. Leucine Rich α-2 Glycoprotein: A Novel Neutrophil Granule Protein and Modulator of Myelopoiesis.

    Directory of Open Access Journals (Sweden)

    Lawrence J Druhan

    Full Text Available Leucine-rich α2 glycoprotein (LRG1, a serum protein produced by hepatocytes, has been implicated in angiogenesis and tumor promotion. Our laboratory previously reported the expression of LRG1 in murine myeloid cell lines undergoing neutrophilic granulocyte differentiation. However, the presence of LRG1 in primary human neutrophils and a role for LRG1 in regulation of hematopoiesis have not been previously described. Here we show that LRG1 is packaged into the granule compartment of human neutrophils and secreted upon neutrophil activation to modulate the microenvironment. Using immunofluorescence microscopy and direct biochemical measurements, we demonstrate that LRG1 is present in the peroxidase-negative granules of human neutrophils. Exocytosis assays indicate that LRG1 is differentially glycosylated in neutrophils, and co-released with the secondary granule protein lactoferrin. Like LRG1 purified from human serum, LRG1 secreted from activated neutrophils also binds cytochrome c. We also show that LRG1 antagonizes the inhibitory effects of TGFβ1 on colony growth of human CD34+ cells and myeloid progenitors. Collectively, these data invoke an additional role for neutrophils in innate immunity that has not previously been reported, and suggest a novel mechanism whereby neutrophils may modulate the microenvironment via extracellular release of LRG1.

  9. Pharmacokinetic and imaging studies of the hepatobiliary agent sup(99m)Tc-pyridoxal leucine

    International Nuclear Information System (INIS)

    Sawas-Dimopoulou, C.; Chiotellis, E.; Dassiou, A.; Papanicolaou, N.; Simitzis, G.; Koutoulidis, K.; Hadzilouka-Mantaka, A.

    1978-01-01

    An investigation into the usefulness of sup(99m)Tc-pyridoxal leucine has demonstrated its advantages over 131 I-rose bengal in the diagnosis of patients with several liver and gall bladder complaints. Toxicity studies in mice, rabbits and dogs showed no histological signs of tissular lesions at doses of up to 5000 to 25,000 times the clinical dose. Visualization of the liver, gall bladder and biliary excretion into intestines was rapid. The appearance of activity into the intestines was delayed in patients with partial obstruction of the common bile duct. Insufficient diagnostic information was provided in jaundiced patients with higher levels of bilirubin (7 to 12 mg%). These patients showed reduced liver uptake with high background, and intestinal activity was not always clearly visualized in an 18 h study. At bilirubin levels higher than 12 mg% no liver uptake was usually observed, but only renal activity. 131 I-rose bengal was preferable for the differential diagnosis of obstructive jaundice in these patients. (U.K.)

  10. LRRML: a conformational database and an XML description of leucine-rich repeats (LRRs

    Directory of Open Access Journals (Sweden)

    Stark Robert W

    2008-11-01

    Full Text Available Abstract Background Leucine-rich repeats (LRRs are present in more than 6000 proteins. They are found in organisms ranging from viruses to eukaryotes and play an important role in protein-ligand interactions. To date, more than one hundred crystal structures of LRR containing proteins have been determined. This knowledge has increased our ability to use the crystal structures as templates to model LRR proteins with unknown structures. Since the individual three-dimensional LRR structures are not directly available from the established databases and since there are only a few detailed annotations for them, a conformational LRR database useful for homology modeling of LRR proteins is desirable. Description We developed LRRML, a conformational database and an extensible markup language (XML description of LRRs. The release 0.2 contains 1261 individual LRR structures, which were identified from 112 PDB structures and annotated manually. An XML structure was defined to exchange and store the LRRs. LRRML provides a source for homology modeling and structural analysis of LRR proteins. In order to demonstrate the capabilities of the database we modeled the mouse Toll-like receptor 3 (TLR3 by multiple templates homology modeling and compared the result with the crystal structure. Conclusion LRRML is an information source for investigators involved in both theoretical and applied research on LRR proteins. It is available at http://zeus.krist.geo.uni-muenchen.de/~lrrml.

  11. Evolutionary and Expression Analyses of the Apple Basic Leucine Zipper Transcription Factor Family

    Directory of Open Access Journals (Sweden)

    Jiao eZhao

    2016-03-01

    Full Text Available Transcription factors (TFs play essential roles in the regulatory networks controlling many developmental processes in plants. Members of the basic leucine (Leu zipper (bZIP TF family, which is unique to eukaryotes, are involved in regulating diverse processes, including flower and vascular development, seed maturation, stress signaling and defense responses to pathogens. The bZIP proteins have a characteristic bZIP domain composed of a DNA-binding basic region and a Leu zipper dimerization region. In this study, we identified 112 apple (Malus domestica Borkh bZIP TF-encoding genes, termed MdbZIP genes. Synteny analysis indicated that segmental and tandem duplication events, as well as whole genome duplication, have contributed to the expansion of the apple bZIP family. The family could be divided into 11 groups based on structural features of the encoded proteins, as well as on the phylogenetic relationship of the apple bZIP proteins to those of the model plant Arabidopsis thaliana (AtbZIP genes. Synteny analysis revealed that several paired MdbZIP genes and AtbZIP gene homologs were located in syntenic genomic regions. Furthermore, expression analyses of group A MdbZIP genes showed distinct expression levels in ten different organs. Moreover, changes in these expression profiles in response to abiotic stress conditions and various hormone treatments identified MdbZIP genes that were responsive to high salinity and drought, as well as to different phytohormones.

  12. Are the Bcaas/Leucine Supplementation Effects on Exercise-Induced Muscle Damage Related Immunity Response or to Hmβ?

    OpenAIRE

    Humberto Nicastro

    2014-01-01

    Branched-chain amino acids (BCAAs), mainly leucine, have been described as potential modulators of resistance exercise-induced muscle adaptations which includes stimulation of muscle protein synthesis and attenuation of proteolysis. However, until the moment, there are no well controlled chronic studies (randomized, double-blind and placebo-controlled) in humans assessing the effects of BCAAs/leucine supplementation on muscle hypertrophy and strength. The most well documented benefits of BCAA...

  13. Enhanced gene expression in tumors after intravenous administration of arginine-, lysine- and leucine-bearing polypropylenimine polyplex.

    Science.gov (United States)

    Aldawsari, Hibah; Edrada-Ebel, Ruangelie; Blatchford, David R; Tate, Rothwelle J; Tetley, Laurence; Dufès, Christine

    2011-09-01

    The possibility of using non-viral gene delivery systems for the treatment of cancer is currently limited by their lower transfection efficacy compared to viral systems. On the basis that amino acids such as arginine, lysine and leucine were involved in enhancing DNA transportation into cells, we hypothesized that the grafting of these amino acids to the highly promising generation 3 diaminobutyric polypropylenimine (DAB) dendrimer would improve its transfection efficacy in cancer cells. In this work we demonstrated that the conjugation of arginine, lysine and leucine to the dendrimer led to an enhanced anti-proliferative activity of the polyplexes, by up to 47-fold for DAB-Lys in T98G cancer cells compared to the unmodified polyplex in vitro. In vivo, the intravenous administration of amino acid-bearing DAB polyplexes resulted in a significantly improved tumor gene expression, with the highest gene expression level observed after treatment with DAB-Lys polyplex. Arginine, lysine and leucine-bearing generation 3 polypropylenimine polymers are therefore highly promising gene delivery systems for gene transfection in tumors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Improved muscle function and quality after diet intervention with leucine-enriched whey and antioxidants in antioxidant deficient aged mice.

    Science.gov (United States)

    van Dijk, Miriam; Dijk, Francina J; Bunschoten, Annelies; van Dartel, Dorien A M; van Norren, Klaske; Walrand, Stephane; Jourdan, Marion; Verlaan, Sjors; Luiking, Yvette

    2016-04-05

    Antioxidant (AOX) deficiencies are commonly observed in older adults and oxidative stress has been suggested to contribute to sarcopenia. Here we investigate if 1) low levels of dietary antioxidants had a negative impact on parameters of muscle mass, function and quality, and 2) to study if nutritional interventions with AOX and/or leucine-enriched whey protein could improve these muscle parameters in aged mice. 18-months-old mice were fed a casein-based antioxidant-deficient (lowox) diet or a casein-based control-diet (CTRL) for 7 months. During the last 3 months, lowox-mice were subjected to either: a) continued lowox, b) supplementation with vitamin A/E, Selenium and Zinc (AOX), c) substitution of casein with leucine-enriched whey protein (PROT) or d) a combination of both AOX and PROT (TOTAL). After 7 months lowox-mice displayed lower muscle strength and more muscle fatigue compared to CTRL. Compared to lowox-mice, PROT-mice showed improved muscle power, grip strength and less muscle fatigue. AOX-mice showed improved oxidative status, less muscle fatigue, improved grip strength and mitochondrial dynamics compared to lowox-mice. The TOTAL-mice showed the combined effects of both interventions compared to lowox-mice. In conclusion, nutritional intervention with AOX and/or leucine-enriched whey protein can play a role in improving muscle health in a AOX-deficient mouse model.

  15. Comparative genome analysis reveals an absence of leucine-rich repeat pattern-recognition receptor proteins in the kingdom Fungi.

    Directory of Open Access Journals (Sweden)

    Darren M Soanes

    2010-09-01

    Full Text Available In plants and animals innate immunity is the first line of defence against attack by microbial pathogens. Specific molecular features of bacteria and fungi are recognised by pattern recognition receptors that have extracellular domains containing leucine rich repeats. Recognition of microbes by these receptors induces defence responses that protect hosts against potential microbial attack.A survey of genome sequences from 101 species, representing a broad cross-section of the eukaryotic phylogenetic tree, reveals an absence of leucine rich repeat-domain containing receptors in the fungal kingdom. Uniquely, however, fungi possess adenylate cyclases that contain distinct leucine rich repeat-domains, which have been demonstrated to act as an alternative means of perceiving the presence of bacteria by at least one fungal species. Interestingly, the morphologically similar osmotrophic oomycetes, which are taxonomically distant members of the stramenopiles, possess pattern recognition receptors with similar domain structures to those found in plants.The absence of pattern recognition receptors suggests that fungi may possess novel classes of pattern-recognition receptor, such as the modified adenylate cyclase, or instead rely on secretion of anti-microbial secondary metabolites for protection from microbial attack. The absence of pattern recognition receptors in fungi, coupled with their abundance in oomycetes, suggests this may be a unique characteristic of the fungal kingdom rather than a consequence of the osmotrophic growth form.

  16. Elaboration of biscuits with oatmeal and fat palm with added L-leucine and calcium for sarcopenia

    Directory of Open Access Journals (Sweden)

    Telma Elita Bertolin

    2013-06-01

    Full Text Available The objective of this study was to evaluate the effect of the addition of oatmeal and palm fat in the elaboration of biscuits with added L-leucine and calcium in order to develop a product for sarcopenia in the elderly. The biscuits, or cookies, were elaborated applying a central composite rotational design with surface response methodology, and the significant linear, quadratic and interaction terms were used in the second order mathematical model. Physical, physicochemical and sensory analyses were performed by a trained panel. Based on the best results obtained, three cookie formulations were selected for sensory evaluation by the target group and physicochemical determinations. The formulations with the highest sensory scores for appearance and texture and medium scores for color and expansion index were selected. The addition of calcium and leucine increased significantly the concentration of these components in the biscuits elaborated resulting in a cookie with more than 30% of DRI (Dietary Reference Intake for calcium and leucine. The formulations selected showed high acceptance by the target group; therefore, they can be included in the diet of elderly with sarcopenia as a functional food.

  17. Comparative genome analysis reveals an absence of leucine-rich repeat pattern-recognition receptor proteins in the kingdom Fungi.

    Science.gov (United States)

    Soanes, Darren M; Talbot, Nicholas J

    2010-09-14

    In plants and animals innate immunity is the first line of defence against attack by microbial pathogens. Specific molecular features of bacteria and fungi are recognised by pattern recognition receptors that have extracellular domains containing leucine rich repeats. Recognition of microbes by these receptors induces defence responses that protect hosts against potential microbial attack. A survey of genome sequences from 101 species, representing a broad cross-section of the eukaryotic phylogenetic tree, reveals an absence of leucine rich repeat-domain containing receptors in the fungal kingdom. Uniquely, however, fungi possess adenylate cyclases that contain distinct leucine rich repeat-domains, which have been demonstrated to act as an alternative means of perceiving the presence of bacteria by at least one fungal species. Interestingly, the morphologically similar osmotrophic oomycetes, which are taxonomically distant members of the stramenopiles, possess pattern recognition receptors with similar domain structures to those found in plants. The absence of pattern recognition receptors suggests that fungi may possess novel classes of pattern-recognition receptor, such as the modified adenylate cyclase, or instead rely on secretion of anti-microbial secondary metabolites for protection from microbial attack. The absence of pattern recognition receptors in fungi, coupled with their abundance in oomycetes, suggests this may be a unique characteristic of the fungal kingdom rather than a consequence of the osmotrophic growth form.

  18. Friedelin Synthase from Maytenus ilicifolia: Leucine 482 Plays an Essential Role in the Production of the Most Rearranged Pentacyclic Triterpene

    Science.gov (United States)

    Souza-Moreira, Tatiana M.; Alves, Thaís B.; Pinheiro, Karina A.; Felippe, Lidiane G.; de Lima, Gustavo M. A.; Watanabe, Tatiana F.; Barbosa, Cristina C.; Santos, Vânia A. F. F. M.; Lopes, Norberto P.; Valentini, Sandro R.; Guido, Rafael V. C.; Furlan, Maysa; Zanelli, Cleslei F.

    2016-11-01

    Among the biologically active triterpenes, friedelin has the most-rearranged structure produced by the oxidosqualene cyclases and is the only one containing a cetonic group. In this study, we cloned and functionally characterized friedelin synthase and one cycloartenol synthase from Maytenus ilicifolia (Celastraceae). The complete coding sequences of these 2 genes were cloned from leaf mRNA, and their functions were characterized by heterologous expression in yeast. The cycloartenol synthase sequence is very similar to other known OSCs of this type (approximately 80% identity), although the M. ilicifolia friedelin synthase amino acid sequence is more related to β-amyrin synthases (65-74% identity), which is similar to the friedelin synthase cloned from Kalanchoe daigremontiana. Multiple sequence alignments demonstrated the presence of a leucine residue two positions upstream of the friedelin synthase Asp-Cys-Thr-Ala-Glu (DCTAE) active site motif, while the vast majority of OSCs identified so far have a valine or isoleucine residue at the same position. The substitution of the leucine residue with valine, threonine or isoleucine in M. ilicifolia friedelin synthase interfered with substrate recognition and lead to the production of different pentacyclic triterpenes. Hence, our data indicate a key role for the leucine residue in the structure and function of this oxidosqualene cyclase.

  19. Improved muscle function and quality after diet intervention with leucine-enriched whey and antioxidants in antioxidant deficient aged mice

    Science.gov (United States)

    van Dijk, Miriam; Dijk, Francina J.; Bunschoten, Annelies; van Dartel, Dorien A.M.; van Norren, Klaske; Walrand, Stephane; Jourdan, Marion; Verlaan, Sjors; Luiking, Yvette

    2016-01-01

    Antioxidant (AOX) deficiencies are commonly observed in older adults and oxidative stress has been suggested to contribute to sarcopenia. Here we investigate if 1) low levels of dietary antioxidants had a negative impact on parameters of muscle mass, function and quality, and 2) to study if nutritional interventions with AOX and/or leucine-enriched whey protein could improve these muscle parameters in aged mice. 18-months-old mice were fed a casein-based antioxidant-deficient (lowox) diet or a casein-based control-diet (CTRL) for 7 months. During the last 3 months, lowox-mice were subjected to either: a) continued lowox, b) supplementation with vitamin A/E, Selenium and Zinc (AOX), c) substitution of casein with leucine-enriched whey protein (PROT) or d) a combination of both AOX and PROT (TOTAL). After 7 months lowox-mice displayed lower muscle strength and more muscle fatigue compared to CTRL. Compared to lowox-mice, PROT-mice showed improved muscle power, grip strength and less muscle fatigue. AOX-mice showed improved oxidative status, less muscle fatigue, improved grip strength and mitochondrial dynamics compared to lowox-mice. The TOTAL-mice showed the combined effects of both interventions compared to lowox-mice. In conclusion, nutritional intervention with AOX and/or leucine-enriched whey protein can play a role in improving muscle health in a AOX-deficient mouse model. PMID:26943770

  20. Freudenthal Dual Lagrangians

    CERN Document Server

    Borsten, L; Ferrara, S; Marrani, A

    2013-01-01

    The global U-dualities of extended supergravity have played a central role in differentiating the distinct classes of extremal black hole solutions. When the U-duality group satisfies certain algebraic conditions, as is the case for a broad class of supergravities, the extremal black holes enjoy a further symmetry known as Freudenthal duality (F-duality), which although distinct from U-duality preserves the Bekenstein-Hawking entropy. Here it is shown that, by adopting the doubled Lagrangian formalism, F-duality, defined on the doubled field strengths, is not only a symmetry of the black hole solutions, but also of the equations of motion themselves. A further role for F-duality is introduced in the context of world-sheet actions. The Nambu-Goto world-sheet action in any (t, s) signature spacetime can be written in terms of the F-dual. The corresponding field equations and Bianchi identities are then related by F-duality allowing for an F-dual formulation of Gaillard-Zumino duality on the world-sheet. An equi...

  1. Investigations of a compartmental model for leucine kinetics using non-linear mixed effects models with ordinary and stochastic differential equations.

    Science.gov (United States)

    Berglund, Martin; Sunnåker, Mikael; Adiels, Martin; Jirstrand, Mats; Wennberg, Bernt

    2012-12-01

    Non-linear mixed effects (NLME) models represent a powerful tool to simultaneously analyse data from several individuals. In this study, a compartmental model of leucine kinetics is examined and extended with a stochastic differential equation to model non-steady-state concentrations of free leucine in the plasma. Data obtained from tracer/tracee experiments for a group of healthy control individuals and a group of individuals suffering from diabetes mellitus type 2 are analysed. We find that the interindividual variation of the model parameters is much smaller for the NLME models, compared to traditional estimates obtained from each individual separately. Using the mixed effects approach, the population parameters are estimated well also when only half of the data are used for each individual. For a typical individual, the amount of free leucine is predicted to vary with a standard deviation of 8.9% around a mean value during the experiment. Moreover, leucine degradation and protein uptake of leucine is smaller, proteolysis larger and the amount of free leucine in the body is much larger for the diabetic individuals than the control individuals. In conclusion, NLME models offers improved estimates for model parameters in complex models based on tracer/tracee data and may be a suitable tool to reduce data sampling in clinical studies.

  2. Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity

    Science.gov (United States)

    Melnik, Bodo C.

    2012-01-01

    Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1). Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases. PMID:22523661

  3. Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity

    Directory of Open Access Journals (Sweden)

    Bodo C. Melnik

    2012-01-01

    Full Text Available Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1. Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.

  4. Asymmetry in Dual Language Practice

    Directory of Open Access Journals (Sweden)

    Audrey Amrein

    2000-01-01

    Full Text Available The capacity for dual-language programs to deliver specific benefits to students with different primary and secondary language skills continues to be debated. Individuals favoring dual language assert that as it relies upon a reciprocal approach, dual language students acquire dual language proficiency without the need for teachers to translate from one language to another. By utilizing and conserving the language skills that students bring, dual language students also gain cross-cultural understandings and an expanded opportunity to realize academic success in the future. Research that explores whether these programs meet the needs of monolingual and bilingual students is limited. The intent of this study is not to criticize dual language practice. Instead, it is to describe a newly implemented dual language immersion program that exists and operates in Phoenix, Arizona. In particular, this study examines the practices of dual language teachers at Leigh Elementary School and the challenges encountered as school personnel worked to provide students with different primary and secondary language skills increased opportunities to learn.

  5. Dual-core Itanium Processor

    CERN Multimedia

    2006-01-01

    Intel’s first dual-core Itanium processor, code-named "Montecito" is a major release of Intel's Itanium 2 Processor Family, which implements the Intel Itanium architecture on a dual-core processor with two cores per die (integrated circuit). Itanium 2 is much more powerful than its predecessor. It has lower power consumption and thermal dissipation.

  6. A potential strategy for counteracting age-related sarcopenia: preliminary evidence of combined exercise training and leucine supplementation.

    Science.gov (United States)

    Xia, Z; Cholewa, J M; Zhao, Y; Yang, Y; Shang, H; Jiang, H; Su, Q; Zanchi, N E

    2017-12-13

    Previous research has demonstrated the positive effects of concurrent/combined aerobic and resistance exercise or leucine supplementation on skeletal muscle protein synthesis (MPS) and hypertrophy in aging organisms. However, the effects of a multimodal intervention which combines both aerobic and resistance exercise and leucine supplementation has not been fully elucidated. Eighteen month old and 2 month old C57BL/6 mice were assigned to aging control (AC, n = 8), aging and multimodal intervention (AMI, n = 8) and young control (YC, n = 8). Mice in the YC and AC groups were fed an alanine-rich diet (3.4%), and mice in the AMI group received an isonitrogenous leucine-supplemented (5%) diet in combination with combined aerobic (30 minutes swimming) and resistance exercise training (incremental jumping submersed in water with overload corresponding to 40%-50% body weight) for a total of 4 weeks. The gastrocnemius muscles were dissected for western blotting detection (signaling proteins involved in MPS) and the ex vivo determination of protein synthesis and protein content. The muscle strength of the hind limbs was measured pre-experiment and repeated once per week on Sunday for 4 weeks. Mice in the AC and AMI groups showed lower ex vivo protein synthesis, protein content, expression of signaling proteins involved in MPS, maximal grip strength but higher plasma cortisol compared with the YC group post intervention. When compared to AC mice, the multimodal treatment led to lower activity of Sestrin2, higher expression of PI3K III and the phosphorylation of mTOR, p70S6K and 4E-BP1, as well as higher plasma leucine, wet gastrocnemius muscle weight and muscle weight to body weight ratio. Furthermore, the multimodal intervention induced more pronounced anabolic response such as higher ex vivo protein synthesis rate, total protein content, and myofibrillar fractions in gastrocnemius muscle, and greater maximum grip strength. The present research shows that a multimodal

  7. Dual Tank Fuel System

    Science.gov (United States)

    Wagner, Richard William; Burkhard, James Frank; Dauer, Kenneth John

    1999-11-16

    A dual tank fuel system has primary and secondary fuel tanks, with the primary tank including a filler pipe to receive fuel and a discharge line to deliver fuel to an engine, and with a balance pipe interconnecting the primary tank and the secondary tank. The balance pipe opens close to the bottom of each tank to direct fuel from the primary tank to the secondary tank as the primary tank is filled, and to direct fuel from the secondary tank to the primary tank as fuel is discharged from the primary tank through the discharge line. A vent line has branches connected to each tank to direct fuel vapor from the tanks as the tanks are filled, and to admit air to the tanks as fuel is delivered to the engine.

  8. Dual THz comb spectroscopy

    Science.gov (United States)

    Yasui, Takeshi

    2017-08-01

    Optical frequency combs are innovative tools for broadband spectroscopy because a series of comb modes can serve as frequency markers that are traceable to a microwave frequency standard. However, a mode distribution that is too discrete limits the spectral sampling interval to the mode frequency spacing even though individual mode linewidth is sufficiently narrow. Here, using a combination of a spectral interleaving and dual-comb spectroscopy in the terahertz (THz) region, we achieved a spectral sampling interval equal to the mode linewidth rather than the mode spacing. The spectrally interleaved THz comb was realized by sweeping the laser repetition frequency and interleaving additional frequency marks. In low-pressure gas spectroscopy, we achieved an improved spectral sampling density of 2.5 MHz and enhanced spectral accuracy of 8.39 × 10-7 in the THz region. The proposed method is a powerful tool for simultaneously achieving high resolution, high accuracy, and broad spectral coverage in THz spectroscopy.

  9. Dual coolant blanket concept

    International Nuclear Information System (INIS)

    Malang, S.; Schleisiek, K.

    1994-11-01

    A self-cooled liquid metal breeder blanket with helium-cooled first wall ('Dual Coolant Blanket Concept') for a fusion DEMO reactor is described. This is one of the four blanket concepts under development in the frame of the European fusion technology program with the aim to select in 1995 the two most promising ones for further development. Described are the design of the blankets including the ancillary loop system and the results of the theoretical and experimental work in the fields of neutronics, magnetohydrodynamics, thermohydraulics, mechanical stresses, compatibility and purification of lead-lithium, tritium control, safety, reliability, and electrically insulating coatings. The remaining open questions and the required R and D programme are identified. (orig.) [de

  10. Bacterial production in Guanabara Bay (Rio de Janeiro, Brazil evaluated by ³H-leucine incorporation

    Directory of Open Access Journals (Sweden)

    Alessandra M. Gonzalez

    2000-01-01

    Full Text Available The aim of this work was to evaluate the necessary ³H-leucine concentration to estimate bacterial production in Guanabara Bay through saturation curves. A second aim was to collect preliminary data of bacterial production in two distinct sites corresponding to different water qualities: Urca inlet and Governador Island. Saturation curves were made with water samples taken at the main circulation channel of the bay, Paquetá Island, and the two sites mentioned before. The ³H-leucine curves showed similar pattern for all studied areas, indicating the ideal isotope concentration to be 10 nM. Bacterial biomass production ranged from 0.40 to 4.53 µgC L-1 h-1 in Urca and from 3.86 to 73.72 µgC L-1 h-1 in Governador Island indicating the relationship between nutrients and organic matter supply and bacterial productivity. This work is an important reference for studies on trophodynamics, biogeochemical cycles and modelling in Guanabara Bay.O objetivo desse trabalho foi realizar curvas de saturação a fim de otimizar a concentração de ³H-leucina necessária para avaliar produção bacteriana na Baía de Guanabara. Objetivou-se ainda a aquisição de dados preliminares de produção bacteriana em dois locais distintos em termos de qualidade de água : enseada da Urca e Ilha do Governador. As amostras para as curvas foram obtidas na região do Canal Central e na Ilha de Paquetá, além dos dois locais de coleta citados acima. Seguiu-se a metodologia descrita por Kirchman et al. (1985 e modificada por Smith & Azam (1992. As curvas de ³H-leucina mostraram um padrão semelhante para todas as áreas estudadas, indicando a concentração ótima de isótopo de 10 nM. A produção de biomassa bacteriana variou de 0,40 a 4,53 µgC L-1 h-1 na Urca e de 3,86 a 73,72 µgC L-1 h-1 na Ilha do Governador confirmando a relação entre a disponibilidade de nutrientes e matéria orgânica e o aumento da produtividade bacteriana. Essas análises poderão ser

  11. Leucine-Rich repeat receptor kinases are sporadically distributed in eukaryotic genomes

    Directory of Open Access Journals (Sweden)

    Diévart Anne

    2011-12-01

    Full Text Available Abstract Background Plant leucine-rich repeat receptor-like kinases (LRR-RLKs are receptor kinases that contain LRRs in their extracellular domain. In the last 15 years, many research groups have demonstrated major roles played by LRR-RLKs in plants during almost all developmental processes throughout the life of the plant and in defense/resistance against a large range of pathogens. Recently, a breakthrough has been made in this field that challenges the dogma of the specificity of plant LRR-RLKs. Results We analyzed ~1000 complete genomes and show that LRR-RK genes have now been identified in 8 non-plant genomes. We performed an exhaustive phylogenetic analysis of all of these receptors, revealing that all of the LRR-containing receptor subfamilies form lineage-specific clades. Our results suggest that the association of LRRs with RKs appeared independently at least four times in eukaryotic evolutionary history. Moreover, the molecular evolutionary history of the LRR-RKs found in oomycetes is reminiscent of the pattern observed in plants: expansion with amplification/deletion and evolution of the domain organization leading to the functional diversification of members of the gene family. Finally, the expression data suggest that oomycete LRR-RKs may play a role in several stages of the oomycete life cycle. Conclusions In view of the key roles that LRR-RLKs play throughout the entire lifetime of plants and plant-environment interactions, the emergence and expansion of this type of receptor in several phyla along the evolution of eukaryotes, and particularly in oomycete genomes, questions their intrinsic functions in mimicry and/or in the coevolution of receptors between hosts and pathogens.

  12. pH-jump induced leucine zipper folding beyond the diffusion limit.

    Science.gov (United States)

    Donten, Mateusz L; Hassan, Shabir; Popp, Alexander; Halter, Jonathan; Hauser, Karin; Hamm, Peter

    2015-01-29

    The folding of a pH-sensitive leucine zipper, that is, a GCN4 mutant containing eight glutamic acid residues, has been investigated. A pH-jump induced by a caged proton (o-nitrobenzaldehyde, oNBA) is employed to initiate the process, and time-resolved IR spectroscopy of the amide I band is used to probe it. The experiment has been carefully designed to minimize the buffer capacity of the sample solution so that a large pH jump can be achieved, leading to a transition from a completely unfolded to a completely folded state with a single laser shot. In order to eliminate the otherwise rate-limiting diffusion-controlled step of the association of two peptides, they have been covalently linked. The results for the folding kinetics of the cross-linked peptide are compared with those of an unlinked peptide, which reveals a detailed picture of the folding mechanism. That is, folding occurs in two steps, one on an ∼1-2 μs time scale leading to a partially folded α-helix even in the monomeric case and a second one leading to the final coiled-coil structure on distinctively different time scales of ∼30 μs for the cross-linked peptide and ∼200 μs for the unlinked peptide. By varying the initial pH, it is found that the folding mechanism is consistent with a thermodynamic two-state model, despite the fact that a transient intermediate is observed in the kinetic experiment.

  13. Abscisic-acid-dependent basic leucine zipper (bZIP) transcription factors in plant abiotic stress.

    Science.gov (United States)

    Banerjee, Aditya; Roychoudhury, Aryadeep

    2017-01-01

    One of the major causes of significant crop loss throughout the world is the myriad of environmental stresses including drought, salinity, cold, heavy metal toxicity, and ultraviolet-B (UV-B) rays. Plants as sessile organisms have evolved various effective mechanism which enable them to withstand this plethora of stresses. Most of such regulatory mechanisms usually follow the abscisic-acid (ABA)-dependent pathway. In this review, we have primarily focussed on the basic leucine zipper (bZIP) transcription factors (TFs) activated by the ABA-mediated signalosome. Upon perception of ABA by specialized receptors, the signal is transduced via various groups of Ser/Thr kinases, which phosphorylate the bZIP TFs. Following such post-translational modification of TFs, they are activated so that they bind to specific cis-acting sequences called abscisic-acid-responsive elements (ABREs) or GC-rich coupling elements (CE), thereby influencing the expression of their target downstream genes. Several in silico techniques have been adopted so far to predict the structural features, recognize the regulatory modification sites, undergo phylogenetic analyses, and facilitate genome-wide survey of TF under multiple stresses. Current investigations on the epigenetic regulation that controls greater accessibility of the inducible regions of DNA of the target gene to the bZIP TFs exclusively under stress situations, along with the evolved stress memory responses via genomic imprinting mechanism, have been highlighted. The potentiality of overexpression of bZIP TFs, either in a homologous or in a heterologous background, in generating transgenic plants tolerant to various abiotic stressors have also been addressed by various groups. The present review will provide a coherent documentation on the functional characterization and regulation of bZIP TFs under multiple environmental stresses, with the major goal of generating multiple-stress-tolerant plant cultivars in near future.

  14. Seizure semiology in leucine-rich glioma-inactivated protein 1 antibody-associated limbic encephalitis.

    Science.gov (United States)

    Chen, Chao; Wang, Xiu; Zhang, Chao; Cui, Tao; Shi, Wei-Xiong; Guan, Hong-Zhi; Ren, Hai-Tao; Shao, Xiao-Qiu

    2017-12-01

    The objective of this study was to advance the characterization of seizure semiology in leucine-rich glioma-inactivated protein 1 (LGI1) antibody-associated limbic encephalitis (LE). Eighteen patients diagnosed with LGI1 LE were identified. Seizure semiology, demographic features, MRI and fluorodeoxyglucose positron emission tomography (FDG-PET), electroencephalograms, and outcomes following immunotherapy were evaluated. Patients were divided into the following groups based on seizure semiology: faciobrachial dystonic seizure only (FBDS-only, n=4), epileptic seizure without FBDS (Non-FBDS, n=6), and FBDS plus epileptic seizure (FBDS+, n=8). In the group with Non-FBDS, the majority of patients (5/6) manifested mesial temporal lobe epilepsy (MTLE) like semiology (i.e., fear, epigastric rising, staring, and automatisms) with a frequency of 7±5 times per day and a duration of 15.3±14.3s. In the group with FBDS+, the distinctive symptom was FBDS followed by epileptic events, especially automatisms (7/8), with a frequency of 16±12 times per day and a duration of 13.0±8.0s. In these cases, 67% and 50% of the patients showed abnormalities on MRI and FDG-PET, respectively, and the mesial temporal lobe structures were most often involved. Ictal discharges were observed in 0/4, 6/6, and 8/8 of the patients in the groups with FBDS only, Non-FBDS, and FBDS+, respectively. The temporal lobe was mainly affected. Immunotherapy had favorable therapeutic effects. The LGI1 LE should be considered as one disease syndrome with a series of clinical manifestation. Identifying types of unique semiology features will facilitate the early diagnosis and the timely initiation of immunotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The SALM/Lrfn family of leucine-rich repeat-containing cell adhesion molecules.

    Science.gov (United States)

    Nam, Jungyong; Mah, Won; Kim, Eunjoon

    2011-07-01

    Synaptic adhesion molecules play important roles in various stages of neuronal development, including neurite outgrowth and synapse formation. The SALM (synaptic adhesion-like molecule) family of adhesion molecules, also known as Lrfn, belongs to the superfamily of leucine-rich repeat (LRR)-containing adhesion molecules. Proteins of the SALM family, which includes five known members (SALMs 1-5), have been implicated in the regulation of neurite outgrowth and branching, and synapse formation and maturation. Despite sharing a similar domain structure, individual SALM family proteins appear to have distinct functions. SALMs 1-3 contain a C-terminal PDZ-binding motif, which interacts with PSD-95, an abundant postsynaptic scaffolding protein, whereas SALM4 and SALM5 lack PDZ binding. SALM1 directly interacts with NMDA receptors but not with AMPA receptors, whereas SALM2 associates with both NMDA and AMPA receptors. SALMs 1-3 form homo- and heteromeric complexes with each other in a cis manner, whereas SALM4 and SALM5 do not, but instead participate in homophilic, trans-cellular adhesion. SALM3 and SALM5, but not other SALMs, possess synaptogenic activity, inducing presynaptic differentiation in contacting axons. All SALMs promote neurite outgrowth, while SALM4 uniquely increases the number of primary processes extending from the cell body. In addition to these functional diversities, the fifth member of the SALM family, SALM5/Lrfn5, has recently been implicated in severe progressive autism and familial schizophrenia, pointing to the clinical importance of SALMs. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Cytosolic 5'-nucleotidase II interacts with the leucin rich repeat of NLR family member Ipaf.

    Directory of Open Access Journals (Sweden)

    Federico Cividini

    Full Text Available IMP/GMP preferring cytosolic 5'-nucleotidase II (cN-II is a bifunctional enzyme whose activities and expression play crucial roles in nucleotide pool maintenance, nucleotide-dependent pathways and programmed cell death. Alignment of primary amino acid sequences of cN-II from human and other organisms show a strong conservation throughout the entire vertebrata taxon suggesting a fundamental role in eukaryotic cells. With the aim to investigate the potential role of this homology in protein-protein interactions, a two hybrid system screening of cN-II interactors was performed in S. cerevisiae. Among the X positive hits, the Leucin Rich Repeat (LRR domain of Ipaf was found to interact with cN-II. Recombinant Ipaf isoform B (lacking the Nucleotide Binding Domain was used in an in vitro affinity chromatography assay confirming the interaction obtained in the screening. Moreover, co-immunoprecipitation with proteins from wild type Human Embryonic Kidney 293 T cells demonstrated that endogenous cN-II co-immunoprecipitated both with wild type Ipaf and its LRR domain after transfection with corresponding expression vectors, but not with Ipaf lacking the LRR domain. These results suggest that the interaction takes place through the LRR domain of Ipaf. In addition, a proximity ligation assay was performed in A549 lung carcinoma cells and in MDA-MB-231 breast cancer cells and showed a positive cytosolic signal, confirming that this interaction occurs in human cells. This is the first report of a protein-protein interaction involving cN-II, suggesting either novel functions or an additional level of regulation of this complex enzyme.

  17. Consequences of alteration in leucine zipper sequence of melittin in its neutralization of lipopolysaccharide-induced proinflammatory response in macrophage cells and interaction with lipopolysaccharide.

    Science.gov (United States)

    Srivastava, Raghvendra M; Srivastava, Saurabh; Singh, Manish; Bajpai, Virendra Kumar; Ghosh, Jimut Kanti

    2012-01-13

    The bee venom antimicrobial peptide, melittin, besides showing versatile activity against microorganisms also neutralizes lipopolysaccharide (LPS)-induced proinflammatory responses in macrophage cells. However, how the amino acid sequence of melittin contributes in its anti-inflammatory properties is mostly unknown. To determine the importance of the leucine zipper sequence of melittin in its neutralization of LPS-induced inflammatory responses in macrophages and interaction with LPS, anti-inflammatory properties of melittin and its three analogues and their interactions with LPS were studied in detail. Two of these analogues, namely melittin Mut-1 (MM-1) and melittin Mut-2 (MM-2), possess leucine to alanine substitutions in the single and double heptadic leucine residue(s) of melittin, respectively, whereas the third analogue is a scrambled peptide (Mel-SCR) that contains the amino acid composition of melittin with minor rearrangement in its leucine zipper sequence. Although MM-1 partly inhibited the production of proinflammatory cytokines in RAW 264.7 and rat primary macrophage cells in the presence of LPS, MM-2 and Mel-SCR were negligibly active. A progressive decrease in interaction of melittin with LPS, aggregation in LPS, and dissociation of LPS aggregates with alteration in the leucine zipper sequence of melittin was observed. Furthermore, with alteration in the leucine zipper sequence of melittin, these analogues failed to exhibit cellular responses associated with neutralization of LPS-induced inflammatory responses in macrophage cells by melittin. The data indicated a probable important role of the leucine zipper sequence of melittin in neutralizing LPS-induced proinflammatory responses in macrophage cells as well as in its interaction with LPS.

  18. Dual of QCD with One Adjoint Fermion

    DEFF Research Database (Denmark)

    Mojaza, Matin; Nardecchia, Marco; Pica, Claudio

    2011-01-01

    We construct the magnetic dual of QCD with one adjoint Weyl fermion. The dual is a consistent solution of the 't Hooft anomaly matching conditions, allows for flavor decoupling and remarkably constitutes the first nonsupersymmetric dual valid for any number of colors. The dual allows to bound...

  19. Nuclearity for dual operator spaces

    Indian Academy of Sciences (India)

    In this short paper, we study the nuclearity for the dual operator space V ∗ of an operator space . We show that V ∗ is nuclear if and only if V ∗ ∗ ∗ is injective, where V ∗ ∗ ∗ is the third dual of . This is in striking contrast to the situation for general operator spaces. This result is used to prove that V ∗ ∗ is nuclear if and ...

  20. Symmetries of the dual metrics

    International Nuclear Information System (INIS)

    Baleanu, D.

    1998-01-01

    The geometric duality between the metric g μν and a Killing tensor K μν is studied. The conditions were found when the symmetries of the metric g μν and the dual metric K μν are the same. Dual spinning space was constructed without introduction of torsion. The general results are applied to the case of Kerr-Newmann metric

  1. Dual temperature concentration system

    International Nuclear Information System (INIS)

    Spevack, J.S.

    1975-01-01

    In a dual temperature isotope exchange system--exemplified by exchange of deuterium and protium between water and hydrogen sulfide gas in hot and cold towers, in which the feed stream (water) containing the desired isotope is passed through a pair of towers maintained at different temperatures wherein it effects isotope exchange with countercurrently circulated auxiliary fluid (H 2 S) and is impoverished in said isotope and then disposed of, e.g. discharged to waste,--the flow of isotope enriched auxiliary fluid between said towers (hot H 2 S saturated with water vapor) is divided and a part thereof is adjusted in its temperature (to cold tower conditions) and then passed to the auxiliary fluid impoverishing (cold) tower, while the remainder of the divided flow of such enriched auxiliary fluid is passed through a subsequent isotope concentration treatment to produce a product more highly enriched in the desired isotope and wherein it is also adjusted in its temperature and is impoverished in said isotope during said subsequent treatment before it is delivered to the said auxiliary fluid impoverishing (cold) tower. Certain provisions are made for returning to the hot tower liquid carried as vapor by the remainder of the divided flow to the subsequent isotope concentration treatment, for recovering sensible and latent heat, and for reducing passage of auxiliary fluid to waste

  2. The Effects of Leucine, Zinc, and Chromium Supplements on Inflammatory Events of the Respiratory System in Type 2 Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    Full Text Available Diabetes mellitus is a major cause of serious micro- and macrovascular diseases that affect nearly every system in the body, including the respiratory system. Non-enzymatic protein glycation due to hyperglycaemic stress has fundamental implications due to the large capillary network and amount of connective tissue in the lung. The current study was designed to determine whether leucine, zinc, and chromium supplementations influence the function and histological structure of the respiratory tract in a rat model of type 2 diabetes. Seventy-seven rats were divided into eleven groups, consisting of 7 animals each. One group served as negative control and insulin and glibenclamide were used as positive control drugs. Thus, eight groups received the nutritional supplements alone or in combination with each other. Nutritional supplements and glibenclamide were added to the drinking water and neutral protamine Hagedorn insulin was subcutaneously injected during the 4 weeks of treatment period. The induction of type 2 diabetes in the rats caused an infiltration of mononuclear cells and edema in the submucosa of the trachea and lung, severe fibrosis around the vessels and airways, and perivascular and peribronchial infiltration of inflammatory cells and fibrin. In the diabetic group, the total inflammation score and Reid index significantly increased. Diabetes induction significantly reduced the total antioxidant status and elevated the lipid peroxidation products in the serum, lung lavage and lung tissue of the diabetic animals. Treatment with nutritional supplements significantly decreased the histopathological changes and inflammatory indices in the diabetic animals. Supplementation of diabetic rats with leucine, zinc, and chromium, alone and in combination, significantly increased the total antioxidant status and lipid peroxidation level in the diabetic animals. The nutritional supplements improved the enzymatic antioxidant activity of catalase

  3. Solvation thermodynamics of L-cystine, L-tyrosine, and L-leucine in aqueous-electrolyte media

    Science.gov (United States)

    Roy, Sanjay; Guin, Partha Sarathi; Mahali, Kalachand; Dolui, Bijoy Krishna

    2017-12-01

    Solubilities of L-cystine, L-tyrosine, and L-leucine in aqueous NaCl media at 298.15 K have been studied. Indispensable and related solvent parameters such as molar mass, molar volume, etc., were also determined. The results are used to evaluate the standard transfer Gibbs free energy, cavity forming enthalpy of transfer, cavity forming transfer Gibbs free energy and dipole-dipole interaction effects during the course of solvation. Various weak interactions involving solute-solvent or solvent-solvent molecules were characterized in order to find their role on the solvation of these amino acids.

  4. A new method for determining the metabolic activity of specific bacterial populations in soil using tritiated leucine and immunomagnetic separation

    DEFF Research Database (Denmark)

    Sengeløv, Gitte; Sørensen, Søren Johannes; Frette, Lone

    2000-01-01

    A new assay, using immunomagnetic separation and uptake of tritiated leucine ([3H]-Leu), was developed for measuring the in situ metabolic activity of specific bacterial populations in soil. Such assays are needed to assess the role individual species play in diverse microbial soil communities...... reduced this unspecific binding, resulting in metabolic activity of the target cells. As expected, a linear relationship...... between activity and temperature was observed, demonstrating the sensitivity of the assay. The method was applied to compare activities of the target strain in bulk soil and in the rhizosphere of barley. Contrary to what was anticipated, no significant difference in metabolic activity was observed....

  5. Structural insight into maternal embryonic leucine zipper kinase (MELK) conformation and inhibition toward structure-based drug design.

    Science.gov (United States)

    Canevari, Giulia; Re Depaolini, Stefania; Cucchi, Ulisse; Bertrand, Jay A; Casale, Elena; Perrera, Claudia; Forte, Barbara; Carpinelli, Patrizia; Felder, Eduard R

    2013-09-17

    Maternal embryonic leucine zipper kinase (MELK) is upregulated in several types of tumor, including breast, prostate, and brain tumors. Its expression is generally associated with cell survival, cell proliferation, and resistance to apoptosis. Therefore, the potential of MELK inhibitors as therapeutic agents is recently attracting considerable interest. Here we report the first structures of MELK in complex with AMP-PNP and with nanomolar inhibitors. Our studies shed light on the role of the MELK UBA domain, provide a characterization of the kinase active site, and identify key residues for achieving high potency, laying the groundwork for structure-based drug design efforts.

  6. Identification of a novel Leucine-rich repeat protein and candidate PP1 regulatory subunit expressed in developing spermatids

    Directory of Open Access Journals (Sweden)

    Sperry Ann O

    2008-01-01

    Full Text Available Abstract Background Spermatogenesis is comprised of a series of highly regulated developmental changes that transform the precursor germ cell into a highly specialized spermatozoon. The last phase of spermatogenesis, termed spermiogenesis, involves dramatic morphological change including formation of the acrosome, elongation and condensation of the nucleus, formation of the flagella, and disposal of unnecessary cytoplasm. A prominent cytoskeletal component of the developing spermatid is the manchette, a unique microtubular structure that surrounds the nucleus of the developing spermatid and is thought to assist in both the reshaping of the nucleus and redistribution of spermatid cytoplasm. Although the molecular motor KIFC1 has been shown to associate with the manchette, its precise role in function of the manchette and the identity of its testis specific protein partners are unknown. The purpose of this study was to identify proteins in the testis that interact with KIFC1 using a yeast 2 hybrid screen of a testis cDNA library. Results Thirty percent of the interacting clones identified in our screen contain an identical cDNA encoding a 40 kD protein. This interacting protein has 4 leucine-rich repeats in its amino terminal half and is expressed primarily in the testis; therefore we have named this protein testis leucine-rich repeat protein or TLRR. TLRR was also found to associate tightly with the KIFC1 targeting domain using affinity chromatography. In addition to the leucine-rich repeats, TLRR contains a consensus-binding site for protein phosphatase-1 (PP1. Immunocytochemistry using a TLRR specific antibody demonstrates that this protein is found near the manchette of developing spermatids. Conclusion We have identified a previously uncharacterized leucine-rich repeat protein that is expressed abundantly in the testis and associates with the manchette of developing spermatids, possibly through its interaction with the KIFC1 molecular motor

  7. Utilization of an amphipathic leucine zipper sequence to design antibacterial peptides with simultaneous modulation of toxic activity against human red blood cells.

    Science.gov (United States)

    Ahmad, Aqeel; Yadav, Sharada Prasad; Asthana, Neeta; Mitra, Kalyan; Srivastava, Swati Prakash; Ghosh, Jimut Kanti

    2006-08-04

    The toxicity of naturally occurring or designed antimicrobial peptides is a major barrier for converting them into drugs. To synthesize antimicrobial peptides with reduced toxicity, several amphipathic peptides were designed based on the leucine zipper sequence. The first one was a leucine zipper peptide (LZP); in others, leucine residues at the a- and/or d-position were substituted with single or double alanine residues. The results showed that LZP and its analogs exhibited appreciable and similar antibacterial activity against the tested gram-positive and gram-negative bacteria. However, the substitution of alanine progressively lowered the toxicity of LZP against human red blood cells (hRBCs). The substitution of leucine with alanine impaired the binding and localization of LZP to hRBCs, but had little effect on the peptide-induced damage of Escherichia coli cells. Although LZP and its analogs exhibited similar permeability, secondary structures, and localization in negatively charged membranes, significant differences were observed among these peptides in zwitterionic membranes. The results suggest a novel approach for designing antibacterial peptides with modulation of toxicity against hRBCs by employing the leucine zipper sequence. Also, to the best of our knowledge, the results demonstrate that this sequence could be utilized to design novel cell-selective molecules for the first time.

  8. In vivo and in vitro effects of growth hormone on the incorporation of [14C]leucine into protein of liver and muscle of the eel

    International Nuclear Information System (INIS)

    Inui, Y.; Ishioka, H.

    1985-01-01

    In vivo administration of ovine GH (2 micrograms/g body wt) increased [ 14 C]leucine incorporation into protein of the liver, skeletal muscle, and opercular muscle of hypophysectomized eels. Addition of ovine GH into the medium slightly increased [ 14 C]leucine incorporation into protein of liver slices during 5 hr in vitro incubation, but did not affect protein synthesis from [ 14 C]leucine in opercular muscle. In vivo pretreatment with ovine GH 48 hr prior to tissue preparation clearly increased [ 14 C]leucine incorporation into protein of liver slices in vitro. However, no statistically significant change was observed for in vitro incorporation of [ 14 C]leucine into protein of opercular muscle of hypophysectomized eels which had been previously treated with ovine GH. These results indicate that ovine GH has a protein anabolic action in the liver and muscle of the eel and that compared to mammals a rather long lag period is needed to elicit such protein anabolic actions of GH in these animals

  9. The N-terminal leucine-zipper motif in PTRF/cavin-1 is essential and sufficient for its caveolae-association

    International Nuclear Information System (INIS)

    Wei, Zhuang; Zou, Xinle; Wang, Hongzhong; Lei, Jigang; Wu, Yuan; Liao, Kan

    2015-01-01

    Highlight: • The N-terminal leucine-zipper motif in PTRF/cavin-1 determines caveolar association. • Different cellular localization of PTRF/cavin-1 influences its serine 389 and 391 phosphorylation state. • PTRF/cavin-1 regulates cell motility via its caveolar association. - Abstract: PTRF/cavin-1 is a protein of two lives. Its reported functions in ribosomal RNA synthesis and in caveolae formation happen in two different cellular locations: nucleus vs. plasma membrane. Here, we identified that the N-terminal leucine-zipper motif in PTRF/cavin-1 was essential for the protein to be associated with caveolae in plasma membrane. It could counteract the effect of nuclear localization sequence in the molecule (AA 235–251). Deletion of this leucine-zipper motif from PTRF/cavin-1 caused the mutant to be exclusively localized in nuclei. The fusion of this leucine-zipper motif with histone 2A, which is a nuclear protein, could induce the fusion protein to be exported from nucleus. Cell migration was greatly inhibited in PTRF/cavin-1 −/− mouse embryonic fibroblasts (MEFs). The inhibited cell motility could only be rescued by exogenous cavin-1 but not the leucine-zipper motif deleted cavin-1 mutant. Plasma membrane dynamics is an important factor in cell motility control. Our results suggested that the membrane dynamics in cell migration is affected by caveolae associated PTRF/cavin-1

  10. T cell receptor zeta allows stable expression of receptors containing the CD3gamma leucine-based receptor-sorting motif

    DEFF Research Database (Denmark)

    Dietrich, J; Geisler, C

    1998-01-01

    The leucine-based motif in the T cell receptor (TCR) subunit CD3gamma constitutes a strong internalization signal. In fully assembled TCR this motif is inactive unless phosphorylated. In contrast, the motif is constitutively active in CD4/CD3gamma and Tac/CD3gamma chimeras independently of phosph......The leucine-based motif in the T cell receptor (TCR) subunit CD3gamma constitutes a strong internalization signal. In fully assembled TCR this motif is inactive unless phosphorylated. In contrast, the motif is constitutively active in CD4/CD3gamma and Tac/CD3gamma chimeras independently...... to mask the CD3gamma leucine-based motif. By studying CD4/CD3gamma and CD16/CD3gamma chimeras, we found that CD16/CD3gamma chimeras associated with TCRzeta. The CD16/CD3gamma-TCRzeta complexes were stably expressed at the cell surface and had a low spontaneous internalization rate, indicating...... that the leucine-based motif in these complexes was inactive. In contrast, the CD4/CD3gamma chimeras did not associate with TCRzeta, and the leucine-based motif in these chimeras was constitutively active resulting in a high spontaneous internalization rate and low expression of the chimeras at the cell surface...

  11. Commonly used Saccharomyces cerevisiae strains (e.g. BY4741, W303) are growth sensitive on synthetic complete medium due to poor leucine uptake.

    Science.gov (United States)

    Cohen, Ruth; Engelberg, David

    2007-08-01

    It is reported that some of the widely used laboratory strains of Saccharomyces cerevisiae (e.g. W303, BY4741) are sensitive to synthetic media containing all 20 amino acids [e.g. synthetic complete (SC) medium or supplemented minimal medium]. To determine the molecular basis for this unexpected sensitivity, a genomic library was screened and three genes were identified that, when overexpressed, rescue cells from this phenotype. Two of the 'rescuing' genes, BAP2 and TAT1, are related to transport of leucine, and one, LEU2, to synthesis of leucine, showing that sensitivity to SC medium is associated with the leu2 mutation. The sensitive strains seem incapable of transporting leucine when grown on synthetic complete media. This effect of the leu2 mutation should be taken into consideration when analyzing the results of genetic screens and other experiments performed with these strains.

  12. Effects of "Bioactive" amino acids leucine, glutamate, arginine and tryptophan on feed intake and mRNA expression of relative neuropeptides in broiler chicks

    Directory of Open Access Journals (Sweden)

    Wang Songbo

    2012-08-01

    Full Text Available Abstract Feed intake control is vital to ensuring optimal nutrition and achieving full potential for growth and development in poultry. The aim of the present study was to investigate the effects of L-leucine, L-glutamate, L-tryptophan and L-arginine on feed intake and the mRNA expression levels of hypothalamic Neuropeptide involved in feed intake regulation in broiler chicks. Leucine, glutamate, tryptophan or arginine was intra-cerebroventricularly (ICV administrated to 4d-old broiler chicks respectively and the feed intake were recorded at various time points. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of Neuropeptide Y (NPY, agouti related protein (AgRP, pro-opiomelanocortin (POMC, melanocortin receptor 4 (MC4R and corticotrophin releasing factor (CRF. Our results showed that ICV administration of L-leucine (0.15 or 1.5  μmol significantly (P P 

  13. Amino acid transport across the tonoplast of vacuoles isolated from barley mesophyll protoplasts: Uptake of alanine, leucine, and glutamine

    International Nuclear Information System (INIS)

    Dietz, K.J.; Jaeger, R.; Kaiser, G.; Martinoia, E.

    1990-01-01

    Mesophyll protoplasts from leaves of well-fertilized barley (Hordeum vulgare L.) plants contained amino acids at concentrations as high as 120 millimoles per liter. With the exception of glutamic acid, which is predominantly localized in the cytoplasm, a major part of all other amino acids was contained inside the large central vacuole. Alanine, leucine, and glutamine are the dominant vacuolar amino acids in barley. Their transport into isolated vacuoles was studied using 14 C-labeled amino acids. Uptake was slow in the absence of ATP. A three- to sixfold stimulation of uptake was observed after addition of ATP or adenylyl imidodiphosphate an ATP analogue not being hydrolyzed by ATPases. Other nucleotides were ineffective in increasing the rate of uptake. ATP-Stimulated amino acid transport was not dependent on the transtonoplast pH or membrane potential. p-Chloromercuriphenylsulfonic acid and n-ethyl maleimide increased transport independently of ATP. Neutral amino acids such as valine or leucine effectively decreased the rate of alanine transport. Glutamine and glycine were less effective or not effective as competitive inhibitors of alanine transport. The results indicate the existence of a uniport translocator specific for neutral or basic amino acids that is under control of metabolic effectors

  14. Effect of leucine-to-methionine substitutions on the diffraction quality of histone chaperone SET/TAF-Iβ/INHAT crystals

    International Nuclear Information System (INIS)

    Senda, Miki; Muto, Shinsuke; Horikoshi, Masami; Senda, Toshiya

    2008-01-01

    The combination of leucine-to-methionine substitutions and optimization of cryoconditions improved the resolution of histone chaperone SET/TAF-Iβ/INHAT crystals from around 5.5 to 2.3 Å without changing the crystallization conditions, allowing successful structure determination of SET/TAF-Iβ/INHAT by the multiwavelength anomalous diffraction method. One of the most frequent problems in crystallization is poor quality of the crystals. In order to overcome this obstacle several methods have been utilized, including amino-acid substitutions of the target protein. Here, an example is presented of crystal-quality improvement by leucine-to-methionine substitutions. A variant protein with three amino-acid substitutions enabled improvement of the crystal quality of the histone chaperone SET/TAF-Iβ/INHAT when combined with optimization of the cryoconditions. This procedure improved the resolution of the SET/TAF-Iβ/INHAT crystals from around 5.5 to 2.3 Å without changing the crystallization conditions

  15. Effect of chromatolysis upon the incorporation of L-4,5-(3H)-leucine into axotomized neurons

    International Nuclear Information System (INIS)

    Soereide, A.J.

    1981-01-01

    Autoradiography was used to compare the rate of protein synthesis in neurons which showed different types of neuronal change after axotomy. Different types of axon reaction were obtained after crush lesion of the facial nerve in rats and young rabbits and after evulsion of the facial nerve in rats. The incorporation of ( 3 H)-leucine into protein was determined after intraperitoneal injection by counting silver grains over facial neurons in autoradiograms prepared from paraffin sections. Crush lesion of the facial nerve in rats was followed by barely discernible changes in the neurons, no chromatolysis, and full functional recovery. The lesion caused a significant transitory increase in the protein synthesis. After nerve evulsion, the same neurons showed a severe central chromatolysis and ultimate nerve cell disintegration. The protein synthesis was unchanged during the early chromotolytic phase after evulsion and decreased at later stages. Crush lesion of the facial nerve in young rabbits was followed by severe central chromotolysis, full functional recovery, and no loss of neurons. There was a moderate increase in the protein synthesis during chromatolysis and a further increase during the phase of recovery. It is concluded that regeneration after axotomy is accompanied by an increase in protein synthesis, regardless of the type of morphologic change in the neurons. Chromatolysis is not a prerequisite for this increase, and the chromatolytic response per se seems to be of minor importance for the extent of incorporation of ( 3 H)-leucine into neuronal proteins. (orig.)

  16. Ursolic acid inhibits leucine-stimulated mTORC1 signaling by suppressing mTOR localization to lysosome.

    Directory of Open Access Journals (Sweden)

    Xiang Ou

    Full Text Available Ursolic acid (UA, a pentacyclic triterpenoid widely found in medicinal herbs and fruits, has been reported to possess a wide range of beneficial properties including anti-hyperglycemia, anti-obesity, and anti-cancer. However, the molecular mechanisms underlying the action of UA remain largely unknown. Here we show that UA inhibits leucine-induced activation of the mechanistic target of rapamycin complex 1 (mTORC1 signaling pathway in C2C12 myotubes. The UA-mediated inhibition of mTORC1 is independent of Akt, tuberous sclerosis complex 1/2 (TSC1/2, and Ras homolog enriched in brain (Rheb, suggesting that UA negatively regulates mTORC1 signaling by targeting at a site downstream of these mTOR regulators. UA treatment had no effect on the interaction between mTOR and its activator Raptor or inhibitor Deptor, but suppressed the binding of RagB to Raptor and inhibited leucine-induced mTOR lysosomal localization. Taken together, our study identifies UA as a direct negative regulator of the mTORC1 signaling pathway and suggests a novel mechanism by which UA exerts its beneficial function.

  17. HPLC Separation of Sulforaphane Enantiomers in Broccoli and Its Sprouts by Transformation into Diastereoisomers Using Derivatization with (S)-Leucine.

    Science.gov (United States)

    Okada, Makiko; Yamamoto, Atsushi; Aizawa, Sen-Ichi; Taga, Atsushi; Terashima, Hiroyuki; Kodama, Shuji

    2017-01-11

    Racemic sulforaphane, which was derivatized with (S)-leucine (l-leucine), was resolved by reversed phase HPLC with UV detection. The optimum mobile phase conditions were found to be 10 mM citric acid (pH 2.8) containing 22% methanol at 35 °C using detection at 254 nm. Sulforaphane enantiomers in florets and stems of five brands of broccoli and leaves and stems of three brands of broccoli sprouts were analyzed by the proposed HPLC method. Both sulforaphane enantiomers were detected in all of the samples. The S/R ratios of sulforaphane in broccoli samples were 1.5-2.6/97.4-98.5% for florets and 5.0-12.1/87.9-95.0% for stems. The S/R ratios in broccoli sprout samples were higher than those in broccoli samples and were found to be 8.3-19.7/80.3-91.7% for leaves and 37.0-41.8/58.2-63.0% for stems. (S)-Sulforaphane detected in the broccoli and its sprout samples was positively identified by separately using an HPLC with a chiral column (Chiralpak AD-RH) and mass spectrometry.

  18. A conserved gene family encodes transmembrane proteins with fibronectin, immunoglobulin and leucine-rich repeat domains (FIGLER

    Directory of Open Access Journals (Sweden)

    Haga Christopher L

    2007-09-01

    Full Text Available Abstract Background In mouse the cytokine interleukin-7 (IL-7 is required for generation of B lymphocytes, but human IL-7 does not appear to have this function. A bioinformatics approach was therefore used to identify IL-7 receptor related genes in the hope of identifying the elusive human cytokine. Results Our database search identified a family of nine gene candidates, which we have provisionally named fibronectin immunoglobulin leucine-rich repeat (FIGLER. The FIGLER 1–9 genes are predicted to encode type I transmembrane glycoproteins with 6–12 leucine-rich repeats (LRR, a C2 type Ig domain, a fibronectin type III domain, a hydrophobic transmembrane domain, and a cytoplasmic domain containing one to four tyrosine residues. Members of this multichromosomal gene family possess 20–47% overall amino acid identity and are differentially expressed in cell lines and primary hematopoietic lineage cells. Genes for FIGLER homologs were identified in macaque, orangutan, chimpanzee, mouse, rat, dog, chicken, toad, and puffer fish databases. The non-human FIGLER homologs share 38–99% overall amino acid identity with their human counterpart. Conclusion The extracellular domain structure and absence of recognizable cytoplasmic signaling motifs in members of the highly conserved FIGLER gene family suggest a trophic or cell adhesion function for these molecules.

  19. Leucine-enriched essential amino acids attenuate muscle soreness and improve muscle protein synthesis after eccentric contractions in rats.

    Science.gov (United States)

    Kato, Hiroyuki; Suzuki, Hiromi; Mimura, Masako; Inoue, Yoshiko; Sugita, Mayu; Suzuki, Katsuya; Kobayashi, Hisamine

    2015-06-01

    Eccentric exercise results in prolonged muscle weakness and muscle soreness, which are typical symptoms of muscle damage. Recovery from muscle damage is related to mammalian target of rapamycin (mTOR) activity. Leucine-enriched essential amino acids (LEAAs) stimulate muscle protein synthesis via activation of the mTOR pathway. Therefore, we investigated the effect of LEAAs on muscle protein synthesis and muscle soreness after eccentric contractions (EC). Male Sprague-Dawley rats (9-11 weeks old) were administered an LEAA solution (AminoL40; containing 40 % leucine and 60 % other essential amino acids) at 1 g/kg body weight or distilled water (control) 30 min before and 10 min after EC. Tibialis anterior (TA) muscle was exposed to 500 EC by electrical stimulation under anesthesia. The fractional synthesis rate (FSR; %/h) in the TA muscle was measured by incorporating L-[ring-(2)H5] phenylalanine into skeletal muscle protein. Muscle soreness was evaluated by the paw withdrawal threshold using the Randal-Selitto test with some modifications from 1 to 3 days after EC. The FSR in the EC-control group (0.147 ± 0.016 %/h) was significantly lower than in the sedentary group (0.188 ± 0.016 %/h, p soreness. Furthermore, AminoL40 administration alleviated the decreased paw withdrawal threshold. These findings suggest that LEAA supplementation improves the rate of muscle protein synthesis and ameliorates muscle soreness after eccentric exercise.

  20. A leucine-rich diet and exercise affect the biomechanical characteristics of the digital flexor tendon in rats after nutritional recovery.

    Science.gov (United States)

    Barbosa, Alexandre Wesley Carvalho; Benevides, Gustavo Pereira; Alferes, Leda Maria Totti; Salomão, Emilianne Miguel; Gomes-Marcondes, Maria Cristina Cintra; Gomes, Laurecir

    2012-01-01

    An increase in the capacity of athletic performance depends on adequate nutrition, which ensures optimal function of the musculoskeletal system, including tendon stability. However, little is known about the status of tendons and extracellular matrix modifications during malnutrition and nutritional recovery when leucine is used in response to exercise conditioning. The purpose of this study was to evaluate the collagen content and biomechanical aspects of the deep digital flexor tendon (DDFT) in malnourished rats submitted to nutritional recovery (control diet or leucine-rich diet) and aerobic physical activity. After 60 days of undernourishment (6% protein diet), the malnourished rats were subsequently nutritionally recovered with a control diet or leucine-rich diet and trained or not (swimming, without overload) for 5 weeks. The biomechanical analysis and quantification of hydroxyproline were assessed in the DDFT in all experimental groups. The leucine-rich diet increased hydroxyproline content in the tension region, independently of the training. In the compression region, hydroxyproline content was higher in the malnourished and leucine-trained groups. Biomechanical analysis showed a lower load in the malnourished and all-trained groups. The lowest stress was observed with control-trained animals. The nutritional-recovered groups showed higher strain values corresponding to control group, while the lowest values were observed in malnourished and trained groups. The results suggest that a leucine-rich diet stimulates collagen synthesis of the DDFT, especially when in combination with physical exercise, and seems to determine the increase of resistance and the biomechanical characteristics of tendons.

  1. The 15N-leucine single-injection method allows for determining endogenous losses and true digestibility of amino acids in cecectomized roosters.

    Directory of Open Access Journals (Sweden)

    Rujiu Hu

    Full Text Available This study was conducted to assess the influence of dietary protein content in poultry when using the 15N-leucine single-injection method to determine endogenous amino acid losses (EAALs in poultry. Forty-eight cecectomized roosters (2.39 ± 0.23 kg were randomly allocated to eight dietary treatments containing protein levels of 0, 3%, 6%, 9%, 12%, 15%, 18% and 21%. Each bird was precisely fed an experimental diet of 25 g/kg of body weight. After feeding, all roosters were subcutaneously injected with a 15N-leucine solution at a dose of 20 mg/kg of body weight. Blood was sampled 23 h after the injection, and excreta samples were continuously collected during the course of the 48-h experiment. The ratio of 15N-enrichment of leucine in crude mucin to free leucine in plasma ranged from 0.664 to 0.763 and remained relatively consistent (P > 0.05 across all treatments. The amino acid (AA profiles of total endogenous AAs, except isoleucine, alanine, aspartic acid, cysteine, proline and serine, were not influenced (P > 0.05 by dietary protein contents. The predominant endogenous AAs in the excreta were glutamic acid, aspartic acid, threonine, serine and proline. The order of the relative proportions of these predominant AAs also remained relatively constant (P > 0.05. The endogenous losses of total AAs determined with the 15N-leucine single-injection method increased curvilinearly with the dietary protein contents. The true digestibility of most AAs and total AAs was independent of their respective dietary protein levels. Collectively, the 15N-leucine single-injection method is appropriate for determining EAALs and the true digestibility of AAs in poultry fed varying levels of protein-containing ingredients.

  2. Leucine supplementation does not affect protein turnover and impairs the beneficial effects of endurance training on glucose homeostasis in healthy mice.

    Science.gov (United States)

    Costa Júnior, José M; Rosa, Morgana R; Protzek, André O; de Paula, Flávia M; Ferreira, Sandra M; Rezende, Luiz F; Vanzela, Emerielle C; Zoppi, Cláudio C; Silveira, Leonardo R; Kettelhut, Isis C; Boschero, Antonio C; de Oliveira, Camila A M; Carneiro, Everardo M

    2015-04-01

    Endurance exercise training as well as leucine supplementation modulates glucose homeostasis and protein turnover in mammals. Here, we analyze whether leucine supplementation alters the effects of endurance exercise on these parameters in healthy mice. Mice were distributed into sedentary (C) and exercise (T) groups. The exercise group performed a 12-week swimming protocol. Half of the C and T mice, designated as the CL and TL groups, were supplemented with leucine (1.5 % dissolved in the drinking water) throughout the experiment. As well known, endurance exercise training reduced body weight and the retroperitoneal fat pad, increased soleus mass, increased VO2max, decreased muscle proteolysis, and ameliorated peripheral insulin sensitivity. Leucine supplementation had no effect on any of these parameters and worsened glucose tolerance in both CL and TL mice. In the soleus muscle of the T group, AS-160(Thr-642) (AKT substrate of 160 kDa) and AMPK(Thr-172) (AMP-Activated Protein Kinase) phosphorylation was increased by exercise in both basal and insulin-stimulated conditions, but it was reduced in TL mice with insulin stimulation compared with the T group. Akt phosphorylation was not affected by exercise but was lower in the CL group compared with the other groups. Leucine supplementation increased mTOR phosphorylation at basal conditions, whereas exercise reduced it in the presence of insulin, despite no alterations in protein synthesis. In trained groups, the total FoxO3a protein content and the mRNA for the specific isoforms E2 and E3 ligases were reduced. In conclusion, leucine supplementation did not potentiate the effects of endurance training on protein turnover, and it also reduced its positive effects on glucose homeostasis.

  3. Acute Exposure to a Precursor of Advanced Glycation End Products Induces a Dual Effect on the Rat Pancreatic Islet Function

    Directory of Open Access Journals (Sweden)

    Ghada Elmhiri

    2014-01-01

    Full Text Available Aim. Chronic diseases are the leading cause of death worldwide. Advanced glycation end products, known as AGEs, are a major risk factor for diabetes onset and maintenance. Methylglyoxal (MG, a highly reactive metabolite of glucose, is a precursor for the generation of endogenous AGEs. Methods. In this current study we incubated in vitro pancreatic islets from adult rats in absence or presence of MG (10 μmol/l with different concentrations of glucose and different metabolic components (acetylcholine, epinephrine, potassium, forskolin, and leucine. Results. Different effects of MG on insulin secretion were evidenced. In basal glucose stimulation (5.6 mM, MG induced a significant (P<0.05 increase of insulin secretion. By contrast, in higher glucose concentrations (8.3 mM and 16.7 mM, MG significantly inhibited insulin secretion (P<0.05. In the presence of potassium, forskolin, and epinephrine, MG enhanced insulin secretion (P<0.05, while when it was incubated with acetylcholine and leucine, MG resulted in a decrease of insulin secretion (P<0.05. Conclusion. We suggest that MG modulates the secretion activity of beta-cell depending on its level of stimulation by other metabolic factors. These results provide insights on a dual acute effect of MG on the pancreatic cells.

  4. The vibrational spectrum of the hydrated alanine-leucine peptide in the amide region from IR experiments and first principles calculations

    Science.gov (United States)

    Hassan, Irtaza; Donati, Luca; Stensitzki, Till; Keller, Bettina G.; Heyne, Karsten; Imhof, Petra

    2018-04-01

    We have combined infrared (IR) experiments with molecular dynamics (MD) simulations in solution at finite temperature to analyse the vibrational signature of the small floppy peptide Alanine-Leucine. IR spectra computed from first-principles MD simulations exhibit no distinct differences between conformational clusters of α -helix or β -sheet-like folds with different orientations of the bulky leucine side chain. All computed spectra show two prominent bands, in good agreement with the experiment, that are assigned to the stretch vibrations of the carbonyl and carboxyl group, respectively. Variations in band widths and exact maxima are likely due to small fluctuations in the backbone torsion angles.

  5. Effect of glucagon on cyclic AMP, albumin metabolism and incorporation of 14C-leucine into proteins in isolated parenchymal rat liver cells

    DEFF Research Database (Denmark)

    Dich, J; Gluud, C N

    1976-01-01

    wet wt. This is about the rate found in the perfused liver, Glucagon (10(-8-10(-6) M) inhibited albumin secretion and the incorporation of 14C-leucine into albumin, into total proteins in the medium and into total proteins in the cell suspension. The effect of glucagon on albumin secretion...... is compatible with an effect on the rate of synthesis. A positive correlation existed between the maximal level of cyclic AMP after glucagon administration and the inhibition of both albumin secretion and the incorporation of 149leucine....

  6. The CD3 gamma leucine-based receptor-sorting motif is required for efficient ligand-mediated TCR down-regulation

    DEFF Research Database (Denmark)

    von Essen, Marina; Menné, Charlotte; Nielsen, Bodil L

    2002-01-01

    . The other pathway is dependent on protein kinase C (PKC)-mediated activation of the CD3 gamma di-leucine-based receptor-sorting motif. Previous studies have failed to demonstrate a connection between ligand- and PKC-induced TCR down-regulation. Thus, although an apparent paradox, the dogma has been...... that ligand- and PKC-induced TCR down-regulations are not interrelated. By analyses of a newly developed CD3 gamma-negative T cell variant, freshly isolated and PHA-activated PBMC, and a mouse T cell line, we challenged this dogma and demonstrate in this work that PKC activation and the CD3 gamma di-leucine...

  7. Masking of the CD3 gamma di-leucine-based motif by zeta is required for efficient T-cell receptor expression

    DEFF Research Database (Denmark)

    Lauritsen, Jens Peter H; Bonefeld, Charlotte Menné; von Essen, Marina

    2004-01-01

    containing the di-leucine-based endocytosis motif of the TCR subunit CD3 gamma have indicated that the zeta chain can mask this motif. In this study, we show that successive truncations of the cytoplasmic tail of zeta led to reduced surface expression levels of completely assembled TCR complexes. The reduced...... TCR expression levels were caused by an increase in the TCR endocytic rate constant in combination with an unaffected exocytic rate constant. Furthermore, the TCR degradation rate constant was increased in cells with truncated zeta. Introduction of a CD3 gamma chain with a disrupted di-leucine...

  8. Effect of ascorbate, nitrate and nitrite on the amount of flavour compounds produced from leucine by Staphylococcus xylosus and Staphylococcus carnosus

    DEFF Research Database (Denmark)

    Olesen, Pelle Thonning; Stahnke, Louise Heller; Talon, R.

    2004-01-01

    Resting cells of Staphylococcus xylosus and S. carnosus were incubated with ascorbate, nitrate and nitrite in defined reaction medium and their degradation of H-3-labelled leucine into methyl-branched catabolites were studied using HPLC/radiometric detection. The experiments were carried out...... with and without addition of alpha-ketoglutarate. The main catabolic product of leucine degradation was 3-methylbutanoic acid but also small amounts of alpha-hydroxy isocaproic acid were produced. Nitrite addition lowered the concentration of 3-methylbutanoic acid for both Staphylococcus species and this effect...

  9. CD3 gamma contains a phosphoserine-dependent di-leucine motif involved in down-regulation of the T cell receptor

    DEFF Research Database (Denmark)

    Dietrich, J; Hou, X; Wegener, A M

    1994-01-01

    -regulation of the TCR. Furthermore, analysis of a series of CD3 gamma truncation mutants indicated that in addition to S126 phosphorylation a motif C-terminal of S126 was required for TCR down-regulation. Point mutation analyses confirmed this observation and demonstrated that a membrane-proximal di-leucine motif (L131......, indicating that the TCR was down-regulated by endocytosis via clathrin coated pits. Based on the present results and previously published observations on intracellular receptor sorting, a general model for intracellular sorting of receptors containing di-leucine- or tyrosine-based motifs is proposed....

  10. Effect of insulin on albumin production and incorporation of 14C-leucine into proteins in isolated parenchymal liver cells from normal rats

    DEFF Research Database (Denmark)

    Dich, J; Gluud, C N

    1975-01-01

    Parenchymal rat liver cells were isolated by a modification of the collagenase method of Quistorff, Bondesen and Grunnet. The cells secreted albumin into the medium and incorporated 14C-leucine both into cell proteins and proteins secreted into the medium. Albumin production measured from...... the immunologically determined increment in the incubation medium was 1.7 +/- 0.2 mug albumin/min per g liver wet wt. This is about 30% of the rate of production in the perfused liver. Addition of insulin (10(-6)-10(-10) M) enhanced albumin production (50-17%), and incorporation of 14C-leucine both into albumin (50...

  11. Whey and casein labelled with L-[1-13C]-leucine and muscle protein synthesis: effect of resistance exercise and protein ingestion

    DEFF Research Database (Denmark)

    Reitelseder, Søren; Agergaard, Jakob; Doessing, Simon

    2011-01-01

    to a single bolus intake of whey or casein after performance of heavy resistance exercise. Young male individuals were randomly assigned to participate in two protein trials (n = 9) or one control trial (n = 8). Infusion of l-[1-(13)C]leucine was carried out, and either whey, casein (0.3 g/kg lean body mass......), or a noncaloric control drink was ingested immediately after exercise. l-[1-(13)C]leucine-labeled whey and casein were used while muscle protein synthesis (MPS) was assessed. Blood and muscle tissue samples were collected to measure systemic hormone and amino acid concentrations, tracer enrichments...

  12. Physician dual practice: A review of literature

    DEFF Research Database (Denmark)

    Socha, Karolina; Bech, Mickael

    2010-01-01

    of dual practice effects for the public health care. Methods A systematic literature review identified 23 positions on the subject consisting of journal articles, academic working papers, book chapter, and publications of the WHO. Results The subject is short on evidence. Theoretical analyses indicate...... of the public one mainly to increase income, it remains uncertain whether dual practice is an income-maximising combination of jobs. Moreover, costs of enforcing restrictions on dual practice are rarely considered. Conclusions Further research is needed that compares dual practitioners and other physicians...... in uniform settings, investigates how the dual practitioners divide labour between the two jobs, and analyses the costs of enforcing restrictions on dual practice....

  13. Dual recycling for GEO 600

    International Nuclear Information System (INIS)

    Grote, H; Freise, A; Malec, M; Heinzel, G; Willke, B; Lueck, H; Strain, K A; Hough, J; Danzmann, K

    2004-01-01

    Dual recycling is the combination of signal recycling and power recycling; both optical techniques improve the shot-noise-limited sensitivity of interferometric gravitational-wave detectors. In addition, signal recycling can reduce the loss of light power due to imperfect interference and allows us, in principle, to beat the standard quantum limit. The interferometric gravitational-wave detector GEO 600 is the first of the kilometre-scale detectors to use signal recycling. We have recently equipped the detector with a signal-recycling mirror with a transmittance of 1%. In this paper, we present details of the detector commissioning and the first locks of the dual-recycled interferometer

  14. Pairs of dual periodic frames

    DEFF Research Database (Denmark)

    Christensen, Ole; Goh, Say Song

    2012-01-01

    The time–frequency analysis of a signal is often performed via a series expansion arising from well-localized building blocks. Typically, the building blocks are based on frames having either Gabor or wavelet structure. In order to calculate the coefficients in the series expansion, a dual frame...... is needed. The purpose of the present paper is to provide constructions of dual pairs of frames in the setting of the Hilbert space of periodic functions L2(0,2π). The frames constructed are given explicitly as trigonometric polynomials, which allows for an efficient calculation of the coefficients...

  15. UWB dual burst transmit driver

    Science.gov (United States)

    Dallum, Gregory E [Livermore, CA; Pratt, Garth C [Discovery Bay, CA; Haugen, Peter C [Livermore, CA; Zumstein, James M [Livermore, CA; Vigars, Mark L [Livermore, CA; Romero, Carlos E [Livermore, CA

    2012-04-17

    A dual burst transmitter for ultra-wideband (UWB) communication systems generates a pair of precisely spaced RF bursts from a single trigger event. An input trigger pulse produces two oscillator trigger pulses, an initial pulse and a delayed pulse, in a dual trigger generator. The two oscillator trigger pulses drive a gated RF burst (power output) oscillator. A bias driver circuit gates the RF output oscillator on and off and sets the RF burst packet width. The bias driver also level shifts the drive signal to the level that is required for the RF output device.

  16. Dual recycling for GEO 600

    CERN Document Server

    Heinzel, G; Grote, H; Strain, K; Danzmann, K

    2002-01-01

    Dual recycling is the combination of power recycling and signal recycling. GEO 600, a German-British interferometric gravitational wave detector being built in Germany, has no arm cavities and needs to use dual recycling from the beginning, while the other interferometric detectors may use it at a later stage to enhance their sensitivity. The control scheme to be used in GEO 600 has been demonstrated at the Garching 30 m prototype. This paper summarizes those results and the adaptions necessary in order to apply the scheme for GEO 600.

  17. CARDIOVASCULAR ENDOCRINOLOGY Dual RAAS blockade has dual effects on outcome

    NARCIS (Netherlands)

    Heerspink, Hiddo J. Lambers; de Zeeuw, Dick

    Makani and colleagues report that dual blockade of the renin-angiotensin-aldosterone system is associated with harm despite previous studies showing that this approach decreases blood pressure and albuminuria. Do these results imply that we should abandon surrogate markers? Or should we become more

  18. Dual Diagnosis: Substance Abuse and Mental Illness

    Science.gov (United States)

    ... an effective dual diagnosis treatment plan. In particular, cognitive behavioral therapy ( CBT ) helps people with dual diagnosis learn how ... groups for people recovering from alcohol or drug addiction. Be sure to find a group that understands ...

  19. A dual method for maximum entropy restoration

    Science.gov (United States)

    Smith, C. B.

    1979-01-01

    A simple iterative dual algorithm for maximum entropy image restoration is presented. The dual algorithm involves fewer parameters than conventional minimization in the image space. Minicomputer test results for Fourier synthesis with inadequate phantom data are given.

  20. Dual-Doppler Feasibility Study

    Science.gov (United States)

    Huddleston, Lisa L.

    2012-01-01

    When two or more Doppler weather radar systems are monitoring the same region, the Doppler velocities can be combined to form a three-dimensional (3-D) wind vector field thus providing for a more intuitive analysis of the wind field. A real-time display of the 3-D winds can assist forecasters in predicting the onset of convection and severe weather. The data can also be used to initialize local numerical weather prediction models. Two operational Doppler Radar systems are in the vicinity of Kennedy Space Center (KSC) and Cape Canaveral Air Force Station (CCAFS); these systems are operated by the 45th Space Wing (45 SW) and the National Weather Service Melbourne, Fla. (NWS MLB). Dual-Doppler applications were considered by the 45 SW in choosing the site for the new radar. Accordingly, the 45th Weather Squadron (45 WS), NWS MLB and the National Aeronautics and Space Administration tasked the Applied Meteorology Unit (AMU) to investigate the feasibility of establishing dual-Doppler capability using the two existing systems. This study investigated technical, hardware, and software requirements necessary to enable the establishment of a dual-Doppler capability. Review of the available literature pertaining to the dual-Doppler technique and consultation with experts revealed that the physical locations and resulting beam crossing angles of the 45 SW and NWS MLB radars make them ideally suited for a dual-Doppler capability. The dual-Doppler equations were derived to facilitate complete understanding of dual-Doppler synthesis; to determine the technical information requirements; and to determine the components of wind velocity from the equation of continuity and radial velocity data collected by the two Doppler radars. Analysis confirmed the suitability of the existing systems to provide the desired capability. In addition, it is possible that both 45 SW radar data and Terminal Doppler Weather Radar data from Orlando International Airport could be used to alleviate any

  1. Dual Headquarters Involvement in Multibusiness Firms

    DEFF Research Database (Denmark)

    Nell, Phillip Christopher; Kappen, Philip; Dellestrand, Henrik

    development projects of subsidiaries. Analyses of 85 innovation development projects reveal that dual innovation importance (innovation that is important for the division and the rest of the firm), and dual dual embeddedness (innovating subsidiary is embedded both within the division and in the rest...... of the firm) lead to greater dual headquarters involvement, especially when the innovation development network is large. The results contribute to the literature on complex parenting and theory of selective headquarters involvement....

  2. Dual Enrollment in Spanish: One Working Model

    Science.gov (United States)

    Bloom, Melanie; Chambers, Laura

    2009-01-01

    Dual enrollment is now a nation-wide phenomenon as all 50 states currently offer some form of dual-enrollment program to secondary-school students (Karp, Bailey, Hughes, and Fermin 2005). However, dual enrollment itself is often difficult to define as programs vary from school to school (Jordan, Cavalluzzo, and Corallo 2006). Therefore, language…

  3. 7 CFR 247.19 - Dual participation.

    Science.gov (United States)

    2010-01-01

    ... CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.19 Dual participation. (a) What must State and local agencies do to prevent and detect dual participation? The State agency must work with... 7 Agriculture 4 2010-01-01 2010-01-01 false Dual participation. 247.19 Section 247.19 Agriculture...

  4. Sparsity and spectral properties of dual frames

    DEFF Research Database (Denmark)

    Krahmer, Felix; Kutyniok, Gitta; Lemvig, Jakob

    2013-01-01

    We study sparsity and spectral properties of dual frames of a given finite frame. We show that any finite frame has a dual with no more than $n^2$ non-vanishing entries, where $n$ denotes the ambient dimension, and that for most frames no sparser dual is possible. Moreover, we derive an expressio...

  5. Dual Enrollment for High School Students

    Science.gov (United States)

    Edwards, Linsey; Hughes, Katherine

    2011-01-01

    Dual enrollment programs allow high school students to enroll in college courses and potentially earn college credit. The term concurrent enrollment is sometimes used interchangeably with dual enrollment, and sometimes to refer to a particular model of dual enrollment. In some programs, students earn high school and college credit simultaneously;…

  6. Dual temperature isotope exchange system

    International Nuclear Information System (INIS)

    Spevack, J.S.

    1976-01-01

    Improvements in the method for isotope concentration by dual temperature exchange between feed and auxiliary fluids in a multistage system are described. In a preferred embodiment the first is a vaporizable liquid and the auxiliary fluid a gas, comprising steps for improving the heating and/or cooling and/or humidifying and/or dehumidifying operations

  7. Dual Processing and Diagnostic Errors

    Science.gov (United States)

    Norman, Geoff

    2009-01-01

    In this paper, I review evidence from two theories in psychology relevant to diagnosis and diagnostic errors. "Dual Process" theories of thinking, frequently mentioned with respect to diagnostic error, propose that categorization decisions can be made with either a fast, unconscious, contextual process called System 1 or a slow, analytical,…

  8. Dual fields and E11

    International Nuclear Information System (INIS)

    Riccioni, Fabio; West, Peter

    2007-01-01

    We show that the adjoint representation of E 11 contains generators corresponding to the infinite possible dual descriptions of the bosonic on-shell degrees of freedom of eleven-dimensional supergravity. We also give an interpretation for the fields corresponding to many of the other generators in the adjoint representation

  9. Effects of insulin-like growth factor-I, insulin, and leucine on protein turnover and pathways that regulate ubiquitin ligase expression in rainbow trout primary myocytes

    Science.gov (United States)

    The effects of insulin-like growth factor-I (IGF-I), insulin, and leucine on protein turnover and pathways that regulate proteolytic gene expression and protein polyubiquitination were investigated in primary cultures of four day old rainbow trout myocytes. Supplementing media with 100 nM IGF-I inc...

  10. Differential regulation of leucine-rich primary response gene 1 (LRPR1) mRNA expression in rat testis and ovary

    NARCIS (Netherlands)

    K.E. Slegtenhorst-Eegdeman; M. Verhoef-Post (Miriam); M. Parvinen; J.A. Grootegoed (Anton); A.P.N. Themmen (Axel)

    1998-01-01

    textabstractIn immature rat Sertoli cells, leucine-rich primary response gene 1 (LRPR1) represents a follicle stimulating hormone (FSH)-responsive gene; the function of the encoded protein is not yet known. LRPR1 mRNA expression is up-regulated very rapidly and

  11. Molecular recognition of carboxylates in the protein leucine zipper by a multivalent supramolecular ligand: residue-specific, sensitive and label-free probing by UV resonance Raman spectroscopy.

    Science.gov (United States)

    Zakeri, B; Niebling, S; Martinéz, A G; Sokkar, P; Sanchez-Garcia, E; Schmuck, C; Schlücker, S

    2018-01-17

    Ultraviolet resonance Raman (UVRR) spectroscopy is a selective, sensitive and label-free vibrational spectroscopic technique. Here, we demonstrate as proof of concept that UVRR can be used for probing the recognition between a multivalent supramolecular ligand and acidic residues in leucine zipper, an α-helical structural motif of many proteins.

  12. The Tomato Nucleotide-binding Leucine-rich Repeat (NLR) Immune Receptor I-2 Couples DNA-Binding to Nucleotide-Binding Domain Nucleotide Exchange

    NARCIS (Netherlands)

    Fenyk, S.; Dixon, C.H.; Gittens, W.H.; Townsend, P.D.; Sharples, G.J.; Pålsson, L.O.; Takken, F.L.W.; Cann, M.J.

    2016-01-01

    Plant nucleotide-binding leucine-rich repeat (NLR) proteins enable plants to recognise and respond to pathogen attack. Previously, we demonstrated that the Rx1 NLR of potato is able to bind and bend DNA in vitro. DNA binding in situ requires its genuine activation following pathogen perception.

  13. Effect of inhibitory avoidance trainning, ACTH, beta-endorphin and adrenaline on the incorporation of 14C-leucine into synaptosomal proteins of rat hypothalamus, amygdala and hippocampus

    International Nuclear Information System (INIS)

    Dalmaz, C.; Maia, H.M.M.; Izquierdo, I.

    1986-01-01

    'In vitro' incorporation of leucine to protein was studied in synaptosomes isolated from the hypothalamus, amygdala and hippocampus of rats submitted to inhibitory avoidance training or to the i.p. injection of ACTH, beta-endorphin or adrenaline; or in synaptosomes incubated with these substances. (M.A.C.) [pt

  14. The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta-analysis.

    Science.gov (United States)

    Xu, Zhe-rong; Tan, Zhong-ju; Zhang, Qin; Gui, Qi-feng; Yang, Yun-mei

    2015-01-14

    In the present study, we performed a meta-analysis to assess the ability of leucine supplementation to increase the muscle protein fraction synthetic rate and to augment lean body mass or leg lean mass in elderly patients. A literature search was conducted on Medline, Cochrane, EMBASE and Google Scholar databases up to 31 December 2013 for clinical trials that investigated the administration of leucine as a nutrient that affects muscle protein metabolism and muscle mass in elderly subjects. The included studies were randomised controlled trials. The primary outcome for the meta-analysis was the protein fractional synthetic rate. Secondary outcomes included lean body mass and leg lean mass. A total of nine studies were included in the meta-analysis. The results showed that the muscle protein fractional synthetic rate after intervention significantly increased in the leucine group compared with the control group (pooled standardised difference in mean changes 1·08, 95% CI 0·50, 1·67; Pmass (pooled standardised difference in mean changes 0·18, 95% CI - 0·18, 0·54; P= 0·318) or leg lean mass (pooled standardised difference in mean changes 0·006, 95% CI - 0·32, 0·44; P= 0·756). These findings suggest that leucine supplementation is useful to address the age-related decline in muscle mass in elderly individuals, as it increases the muscle protein fractional synthetic rate.

  15. Effect of ascorbate, nitrate and nitrite on the amount of flavour compounds produced from leucine by Staphylococcus xylosus and Staphylococcus carnosus

    DEFF Research Database (Denmark)

    Olesen, Pelle Thonning; Stahnke, Louise Heller; Talon, R.

    2004-01-01

    Resting cells of Staphylococcus xylosus and S. carnosus were incubated with ascorbate, nitrate and nitrite in defined reaction medium and their degradation of H-3-labelled leucine into methyl-branched catabolites were studied using HPLC/radiometric detection. The experiments were carried out with...

  16. Co-ingestion of a protein hydrolysate with or without additional leucine effectively reduces postprandial blood glucose excursions in type 2 diabetic men

    NARCIS (Netherlands)

    Manders, R.J.; Koopman, R.; Sluijsmans, W.E.; Berg, R. van den; Verbeek, K.; Saris, W.H.; Wagenmakers, A.J.; Loon, L.J. van

    2006-01-01

    This study examined postprandial plasma insulin and glucose responses after co-ingestion of an insulinotropic protein (Pro) hydrolysate with and without additional free leucine with a single bolus of carbohydrate (Cho). Male patients with long-standing Type 2 diabetes (n = 10) and healthy controls

  17. Effect of infection by Phytophthora infestans and treatment with its zoosporial components on uptake of 3H-leucine and protein synthesis potato tuber tissue

    International Nuclear Information System (INIS)

    Nishimura, Norio; Tomiyama, Kohei; Doke, Noriyuki

    1978-01-01

    Both sides of aged disks of potato tubers were inoculated with incompatible race 0 or compatible race 1 of P. infestans. The uptake of radioactivity from 3 H-leucine into the disks was greatly reduced by the infection with the incompatible race, but the ratio of incorporated radioactivity in the acid soluble fraction of the disks to total radioactivity in the 20,000 x g supernatant was increased by the infection with the incompatible race 0. In case of the compatible race 1, the infection had less effect on the incorporation ratio of the radioactivity into the acid insoluble fraction than the case of the race 0. The results suggested that the reduction in 3 H-leucine uptake may be due to alteration of the physiological activity of host plasma membrane, instead of the reduction of metabolic activity. The treatment of tuber disks with the insoluble fraction of the zoosporial homogenate of race 0 or race 1 greatly reduced the uptake of 3 H-leucine by the disks. The supernatant fraction of the zoosporial homogenate also reduced the uptake, but the effect was lost by dialysis. The results suggest that some substances in the insoluble components of the zoosporial homogenate of P. infestans may be at least one cause of the reduction in the uptake of 3 H-leucine which begins to occur at very early period of the inoculation with race 0 or race 1 while penetration has not yet occurred. (Kobatake, H.)

  18. Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

    NARCIS (Netherlands)

    Beilina, Alexandria; Rudenko, Iakov N.; Kaganovich, Alice; Civiero, Laura; Chau, Hien; Kalia, Suneil K.; Kalia, Lorraine V.; Lobbestael, Evy; Chia, Ruth; Ndukwe, Kelechi; Ding, Jinhui; Nalls, Mike A.; Olszewski, Maciej; Hauser, David N.; Kumaran, Ravindran; Lozano, Andres M.; Baekelandt, Veerle; Greene, Lois E.; Taymans, Jean-Marc; Greggio, Elisa; Cookson, Mark R.; Plagnol, Vincent; Martinez, Maria; Hernandez, Dena G.; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simón-Sánchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Arepalli, Sampath; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M. A.; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chong, Sean; Clarke, Carl E.; Cooper, J. Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Gibbs, J. Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gústafsson, Omar; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; München, Helmholtz Zentrum; Jónsson, Pálmi V.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R.; Morrison, Karen E.; Mudanohwo, Ese; O'Sullivan, Sean S.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; Smith, Colin; Spencer, Chris C. A.; Stefánsson, Hreinn; Steinberg, Stacy; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Stefánsson, Kári; Hardy, John; Heutink, Peter; Brice, Alexis; Gasser, Thomas; Singleton, Andrew B.; Wood, Nicholas W.; Chinnery, Patrick F.; Ferrucci, Luigi; Johnson, Robert; Longo, Dan L.; Majounie, Elisa; Nalls, Michael A.; O'Brien, Richard; Troncoso, Juan; van der Brug, Marcel; Zielke, H. Ronald; Zonderman, Alan B.

    2014-01-01

    Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein-protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and

  19. Effect of L-Tryptophan and L-Leucine on Gut Hormone Secretion, Appetite Feelings and Gastric Emptying Rates in Lean and Non-Diabetic Obese Participants

    DEFF Research Database (Denmark)

    Meyer-Gerspach, Anne Christin; Häfliger, Simon; Meili, Julian

    2016-01-01

    in relation to peptide release. In contrast, the role of proteins or amino acids is less clear. Our aim was to compare the effects of the amino acids L-tryptophan (L-trp) and L-leucine (L-leu) separately on gastric emptying and gut peptide secretion. PARTICIPANTS/METHODS: The study was conducted...

  20. Evaluation of the leucine incorporation technique for detection of pollution-induced community tolerance to copper in a long-term agricultural field trial with urban waste fertilizers

    DEFF Research Database (Denmark)

    Lekfeldt, Jonas Duus Stevens; Magid, Jakob; Holm, Peter Engelund

    2014-01-01

    Copper (Cu) is known to accumulate in agricultural soils receiving urban waste products as fertilizers. We here report the use of the leucine incorporation technique to determine pollution-induced community tolerance (Leu-PICT) to Cu in a long-term agricultural field trial. A significantly...

  1. Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study

    DEFF Research Database (Denmark)

    Celicanin, M; Blaabjerg, Morten; Maersk-Moller, C

    2017-01-01

    BACKGROUND AND PURPOSE: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2...

  2. TCR comodulation of nonengaged TCR takes place by a protein kinase C and CD3 gamma di-leucine-based motif-dependent mechanism

    DEFF Research Database (Denmark)

    Bonefeld, Charlotte Menné; Rasmussen, B. A.; Lauritsen, J P

    2003-01-01

    of comodulation. Like internalization of engaged TCR, comodulation was dependent on protein tyrosine kinase activity. Finally, we found that in contrast to internalization of engaged TCR, comodulation was highly dependent on protein kinase C activity and the CD3 gamma di-leucine-based motif. Based...

  3. The Leucine transporter from Aquifex aeolicus as a model for the Neurotransmitter Sodium Symporters – insights into function and ligand binding

    DEFF Research Database (Denmark)

    Kantcheva, Adriana Krassimirova

    In her PhD studies, Adriana K. Kantcheva looked into the structural perspective of a bacterial transporter – the leucine transporter from Aquifex aeolicus (LeuT) – which is a homologue to neurotransmitter sodium symporters (NSS) found in humans, such as the serotonin transporter. Two crystal...

  4. Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression

    DEFF Research Database (Denmark)

    Koefoed, Pernille; Woldbye, David P. D.; Hansen, Thomas v. O.

    2012-01-01

    disease controls with schizophrenia. Possible functional consequences of Leu7Pro were explored in vitro. Results: In contrast to previous studies, Pro7 appeared to be a risk allele for depression, being significantly more frequent in the depression sample (5.5 n = 593; p = 0.009; odds ratio, OR: 1......Objective: There is clear evidence of a genetic component in major depression, and several studies indicate that neuropeptide Y (NPY) could play an important role in the pathophysiology of the disease. A well-known polymorphism encoding the substitution of leucine to proline in the signal peptide...... sequence of NPY (Leu7Pro variation) was previously found to protect against depression. Our study aimed at replicating this association in a large Danish population with major depression. Method: Leu7Pro was studied in a sample of depressed patients and ethnically matched controls, as well as psychiatric...

  5. The affection of APA microcapsulation on catecholamine and leucine-enkephalin secretion from the bovine adrenal medullary chromaffin cells

    International Nuclear Information System (INIS)

    Guo Shuilong; Cui Xin; Luo Yun; Xue Yilong

    2002-01-01

    The affection of alginate-polylysine-alginate (APA) microcapsulation on catecholamine (CA) and leucine-enkephalin (L-EK) secretion from bovine adrenal medullary chromaffin cells was analysed. Encapsulating BCCs with the APA microcapsulation, the secretion of CA and L-EK in encapsulated BCCs was detected by high-performance liquid chromatography-electrochemical assay and radioimmunoassay, respectively. There is little difference between the encapsulated BCCs and the non-encapsulated BCCs in the secretion of epinephrine (E) and noradrenaline (NE) but the secretion of dopamine (DA) and L-EK in several points decline. The studies indicated that APA microcapsulation of BCCs didn't affect the secretion of E and NE, but did the secretion DA and L-EK in forepart

  6. Maternal embryonic leucine zipper kinase is stabilized in mitosis by phosphorylation and is partially degraded upon mitotic exit

    International Nuclear Information System (INIS)

    Badouel, Caroline; Chartrain, Isabelle; Blot, Joelle; Tassan, Jean-Pierre

    2010-01-01

    MELK (maternal embryonic leucine zipper kinase) is a cell cycle dependent protein kinase involved in diverse cell processes including cell proliferation, apoptosis, cell cycle and mRNA processing. Noticeably, MELK expression is increased in cancerous tissues, upon cell transformation and in mitotically-blocked cells. The question of how MELK protein level is controlled is therefore important. Here, we show that MELK protein is restricted to proliferating cells derived from either cancer or normal tissues and that MELK protein level is severely decreased concomitantly with other cell cycle proteins in cells which exit the cell cycle. Moreover, we demonstrate in human HeLa cells and Xenopus embryos that approximately half of MELK protein is degraded upon mitotic exit whereas another half remains stable during interphase. We show that the stability of MELK protein in M-phase is dependent on its phosphorylation state.

  7. Maternal embryonic leucine zipper kinase is stabilized in mitosis by phosphorylation and is partially degraded upon mitotic exit

    Energy Technology Data Exchange (ETDEWEB)

    Badouel, Caroline; Chartrain, Isabelle; Blot, Joelle [CNRS UMR 6061 Genetique et Developpement, Universite de Rennes 1, IFR140 GFAS, Faculte de medecine, 2 avenue du Professeur Leon Bernard, CS 34317, 35043 Rennes Cedex (France); Tassan, Jean-Pierre, E-mail: jean-pierre.tassan@univ-rennes1.fr [CNRS UMR 6061 Genetique et Developpement, Universite de Rennes 1, IFR140 GFAS, Faculte de medecine, 2 avenue du Professeur Leon Bernard, CS 34317, 35043 Rennes Cedex (France)

    2010-08-01

    MELK (maternal embryonic leucine zipper kinase) is a cell cycle dependent protein kinase involved in diverse cell processes including cell proliferation, apoptosis, cell cycle and mRNA processing. Noticeably, MELK expression is increased in cancerous tissues, upon cell transformation and in mitotically-blocked cells. The question of how MELK protein level is controlled is therefore important. Here, we show that MELK protein is restricted to proliferating cells derived from either cancer or normal tissues and that MELK protein level is severely decreased concomitantly with other cell cycle proteins in cells which exit the cell cycle. Moreover, we demonstrate in human HeLa cells and Xenopus embryos that approximately half of MELK protein is degraded upon mitotic exit whereas another half remains stable during interphase. We show that the stability of MELK protein in M-phase is dependent on its phosphorylation state.

  8. VUV action spectroscopy of protonated leucine-enkephalin peptide in the 6-14 eV range

    Energy Technology Data Exchange (ETDEWEB)

    Ranković, M. Lj. [Institute of Physics Belgrade, University of Belgrade, Pregrevica 118, 11080 Belgrade (Serbia); Canon, F. [INRA, UMR1324 Centre des Sciences du Goût et de l’Alimentation, F-21000 Dijon (France); Nahon, L. [SOLEIL, l’Orme des Merisiers, St Aubin, BP48, 91192 Gif sur Yvette Cedex (France); Giuliani, A. [SOLEIL, l’Orme des Merisiers, St Aubin, BP48, 91192 Gif sur Yvette Cedex (France); INRA, UAR1008, CEPIA, Rue de la Géraudière, BP 71627, 44316 Nantes (France); Milosavljević, A. R., E-mail: vraz@ipb.ac.rs [Institute of Physics Belgrade, University of Belgrade, Pregrevica 118, 11080 Belgrade (Serbia); Radiation Laboratory, University of Notre Dame, Notre Dame, Indiana 46556 (United States)

    2015-12-28

    We have studied the Vacuum Ultraviolet (VUV) photodissociation of gas-phase protonated leucine-enkephalin peptide ion in the 5.7 to 14 eV photon energy range by coupling a linear quadrupole ion trap with a synchrotron radiation source. We report VUV activation tandem mass spectra at 6.7, 8.4, and 12.8 eV photon energies and photodissociation yields for a number of selected fragments. The obtained results provide insight into both near VUV radiation damage and electronic properties of a model peptide. We could distinguish several absorption bands and assign them to particular electronic transitions, according to previous theoretical studies. The photodissociation yields appear to be very different for the various observed fragmentation channels, depending on both the types of fragments and their position along the peptide backbone. The present results are discussed in light of recent gas-phase spectroscopic data on peptides.

  9. A Petunia Homeodomain-Leucine Zipper Protein, PhHD-Zip, Plays an Important Role in Flower Senescence

    Science.gov (United States)

    Chang, Xiaoxiao; Donnelly, Linda; Sun, Daoyang; Rao, Jingping; Reid, Michael S.; Jiang, Cai-Zhong

    2014-01-01

    Flower senescence is initiated by developmental and environmental signals, and regulated by gene transcription. A homeodomain-leucine zipper transcription factor, PhHD-Zip, is up-regulated during petunia flower senescence. Virus-induced gene silencing of PhHD-Zip extended flower life by 20% both in unpollinated and pollinated flowers. Silencing PhHD-Zip also dramatically reduced ethylene production and the abundance of transcripts of genes involved in ethylene (ACS, ACO), and ABA (NCED) biosynthesis. Abundance of transcripts of senescence-related genes (SAG12, SAG29) was also dramatically reduced in the silenced flowers. Over-expression of PhHD-Zip accelerated petunia flower senescence. Furthermore, PhHD-Zip transcript abundance in petunia flowers was increased by application of hormones (ethylene, ABA) and abiotic stresses (dehydration, NaCl and cold). Our results suggest that PhHD-Zip plays an important role in regulating petunia flower senescence. PMID:24551088

  10. Maternal Embryonic Leucine Zipper Kinase (MELK: A Novel Regulator in Cell Cycle Control, Embryonic Development, and Cancer

    Directory of Open Access Journals (Sweden)

    Pengfei Jiang

    2013-10-01

    Full Text Available Maternal embryonic leucine zipper kinase (MELK functions as a modulator of intracellular signaling and affects various cellular and biological processes, including cell cycle, cell proliferation, apoptosis, spliceosome assembly, gene expression, embryonic development, hematopoiesis, and oncogenesis. In these cellular processes, MELK functions by binding to numerous proteins. In general, the effects of multiple protein interactions with MELK are oncogenic in nature, and the overexpression of MELK in kinds of cancer provides some evidence that it may be involved in tumorigenic process. In this review, our current knowledge of MELK function and recent discoveries in MELK signaling pathway were discussed. The regulation of MELK in cancers and its potential as a therapeutic target were also described.

  11. A Petunia homeodomain-leucine zipper protein, PhHD-Zip, plays an important role in flower senescence.

    Science.gov (United States)

    Chang, Xiaoxiao; Donnelly, Linda; Sun, Daoyang; Rao, Jingping; Reid, Michael S; Jiang, Cai-Zhong

    2014-01-01

    Flower senescence is initiated by developmental and environmental signals, and regulated by gene transcription. A homeodomain-leucine zipper transcription factor, PhHD-Zip, is up-regulated during petunia flower senescence. Virus-induced gene silencing of PhHD-Zip extended flower life by 20% both in unpollinated and pollinated flowers. Silencing PhHD-Zip also dramatically reduced ethylene production and the abundance of transcripts of genes involved in ethylene (ACS, ACO), and ABA (NCED) biosynthesis. Abundance of transcripts of senescence-related genes (SAG12, SAG29) was also dramatically reduced in the silenced flowers. Over-expression of PhHD-Zip accelerated petunia flower senescence. Furthermore, PhHD-Zip transcript abundance in petunia flowers was increased by application of hormones (ethylene, ABA) and abiotic stresses (dehydration, NaCl and cold). Our results suggest that PhHD-Zip plays an important role in regulating petunia flower senescence.

  12. A Petunia homeodomain-leucine zipper protein, PhHD-Zip, plays an important role in flower senescence.

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Chang

    Full Text Available Flower senescence is initiated by developmental and environmental signals, and regulated by gene transcription. A homeodomain-leucine zipper transcription factor, PhHD-Zip, is up-regulated during petunia flower senescence. Virus-induced gene silencing of PhHD-Zip extended flower life by 20% both in unpollinated and pollinated flowers. Silencing PhHD-Zip also dramatically reduced ethylene production and the abundance of transcripts of genes involved in ethylene (ACS, ACO, and ABA (NCED biosynthesis. Abundance of transcripts of senescence-related genes (SAG12, SAG29 was also dramatically reduced in the silenced flowers. Over-expression of PhHD-Zip accelerated petunia flower senescence. Furthermore, PhHD-Zip transcript abundance in petunia flowers was increased by application of hormones (ethylene, ABA and abiotic stresses (dehydration, NaCl and cold. Our results suggest that PhHD-Zip plays an important role in regulating petunia flower senescence.

  13. Incorporation of [14C]-L-leucine in splenic and hepatic tissue of rats 'chemically splenectomized' by ethyl palmitate

    International Nuclear Information System (INIS)

    Sebestik, V.; Kselikova, M.; Freiova, M.; Potmesilova, I.

    1978-01-01

    In experiments with 'chemically splenectomized' rats by an i.v. application of ethyl palmitate (EP) emulsion and using [ 14 C]-L-leucine, the protein synthesis in spleen and liver was followed. Two hours following EP application protein synthesis in the spleen was significantly decreased; after 24 hrs and 4 days the incorporation increased moderately above normal values, and in the subsequent intervals protein synthesis was again lowered. In the liver a significant increase of protein synthesis 24 hrs and 4 days after EP injection was observed. Changes of proteins synthesis in the spleen are evidently related to damage of the tissue and its subsequent regeneration. Changes in the liver are manifestations rather of an increased metabolic load during EP degradation. (author)

  14. Posterior amorphous corneal dystrophy is associated with a deletion of small leucine-rich proteoglycans on chromosome 12.

    Directory of Open Access Journals (Sweden)

    Michelle J Kim

    Full Text Available Posterior amorphous corneal dystrophy (PACD is a rare, autosomal dominant disorder affecting the cornea and iris. Next-generation sequencing of the previously identified PACD linkage interval on chromosome 12q21.33 failed to yield a pathogenic mutation. However, array-based copy number analysis and qPCR were used to detect a hemizygous deletion in the PACD linkage interval containing 4 genes encoding small leucine-rich proteoglycans (SLRPs: KERA, LUM, DCN, and EPYC. Two other unrelated families with PACD also demonstrated deletion of these SLRPs, which play important roles in collagen fibrillogenesis and matrix assembly. Given that these genes are essential to the maintenance of corneal clarity and the observation that knockout murine models display corneal phenotypic similarities to PACD, we provide convincing evidence that PACD is associated with haploinsufficiency of these SLRPs.

  15. Leucine-rich repeat kinase-1 regulates osteoclast function by modulating RAC1/Cdc42 Small GTPase phosphorylation and activation.

    Science.gov (United States)

    Zeng, Canjun; Goodluck, Helen; Qin, Xuezhong; Liu, Bo; Mohan, Subburaman; Xing, Weirong

    2016-10-01

    Leucine-rich repeat kinase-1 (Lrrk1) consists of ankyrin repeats (ANK), leucine-rich repeats (LRR), a GTPase-like domain of Roc (ROC), a COR domain, a serine/threonine kinase domain (KD), and WD40 repeats (WD40). Previous studies have revealed that knockout (KO) of Lrrk1 in mice causes severe osteopetrosis, and a human mutation of Lrrk1 leads to osteosclerotic metaphysial dysplasia. The molecular mechanism by which Lrrk1 regulates osteoclast function is unknown. In this study, we generated a series of Lrrk1 mutants and evaluated their ability to rescue defective bone resorption in Lrrk1-deficient osteoclasts by use of pit formation assays. Overexpression of Lrrk1 or LRR-truncated Lrrk1, but not ANK-truncated Lrrk1, WD40-truncated Lrrk1, Lrrk1-KD, or K651A mutant Lrrk1, rescued bone resorption function of Lrrk1 KO osteoclasts. We next examined whether RAC1/Cdc42 small GTPases are direct substrates of Lrrk1 in osteoclasts. Western blot and pull-down assays revealed that Lrrk1 deficiency in osteoclasts resulted in reduced phosphorylation and activation of RAC1/Cdc42. In vitro kinase assays confirmed that recombinant Lrrk1 phosphorylated RAC1-GST protein, and immunoprecipitation showed that the interaction of Lrrk1 with RAC1 occurred within 10 min after RANKL treatment. Overexpression of constitutively active Q61L RAC1 partially rescued the resorptive function of Lrrk1-deficient osteoclasts. Furthermore, lack of Lrrk1 in osteoclasts led to reduced autophosphorylation of p21 protein-activated kinase-1 at Ser 144 , catalyzed by RAC1/Cdc42 binding and activation. Our data indicate that Lrrk1 regulates osteoclast function by directly modulating phosphorylation and activation of small GTPase RAC1/Cdc42 and that its function depends on ANK, ROC, WD40, and kinase domains. Copyright © 2016 the American Physiological Society.

  16. Amyloid β (1-40) Toxicity Depends on the Molecular Contact between Phenylalanine 19 and Leucine 34.

    Science.gov (United States)

    Korn, Alexander; McLennan, Steffane; Adler, Juliane; Krueger, Martin; Surendran, Dayana; Maiti, Sudipta; Huster, Daniel

    2017-12-27

    The formation of the hydrophobic contact between phenylalanine 19 (F19) and leucine 34 (L34) of amyloid β (1-40) (Aβ(1-40)) is known to be an important step in the fibrillation of Aβ(1-40) peptides. Mutations of this putatively early molecular contact were shown to strongly influence the toxicity of Aβ(1-40) ( Das et al. ( 2015 ) ACS Chem. Neurosci. 6 , 1290 - 1295 ). Any mutation of residue F19 completely abolished the toxicity of Aβ(1-40), suggesting that a proper F19-L34 contact is crucial also for the formation of transient oligomers. In this work, we investigate a series of isomeric substitutions of L34, namely, d-leucine, isoleucine, and valine, to study further details of this molecular contact. These replacements represent very minor alterations in the Aβ(1-40) structure posing the question how these alterations challenge the fibrillation kinetics, structure, dynamics, and toxicity of the Aβ(1-40) aggregates. Our work involves kinetic studies using thioflavin T, transmission electron microscopy, X-ray diffraction for the analysis of the fibril morphology, and nuclear magnetic resonance experiments for local structure and molecular dynamics investigations. Combined with cell toxicity assays of the mutated Aβ(1-40) peptides, the physicochemical and biological importance of the early folding contact between F19 and L34 in Aβ(1-40) is underlined. This implies that the F19-L34 contact influences a broad range of different processes including the initiation of fibrillation, oligomer stability, fibril elongation, local fibril structure, and dynamics and cellular toxicity. These processes do not only cover a broad range of diverse mechanisms, but also proved to be highly sensitive to minor modulations of this crucial contact. Furthermore, our work shows that the contact is not simply mediated by general hydrophobic interactions, but also depends on stereospecific mechanisms.

  17. Tyrosine kinase, aurora kinase and leucine aminopeptidase as attractive drug targets in anticancer therapy - characterisation of their inhibitors.

    Science.gov (United States)

    Ziemska, Joanna; Solecka, Jolanta

    Cancers are the leading cause of deaths all over the world. Available anticancer agents used in clinics exhibit low therapeutic index and usually high toxicity. Wide spreading drug resistance of cancer cells induce a demanding need to search for new drug targets. Currently, many on-going studies on novel compounds with potent anticancer activity, high selectivity as well as new modes of action are conducted. In this work, we describe in details three enzyme groups, which are at present of extensive interest to medical researchers and pharmaceutical companies. These include receptor tyrosine kinases (e.g. EGFR enzymes) and non-receptor tyrosine kinases (Src enzymes), type A, B and C Aurora kinases and aminopeptidases, especially leucine aminopeptidase. We discuss classification of these enzymes, biochemistry as well as their role in the cell cycle under normal conditions and during cancerogenesis. Further on, the work describes enzyme inhibitors that are under in vitro, preclinical, clinical studies as well as drugs available on the market. Both, chemical structures of discovered inhibitors and the role of chemical moieties in novel drug design are discussed. Described enzymes play essential role in cell cycle, especially in mitosis (Aurora kinases), cell differentiation, growth and apoptosis (tyrosine kinases) as well as G1/S transition (leucine aminopeptidase). In cancer cells, they are overexpressed and only their inhibition may stop tumor progression. This review presents the clinical outcomes of selected inhibitors and argues the safety of drug usage in human volunteers. Clinical studies of EGFR and Src kinase inhibitors in different tumors clearly show the need for molecular selection of patients (to those with mutations in genes coding EGFR and Src) to achieve positive clinical response. Current data indicates the great necessity for new anticancer treatment and actions to limit off-target activity.

  18. New poly(ester urea) derived from L-leucine: Electrospun scaffolds loaded with antibacterial drugs and enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Díaz, Angélica; Valle, Luis J. del [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain); Tugushi, David; Katsarava, Ramaz [Institute of Chemistry and Molecular Engineering, Agricultural University of Georgia, 13 km. David Aghmashenebeli Alley, Tblisi 0131, Georgia (United States); Puiggalí, Jordi, E-mail: Jordi.Puiggali@upc.edu [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain)

    2015-01-01

    Electrospun scaffolds from an amino acid containing poly(ester urea) (PEU) were developed as promising materials in the biomedical field and specifically in tissue engineering applications. The selected poly(ester urea) was obtained with a high yield and molecular weight by reaction of phosgene with a bis(α-aminoacyl)-α,ω-diol-diester monomer. The polymer having L-leucine, 1,6-hexanediol and carbonic acid units had a semicrystalline character and relatively high glass transition and melting temperatures. Furthermore it was highly soluble in most organic solvents, an interesting feature that facilitated the electrospinning process and the effective incorporation of drugs with bactericidal activity (e.g. biguanide derivatives such as clorhexidine and polyhexamethylenebiguanide) and enzymes (e.g. α-chymotrypsin) that accelerated the degradation process. Continuous micro/nanofibers were obtained under a wide range of processing conditions, being diameters of electrospun fibers dependent on the drug and solvent used. Poly(ester urea) samples were degradable in media containing lipases and proteinases but the degradation rate was highly dependent on the surface area, being specifically greater for scaffolds with respect to films. The high hydrophobicity of new scaffolds had repercussions on enzymatic degradability since different weight loss rates were found depending on how samples were exposed to the medium (e.g. forced or non-forced immersion). New scaffolds were biocompatible, as demonstrated by adhesion and proliferation assays performed with fibroblast and epithelial cells. - Highlights: • Electrospun scaffolds from a biodegradable poly(ester urea) have been prepared. • Scaffolds were effectively loaded with bactericide agents. • Enzymatic degradability of the L-leucine derived poly(ester urea) was demonstrated. • Enzymes that accelerate degradation were incorporated in the electrospun fibers. • Cell adhesion/proliferation assays demonstrated

  19. The hypersensitive induced reaction and leucine-rich repeat proteins regulate plant cell death associated with disease and plant immunity.

    Science.gov (United States)

    Choi, Hyong Woo; Kim, Young Jin; Hwang, Byung Kook

    2011-01-01

    Pathogen-induced programmed cell death (PCD) is intimately linked with disease resistance and susceptibility. However, the molecular components regulating PCD, including hypersensitive and susceptible cell death, are largely unknown in plants. In this study, we show that pathogen-induced Capsicum annuum hypersensitive induced reaction 1 (CaHIR1) and leucine-rich repeat 1 (CaLRR1) function as distinct plant PCD regulators in pepper plants during Xanthomonas campestris pv. vesicatoria infection. Confocal microscopy and protein gel blot analyses revealed that CaLRR1 and CaHIR1 localize to the extracellular matrix and plasma membrane (PM), respectively. Bimolecular fluorescent complementation and coimmunoprecipitation assays showed that the extracellular CaLRR1 specifically binds to the PM-located CaHIR1 in pepper leaves. Overexpression of CaHIR1 triggered pathogen-independent cell death in pepper and Nicotiana benthamiana plants but not in yeast cells. Virus-induced gene silencing (VIGS) of CaLRR1 and CaHIR1 distinctly strengthened and compromised hypersensitive and susceptible cell death in pepper plants, respectively. Endogenous salicylic acid levels and pathogenesis-related gene transcripts were elevated in CaHIR1-silenced plants. VIGS of NbLRR1 and NbHIR1, the N. benthamiana orthologs of CaLRR1 and CaHIR1, regulated Bax- and avrPto-/Pto-induced PCD. Taken together, these results suggest that leucine-rich repeat and hypersensitive induced reaction proteins may act as cell-death regulators associated with plant immunity and disease.

  20. BACE1 protein endocytosis and trafficking are differentially regulated by ubiquitination at lysine 501 and the Di-leucine motif in the carboxyl terminus.

    Science.gov (United States)

    Kang, Eugene L; Biscaro, Barbara; Piazza, Fabrizio; Tesco, Giuseppina

    2012-12-14

    β-Site amyloid precursor protein-cleaving enzyme (BACE1) is a membrane-tethered member of the aspartyl proteases that has been identified as β-secretase. BACE1 is targeted through the secretory pathway to the plasma membrane and then is internalized to endosomes. Sorting of membrane proteins to the endosomes and lysosomes is regulated by the interaction of signals present in their carboxyl-terminal fragment with specific trafficking molecules. The BACE1 carboxyl-terminal fragment contains a di-leucine sorting signal ((495)DDISLL(500)) and a ubiquitination site at Lys-501. Here, we report that lack of ubiquitination at Lys-501 (BACE1K501R) does not affect the rate of endocytosis but produces BACE1 stabilization and accumulation of BACE1 in early and late endosomes/lysosomes as well as at the cell membrane. In contrast, the disruption of the di-leucine motif (BACE1LLAA) greatly impairs BACE1 endocytosis and produces a delayed retrograde transport of BACE1 to the trans-Golgi network (TGN) and a delayed delivery of BACE1 to the lysosomes, thus decreasing its degradation. Moreover, the combination of the lack of ubiquitination at Lys-501 and the disruption of the di-leucine motif (BACE1LLAA/KR) produces additive effects on BACE1 stabilization and defective internalization. Finally, BACE1LLAA/KR accumulates in the TGN, while its levels are decreased in EEA1-positive compartments indicating that both ubiquitination at Lys-501 and the di-leucine motif are necessary for the trafficking of BACE1 from the TGN to early endosomes. Our studies have elucidated a differential role for the di-leucine motif and ubiquitination at Lys-501 in BACE1 endocytosis, trafficking, and degradation and suggest the involvement of multiple adaptor molecules.

  1. BACE1 Protein Endocytosis and Trafficking Are Differentially Regulated by Ubiquitination at Lysine 501 and the Di-leucine Motif in the Carboxyl Terminus*

    Science.gov (United States)

    Kang, Eugene L.; Biscaro, Barbara; Piazza, Fabrizio; Tesco, Giuseppina

    2012-01-01

    β-Site amyloid precursor protein-cleaving enzyme (BACE1) is a membrane-tethered member of the aspartyl proteases that has been identified as β-secretase. BACE1 is targeted through the secretory pathway to the plasma membrane and then is internalized to endosomes. Sorting of membrane proteins to the endosomes and lysosomes is regulated by the interaction of signals present in their carboxyl-terminal fragment with specific trafficking molecules. The BACE1 carboxyl-terminal fragment contains a di-leucine sorting signal (495DDISLL500) and a ubiquitination site at Lys-501. Here, we report that lack of ubiquitination at Lys-501 (BACE1K501R) does not affect the rate of endocytosis but produces BACE1 stabilization and accumulation of BACE1 in early and late endosomes/lysosomes as well as at the cell membrane. In contrast, the disruption of the di-leucine motif (BACE1LLAA) greatly impairs BACE1 endocytosis and produces a delayed retrograde transport of BACE1 to the trans-Golgi network (TGN) and a delayed delivery of BACE1 to the lysosomes, thus decreasing its degradation. Moreover, the combination of the lack of ubiquitination at Lys-501 and the disruption of the di-leucine motif (BACE1LLAA/KR) produces additive effects on BACE1 stabilization and defective internalization. Finally, BACE1LLAA/KR accumulates in the TGN, while its levels are decreased in EEA1-positive compartments indicating that both ubiquitination at Lys-501 and the di-leucine motif are necessary for the trafficking of BACE1 from the TGN to early endosomes. Our studies have elucidated a differential role for the di-leucine motif and ubiquitination at Lys-501 in BACE1 endocytosis, trafficking, and degradation and suggest the involvement of multiple adaptor molecules. PMID:23109336

  2. Reduced muscular fatigue after a 12-week leucine-rich amino acid supplementation combined with moderate training in elderly: a randomised, placebo-controlled, double-blind trial.

    Science.gov (United States)

    Reule, Claudia A; Scholz, Claudia; Schoen, Christiane; Brown, Niklas; Siepelmeyer, Anne; Alt, Wilfried W

    2016-01-01

    Age-related muscle loss is characterised by a progressing decrease in muscle mass, strength and function. Besides resistance training and physical activity, appropriate nutrition that is rich in protein, especially branched-chain amino acids, is very important to support training effects and positively influence the protein synthesis to degradation ratio. The purpose of this study was to evaluate the effect of a 12-week leucine-rich amino acid supplementation in combination with moderate training. Forty-eight healthy subjects exercised for 30 min three times per week and received either a leucine-rich amino acid supplementation or a placebo. Before and after supplementation, volunteers performed an exhaustive eccentric exercise protocol. Maximal concentric strength, muscle soreness, creatine kinase (CK), type II collagen collagenase cleavage neoepitope (C2C), C propeptide of type II procollagen (CP2) and safety assessments were performed before exercise and after 3, 24, 48 and 72 hours. The supplementation with leucine resulted in reduced loss of strength at 0 and 3 hours after downhill walking compared with the placebo (p=0.0439). The reduction of C2C/CP2 ratio deflection was significantly increased (p=0.038) due to leucine compared with the placebo. The same tendency could be observed for the recovery phase. No significant supplement effects for muscle soreness and CK could be observed. The principle findings show that leucine-rich amino acid supplementation can counteract the negative effects of eccentric exercise. The treatment resulted in a reduction of exercise-induced strength loss.

  3. Body weight and energy homeostasis was not affected in C57BL/6 mice fed high whey protein or leucine-supplemented low-fat diets.

    Science.gov (United States)

    Noatsch, Anne; Petzke, Klaus J; Millrose, Marion K; Klaus, Susanne

    2011-09-01

    Leucine is suggested to act as nutrient signal of high-protein diets regulating pathways associated with an alleviation of metabolic syndrome parameters. However, the subject remains controversial. The aim of this study was to assess and to compare the effects of high-protein diets with dietary leucine supplementation in mice, particularly on energy homeostasis, body composition, and expression of uncoupling protein (UCP), which are suggested to decrease food energy efficiency. Male C57BL/6 mice were exposed for 14 weeks to semi-synthetic diets containing either 20% (adequate protein content, AP) or 50% whey protein (high-protein content, HP). A third group was fed the AP diet supplemented with L-leucine (AP + L) corresponding to the leucine content of the HP diet. The total fat content was 5% (w/w). Body weight gain, body composition, energy expenditure, and protein expression of UCP1 in brown adipose tissue, and UCP3 in skeletal muscle were not different between groups. In HP-fed mice, a stronger increase in blood glucose levels was detected during glucose tolerance tests compared to AP and AP + L, whereas plasma insulin was similar in all groups. Leucine supplementation did not affect glucose tolerance. Plasma cholesterol was significantly decreased in HP and AP + L when compared to AP. Plasma triglyceride concentrations were increased twofold in HP-fed mice when compared to AP + L and AP groups. Liver and skeletal muscle triglyceride and glycogen concentrations were similar in all groups. Postabsorptive plasma concentrations of branched-chain amino acids were not significantly increased after exposure to HP and AP + L diets, whereas those of lysine were decreased in HP and AP + L mice when compared to AP (P supplementation has no significant effect on energy homeostasis and UCP expression compared with AP diets when feeding a low-fat diet. The use of high-quality whey protein might at least in part explain the results obtained.

  4. Contrarily to whey and high protein diets, dietary free leucine supplementation cannot reverse the lack of recovery of muscle mass after prolonged immobilization during ageing.

    Science.gov (United States)

    Magne, Hugues; Savary-Auzeloux, Isabelle; Migné, Carole; Peyron, Marie-Agnès; Combaret, Lydie; Rémond, Didier; Dardevet, Dominique

    2012-04-15

    During ageing, immobilization periods increase and are partially responsible of sarcopaenia by inducing a muscle atrophy which is hardly recovered from. Immobilization-induced atrophy is due to an increase of muscle apoptotic and proteolytic processes and decreased protein synthesis. Moreover, previous data suggested that the lack of muscle mass recovery might be due to a defect in protein synthesis response during rehabilitation. This study was conducted to explore protein synthesis during reloading and leucine supplementation effect as a nutritional strategy for muscle recovery. Old rats (22–24 months old) were subjected to unilateral hindlimb casting for 8 days (I8) and allowed to recover for 10–40 days (R10–R40). They were fed a casein (±leucine) diet during the recovery. Immobilized gastrocnemius muscles atrophied by 20%, and did not recover even at R40. Amount of polyubiquitinated conjugates and chymotrypsin- and trypsin-like activities of the 26S proteasome increased. These changes paralleled an ‘anabolic resistance' of the protein synthesis at the postprandial state (decrease of protein synthesis, P-S6 and P-4E-BP1). During the recovery, proteasome activities remained elevated until R10 before complete normalization and protein synthesis was slightly increased. With free leucine supplementation during recovery, if proteasome activities were normalized earlier and protein synthesis was higher during the whole recovery, it nevertheless failed in muscle mass gain. This discrepancy could be due to a ‘desynchronization' between the leucine signal and the availability of amino acids coming from casein digestion. Thus, when supplemented with leucine-rich proteins (i.e. whey) and high protein diets, animals partially recovered the muscle mass loss.

  5. Effect of partially purified components of zoospores and mycelia of phytophthora infestans on uptake of 3H-leucine by potato tuber disks

    International Nuclear Information System (INIS)

    Nishimura, Norio; Tomiyama, Kohei; Doke, Noriyuki

    1980-01-01

    The zoosporial component of Phytophthora infestans, which was previously reported to cause reduction of 3 H-leucine uptake by potato tuber disks, was partially purified. Precipitate (A-fraction) was obtained by homogenizing zoospores with acetate buffer at pH 4.5 and centrifuging at 20,000 x g, and the A-fraction was suspended in borate buffer at pH 8.8, boiled for 1 hr and then centrifuged at 20,000 x g, giving the precipitate (B-fraction) and supernatant (C-fraction). Ten ml of 10 mM tris-HCl buffer containing 1 mM CaCl 2 at pH 7.4 was used to suspend A and B-fraction. The buffer was used as a control. A, B and C fractions obtained from 5 - 6 x 10 6 zoosprores reducted uptake of 3 H-leucine by the tuber disks of potato cv. Rishiri, but the inhibition rates caused by these fractions differed markedly. However, very high correlation was found between inhibition rates of 3 H-leucine uptake and sugar contents of these fractions. There was no difference in the inhibition rates between the zoosporial components of incompatible and compatible races, when the activities were expressed in terms of the sugar contents. The mycelial components of P. infestans extracted by the modified method of Lisker and Kuc which was used to extract phytoalexin elicitor from that of P. infestans, also had the same effect as the zoosporial components (A, B, and C-fraction) on 3 H-leucine uptake by the disks. C-fraction containing 15 μg of sugar per ml sufficed to inhibit 3 H-leucine uptake at the maximum rate, and the maximum rate of inhibition was attained within 2 hr after the zoosporial component (C-fraction containing 30 μg sugar/ml) was administered to the disks. (author)

  6. Wavelet frames and their duals

    DEFF Research Database (Denmark)

    Lemvig, Jakob

    2008-01-01

    This thesis is concerned with computational and theoretical aspects of wavelet frame analysis in higher dimensions and, in particular, with the study of so-called dual frames of wavelet frames. A frame is a system of "simple" functions or building blocks which deliver ways of analyzing signals....... The signals are then represented by linear combinations of the building blocks with coefficients found by an associated frame, called a dual frame. A wavelet frame is a frame where the building blocks are stretched (dilated) and translated versions of a single function; such a frame is said to have wavelet...... structure. The dilation of the wavelet building blocks in higher dimension is done via a square matrix which is usually taken to be integer valued. In this thesis we step away from the "usual" integer, expansive dilation and consider more general, expansive dilations. In most applications of wavelet frames...

  7. Vacuum transitions in dual models

    International Nuclear Information System (INIS)

    Pashnev, A.I.; Volkov, D.V.; Zheltukhin, A.A.

    1976-01-01

    The investigation is continued of the spontaneous vacuum transition problem in the Neview-Schwartz dual model (NSDM). It is shown that vacuum transitions allow disclosing of supplementary degeneration in the resonance state spectrum. The dual amplitudes possess an internal structure corresponding to the presence of an infinite number of quarks with increasing masses and retained charges. The Adler principle holds. Analytic continuation on the constant of induced vacuum transitions makes it possible to establish the existence of spontaneous vacuum transitions in the NSDM. The consequence of this fact is the exact SU(2) symmetry of π, rho meson trajectories and the Higgs mechanism in the model. In this case the ratios of masses of particles leading trajectories are analogous to those obtained in the current algebra. It is shown that in the NSDM there arises chiral SU(2) x SU(2) x U(1) x U(1) x ... symmetry resulting from spontaneous vacuum transitions

  8. Dual arm master controller concept

    International Nuclear Information System (INIS)

    Kuban, D.P.; Perkins, G.S.

    1984-01-01

    The Advanced Servomanipulator (ASM) slave was designed with an anthropomorphic stance, gear/torque tube power drives, and modular construction. These features resulted in increased inertia, friction, and backlash relative to tape-driven manipulators. Studies were performed which addressed the human factors design and performance trade-offs associated with the corresponding master controller best suited for the ASM. The results of these studies, as well as the conceptual design of the dual arm master controller, are presented. 6 references, 3 figures

  9. Tobacco and psychiatric dual disorders.

    Science.gov (United States)

    Graham, Noni A; Frost-Pineda, Kimberly; Gold, Mark S

    2007-01-01

    Smoking is a leading cause of morbidity and premature mortality in the United States. The relationship between tobacco smoking and several forms of cancer, heart disease, stroke, chronic lung disease, and other medical diseases is well recognized and accepted. Recent epidemiological studies are now focusing on the link between tobacco use and psychiatric diseases. Experts now suggest that in the differential diagnosis of "smoker," depression, alcohol dependence, and schizophrenia are highest on the list. Studies are also focusing on the role of secondhand tobacco exposure, either in utero or during childhood, in the risk of dual disorders. Prenatal exposure may alter gene expression and change the risk for a variety of life-long psychiatric diseases, e.g., ADD/ADHD, antisocial personality disorders, substance use disorders, and major depression. Considerable time and effort have been devoted to studying the link between smoking and depression and also schizophrenia. We will focus on less well-studied areas in tobacco use and psychiatric dual disorders (including eating disorders), prenatal and early childhood secondhand smoke (SHS) exposure, and the relationship to the genesis of these dual disorders.

  10. Dual targeting of peroxisomal proteins

    Directory of Open Access Journals (Sweden)

    Julia eAst

    2013-10-01

    Full Text Available Cellular compartmentalization into organelles serves to separate biological processes within the environment of a single cell. While some metabolic reactions are specific to a single organelle, others occur in more than one cellular compartment. Specific targeting of proteins to compartments inside of eukaryotic cells is mediated by defined sequence motifs. To achieve multiple targeting to different compartments cells use a variety of strategies. Here, we focus on mechanisms leading to dual targeting of peroxisomal proteins. In many instances, isoforms of peroxisomal proteins with distinct intracellular localization are encoded by separate genes. But also single genes can give rise to differentially localized proteins. Different isoforms can be generated by use of alternative transcriptional start sites, by differential splicing or ribosomal read-through of stop codons. In all these cases different peptide variants are produced, of which only one carries a peroxisomal targeting signal. Alternatively, peroxisomal proteins contain additional signals that compete for intracellular targeting. Dual localization of proteins residing in both the cytoplasm and in peroxisomes may also result from use of inefficient targeting signals. The recent observation that some bona fide cytoplasmic enzymes were also found in peroxisomes indicates that dual targeting of proteins to both the cytoplasm and the peroxisome might be more widespread. Although current knowledge of proteins exhibiting only partial peroxisomal targeting is far from being complete, we speculate that the metabolic capacity of peroxisomes might be larger than previously assumed.

  11. Training Changes Professionals’ Attitudes Towards Dual Diagnosis

    DEFF Research Database (Denmark)

    Pinderup, Pernille

    2016-01-01

    Studies have shown that mental health professionals in many cases have counterproductive attitudes towards patients with mental illnesses and comorbid substance use disorders (dual diagnosis). This is problematic because professionals’ attitudes are important for both the therapeutic alliance...... and treatment outcome. This study tested whether providing training in dual diagnosis treatment to mental health professionals will affect their attitudes positively. Twenty-one professionals completed a questionnaire on attitudes towards working with dual diagnosis (Comorbidity Problems Perceptions...

  12. Effects of dietary leucine supplementation on the hepatic mitochondrial biogenesis and energy metabolism in normal birth weight and intrauterine growth-retarded weanling piglets.

    Science.gov (United States)

    Su, Weipeng; Xu, Wen; Zhang, Hao; Ying, Zhixiong; Zhou, Le; Zhang, Lili; Wang, Tian

    2017-04-01

    The study was conducted to evaluate the effects of dietary leucine supplementation on mitochondrial biogenesis and energy metabolism in the liver of normal birth weight (NBW) and intrauterine growth-retarded (IUGR) weanling piglets. A total of sixteen pairs of NBW and IUGR piglets from sixteen sows were selected according to their birth weight. At postnatal day 14, all piglets were weaned and fed either a control diet or a leucine-supplemented diet for 21 d. Thereafter, a 2 × 2 factorial experimental design was used. Each treatment consisted of eight replications with one piglet per replication. Compared with NBW piglets, IUGR piglets had a decreased ( P supplementation increased ( P supplemented diet exhibited increases ( P supplementation may exert beneficial effects on mitochondrial biogenesis and energy metabolism in NBW and IUGR weanling piglets.

  13. Breath test measurements in combination with indirect calorimetry for estimation of 13C-leucine oxidation in mink (Mustela vison)

    DEFF Research Database (Denmark)

    Tauson, Anne-Helene; Ali, Abdalla; Kanska, Katarzyna

    2000-01-01

    Gas exchange measurements by means of indirect calorimetry can be used to calculate quantitative substrate oxidation. The results represents average net oxidation values (substrate disappearance rate), but they cannot describe the dynamics of the oxidation processes. Breath test measurements...... was significant (P=0.03), values generally being lower during fasting, indicating a lower rate of leucine oxidation. It was concluded that the present results clearly demonstrate differences in rate of oxidation of leucine between fed and fasted animals....... to feeding and fasting. Twelve 1-year-old male mink (Mustela vison) were measured in each five consecutive periods by means of indirect calorimetry and simultaneous breath test. In Periods 1, 3 and 5, each lasting 3 days, the animals were fed ad libitum and Periods 2 and 4 were fasting periods, each of 48 h...

  14. Fine-tuning of T-cell development by the CD3γ di-leucine-based TCR-sorting motif

    DEFF Research Database (Denmark)

    Lauritsen, Jens Peter Holst; Boding, Lasse; Buus, Terkild B

    2015-01-01

    The CD3γ di-leucine-based (diL) receptor-sorting motif plays a central role in TCR down-regulation and in clonal expansion of virus-specific T cells. However, the role of the CD3γ diL motif in T-cell development is not known. In this study, we show that protein kinase C-induced TCR down-regulatio......The CD3γ di-leucine-based (diL) receptor-sorting motif plays a central role in TCR down-regulation and in clonal expansion of virus-specific T cells. However, the role of the CD3γ diL motif in T-cell development is not known. In this study, we show that protein kinase C-induced TCR down...

  15. Dual function of the nuclear export signal of the Borna disease virus nucleoprotein in nuclear export activity and binding to viral phosphoprotein.

    Science.gov (United States)

    Yanai, Mako; Sakai, Madoka; Makino, Akiko; Tomonaga, Keizo

    2017-07-11

    Borna disease virus (BoDV), which has a negative-sense, single-stranded RNA genome, causes persistent infection in the cell nucleus. The nuclear export signal (NES) of the viral nucleoprotein (N) consisting of leucine at positions 128 and 131 and isoleucine at positions 133 and 136 overlaps with one of two predicted binding sites for the viral phosphoprotein (P). A previous study demonstrated that higher expression of BoDV-P inhibits nuclear export of N; however, the function of N NES in the interaction with P remains unclear. We examined the subcellular localization, viral polymerase activity, and P-binding ability of BoDV-N NES mutants. We also characterized a recombinant BoDV (rBoDV) harboring an NES mutation of N. BoDV-N with four alanine-substitutions in the leucine and isoleucine residues of the NES impaired its cytoplasmic localization and abolished polymerase activity and P-binding ability. Although an alanine-substitution at position 131 markedly enhanced viral polymerase activity as determined by a minigenome assay, rBoDV harboring this mutation showed expression of viral RNAs and proteins relative to that of wild-type rBoDV. Our results demonstrate that BoDV-N NES has a dual function in BoDV replication, i.e., nuclear export of N and an interaction with P, affecting viral polymerase activity in the nucleus.

  16. Effects of metenkephalin on the formation and fixation of defensive temporal associations and on the incorporation of C14-leucine in brain proteins of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Kruglikov, R.I.; Gol' dberg, M.V.; Maizelis, M.Y.A.; Zabludovskii, A.L.

    When 25 microgram of metenkephalin is injected subcutaneously into rats, the development of temporal associations is somewhat impaired, but the fixation of them is enhanced. The latter effect is observed more clearly when metenkephalin is injected not before, but immediately after the development of conditioned reflexes. Under the influence of metenkephalin, there is an increase in the incorporation of C14-leucine into the insoluble proteins of the hippocampus and basal ganglia. It is hypothesized that metenkephalin mainly affects the process of consolidation.

  17. Repression of branched-chain amino acid synthesis in Staphylococcus aureus is mediated by isoleucine via CodY, and by a leucine-rich attenuator peptide.

    Directory of Open Access Journals (Sweden)

    Julienne C Kaiser

    2018-01-01

    Full Text Available Staphylococcus aureus requires branched-chain amino acids (BCAAs; isoleucine, leucine, valine for protein synthesis, branched-chain fatty acid synthesis, and environmental adaptation by responding to their availability via the global transcriptional regulator CodY. The importance of BCAAs for S. aureus physiology necessitates that it either synthesize them or scavenge them from the environment. Indeed S. aureus uses specialized transporters to scavenge BCAAs, however, its ability to synthesize them has remained conflicted by reports that it is auxotrophic for leucine and valine despite carrying an intact BCAA biosynthetic operon. In revisiting these findings, we have observed that S. aureus can engage in leucine and valine synthesis, but the level of BCAA synthesis is dependent on the BCAA it is deprived of, leading us to hypothesize that each BCAA differentially regulates the biosynthetic operon. Here we show that two mechanisms of transcriptional repression regulate the level of endogenous BCAA biosynthesis in response to specific BCAA availability. We identify a trans-acting mechanism involving isoleucine-dependent repression by the global transcriptional regulator CodY and a cis-acting leucine-responsive attenuator, uncovering how S. aureus regulates endogenous biosynthesis in response to exogenous BCAA availability. Moreover, given that isoleucine can dominate CodY-dependent regulation of BCAA biosynthesis, and that CodY is a global regulator of metabolism and virulence in S. aureus, we extend the importance of isoleucine availability for CodY-dependent regulation of other metabolic and virulence genes. These data resolve the previous conflicting observations regarding BCAA biosynthesis, and reveal the environmental signals that not only induce BCAA biosynthesis, but that could also have broader consequences on S. aureus environmental adaptation and virulence via CodY.

  18. Adding Fish Oil to Whey Protein, Leucine, and Carbohydrate Over a Six-Week Supplementation Period Attenuates Muscle Soreness Following Eccentric Exercise in Competitive Soccer Players.

    Science.gov (United States)

    Philpott, Jordan D; Donnelly, Chris; Walshe, Ian H; MacKinley, Elizabeth E; Dick, James; Galloway, Stuart D R; Tipton, Kevin D; Witard, Oliver C

    2018-01-01

    Soccer players often experience eccentric exercise-induced muscle damage given the physical demands of soccer match-play. Since long chain n-3 polyunsaturated fatty acids (n-3PUFA) enhance muscle sensitivity to protein supplementation, dietary supplementation with a combination of fish oil-derived n-3PUFA, protein, and carbohydrate may promote exercise recovery. This study examined the influence of adding n-3PUFA to a whey protein, leucine, and carbohydrate containing beverage over a six-week supplementation period on physiological markers of recovery measured over three days following eccentric exercise. Competitive soccer players were assigned to one of three conditions (2 × 200 mL): a fish oil supplement beverage (FO; n = 10) that contained n-3PUFA (1100 mg DHA/EPA-approximately 550 mg DHA, 550 mg EPA), whey protein (15 g), leucine (1.8 g), and carbohydrate (20 g); a protein supplement beverage (PRO; n = 10) that contained whey protein (15 g), leucine (1.8 g), and carbohydrate (20 g); and a carbohydrate supplement beverage (CHO; n = 10) that contained carbohydrate (24 g). Eccentric exercise consisted of unilateral knee extension/flexion contractions on both legs separately. Maximal force production was impaired by 22% during the 72-hour recovery period following eccentric exercise (p soccer performance, or blood c-reactive protein concentrations were observed between groups. In conclusion, the addition of n-3PUFA to a beverage containing whey protein, leucine, and carbohydrate ameliorates the increase in muscle soreness and blood concentrations of creatine kinase following eccentric exercise in competitive soccer players.

  19. Free leucine supplementation during an 8-week resistance training program does not increase muscle mass and strength in untrained young adult subjects.

    Science.gov (United States)

    Aguiar, Andreo Fernando; Grala, Alan Pablo; da Silva, Rubens Alexandre; Soares-Caldeira, Lúcio Flávio; Pacagnelli, Francis Lopes; Ribeiro, Alex Silva; da Silva, Douglas Kratki; de Andrade, Walquíria Batista; Balvedi, Mario Carlos Welin

    2017-07-01

    The purpose of this study was to examine the effects of free leucine supplementation on changes in skeletal muscle mass and strength during a resistance training (RT) program in previously untrained, young subjects. In a double-blind, randomized, placebo-controlled study, 20 healthy young (22 ± 2 years) participants were assigned to two groups: a placebo-supplement group (PLA, N = 10) or a leucine-supplement group (LEU, N = 10). Both groups underwent an 8-week hypertrophic RT program (2 days/week), consuming an equivalent amount of leucine (3.0 g/day in a single post-training dose) or placebo (cornstarch). Quadriceps muscle strength, cross-sectional area (CSA) of the vastus lateralis (VL), and rectus femoris (RF), as well as the habitual dietary intake were assessed before and after the 8-week intervention period. There was a similar improvement in muscle strength (Leg press, LEU: +33% vs. PLA: +37%; P > 0.05, and knee extension, LEU: +31% vs. PLA: 34%; P > 0.05) and CSA (VL, LEU: 8.9% vs. PLA: 9.6%; P > 0.05, and RF, LEU: +21.6% vs. PLA: + 16.4%; P > 0.05) in the both groups from pre- to post-training. In addition, there was no significant (P > 0.05) difference in daily dietary intake between the LEU and PLA groups before and after the intervention period. Free leucine supplementation (3.0 g/day post-training) does not increase muscle strength or CSA during RT in healthy young subjects consuming adequate dietary protein intake.

  20. Reduced muscular fatigue after a 12-week leucine-rich amino acid supplementation combined with moderate training in elderly: a randomised, placebo-controlled, double-blind trial

    OpenAIRE

    Reule, Claudia A; Scholz, Claudia; Schoen, Christiane; Brown, Niklas; Siepelmeyer, Anne; Alt, Wilfried W

    2017-01-01

    Background Age-related muscle loss is characterised by a progressing decrease in muscle mass, strength and function. Besides resistance training and physical activity, appropriate nutrition that is rich in protein, especially branched-chain amino acids, is very important to support training effects and positively influence the protein synthesis to degradation ratio. Aim The purpose of this study was to evaluate the effect of a 12-week leucine-rich amino acid supplementation in combination wit...

  1. Molecular cloning and characterization of the family of feline leucine-rich glioma-inactivated (LGI) genes, and mutational analysis in familial spontaneous epileptic cats

    OpenAIRE

    Yu, Yoshihiko; Hasegawa, Daisuke; Fujiwara-Igarashi, Aki; Hamamoto, Yuji; Mizoguchi, Shunta; Kuwabara, Takayuki; Fujita, Michio

    2017-01-01

    Background Leucine-rich glioma-inactivated (LGI) proteins play a critical role in synaptic transmission. Dysfunction of these genes and encoded proteins is associated with neurological disorders such as genetic epilepsy or autoimmune limbic encephalitis in animals and human. Familial spontaneous epileptic cats (FSECs) are the only feline strain and animal model of familial temporal lobe epilepsy. The seizure semiology of FSECs comprises recurrent limbic seizures with or without evolution into...

  2. Proteome Analysis of Human Arterial Tissue Discloses Associations Between the Vascular Content of Small Leucine-Rich Repeat Proteoglycans and Pulse Wave Velocity

    DEFF Research Database (Denmark)

    Lyck Hansen, Maria; Beck, Hans Christian; Irmukhamedov, Akhmadjon

    2015-01-01

    spectrometry/mass spectrometry. Of 418 quantified proteins, 28 were differentially expressed between the groups with high and low PWV (Pleucine-rich repeat proteoglycans displayed significant differences between the 2 groups (P=0...... in the arterial amounts of small leucine-rich proteoglycans, known to be involved in collagen fibrillogenesis, and of some nonfibrillar collagens in combination with alterations in proteins related to functions of the human arterial smooth muscle are associated with arterial stiffness, as determined by PWV....

  3. Genome-Wide Comparative Analyses Reveal the Dynamic Evolution of Nucleotide-Binding Leucine-Rich Repeat Gene Family among Solanaceae Plants

    OpenAIRE

    Seo, Eunyoung; Kim, Seungill; Yeom, Seon-In; Choi, Doil

    2016-01-01

    Plants have evolved an elaborate innate immune system against invading pathogens. Within this system, intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors are known play critical roles in effector-triggered immunity (ETI) plant defense. We performed genome-wide identification and classification of NLR-coding sequences from the genomes of pepper, tomato, and potato using fixed criteria. We then compared genomic duplication and evolution features. We identified intact 267...

  4. Coisotropic Submanifolds and Dual Pairs

    Science.gov (United States)

    Cattaneo, Alberto S.

    2014-03-01

    The Poisson sigma model is a widely studied two-dimensional topological field theory. This note shows that boundary conditions for the Poisson sigma model are related to coisotropic submanifolds (a result announced in [math.QA/0309180]) and that the corresponding reduced phase space is a (possibly singular) dual pair between the reduced spaces of the given two coisotropic submanifolds. In addition the generalization to a more general tensor field is considered and it is shown that the theory produces Lagrangian evolution relations if and only if the tensor field is Poisson.

  5. Dual arm master controller development

    International Nuclear Information System (INIS)

    Kuban, D.P.; Perkins, G.S.

    1985-01-01

    The advanced servomanipulator (ASM) slave was designed with an anthropomorphic stance, gear/torque tube power drives, and modular construction. These features resulted in increased inertia, friction, and backlash relative to tape-driven manipulators. Studies were performed which addressed the human factors design and performance trade-offs associated with the corresponding master controller best suited for the ASM. The results of these studies, as well as the conceptual design of the dual arm master controller, are presented. This work was performed as part of the Consolidated Fuel Reprocessing Program at the Oak Ridge National Laboratory. 5 refs., 7 figs., 1 tab

  6. Global gene expression profiling in Escherichia coli K12. The effects of leucine-responsive regulatory protein.

    Science.gov (United States)

    Hung, She-pin; Baldi, Pierre; Hatfield, G Wesley

    2002-10-25

    Leucine-responsive regulatory protein (Lrp) is a global regulatory protein that affects the expression of multiple genes and operons in bacteria. Although the physiological purpose of Lrp-mediated gene regulation remains unclear, it has been suggested that it functions to coordinate cellular metabolism with the nutritional state of the environment. The results of gene expression profiles between otherwise isogenic lrp(+) and lrp(-) strains of Escherichia coli support this suggestion. The newly discovered Lrp-regulated genes reported here are involved either in small molecule or macromolecule synthesis or degradation, or in small molecule transport and environmental stress responses. Although many of these regulatory effects are direct, others are indirect consequences of Lrp-mediated changes in the expression levels of other global regulatory proteins. Because computational methods to analyze and interpret high dimensional DNA microarray data are still an early stage, much of the emphasis of this work is directed toward the development of methods to identify differentially expressed genes with a high level of confidence. In particular, we describe a Bayesian statistical framework for a posterior estimate of the standard deviation of gene measurements based on a limited number of replications. We also describe an algorithm to compute a posterior estimate of differential expression for each gene based on the experiment-wide global false positive and false negative level for a DNA microarray data set. This allows the experimenter to compute posterior probabilities of differential expression for each individual differential gene expression measurement.

  7. Enhanced gene expression in tumors after intravenous administration of arginine-, lysine- and leucine-bearing polyethylenimine polyplex.

    Science.gov (United States)

    Aldawsari, Hibah; Raj, Behin Sundara; Edrada-Ebel, RuAngelie; Blatchford, David R; Tate, Rothwelle J; Tetley, Laurence; Dufès, Christine

    2011-10-01

    The potential of gene therapy to treat cancer is currently limited by the low expression of therapeutic genes in the tumors. Because amino acids are known to have excellent properties in cell penetration and gene expression regulation, we investigated if the conjugation of arginine (Arg), lysine (Lys) and leucine (Leu) onto the surface of the gene delivery system polyethylenimine (PEI) could lead to an improved gene expression in tumors. The intravenous administration of Arg-, Lys- and Leu-bearing PEI polyplexes led to a significant increase of gene expression in the tumor, with a β-galactosidase expression amount at least threefold higher than that obtained after treatment with unmodified PEI polyplex. The three amino acid-bearing PEI polyplexes led to similar levels of gene expression in the tumor. The treatments were well tolerated by the mice. Arg-, Lys- and Leu-bearing PEI polyplexes are therefore highly promising gene delivery systems for cancer therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Leucine-Enriched Essential Amino Acids Augment Muscle Glycogen Content in Rats Seven Days after Eccentric Contraction.

    Science.gov (United States)

    Kato, Hiroyuki; Miura, Kyoko; Suzuki, Katsuya; Bannai, Makoto

    2017-10-23

    Eccentric contractions induce muscle damage, which impairs recovery of glycogen and adenosine tri-phosphate (ATP) content over several days. Leucine-enriched essential amino acids (LEAAs) enhance the recovery in muscles that are damaged after eccentric contractions. However, the role of LEAAs in this process remains unclear. We evaluated the content in glycogen and high energy phosphates molecules (phosphocreatine (PCr), adenosine di-phosphate (ADP) and ATP) in rats that were following electrically stimulated eccentric contractions. Muscle glycogen content decreased immediately after the contraction and remained low for the first three days after the stimulation, but increased seven days after the eccentric contraction. LEAAs administration did not change muscle glycogen content during the first three days after the contraction. Interestingly, however, it induced a further increase in muscle glycogen seven days after the stimulation. Contrarily, ATP content decreased immediately after the eccentric contraction, and remained lower for up to seven days after. Additionally, LEAAs administration did not affect the ATP content over the experimental period. Finally, ADP and PCr levels did not significantly change after the contractions or LEAA administration. LEAAs modulate the recovery of glycogen content in muscle after damage-inducing exercise.

  9. Leucine-Enriched Essential Amino Acids Augment Muscle Glycogen Content in Rats Seven Days after Eccentric Contraction

    Directory of Open Access Journals (Sweden)

    Hiroyuki Kato

    2017-10-01

    Full Text Available Eccentric contractions induce muscle damage, which impairs recovery of glycogen and adenosine tri-phosphate (ATP content over several days. Leucine-enriched essential amino acids (LEAAs enhance the recovery in muscles that are damaged after eccentric contractions. However, the role of LEAAs in this process remains unclear. We evaluated the content in glycogen and high energy phosphates molecules (phosphocreatine (PCr, adenosine di-phosphate (ADP and ATP in rats that were following electrically stimulated eccentric contractions. Muscle glycogen content decreased immediately after the contraction and remained low for the first three days after the stimulation, but increased seven days after the eccentric contraction. LEAAs administration did not change muscle glycogen content during the first three days after the contraction. Interestingly, however, it induced a further increase in muscle glycogen seven days after the stimulation. Contrarily, ATP content decreased immediately after the eccentric contraction, and remained lower for up to seven days after. Additionally, LEAAs administration did not affect the ATP content over the experimental period. Finally, ADP and PCr levels did not significantly change after the contractions or LEAA administration. LEAAs modulate the recovery of glycogen content in muscle after damage-inducing exercise.

  10. [Study of human leucine-rich amelogenin peptide and its regulation of mineralization by cryogenic transmission electron microscopy].

    Science.gov (United States)

    Kun, Tian; Xiaoyun, Feng; Qin, Du; Chuhang, Liao; Xiaohua, Ren

    2017-02-01

    Recombinant human leucine-rich amelogenin peptide (LRAP) was studied by cryogenic transmission electron microscopy (TEM); evaluation focused on its self-assembly and crystal growth in vitro. Human LRAP was recombined through prokaryotic expression vector pCold-SUMO and transformed into Escherichia coli BL21plys to acquire purified proteins. Cryogen TEM recorded assembly and self-assembling of LRAP from pH 3.5 to pH 8.0, and the hydroxyapatite crystal growth in the mixture of LRAP protein solution and artificial saliva was observed using TEM and selected area electron diffraction. More than 90% purity LRAP was expressed, purified and identified as described in methods. LRAP linked into oligomers, nanospheres, nanochains, and microribbons, whereas pH value increased from 3.5 to 8.0. Mature hydroxyapatite crystal growth was guided in artificial saliva filled with calcium phosphate. LRAP is simplified amelogenin functional domain and conserved the basic characters of amelogenin such as self-assembling and inducing crystallization along c axis. In the area of acellular synthesis of hydroxyapatite using extracellular enamel matrix protein, LRAP is one of candidate repair materials for irregular hard tissue defection.
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  11. The role of red blood cell S-nitrosation in nitrite bioactivation and its modulation by leucine and glucose

    Directory of Open Access Journals (Sweden)

    Nadeem Wajih

    2016-08-01

    Full Text Available Previous work has shown that red blood cells (RBCs reduce nitrite to NO under conditions of low oxygen. Strong support for the ability of red blood cells to promote nitrite bioactivation comes from using platelet activation as a NO-sensitive process. Whereas addition of nitrite to platelet rich plasma in the absence of RBCs has no effect on inhibition of platelet activation, when RBCs are present platelet activation is inhibited by an NO-dependent mechanism that is potentiated under hypoxia. In this paper, we demonstrate that nitrite bioactivation by RBCs is blunted by physiologically-relevant concentrations of nutrients including glucose and the important signaling amino acid leucine. Our mechanistic investigations demonstrate that RBC mediated nitrite bioactivation is largely dependent on nitrosation of RBC surface proteins. These data suggest a new expanded paradigm where RBC mediated nitrite bioactivation not only directs blood flow to areas of low oxygen but also to areas of low nutrients. Our findings could have profound implications for normal physiology as well as pathophysiology in a variety of diseases including diabetes, sickle cell disease, and arteriosclerosis.

  12. Isolation and characterization of Leucine dehydrogenase from a thermophilic Citrobacter freundii JK-91strain Isolated from Jask Port.

    Science.gov (United States)

    Mahdizadehdehosta, Rahman; Kianmehr, Anvarsadat; Khalili, Ahmad

    2013-09-01

    Leucine dehydrogenase (LeuDH; EC 1.4.1.9) belongs to the amino acid dehydrogenase family and isused as a biocatalyst in medical and pharmaceutical industries (1). This study reported deals with the isolation and characterization of LeuDH from a thermophilic bacterium isolated from Jask Port in the Province of Hormozgan. Aliquots of soil and water samples were cultured in LEU specific medium and thermophilc bacteria that exhibited LeuDH activity were isolated and characterized biochemically. The LeuDH was purified and characterized in regard to the effects of pH and temperature on the activity, as well as its molecular weight determination. A thermophilic bacterium, Citrobacter freundii strain JK-9 was identified and found to exhibit LeuDH activity. The enzyme characterization revealed that LeuDH exhibits higher activity at temperature range of 60 to 75°C (optimum of 60°C) and an optimum pH of activity at pH 10.5. The K m value of LeuDH is 1.2 mM, while its molecular weight is about 320 kDa, and consisted of eight subunits identical in molecular mass (40 kDa). Briefly, a thermostableLeuDH enzyme from a strain of C. freundii was isolated and characterized. Our data indicate that the C. freundii enzyme has potential for use in biotechnological applications.

  13. Silencing of a unique integrated domain nucleotide-binding leucine-rich repeat gene in wheat abolishes Diuraphis noxia resistance.

    Science.gov (United States)

    Nicolis, Vittorio Filippo; Venter, Eduard

    2018-03-13

    Plants respond in a similar manner to aphid feeding as to pathogen attack. Diuraphis noxia is a specialist aphid, feeding only on selected grasses that include wheat, barley, and oats. The wheat-Diuraphis noxia interaction is characterized by very similar responses as seen in wheat-pathogen interactions with none of the underlying resistance pathways and genes characterized yet. From wheat harboring the Dn1 resistance gene, we have identified a nucleotide-binding leucine-rich repeat (NLR) gene containing two integrated domains (IDs). These are three C-terminus ankyrin repeat-domains and an N-terminus WRKY domain. The NLR core of the gene can be traced through speciation events within the grass family, with a recent WRKY domain integration that is Triticum specific. Virus induced gene silencing of the gene in a resistant wheat line resulted in the abolishment of the resistance response and induced a highly susceptible phenotype. Silenced plants supported a higher number of aphids similar to the susceptible NIL and the intrinsic rate of increase of the aphids matched that of aphids feeding on the susceptible NIL. The presence of the gene is necessary for Dn1 resistance and we have named the gene Associated with Dn resistance 1 (Adr1) to reflect this function.

  14. Behavior of leucine-rich repeat-containing G-protein coupled receptor 5-expressing cells in the reprogramming process

    Directory of Open Access Journals (Sweden)

    Yuko Arioka

    2017-04-01

    Full Text Available It remains unclear what cells are proper for the generation of induced pluripotent stem cells (iPSCs. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5 is well known as a tissue stem cell and progenitor marker, both of which are reported to be sensitive to reprogramming. In the present study, we examined the reprogramming behavior of Lgr5-expressing cells (Lgr5+ cells. First, we compared reprogramming behavior using mouse Lgr5+ and Lgr5 negative (Lgr5− hair follicles (HFs. The number of alkaline phosphatase staining-positive cells was lesser in a well of Lgr5+ HFs than in Lgr5− HFs; however, the ratio of Nanog+ SSEA1+ cells in the cell mixture derived from Lgr5+ HFs was much higher than that from Lgr5− HFs. Lgr5+ cells could be induced from mouse embryonic fibroblasts (MEFs after transduction with Yamanaka factors. As shown in HFs, the progeny of Lgr5+ cells arising from MEFs highly converted into Nanog+ cells and did not form Nanog− colonies. The progeny represented the status of the late reprogramming phase to a higher degree than the nonprogeny. We also confirmed this using human Lg5+ cells. Our findings suggest that the use of Lgr5+ cells will minimize sorting efforts for obtaining superior iPSCs.

  15. Identification of glucocorticoid-induced leucine zipper as a key regulator of tumor cell proliferation in epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Fernandez Hervé

    2009-10-01

    Full Text Available Abstract Background Little is known about the molecules that contribute to tumor progression of epithelial ovarian cancer (EOC, currently a leading cause of mortality from gynecological malignancies. Glucocorticoid-Induced Leucine Zipper (GILZ, an intracellular protein widely expressed in immune tissues, has been reported in epithelial tissues and controls some of key signaling pathways involved in tumorigenesis. However, there has been no report on GILZ in EOC up to now. The objectives of the current study were to examine the expression of GILZ in EOC and its effect on tumor cell proliferation. Results GILZ expression was measured by immunohistochemical staining in tissue sections from 3 normal ovaries, 7 benign EOC and 50 invasive EOC. GILZ was not detected on the surface epithelium of normal ovaries and benign tumors. In contrast, it was expressed in the cytoplasm of tumor cells in 80% EOC specimens. GILZ immunostaining scores correlated positively to the proliferation marker Ki-67 (Spearman test in univariate analysis, P P Conclusion The present study is the first to identify GILZ as a molecule produced by ovarian cancer cells that promotes cell cycle progression and proliferation. Our findings clearly indicate that GILZ activates AKT, a crucial signaling molecule in tumorigenesis. GILZ thus appears as a potential key molecule in EOC.

  16. Glycogen synthase kinase-3β regulates leucine-309 demethylation of protein phosphatase-2A via PPMT1 and PME-1.

    Science.gov (United States)

    Yao, Xiu-Qing; Li, Xia-Chun; Zhang, Xiao-Xue; Yin, Yang-Yang; Liu, Bin; Luo, Dan-Ju; Wang, Qun; Wang, Jian-Zhi; Liu, Gong-Ping

    2012-07-30

    Protein phosphatase-2A (PP2A) activity is significantly suppressed in Alzheimer's disease. We have reported that glycogen synthase kinase-3β (GSK-3β) inhibits PP2A via upregulating the phosphorylation of PP2A catalytic subunit (PP2A(C)). Here we studied the effects of GSK-3β on the inhibitory demethylation of PP2A at leucine-309 (dmL309-PP2A(C)). We found that GSK-3β regulates dmL309-PP2A(C) level by regulating PME-1 and PPMT1. Knockdown of PME-1 or PPMT1 eliminated the effects of GSK-3β on PP2A(C). GSK-3 could negatively regulate PP2A regulatory subunit protein level. We conclude that GSK-3β can inhibit PP2A by increasing the inhibitory L309-demethylation involving upregulation of PME-1 and inhibition of PPMT1. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. Placental Leucine Aminopeptidase- and Aminopeptidase A- Deficient Mice Offer Insight concerning the Mechanisms Underlying Preterm Labor and Preeclampsia

    Directory of Open Access Journals (Sweden)

    Shigehiko Mizutani

    2011-01-01

    Full Text Available Preeclampsia and preterm delivery are important potential complications in pregnancy and represent the leading causes for maternal and perinatal morbidity and mortality. The mechanisms underlying both diseases remain unknown, thus available treatments (beta2-stimulants and magnesium sulfate are essentially symptomatic. Both molecules have molecular weights less than 5–8 kDa, cross the placental barrier, and thus exert their effects on the fetus. The fetus produces peptides that are highly vasoactive and uterotonic and increase in response to maternal stress and with continued development. Fetal peptides are also small molecules that inevitably leak across into the maternal circulation. Aminopeptidases such as placental leucine aminopeptidase (P-LAP and aminopeptidase A (APA are large molecules that do not cross the placental barrier. We have shown that APA acts as an antihypertensive agent in the pregnant spontaneously hypertensive rat by degrading vasoactive peptides and as a result returns the animal to a normotensive state. P-LAP also acts as an antiuterotonic agent by degrading uterotonic peptides and thus prolongs gestation in the pregnant mouse. Given the ever increasing worldwide incidences of preeclampsia and preterm labor, it is imperative that new agents be developed to safely prolong gestation. We believe that the use of aminopeptidases hold promise in this regard.

  18. Volumetric study of aqueous proline-leucine solutions from (283.15 to 318.15) K

    International Nuclear Information System (INIS)

    Mendonca, Angela F.S.S.; Barbas, Maria Joao A.; Freitas, Jose M.; Lampreia, Isabel M.S.

    2004-01-01

    Density data for very diluted aqueous solutions of proline-leucine are reported for eight different temperatures from (283.15 to 318.15) K. Measurements were made using a vibrating tube densimeter. Apparent molar volumes of the dipeptide were calculated, at each temperature, and least squares fitted to linear equations. A weighted method with weighting factors inversely proportional to the square of the individual uncertainties has been used. Limiting partial molar volumes, V m,2 ∞ and S v values were obtained from the intercepts and slopes of those equations. Negative slopes were obtained for the lower temperatures against positive values for the higher. Trends of the values obtained are an evidence of the overwhelming contribution of the hydrophobic interactions at lower temperatures. Limiting partial molar isobaric expansions, E P,m,2 ∞ , have been also calculated using the temperature derivatives of the corresponding volumes, showing negative values. The decrease of their absolute values, with increasing temperature, points out to predominant structure maker behaviour of the solute

  19. Leucine rich repeats are the main epitopes in Leishmania infantum PSA during canine and human visceral leishmaniasis.

    Science.gov (United States)

    Boceta, C; Alonso, C; Jiménez-Ruiz, A

    2000-02-01

    The PSA protein is one of the major antigens of the surface of the Leishmania infantum parasite membrane. We describe the immune humoral response against the PSA in dogs and human patients with visceral leishmaniasis caused by L. infantum. The immunodominant region of the PSA was determined by subcloning, expression and purification of three fragments covering the complete protein. The analysis revealed that the antibodies are mostly directed against the central region, which is formed exclusively by leucine rich repeats. This region is recognized by 100% of the sera from the infected dogs and 40% of the human sera. These percentages are significantly higher than those observed when the complete protein was used as antigen. The analysis of the isotype of the G immunoglobulins raised against the immunodominant determinants of the PSA indicates that both IgG1 and IgG2 classes are produced during natural infections but that the IgG2 predominates over that of the IgG1.

  20. A leucine-rich repeat motif of Leishmania parasite surface antigen 2 binds to macrophages through the complement receptor 3.

    Science.gov (United States)

    Kedzierski, Lukasz; Montgomery, Jacqui; Bullen, Denise; Curtis, Joan; Gardiner, Elizabeth; Jimenez-Ruiz, Antonio; Handman, Emanuela

    2004-04-15

    Membrane glycoconjugates on the Leishmania parasites, notably leishmanolysin and lipophosphoglycan, have been implicated in attachment and invasion of host macrophages. However, the function of parasite surface Ag 2 (PSA-2) and membrane proteophosphoglycan (PPG) has not been elucidated. In this study we demonstrate that native and recombinant Leishmania infantum PSA-2, which consists predominantly of 15 leucine-rich repeats (LRR) and a recombinant LRR domain derived from L. major PPG, bind to macrophages. The interaction is restricted to macrophages and appears to be calcium independent. We have investigated the PSA-2-macrophage interaction to identify the host receptor involved in binding and we show that binding of PSA-2 to macrophages can be blocked by Abs to the complement receptor 3 (CR3, Mac-1). Data derived from mouse macrophage studies were further confirmed using cell lines expressing human CR3, and showed that PSA-2 also binds to the human receptor. This is the first demonstration of a functional role for PSA-2. Our data indicate that in addition to leishmanolysin and lipophosphoglycan, parasite attachment and invasion of macrophages involve a third ligand comprising the LRRs shared by PSA-2 and PPG and that these interactions occur via the CR3.

  1. The polarization of the G-protein activated potassium channel GIRK5 to the vegetal pole of Xenopus laevis oocytes is driven by a di-leucine motif.

    Science.gov (United States)

    Díaz-Bello, Beatriz; Rangel-García, Claudia I; Salvador, Carolina; Carrisoza-Gaytán, Rolando; Escobar, Laura I

    2013-01-01

    The G protein-coupled inwardly-rectifying potassium channels (known as GIRK or Kir3) form functional heterotetramers gated by G-βγ subunits. GIRK channels participate in heart rate modulation and neuronal postsynaptic inhibition in mammals. In Xenopus laevis oocytes, GIRK5 is a functional homomultimer. Previously, we found that phosphorylation of a tyrosine (Y16) at its N-terminus downregulates the surface expression of GIRK5. In this work, we elucidated the subcellular localization and trafficking of GIRK5 in oocytes. Several EGFP-GIRK5 chimeras were produced and an ECFP construct was used to identify the endoplasmic reticulum (ER). Whereas GIRK5-WT was retained in the ER at the animal pole, the phospho-null GIRK5-Y16A was localized to the vegetal pole. Interestingly, a construct with an N-terminal Δ25 deletion produced an even distribution of the channel in the whole oocyte. Through an alanine-scan, we identified an acidic cluster/di-leucine sorting-signal recognition motif between E17 and I22. We quantified the effect of each amino acid residue within this di-leucine motif in determining the distribution of GIRK5 to the animal and vegetal poles. We found that Y16 and I22 contributed to functional expression and were dominant in the polarization of GIRK5. We thus conclude that the N-terminal acidic di-leucine motif of GIRK5 determines its retention and polarized trafficking within Xl oocytes.

  2. A Whole-Cell Surface Plasmon Resonance Sensor Based on a Leucine Auxotroph of Escherichia coli Displaying a Gold-Binding Protein: Usefulness for Diagnosis of Maple Syrup Urine Disease.

    Science.gov (United States)

    Woo, Min-Ah; Park, Jung Hun; Cho, Daeyeon; Sim, Sang Jun; Kim, Moon Il; Park, Hyun Gyu

    2016-03-01

    We developed a whole-cell surface plasmon resonance (SPR) sensor based on a leucine auxotroph of Escherichia coli displaying a gold-binding protein (GBP) in response to cell growth and applied this sensor to the diagnosis of maple syrup urine disease, which is represented by the elevated leucine level in blood. The leucine auxotroph was genetically engineered to grow displaying GBP in a proportion to the concentration of target amino acid leucine. The GBP expressed on the surface of the auxotrophs directly bound to the golden surface of an SPR chip without the need for any additional treatment or reagents, which consequently produced SPR signals used to determine leucine levels in a test sample. Gold nanoparticles (GNPs) were further applied to the SPR system, which significantly enhanced the signal intensity up to 10-fold by specifically binding to GBP expressed on the cell surface. Finally, the diagnostic utility of our system was demonstrated by its employment in reliably determining different statuses of maple syrup urine disease based on a known cutoff level of leucine. This new approach based on an amino acid-auxotrophic E. coli strain expressing a GBP that binds to an SPR sensor holds great promise for detection of other metabolic diseases of newborn babies including homocystinuria and phenylketonuria, which are also associated with abnormal levels of amino acids.

  3. Robot Kinematics, using Dual Quaternions

    Directory of Open Access Journals (Sweden)

    Mahmoud Gouasmi

    2012-03-01

    Full Text Available From the point of view of classical mechanics, deriving the equations of motion for systems of coupled rigid bodies is regarded as a straightforward procedure: once a suitable set of generalized coordinates and reference frames have been chosen, what remains is to either apply Lagrange’s equations or Newton and Euler’s equations to obtain the differential equations of motion. As the complexity of multibody system increases, the need for more elegant formulation of the equation of motion becomes an issue of paramount importance. Our primary focus is on the kinematic analysis of rigid bodies and serial manipulators (robotic systems  using simultaneously, both homogeneous transformations (4x4 matrices and Dual Quaternions, for the sake of results comparisons (cost,complexity,storage capacity etc. . This paper has been done mainly for educational and peadagogical purposes, hoping that the scientific community will finally adopt and use Dual Quaternions at least when dealing with multibody systems and specially robotics.

  4. Dual wound dc brush motor gearhead

    Science.gov (United States)

    Henson, Barrie W.

    1986-01-01

    The design requirements, the design, development tests and problems, the qualification and life test and the findings of the strip examination of a dual wound DC brushed motor gearhead are described. It is the only space qualified dual wound dc brushed motor gearhead in Europe.

  5. Dual-Career Couples: Keeping Them Together.

    Science.gov (United States)

    Wolf-Wendel, Lisa E.; Twombly, Susan; Rice, Suzanne

    2000-01-01

    Reports results of a survey of 360 chief academic officers at member institutions of the American Association of Colleges and Universities regarding their policies and practices for assisting dual-career couples. Examines the motivations, barriers, consequences, and policy implications of institutional responses to dual-career couples. (DB)

  6. Symmetries of Taub-NUT dual metrics

    International Nuclear Information System (INIS)

    Baleanu, D.; Codoban, S.

    1998-01-01

    Recently geometric duality was analyzed for a metric which admits Killing tensors. An interesting example arises when the manifold has Killing-Yano tensors. The symmetries of the dual metrics in the case of Taub-NUT metric are investigated. Generic and non-generic symmetries of dual Taub-NUT metric are analyzed

  7. Quotient functions of dual quermassintegrals | Zhao | Quaestiones ...

    African Journals Online (AJOL)

    Motivated by the notion of volume difference functions, we introduce quotient functions of dual quermassintegrals and establish Brunn-Minkowski type inequalities for them, which have several recent results as special cases. Keywords: Volume difference function, dual quermassintegrals, quotient function, radial Blaschke ...

  8. Adherence to dual method contraceptive use

    Science.gov (United States)

    Peipert, Jeffrey F.; Zhao, Qiuhong; Meints, Laura; Peipert, Benjamin J.; Redding, Colleen A.; Allsworth, Jenifer E.

    2013-01-01

    Background Patient characteristics associated with adherence to dual method contraceptive use are not known. Study Design Project PROTECT was a 24-month long randomized trial designed to promote the use of dual methods of contraception using an individualized computer-based intervention or enhanced standard care counseling intervention. We analyzed 463 women with follow-up data and examined sustained dual method use (reported at 2+ interviews). Results While 32% initiated dual method contraceptive use, only 9% reported sustained use. Education increased (RRadj = 4.42; 95%CI 1.19-16.42), substance abuse decreased (RRadj = 0.49; 95%CI 0.24-0.97), no contraceptive use at baseline decreased (RRadj = 0.32; 95%CI 0.11-0.92), and contraceptive stage of change increased (RRadj =5.04; 95%CI 1.09-23.4) adherence to dual method use. Conclusion To effectively prevent sexually transmitted diseases (STIs) and unplanned pregnancies, dual method use must be consistent and sustained. Future interventions to promote dual method use should focus on high-risk groups and additional dual method combinations (e.g., barrier plus intrauterine devices or implants). PMID:21843690

  9. Unraveling executive functioning in dual diagnosis

    NARCIS (Netherlands)

    Duijkers, J.C.L.M.; Vissers, C.T.W.M.; Egger, J.I.M.

    2016-01-01

    In mental health, the term dual-diagnosis is used for the co-occurrence of Substance Use Disorder (SUD) with another mental disorder. These co-occurring disorders can have a shared cause, and can cause/intensify each other's expression. Forming a threat to health and society, dual-diagnosis is

  10. A Dual Processing Approach to Stereotype Change.

    Science.gov (United States)

    Johnston, Lucy; Coolen, Petra

    1995-01-01

    Considered stereotype change within a framework of dual process models. Using three experiments, manipulated task involvement, source credibility, and message quality. Findings proved dual process as appropriate when considering the processing of stereotype-disconfirming information and processing's impact on existing stereotypes. Different…

  11. Dual leadership in a hospital practice

    DEFF Research Database (Denmark)

    Thude, Bettina Ravnborg; Thomsen, Svend Erik; Stenager, Egon

    2017-01-01

    , this study aims to analyse three different dual leadership pairs at a Danish hospital. Furthermore, this study develops a tool to characterize dual leadership teams from each other. Design/methodology/approach This is a qualitative study using semi-structured interviews. Six leaders were interviewed...... to clarify how dual leadership works in a hospital context. All interviews were transcribed and coded. During coding, focus was on the nine principles found in the literature and another principle was found by looking at the themes that were generic for all six interviews. Findings Results indicate...... in the hospital context and develops a categorizing tool for being able to distinguish dual leadership teams from each other. It is important to reveal if there are any indicators that can be used for optimising dual leadership teams in the health-care sector and in other organisations....

  12. Dual Headquarters Involvement in Subsidiary Innovation

    DEFF Research Database (Denmark)

    Nell, Phillip Christopher; Kappen, Philip; Dellestrand, Henrik

    innovation importance, i.e., an innovation that is important for the division and the corporate level, drives dual headquarters involvement in innovation development. Contrary to expectations, no significant effect of dual embeddedness on dual headquarters involvement is found. The network size....... The current paper takes on this neglected question by empirically investigating corporate and divisional headquarters direct involvement in innovation development projects at the subsidiary level. Analyses that draw upon 85 innovation development projects in 23 multinational enterprises reveal that dual...... of the developing subsidiary positively moderates the two aforementioned effects on dual headquarters involvement in innovation development. The results lend support for the notion that parenting in complex structures entails complex headquarters structures. Thus, the results question simplistic views...

  13. Dual Headquarters Involvement in Subsidiary Innovation

    DEFF Research Database (Denmark)

    Dellestrand, Henrik; Kappen, Philip; Nell, Phillip Christopher

    2014-01-01

    innovation importance, i.e., an innovation that is important for the division and the corporate level, drives dual headquarters involvement in innovation development. Contrary to expectations, no significant effect of dual embeddedness on dual headquarters involvement is found. The network size....... The current paper takes on this neglected question by empirically investigating corporate and divisional headquarters direct involvement in innovation development projects at the subsidiary level. Analyses that draw upon 85 innovation development projects in 23 multinational enterprises reveal that dual...... of the developing subsidiary positively moderates the two aforementioned effects on dual headquarters involvement in innovation development. The results lend support for the notion that parenting in complex structures entails complex headquarters structures. Thus, the results question simplistic views...

  14. Dual Headquarters Involvement in Subsidiary Innovation

    DEFF Research Database (Denmark)

    Dellestrand, Henrik; Kappen, Philip; Nell, Phillip Christopher

    2014-01-01

    . The current paper takes on this neglected question by empirically investigating corporate and divisional headquarters direct involvement in innovation development projects at the subsidiary level. Analyses that draw upon 85 innovation development projects in 23 multinational enterprises reveal that dual...... innovation importance, i.e., an innovation that is important for the division and the corporate level, drives dual headquarters involvement in innovation development. Contrary to expectations, no significant effect of dual embeddedness on dual headquarters involvement is found. The network size...... of the developing subsidiary positively moderates the two aforementioned effects on dual headquarters involvement in innovation development. The results lend support for the notion that parenting in complex structures entails complex headquarters structures. Thus, the results question simplistic views...

  15. Synthesis, Crystal Structure and Luminescent Property of Cd (II Complex with N-Benzenesulphonyl-L-leucine

    Directory of Open Access Journals (Sweden)

    Xishi Tai

    2012-09-01

    Full Text Available A new trinuclear Cd (II complex [Cd3(L6(2,2-bipyridine3] [L = N-phenylsulfonyl-L-leucinato] has been synthesized and characterized by elemental analysis, IR and X-ray single crystal diffraction analysis. The results show that the complex belongs to the orthorhombic, space group P212121 with a = 16.877(3 Å, b = 22.875(5 Å, c = 29.495(6 Å, α = β = γ = 90°, V = 11387(4 Å3, Z = 4, Dc= 1.416 μg·m−3, μ = 0.737 mm−1, F (000 = 4992, and final R1 = 0.0390, ωR2 = 0.0989. The complex comprises two seven-coordinated Cd (II atoms, with a N2O5 distorted pengonal bipyramidal coordination environment and a six-coordinated Cd (II atom, with a N2O4 distorted octahedral coordination environment. The molecules form one dimensional chain structure by the interaction of bridged carboxylato groups, hydrogen bonds and p-p interaction of 2,2-bipyridine. The luminescent properties of the Cd (II complex and N-Benzenesulphonyl-L-leucine in solid and in CH3OH solution also have been investigated.

  16. Leucine content of dietary proteins is a determinant of postprandial skeletal muscle protein synthesis in adult rats

    Directory of Open Access Journals (Sweden)

    Norton Layne E

    2012-07-01

    Full Text Available Abstract Background Leucine (Leu regulates muscle protein synthesis (MPS producing dose-dependent plasma Leu and MPS responses from free amino acid solutions. This study examined the role of Leu content from dietary proteins in regulation of MPS after complete meals. Methods Experiment 1 examined 4 protein sources (wheat, soy, egg, and whey with different Leu concentrations (6.8, 8.0, 8.8, and 10.9% (w/w, respectively on the potential to increase plasma Leu, activate translation factors, and stimulate MPS. Male rats (~250 g were trained for 14 day to eat 3 meals/day consisting of 16/54/30% of energy from protein, carbohydrates and fats. Rats were killed on d14 either before or 90 min after consuming a 4 g breakfast meal. Experiment 2 compared feeding wheat, whey, and wheat + Leu to determine if supplementing the Leu content of the wheat meal would yield similar anabolic responses as whey. Results In Experiment 1, only whey and egg groups increased post-prandial plasma Leu and stimulated MPS above food-deprived controls. Likewise, greater phosphorylation of p70 S6 kinase 1 (S6K1 and 4E binding protein-1 (4E-BP1 occurred in whey and egg groups versus wheat and soy groups. Experiment 2 demonstrated that supplementing wheat with Leu to equalize the Leu content of the meal also equalized the rates of MPS. Conclusion These findings demonstrate that Leu content is a critical factor for evaluating the quantity and quality of proteins necessary at a meal for stimulation of MPS.

  17. Hypoglycemic and Hypolipidemic Effects of Leucine, Zinc, and Chromium, Alone and in Combination, in Rats with Type 2 Diabetes.

    Science.gov (United States)

    Sadri, Hassan; Larki, Negar Nowroozi; Kolahian, Saeed

    2017-12-01

    For the increasing development of diabetes, dietary habits and using appropriate supplements can play important roles in the treatment or reduction of risk for this disease. The objective of this study was to investigate the effects of leucine (Leu), zinc (Zn), and chromium (Cr) supplementation, alone or in combination, in rats with type 2 diabetes (T2D). Seventy-seven adult male Wistar rats were randomly assigned in 11 groups, using nutritional supplements and insulin (INS) or glibenclamide (GLC). Supplementing Leu significantly reduced blood glucose, triglycerides (TG), nonesterified fatty acids (NEFA), low-density lipoprotein (LDL), and increased high-density lipoprotein (HDL) concentrations compared to vehicle-treated T2D animals, and those improvements were associated with reduced area under the 2-h blood glucose response curve (AUC). Supplementation of T2D animals with Zn improved serum lipid profile as well as blood glucose concentrations but was not comparable with the INS, GLC, and Leu groups. Supplementary Cr did not improve blood glucose and AUC in T2D rats, whereas it reduced serum TG and LDL and increased HDL concentrations. In conclusion, supplementation of diabetic rats with Leu was more effective in improving blood glucose and consequently decreasing glucose AUC than other nutritional supplements. Supplementary Zn and Cr only improved serum lipid profile. The combination of the nutritional supplements did not improve blood glucose level. Nevertheless, supplementation with Leu-Zn, Leu-Cr, Zn-Cr, and Leu-Zn-Cr led to an improved response in serum lipid profile over each supplement given alone.

  18. Genomic dissection and expression profiling revealed functional divergence in Triticum aestivum leucine rich repeat receptor like kinases (TaLRRKs

    Directory of Open Access Journals (Sweden)

    Shumayla .

    2016-09-01

    Full Text Available The leucine rich repeat receptor like kinases (LRRK constitute the largest subfamily of receptor like kinases (RLK, which play critical roles in plant development and stress responses. Herein, we identified 531 TaLRRK genes in Triticum aestivum (bread wheat, which were distributed throughout the A, B, and D sub-genomes and chromosomes. These were clustered into 233 homologous groups, which were mostly located on either homeologous chromosomes from various sub-genomes or in proximity on the same chromosome. A total of 255 paralogous genes were predicted which depicted the role of duplication events in expansion of this gene family. Majority of TaLRRKs consisted of trans-membrane region and localized on plasma-membrane. The TaLRRKs were further categorized into eight phylogenetic groups with numerous subgroups on the basis of sequence homology. The gene and protein structure in terms of exon/intron ratio, domains and motifs organization were found to be variably conserved across the different phylogenetic groups/subgroups, which indicated a potential divergence and neofunctionalization during evolution. High-throughput transcriptome data and quantitative real time PCR analyses in various developmental stages, and biotic and abiotic (heat, drought and salt stresses provided insight into modus operandi of TaLRRKs during these conditions. Distinct expression of majority of stress responsive TaLRRKs homologous genes suggested their specified role in a particular condition. These results provided a comprehensive analysis of various characteristic features including functional divergence, which may provide the way for future functional characterization of this important gene family in bread wheat.

  19. Free energy of a potassium ion in a model of the channel formed by an amphipathic leucine-serine peptide.

    Science.gov (United States)

    Smith, Graham R; Sansom, Mark S P

    2002-06-01

    We use molecular dynamics simulations to investigate the position-dependent free energy of a potassium ion in a model of an ion channel formed by the synthetic amphipathic leucine-serine peptide, LS3. The channel model is a parallel bundle of six LS3 helices around which are packed 146 methane-like spheres in order to mimic a membrane. At either end of and within the channel are 1051 water molecules, plus four ions (two potassium and two chloride). The free energy of a potassium ion in the channel was estimated using the weighted histogram analysis (WHAM) method. This is the first time to our knowledge that such a calculation has been carried out as a function of the position of an ion in three dimensions within a channel. The results indicate that for this channel, which is lined by hydrophilic serine sidechains, there is a relatively weak dependence of the free energy on the axial/off-axial position of the ion. There are some off-axis local minima, especially in the C-terminal half of the channel. Using the free energy results, a single channel current-voltage curve was estimated using a one-dimensional Nernst-Planck equation. Although reasonable agreement with experiment is achieved for K(+) ions flowing from the N-terminal to the C-terminal mouth, in the opposite direction the current is underestimated. This underestimation may be a consequence of under-sampling of the conformational dynamics of the channel. We suggest that our simulations may have captured, for example, a sub-conductance level (i.e. an incompletely open state) of the LS3 channel.

  20. X-linked familial exudative vitreoretinopathy caused by an arginine to leucine substitution in exon 3 of the Norrie gene

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, K.; Perry, Y.M.; Ferrell, R.E. [Univ. of Pittsburg, PA (United States)] [and others

    1994-09-01

    Familial exudative vitreoretinopathy (FEVR) is a disorder characterized by abnormal vascularization of the peripheral retina affecting both the retina and the vitreous body. This is a bilateral disorder and leads to a clinical phenotype resembling retinopathy of prematurity, but affected individuals experience a normal gestational period, and they do not have a history of oxygen therapy. Manifestations of the disorder may include retinal folds, retinal traction, sub- or intraretinal exudates, and in severe cases enophthalmos or phthisis ultimately leading to blindness. Autosomal dominant and X-linked patterns of segregation have been reported. We studied a large three-generation family in which FEVR segregated as an X-linked recessive trait. The Norrie gene was examined because of a prior report of mutation in this gene in a small X-linked FEVR family. Exons 1-3 of the Norrie gene were amplified and screened for mutations by single stranded conformational analysis. A variant conformer of exon 3 was observed in an affected male and in combination with the normal conformer in an obligate carrier female. Sequence analysis revealed a G{r_arrow}T transversion destroying an MspI restriction site. The mutation was present in all affected males, and all obligate carrier females were heterozygous for the mutation. The mutation was not present in unaffected males or in 108 randomly selected normal females. The G{r_arrow}T mutation leads to the substitution of a hydrophobic leucine residue for the positively charged arginine normally present at position 121 of the Norrie gene product. This study confirms that mutation in the Norrie gene can lead to the FEVR phenotype and the existence of allelic heterogeneity.

  1. A conservative isoleucine to leucine mutation causes major rearrangements and cold sensitivity in KlenTaq1 DNA polymerase.

    Science.gov (United States)

    Wu, Eugene Y; Walsh, Amanda R; Materne, Emma C; Hiltner, Emily P; Zielinski, Bryan; Miller, Bill R; Mawby, Lily; Modeste, Erica; Parish, Carol A; Barnes, Wayne M; Kermekchiev, Milko B

    2015-01-27

    Assembly of polymerase chain reactions at room temperature can sometimes lead to low yields or unintentional products due to mispriming. Mutation of isoleucine 707 to leucine in DNA polymerase I from Thermus aquaticus substantially decreases its activity at room temperature without compromising its ability to amplify DNA. To understand why a conservative change to the enzyme over 20 Å from the active site can have a large impact on its activity at low temperature, we solved the X-ray crystal structure of the large (5'-to-3' exonuclease-deleted) fragment of Taq DNA polymerase containing the cold-sensitive mutation in the ternary (E-DNA-ddNTP) and binary (E-DNA) complexes. The I707L KlenTaq1 ternary complex was identical to the wild-type in the closed conformation except for the mutation and a rotamer change in nearby phenylalanine 749, suggesting that the enzyme should remain active. However, soaking out of the nucleotide substrate at low temperature results in an altered binary complex made possible by the rotamer change at F749 near the tip of the polymerase O-helix. Surprisingly, two adenosines in the 5'-template overhang fill the vacated active site by stacking with the primer strand, thereby blocking the active site at low temperature. Replacement of the two overhanging adenosines with pyrimidines substantially increased activity at room temperature by keeping the template overhang out of the active site, confirming the importance of base stacking. These results explain the cold-sensitive phenotype of the I707L mutation in KlenTaq1 and serve as an example of a large conformational change affected by a conservative mutation.

  2. The pattern of proline, glutamic acid, and leucine-rich protein 1 expression in Chinese women with primary breast cancer.

    Science.gov (United States)

    Zhang, Yanzhi; Wang, Peng; Shi, Mumu; Sasano, Hironobu; Chan, Monica S M; Dai, Jiali; Guo, Lunshu; Liu, Ming; Wang, Xiaoyan; Ma, Ying; Wang, Lin

    2014-03-24

    Disparities of biomarkers' expression in breast cancer across different races and ethnicities have been well documented. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel ER coregulator, has been considered as a promising biomarker of breast cancer prognosis; however, the pattern of PELP1 expression in Chinese women with breast cancer has never been investigated. This study aims to provide useful reference on possible racial or ethnic differences of PELP1 expression in breast cancer by exploring the pattern of PELP1 expression in Chinese women with primary breast cancer. The expression of PELP1 in primary breast cancer samples from 130 Chinese female patients was detected by immunohistochemistry and correlated to other clinicopathological parameters; for comparison, the expression of PELP1 in 26 benign breast fibroadenomas was also examined. The overall value of the PELP1 H-score in breast cancer was significantly higher than that in breast fibroadenoma (p<0.001). In our breast cancer patients, the ER/HER-2-positive group had significantly higher PELP1 H-scores than their negative counterparts (p=0.003 for ER and p=0.022 for HER-2); the Ki-67-high group also showed significantly higher PELP1 H-scores than the Ki-67-low group (p=0.008). No significant association between PELP1 H-scores and other clinicopathological parameters was found. Finally, the PELP1 H-score in breast cancers of the luminal B subtype was significantly higher than that in the triple negative subtype (p=0.002). Overexpression of PELP1 in Chinese women with primary breast cancer appears to be associated with biomarkers of poor outcome; these results are similar to other reports based on Western populations.

  3. Critical role for a single leucine residue in leukemia induction by E2A-PBX1.

    Science.gov (United States)

    Bayly, Richard; Murase, Takayuki; Hyndman, Brandy D; Savage, Rachel; Nurmohamed, Salima; Munro, Kim; Casselman, Richard; Smith, Steven P; LeBrun, David P

    2006-09-01

    In roughly 5% of cases of acute lymphoblastic leukemia, a chromosomal translocation leads to expression of the oncogenic protein E2A-PBX1. The N-terminal portion of E2A-PBX1, encoded by the E2A gene, is identical in sequence to the corresponding portion of the E proteins E12/E47 and includes transcriptional activation domains. The C terminus consists of most of the HOX interacting transcription factor PBX1, including its DNA-binding homeodomain. Structure-function correlative experiments have suggested that oncogenesis by E2A-PBX1 requires an activation domain, called AD1, at the extreme N terminus. We recently demonstrated that a potentially helical portion of AD1 interacts directly with the transcriptional coactivator protein cyclic AMP response element-binding protein (CBP) and that this interaction is essential in the immortalization of primary bone marrow cells in tissue culture. Here we show that a conserved LXXLL motif within AD1 is required in the interaction between E2A-PBX1 and the KIX domain of CBP. We show by circular dichroism spectroscopy that the LXXLL-containing portion of AD1 undergoes a helical transition upon interacting with the KIX domain and that amino acid substitutions that prevent helix formation prevent both the KIX interaction and cell immortalization by E2A-PBX1. Perhaps most strikingly, substitution of a single, conserved leucine residue (L20) within the LXXLL motif impairs leukemia induction in mice after transplantation with E2A-PBX1-expressing bone marrow. The KIX domain of CBP mediates well-characterized interactions with several transcription factors of relevance to leukemia induction. Circumstantial evidence suggests that the side chain of L20 might interact with a deep hydrophobic pocket in the KIX domain. Therefore, our results serve to identify a potential new drug target.

  4. A Conservative Isoleucine to Leucine Mutation Causes Major Rearrangements and Cold Sensitivity in KlenTaq1 DNA Polymerase

    Science.gov (United States)

    2015-01-01

    Assembly of polymerase chain reactions at room temperature can sometimes lead to low yields or unintentional products due to mispriming. Mutation of isoleucine 707 to leucine in DNA polymerase I from Thermus aquaticus substantially decreases its activity at room temperature without compromising its ability to amplify DNA. To understand why a conservative change to the enzyme over 20 Å from the active site can have a large impact on its activity at low temperature, we solved the X-ray crystal structure of the large (5′-to-3′ exonuclease-deleted) fragment of Taq DNA polymerase containing the cold-sensitive mutation in the ternary (E–DNA–ddNTP) and binary (E–DNA) complexes. The I707L KlenTaq1 ternary complex was identical to the wild-type in the closed conformation except for the mutation and a rotamer change in nearby phenylalanine 749, suggesting that the enzyme should remain active. However, soaking out of the nucleotide substrate at low temperature results in an altered binary complex made possible by the rotamer change at F749 near the tip of the polymerase O-helix. Surprisingly, two adenosines in the 5′-template overhang fill the vacated active site by stacking with the primer strand, thereby blocking the active site at low temperature. Replacement of the two overhanging adenosines with pyrimidines substantially increased activity at room temperature by keeping the template overhang out of the active site, confirming the importance of base stacking. These results explain the cold-sensitive phenotype of the I707L mutation in KlenTaq1 and serve as an example of a large conformational change affected by a conservative mutation. PMID:25537790

  5. Constitutive expression of the Poplar FD-like basic leucine zipper transcription factor alters growth and bud development.

    Science.gov (United States)

    Parmentier-Line, Cécile M; Coleman, Gary D

    2016-01-01

    In poplar, the CO/FT regulatory module mediates seasonal growth cessation. Although FT interacts with the basic leucine zipper transcription factor FD, surprisingly little is known about the possible role of FD in bud development and growth cessation in trees. In this study, we examined the expression and localization of the poplar FD homolog, PtFD1, during short-day (SD)-induced bud development, and the consequences of overexpressing PtFD1 on bud development and shoot growth. PtFD1 was primarily expressed in apical and axillary buds and exhibited a transient increase in expression during the initial stages of SD-induced bud development. This transient increase declined with continued SD treatment. When PtFD1 was overexpressed in poplar, SD-induced growth cessation and bud formation were abolished. PTFD1 overexpression also resulted in precocious flowering of juvenile plants in long-day (LD) photoperiods. Because the phenotypes associated with overexpression of PtFD1 are similar to those observe when poplar FT1 is overexpressed (Science, 312, 2006, 1040), the expression and diurnal patterns of expression of both poplar FT1 and FT2 were characterized in PtFD1 overexpression poplars and found to be altered. DNA microarray analysis revealed few differences in gene expression between PtFD1 overexpressing poplars in LD conditions while extensive levels of differential gene expression occur in SD-treated plants. These results enforce the connection between the regulation of flowering and the regulation of growth cessation and bud development in poplar. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  6. Addition of arginine and leucine to low or normal protein diets: performance, carcass characteristics and intramuscular fat of finishing pigs

    International Nuclear Information System (INIS)

    Tous, N.; Lizardo, R.; Vilà, B.; Gispert, M.; Font-i-Furnols, M.; Esteve-Garcia, E.

    2016-01-01

    The effect of dietary crude protein (CP) reduction, supplementation with arginine or leucine on intramuscular fat (IMF) content was evaluated in (Landrace × Duroc) × Pietrain pigs. One-hundred and eight barrows (67 ± 4 kg) were assigned to six diets (n=6 pens of 3 pigs each): four normal CP diets containing 16% CP from 60 to 90 kg and 13% CP from 90 to 115 kg live weight (normal protein; normal protein high Arg, normal protein high Leu or normal protein high Arg and Leu) and two low CP diets containing 14% CP from 60 to 90 kg and 11.8% CP from 90 to 115 kg live weight (with or without supplementation of both amino acids). The high Leu and Arg diets were supplemented to obtain ratios of standard ileal digestible Leu/Lys and Arg/Lys of 4 and 2, respectively. While feed to gain ratio tended to increase (p<0.05), final weight (p<0.01), average daily feed intake (ADFI) (p<0.05) and average daily gain (ADG) (p<0.01) were reduced in animals fed low-protein diets supplemented with Arg and Leu compared to the ones fed low-protein diet unsupplemented. Marbling and IMF content in loin were reduced when Arg was supplemented (p<0.05) in normal protein diets. Supplementing these diets with Arg also reduced belly weight (p<0.01) and increased lean meat percentage (p<0.05). Contrary to the initial hypothesis, reduction of CP or dietary supplementation with Leu had no effect on IMF content and supplementation with Arg reduced it.

  7. Basic leucine zipper protein Cnc-C is a substrate and transcriptional regulator of the Drosophila 26S proteasome.

    Science.gov (United States)

    Grimberg, Kristian Björk; Beskow, Anne; Lundin, Daniel; Davis, Monica M; Young, Patrick

    2011-02-01

    While the 26S proteasome is a key proteolytic complex, little is known about how proteasome levels are maintained in higher eukaryotic cells. Here we describe an RNA interference (RNAi) screen of Drosophila melanogaster that was used to identify transcription factors that may play a role in maintaining levels of the 26S proteasome. We used an RNAi library against 993 Drosophila transcription factor genes to identify genes whose suppression in Schneider 2 cells stabilized a ubiquitin-green fluorescent protein reporter protein. This screen identified Cnc (cap 'n' collar [CNC]; basic region leucine zipper) as a candidate transcriptional regulator of proteasome component expression. In fact, 20S proteasome activity was reduced in cells depleted of cnc. Immunoblot assays against proteasome components revealed a general decline in both 19S regulatory complex and 20S proteasome subunits after RNAi depletion of this transcription factor. Transcript-specific silencing revealed that the longest of the seven transcripts for the cnc gene, cnc-C, was needed for proteasome and p97 ATPase production. Quantitative reverse transcription-PCR confirmed the role of Cnc-C in activation of transcription of genes encoding proteasome components. Expression of a V5-His-tagged form of Cnc-C revealed that the transcription factor is itself a proteasome substrate that is stabilized when the proteasome is inhibited. We propose that this single cnc gene in Drosophila resembles the ancestral gene family of mammalian nuclear factor erythroid-derived 2-related transcription factors, which are essential in regulating oxidative stress and proteolysis.

  8. Leucine responsive regulatory protein is involved in methionine metabolism and polyamine homeostasis in acetic acid bacterium Komagataeibacter europaeus.

    Science.gov (United States)

    Ishii, Yuri; Akasaka, Naoki; Sakoda, Hisao; Hidese, Ryota; Fujiwara, Shinsuke

    2018-01-01

    The leucine responsive regulatory protein (Lrp) is a global transcription factor that regulates the expression of genes involved in amino acid metabolism. To identify metabolic pathways and related genes under the control of Lrp in the acetic acid bacterium Komagataeibacter europaeus, the Kelrp null mutant (KGMA7110), which requires supplementation of all 20 amino acids for normal growth, was cultivated in minimal media containing or lacking particular amino acids. The results confirmed that KGMA7110 was auxotrophic for methionine and its catabolites S-adenosylmethionine (SAM) and spermidine (SPD). Quantitative reverse-transcription PCR analysis revealed lower metK (SAM synthetase) and mdtI (SPD efflux pump) expression in KGMA7110 than in wild-type KGMA0119. By contrast, these genes were significantly up-regulated in the Kelrp mutant lacking the putative C-terminal ligand-sensing domain (KGMA7203), indicating abnormal regulation of target genes by the KeLrp variant in KGMA7203. KGMA7110 (0.69±0.27 μM) and KGMA7203 (4.90±0.61 μM) excreted lower and higher quantities of SPD, respectively, than KGMA0119 (2.28±0.26 μM). This was attributed to imbalanced carbon flow caused by Kelrp disruption that respectively attenuated and stimulated metK and mdtI expression. These findings indicate that KeLrp plays a key role in SAM biosynthesis and intracellular polyamine homeostasis in K. europaeus. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  9. Divergent effects of endogenous and exogenous glucocorticoid-induced leucine zipper in animal models of inflammation and arthritis.

    Science.gov (United States)

    Ngo, Devi; Beaulieu, Elaine; Gu, Ran; Leaney, Alexandra; Santos, Leilani; Fan, Huapeng; Yang, Yuanhang; Kao, Wenping; Xu, Jiake; Escriou, Virginie; Loiler, Scott; Vervoordeldonk, Margriet J; Morand, Eric F

    2013-05-01

    Glucocorticoid-induced leucine zipper (GILZ) has effects on inflammatory pathways that suggest it to be a key inhibitory regulator of the immune system, and its expression is exquisitely sensitive to induction by glucocorticoids. We undertook this study to test our hypothesis that GILZ deficiency would exacerbate experimental immune-mediated inflammation and impair the effects of glucocorticoids on inflammation and, correspondingly, that exogenous GILZ would inhibit these events. GILZ(-/-) mice were generated using the Cre/loxP system, and responses were studied in delayed-type hypersensitivity (DTH), antigen-induced arthritis (AIA), K/BxN serum-transfer arthritis, and lipopolysaccharide (LPS)-induced cytokinemia. Therapeutic expression of GILZ via administration of recombinant adeno-associated virus expressing the GILZ gene (GILZ-rAAV) was compared to the effects of glucocorticoid in collagen-induced arthritis (CIA). Increased T cell proliferation and DTH were observed in GILZ(-/-) mice, but neither AIA nor K/BxN serum-transfer arthritis was affected, and GILZ deficiency did not affect LPS-induced cytokinemia. Deletion of GILZ did not impair the effects of exogenous glucocorticoids on CIA or cytokinemia. In contrast, overexpression of GILZ in joints significantly inhibited CIA, with an effect similar to that of dexamethasone. Despite effects on T cell activation, GILZ deficiency had no effect on effector pathways of arthritis and was unexpectedly redundant with effects of glucocorticoids. These findings do not support the hypothesis that GILZ is central to the actions of glucocorticoids, but the efficacy of exogenous GILZ in CIA suggests that further evaluation of GILZ in inflammatory disease is required. Copyright © 2013 by the American College of Rheumatology.

  10. Recombinant expression of TLR5 proteins by ligand supplementation and a leucine-rich repeat hybrid technique

    Science.gov (United States)

    Wilson, Ian A.

    2013-01-01

    Vertebrate TLR5 directly binds bacterial flagellin proteins and activates innate immune responses against pathogenic flagellated bacteria. Structural and biochemical studies on the TLR5/flagellin interaction have been challenging due to the technical difficulty in obtaining active recombinant proteins of TLR5 ectodomain (TLR5-ECD). We recently succeeded in production of the N-terminal leucine rich repeats (LRRs) of Danio rerio (dr) TLR5-ECD in a hybrid with another LRR protein, hagfish variable lymphocyte receptor (VLR), and determined the crystal structure of its complex with flagellin D1–D2–D3 domains. Although the structure provides valuable information about the interaction, it remains to be revealed how the C-terminal region of TLR5-ECD contributes to the interaction. Here, we present two methods to obtain recombinant TLR5 proteins that contain the C-terminal region in a baculovirus expression system. First, production of biologically active full-length drTLR5-ECD was substantially enhanced by supplementation of expression culture with purified flagellin proteins. Second, we designed TLR5-VLR hybrids using an LRR hybrid technology by single and double LRR fusions and were able to express diverse regions of drTLR5-ECD, allowing us to detect a previously unidentified TLR5/flagellin interaction. The drTLR5-VLR hybrid technique was also successfully applied to human TLR5-ECD whose expression has been highly problematic. These alternative TLR5 expression strategies provide an opportunity to obtain a complete view of the TLR5/flagellin interaction and can be applied to other LRR proteins. PMID:22989748

  11. A dietary supplementation with leucine and antioxidants is capable to accelerate muscle mass recovery after immobilization in adult rats.

    Directory of Open Access Journals (Sweden)

    Isabelle Savary-Auzeloux

    Full Text Available Prolonged inactivity induces muscle loss due to an activation of proteolysis and decreased protein synthesis; the latter is also involved in the recovery of muscle mass. The aim of the present work was to explore the evolution of muscle mass and protein metabolism during immobilization and recovery and assess the effect of a nutritional strategy for counteracting muscle loss and facilitating recovery. Adult rats (6-8 months were subjected to unilateral hindlimb casting for 8 days (I0-I8 and then permitted to recover for 10 to 40 days (R10-R40. They were fed a Control or Experimental diet supplemented with antioxidants/polyphenols (AOX (I0 to I8, AOX and leucine (AOX + LEU (I8 to R15 and LEU alone (R15 to R40. Muscle mass, absolute protein synthesis rate and proteasome activities were measured in gastrocnemius muscle in casted and non-casted legs in post prandial (PP and post absorptive (PA states at each time point. Immobilized gastrocnemius protein content was similarly reduced (-37% in both diets compared to the non-casted leg. Muscle mass recovery was accelerated by the AOX and LEU supplementation (+6% AOX+LEU vs. Control, P<0.05 at R40 due to a higher protein synthesis both in PA and PP states (+23% and 31% respectively, Experimental vs. Control diets, P<0.05, R40 without difference in trypsin- and chymotrypsin-like activities between diets. Thus, this nutritional supplementation accelerated the recovery of muscle mass via a stimulation of protein synthesis throughout the entire day (in the PP and PA states and could be a promising strategy to be tested during recovery from bed rest in humans.

  12. Addition of arginine and leucine to low or normal protein diets: performance, carcass characteristics and intramuscular fat of finishing pigs

    Energy Technology Data Exchange (ETDEWEB)

    Tous, N.; Lizardo, R.; Vilà, B.; Gispert, M.; Font-i-Furnols, M.; Esteve-Garcia, E.

    2016-07-01

    The effect of dietary crude protein (CP) reduction, supplementation with arginine or leucine on intramuscular fat (IMF) content was evaluated in (Landrace × Duroc) × Pietrain pigs. One-hundred and eight barrows (67 ± 4 kg) were assigned to six diets (n=6 pens of 3 pigs each): four normal CP diets containing 16% CP from 60 to 90 kg and 13% CP from 90 to 115 kg live weight (normal protein; normal protein high Arg, normal protein high Leu or normal protein high Arg and Leu) and two low CP diets containing 14% CP from 60 to 90 kg and 11.8% CP from 90 to 115 kg live weight (with or without supplementation of both amino acids). The high Leu and Arg diets were supplemented to obtain ratios of standard ileal digestible Leu/Lys and Arg/Lys of 4 and 2, respectively. While feed to gain ratio tended to increase (p<0.05), final weight (p<0.01), average daily feed intake (ADFI) (p<0.05) and average daily gain (ADG) (p<0.01) were reduced in animals fed low-protein diets supplemented with Arg and Leu compared to the ones fed low-protein diet unsupplemented. Marbling and IMF content in loin were reduced when Arg was supplemented (p<0.05) in normal protein diets. Supplementing these diets with Arg also reduced belly weight (p<0.01) and increased lean meat percentage (p<0.05). Contrary to the initial hypothesis, reduction of CP or dietary supplementation with Leu had no effect on IMF content and supplementation with Arg reduced it.

  13. Meal Distribution of Dietary Protein and Leucine Influences Long-Term Muscle Mass and Body Composition in Adult Rats.

    Science.gov (United States)

    Norton, Layne E; Wilson, Gabriel J; Moulton, Christopher J; Layman, Donald K

    2017-02-01

    Protein quantity and quality at a meal affect muscle protein synthesis (MPS); however, long-term effects of protein distribution at individual meals on adult muscle mass remain unknown. We used a precise feeding protocol in adult rats to determine if optimizing postmeal MPS response by modifying the meal distribution of protein, and the amino acid leucine (Leu), would affect muscle mass. Two studies were conducted with the use of male Sprague-Dawley rats (∼300 g) trained to consume 3 meals/d, then assigned to diet treatments with identical macronutrient contents (16% of energy from protein, 54% from carbohydrates, and 30% from fat) but differing in protein quality or meal distribution. Study 1 provided 16% protein at each meal with the use of whey, egg white, soy, or wheat gluten, with Leu concentrations of 10.9%, 8.8%, 7.7%, and 6.8% (wt:wt), respectively. Study 2 used whey protein with 16% protein at each meal [balanced distribution (BD)] or meals with 8%, 8%, and 27% protein [unbalanced distribution (UD)]. MPS and translation factors 4E binding protein 1 (4E-BP1) and ribosomal protein p70S6 (S6K) were determined before and after breakfast meals at 2 and 11 wk. Muscle weights and body composition were measured at 11 wk. In study 1, the breakfast meal increased MPS and S6K in whey and egg treatments but not in wheat or soy treatments. Gastrocnemius weight was greater in the whey group (2.20 ± 0.03 g) than the soy group (1.95 ± 0.04 g) (P 20% more body fat than the soy, egg, or whey groups (P protein and Leu influences MPS and long-term changes in adult muscle mass. © 2017 American Society for Nutrition.

  14. Dual Syntax for XML Languages

    DEFF Research Database (Denmark)

    Brabrand, Claus; Møller, Anders; Schwartzbach, Michael Ignatieff

    2008-01-01

    XML is successful as a machine processable data interchange format, but it is often too verbose for human use. For this reason, many XML languages permit an alternative more legible non-XML syntax. XSLT stylesheets are often used to convert from the XML syntax to the alternative syntax; however......, such transformations are not reversible since no general tool exists to automatically parse the alternative syntax back into XML. We present XSugar, which makes it possible to manage dual syntax for XML languages. An XSugar specification is built around a context-free grammar that unifies the two syntaxes...... of a language. Given such a specification, the XSugar tool can translate from alternative syntax to XML and vice versa. Moreover, the tool statically checks that the transformations are reversible and that all XML documents generated from the alternative syntax are valid according to a given XML schema....

  15. Dual Syntax for XML Languages

    DEFF Research Database (Denmark)

    Brabrand, Claus; Møller, Anders; Schwartzbach, Michael Ignatieff

    2005-01-01

    XML is successful as a machine processable data interchange format, but it is often too verbose for human use. For this reason, many XML languages permit an alternative more legible non-XML syntax. XSLT stylesheets are often used to convert from the XML syntax to the alternative syntax; however......, such transformations are not reversible since no general tool exists to automatically parse the alternative syntax back into XML. We present XSugar, which makes it possible to manage dual syntax for XML languages. An XSugar specification is built around a context-free grammar that unifies the two syntaxes...... of a language. Given such a specification, the XSugar tool can translate from alternative syntax to XML and vice versa. Moreover, the tool statically checks that the transformations are reversible and that all XML documents generated from the alternative syntax are valid according to a given XML schema....

  16. LAMPF dual-energy operation

    International Nuclear Information System (INIS)

    Hagerman, D.C.; Hill, R.E.; Hunter, W.T.; Macek, R.J.; van Dyck, O.B.

    1981-01-01

    The Los Alamos Meson Physics Facility (LAMPF) operated with simultaneous H + and H - beams until June 1980, when a method of providing a variable energy H - beam as well as a full-energy H + beam was brought into use. The scheme is based on time sharing between H + and H - beam pulses. It is now possible to provide H - beams with energy as low as 300 MeV along with the usual 800-MeV H + beams. The method requires a reduction in duty factor of the H + and H - beams; however, the total duty factor has been increased to 9% which compensates in large measure for the reduction due to dual-energy operation. The necessary modifications to the beam switchyard and accelerator timing systems are described

  17. Dual-band infrared camera

    Science.gov (United States)

    Vogel, H.; Schlemmer, H.

    2005-10-01

    Every year, numerous accidents happen on European roads due to bad visibility (fog, night, heavy rain). Similarly, the dramatic aviation accidents of year 2001 in Milan and Zurich have reminded us that aviation safety is equally affected by reduced visibility. A dual-band thermal imager was developed in order to raise human situation awareness under conditions of reduced visibility especially in the automotive and aeronautical context but also for all transportation or surveillance tasks. The chosen wavelength bands are the Short Wave Infrared SWIR and the Long Wave Infrared LWIR band which are less obscured by reduced visibility conditions than the visible band. Furthermore, our field tests clearly show that the two different spectral bands very often contain complementary information. Pyramidal fusion is used to integrate complementary and redundant features of the multi-spectral images into a fused image which can be displayed on a monitor to provide more and better information for the driver or pilot.

  18. GOES-R Dual Isolation

    Science.gov (United States)

    Freesland, Doug; Carter, Delano; Chapel, Jim; Clapp, Brian; Howat, John; Krimchansky, Alexander

    2015-01-01

    The Geostationary Operational Environmental Satellite-R Series (GOES-R) is the first of the next generation geostationary weather satellites, scheduled for delivery in late 2015. GOES-R represents a quantum increase in Earth and solar weather observation capabilities, with 4 times the resolution, 5 times the observation rate, and 3 times the number of spectral bands for Earth observations. With the improved resolution, comes the instrument suite's increased sensitive to disturbances over a broad spectrum 0-512 Hz. Sources of disturbance include reaction wheels, thruster firings for station keeping and momentum management, gimbal motion, and internal instrument disturbances. To minimize the impact of these disturbances, the baseline design includes an Earth Pointed Platform (EPP), a stiff optical bench to which the two nadir pointed instruments are collocated together with the Guidance Navigation & Control (GN&C) star trackers and Inertial Measurement Units (IMUs). The EPP is passively isolated from the spacecraft bus with Honeywell D-Strut isolators providing attenuation for frequencies above approximately 5 Hz in all six degrees-of-freedom. A change in Reaction Wheel Assembly (RWA) vendors occurred very late in the program. To reduce the risk of RWA disturbances impacting performance, a secondary passive isolation system manufactured by Moog CSA Engineering was incorporated under each of the six 160 Nms RWAs, tuned to provide attenuation at frequencies above approximately 50 Hz. Integrated wheel and isolator testing was performed on a Kistler table at NASA Goddard Space Flight Center. High fidelity simulations were conducted to evaluate jitter performance for four topologies: 1) hard mounted no isolation, 2) EPP isolation only, 2) RWA isolation only, and 4) dual isolation. Simulation results demonstrate excellent performance relative to the pointing stability requirements, with dual isolated Line of Sight (LOS) jitter less than 1 micron rad.

  19. Dual antiretroviral therapy for HIV infection.

    Science.gov (United States)

    Soriano, Vicente; Fernandez-Montero, Jose Vicente; Benitez-Gutierrez, Laura; Mendoza, Carmen de; Arias, Ana; Barreiro, Pablo; Peña, José M; Labarga, Pablo

    2017-08-01

    For two decades, triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy. At this time, combinations of dolutegravir plus rilpivirine represent the best dual regimen. Longer follow-up and larger study populations are needed before supporting dolutegravir plus lamivudine. In contrast, dual therapy based on maraviroc is less effective. Although dual regimens with boosted protease inhibitors plus either lamivudine or raltegravir may be effective, they are penalized by metabolic side effects and risk for drug interactions. The newest dual regimens could save money, reduce toxicity and spare drug options for the future. For the first time in HIV therapeutics, less can be more. Dual therapy switching has set up a new paradigm in HIV treatment that uses induction-maintenance.

  20. Novel CFT duals for extreme black holes

    International Nuclear Information System (INIS)

    Chen Bin; Zhang Jiaju

    2012-01-01

    In this paper, we study the CFT duals for extreme black holes in the stretched horizon formalism. We consider the extremal RN, Kerr-Newman-AdS-dS, as well as the higher dimensional Kerr-AdS-dS black holes. In all these cases, we reproduce the well-established CFT duals. Actually we show that for stationary extreme black holes, the stretched horizon formalism always gives rise to the same dual CFT pictures as the ones suggested by ASG of corresponding near horizon geometries. Furthermore, we propose new CFT duals for 4D Kerr-Newman-AdS-dS and higher dimensional Kerr-AdS-dS black holes. We find that every dual CFT is defined with respect to a rotation in certain angular direction, along which the translation defines a U(1) Killing symmetry. In the presence of two sets of U(1) symmetry, the novel CFT duals are generated by the modular group SL(2,Z), and for n sets of U(1) symmetry there are general CFT duals generated by T-duality group SL(n,Z).

  1. Effects of Whey, Soy or Leucine Supplementation with 12 Weeks of Resistance Training on Strength, Body Composition, and Skeletal Muscle and Adipose Tissue Histological Attributes in College-Aged Males

    Directory of Open Access Journals (Sweden)

    C. Brooks Mobley

    2017-09-01

    Full Text Available We sought to determine the effects of L-leucine (LEU or different protein supplements standardized to LEU (~3.0 g/serving on changes in body composition, strength, and histological attributes in skeletal muscle and adipose tissue. Seventy-five untrained, college-aged males (mean ± standard error of the mean (SE; age = 21 ± 1 years, body mass = 79.2 ± 0.3 kg were randomly assigned to an isocaloric, lipid-, and organoleptically-matched maltodextrin placebo (PLA, n = 15, LEU (n = 14, whey protein concentrate (WPC, n = 17, whey protein hydrolysate (WPH, n = 14, or soy protein concentrate (SPC, n = 15 group. Participants performed whole-body resistance training three days per week for 12 weeks while consuming supplements twice daily. Skeletal muscle and subcutaneous (SQ fat biopsies were obtained at baseline (T1 and ~72 h following the last day of training (T39. Tissue samples were analyzed for changes in type I and II fiber cross sectional area (CSA, non-fiber specific satellite cell count, and SQ adipocyte CSA. On average, all supplement groups including PLA exhibited similar training volumes and experienced statistically similar increases in total body skeletal muscle mass determined by dual X-ray absorptiometry (+2.2 kg; time p = 0.024 and type I and II fiber CSA increases (+394 μm2 and +927 μm2; time p < 0.001 and 0.024, respectively. Notably, all groups reported increasing Calorie intakes ~600–800 kcal/day from T1 to T39 (time p < 0.001, and all groups consumed at least 1.1 g/kg/day of protein at T1 and 1.3 g/kg/day at T39. There was a training, but no supplementation, effect regarding the reduction in SQ adipocyte CSA (−210 μm2; time p = 0.001. Interestingly, satellite cell counts within the WPC (p < 0.05 and WPH (p < 0.05 groups were greater at T39 relative to T1. In summary, LEU or protein supplementation (standardized to LEU content does not provide added benefit in increasing whole-body skeletal muscle mass or strength above PLA

  2. A new Fenchel dual problem in vector optimization

    Indian Academy of Sciences (India)

    Abstract. We introduce a new Fenchel dual for vector optimization problems inspired by the form of the Fenchel dual attached to the scalarized primal multiobjective problem. For the vector primal-dual pair we prove weak and strong duality. Furthermore, we recall two other Fenchel-type dual problems introduced in the past ...

  3. Properties of dual codes defined by nondegenerate forms

    Directory of Open Access Journals (Sweden)

    Steve Szabo

    2017-01-01

    Full Text Available Dual codes are defined with respect to non-degenerate sesquilinear or bilinear forms over a finite Frobenius ring. These dual codes have the properties one expects from a dual code: they satisfy a double-dual property, they have cardinality complementary to that of the primal code, and they satisfy the MacWilliams identities for the Hamming weight.

  4. Effects of leucine supplementation and serum withdrawal on branched-chain amino acid pathway gene and protein expression in mouse adipocytes.

    Directory of Open Access Journals (Sweden)

    Abderrazak Kitsy

    Full Text Available The essential branched-chain amino acids (BCAA, leucine, valine and isoleucine, are traditionally associated with skeletal muscle growth and maintenance, energy production, and generation of neurotransmitter and gluconeogenic precursors. Recent evidence from human and animal model studies has established an additional link between BCAA levels and obesity. However, details of the mechanism of regulation of BCAA metabolism during adipogenesis are largely unknown. We interrogated whether the expression of genes and proteins involved in BCAA metabolism are sensitive to the adipocyte differentiation process, and responsive to nutrient stress from starvation or BCAA excess. Murine 3T3-L1 preadipocytes were differentiated to adipocytes under control conditions and under conditions of L-leucine supplementation or serum withdrawal. RNA and proteins were isolated at days 0, 4 and 10 of differentiation to represent pre-differentiation, early differentiation and late differentiation stages. Expression of 16 BCAA metabolism genes was quantified by quantitative real-time PCR. Expression of the protein levels of branched-chain amino acid transaminase 2 (Bcat2 and branched-chain alpha keto acid dehydrogenase (Bckdha was quantified by immunoblotting. Under control conditions, all genes displayed induction of gene expression during early adipogenesis (Day 4 compared to Day 0. Leucine supplementation resulted in an induction of Bcat2 and Bckdha genes during early and late differentiation. Western blot analysis demonstrated condition-specific concordance between gene and protein expression. Serum withdrawal resulted in undetectable Bcat2 and Bckdha protein levels at all timepoints. These results demonstrate that the expression of genes related to BCAA metabolism are regulated during adipocyte differentiation and influenced by nutrient levels. These results provide additional insights on how BCAA metabolism is associated with adipose tissue function and extends our

  5. Isolation of a novel leucine-rich repeat receptor-like kinase (OsLRR2 gene from rice and analysis of its relation to abiotic stress responses

    Directory of Open Access Journals (Sweden)

    Yongrong Liao

    2017-01-01

    Full Text Available Leucine-rich repeat receptor-like kinase protein (LRR-RLK is involved in a wide range of biological pathways. So far, the function of LRR-RLK in the growth, developmental processes and various external stimuli has still not been clearly elucidated in rice (Oryza sativa L.. To understand the mechanism(s underlying stress response and to discover novel stress-tolerance genes in rice, we analysed a global genome expression profiling of the indica cultivar Pei'ai 64S subjected to cold, drought or heat stresses. Expression profiles were obtained for leaf and panicle tissues at seedling, booting and heading stages from plants under no stress, or cold, drought or heat stress, using the GeneChip Rice Genome Array (Affymetrix representing 51279 transcripts from japonica and indica rice. We identified a gene, OsLRR2 (Oryza sativa L. leucine-rich repeat receptor-like kinase 2, GenBank accession: EAZ02952.1, which was highly up-regulated under cold and drought stress. In order to study its function in stress tolerance, we cloned the cDNA of the gene through amplification by reverse-transcription polymerase chain reaction. Sequence analysis showed that the cDNA encodes a protein of 375 amino-acid residues with molecular weight of ≈40.62 kD and pI of ≈5.75. The sequence databases search found that the open reading frame of OsLRR2 contained a leucine-rich repeats domain. Analysis of the putative promoter region for candidate cis-regulatory elements identified five matches to cis-elements related to stress responses, suggesting that OsLRR2 could be considered a new candidate gene involved in stress tolerance in rice.

  6. A conserved leucine zipper-like motif accounts for strong tetramerization capabilities of SEPALLATA-like MADS-domain transcription factors.

    Science.gov (United States)

    Rümpler, Florian; Theißen, Günter; Melzer, Rainer

    2018-02-21

    The development of angiosperm flowers is regulated by homeotic MIKC-type MADS-domain transcription factors that activate or repress target genes via the formation of DNA-bound, organ specific tetrameric complexes. The protein-protein interaction (PPI) capabilities differ considerably between different MIKC-type proteins. The floral homeotic protein SEPALLATA3 (SEP3) acts as a hub that incorporates numerous other MADS-domain proteins into tetrameric complexes that would otherwise not form. However, the molecular mechanisms that underlie these promiscuous interactions remain largely unknown. In this study we created a collection of amino acid substitution mutants of SEP3 to quantify the contribution of individual residues on protein tetramerization during DNA-binding, employing methods of molecular biophysics. We show that leucine residues at certain key positions form a leucine zipper structure that is essential for tetramerization of SEP3, whereas the introduction of physicochemically very similar residues at respective sites impedes the formation of DNA-bound tetramers. Comprehensive molecular evolutionary analyses of MADS-domain proteins from a diverse set of flowering plants revealed exceedingly high conservation of the identified leucine residues within SEP3-subfamily proteins throughout angiosperm evolution. In contrast, MADS-domain proteins that are unable to tetramerize among themselves exhibit preferences for other amino acids at homologous sites. Our findings indicate that the subfamily-specific conservation of amino acid residues at just a few key positions account for subfamily-specific interaction capabilities of MADS-domain transcription factors and shaped the present-day structure of the PPI network controlling flower development.

  7. Sample Dilution and Bacterial Community Composition Influence Empirical Leucine-to-Carbon Conversion Factors in Surface Waters of the World's Oceans

    KAUST Repository

    Teira, Eva

    2015-09-25

    The transformation of leucine incorporation rates to prokaryotic carbon production rates requires the use of either theoretical or empirically determined conversion factors. Empirical leucine-to-carbon conversion factors (eCFs) vary widely across environments, and little is known about their potential controlling factors. We conducted 10 surface seawater manipulation experiments across the world\\'s oceans, where the growth of the natural prokaryotic assemblages was promoted by filtration (i.e., removal of grazers [F treatment]) or filtration combined with dilution (i.e., also relieving resource competition [FD treatment]). The impact of sunlight exposure was also evaluated in the FD treatments, and we did not find a significant effect on the eCFs. The eCFs varied from 0.09 to 1.47 kg C mol Leu−1 and were significantly lower in the FD than in the F samples. Also, changes in bacterial community composition during the incubations, as assessed by automated ribosomal intergenic spacer analysis (ARISA), were more pronounced in the FD than in the F treatments, compared to unmanipulated controls. Thus, we discourage the common procedure of diluting samples (in addition to filtration) for eCF determination. The eCFs in the filtered treatment were negatively correlated with the initial chlorophyll a concentration, picocyanobacterial abundance (mostly Prochlorococcus), and the percentage of heterotrophic prokaryotes with high nucleic acid content (%HNA). The latter two variables explained 80% of the eCF variability in the F treatment, supporting the view that both Prochlorococcus and HNA prokaryotes incorporate leucine in substantial amounts, although this results in relatively low carbon production rates in the oligotrophic ocean.

  8. The polarization of the G-protein activated potassium channel GIRK5 to the vegetal pole of Xenopus laevis oocytes is driven by a di-leucine motif.

    Directory of Open Access Journals (Sweden)

    Beatriz Díaz-Bello

    Full Text Available The G protein-coupled inwardly-rectifying potassium channels (known as GIRK or Kir3 form functional heterotetramers gated by G-βγ subunits. GIRK channels participate in heart rate modulation and neuronal postsynaptic inhibition in mammals. In Xenopus laevis oocytes, GIRK5 is a functional homomultimer. Previously, we found that phosphorylation of a tyrosine (Y16 at its N-terminus downregulates the surface expression of GIRK5. In this work, we elucidated the subcellular localization and trafficking of GIRK5 in oocytes. Several EGFP-GIRK5 chimeras were produced and an ECFP construct was used to identify the endoplasmic reticulum (ER. Whereas GIRK5-WT was retained in the ER at the animal pole, the phospho-null GIRK5-Y16A was localized to the vegetal pole. Interestingly, a construct with an N-terminal Δ25 deletion produced an even distribution of the channel in the whole oocyte. Through an alanine-scan, we identified an acidic cluster/di-leucine sorting-signal recognition motif between E17 and I22. We quantified the effect of each amino acid residue within this di-leucine motif in determining the distribution of GIRK5 to the animal and vegetal poles. We found that Y16 and I22 contributed to functional expression and were dominant in the polarization of GIRK5. We thus conclude that the N-terminal acidic di-leucine motif of GIRK5 determines its retention and polarized trafficking within Xl oocytes.

  9. Effects of irradiation on intracellular protein synthesis in demilune of mouse sublingual gland; Study of electron microscopic autoradiography with [sup 3]H-leucine

    Energy Technology Data Exchange (ETDEWEB)

    Ohki, Ikuko; Nasu, Masanori; Matsunaga, Hajime; Furumoto, Keiichi (Nippon Dental Univ., Tokyo (Japan))

    1994-08-01

    The effects of radiation on amino acid transport in demilune of the sublingual glands were examined in mice. After 10 Gy X-ray irradiation to the submandibular region, [sup 3]H-leucine was administered to these mice. Three days after irradiation, light microscopic autoradiograms and electron microscopic autoradiograms were obtained to determine the silver grain count in demilune and the distribution of silver grain in the organelles of these cells involved in protein synthesis. Both non-irradiated and irradiated groups showed a peak count 30 minutes after the administration of [sup 3]H-leucine and a tendency to decrease in the count thereafter. The magnitude of the chronological change in this parameter was smaller in the irradiated group than in the non-irradiated group. The percentage of silver grain in the rough endoplasmic reticulum also reached a peak 30 minutes after [sup 3]H-leucine administration in both non-irradiated and irradiated groups. Thereafter the percentage tended to decrease with time in the non-irradiated group. In the irradiated group, on the other hand, the percentage showed little change from the peak level at 60, 120, and 180 minutes. In the non-irradiated group, the percentage of silver grain in the Golgi apparatus was relatively high at 30 and 60 minutes. The percentage tended to be low at 120 and 180 minutes in the irradiated group. In the non-irradiated group, the percentage of silver grain in condencing vacuoles reached a peak at 60 minutes and decreased gradually thereafter. This parameter reached a peak at 30 minutes in the irradiated group. The percentage of silver grain in the secretory granules increased with time in both non-irradiated and irradiated groups. At 30 and 60 minutes, the percentage was significantly higher in the irradiated group than in the non-irradiated group. At 180 minutes, however, it was significantly lower in the irradiated group than in the non-irradiated group. (author).

  10. Expanded roles of leucine-responsive regulatory protein in transcription regulation of the Escherichia coli genome: Genomic SELEX screening of the regulation targets

    OpenAIRE

    Shimada, Tomohiro; Saito, Natsumi; Maeda, Michihisa; Tanaka, Kan; Ishihama, Akira

    2015-01-01

    Leucine-responsive regulatory protein (Lrp) is a transcriptional regulator for the genes involved in transport, biosynthesis and catabolism of amino acids in Escherichia coli. In order to identify the whole set of genes under the direct control of Lrp, we performed Genomic SELEX screening and identified a total of 314 Lrp-binding sites on the E. coli genome. As a result, the regulation target of Lrp was predicted to expand from the hitherto identified genes for amino acid metabolism to a set ...

  11. Authentication of pure L-leucine products manufactured in China by discriminating between plant and animal sources using nitrogen stable isotope technique.

    Science.gov (United States)

    Huang, Jingyu; Nkrumah, Philip N; Appiah-Sefah, Gloria; Tang, Shijiang

    2013-03-01

     L-leucine products among other branched chain amino acid supplements are highly susceptible to economically motivated adulteration. Curbing this menace is critical and timely. Hence, the δ(15) N composition of the L-leucine derived from plants and animals sources was estimated. The trophic enrichment phenomenon of δ(15) N composition was utilized to elucidate the sources. We finally established the distinction between the respective sources. Samples of plant sources (maize and soybean) and that of animal sources (pig fur and duck feather) were analyzed for δ(15) N isotopic signatures. An elemental analyzer which was connected to an isotope ratio mass spectrometer operated in the continuous flow mode was utilized. The raw materials were obtained from China. Statistical analysis was performed using descriptive statistics and one-way analysis of variance. The results indicated lower δ(15) N values of range -0.7344‰ to 2.384‰ and 1.032‰ to 2.064‰ for maize and soybean samples, respectively. Whereas, a range of 3.860‰ to 6.011‰ and 5.875‰ to 6.011‰ was, respectively, detected in pig fur and duck feather samples. The δ(15) N difference in plants and animals samples was significant (F = 165.0; P = 1.675 E-10 for maize and pig fur samples; F = 212.8; P = 0.0001284 for soybean and duck feather samples). It was observed that δ(15) N trophic enrichment is helpful in elucidating the respective sources. The authors can emphatically assert that the range of δ(15) N composition of L-leucine derived from plants sources within the study area is -1.000‰ to 3.000‰ whereas the range in animal sources is 4.000‰ to 9.000‰. Practical Application This study provides a reliable approach in verifying the authenticity of not only L-leucine products but also other branched chain amino acid supplements and thereby would help in fraud detection of any economically motivated adulteration and mislabeling of these products. When coupled with H and O stable

  12. SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element.

    OpenAIRE

    Hua, X; Yokoyama, C; Wu, J; Briggs, M R; Brown, M S; Goldstein, J L; Wang, X

    1993-01-01

    We report the cDNA cloning of SREBP-2, the second member of a family of basic-helix-loop-helix-leucine zipper (bHLH-Zip) transcription factors that recognize sterol regulatory element 1 (SRE-1). SRE-1, a conditional enhancer in the promoters for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A synthase genes, increases transcription in the absence of sterols and is inactivated when sterols accumulate. Human SREBP-2 contains 1141 amino acids and is 47% identical t...

  13. Native whey protein with high levels of leucine results in similar post-exercise muscular anabolic responses as regular whey protein: a randomized controlled trial.

    Science.gov (United States)

    Hamarsland, Håvard; Nordengen, Anne Lene; Nyvik Aas, Sigve; Holte, Kristin; Garthe, Ina; Paulsen, Gøran; Cotter, Matthew; Børsheim, Elisabet; Benestad, Haakon B; Raastad, Truls

    2017-01-01

    Protein intake is essential to maximally stimulate muscle protein synthesis, and the amino acid leucine seems to possess a superior effect on muscle protein synthesis compared to other amino acids. Native whey has higher leucine content and thus a potentially greater anabolic effect on muscle than regular whey (WPC-80). This study compared the acute anabolic effects of ingesting 2 × 20 g of native whey protein, WPC-80 or milk protein after a resistance exercise session. A total of 24 young resistance trained men and women took part in this double blind, randomized, partial crossover, controlled study. Participants received either WPC-80 and native whey ( n  = 10), in a crossover design, or milk ( n  = 12). Supplements were ingested immediately (20 g) and two hours after (20 g) a bout of heavy-load lower body resistance exercise. Blood samples and muscle biopsies were collected to measure plasma concentrations of amino acids by gas-chromatography mass spectrometry, muscle phosphorylation of p70S6K, 4E-BP1 and eEF-2 by immunoblotting, and mixed muscle protein synthesis by use of [ 2 H 5 ]phenylalanine-infusion, gas-chromatography mass spectrometry and isotope-ratio mass spectrometry. Being the main comparison, differences between native whey and WPC-80 were analysed by a one-way ANOVA and comparisons between the whey supplements and milk were analysed by a two-way ANOVA. Native whey increased blood leucine concentrations more than WPC-80 and milk ( P  whey ingestion induced a greater phosphorylation of p70S6K than milk 180 min after exercise ( P  = 0.03). Muscle protein synthesis rates increased 1-3 h hours after exercise with WPC-80 (0.119%), and 1-5 h after exercise with native whey (0.112%). Muscle protein synthesis rates were higher 1-5 h after exercise with native whey than with milk (0.112% vs. 0.064, P  = 0.023). Despite higher-magnitude increases in blood leucine concentrations with native whey, it was not superior to WPC-80

  14. A virtual high-throughput screening approach to the discovery of novel inhibitors of the bacterial leucine transporter, LeuT

    DEFF Research Database (Denmark)

    Simmons, Katie J; Gotfryd, Kamil; Billesbølle, Christian B

    2013-01-01

    Abstract Membrane proteins are intrinsically involved in both human and pathogen physiology, and are the target of 60% of all marketed drugs. During the past decade, advances in the studies of membrane proteins using X-ray crystallography, electron microscopy and NMR-based techniques led to the e...... this is a virtual high-throughput screening (vHTS) technique initially developed for soluble proteins. This paper describes application of this technique to the discovery of inhibitors of the leucine transporter (LeuT), a member of the neurotransmitter:sodium symporter (NSS) family....

  15. Braking System Integration in Dual Mode Systems

    Science.gov (United States)

    1974-05-01

    An optimal braking system for Dual Mode is a complex product of vast number of multivariate, interdependent parameters that encompass on-guideway and off-guideway operation as well as normal and emergency braking. : Details of, and interralations amo...

  16. The structure of dual Grassmann codes

    DEFF Research Database (Denmark)

    Beelen, Peter; Pinero, Fernando

    2016-01-01

    In this article we study the duals of Grassmann codes, certain codes coming from the Grassmannian variety. Exploiting their structure, we are able to count and classify all their minimum weight codewords. In this classification the lines lying on the Grassmannian variety play a central role....... Related codes, namely the affine Grassmann codes, were introduced more recently in Beelen et al. (IEEE Trans Inf Theory 56(7):3166–3176, 2010), while their duals were introduced and studied in Beelen et al. (IEEE Trans Inf Theory 58(6):3843–3855, 2010). In this paper we also classify and count the minimum...... weight codewords of the dual affine Grassmann codes. Combining the above classification results, we are able to show that the dual of a Grassmann code is generated by its minimum weight codewords. We use these properties to establish that the increase of value of successive generalized Hamming weights...

  17. Dual Eligibles and Potentially Avoidable Hospitalizations

    Data.gov (United States)

    U.S. Department of Health & Human Services — About 25 percent of the hospitalizations for dual eligible beneficiaries in 2005 were potentially avoidable. Medicare and Medicaid spending for those potentially...

  18. Dual Enrollment Participation from the Student Perspective

    Science.gov (United States)

    Kanny, M. Allison

    2015-01-01

    This chapter examines the experiences of five high school students previously enrolled in dual enrollment courses, and discusses the perceived benefits and disadvantages of these experiences from the student perspective.

  19. Dual Career Marriages: Elements for Potential Success.

    Science.gov (United States)

    Maples, Mary F.

    1981-01-01

    Examines the family and work relationships of dual career couples and discusses the advantages and disadvantages of these relationships. Various ingredients including personality traits that contribute to the success of the two-career partnership are listed. (RC)

  20. Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

    Science.gov (United States)

    Wegner, Florian; Wilke, Florian; Raab, Peter; Tayeb, Said Ben; Boeck, Anna-Lena; Haense, Cathleen; Trebst, Corinna; Voss, Elke; Schrader, Christoph; Logemann, Frank; Ahrens, Jörg; Leffler, Andreas; Rodriguez-Raecke, Rea; Dengler, Reinhard; Geworski, Lilli; Bengel, Frank M; Berding, Georg; Stangel, Martin; Nabavi, Elham

    2014-06-20

    Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

  1. Global expression analysis of nucleotide binding site-leucine rich repeat-encoding and related genes in Arabidopsis

    Science.gov (United States)

    Tan, Xiaoping; Meyers, Blake C; Kozik, Alexander; West, Marilyn AL; Morgante, Michele; St Clair, Dina A; Bent, Andrew F; Michelmore, Richard W

    2007-01-01

    Background Nucleotide binding site-leucine rich repeat (NBS-LRR)-encoding genes comprise the largest class of plant disease resistance genes. The 149 NBS-LRR-encoding genes and the 58 related genes that do not encode LRRs represent approximately 0.8% of all ORFs so far annotated in Arabidopsis ecotype Col-0. Despite their prevalence in the genome and functional importance, there was little information regarding expression of these genes. Results We analyzed the expression patterns of ~170 NBS-LRR-encoding and related genes in Arabidopsis Col-0 using multiple analytical approaches: expressed sequenced tag (EST) representation, massively parallel signature sequencing (MPSS), microarray analysis, rapid amplification of cDNA ends (RACE) PCR, and gene trap lines. Most of these genes were expressed at low levels with a variety of tissue specificities. Expression was detected by at least one approach for all but 10 of these genes. The expression of some but not the majority of NBS-LRR-encoding and related genes was affected by salicylic acid (SA) treatment; the response to SA varied among different accessions. An analysis of previously published microarray data indicated that ten NBS-LRR-encoding and related genes exhibited increased expression in wild-type Landsberg erecta (Ler) after flagellin treatment. Several of these ten genes also showed altered expression after SA treatment, consistent with the regulation of R gene expression during defense responses and overlap between the basal defense response and salicylic acid signaling pathways. Enhancer trap analysis indicated that neither jasmonic acid nor benzothiadiazole (BTH), a salicylic acid analog, induced detectable expression of the five NBS-LRR-encoding genes and one TIR-NBS-encoding gene tested; however, BTH did induce detectable expression of the other TIR-NBS-encoding gene analyzed. Evidence for alternative mRNA polyadenylation sites was observed for many of the tested genes. Evidence for alternative splicing

  2. Global expression analysis of nucleotide binding site-leucine rich repeat-encoding and related genes in Arabidopsis

    Directory of Open Access Journals (Sweden)

    St Clair Dina A

    2007-10-01

    Full Text Available Abstract Background Nucleotide binding site-leucine rich repeat (NBS-LRR-encoding genes comprise the largest class of plant disease resistance genes. The 149 NBS-LRR-encoding genes and the 58 related genes that do not encode LRRs represent approximately 0.8% of all ORFs so far annotated in Arabidopsis ecotype Col-0. Despite their prevalence in the genome and functional importance, there was little information regarding expression of these genes. Results We analyzed the expression patterns of ~170 NBS-LRR-encoding and related genes in Arabidopsis Col-0 using multiple analytical approaches: expressed sequenced tag (EST representation, massively parallel signature sequencing (MPSS, microarray analysis, rapid amplification of cDNA ends (RACE PCR, and gene trap lines. Most of these genes were expressed at low levels with a variety of tissue specificities. Expression was detected by at least one approach for all but 10 of these genes. The expression of some but not the majority of NBS-LRR-encoding and related genes was affected by salicylic acid (SA treatment; the response to SA varied among different accessions. An analysis of previously published microarray data indicated that ten NBS-LRR-encoding and related genes exhibited increased expression in wild-type Landsberg erecta (Ler after flagellin treatment. Several of these ten genes also showed altered expression after SA treatment, consistent with the regulation of R gene expression during defense responses and overlap between the basal defense response and salicylic acid signaling pathways. Enhancer trap analysis indicated that neither jasmonic acid nor benzothiadiazole (BTH, a salicylic acid analog, induced detectable expression of the five NBS-LRR-encoding genes and one TIR-NBS-encoding gene tested; however, BTH did induce detectable expression of the other TIR-NBS-encoding gene analyzed. Evidence for alternative mRNA polyadenylation sites was observed for many of the tested genes. Evidence for

  3. Global expression analysis of nucleotide binding site-leucine rich repeat-encoding and related genes in Arabidopsis.

    Science.gov (United States)

    Tan, Xiaoping; Meyers, Blake C; Kozik, Alexander; West, Marilyn A L; Morgante, Michele; St Clair, Dina A; Bent, Andrew F; Michelmore, Richard W

    2007-10-23

    Nucleotide binding site-leucine rich repeat (NBS-LRR)-encoding genes comprise the largest class of plant disease resistance genes. The 149 NBS-LRR-encoding genes and the 58 related genes that do not encode LRRs represent approximately 0.8% of all ORFs so far annotated in Arabidopsis ecotype Col-0. Despite their prevalence in the genome and functional importance, there was little information regarding expression of these genes. We analyzed the expression patterns of approximately 170 NBS-LRR-encoding and related genes in Arabidopsis Col-0 using multiple analytical approaches: expressed sequenced tag (EST) representation, massively parallel signature sequencing (MPSS), microarray analysis, rapid amplification of cDNA ends (RACE) PCR, and gene trap lines. Most of these genes were expressed at low levels with a variety of tissue specificities. Expression was detected by at least one approach for all but 10 of these genes. The expression of some but not the majority of NBS-LRR-encoding and related genes was affected by salicylic acid (SA) treatment; the response to SA varied among different accessions. An analysis of previously published microarray data indicated that ten NBS-LRR-encoding and related genes exhibited increased expression in wild-type Landsberg erecta (Ler) after flagellin treatment. Several of these ten genes also showed altered expression after SA treatment, consistent with the regulation of R gene expression during defense responses and overlap between the basal defense response and salicylic acid signaling pathways. Enhancer trap analysis indicated that neither jasmonic acid nor benzothiadiazole (BTH), a salicylic acid analog, induced detectable expression of the five NBS-LRR-encoding genes and one TIR-NBS-encoding gene tested; however, BTH did induce detectable expression of the other TIR-NBS-encoding gene analyzed. Evidence for alternative mRNA polyadenylation sites was observed for many of the tested genes. Evidence for alternative splicing was

  4. Soliton dual frequency combs in crystalline microresonators.

    Science.gov (United States)

    Pavlov, N G; Lihachev, G; Koptyaev, S; Lucas, E; Karpov, M; Kondratiev, N M; Bilenko, I A; Kippenberg, T J; Gorodetsky, M L

    2017-02-01

    We present a novel compact dual-comb source based on a monolithic optical crystalline MgF2 multi-resonator stack. The coherent soliton combs generated in the two microresonators of the stack with the repetition rate of 12.1 GHz and difference of 1.62 MHz provided after heterodyning a 300 MHz wide radio frequency comb. An analogous system can be used for dual-comb spectroscopy, coherent LIDAR applications, and massively parallel optical communications.

  5. A reliable dual Blumlein device

    Science.gov (United States)

    Noggle, R. C.; Adler, R. J.; Hendricks, K. J.

    1989-11-01

    In this article, we describe the 500 kV, 100 kA (each arm) GEMINI dual Blumlein accelerator at the Air Force Weapons Laboratory. Novel isolation, trigger, and trigger timing techniques are utilized in this device in order to allow two Blumleins to be charged by one Marx generator, and discharged at different times. The timing circuits are unique in that they make use of saturable magnetic circuits to provide the relative timing of the two outputs. We demonstrate that this technique is reliable, reproducible, and straightforward. We isolate the two Blumlein switches using an inductor wound so that it has minimal inductance when both Blumleins are charging, but maximum inductance when one is fired and the second Blumlein is delayed. Utilization of this technique allows us to isolate the two Blumleins without using resistive isolation with its associated energy loss, or simple inductive isolation with the associated cost in increasing the water line charge time. Complete operational and design data is presented, along with detailed data from the switch trigger arms.

  6. Nanobody Based Dual Specific CARs

    Directory of Open Access Journals (Sweden)

    Stijn De Munter

    2018-01-01

    Full Text Available Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR. High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.

  7. Nanobody Based Dual Specific CARs.

    Science.gov (United States)

    De Munter, Stijn; Ingels, Joline; Goetgeluk, Glenn; Bonte, Sarah; Pille, Melissa; Weening, Karin; Kerre, Tessa; Abken, Hinrich; Vandekerckhove, Bart

    2018-01-30

    Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv) is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR). High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.

  8. Improving Sustainability through a Dual Audit System

    Directory of Open Access Journals (Sweden)

    Shun-Ji Jin

    2018-01-01

    Full Text Available As a consequence of a large-scale accounting fraud, China implemented a dual audit system for listed companies issuing foreign stocks (B shares and H shares from 2001 to 2006, before adopting Chinese-IFRS in 2007. At the end of 2010, the EU proposed that listed corporations over a certain size should be required to implement a joint audit system. However, only a few countries have implemented this system, and thus, data and references are extremely limited. The dual audit system is called the “twin” of the joint audit system. We analyze whether the dual system improves a company’s earnings quality. Earnings quality is studied by means of real earnings management, and the variable of loss aversion. We find that real earnings management of dual audited enterprises is lower than that of single audited (A-share enterprises, and the inclination toward loss aversion of enterprises in the foreign share market has not increased significantly relative to the A-share enterprises after the abolition of the dual audit system. The results indicate that a dual audit system improves earnings quality. We expect that the conclusions of this research will resolve the issues and concerns about the joint audit system.

  9. Myocardial perfusion imaging with dual energy CT

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Kwang Nam [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); De Cecco, Carlo N. [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Caruso, Damiano [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Radiological Sciences, Oncology and Pathology, University of Rome “Sapienza”, Rome (Italy); Tesche, Christian [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Department of Cardiology and Intensive Care Medicine, Heart Center Munich-Bogenhausen, Munich (Germany); Spandorfer, Adam; Varga-Szemes, Akos [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Schoepf, U. Joseph, E-mail: schoepf@musc.edu [Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC (United States); Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC (United States)

    2016-10-15

    Highlights: • Stress dual-energy sCTMPI offers the possibility to directly detect the presence of myocardial perfusion defects. • Stress dual-energy sCTMPI allows differentiating between reversible and fixed myocardial perfusion defects. • The combination of coronary CT angiography and dual-energy sCTMPI can improve the ability of CT to detect hemodynamically relevant coronary artery disease. - Abstract: Dual-energy CT (DECT) enables simultaneous use of two different tube voltages, thus different x-ray absorption characteristics are acquired in the same anatomic location with two different X-ray spectra. The various DECT techniques allow material decomposition and mapping of the iodine distribution within the myocardium. Static dual-energy myocardial perfusion imaging (sCTMPI) using pharmacological stress agents demonstrate myocardial ischemia by single snapshot images of myocardial iodine distribution. sCTMPI gives incremental values to coronary artery stenosis detected on coronary CT angiography (CCTA) by showing consequent reversible or fixed myocardial perfusion defects. The comprehensive acquisition of CCTA and sCTMPI offers extensive morphological and functional evaluation of coronary artery disease. Recent studies have revealed that dual-energy sCTMPI shows promising diagnostic accuracy for the detection of hemodynamically significant coronary artery disease compared to single-photon emission computed tomography, invasive coronary angiography, and cardiac MRI. The aim of this review is to present currently available DECT techniques for static myocardial perfusion imaging and recent clinical applications and ongoing investigations.

  10. Dual Treatments as Starting Point for Integrative Perceptions in Teaching Mathematics

    Science.gov (United States)

    Kërënxhi, Svjetllana; Gjoci, Pranvera

    2015-01-01

    In this paper, we recommend mathematical teaching through dual treatments. The dual treatments notion, classified in dual interpretations, dual analyses, dual solutions, and dual formulations, is explained through concrete examples taken from mathematical textbooks of elementary education. Dual treatments provide opportunities for creating…

  11. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway

    International Nuclear Information System (INIS)

    Onder, Zeynep; Chang, Vivian; Moroianu, Junona

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP–8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), 76 IRTFQELLF 84 , within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. - Highlights: • HPV8 E7 has a leucine-rich NES within its zinc-binding domain that mediates its nuclear export. • CRM1 nuclear export receptor interacts with HPV8 E7 and mediates its export. • Identification of the critical hydrophobic amino acids of the NES of HPV8 E7

  12. Targeting Inflammation and Downstream Protein Metabolism in Sarcopenia: A Brief Up-Dated Description of Concurrent Exercise and Leucine-Based Multimodal Intervention

    Directory of Open Access Journals (Sweden)

    Zhi Xia

    2017-06-01

    Full Text Available Sarcopenia is defined as the progressive loss of muscle mass with age, and poses a serious threat to the physiological and psychological health of the elderly population with consequential economic and social burdens. Chronic low-grade inflammation plays a central role in the development of sarcopenia such that it alters cellular protein metabolism to favor proteolysis over synthesis, and thereby accelerates muscular atrophy. The purpose of this review is to highlight how exercise and nutrition intervention strategies can attenuate or treat sarcopenia. Resistance exercise increases not only muscle mass but also muscle strength, while aerobic exercise is able to ameliorate the age-related metabolic disorders. Concurrent exercise training integrates the advantages of both aerobic and resistance exercise, and may exert a significant synergistic effect in the aging organism. Higher protein intakes rich in the amino acid leucine appear to restore skeletal muscle protein metabolism balance by rescuing protein synthesis in older adults. There is good reason to believe that a multimodal treatment, a combination of exercise and increased leucine consumption in the diet, can combat some of the muscle loss associated with aging. Future research is needed to consolidate these findings to humans, and to further clarify to what extent and by which mechanisms protein metabolism might be directly involved in sarcopenia pathogenesis and the multimodal treatment responses.

  13. L-leucine and SPNS1 coordinately ameliorate dysfunction of autophagy in mouse and human Niemann-Pick type C disease.

    Science.gov (United States)

    Yanagisawa, Hiroko; Ishii, Tomohiro; Endo, Kentaro; Kawakami, Emiko; Nagao, Kazuaki; Miyashita, Toshiyuki; Akiyama, Keiko; Watabe, Kazuhiko; Komatsu, Masaaki; Yamamoto, Daisuke; Eto, Yoshikatsu

    2017-11-21

    Lysosomal storage disorders are characterized by progressive accumulation of undigested macromolecules within the cell due to lysosomal dysfunction. 573C10 is a Schwann cell line derived from a mouse model of Niemann-Pick type C disease-1, NPC (-/-). Under serum-starved conditions, NPC (-/-) cells manifested impaired autophagy accompanied by an increase in the amount of p62 and lysosome enlargement. Addition of L-leucine to serum-starved NPC (-/-) cells ameliorated the enlargement of lysosomes and the p62 accumulation. Similar autophagy defects were observed in NPC (-/-) cells even without serum starvation upon the knockdown of Spinster-like 1 (SPNS1), a putative transporter protein thought to function in lysosomal recycling. Conversely, SPNS1 overexpression impeded the enlargement of lysosomes, p62 accumulation and mislocalization of the phosphorylated form of the mechanistic Target of rapamycin in NPC (-/-) cells. In addition, we found a reduction in endogenous SPNS1 expression in fibroblasts derived from NPC-1 patients compared with normal fibroblasts. We propose that SPNS1-dependent L-leucine export across the lysosomal membrane is a key step for triggering autophagy, and that this mechanism is impaired in NPC-1.

  14. Effects of steroids and sex reversal on intestinal absorption of L-(/sup 14/C)leucine in vivo, in rainbow trout, Salmo gairdneri

    Energy Technology Data Exchange (ETDEWEB)

    Habibi, H.R.; Ince, B.W.

    1983-12-01

    The effects of steroids (17 alpha-methyltestosterone (MT), 17 beta-oestradiol (E2)), and of sex reversal (XX male) on intestinal absorption and accumulation of L-(/sup 14/C)leucine (5 mM), were investigated in unanaesthetized rainbow trout (Salmo gairdneri), using an in vivo gut perfusion technique. Each steroid was luminally perfused through the gut at a concentration of 50 micrograms/ml perfusate, during five separate perfusions carried out on the same fish at 30-min intervals (perfusion periods 1 to 5), for a total of 120 min at 14 degrees. Experiments were also conducted on masculinized, genetically female trout (XX male) with steroid-free perfusate. MT treatment significantly increased the intestinal absorption of radioleucine during periods 1 and 2, whilst E2 was without effect. Neither MT nor E2 influenced intestinal accumulation (mid- and hindgut) of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. Sex reversal, however, whilst having no effect on leucine absorption, nevertheless significantly increased intestinal accumulation of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. The effects observed in the present study are in agreement with previous work in trout using everted gut sac preparations. It is suggested that the growth-promoting effects of anabolic-androgenic steroids in fish may be partly explained by their action on gastrointestinal function.

  15. Effects of steroids and sex reversal on intestinal absorption of L-[14C]leucine in vivo, in rainbow trout, Salmo gairdneri

    International Nuclear Information System (INIS)

    Habibi, H.R.; Ince, B.W.

    1983-01-01

    The effects of steroids (17 alpha-methyltestosterone (MT), 17 beta-oestradiol (E2)), and of sex reversal (XX male) on intestinal absorption and accumulation of L-[ 14 C]leucine (5 mM), were investigated in unanaesthetized rainbow trout (Salmo gairdneri), using an in vivo gut perfusion technique. Each steroid was luminally perfused through the gut at a concentration of 50 micrograms/ml perfusate, during five separate perfusions carried out on the same fish at 30-min intervals (perfusion periods 1 to 5), for a total of 120 min at 14 degrees. Experiments were also conducted on masculinized, genetically female trout (XX male) with steroid-free perfusate. MT treatment significantly increased the intestinal absorption of radioleucine during periods 1 and 2, whilst E2 was without effect. Neither MT nor E2 influenced intestinal accumulation (mid- and hindgut) of radioleucine, and accumulation of 14 C-solutes in skeletal muscle. Sex reversal, however, whilst having no effect on leucine absorption, nevertheless significantly increased intestinal accumulation of radioleucine, and accumulation of 14 C-solutes in skeletal muscle. The effects observed in the present study are in agreement with previous work in trout using everted gut sac preparations. It is suggested that the growth-promoting effects of anabolic-androgenic steroids in fish may be partly explained by their action on gastrointestinal function

  16. Effects of dietary leucine supplementation in low crude protein diets on performance, nitrogen balance, whole-body protein turnover, carcass characteristics and meat quality of finishing pigs.

    Science.gov (United States)

    Zhang, Shihai; Chu, Licui; Qiao, Shiyan; Mao, Xiangbing; Zeng, Xiangfang

    2016-07-01

    Eighteen Duroc × Landrace × Yorkshire barrows, with an average initial body weight (BW) of 75.4 ± 2.0 kg, were randomly allotted to one of three diets with six replicates per treatment for 25 days. The diets comprised a normal protein diet (NP, 14.5% crude protein), a low crude protein diet supplemented with 0.27% alanine (LP + Ala, 10.0% crude protein), or a low crude protein diet supplemented with 0.40% leucine (LP + Leu, 10.0% crude protein). The whole-body protein synthesis rate, whole-body protein breakdown rate and protein deposition rate in pigs fed the LP + Leu diet were similar to the NP diet (P > 0.05), and both were significantly higher than pigs fed the LP + Ala diet (P supplementation of leucine in low protein diet could stimulate protein deposition and improve the meat quality of finishing pigs more than an alanine-supplemented one. © 2015 Japanese Society of Animal Science.

  17. Local helix content and RNA-binding activity of the N-terminal leucine-repeat region of hepatitis delta antigen

    Energy Technology Data Exchange (ETDEWEB)

    Cheng Jyawei; Lin Ijin; Lou Yuanchou; Pai Mingtao [National Tsing Hua University, Department of Life Science (China); Wu Hueynan [Academia Sinica, Institute of Molecular Biology (China)

    1998-07-15

    Hepatitis delta virus (HDV) is a satellite virus of the hepatitis B virus (HBV) which provides the surface antigen for the viral coat. Our results show that the N-terminal leucine-repeat region of hepatitis delta antigen (HDAg), encompassing residues 24-50, binds to the autolytic domain of HDV genomic RNA and attenuates its autolytic activity. The solution conformation of a synthetic peptide corresponding to residues 24-50 of HDAg as determined by two-dimensional {sup 1}H NMR and circular dichroism techniques is found to be an {alpha}-helix. The local helix content of this peptide was analyzed by NOEs and coupling constants. Mutagenesis studies indicate that Lys{sup 38}, Lys{sup 39}, and Lys{sup 40} within this {alpha}-helical peptide may be directly involved in RNA binding. A structural knowledge of the N-terminal leucine-repeat region of HDAg thus provides a molecular basis for understanding its role in the interaction with RNA.

  18. Nuclear export of cutaneous HPV8 E7 oncoprotein is mediated by a leucine-rich nuclear export signal via a CRM1 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Onder, Zeynep; Chang, Vivian; Moroianu, Junona, E-mail: moroianu@bc.edu

    2015-01-01

    We recently determined that the nuclear import of cutaneous beta genus HPV8 E7 oncoprotein it is mediated by its zinc-binding domain via direct hydrophobic interactions with the FG nucleoporins Nup62 and Nup153 (Onder and Moroianu, 2014). Here we investigated the nuclear export of HPV8 E7 oncoprotein using confocal microscopy after transfections of HeLa cells with EGFP–8cE7 and mutant plasmids and treatment with Ratjadone A nuclear export inhibitor. We determined that HPV8 E7 contains a leucine-rich nuclear export signal (NES), {sub 76}IRTFQELLF{sub 84}, within its zinc-binding domain that mediates its nuclear export via a CRM1 pathway. We found that HPV8 E7 interacts with CRM1 and that the hydrophobic amino acid residues I76, F79 and L82 of the NES are essential for this interaction and for nuclear export of HPV8 E7 oncoprotein. - Highlights: • HPV8 E7 has a leucine-rich NES within its zinc-binding domain that mediates its nuclear export. • CRM1 nuclear export receptor interacts with HPV8 E7 and mediates its export. • Identification of the critical hydrophobic amino acids of the NES of HPV8 E7.

  19. A novel l-leucine modified Sol-Gel-Carbon electrode for simultaneous electrochemical detection of homovanillic acid, dopamine and uric acid in neuroblastoma diagnosis.

    Science.gov (United States)

    Khamlichi, Redouan El; Bouchta, Dounia; Anouar, El Hassane; Atia, Mounia Ben; Attar, Aisha; Choukairi, Mohamed; Tazi, Saloua; Ihssane, Raissouni; Faiza, Chaoukat; Khalid, Draoui; Khalid, Riffi Temsamani

    2017-02-01

    Neuroblastoma is a pediatric neuroblastic tumor arising in the sympathetic nervous crest cells. A high grade of Neuroblastoma is characterized by a high urinary excretion of homovanillic acid and dopamine. In this work l-leucine modified Sol-Gel-Carbon electrode was used for a sensitive voltammetric determination of homovanillic acid and dopamine in urine. The electrochemical response characteristics were investigated by cyclic and differential pulse voltammetry; the modified electrode has shown an increase in the effective area of up to 40%, a well-separated oxidation peaks and an excellent electrocatalytic activity. High sensitivity and selectivity in the linear range of 0,4-100μML -1 of homovanillic acid and 10-120μML -1 of dopamine were also obtained. Moreover, a sub-micromolar limit of detection of 0.1μM for homovanillic acid and 1.0μM for the dopamine was achieved. Indeed, high reproducibility with simple preparation and regeneration of the electrode surface made this electrode very suitable for the determination of homovanillic acid and dopamine in pharmaceutical and clinical preparations. The mechanism of homovanillic acid and the electrochemical oxidation at l-leucine modified Sol-Gel-Carbon electrode is described out the B3P86/6-31+G(d,p) level of theory as implemented in Gaussian software. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Biosynthesis of rat sperm outer dense fibers during spermiogenesis. In vivo incorporation of (/sup 3/H)leucine into the fibrillar complex

    Energy Technology Data Exchange (ETDEWEB)

    Vera, J.C.; Brito, M.; Burzio, L.O.

    1987-02-01

    The temporal incorporation profile of (/sup 3/H)leucine into the outer dense fiber polypeptides was determined after the intratesticular injection of the radioisotope. Groups of four rats were killed on alternate days after injection, and the outer dense fibers were isolated from the caput epididymal sperm. The radioactivity incorporated into the whole sperm and into the isolated fibers showed a sharp peak at 10 days after injection. Therefore, considering the known kinetics of spermatogenesis in the rat, the maximal incorporation of radioactivity into the fibers occurred during the second half of spermiogenesis. The radioactivity incorporated into the six major polypeptides of the fibers separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate accounted for 95 percent of the total radioactivity associated with the isolated fibrillar complex. Furthermore, analysis of the time-course incorporation of (/sup 3/H)leucine into the polypeptides of the fibers indicated that the maximal incorporation into each of the six major components took place within the same period of time. Using two different procedures, the specific activity of each major polypeptide was determined at the time of maximal incorporation. It was found that the specific activity of the most abundant components (molecular weights of 30,400 plus 26,000) was approximately twice that of the other polypeptides.

  1. Dual Comb Fourier Transform Spectroscopy

    Science.gov (United States)

    Hänsch, T. W.; Picqué, N.

    2010-06-01

    The advent of laser frequency combs a decade ago has already revolutionized optical frequency metrology and precision spectroscopy. Extensions of laser combs from the THz region to the extreme ultraviolet and soft x-ray frequencies are now under exploration. Such laser combs have become enabling tools for a growing tree of applications, from optical atomic clocks to attosecond science. Recently, the millions of precisely controlled laser comb lines that can be produced with a train of ultrashort laser pulses have been harnessed for highly multiplexed molecular spectroscopy. Fourier multi-heterodyne spectroscopy, dual comb spectroscopy, or asynchronous optical sampling spectroscopy with frequency combs are emerging as powerful new spectroscopic tools. Even the first proof-of-principle experiments have demonstrated a very exciting potential for ultra-rapid and ultra-sensitive recording of complex molecular spectra. Compared to conventional Fourier transform spectroscopy, recording times could be shortened from seconds to microseconds, with intriguing prospects for spectroscopy of short lived transient species. Longer recording times allow high resolution spectroscopy of molecules with extreme precision, since the absolute frequency of each laser comb line can be known with the accuracy of an atomic clock. The spectral structure of sharp lines of a laser comb can be very useful even in the recording of broadband spectra without sharp features, as they are e.g. encountered for molecular gases or in the liquid phase. A second frequency comb of different line spacing permits the generation of a comb of radio frequency beat notes, which effectively map the optical spectrum into the radio frequency regime, so that it can be recorded with a single fast photodetector, followed by digital signal analysis. In the time domain, a pulse train of a mode-locked femtosecond laser excites some molecular medium at regular time intervals. A second pulse train of different repetition

  2. Dual-Compartment Inflatable Suitlock

    Science.gov (United States)

    Kennedy, Kriss J.; Guirgis, Peggy L.; Boyle, Robert M.

    2013-01-01

    There is a need for an improvement over current NASA Extravehicular Activity (EVA) technology. The technology must allow the capacity for quicker, more efficient egress/ingress, allow for shirtsleeve suit maintenance, be compact in transport, and be applicable to environments ranging from planetary surface (partial-g) to orbital or deep space zero-g environments. The technology must also be resistant to dust and other foreign contaminants that may be present on or around a planetary surface. The technology should be portable, and be capable of docking with a variety of habitats, ports, stations, vehicles, and other pressurized modules. The Dual-Compartment Inflatable Suitlock (DCIS) consists of three hard inline bulkheads, separating two cylindrical membrane-walled compartments. The Inner Bulkhead can be fitted with a variety of hatch types, docking flanges, and mating hardware, such as the Common Berthing Mechanism (CBM), for the purpose of mating with vehicles, habitats, and other pressurized modules. The Inner Bulkhead and Center Bulkhead function as the end walls of the Inner Compartment, which during operations, would stay pressurized, either matching the pressure of the habitat or acting as a lower-pressure transitional volume. The Inner Compartment contains donning/doffing fixtures and inner suit-port hatches. The Center Bulkhead has two integrated suit-ports along with a maintenance hatch. The Center Bulkhead and Outer Bulkhead function as the end walls of the Outer Compartment, which stays at vacuum during normal operations. This allows the crewmember to quickly don a suit, and egress the suitlock without waiting for the Outer Compartment to depressurize. The Outer Compartment can be pressurized infrequently for both nominal and off-nominal suit maintenance tasks, allowing shirtsleeve inspections and maintenance/repair of the environmental suits. The Outer Bulkhead has a pressure-assisted hatch door that stays open and stowed during EVA operations, but can

  3. Dual Career Couples in Academia, International Mobility and Dual Career Services in Europe

    Science.gov (United States)

    Tzanakou, Charikleia

    2017-01-01

    The number of dual career couples in academia is growing due to the increasing proportion of women with a doctoral degree and the greater propensity of women to choose another academic as their partner. At the same time, international mobility is required for career advancement in academia, creating challenges for dual career couples where both…

  4. Data sharing and dual-use issues.

    Science.gov (United States)

    Bezuidenhout, Louise

    2013-03-01

    The concept of dual-use encapsulates the potential for well-intentioned, beneficial scientific research to also be misused by a third party for malicious ends. The concept of dual-use challenges scientists to look beyond the immediate outcomes of their research and to develop an awareness of possible future (mis)uses of scientific research. Since 2001 much attention has been paid to the possible need to regulate the dual-use potential of the life sciences. Regulation initiatives fall under two broad categories-those that develop the ethical education of scientists and foster an awareness and responsibility of dual-use issues, and those which assess the regulation of information being generated by current research. Both types of initiatives are premised on a cautious, risk-adverse philosophy which advocates careful examination of all future endpoints of research endeavors. This caution advocated within initiatives such as pre-publication review of journal articles contrasts to the obligation to share underpinning data sharing discussions. As the dual-use debate has yet to make a significant impact on data sharing discussions (and vice versa) it is possible that these two areas of knowledge control may present areas of ethical conflict for scientists, and thus need to be more closely examined. This paper examines the tension between the obligation to share exemplified by data sharing principles and the concerns raised by the risk-cautious culture of the dual-use debates. The paper concludes by reflecting on the issues of responsibility as raised by dual-use as relating to data sharing, such as the chain of custody for shared data.

  5. Unraveling Executive Functioning in Dual Diagnosis.

    Science.gov (United States)

    Duijkers, Judith C L M; Vissers, Constance Th W M; Egger, Jos I M

    2016-01-01

    In mental health, the term dual-diagnosis is used for the co-occurrence of Substance Use Disorder (SUD) with another mental disorder. These co-occurring disorders can have a shared cause, and can cause/intensify each other's expression. Forming a threat to health and society, dual-diagnosis is associated with relapses in addiction-related behavior and a destructive lifestyle. This is due to a persistent failure to control impulses and the maintaining of inadequate self-regulatory behavior in daily life. Thus, several aspects of executive functioning like inhibitory, shifting and updating processes seem impaired in dual-diagnosis. Executive (dys-)function is currently even seen as a shared underlying key component of most mental disorders. However, the number of studies on diverse aspects of executive functioning in dual-diagnosis is limited. In the present review, a systematic overview of various aspects of executive functioning in dual-diagnosis is presented, striving for a prototypical profile of patients with dual-diagnosis. Looking at empirical results, inhibitory and shifting processes appear to be impaired for SUD combined with schizophrenia, bipolar disorder or cluster B personality disorders. Studies involving updating process tasks for dual-diagnosis were limited. More research that zooms in to the full diversity of these executive functions is needed in order to strengthen these findings. Detailed insight in the profile of strengths and weaknesses that underlies one's behavior and is related to diagnostic classifications, can lead to tailor-made assessment and indications for treatment, pointing out which aspects need attention and/or training in one's self-regulative abilities.

  6. Simultaneous direct holographic fabrication of photonic cavity and graded photonic lattice with dual periodicity, dual basis, and dual symmetry.

    Science.gov (United States)

    Lowell, D; Lutkenhaus, J; George, D; Philipose, U; Chen, B; Lin, Y

    2017-06-26

    For the first time, to the authors' best knowledge, this paper demonstrates the digital, holographic fabrication of graded, super-basis photonic lattices with dual periodicity, dual basis, and dual symmetry. Pixel-by-pixel phase engineering of the laser beam generates the highest resolution in a programmable spatial light modulator (SLM) for the direct imaging of graded photonic super-lattices. This technique grants flexibility in designing 2-D lattices with size-graded features, differing periodicities, and differing symmetries, as well as lattices having simultaneously two periodicities and two symmetries in high resolutions. By tuning the diffraction efficiency ratio from the SLM, photonic cavities can also be generated in the graded super-lattice simultaneously through a one-exposure process. A high quality factor of over 1.56 × 10 6 for a cavity mode in the graded photonic lattice with a large super-cell is predicted by simulations.

  7. Sequence characterization of hypervariable regions in the soybean genome: leucine-rich repeats and simple sequence repeats

    Directory of Open Access Journals (Sweden)

    Everaldo G. de Barros

    2000-06-01

    Full Text Available The genetic basis of cultivated soybean is rather narrow. This observation has been confirmed by analysis of agronomic traits among different genotypes, and more recently by the use of molecular markers. During the construction of an RFLP soybean map (Glycine soja x Glycine max the two progenitors were analyzed with over 2,000 probes, of which 25% were polymorphic. Among the probes that revealed polymorphisms, a small proportion, about 0.5%, hybridized to regions that were highly polymorphic. Here we report the sequencing and analysis of five of these probes. Three of the five contain segments that encode leucine-rich repeat (LRR sequence homologous to known disease resistance genes in plants. Two other probes are relatively AT-rich and contain segments of (An/(Tn. DNA segments corresponding to one of the probes (A45-10 were amplified from nine soybean genotypes. Partial sequencing of these amplicons suggests that deletions and/or insertions are responsible for the extensive polymorphism observed. We propose that genes encoding LRR proteins and simple sequence repeat region prone to slippage are some of the most hypervariable regions of the soybean genome.A base genética da soja cultivada é relativamente estreita. Essa observação foi confirmada por análises de características agronômicas entre diferentes genótipos e, mais recentemente, pelo uso de marcadores moleculares. Durante a construção de um mapa de RFLP da soja (Glycine soja x Glycine max, os dois progenitores foram analisados com mais de 2000 sondas, das quais 25% eram polimórficas. Entre as sondas que revelaram polimorfismos, uma pequena proporção, cerca de 0,5%, hibridizou com regiões que eram altamente polimórficas. Neste trabalho, são apresentados o seqüenciamento e análise de cinco dessas sondas. Três dessas sondas contêm segmentos que codificam repetições ricas em leucina que são homólogas a genes de resistência a doenças já conhecidos em plantas. As duas

  8. Dual model of vocational education: Austrian example

    Directory of Open Access Journals (Sweden)

    Tomić Milica

    2015-01-01

    Full Text Available Dual education, as a form of secondary vocational education means that education and practical training are held on two locations - in school and in a company (organization, factory and that these two institutions jointly participate in the realization of vocational education. The paper presents an account of the functioning of dual education in Austria. In that framework special attention was paid to law regulations in this field, the modes of dual education, progression through the system and the perspectives of the young in the labour market. Among the key features of dual education which are, at the same time, considered the factors of its successfulness, the following stand out: active role of social partners in the conceptualization and realization of vocational education; intensive practical training of high quality; systemic interrelatedness of vocational schools and firms where practical training is provided, the compliance of the offer of educational profiles and the needs of labour market; the system of stimulation for the firms that provide professional training for students, clear legislation and the system of professional qualifications. Yet, the challenges of dual educations are not neglected in the paper.

  9. Doubling (Dual) Hahn Polynomials: Classification and Applications

    Science.gov (United States)

    Oste, Roy; Van der Jeugt, Joris

    2016-01-01

    We classify all pairs of recurrence relations in which two Hahn or dual Hahn polynomials with different parameters appear. Such couples are referred to as (dual) Hahn doubles. The idea and interest comes from an example appearing in a finite oscillator model [Jafarov E.I., Stoilova N.I., Van der Jeugt J., J. Phys. A: Math. Theor. 44 (2011), 265203, 15 pages, arXiv:1101.5310]. Our classification shows there exist three dual Hahn doubles and four Hahn doubles. The same technique is then applied to Racah polynomials, yielding also four doubles. Each dual Hahn (Hahn, Racah) double gives rise to an explicit new set of symmetric orthogonal polynomials related to the Christoffel and Geronimus transformations. For each case, we also have an interesting class of two-diagonal matrices with closed form expressions for the eigenvalues. This extends the class of Sylvester-Kac matrices by remarkable new test matrices. We examine also the algebraic relations underlying the dual Hahn doubles, and discuss their usefulness for the construction of new finite oscillator models.

  10. What is the dual of a dipole?

    Energy Technology Data Exchange (ETDEWEB)

    Alday, Luis F. [Institute for Theoretical Physics and Spinoza Institute, Utrecht University, 3508 TD Utrecht (Netherlands)]. E-mail: l.f.alday@phys.uu.nl; Boer, Jan de [Instituut voor Theoretische Fysica, Valckenierstraat 65, 1018 XE Amsterdam (Netherlands)]. E-mail: jdeboer@science.uva.nl; Messamah, Ilies [Instituut voor Theoretische Fysica, Valckenierstraat 65, 1018 XE Amsterdam (Netherlands)]. E-mail: imessama@science.uva.nl

    2006-07-03

    We study gravitational solutions that admit a dual CFT description and carry non-zero dipole charge. We focus on the black ring solution in AdS{sub 3}xS{sup 3} and extract from it the one-point functions of all CFT operators dual to scalar excitations of the six-dimensional metric. In the case of small black rings, characterized by the level N, angular momentum J and dipole charge q{sub 3}, we show how the large N and J dependence of the one-point functions can be reproduced, under certain assumptions, directly from a suitable ensemble in the dual CFT. Finally we present a simple toy model that describes the thermodynamics of the small black ring for arbitrary values of the dipole charge.

  11. Analytic continuation of dual Feynman amplitudes

    International Nuclear Information System (INIS)

    Bleher, P.M.

    1981-01-01

    A notion of dual Feynman amplitude is introduced and a theorem on the existence of analytic continuation of this amplitude from the convergence domain to the whole complex is proved. The case under consideration corresponds to massless power propagators and the analytic continuation is constructed on the propagators powers. Analytic continuation poles and singular set of external impulses are found explicitly. The proof of the theorem on the existence of analytic continuation is based on the introduction of α-representation for dual Feynman amplitudes. In proving, the so-called ''trees formula'' and ''trees-with-cycles formula'' are established that are dual by formulation to the trees and 2-trees formulae for usual Feynman amplitudes. (Auth.)

  12. Dual vector multiplet coupled to dual N=1 supergravity in 10D

    International Nuclear Information System (INIS)

    Nishino, Hitoshi; Rajpoot, Subhash

    2005-01-01

    We couple in superspace a dual vector multiplet (C m 1 ...m 7 ,λ α ) to the dual version of N=1 supergravity (e m a ,ψ m α ,M m 1 ...m 6 ,χ α ,Φ) in ten dimensions. The 7-form field C has its 8-form field strength H dual to the 2-form field strength F of the conventional vector multiplet. To simplify the computation, we use so-called beta-function-favored superspace constraints for dual supergravity developed for β-function computations. As in a more conventional constraint set, the H-Bianchi identity must have the form N and F, where N is the 7-form field strength in dual supergravity. The potential anomaly for the dual vector multiplet can be cancelled for the particular gauge group U(1) 496 by the Green-Schwarz mechanism. As a by-product, we also give the globally supersymmetric Abelian Dirac-Born-Infeld interactions for the dual vector multiplet for the first time

  13. NMR-based metabonomic analysis of MnO-embedded iron oxide nanoparticles as potential dual-modal contrast agents

    Science.gov (United States)

    Li, Jinquan; Zhou, Zijian; Feng, Jianghua; Cai, Shuhui; Gao, Jinhao; Chen, Zhong

    2014-05-01

    MnO-embedded iron oxide nanoparticles (MnIO-NPs) can be treated as potential dual-modal contrast agents. However, their overall bio-effects and potential toxicity remain unknown. In this study, the metabolic effects of MnIO-NPs (dosed at 1 and 5 mg Fe/kg) on Sprague-Dawley rats were investigated using metabonomic analysis, histopathological examination, and conventional biochemical analysis. The histological changes included a focal inflammation in the liver at high-dose and a slightly enlarged area of splenic white pulp after 48 h post-dose. Blood biochemical analysis showed that albumin, globulins, aspartate aminotransferase, lactate dehydrogenase, blood urea nitrogen, and glucose changed distinctly compared to the control. The metabonomic analysis of body fluids (serum and urine) and tissues (liver, kidney, and spleen) indicated that MnIO-NPs induced metabolic perturbation in rats including energy, nucleotides, amino acids and phospholipid metabolisms. Besides, the variations of supportive nutrients: valine, leucine, isoleucine, nicotinamide adenine dinucleotide (phosphate), and nicotinamide, and the conjugation substrates: glycine, taurine, glutamine, glutathione, and methyl donors (formate, sarcosine, dimethylglycine, choline, and betaine) were involved in detoxification reaction of MnIO-NPs. The obtained information would provide identifiable ground for the candidate selection and optimization.

  14. Humanity's Dual Response to Dogs and Wolves.

    Science.gov (United States)

    Treves, Adrian; Bonacic, Cristian

    2016-07-01

    Dogs were first domesticated 31 000-41 000 years ago. Humanity has experienced ecological costs and benefits from interactions with dogs and wolves. We propose that humans inherited a dual response of attraction or aversion that expresses itself independently to domestic and wild canids. The dual response has had far-reaching consequences for the ecology and evolution of all three taxa, including today's global 'ecological paw print' of 1 billion dogs and recent eradications of wolves. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Pressure Transient Analysis of Dual Fractal Reservoir

    Directory of Open Access Journals (Sweden)

    Xiao-Hua Tan

    2013-01-01

    Full Text Available A dual fractal reservoir transient flow model was created by embedding a fracture system simulated by a tree-shaped fractal network into a matrix system simulated by fractal porous media. The dimensionless bottom hole pressure model was created using the Laplace transform and Stehfest numerical inversion methods. According to the model's solution, the bilogarithmic type curves of the dual fractal reservoirs are illustrated, and the influence of different fractal factors on pressure transient responses is discussed. This semianalytical model provides a practical and reliable method for empirical applications.

  16. Tuning controllers using the dual Youla parameterization

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik; Stoustrup, Jakob

    2000-01-01

    This paper describes the application of the Youla parameterization of all stabilizing controllers and the dual Youla parameterization of all systems stabilized by a given controller in connection with tuning of controllers. In the uncertain case, it is shown that the use of the Youla parameteriza......This paper describes the application of the Youla parameterization of all stabilizing controllers and the dual Youla parameterization of all systems stabilized by a given controller in connection with tuning of controllers. In the uncertain case, it is shown that the use of the Youla...

  17. Dual waveband compact catadioptric imaging spectrometer

    Science.gov (United States)

    Chrisp, Michael P.

    2012-12-25

    A catadioptric dual waveband imaging spectrometer that covers the visible through short-wave infrared, and the midwave infrared spectral regions, dispersing the visible through shortwave infrared with a zinc selenide grating and midwave infrared with a sapphire prism. The grating and prism are at the cold stop position, enabling the pupil to be split between them. The spectra for both wavebands are focused onto the relevant sections of a single dual waveband detector. Spatial keystone distortion is controlled to less than one tenth of a pixel over the full wavelength range, facilitating the matching of the spectra in the midwave infrared with the shorter wavelength region.

  18. Supergravity dual of c-extremization

    Science.gov (United States)

    Karndumri, Parinya; Ó Colgáin, Eoin

    2013-05-01

    Recently, a general principle, called c-extremization, which determines the exact R symmetry of two-dimensional conformal field theories with N=(0,2) supersymmetry, was identified. In this work we show that the supergravity dual corresponds to the extremization of the T tensor of N=2 gauged supergravity in three dimensions. To support this claim, we demonstrate that the expected central charge of conformal field theories arising from twisted compactifications of four-dimensional N=4 Super-Yang-Mills on Riemann surfaces, whose gravity dual is a reduction of five-dimensional U(1)3 gauged supergravity, is recovered in the three-dimensional framework.

  19. How self-dual is QCD?

    International Nuclear Information System (INIS)

    Alexandru, Andrei; Horváth, Ivan

    2012-01-01

    Vacuum characteristics quantifying dynamical tendency toward self-duality in gauge theories could be used to judge the relevance of classical solutions or the viability of classically motivated vacuum models. Here we decompose the field strength of equilibrium gauge configurations into self-dual and anti-self-dual parts, and apply absolute X-distribution method to the resulting polarization dynamics in order to construct such characteristics. Using lattice regularization and focusing on pure-glue SU(3) gauge theory at zero temperature, we find evidence for positive but very small dynamical tendency for self-duality of vacuum in the continuum limit.

  20. Dual Causality and the Autonomy of Biology.

    Science.gov (United States)

    Bock, Walter J

    2017-03-01

    Ernst Mayr's concept of dual causality in biology with the two forms of causes (proximate and ultimate) continues to provide an essential foundation for the philosophy of biology. They are equivalent to functional (=proximate) and evolutionary (=ultimate) causes with both required for full biological explanations. The natural sciences can be classified into nomological, historical nomological and historical dual causality, the last including only biology. Because evolutionary causality is unique to biology and must be included for all complete biological explanations, biology is autonomous from the physical sciences.