Sample records for alpha activity indicator

  1. Resting alpha activity predicts learning ability in alpha neurofeedback


    Wenya eNan; Feng eWan; Mang I eVai; Agostinho eRosa


    Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the tr...

  2. Resting alpha activity predicts learning ability in alpha neurofeedback

    Directory of Open Access Journals (Sweden)

    Wenya eNan


    Full Text Available Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the training parameter changes between two periods, within a short period and across the whole training time. It was found that the resting alpha amplitude measured before training had significant positive correlations with all learning indices and could be used as a predictor for the learning ability prediction. This finding would help the researchers in not only predicting the training efficacy in individuals but also gaining further insight into the mechanisms of alpha neurofeedback.

  3. Distribution of alpha-amylase activity in selected broiler tissues. (United States)

    Rodeheaver, D P; Wyatt, R D


    In an examination of broiler alpha-amylase, significant variation in the serum enzyme activity level was noted, adult levels were lower than those of young chicks. Analysis of alpha-amylase activity in various body fluids and tissues of 11-day and 7-week-old broilers indicated that the liver cannot be considered a source of alpha-amylase, although there was activity in both liver tissue and bile of 10 units/g wet weight and 35 units/100 ml, respectively. Fluid from the oral cavity had low levels of alpha-amylase activity, less than 100 units/100 ml, which decreased with age, indicating that the salivary glands may synthesize some alpha-amylase but are not a primary source. Sonication of the pancreatic homogenates was found to significantly increase the apparent activity of alpha-amylase 35-fold over unsonicated homogenates. The pancreas was the major source of alpha-amylase with activities ranging from 89 X 10(2) to 445 X 10(2) units/g wet weight. The level of activity increased with age of the bird. The electrophoretic zymograms of serum, liver, and pancreatic homogenates indicate a similar pancreatic origin for the alpha-amylase found in each tissue or fluid.

  4. Alpha spindles as neurophysiological correlates indicating attentional shift in a simulated driving task. (United States)

    Sonnleitner, Andreas; Simon, Michael; Kincses, Wilhelm E; Buchner, Axel; Schrauf, Michael


    The intention of this paper is to describe neurophysiological correlates of driver distraction with highly robust parameters in the EEG (i.e. alpha spindles). In a simulated driving task with two different secondary tasks (i.e. visuomotor, auditory), N=28 participants had to perform full stop brakes reacting to appearing stop signs and red traffic lights. Alpha spindle rate was significantly higher during an auditory secondary task and significantly lower during a visuomotor secondary task as compared to driving only. Alpha spindle duration was significantly shortened during a visuomotor secondary task. The results are consistent with the assumption that alpha spindles indicate active inhibition of visual information processing. Effects on the alpha spindles while performing secondary tasks on top of the driving task indicate attentional shift according to the task modality. As compared to alpha band power, both the measures of alpha spindle rate and alpha spindle duration were less vulnerable to artifacts and the effect sizes were larger, allowing for a more accurate description of the current driver state.

  5. Characterization of a stable, major DNA polymerase alpha species devoid of DNA primase activity.


    Kaiserman, H B; Benbow, R. M.


    We have purified from Xenopus laevis ovaries a major DNA polymerase alpha species that lacked DNA primase activity. This primase-devoid DNA polymerase alpha species exhibited the same sensitivity as the DNA polymerase DNA primase alpha to BuAdATP and BuPdGTP, nucleotide analogs capable of distinguishing between DNA polymerase delta and DNA polymerase DNA primase alpha. The primase-devoid DNA polymerase alpha species also lacked significant nuclease activity indicative of the alpha-like (rathe...

  6. Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Kawada, Teruo, E-mail: [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)


    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected

  7. Uncertainty in magnetic activity indices

    Institute of Scientific and Technical Information of China (English)


    Magnetic activity indices are widely used in theoretical studies of solar-terrestrial coupling and space weather prediction. However, the indices suffer from various uncertainties, which limit their application and even mislead to incorrect conclu-sion. In this paper we analyze three most popular indices, Kp, AE and Dst. Three categories of uncertainties in magnetic indices are discussed: "data uncertainty" originating from inadequate data processing, "station uncertainty" caused by in-complete station covering, and "physical uncertainty" stemming from unclear physical mechanism. A comparison between magnetic disturbances and related indices indicate that the residual Sq will cause an uncertainty of 1―2 in K meas-urement, the uncertainty in saturated AE is as much as 50%, and the uncertainty in Dst index caused by the partial ring currents is about a half of the partial ring cur-rent.

  8. Chromospheric activity as age indicator

    CERN Document Server

    Pace, Giancarlo


    Chromospheric activity has been calibrated and widely used as age indicator. However, it has been suggested that the viability of such an age indicator is, in the best case, limited to stars younger than about 1.5 Gyr. I aim to define the age range for which chromospheric activity is a robust astrophysical clock. I collected literature measurements of the S-index in field stars, which is a measure of the strength of the H and K lines of the Ca II and a proxy for chromospheric activity, and exploited the homogeneous database of temperature and age determinations for field stars provided by the Geneva-Copenhagen survey of the Solar neighbourhood. Field data, inclusive data previously used to calibrate chromospheric ages, confirm the result found using open cluster data, i.e. there is no decay of chromospheric activity after about 2 Gyr. The only existing indication supporting the viability of chromospheric ages larger than 2 Gyr, is the similarity of chromospheric activity levels in the components of 35 dwarf b...

  9. Lucid dreaming and alpha activity: a preliminary report. (United States)

    Ogilvie, R D; Hunt, H T; Tyson, P D; Lucescu, M L; Jeakins, D B


    10 good dream recallers spent 2 nights in the sleep lab during which they were awakened 4 times per night from REM sleep, twice during their highest alpha activity in REM, and twice during low REM alpha. 5 were given alpha feedback training prior to sleep onset. Arousals from high alpha REM sleep yielded significantly higher lucidity ratings. Alpha feedback had no effect upon lucidity or REM alpha levels. Similarities between lucid dreams and meditative phenomena are discussed.

  10. Lucid dreaming and alpha activity: a preliminary report. (United States)

    Ogilvie, R D; Hunt, H T; Tyson, P D; Lucescu, M L; Jeakins, D B


    10 good dream recallers spent 2 nights in the sleep lab during which they were awakened 4 times per night from REM sleep, twice during their highest alpha activity in REM, and twice during low REM alpha. 5 were given alpha feedback training prior to sleep onset. Arousals from high alpha REM sleep yielded significantly higher lucidity ratings. Alpha feedback had no effect upon lucidity or REM alpha levels. Similarities between lucid dreams and meditative phenomena are discussed. PMID:7162915

  11. Adsorption behavior of alpha -cypermethrin on cork and activated carbon. (United States)

    Domingues, Valentina F; Priolo, Giuseppe; Alves, Arminda C; Cabral, Miguel F; Delerue-Matos, Cristina


    Studies were undertaken to determine the adsorption behavior of alpha -cypermethrin [R)-alpha -cyano-3-phenoxybenzyl(1S)-cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate, and (S)-alpha-cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate] in solutions on granules of cork and activated carbon (GAC). The adsorption studies were carried out using a batch equilibrium technique. A gas chromatograph with an electron capture detector (GC-ECD) was used to analyze alpha -cypermethrin after solid phase extraction with C18 disks. Physical properties including real density, pore volume, surface area and pore diameter of cork were evaluated by mercury porosimetry. Characterization of cork particles showed variations thereby indicating the highly heterogeneous structure of the material. The average surface area of cork particles was lower than that of GAC. Kinetics adsorption studies allowed the determination of the equilibrium time - 24 hours for both cork (1-2 mm and 3-4 mm) and GAC. For the studied alpha -cypermethrin concentration range, GAC revealed to be a better sorbent. However, adsorption parameters for equilibrium concentrations, obtained through the Langmuir and Freundlich models, showed that granulated cork 1-2 mm have the maximum amount of adsorbed alpha-cypermethrin (q(m)) (303 microg/g); followed by GAC (186 microg/g) and cork 3-4 mm (136 microg/g). The standard deviation (SD) values, demonstrate that Freundlich model better describes the alpha -cypermethrin adsorption phenomena on GAC, while alpha -cypermethrin adsorption on cork (1-2 mm and 3-4 mm) is better described by the Langmuir. In view of the adsorption results obtained in this study it appears that granulated cork may be a better and a cheaper alternative to GAC for removing alpha -cypermethrin from water.

  12. Effect of chemicals on fungal alpha-amylase activity. (United States)

    Ali, F S; Abdel-Moneim, A A


    The effect of 8 growth regulators at concentrations of 1,000, 5,000 and 10,000 ppm on the activity of fungal (Aspergillus flavus var. columnaris) alpha-amylase was studied. Indol acetic acid (IAA) and naphthalene acetic acid (NAA) inhibited alpha-amylase activity by 2% and 7% at 1,000 ppm. The other 6 growth regulators, indol butyric acid (IBA), gibberellic acid, cumarin, cycocel (CCC), atonik-G and kylar, did not inhibit but stimulated alpha-amylase activity (0 to 9%) at 1,000 ppm. All growth regulators studied inhibited alpha-amylase activity at 5,000 and 10,000 ppm concentration except kylar. The effect of organic acids and formaldehyde at 0.01, 0.005, and 0.001 M was studied. Acetic acid stimulated alpha-amylase at all concentrations, but formic acid, oxalic acid, lactic acid and citric acid inhibited alpha-amylase activity by 91, 100, 100 and 79%, respectively, at a concentration of 0.01 M, while by 31, 100, 15 and 20%, respectively, at 0.005 M. Formaldehyde induced 7, 3 and 2% inhibition at 0.01, 0.005 and 0.001 M, respectively. At 0.01 M either sorbitol or fructose inhibited alpha-amylase by 8%, Maltose 7%, sucrose 6%, phenol, glucose and galactose each by 5%, ethanol, glycerol, arabinose and sodium benzoate each by 4%, isopropanol and mannitol 1%, but methanol and ammonium citrate dibasic did not inhibit alpha-amylase. The results indicate that CuCl2, SnCl2, AgNO3 and Fe2(SO4)3 were the strongest inhibitors, followed by Cd(C2H3O2), HgCl2, Na2-EDTA, Na2HPO4, and CaCl2 in decreasing order. NaCl, NaBr and Mn SO4 did not inhibit alpha-amylase at concentrations from 10 mM to 0.01 mM. PMID:2515680

  13. H$_{\\alpha}$ line as an indicator of envelope presence around the Cepheid Polaris Aa ($\\alpha~ UMi$)

    CERN Document Server

    Usenko, I A; Klochkova, V G; Tavolzhanskaya, N S


    We present the results of the radial velocity ($RV$) measurements of metallic lines as well as H$_{\\alpha}$ (H$_{\\beta}$) obtained in 55 high-resolution spectra of the Cepheid $\\alpha$ UMi (Polaris Aa) in 1994-2010. While the $RV$ amplitudes of these lines are roughly equal, their mean $RV$ begin to differ essentially with growth of the Polaris Aa pulsational activity. This difference is accompanied by the H$_{\\alpha}$ line core asymmetries on the red side mainly (so-called knife-like profiles) and reaches 8-12 km/s in 2003 with a subsequent decrease to 1.5-2 km/s. We interpret a so unusual behaviour of the H$_{\\alpha}$ line core as dynamical changes in the envelope around Polaris Aa.

  14. Concentration levels of alpha emitting radionuclides in natural waters. Implications in the use of various radionuclides of reference for the determination of total alpha activity index; Niveles de concentracion de radionucleidos emisores alfa en aguas de origen natural. Implicaciones en el uso de los distintos radionucleidos de referencia para la determinacion del indice de actividad total alfa

    Energy Technology Data Exchange (ETDEWEB)

    Corbacho, J. A.; Baeza, A.; Guillen, J.; Valles, I.; Serrano, I.; Camacho, A.; Montana, M.


    The present study was carried out a statistical evaluation of the natural radioactive contents of a large number of water samples collected at different points of the Spanish geography, in order to meet its controlling radioactive composition and assessing the implications of total alpha activity index can have in this type of samples. (Author)

  15. The activity of granulocyte alpha-amylase in acute appendicitis. (United States)

    Zakrzewska, I; Gajda, R


    The activity of alpha-amylase was measured in isolated granulocytes, serum and urine of 35 patients with acute appendicitis. The measurements were performed before operation and on the 7th day after operation. Slightly increased activity of alpha-amylase was found in the serum and urine of 15 patients. On the 7th day after operation the activity of this enzyme reached normal value. The activity of granulocyte alpha-amylase was elevated in 22 patients. In 2 of them the increased activity still maintained on the 7th day after operation. Positive correlation between the serum and granulocyte alpha-amylase activities was found. These observations allow to conclude that granulocytes are the source of increased alpha-amylase activity in the serum of patients with acute appendicitis.

  16. The activity of granulocyte alpha-amylase in acute appendicitis. (United States)

    Zakrzewska, I; Gajda, R


    The activity of alpha-amylase was measured in isolated granulocytes, serum and urine of 35 patients with acute appendicitis. The measurements were performed before operation and on the 7th day after operation. Slightly increased activity of alpha-amylase was found in the serum and urine of 15 patients. On the 7th day after operation the activity of this enzyme reached normal value. The activity of granulocyte alpha-amylase was elevated in 22 patients. In 2 of them the increased activity still maintained on the 7th day after operation. Positive correlation between the serum and granulocyte alpha-amylase activities was found. These observations allow to conclude that granulocytes are the source of increased alpha-amylase activity in the serum of patients with acute appendicitis. PMID:7497089

  17. EEG alpha activity reflects motor preparation rather than the mode of action selection

    Directory of Open Access Journals (Sweden)

    Marie-Pierre eDeiber


    Full Text Available Alpha-band activity (8-13 Hz is suppressed by sensory stimulation and movements, modulated by attention, working memory and mental tasks and may be sensitive to higher motor control functions. The aim of the present study was to examine alpha oscillatory activity during the preparation of simple left or right finger movements, contrasting the external and internal mode of action selection. Three preparation conditions were examined using a precueing paradigm with S1 as the preparatory and S2 as the imperative cue: Full, laterality instructed by S1; Free, laterality freely selected and None, laterality instructed by S2. Time-frequency analysis was performed in the alpha frequency range during the S1-S2 interval, and alpha motor-related amplitude asymmetries (MRAA were also calculated. The significant MRAA during the Full and Free conditions indicated effective external and internal motor response preparation. In the absence of specific motor preparation (None, a posterior alpha power decrease (event-related desynchronization, ERD dominated, reflecting the main engagement of attentional resources. In Full and Free motor preparation, posterior alpha ERD was accompanied by a midparietal alpha power increase (event-related synchronization, ERS, suggesting a concomitant inhibition of task-irrelevant visual activity. In both Full and Free motor preparation, analysis of alpha power according to MRAA amplitude revealed two types of functional activation patterns: 1 a motor alpha pattern, with predominantly midparietal alpha ERS and large MRAA corresponding to lateralized motor activation/visual inhibition and 2 an attentional alpha pattern, with dominating right posterior alpha ERD and small MRAA reflecting visuospatial attention. The present results suggest that alpha oscillatory patterns do not resolve the selection mode of action, but rather distinguish separate functional strategies of motor preparation. 

  18. Intraperitoneal alpha-radioimmunotherapy in mice using different specific activities

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Haglund, Elin;


    The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At.......The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At....

  19. Measurement of total alpha activity in water; Messung der Gesamt-Alpha-Aktivitaet in Wasser

    Energy Technology Data Exchange (ETDEWEB)

    Eikenberg, Jost [Paul Scherrer Institut (PSI), Villigen (Switzerland). Abt. fuer Strahlenschutz und Sicherheit; Florschuetz, Bernd [Hessisches Landesamt fuer Umwelt und Geologie, Kassel (Germany). Dezernat 15 - Strahlenschutz; Salvamoser, Josef [Institut fuer Angewandte Isotopen-, Gas- und Umweltuntersuchungen, Woerthsee (Germany); Steinkopff, Thomas [Deutscher Wetterdienst, Offenbach am Main (Germany); Wilhelm, Christoph [Karlsruher Institut fuer Technologie (KIT), Eggenstein-Leopoldshafen (Germany). Sicherheitsmanagement - Analytische Labore; Wisser, Sascha [FCI, Mainz (Germany)


    The article describes the measurement of the total alpha activity in an (evaporated) liquid sample, and the various sample preparation methods for measurements with proportional counters or LSC. (orig.)

  20. Stress affects salivary alpha-Amylase activity in bonobos. (United States)

    Behringer, Verena; Deschner, Tobias; Möstl, Erich; Selzer, Dieter; Hohmann, Gottfried


    Salivary alpha-Amylase (sAA) is a starch digesting enzyme. In addition to its function in the context of nutrition, sAA has also turned out to be useful for monitoring sympathetic nervous system activity. Recent studies on humans have found a relationship between intra-individual changes in sAA activity and physical and psychological stress. In studies on primates and other vertebrates, non-invasive monitoring of short-term stress responses is usually based on measurements of cortisol levels, which are indicative of hypothalamic-pituitary-adrenal activity. The few studies that have used both cortisol levels and sAA activity indicate that these two markers may respond differently and independently to different types of stress such that variation in the degree of the activation of different stress response systems might reflect alternative coping mechanisms or individual traits. Here, we present the first data on intra- and inter-individual variation of sAA activity in captive bonobos and compare the results with information from other ape species and humans. Our results indicate that sAA activity in the bonobo samples was significantly lower than in the human samples but within the range of other great ape species. In addition, sAA activity was significantly higher in samples collected at times when subjects had been exposed to stressors (judged by changes in behavioral patterns and cortisol levels) than in samples collected at other times. Our results indicate that bonobos possess functioning sAA and, as in other species, sAA activity is influenced by autonomic nervous system activity. Monitoring sAA activity could therefore be a useful tool for evaluating stress in bonobos. PMID:21945369

  1. Importance of salt in the production matrix of the efficiency curve for the determination of the total alpha activity in water samples; Importancia de la matriz salina en la fabricacion de la curva de eficiencia para la determinacion del indice de actividad alfa total en muestras de agua

    Energy Technology Data Exchange (ETDEWEB)

    Baeza, A.; Corbacho, J. A.


    The determination of total alpha activity by the evaporation method allows obtaining, from a quick and inexpensive technique, the order of magnitude of the total activity of all alpha emitters present in a sample of water. This study shows that the detection efficiency curve varies significantly depending on the sodium salt is used to manufacture calibration and/or reference radionuclide used. (Author)

  2. Alpha activity in Indian thermal springs

    International Nuclear Information System (INIS)

    Background: Dissolved radon is contained in natural water due to primordial uranium in rocks and soils with which it comes in contact. There is dual exposure from radon in water i.e. due to inhalation of the radon released from the water into the ambient air and through ingestion when water is used for drinking. As radon contaminated water adversely affects the health, it is therefore fundamental from health and hygiene point of view to measure radium concentration and radon exhalation rates in water.Materials and Methods: LR-115, Type-II plastic track detectors were used to measure the radium concentration and radon exhalation rate in water samples collected from various thermal springs. The alpha tracks registered were counted by optical microscope at suitable magnification and converted into radium concentration and subsequently radon exhalation rates were measured. Results: The radon concentration emanated from water samples(air borne) varied from 84 Bqm-3 to 827 Bqm-3 with an average of 429± 12.72 Bqm-3 and the dissolved radon concentration varied from 5.65 Bq 1-1 to 55.66 Bq 1-1 with an average of 28.88± 0.85 Bq 1-1. The radon mass exhalation rates varied from 2.37 m Bq kg-1 hr-1 to 23.39 mBq kg-1 hr-1 with an average of 12.14 ±0.36 mBq kg-1 hr-1 and surface exhalation rates from 52.34 mBq m-2 hr-1 to 515.29 mBq m-2 hr-1 with an average of 267.36 ± 7.93 from different thermal spring water samples. The radium concentration varied from 0.3 0 Bq 1-1 to 2.93 Bq 1-1 with an average of 1.52 ± 0.045 Bq 1-1. Results indicate that the thermal spring water, which is also being used for drinking, is safe as far as radium concentration is concerned with the exception of a few isolated thermal spring sources

  3. alpha-Glycosidase inhibitory activity of hexagalloylglucose from the galls of Quercus infectoria. (United States)

    Hwang, J K; Kong, T W; Baek, N I; Pyun, Y R


    Hexagalloylglucose (3-O-digalloyl-1,2,4,6-tetra-O-galloyl-beta-D- glucose), which was isolated from the methanol extract of the galls of Quercus infectoria, significantly inhibited alpha-glycosidases such as sucrase, maltase and isomaltase. Its inhibitory activity was comparable to acarbose being used as a hypoglycemic agent, while the inhibitory activity on alpha-amylase was approximately 10 times lower than that of acarbose. The results indicate that, when compared to acarbose, hexagalloylglucose might reduce the side effects by reducing inhibition of alpha-amylase. PMID:10821056

  4. Activation of peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) suppresses postprandial lipidemia through fatty acid oxidation in enterocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Rino [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Takahashi, Nobuyuki, E-mail: [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Murota, Kaeko [Department of Life Science, School of Science and Engineering, Kinki University, Osaka 770-8503 (Japan); Yamada, Yuko [Laboratory of Physiological Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Niiya, Saori; Kanzaki, Noriyuki; Murakami, Yoko [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Moriyama, Tatsuya [Department of Applied Cell Biology, Graduate School of Agriculture, Kinki University, Nara 631-8505 (Japan); Goto, Tsuyoshi; Kawada, Teruo [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)


    production of CO{sub 2} and acid soluble metabolites in enterocytes. Moreover, bezafibrate treatment suppressed postprandial lipidemia after oral administration of olive oil to the mice. These findings indicate that PPAR{alpha} activation suppresses postprandial lipidemia through enhancement of fatty acid oxidation in enterocytes, suggesting that intestinal lipid metabolism regulated by PPAR{alpha} activity is a novel target of PPAR{alpha} agonist for decreasing circulating levels of lipids under postprandial conditions.

  5. Critical indices for reversible gamma-alpha phase transformation in metallic cerium (United States)

    Soldatova, E. D.; Tkachenko, T. B.


    Critical indices for cerium have been determined within the framework of the pseudobinary solution theory along the phase equilibrium curve, the critical isotherm, and the critical isobar. The results obtained verify the validity of relationships proposed by Rushbrook (1963), Griffiths (1965), and Coopersmith (1968). It is concluded that reversible gamma-alpha transformation in metallic cerium is a critical-type transformation, and cerium has a critical point on the phase diagram similar to the critical point of the liquid-vapor system.

  6. Gamma power is phase-locked to posterior alpha activity.

    Directory of Open Access Journals (Sweden)

    Daria Osipova

    Full Text Available Neuronal oscillations in various frequency bands have been reported in numerous studies in both humans and animals. While it is obvious that these oscillations play an important role in cognitive processing, it remains unclear how oscillations in various frequency bands interact. In this study we have investigated phase to power locking in MEG activity of healthy human subjects at rest with their eyes closed. To examine cross-frequency coupling, we have computed coherence between the time course of the power in a given frequency band and the signal itself within every channel. The time-course of the power was calculated using a sliding tapered time window followed by a Fourier transform. Our findings show that high-frequency gamma power (30-70 Hz is phase-locked to alpha oscillations (8-13 Hz in the ongoing MEG signals. The topography of the coupling was similar to the topography of the alpha power and was strongest over occipital areas. Interestingly, gamma activity per se was not evident in the power spectra and only became detectable when studied in relation to the alpha phase. Intracranial data from an epileptic subject confirmed these findings albeit there was slowing in both the alpha and gamma band. A tentative explanation for this phenomenon is that the visual system is inhibited during most of the alpha cycle whereas a burst of gamma activity at a specific alpha phase (e.g. at troughs reflects a window of excitability.

  7. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. (United States)

    Lin, Jiandie; Wu, Hai; Tarr, Paul T; Zhang, Chen-Yu; Wu, Zhidan; Boss, Olivier; Michael, Laura F; Puigserver, Pere; Isotani, Eiji; Olson, Eric N; Lowell, Bradford B; Bassel-Duby, Rhonda; Spiegelman, Bruce M


    The biochemical basis for the regulation of fibre-type determination in skeletal muscle is not well understood. In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibres are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibres. We have previously identified a transcriptional co-activator, peroxisome-proliferator-activated receptor-gamma co-activator-1 (PGC-1 alpha), which is expressed in several tissues including brown fat and skeletal muscle, and that activates mitochondrial biogenesis and oxidative metabolism. We show here that PGC-1 alpha is expressed preferentially in muscle enriched in type I fibres. When PGC-1 alpha is expressed at physiological levels in transgenic mice driven by a muscle creatine kinase (MCK) promoter, a fibre type conversion is observed: muscles normally rich in type II fibres are redder and activate genes of mitochondrial oxidative metabolism. Notably, putative type II muscles from PGC-1 alpha transgenic mice also express proteins characteristic of type I fibres, such as troponin I (slow) and myoglobin, and show a much greater resistance to electrically stimulated fatigue. Using fibre-type-specific promoters, we show in cultured muscle cells that PGC-1 alpha activates transcription in cooperation with Mef2 proteins and serves as a target for calcineurin signalling, which has been implicated in slow fibre gene expression. These data indicate that PGC-1 alpha is a principal factor regulating muscle fibre type determination. PMID:12181572

  8. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Maëlle Lempereur


    Full Text Available Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L. which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box. In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells. Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif.

  9. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells. (United States)

    Lempereur, Maëlle; Majewska, Claire; Brunquers, Amandine; Wongpramud, Sumalee; Valet, Bénédicte; Janssens, Philippe; Dillemans, Monique; Van Nedervelde, Laurence; Gallo, Dominique


    Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L.) which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα) antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box). In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells). Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif. PMID:27190515

  10. Radioactivity Measurement Method for Environmental Monitoring Gross Alpha/beta Activities in Drinking Water in Turkey. (United States)

    Kahraman, Gülten; Aslan, Nazife; Şahin, Mihriban; Yüksek, Simay


    The determination of gross alpha/beta activity concentrations of drinking water is the first step of the environmental monitoring studies and can provide a rapid evaluation of the radioactive content of a sample. In this study, a procedure using liquid scintillation spectrometry (LSS) for the simultaneously monitoring of gross alpha/beta activity concentration in drinking water was determined, verificated with proficiency test sample and applied to the real drinking water samples in Turkey. The results indicate that the method provides good accuracy and precision. LSS can be employed as a screening technique in high activity concentrations. PMID:26454594

  11. Modulation of the chaperone-like activity of bovine alpha-crystallin. (United States)

    Clark, J I; Huang, Q L


    The effects of pantethine, glutathione, and selected chemical reagents on the anti-aggregation activity of alpha-crystallin was evaluated. Protein aggregation was monitored by light scattering of solutions of denatured beta L-crystallin or alcohol dehydrogenase (ADH). The ratios of beta L-crystallin/alpha-crystallin and ADH/alpha-crystallin were adjusted so that partial inhibition of protein aggregation at 60 degrees C or 37 degrees C, respectively, was observed and modulation of the chaperone action of alpha-crystallin could be evaluated easily with selected endogenous metabolites. Enhancement of the anti-aggregation activity in the beta L-crystallin assay was strongest with pantethine, which appeared to interact with alpha-crystallin. Enhancement of the anti-aggregation activity in the ADH assay was strongest with glutathione which appeared to interact with ADH. The results indicated that the products of common metabolic pathways can modulate the chaperone-like effects of alpha-crystallin on protein aggregation. PMID:8986785

  12. Alpha-activities in environmental samples

    International Nuclear Information System (INIS)

    Determination of 239Pu(240Pu) in human lungs from autopsies show for the period 1961 - 1965 lung burdens between 150 - 600 fCi and about 50 fCi/organ for the years 1978/79. In some cases also 241Am and 234U/238U contents were analyzed. Air concentration measurements concerning 239Pu(240Pu) and uranium isotopes were carried out using air filters taken between 1962 - 1979 at a sampling station in Vienna. Additionally performed investigations about the α-activity of typical food stuffs allow a rough estimation of the intake for the general population. Based on statistical data and the results of activity measurements especially of 210Po, 226Ra, 232Th and U(nat) in coals and the ashes, emissions from coal fired stationary sources are discussed. (Author)

  13. Human ADAM 12 (meltrin alpha) is an active metalloprotease

    DEFF Research Database (Denmark)

    Loechel, F; Gilpin, B J; Engvall, E;


    The ADAMs (a disintegrin and metalloprotease) are a family of multidomain proteins with structural homology to snake venom metalloproteases. We recently described the cloning and sequencing of human ADAM 12 (meltrin alpha). In this report we provide evidence that the metalloprotease domain of ADAM...... 12 is catalytically active. We used the trapping mechanism of alpha2-macroglobulin to assay for protease activity of wild-type and mutant ADAM 12 proteins produced in a COS cell transfection system. We found that ADAM 12 is synthesized as a zymogen, with the prodomain maintaining the metalloprotease...... in a latent form, probably by means of a cysteine switch. The zymogen could be activated chemically by alkylation with N-ethylmaleimide. Cleavage of the prodomain at a site for a furin-like endopeptidase resulted in an ADAM 12 protein with proteolytic activity. The protease activity was sensitive...

  14. H$_\\alpha$-activity and ages for stars in the SARG survey

    CERN Document Server

    Sissa, E; Desidera, S; Fiorenzano, A F Martinez; Bonfanti, A; Carolo, E; Vassallo, D; Claudi, R U; Endl, M; Cosentino, R


    Stellar activity influences radial velocity (RV) measurements and can also mimic the presence of orbiting planets. As part of the search for planets around the components of wide binaries performed with the SARG High Resolution Spectrograph at the TNG, it was discovered that HD 200466A shows strong variation in RV that is well correlated with the activity index based on H$_\\alpha$. We used SARG to study the H$_\\alpha$ line variations in each component of the binaries and a few bright stars to test the capability of the H$_\\alpha$ index of revealing the rotation period or activity cycle. We also analysed the relations between the average activity level and other physical properties of the stars. We finally tried to reveal signals in the RVs that are due to the activity. At least in some cases the variation in the observed RVs is due to the stellar activity. We confirm that H$_\\alpha$ can be used as an activity indicator for solar-type stars and as an age indicator for stars younger than 1.5 Gyr.

  15. In vitro anti-inflammatory activities of new steroidal antedrugs: [16alpha,17alpha-d] Isoxazoline and [16alpha,17alpha-d]-3'-hydroxy-iminoformyl isoxazoline derivatives of prednisolone and 9alpha-fluoroprednisolone. (United States)

    Park, Kwan-K; Ko, Dong-H; You, Z; Khan, M Omar F; Lee, Henry J


    A series of new anti-inflammatory steroidal antedrugs with C-16,17-isoxazoline ring system were synthesized and their pharmacological activities were evaluated. We reported earlier that these compounds are promising antedrugs based on the results of 5-day rat croton oil ear edema assay. In the present study, most of these compounds showed high binding affinities to the glucocorticoid receptor of liver cytosol. 21-acetyloxy-9alpha-fluoro-11beta-hydroxy-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d] isoxazoline (FP-ISO-21AC) and 11beta,21-dihydroxy-9alpha-fluoro-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d] isoxazoline (FP-ISO-21OH) were found 5.0-, 5.3-fold more potent than prednisolone, respectively. Inhibitory effects of the antedrugs on the nitric oxide (NO) production were assessed using LPS-stimulated RAW 264.7 murine macrophage cells. All these steroidal antedrugs exhibited concentration-dependent inhibition of NO production, but their relative potencies were lower than prednisolone. In vitro metabolism study in rat plasma showed that FP-ISO-21AC and 21-acetyloxy-9alpha-fluoro-11beta-hydroxy-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d]-3'-hydroxyiminoformyl isoxazoline (FP-OXIM-21AC) were hydrolyzed rapidly, with the half-lives of 2.1 and 4.2 min, respectively. The half-lives of FP-ISO-21OH and 11beta,21-dihydroxy-9alpha-fluoro-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d]-3'-hydroxyiminoformyl isoxazoline (FP-OXIM-21OH) were 92.2 and 110.2 min, respectively. PMID:16309722

  16. Antiviral activity of bacteria-derived human alpha interferons against encephalomyocarditis virus infection of mice.


    Weck, P K; Rinderknecht, E; Estell, D A; Stebbing, N


    Bacteria-derived human leukocyte interferon (IFN) subtypes, IFN-alpha A, -alpha B, and -alpha D, and two hybrid IFNs, IFN-alpha AD and -alpha DA, were examined for both in vitro and in vivo antiviral activity. Two of these materials in highly purified form (IFN-alpha D and -alpha D) protect mice against lethal doses of encephalomyocarditis virus infection. A single dose of 1 microgram of protein of IFN-alpha D 3 h before infection conferred protection in both BDF1 and CD-1 mice against enceph...

  17. HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia.

    Directory of Open Access Journals (Sweden)

    Freya M Mowat

    Full Text Available BACKGROUND: Hypoxia plays a key role in ischaemic and neovascular disorders of the retina. Cellular responses to oxygen are mediated by hypoxia-inducible transcription factors (HIFs that are stabilised in hypoxia and induce the expression of a diverse range of genes. The purpose of this study was to define the cellular specificities of HIF-1alpha and HIF-2alpha in retinal ischaemia, and to determine their correlation with the pattern of retinal hypoxia and the expression profiles of induced molecular mediators. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the tissue distribution of retinal hypoxia during oxygen-induced retinopathy (OIR in mice using the bio-reductive drug pimonidazole. We measured the levels of HIF-1alpha and HIF-2alpha proteins by Western blotting and determined their cellular distribution by immunohistochemistry during the development of OIR. We measured the temporal expression profiles of two downstream mediators, vascular endothelial growth factor (VEGF and erythropoietin (Epo by ELISA. Pimonidazole labelling was evident specifically in the inner retina. Labelling peaked at 2 hours after the onset of hypoxia and gradually declined thereafter. Marked binding to Müller glia was evident during the early hypoxic stages of OIR. Both HIF-1alpha and HIF-2alpha protein levels were significantly increased during retinal hypoxia but were evident in distinct cellular distributions; HIF-1alpha stabilisation was evident in neuronal cells throughout the inner retinal layers whereas HIF-2alpha was restricted to Müller glia and astrocytes. Hypoxia and HIF-alpha stabilisation in the retina were closely followed by upregulated expression of the downstream mediators VEGF and EPO. CONCLUSIONS/SIGNIFICANCE: Both HIF-1alpha and HIF-2alpha are activated in close correlation with retinal hypoxia but have contrasting cell specificities, consistent with differential roles in retinal ischaemia. Our findings suggest that HIF-2alpha activation

  18. Diabetes or peroxisome proliferator-activated receptor alpha agonist increases mitochondrial thioesterase I activity in heart (United States)

    Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a transcriptional regulator of the expression of mitochondrial thioesterase I (MTE-I) and uncoupling protein 3 (UCP3), which are induced in the heart at the mRNA level in response to diabetes. Little is known about the regulation of pr...

  19. Two farnesoid X receptor alpha isoforms in Japanese medaka (Oryzias latipes) are differentially activated in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Howarth, Deanna L. [Integrated Toxicology and Environmental Health Program and Nicholas School of the Environment and Earth Sciences, Duke University, Durham, NC 27708 (United States); Hagey, Lee R. [Department of Medicine, University of California at San Diego, La Jolla, CA 92093 (United States); Law, Sheran H.W. [Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695 (United States); Ai, Ni [Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854 (United States); Krasowski, Matthew D. [Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA (United States); Ekins, Sean [Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854 (United States); Collaboration in Chemistry, Jenkintown, PA 19046 (United States); Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD 21201 (United States); Moore, John T. [GlaxoSmithKline Discovery Research, Research Triangle Park, NC 27709 (United States); Kollitz, Erin M. [Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695 (United States); Hinton, David E. [Integrated Toxicology and Environmental Health Program and Nicholas School of the Environment and Earth Sciences, Duke University, Durham, NC 27708 (United States); Kullman, Seth W., E-mail: [Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695 (United States)


    The nuclear receptor farnesoid X receptor alpha (FXR{alpha}, NR1H4) is activated by bile acids in multiple species including mouse, rat, and human and in this study we have identified two isoforms of Fxr{alpha} in Japanese medaka (Oryzias latipes), a small freshwater teleost. Both isoforms share a high amino acid sequence identity to mammalian FXR{alpha} ({approx}70% in the ligand-binding domain). Fxr{alpha}1 and Fxr{alpha}2 differ within the AF1 domain due to alternative splicing at the fourth intron-exon boundary. This process results in Fxr{alpha}1 having an extended N-terminus compared to Fxr{alpha}2. A Gal4DBD-Fxr{alpha}LBD fusion construct was activated by chenodeoxycholic, cholic, deoxycholic and lithocholic acids, and the synthetic agonist GW4064 in transient transactivation assays. Activation of the Gal4DBD-Fxr{alpha}LBD fusion construct was enhanced by addition of PGC-1{alpha}, as demonstrated through titration assays. Surprisingly, when the full-length versions of the two Fxr{alpha} isoforms were compared in transient transfection assays, Fxr{alpha}2 was activated by C{sub 24} bile acids and GW4064, while Fxr{alpha}1 was not significantly activated by any of the compounds tested. Since the only significant difference between the full-length constructs was sequence in the AF1 domain, these experiments highlight a key functional region in the Fxr{alpha} AF1 domain. Furthermore, mammalian two-hybrid studies demonstrated the ability of Fxr{alpha}2, but not Fxr{alpha}1, to interact with PGC-1{alpha} and SRC-1, and supported our results from the transient transfection reporter gene activation assays. These data demonstrate that both mammalian and teleost FXR (Fxr{alpha}2 isoform) are activated by primary and secondary bile acids.

  20. 5-Azacytidine treatment of HA-A melanoma cells induces Sp1 activity and concomitant transforming growth factor alpha expression. (United States)

    Shin, T H; Paterson, A J; Grant, J H; Meluch, A A; Kudlow, J E


    Evidence indicates DNA methylation as a part of the regulatory machinery controlling mammalian gene expression. The human melanoma cell line HA-A expresses low levels of transforming growth factor alpha (TGF-alpha). TGF-alpha mRNA accumulated, however, in response to DNA demethylation induced by a nucleoside analog, 5-azacytidine (5-azaC). The importance of DNA methylation in the TGF-alpha promoter region was examined by a transient transfection assay with luciferase reporter plasmids containing a portion of the TGF-alpha promoter. 5-azaC treatment of HA-A cells before the transfection caused a significant increase in the luciferase activity. Since input plasmids were confirmed to remain unmethylated, DNA demethylation of the TGF-alpha promoter itself does not account for the observed increase in TGF-alpha mRNA. Using an electrophoretic mobility shift assay, enhanced formation of protein-TGF-alpha promoter complex was detected in response to 5-azaC treatment. This 5-azaC-induced complex was shown to contain the transcription factor Sp1 by the following criteria: the protein-DNA complex formed on the TGF-alpha promoter contained immunoreactive Sp1; the mobility of the complex in an electrophoretic mobility shift assay was similar to that formed by recombinant Sp1; and DNase I footprinting analysis demonstrated that the 5-azaC-induced complex produced a footprint on the TGF-alpha promoter identical to that of authentic Sp1. These observations suggest that 5-azaC induces TGF-alpha expression by augmenting the Sp1 activity. However, neither the Sp1 mRNA nor its protein was induced by 5-azaC. These results suggest that in HA-A cells, TGF-alpha expression is down-modulated by DNA methylation. In addition, this process may involve the specific regulation of Sp1 activity without altering the amount of the transcription factor. Images PMID:1380648

  1. DMPD: What is disrupting IFN-alpha's antiviral activity? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15283983 What is disrupting IFN-alpha's antiviral activity? Mbow ML, Sarisky RT. Tr...ends Biotechnol. 2004 Aug;22(8):395-9. (.png) (.svg) (.html) (.csml) Show What is disrupting IFN-alpha's antiviral activity...? PubmedID 15283983 Title What is disrupting IFN-alpha's antiviral activity? Authors Mbow ML,

  2. Activating STAT3 Alpha for Promoting Healing of Neurons (United States)

    Conway, Greg


    A method of promoting healing of injured or diseased neurons involves pharmacological activation of the STAT3 alpha protein. Usually, injured or diseased neurons heal incompletely or not at all for two reasons: (1) they are susceptible to apoptosis (cell death); and (2) they fail to engage in axogenesis that is, they fail to re-extend their axons to their original targets (e.g., muscles or other neurons) because of insufficiency of compounds, denoted neurotrophic factors, needed to stimulate such extension. The present method (see figure) of treatment takes advantage of prior research findings to the effect that the STAT3 alpha protein has anti-apoptotic and pro-axogenic properties.

  3. Mindfulness-of-breathing exercise modulates EEG alpha activity during cognitive performance. (United States)

    Bing-Canar, Hanaan; Pizzuto, Jacquelyne; Compton, Rebecca J


    The present study investigated whether engaging in a mindful breathing exercise would affect EEG oscillatory activity associated with self-monitoring processes, based on the notion that mindfulness enhances attentional awareness. Participants were assigned to either an audio exercise in mindful breathing or an audio control condition, and then completed a Stroop task while EEG was recorded. The primary EEG measure of interest was error-related alpha suppression (ERAS), an index of self-monitoring in which alpha power is reduced, suggesting mental engagement, following errors compared to correct responses. Participants in the mindful-breathing condition showed increased alpha power during the listening exercise and enhanced ERAS during the subsequent Stroop task. These results indicate enhanced error-monitoring among those in the mindful-breathing group. PMID:27245493

  4. Transcriptional activation of the mouse obese (ob) gene by CCAAT/enhancer binding protein alpha

    DEFF Research Database (Denmark)

    Hwang, C S; Mandrup, S; MacDougald, O A;


    Like other adipocyte genes that are transcriptionally activated by CCAAT/enhancer binding protein alpha (C/EBP alpha) during preadipocyte differentiation, expression of the mouse obese (ob) gene is immediately preceded by the expression of C/EBP alpha. While the 5' flanking region of the mouse ob......, these findings implicate C/EBP alpha as a transcriptional activator of the ob gene promoter and identify the functional C/EBP binding site in the promoter....

  5. TNF-alpha-induced mitochondrial alterations in human T cells requires FADD and caspase-8 activation but not RIP and caspase-3 activation. (United States)

    Shakibaei, Mehdi; Sung, Bokyung; Sethi, Gautam; Aggarwal, Bharat B


    Although much is known about how TNF-alpha induces apoptosis in the presence of inhibitors of protein synthesis, little is known about how it induces apoptosis without these inhibitors. In this report we investigated temporal sequence of events induced by TNF-alpha in the absence of protein synthesis. Regardless of whether we measured the effects by plasma membrane phosphotidylserine accumulation, by DNA strand breaks, or activation of caspases, significant changes were observed only between 12-24 h of TNF-alpha treatment. One of the earliest changes observed after TNF-alpha treatment was mitochondrial swelling at 10 min; followed by cytochrome c and Smac release at 10-30 min, and then heterochromatin clumping occurred at 60 min. While genetic deletion of receptor-interaction protein (RIP) had no effect on TNF-alpha-induced mitochondrial damage, deletion of Fas-associated death domain (FADD) abolished the TNF-induced mitochondrial swelling. Since pan-caspase inhibitor z-VAD-fmk abolished the TNF-alpha-induced mitochondrial changes, z-DEVD-fmk, an inhibitor of caspase-3 had no effect, suggesting that TNF-alpha-induced mitochondrial changes or cytochrome c and Smac release requires caspase-8 but not caspase-3 activation. Overall, our results indicated that mitochondrial changes are early events in TNF-alpha-induced apoptosis and that these mitochondrial changes require recruitment of FADD and caspase-8 activation, but not caspase-3 activation or RIP recruitment. PMID:20136500

  6. Potentiation of mitomycin C and porfiromycin antitumor activity in solid tumor models by recombinant human interleukin 1 alpha. (United States)

    Braunschweiger, P G; Jones, S A; Johnson, C S; Furmanski, P


    The time- and dose-dependent effects of recombinant human interleukin 1 alpha (IL-1 alpha) on the antitumor activity of mitomycin C (MMC) and porfiromycin (PORF) were studied in RIF-1 and Panc02 solid tumor model systems. IL-1 alpha produced dose-dependent sensitization of clonogenic RIF-1 tumor cells to MMC in vivo. IL-1 alpha chemosensitization was highly schedule dependent, and the most efficacious schedules produced dose-modifying factors of 3.6 and 5.1 for MMC and PORF, respectively. More than additive clonogenic cell kill after IL-1 alpha-chemotherapy combinations reflected increased cellular sensitivity to MMC and PORF. The combinations also produced marked decreases in the yield of viable tumor cells, suggesting that the bioreductive drugs may have also potentiated the microvascular injury and ischemia produced by IL-1 alpha. Dexamethasone inhibited and ketoconazole, an inhibitor of corticosterone biosynthesis, enhanced IL-1 alpha-mediated chemosensitization in these models. IL-1 alpha mediated chemosensitization to MMC, and PORF was also demonstrated by tumor growth inhibition in the RIF-1 model and increased survival of mice in the spontaneously metastasizing Panc02 system. Chemosensitization of bone marrow spleen colony-forming units was not seen. IL-1 alpha (1000 units/ml) had no effect on MMC and PORF cytotoxicity in RIF-1 and PORF cell lines in vitro. The results indicate that the tumor-specific IL-1 alpha-induced pathophysiologies can sensitize solid tumors to agents which are preferentially activated, retained, and cytotoxic to cells under hypoxic conditions. Our results suggest that strategies combining bioreductively activated hypoxic cell cytotoxins and biological agents might offer efficacious alternatives or adjuvants to conventional combination approaches. PMID:1913664

  7. Alpha-amylase activity in blood increases after pharmacological, but not psychological, activation of the adrenergic system


    Nater, Urs M.; Roberto La Marca; Katja Erni; Ulrike Ehlert


    BACKGROUND & AIM: Alpha-amylase in both blood and saliva has been used as a diagnostic parameter. While studies examining alpha-amylase activity in saliva have shown that it is sensitive to physiological and psychological challenge of the adrenergic system, no challenge studies have attempted to elucidate the role of the adrenergic system in alpha-amylase activity in blood. We set out to examine the impact of psychological and pharmacological challenge on alpha-amylase in blood in two separat...

  8. Real-time MEG neurofeedback training of posterior alpha activity modulates subsequent visual detection performance

    NARCIS (Netherlands)

    Okazaki, Y.O.; Horschig, J.; Luther, L.M.; Oostenveld, R.; Murakami, I.; Jensen, O.


    It has been demonstrated that alpha activity is lateralized when attention is directed to the left or right visual hemifield. We investigated whether real-time neurofeedback training of the alpha lateralization enhances participants' ability to modulate posterior alpha lateralization and causes subs

  9. Mode of action and functional significance of 7alpha-hydroxypregnenolone stimulating locomotor activity

    Directory of Open Access Journals (Sweden)

    Shogo eHaraguchi


    Full Text Available Previous studies over the past two decades have demonstrated that the brain and other nervous systems possess key steroidogenic enzymes and produces pregnenolone and other various neurosteroids in vertebrates in general. Recently, 7alpha-hydroxypregnenolone, a novel bioactive neurosteroid, was identified in the brain of newts and quail. Importantly, this novel neurosteroid is produced from pregnenolone through the enzymatic activity of cytochrome P4507alpha and acts on brain tissue as a neuronal modulator to stimulate locomotor activity in these vertebrates. Subsequently, the mode of action of 7alpha-hydroxypregnenolone was demonstrated. 7alpha-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7alpha-hydroxypregnenolone in the regulation of locomotor activity, diurnal and seasonal changes in 7alpha-hydroxypregnenolone synthesis were further characterized. Melatonin derived from the pineal gland and eyes regulates 7alpha-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7alpha-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7alpha-hydroxypregnenolone mediates corticosterone action to modulate locomotor activity under stress. This review summarizes the current knowledge regarding the mode of action and functional significance of 7alpha-hydroxypregnenolone, a newly identified bioactive neurosteroid stimulating locomotor activity.

  10. Glutathione transferase classes alpha, pi, and mu: GSH activation mechanism. (United States)

    Dourado, Daniel F A R; Fernandes, Pedro Alexandrino; Ramos, Maria João


    Since the early 1960s, glutathione transferases (GSTs) have been described as detoxification enzymes. In fact, GSTs are the most important enzymes involved in the metabolism of electrophilic xenobiotic/endobiotic compounds. These enzymes are able to catalyze the nucleophilic addition of glutathione (GSH) sulfur thiolate to a wide range of electrophilic substrates, building up a less toxic and more soluble compound. Cytosolic classes alpha, pi, and mu are the most extensively studied GSTs. However, many of the catalytic events are still poorly understood. In the present work, we have resorted to density functional theory (DFT) and to potential of mean force (PMF) calculations to determine the GSH activation mechanism of GSTP1-1 and GSTM1-1 isoenzymes. For the GSTP1-1 enzyme, we have demonstrated that a water molecule, after an initial conformational rearrangement of GSH, can assist a proton transfer between the GSH cysteine thiol (GSH-SH) and the GSH glutamate alpha carboxylate (GSH-COO(-)) groups. The energy barrier associated with the proton transfer is 11.36 kcal·mol(-1). The GSTM1-1 enzyme shows a completely different behavior from the previous isoenzyme. In this case, two water molecules, positioned between the GSH-SH and the ξ N atom of His107, working like a bridge, are able to promote the proton transfer between these two active groups with an energy barrier of 7.98 kcal·mol(-1). All our results are consistent with all the enzymes kinetics and mutagenesis experimental studies.

  11. The liver-enriched transcription factor CREBH is nutritionally regulated and activated by fatty acids and PPAR{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Danno, Hirosuke; Ishii, Kiyo-aki; Nakagawa, Yoshimi; Mikami, Motoki; Yamamoto, Takashi; Yabe, Sachiko; Furusawa, Mika; Kumadaki, Shin; Watanabe, Kazuhisa; Shimizu, Hidehisa; Matsuzaka, Takashi; Kobayashi, Kazuto; Takahashi, Akimitsu; Yatoh, Shigeru; Suzuki, Hiroaki; Yamada, Nobuhiro [Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba Ibaraki 305-8575 (Japan); Shimano, Hitoshi, E-mail: [Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba Ibaraki 305-8575 (Japan)


    To elucidate the physiological role of CREBH, the hepatic mRNA and protein levels of CREBH were estimated in various feeding states of wild and obesity mice. In the fast state, the expression of CREBH mRNA and nuclear protein were high and profoundly suppressed by refeeding in the wild-type mice. In ob/ob mice, the refeeding suppression was impaired. The diet studies suggested that CREBH expression was activated by fatty acids. CREBH mRNA levels in the mouse primary hepatocytes were elevated by addition of the palmitate, oleate and eicosapenonate. It was also induced by PPAR{alpha} agonist and repressed by PPAR{alpha} antagonist. Luciferase reporter gene assays indicated that the CREBH promoter activity was induced by fatty acids and co-expression of PPAR{alpha}. Deletion studies identified the PPRE for PPAR{alpha} activation. Electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) assay confirmed that PPAR{alpha} directly binds to the PPRE. Activation of CREBH at fasting through fatty acids and PPAR{alpha} suggest that CREBH is involved in nutritional regulation.

  12. High theta and low alpha powers may be indicative of BCI-illiteracy in motor imagery.

    Directory of Open Access Journals (Sweden)

    Minkyu Ahn

    Full Text Available In most brain computer interface (BCI systems, some target users have significant difficulty in using BCI systems. Such target users are called 'BCI-illiterate'. This phenomenon has been poorly investigated, and a clear understanding of the BCI-illiteracy mechanism or a solution to this problem has not been reported to date. In this study, we sought to demonstrate the neurophysiological differences between two groups (literate, illiterate with a total of 52 subjects. We investigated recordings under non-task related state (NTS which is collected during subject is relaxed with eyes open. We found that high theta and low alpha waves were noticeable in the BCI-illiterate relative to the BCI-literate people. Furthermore, these high theta and low alpha wave patterns were preserved across different mental states, such as NTS, resting before motor imagery (MI, and MI states, even though the spatial distribution of both BCI-illiterate and BCI-literate groups did not differ. From these findings, an effective strategy for pre-screening subjects for BCI illiteracy has been determined, and a performance factor that reflects potential user performance has been proposed using a simple combination of band powers. Our proposed performance factor gave an r = 0.59 (r(2 = 0.34 in a correlation analysis with BCI performance and yielded as much as r = 0.70 (r(2 = 0.50 when seven outliers were rejected during the evaluation of whole data (N = 61, including BCI competition datasets (N = 9. These findings may be directly applicable to online BCI systems.

  13. Chaperone-like activity of alpha-cyclodextrin via hydrophobic nanocavity to protect native structure of ADH. (United States)

    Barzegar, Abolfazl; Moosavi-Movahedi, Ali A; Mahnam, Karim; Ashtiani, Saman Hosseini


    The chaperone action of alpha-cyclodextrin (alpha-CyD), based on providing beneficial microenvironment of hydrophobic nanocavity to form molecular complex with alcohol dehydrogenase (ADH) was examined by experimental and computational techniques. The results of UV-vis and dynamic light scattering (DLS) indicated that the chaperone-like activity of alpha-CyD depends on molecular complex formation between alpha-CyD and ADH, which caused to decrease the amount and size of polymerized molecules. Computational calculations of molecular dynamic (MD) simulations and blind docking (BD) demonstrated that alpha-CyD acts as an artificial chaperone because of its high affinity to the region of ADH's two chains interface. The hydrophobic nanocavity of alpha-CyD has the ability to form inclusion complex due to the presence of phenyl ring of aromatic phenylalanine (Phe) residue in the dimeric intersection area. Delocalization of ADH subunits, which causes the exposure of Phe110, takes part in the enzyme polymerization and has proven to be beneficial for aggregation inhibition and solubility enhancement within the host alpha-CyD-nanocavity.

  14. Nitration of tyrosyl residues in human alpha-lactalbumin. Effect on lactose synthase specifier activity. (United States)

    Prieels, J P; Dolmans, M; Leonis, J; Brew, K


    Alpha-Lactalbumin isolated from human milk was reacted with tetranitromethane in molar excess of 8-32 mol/mol of tyrosine. After gel filtration on Sephadex G-75, followed by chromatographic fractionation using DEAE-Sephadex A-25, three main components were separated, which differed from one another in the extent of nitration. These protein fractions were found to contain, respectively, one and two nitrotyrosine residues, or two nitrotyrosine residues together with one nitrotryptophan. The lactose synthase specifier activity of each of these components was measured and compared with that of unsubstituted alpha-lactalbumin. Comparison of kinetic parameters showed the chemically modified proteins to be only slightly less active when tyrosines were the sole residues modified. In sharp contrast the additional nitration of a single tryptophan residue totally abolished the specifying activity of alpha-lactalbumin. Circular dichroism spectra of the tryptophan derivative revealed some structural alteration when compared with the other two and with the native protein. The conclusion could also be confirmed by using a double-immunodiffusion technique. After hydrolysis of the derivatives with thermolysin, it was possible to localize the substituted residues in the known sequence of human alpha-lactalbumin. Tyrosine-103 was found to be more easily nitrated than tyrosine-18. These two residues seem, therefore, to be on the outer surface of the molecule and more exposed than tyrosine-36 and tyrosine-50. Some precautions are indicated in the use of tetranitromethane as a nitrating agent on the basis of complex products observed in the nitration of the free amino acids tyrosine and tryptophan and their derivatives. PMID:812700

  15. Conditional expression of constitutively active estrogen receptor {alpha} in chondrocytes impairs longitudinal bone growth in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Kazuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Tsukui, Tohru [Experimental Animal Laboratory, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Imazawa, Yukiko; Horie-Inoue, Kuniko [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Inoue, Satoshi, E-mail: [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)


    Highlights: Black-Right-Pointing-Pointer Conditional transgenic mice expressing constitutively active estrogen receptor {alpha} (caER{alpha}) in chondrocytes were developed. Black-Right-Pointing-Pointer Expression of caER{alpha} in chondrocytes impaired longitudinal bone growth in mice. Black-Right-Pointing-Pointer caER{alpha} affects chondrocyte proliferation and differentiation. Black-Right-Pointing-Pointer This mouse model is useful for understanding the physiological role of ER{alpha}in vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caER{alpha}{sup ColII}, expressing constitutively active mutant estrogen receptor (ER) {alpha} in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caER{alpha}{sup ColII} mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caER{alpha}{sup ColII} mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caER{alpha}{sup ColII} mice. These results suggest that ER{alpha} is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

  16. Design of a Quality Control Program for the Measurement of Gross Alpha and Gross Beta Activities (LMPR-CIEMAT)

    International Nuclear Information System (INIS)

    In accordance with international standards, general requirements for testing laboratories have to include a quality system for planning, implementing, and assessing the work performed by the organization and for carrying out required quality assurance and quality control. The purpose of internal laboratory quality control is to monitor performance, identify problems, and initiate corrective actions. This report describes the internal quality control to monitor the gross alpha and beta activities determination. Identification of specific performance indicators, the principles that govern their use and statistical means of evaluation are explained. Finally, calculation of alpha and beta specific activities, uncertainties and detection limits are performed. (Author) 10 refs.

  17. Binding of receptor-recognized forms of alpha2-macroglobulin to the alpha2-macroglobulin signaling receptor activates phosphatidylinositol 3-kinase. (United States)

    Misra, U K; Pizzo, S V


    Ligation of the alpha2-macroglobulin (alpha2M) signaling receptor by receptor-recognized forms of alpha2M (alpha2M*) initiates mitogenesis secondary to increased intracellular Ca2+. We report here that ligation of the alpha2M signaling receptor also causes a 1. 5-2.5-fold increase in wortmannin-sensitive phosphatidylinositol 3-kinase (PI3K) activity as measured by the quantitation of phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 formation was alpha2M* concentration-dependent with a maximal response at approximately 50 pM ligand concentration. The peak formation of PIP3 occurred at 10 min of incubation. The alpha2M receptor binding fragment mutant K1370R which binds to the alpha2M signaling receptor activating the signaling cascade, increased PIP3 formation by 2-fold. The mutant K1374A, which binds very poorly to the alpha2M signaling receptor, did not cause any increase in PIP3 formation. alpha2M*-induced DNA synthesis was inhibited by wortmannin. 1, 2Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acetoxymethylester a chelator of intracellular Ca2+, drastically reduced alpha2M*-induced increases in PIP3 formation. We conclude that PI3K is involved in alpha2M*-induced mitogenesis in macrophages and intracellular Ca2+ plays a role in PI3K activation. PMID:9593670

  18. Left temporal alpha band activity increases during working memory retention of pitches

    NARCIS (Netherlands)

    Van Dijk, H.; Nieuwenhuis, I.L.C.; Jensen, O.


    The functional role and regional specificity of similar to 10 Hz alpha band activity remains of debate. Alpha band activity is strongly modulated in visual working memory tasks and it has been proposed to subserve resource allocation by disengaging task-irrelevant regions. It remains unknown if alph

  19. Activity of L-alpha-amino acids at the promiscuous goldfish odorant receptor 5.24

    DEFF Research Database (Denmark)

    Christiansen, Bolette; Wellendorph, Petrine; Bräuner-Osborne, Hans


    report the agonist activities of the 20 proteinogenic L-alpha-amino acids, and L-ornithine and L-citrulline, measured in an intracellular calcium release assay in mammalian tsA cells. The results show that receptor 5.24 is broadly activated by 19 of the tested L-alpha-amino acids and displays...

  20. Evidence of Environmental Dependencies of Type Ia Supernovae from the Nearby Supernova Factory indicated by Local H{\\alpha}

    CERN Document Server

    Rigault, M; Aldering, G; Antilogus, P; Aragon, C; Bailey, S; Baltay, C; Bongard, S; Buton, C; Canto, A; Cellier-Holzem, F; Childress, M; Chotard, N; Fakhouri, H K; Feindt, U; Fleury, M; Gangler, E; Greskovic, P; Guy, J; Kim, A G; Kowalski, M; Lombardo, S; Nordin, J; Nugent, P; Pain, R; Pécontal, E; Pereira, R; Perlmutter, S; Rabinowitz, D; Runge, K; Saunders, C; Scalzo, R; Smadja, G; Tao, C; Thomas, R C; Weaver, B A


    (Abridged) We study the host galaxy regions in close proximity to Type Ia supernovae (SNe Ia) to analyze relations between the properties of SN Ia events and environments most similar to where their progenitors formed. We focus on local H\\alpha\\ emission as an indicator of young environments. The Nearby Supernova Factory has obtained flux-calibrated spectral timeseries for SNe Ia using integral field spectroscopy, allowing the simultaneous measurement of the SN and its immediate vicinity. For 89 SNe Ia we measure H\\alpha\\ emission tracing ongoing star formation within a 1 kpc radius around each SN. This constitutes the first direct study of the local environment for a large sample of SNe Ia also having accurate luminosity, color and stretch measurements. We find that SNe Ia with local H\\alpha\\ emission are redder by 0.036+/-0.017 mag, and that the previously-noted correlation between stretch and host mass is entirely driven by the SNe Ia coming from passive regions. Most importantly, the mean standardized bri...

  1. AMP-activated protein kinase-regulated activation of the PGC-1alpha promoter in skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Isabella Irrcher

    Full Text Available The mechanisms by which PGC-1alpha gene expression is controlled in skeletal muscle remains largely undefined. Thus, we sought to investigate the transcriptional regulation of PGC-1alpha using AICAR, an activator of AMPK, that is known to increase PGC-1alpha expression. A 2.2 kb fragment of the human PGC-1alpha promoter was cloned and sequence analysis revealed that this TATA-less sequence houses putative consensus sites including a GC-box, a CRE, several IRSs, a SRE, binding sites for GATA, MEF2, p 53, NF-kappaB, and EBox binding proteins. AMPK activation for 24 hours increased PGC-1alpha promoter activity with concomitant increases in mRNA expression. The effect of AICAR on transcriptional activation was mediated by an overlapping GATA/EBox binding site at -495 within the PGC-1alpha promoter based on gel shift analyses that revealed increases in GATA/EBox DNA binding. Mutation of the EBox within the GATA/EBox binding site in the promoter reduced basal promoter activity and completely abolished the AICAR effect. Supershift analyses identified USF-1 as a DNA binding transcription factor potentially involved in regulating PGC-1alpha promoter activity, which was confirmed in vivo by ChIP. Overexpression of either GATA-4 or USF-1 alone increased the p851 PGC-1alpha promoter activity by 1.7- and 2.0-fold respectively, while co-expression of GATA-4 and USF-1 led to an additive increase in PGC-1alpha promoter activity. The USF-1-mediated increase in PGC-1alpha promoter activation led to similar increases at the mRNA level. Our data identify a novel AMPK-mediated regulatory pathway that regulates PGC-1alpha gene expression. This could represent a potential therapeutic target to control PGC-1alpha expression in skeletal muscle.

  2. Interplanetary Lyman $\\alpha$ line profiles: variations with solar activity cycle

    CERN Document Server

    Quemerais, E; Bertaux, J L; Koutroumpa, D; Clarke, J; Kyrola, E; Schmidt, W; Qu\\'emerais, Eric; Lallement, Rosine; Bertaux, Jean-Loup; Koutroumpa, Dimitra; Clarke, John; Kyrola, Erkki; Schmidt, Walter


    Interplanetary Lyman alpha line profiles are derived from the SWAN H cell data measurements. The measurements cover a 6-year period from solar minimum (1996) to after the solar maximum of 2001. This allows us to study the variations of the line profiles with solar activity. These line profiles were used to derive line shifts and line widths in the interplanetary medium for various angles of the LOS with the interstellar flow direction. The SWAN data results were then compared to an interplanetary background upwind spectrum obtained by STIS/HST in March 2001. We find that the LOS upwind velocity associated with the mean line shift of the IP \\lya line varies from 25.7 km/s to 21.4 km/s from solar minimum to solar maximum. Most of this change is linked with variations in the radiation pressure. LOS kinetic temperatures derived from IP line widths do not vary monotonically with the upwind angle of the LOS. This is not compatible with calculations of IP line profiles based on hot model distributions of interplanet...

  3. Single amino acid changes that render human IFN-alpha 2 biologically active on mouse cells.


    Weber, H.; Valenzuela, D; Lujber, G; Gubler, M; Weissmann, C


    Human IFN-alpha 1 and IFN-alpha 2 differ in 28 of 166 amino acids and show very different specific antiviral activities on human and murine cells. We have identified, by hybrid scanning and site-directed mutagenesis, three residues in IFN-alpha 2, in positions 121, 125 and 132 which, when replaced individually or jointly by their IFN-alpha 1 counterparts, modify its activity on mouse cells by up to 400-fold. We argue that these residues are involved in direct contacts with the mouse interfero...

  4. Selection of the appropriate radionuclide source for the efficiency calibration in methods of determining gross alpha activity in water. (United States)

    Corbacho, J A; Zapata-García, D; Montaña, M; Fons, J; Camacho, A; Guillén, J; Serrano, I; Baeza, A; Llauradó, M; Vallés, I


    Measuring the gross alpha activity in water samples is a rapid, straightforward way of determining whether the water might contain a radionuclide concentration whose consumption would imply a total indicative dose (TID) greater than some reference limit - currently set at 0.1 mSv/y in Europe. There are several methods used for such measurements. Two of them are desiccation with the salts being deposited on a planchet, and coprecipitation. The main advantage of these two methods is their ease of implementation and low cost of preparing the source to measure. However, there is considerable variability in the selection of the most suitable radioactive reference standard against which to calculate the water's gross alpha activity. The goal of this paper is to propose the most appropriate reference radionuclides to use as standards in determining gross alpha activities with these two methods, taking into account the natural radioactive characteristics of a wide range of waters collected at different points in Spain. Thus, the results will be consistent with each other and representative of the sum of alpha activities of all the alpha-emitters contained in a sample. PMID:26397746

  5. Thalamic involvement in the regulation of alpha EEG activity in psychiatric patients

    International Nuclear Information System (INIS)

    Aim: The thalamus is considered to be an important sub-cortical system involved in modulation of cortical activities. A relationship between thalamic activity and surface EEG was recently reported. In this study we evaluated a group of patients with psychiatric disorders who presented with asymmetric perfusion of the thalamus based on brain SPECT HMPAO studies. We predicted that asymmetrical activity of the thalamus would have asymmetrically distributed surface qEEG activity patterns. Materials and Methods: Twenty-three male psychiatric patients (age 54±14) with a primary diagnosis of depression and co-morbid substance abuse (83%) were studied with qEEG and HMPAO brain SPECT. The HMPAO ligand was administered while the EEG activity was being recorded. The SPECT analysis was conducted by means of ROI and SPM. ROI regions were determined based on the Talairach atlas coordinate system. ROI locations were verified by the automated utility, Talairach Demon. QEEG data was analyzed by a standardized protocol involving the NxLink database. Correlations between SPECT findings and qEEG absolute power were calculated. Results: Patients were divided into two groups based on thalamic perfusion patterns. Group 1 (Gr 1) had decreased perfusion to the right thalamus whereas Group 2 (Gr 2) had decreased perfusion to the left thalamus. SPM comparison of the patient groups to normal control subjects indicated significant findings. Comparison of Gr 1 to controls showed increased activity in the left temporal lobe and vermis. Decreased activity was observed in the left and right medial frontal lobes (right Brodmann 9;left Brodmann 6) as well as the left (Brodmann 30) and right (Brodmann 24) cingulate. Gr 2 comparison showed increased activity in the right middle frontal gyrus (Brodmann 10) and left inferior parietal lobe. Decreased activity was found in the left inferior frontal lobe (Brodmann 47). A positive correlation between alpha power and thalamic perfusion was identified in Gr

  6. Assessment of alpha activity of building materials commonly used in West Bengal, India

    International Nuclear Information System (INIS)

    This paper, reports for the first time, an extensive study of alpha activity of all widely used building materials (plaster of Paris, stone chips, marble, white cement, mosaic stone, limestone, sand, granite, cement brick, asbestos, red brick, cement tile, ceramic tile and ceramics) in West Bengal, India. The alpha activities have been measured using Solid State Nuclear Track Detector (SSNTD), a very sensitive detector for alpha particles. The samples were collected from local markets of Kolkata. The measured average alpha activities ranged from 22.7 ± 2.5 to 590.6 ± 16.8 Bq kg-1. The alpha activity of ceramic tiles was highest and provides additional data to estimate the effect of environmental radiation exposure on human health

  7. Activation of two new alpha(1,3)fucosyltransferase activities in Chinese hamster ovary cells by 5-azacytidine. (United States)

    Potvin, B; Stanley, P


    Several mammalian alpha(1,3)fucosyltransferases (alpha[1,3]Fuc-T) that synthesize carbohydrates containing alpha(1,3)fucosylated lactosamine units have been identified. Although Chinese hamster ovary (CHO) cells do not express alpha(1,3)Fuc-T activity, the rare mutants LEC11 and LEC12, isolated after mutagenesis or DNA transfection, each express an alpha(1,3)Fuc-T that may be distinguished by several criteria. Two new CHO mutants possessing alpha(1,3)Fuc-T activity (LEC29 and LEC30) have now been isolated after treatment of a CHO cell population with 5-azacytidine (5-AzaC), ethylnitrosourea (ENU), or 5-AzaC followed by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Like LEC12, both mutants possess an N-ethylmaleimide-resistant alpha(1,3)Fuc-T activity that can utilize a variety of acceptors and both express the Lewis X (Lex) determinant (Gal beta[1,4](Fuc alpha[1,3])GlcNAc beta 1)) but not the sialyl alpha(2,3)Lex determinant on cell-surface carbohydrates. However, LEC29 and LEC30 may be distinguished from LEC11 and LEC12, as well as from each other, on the basis of their unique patterns of lectin resistance and their abilities to bind the VIM-2 monoclonal antibody that recognizes carbohydrates terminating in NeuNAc alpha(2,3)Gal beta(1,4)GlcNAc beta(1,3)Gal beta(1,4)(Fuc alpha[1,3])GlcNAc beta and also by the different in vitro substrate specificities and kinetic properties of their respective alpha(1,3)Fuc-T activities. The combined data provide good evidence that the LEC29 and LEC30 alpha(1,3)Fuc-Ts are novel transferases encoded by distinct gene products. PMID:1724918

  8. Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation. (United States)

    Mohamad, Saharuddin B; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi


    Alpha-N-acetyl galactosaminidase (alpha-NaGalase) has been reported to accumulate in serum of cancer patients and be responsible for deglycosylation of Gc protein, which is a precursor of GcMAF-mediated macrophage activation cascade, finally leading to immunosuppression in advanced cancer patients. We studied the biochemical characterization of alpha-NaGalase from several human tumor cell lines. We also examined its effect on the potency of GcMAF to activate mouse peritoneal macrophage to produce superoxide in GcMAF-mediated macrophage activation cascade. The specific activity of alpha-NaGalases from human colon tumor cell line HCT116, human hepatoma cell line HepG2, and normal human liver cells (Chang liver cell line) were evaluated using two types of substrates; GalNAc-alpha-PNP (exo-type substrate) and Gal-beta-GalNAc-alpha-PNP (endo-type substrate). Tumor-derived alpha-NaGalase having higher activity than normal alpha-NaGalase, had higher substrate specificity to the exo-type substrate than to the endo-type substrate, and still maintained its activity at pH 7. GcMAF enhance superoxide production in mouse macrophage, and pre-treatment of GcMAF with tumor cell lysate reduce the activity. We conclude that tumor-derived alpha-NaGalase is different in biochemical characterization compared to normal alpha-NaGalase from normal Chang liver cells. In addition, tumor cell-derived alpha-NaGalase decreases the potency of GcMAF on macrophage activation. PMID:12062184

  9. Biologically active monoiodinated alpha-MSH derivatives for receptor binding studies using human melanoma cells

    International Nuclear Information System (INIS)

    Three different monoiodinated radioligands of alpha-MSH (alpha-melanocyte-stimulating hormone) were compared in a binding assay with human D10 melanoma cells: [Tyr(125I)2]-alpha-MSH, [Tyr(125I)2,NIe4]-alpha-MSH, and [Tyr(125I)2,NIe4,D-Phe7]-alpha-MSH. They were prepared either by the classical chloramine T method or by the Enzymobead method. A simple and rapid purification scheme was developed consisting of a primary separation on reversed-phase C18 silica cartridges immediately after the iodination, followed by HPLC purification before each binding experiment. Biological testing of the three radioligands showed that they all retained high melanotropic activity in the B16 melanin assay and the Anolis melanophore assay. However, in human D10 melanoma cells, [Tyr(125I)2,NIe4]-alpha-MSH led to a high degree of non-specific binding to the cells which could not be displaced by excess alpha-MSH and only partially by [NIe4]-alpha-MSH. The [Tyr(125I)2,NIe4,D-Phe7]-alpha-MSH tracer gave similar results but with a much lower proportion of non-specific binding. On the other hand, [Tyr(125I)2]-alpha-MSH proved to be an excellent radioligand whose non-specific binding to the D10 cells was not higher than 20% of the total binding

  10. Activity of alpha-1, 4-glucosidase in furazolidone-induced glycogenosis. (United States)

    Czarnecki, C M; Salam, A; Caldwell, R; Jankus, E F


    Furazolidone (FZ) at 700 and 800 p.p.m. was added to feed mixtures fed turkey poults two and three weeks posthatching, respectively, to induce acute experimental cardiomyopathy. Poults in the control pen received the same ration but without FZ. From EKG data obtained at 2, 4, and 5 weeks of age, control unaffected and experimental affected poults were selected for sacrifice. Poults were sacrificed by cervical dislocation and appropriate samples of hepatic tissue were removed for assays of activity of alpha-1, 4-glucosidase. Results indicate that enzyme activity in affected FZ-treated poults is similar to that in unaffected control poults. Lack of significant differences in activity of this lysosomal enzyme suggests that FZ-induced glycogenosis may be related to the adult form of idiopathic generalized glucogenosis, the etiology of which remains unidentified. PMID:353772

  11. Synthesis, antifeedant activity against Coleoptera and 3D QSAR study of alpha-asarone derivatives. (United States)

    Łozowicka, B; Kaczyński, P; Magdziarz, T; Dubis, A T


    For the first time, a set of 56 compounds representing structural derivatives of naturally occurring alpha-asarone as an antifeedants against stored product pests Sitophilus granarius L., Trogoderma granarium Ev., and Tribolium confusum Duv., were subjected to the 3D QSAR studies. Three-dimensional quantitative structure-activity relationships (3D-QSAR) for 56 compounds, including 15 newly synthesized, were performed using comparative molecular field analysis s-CoMFA and SOM-CoMSA techniques. QSAR was conducted based on a combination of biological activity (against Coleoptera larvae and beetles) and various geometrical, topological, quantum-mechanical, electronic, and chromatographic descriptors. The CoMSA formalism coupled with IVE (CoMSA-IVE) allowed us to obtain highly predictive models for Trogoderma granarium Ev. larvae. We have found that this novel method indicates a clear molecular basis for activity and lipophilicity. This investigation will facilitate optimization of the design of new potential antifeedants. PMID:24601760

  12. ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes

    DEFF Research Database (Denmark)

    Hao, Qin; Hansen, Jacob B; Petersen, Rasmus K;


    regulatory element-binding protein-1c (SREBP1c) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC1alpha) in brown and inguinal white adipose tissues, but not in epididymal white adipose tissue. Using in vitro models of white and brown adipocytes we demonstrate that beta......Cold adaptation elicits a paradoxical simultaneous induction of fatty acid synthesis and beta-oxidation in brown adipose tissue. We show here that cold exposure coordinately induced liver X receptor alpha (LXRalpha), adipocyte determination and differentiation-dependent factor 1 (ADD1)/sterol...... as a regulator of PGC1alpha expression in brown adipose tissue....

  13. Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hay-Schmidt, Anders; Hansen, Henrik H;


    alpha(7) nicotinic acetylcholine receptor (nAChR) agonists are candidates for the treatment of cognitive deficits in schizophrenia. Selective alpha(7) nAChR agonists, such as SSR180711, activate neurons in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (ACCshell) in rats, regions...

  14. The histeresis of the indices of solar activity and of the ionospheric indices in 11-yr cycles. The histeresis of the stellar activity indices in the cyclic activity similar to the Sun

    CERN Document Server

    Bruevich, E A; Kazachevskaya, T V; Katyushina, V V; Nusinov, A A


    The analysis of the effect of the hysteresis, which manifests itself in an ambiguous relationship of radiation from the photosphere, chromosphere and corona on the rise and decline phases of the solar and stellar activity cycles have done. Some indices of solar activity: the flux of the hydrogen Lyman-alpha emission, the 10.7 cm flux, the sunspot number SSN, the flux in the coronal green line 530.3 nm, the solar constant TSI and the 280 nm Mg II flux were studied. The stars with the well-determined cycles were examined to detect the effect of hysteresis between the chromosphere's S-index CaII fluxes versus the photosphere's fluxes Fphotosphere.

  15. Coefficient Alpha


    Panayiotis Panayides


    Heavy reliance on Cronbach’s alpha has been standard practice in many validation studies. However, there seem to be two misconceptions about the interpretation of alpha. First, alpha is mistakenly considered as an indication of unidimensionality and second, that the higher the value of alpha the better. The aim of this study is to clarify these misconceptions with the use of real data from the educational setting. Results showed that high alpha values can be obtained in multidimensional scale...

  16. Cytosolic PLA2(alpha) activation in Purkinje neurons and its role in AMPA-receptor trafficking. (United States)

    Mashimo, Masato; Hirabayashi, Tetsuya; Murayama, Toshihiko; Shimizu, Takao


    Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) selectively releases arachidonic acid from membrane phospholipids and has been proposed to be involved in the induction of long-term depression (LTD), a form of synaptic plasticity in the cerebellum. This enzyme requires two events for its full activation: Ca(2+)-dependent translocation from the cytosol to organelle membranes in order to access phospholipids as substrates, and phosphorylation by several kinases. However, the subcellular distribution and activation of cPLA(2)alpha in Purkinje cells and the role of arachidonic acid in cerebellar LTD have not been fully elucidated. In cultured Purkinje cells, stimulation of AMPA receptors, but not metabotropic glutamate receptors, triggered translocation of cPLA(2)alpha to the somatic and dendritic Golgi compartments. This translocation required Ca(2+) influx through P-type Ca(2+) channels. AMPA plus PMA, a chemical method for inducing LTD, released arachidonic acid via phosphorylation of cPLA(2)alpha. AMPA plus PMA induced a decrease in surface GluR2 for more than 2 hours. Interestingly, this reduction was occluded by a cPLA(2)alpha-specific inhibitor. Furthermore, PMA plus arachidonic acid caused the prolonged internalization of GluR2 without activating AMPA receptors. These results suggest that cPLA(2)alpha regulates the persistent decrease in the expression of AMPA receptors, underscoring the role of cPLA(2)alpha in cerebellar LTD. PMID:18713832

  17. Study of alpha activity in the region of rare earths

    International Nuclear Information System (INIS)

    The alpha decay half-lives of the Nd144, Cd152 and Er162 isotopes were redetermined using Ilford L4 nuclear emulsions charged with rare earth complexes of natural isotopic composition. The results were compared to results obtained by other authors, and with results calculated by potential barrier penetration theory. (M.C.K.)

  18. Simulated Microgravity Reduces TNF-Alpha Activity, Suppresses Glucose Uptake and Enhances Arginine Flux in Pancreatic Islets of Langerhans (United States)

    Tobin, Brian W.; Leeper-Woodford, Sandra K.; Hashemi, Brian B.; Smith, Scott M.; Sams, Clarence F.; Paloski, W. H. (Technical Monitor)


    The present studies were designed to determine effects of microgravity upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF - alpha) activity and indices of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1726+/-117,150 u IEU) from Wistar Furth rats were treated as: 1) HARV (High Aspect Ratio Vessel cell culture) , 2) HARV plus LPS 3) static culture, 4) static culture plus LPS TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (parginine in islets cultured in HARVs. While nitrogenous compound analysis indicated a ubiquitous reliance upon glutamine in all experimental groups, arginine was converted to ornithine at a two-fold greater rate in the islets cultured in the HARV microgravity paradigm (p<0.05). These studies demonstrate alterations in LPS induced TNF-alpha production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV paradigm. These alterations in fuel homeostasis may be promulgated by gravity averaged cell culture methods or by three dimensional cell assembly.

  19. Gross alpha and gross beta activity in the products and by-product of amang tin tailings process

    International Nuclear Information System (INIS)

    Gross alpha and gross beta activities were determined for mineral samples collected from five amang tailing factories. The measured activity of alpha ranged from 31 to 220,000 Bq kg-1 with an average 9,154 Bq kg-1, whereas for beta activity ranged from 9 to 552,000 Bq kg-1 with an average 19,811 Bq kg-1. The higher gross alpha and gross beta observed of monazite while the lowest recorded of waste (sand) and pyrite for gross alpha and gross beta activity respectively. The minimum detectable activities were 180 and 40 Bq kg-1 for gross alpha and gross beta respectively. (author)

  20. Long-term stellar activity variations of stars from the HARPS M-dwarf sample: Comparison between activity indices

    CERN Document Server

    da Silva, J Gomes; Bonfils, X


    We used four known chromospheric activity indicators to measure long-term activity variations in a sample of 23 M-dwarf stars from the HARPS planet search program. We compared the indices using weighted Pearson correlation coefficients and found that in general (i) the correlation between $S_{CaII}$ and \\ion{Na}{i} is very strong and does not depend on the activity level of the stars, (ii) the correlation between our $S_{CaII}$ and H$\\alpha$ seems to depend on the activity level of the stars, and (iii) there is no strong correlation between $S_{CaII}$ and \\ion{He}{i} for these type of stars.

  1. Cortical alpha activity reflects the degree of confidence in committing to an action

    Directory of Open Access Journals (Sweden)

    Jan eKubanek


    Full Text Available When we make a decision, we experience a degree of confidence that our choice may lead to a desirable outcome. Recent studies in animals have probed the subjective aspects of the choice confidence using confidence-reporting tasks. These studies showed that estimates of the choice confidence substantially modulate neural activity in multiple regions of the brain. Building on these findings, we investigated the neural representation of the confidence in a choice in humans who explicitly reported the confidence in their choice. Subjects performed a perceptual decision task in which they decided between choosing a button press or a saccade while we recorded EEG activity. Following each choice, subjects indicated whether they were sure or unsure about the choice. We found that alpha activity strongly encodes a subject’s confidence level in a forthcoming button press choice. The neural effect of the subjects’ confidence was independent of the reaction time, of eye movement, and of activity of forearm muscles. Furthermore, the effect was not explained by the sensory input modeled by a decision variable. Neither could the effect be explained by a general cognitive state, such as arousal or reward expectation, because the effect was specifically observed during button press choices and not during saccade choices. The neural effect of the confidence in the ensuing button press choice was strong enough that we could predict, from independent single trial neural signals, whether a subject was going to be sure or unsure of its button press choice. In sum, alpha activity in human cortex provides a window into the degree of a forming commitment to make a hand movement.

  2. Inhibition of activated protein C by recombinant alpha 1-antitrypsin variants with substitution of arginine or leucine for methionine358

    NARCIS (Netherlands)

    Heeb, M.J.; Bischoff, Rainer; Courtney, M.; Griffin, J.H.


    alpha 1-Antitrypsin (alpha 1-AT) was recently identified as a major physiologic plasma inhibitor of activated protein C. The reaction with activated protein C of recombinant alpha 1-AT containing amino acid substitutions at the reactive center was studied. The substitution of Arg358 for Met, as obse

  3. Relations of PC indices to further geophysical activity parameters. (United States)

    Stauning, P.


    The Polar Cap (PC) indices, PCN for the index values derived from Thule magnetic data and PCS derived from Vostok data, relate to the polar cap ionospheric plasma convection driven mainly by the interaction of the solar wind with the magnetosphere. Thus, the PC indices serve to monitor the input power from the solar wind which drives a range of geophysical disturbances such as magnetic storms and substorms, energization of the plasma trapped in the Earth's near space, auroral activity, and heating of the upper atmosphere. The presentation will demonstrate the relations between the PC indices and further parameters and indices used to describe geophysical activity such as polar cap potentials, auroral electrojet activity, Joule and particle heating of the upper atmosphere, mid-latitude magnetic variations, and ring current indices Dst, SYM-H and ASY-H.

  4. Radiographic findings and Gs-alpha bioactivity studies and mutation screening in acrodysostosis indicate a different etiology from pseudohypoparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Graham, J.M. Jr.; Krakow, D.; Smith, A.K.; Lachman, R.S. [UCLA, Los Angeles, CA (United States). School of Medicine; Tolo, V.T. [Div. of Orthopedics, Children' s Hospital of Los Angeles, CA (United States)


    Acrodysostosis is an uncommon skeletal dysplasia associated with nasal hypoplasia, midface deficiency, severe brachydactyly, and varying degrees of hearing loss and mental retardation. Previous publications have suggested that it may be difficult to distinguish acrodystostosis from pseudohypoparathyroidism on clinical grounds, but acrodysostosis does appear to have distinct clinical and radiologic findings. Spinal stenosis is an underappreciated risk in acrodysostosis, despite the reported loss of normal caudal widening of the lumbar interpediculate distance on AP spine radiographs in the original report of this disorder by Robinow et al., with confirmation of these radiographic findings by Butler et al. We report two sporadic cases of acrodysostosis, one of which required decompressive laminectomy for symptomatic spinal stenosis, and review 11 cases of acrodysostosis from 9 families that were submitted to the International Skeletal Dysplasia Registry. The objective of this report is to determine the frequency and severity of spinal stenosis in patients with acrodysostosis and to summarize the clinical and radiographic findings of acrodysostosis in an effort to distinguish acrodysostosis clearly from pseudohypoparathyroidism. The pattern of brachydactyly differs between these two conditions, and varying degrees of spinal stenosis are characteristic of acrodysostosis. Both our index patients with acrodysostosis had normal bioactivity of the alpha subunit of the Gs protein, therefore indicating that acrodysostosis has a different pathogenesis from pseudohypoparathyroidism. Furthermore, single-strand confirmational polymorphism (SSCP) analysis failed to demonstrate any confirmational alterations in the coding exons of the Gs alpha gene. These radiographic and laboratory findings substantiate that acrodysostosis is clinically different from pseudohypoparathyroidism and that it is necessary to follow patients with acrodysostosis for signs of spinal stenosis. (orig.)

  5. Measurement of natural radioactivity in chemical fertilizer and agricultural soil: evidence of high alpha activity. (United States)

    Ghosh, Dipak; Deb, Argha; Bera, Sukumar; Sengupta, Rosalima; Patra, Kanchan Kumar


    People are exposed to ionizing radiation from the radionuclides that are present in different types of natural sources, of which phosphate fertilizer is one of the most important sources. Radionuclides in phosphate fertilizer belonging to 232Th and 238U series as well as radioisotope of potassium (40K) are the major contributors of outdoor terrestrial natural radiation. The study of alpha activity in fertilizers, which is the first ever in West Bengal, has been performed in order to determine the effect of the use of phosphate fertilizers on human health. The data have been compared with the alpha activity of different types of chemical fertilizers. The measurement of alpha activity in surface soil samples collected from the cultivated land was also performed. The sampling sites were randomly selected in the cultivated land in the Midnapore district, which is the largest district in West Bengal. The phosphate fertilizer is widely used for large agricultural production, mainly potatoes. The alpha activities have been measured using solid-state nuclear track detectors (SSNTD), a very sensitive detector for alpha particles. The results show that alpha activity of those fertilizer and soil samples varies from 141 Bq/kg to 2,589 Bq/kg and from 109 Bq/kg to 660 Bq/kg, respectively. These results were used to estimate environmental radiation exposure on human health contributed by the direct application of fertilizers.

  6. Saccharomyces cerevisiae nuclear fusion requires prior activation by alpha factor.


    Rose, M D; Price, B R; Fink, G. R.


    We have developed a protocol for efficient fusion of spheroplasts of the same mating type. Nuclear fusion in this whole-cell system is also efficient and closely parallels nuclear fusion in heterosexual mating of intact cells. In the spheroplast fusion system, nuclear fusion is dependent on both the KAR1 gene and prior exposure to alpha factor. The major products of nuclear fusion in the spheroplast fusion assay were true diploids that were homozygous at the mating-type locus. An additional 1...

  7. Absolute measurements of the alpha-gamma emitters activities by a sum-coincidence method

    International Nuclear Information System (INIS)

    The absolute activity of U-235 contained in a UO2 sample, using a sum-coincidence circuit which selected only the alpha particles which were simultaneous with the well known 184 Kev gamma radiation from Th-231. The alpha particles were detected by ZnS(Ag) scintillator specially designed to show its maximun efficiency for U-235 alpha particles, whereas the gamma radiation was detected by NaI(Tl) scintillation detector. The values obtained for the half-life of U-235 was compared with data from various observers using different experimental techniques. (Author)

  8. The topography of alpha-band activity tracks the content of spatial working memory. (United States)

    Foster, Joshua J; Sutterer, David W; Serences, John T; Vogel, Edward K; Awh, Edward


    Working memory (WM) is a system for the online storage of information. An emerging view is that neuronal oscillations coordinate the cellular assemblies that code the content of WM. In line with this view, previous work has demonstrated that oscillatory activity in the alpha band (8-12 Hz) plays a role in WM maintenance, but the exact contributions of this activity have remained unclear. Here, we used an inverted spatial encoding model in combination with electroencephalography (EEG) to test whether the topographic distribution of alpha-band activity tracks spatial representations held in WM. Participants in three experiments performed spatial WM tasks that required them to remember the precise angular location of a sample stimulus for 1,000-1,750 ms. Across all three experiments, we found that the topographic distribution of alpha-band activity tracked the specific location that was held in WM. Evoked (i.e., activity phase-locked to stimulus onset) and total (i.e., activity regardless of phase) power across a range of low-frequency bands transiently tracked the location of the sample stimulus following stimulus onset. However, only total power in the alpha band tracked the content of spatial WM throughout the memory delay period, which enabled reconstruction of location-selective channel tuning functions (CTFs). These findings demonstrate that alpha-band activity is directly related to the coding of spatial representations held in WM and provide a promising method for tracking the content of this online memory system.

  9. UV-Activated Luminescence/Colourimetric O2 Indicator

    Directory of Open Access Journals (Sweden)

    Andrew Mills


    Full Text Available An oxygen indicator is described, comprising nanoparticles of titania dispersed in hydroxyethyl cellulose (HEC polymer film containing a sacrificial electron donor, glycerol, and the redox indicator, indigo-tetrasulfonate (ITS. The indicator is blue- coloured in the absence of UV light, however upon exposure to UV light it not only loses its colour but also luminesces, unless and until it is exposed to oxygen, whereupon its original colour is restored. The initial photobleaching spectral (absorbance and luminescence response characteristics in air and in vacuum are described and discussed in terms of a simple reaction scheme involving UV activation of the titania photocatalyst particles, which are used to reduce the redox dye, ITS, to its leuco form, whilst simultaneously oxidising the glycerol to glyceraldehye. The response characteristics of the activated, that is, UV photobleached, form of the indicator to oxygen are also reported and the possible uses of such an indicator to measure ambient O2 levels are discussed.

  10. Activation of Peroxisome Proliferator-Activated Receptor Alpha Improves Aged and UV-Irradiated Skin by Catalase Induction (United States)

    Shin, Mi Hee; Lee, Se-Rah; Kim, Min-Kyoung; Shin, Chang-Yup


    Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear hormone receptor involved in the transcriptional regulation of lipid metabolism, fatty acid oxidation, and glucose homeostasis. Its activation stimulates antioxidant enzymes such as catalase, whose expression is decreased in aged human skin. Here we investigated the expression of PPARα in aged and ultraviolet (UV)-irradiated skin, and whether PPARα activation can modulate expressions of matrix metalloproteinase (MMP)-1 and procollagen through catalase regulation. We found that PPARα mRNA level was significantly decreased in intrinsically aged and photoaged human skin as well as in UV-irradiated skin. A PPARα activator, Wy14643, inhibited UV-induced increase of MMP-1 and decrease of procollagen expression and caused marked increase in catalase expression. Furthermore, production of reactive oxygen species (ROS) was suppressed by Wy14643 in UV-irradiated and aged dermal fibroblasts, suggesting that the PPARα activation-induced upregulation of catalase leads to scavenging of ROS produced due to UV irradiation or aging. PPARα knockdown decreased catalase expression and abolished the beneficial effects of Wy14643. Topical application of Wy14643 on hairless mice restored catalase activity and prevented MMP-13 and inflammatory responses in skin. Our findings indicate that PPARα activation triggers catalase expression and ROS scavenging, thereby protecting skin from UV-induced damage and intrinsic aging. PMID:27611371

  11. Biological activity of 1. cap alpha. -hydroxyvitamin D/sub 2/ in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Reeve, L.E.; Schnoes, H.K.; DeLuca, H.F.


    The biological activity of 1..cap alpha..-hydroxyvitamin D/sub 2/ has been determined in vitamin D-deficient rats. In the calcification of the rachitic epiphyseal plate, 1..cap alpha..-hydroxyvitamin D/sub 2/ is more active than 25-hydroxyvitamin D/sub 3/, while it is equally active in stimulating intestinal calcium absorption. On the other hand, it is much less active (one-third to one-fifth) than 25-hydroxyvitamin D/sub 3/ in the mobilization of calcium from bone. In both the intestinal and bone responses, 1..cap alpha..-hydroxyvitamin D/sub 2/ (312 pmol) is active in nephrectomized rats while 15-hydroxyvitamin D/sub 3/ is not.

  12. Proxima Centauri as a Benchmark for Stellar Activity Indicators in the Near Infrared

    CERN Document Server

    Robertson, Paul; Mahadevan, Suvrath; Roy, Arpita; Ramsey, Lawrence W


    A new generation of dedicated Doppler spectrographs will attempt to detect low-mass exoplanets around mid-late M stars at near infrared (NIR) wavelengths, where those stars are brightest and have the most Doppler information content. A central requirement for the success of these instruments is to properly measure the component of radial velocity (RV) variability contributed by stellar magnetic activity and to account for it in exoplanet models of RV data. The wavelength coverage for many of these new instruments will not include the Ca II H&K or H-alpha lines, the most frequently used absorption-line tracers of magnetic activity. Thus, it is necessary to define and characterize NIR activity indicators for mid-late M stars in order to provide simultaneous activity metrics for NIR RV data. We have used the high-cadence UVES observations of the M5.5 dwarf Proxima Centauri from Fuhrmeister et al. (2011) to compare the activity sensitivity of 8 NIR atomic lines to that of H-alpha. We find that equivalent widt...

  13. 5-Azacytidine treatment of HA-A melanoma cells induces Sp1 activity and concomitant transforming growth factor alpha expression.


    Shin, T H; Paterson, A. J.; Grant, J H; Meluch, A A; Kudlow, J E


    Evidence indicates DNA methylation as a part of the regulatory machinery controlling mammalian gene expression. The human melanoma cell line HA-A expresses low levels of transforming growth factor alpha (TGF-alpha). TGF-alpha mRNA accumulated, however, in response to DNA demethylation induced by a nucleoside analog, 5-azacytidine (5-azaC). The importance of DNA methylation in the TGF-alpha promoter region was examined by a transient transfection assay with luciferase reporter plasmids contain...

  14. An application of LSC method for the measurement of gross alpha and beta activities in spiked water and drinking water samples

    Directory of Open Access Journals (Sweden)

    Çakal Gaye Özgür


    Full Text Available In this study, after the pulse shape calibration of a liquid scintillation counting (LSC spectrometer (Quantulus 1220, the effi ciency was determined depending on sample quenching parameters. Then, gross alpha and beta activities in two spiked water samples obtained from International Atomic Energy Agency (IAEA were used for the validation of the ASTM D7283-06 method, which is a standard test method for alpha and beta activity in water by LSC. Later, the drinking water samples (35 tap water and 9 bottled water obtained from different districts of Ankara, Turkey, were measured. The maximum gross alpha activities are measured to be 0.08 Bq/L for tap waters and 0.13 Bq/L for bottled waters, whereas the maximum gross beta activities are found to be 0.18 Bq/L for tap waters and 0.16 Bq/L for bottled waters. These results indicate that these drinking water samples are below the required limits, which are 0.1 Bq/L for alpha emitting radionuclides and 1 Bq/L for beta emitting radionuclides. As a result, gross alpha and beta activities in drinking water of Ankara were determined accurately by this validated LSC method. It is also worth noting that LSC is a rapid and accurate method for the determination of gross alpha and beta activities without requiring a tedious sample preparation.

  15. Design of a leading indicator for Costa Rican economic activity

    Directory of Open Access Journals (Sweden)

    Carlos Chaverri Morales


    Full Text Available This paper presents the results of estimating three leading indicators for the turning points of the economic activity in Costa Rica. This was done following the methodology proposed by the Organization for Economic Cooperation and Development (OECD. The Monthly Economic Activity Index (IMAE in Spanish was selected as the reference variable.  A total of 270 data series were analyzed including monetary, real and job market variables, as well as price indices, external sector indicators and fiscal sector variables. The real sector information was disaggregated into three levels, which included the classification of data at an industrial level using the International Standard Industrial Classification (ISIC with two digits, information from the agricultural sector based on the Central Product Classification (CPC and information from the manufacturing sector.  A leading indicator was developed for each level of aggregation, resulting in average leads of 7 to 12 months compared to the reference variable.

  16. Special Form Testing of Sealed Source Encapsulation for High-Alpha-Activity Actinide Materials

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Oscar A [ORNL


    In the United States all transportation of radioactive material is regulated by the U.S. Department of Transportation (DOT). Beginning in 2008 a new type of sealed-source encapsulation package was developed and tested by Oak Ridge National Laboratory (ORNL). These packages contain high-alpha-activity actinides and are regulated and transported in accordance with the requirements for DOT Class 7 hazardous material. The DOT provides specific regulations pertaining to special form encapsulation designs. The special form designation indicates that the encapsulated radioactive contents have a very low probability of dispersion even when subjected to significant structural events. The special form designs have been shown to simplify the delivery, transport, acceptance, and receipt processes. It is intended for these sealed-source encapsulations to be shipped to various facilities making it very advantageous for them to be certified as special form. To this end, DOT Certificates of Competent Authority (CoCAs) have been sought for the design suitable for containing high-alpha-activity actinide materials. This design consists of the high-alpha-activity material encapsulated within a triangular zirconia canister, referred to as a ZipCan, tile that is then enclosed by a spherical shell. The spherical shell design, with ZipCan tile inside, was tested for compliance with the special form regulations found in 49 CFR 173.469. The spherical enclosure was subjected to 9-m impact, 1 m percussion, and 10-minute thermal tests at the Packaging Evaluation Facility located at the National Transportation Research Center in Knoxville, TN USA and operated by ORNL. Before and after each test, the test units were subjected to a helium leak check and a bubble test. The ZipCan tiles and core were also subjected to the tests required for ISO 2919:2012(E), including a Class IV impact test and heat test and subsequently subjected to helium leakage rate tests [49 CFR 173.469(a)(4)(i)]. The impact

  17. Absolute alpha activity measurements of some plants growing in monazite bearing soils in Sri Lanka

    Energy Technology Data Exchange (ETDEWEB)

    Mahawatte, P.; Hewamanna, R. (Colombo Univ. (Sri Lanka). Radioisotope Centre)


    Deposits of monazite bearing soils occur along the Southwest, West and East Coasts of Sri Lanka. High levels of gamma activity in some plant species growing in the West Coast have been reported. The high levels were due to the presence of the daughter nuclides of {sup 232}Th, most of which are alpha emitters. Absolute alpha activity measurements of ash samples of some plants growing in monazite bearing soils were carried out using the alpha sensitive polymeric nuclear track detector CR-39. The values ranged from 60-1900 mBq/g and were in good agreement with the values obtained from conventional scintillation counting method. The activity concentration of {sup 228}Th in the ash samples was also calculated by measuring the activity concentration of emanated thoron trapped inside a glass bottle with the use of a CR-39 track detector. (author).

  18. Absolute alpha activity measurements of some plants growing in monazite bearing soils in Sri Lanka

    International Nuclear Information System (INIS)

    Deposits of monazite bearing soils occur along the Southwest, West and East Coasts of Sri Lanka. High levels of gamma activity in some plant species growing in the West Coast have been reported. The high levels were due to the presence of the daughter nuclides of 232Th, most of which are alpha emitters. Absolute alpha activity measurements of ash samples of some plants growing in monazite bearing soils were carried out using the alpha sensitive polymeric nuclear track detector CR-39. The values ranged from 60-1900 mBq/g and were in good agreement with the values obtained from conventional scintillation counting method. The activity concentration of 228Th in the ash samples was also calculated by measuring the activity concentration of emanated thoron trapped inside a glass bottle with the use of a CR-39 track detector. (author)

  19. Constructing Global Production Activity Indices: The Chemical Industry


    Saswati Mahapatra; Thomas K Swift


    This article first presents the challenges involved in constructing consistent, timely, and reliable short-term measures of national, regional, and global industry activity. The chemical industry is used as a case study. Second, this article presents the comparison of the movement or fluctuations in industrial production indices and chemical production indices that aid in determining if production in the chemical industry can be used as a proxy for total production in an economy. The American...

  20. Salivary type alpha-amylase activity in serum and in urine of patients with lung adenocarcinoma

    International Nuclear Information System (INIS)

    Total alpha-amylase activity in sera and urine of 30 patients with lung adenocarcinoma has been tested. The results were compared with control group of 30 healthy voluntaries. The activity of pancreatic type was differentiated from salivary alpha amylase. Salivary type was inhibited selectively by Triticum aestivum. Higher levels of total and salivary type amylase were noted in patients with lung adenocarcinoma in comparison to healthy control. The increase was significant (p<0.005). Correlation was observed between the activity of salivary type amylase and the stage of adenocarcinoma. (author)

  1. Effects of hydrophobicity on the antifungal activity of alpha-helical antimicrobial peptides.

    NARCIS (Netherlands)

    Jiang, Z.; Kullberg, B.J.; Lee, H van der; Vasil, A.I.; Hale, J.D.; Mant, C.T.; Hancock, R.E.; Vasil, M.L.; Netea, M.G.; Hodges, R.S.


    We utilized a series of analogs of D-V13K (a 26-residue amphipathic alpha-helical antimicrobial peptide, denoted D1) to compare and contrast the role of hydrophobicity on antifungal and antibacterial activity to the results obtained previously with Pseudomonas aeruginosa strains. Antifungal activity

  2. Microbial Activity Indices: Sensitive Soil Quality Indicators for Trace Metal Stress

    Institute of Scientific and Technical Information of China (English)



    Physicochemical properties, total and DTPA (diethylenetriaminepentaacetic acid)-extractable Cu, Zn, Pb and Cd contents, microbial biomass carbon (C) content and the organic C mineralization rate of the soils in a long-term trace metal-contaminated paddy region of Guangdong, China were determined to assess the sensitivity of microbial indices to moderately metal-contaminated paddy soils. The mean contents of total Cu, Zn, Pb and Cd were 251,250, 171, and 2.4mg kg-1 respectively. DTPA-extractable metals were correlated positively and significantly with total metals, CEC, and organic C (except for DTPA-extractable Cd), while they were negatively and highly significantly correlated with pH, total Fe and Mn. Metal stress resulted in relatively low ratios of microbial biomass C to organic C and in remarkable inhibition of the microbial metabolic quotient and C mineralization rate, which eventually led to increases in soil organic C and C/N. Moreover, microbial respiratory activity showed a stronger correlation to DTPA-extractable metals than to total metal content. Likewise, in the acid paddy soils some "linked" microbial activity indices, such as metabolic quotient and ratios of basal respiration to organic C, especially during initial incubation, were found to be more sensitive indicators of soil trace metal contamination than microbial biomass C or basal respiration alone.

  3. Effect of radioactive isotope 32P upon alpha amylase activity and glucose concentration in chickens

    International Nuclear Information System (INIS)

    An attempt has been made to investigate whether alpha amylase activity and glucose concentration in blood plasma can serve as the help in establishing on early diagnosis of organic or functional damage caused by ionizing radiation in chickens. Fifty day old hybrid chickens of heavy 'Jata' breeds of both sexes, were treated by 32P administered intramusculary as sodium orthophosphate in a single dose of 333 MBq per kilogram of body weight. Blood samples was taken from the wing vein on day 1, 3, 5, 7 and 10 after administration of 32P. Alpha amylase activity and glucose concentration were determined spectrophotometrically using kits produced by 'Radonja', Sisak. Alpha amylase activity was decreased and glucose concentration was increased during investigated period. Yet, the further investigations are needed to find out whether these two parameters can be used for early diagnosis of injury in chicken organism by ionizing radiation. (author)

  4. Antecedent occipital alpha band activity predicts the impact of oculomotor events in perceptual switching

    Directory of Open Access Journals (Sweden)

    Hironori eNakatani


    Full Text Available Oculomotor events such as blinks and saccades transiently interrupt the visual input and, even though this mostly goes undetected, these brief interruptions could still influence the percept. In particular, both blinking and saccades facilitate switching in ambiguous figures such as the Necker cube. To investigate the neural state antecedent to these oculomotor events during the perception of an ambiguous figure, we measured the human scalp electroencephalogram (EEG. When blinking led to perceptual switching, antecedent occipital alpha band activity exhibited a transient increase in amplitude. When a saccade led to switching, a series of transient increases and decreases in amplitude was observed in the antecedent occipital alpha band activity. Our results suggest that the state of occipital alpha band activity predicts the impact of oculomotor events on the percept.

  5. Enzyme activities by indicator of quality in organic soil (United States)

    Raigon Jiménez, Mo; Fita, Ana Delores; Rodriguez Burruezo, Adrián


    The analytical determination of biochemical parameters, as soil enzyme activities and those related to the microbial biomass is growing importance by biological indicator in soil science studies. The metabolic activity in soil is responsible of important processes such as mineralization and humification of organic matter. These biological reactions will affect other key processes involved with elements like carbon, nitrogen and phosphorus , and all transformations related in soil microbial biomass. The determination of biochemical parameters is useful in studies carried out on organic soil where microbial processes that are key to their conservation can be analyzed through parameters of the metabolic activity of these soils. The main objective of this work is to apply analytical methodologies of enzyme activities in soil collections of different physicochemical characteristics. There have been selective sampling of natural soils, organic farming soils, conventional farming soils and urban soils. The soils have been properly identified conserved at 4 ° C until analysis. The enzyme activities determinations have been: catalase, urease, cellulase, dehydrogenase and alkaline phosphatase, which bring together a representative group of biological transformations that occur in the soil environment. The results indicate that for natural and agronomic soil collections, the values of the enzymatic activities are within the ranges established for forestry and agricultural soils. Organic soils are generally higher level of enzymatic, regardless activity of the enzyme involved. Soil near an urban area, levels of activities have been significantly reduced. The vegetation cover applied to organic soils, results in greater enzymatic activity. So the quality of these soils, defined as the ability to maintain their biological productivity is increased with the use of cover crops, whether or spontaneous species. The practice of cover based on legumes could be used as an ideal choice

  6. Peroxisome Proliferator-Activated Receptor-alpha Is a Functional Target of p63 in Adult Human Keratinocytes

    DEFF Research Database (Denmark)

    Pozzi, Silvia; Boergesen, Michael; Sinha, Satrajit;


    healing process, is a target of p63 in human keratinocytes. Silencing of p63 by RNA interference and transient transfections showed that p63 represses PPARalpha through a functional region of promoter B. Chromatin immunoprecipitation analyses indicate that p63 is bound to this region, in the absence......p63 is a master switch in the complex network of signaling pathways controlling the establishment and maintenance of stratified epithelia. We provide evidence that peroxisome proliferator-activated receptor-alpha (PPARalpha), a ligand-activated nuclear receptor that participates in the skin wound...

  7. Catalposide is a natural agonistic ligand of peroxisome proliferator-activated receptor-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hae; Jun, Hee-jin; Hoang, Minh-Hien; Jia, Yaoyao [Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Han, Xiang Hua [College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Lee, Dong-Ho [Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Lee, Hak-Ju [Division of Green Business Management, Department of Forest Resources Utilization, Korean Forest Research Institute, Seoul 130-712 (Korea, Republic of); Hwang, Bang Yeon, E-mail: [College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Lee, Sung-Joon, E-mail: [Division of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Department of Biotechnology, Graduate School of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)


    Highlights: Black-Right-Pointing-Pointer Catalposide is a novel ligand for PPAR{alpha}. Black-Right-Pointing-Pointer Cell stimulated with catalposide improved fatty acid uptake, regulated target genes in fatty acid {beta}-oxidation and synthesis. Black-Right-Pointing-Pointer Catalposdie reduces hepatic triacylglycerides. Black-Right-Pointing-Pointer Theses demonstrate catalposide could ameliorate hyperlipidemia and hepatic steatosis. -- Abstract: Peroxisome proliferator-activated receptor-alpha (PPAR{alpha}) is a nuclear receptor that regulates the expression of genes related to cellular lipid uptake and oxidation. Thus, PPAR{alpha} agonists may be important in the treatment of hypertriglyceridemia and hepatic steatosis. In this study, we demonstrated that catalposide is a novel natural PPAR{alpha} agonist, identified from reporter gene assay-based activity screening with approximately 900 natural plant and seaweed extracts. Results of time-resolved fluorescence resonance energy transfer analyses suggested that the compound interacted directly with the ligand-binding domain of PPAR{alpha}. Cultured hepatocytes stimulated with catalposide exhibited significantly reduced cellular triglyceride concentrations, by 21%, while cellular uptake of fatty acids was increased, by 70% (P < 0.05). Quantitative PCR analysis revealed that the increase in cellular fatty acid uptake was due to upregulation of fatty acid transporter protein-4 (+19% vs. the control) in cells stimulated with catalposide. Additionally, expression of genes related to fatty acid oxidation and high-density lipoprotein metabolism were upregulated, while that of genes related to fatty acid synthesis were suppressed. In conclusion, catalposide is hypolipidemic by activation of PPAR{alpha} via a ligand-mediated mechanism that modulates the expression of in lipid metabolism genes in hepatocytes.

  8. Right prefrontal TMS disrupts interregional anticipatory EEG alpha activity during shifting of visuospatial attention

    Directory of Open Access Journals (Sweden)

    Paul eSauseng


    Full Text Available Visual attention can be shifted in space without moving the eyes. Amplitude decrease of rhythmical brain activity around 10 Hz (so called alpha activity at contralateral posterior sites has been reported during covert shifts of visuospatial attention to one visual hemifield. Alpha amplitude increase, on the other hand, can be found at ipsilateral visual cortex. There is some evidence suggesting an involvement of prefrontal brain areas during the control of attention-related anticipatory alpha amplitude asymmetry. However, the exact neural mechanism by which prefrontal cortex influences visual processing has not been completely clear yet. This open question has been studied in detail using a multimodal approach combining transcranial magnetic stimulation (TMS and multichannel electroencephalography (EEG in healthy humans. Slow (1 Hz repetitive TMS inducing an inhibitory effect at the stimulation site was delivered either to right frontal eye field or a control site (vertex. Subsequently, participants had to perform a spatial cueing task in which covert shifts of attention were required to either the left or the right visual hemi-field. After stimulation at the vertex (control condition a pattern of anticipatory, attention-related ipsilateral alpha increase / contralateral alpha decrease over posterior recording sites could be obtained. Additionally, there was pronounced coupling between (in particular right FEF and posterior brain sites. When, however, the right prefrontal cortex had been virtually lesioned preceding the task, these EEG correlates of visuospatial attention were attenuated. Notably, the effect of TMS at the right FEF on interregional fronto-parietal alpha coupling predicted the effect on response times. This suggests that visual attention processes associated with posterior EEG alpha activity are at least partly top-down controlled by the prefrontal cortex.

  9. Effects of central imidazolinergic and alpha2-adrenergic activation on water intake

    Directory of Open Access Journals (Sweden)

    Sugawara A.M.


    Full Text Available Non-adrenergic ligands that bind to imidazoline receptors (I-R, a selective ligand that binds to alpha2-adrenoceptors (alpha2-AR and mixed ligands that bind to both receptors were tested for their action on water intake behavior of 24-h water-deprived rats. All drugs were injected into the third cerebral ventricle. Except for agmatine (80 nmol, mixed ligands binding to I-R/alpha2-AR such as guanabenz (40 nmol and UK 14304 (20 nmol inhibited water intake by 65% and up to 95%, respectively. The selective non-imidazoline alpha2-AR agonist, alpha-methylnoradrenaline, produced inhibition of water intake similar to that obtained with guanabenz, but at higher doses (80 nmol. The non-adrenergic I-R ligands histamine (160 nmol, mixed histaminergic and imidazoline ligand and imidazole-4-acetic acid (80 nmol, imidazoline ligand did not alter water intake. The results show that selective, non-imidazoline alpha2-AR activation suppresses water intake, and suggest that the action on imidazoline sites by non-adrenergic ligands is not sufficient to inhibit water intake.

  10. alpha-MSH enhances activity-based anorexia

    NARCIS (Netherlands)

    Hillebrand, Jacquelien J G; Kas, Martien J H; Adan, Roger A H


    Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa (AN). In ABA, scheduled feeding in combination with voluntary access to running wheels, results in hyperactivity, hypophagia, body weight loss and activation of the HPA axis. Since stimulation of the melanocortin (MC) sy

  11. [Effect of adrenal stress on activity of proteinase and alpha-1-proteinase inhibitor in rats]. (United States)

    Samokhina, L M; Kaliman, P A


    The effect of adrenal stress on the proteinase and alpha-1-proteinase inhibitor activities in blood serum and cytosols of the rat organs were investigated. The reliable change was marked only in the alpha-1-PI level research of lung tissue cytosol. The proteolysis suppression was revealed in the heart and kidney tissue, while the proteolysis activation was revealed in serum and less in the lung tissue cytosol. Changes in proteinase level in the myocardium and kidney tissue play the primary role in respect to those of the other research liquids under study. PMID:7747353

  12. A functional Rev-erb alpha responsive element located in the human Rev-erb alpha promoter mediates a repressing activity.


    Adelmant, G; Bègue, A. (Alain); Stéhelin, D; Laudet, V


    Rev-erb alpha belongs to the nuclear receptor superfamily, which contains receptors for steroids, thyroid hormones, retinoic acid, and vitamin D, as well as "orphan" receptors. No ligand has been found for Rev-erb alpha to date, making it one of these orphan receptors. Similar to some other orphan receptors, Rev-erb alpha has been shown to bind DNA as a monomer on a specific sequence called a Rev-erb alpah responsive element (RevRE), but its transcriptional activity remains unclear. In this p...


    Directory of Open Access Journals (Sweden)

    Orlov A. I.


    Full Text Available Of the many urgent problems of Science about Science, we consider methods for estimation of the effectiveness and quality of the scientific activities of the researcher, of the organization, of the magazine. Performance indicators of scientific activity are used as an important part in the estimation of higher education institutions, the innovative capacity of enterprises, etc. To estimate the effectiveness of scientific activity is natural to use intellectual tools which are well-established in other subject areas. This will include, in particular, the balanced scorecard, based on key performance indicators (hence the title of this article, as well as controlling, primarily controlling of research activities. There are two more developed and widely used tools for estimation the effectiveness of the scientific activity - the scientometric indicators and the expert estimators. Their critical analysis is the subject of this article. Different versions of manipulating of values of scientometric indicators in the Russian Federation, in our estimation, are still relatively rare. Perhaps this is due to the relatively short period of their use in the management of science. Since an indicator such as citation index (the number of citations of publications of researcher, allows estimating its contribution to science, the use of this scientometric indicator for the management of science is justified. At the same time, the number of publications and especially h-index is not possible to objectively estimate the effectiveness of research activities, particularly in view of the properties of the real bibliometric databases. Expert procedures have several disadvantages. In this article we discuss the real effectiveness of expert procedures in the areas of their application, as conferring academic degrees and elections to the National Academy of Sciences (primarily in the Russian Academy of Sciences. The basic principles of expertise in these areas remain the

  14. A new serum indicator of activity of interstitial pneumonitis

    International Nuclear Information System (INIS)

    Serum levels of a high molecular weight circulating antigen KL-6, which is detected by sandwich assay using a monoclonal antibody KL-6 against a sialylated carbohydrate antigen, were examined for usefulness in monitoring the activity of interstitial pneumonitis. Of the 59 interstitial pneumonitis patients, 34 (58%) exhibited abnormally high levels of KL-6 antigen in their sera and no significant correlation between serum KL-6 values and lactic dehydrogenase activities was noted. Moreover, KL-6 antigen levels showed a positive correlation with the degree of clinical activity of the disease as measured by 67Ga-citrate scintigram and clinical outcome over time. These data suggest that serum KL-6 antigen may be a new useful indicator for estimating the degree of activity of interstitial pneumonitis, although it cannot be used for differential diagnosis of this disease from other malignant and nonmalignant diseases showing abnormally high levels of KL-6 antigen. (author)

  15. Kinesthetic and Vestibular Information Modulate Alpha Activity during Spatial Navigation: A Mobile EEG Study

    Directory of Open Access Journals (Sweden)

    Benedikt Valerian Ehinger


    Full Text Available In everyday life, spatial navigation involving locomotion provides congruent visual, vestibular and kinesthetic information that need to be integrated. Yet, previous studies on human brain activity during navigation focus on stationary setups, neglecting vestibular and kinesthetic feedback. The aim of our work is to uncover the influence of those sensory modalities on cortical processing. We developed a fully immersive virtual reality setup combined with high-density mobile electroencephalography (EEG. Participants traversed one leg of a triangle, turned on the spot, continued along the second leg and finally indicated the location of their starting position. Vestibular and kinesthetic information was provided either in combination, as isolated sources of information or not at all within a 2x2 full factorial intra-subjects design. EEG data were processed by clustering independent components, and time-frequency spectrograms were calculated. In parietal, occipital and temporal clusters, we detected alpha suppression during the turning movement, which is associated with a heightened demand of visuo-attentional processing, and closely resembles results reported in previous stationary studies. This decrease is present in all conditions and therefore seems to generalize to more natural settings. Yet, in incongruent conditions, when different sensory modalities did not match, the decrease is significantly stronger. Additionally, in more anterior areas, we found that providing only vestibular but no kinesthetic information results in alpha increase. These observations demonstrate that stationary experiments omit important aspects of sensory feedback. Therefore, it is important to develop more natural experimental settings in order to capture a more complete picture of neural correlates of spatial navigation.

  16. Studies of the Gly482Ser polymorphism of the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) gene in Danish subjects with the metabolic syndrome

    DEFF Research Database (Denmark)

    Ambye, Louise; Rasmussen, Susanne; Fenger, Mogens;


    The peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) is a novel transcriptional co-activator that holds an important role in lipid and glucose metabolism. PGC-1alpha is a candidate gene for the metabolic syndrome (MS) as well as type 2 diabetes. Recent studies...

  17. Stellate Ganglion Block Reduces the Radicular Pain and Salivary Alpha-Amylase Activity in Patients with Cervical Spondylosis

    Directory of Open Access Journals (Sweden)

    Takashi Egashira


    .g., cervical herniated intervertebral disc, disc bulging, and neuro-foramen narrowing. Conclusion The results indicate that SGB shows the reduction of VAS scale and the concentration of salivary alpha-amylase in patients with cervical spondylosis. These results show that salivary alpha-amylase activity could reflect the physical stress with radicular pain.

  18. Measurement of alpha activity from leaves and roots of radish plant enhanced by fertilizers

    Directory of Open Access Journals (Sweden)

    Amit Kumar


    Full Text Available The addition of inorganic phosphate fertilizers to soil and crops is a common practice for increasing crop production in worldwide. The fertilizers in soil causes an increase in the radionuclides content along with the essential nutrients that can transfer from soil to various parts of plants. The aim of this work is to measure the alpha activity from various part of radish plant. The measurement of alpha activity was performed by track etch technique using LR-115 detectors. The results show that the alpha track density from lower part of leaves is higher than that from upper part. The alpha track density from upper and lower part of leaves varied from 12 ± 1.9 to 40.8 ± 1.9 tr cm−2 and 16 ± 2.2 to 51.3 ± 3.3 tr cm−2 respectively while it varied from 45 ± 4 to 135 ± 4 tr cm−2 for edible part of plants. With age of plants the radionuclide contents continuously get accumulated in the different part of plant and hence increase in alpha track density was observed during present work. The track density for plants grown with phosphate fertilizers was found to be higher compare to organic and urea fertilizers.

  19. Rapid determination of gross alpha/beta activity in milk using liquid scintilation counter technique

    Directory of Open Access Journals (Sweden)

    Sas Daniel


    Full Text Available Rapid determination of gross alpha and beta emitters in milk by liquid scintillation counter is discussed. This method is based on direct addition of different types of milk into scintillation cocktail and therefore it is very promising for fast determination of alpha/beta activity due to direct alpha and beta separation, measurement in close 4p geometry and without sample treatment. The selected group of radionuclides was chosen with the respect to military significance, radio-toxicity, and possibility of potential misuse. As model radionuclides 241Am, 239Pu, and 90Sr were selected. The Liquid Scintilation Counter Hidex 300 SL equipped with triple-double-coincidence-ratio technique was used for sample measurement. The aim of the work was focused on comparison of different cocktails produced by Hidex and Perkin Elmer, choosing the best cocktail based on our measurement results and adjustment of its appropriate volume. Furthermore, the optimization of ratio between the volume of scintillation cocktail and the volume of urine was investigated with the respect to the model radionuclides. According to the obtained results, the efficiency for alpha emitters was greater than 85% and for beta, greater than 95%. The obtained results allowed this method to be used for rapid determination of gross alpha/beta activity in cases where time is an essence, such as first responders or mass-scale samples, where ordinary means suffer from lack of capacity or simply collapse under the onslaught.

  20. Sensorimotor alpha activity is modulated in response to the observation of pain in others

    Directory of Open Access Journals (Sweden)

    Stephen eWhitmarsh


    Full Text Available The perception-action account of empathy states that observation of another person's state automatically activates a similar state in the observer. It is still unclear in what way ongoing sensorimotor alpha oscillations are involved in this process. Although they have been repeatedly been implicated in (biological action observation and understanding communicative gestures, less is known about their role in vicarious pain observation. Their role is understood as providing a graded inhibition through functional inhibition, thereby streamlining information flow through the cortex. Although alpha oscillations have been shown to have at least visual and sensorimotor origins, only the latter are expected to be involved in the empathetic response. Here, we used magnetoencephalography (MEG, allowing us to spatially distinguish and localize oscillatory components using beamformer source reconstruction. Subjects observed realistic pictures of limbs in painful and no-pain (control conditions. As predicted, time-frequency analysis indeed showed increased alpha suppression in the pain condition compared to the no-pain (control condition. Although both pain and non-pain conditions suppressed alpha and beta band activity at both posterior and central sensors, the pain condition suppressed alpha more only at central sensors. Source reconstruction localized these differences along the central sulcus. Our results could not be accounted by differences in the evoked fields, suggesting a unique role of oscillatory activity in empathetic responses. We argue that alpha oscillations provide a unique measure of the underlying functional architecture of the brain, suggesting an automatic disinhibition of the sensorimotor cortices in response to the observation of pain in others.

  1. Staphylococcus aureus alpha-toxin-induced cell death : predominant necrosis despite apoptotic caspase activation

    NARCIS (Netherlands)

    Essmann, F; Bantel, H; Totzke, G; Engels, I H; Sinha, B; Schulze-Osthoff, K; Jänicke, R U


    Recent data suggest that alpha-toxin, the major hemolysin of Staphylococcus aureus, induces cell death via the classical apoptotic pathway. Here we demonstrate, however, that although zVAD-fmk or overexpression of Bcl-2 completely abrogated caspase activation and internucleosomal DNA fragmentation,

  2. Low geometry counter for the absolute measurement of the activity of alpha-emitting sources

    International Nuclear Information System (INIS)

    A low-geometry counter is described which allows the absolute determination of the activity for alpha-emitting sources. A Si implanted detector is used to obtain the spectrum of the sample. Two samples are measured with this counter and a 2 π gridded ion chamber. The results an their uncertainties for both instruments are discussed. (Author)

  3. Activation of AMPK alpha and gamma-isoform complexes in the intact ischemic rat heart (United States)

    AMP-activated protein kinase (AMPK) plays a key role in modulating cellular metabolic processes. AMPK, a serine-threonine kinase, is a heterotrimeric complex of catalytic alpha-subunits and regulatory beta- and gamma-subunits with multiple isoforms. Mutations in the cardiac gamma(2)-isoform have bee...

  4. Receptor density is key to the alpha2/beta interferon differential activities. (United States)

    Moraga, Ignacio; Harari, Daniel; Schreiber, Gideon; Uzé, Gilles; Pellegrini, Sandra


    Multiple type I interferons (IFN-alpha/beta) elicit Jak/Stat activation, rapid gene induction, and pleiotropic effects, such as differentiation, antiviral protection, and blocks in proliferation, which are dependent on the IFN subtype and the cellular context. To date, ligand- and receptor-specific molecular determinants underlying IFN-alpha/beta differential activities or potencies have been well characterized. To analyze cellular determinants that impact subtype-specific potency, human fibrosarcoma U5A-derived clones, exhibiting a gradient of IFN sensitivity by virtue of increasing receptor levels, were monitored for Jak/Stat signaling, gene induction, cell cycle lengthening, and apoptosis. In cells with scarce receptors, IFN-beta was more potent than IFN-alpha2 in antiproliferative activity, while the two subtypes were equipotent in all other readouts. Conversely, in cells with abundant receptors, IFN-alpha2 matched or even surpassed IFN-beta in all readouts tested. Our results suggest that the differential activities of the IFN subtypes are dictated not only by the intrinsic ligand/receptor binding kinetics but also by the density of cell surface receptor components.

  5. A rapid method for the autoradiography of alpha active air sample filters

    International Nuclear Information System (INIS)

    The report describes an improved version of a technique using a phosphor screen and an optical photographic emulsion to detect alpha-active particles. The sensitivity of the technique when using 'instant' high speed polaroid film is reported. The equipment has been designed to produce rapid results and does not need 'darkroom' conditions. (author)

  6. Phytanic acid oxidation: normal activation and transport yet defective alpha-hydroxylation of phytanic acid in peroxisomes from Refsum disease and rhizomelic chondrodysplasia punctata. (United States)

    Pahan, K; Khan, M; Singh, I


    In humans the oxidation of phytanic acid is a peroxisomal function. To understand the possible mechanisms for the pathognomic accumulation of phytanic acid in plasma and body fluids of Refsum disease (RD) and rhizomelic chondrodysplasia punctata (RCDP), we investigated activities of various steps (activation, transport, and oxidation) in the metabolism of phytanic acid in peroxisomes isolated from cultured skin fibroblasts from control, RD, and RCDP subjects. Activation of phytanic acid was normal in peroxisomes from both RD and RCDP. Transport of phytanic acid or phytanoyl-CoA in the absence or presence of fatty acid activating cofactors (ATP, MgCl2, and CoASH) into peroxisomes isolated from RD and RCDP skin fibroblasts was also similar to that of peroxisomes from control fibroblasts. Defective oxidation of [(2,3)-3H]- or [1-14C]phytanic acid, or [1-14C]phytanoyl-CoA (substrate for the first step of alpha-oxidation) but normal oxidation of [1-14C] alpha-hydroxyphytanic acid (substrate for the second step of the alpha-oxidation pathway) in peroxisomes from RD clearly demonstrates that excessive accumulation of phytanic acid in plasma and body fluids of RD is due to the deficiency of phytanic acid alpha-hydroxylase in peroxisomes. However, in RCDP peroxisomes, in addition to deficient oxidation of [1-14C]phytanic acid or phytanoyl-CoA or [(2,3)-3H]phytanic acid, the oxidation of [1-14C] alpha-hydroxyphytanic acid was also deficient, indicating that in RCDP the activities both of alpha-hydroxylation of phytanic acid and decarboxylation of alpha-hydroxyphytanic acid are deficient. These observations indicate that peroxisomal membrane functions (phytanic acid activation and transport) in phytanic acid metabolism are normal in both RD and RCDP. The defect in RD is in the alpha-hydroxylation of phytanic acid; whereas in RCDP both alpha-hydroxylation of phytanic acid as well as decarboxylation of alpha-hydroxyphytanic acid are deficient.

  7. Cloning and biologic activities of a bovine interferon-alpha isolated from the epithelium of a rotavirus-infected calf. (United States)

    Chaplin, P J; Entrican, G; Gelder, K I; Collins, R A


    A cDNA encoding a distinct bovine (Bo) interferon (IFN) alpha, designated BoIFN-alpha E, was generated from gut epithelial cells isolated from a rotavirus-infected calf. The BoIFN-alpha E cDNA sequence shared a greater than 90% identity with the other BoIFN-alpha subtypes. The cDNA encoding BoIFN-alpha E has been expressed in insect cells using the baculovirus Autographa californica nuclear polyhedrosis virus (AcMNPV) as a vector. Insect cells infected with recombinant virus secreted a protein with a relative molecular mass of 19,500 into the culture medium not observed in cells infected with wild-type AcMNPV. Supernatants harvested from cultures of insect cells infected with the recombinant AcMNPV encoding IFN-alpha E inhibited the replication of Semliki Forest virus in a bovine cell line and typically showed 10(6) dilution units/ml of antiviral activity. However, differences were observed between the activities of recombinant BoIFN-alpha E and BoIFN-alpha 1 1 on the proliferation of WC1+ gamma/delta T cells. Purified ( > 99%) WC1+ gamma/delta T cells failed to proliferate to IFN-alpha 1 1 or concanavalin A and IFN-alpha E acted as a weak proliferative signal to these cells, demonstrating a functional difference between two closely related BoIFN-alpha subtypes. PMID:8640447

  8. Active fiber optic technologies used as tamper-indicating devices

    International Nuclear Information System (INIS)

    The Sandia National Laboratories (SNL) Safeguards and Seals Evaluation Program is evaluating new fiber optic active seal technologies for use at Department of Energy (DOE) facilities. The goal of the program is to investigate active seal technologies that can monitor secured containers storing special nuclear materials (SNM) within DOE vaults. Specifically investigated were active seal technologies that can be used as tamper-indicating devices to monitor secured containers within vaults while personnel remain outside the vault area. Such a system would allow minimal access into vaults while ensuring container content accountability. The purpose of this report is to discuss tamper-indicating devices that were evaluated for possible DOE use. While previous seal evaluations (Phase I and II) considered overall facility applications, this discussion focuses specifically on their use in vault storage situations. The report will highlight general background information, specifications and requirements, and test procedures. Also discussed are the systems available from four manufacturers: Interactive Technologies, Inc., Fiber SenSys, Inc., Inovonics, Inc., and Valve Security Systems

  9. Active fiber optic technologies used as tamper-indicating devices

    Energy Technology Data Exchange (ETDEWEB)

    Horton, P.R.V.; Waddoups, I.G.


    The Sandia National Laboratories (SNL) Safeguards and Seals Evaluation Program is evaluating new fiber optic active seal technologies for use at Department of Energy (DOE) facilities. The goal of the program is to investigate active seal technologies that can monitor secured containers storing special nuclear materials (SNM) within DOE vaults. Specifically investigated were active seal technologies that can be used as tamper-indicating devices to monitor secured containers within vaults while personnel remain outside the vault area. Such a system would allow minimal access into vaults while ensuring container content accountability. The purpose of this report is to discuss tamper-indicating devices that were evaluated for possible DOE use. While previous seal evaluations (Phase I and II) considered overall facility applications, this discussion focuses specifically on their use in vault storage situations. The report will highlight general background information, specifications and requirements, and test procedures. Also discussed are the systems available from four manufacturers: Interactive Technologies, Inc., Fiber SenSys, Inc., Inovonics, Inc., and Valve Security Systems.

  10. Dual effects of alpha-arbutin on monophenolase and diphenolase activities of mushroom tyrosinase.

    Directory of Open Access Journals (Sweden)

    Liang Qin

    Full Text Available The effects of α-arbutin on the monophenolase and diphenolase activities of mushroom tyrosinase were investigated. The results showed that α-arbutin inhibited monophenolase activity but it activated diphenolase activity. For monophenolase activity, IC50 value was 4.5 mmol · L(-1 and 4.18 mmol · L(-1 of α-arbutin could extend the lag time from 40.5 s to 167.3 s. Alpha- arbutin is proposed to be regarded as a triphenolic substrate by the enzyme during catalyzation, leading to the suicide inactivation of the active site of tyrosinase. For diphenolase activity, α-arbutin acted as an activator and its activation mechanism was mixed type activation. To reveal such activation, it should be mainly refered to the conformational changes in tyrosinase caused by the interaction of α-arbutin with residues located at the entrance to the active site, and the decrease of the effect of suicide inactivation.

  11. Dual effects of alpha-arbutin on monophenolase and diphenolase activities of mushroom tyrosinase. (United States)

    Qin, Liang; Wu, Yang; Liu, Youting; Chen, Yiming; Zhang, Peng


    The effects of α-arbutin on the monophenolase and diphenolase activities of mushroom tyrosinase were investigated. The results showed that α-arbutin inhibited monophenolase activity but it activated diphenolase activity. For monophenolase activity, IC50 value was 4.5 mmol · L(-1) and 4.18 mmol · L(-1) of α-arbutin could extend the lag time from 40.5 s to 167.3 s. Alpha- arbutin is proposed to be regarded as a triphenolic substrate by the enzyme during catalyzation, leading to the suicide inactivation of the active site of tyrosinase. For diphenolase activity, α-arbutin acted as an activator and its activation mechanism was mixed type activation. To reveal such activation, it should be mainly refered to the conformational changes in tyrosinase caused by the interaction of α-arbutin with residues located at the entrance to the active site, and the decrease of the effect of suicide inactivation.

  12. The use of the long-range alpha detector (LRAD) for alpha emission surveys at active and inactive firing sites

    International Nuclear Information System (INIS)

    Surveys were carried out at five different firing sites at Los Alamos National Laboratory to measure residual alpha emissions in earth contaminated with natural and depleted uranium. This contamination is caused by controlled experimental explosions during testing of the non fissile components of nuclear weapons. Two conclusions were reached: the first is that post shot clearing of the experimental areas is effective at removing contamination and the second is that the diminution of alpha emissions due to aging is small

  13. Fluconazole Binding and Sterol Demethylation in Three CYP51 Isoforms Indicate Differences in Active Site Topology

    Energy Technology Data Exchange (ETDEWEB)

    Bellamine, A.; Lepesheva, Galina I.; Waterman, Mike (Vanderbilt)


    14{alpha}-Demethylase (CYP51) is a key enzyme in all sterol biosynthetic pathways (animals, fungi, plants, protists, and some bacteria), catalyzing the removal of the C-14 methyl group following cyclization of squalene. Based on mutations found in CYP51 genes from Candida albicans azole-resistant isolates obtained after fluconazole treatment of fungal infections, and using site-directed mutagenesis, we have found that fluconazole binding and substrate metabolism vary among three different CYP51 isoforms: human, fungal, and mycobacterial. In C. albicans, the Y132H mutant from isolates shows no effect on fluconazole binding, whereas the F145L mutant results in a 5-fold increase in its IC{sub 50} for fluconazole, suggesting that F145 (conserved only in fungal 14{alpha}-demethylases) interacts with this azole. In C. albicans, F145L accounts, in part, for the difference in fluconazole sensitivity reported between mammals and fungi, providing a basis for treatment of fungal infections. The C. albicans Y132H and human Y145H CYP51 mutants show essentially no effect on substrate metabolism, but the Mycobacterium tuberculosis F89H CYP51 mutant loses both its substrate binding and metabolism. Because these three residues align in the three isoforms, the results indicate that their active sites contain important structural differences, and further emphasize that fluconazole and substrate binding are uncoupled properties.

  14. Quantification of activity by alpha-camera imaging and small-scale dosimetry within ovarian carcinoma micrometastases treated with targeted alpha therapy

    DEFF Research Database (Denmark)

    Chouin, N; Lindegren, S; Jensen, Holger;


    Targeted alpha therapy (TAT) a promising treatment for small, residual, and micrometastatic diseases has questionable efficacy against malignant lesions larger than the α-particle range, and likely requires favorable intratumoral activity distribution. Here, we characterized and quantified the...... activity distribution of an alpha-particle emitter radiolabelled antibody within >100-µm micrometastases in a murine ovarian carcinoma model. Nude mice bearing ovarian micrometastases were injected intra-peritoneally with 211At-MX35 (total injected activity 6 MBq, specific activity 650 MBq/mg). Animals......% IA/g at 4 h) in the outer tumor layer and a sharp drop beyond a depth of 50 µm. Small-scale dosimetry was performed on a multi-cellular micrometastasis model, using time-integrated activities derived from the experimental data. With injected activity of 400 kBq, tumors exhibiting uniform activity...

  15. The determination of the thermodynamic activity of antimony in alpha-iron

    International Nuclear Information System (INIS)

    In this paper a method is suggested for determining the thermodynamic activity of antimony dissolved in alpha-iron, based on the study of antimony distribution between the two phases: liquid lead and solid iron. By this method, it was found that solid solutions of antimony in alpha-iron can be distinguished by positive divergences from the ideal state. Over a fairly wide range of concentrations, solutions of antimony in iron obey Henry's law. Special experiments on the distribution of antimony between lead and liquid iron showed that in the liquid state also the iron-antimony system is marked by positive divergences from the ideal state when small concentrations of antimony are present. The heat required for the solution of antimony in alpha-iron, and the excess partial molar entropy, were calculated from the activity temperature. The results were used for accurately locating the line showing the solubility limit of antimony in alpha-iron. Since alloys of antimony with iron were obtained by diffusion saturation and not by cooling from the liquid state, there was no liquefaction. Thus the lattice constant of the alloys and its relation to the alloy concentration could be reliably determined. The solubility limit established from X-ray data agrees with that obtained with Sb124. (author)

  16. Optogenetic Monitoring of Synaptic Activity with Genetically Encoded Voltage Indicators (United States)

    Nakajima, Ryuichi; Jung, Arong; Yoon, Bong-June; Baker, Bradley J.


    The age of genetically encoded voltage indicators (GEVIs) has matured to the point that changes in membrane potential can now be observed optically in vivo. Improving the signal size and speed of these voltage sensors has been the primary driving forces during this maturation process. As a result, there is a wide range of probes using different voltage detecting mechanisms and fluorescent reporters. As the use of these probes transitions from optically reporting membrane potential in single, cultured cells to imaging populations of cells in slice and/or in vivo, a new challenge emerges—optically resolving the different types of neuronal activity. While improvements in speed and signal size are still needed, optimizing the voltage range and the subcellular expression (i.e., soma only) of the probe are becoming more important. In this review, we will examine the ability of recently developed probes to report synaptic activity in slice and in vivo. The voltage-sensing fluorescent protein (VSFP) family of voltage sensors, ArcLight, ASAP-1, and the rhodopsin family of probes are all good at reporting changes in membrane potential, but all have difficulty distinguishing subthreshold depolarizations from action potentials and detecting neuronal inhibition when imaging populations of cells. Finally, we will offer a few possible ways to improve the optical resolution of the various types of neuronal activities. PMID:27547183

  17. H$\\alpha$ Emission From Active Equal-mass, Wide M Dwarf Binaries

    CERN Document Server

    Gunning, Heather C; Davenport, James R A; Dhital, Saurav; Hawley, Suzanne L; West, Andrew A


    We identify a sample of near-equal mass wide binary M dwarf systems from the SLoWPoKES catalog of common proper-motion binaries and obtain follow-up observations of their chromospheric activity as measured by the H$\\alpha$ emission line. We present optical spectra for both components of 48 candidate M dwarf binaries, confirming their mid-M spectral types. Of those 48 coeval pairs, we find eight with H$\\alpha$ emission from both components, three with weak emission in one component and no emission in the other, and 37 with two inactive components. We find that of the eleven pairs with at least one active component, only three follow the net trend of decreasing activity strength $L_{\\rm H\\alpha}/L_{\\rm bol}$ with later spectral type. The difference in quiescent activity strength between the A and B components is larger than what would be expected based on the small differences in color (mass). For five binaries with two active components, we present 47 hours of time-resolved spectroscopy, observed on the ARC 3....

  18. Chemical modification of an alpha 3-fucosyltransferase; definition of amino acid residues essential for enzyme activity. (United States)

    Britten, C J; Bird, M I


    The biosynthesis of the carbohydrate antigen sialyl Lewis X (sLe(x)) is dependent on the activity of an alpha 3-fucosyltransferase (EC, GDP-fucose:Gal beta (1-4)GlcNAc-R alpha (1-3)fucosyltransferase). This enzyme catalyses the transfer of fucose from GDP-beta-fucose to the 3-OH of N-acetylglucosamine present in lactosamine acceptors. In this report, we have investigated the amino acids essential for the activity of a recombinant alpha 3-fucosyltransferase (FucT-VI) through chemical modification of the enzyme with group-selective reagents. FucT-VI activity was found to be particularly sensitive to the histidine-selective reagent diethylpyrocarbonate and the cysteine reagent N-ethylmaleimide, with IC50 values of less than 200 microM. Reagents selective for arginine and lysine had no effect on enzyme activity. The inclusion of GDP-beta-fucose during preincubation with NEM reduces the rate of inactivation whereas inclusion of an acceptor saccharide for the enzyme, Gal beta (1-4)GlcNAc, had no effect. No protective effect with either GDP-beta-fucose or Gal beta (1-4)GlcNAc was observed on treatment of the enzyme with diethylpyrocarbonate. These data suggest that in addition to an NEM-reactive cysteine in, or adjacent to, the substrate-binding site of the enzyme, FucT-VI possesses histidine residue(s) that are essential for enzyme activity.

  19. Perineural alpha(2A)-adrenoceptor activation inhibits spinal cord neuroplasticity and tactile allodynia after nerve injury.


    Lavand'homme, Patricia; Ma, Weiya; Kock, Marc De; Eisenach, James C.


    BACKGROUND: Nerve injury in animals increases alpha(2)-adrenoceptor expression in dorsal root ganglion cells and results in novel excitatory responses to their activation, perhaps leading to the phenomenon of sympathetically maintained pain. In contrast to this notion, peripheral alpha(2)-adrenoceptor stimulation fails to induce pain in patients with chronic pain. We hypothesized that alpha(2) adrenoceptors at the site of nerve injury play an inhibitory, not excitatory role. METHODS: Partial ...

  20. Phase I Final Report: Ultra-Low Background Alpha Activity Counter

    International Nuclear Information System (INIS)

    easily distinguish between these two risetimes and thereby count only alpha particles emitted by the sample. Alpha particles emitted from the sample tray are absorbed in the rear of the sample, so the tray's emissivity does not contribute to the background either. Extensions of the method to the counter's sidewalls similarly allow us to reject alpha particles emitted from the sidewalls. We can thus able obtain background rates over a factor of 1000 lower than in conventional instruments without active background rejection. Extending this principle to count at the 0.00001 alpha/cm2/hour, level encounters difficulties because there will typically be only 2.4 alpha particles per square meter per day. Since about 6 counts are required to measure activity at the 95% confidence level, large sample areas are required to make measurements in reasonable times. Unfortunately, increasing the counter's anode area to a square meter raises its capacitance so much that the preamplifier noise levels swamp the alpha particle signals and make counting impossible. In this SBIR we worked to solve this dilemma by segmenting the single large area electrode into several smaller, lower capacitance electrodes that could still detect the alpha particles reliably. Each electrode would have its own electronic and we would capture signals from all of them in coincidence (since an alpha track might well deposit charge on more than one electrode), a technique in which XIA is experienced. Therefore, in Phase I we worked to show proof of principle by subdividing our original 1,800 cm2 electrode into 4 square segments, each 625 cm2 and demonstrating that signal noise on individual channels reduced as expected. Because the Phase II counter with a 1 m2 segmented anode would require 16 segments plus a segmented guard as well, we also designed low cost signal processing electronics to instrument it in Phase II. Our Phase I effort met our major proof of principle goals. In particular, reducing the anode size

  1. Relationship between ionospheric electric fields and magnetic activity indices (United States)

    Shirapov, D. Sh.


    The relations between electric fields in the daytime and nighttime sectors of the polar ionosphere and magnetic activity indices of auroral region (AL) and northern polar cap (PCN) are studied. It is found that the above relations do exist and are described by: a) equations U {pc/(1)} (kV) = 27.62 + 21.43PCN with a correlation coefficient R = 0.87 and U {pc/(1)} (kV) = 4.06 + 49.21PCN - 6.24 PCN2 between the difference in the electric potentials across the polar cap in the daytime sector U {pc/(1)} and PCN and b) regression equation U {pc/(2)} (kV) = 23.33 + 0.08|AL| with R = 0.86 between the difference in the electric potentials across the polar cap in the nighttime sector U {pc/(2)} and |AL|. It is shown that: a) it is possible to use the AL and PCN indices for real-time diagnostics of instantaneous values of the electric fields in the daytime and nighttime sectors of the polar ionosphere in the process of a substorm development; b) at the expansion phase of a substorm, due to calibration of PCN values by the values of the solar wind electric field E sw, the PCN index does not feel the contribution of the western electrojet and, accordingly, the contribution of the nighttime ionospheric electric field U {pc/(2)}, governed by the reconnection in the magnetospheric tail.

  2. Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function

    DEFF Research Database (Denmark)

    Hansen, Sara K; Párrizas, Marcelina; Jensen, Maria L;


    Mutations in the genes encoding hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-1alpha impair insulin secretion and cause maturity onset diabetes of the young (MODY). HNF-4alpha is known to be an essential positive regulator of HNF-1alpha. More recent data demonstrates that HNF-4alpha......, and consequently in reduced HNF-1alpha-dependent activation. These findings provide genetic evidence that HNF-1alpha serves as an upstream regulator of HNF-4alpha and interacts directly with the P2 promoter in human pancreatic cells. Furthermore, they indicate that this regulation is essential to maintain normal...

  3. Transiting the Sun II: The impact of stellar activity on Lyman-$\\alpha$ transits

    CERN Document Server

    Llama, J


    High-energy observations of the Sun provide an opportunity to test the limits of our ability to accurately measure properties of transiting exoplanets in the presence of stellar activity. Here we insert transits of a hot Jupiter into continuous disk integrated data of the Sun in Lyman-alpha (Ly$\\alpha$) from NASA's SDO/EVE instrument to assess the impact of stellar activity on the measured planet-to-star radius ratio $(\\textrm{R}_\\textrm{p}/\\textrm{R}_\\star)$. In 75% of our simulated light curves we measure the correct radius ratio; however, incorrect values can be measured if there is significant short term variability in the light curve. The maximum measured value of $(\\textrm{R}_\\textrm{p}/\\textrm{R}_\\star)$ is $50\\%$ larger than the input value, which is much smaller than the large Ly$\\alpha$ transit depths that have been reported in the literature, suggesting that for stars with activity levels comparable to the Sun, stellar activity alone cannot account for these deep transits. We ran simulations withou...

  4. Brain correlates underlying creative thinking: EEG alpha activity in professional vs. novice dancers. (United States)

    Fink, Andreas; Graif, Barbara; Neubauer, Aljoscha C


    Neuroscientific research on creativity has revealed valuable insights into possible brain correlates underlying this complex mental ability domain. However, most of the studies investigated brain activity during the performance of comparatively simple (verbal) type of tasks and the majority of studies focused on samples of the normal population. In this study we investigate EEG activity in professional dancers (n=15) who have attained a high level of expertise in this domain. This group was compared with a group of novices (n=17) who have only basic experience in dancing and completed no comprehensive training in this field. The EEG was recorded during performance of two different dancing imagery tasks which differed with respect to creative demands. In the first task participants were instructed to mentally perform a dance which should be as unique and original as possible (improvisation dance). In the waltz task they were asked to imagine dancing the waltz, a standard dance which involves a sequence of monotonous steps (lower creative demands). In addition, brain activity was also measured during performance of the Alternative Uses test. We observed evidence that during the generation of alternative uses professional dancers show stronger alpha synchronization in posterior parietal brain regions than novice dancers. During improvisation dance, professional dancers exhibited more right-hemispheric alpha synchronization than the group of novices did, while during imagining dancing the waltz no significant group differences emerged. The findings complement and extend existing findings on the relationship between EEG alpha activity and creative thinking. PMID:19269335

  5. IFN-alpha5 mediates stronger Tyk2-stat-dependent activation and higher expression of 2',5'-oligoadenylate synthetase than IFN-alpha2 in liver cells


    Larrea, E. (Esther); Aldabe, R; Riezu-Boj, J I; Guitart, A. (Anunciata); Civeira, M P; Prieto, J.; Baixeras, E.


    Interferon-alpha5 (IFN-alpha5) is the main IFN-alpha subtype expressed in the liver. Hepatitis C virus (HCV) infection is associated with low IFN-alpha5 mRNA levels, possibly reflecting an escape mechanism of the virus. In this work, we sought to compare IFN-alpha2 and IFN-alpha5 with respect to activation of early cell signaling cascades and induction of antiviral genes in the human hepatoma HepG2 and Huh7 cell lines. We found that the Tyr701 phosphorylation kinetics of Stat1 mediated by IFN...

  6. Discovery of an Oxybenzylglycine Based Peroxisome Proliferator Activated Receptor Alpha Selective

    Energy Technology Data Exchange (ETDEWEB)

    Li, J.; Kennedy, L; Shi, Y; Tao, S; Ye, X; Chen, S; Wang, Y; Hernandez, A; Wang, W; et al.


    An 1,3-oxybenzylglycine based compound 2 (BMS-687453) was discovered to be a potent and selective peroxisome proliferator activated receptor (PPAR) {alpha} agonist, with an EC{sub 50} of 10 nM for human PPAR{alpha} and {approx}410-fold selectivity vs human PPAR{gamma} in PPAR-GAL4 transactivation assays. Similar potencies and selectivity were also observed in the full length receptor co-transfection assays. Compound 2 has negligible cross-reactivity against a panel of human nuclear hormone receptors including PPAR{delta}. Compound 2 demonstrated an excellent pharmacological and safety profile in preclinical studies and thus was chosen as a development candidate for the treatment of atherosclerosis and dyslipidemia. The X-ray cocrystal structures of the early lead compound 12 and compound 2 in complex with PPAR{alpha} ligand binding domain (LBD) were determined. The role of the crystal structure of compound 12 with PPAR{alpha} in the development of the SAR that ultimately resulted in the discovery of compound 2 is discussed.

  7. Cochlear power flux as an indicator of mechanical activity. (United States)

    Diependaal, R J; de Boer, E; Viergever, M A


    The question of whether one can conclude just from basilar membrane (BM) vibration data that the cochlea is an active mechanical system is addressed. To this end, a method is developed which computes the power flux through a channel cross section of a short-wave cochlear model from a given BM vibration pattern. The power flux is an important indicator of mechanical activity because a rise in this function corresponds to creation of mechanical energy. The power flux method is applied to BM velocity patterns as measured by Johnstone and Yates [J. Acoust. Soc. Am. 55, 584-587 (1974)] and by Sellick et al. [Hear. Res. 10, 101-108 (1983)] in the guinea pig and by Robles et al. [Peripheral Auditory Mechanisms, edited by J.B. Allen, J.L. Hall, A.E. Hubbard, S.T. Neely, and A. Tubis (Springer, New York, 1986a), pp. 121-128, and J. Acoust. Soc. Am. 80, 1364-1374 (1986b)] in the chinchilla. Before the calculations are performed, the BM data are interpolated and smoothed in order to avoid numerical errors as a result of too few and noisy data points. The choice of the smoothing method influences the computed power flux function considerably. Nevertheless, the calculations appear to make a clear distinction between the "old" data, showing broad BM tuning (Johnstone and Yates, 1974), and the "new" data, in which the response is much more peaked (Sellick et al., 1983; Robles et al., 1986a, b). The former do not give rise to a significant increase of the power flux; the latter do, although less convincingly for the Sellick et al. (1983) data than for the Robles et al. (1986a,b) data. It is thus concluded that the recently obtained, sharply tuned BM responses reflect the presence of mechanical activity in the cochlea.

  8. Derivatives of benzimidazole: vasodilator activity of 2-(p-chloro-alpha-hydroxybenzyl)-benzimidazole hydrochloride. Preliminary study. (United States)

    Demenge, P; Carraz, G; Luu Duc, C; Silice, C


    The effects of 2-(p-chloro-alpha-hydroxybenzyl)-benzimidazole hydrochloride (HBBPC) have been studied in the rabbit and rat. Most of these studies were performed comparatively with reference vasodilators and papaverine. HBBPC vasodilator activity is nearly the same as that of papaverine in the isolated rabbit ear. The characteristic of the vasoactive action of HBBPC seems to reside in its duration. The mechanism of action of HBBPC seems of peripheral type, that is to say it acts on the vascular smooth muscle.

  9. Activation of the glycoprotein hormone alpha-subunit promoter by a LIM-homeodomain transcription factor.


    Roberson, M S; Schoderbek, W E; Tremml, G; Maurer, R A


    Recently, a pituitary-specific enhancer was identified within the 5' flanking region of the mouse glycoprotein hormone alpha-subunit gene. This enhancer is active in pituitary cells of the gonadotrope and thyrotrope lineages and has been designated the pituitary glycoprotein hormone basal element (PGBE). In the present studies, we sought to isolate and characterize proteins which interact with the PGBE. Mutagenesis experiments identified a 14-bp imperfect palindrome that is required for bindi...

  10. Adaptation of peroxisome proliferator-activated receptor alpha to hibernation in bats


    Han, Yijie; Zheng, Guantao; Yang, Tianxiao; Zhang, Shuyi; Dong, Dong; Pan, Yi-Hsuan


    Background Hibernation is a survival mechanism in the winter for some animals. Fat preserved instead of glucose produced is the primary fuel during winter hibernation of mammals. Many genes involved in lipid metabolism are regulated by the peroxisome proliferator-activated receptor alpha (PPARα). The role of PPARα in hibernation of mammals remains largely unknown. Using a multidisciplinary approach, we investigated whether PPARα is adapted to hibernation in bats. Results Evolutionary analyses...

  11. Modulation of transmission in rat sympathetic ganglia by activation of presynaptic alpha- and beta-adrenoceptors.


    Medgett, I.C.


    1 Conditions under which transmission in rat isolated superior cervical ganglia may be affected by activation of presynaptic alpha- and beta-adrenoceptors have been investigated by means of an extracellular recording method. 2 Clonidine caused a small hyperpolarization of the ganglia (mean EC50 approximately 2 nM) in unstimulated preparations; with continuous preganglionic stimulation at 0.2 Hz, clonidine markedly decreased the height of the compound action potential (mean EC50 approximately ...

  12. The nicotinic alpha7 acetylcholine receptor agonist ssr180711 is unable to activate limbic neurons in mice overexpressing human amyloid-beta1-42

    DEFF Research Database (Denmark)

    Soderman, A.; Spang-Thomsen, Mogens; Hansen, H.;


    Recent studies have demonstrated that amyloid-beta1-42 (Abeta1-42) binds to the nicotinergic alpha7 acetylcholine receptor (alpha7 nAChR) and that the application of Abeta1-42 to cells inhibits the function of the alpha7 nAChR. The in vivo consequences of the pharmacological activation of the alpha...

  13. Involvement of vacuolar sequestration and active transport in tolerance of Saccharomyces cerevisiae to hop iso-alpha-acids. (United States)

    Hazelwood, Lucie A; Walsh, Michael C; Pronk, Jack T; Daran, Jean-Marc


    The hop plant, Humulus lupulus L., has an exceptionally high content of secondary metabolites, the hop alpha-acids, which possess a range of beneficial properties, including antiseptic action. Studies performed on the mode of action of hop iso-alpha-acids have hitherto been restricted to lactic acid bacteria. The present study investigated molecular mechanisms of hop iso-alpha-acid resistance in the model eukaryote Saccharomyces cerevisiae. Growth inhibition occurred at concentrations of hop iso-alpha-acids that were an order of magnitude higher than those found with hop-tolerant prokaryotes. Chemostat-based transcriptome analysis and phenotype screening of the S. cerevisiae haploid gene deletion collection were used as complementary methods to screen for genes involved in hop iso-alpha-acid detoxification and tolerance. This screening and further analysis of deletion mutants confirmed that yeast tolerance to hop iso-alpha-acids involves three major processes, active proton pumping into the vacuole by the vacuolar-type ATPase to enable vacuolar sequestration of iso-alpha-acids and alteration of cell wall structure and, to a lesser extent, active export of iso-alpha-acids across the plasma membrane. Furthermore, iso-alpha-acids were shown to affect cellular metal homeostasis by acting as strong zinc and iron chelators.

  14. Plasmin-induced migration requires signaling through protease-activated receptor 1 and integrin alpha(9)beta(1). (United States)

    Majumdar, Mousumi; Tarui, Takehiko; Shi, Biao; Akakura, Nobuaki; Ruf, Wolfram; Takada, Yoshikazu


    Plasmin is a major extracellular protease that elicits intracellular signals to mediate platelet aggregation, chemotaxis of peripheral blood monocytes, and release of arachidonate and leukotriene from several cell types in a G protein-dependent manner. Angiostatin, a fragment of plasmin(ogen), is a ligand and an antagonist for integrin alpha(9)beta(1). Here we report that plasmin specifically interacts with alpha(9)beta(1) and that plasmin induces of cells expressing migration recombinant alpha(9)beta(1) (alpha(9)-Chinese hamster ovary (CHO) cells). Migration was dependent on an interaction of the kringle domains of plasmin with alpha(9)beta(1) as well as the catalytic activity of plasmin. Angiostatin, representing the kringle domains of plasmin, alone did not induce the migration of alpha(9)-CHO cells, but simultaneous activation of the G protein-coupled protease-activated receptor (PAR)-1 with an agonist peptide induced the migration on angiostatin, whereas PAR-2 or PAR-4 agonist peptides were without effect. Furthermore, a small chemical inhibitor of PAR-1 (RWJ 58259) and a palmitoylated PAR-1-blocking peptide inhibited plasmin-induced migration of alpha(9)-CHO cells. These results suggest that plasmin induces migration by kringle-mediated binding to alpha(9)beta(1) and simultaneous proteolytic activation of PAR-1. PMID:15247268

  15. Sight restoration after congenital blindness does not reinstate alpha oscillatory activity in humans. (United States)

    Bottari, Davide; Troje, Nikolaus F; Ley, Pia; Hense, Marlene; Kekunnaya, Ramesh; Röder, Brigitte


    Functional brain development is characterized by sensitive periods during which experience must be available to allow for the full development of neural circuits and associated behavior. Yet, only few neural markers of sensitive period plasticity in humans are known. Here we employed electroencephalographic recordings in a unique sample of twelve humans who had been blind from birth and regained sight through cataract surgery between four months and 16 years of age. Two additional control groups were tested: a group of visually impaired individuals without a history of total congenital blindness and a group of typically sighted individuals. The EEG was recorded while participants performed a visual discrimination task involving intact and scrambled biological motion stimuli. Posterior alpha and theta oscillations were evaluated. The three groups showed indistinguishable behavioral performance and in all groups evoked theta activity varied with biological motion processing. By contrast, alpha oscillatory activity was significantly reduced only in individuals with a history of congenital cataracts. These data document on the one hand brain mechanisms of functional recovery (related to theta oscillations) and on the other hand, for the first time, a sensitive period for the development of alpha oscillatory activity in humans.

  16. Heat shock inhibits. alpha. -amylase synthesis in barley aleurone without inhibiting the activity of endoplasmic reticulum marker enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Sticher, L.; Biswas, A.K.; Bush, D.S.; Jones, R.L. (Univ. of California, Berkeley (USA))


    The effects of heat shock on the synthesis of {alpha}-amylase and on the membranes of the endoplasmic reticulum (ER) of barley (Hordeum vulgare) aleurone were studied. Heat shock, imposed by raising the temperature of incubation from 25{degree}C to 40{degree}C for 3 hours, inhibits the accumulation of {alpha}-amylase and other proteins in the incubation medium of barley aleurone layers treated with gibberellic acid and Ca{sup 2+}. When ER is isolated from heat-shocked aleurone layers, less newly synthesized {alpha}-amylase is found associated with this membrane system. ER membranes, as indicated by the activities of NADH cytochrome c reductase and ATP-dependent Ca{sup 2+} transport, are not destroyed by heat stress, however. Although heat shock did not reduce the activity of ER membrane marker enzymes, it altered the buoyant density of these membranes. Whereas ER from control tissue showed a peak of marker enzyme activity at 27% to 28% sucrose (1.113-1.120 grams per cubic centimeter), ER from heat-shocked tissue peaked at 30% to 32% sucrose (1.127-1.137 grams per cubic centimeter). The synthesis of a group of proteins designated as heat-shock proteins (HSPs) was stimulated by heat shock. These HSPs were localized to different compartments of the aleurone cell. Several proteins ranging from 15 to 30 kilodaltons were found in the ER and the mitochondrial/plasma membrane fractions of heat-shocked cells, but none of the HSPs accumulated in the incubation medium of heat-shocked aleurone layers.

  17. Brain-computer interfacing using modulations of alpha activity induced by covert shifts of attention

    Directory of Open Access Journals (Sweden)

    Schmidt Nico M


    Full Text Available Abstract Background Visual brain-computer interfaces (BCIs often yield high performance only when targets are fixated with the eyes. Furthermore, many paradigms use intense visual stimulation, which can be irritating especially in long BCI sessions. However, BCIs can more directly directly tap the neural processes underlying visual attention. Covert shifts of visual attention induce changes in oscillatory alpha activity in posterior cortex, even in the absence of visual stimulation. The aim was to investigate whether different pairs of directions of attention shifts can be reliably differentiated based on the electroencephalogram. To this end, healthy participants (N = 8 had to strictly fixate a central dot and covertly shift visual attention to one out of six cued directions. Results Covert attention shifts induced a prolonged alpha synchronization over posterior electrode sites (PO and O electrodes. Spectral changes had specific topographies so that different pairs of directions could be differentiated. There was substantial variation across participants with respect to the direction pairs that could be reliably classified. Mean accuracy for the best-classifiable pair amounted to 74.6%. Furthermore, an alpha power index obtained during a relaxation measurement showed to be predictive of peak BCI performance (r = .66. Conclusions Results confirm posterior alpha power modulations as a viable input modality for gaze-independent EEG-based BCIs. The pair of directions yielding optimal performance varies across participants. Consequently, participants with low control for standard directions such as left-right might resort to other pairs of directions including top and bottom. Additionally, a simple alpha index was shown to predict prospective BCI performance.

  18. Interaction of human tissue plasminogen activator (t-PA) with pregnancy zone protein: a comparative study with t-PA-alpha2-macroglobulin interaction. (United States)

    Sánchez, M C; Chiabrando, G A; Guglielmone, H A; Bonacci, G R; Rabinovich, G A; Vides, M A


    Human pregnancy zone protein (PZP) is a major pregnancy-associated plasma protein strongly related to alpha2-macroglobulin (alpha2-M). Interactions of tissue plasminogen activator (t-PA) with PZP and alpha2-M were both investigated in vitro and the complexes were analyzed by polyacrylamide gel electrophoresis (PAGE). The results demonstrated that PZP-t-PA complex formation was evident within 1 h of incubation, whereas alpha2-M-t-PA complexes were formed after 18 h. Conclusions were supported by the following evidence: (i) PZP and alpha2-M complexes revealed changes of the mobility rate in non-denaturing PAGE, similar to those observed with alpha-Ms-chymotrypsin; (ii) both PZP and alpha2-M formed complexes of molecular size >360 kDa by SDS-PAGE, in accordance with the covalent binding of t-PA, which was previously reported for other proteinases; and (iii) PZP underwent a specific cleavage of the bait region with appearence of fragments of 85-90 kDa as judged by reducing SDS-PAGE. In contrast, the proteolytic attack on alpha2-M was found to occur more slowly, requiring several hours of incubation with t-PA for generation of an appreciable amount of fragments of 85-90 kDa. The appearance of free SH-groups of alpha-Ms was further investigated by titration with 5, 5'-dithiobis(2-nitrobenzoic acid). The maximal level of SH-groups raised was 3.9 mol/mol of PZP and 3.5 mol/mol of alpha2-M, indicating approximately one SH-group for each 180-kDa subunit. Finally, t-PA activity in PZP-t-PA complex was evaluated by measuring the hydrolysis of the chromogenic substrate Flavigen t-PA. Our results revealed that prolongation of the incubation period of this complex increased t-PA-mediated hydrolysis of Flavigen t-PA until a plateau was reached, approximately between 60 and 120 min. The present study suggests that PZP, by binding to t-PA, may contribute to the control of the activity of proteinases derived from fibrinolytic systems.

  19. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Tachibana, Keisuke, E-mail: [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Takeuchi, Kentaro; Inada, Hirohiko [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yamasaki, Daisuke [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ishimoto, Kenji [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko [Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904 (Japan); Doi, Takefumi [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)


    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial {beta}-oxidation. The peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is a ligand-activated transcription factor that plays an important role in the regulation of {beta}-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPAR{alpha} and found that PPAR{alpha} induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPAR{alpha} regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  20. Recent advances in the discovery of alpha1-adrenoceptor agonists. (United States)

    Bishop, Michael J


    The alpha(1) adrenoceptors are three of nine well-characterized receptors that are activated by epinephrine and norepinephrine. Agonists acting at the alpha(1) adrenoceptors produce numerous physiological effects, and are used therapeutically for several indications. Many known alpha(1) adrenoceptor agonists are alpha(1A) selective, but the discovery of highly selective alpha(1B) and alpha(1D) adrenoceptor agonists has proven to be an extremely difficult goal to achieve. This review will focus on recent advances in the discovery, development and clinical utility of subtype-specific alpha(1) agonists as well as contributions to our understanding of agonist-receptor interactions.

  1. Effect of salivary gland adenocarcinoma cell-derived alpha-N-acetylgalactosaminidase on the bioactivity of macrophage activating factor. (United States)

    Matsuura, Takashi; Uematsu, Takashi; Yamaoka, Minoru; Furusawa, Kiyofumi


    The aim of this study was to clarify the effects of alpha-N-acetylgalactosaminidase (alpha-NaGalase) produced by human salivary gland adenocarcinoma (SGA) cells on the bioactivity of macrophage-activating factor (GcMAF). High exo-alpha-NaGalase activity was detected in the SGA cell line HSG. HSG alpha-NaGalase had both exo- and endo-enzyme activities, cleaving the Gal-GalNAc and GalNAc residues linked to Thr/Ser but not releasing the [NeuAc2-6]GalNac residue. Furthermore, GcMAF enzymatically prepared from the Gc protein enhanced the superoxide-generation capacity and phagocytic activity of monocytes/macrophages. However, GcMAF treated with purified alpha-NaGalase did not exhibit these effects. Thus, HSG possesses the capacity to produce larger quantities of alpha-NaGalase, which inactivates GcMAF produced from Gc protein, resulting in reduced phagocytic activity and superoxide-generation capacity of monocytes/macrophages. The present data strongly suggest that HSG alpha-NaGalase acts as an immunodeficiency factor in cancer patients. PMID:14767536

  2. Enzymic synthesis of alpha- and beta-D-glucosides of 1-deoxynojirimycin and their glycosidase inhibitory activities. (United States)

    Asano, N; Oseki, K; Kaneko, E; Matsui, K


    1-Deoxynojirimycin (1) is a potent inhibitor of mammalian and rice alpha-glucosidase. Several glucosides of 1 were synthesized by use of the native and immobilized enzyme and their effect on various enzymes was investigated. Transglucosylation reactions using rice alpha-glucosidase, yeast alpha- and beta-glucosidases purified from Rhodotorula lactosa were performed with maltose or cellobiose as a glucose donor and N-(benzyloxycarbonyl)-1-deoxynojirimycin (2) as an acceptor. The transglucosylation reaction using native rice alpha-glucosidase afforded 3-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (4), 4-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (5), and 2-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (3) in yields of 40, 13, and 2%, respectively, after 30 min. The transglucosylation reaction using immobilized rice alpha-glucosidase was similar to that using the native enzyme. In the system using native yeast alpha-glucosidase, 3, 5, and 4 were formed in yields of 34, 13, and 6%, respectively, after 15 h. The immobilization of yeast alpha-glucosidase caused a significant decrease in transglucosylation activity. Yeast beta-glucosidase showed a high transglucosylation activity and incubation with the reaction system afforded 2-O-beta-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (6) and 4-O-beta-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (7) in yields of 69 and 3%, respectively, after 3 h. The transglucosylation reaction using immobilized yeast beta-glucosidase preferentially afforded 6 in a yield of 73% after 3 h. After removal of N-benzyloxycarbonyl group from the product glucosides, their glycosidase inhibitory activities were measured. 3-O-alpha-D-Glucopyranosyl-1-deoxynojirimycin (9) retained the potent inhibition of 1 against rat intestinal sucrase activity and was more effective than 1 against rice alpha-glucosidase. 4-O-alpha-D-Glucopyranosyl-1-deoxynojirimycin (10

  3. Thy-1 attenuates TNF-alpha-activated gene expression in mouse embryonic fibroblasts via Src family kinase.

    Directory of Open Access Journals (Sweden)

    Bin Shan

    Full Text Available Heterogeneous surface expression of Thy-1 in fibroblasts modulates inflammation and may thereby modulate injury and repair. As a paradigm, patients with idiopathic pulmonary fibrosis, a disease with pathologic features of chronic inflammation, demonstrate an absence of Thy-1 immunoreactivity within areas of fibrotic activity (fibroblast foci in contrast to the predominant Thy-1 expressing fibroblasts in the normal lung. Likewise, Thy-1 deficient mice display more severe lung fibrosis in response to an inflammatory injury than wildtype littermates. We investigated the role of Thy-1 in the response of fibroblasts to the pro-inflammatory cytokine TNF-alpha. Our study demonstrates distinct profiles of TNF-alpha-activated gene expression in Thy-1 positive (Thy-1+ and negative (Thy-1- subsets of mouse embryonic fibroblasts (MEF. TNF-alpha induced a robust activation of MMP-9, ICAM-1, and the IL-8 promoter driven reporter in Thy-1- MEFs, in contrast to only a modest increase in Thy-1+ counterparts. Consistently, ectopic expression of Thy-1 in Thy-1- MEFs significantly attenuated TNF-alpha-activated gene expression. Mechanistically, TNF-alpha activated Src family kinase (SFK only in Thy-1- MEFs. Blockade of SFK activation abrogated TNF-alpha-activated gene expression in Thy-1- MEFs, whereas restoration of SFK activation rescued the TNF-alpha response in Thy-1+ MEFs. Our findings suggest that Thy-1 down-regulates TNF-alpha-activated gene expression via interfering with SFK- and NF-kappaB-mediated transactivation. The current study provides a novel mechanistic insight to the distinct roles of fibroblast Thy-1 subsets in inflammation.

  4. Identification of a mutation affecting an alanine-alpha-ketoisovalerate transaminase activity in Escherichia coli K-12. (United States)

    Falkinham, J O


    A mutation affecting alanine-alpha-ketoisovalerate transaminase activity has been shown to be cotransducible with ilv gene cluster. The transaminase deficiency results in conditional isoleucine auxotrophy in the presence of alanine. PMID:396446

  5. Protection against myocardial ischaemia/reperfusion injury by PPAR-alpha activation is related to production of nitric oxide and endothelin-1

    DEFF Research Database (Denmark)

    Bulhak, A A; Sjöquist, P-O; Xu, C-B;


    BACKGROUND: Ligands of peroxisome proliferator-activated receptor alpha (PPAR-alpha) have been shown to reduce ischaemia/reperfusion injury. The mechanisms behind this effect are not well known. We hypothesized that activation of PPAR-alpha exerts cardioprotection via a mechanism related to nitri....... CONCLUSION: The results suggest that the PPAR-alpha activation protects the rat myocardium against ischaemia/ reperfusion injury via a mechanism related to production of NO, and possibly ET-1....

  6. Gross alpha activity as an estimator of radium-226 activity in soils and tailings at an inactive uranium mill tailings site

    Energy Technology Data Exchange (ETDEWEB)

    Dreesen, D.R.; Wienke, C.L.


    Gross alpha activity in surface tailings and surface soils from one inactive uranium mill site has been shown to be an accurate estimator of /sup 226/Ra activity. An exponential regression, /sup 226/Ra = 387(e/sup 0.00166..cap alpha../ - 1), where /sup 226/Ra activity is in picoCuries per gram and gross alpha activity is in counts per minute per sample, gave a good fit for samples ranging in gross alpha activity from 3 to 1082 cpm/sample. A linear regression, /sup 226/Ra = 1.05 ..cap alpha.. + 1.78, has been calculated, which shows gross alpha activity to be an excellent estimator of /sup 226/Ra activity in soils contaminated with tailings. The percentage of gross alpha activity attributable to /sup 226/Ra activity has been calculated to be 7.2, 17.6, 18.3, and 17.0 for uncontaminated soils, contaminated soils, tailings, and the total set of samples, respectively.

  7. Synthesis Activity and Structural Analysis of Novel alpha-Hydroxytropolone Inhibitors of Human Immunodeficiency Virus Reverse Transcriptase-Associated Ribonuclease H

    Energy Technology Data Exchange (ETDEWEB)

    S Chung; D Himmel; J Jiang; K Wojtak; J Bauman; J Rausch; J Wilson; J Beutler; C Thomas; et al.


    The {alpha}-hydroxytroplone, manicol (5,7-dihydroxy-2-isopropenyl-9-methyl-1,2,3,4-tetrahydro-benzocyclohepten-6-one), potently and specifically inhibits ribonuclease H (RNase H) activity of human immunodeficiency virus reverse transcriptase (HIV RT) in vitro. However, manicol was ineffective in reducing virus replication in culture. Ongoing efforts to improve the potency and specificity over the lead compound led us to synthesize 14 manicol derivatives that retain the divalent metal-chelating {alpha}-hydroxytropolone pharmacophore. These efforts were augmented by a high resolution structure of p66/p51 HIV-1 RT containing the nonnucleoside reverse transcriptase inhibitor (NNRTI), TMC278 and manicol in the DNA polymerase and RNase H active sites, respectively. We demonstrate here that several modified {alpha}-hydroxytropolones exhibit antiviral activity at noncytotoxic concentrations. Inclusion of RNase H active site mutants indicated that manicol analogues can occupy an additional site in or around the DNA polymerase catalytic center. Collectively, our studies will promote future structure-based design of improved {alpha}-hydroxytropolones to complement the NRTI and NNRTI currently in clinical use.

  8. Tat-APE1/ref-1 protein inhibits TNF-alpha-induced endothelial cell activation. (United States)

    Song, Yun Jeong; Lee, Ji Young; Joo, Hee Kyoung; Kim, Hyo Shin; Lee, Sang Ki; Lee, Kwon Ho; Cho, Chung-Hyun; Park, Jin Bong; Jeon, Byeong Hwa


    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/ref-1) is a multifunctional protein involved both in DNA base excision repair and redox regulation. In this study we evaluated the protective role of Tat-mediated APE1/ref-1 transduction on the tumor necrosis factor (TNF)-alpha-activated endothelial activation in cultured human umbilical vein endothelial cells. To construct Tat-APE1/ref-1 fusion protein, human full length of APE1/ref-1 was fused with Tat-protein transduction domain. Purified Tat-APE1/ref-1 fusion protein efficiently transduced cultured endothelial cells in a dose-dependent manner and reached maximum expression at 1h after incubation. Transduced Tat-APE1/ref-1 showed inhibitory activity on the TNF-alpha-induced monocyte adhesion and vascular cell adhesion molecule-1 expression in cultured endothelial cells. These results suggest Tat-APE1/ref-1 might be useful to reduce vascular endothelial activation or vascular inflammatory disorders.

  9. Serine proteinase inhibition by the active site titrant N alpha-(N, N-dimethylcarbamoyl)-alpha-azaornithine p-nitrophenyl ester. A comparative study. (United States)

    Ascenzi, P; Balliano, G; Gallina, C; Polticelli, F; Bolognesi, M


    Kinetics for the hydrolysis of the chromogenic active-site titrant N alpha-(N,N-dimethylcarbamoyl)-alpha-azaornithine p-nitrophenyl ester (Dmc-azaOrn-ONp) catalysed by bovine beta-trypsin, bovine alpha-thrombin, bovine Factor Xa, human alpha-thrombin, human Factor Xa, human Lys77-plasmin, human urinary kallikrein, Mr 33 000 and Mr 54 000 species of human urokinase, porcine pancreatic beta-kallikrein-A and -B and Ancrod (the coagulating serine proteinase from the Malayan pit viper Agkistrodon rhodostoma venom) have been obtained between pH 6.0 and 8.0, at 21.0 degrees C, and analysed in parallel with those for the enzymatic cleavage of N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine p-nitrophenyl ester (Dmc-azaLys-ONp). The enzyme kinetics are consistent with the minimum three-step catalytic mechanism of serine proteinases, the rate-limiting step being represented by the deacylation process. Bovine beta-trypsin kinetics are modulated by the acid-base equilibrium of the His57 catalytic residue (pKa approximately 6.9). Dmc-azaOrn-ONp and Dmc-azaLys-ONp bind stoichiometrically to the serine proteinase active site, and allow the reliable determination of the active enzyme concentration between 1.0 x 10-6 M and 3.0 x 10-4 M. The affinity and the reactivity for Dmc-azaOrn-ONp (expressed by Ks and k+2/Ks, respectively) of the serine proteinases considered are much lower than those for Dmc-azaLys-ONp. The very different affinity and reactivity properties for Dmc-azaOrn-ONp and Dmc-azaLys-ONp have been related to the different size of the ornithine/lysine side chains, and to the ensuing different positioning of the active-site titrants upon binding to the enzyme catalytic centre (i.e. to P1-S1 recognition). These data represent the first detailed comparative investigation on the catalytic properties of serine proteinases towards an ornithine derivative (i. e. Dmc-azaOrn-ONp).

  10. Influence of peroxisome proliferator-activated receptor alpha agonists on the intracellular turnover and secretion of apolipoprotein (Apo) B-100 and ApoB-48. (United States)

    Lindén, Daniel; Lindberg, Karin; Oscarsson, Jan; Claesson, Catharina; Asp, Lennart; Li, Lu; Gustafsson, Maria; Borén, Jan; Olofsson, Sven-Olof


    The peroxisome proliferator-activated receptor (PPAR) alpha agonist WY 14,643 increased the secretion of apolipoprotein (apo) B-100, but not that of apoB-48, and decreased triglyceride biosynthesis and secretion from primary rat hepatocytes. These effects resulted in decreased secretion of apoB-100-very low density lipoprotein (VLDL) and an increased secretion of apoB-100 on low density lipoproteins/intermediate density lipoproteins. ApoB-48-VLDL was also replaced by more dense particles. The proteasomal inhibitor lactacystin did not influence the recovery of apoB-100 or apoB-48 in primary rat hepatocytes, indicating that co-translational (proteasomal) degradation is of less importance in these cells. Treatment with WY 14,643 made the recovery of apoB-100 sensitive to lactacystin, most likely reflecting the decreased biosynthesis of triglycerides. The PPAR alpha agonist induced a significant increase in the accumulation of pulse-labeled apoB-100 even after a short pulse (2-5 min). There was also an increase in apoB-100 nascent polypeptides, indicating that the co-translational degradation of apoB-100 was inhibited. However, a minor influence on an early posttranslation degradation cannot be excluded. This decreased co-translational degradation of apoB-100 explained the increased secretion of the protein. The levels of apoB-48 remained unchanged during these pulse-chase experiments, and albumin production was not affected, indicating a specific effect of PPAR alpha agonists on the co-translational degradation of apoB-100. These findings explain the difference in the rate of secretion of the two apoB proteins seen after PPAR alpha activation. PPAR alpha agonists increased the expression and biosynthesis of liver fatty acid-binding protein (LFABP). Increased expression of LFABP by transfection of McA-RH7777 cells increased the secretion of apoB-100, decreased triglyceride biosynthesis and secretion, and increased PPAR alpha mRNA levels. These findings suggest that

  11. Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the hemagglutinin of influenza virus. (United States)

    Yamamoto, Nobuto; Urade, Masahiro


    Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal macrophage activating factor (MAF). The precursor activity of serum Gc protein was reduced in all influenza virus-infected patients. These patient sera contained alpha-N-acetylgalactosaminidase (Nagalase) that deglycosylates Gc protein. Deglycosylated Gc protein cannot be converted to MAF, thus it loses the MAF precursor activity, leading to immunosuppression. An influenza virus stock contained a large amount of Nagalase activity. A sucrose gradient centrifugation analysis of the virus stock showed that the profile of Nagalase activity corresponds to that of hemagglutinating activity. When these gradient fractions were treated with 0.01% trypsin for 30 min, the Nagalase activity of each fraction increased significantly, suggesting that the Nagalase activity resides on an outer envelope protein of the influenza virion and is enhanced by the proteolytic process. After disruption of influenza virions with sodium deoxycholate, fractionation of the envelope proteins with mannose-specific lectin affinity column along with electrophoretic analysis of the Nagalase peak fraction revealed that Nagalase is the intrinsic component of the hemagglutinin (HA). Cloned HA protein exhibited Nagalase activity only if treated with trypsin. Since both fusion capacity and Nagalase activity of HA protein are expressed by proteolytic cleavage, Nagalase activity appears to be an enzymatic basis for the fusion process. Thus, Nagalase plays dual roles in regulating both infectivity and immunosuppression. PMID:15848273

  12. Design quality control of the activity determination total alpha liquid effluents; Diseno de control de calidad de la determinacion de actividad alfa total en efluentes liquidos

    Energy Technology Data Exchange (ETDEWEB)

    Yague, L.; Alvarez, A.; Navarro, N.; Noguerales, C.


    The total alpha activity index is the joint action of all alpha emissions in a sample. This is a very useful in designing the analytical control of liquid effluent into the environment. Presents the design of quality control applied to the determination of total alpha activity.

  13. Platelet activation risk index as a prognostic thrombosis indicator. (United States)

    Zlobina, K E; Guria, G Th


    Platelet activation in blood flow under high, overcritical shear rates is initiated by Von Willebrand factor. Despite the large amount of experimental data that have been obtained, the value of the critical shear rate, above which von Willebrand factor starts to activate platelets, is still controversial. Here, we recommend a theoretical approach to elucidate how the critical blood shear rate is dependent on von Willebrand factor size. We derived a diagram of platelet activation according to the shear rate and von Willebrand factor multimer size. We succeeded in deriving an explicit formula for the dependence of the critical shear rate on von Willebrand factor molecule size. The platelet activation risk index was introduced. This index is dependent on the flow conditions, number of monomers in von Willebrand factor, and platelet sensitivity. Probable medical applications of the platelet activation risk index as a universal prognostic index are discussed. PMID:27461235

  14. The selective alpha7 nicotinic acetylcholine receptor agonist A-582941 activates immediate early genes in limbic regions of the forebrain

    DEFF Research Database (Denmark)

    Thomsen, M S; Mikkelsen, J D; Timmermann, D B;


    Due to the cognitive-enhancing properties of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) agonists, they have attracted interest for the treatment of cognitive disturbances in schizophrenia. Schizophrenia typically presents in late adolescence or early adulthood. It is therefore important...... regions critically involved in working memory and attention. Furthermore, this effect is more pronounced in juvenile than adult rats, indicating that the juvenile forebrain is more responsive to alpha7 nAChR stimulation. This observation may be relevant in the treatment of juvenile-onset schizophrenia....

  15. A possible long-term activity cycle for {\\iota} Horologii: First results from the HK{\\alpha} & SPI-HK{\\alpha} projects

    CERN Document Server

    Flores, Matías G; Saffe, Carlos E; Mauas, Pablo J D


    To detect stellar activity cycles and study the possible star-planet interactions (SPI's), we have developed both HK$\\alpha$ and SPI-HK$\\alpha$ projects since 1999 and 2012 respectively. In this work, we present preliminary results of possible SPI's studying the chromospheric activity and look for possible correlations between stellar activity and stellar/planetary parameters. We find that for stars with similar T$_{eff}$, stellar activity increases with the mass of the planet, similar to previous works. However, stellar ages can also play a role and a larger stellar sample is needed to verify these trends. We also note that some of these stars present a remarkably high level of chromospheric activity, even comparable with RSCvn or BY Dra active stars. In addition, we do not observe any correlation between stellar activity and semi-major axis. We present the first long-term activity study of the star $\\iota$ Horologii, a young solar-type star which hosts a non-transiting Jovian planet and presents a high acti...

  16. Two farnesoid X receptor alpha isoforms in Japanese medaka (Oryzias latipes) are differentially activated in vitro


    Howarth, Deanna L.; Hagey, Lee R.; Law, Sheran H.W.; Ai, Ni; Krasowski, Matthew D.; Ekins, Sean; Moore, John T.; Erin M Kollitz; Hinton, David E.; Kullman, Seth W.


    The nuclear receptor farnesoid X receptor alpha (FXRα, NR1H4) is activated by bile acids in multiple species including mouse, rat, and human and in this study we have identified two isoforms of Fxrα in Japanese medaka (Oryzias latipes), a small freshwater teleost. Both isoforms share a high amino acid sequence identity to mammalian FXRα (~70% in the ligand-binding domain). Fxrα1 and Fxrα2 differ within the AF1 domain due to alternative splicing at the fourth intron-exon boundary. This process...

  17. Highly Potent, Water Soluble Benzimidazole Antagonist for Activated (alpha)4(beta)1 Integrin

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, R D; Andrei, M; Lau, E Y; Lightstone, F C; Liu, R; Lam, K S; Kurth, M J


    The cell surface receptor {alpha}{sub 4}{beta}{sub 1} integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC{sub 50} = 305 pM]. With exceptional solubility, this finding has potential for improving PK to help diagnose and treat lymphomas.

  18. The low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor regulates cell surface plasminogen activator activity on human trophoblast cells. (United States)

    Zhang, J C; Sakthivel, R; Kniss, D; Graham, C H; Strickland, D K; McCrae, K R


    The low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor (LRP/alpha2MR) mediates the internalization of numerous ligands, including prourokinase (pro-UK) and complexes between two-chain urokinase (tc-u-PA) and plasminogen activator inhibitor type-1 (PAI-1). It has been suggested that through its ability to internalize these ligands, LRP/alpha2MR may regulate the expression of plasminogen activator activity on cell surfaces; this hypothesis, however, has not been experimentally confirmed. To address this issue, we assessed the ability of LRP/alpha2MR to regulate plasminogen activator activity on human trophoblast cells, which express both LRP/alpha2MR and the urokinase receptor (uPAR). Trophoblasts internalized and degraded exogenous 125I-pro-UK (primarily following its conversion to tc-u-PA and incorporation into tc-u-PA.PAI complexes) in an LRP/alpha2MR-dependent manner, which was inhibited by the LRP/alpha2MR receptor-associated protein. Receptor-associated protein also caused a approximately 50% reduction in cell surface plasminogen activator activity and delayed the regeneration of unoccupied uPAR by cells on which uPAR were initially saturated with pro-UK. Identical effects were caused by anti-LRP/alpha2MR antibodies. These results demonstrate that LRP/alpha2MR promotes the expression of cell surface plasminogen activator activity on trophoblasts by facilitating the clearance of tc-u-PA.PAI complexes and regeneration of unoccupied cell surface uPAR. PMID:9822706

  19. Active Epilepsy as Indicator of Neurocysticercosis in Rural Northwest India


    Gupta, V. P.; Shiveta Razdan; Rajesh Sharma; Pandita, K. K.; Sushil Razdan; Sunil Kumar Raina


    Objective. To determine the contribution of neurocysticercosis as a cause for active epilepsy and to establish Neurocysticercosis as major definable risk of epilepsy in our setup. Methods. We conducted a door-to-door survey of 2,209 individuals of Bhore Pind and Bhore Kullian villages in Chattah zone of district Jammu (Jumma and Kashmir, Northwest India) to identify patients with symptomatic epilepsy. Patients with active epilepsy were investigated with neuroimaging techniques to establish di...

  20. Geomorphic Indices in the Assessment of Tectonic Activity in Forearc of the Active Mexican Subduction Zone (United States)

    Gaidzik, K.; Ramirez-Herrera, M. T.


    Rapid development of GIS techniques and constant advancement of digital elevation models significantly improved the accuracy of extraction of information on active tectonics from landscape features. Numerous attempts were made to quantitatively evaluate recent tectonic activity using GIS and DEMs, and a set of geomorphic indices (GI), however these studies focused mainly on sub-basins or small-scale areal units. In forearc regions where crustal deformation is usually large-scale and do not concentrate only along one specific fault, an assessment of the complete basin is more accurate. We present here the first attempt to implement thirteen GI in the assessment of active tectonics of a forearc region of an active convergent margin using the entire river basins. The GIs were divided into groups: BTAI - basin geomorphic indices (reflecting areal erosion vs. tectonics) and STAI - stream geomorphic indices (reflecting vertical erosion vs. tectonics). We calculated selected indices for 9 large (> 450 km2) drainage basins. Then we categorized the obtained results of each index into three classes of relative tectonic activity: 1 - high, 2 - moderate, and 3 - low. Finally we averaged these classes for each basin to determine the tectonic activity level (TAI). The analysis for the case study area, the Guerrero sector at the Mexican subduction zone, revealed high tectonic activity in this area, particularly in its central and, to a lesser degree, eastern part. This pattern agrees with and is supported by interpretation of satellite images and DEM, and field observations. The results proved that the proposed approach indeed allows identification and recognition of areas witnessing recent tectonic deformation. Moreover, our results indicated that, even though no large earthquake has been recorded in this sector for more than 100 years, the area is highly active and may represent a seismic hazard for the region.

  1. N-terminal amino acids of bovine alpha interferons are relevant for the neutralization of their antiviral activity

    Directory of Open Access Journals (Sweden)

    Barreto Filho J.B.


    Full Text Available The structure-function relationship of interferons (IFNs has been studied by epitope mapping. Epitopes of bovine IFNs, however, are practically unknown, despite their importance in virus infections and in the maternal recognition of pregnancy. It has been shown that recombinant bovine (rBoIFN-alphaC and rBoIFN-alpha1 differ only in 12 amino acids and that the F12 monoclonal antibody (mAb binds to a linear sequence of residues 10 to 34. We show here that the antiviral activities of these two IFNs were neutralized by the F12 mAb to different extents using two tests. In residual activity tests the antiviral activity dropped by more than 99% with rBoIFN-alphaC and by 84% with rBoIFN-alpha1. In checkerboard antibody titrations, the F12 mAb titer was 12,000 with rBoIFN-alphaC and only 600 with rBoIFN-alpha1. Since these IFNs differ in their amino acid sequence at positions 11, 16 and 19 of the amino terminus, only these amino acids could account for the different neutralization titers, and they should participate in antibody binding. According to the three-dimensional structure described for human and murine IFNs, these amino acids are located in the alpha helix A; amino acids 16 and 19 of the bovine IFNs would be expected to be exposed and could bind to the antibody directly. The amino acid at position 11 forms a hydrogen bond in human IFNs-alpha and it is possible that, in bovine IFNs-alpha, the F12 mAb, binding near position 11, would disturb this hydrogen bond, resulting in the difference in the extent of neutralization observed.

  2. Evidence that 17alpha-estradiol is biologically active in the uterine tissue: Antiuterotonic and antiuterotrophic action

    Directory of Open Access Journals (Sweden)

    Navarrete Erika


    Full Text Available Abstract Background 17alpha-Estradiol has been considered as the hormonally inactive isomer of 17beta-estradiol. Recently, nongenomic (smooth muscle relaxation and genomic (light estrogenic activity effects of 17alpha-estradiol have been reported, but no reports have yet determined its possible antiestrogenic activity. Therefore, this study investigated: the nongenomic action of 17alpha-estradiol on uterine contractile activity and its potential agonist-antagonist activity on uterine growth. Methods Uterine rings from rats were isometrically recorded. Different concentrations (0.2–200 microM of 17alpha-estradiol were tested on spontaneous contraction and equimolarly compared with 17beta-estradiol. To examine the mechanism of 17alpha-estradiol action, its effect was studied in presence of beta2-antagonist (propranolol, antiestrogens (tamoxifen and ICI 182,780 or inhibitors of protein synthesis (cycloheximide and transcription (actinomycin D. Moreover, contractions induced by high potassium (KCl solution or calcium in depolarized tissues by KCl-calcium free solution were exposed to 17alpha-estradiol. Collaterally, we performed an uterotrophic assay in adult ovariectomized rats measuring the uterine wet weight. The administration for three days of 0.3 microM/day/Kg 17beta-estradiol was equimolarly compared with the response produced by 17alpha-estradiol. Antiuterotrophic activity was assayed by administration of 0.3 microM/day/Kg 17beta-estradiol and various doses ratios (1:1, 1:3, 1:5, and 1:100 of 17alpha-estradiol. Results The estradiol isomers elicited an immediate relaxation, concentration-dependent and reversible on spontaneous contraction. 17alpha-Estradiol presented lower potency than 17beta-estradiol although it did not antagonize 17beta-estradiol-induced relaxation. Relaxation to 17alpha-estradiol was not inhibited by propranolol, tamoxifen, ICI 182,780, cycloheximide or actinomycin D. The KCl contractions were also sensitive to 17alpha

  3. Synthesis of 16 alpha-3H androgen and estrogen substrates for 16 alpha-hydroxylase. (United States)

    Cantineau, R; Kremers, P; De Graeve, J; Cornelis, A; Laszlo, P; Gielen, J E; Lambotte, R


    The synthesis of 16 alpha-3H androgens and estrogens is described. 1-(3H)-Acetic acid in the presence of zinc dust reacts with 16 alpha-bromo-17-ketosteroids to produce 16 alpha-3H-17-ketosteroids. This chemical reaction was used to prepare 16 alpha-3H-dehydroepiandrosterone (I) and 16 alpha-3H-estrone acetate (XI) from 16 alpha-bromo-dehydroepiandrosterone (X) and from 16 alpha-bromo-estrone acetate (XII), respectively. Using appropriate microbiological techniques, it was possible to convert these radiolabelled substrates into 16 alpha-3H-androstenedione (II) and 16 alpha-3H-estradiol-17 beta (VII). 16 alpha-3H-Estrone (VI) was obtained by the chemical hydrolysis of 16 alpha-3H-estrone acetate. The label distribution as determined by microbiological 16 alpha-hydroxylations indicated a specific labelling of 77% for androgens and 65% for estrogens in the 16 alpha position. These substrates can be used for measuring the 16 alpha hydroxylase activity, an important step in the biosynthesis of estriol (VIII) and estetrol (IX). PMID:7013160

  4. Effect of TNF{alpha} on activities of different promoters of human apolipoprotein A-I gene

    Energy Technology Data Exchange (ETDEWEB)

    Orlov, Sergey V., E-mail: [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Mogilenko, Denis A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Shavva, Vladimir S. [Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation); Dizhe, Ella B.; Ignatovich, Irina A. [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Perevozchikov, Andrej P., E-mail: [Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St. Petersburg (Russian Federation); Department of Embryology, St. Petersburg State University, 199034 St. Petersburg (Russian Federation)


    Research highlights: {yields} TNF{alpha} stimulates the distal alternative promoter of human apoA-I gene. {yields} TNF{alpha} acts by weakening of promoter competition within apoA-I gene (promoter switching). {yields} MEK1/2 and nuclear receptors PPAR{alpha} and LXRs take part in apoA-I promoter switching. -- Abstract: Human apolipoprotein A-I (ApoA-I) is a major structural and functional protein component of high-density lipoproteins. The expression of the apolipoprotein A-I gene (apoA-I) in hepatocytes is repressed by pro-inflammatory cytokines such as IL-1{beta} and TNF{alpha}. Recently, two novel additional (alternative) promoters for human apoA-I gene have been identified. Nothing is known about the role of alternative promoters in TNF{alpha}-mediated downregulation of apoA-I gene. In this article we report for the first time about the different effects of TNF{alpha} on two alternative promoters of human apoA-I gene. Stimulation of HepG2 cells by TNF{alpha} leads to activation of the distal alternative apoA-I promoter and downregulation of the proximal alternative and the canonical apoA-I promoters. This effect is mediated by weakening of the promoter competition within human apoA-I 5'-regulatory region (apoA-I promoter switching) in the cells treated by TNF{alpha}. The MEK1/2-ERK1/2 cascade and nuclear receptors PPAR{alpha} and LXRs are important for TNF{alpha}-mediated apoA-I promoter switching.

  5. Activation cross sections of longer-lived radionuclides produced in germanium by alpha particle irradiation (United States)

    Takács, S.; Takács, M. P.; Ditrói, F.; Aikawa, M.; Haba, H.; Komori, Y.


    The cross sections of alpha particles induced nuclear reactions on natural germanium were investigated by using the standard stacked foil target technique, the activation method and high resolution gamma spectrometry. Targets with thickness of about 1 μm were prepared from natural Ge by vacuum evaporation onto 25 μm thick polyimide (Kapton) backing foils. Stacks were composed of Kapton-Ge-Ge-Kapton sandwich target foils and additional titanium monitor foils with nominal thickness of 11 μm to monitor the beam parameters using the natTi(α,x)51Cr reaction. The irradiations were done with Eα = 20.7 and Eα = 51.25 MeV, Iα = 50 nA alpha particle beams for about 1 h. Direct or cumulative activation cross sections were determined for production of the 72,73,75Se, 71,72,74,76,78As, and 69Ge radionuclides. The obtained experimental cross sections were compared to the results of theoretical calculations taken from the TENDL data library based on the TALYS computer code. A comparison was made with available experimental data measured earlier. Thick target yields were deduced from the experimental cross sections and compared with the data published before.

  6. Comparative study of alpha amylase inhibitory activity of flavonoids of Vitex negundo Linn. and Andrographis paniculata Nees


    Keerti Gautam; Padma Kumar; Chitra Jain


    Background: One important therapeutic approach for the treatment of Type 2 Diabetes Mellitus is by decreasing the postprandial increase of glucose. This is possible by inhibiting certain carbohydrate hydrolyzing enzymes like alpha-amylase. Aim: The objective of the present study was to evaluate the alpha amylase inhibitory activity of flavonoids extracts of different parts of Vitex negundo Linn and Andrographis paniculata Nees. Materials and Methods: In the present study, the percentage inhib...

  7. Active Epilepsy as Indicator of Neurocysticercosis in Rural Northwest India

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Raina


    Full Text Available Objective. To determine the contribution of neurocysticercosis as a cause for active epilepsy and to establish Neurocysticercosis as major definable risk of epilepsy in our setup. Methods. We conducted a door-to-door survey of 2,209 individuals of Bhore Pind and Bhore Kullian villages in Chattah zone of district Jammu (Jumma and Kashmir, Northwest India to identify patients with symptomatic epilepsy. Patients with active epilepsy were investigated with neuroimaging techniques to establish diagnosis of NCC (neurocysticercosis. Results. Among 25 patients with epilepsy 10(40% had CT/MR evidence of past or recent NCC infection. This gave us the point prevalence of 4.5/1000 for Neurocysticercosis in our study population. Interpretation. The study shows a high prevalence of NCC accounting for symptomatic epilepsy in our part of India.

  8. Synthetic activity indicators for M-type dwarf stars

    CERN Document Server

    Wedemeyer, Sven


    Here, we present a set of time-dependent 3D RMHD simulations of a M-dwarf star representative of AD Leo, which extend from the upper convection zone into the chromosphere. The 3D model atmospheres are characterized by a very dynamic and intermittent structure on small spatial and temporal scales and a wealth of physical processes, which by nature cannot be described by means of 1D static model atmospheres. Artificial observations of these models imply that a combination of complementary diagnostics such as Ca II lines and the continuum intensity from UV to millimeter wavelengths, probe various properties of the dynamics, thermal and magnetic structure of the photosphere and the chromosphere and thus provide measures of stellar activity, which can be compared to observations. The complicated magnetic field structure and its imprint in synthetic diagnostics may have important implications for the understanding and characterization of stellar activity and with it possibly for the evaluation of planetary habitabi...

  9. Bacteria bioluminescent activity as an indicator of geomagnetic disturbances

    International Nuclear Information System (INIS)

    The effect of geomagnetic disturbances and storms on bioluminescence activity of bacterium were investigated. The bioluminescence intensity change depended on amplitude and continuous of geomagnetic storms. It is assumed, that the synchronization of luminous radiation take place in cellos when frequency of geomagnetic disturbances approached to an intrinsic one of a bioluminescence system. High sensitivity of bioluminescence of geomagnetic storms was detected. 5 refs., 4 figs

  10. 7alpha-Hydroxypregnenolone, a new key regulator of locomotor activity of vertebrates: Identification, mode of action and functional significance

    Directory of Open Access Journals (Sweden)

    Kazuyoshi eTsutsui


    Full Text Available Steroids synthesized de novo by the central and peripheral nervous systems are called neurosteroids. The formation of neurosteroids from cholesterol in the brain was originally demonstrated in mammals by Baulieu and colleagues. Our studies over the past two decades have also shown that, in birds and amphibians as in mammals, the brain expresses several kinds of steroidogenic enzymes and produces a variety of neurosteroids. Thus, de novo neurosteroidogenesis from cholesterol is a conserved property that occurs throughout vertebrates. However, the biosynthetic pathways of neurosteroids in the brain of vertebrates was considered to be still incompletely elucidated. Recently, 7alpha-hydroxypregnenolone was identified as a novel bioactive neurosteroid stimulating locomotor activity in the brain of newts and quail through activation of the dopaminergic system. Subsequently, diurnal and seasonal changes in synthesis of 7alpha-hydroxypregnenolone in the brain were demonstrated. Interestingly, melatonin derived from the pineal gland and eyes regulates 7alpha-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7alpha-hydroxypregnenolone synthesis in the brain, and may also induce seasonal locomotor changes. This review highlights the identification, mode of action and functional significance of 7alpha-hydroxypregnenolone, a new key regulator of locomotor activity of vertebrates, in terms of diurnal and seasonal changes in 7alpha-hydroxypregnenolone synthesis, and describes some of their regulatory mechanisms.

  11. NAD(P)H oxidase/nitric oxide interactions in peroxisome proliferator activated receptor (PPAR){alpha}-mediated cardiovascular effects

    Energy Technology Data Exchange (ETDEWEB)

    Newaz, Mohammad [Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004 (United States); Blanton, Ahmad [Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004 (United States); Fidelis, Paul [Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004 (United States); Oyekan, Adebayo [Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004 (United States)]. E-mail: Oyekan_AO@TSU.EDU


    Activation of peroxisome proliferator activated receptor (PPAR){alpha} and its protective role in cardiovascular function has been reported but the exact mechanism(s) involved is not clear. As we have shown that PPAR{alpha} ligands increased nitric oxide (NO) production and cardiovascular function is controlled by a balance between NO and free radicals, we hypothesize that PPAR{alpha} activation tilts the balance between NO and free radicals and that this mechanism defines the protective effects of PPAR{alpha} ligands on cardiovascular system. Systolic blood pressure (SBP) was greater in PPAR{alpha} knockout (KO) mice compared with its wild type (WT) litter mates (130 {+-} 10 mmHg versus 107 {+-} 4 mmHg). L-NAME (100 mg/L p.o.), the inhibitor of NO production abolished the difference between PPAR{alpha} KO and WT mice. In kidney homogenates, tissue lipid hydroperoxide generation was greater in KO mice (11.8 {+-} 1.4 pM/mg versus 8.3 {+-} 0.6 pM/mg protein). This was accompanied by a higher total NOS activity (46 {+-} 6%, p < 0.05) and a {approx}3 fold greater Ca{sup 2+}-dependent NOS activity in kidney homogenates of untreated PPAR{alpha} WT compared with the KO mice. Clofibrate, a PPAR{alpha} ligand, increased NOS activity in WT but not KO mice. Bezafibrate (30 mg/kg) reduced SBP in conscious rats (19 {+-} 4%, p < 0.05), increased urinary NO excretion (4.06 {+-} 0.53-7.07 {+-} 1.59 {mu}M/24 h; p < 0.05) and reduced plasma 8-isoprostane level (45.8 {+-} 15 {mu}M versus 31.4 {+-} 8 {mu}M), and NADP(H) oxidase activity (16 {+-} 5%). Implantation of DOCA pellet (20 mg s.c.) in uninephrectomized mice placed on 1% NaCl drinking water increased SBP by a margin that was markedly greater in KO mice (193 {+-} 13 mmHg versus 130 {+-} 12 mmHg). In the rat, DOCA increased SBP and NAD(P)H oxidase activity and both effects were diminished by clofibrate. In addition, clofibrate reduced ET-1 production in DOCA/salt hypertensive rats. Thus, apart from inhibition of ET-1 production

  12. The 222 Rn Volume Radioactivity Response of AlphaGUARD Radon Monitor in Active/passive Mode%AlphaGUARD 在主/被动模式下对222 Rn体积活度的响应

    Institute of Scientific and Technical Information of China (English)

    陆小军; 何林锋; 徐一鹤; 曹振; 孙训; 唐方东


    AlphaGUARD radon monitor is the most stable and accurate radon detector at present , widely used as radon measurement standard delivery device at home and abroad .This paper introduced the AlphaGUARD ra-don volume activity response from low to high volume of radio -activity based on the actual applications , and made a comparative analysis of AlphaGUARD measuring radon activity in two modes .the results showed that:Firstly, the volume activity response of AlphaGUARD at active mode is smaller than the response at passive mode ;secondly , AlphaGUARD volume activity response doesn't changes with flow rate of sampling pump obvi-ously;thirdly, the222 Rn measurement repeatability decreases with the increase of 222 Rn volume activity, but not varied with the sampling flow rate .%AlphaGUARD是目前技术性能最优的测氡仪之一,常用作氡测量传递标准。文章介绍了AlphaGUARD主动与被动测量模式的原理,对AlphaGUARD在主动和被动两种工作模式下和不同采样流速下的氡体积活度响应作了分析对比,实验结果表明:主动模式下AlphaGUARD体积活度响应小于在被动模式下,采样流速对AlphaGUARD的体积活度响应无明显影响;AlphaGUARD对222 Rn体积活度的测量重复性随222 Rn体积活度的增大而减小,但是尚得不到其重复性随采样流量的变化规律。

  13. Peroxisome proliferator-activated receptor-alpha control of lipid and glucose metabolism in human white adipocytes. (United States)

    Ribet, Carole; Montastier, Emilie; Valle, Carine; Bezaire, Véronic; Mazzucotelli, Anne; Mairal, Aline; Viguerie, Nathalie; Langin, Dominique


    This work aimed at characterizing the role of peroxisome proliferator-activated receptors (PPAR)alpha in human white adipocyte metabolism and at comparing PPAR alpha and PPAR gamma actions in these cells. Primary cultures of human fat cells were treated with the PPAR alpha agonist GW7647 or the PPAR gamma agonist rosiglitazone. Changes in gene expression were determined using DNA microarrays and quantitative RT-PCR. Western blot and metabolic studies were performed to identify the biological effects elicited by PPAR agonist treatments. GW7647 induced an up-regulation of beta-oxidation gene expression and increased palmitate oxidation. Unexpectedly, glycolysis was strongly reduced at transcriptional and functional levels by GW7647 leading to a decrease in pyruvate and lactate production. Glucose oxidation was decreased. Triglyceride esterification and de novo lipogenesis were inhibited by the PPAR alpha agonist. GW7647-induced alterations were abolished by a treatment with a PPAR alpha antagonist. Small interfering RNA-mediated extinction of PPAR alpha gene expression in hMADS adipocytes attenuated GW7647 induction of palmitate oxidation. Rosiglitazone had no major impact on glycolysis and beta-oxidation. Altogether these results show that PPAR alpha can selectively up-regulate beta-oxidation and decrease glucose utilization in human white adipocytes. PMID:19887568

  14. Phaeophytins from Thyrsacanthus ramosissimus Moric. with inhibitory activity on human DNA topoisomerase II-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Cabral, Analucia Guedes Silveira; Tenorio-Souza, Fabio Henrique; Moura, Marcelo Dantas; Mota, Sabrina Gondim Ribeiro; Silva Lins, Antonio Claudio da; Dias, Celidarque da Silva; Barbosa-Filho, Jose Maria [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Ciencias Frmaceuticas; Giulietti, Ana Maria [Universidade Estadual de Feira de Santana, Feira de Santana, BA (Brazil). Dept. de Ciencias Biologicas; Silva, Tania Maria Sarmento da [Universidade Federal Rural de Pernambuco, Recife, PE (Brazil). Dept. de Ciencias Moleculares; Santos, Creusioni Figueredo dos, E-mail: [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Biologia Molecular


    Our study reports the extraction and isolation of a new phaeophytin derivative 15{sup 1}-hydroxy-(15{sup 1}-S)-porphyrinolactone, designated anamariaine (1) herein, isolated from the chloroform fraction of aerial parts of Thyrsacanthus ramosissimus Moric. along with the known 15{sup 1}-ethoxy-(15{sup 1}-S)-porphyrinolactone (2). These compounds were identified by usual spectroscopic methods. Both compounds were subjected to in vitro (inhibitory activity) tests by means of supercoiled DNA relaxation techniques and were shown to display inhibitory activity against human DNA topoisomerase II-{alpha} at 50 {mu}M. Interconversion of these two pigments under the mild conditions of the isolation techniques should be highly unlikely but cannot be entirely ruled out. (author)

  15. Extracellular Enzyme Activity assay as indicator of soil microbial functional diversity and activity

    DEFF Research Database (Denmark)

    Hendriksen, Niels Bohse; Winding, Anne


    Extracellular Enzyme Activity assay as indicator of soil microbial functional diversity and activity Niels Bohse Hendriksen, Anne Winding. Department of Environmental Science, Aarhus University, 4000 Roskilde, Denmark Soil enzymes originate from a variety of organisms, notably fungi and bacteria...... and especially hydrolytic extracellular enzymes are of pivotal importance for decomposition of organic substrates and biogeochemical cycling. Their activity reflects the functional diversity and activity of the microorganisms involved in decomposition processes which are essential processes for soil functioning...... and soil ecosystem services. The soil enzyme activity has been measured by the use of fluorogenic model substrates e.g. methylumbelliferyl (MUF) substrates for a number of enzymes involved in the degradation of polysaccharides as cellulose, hemicellulose and chitin, while degradation of proteins has been...

  16. Extracellular enzyme activity assay as indicator of soil microbial functional diversity and activity

    DEFF Research Database (Denmark)

    Hendriksen, Niels Bohse; Winding, Anne


    Extracellular enzyme activity assay as indicator of soil microbial functional diversity and activity Niels Bohse Hendriksen, Anne Winding. Department of Environmental Science, Aarhus University, 4000 Roskilde, Denmark Soils provide numerous essential ecosystem services such as carbon cycling...... of soil microbial functions is still needed. In soil, enzymes originate from a variety of organisms, notably fungi and bacteria and especially hydrolytic extracellular enzymes are of pivotal importance for decomposition of organic substrates and biogeochemical cycling. Their activity will reflect...... the functional diversity and activity of the microorganisms involved in decomposition processes. Their activity has been measured by the use of fluorogenic model substrates e.g. methylumbelliferyl (MUF) substrates for a number of enzymes involved in the degradation of polysacharides as cellulose, hemicellulose...

  17. HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor

    Directory of Open Access Journals (Sweden)

    Joos Ulrich


    Full Text Available Abstract Background Hypoxia-inducible factor 1 (HIF-1 is a transcription factor, which plays a central role in biologic processes under hypoxic conditions, especially concerning tumour angiogenesis. HIF-1α is the relevant, oxygen-dependent subunit and its overexpression has been associated with a poor prognosis in a variety of malignant tumours. Therefore, HIF-1α expression in early stage oral carcinomas was evaluated in relation to established clinico-pathological features in order to determine its value as a prognostic marker. Methods 85 patients with histologically proven surgically treated T1/2 squamous cell carcinoma (SCC of the oral floor were eligible for the study. Tumor specimens were investigated by means of tissue micro arrays (TMAs and immunohistochemistry for the expression of HIF-1. Correlations between clinical features and the expression of HIF-1 were evaluated by Kaplan-Meier curves, log-rank tests and multivariate Cox regression analysis. Results HIF-1α was frequently overexpressed in a probably non-hypoxia related fashion. The expression of HIF-1α was related with a significantly improved 5-year survival rate (p Conclusion HIF-1α overexpression is an indicator of favourable prognosis in T1 and T2 SCC of the oral floor. Node negative patients lacking HIF-1α expression may therefore be considered for adjuvant radiotherapy.

  18. Stimulation of receptor protein-tyrosine phosphatase alpha activity and phosphorylation by phorbol ester

    DEFF Research Database (Denmark)

    den Hertog, J; Sap, J; Pals, C E;


    Receptor Protein-Tyrosine Phosphatase alpha (RPTP alpha) is a transmembrane protein with two cytoplasmic catalytic protein-tyrosine phosphatase (PTP) domains and a relatively short (123 amino acids) extracellular domain. Here we report that treatment of transfected cells that express RPTP alpha...

  19. Medial profrontal cortex and anterior cingulate cortex in the generation of alpha activity induced by transcendental meditation: a magnetoencephalographic study.

    Directory of Open Access Journals (Sweden)



    Full Text Available

    Previous EEG studies have shown that transcendental meditation (TM increases frontal and central alpha activity. The present study was aimed at identifying the source of this alpha activity using magnetoencephalography (MEG and electroencephalography (EEG simultaneously on eight TM practitioners before, during, and after TM. The magnetic field potentials corresponding to TM-induced alpha activities on EEG recordings were extracted, and we attempted to localize the dipole sources using the multiple signal classification (MUSIC algorithm, equivalent current dipole source analysis, and the multiple spatio-temporal dipole model. Since the dipoles were mapped to both the medial prefrontal cortex (mPFC and anterior cingulate cortex (ACC, it is suggested that the mPFC and ACC play an important role in brain activity induced by TM.

  20. HIF1-alpha overexpression indicates a good prognosis in early stage squamous cell carcinomas of the oral floor

    International Nuclear Information System (INIS)

    Hypoxia-inducible factor 1 (HIF-1) is a transcription factor, which plays a central role in biologic processes under hypoxic conditions, especially concerning tumour angiogenesis. HIF-1α is the relevant, oxygen-dependent subunit and its overexpression has been associated with a poor prognosis in a variety of malignant tumours. Therefore, HIF-1α expression in early stage oral carcinomas was evaluated in relation to established clinico-pathological features in order to determine its value as a prognostic marker. 85 patients with histologically proven surgically treated T1/2 squamous cell carcinoma (SCC) of the oral floor were eligible for the study. Tumor specimens were investigated by means of tissue micro arrays (TMAs) and immunohistochemistry for the expression of HIF-1. Correlations between clinical features and the expression of HIF-1 were evaluated by Kaplan-Meier curves, log-rank tests and multivariate Cox regression analysis. HIF-1α was frequently overexpressed in a probably non-hypoxia related fashion. The expression of HIF-1α was related with a significantly improved 5-year survival rate (p < 0.01) and a significantly increased disease free period (p = 0.01) independent from nodal status and tumour size. In primary node negative T1/T2 SCC of the oral floor, absence of HIF-1α expression specified a subgroup of high-risk patients (p < 0.05). HIF-1α overexpression is an indicator of favourable prognosis in T1 and T2 SCC of the oral floor. Node negative patients lacking HIF-1α expression may therefore be considered for adjuvant radiotherapy

  1. Activation of Penile Proadipogenic Peroxisome Proliferator-Activated Receptor with an Estrogen: Interaction with Estrogen Receptor Alpha during Postnatal Development

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Mansour


    Full Text Available Exposure to the estrogen receptor alpha (ER ligand diethylstilbesterol (DES between neonatal days 2 to 12 induces penile adipogenesis and adult infertility in rats. The objective of this study was to investigate the in vivo interaction between DES-activated ER and the proadipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPAR. Transcripts for PPARs , , and and 1a splice variant were detected in Sprague-Dawley normal rat penis with PPAR predominating. In addition, PPAR1b and PPAR2 were newly induced by DES. The PPAR transcripts were significantly upregulated with DES and reduced by antiestrogen ICI 182, 780. At the cellular level, PPAR protein was detected in urethral transitional epithelium and stromal, endothelial, neuronal, and smooth muscular cells. Treatment with DES activated ER and induced adipocyte differentiation in corpus cavernosum penis. Those adipocytes exhibited strong nuclear PPAR expression. These results suggest a biological overlap between PPAR and ER and highlight a mechanism for endocrine disruption.

  2. Modeling Steroid 5alpha-reductase and Characterizing Its Potential Active Sites

    Institute of Scientific and Technical Information of China (English)

    OU Min-Rui; LI Jun-Qian


    Steroid 5alpha-reductase of human is an enzyme in the biosynthetic pathway from testosterone (T) to dihydrotestosterone (DHT). Up to now, no crystal structure of this enzyme has been reported. However, knowledge of the tertiary structure and possible active sites is essential for understanding the catalysis mechanism and for the design of inhibitors. A model with putative active sites has been created and evaluated by using homology modeling and molecular docking techniques based on the bioinformatics knowledge. The homology model is optimized in Swiss PDB Viewer with MM method and substrate structures before docking are also optimized on HF/6-31G. The active site for the docking of NADP, T, DHT and Finasteride is located near the N-terminus of enzyme. Four active amino acids in the active site are identified as Ala26, Arg53, Arg176 and Lys177. Reaction procedure, binding pattern of active sites, the types of weak interaction and so on are also discussed.

  3. Insights into the electrochemical activity of nanosized {alpha}-LiFeO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Morales, J.; Santos-Pena, J.; Trocoli, R. [Departamento de Quimica Inorganica e Ingenieria Quimica, Edificio Marie Curie, Campus de Rabanales, Universidad de Cordoba, Cordoba 14071 (Spain); Franger, S. [Laboratoire de Physico-Chimie de l' Etat Solide, ICMMO, Universite Paris XI, Orsay 91405 (France); Rodriguez-Castellon, E. [Departamento de Quimica Inorganica, Cristalografia y Mineralogia, Campus de Teatinos, Universidad de Malaga, Malaga 29071 (Spain)


    In recent work [J. Morales, J. Santos-Pena, Electrochem. Commun. 9 (2007) 2116], we prepared nanosized {alpha}-LiFeO{sub 2} with increased electrochemical activity in lithium cells relative to various lithium ferrite polymorphs. In this work, we studied the previous electrodes in different charge states in order to obtain a more accurate picture of the phenomena occurring during cycling. Exsitu X-ray photoelectron spectroscopy (XPS) measurements confirmed the oxidation/reduction of iron atoms during the charge/discharge process. The electrochemical impedance spectroscopy results suggested that the electrolyte is not oxidised during the first charge, but rather than a solid electrolyte interface is formed after one cycle. Also, thermal tests revealed that Fe(IV) present in the electrodes reacted with the electrolyte to form oxidised carbon species. Finally, {alpha}-LiFeO{sub 2} was tested as a positive electrode material in a lithium battery under different regimes. Stabilised capacities up to 150 mAh g{sup -1} were obtained under a C/4 regime. This lithium ferrite is therefore an attractive alternative to LiCoO{sub 2}. (author)

  4. Use of proportional gas scintillator in absolute measurements of alpha-gamma emitter activities

    International Nuclear Information System (INIS)

    The absolute activity of U-235 contained in a U3 O8 sample was measured utilizing a sum-coincidence circuit which selects only the alpha particles which are simultaneous with the 143 KeV and 186 KeV gamma radiations from the Th-231 (product nucleus). The alpha particles were detected by means of a new type of a gas scintillating chamber, in which the light emitted by excitation of the gas atoms, due to the passage of a charged incoming particle, has its intensity increased by the action of an applied electric field. The gamma radiations were detected by means of a NaI(Tl) 1'' x 11/2'' scintillation detector. The value obtained for the half-life of U-235 was compared with the data available from various observers which used different experimental techniques. It is shown tht the results, are in excellent agreement with the best international data available on the subject and that, therefore, the sum-coincidence technique constitutes an important method for such measurements. (Author)

  5. Active terahertz imaging with Ne indicator lamp detector arrays (United States)

    Kopeika, N. S.; Abramovich, A.; Yadid-Pecht, O.; Yitzhaky, Y.


    The advantages of terahertz (THz) imaging are well known. They penetrate well most non-conducting media and there are no known biological hazards, This makes such imaging systems important for homeland security, as they can be used to image concealed objects and often into rooms or buildings from the outside. There are also biomedical applications that are arising. Unfortunately, THz imaging is quite expensive, especially for real time systems, largely because of the price of the detector. Bolometers and pyroelectric detectors can each easily cost at least hundreds of dollars if not more, thus making focal plane arrays of them quite expensive. We have found that common miniature commercial neon indicator lamps costing typically about 30 cents each exhibit high sensitivity to THz radiation [1-3], with microsecond order rise times, thus making them excellent candidates for such focal plane arrays. NEP is on the order of 10-10 W/Hz1/2. Significant improvement of detection performance is expected when heterodyne detection is used Efforts are being made to develop focal plane array imagers using such devices at 300 GHz. Indeed, preliminary images using 4x4 arrays have already been obtained. An 8x8 VLSI board has been developed and is presently being tested. Since no similar imaging systems have been developed previously, there are many new problems to be solved with such a novel and unconventional imaging system. These devices act as square law detectors, with detected signal proportional to THz power. This allows them to act as mixers in heterodyne detection, thus allowing NEP to be reduced further by almost two orders of magnitude. Plans are to expand the arrays to larger sizes, and to employ super resolution techniques to improve image quality beyond that ordinarily obtainable at THz frequencies.

  6. Innovative techniques to analyze time series of geomagnetic activity indices (United States)

    Balasis, Georgios; Papadimitriou, Constantinos; Daglis, Ioannis A.; Potirakis, Stelios M.; Eftaxias, Konstantinos


    Magnetic storms are undoubtedly among the most important phenomena in space physics and also a central subject of space weather. The non-extensive Tsallis entropy has been recently introduced, as an effective complexity measure for the analysis of the geomagnetic activity Dst index. The Tsallis entropy sensitively shows the complexity dissimilarity among different "physiological" (normal) and "pathological" states (intense magnetic storms). More precisely, the Tsallis entropy implies the emergence of two distinct patterns: (i) a pattern associated with the intense magnetic storms, which is characterized by a higher degree of organization, and (ii) a pattern associated with normal periods, which is characterized by a lower degree of organization. Other entropy measures such as Block Entropy, T-Complexity, Approximate Entropy, Sample Entropy and Fuzzy Entropy verify the above mentioned result. Importantly, the wavelet spectral analysis in terms of Hurst exponent, H, also shows the existence of two different patterns: (i) a pattern associated with the intense magnetic storms, which is characterized by a fractional Brownian persistent behavior (ii) a pattern associated with normal periods, which is characterized by a fractional Brownian anti-persistent behavior. Finally, we observe universality in the magnetic storm and earthquake dynamics, on a basis of a modified form of the Gutenberg-Richter law for the Tsallis statistics. This finding suggests a common approach to the interpretation of both phenomena in terms of the same driving physical mechanism. Signatures of discrete scale invariance in Dst time series further supports the aforementioned proposal.

  7. Application of neural network method to detect type of uranium contamination by estimation of activity ratio in environmental alpha spectra. (United States)

    Einian, M R; Aghamiri, S M R; Ghaderi, R


    The discrimination of the composition of environmental and non-environmental materials by the estimation of the (234)U/(238)U activity ratio in alpha-particle spectrometry is important in many applications. If the interfering elements are not completely separated from the uranium, they can interfere with the determination of (234)U. Thickness as a result of the existence of iron in the source preparation phase and their alpha lines can broaden the alpha line of (234)U in alpha spectra. Therefore, the asymmetric broadening of the alpha line of (234)U and overlapping of peaks make the analysis of the alpha particle spectra and the interpretation of the results difficult. Applying Artificial Neural Network (ANN) to a spectrometry system is a good idea because it eliminates limitations of classical approaches by extracting the desired information from the input data. In this work, the average of a partial uranium raw spectrum, were considered. Each point that its slope was of the order of 0-1% per 10 channels, was used as input to the multi-layer feed forward error-back propagation network. The network was trained by an alpha spectrum library which has been developed in the present work. The training data in this study was actual spectral data with any reasonable thickness and interfering elements. According to the results, the method applied to estimate the activity ratio in this work, can examine the alpha spectrum for peaks which would not be expected for a source of given element and provide the clues about composition of uranium contamination in the environmental samples in a fast screening and classifying procedures.

  8. Activation of podocytes by mesangial-derived TNF-alpha: glomerulo-podocytic communication in IgA nephropathy. (United States)

    Lai, Kar Neng; Leung, Joseph C K; Chan, Loretta Y Y; Saleem, Moin A; Mathieson, Peter W; Lai, Fernand M; Tang, Sydney C W


    We have previously documented that human mesangial cell (HMC)-derived TNF-alpha is an important mediator involved in the glomerulo-tubular communication in the development of interstitial damage in IgA nephropathy (IgAN). With the strategic position of podocytes, we further examined the role of mesangial cells in the activation of podocytes in IgAN. There was no binding of IgA from patients with IgAN to podocytes. Podocytes cultured with IgA from patients with IgAN did not induce the release of growth factors or cytokines. Furthermore, podocytes did not express mRNA of known IgA receptors. In contrast, IgA-conditioned medium (IgA-HMC medium) prepared by culturing HMC with IgA from patients with IgAN for 48 h significantly increased the gene expression and protein synthesis of TNF-alpha by podocytes with a 17-fold concentration above that of IgA-HMC medium. The upregulation of TNF-alpha expression by podocyte was only abolished by a neutralizing antibody against TNF-alpha but not by other antibodies. Exogenous TNF-alpha upregulated the synthesis of TNF-alpha by podocytes in an autocrine fashion. IgA-HMC medium prepared with IgA from patients with IgAN also significantly upregulated the expression of both TNF-alpha receptor 1 and 2 in podocytes. Our in vitro finding suggests podocytes may play a contributory role in the development of interstitial damage in IgAN by amplifying the activation of tubular epithelial cells with enhanced TNF-alpha synthesis after inflammatory changes of HMC.

  9. Activated AMPK inhibits PPAR-{alpha} and PPAR-{gamma} transcriptional activity in hepatoma cells. (United States)

    Sozio, Margaret S; Lu, Changyue; Zeng, Yan; Liangpunsakul, Suthat; Crabb, David W


    AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-α (PPAR-α) are critical regulators of short-term and long-term fatty acid oxidation, respectively. We examined whether the activities of these molecules were coordinately regulated. H4IIEC3 cells were transfected with PPAR-α and PPAR-γ expression plasmids and a peroxisome-proliferator-response element (PPRE) luciferase reporter plasmid. The cells were treated with PPAR agonists (WY-14,643 and rosiglitazone), AMPK activators 5-aminoimidazole-4-carboxamide riboside (AICAR) and metformin, and the AMPK inhibitor compound C. Both AICAR and metformin decreased basal and WY-14,643-stimulated PPAR-α activity; compound C increased agonist-stimulated reporter activity and partially reversed the effect of the AMPK activators. Similar effects on PPAR-γ were seen, with both AICAR and metformin inhibiting PPRE reporter activity. Compound C increased basal PPAR-γ activity and rosiglitazone-stimulated activity. In contrast, retinoic acid receptor-α (RAR-α), another nuclear receptor that dimerizes with retinoid X receptor (RXR), was largely unaffected by the AMPK activators. Compound C modestly increased AM580 (an RAR agonist)-stimulated activity. The AMPK activators did not affect PPAR-α binding to DNA, and there was no consistent correlation between effects of the AMPK activators and inhibitor on PPAR and the nuclear localization of AMPK-α subunits. Expression of either a constitutively active or dominant negative AMPK-α inhibited basal and WY-14,643-stimulated PPAR-α activity and basal and rosiglitazone-stimulated PPAR-γ activity. We concluded that the AMPK activators AICAR and metformin inhibited transcriptional activities of PPAR-α and PPAR-γ, whereas inhibition of AMPK with compound C activated both PPARs. The effects of AMPK do not appear to be mediated through effects on RXR or on PPAR/RXR binding to DNA. These effects are independent of kinase activity and instead appear to

  10. Maltose effects on barley malt diastatic power enzyme activity and thermostability at high isothermal mashing temperature: II. Alpha-amylase (United States)

    Maltose, the primary product of starch degradation during mashing, has the potential as a compatible solute to affect the activity of and increase the thermostability of barley malt alpha-amylase activity at high temperatures used in mashing and temperatures above those normally used in mashing. To ...

  11. Peroxisome proliferator-activated receptor alpha induction of uncoupling protein 2 protects against acetaminophen-induced liver toxicity. (United States)

    Patterson, Andrew D; Shah, Yatrik M; Matsubara, Tsutomu; Krausz, Kristopher W; Gonzalez, Frank J


    Acetaminophen (APAP) overdose causes acute liver failure in humans and rodents due in part to the destruction of mitochondria as a result of increased oxidative stress followed by hepatocellular necrosis. Activation of the peroxisome proliferator-activated receptor alpha (PPARα), a member of the nuclear receptor superfamily that controls the expression of genes encoding peroxisomal and mitochondrial fatty acid β-oxidation enzymes, with the experimental ligand Wy-14,643 or the clinically used fibrate drug fenofibrate, fully protects mice from APAP-induced hepatotoxicity. PPARα-humanized mice were also protected, whereas Ppara-null mice were not, thus indicating that the protection extends to human PPARα and is PPARα-dependent. This protection is due in part to induction of the PPARα target gene encoding mitochondrial uncoupling protein 2 (UCP2). Forced overexpression of UCP2 protected wildtype mice against APAP-induced hepatotoxicity in the absence of PPARα activation. Ucp2-null mice, however, were sensitive to APAP-induced hepatotoxicity despite activation of PPARα with Wy-14,643. Protection against hepatotoxicity by UCP2-induction through activation of PPARα is associated with decreased APAP-induced c-jun and c-fos expression, decreased phosphorylation of JNK and c-jun, lower mitochondrial H(2)O(2) levels, increased mitochondrial glutathione in liver, and decreased levels of circulating fatty acyl-carnitines. These studies indicate that the PPARα target gene UCP2 protects against elevated reactive oxygen species generated during drug-induced hepatotoxicity and suggest that induction of UCP2 may also be a general mechanism for protection of mitochondria during fatty acid β-oxidation.

  12. Terpenoids with alpha-glucosidase inhibitory activity from the submerged culture of Inonotus obliquus. (United States)

    Ying, You-Min; Zhang, Lin-Yan; Zhang, Xia; Bai, Hai-Bo; Liang, Dong-E; Ma, Lie-Feng; Shan, Wei-Guang; Zhan, Zha-Jun


    Lanostane-type triterpenoids, inotolactones A and B, a drimane-type sesquiterpenoid, inotolactone C, and five known terpenoids 6β-hydroxy-trans-dihydroconfertifolin, inotodiol, 3β,22-dihydroxyanosta-7,9(11),24-triene, 3β-hydroxycinnamolide, and 17-hydroxy-ent-atisan-19-oic acid, were isolated from the submerged culture of chaga mushroom, Inonotus obliquus. Their structures were characterized by spectroscopic methods, including MS and NMR (1D and 2D) spectroscopic techniques. Inotolactones A and B, examples of lanostane-type triterpenoids bearing α,β-dimethyl, α,β-unsaturated δ-lactone side chains, exhibited more potent alpha-glucosidase inhibitory activities than the positive control acarbose. This finding might be related to the anti-hyperglycemic properties of the fungus and to its popular role as a diabetes treatment. In addition, a drimane-type sesquiterpenoid and an atisane-type diterpenoid were isolated from I. obliquus. PMID:25446238

  13. Alpha capture reaction cross section measurements on Sb isotopes by activation method (United States)

    Korkulu, Z.; Özkan, N.; Kiss, G. G.; Szücs, T.; Fülöp, Zs; Güray, R. T.; Gyürky, Gy; Halász, Z.; Somorjai, E.; Török, Zs; Yalçin, C.


    Alpha induced reactions on natural and enriched antimony targets were investigated via the activation technique in the energy range from 9.74 MeV to 15.48 MeV, close to the upper end of the Gamow window at a temperature of 3 GK relevant to the γ-process. The experiments were carried out at the Institute for Nuclear Research, the Hungarian Academy of Sciences (MTA Atomki). 121Sb(α,γ)125I, 121Sb(α,n)124I and 123Sb(α,n)126I reactions were measured using a HPGe detector. In this work, the 121Sb(α,n)124 cross section results and the comparison with the theoretical predictions (obtained with standard settings of the statistical model codes NON-SMOKER and TALYS) were presented.

  14. Direct interaction of the kringle domain of urokinase-type plasminogen activator (uPA) and integrin alpha v beta 3 induces signal transduction and enhances plasminogen activation. (United States)

    Tarui, Takehiko; Akakura, Nobuaki; Majumdar, Mousumi; Andronicos, Nicholas; Takagi, Junichi; Mazar, Andrew P; Bdeir, Khalil; Kuo, Alice; Yarovoi, Serge V; Cines, Douglas B; Takada, Yoshikazu


    It has been questioned whether there are receptors for urokinase-type plasminogen activator (uPA) that facilitate plasminogen activation other than the high affinity uPA receptor (uPAR/CD87) since studies of uPAR knockout mice did not support a major role of uPAR in plasminogen activation. uPA also promotes cell adhesion, chemotaxis, and proliferation besides plasminogen activation. These uPA-induced signaling events are not mediated by uPAR, but mediated by unidentified, lower-affinity receptors for the uPA kringle. We found that uPA binds specifically to integrin alpha v beta 3 on CHO cells depleted of uPAR. The binding of uPA to alpha v beta 3 required the uPA kringle domain. The isolated uPA kringle domain binds specifically to purified, recombinant soluble, and cell surface alpha v beta 3, and other integrins (alpha 4 beta 1 and alpha 9 beta 1), and induced migration of CHO cells in an alpha v beta 3-dependent manner. The binding of the uPA kringle to alpha v beta 3 and uPA kringle-induced alpha v beta 3-dependent cell migration were blocked by homologous plasminogen kringles 1-3 or 1-4 (angiostatin), a known integrin antagonist. We studied whether the binding of uPA to integrin alpha v beta 3 through the kringle domain plays a role in plasminogen activation. On CHO cell depleted of uPAR, uPA enhanced plasminogen activation in a kringle and alpha v beta 3-dependent manner. Endothelial cells bound to and migrated on uPA and uPA kringle in an alpha v beta 3-dependent manner. These results suggest that uPA binding to integrins through the kringle domain plays an important role in both plasminogen activation and uPA-induced intracellular signaling. The uPA kringle-integrin interaction may represent a novel therapeutic target for cancer, inflammation, and vascular remodeling. PMID:16525582

  15. Acetylsalicylic acid regulates MMP-2 activity and inhibits colorectal invasion of murine B16F0 melanoma cells in C57BL/6J mice: effects of prostaglandin F(2)alpha. (United States)

    Tsai, Chin-Shaw Stella; Luo, Shue-Fen; Ning, Chung-Chu; Lin, Chien-Liang; Jiang, Ming-Chung; Liao, Ching-Fong


    Epidemiological studies indicate that acetylsalicylic acid may reduce the risk of mortality due to colon cancers. Metastasis is the major cause of cancer death. Matrix metalloproteinases (MMPs) play important roles in tumor invasion regulation, and prostaglandin F(2)alpha (PGF(2)alpha) is a key stimulator of MMP production. Thus, we investigated whether acetylsalicylic acid regulated MMP activity and the invasion of cancer cells and whether PGF(2)alpha attenuated acetylsalicylic acid-inhibited invasion of cancer cells. Gelatin-based zymography assays showed that acetylsalicylic acid inhibited the MMP-2 activity of B16F0 melanoma cells. Matrigel-based chemoinvasion assays showed that acetylsalicylic acid inhibited the invasion of B16F0 cells. Acetylsalicylic acid can inhibit PGF(2)alpha synthesis and PGF(2)alpha is a key stimulator of MMP-2 production. Our data showed that PGF(2)alpha treatment attenuated the acetylsalicylic acid-inhibited invasion of B16F0 cells. In animal experiments, acetylsalicylic acid reduced colorectal metastasis of B16F0 cells in C57BL/6J mice by 44%. Our results suggest that PGF(2)alpha is a therapeutic target for metastasis inhibition and acetylsalicylic acid may possess anti-metastasis ability.

  16. Evidence for unfolded protein response activation in monocytes from individuals with alpha-1 antitrypsin deficiency.

    LENUS (Irish Health Repository)

    Carroll, Tomás P


    The hereditary disorder alpha-1 antitrypsin (AAT) deficiency results from mutations in the SERPINA1 gene and presents with emphysema in young adults and liver disease in childhood. The most common form of AAT deficiency occurs because of the Z mutation, causing the protein to fold aberrantly and accumulate in the endoplasmic reticulum (ER). This leads to ER stress and contributes significantly to the liver disease associated with the condition. In addition to hepatocytes, AAT is also synthesized by monocytes, neutrophils, and epithelial cells. In this study we show for the first time that the unfolded protein response (UPR) is activated in quiescent monocytes from ZZ individuals. Activating transcription factor 4, X-box binding protein 1, and a subset of genes involved in the UPR are increased in monocytes from ZZ compared with MM individuals. This contributes to an inflammatory phenotype with ZZ monocytes exhibiting enhanced cytokine production and activation of the NF-kappaB pathway when compared with MM monocytes. In addition, we demonstrate intracellular accumulation of AAT within the ER of ZZ monocytes. These are the first data showing that Z AAT protein accumulation induces UPR activation in peripheral blood monocytes. These findings change the current paradigm regarding lung inflammation in AAT deficiency, which up until now was derived from the protease-anti-protease hypothesis, but which now must include the exaggerated inflammatory response generated by accumulated aberrantly folded AAT in circulating blood cells.

  17. Reward bias and lateralization in gambling behavior: behavioral activation system and alpha band analysis. (United States)

    Balconi, Michela; Finocchiaro, Roberta; Canavesio, Ylenia; Messina, Rossella


    The present research explored the main factors that can influence subjects' choices in the case of decisions. In order to elucidate the individual differences that influence the decisional processes, making their strategies more or less advantageous, we tested the effect of a reward sensitivity in the behavioral activation system (BAS-Reward) constructed on the ability to distinguish between high- and low-risk decisions. Secondly, the lateralization effect, related to increased activation of the left (BAS-related) hemisphere, was explored. Thirty-one subjects were tested using the Iowa Gambling Task, and the BAS-Reward measure was applied to distinguish between high-BAS and low-BAS groups. Behavioral responses (gain/loss options) and alpha-band modulation were considered. It was found that high-BAS group increased their tendency to opt in favor of the immediate reward (loss strategy) rather than the long-term option (win strategy). Secondly, high-BAS subjects showed an increased left-hemisphere activation in response to losing (with immediate reward) choices in comparison with low-BAS subjects. A "reward bias" effect was supposed to explain both the bad strategy and the unbalanced hemispheric activation for high-BAS and more risk-taking subjects.

  18. 20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes.

    Directory of Open Access Journals (Sweden)

    Zorica Janjetovic

    Full Text Available The side chain of vitamin D3 is hydroxylated in a sequential manner by cytochrome P450scc (CYP11A1 to form 20-hydroxycholecalciferol, which can induce growth arrest and differentiation of both primary and immortalized epidermal keratinocytes. Since nuclear factor-kappaB (NF-kappaB plays a pivotal role in the regulation of cell proliferation, differentiation and apoptosis, we examined the capability of 20-hydroxycholecalciferol to modulate the activity of NF-kappaB, using 1,25-dihydroxycholecalciferol (calcitriol as a positive control. 20-hydroxycholecalciferol inhibits the activation of NFkappaB DNA binding activity as well as NF-kappaB-driven reporter gene activity in keratinocytes. Also, 20-hydroxycholecalciferol induced significant increases in the mRNA and protein levels of the NF-kappaB inhibitor protein, IkappaB alpha, in a time dependent manner, while no changes in total NF-kappaB-p65 mRNA or protein levels were observed. Another measure of NF-kappaB activity, p65 translocation from the cytoplasm into the nucleus was also inhibited in extracts of 20-hydroxycholecalciferol treated keratinocytes. Increased IkappaB alpha was concomitantly observed in cytosolic extracts of 20-hydroxycholecalciferol treated keratinocytes, as determined by immunoblotting and immunofluorescent staining. In keratinocytes lacking vitamin D receptor (VDR, 20-hydroxycholecalciferol did not affect IkappaB alpha mRNA levels, indicating that it requires VDR for its action on NF-kappaB activity. Comparison of the effects of calcitrol, hormonally active form of vitamin D3, with 20-hydrocholecalciferol show that both agents have a similar potency in inhibiting NF-kappaB. Since NF-kappaB is a major transcription factor for the induction of inflammatory mediators, our findings indicate that 20-hydroxycholecalciferol may be an effective therapeutic agent for inflammatory and hyperproliferative skin diseases.

  19. The properties of the single chicken MHC classical class II alpha chain ( B-LA) gene indicate an ancient origin for the DR/E-like isotype of class II molecules

    DEFF Research Database (Denmark)

    Salomonsen, Jan; Marston, Denise; Avila, David;


    significantly in the peptide-binding alpha(1) domain. The cDNA and genomic DNA sequences from chickens of diverse origins show few alleles, which differ in only four nucleotides and one amino acid. In contrast, significant restriction fragment length polymorphism is detected by Southern blot analysis of genomic...... DNA, suggesting considerable diversity around the gene. Analysis of a large back-cross family indicates that the class II alpha chain locus ( B-LA) is located roughly 5.6 cM from the MHC locus, which encodes the classical class II beta chains. Thus the chicken class II alpha chain gene is like the...

  20. Two farnesoid X receptor alpha isoforms in Japanese medaka (Oryzias latipes) are differentially activated in vitro

    International Nuclear Information System (INIS)

    The nuclear receptor farnesoid X receptor alpha (FXRα, NR1H4) is activated by bile acids in multiple species including mouse, rat, and human and in this study we have identified two isoforms of Fxrα in Japanese medaka (Oryzias latipes), a small freshwater teleost. Both isoforms share a high amino acid sequence identity to mammalian FXRα (∼70% in the ligand-binding domain). Fxrα1 and Fxrα2 differ within the AF1 domain due to alternative splicing at the fourth intron-exon boundary. This process results in Fxrα1 having an extended N-terminus compared to Fxrα2. A Gal4DBD-FxrαLBD fusion construct was activated by chenodeoxycholic, cholic, deoxycholic and lithocholic acids, and the synthetic agonist GW4064 in transient transactivation assays. Activation of the Gal4DBD-FxrαLBD fusion construct was enhanced by addition of PGC-1α, as demonstrated through titration assays. Surprisingly, when the full-length versions of the two Fxrα isoforms were compared in transient transfection assays, Fxrα2 was activated by C24 bile acids and GW4064, while Fxrα1 was not significantly activated by any of the compounds tested. Since the only significant difference between the full-length constructs was sequence in the AF1 domain, these experiments highlight a key functional region in the Fxrα AF1 domain. Furthermore, mammalian two-hybrid studies demonstrated the ability of Fxrα2, but not Fxrα1, to interact with PGC-1α and SRC-1, and supported our results from the transient transfection reporter gene activation assays. These data demonstrate that both mammalian and teleost FXR (Fxrα2 isoform) are activated by primary and secondary bile acids.

  1. Impairment of natural killer cell activity in Indian kala-azar: restoration of activity by interleukin 2 but not by alpha or gamma interferon.


    Manna, P P; Bharadwaj, D.; Bhattacharya, S.; Chakrabarti, G; Basu, D; Mallik, K K; Bandyopadhyay, S.


    Indian kala-azar patients have normal numbers of peripheral blood NK cells but impaired functional activity due to decreased binding and lysis of target cells. This impairment of NK activity could not be corrected by exogenous recombinant human alpha or gamma interferon. However, recombinant human interleukin 2 was able to restore this activity by augmenting conjugate formation and lysis of target cells.

  2. Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Timmerman, Daniel B;


    AChR agonists improves learning, memory, and attentional function in variety of animal models, and pro-cognitive effects of alpha(7) nAChR agonists have recently been demonstrated in patients with schizophrenia or Alzheimer's disease. The alpha(7) nAChR desensitizes rapidly in vitro, and this has been a major......Agonists and positive allosteric modulators of the alpha(7) nicotinic acetylcholine receptor (nAChR) are currently being developed for the treatment of cognitive disturbances in patients with schizophrenia or Alzheimer's disease. This review describes the neurobiological properties of the alpha n...... concern in the development of alpha(7) nAChR agonists as putative drugs. Our review of the existing literature shows that development of tolerance to the behavioral effects of alpha(7) nAChR agonists does not occur in animal models or humans. However, the long-term memory-enhancing effects seen in animal...

  3. Exogenous Alpha-Synuclein Alters Pre- and Post-Synaptic Activity by Fragmenting Lipid Rafts. (United States)

    Emanuele, Marco; Esposito, Alessandro; Camerini, Serena; Antonucci, Flavia; Ferrara, Silvia; Seghezza, Silvia; Catelani, Tiziano; Crescenzi, Marco; Marotta, Roberto; Canale, Claudio; Matteoli, Michela; Menna, Elisabetta; Chieregatti, Evelina


    Alpha-synuclein (αSyn) interferes with multiple steps of synaptic activity at pre-and post-synaptic terminals, however the mechanism/s by which αSyn alters neurotransmitter release and synaptic potentiation is unclear. By atomic force microscopy we show that human αSyn, when incubated with reconstituted membrane bilayer, induces lipid rafts' fragmentation. As a consequence, ion channels and receptors are displaced from lipid rafts with consequent changes in their activity. The enhanced calcium entry leads to acute mobilization of synaptic vesicles, and exhaustion of neurotransmission at later stages. At the post-synaptic terminal, an acute increase in glutamatergic transmission, with increased density of PSD-95 puncta, is followed by disruption of the interaction between N-methyl-d-aspartate receptor (NMDAR) and PSD-95 with ensuing decrease of long term potentiation. While cholesterol loading prevents the acute effect of αSyn at the presynapse; inhibition of casein kinase 2, which appears activated by reduction of cholesterol, restores the correct localization and clustering of NMDARs.

  4. Exogenous Alpha-Synuclein Alters Pre- and Post-Synaptic Activity by Fragmenting Lipid Rafts

    Directory of Open Access Journals (Sweden)

    Marco Emanuele


    Full Text Available Alpha-synuclein (αSyn interferes with multiple steps of synaptic activity at pre-and post-synaptic terminals, however the mechanism/s by which αSyn alters neurotransmitter release and synaptic potentiation is unclear. By atomic force microscopy we show that human αSyn, when incubated with reconstituted membrane bilayer, induces lipid rafts' fragmentation. As a consequence, ion channels and receptors are displaced from lipid rafts with consequent changes in their activity. The enhanced calcium entry leads to acute mobilization of synaptic vesicles, and exhaustion of neurotransmission at later stages. At the post-synaptic terminal, an acute increase in glutamatergic transmission, with increased density of PSD-95 puncta, is followed by disruption of the interaction between N-methyl-d-aspartate receptor (NMDAR and PSD-95 with ensuing decrease of long term potentiation. While cholesterol loading prevents the acute effect of αSyn at the presynapse; inhibition of casein kinase 2, which appears activated by reduction of cholesterol, restores the correct localization and clustering of NMDARs.

  5. Rectal administration of d-alpha tocopherol for active ulcerative colitis: A preliminary report

    Institute of Scientific and Technical Information of China (English)

    Seyed Amir Mirbagheri; Behtash Ghazi Nezami; Solmaz Assa; Mannan Hajimahmoodi


    AIM: To investigate the anti-oxidant and anti-neutrophil recruitment effects of rectal d-alpha (d-α) tocopherol administration on mild and moderately active ulcerative colitis (UC).METHODS: Fifteen patients with mild and moderately active ulcerative colitis were enrolled in an open-label study of d-α tocopherol enema (8000 U/d) for 12 wk. All patients were receiving concomitant therapy with 5-aminosalicylic acid derivatives (5-ASA) and/or immunomodulator medications. Endoscopic evaluation was performed at baseline and after 4th and 12th weeks. Disease activity was measured with the Mayo disease activity index (DAI) and remission was defined as DAI of≤2 with no blood in stool. Clinical response was defined as a DAI reduction of≥2.RESULTS: At the end of 12th week, the average DAI score significantly decreased compared to the beginning of the study (2.3±0.37 vs 8±0.48, P < 0.0001). One patient was withdrawn after 3 wk for being unavailable to follow-up. On the 4th week of therapy, 12 patients showed clinical response, 3 of whom (21.4%) achieving remission. After 12 wk, all 14 patients responded clinically to the therapy and remission was induced in 9 of them (64%). No patient reported adverse events or was hospitalized due to worsened disease activity.CONCLUSION: This preliminary report suggests that rectal d-α tocopherol may represent a novel therapy for mild and moderately active UC. The observed results might be due to the anti-inflammatory and anti-oxidative properties of vitamin E.

  6. DL-alpha-difluoromethyl[3,4-3H]arginine metabolism in tobacco and mammalian cells. Inhibition of ornithine decarboxylase activity after arginase-mediated hydrolysis of DL-alpha-difluoromethylarginine to DL-alpha-difluoromethylornithine. (United States)

    Slocum, R D; Bitonti, A J; McCann, P P; Feirer, R P


    DL-alpha-Difluoromethylarginine (DFMA) is an enzyme-activated irreversible inhibitor of arginine decarboxylase (ADC) in vitro. DFMA has also been shown to inhibit ADC activities in a variety of plants and bacteria in vivo. However, we questioned the specificity of this inhibitor for ADC in tobacco ovary tissues, since ornithine decarboxylase (ODC) activity was strongly inhibited as well. We now show that [3,4-3H]DFMA is metabolized to DL-alpha-difluoromethyl[3,4-3H]ornithine [( 3,4-3H]DFMO), the analogous mechanism-based inhibitor of ODC, by tobacco tissues in vivo. Both tobacco and mammalian (mouse, bovine) arginases (EC hydrolyse DFMA to DFMO in vitro, suggesting a role for this enzyme in mediating the indirect inhibition of ODC by DFMA in tobacco. These results suggest that DFMA may have other effects, in addition to the inhibition of ADC, in tissues containing high arginase activities. The recent development of potent agmatine-based ADC inhibitors should permit selective inhibition of ADC, rather than ODC, in such tissues, since agmatine is not a substrate for arginase.

  7. Cytochrome P450c17 (steroid 17. cap alpha. -hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues

    Energy Technology Data Exchange (ETDEWEB)

    Chung, B.; Picado-Leonard, J.; Haniu, M.; Bienkowski, M.; Hall, P.F.; Shively, J.E.; Miller, W.L.


    P450c17 is the single enzyme mediating both 17..cap alpha..-hydroxylase (steroid 17..cap alpha..-monooxygenase, EC and 17,20 lyase activities in the synthesis of steroid hormones. It has been suggested that different P450c17 isozymes mediate these activities in the adrenal gland and testis. The authors sequenced 423 of the 509 amino acids (83%) of the porcine adrenal enzyme; based on this partial sequence, a 128-fold degenerate 17-mer was synthesized and used to screen a porcine adrenal cDNA library. This yielded a 380-base cloned cDNA, which in turn was used to isolate several human adrenal cDNAs. The longest of these, lambda hac 17-2, is 1754 base pairs long and includes the full-length coding region, the complete 3'-untranslated region, and 41 bases of the 5'-untranslated region. This cDNA encodes a protein of 508 amino acids having a predicted molecular weight of 57,379.82. High-stringency screening of a human testicular cDNA library yielded a partial clone containing 1303 identical bases. RNA gel blots and nuclease S1-protection experiments confirm that the adrenal and testicular P450c17 mRNAs are indistinguishable. These data indicate that the testis possesses a P450c17 identical to that in the adrenal. The human amino acid sequence is 66.7% homologous to the corresponding regions of the porcine sequence, and the human cDNA and amino acid sequences are 80.1 and 70.3% homologous, respectively, to bovine adrenal P450c17 cDNA. Both comparisons indicate that a central region comprising amino acid residues 160-268 is hypervariable among these species of P450c17.

  8. Comparative analysis of electroencephalographic tests of alpha activity attenuation in evaluation of involuntary falling asleep in healthy adults

    Directory of Open Access Journals (Sweden)

    Šundrić Zvonko


    Full Text Available Introduction. Decrease of daily alertness is a common cause of accidents in the work place, especially traffic accidents. Therefore, an increasing interest exists to determine reliable indicators of a tendency to fall asleep involuntarily. Objective. To determine an optimal electroencephalographic (EEG indicator of an involuntary tendency to fall asleep, we performed a study on neurologically healthy subjects, after one night of sleep deprivation. Total sleep deprivation was aimed at increasing daily sleepiness in healthy subjects, providing us with an opportunity to test different methods of evaluation. Methods. We applied a visual analogue scale for sleepiness (VASS, EEG registration with the specific test of alpha activity attenuation (TAA in 87 healthy subjects. The test was performed in a standard way (sTAA as well as in accordance with new modifications related to changes of EEG filter width in the range from 5 to 32 Hz (mTAA. Results. After sleep deprivation, we observed involuntary falling asleep in 54 subjects. The comparison of VASS results showed no differences, contrary to a more objective TAA. Between two variants of TAA, the modified test provided us with a better prediction for subjects who would fall asleep involuntarily. Conclusion. The application of a more objective EEG test in evaluation of daily alertness represents the optimal method of testing. Modified TAA attracts special attention, offering a simple solution for reliable testing of decreased daily alertness in medical services related to professional aircraft personnel.

  9. The combination of IL-21 and IFN-alpha boosts STAT3 activation, cytotoxicity and experimental tumor therapy

    DEFF Research Database (Denmark)

    Eriksen, Karsten W; Søndergaard, Henrik; Woetmann, Anders;


    such as IFN-alpha and IL-2 have multiple and severe side effects. Accordingly, they are generally used at sub-optimal doses, which limit their clinical efficacy. Here we hypothesized that a combination of IFN-alpha and IL-21, a novel cytokine of the IL-2 family with anti-cancer effects, will increase the anti......-cancer efficacy at sub-optimal cytokine doses. We show that the combined stimulation of target-cells with IFN-alpha and IL-21 triggers an increased STAT3 activation whereas the activation of other STATs including STAT1/2 is unaffected. In parallel, the combined stimulation with IFN-alpha and IL-21 triggers...... a selective increase in MHC class I expression and NK- and CD8(+) T-cell-mediated cytotoxicity. In an experimental in vivo model of renal carcinoma, the combined treatment of IFN-alpha and IL-21 also produces a significant anti-cancer effect as judged by an inhibition of tumor growth and an increased survival...

  10. alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes. (United States)

    Abdel-Malek, Zalfa A; Ruwe, Andrew; Kavanagh-Starner, Renny; Kadekaro, Ana Luisa; Swope, Viki; Haskell-Luevano, Carrie; Koikov, Leonid; Knittel, James J


    One skin cancer prevention strategy that we are developing is based on synthesizing and testing melanocortin analogs that reduce and repair DNA damage resulting from exposure to solar ultraviolet (UV) radiation, in addition to stimulating pigmentation. Previously, we reported the effects of tetrapeptide analogs of alpha-melanocortin (alpha-MSH) that were more potent and stable than the physiological alpha-MSH, and mimicked its photoprotective effects against UV-induced DNA damage in human melanocytes. Here, we report on a panel of tripeptide analogs consisting of a modified alpha-MSH core His(6)-d-Phe(7)-Arg(8), which contained different N-capping groups, C-terminal modifications, or arginine mimics. The most potent tripeptides in activating cAMP formation and tyrosinase of human melanocytes were three analogs with C-terminal modifications. The most effective C-terminal tripeptide mimicked alpha-MSH in reducing hydrogen peroxide generation and enhancing nucleotide excision repair following UV irradiation. The effects of these three analogs required functional MC1R, as they were absent in human melanocytes that expressed non-functional receptor. These results demonstrate activation of the MC1R by tripeptide melanocortin analogs. Designing small analogs for topical delivery should prove practical and efficacious for skin cancer prevention.

  11. A polymorphic autoregulatory hormone response element in the human estrogen-related receptor alpha (ERRalpha) promoter dictates peroxisome proliferator-activated receptor gamma coactivator-1alpha control of ERRalpha expression. (United States)

    Laganière, Josée; Tremblay, Gilles B; Dufour, Catherine R; Giroux, Sylvie; Rousseau, François; Giguère, Vincent


    The orphan nuclear estrogen-related receptor alpha (ERRalpha) and transcriptional cofactor peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) are involved in the regulation of energy metabolism. Recently, extensive cross-talk between PGC-1alpha and ERRalpha has been demonstrated. The presence of PGC-1alpha is associated with an elevated expression of ERRalpha, and the two proteins can influence the transcriptional activities of one another. Using a candidate gene approach to detect regulatory variants within genes encoding nuclear receptors, we have identified a 23-bp sequence (ESRRA23) containing two nuclear receptor recognition half-site motifs that is present in 1-4 copies within the promoter of the human ESRRA gene encoding ERRalpha. The ESRRA23 sequence contains a functional ERR response element that is specifically bound by ERRalpha, and chromatin immunoprecipitation shows that endogenous ERRalpha occupies its own promoter in vivo. Strikingly, introduction of PGC-1alpha in HeLa cells by transient transfection induces the activity of the ESRRA promoter in a manner that is dependent on the presence of the ESRRA23 element and on its dosage. Coexpression of ERRalpha and PGC-1alpha results in a synergistic activation of the ESRRA promoter. In experiments using ERRalpha null fibroblasts, the ability of PGC-1alpha to stimulate the ESRRA promoter is considerably reduced but can be restored by addition of ERRalpha. Taken together, these results demonstrate that an interdependent ERRalpha/PGC-1alpha-based transcriptional pathway targets the ESRRA23 element to dictate the level of ERRalpha expression. This study further suggests that this regulatory polymorphism may provide differential responses to ERRalpha/PGC-1alpha-mediated metabolic cues in the human population.

  12. Regulation of skeletal muscle cell plasticity by the peroxisome proliferator-activated receptor gamma coactivator 1alpha


    Handschin, C.


    Exercise triggers a pleiotropic response in skeletal muscle, which results in a profound remodeling of this tissue. Physical activity-dependent muscle fiber plasticity is regulated by a number of distinct signaling pathways. Even though most of these pathways are activated by different stimuli and in a temporally and spatially separated manner during exercise, many of the major signal transduction events converge on the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-...

  13. In vitro alpha glucosidase inhibition and free-radical scavenging activity of propolis from Thai stingless bees in mangosteen orchard

    Directory of Open Access Journals (Sweden)

    Boonyadist Vongsak


    Full Text Available ABSTRACTThe chemical component and biological activity of propolis depend on flora area of bee collection and bee species. In the study, the propolis from three stingless bee species, Lepidotrigona ventralis Smith, Lepidotrigona terminata Smith, and Tetragonula pagdeni Schwarz, was collected in the same region of mangosteen garden from Thailand. Total phenolic content, alpha glucosidase inhibitory effect, and free-radical scavenging activity using FRAP, ABTS, DPPH assays were determined. The most potent activity of propolis extract was investigated for bioactive compounds and their quantity. The ethanol extract of T. pagdeni propolis had the highest total phenolic content 12.83 ± 0.72 g of gallic acid equivalents in 100 g of the extract, and the strongest alpha glucosidase inhibitory effect with the IC50 of 70.79 ± 6.44 µg/ml. The free-radical scavenging activity evaluated by FRAP, ABTS, DPPH assays showed the FRAP value of 279.70 ± 20.55 µmol FeSO4 equivalent/g extract and the IC50 of 59.52 ± 10.76 and 122.71 ± 11.76 µg/ml, respectively. Gamma- and alpha-mangostin from T. pagdeni propolis extract were isolated and determined for the biological activity. Gamma-mangostin exhibited the strongest activity for both alpha glucosidase inhibitory effect and free-radical scavenging activity. Using HPLC quantitative analysis method, the content of gamma- and alpha-mangostin in the extract was found to be 0.94 ± 0.01 and 2.77 ± 0.08% (w/w, respectively. These findings suggested that T. pagdeni propolis may be used as a more suitable raw material for nutraceutical and pharmaceutical products and these mangostin derivatives as markers.

  14. Modulation of the transient receptor potential vanilloid channel TRPV4 by 4alpha-phorbol esters: a structure-activity study

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjaer; Pagani, Alberto; Minassi, Alberto;


    The mechanism of activation of the transient receptor potential vanilloid 4 (TRPV4) channel by 4alpha-phorbol esters was investigated by combining information from chemical modification of 4alpha-phorbol-didecanoate (4alpha-PDD, 2a), site-directed mutagenesis, Ca(2+) imaging, and electrophysiolog...... of TRPV4 activation by small molecules and obtain information for the rational design of structurally simpler ligands for this ion channel....

  15. Modulation of Posterior Alpha Activity by Spatial Attention Allows for Controlling A Continuous Brain-Computer Interface

    NARCIS (Netherlands)

    Horschig, J.M.; Oosterheert, W.; Oostenveld, R.; Jensen, O.


    Here we report that the modulation of alpha activity by covert attention can be used as a control signal in an online brain-computer interface, that it is reliable, and that it is robust. Subjects were instructed to orient covert visual attention to the left or right hemifield. We decoded the direct

  16. A novel in vivo model to study endochondral bone formation; HIF-1 alpha activation and BMP expression

    NARCIS (Netherlands)

    Emans, Pieter J.; Spaapen, Frank; Surtel, Don A. M.; Reilly, Keryn M.; Cremers, Andy; van Rhijn, Lodewijk W.; Bulstra, Sjoerd K.; Voncken, Jan Willem; Kuijer, Roel


    Numerous growth and transcription factors have been implicated in endochondral bone fort-nation of the growth plate. Many of these factors are up-regulated during hypoxia and downstream of Hypoxia-Inducible Factor (HIF)-1 alpha activation. However, the specific function of these factors, in the cont

  17. Chemokine stromal cell-derived factor 1alpha activates basophils by means of CXCR4

    DEFF Research Database (Denmark)

    Jinquan, T; Jacobi, H H; Jing, C;


    The CXC chemokine receptor 4 (CXCR4) is predominantly expressed on inactivated naive T lymphocytes, B lymphocytes, dendritic cells, and endothelial cells. CXC chemokine stromal cell-derived factor 1alpha (SDF-1alpha) is the only known ligand for CXCR4. To date, the CXCR4 expression and function o...

  18. alpha(7) Nicotinic acetylcholine receptor activation prevents behavioral and molecular changes induced by repeated phencyclidine treatment

    DEFF Research Database (Denmark)

    Thomsen, Morten Skøtt; Christensen, Ditte Z; Hansen, Henrik H;


    in a modified Y-maze test. Polymorphisms in the alpha(7) nicotinic acetylcholine receptor (nAChR) gene have been linked to schizophrenia. Here we demonstrate that acute administration of the selective alpha(7) nAChR partial agonist SSR180711 dose-dependently reversed the behavioral impairment induced by PCP...

  19. Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Timmerman, Daniel B;


    Agonists and positive allosteric modulators of the alpha(7) nicotinic acetylcholine receptor (nAChR) are currently being developed for the treatment of cognitive disturbances in patients with schizophrenia or Alzheimer's disease. This review describes the neurobiological properties of the alpha n...

  20. Alpha 1 Antitrypsin Inhibits Dendritic Cell Activation and Attenuates Nephritis in a Mouse Model of Lupus. (United States)

    Elshikha, Ahmed S; Lu, Yuanqing; Chen, Mong-Jen; Akbar, Mohammad; Zeumer, Leilani; Ritter, Andrea; Elghamry, Hanaa; Mahdi, Mahmoud A; Morel, Laurence; Song, Sihong


    Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution and considerable mortality and morbidity. Although the pathogenesis of this disease remains elusive, over-reactive dendritic cells (DCs) play a critical role in the disease development. It has been shown that human alpha-1 antitrypsin (hAAT) has protective effects in type 1 diabetes and rheumatoid arthritis mouse models. In the present study, we tested the effect of AAT on DC differentiation and functions, as well as its protective effect in a lupus-prone mouse model. We showed that hAAT treatment significantly inhibited LPS (TLR4 agonist) and CpG (TLR9 agonist) -induced bone-marrow (BM)-derived conventional and plasmacytoid DC (cDC and pDC) activation and reduced the production of inflammatory cytokines including IFN-I, TNF-α and IL-1β. In MRL/lpr mice, hAAT treatment significantly reduced BM-derived DC differentiation, serum autoantibody levels, and importantly attenuated renal pathology. Our results for the first time demonstrate that hAAT inhibits DC activation and function, and it also attenuates autoimmunity and renal damage in the MRL/lpr lupus model. These results imply that hAAT has a therapeutic potential for the treatment of SLE in humans. PMID:27232337

  1. Berberine is a potent agonist of peroxisome proliferator activated receptor alpha. (United States)

    Yu, Huarong; Li, Changqing; Yang, Junqing; Zhang, Tao; Zhou, Qixin


    Although berberine has hypolipidemic effects with a high affinity to nuclear proteins, the underlying molecular mechanism for this effect remains unclear. Here, we determine whether berberine is an agonist of peroxisome proliferator-activated receptor alpha (PPARalpha), with a lipid-lowering effect. The cell-based reporter gene analysis showed that berberine selectively activates PPARalpha (EC50 =0.58 mM, Emax =102.4). The radioligand binding assay shows that berberine binds directly to the ligand-binding domain of PPARalpha (Ki=0.73 mM) with similar affinity to fenofibrate. The mRNA and protein levels of CPT-Ialpha gene from HepG2 cells and hyperlipidemic rat liver are remarkably up-regulated by berberine, and this effect can be blocked by MK886, a non-competitive antagonist of PPARalpha. A comparison assay in which berberine and fenofibrate were used to treat hyperlipidaemic rats for three months shows that these drugs produce similar lipid-lowering effects, except that berberine increases high-density lipoprotein cholesterol more effectively than fenofibrate. These findings provide the first evidence that berberine is a potent agonist of PPARalpha and seems to be superior to fenofibrate for treating hyperlipidemia. PMID:27100490

  2. Design of a Quality Control Program for the Measurement of Gross Alpha and Gross Beta Activities (LMPR-CIEMAT); Diseno del Control de Calidad de las Medidas de Actividad Alfa-Beta Total (LMPR-CIEMAT)

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, A.; Yague, L.; Gasco, C.; Navarro, N.; Higueras, E.; Noguerales, C.


    In accordance with international standards, general requirements for testing laboratories have to include a quality system for planning, implementing, and assessing the work performed by the organization and for carrying out required quality assurance and quality control. The purpose of internal laboratory quality control is to monitor performance, identify problems, and initiate corrective actions. This report describes the internal quality control to monitor the gross alpha and beta activities determination. Identification of specific performance indicators, the principles that govern their use and statistical means of evaluation are explained. Finally, calculation of alpha and beta specific activities, uncertainties and detection limits are performed. (Author) 10 refs.

  3. Tumor necrosis factor-alpha induced expression of matrix metalloproteinase-9 through p21-activated Kinase-1

    Directory of Open Access Journals (Sweden)

    Garner Warren


    Full Text Available Abstract Background Expressed in embryonic development, matrix metalloprotein-9 (MMP-9 is absent in most of developed adult tissues, but recurs in inflammation during tissue injury, wound healing, tumor formation and metastasis. Expression of MMP-9 is tightly controlled by extracellular cues including pro-inflammatory cytokines and extracellular matrix (ECM. While the pathologic functions of MMP-9 are evident, the intracellular signaling pathways to control its expression are not fully understood. In this study we investigated mechanism of cytokine induced MMP-9 with particular emphasis on the role of p21-activated-kinase-1 (PAK1 and the down stream signaling. Results In response to TNF-alpha or IL-1alpha, PAK1 was promptly activated, as characterized by a sequential phosphorylation, initiated at threonine-212 followed by at threonine-423 in the activation loop of the kinase, in human skin keratinocytes, dermal fibroblasts, and rat hepatic stellate cells. Ectopic expression of PAK1 variants, but not p38 MAP kinase, impaired the TNF-alpha-induced MMP-9 expression, while other MMPs such as MMP-2, -3 and -14 were not affected. Activation of Jun N-terminal kinase (JNK and NF-kappaB has been demonstrated to be essential for MMP-9 expression. Expression of inactive PAK1 variants impaired JNK but not NF-kappaB activation, which consequently suppressed the 5'-promoter activities of the MMP-9 gene. After the cytokine-induced phosphorylation, both ectopically expressed and endogenous PAK1 proteins were promptly accumulated even in the condition of suppressing protein synthesis, suggesting the PAK1 protein is stabilized upon TNF-alpha stimulation. Stabilization of PAK1 protein by TNF-alpha treatment is independent of the kinase catalytic activity and p21 GTPase binding capacities. In contrast to epithelial cells, mesenchymal cells require 3-dimensional type-I collagen in response to TNF-alpha to massively express MMP-9. The collagen effect is mediated, in

  4. Plasminogen activator inhibitor type 1 interacts with alpha3 subunit of proteasome and modulates its activity. (United States)

    Boncela, Joanna; Przygodzka, Patrycja; Papiewska-Pajak, Izabela; Wyroba, Elzbieta; Osinska, Magdalena; Cierniewski, Czeslaw S


    Plasminogen activator inhibitor type-1 (PAI-1), a multifunctional protein, is an important physiological regulator of fibrinolysis, extracellular matrix homeostasis, and cell motility. Recent observations show that PAI-1 may also be implicated in maintaining integrity of cells, especially with respect to cellular proliferation or apoptosis. In the present study we provide evidence that PAI-1 interacts with proteasome and affects its activity. First, by using the yeast two-hybrid system, we found that the α3 subunit of proteasome directly interacts with PAI-1. Then, to ensure that the PAI-1-proteasome complex is formed in vivo, both proteins were coimmunoprecipitated from endothelial cells and identified with specific antibodies. The specificity of this interaction was evidenced after transfection of HeLa cells with pCMV-PAI-1 and coimmunoprecipitation of both proteins with anti-PAI-1 antibodies. Subsequently, cellular distribution of the PAI-1-proteasome complexes was established by immunogold staining and electron microscopy analyses. Both proteins appeared in a diffuse cytosolic pattern but also could be found in a dense perinuclear and nuclear location. Furthermore, PAI-1 induced formation of aggresomes freely located in endothelial cytoplasm. Increased PAI-1 expression abrogated degradation of degron analyzed after cotransfection of HeLa cells with pCMV-PAI-1 and pd2EGFP-N1 and prevented degradation of p53 as well as IκBα, as evidenced both by confocal microscopy and Western immunoblotting.

  5. The Cyclooctadepsipeptide Anthelmintic Emodepside Differentially Modulates Nematode, Insect and Human Calcium-Activated Potassium (SLO Channel Alpha Subunits.

    Directory of Open Access Journals (Sweden)

    Anna Crisford

    Full Text Available The anthelmintic emodepside paralyses adult filarial worms, via a mode of action distinct from previous anthelmintics and has recently garnered interest as a new treatment for onchocerciasis. Whole organism data suggest its anthelmintic action is underpinned by a selective activation of the nematode isoform of an evolutionary conserved Ca2+-activated K+ channel, SLO-1. To test this at the molecular level we compared the actions of emodepside at heterologously expressed SLO-1 alpha subunit orthologues from nematode (Caenorhabditis elegans, Drosophila melanogaster and human using whole cell voltage clamp. Intriguingly we found that emodepside modulated nematode (Ce slo-1, insect (Drosophila, Dm slo and human (hum kcnma1SLO channels but that there are discrete differences in the features of the modulation that are consistent with its anthelmintic efficacy. Nematode SLO-1 currents required 100 μM intracellular Ca2+ and were strongly facilitated by emodepside (100 nM; +73.0 ± 17.4%; n = 9; p < 0.001. Drosophila Slo currents on the other hand were activated by emodepside (10 μM in the presence of 52 nM Ca2+ but were inhibited in the presence of 290 nM Ca2+ and exhibited a characteristic loss of rectification. Human Slo required 300 nM Ca2+ and emodepside transiently facilitated currents (100 nM; +33.5 ± 9%; n = 8; p<0.05 followed by a sustained inhibition (-52.6 ± 9.8%; n = 8; p < 0.001. This first cross phyla comparison of the actions of emodepside at nematode, insect and human channels provides new mechanistic insight into the compound's complex modulation of SLO channels. Consistent with whole organism behavioural studies on C. elegans, it indicates its anthelmintic action derives from a strong activation of SLO current, not observed in the human channel. These data provide an important benchmark for the wider deployment of emodepside as an anthelmintic treatment.

  6. A P-loop Mutation in G[alpha] Subunits Prevents Transition to the Active State: Implications for G-protein Signaling in Fungal Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bosch, Dustin E.; Willard, Francis S.; Ramanujam, Ravikrishna; Kimple, Adam J.; Willard, Melinda D.; Naqvi, Naweed I.; Siderovski, David P. (UNC); (Singapore)


    Heterotrimeric G-proteins are molecular switches integral to a panoply of different physiological responses that many organisms make to environmental cues. The switch from inactive to active G{alpha}{beta}{gamma} heterotrimer relies on nucleotide cycling by the G{alpha} subunit: exchange of GTP for GDP activates G{alpha}, whereas its intrinsic enzymatic activity catalyzes GTP hydrolysis to GDP and inorganic phosphate, thereby reverting G{alpha} to its inactive state. In several genetic studies of filamentous fungi, such as the rice blast fungus Magnaporthe oryzae, a G42R mutation in the phosphate-binding loop of G{alpha} subunits is assumed to be GTPase-deficient and thus constitutively active. Here, we demonstrate that G{alpha}(G42R) mutants are not GTPase deficient, but rather incapable of achieving the activated conformation. Two crystal structure models suggest that Arg-42 prevents a typical switch region conformational change upon G{alpha}{sub i1}(G42R) binding to GDP {center_dot} AlF{sub 4}{sup -} or GTP, but rotameric flexibility at this locus allows for unperturbed GTP hydrolysis. G{alpha}(G42R) mutants do not engage the active state-selective peptide KB-1753 nor RGS domains with high affinity, but instead favor interaction with G{beta}{gamma} and GoLoco motifs in any nucleotide state. The corresponding G{alpha}{sub q}(G48R) mutant is not constitutively active in cells and responds poorly to aluminum tetrafluoride activation. Comparative analyses of M. oryzae strains harboring either G42R or GTPase-deficient Q/L mutations in the G{alpha} subunits MagA or MagB illustrate functional differences in environmental cue processing and intracellular signaling outcomes between these two G{alpha} mutants, thus demonstrating the in vivo functional divergence of G42R and activating G-protein mutants.

  7. Critical review for the determination of the minimum detectable activity (MDA) of alpha-emitter radionuclides in environmental samples

    International Nuclear Information System (INIS)

    Different criteria for the calculation of the Minimum Detectable Activity (MDA) of an alpha emitter in environmental levels are reviewed in this report. Practical examples of its application to previously analyzed samples are shown. The authors propose a criteria based on prior calculations that applies to the radiochemical activities performed in the laboratory. The calculation procedure has been discussed with scientist from other laboratories in order to establish a general criteria to calculate the MDA

  8. Separation and removal of alpha activity from glass-ware wash solutions containing surfactants in mild acidic medium

    International Nuclear Information System (INIS)

    One of the laboratory radioactive waste solutions, having Teepol, detergent powder and nitric acid, contained alpha activity in the range of 5000 to 22000 cpm/mL. A combination of two techniques i.e. first passing through an extraction chromatographic column containing a commercially available reagent, Cyanex-923 (trialkylphosphine oxide, TRPO) adsorbed on Chromosorb-102 or silica gel followed by passing the effluent through a macroporous cation exchanger, brought the activity level to near disposable to sink limits. (author)

  9. Alpha-amylase inhibitory activity and sterol composition of the marine algae, Sargassum glaucescens

    Directory of Open Access Journals (Sweden)

    Nasrin Payghami


    Full Text Available Background: Sargassum species (phaeophyceae are economically important brown algae in southern parts of Iran. Sargassum is mainly harvested as a row material in alginate production industries and is a source of plant foods or plant bio-stimulants even a component of animal foods. Objective: In this study, Sargassum glaucescens, collected from the seashore of Chabahar, was employed for phytochemical and biological evaluations. Materials and Methods: For that purpose, the dried algae was extracted by methanol and subjected to different chromatographic separation methods. Results: Six sterols, fucosterol (1, 24(S-hydroxy-24-vinylcholesterol (2, 24(R-hydroxy-24-vinylcholesterol (3, stigmasterol (4, β-sitosterol (5 and cholesterol (6 were identified by spectroscopic methods including 1 H-NMR, 13 C-NMR and mass spectroscopy. In vitro alpha-amylase inhibitory test was performed on the methanolic extract and the results revealed a potent inhibition (IC 50 = 8.9 ± 2.4 mg/mL of the enzyme compared to acarbose as a positive control. Conclusion: Various biological activities and distribution of sterols in Sargassum genus have been critically reviewed here. The results concluded that these algae are a good candidate for further anti-diabetic investigations in animals and human.

  10. beta-Naphthoflavone protects from peritonitis by reducing TNF-alpha-induced endothelial cell activation. (United States)

    Hsu, Sheng-Yao; Liou, Je-Wen; Cheng, Tsung-Lin; Peng, Shih-Yi; Lin, Chi-Chen; Chu, Yuan-Yuan; Luo, Wei-Cheng; Huang, Zheng-Kai; Jiang, Shinn-Jong


    β-Naphthoflavone (β-NF), a ligand of the aryl hydrocarbon receptor, has been shown to possess anti-oxidative properties. We investigated the anti-oxidative and anti-inflammatory potential of β-NF in human microvascular endothelial cells treated with tumor necrosis factor-alpha (TNF-α). Pretreatment with β-NF significantly inhibited TNF-α-induced intracellular reactive oxygen species, translocation of p67(phox), and TNF-α-induced monocyte binding and transmigration. In addition, β-NF significantly inhibited TNF-α-induced ICAM-1 and VCAM-1 expression. The mRNA expression levels of the inflammatory cytokines TNF-α and IL-6 were reduced by β-NF, as was the infiltration of white blood cells, in a peritonitis model. The inhibition of adhesion molecules was associated with suppressed nuclear translocation of NF-κB p65 and Akt, and suppressed phosphorylation of ERK1/2 and p38. The translocation of Egr-1, a downstream transcription factor involved in the MEK-ERK signaling pathway, was suppressed by β-NF treatment. Our findings show that β-NF inhibits TNF-α-induced NF-kB and ERK1/2 activation and ROS generation, thereby suppressing the expression of adhesion molecules. This results in reduced adhesion and transmigration of leukocytes in vitro and prevents the infiltration of leukocytes in a peritonitis model. Our findings also suggest that β-NF might prevent TNF-α-induced inflammation.

  11. Alpha-latrotoxin modulates the secretory machinery via receptor-mediated activation of protein kinase C. (United States)

    Liu, Jie; Wan, Qunfang; Lin, Xianguang; Zhu, Hongliang; Volynski, Kirill; Ushkaryov, Yuri; Xu, Tao


    The hypothesis whether alpha-latrotoxin (LTX) could directly regulate the secretory machinery was tested in pancreatic beta cells using combined techniques of membrane capacitance (Cm) measurement and Ca2+ uncaging. Employing ramp increase in [Ca2+]i to stimulate exocytosis, we found that LTX lowers the Ca2+ threshold required for exocytosis without affecting the size of the readily releasable pool (RRP). The burst component of exocytosis in response to step-like [Ca2+]i increase generated by flash photolysis of caged Ca2+ was also speeded up by LTX treatment. LTX increased the maximum rate of exocytosis compared with control responses with similar postflash [Ca2+]i and shifted the Ca2+ dependence of the exocytotic machinery toward lower Ca2+ concentrations. LTXN4C, a LTX mutant which cannot form membrane pores or penetrate through the plasma membrane but has similar affinity for the receptors as the wild-type LTX, mimicked the effect of LTX. Moreover, the effects of both LTX and LTXN4C) were independent of intracellular or extracellular Ca2+ but required extracellular Mg2+. Our data propose that LTX, by binding to the membrane receptors, sensitizes the fusion machinery to Ca2+ and, hence, may permit release at low [Ca2+]i level. This sensitization is mediated by activation of protein kinase C. PMID:16101679

  12. Synthesis of 16 alpha-/sub 3/H androgen and estrogen substrates for 16 alpha-hydroxylase

    Energy Technology Data Exchange (ETDEWEB)

    Cantineau, R.; Kremers, P.; De Graeve, J.; Cornelis, A.; Laszlo, P.; Gielen, J.E.; Lambotte, R.


    The synthesis of 16 alpha-/sup 3/H androgens and estrogens is described. 1-(/sup 3/H)-Acetic acid in the presence of zinc dust reacts with 16 alpha-bromo-17-ketosteroids to produce 16 alpha-/sup 3/H-17-ketosteroids. This chemical reaction was used to prepare 16 alpha-/sup 3/H-dehydroepiandrosterone (I) and 16 alpha-/sub 4/H-estrone acetate (XI) from 16 alpha-bromo-dehydroepiandrosterone (X) and from 16 alpha-bromo-estrone acetate (XII), respectively. Using appropriate microbiological techniques, it was possible to convert these radiolabelled substrates into 16 alpha-/sup 3/H-androstenedione (II) and 16 alpha-/sup 3/H-estradiol-17 beta (VII). 16 alpha-/sup 3/H-Estrone (VI) was obtained by the chemical hydrolysis of 16 alpha-/sup 3/H-estrone acetate. The label distribution as determined by microbiological 16 alpha-hydroxylations indicated a specific labelling of 77% for androgens and 65% for estrogens in the 16 alpha position. These substrates can be used for measuring the 16 alpha hydroxylase activity, an important step in the biosynthesis of estriol (VIII) and estetrol (IX).

  13. Activity of the Na,K-ATPase alpha4 isoform is important for membrane potential, intracellular Ca2+, and pH to maintain motility in rat spermatozoa. (United States)

    Jimenez, Tamara; Sánchez, Gladis; Wertheimer, Eva; Blanco, Gustavo


    While the function of the ubiquitous Na,K-ATPase alpha1 subunit has been well documented, the role of the sperm-specific alpha4 isoform of this ion transporter is less known. We have explored the importance of alpha4 in rat sperm physiology by taking advantage of the high sensitivity of this isoform for the inhibitor ouabain. Using concentrations that selectively block alpha4 activity, we found ouabain to reduce not only sperm total motility, but also multiple parameters of sperm movement, including progressive motility, straight line, curvilinear, and average path velocities, lateral head displacement, beat cross frequency, and linearity. According to a direct role of alpha4 in Na(+) transport, ouabain inhibition of alpha4 increased [Na(+)](i) in the male gametes. In addition, interference of alpha4 activity with ouabain produced cell membrane depolarization, diminished pH, and increased [Ca(2)(+)](i) in spermatozoa. Inhibition of alpha4 was sufficient to cause all these effects and additional blockage of alpha1, the other Na,K-ATPase alpha isoform expressed in sperm, and higher doses of ouabain did not result in further changes in the cell parameters studied. These results show that alpha4 is the Na,K-ATPase isoform primarily involved in controlling the transmembrane Na(+) gradient in sperm, and that alpha4 activity is necessary for maintaining membrane potential, [Ca(2)(+)](i), and [H(+)](i) in the cells. The high dependence of sperm motility on membrane excitability, [Ca(2)(+)](i), and acid-base balance suggests that their regulation is the mechanism by which alpha4 maintains motility of the male gametes.

  14. Building gene expression signatures indicative of transcription factor activation to predict AOP modulation (United States)

    Building gene expression signatures indicative of transcription factor activation to predict AOP modulation Adverse outcome pathways (AOPs) are a framework for predicting quantitative relationships between molecular initiatin...

  15. Lipidated alpha-Peptide/beta-Peptoid Hybrids with Potent Antiinflammatory Activity

    DEFF Research Database (Denmark)

    Skovbakke, Sarah L.; Larsen, Camilla J.; Heegaard, Peter M. H.;


    , in contrast to polymyxin B, displayed only minor activity in the Limulus amebocyte lysate assay. Flow cytometry data showed specific interaction of a fluorophore-labeled lipidated a-peptide/beta-peptoid hybrid with monocytes and granulocytes indicating a cellular target expressed by these leukocyte subsets....

  16. The island of alpha activity close to the double magic nucleus 100Sn

    International Nuclear Information System (INIS)

    Up to now, 14 alpha emitters have been identified among the neutrondeficient isotopes of Te, I, Xe and Cs. None of the nine formulae of 1975 mass predictions can reproduce the Q-values of all these alpha emitters. Nevertheless, one can say that some good estimates are obtained by using the masses given by: Myers; Groote-Hilf-Takahashi, Liran Zeldes; Jaenecke-Eynon and Jaenecke. If the Q-value is known, our semiempirical formula, based on the fission theory of alpha decay, allow to obtain the best estimates of the partial life-times. This relationship is used to predict new alpha emitters with atomic numbers Z = 52-61. (authors)

  17. Triiodothyronine causes rapid reversal of alpha 1/cyclic adenosine monophosphate synergism on brown adipocyte respiration and type II deiodinase activity. (United States)

    Noronha, M; Raasmaja, A; Moolten, N; Larsen, P R


    Previous studies have shown that thyroid status affects the response of brown adipose tissue (BAT) to the sympathetic nervous system. For example, hypothyroidism is associated with the development of a marked synergism between alpha 1- and beta-adrenergic pathways to stimulate type II iodothyronine 5'-deiodinase activity. Hypothyroidism also attenuates the respiratory response (thermogenesis) of isolated brown adipocytes to norepinephrine. To explore the interactions of the sympathetic nervous system and thyroid status in these cells, we compared the thermogenic and 5'-deiodinase responses to adrenergic agonists in isolated brown adipocytes from hypothyroid rats during treatment with 3,5,3'-triiodothyronine (T3). The fivefold synergism of alpha 1- and beta-adrenergic catecholamines to increase the deiodinase activity was progressively reduced, reaching a control euthyroid value of unity after 5 days of T3 treatment. Hypothyroidism reduced both the O2max (twofold to threefold) and increased the concentration of agonist required for 50% stimulation (10-fold) for both norepinephrine and forskolin. In hypothyroid cells, there was a twofold synergism between the alpha 1-agonist cirazoline and forskolin to increase respiration, which was blocked by prazosin and reproduced by the calcium ionophore, A23187. This synergistic effect of the alpha 1-agonist was lost within 2 days of T3 administration. These studies identify a second Ca(2+)-dependent intra-adrenergic synergism, which functions to ameliorate the reduced cyclic adenosine monophosphate (cAMP) responsiveness of the hypothyroid brown adipocyte. PMID:1683679

  18. The role of 14-3-3{beta} in transcriptional activation of estrogen receptor {alpha} and its involvement in proliferation of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoonseo; Kim, Hyungjin; Jang, Sung-Wuk [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Ko, Jesang, E-mail: [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of)


    Highlights: {yields} 14-3-3{beta} interacts with ER{alpha} and the interaction is Akt-dependent. {yields} 14-3-3{beta} regulates the transcriptional activity of ER{alpha} in a ligand-dependent manner. {yields} 14-3-3{beta} increases expressions of ER{alpha} target genes. {yields} 14-3-3{beta} increases breast cancer cell proliferation. -- Abstract: The estrogen receptor (ER) functions as a transcription factor that mediates the effects of estrogen. ER{alpha}, which plays a crucial role in the development and progression of breast cancer, is activated by estrogen binding, leading to receptor phosphorylation, dimerization, and recruitment of co-activators and chaperons to the estrogen-bound receptor complex. The 14-3-3 proteins bind to target proteins via phosphorylation and influence many cellular events by altering their subcellular localization or acting as a chaperone. However, regulation of ER{alpha} expression and transactivation by the 14-3-3 proteins has not been reported. We demonstrate that 14-3-3{beta} functions as a positive regulator of ER{alpha} through a direct protein-protein interaction in an estrogen-dependent manner. Ectopic expression of 14-3-3{beta} stimulated ER{alpha}-mediated transcriptional activity in MCF-7 breast cancer cells. Enhanced ER{alpha} transcriptional activity due to 14-3-3{beta} increased the expressions of the endogenous ER{alpha} target genes, leading to proliferation of breast cancer cells. We suggest that 14-3-3{beta} has oncogenic potential in breast cancer via binding to ER{alpha} and activation of the transcriptional activity of ER{alpha}.

  19. Mechanisms of transcriptional activation of the mouse claudin-5 promoter by estrogen receptor alpha and beta. (United States)

    Burek, Malgorzata; Steinberg, Katrin; Förster, Carola Y


    Claudin-5 is an integral membrane protein and a critical component of endothelial tight junctions that control paracellular permeability. Claudin-5 is expressed at high levels in the brain vascular endothelium. Estrogens have multiple effects on vascular physiology and function. The biological actions of estrogens are mediated by two different estrogen receptor (ER) subtypes, ER alpha and ER beta. Estrogens have beneficial effects in several vascular disorders. Recently we have cloned and characterized a murine claudin-5 promoter and demonstrated 17beta-estradiol (E2)-mediated regulation of claudin-5 in brain and heart microvascular endothelium on promoter, mRNA and protein level. Sequence analysis revealed a putative estrogen response element (ERE) and a putative Sp1 transcription factor binding site in the claudin-5 promoter. The aim of the present study was to further characterize the estrogen-responsive elements of claudin-5 promoter. First, we introduced point mutations in ERE or Sp1 site in -500/+111 or in Sp1 site of -268/+111 claudin-5 promoter construct, respectively. Basal and E2-mediated transcriptional activation of mutated constructs was abrogated in the luciferase reporter gene assay. Next, we examined whether estrogen receptor subtypes bind to the claudin-5 promoter region. For this purpose we performed chromatin immunoprecipitation assays using anti-estrogen receptor antibodies and cellular lysates of E2-treated endothelial cells followed by quantitative PCR analysis. We show enrichment of claudin-5 promoter fragments containing the ERE- and Sp1-binding site in immunoprecipitates after E2 treatment. Finally, in a gel mobility shift assay, we demonstrated DNA-protein interaction of both ER subtypes at ERE. In summary, this study provides evidence that both a non-consensus ERE and a Sp1 site in the claudin-5 promoter are functional and necessary for the basal and E2-mediated activation of the promoter.

  20. Expression and Purification of PI3 Kinase {alpha} and Development of an ATP Depletion and an AlphaScreen PI3 Kinase Activity Assay

    DEFF Research Database (Denmark)

    Boldyreff, Brigitte; Rasmussen, Tine L; Jensen, Hans H;


    Phosphoinositide-3-kinases are important targets for drug development because many proteins in the PI3 kinase signaling pathway are mutated, hyperactivated, or overexpressed in human cancers. Here, the authors coexpressed the human class Ia PI3 kinase p110alpha catalytic domain with an N...... was optimized by testing different lipids as substrates, as well as various kinase and lipid concentrations. Furthermore, they analyzed autophosphorylation of p110alpha/p85alpha and determined the IC50 for wortmannin, a known PI3 kinase inhibitor. The IC50 for wortmannin was determined to be 7 nM. From...... a selection of substrates, phosphatidylinositol-4, 5-biphosphate turned out to be the best substrate at a concentration of 50 microM. p110alpha/p85alpha underwent autophosphorylation most prominently at the p85alpha subunit. However, in the presence of lipid substrate, the autophosphorylation was negligible...

  1. High specific activity N-Acetyl-3{sup H}-{alpha}-Aspartyl- L-Glutamic at micro mole scale; Sintesis de N-Acetil-3{sup H}- {alpha} -Aspartil-Glutamico a escala de Micromoles

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, C.


    High specific activity N-Acetyl-3{sup H}- {alpha} -Aspartyl-I-Glutamic acid at micro mole scale in prepared acetylating L- {alpha} -Aspartyl-L-glutamic with 3{sup H}-acetic anhydride in re distilled toluene. The product le purified through cationic and anionic columns. The radiochemical purity as determined by thin-layer chromatography is greater then 99% at the time preparation. (Author) 5 refs.

  2. [Characteristics of cortical activity in persons with high and low verbal creativity: analysis of alpha1,2 rhythms]. (United States)

    Razumnikova, O M; Tarasova, I V; Vol'f, N V


    Creativity-related changes in alpha power in low-frequency (8-10 Hz) and high-frequency (10-13 Hz) bands were studied in university students having regard to generation of original ideas during performance of two verbal tasks. A high-creative group enrolled 16 subjects asked to generate original words--associates to the triads of verbal stimuli and 14 subjects who were asked to compose a sentence using triads of nouns from remote semantic categories. Low-creative groups included 22 and 13 individuals, respectively. In low-frequency band, highly creative subjects showed a higher level of alpha power than low creative individuals. In the high-frequency band, task-related alpha2 power desynchronization was different in these groups: high-creative individuals had higher power score than low-creative mostly in the anterior and parietal cortical areas. These data and a factor structure of alpha rhythm indices may be evidence of different strategies of information selection in highly and low creative persons.

  3. Happiness Indices among Persons with Profound and Severe Disabilities during Leisure and Work Activities: A Comparison. (United States)

    Yu, Dickie C. T.; Spevack, Sara; Hiebert, Rene; Martin, Toby L.; Goodman, Ryan; Martin, Todd G.; Harapiak, Shayla; Martin, Garry L.


    Happiness indices were observed during naturally occurring work and leisure activities for individuals with severe (n=12) and profound (n=7) disabilities. Both groups showed more happiness indices during leisure activities, although the difference for the profound group was smaller. There was also a significant difference between groups for…

  4. Methodological foundations of evaluation of effectiveness indicators of small-scale business activities

    Directory of Open Access Journals (Sweden)

    Ivanova T.


    Full Text Available The methodological approach to the measurement of financial indicators of small-scale enterprises has been developed. It enables to secure the comparability of financial condition indicators and the results of small-scale enterprise activities, and also to develop the methods of vertical integral estimate calculation at separate aspects of financial condition and the results of smallscale enterprise activities.

  5. Neural activity changes underlying the working memory deficit in alpha-CaMKII heterozygous knockout mice

    Directory of Open Access Journals (Sweden)

    Naoki Matsuo


    Full Text Available The alpha-isoform of calcium/calmodulin-dependent protein kinase II (α-CaMKII is expressed abundantly in the forebrain and is considered to have an essential role in synaptic plasticity and cognitive function. Previously, we reported that mice heterozygous for a null mutation of α-CaMKII (α-CaMKII+/- have profoundly dysregulated behaviors including a severe working memory deficit, which is an endophenotype of schizophrenia and other psychiatric disorders. In addition, we found that almost all the neurons in the dentate gyrus (DG of the mutant mice failed to mature at molecular, morphological and electrophysiological levels. In the present study, to identify the brain substrates of the working memory deficit in the mutant mice, we examined the expression of the immediate early genes (IEGs, c-Fos and Arc, in the brain after a working memory version of the eight-arm radial maze test. c-Fos expression was abolished almost completely in the DG and was reduced significantly in neurons in the CA1 and CA3 areas of the hippocampus, central amygdala, and medial prefrontal cortex (mPFC. However, c-Fos expression was intact in the entorhinal and visual cortices. Immunohistochemical studies using arc promoter driven dVenus transgenic mice demonstrated that arc gene activation after the working memory task occurred in mature, but not immature neurons in the DG of wild-type mice. These results suggest crucial insights for the neural circuits underlying spatial mnemonic processing during a working memory task and suggest the involvement of α-CaMKII in the proper maturation and integration of DG neurons into these circuits.

  6. Observation of Hysteresis between Solar Activity Indicators and -mode Frequency Shifts for Solar Cycle 22

    Indian Academy of Sciences (India)

    S. C. Tripathy; Brajesh Kumar; Kiran Jain; A. Bhatnagar


    Using intermediate degree p-mode frequency data sets for solar cycle 22, we find that the frequency shifts and magnetic activity indicators show a ``hysteresis" phenomenon. It is observed that the magnetic indices follow different paths for the ascending and descending phases of the solar cycle while for radiative indices, the separation between the paths are well within the error limits.

  7. Structural determinants within residues 180-199 of the rodent. alpha. 5 nicotinic acetylcholine receptor subunit involved in. alpha. -bungarotoxin binding

    Energy Technology Data Exchange (ETDEWEB)

    McLane, K.E.; Xiadong Wu; Conti-Tronconi, B.M. (Univ. of Minnesota, St. Paul (United States))


    Synthetic peptides corresponding to sequence segments of the nicotinic acetylcholine receptor (nAChR) {alpha} subunits have been used to identify regions that contribute to formation of the binding sites for cholinergic ligands. The authors have previously defined {alpha}-bungarotoxin ({alpha}-BTX) binding sequences between residues 180 and 199 of a putative rat neuronal nAChR {alpha} subunit, designated {alpha}5, and between residues 181 and 200 of the chick neuronal {alpha}7 and {alpha}8 subunits. These sequences are relatively divergent compared with the Torpedo and muscle nAChR {alpha}1 {alpha}-BTX binding sites, which indicates a serious limitation of predicting functional domains of proteins based on homology in general. Given the highly divergent nature of the {alpha}5 sequence, they were interested in determining the critical amino acid residues for {alpha}-BTX binding. In the present study, the effects of single amino acid substitutions of Gly or Ala for each residue of the rat {alpha}(180-199) sequence were tested, using a competition assay, in which peptides compete for {sup 125}I-{alpha}-BTX binding with native Torpedo nAChR. These results indicate that a disulfide bridge between the vicinal cysteines at positions 191 and 192 of the {alpha}5 sequence is not an absolute requirement for {alpha}-BTX binding activity.

  8. Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity.

    Directory of Open Access Journals (Sweden)

    C S James Ho

    Full Text Available HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells.

  9. Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity. (United States)

    Ho, C S James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard


    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells.


    Directory of Open Access Journals (Sweden)

    I. K. Romanovich


    Full Text Available The present work gives an analysis of the data on natural radionuclides content in drinking-water of Russian Federation groundwater supplies obtained in long-term investigations. On the basis of the mentioned analysis estimation of population internal exposure doses from the drinking-water consumption is carried out and optimal value for initial screening gross alpha activity concentration level is suggested. 

  11. Effect of communities of ammonia-oxidizing bacteria on degradation of 17-alpha-ethynylestradiol by nitrifying activated sludge

    Energy Technology Data Exchange (ETDEWEB)

    Limpiyakorn, T.; Sermwaraphan, P.; Kurisu, F.


    An endocrine disrupting compound, 17-alpha-ethynylestradiol (EE2), is a synthetic estrogen used as a key ingredient in oral contraceptives pill. this persistent organic pollutant, no biodegradable by most microorganisms, is discharged via municipal waste streams to natural receiving waters. Recently, it was found that ammonia-oxidizing bacteria (AOB) in nitrifying activated sludge (NAS) enriched with high ammonium loads can degrade EE2 via co-metabolism during ammonia oxidation. (Author)

  12. Immobilization of lipase on epoxy activated (1-->3)-alpha-D-glucan isolated from Penicillium chrysongenum. (United States)

    Wang, Tianqi; Li, Hanxiang; Nie, Kaili; Tan, Tianwei


    A water-insoluble linear (1-->3)-alpha-D-glucan was isolated from Penicillium mycelia. Three kinds of epoxy-activated microspheres of this glucan were prepared as supports for Candida sp. lipase (EC3.1.1.3) immobilization. The highest immobilization yield was 36.4%. The specific activity was 26.85 U/mg, and only 4.1% of activity was lost in comparison with the free enzyme used for immobilization. The higher thermal stability, storage stability, and reusability of the immobilized lipase make it a potential candidate for wide application. PMID:17151459

  13. [Antiviral activity of extracts of transgenic cichory and lettuce plants with the human interferon alpha-2b gene]. (United States)

    Matveeva, N A; Kudriavets, Iu I; Likhova, A A; Shakhovskiĭ, A M; Bezdenezhnykh, N A; Kvasko, E Iu


    Biological activity of protein extracts from transgenic plants of chicory Cichorium intybus L. and lettuce Lactuca sativa L. with human interferon alpha2b gene was investigated against vesicular stomatitis virus. It was shown that the extracts from the hairy roots of chicory and lettuce transformed by A. rhizogenes possess the antiviral activity 1620...5400 IU/g weight, and the extracts from leaves of the plants transformed by A. tumefaciens--till 9375 IU/g weight. Dependence of plant extract biological activity on the transformation vector was shown. PMID:23342646

  14. Scaling and organization of electroencephalographic background activity and alpha rhythm in healthy young adults. (United States)

    Lin, D C; Sharif, A; Kwan, H C


    The coexistence of the broad-band fluctuation and alpha rhythm of the brain dynamics is studied based on the zero-crossing property of the local electroencephalographic (EEG) recording in eyes closed and eyes open. A two-component zero-crossing scenario, consisting of a broad-band fractal and narrow-band rhythm components, is assumed. Scaling is found in the power law distribution p(tau) approximately tau(-nu) of the crossing time interval tau of the broad-band fluctuation. In alpha dominant brain state, the alpha rhythm interval L also exhibits scaling in the form of power law distribution: p(L) approximately L(phi). Our main result is the relationship nu + phi approximately 3 that characterizes the organization of these two prominent features of the brain dynamics. The possible role of self-organized criticality of punctuated equilibrium in this organization is discussed. PMID:16897091

  15. Effects of water activity and aqueous solvent ordering on thermal stability of lysozyme, alpha-chymotrypsinogen A, and alcohol dehydrogenase. (United States)

    Matsue, S; Fujii, T; Miyawaki, O


    Effects of water activity (aW) and solvent ordering were separately analyzed on the thermal unfolding of lysozyme and alpha-chymotrypsinogen A, and also on the thermal deactivation of yeast alcohol dehydrogenase (YADH) in aqueous solutions with various additives. With the coexistence of additives, water activity was the determinant of the extent of the change in the thermal stability of proteins while solvent ordering was the determinant of the direction of the change. The parameter alpha, determined from the activity coefficient of water, representing the deviation of aW from that of the ideal solution, was useful as a quantitative index of the solvent ordering showing good correlations with the unfolding temperature and enthalpy of lysozyme and alpha-chymotrypsinogen A and also with the thermal deactivation rate constant of YADH at a constant aW. Solvent ordering seemed to affect the thermal stability of proteins mainly through its effect on the intramolecular hydrophobic interaction among amino acid residues in a protein molecule but the contribution of the electrostatic interaction including hydrogen bonding through the change in permittivity of solution was also suggested.

  16. Evidence for a Dual Role of an Active Site Histidine in [alpha]-Amino-[beta]-carboxymuconate-[epsilon]-semialdehyde Decarboxylase

    Energy Technology Data Exchange (ETDEWEB)

    Huo, Lu; Fielding, Andrew J.; Chen, Yan; Li, Tingfeng; Iwaki, Hiroaki; Hosler, Jonathan P.; Chen, Lirong; Hasegawa, Yoshie; Que, Jr., Lawrence; Liu, Aimin (GSU); (Kansai); (UMMC); (UMM)


    The previously reported crystal structures of {alpha}-amino-{beta}-carboxymuconate-{epsilon}-semialdehyde decarboxylase (ACMSD) show a five-coordinate Zn(II)(His){sub 3}(Asp)(OH{sub 2}) active site. The water ligand is H-bonded to a conserved His228 residue adjacent to the metal center in ACMSD from Pseudomonas fluorescens (PfACMSD). Site-directed mutagenesis of His228 to tyrosine and glycine in this study results in a complete or significant loss of activity. Metal analysis shows that H228Y and H228G contain iron rather than zinc, indicating that this residue plays a role in the metal selectivity of the protein. As-isolated H228Y displays a blue color, which is not seen in wild-type ACMSD. Quinone staining and resonance Raman analyses indicate that the blue color originates from Fe(III)-tyrosinate ligand-to-metal charge transfer. Co(II)-substituted H228Y ACMSD is brown in color and exhibits an electron paramagnetic resonance spectrum showing a high-spin Co(II) center with a well-resolved {sup 59}Co (I = 7/2) eight-line hyperfine splitting pattern. The X-ray crystal structures of as-isolated Fe-H228Y (2.8 {angstrom}) and Co-substituted (2.4 {angstrom}) and Zn-substituted H228Y (2.0 {angstrom} resolution) support the spectroscopic assignment of metal ligation of the Tyr228 residue. The crystal structure of Zn-H228G (2.6 {angstrom}) was also determined. These four structures show that the water ligand present in WT Zn-ACMSD is either missing (Fe-H228Y, Co-H228Y, and Zn-H228G) or disrupted (Zn-H228Y) in response to the His228 mutation. Together, these results highlight the importance of His228 for PfACMSD's metal specificity as well as maintaining a water molecule as a ligand of the metal center. His228 is thus proposed to play a role in activating the metal-bound water ligand for subsequent nucleophilic attack on the substrate.

  17. TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)


    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  18. Design and performance of an ionisation chamber for the measurement of low alpha-activities

    CERN Document Server

    Hartmann, Andreas; Krüger, Felix; Sobiella, Manfred; Wilsenach, Heinrich; Zuber, Kai


    A new ionisation chamber for alpha-spectroscopy has been built from radio-pure materials for the purpose of investigating long lived alpha-decays. The measurement makes use of pulse shape analysis to discriminate between signal and background events. The design and performance of the chamber is described in this paper. A background rate of ($10.9 \\pm 0.6$) counts per day in the energy region of 1 MeV to 9 MeV was achieved with a run period of 30.8 days. The background is dominantly produced by radon daughters.

  19. Activation of p115-RhoGEF Requires Direct Association of G[alpha subscript 13] and the Dbl Homology Domain

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhe; Guo, Liang; Hadas, Jana; Gutowski, Stephen; Sprang, Stephen R.; Sternweis, Paul C. (IIT); (UTSMC); (Montana)


    RGS-containing RhoGEFs (RGS-RhoGEFs) represent a direct link between the G{sub 12} class of heterotrimeric G proteins and the monomeric GTPases. In addition to the canonical Dbl homology (DH) and pleckstrin homology domains that carry out the guanine nucleotide exchange factor (GEF) activity toward RhoA, these RhoGEFs also possess RGS homology (RH) domains that interact with activated {alpha} subunits of G{sub 12} and G{sub 13}. Although the GEF activity of p115-RhoGEF (p115), an RGS-RhoGEF, can be stimulated by G{alpha}{sub 13}, the exact mechanism of the stimulation has remained unclear. Using combined studies with small angle x-ray scattering, biochemistry, and mutagenesis, we identify an additional binding site for activated G{alpha}{sub 13} in the DH domain of p115. Small angle x-ray scattering reveals that the helical domain of G{alpha}{sub 13} docks onto the DH domain, opposite to the surface of DH that binds RhoA. Mutation of a single tryptophan residue in the {alpha}3b helix of DH reduces binding to activated G{alpha}{sub 13} and ablates the stimulation of p115 by G{alpha}{sub 13}. Complementary mutations at the predicted DH-binding site in the {alpha}B-{alpha}C loop of the helical domain of G{alpha}{sub 13} also affect stimulation of p115 by G{alpha}{sub 13}. Although the GAP activity of p115 is not required for stimulation by G{alpha}{sub 13}, two hydrophobic motifs in RH outside of the consensus RGS box are critical for this process. Therefore, the binding of G{alpha}{sub 13} to the RH domain facilitates direct association of G{alpha}{sub 13} to the DH domain to regulate its exchange activity. This study provides new insight into the mechanism of regulation of the RGS-RhoGEF and broadens our understanding of G protein signaling.

  20. Association of Workplace Stressors with Salivary Alpha-Amyl-ase Activity Levels among Fresh Fruit Bunch Cutters in Se¬langor

    Directory of Open Access Journals (Sweden)

    Nur Sabrina MOHD NASIR


    Full Text Available Background: A cross sectional study was conducted to determine the association between occupational stress risk factors and salivary alpha-amylase activity levels among fresh fruit bunch (ffb cutters at oil palm plantation. Methods: A total of 109 ffb cutters were selected from two oil palm plantations in Pulau Carey, Selangor at west coast of Malaysia in 2015. Questionnaires were used to determine socio-demographics and occupation information, distress level were determined by using translated 12-items-General Health Questionnaire (GHQ. Kestrel Heat Stress Tracker 4400 was used to measure wet bulb globe temperature (WBGT for heat stress exposure. Posture analysis was examined based on Rapid Upper Limb Assessment (RULA method in evaluating working posture and Borg CR-10 scale was rated by ffb cutters to determine exerted force during harvesting process. Stress response system was determined by measuring salivary alpha-amylase (sAA activity by using sAA kinetic enzyme assay kit (Salimetrics.Results: 35.8% of ffb cutter had high score indicating psychological distress. 49.5% of the cutters had high heat stress exposure. 91.8% used force exertion of 50%MVC and above to cut fresh fruit bunches and 62.4% were classified in Action Level 4 under RULA. 77.0% of the ffb cutters showed high levels of sAA activity after cutting fresh fruit bunches. Conclusion: Workplace stressors such as working environment and ergonomics risk factors play a role to develop stress at workplace among ffb cutters. Therefore, stress preventive measures are needed to reduce the stressors at workplace.Keywords: Psychological distress, Salivary alpha-amylase, Heat stress exposure, Oil palm plantation

  1. Relating Alpha Power and Phase to Population Firing and Hemodynamic Activity Using a Thalamo-cortical Neural Mass Model.

    Directory of Open Access Journals (Sweden)

    Robert Becker


    Full Text Available Oscillations are ubiquitous phenomena in the animal and human brain. Among them, the alpha rhythm in human EEG is one of the most prominent examples. However, its precise mechanisms of generation are still poorly understood. It was mainly this lack of knowledge that motivated a number of simultaneous electroencephalography (EEG - functional magnetic resonance imaging (fMRI studies. This approach revealed how oscillatory neuronal signatures such as the alpha rhythm are paralleled by changes of the blood oxygenation level dependent (BOLD signal. Several such studies revealed a negative correlation between the alpha rhythm and the hemodynamic BOLD signal in visual cortex and a positive correlation in the thalamus. In this study we explore the potential generative mechanisms that lead to those observations. We use a bursting capable Stefanescu-Jirsa 3D (SJ3D neural-mass model that reproduces a wide repertoire of prominent features of local neuronal-population dynamics. We construct a thalamo-cortical network of coupled SJ3D nodes considering excitatory and inhibitory directed connections. The model suggests that an inverse correlation between cortical multi-unit activity, i.e. the firing of neuronal populations, and narrow band local field potential oscillations in the alpha band underlies the empirically observed negative correlation between alpha-rhythm power and fMRI signal in visual cortex. Furthermore the model suggests that the interplay between tonic and bursting mode in thalamus and cortex is critical for this relation. This demonstrates how biophysically meaningful modelling can generate precise and testable hypotheses about the underpinnings of large-scale neuroimaging signals.

  2. ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor.

    Directory of Open Access Journals (Sweden)

    Elton Zeqiraj


    Full Text Available Pseudokinases lack essential residues for kinase activity, yet are emerging as important regulators of signal transduction networks. The pseudokinase STRAD activates the LKB1 tumour suppressor by forming a heterotrimeric complex with LKB1 and the scaffolding protein MO25. Here, we describe the structure of STRADalpha in complex with MO25alpha. The structure reveals an intricate web of interactions between STRADalpha and MO25alpha involving the alphaC-helix of STRADalpha, reminiscent of the mechanism by which CDK2 interacts with cyclin A. Surprisingly, STRADalpha binds ATP and displays a closed conformation and an ordered activation loop, typical of active protein kinases. Inactivity is accounted for by nonconservative substitution of almost all essential catalytic residues. We demonstrate that binding of ATP enhances the affinity of STRADalpha for MO25alpha, and conversely, binding of MO25alpha promotes interaction of STRADalpha with ATP. Mutagenesis studies reveal that association of STRADalpha with either ATP or MO25alpha is essential for LKB1 activation. We conclude that ATP and MO25alpha cooperate to maintain STRADalpha in an "active" closed conformation required for LKB1 activation. It has recently been demonstrated that a mutation in human STRADalpha that truncates a C-terminal region of the pseudokinase domain leads to the polyhydramnios, megalencephaly, symptomatic epilepsy (PMSE syndrome. We demonstrate this mutation destabilizes STRADalpha and prevents association with LKB1. In summary, our findings describe one of the first structures of a genuinely inactive pseudokinase. The ability of STRADalpha to activate LKB1 is dependent on a closed "active" conformation, aided by ATP and MO25alpha binding. Thus, the function of STRADalpha is mediated through an active kinase conformation rather than kinase activity. It is possible that other pseudokinases exert their function through nucleotide binding and active conformations.

  3. Facilitation and inhibition in attention: Functional dissociation of pre-stimulus alpha activity, P1, and N1 components. (United States)

    Slagter, H A; Prinssen, S; Reteig, L C; Mazaheri, A


    Attention--the ability to attend to some things while ignoring others - can be best described as an emergent property of many neural mechanisms, facilitatory and inhibitory, working together to resolve competition for processing resources and control of behavior. Previous EEG and MEG studies examining the neural mechanisms underlying facilitation and inhibition of stimulus processing typically used paradigms requiring alternating shifts of attention in the spatial domain, with stimuli occurring at both attended and unattended locations. These studies generally observed greater pre-stimulus alpha oscillations over task-irrelevant vs. relevant posterior regions and bilateral attentional modulations of early sensory processing. In contrast, in the current series of experiments, participants continuously attended to only one hemifield and stimuli were only presented at the attended location, affording us an opportunity to elucidate the inhibitory and facilitatory effects of attention in the brain in a context in which spatial relevance was fixed. We found that continuous attention to one hemifield did not modulate prestimulus alpha activity in ipsilateral regions but did result in a perfectly lateralized P1 attention effect to ipsilateral posterior regions. Moreover, we found a bilateral N1 effect. These findings suggest that pre-stimulus alpha activity, the P1 and the N1 reflect qualitatively different aspects of attention; While pre-stimulus alpha-band activity may reflect a top-down inhibitory mechanism that critically depends on functional competition between task-relevant and irrelevant sensory regions, the ipsilateral P1 effect may reflect stimulus-triggered blocking of sensory processing in irrelevant networks, and the N1 effect facilitation of task-relevant processing.

  4. A comparative study of alpha amylase inhibitory activities of common anti-diabetic plants at Kharagpur 1 block

    Directory of Open Access Journals (Sweden)

    Dineshkumar B


    Full Text Available In India, the prevalence of diabetes mellitus is on the increase and needs to be addressed appropriately. In this study area, herbal remedies are considered convenient for management of Type 2 diabetes with postprandial hyperglycemia due to their traditional acceptability and availability, low costs, lesser side effects. Comparative evaluation of alpha amylase inhibitory activities of selected plants extracts. Kharagpur is situated in the Midnapur West district of West Bengal in India. In this district, diabetes prevalence is comparatively high. Ten common plants in IIT Kharagpur 1 Block namely, Acalypha indica, Allium cepa, Allium sativum, Azadirachta indica, Musa sapientum, Mangifera indica, Murraya, Ocimum sanctum, Phyllanthus amarus and Tinospora cordifolia were tested for their alpha amylase inhibitory activities to establish anti-diabetic potentials. The plant extracts were prepared sequentially with petroleum ether, hexane, chloroform, ethanol and aqueous. The extracts obtained were subjected to in vitro alpha amylase inhibitory assay using starch azure as a substrate and porcine pancreatic amylase as the enzyme. Statistical difference and linear regression analysis were performed by using Graphpad prism 5 statistical software. Ethanol extracts of Mangifera indica, Azadirachta indica and petroleum ether extract of Murraya koenigii (at a concentrations 10-100μg/ml showed maximum percentage inhibition on alpha amylase activity with an IC 50 value of 37.86 ± 0.32μg/ml, 62.99 ± 1.20μg/ml and 59.0 ± 0.51μg/ml respectively when compared with acarbose (IC 50 value 83.33 ± 0.75μg/ml. The results showing that Mangifera indica, Azadirachta indica and Murraya koenigii might be effective in lowering post prandial hyperglycemia.

  5. Induction of sensitivity to the cytotoxic action of tumor necrosis factor alpha by adenovirus E1A is independent of transformation and transcriptional activation. (United States)

    Ames, R S; Holskin, B; Mitcho, M; Shalloway, D; Chen, M J


    We have previously shown that expression of the adenovirus E1A 12S or 13S products in NIH 3T3 fibroblasts induces susceptibility to the cytotoxic actions of tumor necrosis factor alpha (TNF alpha). A large number of studies have mapped the multiple biological functions of the 12S and 13S products to three highly conserved regions (CR) within the E1A sequence. Here we used plasmids coding for E1A deletion and point mutants in these regions to generate target cell lines for TNF alpha cytotoxicity assays to determine which regions and functions are necessary for the induction of TNF alpha sensitivity. Expression of CR1 was required for the induction of TNF alpha sensitivity. This finding did not reflect a requirement for transforming or transcriptional repression activity, since some mutants that were defective in both of these properties were able to induce TNF alpha sensitivity. CR2 transformation-defective point mutants, but not a CR2/3 region deletion mutant, were also able to induce sensitivity. In addition, NIH 3T3 cells expressing the retroviral transcription activators tat from human immunodeficiency virus type 1 and tax from human T-lymphotropic virus type I were not sensitive to TNF alpha. However, the possibility that E1A-mediated transcriptional activation can augment the induction of TNF alpha sensitivity is not excluded. Comparison of data from previous biological studies with the TNF alpha cytotoxicity assays presented here suggested that the mechanism by which E1A induces sensitivity to TNF alpha in NIH 3T3 cells is independent of many of the known E1A biological functions, including transformation in cooperation with ras, immortalization, induction of DNA synthesis in quiescent cells, and transcriptional repression. A novel E1A-mediated effect may be involved, although our data do not exclude the possibility that sensitization to TNF alpha is mediated through E1A binding to cellular proteins. PMID:2143540

  6. Reflection of disease activity in rheumatoid arthritis by indices of activation of the classical complement pathway.


    Makinde, V A; Senaldi, G; Jawad, A S; Berry, H; Vergani, D


    Levels of C4d, a fragment of C4 generated during activation of the classical complement pathway, were measured in the plasma of 77 patients with rheumatoid arthritis and 30 healthy subjects. Disease activity was judged according to Ritchie's articular index to be mildly active in 31 (group 1), moderately active in 29 (group 2), and severely active in 17 patients (group 3). Plasma levels of C3d, a fragment of C3, and serum levels of C4, C3, and immune complexes were also measured. The ratios C...

  7. Peroxisome proliferator-activated receptor {alpha} agonists modulate Th1 and Th2 chemokine secretion in normal thyrocytes and Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Antonelli, Alessandro, E-mail: [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Ferrari, Silvia Martina, E-mail: [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Frascerra, Silvia, E-mail: [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Corrado, Alda, E-mail: [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Pupilli, Cinzia, E-mail: [Endocrinology Unit, Azienda Ospedaliera Careggi and University of Florence, Viale Morgagni 85, I-50134, Florence (Italy); Bernini, Giampaolo, E-mail: [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Benvenga, Salvatore, E-mail: [Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Messina, Piazza Pugliatti 1, I-98122, Messina (Italy); Ferrannini, Ele, E-mail: [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Fallahi, Poupak, E-mail: [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy)


    Until now, no data are present about the effect of peroxisome proliferator-activated receptor (PPAR){alpha} activation on the prototype Th1 [chemokine (C-X-C motif) ligand (CXCL)10] (CXCL10) and Th2 [chemokine (C-C motif) ligand 2] (CCL2) chemokines secretion in thyroid cells. The role of PPAR{alpha} and PPAR{gamma} activation on CXCL10 and CCL2 secretion was tested in Graves' disease (GD) and control primary thyrocytes stimulated with interferon (IFN){gamma} and tumor necrosis factor (TNF){alpha}. IFN{gamma} stimulated both CXCL10 and CCL2 secretion in primary GD and control thyrocytes. TNF{alpha} alone stimulated CCL2 secretion, while had no effect on CXCL10. The combination of IFN{gamma} and TNF{alpha} had a synergistic effect both on CXCL10 and CCL2 chemokines in GD thyrocytes at levels comparable to those of controls. PPAR{alpha} activators inhibited the secretion of both chemokines (stimulated with IFN{gamma} and TNF{alpha}) at a level higher (for CXCL10, about 60-72%) than PPAR{gamma} agonists (about 25-35%), which were confirmed to inhibit CXCL10, but not CCL2. Our data show that CCL2 is modulated by IFN{gamma} and TNF{alpha} in GD and normal thyrocytes. Furthermore we first show that PPAR{alpha} activators inhibit the secretion of CXCL10 and CCL2 in thyrocytes, suggesting that PPAR{alpha} may be involved in the modulation of the immune response in the thyroid.

  8. Alpha-Tocopherol modulates transcriptional activities that affect essential biological processes in Bovine Cells (United States)

    Alpha-tocopherol is the major isoform of vitamin E. after nearly 100 years of research and countless publications, the physiological functions of vitamin E remain mysterious to a certain degree. Nevertheless, vitamin E is one of the most commonly used single nutrient supplements. Recent data has su...

  9. Expression of biologically active human interferon alpha 2 in aloe vera (United States)

    We have developed a system for transgenic expression of proteins in Aloe Vera. Using this approach we have generated plants expressing the human gene interferon alpha 2, IFNa2. IFNa2 is a small secreted cytokine that plays a vital role in regulating the body’s immune response to viral infections a...

  10. Alpha emitters in nuclear waste. Extension of the procedure for low and medium level activity waste

    International Nuclear Information System (INIS)

    The present paper describes a separative method for the determination of U, Pu, Am, Np, Th and Cm as alpha emitters and 3H, Sr, and Ni as beta emitters, when present in aqueous samples of nuclear waste, by using chromatographic separations, liquid scintillation counting and alpha spectrometry. The main separation is performed in one step by coprecipitation of the alpha emitters with yttrium hydroxide at pH = 9-10 after distillation of tritium until dryness and dissolution of the residue in 2M HCI. Actinides are precipitated while strontium and nickel remain in supernatant. Nickel is separated by precipitation with dimetyglioxime in the supernatant and measured by LSC. Strontium is separated by chromatography after conditioning the supernatant (which also contained nickel) and measured by LSC. The actinides fraction is re dissolved in nitric acid and percolated through three chromatographic columns (TEVA, U-TEVA and TRU-SPEC) conditioning the different fractions for measuring by alpha spectrometry. The spectra of the different fractions are presented together with the detection limits and the recoveries obtained on spiked samples. (author)

  11. Inhibition of HIF-1{alpha} activity by BP-1 ameliorates adjuvant induced arthritis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Shankar, J. [Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago (United States); Thippegowda, P.B., E-mail: [Department of Pharmacology, (M/C 868), College of Medicine, University of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612 (United States); Kanum, S.A. [Department of Chemistry, Yuvaraj' s College, University of Mysore, Mysore (India)


    Rheumatoid arthritis (RA) is a chronic inflammatory, angiogenic disease. Inflamed synovitis is a hallmark of RA which is hypoxic in nature. Vascular endothelial growth factor (VEGF), one of the key regulators of angiogenesis, is overexpressed in the pathogenesis of RA. VEGF expression is regulated by hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), a master regulator of homeostasis which plays a pivotal role in hypoxia-induced angiogenesis. In this study we show that synthetic benzophenone analogue, 2-benzoyl-phenoxy acetamide (BP-1) can act as a novel anti-arthritic agent in an experimental adjuvant induced arthritis (AIA) rat model by targeting VEGF and HIF-1{alpha}. BP-1 administered hypoxic endothelial cells and arthritic animals clearly showed down regulation of VEGF expression. Further, BP-1 inhibits nuclear translocation of HIF-1{alpha}, which in turn suppresses transcription of the VEGF gene. These results suggest a further possible clinical application of the BP-1 derivative as an anti-arthritic agent in association with conventional chemotherapeutic agents.


    Starch is an extremely abundant, economical and versatile industrial commodity. Many industrial uses of starch depend on hydrolyzing the polymer for the conversion of glucose and maltodextrins. Starch hydrolysis is frequently achieved by utilizing alpha-amylase, which is an endo-acting enzyme that...

  13. Measurement of very low alpha activity in water; Medida de muy baja actividad alfa en aguas

    Energy Technology Data Exchange (ETDEWEB)

    Crespo, M. T.; Acena, M. L.


    Measurement of very low levels of alpha-emitting nuclides in water needs substantial improvements. A system based on the adsorbing properties manganese dioxide eliminates the need for transporting very large volumes of water and increases the sensitivity of the measurement. (Author) 21 refs.

  14. Rapid component I(Kr) of cardiac delayed rectifier potassium currents in guinea-pig is inhibited by alpha(1)-adrenoreceptor activation via protein kinase A and protein kinase C-dependent pathways. (United States)

    Wang, Sen; Xu, Dong-Jie; Cai, Jing-Bo; Huang, Yuan-Zhu; Zou, Jian-Gang; Cao, Ke-Jiang


    Ventricular tachyarrhythmias are often precipitated by physical or emotional stress, indicating a link between increased adrenergic stimulation and cardiac ion channel activity. Human ether-a-go-go related gene (hERG) potassium channels conduct the rapid component of delayed rectifier potassium current, I(kr), a crucial component for action potential repolarization. To evaluate the correlation between increased alpha(1)-adrenergic activity and the rapid component of cardiac I(kr), whole-cell patch-clamp recording was performed in isolated guinea-pig ventricular myocytes. Stimulation of alpha(1)-adrenoceptors using phenylephrine (0.1 nM-100 microM) reduced I(kr) current in a dose-dependent manner at 37 degrees C. Phenylephrine (0.1 microM) reduced I(kr) current to 66.83+/-3.16%. Chelerythrine (1 microM), a specific inhibitor of protein kinase C (PKC) completely inhibited the changes in I(kr) trigged by 0.1 microM phenylephrine. KT5720 (2.5 microM), a specific inhibitor of protein kinase A (PKA) partially inhibited the current decrease induced by 0.1 microM phenylephrine. Both chelerythrine and KT5720 drastically reduced the phenylephrine-induced effects, indicating possible involvement of PKC and PKA in the alpha(1)-adrenergic inhibition of I(kr). Our data suggest a link between I(kr) and the alpha(1)-adrenoceptor, involving activation of PKC and PKA in arrhythmogenesis.

  15. [Constituents relating to anti-oxidative and alpha-glucosidase inhibitory activities in Yacon aerial part extract]. (United States)

    Terada, Sumio; Ito, Kikuo; Yoshimura, Akira; Noguchi, Naoto; Ishida, Takashi


    Hot water extract of the aerial part of Yacon (Smallanthus sonchifolia, Compositae) showed potent free radical-scavenging activity and inhibitory effects on lipid peroxidation in rat brain homogenate. The most potent antioxidative activity focused on the 50% MeOH-eluted fraction on DIAION HP-20 column chromatography. The structure of the major component in the fraction was identified as 2,3,5-tricaffeoylaltraric acid (TCAA) based on spectroscopic evidence. The antioxidative activity of TCAA is superior to that of natural antioxidants such as (+/-)-catechin, alpha-tocopherol, and ellagic acid, and TCAA also showed selective maltase-inhibitory activity (IC(50) 49 microg/ml). As the hypoglycemic activity of Yacon extract was described in a previous report, the present results showing that the aerial part of Yacon has strong antioxidative activity may encourage its potential use as a food supplement to prevent type II diabetes. PMID:16880725

  16. Optimization and Modeling of Ultrasound-assisted Extraction of Polysaccharides from Cynomorium songaricum and &alpha-glucosidase Inhibitory Activity

    Directory of Open Access Journals (Sweden)

    Tao Guo


    Full Text Available In the study, the extraction processing of polysaccharides from Cynomorium songaricum was optimized by Response Surface Methodology (RSM and projected by a computer-stimulated Artificial Neural Network (ANN. The optimal process conditions were obtained as follows: extraction temperature 55C, solid-liquid ratio 1:10, power 175 W. Under optimized conditions, The R2 value of 0.99391 and an MSE value of 0.0495 suggested a good generalization of the network and showed a good agreement between the experimental and predicted values. On the other hand, the results also suggested that polysaccharides from Cynomorium songaricum had &alpha-glucosidase inhibitory activity with an IC50 of 8.316 &mug/mL and may be a potential &alpha-glucosidase inhibitory.

  17. A survey of strippable and tie-down coatings for use in the decommissioning of alpha-active facilities

    International Nuclear Information System (INIS)

    The paper concerns temporary coatings for use in decommissioning operations of alpha-active facilities. The various temporary coating options are described with respect to: decontamination by removal of a previously applied protective coating, and the in-situ application of a coating for tie-down or decontamination duties. The specifications for coating systems to be used in active areas are defined in general terms. A survey of currently available temporary coating material is given, as well as the suitability of commercially available coating systems. (U.K.)

  18. Age and heat exposure-dependent changes in antioxidant enzymes activities in rat's liver and brain mitochondria: role of alpha-tocopherol. (United States)

    Stojkovski, V; Hadzi-Petrushev, N; Ilieski, V; Sopi, R; Gjorgoski, I; Mitrov, D; Jankulovski, N; Mladenov, M


    To investigate the role of mitochondrial antioxidant capacity during increased susceptibility to heat accompanied by the aging, young and aged Wistar rats were exposed on heat for 60 min. After heat exposure, hepatic and brain mitochondria were isolated. Our results revealed changes in antioxidant enzyme activities in liver and brain mitochondria from young and to a greater extent in aged rats. Our measurements of MnSOD, GPx and GR activity indicate greater reactive oxygen species production from the mitochondria of aged heat exposed in comparison to young heat exposed rats. Also in the aged rats, the effect of alpha-tocopherol treatment in the prevention of oxidative stress occurred as a result of heat exposure, is less pronounced. Taken together, our data suggest that mitochondria in aged rats are more vulnerable and less able to prevent oxidative changes that occur in response to acute heat exposure.

  19. Effects of L-carnitine against oxidative stress in human hepatocytes: involvement of peroxisome proliferator-activated receptor alpha

    Directory of Open Access Journals (Sweden)

    Li Jin-Lian


    Full Text Available Abstract Background Excessive oxidative stress and lipid peroxidation have been demonstrated to play important roles in the production of liver damage. L-carnitine is a natural substance and acts as a carrier for fatty acids across the inner mitochondrial membrane for subsequent beta-oxidation. It is also an antioxidant that reduces metabolic stress in the cells. Recent years L-carnitine has been proposed for treatment of various kinds of disease, including liver injury. This study was conducted to evaluate the protective effect of L-carnitine against hydrogen peroxide (H2O2-induced cytotoxicity in a normal human hepatocyte cell line, HL7702. Methods We analyzed cytotoxicity using MTT assay and lactate dehydrogenase (LDH release. Antioxidant activity and lipid peroxidation were estimated by reactive oxygen species (ROS levels, activities and protein expressions of superoxide dismutase (SOD and catalase (CAT, and malondialdehyde (MDA formation. Expressions of peroxisome proliferator-activated receptor (PPAR-alpha and its target genes were evaluated by RT-PCR or western blotting. The role of PPAR-alpha in L-carnitine-enhanced expression of SOD and CAT was also explored. Statistical analysis was performed by a one-way analysis of variance, and its significance was assessed by Dennett's post-hoc test. Results The results showed that L-carnitine protected HL7702 cells against cytotoxity induced by H2O2. This protection was related to the scavenging of ROS, the promotion of SOD and CAT activity and expression, and the prevention of lipid peroxidation in cultured HL7702 cells. The decreased expressions of PPAR-alpha, carnitine palmitoyl transferase 1 (CPT1 and acyl-CoA oxidase (ACOX induced by H2O2 can be attenuated by L-carnitine. Besides, we also found that the promotion of SOD and CAT protein expression induced by L-carnitine was blocked by PPAR-alpha inhibitor MK886. Conclusions Taken together, our findings suggest that L-carnitine could protect HL


    Compound specific isotope analysis was combined with phospholipid fatty acid (PLFA) analysis to identify methanotrophic activity in members of the sedimentary microbial community in the Altamaha and Savannah River estuaries in Georgia. 13C-depleted PLFAs indicate methane utilizat...

  1. Sensing Cardiac Electrical Activity With a Cardiac Myocyte--Targeted Optogenetic Voltage Indicator

    NARCIS (Netherlands)

    Chang Liao, Mei-Ling; de Boer, Teun P; Mutoh, Hiroki; Raad, Nour; Richter, Claudia; Wagner, Eva; Downie, Bryan R; Unsöld, Bernhard; Arooj, Iqra; Streckfuss-Bömeke, Katrin; Döker, Stephan; Luther, Stefan; Guan, Kaomei; Wagner, Stefan; Lehnart, Stephan E; Maier, Lars S; Stühmer, Walter; Wettwer, Erich; van Veen, Toon; Morlock, Michael M; Knöpfel, Thomas; Zimmermann, Wolfram-Hubertus


    RATIONALE: Monitoring and controlling cardiac myocyte activity with optogenetic tools offer exciting possibilities for fundamental and translational cardiovascular research. Genetically encoded voltage indicators may be particularly attractive for minimal invasive and repeated assessments of cardiac

  2. Mid-infrared Spectral Indicators of Star Formation and Active Galactic Nucleus Activity in Normal Galaxies

    NARCIS (Netherlands)

    Treyer, Marie; Schiminovich, David; Johnson, Benjamin D.; O'Dowd, Matt; Martin, Christopher D.; Wyder, Ted; Charlot, Stephane; Heckman, Timothy; Martins, Lucimara; Seibert, Mark; van der Hulst, J. M.


    We investigate the use of mid-infrared (MIR) polycyclic aromatic hydrocarbon (PAH) bands, the continuum, and emission lines as probes of star formation (SF) and active galactic nucleus (AGN) activity in a sample of 100 "normal" and local (z similar to 0.1) emission-line galaxies. The MIR spectra wer

  3. Synergistic effect of vasoactive intestinal peptides on TNF-alpha-induced IL-6 synthesis in osteoblasts: amplification of p44/p42 MAP kinase activation. (United States)

    Natsume, Hideo; Tokuda, Haruhiko; Mizutani, Jun; Adachi, Seiji; Matsushima-Nishiwaki, Rie; Minamitani, Chiho; Kato, Kenji; Kozawa, Osamu; Otsuka, Takanobu


    We previously showed that tumor necrosis factor-alpha (TNF-alpha) stimulates synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, via p44/p42 mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase/Akt in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of vasoactive intestinal peptide (VIP) on TNF-alpha-induced IL-6 synthesis in these cells. VIP, which by itself slightly stimulated IL-6 synthesis, synergistically enhanced the TNF-alpha-induced IL-6 synthesis in MC3T3-E1 cells. The synergistic effect of VIP on the TNF-alpha-induced IL-6 synthesis was concentration-dependent in the range between 1 and 70 nM. We previously reported that VIP stimulated cAMP production in MC3T3-E1 cells. Forskolin, a direct activator of adenylyl cyclase, or 8-bromoadenosine-3',5'-cyclic monophosphate (8bromo-cAMP), a plasma membrane-permeable cAMP analogue, markedly enhanced the TNF-alpha-induced IL-6 synthesis as well as VIP. VIP markedly up-regulated the TNF-alpha-induced p44/p42 MAP kinase phosphorylation. The Akt phosphorylation stimulated by TNF-alpha was only slightly affected by VIP. PD98059, a specific inhibitor of MEK1/2, significantly suppressed the enhancement of TNF-alpha-induced IL-6 synthesis by VIP. The synergistic effect of a combination of VIP and TNF-alpha on the phosphorylation of p44/p42 MAP kinase was diminished by H-89, an inhibitor of cAMP-dependent protein kinase. These results strongly suggest that VIP synergistically enhances TNF-alpha-stimulated IL-6 synthesis via up-regulating p44/p42 MAP kinase through the adenylyl cyclase-cAMP system in osteoblasts.

  4. Active Video Games and Health Indicators in Children and Youth: A Systematic Review


    LeBlanc, Allana G; Jean-Philippe Chaput; Allison McFarlane; Colley, Rachel C; David Thivel; Biddle, Stuart J.H.; Ralph Maddison; Leatherdale, Scott T; Tremblay, Mark S.


    BACKGROUND: Active video games (AVGs) have gained interest as a way to increase physical activity in children and youth. The effect of AVGs on acute energy expenditure (EE) has previously been reported; however, the influence of AVGs on other health-related lifestyle indicators remains unclear. OBJECTIVE: This systematic review aimed to explain the relationship between AVGs and nine health and behavioural indicators in the pediatric population (aged 0-17 years). DATA SOURCES: Online databases...

  5. N-acetyl -β-D-glucosaminidase activity in cow milk as an indicator of mastitis. (United States)

    Hovinen, Mari; Simojoki, Heli; Pösö, Reeta; Suolaniemi, Jenni; Kalmus, Piret; Suojala, Leena; Pyörälä, Satu


    Activity of lysosomal N-acetyl-β-d-glucosaminidase (NAGase) in milk has been used as an indicator of bovine mastitis. We studied NAGase activity of 808 milk samples from healthy quarters and quarters of cows with spontaneous subclinical and clinical mastitis. Associations between milk NAGase activity and milk somatic cell count (SCC), mastitis causing pathogen, quarter, parity, days in milk (DIM) and season were studied. In addition, the performance of NAGase activity in detecting clinical and subclinical mastitis and distinguishing infections caused by minor and major bacteria was investigated. Our results indicate that NAGase activity can be used to detect both subclinical and clinical mastitis with a high level of accuracy (0·85 and 0·99). Incomplete correlation between NAGase activity and SCC suggests that a substantial proportion of NAGase activity comes from damaged epithelial cells of the udder in addition to somatic cells. We therefore recommend determination of NAGase activity from quarter foremilk after at least six hours from the last milking using the method described. Samples should be frozen before analysis. NAGase activity should be interpreted according to DIM, at least during the first month of lactation. Based on the results of the present study, a reference value for normal milk NAGase activity of 0·1-1·04 pmoles 4-MU/min/μl for cows with ≥30 DIM (196 samples) could be proposed. We consider milk NAGase activity to be an accurate indicator of subclinical and clinical mastitis. PMID:27210494


    Directory of Open Access Journals (Sweden)

    S. V. Melnikova


    Full Text Available Amylolytic activity indicators of oral liquid of dentists in different conditions of professional activity at outpatient dental care and lectures have been studied. We observed an increase in amylolytic activity of oral liquid of dentists men and women after outpatient dental care, that indicates the activation of the sympathetic-adrenal system in response to the professional stress. We also identified the gender-specific response to the α-amylase load in professional dentists: male amylolytic activity of oral fluid was higher than female. In the group of male and female dentist cadets we registered the decrease of amylolytic activity of oral fluid. The correlation analysis revealed a negative relationship between the level of α-amylase and rigidity in a group of male dentists. We suggested that male dentists reduced their adaptation to the psychosocial conditions under job stress. Keywords: dentist, professional activity, professional stress, outpatient dental care, lectures, amylolytic activity of oral fluid.

  7. PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPAR{gamma} activation in the liver

    Energy Technology Data Exchange (ETDEWEB)

    Oishi, Katsutaka, E-mail: [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Uchida, Daisuke [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki (Japan); Ohkura, Naoki [Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa (Japan); Horie, Shuichi [Department of Clinical Biochemistry, Kagawa Nutrition University, Sakado, Saitama (Japan)


    Research highlights: {yields} PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression. {yields} Hepatic expressions of PPAR{gamma} and PCG-1{alpha} are induced by a ketogenic diet. {yields} PPAR{gamma} antagonist attenuates a ketogenic diet-induced PAI-1 expression. {yields} Ketogenic diet advances the phase of circadian clock in a PPAR{alpha}-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPAR{alpha}-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPAR{alpha}-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPAR{alpha} target genes such as Cyp4A10 and FGF21 was damped in PPAR{alpha}-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPAR{alpha}-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPAR{alpha} activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPAR{gamma} and its coactivator PCG-1{alpha} were more effectively induced in PPAR{alpha}-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPAR{gamma} antagonist, in both WT and PPAR{alpha

  8. Analysis of the Heat Shock Response in Mouse Liver Reveals Transcriptional Dependence on the Nuclear Receptor Peroxisome Proliferator-Activated Receptor alpha (PPARα) (United States)

    BACKGROUND: The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) regulates responses to chemical or physical stress in part by altering expression of genes involved in proteome maintenance. Many of these genes are also transcriptionally regulated by h...

  9. Development of Rapid Radiochemical Method for Gross Alpha and Gross Beta Activity Concentration in Flowback and Produced Waters from Hydraulic Fracturing Operations (United States)

    This report summarizes the development and validation of an improved method for the Determination of Gross Alpha and Gross Beta Activity in Flowback and Produced Waters from Hydraulic Fracturing Operations (FPWHFO). Flowback and produced waters are characterized by high concentra...

  10. Low-level electrical currents and brain indicators of behavioral activation

    Directory of Open Access Journals (Sweden)

    F. Lolas


    Full Text Available Distinguishing between slow brain potential correlates of arousal and activation on the basis of their functional role and temporal involvement during a reaction-time task, data are presented which suggest that weak electrical polarizing currents applied to the head in human subjects modify predominantly activation indicators rather than arousal ones.

  11. Modulation of Posterior Alpha Activity by Spatial Attention Allows for Controlling A Continuous Brain-Computer Interface. (United States)

    Horschig, Jörn M; Oosterheert, Wouter; Oostenveld, Robert; Jensen, Ole


    Here we report that the modulation of alpha activity by covert attention can be used as a control signal in an online brain-computer interface, that it is reliable, and that it is robust. Subjects were instructed to orient covert visual attention to the left or right hemifield. We decoded the direction of attention from the magnetoencephalogram by a template matching classifier and provided the classification outcome to the subject in real-time using a novel graphical user interface. Training data for the templates were obtained from a Posner-cueing task conducted just before the BCI task. Eleven subjects participated in four sessions each. Eight of the subjects achieved classification rates significantly above chance level. Subjects were able to significantly increase their performance from the first to the second session. Individual patterns of posterior alpha power remained stable throughout the four sessions and did not change with increased performance. We conclude that posterior alpha power can successfully be used as a control signal in brain-computer interfaces. We also discuss several ideas for further improving the setup and propose future research based on solid hypotheses about behavioral consequences of modulating neuronal oscillations by brain computer interfacing. PMID:25388661

  12. Xalpha-DVM investigation of double water molecule interactions with active sites of alpha- and beta-subunits of hemoglobin (United States)

    Yuryeva, Elmira I.

    In this work, the results of Xalpha-discrete variation method calculations of the electronic structure and interatomic parameters of chemical bonding between iron (II) and oxygen molecule with and without extra electrons and protons in active site (AS) of alpha- and beta-subunits of oxyhemoglobin are presented. The Skulachev model of O2 molecule existing in respiration medium in the 2H2O form was used. The introduction of extra electrons does not change considerably the interaction of the iron atom with the O2 oxygen molecule, but strengthens the repulsion in the Fe bond N bonds. In this case, the estimated effective charge of the iron atom is +1.8/1.5e for AS of alpha-/beta-subunits of oxyhemoglobin, and the magnetic moment of iron atoms becomes zero. The deoxygenation effect of the AS of the alpha- and beta-subunits of oxyhemoglobin is due to the ability of extra protons to break down covalent attraction between the iron atom and the nearest oxygen atom and also to weakening of the repulsive component of the covalent Fe bond N interactions.

  13. Modelling Dynamics of Main Indicators of Economic Activity of Households of Ukraine

    Directory of Open Access Journals (Sweden)

    Zhuk Mykola O.


    Full Text Available The goal of the article is the study of the structure of the system of economic activity of households in Ukraine and dynamics of interconnections between the main indicators of its functioning. In order to study dynamics of main indicators of the system of economic activity of households, the article uses tools of econometric vector-autoregression modelling (VAR models. Based on the existing statistical data and a developed VAR model, the article studies individual and aggregate influence of lag values of indicators upon their current values, system reaction on main indicators impulses, analyses dynamics of change of explanation of dispersion of some indicators with others, and conducts two types of forecasts that reflect a general tendency of development of economic activity of households in Ukraine. High accuracy of forecasts obtained with the help of the proposed econometric model testifies to a possibility of its practical application for assessment of the state of main indicators of economic activity of households of Ukraine. The article applies for the first time the tools of VAR modelling for the study of economic activity of households in Ukraine, which expands possibilities of use of mathematical and statistical methods and models in this field of economy.

  14. Antioxidant activity of flavonoids: a QSAR modeling using Fukui indices descriptors. (United States)

    Djeradi, Houria; Rahmouni, Ali; Cheriti, Abdelkrim


    A QSAR model to predict the antioxidant activity of flavonoid compounds was developed. New electronic structure descriptors which are Fukui indices are correlated to the radical scavenging of flavonoids. These indices are obtained at DFT/B3LYP level of chemical quantum theory. The logIC50 experimental values of antioxidant activity are taken from the literature. The model is based on the multilinear regression method. Both experimental and calculated data of 36 flavonoids compounds were analyzed. A good correlation coefficient (R(2) = 0.8159) is obtained and the antioxidant activities of test compounds are well predicted. PMID:25311723

  15. Estrogen receptor alpha activation enhances mitochondrial function and systemic metabolism in high-fat-fed ovariectomized mice. (United States)

    Hamilton, Dale J; Minze, Laurie J; Kumar, Tanvi; Cao, Tram N; Lyon, Christopher J; Geiger, Paige C; Hsueh, Willa A; Gupte, Anisha A


    Estrogen impacts insulin action and cardiac metabolism, and menopause dramatically increases cardiometabolic risk in women. However, the mechanism(s) of cardiometabolic protection by estrogen remain incompletely understood. Here, we tested the effects of selective activation of E2 receptor alpha (ERα) on systemic metabolism, insulin action, and cardiac mitochondrial function in a mouse model of metabolic dysfunction (ovariectomy [OVX], insulin resistance, hyperlipidemia, and advanced age). Middle-aged (12-month-old) female low-density lipoprotein receptor (Ldlr)(-/-) mice were subjected to OVX or sham surgery and fed "western" high-fat diet (WHFD) for 3 months. Selective ERα activation with 4,4',4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl) (PPT), prevented weight gain, improved insulin action, and reduced visceral fat accumulation in WHFD-fed OVX mice. PPT treatment also elevated systemic metabolism, increasing oxygen consumption and core body temperature, induced expression of several metabolic genes such as peroxisome proliferator-activated receptor gamma, coactivator 1 alpha, and nuclear respiratory factor 1 in heart, liver, skeletal muscle, and adipose tissue, and increased cardiac mitochondrial function. Taken together, selective activation of ERα with PPT enhances metabolic effects including insulin resistance, whole body energy metabolism, and mitochondrial function in OVX mice with metabolic syndrome. PMID:27582063

  16. Physical activity is not associated with spirometric indices in lung-healthy German youth. (United States)

    Smith, Maia P; von Berg, Andrea; Berdel, Dietrich; Bauer, Carl-Peter; Hoffmann, Barbara; Koletzko, Sibylle; Nowak, Dennis; Heinrich, Joachim; Schulz, Holger


    In lung disease, physical activity improves lung function and reduces morbidity. However, healthy populations are not well studied. We estimate the relationship between spirometric indices and accelerometric physical activity in lung-healthy adolescents.895 nonsmoking German adolescents without chronic lung disease (45% male, mean±sd age 15.2±0.26 years) from the GINIplus and LISAplus cohorts completed questionnaires, spirometry, 7-day accelerometry and an activity diary. Physical activity was measured as minutes, quintiles and regularity of daily moderate, vigorous and moderate-to-vigorous physical activity (MVPA), participation in sport and active commuting to school. Primary outcomes were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow at 25-75% of FVC; they were separately correlated with physical activity and adjusted for confounders of respiratory function, including early-life exposures.Adolescents averaged 40 min MVPA per day, typical for European youth. 79% participated in sports and 51% commuted actively. An association was suggested between 3% higher FVC (∼100 mL) and either extreme MVPA quintile or percentage of days with >30 min MVPA (plifestyle and physical activity were nonsignificant.Spirometric indices were not significantly associated with active lifestyle or measures of activity in lung-healthy adolescents after adjustment for confounding and multiple-comparison artefacts. PMID:27009173

  17. Role of SSNTD technique in three-step method for total assay of alpha activity in air effluents

    International Nuclear Information System (INIS)

    In the present work, low levels of alpha activity in air effluents were estimated. Currently this essay involves collection of effluent samples and assaying them for the release using ZnS(Ag) based scintillation counter (background=1 cpm). Any activity below 1 cpm (net) therefore goes unreported. Air samples showing activity -6 Bq/m3 (3.73x10-17 Ci/m3) to 36.41x10-6 Bq/m3 (9.84x10-16 Ci/m3) for samples studied over twelve months period. The three step procedure helps to measure total activity without significant burden on SSNTD technique thereby improving the acceptability of the methodology. (author)

  18. Evidence for preferential repair of 3-carbethoxypsoralen plus UVA induced DNA lesions in the active MAT alpha locus in Saccharomyces cerevisiae using the UvrABC assay. (United States)

    Méniel, V; Brouwer, J; Averbeck, D


    The occurrence of preferential repair in Saccharomyces cerevisiae of the active MAT alpha locus compared with the inactive HML alpha locus was confirmed after 254 nm UV irradiation. Experiments carried out using the UvrABC excinuclease assay with the monofunctional furocoumarin 3-carbethoxypsoralen (3-CPs) plus UVA radiation which induce mainly monoadducts in DNA demonstrated preferential repair of the active MAT alpha locus compared with the inactive HML alpha locus in a SIR+ strain. However, as after 254 nm UV irradiation, no difference in the rate of removal of 3-CPs plus UVA induced lesions was observed between the two loci in the sir-3 mutant in which both loci are active. Thus, it appears that 3-CPs plus UVA induced monoadducts as well as pyrimidine dimers are subject to preferential repair.

  19. DMPD: Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and controlof anti-tumor activity in primary macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16846591 Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and controlof anti-tumor activit...Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and controlof anti-tumor activity... IFN-alpha gene regulation and controlof anti-tumor activity in primary macrophages. Authors Solis M, Goubau

  20. Vasodilator activity of 2-(p-chloro-alpha-hydroxybenzyl)benzimidazole (HBBPC) on femoral vascular bed of the rabbit. (United States)

    Demenge, P; Silice, C; Luu Duc, C; Carraz, G


    The effects of 2-(p-chloro-alpha-hydroxybenzyl) benzimidazole HCl (HBBPC) have been studied on the femoral peripheral resistance (i.v. route) and only femoral blood flow (local i.a. injection), in comparison with other vasodilators, i.e., sodium nitroprusside, dihydralazine and piribedil. The vasomotor activity of HBBPC, namely, decreased peripheral resistance and increased femoral blood flow, seems interesting because it begins after pressure has returned to normal. This substance is likely to induce a vasoconstriction in other areas (increased femoral blood flow with decreased peripheral resistance without a fall of blood pressure).

  1. AMP-activated protein kinase is required for the anti-adipogenic effects of alpha-linolenic acid


    Zhou, Xihong; Wu, Weiche; Chen, Jingqing; Wang, Xinxia; Wang, Yizhen


    Background n-3 long chain polyunsaturated fatty acid (n-3 LC PUFA) increases β-oxidation and limits lipid accumulation in adipocytes. The current study was conducted to determine whether their precursor alpha-linolenic acid (ALA) could also exert the above effects and how AMP-activated protein kinase (AMPK) was involved. Methods AMPKα1−/−, AMPKα2−/− mice and wild-type (WT) mice were fed a high-fat diet (HFD) or HFD with ALA. Body weight was recorded weekly and serum was collected. Adipocytes ...

  2. Impacts of Human Activity on Biodiversity——An Approach to Driving Force indicators

    Institute of Scientific and Technical Information of China (English)

    RichardDawson; CaoZhiping


    The impact of human activity on biodiversity is very complicated, making it difficult to design practical indicators for assessment. Currently, state and response indicators are listed within Chapter 15 of Agenda 21, but no mention is made of driving force indicators and how they relate to biodiversity protection. This paper represents an effort to identify and then operationalize the idea of driving force indicators at national level. Five human induced factors affecting blodiversity were discussed: (a) habitat toss and fragmentation; (b) overexploitation of resources; (c) species introduction; (d) pollution; and (e) climate change. From these five factors, a subset was selected to serve as possible driving force indicators: (1) habitat loss, (2) the ratio of exotic species to indigenous ones, and (3) the change in pollution status. Although the three indicators are relatively simple, they cover the most important human impacts on biodiversity and offer the potential for further redefinition and ultimate use within the spirit of biodiversity protection.

  3. LaaA, a novel high-active alkalophilic alpha-amylase from deep-sea bacterium Luteimonas abyssi XH031(T). (United States)

    Song, Qinghao; Wang, Yan; Yin, Chong; Zhang, Xiao-Hua


    Alpha-amylase is a kind of broadly used industrial enzymes, most of which have been exploited from terrestrial organism. Comparatively, alpha-amylase from marine environment was largely undeveloped. In this study, a novel alkalophilic alpha-amylase with high activity, Luteimonas abyssi alpha-amylase (LaaA), was cloned from deep-sea bacterium L. abyssi XH031(T) and expressed in Escherichia coli BL21. The gene has a length of 1428bp and encodes 475 amino acids with a 35-residue signal peptide. The specific activity of LaaA reached 8881U/mg at the optimum pH 9.0, which is obvious higher than other reported alpha-amylase. This enzyme can remain active at pH levels ranging from 6.0 to 11.0 and temperatures below 45°C, retaining high activity even at low temperatures (almost 38% residual activity at 10°C). In addition, 1mM Na(+), K(+), and Mn(2+) enhanced the activity of LaaA. To investigate the function of potential active sites, R227G, D229K, E256Q/H, H327V and D328V mutants were generated, and the results suggested that Arg227, Asp229, Glu256 and Asp328 were total conserved and essential for the activity of alpha-amylase LaaA. This study shows that the alpha-amylase LaaA is an alkali-tolerant and high-active amylase with strong potential for use in detergent industry. PMID:27241296

  4. Forecasting Economic Activity in Germany – How Useful are Sentiment Indicators?


    Schröder, Michael; Hüfner, Felix P.


    We analyze four economic sentiment indicators for the German economy regarding their ability to forecast economic activity. Using cross correlations and Granger causality tests we find that the ifo business expectations (ifo), the Purchasing Managers Index (PMI) and the ZEW Indicator of Economic Sentiment (ZEW) lead the year-on-year growth rate of German industrial production by five months. Taking into account the publication lag of industrial production this lead is even larger. On the cont...

  5. Functional properties of the CaV1.2 calcium channel activated by calmodulin in the absence of alpha2delta subunits. (United States)

    Ravindran, Arippa; Kobrinsky, Evgeny; Lao, Qi Zong; Soldatov, Nikolai M


    Voltage-activated CaV1.2 calcium channels require association of the pore-forming alpha1C subunit with accessory CaVbeta and alpha2delta subunits. Binding of a single calmodulin (CaM) to alpha1C supports Ca2+-dependent inactivation (CDI). The human CaV1.2 channel is silent in the absence of CaVbeta and/or alpha2delta. Recently, we found that coexpression of exogenous CaM (CaMex) supports plasma membrane targeting, gating facilitation and CDI of the channel in the absence of CaVbeta. Here we discovered that CaMex and its Ca2+-insensitive mutant (CaM1234) rendered active alpha1C/CaVbeta channel in the absence of alpha2delta. Coexpression of CaMex with alpha1C and beta2d in calcium-channel-free COS-1 cells recovered gating of the channel and supported CDI. Voltage-dependence of activation was shifted by approximately +40 mV to depolarization potentials. The calcium current reached maximum at +40 mV (20 mM Ca2+) and exhibited approximately 3 times slower activation and 5 times slower inactivation kinetics compared to the wild-type channel. Furthermore, both CaMex and CaM1234 accelerated recovery from inactivation and induced facilitation of the calcium current by strong depolarization prepulse, the properties absent from the human vascular/neuronal CaV1.2 channel. The data suggest a previously unknown action of CaM that in the presence of CaVbeta; translates into activation of the alpha2delta-deficient calcium channel and alteration of its properties. PMID:19106618

  6. Parallax-sensitive remapping of visual space in occipito-parietal alpha-band activity during whole-body motion. (United States)

    Gutteling, T P; Selen, L P J; Medendorp, W P


    Despite the constantly changing retinal image due to eye, head, and body movements, we are able to maintain a stable representation of the visual environment. Various studies on retinal image shifts caused by saccades have suggested that occipital and parietal areas correct for these perturbations by a gaze-centered remapping of the neural image. However, such a uniform, rotational, remapping mechanism cannot work during translations when objects shift on the retina in a more complex, depth-dependent fashion due to motion parallax. Here we tested whether the brain's activity patterns show parallax-sensitive remapping of remembered visual space during whole-body motion. Under continuous recording of electroencephalography (EEG), we passively translated human subjects while they had to remember the location of a world-fixed visual target, briefly presented in front of or behind the eyes' fixation point prior to the motion. Using a psychometric approach we assessed the quality of the memory update, which had to be made based on vestibular feedback and other extraretinal motion cues. All subjects showed a variable amount of parallax-sensitive updating errors, i.e., the direction of the errors depended on the depth of the target relative to fixation. The EEG recordings show a neural correlate of this parallax-sensitive remapping in the alpha-band power at occipito-parietal electrodes. At parietal electrodes, the strength of these alpha-band modulations correlated significantly with updating performance. These results suggest that alpha-band oscillatory activity reflects the time-varying updating of gaze-centered spatial information during parallax-sensitive remapping during whole-body motion. PMID:25505108

  7. Inhibition of human plasma and serum butyrylcholinesterase (EC by alpha-chaconine and alpha-solanine. (United States)

    Nigg, H N; Ramos, L E; Graham, E M; Sterling, J; Brown, S; Cornell, J A


    The purpose of these experiments was to determine the reversibility of alpha-chaconine and alpha-solanine inhibition of human plasma butyrylcholinesterase (BuChE). For the substrate alpha-naphthylacetate, optimal assay conditions were 0.50 M sodium phosphate buffer and a substrate concentration of 3-5 x 10(-4) M. Dibucaine (1 x 10(-5) M) indicated the usual phenotype for all subjects; alpha-chaconine and alpha-solanine at 2.88 x 10(-6) M inhibited BuChE about 70 and 50%, respectively. One- and 24-hr incubations at 1 x 10(-5) M with alpha-chaconine, alpha-solanine, paraoxon, eserine, and ethanol yielded reversible inhibition with dilution except for paraoxon. Twenty-four-hour dialyses of incubations showed no inhibition except for paraoxon. PAGE enzyme activity gels of 1- and 24-hr incubations also showed no inhibition except for paraoxon. alpha-Chaconine and alpha-solanine are reversible inhibitors of human butyrylcholinesterase. At estimated tissue levels, alpha-chaconine, alpha-solanine, and solanidine inhibited BuChE 10-86%. In assays which combined alpha-chaconine, alpha-solanine, and solanidine, inhibition of BuChE was less than additive. No inhibition of albumin alpha-naphthylacetate esterase (an arylesterase) was noted with any inhibitor. The importance of these data to adverse toxicological effects of potato alkaloids is discussed.

  8. Usefulness of Endoscopic Indices in Determination of Disease Activity in Patients with Crohn’s Disease

    Directory of Open Access Journals (Sweden)

    Marcin Kucharski


    Full Text Available Background. Assessment of endoscopic activity of Crohn’s disease (CD is of growing importance both in clinical practice and in clinical trials. The study aimed to assess which of the endoscopic indices used for evaluation of mucosal changes correlates with the currently used clinical indices for determination of disease activity and with the results of histopathological examination. Study. A group of 71 patients with CD and 52 individuals without a diagnosis of GI tract disease as a control group were investigated, considering clinical and histological severity of the disease and the severity of inflammatory changes in the bowel. Evaluation was conducted with the use of clinical, endoscopic, and histopathological indices. Endoscopic indices were then correlated with different clinical and histopathological indices with the aim of finding the strongest correlations. Results and Conclusions. Correlation between the clinical disease activity and the severity of endoscopic lesions in CD was shown in this study to be poor. The results also indicate that the optimal endoscopic index used in the diagnostic stage and in the assessment of treatment effects in CD is Simple Endoscopic Score for Crohn’s Disease (SES-CD.

  9. Synthesis, Characterization and Biological Activities of a New Fluorescent Indicator for the Intracellular Calcium Ions

    Institute of Scientific and Technical Information of China (English)

    HE Huaizhen; LEI Lei; LI Jianli; SHI Zhen


    A novel calcium-selective fluorescent indicator Fluo-3M AM was synthesized by introduction of a methyl group into the Ca2+-chelating moiety and adequately characterized by spectral methods (1H NMR, GC-MS, IR and MALDI-TOF MS). Meanwhile, its fluorescence spectra and some biological activities have been also studied. The results indicate that the new fluorescent indicator has relatively high affinity to calcium and a strong fluorescence signal, which should be useful for biomedical researchers to investigate the effects of calcium ions in biosystems.

  10. Blood coagulation parameters and activity indices in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    A. A. Arshinov


    Full Text Available Objective. To assess coagulation parameters and activity indices in pts with systemic lupus erythematosus (SLE. Material and methods . 86 pts with SLE (83 female and 3 male were examined. 12 of them had antiphospholipid syndrome. Mean age was 35,9±1,5 years (from 18 to 58 years, mean disease duration was 9,8+1,4 years. Control group consisted of 60 healthy volunteers with mean age 37,1+4,1 years. SLE activity assessment was performed with SLAM, SLEDAI and ECLAM indices. Results. SLE pts showed 5-fold (p<0,01 increase of spontaneous platelets aggregation and more than 3-fold increase of factor von Willebrand antigen (FWA concentration. Platelet activation in pts was accompanied by decrease of platelet aggregation with collagen (on 27%, p<0,01. Characteristic sign of coagulation hemostasis activation was significant increase of soluble fibrin-monomer complexes (SFMC concentration on 81 % (p<0,01 so as increase D-dimers level in 53,3% of pts. Fibrinogen concentration was increased on 29%, spontaneous fibrinolysis parameters were decreased on 20%, antithrombin (AT 111 - on 21% in comparison with control. Direct correlation between activity indiccs and SFMC(ECLAM, r=0,5, fibrinogen concentration (SLAM, r=0,34, D- dimers level (ECLAM, r=0,5, spontaneous platelet aggregation (ECLAM, r=0,5 so as inverse correlation with AT III activity (SLEDAI, r-0,73 was revealed. Conclusion. Changes of hemostasis parameters in SLE may serve as predictors of thrombotic disorders development and indication to drug correction of blood coagulation disorders. Direct correlation between blood coagulation system activity and indices of SLE activity.

  11. The influence of economic indicators over the management activities for company in sports


    Sebahattin DEVECIOGLU; Laurentiu-Gabriel TALAGHIR; Teodora Mihaela ICONOMESCU; Carmen CRETU


    The sports activities permanently have attracted investors' attention because the target audience is very varied. Whether they are addressing for sports performance or for sport for all, the companies which provide services or products want to gain the profits. To achieve profits, managers should consider about elements of the company's evolution to profitability besides market demand. The purpose of our paper is that to show some economic indicators which are useful in management activities....

  12. Gross alpha and beta activity analyses in urine-a routine laboratory method for internal human radioactivity detection. (United States)

    Chen, Xiaowen; Zhao, Luqian; Qin, Hongran; Zhao, Meijia; Zhou, Yirui; Yang, Shuqiang; Su, Xu; Xu, Xiaohua


    The aim of this work was to develop a method to provide rapid results for humans with internal radioactive contamination. The authors hypothesized that valuable information could be obtained from gas proportional counter techniques by screening urine samples from potentially exposed individuals rapidly. Recommended gross alpha and beta activity screening methods generally employ gas proportional counting techniques. Based on International Standards Organization (ISO) methods, improvements were made in the evaporation process to develop a method to provide rapid results, adequate sensitivity, and minimum sample preparation and operator intervention for humans with internal radioactive contamination. The method described by an American National Standards Institute publication was used to calibrate the gas proportional counter, and urine samples from patients with or without radionuclide treatment were measured to validate the method. By improving the evaporation process, the time required to perform the assay was reduced dramatically. Compared with the reference data, the results of the validation samples were very satisfactory with respect to gross-alpha and gross-beta activities. The gas flow proportional counting method described here has the potential for radioactivity monitoring in the body. This method was easy, efficient, and fast, and its application is of great utility in determining whether a sample should be analyzed by a more complicated method, for example radiochemical and/or γ-spectroscopy. In the future, it may be used commonly in medical examination and nuclear emergency treatment.Health Phys. 106(5):000-000; 2014.

  13. Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: an experimental study

    Directory of Open Access Journals (Sweden)

    Alper Murat


    Full Text Available Abstract Background Peroxisome proliferators-activated receptor alpha (PPARα activation modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of short-term administration of fenofibrate, a PPARα agonist, on proinflammatory cytokines, apoptosis, and hepatocellular damage in cholestasis. Methods Forty male Wistar rats were randomly divided into four groups: I = sham operated, II = bile duct ligation (BDL, III = BDL + vehicle (gum Arabic, IV = BDL + fenofibrate (100 mg/kg/day. All rats were sacrificed on 7th day after obtaining blood samples and liver tissue. Total bilirubin, aminotransferase (AST, alanine aminotransferase (ALT and alkaline phosphatase (ALP, gamma-glutamyl transferase, (GGT, tumor necrosis factor alpha (TNF-α, interleukin 1 beta (IL-1 β, and total bile acid (TBA in serum, and liver damage scores; portal inflammation, necrosis, bile duct number, in liver tissue were evaluated. Apoptosis in liver was also assessed by immunohistochemical staining. Results Fenofibrate administration significantly reduced serum total bilirubin, AST, ALT, ALP, and GGT, TNF-α, IL-1 β levels, and TBA (P P P P Conclusion Short-term administration of fenofibrate to the BDL rats exerts beneficial effects on hepatocellular damage and apoptosis.

  14. Evaluation of potential implication of membrane estrogen binding sites on ERE-dependent transcriptional activity and intracellular estrogen receptor-alpha regulation in MCF-7 breast cancer cells. (United States)

    Seo, Hye Sook; Leclercq, Guy


    The potential involvement of membrane estrogen binding sites in the induction of ERE-dependent transcriptional activity as well as in the regulation of intracellular estrogen receptor alpha (ER-alpha) level under estradiol (E2) stimulation was investigated. Our approach relied upon the use of two DCC-treated E2-BSA (bovine serum albumin) solutions (E2-6-BSA and E2-17-BSA). The absence of detectable free E2 in these solutions was established. Both E2-BSA conjugates led to a transient dose-dependent stimulation of the expression of ERE-luciferase (LUC) reporter gene in MVLN cells (MCF-7 cells stably transfected with a pVit-tk-LUC reporter plasmid), a property not recorded with free E2, which maintained enhanced transcriptional activity during the whole experiment. A very low concentration of E2 (10 pM) synergistically acted with E2-BSA conjugates. Hence, ERE-dependent transcriptional activity induced by these conjugates appeared to result from their known interactions with membrane estrogen binding sites. Anti-estrogens (AEs: 4-OH-TAM and RU 58,668), which antagonize genomic ER responses, abrogated the luciferase activity induced by E2-BSA conjugates, confirming a potential relationship between membrane-related signals and intracellular ER. Moreover, induction of luciferase was recorded when the cells were exposed to IBMX (3-isobutyl-1-methylxanthine) and cyclic nucleotides (cAMP/cGMP), suggesting the implication of the latter in the signal transduction pathway leading to the expression of the reporter gene. Growth factors (IGF-I, EGF and TGF-alpha) also slightly stimulated luciferase and synergistically acted with 10 pM E2, or 1 microM E2-BSA conjugates, in agreement with the concept of a cross-talk between steroids and peptides acting on the cell membrane. Remarkably, E2-BSA conjugates, IBMX and all investigated growth factors failed to down-regulate intracellular ER in MCF-7 cells, indicating the need for a direct intracellular interaction of the ligand with the

  15. Technology and industrialization in Spanish economy from 1950 to 1960: the patents as technological activity indicators

    International Nuclear Information System (INIS)

    The goal of this research is to study the innovative activity developed in the fifties by the Spanish industry focussing on the foreign technology incorporated in the activity of several industrial sectors. The structure of innovation in each sector has been characterized by using patents as technological activity indicators. The data of patents registered in Spain belonging to the 1950-1960 period have been obtained taking into account the research developed by the Department of Business Administration of the Universidad Politecnica de Madrid through a subsidy granted by the Spanish Patent Office. (Author)

  16. Measuring Innovation Oriented Activities for Business Services: Traditional versus Knowledge Based Indicators


    Steiner, Michael


    Measuring Innovation Oriented Activities: Traditional versus Knowledge Based Indicators and their Differences across Sectors Michael STEINER, Christoph ADAMETZ, Mirjam NOVAKOVIC, Institute of Technology and Regional Policy, JOANNEUM RESEARCH, Elisabethstrasse 20/II, 8010 Graz, Austria and Department of Economics, Karl-Franzens-Universität Graz, Universitätsstraße 15/4, 8010 Graz E-Mail: , , Indicato...

  17. The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project)

    NARCIS (Netherlands)

    Helliwell, P.S.; Fitzgerald, O.; Fransen, J.; Gladman, D.D.; Kreuger, G.G.; Callis-Duffin, K.; McHugh, N.; Mease, P.J.; Strand, V.; Waxman, R.; Azevedo, V.F.; Beltran Ostos, A.; Carneiro, S.; Cauli, A.; Espinoza, L.R.; Flynn, J.A.; Hassan, N.; Healy, P.; Kerzberg, E.M.; Lee, Y.J.; Lubrano, E.; Marchesoni, A.; Marzo-Ortega, H.; Porru, G.; Moreta, E.G.; Nash, P.; Raffayova, H.; Ranza, R.; Raychaudhuri, S.P.; Roussou, E.; Scarpa, R.; Song, Y.W.; Soriano, E.R.; Tak, P.P.; Ujfalussy, I.; Vlam, K. de; Walsh, J.A.


    OBJECTIVE: To develop new composite disease activity indices for psoriatic arthritis (PsA). METHODS: Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to chang

  18. Indicators technology competitive activities of varying skill karate style «kyokushin»

    Directory of Open Access Journals (Sweden)

    Natalya Boychenko


    Full Text Available Purpose: to identify the main indicators of the art of competitive activity karate different qualifications style «kyokushin» and identify their differences. Material and Methods: analysis of video recordings of highly competitive activity karate; teacher observations; methods of mathematical statistics. Results: based on the analysis of video recordings of competitive activity created a model of technical preparedness karate qualifications. The differences in the technique of competitive activity karate different qualifications. Conclusions: it was found a series of karate techniques with different skills, their frequency of use and effectiveness. Confirmed that in the competitive fight karate qualifications dominated series techniques. It is found that the technique of competitive activity highly skilled athletes is very varied combinations strikes in series of two or three strikes and more.

  19. Quality of life and physical activity as indicators of health-preserving competence of teachers

    Directory of Open Access Journals (Sweden)

    Pavlova Iu.A.


    Full Text Available The quality of life and physical activity of teachers of physical culture, basic of health, labour, the defense of Motherland and pedagogue-organizers from secondary schools Lviv region (Ukraine were investigated. The 402 persons (age 24-78 years were surveyed with the use of questionnaires MOS SF 36 and IPAQ. The highest quality of life and level of physical activity have teachers of physical culture. It is considered the quality of life of teachers of other subjects similar to persons with chronic diseases. The level of physical activity in leisure time was particularly low for teachers of Basic of Health and pedagogue-organizers. The teachers spent no more than 433 MET-min/ week for moderate- and vigorous-intensity activity. The level of physical activity of teachers (besides the physical education teachers was insufficient to improve health and indicate about low level of health-preserving competence.

  20. Adverse effects of AMP-activated protein kinase alpha2-subunit deletion and high-fat diet on heart function and ischemic tolerance in aged female mice. (United States)

    Slámová, K; Papoušek, F; Janovská, P; Kopecký, J; Kolář, F


    AMP-activated protein kinase (AMPK) plays a role in metabolic regulation under stress conditions, and inadequate AMPK signaling may be also involved in aging process. The aim was to find out whether AMPK alpha2-subunit deletion affects heart function and ischemic tolerance of adult and aged mice. AMPK alpha2(-/-) (KO) and wild type (WT) female mice were compared at the age of 6 and 18 months. KO mice exhibited subtle myocardial AMPK alpha2-subunit protein level, but no difference in AMPK alpha1-subunit was detected between the strains. Both alpha1- and alpha2-subunits of AMPK and their phosphorylation decreased with advanced age. Left ventricular fractional shortening was lower in KO than in WT mice of both age groups and this difference was maintained after high-fat feeding. Infarct size induced by global ischemia/reperfusion of isolated hearts was similar in both strains at 6 months of age. Aged WT but not KO mice exhibited improved ischemic tolerance compared with the younger group. High-fat feeding for 6 months during aging abolished the infarct size-reduction in WT without affecting KO animals; nevertheless, the extent of injury remained larger in KO mice. The results demonstrate that adverse effects of AMPK alpha2-subunit deletion and high-fat feeding on heart function and myocardial ischemic tolerance in aged female mice are not additive. PMID:26596312

  1. Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans. (United States)

    Valle, Marta; Maqueda, Ana Elda; Rabella, Mireia; Rodríguez-Pujadas, Aina; Antonijoan, Rosa Maria; Romero, Sergio; Alonso, Joan Francesc; Mañanas, Miquel Àngel; Barker, Steven; Friedlander, Pablo; Feilding, Amanda; Riba, Jordi


    Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimentally. Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans. We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind randomized placebo-controlled study involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic users (5 females) participated in four experimental sessions in which they received the following drug combinations: placebo+placebo, placebo+ayahuasca, ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power decreases in the delta, theta and alpha frequency bands. Current density in alpha-band oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca. Pretreatment with ketanserin inhibited neurophysiological modifications, reduced the correlation between alpha and visual effects, and attenuated the intensity of the subjective experience. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans. PMID:27039035

  2. EASY-II: a system for modelling of n, d, p, {\\gamma} and {\\alpha} activation and transmutation processes

    CERN Document Server

    Sublet, Jean-Christophe; Morgan, Guy; Koning, Arjan; Rochman, Dimitri


    EASY-II is designed as a functional replacement for the previous European Activation System, EASY-2010. It has extended nuclear data and new software, FISPACT-II, written in object-style Fortran to provide new capabilities for predictions of activation, transmutation, depletion and burnup. The new FISPACT-II code has allowed us to implement many more features in terms of energy range, up to GeV; incident particles: alpha, gamma, proton, deuteron and neutron; and neutron physics: self-shielding effects, temperature dependence, pathways analysis, sensitivity and error estimation using covariance data. These capabilities cover most application needs: nuclear fission and fusion, accelerator physics, isotope production, waste management and many more. In parallel, the maturity of modern general-purpose libraries such as TENDL-2012 encompassing thousands of target nuclides, the evolution of the ENDF format and the capabilities of the latest generation of processing codes PREPRO-2012, NJOY2012 and CALENDF-2010 have ...

  3. Evaluating practicability of an LSC method for routine monitoring gross alpha and beta activities in water samples in Taiwan

    International Nuclear Information System (INIS)

    A procedure using liquid scintillation counting for the monitoring of gross alpha and beta activities in environmental water was implemented to improve the conventional procedure using GFPC adopted in Taiwan. The new procedure was acquired through calibration and validation, and then was applied to the monitoring of surface water in Taiwan. This procedure can improve 2–4 times of detection efficiencies and takes only 70–80% of analysis time with reliable accuracy. With these features, the newly developed procedure is favorable during emergency situations. - Highlights: ► An improvement of the monitoring of gross α/β activities in water in Taiwan. ► Improving 2–4 times of detection efficiencies and taking 70–80% of analysis time. ► Twenty three sites of surface water were monitored after the Fukushima accident.

  4. H-alpha Activity of Old M Dwarfs: Stellar Cycles and Mean Activity Levels For 93 Low-Mass Stars in the Solar Neighborhood

    CERN Document Server

    Robertson, Paul; Cochran, William D; Dodson-Robinson, Sarah E


    Through the McDonald Observatory M Dwarf Planet Search, we have acquired nearly 3,000 high-resolution spectra of 93 late-type (K5-M5) stars over more than a decade using HET/HRS. This sample provides a unique opportunity to investigate the occurrence of long-term stellar activity cycles for low-mass stars. In this paper, we examine the stellar activity of our targets as reflected in the H-alpha feature. We have identified periodic signals for 6 stars, with periods ranging from days to more than 10 years, and find long-term trends for 7 others. Stellar cycles with P > 1 year are present for at least 5% of our targets. Additionally, we present an analysis of the time-averaged activity levels of our sample, and search for correlations with other stellar properties. In particular, we find that more massive, earlier type (M0-M2) stars tend to be more active than later type dwarfs. Furthermore, high-metallicity stars tend to be more active at a given stellar mass. We also evaluate H-alpha variability as a tracer of...

  5. Active video games and health indicators in children and youth: a systematic review.

    Directory of Open Access Journals (Sweden)

    Allana G LeBlanc

    Full Text Available BACKGROUND: Active video games (AVGs have gained interest as a way to increase physical activity in children and youth. The effect of AVGs on acute energy expenditure (EE has previously been reported; however, the influence of AVGs on other health-related lifestyle indicators remains unclear. OBJECTIVE: This systematic review aimed to explain the relationship between AVGs and nine health and behavioural indicators in the pediatric population (aged 0-17 years. DATA SOURCES: Online databases (MEDLINE, EMBASE, psycINFO, SPORTDiscus and Cochrane Central Database and personal libraries were searched and content experts were consulted for additional material. DATA SELECTION: Included articles were required to have a measure of AVG and at least one relevant health or behaviour indicator: EE (both habitual and acute, adherence and appeal (i.e., participation and enjoyment, opportunity cost (both time and financial considerations, and adverse events, adiposity, cardiometabolic health, energy intake, adaptation (effects of continued play, learning and rehabilitation, and video game evolution (i.e., sustainability of AVG technology. RESULTS: 51 unique studies, represented in 52 articles were included in the review. Data were available from 1992 participants, aged 3-17 years, from 8 countries, and published from 2006-2012. Overall, AVGs are associated with acute increases in EE, but effects on habitual physical activity are not clear. Further, AVGs show promise when used for learning and rehabilitation within special populations. Evidence related to other indicators was limited and inconclusive. CONCLUSIONS: Controlled studies show that AVGs acutely increase light- to moderate-intensity physical activity; however, the findings about if or how AVG lead to increases in habitual physical activity or decreases in sedentary behaviour are less clear. Although AVGs may elicit some health benefits in special populations, there is not sufficient evidence to

  6. Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibalpha

    DEFF Research Database (Denmark)

    Bergmeier, W; Bouvard, D; Eble, J A;


    Although alpha(2)beta(1) integrin (glycoprotein Ia/IIa) has been established as a platelet collagen receptor, its role in collagen-induced platelet activation has been controversial. Recently, it has been demonstrated that rhodocytin (also termed aggretin), a snake venom toxin purified from...... that collagen may activate platelets by a similar mechanism. In contrast to these findings, we provided evidence that rhodocytin does not bind to alpha(2)beta(1) integrin. Here we show that the Cre/loxP-mediated loss of beta(1) integrin on mouse platelets has no effect on rhodocytin-induced platelet activation......, excluding an essential role of alpha(2)beta(1) integrin in this process. Furthermore, proteolytic cleavage of the 45-kDa N-terminal domain of glycoprotein (GP) Ibalpha either on normal or on beta(1)-null platelets had no significant effect on rhodocytin-induced platelet activation. Moreover, mouse platelets...


    Directory of Open Access Journals (Sweden)

    POP Fãnuța


    Full Text Available The activity of any economic entity is aimed at providing objects, works and services meant to fulfill certain social needs, as well as at achieving a certain level of profit which would enable the entreprise to maintain and/or develop in business. In order to reach these objectives, the offer of the entreprise should meet the demand of the market whithin which it activates in terms of: volume (how much it is demanded?, structure (what brands are demanded and what is their share in the total production?, rhythmicity (during what span of time? and level of quality (does the offer of the entity meet the qualitative level demanded by clients?. The entreprise develops interconditioning relations with its external factors, namely clients, suppliers, the state, employees, shareholders, banks, the government and budgetary institutions; the degree to which their expectations are met reflects the efficiency of the activity undertaken. Among the main indicators of performance, one could cite the turnover and the added value that reflect the economic raise of the entity, conditions its strategic position and defines its place in relation to other competitors, within the branch of activity concerned. A high level of turnover and added value guarantees that the economic entity develops a profitable activity, that it is expanding and developing, a fact with consequences upon the main economic-financial indicators but also upon the efficiency of the activity of the economic entity. The main objectives of the present paper are to point out the dynamics of the indicators of volume of activity, of factors of influence and of their strategies of growth. In addition to that, the study tries to ground and analyse theoretical aspects by providing some practical examples based on real data obtained from an economic entity during the period 2008-2011, but also data published by the INSSE for the same period, in order to observe its evolution in relation to other

  8. Phospholipase C Produced by Clostridium botulinum Types C and D:Comparison of Gene, Enzymatic, and Biological Activities with Those of Clostridium perfringens Alpha-toxin

    Directory of Open Access Journals (Sweden)



    Full Text Available Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs, the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

  9. EEG and dementia indicators in AIDS patients' Rorschach test

    Directory of Open Access Journals (Sweden)

    G. Fernandes do Prado


    Full Text Available We studied the EEG and Rorschach test (RT of nineteen AIDS patients and eight normal people in the same age group. Eight patients presented slow alpha rhythms (8 to 9 Hz; three, not-slow alpha rhythms (>9 to 13Hz; and eight, beta rhythms in background activity. Paroxystic activity, characterized by diffuse theta or delta waves, was present in eleven patients. We observed Oberholzer syndrome (organic dementia diagnosed by RT in ten patients and Piotrowski syndrome (organic dementia diagnosed by RT in eleven patients; six presented both. When considering only the group of AIDS patients, we did not observe a significant relation among slow alpha rhythm, not-slow alpha rhythm and the presence of paroxystic activity with the above-mentioned syndromes. AIDS patients with slow alpha rhythms showed a significantly greater number of Piotrowski syndrome dementia indicators when compared to normal individuals or those with slow alpha rhythms. We did not observe the same with Oberholzer syndrome.

  10. Alpha-picolinic Acid Activates Diverse Defense Responses of Salicylic Acid-, Jasmonic Acid/Ethylene- and Ca2 -dependent Pathways in Arabidopsis and Rice Suspension Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANGHai-Kuo; ZHANGXin; LIQun; HEZu-Hua


    Alpha-picolinic acid (PA) is an apoptosis inducer in animal cells, and could elicit hypersensitiv eresponse (HR) in rice, a monocotyledonous model plant. Here we report that PA is an HR inducer in plants. It induced HR in Arabidopsis, a dicotyledonous model plant, including the oxidative burst and cell death. We investigated defense signal transduction activated by PA through marker genes of particular defense pathways in Arabidopsis. The result indicated that both the salicylic acid-dependent and jasmonic acid/ethylene-dependent pathways were activated by PA, in which the marker defense genes PR-1, PR-2 and PDF 1.2 were all induced in dose-dependent and time-course manners. We also observed that the PAinduced reactive oxygen species (ROS) production in rice suspension cells was Ca2+-dependent. Together with our previous studies of PA-induced defense activation in rice, we conclude that PA acts as a nonspecific elicitor in plant defense and has a potential utilization in cellular model establishment of systemicac quired resistance (SAR) activation.

  11. The Presentation of Proper Indicators for Evaluation of WHO Collaboration Centres' Activities in Iran

    Directory of Open Access Journals (Sweden)

    S Motevallizadeh Ardakani


    Full Text Available Background:There are thirteen WHO collaborating centres in Iran which no mechanism or model has ever been foreseen for the evaluation of them.This original research is innovative in Iran, which has been offered by the researcher through a joint research project with WHO.Methods:The aforesaid model has been approved by the International Relation Department of Ministry of Health& education. This was done to develop model and indicators for evaluation of WHOCC's activities in Iran, which includes online survey, reports, literature reviews and website searches, published literature in another country, documents in Undersecretary for Research and Technology of Iranian Ministry of Health and Medical Education.Results:We studied collaboration centres in other countries and then compared these indicators together and presented a proper indicators for evaluation of WHOCC' activities in Iran.Conclusion: Evaluation of WHOCC's activities could be used as a mean for implementing policies and promoting knowledge production. Evaluation of WHOCC' activities is country's requirements.

  12. The alpha7 nicotinic receptor agonist SSR180711 increases activity regulated cytoskeleton protein (Arc) gene expression in the prefrontal cortex of the rat

    DEFF Research Database (Denmark)

    Kristensen, Søren; Thomsen, Morten Skøtt; Hansen, Henrik H;


    Nicotinic alpha7 acetylcholine receptors (alpha7 nAChR) have been shown to enhance attentional function and aspects of memory function in experimental models and in man. The protein Arc encoded by the effector immediate early gene arc or arg3.1 has been shown to be strongly implicated in long......-term memory function. We have sought to determine if alpha7 nAChR mediate the stimulation of arc gene expression, and if so, where in the brain such activation may occur using semi-quantitative in situ hybridisation. Administration of the novel and selective alpha7 nAChR agonist, SSR180711 (1, 3 and 10 mg...

  13. Predicting Economic Activity in Serbia By Constructing Serbian Leading Economic Indicator (SERLEI

    Directory of Open Access Journals (Sweden)

    Sandra S Kamenković


    Full Text Available Timely identification of the next stage of the business cycle, or a shift in economic activity from the previous trend, is a critical factor for the success of counter-cyclical economic policy. This paper is based on the construction of a new leading indicator of the business cycle which, with a certain time lag, suggests the next stage of the business cycle in the Republic of Serbia. SERLEI (Serbian Leading Economic Indicator is tested in the period of expansion and at the beginning of recession in the Serbian economy to show to what extent it was possible to predict a shift in business cycles

  14. Interaction with extracellular matrix proteins influences Lsh/Ity/Bcg (candidate Nramp) gene regulation of macrophage priming/activation for tumour necrosis factor-alpha and nitrite release. (United States)

    Formica, S; Roach, T I; Blackwell, J M


    The murine resistance gene Lsh/Ity/Bcg regulates activation of macrophages for tumour necrosis factor-alpha (TNF-alpha)-dependent production of nitric oxide mediating antimicrobial activity against Leishmania, Salmonella and Mycobacterium. As Lsh is differentially expressed in macrophages from different tissue sites, experiments were performed to determine whether interaction with extracellular matrix (ECM) proteins would influence the macrophage TNF-alpha response. Plating of bone marrow-derived macrophages onto purified fibrinogen or fibronectin-rich L929 cell-derived matrices, but not onto mannan, was itself sufficient to stimulate TNF-alpha release, with significantly higher levels released from congenic B10.L-Lshr compared to C57BL/10ScSn (Lshs) macrophages. Only macrophages plated onto fibrinogen also released measurable levels of nitrites, again higher in Lshr compared to Lshs macrophages. Addition of interferon-gamma (IFN-gamma), but not bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as a second signal enhanced the TNF-alpha and nitrite responses of macrophages plated onto fibrinogen, particularly in the Lshr macrophages. Interaction with fibrinogen and fibronectin also primed macrophages for an enhanced TNF-alpha response to leishmanial parasites, but this was only translated into enhanced nitrite responses in the presence of IFN-gamma. In these experiments, Lshr macrophages remained superior in their TNF-alpha responses throughout, but to a degree which reflected the magnitude of the difference observed on ECM alone. Hence, the specificity for the enhanced TNF-alpha responses of Lshr macrophages lay in their interaction with fibrinogen and fibronectin ECM, while a differential nitrite response was only observed with fibrinogen and/or IFN-gamma. The results are discussed in relation to the possible function of the recently cloned candidate gene Nramp, which has structural identity to eukaryote transporters and an N-terminal cytoplasmic

  15. Soil enzyme activities and their indication for fertility of urban forest soil

    Institute of Scientific and Technical Information of China (English)


    To reveal the biological characteristics of urban forest soil and the effects of soil enzyme on soil fertility as well as the correlation between physicochemical properties and enzyme activities,44 urban forest soil profiles in Nanjing were investigated.Basic soil physicochemical properties and enzyme activities were analyzed in the laboratory.Hydrogen peroxidase,dehydrogenase,alkaline phosphatase,and cellulase were determined by potassium permanphosphate dinatrium colorimetry,and anthrone colorimetry,respectively.The result showed that soil pH,organic carbon (C),and total nitrogen (N) had great effects on hydrogen peroxidase,dehydrogenase,and alkaline phosphatase activities in 0-20 cm thick soil.However,pH only had great effect on hydrogen peroxidase,dehydrogenase,and alkaline phosphatase activities in 20-40 cm thick soil.Hydrogen peroxidase,dehydrogenase,and alkaline phosphatase were important biological indicators for the fertility of urban forest soil.Both in 0-20 cm and 20-40 cm soil,soil enzyme system (hydrogen peroxidase,dehydrogenase,alkaline phosphatase,and cellulase) had a close relationship with a combination of physicochemical indicators (pH,organic C,total N,available K,available P,cation exchange capacity (CEC),and microbial biomass carbon(Cmic)).The more soil enzyme activities there were,the higher the fertility of urban forest soil.

  16. A selective estrogen receptor modulator inhibits TNF-alpha-induced apoptosis by activating ERK1/2 signaling pathway in vascular endothelial cells. (United States)

    Yu, Jing; Eto, Masato; Akishita, Masahiro; Okabe, Tetsuro; Ouchi, Yasuyoshi


    Tumor necrosis factor (TNF-alpha) is a pleiotropic cytokine exerting both inflammatory and cell death activity and is thought to play a role in the pathogenesis of atherosclerosis. The present study was designed to examine whether the raloxifene analogue, LY117018 could inhibit TNF-alpha-induced apoptosis in vascular endothelial cells and to clarify the involved mechanisms. Apoptosis of endothelial cells was determined by DNA fragmentation assay and the activation of caspase-3. LY117018 significantly inhibited TNF-alpha-induced caspase-3 activation and cell DNA fragmentation levels in bovine carotid artery endothelial cells. The inhibitory effect of LY117018 was abolished by an estrogen receptor antagonist ICI 182,780. p38 MAPK, JNK, ERK1/2 and Akt have been shown to act as apoptotic or anti-apoptotic signals. TNF-alpha stimulated the phosphorylation levels of p38 MAPK, JNK, ERK1/2 and Akt in vascular endothelial cells. TNF-alpha-induced apoptosis was significantly decreased by SB203580, a p38 MAPK inhibitor or SP600125, a JNK inhibitor, but was enhanced by an ERK1/2 pathway inhibitor, PD98059 or a PI3-kinase/Akt pathway inhibitor, wortmannin. The anti-apoptotic effect of LY117018 was abrogated only by PD98059 but was not affected by the inhibitors for p38 MAPK, JNK, or Akt. LY117018 stimulated the further increase in phosphorylation of ERK1/2 in TNF-alpha treated endothelial cells but it did not affect phosphorylation levels of p38 MAPK, JNK or Akt. These results suggest that LY 110718 prevents caspase-3 dependent apoptosis induced by TNF-alpha in vascular endothelial cells through activation of the estrogen receptors and the ERK1/2 signaling pathway. PMID:19275968

  17. Transcriptomic signatures of peroxisome proliferator-activated receptor alpha (PPARalpha) in different mouse liver models identify novel aspects of its biology

    NARCIS (Netherlands)

    Szalowska, E.; Tesfay, H.A.; Hijum, S.A.F.T. van; Kersten, S.


    BACKGROUND: The peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor that regulates lipid catabolism and inflammation and is hepatocarcinogenic in rodents. It is presumed that the functions of PPARalpha in liver depend on cross-talk between parenchy

  18. Whole blood assay for NK activity in splenectomized and non-splenectomized hairy cell leukemia patients during IFN-alpha-2b treatment

    DEFF Research Database (Denmark)

    Nielsen, B; Hokland, P; Ellegaard, J;


    Natural killer cell (NK) activity in peripheral blood (PB) was followed longitudinally for up to 2 yr after initiation of low-dose IFN-alpha-2b therapy in nine hairy cell leukemia (HCL) patients. A whole blood NK (WB-NK) assay was employed in order to measure the NK activity per unit blood...


    Starches constitute the main caloric source in the average human diet. The digestion of starches is far more complex than sugars and requires six different enzyme activities to produce free glucose before absorption. Salivary and pancreatic alpha-amylase activities initially hydrolyze internal 1-4 g...

  20. Cysteine desulfurase activity indicates a role for NIFS in metallocluster biosynthesis.


    Zheng, L; White, R H; Cash, V L; Jack, R F; Dean, D R


    Biological nitrogen fixation is catalyzed by nitrogenase, a complex metalloenzyme composed of two separately purifiable component proteins encoded by the structural genes nifH, nifD, and nifK. Deletion of the Azotobacter vinelandii nifS gene lowers the activities of both nitrogenase component proteins. Because both nitrogenase component proteins have metallocluster prosthetic groups that are composed of iron- and sulfur-containing cores, this result indicated that the nifS gene product could ...

  1. Electrospun nanofiber layers with incorporated photoluminescence indicator for chromatography and detection of ultraviolet-active compounds. (United States)

    Kampalanonwat, Pimolpun; Supaphol, Pitt; Morlock, Gertrud E


    For the first time, electrospun nanofiber phases were fabricated with manganese-activated zinc silicate as photoluminescent indicator (UV254) to transfer and enlarge its application to the field of UV-active compounds. By integration of such an indicator, UV-active compounds got visible on the chromatogram. The separation of 7 preservatives and a beverage sample were studied on the novel luminescent polyacrylonitrile layers. The mat thickness and mean fiber diameters were calculated for additions of different UV254 indicator concentrations. The separation efficiency on the photoluminescent layers was characterized by comparison to HPTLC layers and calculation of the plate numbers and resolutions. Some benefits were the reduction in migration distance (3cm), migration time (12min), analyte (10-nL volumes) and mobile phase volumes (1mL). As ultrathin stationary phase, such layers are suited for their integration into the Office Chromatography concept. For the first time, electrospun nanofiber layers were hyphenated with mass spectrometry and the confirmation of compounds was successfully performed using the elution-head based TLC-MS Interface.

  2. Structure-function analysis indicates that sumoylation modulates DNA-binding activity of STAT1

    Directory of Open Access Journals (Sweden)

    Grönholm Juha


    Full Text Available Abstract Background STAT1 is an essential transcription factor for interferon-γ-mediated gene responses. A distinct sumoylation consensus site (ψKxE 702IKTE705 is localized in the C-terminal region of STAT1, where Lys703 is a target for PIAS-induced SUMO modification. Several studies indicate that sumoylation has an inhibitory role on STAT1-mediated gene expression but the molecular mechanisms are not fully understood. Results Here, we have performed a structural and functional analysis of sumoylation in STAT1. We show that deconjugation of SUMO by SENP1 enhances the transcriptional activity of STAT1, confirming a negative regulatory effect of sumoylation on STAT1 activity. Inspection of molecular model indicated that consensus site is well exposed to SUMO-conjugation in STAT1 homodimer and that the conjugated SUMO moiety is directed towards DNA, thus able to form a sterical hindrance affecting promoter binding of dimeric STAT1. In addition, oligoprecipitation experiments indicated that sumoylation deficient STAT1 E705Q mutant has higher DNA-binding activity on STAT1 responsive gene promoters than wild-type STAT1. Furthermore, sumoylation deficient STAT1 E705Q mutant displayed enhanced histone H4 acetylation on interferon-γ-responsive promoter compared to wild-type STAT1. Conclusions Our results suggest that sumoylation participates in regulation of STAT1 responses by modulating DNA-binding properties of STAT1.

  3. Anti-CII antibody as a novel indicator to assess disease activity in systemic lupus erythematosus. (United States)

    He, C; Mao, T; Feng, Y; Song, T; Qin, C; Yan, R; Feng, P


    Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects a variety of organ systems. Anti-dsDNA Abs and complement factors have been used as indicators of lupus activity for more than 50 years. A novel indicator of activation in SLE is reported in this paper. Anti-collagen type II (CII) Ab was obviously elevated in patients with SLE compared to those patients with ankylosing spondylitis (AS) and healthy controls (HCs). Anti-CII-Ab-positive patients with SLE showed significantly higher levels of serum IgG and higher titers of ANA but lower levels of C3 and C4 than controls. A positive correlation was demonstrated between anti-CII Ab and serum IgG in SLE patients (r = 0.50, p < 0.0001). The negative correlations of anti-CII Ab with C3 and C4 were observed in SLE patients (r = -0.36, p = 0.0013; r = -0.37, p = 0.0006, respectively). The reduced anti-CII Ab level was accompanied by decreased level of serum IgG and increased levels of C3 and C4 after regular treatment. Therefore, anti-CII Ab could be a novel indicator for monitoring activity of SLE.

  4. Novel water-resistant UV-activated oxygen indicator for intelligent food packaging. (United States)

    Vu, Chau Hai Thai; Won, Keehoon


    For the first time, alginate polymer has been applied to prevent dyes from leaching out of colorimetric oxygen indicator films, which enable people to notice the presence of oxygen in the package in an economic and simple manner. The dye-based oxygen indicator film suffers from dye leaching upon contact with water. In this work, UV-activated visual oxygen indicator films were fabricated using thionine, glycerol, P25 TiO2, and zein as a redox dye, a sacrificial electron donor, UV-absorbing semiconducting photocatalyst, and an encapsulation polymer, respectively. When this zein-coated film was immersed in water for 24h, the dye leakage was as high as 80.80±0.45%. However, introduction of alginate (1.25%) as the coating polymer considerably diminished the dye leaching to only 5.80±0.06%. This is because the ion-binding ability of alginate could prevent the cation dye from leaching into water. This novel water-resistant UV-activated oxygen indicator was also successfully photo-bleached and regained colour fast in the presence of oxygen. PMID:23578614

  5. Global Indicators Analysis and Consultancy Experience Insights into Correlation between Entrepreneurial Activities and Business Environment

    Directory of Open Access Journals (Sweden)

    Jovan Krivokapić


    Full Text Available Many researches and practical experiences clearly indicate the existence of a strong relationship between entrepreneurial activities and the business environment in which these activities are initiated. Although this topic has been quite ignored until the late twentieth century, a lot of studies and consulting practice have contributed to the fact that there are now a number of theories concerning mentioned correlation. These theories aim to offer a model that would provide better utilization of the possibilities from the business environment which could be very important for the development from both macroeconomic and microeconomic aspects. An increasing number of articles on this topic says enough about its importance, and numerous researches by many reputable globally recognized institutions go in favor of this claim. There are many indicators that observe the economic situation in a country or a region from different aspects, so the analyses of these indicators make it possible to determine the specific relationships between entrepreneurial activities and the local and the global business environment. Given the complexity of these relations, the impact cannot be observed partially, without taking into consideration other important factors, but more detailed analyses, however, result in some useful conclusions, which in the proper context can have a positive impact on many economic factors. It is very important to emphasize the fact that the correlation between the business environment and entrepreneurial activities is bidirectional, since this influence is mutual, so that changes in one of these factors can and usually cause some modifications in the other. Frequent series of such iterations actually lead to changes in the business environment, while entrepreneurial activity changes its shape and affects the economy of a country or a region, which is of particular importance for its competitiveness in the era of globalization.

  6. Lyman-alpha line as a solar activity index for calculations of solar spectrum in the EUV region (United States)

    Nusinov, Anatoliy; Kazachevskaya, Tamara; Katyushina, Valeria; Woods, Thomas

    It is investigated a possibility of retrieval of solar spectrum data using intensity observational data of the only solar spectral line L (Hydrogen Lyman-alpha, 121.6 nm).Using as an example spectra obtained by SEE instruments on TIMED satellite, it was shown, that both for lines and for continuum in the spectral range 27-105 nm, which is essential for ionization processes in the ionosphere, a correlation between their intensities and L was high. Therefore it becomes possible to use L measurements data as a natural solar activity index for calculations of EUV solar emission spectrum for solving aeronomical problems. It is noticed, that EUV model, obtained with using SEE data, does not allow to calculate correctly critical frequencies of ionospheric E-layer owing to low intensities of lines 97.7 and 102.6 nm, which produce the main part of ionization in ionospheric E-region.

  7. EEG Alpha Synchronization Is Related to Top-Down Processing in Convergent and Divergent Thinking (United States)

    Benedek, Mathias; Bergner, Sabine; Konen, Tanja; Fink, Andreas; Neubauer, Aljoscha C.


    Synchronization of EEG alpha activity has been referred to as being indicative of cortical idling, but according to more recent evidence it has also been associated with active internal processing and creative thinking. The main objective of this study was to investigate to what extent EEG alpha synchronization is related to internal processing…

  8. PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer

    DEFF Research Database (Denmark)

    Koefoed Petersen, Rasmus; Benzon Larsen, Signe; Jensen, Ditte Marie;


    of the wildtype Pro-allele of PPARG Pro12Ala in alcohol related breast cancer. In transiently transfected cells, transcriptional activation by PPARγ and the PPARγ-PGC-1α complex was inhibited by ethanol. PPARγ 12Ala-mediated transcription activation was not enhanced by PGC-1α, resulting in allele......-specific transcription activation by the PPARγ 12Pro-PGC-1α complex. Our results suggest that PPARγ and PGC-1α activity is an important determinant of alcohol related breast cancer....

  9. Free cholesterol-induced macrophage apoptosis is mediated by inositol-requiring enzyme 1 alpha-regulated activation of Jun N-terminal kinase

    Institute of Scientific and Technical Information of China (English)

    Fangming Li; Yi Guo; Shenggang Sun; Xin Jiang; Bingshan Tang; Qizhang Wang; Ling Wang


    Macrophage death in advanced atherosclerotic lesions leads to iesional necrosis, possible plaque rupture, and acute vascular occlusion. A likely cause of macrophage death is the accumulation of free cholesterol (FC) leading to activation of endoplasmic reticulum (ER) stress-induced apoptosis.Inositol-requiring enzyme 1 alpha (IRE1α) is an integral membrane protein of the ER that is a key signaling step in cholesterol-induced apoptosis in macrophages, activated by stress in the ER. However, the role of IRE1α in the regulation of ER stress-induced macrophage death and the mechanism for this process are largely unclear.In this study,a cell culture model was used to explore the mechanisms involved in the ER stress pathway of FC-induced macrophage death.The results herein showed that FC loading of macrophages leads to an apoptotic response that is partially dependent on initiation by activation of IRE1α.Taken together,these results showed that the IRE1-apoptosis-signaling kinase 1-c-Jun NH2-terminal kinase cascade pathway was required in this process.Moreover,the data suggested a novel cellular mechanism for cholesterol-induced macrophage death in advanced atherosclerotic lesions.The critical function of this signaling cascade is indicated by prevention of ER stress-induced apoptosis after inhibition of IRE1α,or c-Jun NH2-terminal kinase.

  10. Fecal calprotectin and ulcerative colitis endoscopic activity index as indicators of mucosal healing in ulcerative colitis. (United States)

    Taghvaei, Tarang; Maleki, Iradj; Nagshvar, Farshad; Fakheri, Hafez; Hosseini, Vahid; Valizadeh, Seyed Mohammad; Neishaboori, Hassan


    Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory large bowel disease with recurrent variable periods of exacerbation. The aim of the current study is to evaluate the correlation of UCEIS with fecal calprotectin (FC) level to assess disease activity in UC patients in order to determine whether FC can prognosticate clinical outcome and disease activity of UC instead of colonoscopic evaluation. Our endoscopic investigations revealed the extension of UC as the following: proctitis (11.6%), procto-sigmoiditis (18.5%), left-sided colitis (15.8%), extensive colitis (11.7%), and normal endoscopy (42.4%). Conclusively, we suggest that FC can be used as a reliable tool to evaluate disease activity in ulcerative colitis patients. Moreover, our findings indicate a significant correlation between FC level and mucosal healing. PMID:25366383

  11. Metal ion site engineering indicates a global toggle switch model for seven-transmembrane receptor activation

    DEFF Research Database (Denmark)

    Elling, Christian E; Frimurer, Thomas M; Gerlach, Lars-Ole;


    for monoamine binding in TM-III, was used as the starting point to engineer activating metal ion sites between the extracellular segments of the beta2-adrenergic receptor. Cu(II) and Zn(II) alone and in complex with aromatic chelators acted as potent (EC50 decreased to 0.5 microm) and efficacious agonists...... in sites constructed between positions III:08 (Asp or His), VI:16 (preferentially Cys), and/or VII:06 (preferentially Cys). In molecular models built over the backbone conformation of the inactive rhodopsin structure, the heavy atoms that coordinate the metal ion were located too far away from each other...... to form high affinity metal ion sites in both the bidentate and potential tridentate settings. This indicates that the residues involved in the main ligand-binding pocket will have to move closer to each other during receptor activation. On the basis of the distance constraints from these activating metal...

  12. Correlation study of some solar activity indices in the cycles 21 - 23

    CERN Document Server

    Bruevich, E A


    The correlation coefficients of the linear regression of six solar indices versus F10,7 were analyzed in solar cycles 21, 22 and 23. We also analyzed the interconnection between these indices and F10,7 with help of the approximation by the polynomials of second order. The indices we've studied in this paper are: Wolf numbers - W, 530,3 nm coronal line flux - F530, the total solar irradiance - TSI, Mg II UV-index 280 nm core-to-wing ratio, Flare Index - FI and Counts of flares. In the most cases the regressions of these solar indices versus F10,7 are close to linear except the moments of time near to the minimums and maximums of 11-year activity. For the linear regressions we found that the values of correlation coefficients Kcorr(t) for the indices versus F10,7 and W show the cyclic variations with periods approximately equal to the to half length of 11-year cycle - 5,5 years approximately.

  13. Acute cadmium intoxication induces alpha-class glutathione S-transferase protein synthesis and enzyme activity in rat liver

    International Nuclear Information System (INIS)

    Acute cadmium intoxication affects glutathione S-transferase (GST) in rat liver. It has been found that 24 h after i.p. cadmium administration to rats, at a dose of 2.5 mg CdCl2 kg-1 body weight, the activity of this enzyme in liver cytosol increased by 40%. A less stimulatory effect persisted till 48 h and thereafter the enzyme activity normalized. Since, GST isoenzymes belong to different classes in mammalian tissues, we used quantitative immunoassays to verify which family of GST isoenzymes is influenced by this intoxication. Only alpha-class glutathione S-transferase (α-GST) proteins were detected in rat liver cytosol and their level increased by about 25%, 24 h after cadmium treatment. No pi-GST isoforms were found in liver cytosol from either normal or cadmium-treated rats. Co-administration of actinomycin D with cadmium normalized both the protein level and the activity of α-GST, suggesting that some effect occurs on enzyme transcription of these isoenzymes by this metal. On the other hand, it seems unlikely that the stimulatory effect is due to the high level of peroxides caused by lipid peroxidation, since Vitamin E administration strongly reduced the TBARS level, but did not cause any GST activity decrease

  14. Spontaneous Slow Fluctuation of EEG Alpha Rhythm Reflects Activity in Deep-Brain Structures: A Simultaneous EEG-fMRI Study.

    Directory of Open Access Journals (Sweden)

    Kei Omata

    Full Text Available The emergence of the occipital alpha rhythm on brain electroencephalogram (EEG is associated with brain activity in the cerebral neocortex and deep brain structures. To further understand the mechanisms of alpha rhythm power fluctuation, we performed simultaneous EEGs and functional magnetic resonance imaging recordings in human subjects during a resting state and explored the dynamic relationship between alpha power fluctuation and blood oxygenation level-dependent (BOLD signals of the brain. Based on the frequency characteristics of the alpha power time series (APTS during 20-minute EEG recordings, we divided the APTS into two components: fast fluctuation (0.04-0.167 Hz and slow fluctuation (0-0.04 Hz. Analysis of the correlation between the MRI signal and each component revealed that the slow fluctuation component of alpha power was positively correlated with BOLD signal changes in the brain stem and the medial part of the thalamus and anterior cingulate cortex, while the fast fluctuation component was correlated with the lateral part of the thalamus and the anterior cingulate cortex, but not the brain stem. In summary, these data suggest that different subcortical structures contribute to slow and fast modulations of alpha spectra on brain EEG.


    Directory of Open Access Journals (Sweden)

    Gabriela Vasile


    amylase in two Asian cyprinids namely, bighead carp (Aristichthys nobilis and silver carp (Hypophthalmichthys molitrix. The activity of -amylase has been determined by the Métais-Bieth method, the results obtained being expressed as mg starch / ml x 30 min. Our experimental data evidence some differences between the activity of -amylase from the digestive tube, in the two species under study.

  16. Effects of alpha-AMPK knockout on exercise-induced gene activation in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Jørgensen, Sebastian Beck; Wojtaszewski, Jørgen; Viollet, Benoit;


    We tested the hypothesis that 5'AMP-activated protein kinase (AMPK) plays an important role in regulating the acute, exercise-induced activation of metabolic genes in skeletal muscle, which were dissected from whole-body a2- and a1-AMPK knockout (KO) and wild-type (WT) mice at rest, after treadmi...

  17. Differences in genotoxic activity of alpha-Ni3S2 on human lymphocytes from nickel-hypersensitized and nickel-unsensitized donors. (United States)

    Arrouijal, F Z; Marzin, D; Hildebrand, H F; Pestel, J; Haguenoer, J M


    The genotoxic activity of alpha-Ni3S2 was assessed on human lymphocytes from nickel-hypersensitized (SSL) and nickel-unsensitized (USL) subjects. Three genotoxicity tests were performed: the sister chromatid exchange (SCE) test, the metaphase analysis test and the micronucleus test. (i) The SCE test (3-100 micrograms/ml) showed a weak but statistically significant increase in the number of SCE in both lymphocyte types with respect to controls, USL presenting a slightly higher SCE incidence but only at one concentration. (ii) The metaphase analysis test demonstrated a high dose-dependent clastogenic activity of alpha-Ni3S2 in both lymphocyte types. The frequency of chromosomal anomalies was significantly higher in USL than in SSL for all concentrations applied. (iii) The micronucleus test confirmed the dose-dependent clastogenic activity of alpha-Ni3S2 and the differences already observed between USL and SSL, i.e. the number of cells with micronuclei was statistically higher in USL. Finally, the incorporation study with alpha-63Ni3S2 showed a higher uptake of its solubilized fraction by USL. This allows an explanation of the different genotoxic action of nickel on the two cell types. In this study we demonstrated that hypersensitivity has an influence on the incorporation of alpha-Ni3S2 and subsequently on the different induction of chromosomal aberrations in human lymphocytes. PMID:1602972

  18. [Oxidative stress, the functional activity of beta-cells, and the content of tumor necrosis factor alpha in patients with type II diabetes mellitus]. (United States)

    Klebanova, E M


    The purpose of the study was to investigate the effects of dietotherapy on oxidative stress (OS) condition, the fl-cell functional activity (BCFA), insulin resistance index (IRI), and the serum tumor necrosis factor alpha (alpha-TNF) level in patients with type 2 diabetes mellitus (DM 2). The subjects, 30 patients with DM 2 (9 men, 21 women), aged 42 to 70 (mean age 58.77 +/- 8.86 years), were examined. The duration of DM 2 in the subjects was from 1 month to 5 years. OS parameters, IRI and BCFA, as well as serum alpha-TNF were measured before the study and after 3 months of observation. The tests performed after the end of the study showed that hydrocarbonate exchange remained compensated, and IRI and BCFA were moderately lowered in DM 2 patients on dietotherapy. There was an insignificant elevation of serum alpha-TNF, while the condition of hydrocarbonate exchange had bettered. Changes in OS parameters in patients on dietotherapy evidence that the reserve activity of anti-oxidative system enzymes decreases. Thus, the compensation of hydrocarbonate exchange in DM 2 patients on dietotherapy retains, which is accompanied by a decrease in IRI and BCFA, while serum alpha-TNFincreases insignificantly, and reserved anti-oxidative system enzyme activity decreases moderately. PMID:17087190

  19. Cytotoxic activity of interferon alpha induced dendritic cells as a biomarker of glioblastoma (United States)

    Mishinov, S. V.; Stupak, V. V.; Tyrinova, T. V.; Leplina, O. Yu.; Ostanin, A. A.; Chernykh, E. R.


    Dendritic cells (DCs) are the most potent antigen presenting cells that can play direct role in anti-tumor immune response as killer cells. DC tumoricidal activity can be stimulated greatly by type I IFN (IFNα and IFNβ). In the present study, we examined cytostatic and cytotoxic activity of monocyte-derived IFNα-induced DCs generated from patients with brain glioma and evaluated the potential use of these parameters in diagnostics of high-grade gliomas. Herein, we demonstrated that patient DCs do not possess the ability to inhibit the growth of tumor HEp-2 cell line but low-grade and high-grade glioma patients do not differ significantly in DC cytostatic activity. However, glioma patient DCs are characterized by reduced cytotoxic activity against HEp-2 cells. The impairment of DC cytotoxic function is observed mainly in glioblastoma patients. The cytotoxic activity of DCs against HEp-2 cells below 9% is an informative marker for glioblastomas.

  20. Fetal functional brain age assessed from universal developmental indices obtained from neuro-vegetative activity patterns.

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    Dirk Hoyer

    Full Text Available Fetal brain development involves the development of the neuro-vegetative (autonomic control that is mediated by the autonomic nervous system (ANS. Disturbances of the fetal brain development have implications for diseases in later postnatal life. In that context, the fetal functional brain age can be altered. Universal principles of developmental biology applied to patterns of autonomic control may allow a functional age assessment. The work aims at the development of a fetal autonomic brain age score (fABAS based on heart rate patterns. We analysed n = 113 recordings in quiet sleep, n = 286 in active sleep, and n = 29 in active awakeness from normals. We estimated fABAS from magnetocardiographic recordings (21.4-40.3 weeks of gestation preclassified in quiet sleep (n = 113, 63 females and active sleep (n = 286, 145 females state by cross-validated multivariate linear regression models in a cross-sectional study. According to universal system developmental principles, we included indices that address increasing fluctuation range, increasing complexity, and pattern formation (skewness, power spectral ratio VLF/LF, pNN5. The resulting models constituted fABAS. fABAS explained 66/63% (coefficient of determination R(2 of training and validation set of the variance by age in quiet, while 51/50% in active sleep. By means of a logistic regression model using fluctuation range and fetal age, quiet and active sleep were automatically reclassified (94.3/93.1% correct classifications. We did not find relevant gender differences. We conclude that functional brain age can be assessed based on universal developmental indices obtained from autonomic control patterns. fABAS reflect normal complex functional brain maturation. The presented normative data are supplemented by an explorative study of 19 fetuses compromised by intrauterine growth restriction. We observed a shift in the state distribution towards active awakeness. The lower WGA

  1. Coexistence of dopamine-beta-hydroxylase and activated protein-2 alpha in rat cerebellar Purkinje cells

    Institute of Scientific and Technical Information of China (English)

    Kejian Wang; Wei Li; Shanquan Sun; Zhongqin Ren; Guiqiong He


    BACKGROUND:Tyrosine hydroxylase and phenylethanolamine-n-methyl transferase expression coexist in Purkinje cells of the rat cerebellum.Numerous reports have also been published addressing whether dopamine-beta-hydroxylase (DBH) expression exists in cerebellar Purkinje cells.OBJECTIVE:To investigate the coexistence of DBH and activator protein-2α expression in rat cerebellar Purkinje cells.DESIGN,TIME AND SETTING:A cell morphological study was performed at the Institute of Neuroscience,Chongqing Medical University,China in May 2007.MATERIALS:Ten healthy Wistar rats,of either gender,aged 14 weeks,served as experimental animals.Rabbit anti-mouse DBH,goat anti-mouse activator protein-2α and rabbit anti-mouse β-actin (Santa Cruz Biotechnology,Inc.,USA),horseradish peroxidase-labeled goat anti-rabbit IgG,FITC-labeled mouse anti-rabbit IgG,and Cy3-labeled mouse anti-goat IgG (Boster,Wuhan,China),were used in this study.METHODS:Immunohistochemical staining was used to measure the expression of DBH or activator protein-2α,with double-label immunofluorescence being employed to determine coexpression of both,in the cerebellum of 5 randomly selected rats.Western blot assay was utilized to determine the expression of DBH and activator protein-2α in the cerebellum of the remaining 5 rats.MAIN OUTCOME MEASURES:Expression,localization and coexistence of DBH and activator protein-2α in the cerebellum were measured separately.RESULTS:Immunohistochemical staining demonstrated that cerebellar Purkinje cells stained positive for DBH and activator protein-2α.Western blot assay also demonstrated DBH and activator protein-2α expression in the cerebellum.Double-labeling immunofluorescence showed the coexistence of DBH and activator protein-2α in cerebellar Purkinje cells.CONCLUSION:Norepinephrine and activator protein-2α coexist in rat cerebellar Purkinje cells.

  2. Using geochemical indicators to distinguish high biogeochemical activity in floodplain soils and sediments. (United States)

    Kenwell, Amy; Navarre-Sitchler, Alexis; Prugue, Rodrigo; Spear, John R; Hering, Amanda S; Maxwell, Reed M; Carroll, Rosemary W H; Williams, Kenneth H


    A better understanding of how microbial communities interact with their surroundings in physically and chemically heterogeneous subsurface environments will lead to improved quantification of biogeochemical reactions and associated nutrient cycling. This study develops a methodology to predict potential elevated rates of biogeochemical activity (microbial "hotspots") in subsurface environments by correlating microbial DNA and aspects of the community structure with the spatial distribution of geochemical indicators in subsurface sediments. Multiple linear regression models of simulated precipitation leachate, HCl and hydroxylamine extractable iron and manganese, total organic carbon (TOC), and microbial community structure were used to identify sample characteristics indicative of biogeochemical hotspots within fluvially-derived aquifer sediments and overlying soils. The method has been applied to (a) alluvial materials collected at a former uranium mill site near Rifle, Colorado and (b) relatively undisturbed floodplain deposits (soils and sediments) collected along the East River near Crested Butte, Colorado. At Rifle, 16 alluvial samples were taken from 8 sediment cores, and at the East River, 46 soil/sediment samples were collected across and perpendicular to 3 active meanders and an oxbow meander. Regression models using TOC and TOC combined with extractable iron and manganese results were determined to be the best fitting statistical models of microbial DNA (via 16S rRNA gene analysis). Fitting these models to observations in both contaminated and natural floodplain deposits, and their associated alluvial aquifers, demonstrates the broad applicability of the geochemical indicator based approach. PMID:27145490

  3. The effects measurement of hand massage by the autonomic activity and psychological indicators. (United States)

    Kunikata, Hiroko; Watanabe, Kumi; Miyoshi, Makoto; Tanioka, Tetsuya


    This study examined the effects of hand massage on autonomic activity, anxiety, relaxation and sense of affinity by performing it to healthy people before applying the technic in actual clinical practice. Findings were showed below: 1) the significant increase in the pNN50 and the significant decrease in the heart rate meant the intervention of massage increased the autonomic nervous activity, improved the parasympathetic nerve activity and reduced the sympathetic nerve activity. This means the subjects were considered to be in a state of relaxation. 2) Salivary α amylase has been reported as a possible indicator for sympathetic nerve activity. In this study, there was no significant difference in the salivary α amylase despite a decrease after massage. 3) State anxiety score is temporal situational reactions while being in the state of anxiety and this score decreased significantly after massage. 4) The level of willingness to communicate with other person and the sense of affinity toward the massage-performer had a positive change of 70 percent. From this, it can be considered that a comfortable physical contact between a patient and a nursing profession, who are in a supported-supportive relationship, leads to an effect of shortening the gap in their psychological distance.

  4. Milk catalase activity as an indicator of thermization treatments used in the manufacture of cheddar cheese. (United States)

    Hirvi, Y; Griffiths, M W


    Pilot-scale studies were carried out to determine the effect of different heat treatments on catalase activity during the manufacture and maturation of Cheddar cheese. Three trials were conducted to monitor catalase activity using disk flotation and polarographic methods. Cheese was manufactured from raw milk and from milk that had been treated at 60, 65 and 72 degrees C for 16 s using a high temperature, short time heat exchanger. Catalase activity was also determined in samples of commercial milk and in samples of mild, medium, sharp, and extra sharp Cheddar cheeses obtained from different manufacturers in order to verify that the enzyme could be used as an indicator of the type of heat treatment applied to cheese milk. Catalase activity was present in cheese made from raw milk but was only present at low concentrations in cheese manufactured from thermized milk. However, high catalase activity was observed in commercial samples of sharp and extra sharp Cheddar cheese that was apparently due to the growth of catalase-producing yeasts in the cheese during maturation.

  5. A comparison between the cardio-stress indices of an active and a sedentary population

    Directory of Open Access Journals (Sweden)

    Peet Du Toit


    Full Text Available Our modern lifestyle often results in the importance of physical exercise being overlooked. The increasingly passive way of life has resulted in a notable increase in the prevalence of lifestyle disorders, such as hypertension and some forms of vascular pathology. This study compares the cardio-stress indices (CSIs of active and sedentary individuals to provide insight into the impact of the significant changes that have taken place in the modernised society. The active population consisted of 217 military recruits who had completed 20 weeks of basic military training. The sedentary population (n = 126 was sourced from a traditional tertiary institution where the focus is on attending lectures. Participants from both populations were required to attend three testing sessions, which were held during Week 1, Week 12 and Week 20. Subjects underwent a non-invasive ViportTM test to measure their CSI, heart rate and QRS duration. The results showed that although baseline readings for CSI, blood pressure (BP and heart rate (HR were initially higher among the active population, the commencement of the physical training programme resulted in a steady decline in respect of these three factors to approach healthier margins. However, the CSI for neither population reached the normal range, indicating that although physical activity reduces physiological stress levels, other key factors, namely lifestyle stress levels, must also be taken into account. The study supports the notion that increased physical activity has the potential to reduce the predisposition of an individual to cardiovascular disorders and contributes towards establishing the effect of training on heart health by using CSI as a means of measurement.

  6. Receptor Density Is Key to the Alpha2/Beta Interferon Differential Activities


    Moraga, I.; Harari, D.; Schreiber, G.; Uze, G.; Pellegrini, S.


    Multiple type I interferons (IFN-α/β) elicit Jak/Stat activation, rapid gene induction, and pleiotropic effects, such as differentiation, antiviral protection, and blocks in proliferation, which are dependent on the IFN subtype and the cellular context. To date, ligand- and receptor-specific molecular determinants underlying IFN-α/β differential activities or potencies have been well characterized. To analyze cellular determinants that impact subtype-specific potency, human fibrosarcoma U5A-d...

  7. Alpha-Glucosidase Inhibition and Hypoglycemic Activities of Sweitenia mahagoni Seed Extract


    Tutik Wresdiyat; Siti Sa’diah; Adi Winarto; Venny Febriyani


    Inhibition of α-glucosidase and hypoglycemic activity are two effects commonly used to identify bioactive compounds with potential to treat diabetes. The objectives of this study were to analyse and compare the bioactive compounds and α-glucosidase inhibitory effect of four different types of Swietenia mahagoni seed extract, and to analyse the hypoglycemic activity of the greatest inhibition of α-glucosidase-extract in rats. The extracts were obtained using two different solvents (aqueous and...

  8. Glucose decouples intracellular Ca2+ activity from glucagon secretion in mouse pancreatic islet alpha-cells.

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    Sylvain J Le Marchand

    Full Text Available The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+](i and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+](i and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP channel activity but not on tetrodotoxin-sensitive Na(+ channels. The use of glucagon secretagogues reveals a positive correlation between α-cell [Ca(2+](i and secretion at low glucose levels. Glucose elevation suppresses glucagon secretion even after treatment with secretagogues. Importantly, this inhibition is not mediated by K(ATP channel activity or reduction in α-cell [Ca(2+](i. Our results demonstrate that glucose uncouples the positive relationship between [Ca(2+](i and secretory activity. We conclude that glucose suppression of glucagon secretion is not mediated by inactivation of calcium channels, but instead, it requires a calcium-independent inhibitory pathway.

  9. Do the physical properties of occlusal-indicating media affect muscle activity [EMG) during use? (United States)

    Forrester, Stephanie E; Pain, Matthew T G; Presswood, Ron; Toy, Andy


    Four occlusal marking media (Parkell film, articulating silk, articulating paper and T-Scan foil) were tested to assess whether they affected neuromuscular function during occlusal marking events. Muscle activity of the anterior temporalis (TA) and superficial masseter (MS) muscles were obtained from surface EMG measurements during a slow closure to occlusion followed immediately by a forceful bite and a maximum clench onto each of the various occlusal indicating media. Muscle activity during the whole period of activation and immediately following onset were investigated. Significant differences in neuromuscular function between the occlusal marking media were observed, particularly between the Parkell film and articulating silk as opposed to the articulating paper and the T-Scan foil. The Parkell film and articulating silk gave neuromuscular function very similar to that of natural dentition occlusal contact, while the articulating paper and T-Scan foil showed similarities to occluding onto cotton rolls as previously reported (1). These results suggest that both the thickness and plasticity of the indicating media affect neuromuscular function during occlusion.

  10. The relationship between the level of salivary alpha amylase activity and pain severity in patients with symptomatic irreversible pulpitis


    Ahmadi-Motamayel, Fatemeh; Shahriari, Shahriar; Goodarzi, Mohammad Taghi; Moghimbeigi, Abbas; Jazaeri, Mina; Babaei, Parisa


    Objectives Assessment of dental pain severity is very challenging in dentistry. Previous studies have suggested that elevated salivary alpha amylase may contribute to increased physical stresses. There is a close association between salivary alpha amylase and plasma norepinephrine under stressful physical conditions. The aim of this study was to evaluate the relationship between pain severity and salivary alpha amylase levels in patients with symptomatic irreversible pulpitis. Materials and M...

  11. Radial Velocity Detection of Earth-mass Planets in the Presence of Activity Noise: The Case of Alpha Centauri Bb

    CERN Document Server

    Hatzes, Artie P


    We present an analysis of the publicly available HARPS radial velocity (RV) measurements for Alpha Cen B, a star hosting an Earth-mass planet candidate in a 3.24 day orbit. The goal is to devise robust ways of extracting low-amplitude RV signals of low mass planets in the presence of activity noise. Two approaches were used to remove the stellar activity signal which dominates the RV variations: 1) Fourier component analysis (pre-whitening), and 2) local trend filtering (LTF) of the activity using short time windows of the data. The Fourier procedure results in a signal at P = 3.236 days and K = 0.42 m/s which is consistent with the presence of an Earth-mass planet, but the false alarm probability for this signal is rather high at a few percent. The LTF results in no significant detection of the planet signal, although it is possible to detect a marginal planet signal with this method using a different choice of time windows and fitting functions. However, even in this case the significance of the 3.24-d sign...

  12. Interferon-alpha administration enhances CD8+ T cell activation in HIV infection.

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    Maura Manion

    Full Text Available BACKGROUND: Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation. METHODS: To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNα for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNα treatment. RESULTS: The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (p = 0.006. These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cells = 2.62% at baseline and 2.17% after 12 weeks of interferon therapy. As plasma HIV levels fell with interferon therapy, this was correlated with a "paradoxical" increase in CD8+ T cell activation (p<0.001. CONCLUSION: Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection.

  13. Up-Regulation of Hepatic Alpha-2-HS-Glycoprotein Transcription by Testosterone via Androgen Receptor Activation

    Directory of Open Access Journals (Sweden)

    Jakob Voelkl


    Full Text Available Background/Aims: Fetuin-A (alpha-2-HS-glycoprotein, AHSG, a liver borne plasma protein, contributes to the prevention of soft tissue calcification, modulates inflammation, reduces insulin sensitivity and fosters weight gain following high fat diet or ageing. In polycystic ovary syndrome, fetuin-A levels correlate with free androgen levels, an observation pointing to androgen sensitivity of fetuin-A expression. The present study thus explored whether the expression of hepatic fetuin-A is modified by testosterone. Methods: HepG2 cells were treated with testosterone and androgen receptor antagonist flutamide, and were silenced with androgen receptor siRNA. To test the in vivo relevance, male mice were subjected to androgen deprivation therapy (ADT for 7 weeks. AHSG mRNA levels were determined by quantitative RT-PCR and fetuin-A protein abundance by Western blotting. Results: In HepG2 cells, AHSG mRNA expression and fetuin-A protein abundance were both up-regulated following testosterone treatment. The human alpha-2-HS-glycoprotein gene harbors putative androgen receptor response elements in the proximal 5 kb promoter sequence relative to TSS. The effect of testosterone on AHSG mRNA levels was abrogated by silencing of the androgen receptor in HepG2 cells. Moreover, treatment of HepG2 cells with the androgen receptor antagonist flutamide in presence of endogenous ligands in the medium significantly down-regulated AHSG mRNA expression and fetuin-A protein abundance. In addition, ADT of male mice was followed by a significant decrease of hepatic Ahsg mRNA expression and fetuin-A protein levels. Conclusions: Testosterone participates in the regulation of hepatic fetuin-A expression, an effect mediated, at least partially, by androgen receptor activation.

  14. The Hertzsprung-gap giant 31 Comae in 2013: Magnetic field and activity indicators (United States)

    Borisova, Ana P.; Konstantinova-Antova, Renada; Aurière, Michel; Petit, Pascal; Charbonnel, Corinne


    We have observed the giant star 31 Comae in April and May 2013 with the spectropolarimeter Narval at Pic du Midi Observatory, France. 31 Comae is a single, rapidly rotating giant with rotational period ~6.8 d and vsini ~ 67 km/s. We present measurements and discuss variability of the longitudinal magnetic field (Bl), spectral activity indicators Hα, CaII H&K, Ca II IR triplet and evolutionary status. Our future aim is to perform a Zeeman-Doppler imaging study for the star.

  15. Hard X-ray photon index as an indicator of bolometric correction in active galactic nuclei


    Zhou, Xin-Lin; Zhao, Yong-Heng


    We propose the rest-frame 2-10 keV photon index, \\ga, acting as an indicator of the bolometric correction, \\lb/$L_{\\rm 2-10keV}$ (where \\lb~ is the bolometric luminosity and $L_{\\rm 2-10keV}$ is the rest-frame 2-10 keV luminosity), in radio-quiet active galactic nuclei (AGNs). Correlations between \\ga~ and both bolometric correction and Eddington ratio are presented, based on simultaneous X-ray, UV, and optical observations of reverberation -mapped AGNs. These correlations can be compared wit...

  16. Impact of ICTs on Innovation Activities: Indication for selected European countries

    Directory of Open Access Journals (Sweden)

    Zoroja Jovana


    Full Text Available The development and usage of information and communication technologies (ICTs has particularly increased in the last two decades, while at the same time showing great potential to improve the efficacy of business processes, facilitate and drive innovations, and therefore increase competitiveness. Innovation activities represent an important factor for social and economic change as well as for increasing competitive advantages at both the national and firm levels. This paper focuses on the role that ICTs play in the innovation performance of selected European countries. Using data drawn from the Eurostat and Global Competitiveness Index (2007–2011 and panel regression analysis, research results indicate that ICTs have a significant impact on business innovation activities.

  17. Relating cloud condensation nuclei activity and oxidation level of alpha-pinene secondary organic aerosols

    DEFF Research Database (Denmark)

    Foverskov, Mia Frosch Mogensbæk; Bilde, M.; DeCarlo, P. F.;


    was described by the contribution of the aerosol mass spectrometer (AMS) mass fragment m/z 44 to the total organic signal (f(44)) and the oxygen to carbon molar ratio (O/C), likewise determined with AMS. CCN activity, described by the hygroscopicity parameter kappa, was determined with a CCN counter...... determined: kappa = (0.071 +/- 0.02) . (O/C) + (0.0785 +/- 0.009) for particles with diameter in the range 59-200 nm. Growth kinetics of activating secondary organic aerosols were found to be comparable to those of ammonium sulfate and were not influenced by chemical aging....

  18. Assessment of subclinical atherosclerosis in ankylosing spondylitis: correlations with disease activity indices

    Directory of Open Access Journals (Sweden)

    F.M. Perrotta


    Full Text Available The aim of the study was to evaluate atherosclerosis in ankylosing spondylitis (AS through the assessment of morphological and functional measures of subclinical atherosclerosis. Twenty patients [M/F=12/8, age (median/range 43.5/28-69 years; disease duration (median/range 9.7/1-36 years] with AS classified according to modified New York criteria and twenty age and sex related healthy controls with negative past medical history for cardiovascular events were enrolled in the study. In all patients and controls, the intima-media thickness (IMT of common carotid artery, carotid bulb and internal carotid artery, and the flow-mediated dilatation (FMD of non-dominant arm brachial artery were determined, using a sonographic probe Esaote GPX (Genoa, Italy. Furthermore, we assess the main disease activity and disability indices [bath ankylosing spondylitis disease activity index, ankylosing spondylitis disease activity score-eritrosedimentation rate (ASDAS-ESR, ASDAS-C-reactive protein (CRP, bath ankylosing spondylitis metrology index, bath ankylosing spondylitis functional index and acute phase reactants. Plasmatic values of total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride and homocysteine were carried out in all twenty patients. IMT at carotid bulb was significant higher in patients than in controls (0.67 mm vs 0.54 mm; P=0.03. FMD did not statistically differ between patients and controls (12.5% vs 15%; P>0.05. We found a correlation between IMT at carotid bulb and ESR (rho 0.43; P=0.04. No correlation was found between FMD and disease activity and disability indices. This study showed that in AS patients, without risk factors for cardiovascular disease, carotid bulb IMT, morphological index of subclinical atherosclerosis, is higher than in controls.

  19. Neotectonic activity at the Giant Gjallar Vent (Norwegian Sea) indicates a future phase of active fluid venting (United States)

    Dumke, Ines; Berndt, Christian; Crutchley, Gareth; Couillard, Mélanie; Gay, Aurélien


    The Giant Gjallar Vent (GGV) is a hydrothermal vent complex that formed during the opening of the North Atlantic at about 55 Ma. Sill intrusions into Cretaceous organic-rich sediments led to the production and subsequent vigorous seafloor venting of methane. A later phase of fluid escape occurred in mid-Oligocene times. The GGV is characterised by two pipes of 440 m and 480 m in diameter that reach up to the Base Late Pliocene Unconformity (BLPU) between the Kai and Naust formations. The unconformity is strongly deformed over an area of c. 18,000 km² across the vent, with a positive relief of up to 38 m above the surrounding paleo-seafloor. The overlying sediments of the Naust Formation conformally drape this deformation, smoothing its relief to a maximum of 15 m at the modern seafloor. The sediment drape indicates present inactivity of the vent system, as does the absence of indicators of active fluid escape in the water column during RV METEOR cruise M87-2 in 2012. However, high-resolution 2D seismic and Parasound data from the same cruise, and exploration-type 3D seismic data acquired by Norsk Hydro, show several indications for recent to ongoing activity at the GGV. Beneath the BLPU, strong frequency attenuation and chaotic reflections indicate the presence of free gas. At the edges of the extent of chaotic reflections, subvertical faults cut the unconformity as well as horizons of the lower and middle Naust Formation, suggesting tectonic activity after deposition of these horizons. Neotectonic activity is further indicated by the extensive occurrence of shallow faults apparent in Parasound records in the immediate vicinity of the vent and up to 16 km away. Some of these faults reach the seafloor. The observed deformation and faults may be the result of fluids accumulating beneath the BLPU due to increased loading of the oozy Kai Formation by denser glacigenic Naust sediments. Because of the lower permeability of the Naust Formation, the unconformity acts as a

  20. Folic acid mediates activation of the pro-oncogene STAT3 via the Folate Receptor alpha. (United States)

    Hansen, Mariann F; Greibe, Eva; Skovbjerg, Signe; Rohde, Sarah; Kristensen, Anders C M; Jensen, Trine R; Stentoft, Charlotte; Kjær, Karina H; Kronborg, Camilla S; Martensen, Pia M


    The signal transducer and activator of transcription 3 (STAT3) is a well-described pro-oncogene found constitutively activated in several cancer types. Folates are B vitamins that, when taken up by cells through the Reduced Folate Carrier (RFC), are essential for normal cell growth and replication. Many cancer cells overexpress a glycophosphatidylinositol (GPI)-anchored Folate Receptor α (FRα). The function of FRα in cancer cells is still poorly described, and it has been suggested that transport of folate is not its primary function in these cells. We show here that folic acid and folinic acid can activate STAT3 through FRα in a Janus Kinase (JAK)-dependent manner, and we demonstrate that gp130 functions as a transducing receptor for this signalling. Moreover, folic acid can promote dose dependent cell proliferation in FRα-positive HeLa cells, but not in FRα-negative HEK293 cells. After folic acid treatment of HeLa cells, up-regulation of the STAT3 responsive genes Cyclin A2 and Vascular Endothelial Growth Factor (VEGF) were verified by qRT-PCR. The identification of this FRα-STAT3 signal transduction pathway activated by folic and folinic acid contributes to the understanding of the involvement of folic acid in preventing neural tube defects as well as in tumour growth. Previously, the role of folates in these diseases has been attributed to their roles as one-carbon unit donors following endocytosis into the cell. Our finding that folic acid can activate STAT3 via FRα adds complexity to the established roles of B9 vitamins in cancer and neural tube defects.

  1. Pollution evaluation in the Shahrood River: Do physico-chemical and macroinvertebrate-based indices indicate same responses to anthropogenic activities? (United States)

    Sharifinia, Moslem; Mahmoudifard, Abbas; Imanpour Namin, Javid; Ramezanpour, Zohreh; Yap, Chee Kong


    This study evaluates the impact of anthropogenic activities on the Shahrood River using water physico-chemical variables and macroinvertebrates data sets obtained over a period of 12 months between February 2012 and February 2013 at 8 sampling sites. Biotic indices i.e. FBI and BMWP based on macroinvertebrates and physico-chemical indices (MPI, HPI and NSF-WQI) were employed to evaluate the water quality status in connection with natural- and human-induced pressures. Based on physico-chemical indices, water quality was categorized as low polluted level and it is suitable for drinking purposes. The water quality based on biotic indices was related to the anthropic activities; a clear deterioration of the water quality was observed from upstream to downstream sites. The water quality along the river changed from very good (class I; reference sites) to good (class II; midstream sites) and turned into moderate (class III) and poor (class IV) quality (downstream sites). These findings indicate that biotic indices are more powerful indicators in assessing water quality than physico-chemical indices. Allocapnia, Glossosoma and Hesperoperla were exclusively related to least disturbed sites, and Naididae, Orthocladiinae and Ecdyonurus were found in sites showing notable degradation. Our results recommended that the use of macroinvertebrates could be employed as a cost-effective tool for biomonitoring and controlling of polluted riverine ecosystems in the Middle East. Finally, the results from this study may be useful not only for developing countries, but also for any organization struggling to use macroinvertebrate based indices with restricted financial resources and knowledge. PMID:27343865

  2. Induction of UDP-glucuronosyltransferase activities in Gunn, heterozygous, and Wistar rat livers by pregnenolone-16 alpha-carbonitrile. (United States)

    Watkins, J B; Klaassen, C D


    The effect of pregnenolone-16 alpha-carbonitrile (PCN) on UDP-glucuronosyltransferase (UDP-GT) activity was comprehensively examined in Wistar (JJ), heterozygous (Jj) and Gunn (jj) rats with eleven different acceptors for glucuronic acid. UDP-GT activity after 3-methylcholanthrene (3-MC) and phenobarbital (PB) treatment was studied in additional rats for comparative purposes. Conjugation of group-1 aglycones (1-naphthol and p-nitrophenol) was much lower in Gunn than in Wistar rats. PCN did not alter UDP-GT conjugation of these acceptors. UDP-GT activity toward group-1 aglycones was increased by 3-MC in Wistar and heterozygous rats but was not enhanced in Gunn rats by any inducer. Activity toward group-2 aglycones (morphine, chloramphenicol, valproic acid) was similar in control rats of all genotypes. PCN increased chloramphenicol conjugation, whereas PB enhanced the glucuronidation of all group-2 aglycones in Wistar, heterozygous, and Gunn rats. Conjugation of group-3 acceptors (bilirubin and digitoxigenin monodigitoxoside, DIG) was deficient in Gunn rats and was not inducible. PCN increased glucuronidation of bilirubin and DIG in Wistar and heterozygous rats. The concentration of UDP-glucuronic acid (UDPGA) in liver was similar in control animals of all genotypes and was increased in rats treated with 3-MC. The other inducers did not affect hepatic UDPGA levels. Thus, 3-MC, PB, and PCN induce UDP-GT activities toward different groups of acceptors of glucuronic acid. The results support the hypothesis that PCN induces a form of UDP-GT that preferentially conjugates the group-3 acceptors, bilirubin and DIG.

  3. Activation of P2 late transcription by P2 Ogr protein requires a discrete contact site on the C terminus of the alpha subunit of Escherichia coli RNA polymerase. (United States)

    Wood, L F; Tszine, N Y; Christie, G E


    Bacteriophage P2 late transcription requires the product of the P2 ogr gene. Ogr-dependent transcription from P2 late promoters is blocked by certain point mutations affecting the alpha subunits of the host RNA polymerase. An alanine scan spanning the putative activation target in the alpha C-terminal domain (alphaCTD) was carried out to identify individual residues essential for Ogr-dependent transcription from P2 late promoters. In addition, the effects of alanine substitutions in the regions of the alphaCTD previously reported to affect CAP-dependent activation of the lac promoter and UP-element DNA binding were examined. Residues E286, V287, L289 and L290 in helix 3, and residue L300 at the beginning of helix 4, define a surface-exposed patch on the alphaCTD important for Ogr-dependent activation. These residues, adjacent to the recently identified DNA-binding determinants, constitute a newly identified activation surface for protein:protein contact. Alanine substitutions at some of the residues that affect UP-element DNA binding also impaired activation. This suggests that upstream DNA-alpha contacts, in addition to alpha-Ogr contacts, may be important in P2 late transcription. Other residues implicated in the interaction of alpha with CAP are not required for activation by Ogr, consistent with previous genetic evidence suggesting that these activators contact different sites on the alphaCTD. PMID:9398509

  4. Triclocarban mediates induction of xenobiotic metabolism through activation of the constitutive androstane receptor and the estrogen receptor alpha.

    Directory of Open Access Journals (Sweden)

    Mei-Fei Yueh

    Full Text Available Triclocarban (3,4,4'-trichlorocarbanilide, TCC is used as a broad-based antimicrobial agent that is commonly added to personal hygiene products. Because of its extensive use in the health care industry and resistance to degradation in sewage treatment processes, TCC has become a significant waste product that is found in numerous environmental compartments where humans and wildlife can be exposed. While TCC has been linked to a range of health and environmental effects, few studies have been conducted linking exposure to TCC and induction of xenobiotic metabolism through regulation by environmental sensors such as the nuclear xenobiotic receptors (XenoRs. To identify the ability of TCC to activate xenobiotic sensors, we monitored XenoR activities in response to TCC treatment using luciferase-based reporter assays. Among the XenoRs in the reporter screening assay, TCC promotes both constitutive androstane receptor (CAR and estrogen receptor alpha (ERα activities. TCC treatment to hUGT1 mice resulted in induction of the UGT1A genes in liver. This induction was dependent upon the constitutive active/androstane receptor (CAR because no induction occurred in hUGT1Car(-/- mice. Induction of the UGT1A genes by TCC corresponded with induction of Cyp2b10, another CAR target gene. TCC was demonstrated to be a phenobarbital-like activator of CAR in receptor-based assays. While it has been suggested that TCC be classified as an endocrine disruptor, it activates ERα leading to induction of Cyp1b1 in female ovaries as well as in promoter activity. Activation of ERα by TCC in receptor-based assays also promotes induction of human CYP2B6. These observations demonstrate that TCC activates nuclear xenobiotic receptors CAR and ERα both in vivo and in vitro and might have the potential to alter normal physiological homeostasis. Activation of these xenobiotic-sensing receptors amplifies gene expression profiles that might represent a mechanistic base for

  5. Buffett's Alpha

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Kabiller, David; Heje Pedersen, Lasse

    Berkshire Hathaway has realized a Sharpe ratio of 0.76, higher than any other stock or mutual fund with a history of more than 30 years, and Berkshire has a significant alpha to traditional risk factors. However, we find that the alpha becomes insignificant when controlling for exposures to Betting...

  6. Effects of Organized Physical Activity on Selected Health Indices among Women Older than 55 Years

    Directory of Open Access Journals (Sweden)

    Piotr Zmijewski


    Full Text Available The main aim of this study was to determine health benefits among women older than 55 years who participated in organized, group-based physical activity (OPA. Thirty-five women aged 65.0 ± 7.3 years volunteered for this study. The classical and nonclassical cardiovascular (CVD risk factors were measured before and after a 2-week OPA camp in a remote location and 3 months of OPA. Self-guided physical activity was analyzed 18 months after OPA. Two-week effects included significant decreases in body mass index, waist and hip circumferences, resting systolic and diastolic blood pressure (BP and resting heart rate, improved exercise capacity (EC, improved low-density lipoprotein and high-density lipoprotein (HDL-C, cholesterol, and other atherogenic lipid indices (ALI, and a reduction in 10-year estimated risk of death from CVD. Three-month effects included a further decrease in systolic BP, improvements in EC and HDL-C, and maintenance of lower levels of ALI, as well as lower CVD risk. The implementation of the OPA programme had a positive impact on somatic features, exercise capacity, biochemical indices, and risk for death from CVD. The presented programme can be regarded as an effective element of primary prevention of cardiovascular diseases among women older than 55 years.

  7. Analysis of the heat shock response in mouse liver reveals dependence on the Nuclear Receptor Peroxisome Proliferator-Activated Receptor alpha (PPARalpha)

    NARCIS (Netherlands)

    Vallanat, B.; Anderson, S.P.; Brown-Borg, H.M.; Ren, H.; Kersten, A.H.; Jonnalagadda, S.; Srinivasan, S.; Corton, J.C.


    Background - The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARa) regulates responses to chemical or physical stress in part by altering expression of genes involved in proteome maintenance. Many of these genes are also transcriptionally regulated by heat shock (HS) through

  8. Regulation of hepatic peroxisome proliferator-activated receptor-alpha (PPAR-a) expression but not adiponectin by dietary protein in finishing pigs (United States)

    Dietary soy protein reduction and supplemental leucine (Leu) have been found to decrease leanness and increase muscle lipid content of pig carcasses respectively. Soy protein regulates adiponectin and peroxisome proliferator activated receptor-alpha (PPAR-a) in some species, but the effect of dieta...

  9. Identification of 7alpha-hydroxypregnenolone, a novel bioactive amphibian neurosteroid stimulating locomotor activity, and its physiological roles in the regulation of locomotion. (United States)

    Tsutsui, Kazuyoshi; Haraguchi, Shogo; Matsunaga, Masahiro; Koyama, Teppei; Do Rego, Jean-Luc; Vaudry, Hubert


    We now know that steroids can be synthesized de novo by the brain and the peripheral nervous system. Such steroids are called neurosteroids and de novo neurosteroidogenesis from cholesterol is a conserved property of vertebrate brains. Our studies over the past decade have demonstrated that the brain expresses several kinds of steroidogenic enzymes and produces a variety of neurosteroids in sub-mammalian species. However, neurosteroid biosynthetic pathways in amphibians, as well as other vertebrates may still not be fully mapped. We first found that the newt brain actively produces 7alpha-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. We then demonstrated that 7alpha-hydroxypregnenolone acts as a novel bioactive neurosteroid to stimulate locomotor activity of newt by means of the dopaminergic system. Subsequently, we analyzed the physiological roles of 7alpha-hydroxypregnenolone in the regulation of locomotor activity of newt. This paper summarizes the advances made in our understanding of 7alpha-hydroxypregnenolone, a newly discovered bioactive amphibian neurosteroid stimulating locomotor activity, and its physiological roles in the regulation of locomotion in newt.

  10. Synthesis and structure-activity relationships of 4-fluorophenyl-imidazole p38 alpha MAPK, CK1 delta and JAK2 kinase inhibitors

    NARCIS (Netherlands)

    Seerden, Jean-Paul G.; Leusink-Ionescu, Gabriela; Woudenberg - Vrenken, Titia; Dros, Bas; Molema, Grietje; Kamps, Jan A. A. M.; Kellogg, Richard M.


    The synthesis and structure-activity relationships of novel 4-(4 '-fluorophenyl)imidazoles as selective p38 alpha MAPK, CK1 delta and JAK2 inhibitors with improved water solubility are described. Microwave-assisted multicomponent reactions afforded 4-fluorophenyl-2,5-disubstituted imidazoles. Carbox

  11. L-3-[I-123]iodo-alpha-methyltyrosine scintigraphy in carcinoid tumors : Correlation with biochemical activity and comparison with [In-111-DTPA-D-Phe(1)]-octreotide imaging

    NARCIS (Netherlands)

    Jager, PL; Meijer, WG; Kema, IP; Willemse, PHB; Piers, DA; de Vries, EGE


    Carcinoid tumors can produce serotonin (5-hydroxytryptamine) and catecholamines from the precursors tryptophan and tyrosine. Our aim was to evaluate the tyrosine analog L-3-[I-123]iodo-alpha -methyltyrosine (IMT) in the detection and the determination of biochemical activity of these tumors in compa

  12. HST/ACS H-alpha Imaging of the Carina Nebula: Outflow Activity Traced by Irradiated Herbig-Haro Jets

    CERN Document Server

    Smith, Nathan; Walborn, Nolan R


    We report the discovery of new Herbig-Haro (HH) jets in the Carina Nebula, and we discuss the protostellar outflow activity of a young OB association. These are the first results of an HST/ACS H-alpha imaging survey of Carina. Adding to the one previously known example (HH666), we detect 21 new HH jets, plus 17 new candidate jets, ranging in length from 0.005 to 3 pc. We derive jet mass-loss rates ranging from 8e-9 to 1e-6 Msun/yr, but a comparison to the distribution of jet mass-loss rates in Orion suggests that we may be missing a large fraction of the jets below 1e-8 Msun/yr. A key qualitative result is that even some of the smallest dark globules with sizes of 0.01pc are active sites of ongoing star formation because we see HH jets emerging from them, and that these offer potential analogs to the cradle of our Solar System because of their proximity to dozens of imminent supernovae that will enrich them with radioactive nuclides like 60Fe. HST images reveal proplyd structures in the core of the Tr14 clust...

  13. Hydrothermal synthesis of cubic {alpha}-Fe{sub 2}O{sub 3} microparticles using glycine: Surface characterization, reaction mechanism and electrochemical activity

    Energy Technology Data Exchange (ETDEWEB)

    Yin Chunyang, E-mail: [School of Chemical and Mathematical Sciences, Murdoch University, Murdoch, 6150 WA (Australia); Minakshi, Manickam; Ralph, David E. [School of Chemical and Mathematical Sciences, Murdoch University, Murdoch, 6150 WA (Australia); Jiang Zhongtao [School of Engineering and Energy, Murdoch University, Murdoch, 6150 WA (Australia); Xie Zonghan; Guo Hua [School of Engineering, Edith Cowan University, Joondalup, WA, 6027 (Australia)


    Graphical abstract: Highlights: > We synthesize cubic {alpha}-Fe{sub 2}O{sub 3} (hematite) microparticles. > Their morphological, mineralogical and surface properties are determined. > Reaction mechanism based on thermodynamics and ionic equilibrium concepts are described. > Microparticles have charge capacity of 160 mAh/g and good columbic efficiency of 94%. - Abstract: Cubic {alpha}-Fe{sub 2}O{sub 3} (hematite) microparticles (side lengths = 0.3-1.3 {mu}m) have been synthesized using glycine and ferric chloride via a simple one-step hydrothermal reaction. Their morphological, mineralogical and surface properties have been determined using scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS). XRD analysis indicated that the synthesized {alpha}-Fe{sub 2}O{sub 3} microparticles were minerallogically pure. An increase in hydrothermal reaction duration from 10 to 24 h increased the atomic percentages of {alpha}-Fe{sub 2}O{sub 3} on the surface of the microparticles by almost 8%. The mechanism concerning reactions of species to produce this microparticles precipitate was elucidated based on thermodynamics and ionic equilibrium aspects. In the electrochemical analysis, the synthesized {alpha}-Fe{sub 2}O{sub 3} microparticles (as cathode material) exhibit an approximate charge capacity of 160 mAh/g and excellent coulombic efficiency of 94%.

  14. Bioactive compounds from Carissa opaca roots and xanthine oxidase and alpha-amylase inhibitory activities of their methanolic extract and its fractions in different solvents

    Directory of Open Access Journals (Sweden)

    Ramsha Saeed


    Full Text Available Background: Carissa opaca is known for its many ethnomedicinal uses. There was a need to study its bioactivities and identify its phytochemicals. Objective: The objective was to isolate and identify phytochemicals from roots of C. opaca and to evaluate xanthine oxidase (XO and alpha-amylase inhibitory activities of their methanolic extract and its fractions. Materials and Methods: Methanolic extract of finely divided powder of roots of C. opaca was obtained by cold maceration, followed by its fractionation to obtain hexane, chloroform, ethyl acetate, n-butanolic, and aqueous fractions. Phytochemicals screening was done by standard protocols. XO and alpha-amylase inhibitory activities of the methanolic extract and its fractions were studied. The most active ethyl acetate fraction was subjected to the column and thin layer chromatography to isolate its compounds, which were identified by gas chromatography-mass spectrometry and high-performance liquid chromatography comparison. Results: Methanolic extract displayed significant activity against both the enzymes with IC 50 of 156.0 mg/mL and 5.6 mg/mL for XO and alpha-amylase, respectively. Ethyl acetate fraction showed highest activity against both the enzymes with IC 50 of 129 mg/mL and 4.9 mg/mL for XO and alpha-amylase, respectively. Chloroform fraction had IC 50 of 154.2 mg/mL and 5.5 mg/mL for XO and alpha-amylase, respectively. Aqueous fraction exhibited significant efficacy against alpha-amylase (IC 50 5.0 mg/mL. Hexane fraction showed good activity against alpha-amylase in a dose-dependent manner but exhibited opposite trend against XO. The compounds isolated from ethyl acetate fraction included limonene, vanillin, lupeol, rutin, quercetin, b-sitosterol, Vitamin E, 2-hydroxyacetophenone, naphthalenone, 2,3,3-trimethyl-2-(3-methylbuta-1,3-dienyl-6-methylenecyclohexanone, and 2-benzenedicarboxylic acid, mono(2-ethylhexyl ester. Conclusions: Moderately polar phytochemicals of C. opaca roots

  15. Detection of sialidase (neuraminidase) activity in Actinomyces species by using 2'-(4-methylumbelliferyl)alpha-D-N-acetylneuraminic acid in a filter paper spot test.


    Moncla, B. J.; Braham, P


    A rapid method for the detection of acetylneuraminyl hydrolase, EC (sialidase or neuraminidase), was developed by using 2'-(4-methylumbelliferyl)alpha-D-N-acetylneuraminic acid as substrate in a filter paper spot test. The method was compared to conventional assays that use 2'-(4-methylumbelliferyl)alpha-D-N-acetylneuraminic acid and bovine submaxillary mucin and was found to be in excellent agreement. Organisms with greater than 10 U of enzyme activity (in nanomoles per minute per m...

  16. [Voluntary alpha-power increasing training impact on the heart rate variability]. (United States)

    Bazanova, O M; Balioz, N V; Muravleva, K B; Skoraia, M V


    In order to study the effect of the alpha EEG power increasing training at heart rate variability (HRV) as the index of the autonomic regulation of cognitive functions there were follow tasks: (1) to figure out the impact of biofeedback in the voluntary increasing the power in the individual high-frequency alpha-band effect on heart rate variability and related characteristics of cognitive and emotional spheres, (2) to determine the nature of the relationship between alpha activity indices and heart rate variability, depending on the alpha-frequency EEG pattern at rest (3) to examine how the individual alpha frequency EEG pattern is reflected in changes HRV as a result of biofeedback training. Psychometric indicators of cognitive performance, the characteristics of the alpha-EEG activity and heart rate variability (HRV) as LF/HF and pNN50 were recorded in 27 healthy men aged 18-34 years, before, during, and after 10 sessions of training of voluntary increase in alpha power in the individual high-frequency alpha band with eyes closed. To determine the biofeedback effect on the alpha power increasing training, data subjects are compared in 2 groups: experimental (14) with the real and the control group (13 people)--with mock biofeedback. The follow up effect of trainings was studied through month over the 10 training sessions. Results showed that alpha biofeedback training enhanced the fluency and accuracy in cognitive performance, decreased anxiety and frontal EMG, increased resting frequency, width and power in individual upper alpha range only in participants with low baseline alpha frequency. While mock biofeedback increased resting alpha power only in participants with high baseline resting alpha frequency and did change neither cognitive performance, nor HRV indices. Biofeedback training eliminated the alpha power decrease in response to arithmetic task in both with high and low alpha frequency participants and this effect was followed up over the month. Mock

  17. Alpha-Glucosidase Inhibition and Hypoglycemic Activities of Sweitenia mahagoni Seed Extract

    Directory of Open Access Journals (Sweden)

    Tutik Wresdiyat


    Full Text Available Inhibition of α-glucosidase and hypoglycemic activity are two effects commonly used to identify bioactive compounds with potential to treat diabetes. The objectives of this study were to analyse and compare the bioactive compounds and α-glucosidase inhibitory effect of four different types of Swietenia mahagoni seed extract, and to analyse the hypoglycemic activity of the greatest inhibition of α-glucosidase-extract in rats. The extracts were obtained using two different solvents (aqueous and ethanol and two different methods: maceration and reflux methods. This resulted in four types of extract varying by solvent and extraction method. Testing of these extracts for α-glucosidase inhibitory effect was carried out in vitro using spectrophotometer. Testing for hypoglycemic activity was carried out in vivo using rats. A total of 40 male Sprague-Dawley rats were divided into eight groups: (1 the negative control group, received an oral dose of aquadest only, (2 the positive control group, was given 90% sucrose orally without S. mahagoni seed extract, and five treated groups (3-7, were given 90% sucrose followed by the best extract-ethanolic S. mahagoni seed extract in doses of 100, 200, 300, 400, and 500 mg/kgBW, and (8 the acarbose group, was given 90% sucrose orally followed by acarbose. Glucose levels in each animal were measured at 0, 30, 60, 90, and 120 min after treatment. The results showed the greatest inhibition of α-glucosidase in ethanolic extract, using maceration methods. This ethanolic-maceration S. mahagoni seed extract also showed hypoglycemic effects in hyperglycemic rats at dose from 100 to 500 mg/kgBW. Ethanolic extract of S. mahagoni seed, using maceration method, can be proposed as potential antidiabetic agent.

  18. In silico approach for alpha-amylase inhibitory activity of diosmetin and galangin


    Arumugam Madeswaran; Kuppusamy Asokkumar; Muthuswamy Umamaheswari; Thirumalaisamy Sivashanmugam; Varadharajan Subhadradevi


    Objective: The objective of the current study is to evaluate the α-amylase inhibitory activity of diosmetin and galangin using in silico docking studies.Methods: In this perspective, diosmetin and galangin were prepared for the docking evaluation. Acarbose, a known α-amylase inhibitor was used as the standard. In silico docking studies were carried out using recent version of AutoDock 4.2, which has the basic principle of Lamarckian genetic algorithm.Results: The results showed that the selec...

  19. Development and validation of stability indicating UPLC assay method for ziprasidone active pharma ingredient

    Directory of Open Access Journals (Sweden)

    Sonam Mittal


    Full Text Available Background: Ziprasidone, a novel antipsychotic, exhibits a potent highly selective antagonistic activity on D2 and 5HT2A receptors. Literature survey for ziprasidone revealed several analytical methods based on different techniques but no UPLC method has been reported so far. Aim: Aim of this research paper is to present a simple and rapid stability indicating isocratic, ultra performance liquid chromatographic (UPLC method which was developed and validated for the determination of ziprasidone active pharmaceutical ingredient. Forced degradation studies of ziprasidone were studied under acid, base, oxidative hydrolysis, thermal stress and photo stress conditions. Materials and Methods: The quantitative determination of ziprasidone drug was performed on a Supelco analytical column (100×2.1 mm i.d., 2.7 ΅m with 10 mM ammonium acetate buffer (pH: 6.7 and acetonitrile (ACN as mobile phase with the ratio (55:45-Buffer:ACN at a flow rate of 0.35 ml/ min. For UPLC method, UV detection was made at 318 nm and the run time was 3 min. Developed UPLC method was validated as per ICH guidelines. Results and Conclusion: Mild degradation of the drug substance was observed during oxidative hydrolysis and considerable degradation observed during basic hydrolysis. During method validation, parameters such as precision, linearity, ruggedness, stability, robustness, and specificity were evaluated, which remained within acceptable limits. Developed UPLC method was successfully applied for evaluating assay of Ziprasidone active Pharma ingredient.

  20. Imaging activity in astrocytes and neurons with genetically encoded calcium indicators following in utero electroporation. (United States)

    Gee, J Michael; Gibbons, Meredith B; Taheri, Marsa; Palumbos, Sierra; Morris, S Craig; Smeal, Roy M; Flynn, Katherine F; Economo, Michael N; Cizek, Christian G; Capecchi, Mario R; Tvrdik, Petr; Wilcox, Karen S; White, John A


    Complex interactions between networks of astrocytes and neurons are beginning to be appreciated, but remain poorly understood. Transgenic mice expressing fluorescent protein reporters of cellular activity, such as the GCaMP family of genetically encoded calcium indicators (GECIs), have been used to explore network behavior. However, in some cases, it may be desirable to use long-established rat models that closely mimic particular aspects of human conditions such as Parkinson's disease and the development of epilepsy following status epilepticus. Methods for expressing reporter proteins in the rat brain are relatively limited. Transgenic rat technologies exist but are fairly immature. Viral-mediated expression is robust but unstable, requires invasive injections, and only works well for fairly small genes (option of co-expressing a cytosolic tdTomato protein. A binary system consisting of a plasmid carrying a piggyBac inverted terminal repeat (ITR)-flanked CAG-GCaMP-IRES-tdTomato cassette and a separate plasmid encoding for expression of piggyBac transposase was employed to stably express GCaMP and tdTomato. The plasmids were co-electroporated on embryonic days 13.5-14.5 and astrocytic and neuronal activity was subsequently imaged in acute or cultured brain slices prepared from the cortex or hippocampus. Large spontaneous transients were detected in slices obtained from rats of varying ages up to 127 days. In this report, we demonstrate the utility of this toolset for interrogating astrocytic and neuronal activity in the rat brain. PMID:25926768

  1. In silico approach for alpha-amylase inhibitory activity of diosmetin and galangin

    Directory of Open Access Journals (Sweden)

    Arumugam Madeswaran


    Full Text Available Objective: The objective of the current study is to evaluate the α-amylase inhibitory activity of diosmetin and galangin using in silico docking studies.Methods: In this perspective, diosmetin and galangin were prepared for the docking evaluation. Acarbose, a known α-amylase inhibitor was used as the standard. In silico docking studies were carried out using recent version of AutoDock 4.2, which has the basic principle of Lamarckian genetic algorithm.Results: The results showed that the selected flavonoids showed binding energy ranging between -6.84 kcal/mol to  -5.96 kcal/mol when compared with that of the standard (-1.97 kcal/mol. Inhibition constant (9.73 µM to 42.76 µM and intermolecular energy (-8.33 kcal/mol to -7.15 kcal/mol of the ligands also coincide with the binding energy.Conclusion: Diosmetin and galangin contributed excellent α-amylase inhibitory activity than the standard because of its structural parameters. These molecular docking analyses of the selected compounds could lead to the further development to find the potent α-amylase inhibitors for the treatment of diabetes.  

  2. Influence of liquid medium on the activity of a low-alpha Fischer-Tropsch catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Gormley, R.J.; Zarochak, M.F.; Deffenbaugh, P.W.; Rao, K.R.P.M.


    The purpose of this research was to measure activity, selectivity, and the maintenance of these properties in slurry autoclave experiments with a Fischer-Tropsch (FT) catalyst that was used in the {open_quotes}FT II{close_quotes} bubble-column test, conducted at the Alternative Fuels Development Unit (AFDU) at LaPorte, Texas during May 1994. The catalyst contained iron, copper, and potassium and was formulated to produce mainly hydrocarbons in the gasoline range with lesser production of diesel-range products and wax. The probability of chain growth was thus deliberately kept low. Principal goals of the autoclave work have been to find the true activity of this catalyst in a stirred tank reactor, unhindered by heat or mass transfer effects, and to obtain a steady conversion and selectivity over the approximately 15 days of each test. Slurry autoclave testing of the catalyst in heavier waxes also allows insight into operation of larger slurry bubble column reactors. The stability of reactor operation in these experiments, particularly at loadings exceeding 20 weight %, suggests the likely stability of operations on a larger scale.

  3. ALMA observations of a z~3.1 Protocluster: Star Formation from Active Galactic Nuclei and Lyman-Alpha Blobs in an Overdense Environment

    CERN Document Server

    Alexander, D M; Harrison, C M; Mullaney, J R; Smail, I; Geach, J E; Hickox, R C; Hine, N K; Karim, A; Kubo, M; Lehmer, B D; Matsuda, Y; Rosario, D J; Stanley, F; Swinbank, A M; Umehata, H; Yamada, T


    We exploit ALMA 870um observations to measure the star-formation rates (SFRs) of eight X-ray detected Active Galactic Nuclei (AGNs) in a z~3.1 protocluster, four of which reside in extended Ly-alpha haloes (often termed Ly-alpha blobs: LABs). Three of the AGNs are detected by ALMA and have implied SFRs of ~220-410~M_sun/yr; the non detection of the other five AGNs places SFR upper limits of 100 kpc) do not host more luminous star formation than the smaller LABs, despite being an order of magnitude brighter in Ly-alpha emission. We use these results to discuss star formation as the power source of LABs.

  4. Medicinal flowers. XXIII. New taraxastane-type triterpene, punicanolic acid, with tumor necrosis factor-alpha inhibitory activity from the flowers of Punica granatum. (United States)

    Xie, Yuanyuan; Morikawa, Toshio; Ninomiya, Kiyofumi; Imura, Katsuya; Muraoka, Osamu; Yuan, Dan; Yoshikawa, Masayuki


    The methanolic extract from the flowers of Punica granatum L. (Punicaceae) was found to show inhibitory effect on tumor necrosis factor-alpha (TNF-alpha, 1 ng/ml)-induced cytotoxicity in L929 cells. By bioassay-guided separation, a new taraxastane-type triterpene, punicanolic acid (1), was isolated from the active fraction (ethyl acetate-soluble fraction) together with four triterpenes (2--5), two galloyl glucoses (6, 7), two flavones (8, 9), and beta-sitosterol. Among the constituents, 1, oleanolic acid (2), maslinic acid (4), 1,2,6-tri-O-galloyl beta-D-glucopyranoside (6), 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl beta-D-glucopyranoside (7), and luteolin (8) significantly inhibited TNF-alpha-induced cytotoxicity in L929 cells at 30 microM. PMID:18981621

  5. The radioprotective activities of turpentine-induced inflammation and {alpha}{sub 2}-macroglobulin. The effect of dexamethasone on the radioprotective efficacy of the inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Sevaljevic, L.; Koricanac, G.; Vulovic, M.; Kanazir, D.; Ribarac-Stepic, N. [Vinca Inst. of Nuclear Sciences, Belgrade (Yugoslavia); Dobric, S. [Military Medical Academy, Belgrade (Yugoslavia); Bogojevic, D.; Petrovic, M. [Inst. of Biological Research, Belgrade (Yugoslavia)


    This work was aimed at the radioprotective efficacy of turpentine oil (TO), {alpha}{sub 2}-macroglobulin ({alpha}{sub 2}-M), amifostine (Ami) and/or dexamethasone (Dex). These agents were administrated, alone or in combination, prior to irradiation of rats with 6.7 Gy (LD{sub 50/30}). The survival was recorded daily for 4 weeks after irradiation and body weight, peripheral leukocytes and thrombocytes were measured. The plasma concentration of {alpha}{sub 2}-M and other acute phase proteins were determined by crossed immunoelectrophoresis. All rats receiving {alpha}{sub 2}-M and Ami alone or in combination survived the radiation injury, whereas the rate of survival of TO-treated rats was 90%. Radiation and therapy-induced changes in the expression of acute phase protein genes were atypical for the acute phase reaction. Dex alone was lethal for 45% and 55% of control and irradiated rats, respectively. Pretreatment with 1 mg Dex reduced radioprotective efficacy of TO and Ami to 30% and 40%, respectively. Given together TO and Ami provided 70% protection to rats receiving Dex. The TO and {alpha}{sub 2}-M enhanced the rate of survival from 50% to 90% and 100%, respectively. In the presence of 1 mg Dex the TO-induced radioprotectors and Ami exhibited radiosensitizing rather than radioprotecting activities. (author)


    Directory of Open Access Journals (Sweden)

    O. M. Bazanova


    Full Text Available With the purpose to study the impact of the upper frequency alpha EEG power increasing neurofeedback training (ANFT on the cognitive performance, EEG alpha-activity and heart rate variability (HRV 27 healthy men aged 18–34 years in pre, post and follow up one month 10 sessions ANFT time were investigated. The AFNT enhanced the fluency in cognitive performance, alpha frequency and power in upper frequency range and HRV only in participants with low baseline alpha frequency. While mock AFNT did change neither cognitive performance, nor alpha-activity, nor HRV indices. ANT reduces activation in cognitive load, and this effect persists for a month.

  7. Antiproliferative Activity of Cinnamomum cassia Constituents and Effects of Pifithrin-Alpha on Their Apoptotic Signaling Pathways in Hep G2 Cells

    Directory of Open Access Journals (Sweden)

    Lean-Teik Ng


    Full Text Available Cinnamaldehyde (Cin, cinnamic acid (Ca and cinnamyl alcohol (Cal, major constituents of Cinnamomum cassia, have been shown to possess antioxidant, anti-inflammatory, anticancer and other activities. In this study, our aim was to evaluate the antiproliferative activity of these compounds in human hepatoma Hep G2 cells and examine the effects of pifithrin-alpha (PFTα; a specific p53 inhibitor on their apoptotic signaling transduction mechanism. The antiproliferative activity was measured by XTT assay. Expression of apoptosis-related proteins was detected by western blotting. Results showed that at a concentration of 30 μM, the order of antiproliferative activity in Hep G2 cells was Cin > Ca > Cal. Cin (IC50 9.76 ± 0.67 μM demonstrated an antiproliferative potency as good as 5-fluorouracil (an anti-cancer drug; IC50 9.57 ± 0.61 μM. Further studies on apoptotic mechanisms of Cin showed that it downregulated the expression of Bcl-XL, upregulated CD95 (APO-1, p53 and Bax proteins, as well as cleaving the poly (ADP-ribose polymerase (PARP in a time-dependent pattern. PFTα pre-incubation significantly diminished the effect of Cin-induced apoptosis. It markedly upregulated the anti-apoptotic (Bcl-XL expression and downregulated the pro-apoptotic (Bax expression, as well as effectively blocking the CD95 (APO-1 and p53 expression, and PARP cleavage in Cin-treated cells. This study indicates that Cin was the most potent antiproliferative constituent of C. cassia, and its apoptotic mechanism in Hep G2 cells could be mediated through the p53 induction and CD95 (APO-1 signaling pathways.

  8. pRb controls estrogen receptor alpha protein stability and activity. (United States)

    Caligiuri, Isabella; Toffoli, Giuseppe; Giordano, Antonio; Rizzolio, Flavio


    A cross talk between the Estrogen Receptor (ESR1) and the Retinoblastoma (pRb) pathway has been demonstrated to influence the therapeutic response of breast cancer patients but the full mechanism remains poorly understood. Here we show that the N-terminal domain of pRb interacts with the CD domain of ESR1 to allow for the assembly of intermediate complex chaperone proteins HSP90 and p23. We demonstrated that a loss of pRb in human/mouse breast cells decreases the expression of the ESR1 protein through the proteasome pathway. Our work reveals a novel regulatory mechanism of ESR1 basal turnover and activity and an unanticipated relationship with the pRb tumor suppressor.

  9. Malignant T cells express lymphotoxin alpha and drive endothelial activation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Lauenborg, Britt; Christensen, Louise; Ralfkiaer, Ulrik;


    Lymphotoxin α (LTα) plays a key role in the formation of lymphatic vasculature and secondary lymphoid structures. Cutaneous T cell lymphoma (CTCL) is the most common primary lymphoma of the skin and in advanced stages, malignant T cells spreads through the lymphatic to regional lymph nodes...... to internal organs and blood. Yet, little is known about the mechanism of the CTCL dissemination. Here, we show that CTCL cells express LTα in situ and that LTα expression is driven by aberrantly activated JAK3/STAT5 pathway. Importantly, via TNF receptor 2, LTα functions as an autocrine factor by stimulating...... expression of IL-6 in the malignant cells. LTα and IL-6, together with VEGF promote angiogenesis by inducing endothelial cell sprouting and tube formation. Thus, we propose that LTα plays a role in malignant angiogenesis and disease progression in CTCL and may serve as a therapeutic target in this disease....

  10. Monoclonal Antibodies Targeting the Alpha-Exosite of Botulinum Neurotoxin Serotype/A Inhibit Catalytic Activity.

    Directory of Open Access Journals (Sweden)

    Yongfeng Fan

    Full Text Available The paralytic disease botulism is caused by botulinum neurotoxins (BoNT, multi-domain proteins containing a zinc endopeptidase that cleaves the cognate SNARE protein, thereby blocking acetylcholine neurotransmitter release. Antitoxins currently used to treat botulism neutralize circulating BoNT but cannot enter, bind to or neutralize BoNT that has already entered the neuron. The light chain endopeptidase domain (LC of BoNT serotype A (BoNT/A was targeted for generation of monoclonal antibodies (mAbs that could reverse paralysis resulting from intoxication by BoNT/A. Single-chain variable fragment (scFv libraries from immunized humans and mice were displayed on the surface of yeast, and 19 BoNT/A LC-specific mAbs were isolated by using fluorescence-activated cell sorting (FACS. Affinities of the mAbs for BoNT/A LC ranged from a KD value of 9.0×10-11 M to 3.53×10-8 M (mean KD 5.38×10-9 M and median KD 1.53×10-9 M, as determined by flow cytometry analysis. Eleven mAbs inhibited BoNT/A LC catalytic activity with IC50 values ranging from 8.3 ~73×10-9 M. The fine epitopes of selected mAbs were also mapped by alanine-scanning mutagenesis, revealing that the inhibitory mAbs bound the α-exosite region remote from the BoNT/A LC catalytic center. The results provide mAbs that could prove useful for intracellular reversal of paralysis post-intoxication and further define epitopes that could be targeted by small molecule inhibitors.

  11. Diagnostic Accuracy of Anthropometric Indicators in the Prediction of Urinary Incontinence in Physically Active Older Women. (United States)

    Menezes, Enaiane Cristina; Virtuoso, Janeisa Franck; Capeletto, Eduardo; Silva, Lislayne Luiza da; Chagas, Jodelle Machado; Mazo, Giovana Zarpellon


    Purpose To determine the diagnostic accuracy and the cutoff point of the variables conicity index, waist to height ratio and fat percentage to detect urinary incontinence in physically active older women. Method A total of 152 women were analyzed. The instruments used were the International Physical Activity Questionnaire (IPAQ [Area 4]) to check the level of physical activity, and the Diagnostic Form to obtain sociodemographic data and presence of urinary incontinence. To calculate the conicity index, waist to height ratio and fat percentage, body mass, height and waist circumference were measured. Descriptive and inferential statistics were used. Cutoff points, sensitivity (S) and specificity (SP) were determined by receiver operating characteristic (ROC) curves. A 5% significance level was adopted. Results The prevalence of urinary incontinence was of 32.2%. The cutoff point with better sensitivity and specificity for the conicity index was 1.23 (S = 87.8; SP = 35.9); for the waist to height ratio, it was 0.57 (S = 79.6; SP = 45.6); and for the fat percentage, it was 39.71 (S = 89.8; SP = 42.7). The area under the ROC curve was 0.666 for the conicity index, 0.653 for the waist to height ratio, and 0.660 for the fat percentage. Conclusions The cutoff points for the anthropometric measurements conicity index, waist to height ratio and fat percentage indicate that these measures can be used to predict urinary incontinence in physically active older women. Furthermore, fat percentage seemed to be the best measure for this population. PMID:27571385

  12. Plume indications from hydrothermal activity on Kawio Barat Submarine Volcano, Sangihe Talaud Sea, North Sulawesi, Indonesia (United States)

    Makarim, S.; Baker, E. T.; Walker, S. L.; Wirasantosa, S.; Permana, H.; Sulistiyo, B.; Shank, T. M.; Holden, J. F.; Butterfield, D.; Ramdhan, M.; Adi, R.; Marzuki, M. I.


    Kawio Barat submarine volcano has formed in response to the active tectonic conditions in Sangihe Talaud, an area that lies in the subduction zone between the Molucca Sea Plate and Celebes Sea Plate. Submarine volcanic activity in the western Sangihe volcanic arc is controlled by the west-dipping Molucca Sea Plate as it subducts beneath the Sangihe Arc. A secondary faulting system on Kawio Barat is in a northwest - southeast direction, and creates a network of deep cracks that facilitate hydrothermal discharge in this area. Hydrothermal activity on Kawio Barat was first discovered by joint Indonesia/Australian cruises in 2003. In 2010, as part of the joint US/Indonesian INDEX-SATAL expedition, we conducted CTD casts that confirmed continuing activity. Hydrothermal plumes were detected by light -scattering (LSS) and oxidation-reduction potential (ORP) sensors on the CTD package. LSS anomalies were found between 1600-1900 m, with delta NTU levels of 0.020-0.040. ORP anomalies coincident with the LSS anomalies indicate strong concentrations of reduced species such as H2S and Fe, confirming the hydrothermal origin of the plumes. Images of hydrothermal vents on Kawio Barat Submarine volcano, recorded by high- definition underwater cameras on the ROV “Little Hercules” operated from the NOAA ship Okeanos Explorer, confirmed the presence and sources of the detected vent plumes in the northern and southwest part of the summit in 1800-1900 m depth. In southwest part of this summit chimney, drips of molten sulfur were observed in the proximity of microbal staining.

  13. Unlike PPAR{gamma}, PPAR{alpha} or PPAR{beta}/{delta} activation does not promote human monocyte differentiation toward alternative macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Bouhlel, Mohamed Amine [Univ Lille Nord de France, F-59000 Lille (France); Inserm U545, F-59000 Lille (France); UDSL, F-59000 Lille (France); Institut Pasteur de Lille, F-59019 Lille (France); Brozek, John [Genfit, Loos (France); Derudas, Bruno [Univ Lille Nord de France, F-59000 Lille (France); Inserm U545, F-59000 Lille (France); UDSL, F-59000 Lille (France); Institut Pasteur de Lille, F-59019 Lille (France); Zawadzki, Christophe; Jude, Brigitte [Inserm ERI-9 and Equipe d' Accueil 2693, IFR114, Universite de Lille, Lille (France); Staels, Bart, E-mail: [Univ Lille Nord de France, F-59000 Lille (France); Inserm U545, F-59000 Lille (France); UDSL, F-59000 Lille (France); Institut Pasteur de Lille, F-59019 Lille (France); Chinetti-Gbaguidi, Giulia [Univ Lille Nord de France, F-59000 Lille (France); Inserm U545, F-59000 Lille (France); UDSL, F-59000 Lille (France); Institut Pasteur de Lille, F-59019 Lille (France)


    Macrophages adapt their response to micro-environmental signals. While Th1 cytokines promote pro-inflammatory M1 macrophages, Th2 cytokines promote an 'alternative' anti-inflammatory M2 macrophage phenotype. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors expressed in macrophages where they control the inflammatory response. It has been shown that PPAR{gamma} promotes the differentiation of monocytes into anti-inflammatory M2 macrophages in humans and mice, while a role for PPAR{beta}/{delta} in this process has been reported only in mice and no data are available for PPAR{alpha}. Here, we show that in contrast to PPAR{gamma}, expression of PPAR{alpha} and PPAR{beta}/{delta} overall does not correlate with the expression of M2 markers in human atherosclerotic lesions, whereas a positive correlation with genes of lipid metabolism exists. Moreover, unlike PPAR{gamma}, PPAR{alpha} or PPAR{beta}/{delta} activation does not influence human monocyte differentiation into M2 macrophages in vitro. Thus, PPAR{alpha} and PPAR{beta}/{delta} do not appear to modulate the alternative differentiation of human macrophages.

  14. Antitumor activity of balsam fir oil: production of reactive oxygen species induced by alpha-humulene as possible mechanism of action. (United States)

    Legault, Jean; Dahl, Wivecke; Debiton, Eric; Pichette, André; Madelmont, Jean-Claude


    The antitumor activity of the essential oil of Abies balsamea (balsam fir oil) was evaluated against several solid tumor cell lines including MCF-7, PC-3, A-549, DLD-1, M4BEU and CT-26. Balsam fir oil was found to be active against all the solid tumor cell lines tested, with GI 50 values ranging between 0.76 and 1.7 mg/mL. The oil was analyzed by GC-MS and the cytotoxicity of each oil constituent was determined. Balsam fir oil is essentially constituted of monoterpenes tau; 96 %) and some sesquiterpenes. All the compounds tested were inactive (tau; 250 microM) except for alpha-humulene (GI50 = 55 to 73 microM) which thus seems responsible for the cytotoxicity of the oil. We also tested the cytotoxicity of caryophyllene oxide, which proved inactive, and gamma-caryophyllene which was found to be active against all solid tumor cell lines tested. We evaluated the effects of balsam fir oil and alpha-humulene on the cellular glutathione (GSH) content and on the production of reactive oxygen species (ROS). Balsam fir oil and alpha-humulene induced a dose- and time-dependent decrease in cellular GSH content and an increase in ROS production. These results suggest that GSH depletion and ROS production may be implicated in the cytotoxicity of alpha-humulene and balsam fir oil. PMID:12802719

  15. Ubiquitin carboxyl terminal hydrolase L1 negatively regulates TNF{alpha}-mediated vascular smooth muscle cell proliferation via suppressing ERK activation

    Energy Technology Data Exchange (ETDEWEB)

    Ichikawa, Tomonaga; Li, Jinqing; Dong, Xiaoyu; Potts, Jay D. [Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Tang, Dong-Qi [Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610-0275 (United States); Li, Dong-Sheng, E-mail: [Hubei Key Laboratory of Embryonic Stem Cell Research, Tai He Hospital, Yunyang Medical College, 32 S. Renmin Rd., Shiyan, Hubei 442000 (China); Cui, Taixing, E-mail: [Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States)


    Deubiquitinating enzymes (DUBs) appear to be critical regulators of a multitude of processes such as proliferation, apoptosis, differentiation, and inflammation. We have recently demonstrated that a DUB of ubiquitin carboxyl terminal hydrolase L1 (UCH-L1) inhibits vascular lesion formation via suppressing inflammatory responses in vasculature. However, the precise underlying mechanism remains to be defined. Herein, we report that a posttranscriptional up-regulation of UCH-L1 provides a negative feedback to tumor necrosis factor alpha (TNF{alpha})-mediated activation of extracellular signal-regulated kinases (ERK) and proliferation in vascular smooth muscle cells (VSMCs). In rat adult VSMCs, adenoviral over-expression of UCH-L1 inhibited TNF{alpha}-induced activation of ERK and DNA synthesis. In contrast, over-expression of UCH-L1 did not affect platelet derived growth factor (PDGF)-induced VSMC proliferation and activation of growth stimulating cascades including ERK. TNF{alpha} hardly altered UCH-L1 mRNA expression and stability; however, up-regulated UCH-L1 protein expression via increasing UCH-L1 translation. These results uncover a novel mechanism by which UCH-L1 suppresses vascular inflammation.

  16. Vasoactive intestinal peptide-induced expression of cytochrome P450 cholesterol side-chain cleavage and 17 alpha-hydroxylase enzyme activity in hen granulosa cells. (United States)

    Johnson, A L; Li, Z; Gibney, J A; Malamed, S


    Experiments were conducted to determine whether vasoactive intestinal peptide (VIP) can regulate expression of cytochrome P450 side-chain cleavage (P450scc) and P450 17 alpha-hydroxylase (P450 17 alpha-OH) mRNA levels and enzyme activity in granulosa cells from nonhierarchal (6-8-mm) follicles. Initial studies demonstrated that immunoreactive VIP is localized within the theca (but not granulosa) layer of both resting (< 0.5-mm follicles) and 6-8-mm follicles, thus providing a potential paracrine mechanism of action for VIP. While short-term (3 h) incubation of granulosa cells with VIP (0.001-1.0 microM) failed to stimulate progesterone production from 6-8-mm follicle granulosa cells, a 4-h culture period in the presence of VIP resulted in increased cyclic AMP (cAMP) accumulation, and a 24-h culture period resulted in progesterone synthesis and increased P450scc mRNA levels; control levels of each endpoint measurement were not altered within the period observed. By contrast, culture with the growth factor transforming growth factor alpha (TGF alpha) in the presence of VIP (1 microM) prevented increases in P450scc mRNA levels and progesterone production. Similar effects of VIP and TGF alpha in the presence of VIP were demonstrated for P450 17 alpha-OH mRNA levels and enzyme activity. Finally, there was an additive effect of VIP (0.1 microM) plus recombinant human (rh) FSH (100 mIU) on the initiation of progesterone production in cultured 6-8-mm follicle granulosa cells compared to the addition of VIP or rhFSH alone.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Acyl-CoA esters antagonize the effects of ligands on peroxisome proliferator-activated receptor alpha conformation, DNA binding, and interaction with Co-factors

    DEFF Research Database (Denmark)

    Elholm, M; Dam, I; Jorgensen, C;


    The peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor and a key regulator of lipid homeostasis. Numerous fatty acids and eicosanoids serve as ligands and activators for PPARalpha. Here we demonstrate that S-hexadecyl-CoA, a nonhydrolyzable...... palmitoyl-CoA analog, antagonizes the effects of agonists on PPARalpha conformation and function in vitro. In electrophoretic mobility shift assays, S-hexadecyl-CoA prevented agonist-induced binding of the PPARalpha-retinoid X receptor alpha heterodimer to the acyl-CoA oxidase peroxisome proliferator...... a functional PPARalpha ligand-binding pocket. S-Hexadecyl-CoA prevented ligand-induced interaction between the co-activator SRC-1 and PPARalpha but increased recruitment of the nuclear receptor co-repressor NCoR. In cells, the concentration of free acyl-CoA esters is kept in the low nanomolar range due...

  18. PPAR{alpha} agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Xiaoyang [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, 250012 Jinan, Shandong (China); Division of Cardiothoracic Surgery, The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, BCM 390, One Baylor Plaza, Houston, TX 77030 (United States); Shen, Ying H. [Division of Cardiothoracic Surgery, The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, BCM 390, One Baylor Plaza, Houston, TX 77030 (United States); Li, Chuanbao; Wang, Fei; Zhang, Cheng [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, 250012 Jinan, Shandong (China); Bu, Peili, E-mail: [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, 250012 Jinan, Shandong (China); Zhang, Yun [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, 250012 Jinan, Shandong (China)


    Oxidative stress has been shown to play an important role in the development of hypertensive renal injury. Peroxisome proliferator-activated receptors {alpha} (PPAR{alpha}) has antioxidant effect. In this study, we demonstrated that fenofibrate significantly reduced proteinuria, inflammatory cell recruitment and extracellular matrix (ECM) proteins deposition in the kidney of SHRs without apparent effect on blood pressure. To investigate the mechanisms involved, we found that fenofibrate treatment markedly reduced oxidative stress accompanied by reduced activity of renal NAD(P)H oxidase, increased activity of Cu/Zn SOD, and decreased phosphorylation of p38MAPK and JNK in the kidney of SHRs. Taken together, fenofibrate treatment can protect against hypertensive renal injury without affecting blood pressure by inhibiting inflammation and fibrosis via suppression of oxidative stress and MAPK activity.

  19. Forecast and restoration of geomagnetic activity indices by using the software-computational neural network complex (United States)

    Barkhatov, Nikolay; Revunov, Sergey


    It is known that currently used indices of geomagnetic activity to some extent reflect the physical processes occurring in the interaction of the perturbed solar wind with Earth's magnetosphere. Therefore, they are connected to each other and with the parameters of near-Earth space. The establishment of such nonlinear connections is interest. For such purposes when the physical problem is complex or has many parameters the technology of artificial neural networks is applied. Such approach for development of the automated forecast and restoration method of geomagnetic activity indices with the establishment of creative software-computational neural network complex is used. Each neural network experiments were carried out at this complex aims to search for a specific nonlinear relation between the analyzed indices and parameters. At the core of the algorithm work program a complex scheme of the functioning of artificial neural networks (ANN) of different types is contained: back propagation Elman network, feed forward network, fuzzy logic network and Kohonen layer classification network. Tools of the main window of the complex (the application) the settings used by neural networks allow you to change: the number of hidden layers, the number of neurons in the layer, the input and target data, the number of cycles of training. Process and the quality of training the ANN is a dynamic plot of changing training error. Plot of comparison of network response with the test sequence is result of the network training. The last-trained neural network with established nonlinear connection for repeated numerical experiments can be run. At the same time additional training is not executed and the previously trained network as a filter input parameters get through and output parameters with the test event are compared. At statement of the large number of different experiments provided the ability to run the program in a "batch" mode is stipulated. For this purpose the user a

  20. Active Time Domain Reflectometry for Tamper Indication in Unattended Safeguards Systems

    Energy Technology Data Exchange (ETDEWEB)

    Sheen, David M.; Smith, Leon E.; Tedeschi, Jonathan R.; Moore, David E.; Gavric, Gordan; Conrad, Ryan C.


    The International Atomic Energy Agency (IAEA) continues to expand its use of unattended measurement systems. An increasing number of systems and an expanding family of instruments create challenges in terms of deployment efficiency and the implementation of data authentication measures. In collaboration with the IAEA, tamper-indicating measures to address data-transmission authentication challenges with unattended safeguards systems are under investigation. Pacific Northwest National Laboratory is studying the viability of active time-domain reflectometry (TDR) along two parallel but interconnected paths: (1) swept-frequency TDR as the highly flexible, laboratory gold standard to which field-deployable options can be compared, and (2) a low-cost commercially available spread-spectrum TDR technology as one option for field implementation. This paper describes the TDR methods under investigation and the associated benchtop test-bed, tampering scenarios of interest,, and viability measurement results to date (e.g., comparison of relative sensitivity to tamper scenarios).

  1. Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics

    Directory of Open Access Journals (Sweden)

    Jasper eAkerboom


    Full Text Available Genetically encoded calcium indicators (GECIs are powerful tools for systems neuroscience. Here we describe red, single-wavelength GECIs, RCaMPs, engineered from circular permutation of the thermostable red fluorescent protein mRuby. High-resolution crystal structures of mRuby, the red sensor RCaMP, and the recently published red GECI R-GECO1 give insight into the chromophore environments of the Ca2+-bound state of the sensors and the engineered protein domain interfaces of the different indicators. We characterized the biophysical properties and performance of RCaMP sensors in vitro and in vivo in Caenorhabditis elegans, Drosophila larvae, and larval zebrafish. Further, we demonstrate 2-color calcium imaging both within the same cell (registering mitochondrial and somatic [Ca2+] and between two populations of cells: neurons and astrocytes. Finally, we perform integrated optogenetics experiments, wherein neural activation via channelrhodopsin-2 (ChR2 or a red-shifted variant, and activity imaging via RCaMP or GCaMP, are conducted simultaneously, with the ChR2/RCaMP pair providing independently addressable spectral channels. Using this paradigm, we measure calcium responses of naturalistic and ChR2-evoked muscle contractions in vivo in crawling C. elegans. We systematically compare the RCaMP sensors to R-GECO1, in terms of action potential-evoked fluorescence increases in neurons, photobleaching, and photoswitching. R-GECO1 displays higher Ca2+ affinity and larger dynamic range than RCaMP, but exhibits significant photoactivation with blue and green light, suggesting that integrated channelrhodopsin-based optogenetics using R-GECO1 may be subject to artifact. Finally, we create and test blue, cyan and yellow variants engineered from GCaMP by rational design. This engineered set of chromatic variants facilitates new experiments in functional imaging and optogenetics.

  2. Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 alpha expression and glucokinase activity

    Institute of Scientific and Technical Information of China (English)

    Zhi-Quan Wang; Fu-Er Lu; San-Hua Leng; Xin-Sheng Fang; Guang Chen; Zeng-Si Wang; Li-Ping Dong; Zhong-Qing Yan


    AIM: To observe the effect of berberine on insulin secretion in rat pancreatic islets and to explore its possible molecular mechanism.METHODS: Primary rat islets were isolated from male Sprague-Dawley rats by collagenase digestion and treated with different concentrations (1, 3, 10 and 30 μmol/L) of berberine or 1 μmol/L Glibenclamide (GB) for 24 h. Glucose-stimulated insulin secretion (GSIS) assay was conducted and insulin was determined by radioimmunoassay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (NTT) assay was performed to evaluate cytotoxicity. The mRNA level of hepatic nuclear factor 4 alpha (HNF4α) was determined by reverse transcription polymerase chain reaction (RT-PCR). Indirect immunofluorescence staining and Western blot analysis were employed to detect protein expression of HNF4α in the islets. Glucokinase (GK) activity was measured by spectrophotometric method.RESULTS: Berberine enhanced GSIS rather than basal insulin secretion dose-dependently in rat islets and showed no significant cytotoxicity on islet cells at the concentration of 10 μmol/L. Both mRNA and protein expressions of HNF4α were up-regulated by berberine in a dose-dependent manner, and GK activity was also increased accordingly. However, GB demonstrated no regulatory effects on HNF4α expression or GK activity.CONCLUSION: Berberine can enhance GSIS in rat islets, and probably exerts the insulinotropic effect via a pathway involving HNF4α and GK, which is distinct from sulphonylureas (SUs).

  3. IL-6 cooperates with peroxisome proliferator-activated receptor-alpha-ligands to induce liver fatty acid binding protein (LFABP) up-regulation


    Vida, Margarita; Serrano, Antonia; Romero-Cuevas, Miguel; Pavón, Francisco J.; González-Rodriguez, Águeda; Gavito, Ana L.; Cuesta, Antonio L.; Valverde, Ángela M.; Rodríguez de Fonseca, Fernando; Baixeras, Elena


    [Background]: LFABP plays a critical role in the uptake and intracellular transport of fatty acids (FA) and other peroxisome proliferator-activated receptor alpha (PPARα) ligands. PPARα activation by PPARα ligands bound to LFABP results in gene expression of FA oxidation enzymes and de novo LFABP. The cytokine IL-6 is involved in regulating liver lipid oxidation. [Aims]: To study the ability of IL-6 to modulate the expression of the LFABP in hepatocytes. Methods: HepG2 and mouse primary hepat...

  4. Macroalage as a source of alpha-glucosidase inhibitors

    Institute of Scientific and Technical Information of China (English)


    Alpha-glucosidase inhibitors were screened from organic solvent extracts of macroalgae by a spectrophotometrical method with p-nitrophenyl-D-glucopyranosidase as the substrate. The result indicates that organic crude extracts from some macroalgae such as Rhodomela confervoides (Huds.) Silva, Gracilaria textorii (Suringar) DeToni, Plocamium telfairiae Harv., Dictyopteris divaricata (Okam.) Okam, Ulval pertusa and Enteromorpha intestinalis (L.) Link et al. show strong inhibitory activity of alpha-glucosidase at concentration of 79.6 μg/ml.

  5. Acetylcholine release in mouse hippocampal CA1 preferentially activates inhibitory-selective interneurons via alpha4 beta2* nicotinic receptor activation

    Directory of Open Access Journals (Sweden)

    L. Andrew Bell


    Full Text Available Acetylcholine (ACh release onto nicotinic receptors directly activates subsets of inhibitory interneurons in hippocampal CA1. However, the specific interneurons activated and their effect on the hippocampal network is not completely understood. Therefore, we investigated subsets of hippocampal CA1 interneurons that respond to ACh release through the activation of nicotinic receptors and the potential downstream effects this may have on hippocampal CA1 network function. ACh was optogenetically released in mouse hippocampal slices by expressing the excitatory optogenetic protein oChIEF-tdTomato in medial septum/diagonal band of Broca cholinergic neurons using Cre recombinase-dependent adeno-associated viral mediated transfection. The actions of optogenetically released ACh were assessed on both pyramidal neurons and different interneuron subtypes via whole cell patch clamp methods. Vasoactive intestinal peptide (VIP-expressing interneurons that selectively innervate other interneurons (VIP/IS were excited by ACh through the activation of nicotinic receptors containing alpah4 and beta2 subunits (alpha4 beta2*. ACh release onto VIP/IS was presynaptically inhibited by M2 muscarinic autoreceptors. ACh release produced spontaneous inhibitory postsynaptic current (sIPSC barrages blocked by dihydro-beta-erythroidine in interneurons but not pyramidal neurons. Optogenetic suppression of VIP interneurons did not inhibit these sIPSC barrages suggesting other interneuron-selective interneurons were also excited by 42* nicotinic receptor activation. In contrast, interneurons that innervate pyramidal neuron perisomatic regions were not activated by ACh release onto nicotinic receptors. Therefore, we propose ACh release in CA1 facilitates disinhibition through activation of 42* nicotinic receptors on interneuron-selective interneurons whereas interneurons that innervate pyramidal neurons are less affected by nicotinic receptor activation.

  6. In vitro mutation breeding for seed protein, alpha amylase activity and herbicide resistance in bulrush millet (Peenisetum nigritarum)

    International Nuclear Information System (INIS)

    In vitro mutation breeding in bulrush millet (Penissetum nigritarum) was investigated using chemical mutagenesis followed by selection. Mutations were induced by soaking dry viable seeds at room temperature in 8 mM ethylmethanesulphonate (EMS) for 15 hours or in 64 mM EMS for 3, 6, 9, 12, 15 and 24 hours. After treatment and rinsing in running water, the seeds were germinated in Petri dishes and later transplanted to loamy sand oil and grown to maturity in the greenhouse. Screening and analysis of 2500 M2 plants yielded a broad spectrum of mutations, including leaf variation and agronomically useful attributes such as improved and early germinability (+15% and +10 hours, respectively), and a higher seed protein content, alpha amylase activity and herbicide resistance. EMS did not reduce cell viability, but it produced a high frequency of mutations, accompanied by a relatively low frequency of chromosomal aberrations. The appropriate dosage and duration for mutation breeding was 8 mM for 15 hours or 64 mM for 3 hours. (author). 9 refs, 2 figs, 4 tabs

  7. Discovery of a ~2 hr high frequency X-ray QPO and iron K alpha reverberation in the active galaxy MS 2254.9-3712

    CERN Document Server

    Alston, W N; Markeviciute, J; Fabian, A C; Middleton, M; Lohfink, A; Kara, E; Pinto, C


    We report the discovery of a $\\sim 1.5 \\times 10^{-4}$ Hz ($\\sim 2$ hr) X-ray quasi-periodic oscillation (QPO) in the active galaxy MS 2254.9-3712, using a $\\sim 70$ ks XMM-Newton observation. The QPO is significantly detected in the $1.2 - 5.0$ keV band only, connecting its origin with the primary X-ray power-law continuum. We detect a highly coherent soft lag between the $0.3 - 0.7$ keV and $1.2 - 5.0$ keV energy bands at the QPO and harmonic frequencies, with a 3:2 frequency ratio. An iron K$\\alpha$ reverberation lag is found at the harmonic frequency, indicating the reflecting material subtends some angle to the primary continuum, which is modulated by the QPO mechanism. The coherence at the QPO and harmonic frequencies is ~ unity, whereas the coherence in the broadband noise is decreasing with increasing frequency. Frequency resolved spectroscopy reveals the QPO and harmonic to have a hard energy dependence. These properties of the QPO variability, together with the current black hole mass estimate, $M_{...

  8. Imaging activity in astrocytes and neurons with genetically encoded calcium indicators following in utero electroporation

    Directory of Open Access Journals (Sweden)

    J. Michael eGee


    Full Text Available Complex interactions between networks of astrocytes and neurons are beginning to be appreciated, but remain poorly understood. Transgenic mice expressing fluorescent protein reporters of cellular activity, such as the GCaMP family of genetically encoded calcium indicators, have been used to explore network behavior. However, in some cases, it may be desirable to use long-established rat models that closely mimic particular aspects of human conditions such as Parkinson’s disease and the development of epilepsy following status epilepticus. Methods for expressing reporter proteins in the rat brain are relatively limited. Transgenic rat technologies exist but are fairly immature. Viral-mediated expression is robust but unstable, requires invasive injections, and only works well for fairly small genes (< 5 kb. In utero electroporation offers a valuable alternative. IUE is a proven method for transfecting populations of astrocytes and neurons in the rat brain without the strict limitations on transgene size. We built a toolset of IUE plasmids carrying GCaMP variants 3, 6s or 6f driven by CAG and targeted to the cytosol or the plasma membrane. Because low baseline fluorescence of GCaMP can hinder identification of transfected cells, we included the option of co-expressing a cytosolic tdTomato protein. A binary system consisting of a plasmid carrying a piggyBac inverted terminal repeat-flanked CAG-GCaMP-IRES-tdTomato cassette and a separate plasmid encoding for expression of piggyBac transposase was employed to stably express GCaMP and tdTomato. The plasmids were co-electroporated on embryonic days 13.5-14.5 and astrocytic and neuronal activity was subsequently imaged in acute or cultured brain slices prepared from the cortex or hippocampus. Large spontaneous transients were detected in slices obtained from rats of varying ages up to 127 days. In this report, we demonstrate the utility of this toolset for interrogating astrocytic and neuronal

  9. Adiponectin promotes hyaluronan synthesis along with increases in hyaluronan synthase 2 transcripts through an AMP-activated protein kinase/peroxisome proliferator-activated receptor-{alpha}-dependent pathway in human dermal fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Yamane, Takumi; Kobayashi-Hattori, Kazuo [Department of Nutritional Sciences, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502 (Japan); Oishi, Yuichi, E-mail: [Department of Nutritional Sciences, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502 (Japan)


    Highlights: Black-Right-Pointing-Pointer Adiponectin promotes hyaluronan synthesis along with an increase in HAS2 transcripts. Black-Right-Pointing-Pointer Adiponectin also increases the phosphorylation of AMPK. Black-Right-Pointing-Pointer A pharmacological activator of AMPK increases mRNA levels of PPAR{alpha} and HAS2. Black-Right-Pointing-Pointer Adiponectin-induced HAS2 mRNA expression is blocked by a PPAR{alpha} antagonist. Black-Right-Pointing-Pointer Adiponectin promotes hyaluronan synthesis via an AMPK/PPAR{alpha}-dependent pathway. -- Abstract: Although adipocytokines affect the functions of skin, little information is available on the effect of adiponectin on the skin. In this study, we investigated the effect of adiponectin on hyaluronan synthesis and its regulatory mechanisms in human dermal fibroblasts. Adiponectin promoted hyaluronan synthesis along with an increase in the mRNA levels of hyaluronan synthase 2 (HAS2), which plays a primary role in hyaluronan synthesis. Adiponectin also increased the phosphorylation of AMP-activated protein kinase (AMPK). A pharmacological activator of AMPK, 5-aminoimidazole-4-carboxamide-1{beta}-ribofuranoside (AICAR), increased mRNA levels of peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}), which enhances the expression of HAS2 mRNA. In addition, AICAR increased the mRNA levels of HAS2. Adiponectin-induced HAS2 mRNA expression was blocked by GW6471, a PPAR{alpha} antagonist, in a concentration-dependent manner. These results show that adiponectin promotes hyaluronan synthesis along with increases in HAS2 transcripts through an AMPK/PPAR{alpha}-dependent pathway in human dermal fibroblasts. Thus, our study suggests that adiponectin may be beneficial for retaining moisture in the skin, anti-inflammatory activity, and the treatment of a variety of cutaneous diseases.

  10. Alpha fetoprotein (United States)

    Fetal alpha globulin; AFP ... Greater than normal levels of AFP may be due to: Cancer in testes , ovaries, biliary (liver secretion) tract, stomach, or pancreas Cirrhosis of the liver Liver cancer ...

  11. OSL dating of fluvial terraces for incision rate estimation and indication of neotectonic activity in Pamir (United States)

    Fuchs, M. C.; Gloaguen, R.; Krbetschek, M.; Szulc, A.


    ThePamir owes its special attraction for geo-scientists to being among Earth's largest intra-continental orogens and to display some of the highest uplift rates as well as to host among the most powerful river systems on the planet. The evolution of the drainage network as a proxy for the landscape's response to tectonic signals provides a powerful tool to study neotectonics. The relation between tectonic forcing and surface response is indicated by structural anomalies (e.g. river-capture, river-reversal or -deflection) and spatial differences of process rates (e.g. incision rates). We combine OSL dating with remote sensing tectonic geomorphology in order to determine the zones of active deformation in the Quaternary. The local drainage system of the study region aligns mainly to the east-west-trending belts of shortening, which results from the ongoing northward propagation of the Indian plate. In contrast the major trunk river, the Panj, is unusual in that it deflects northwards and then doubles back to the southwest, cutting the southern and central Pamir doming and several other major Cenozoic deformation zones. We use fluvial terraces along the deflected north-south orientated part including the doubled back prolongation of the more or less normal orientated Panj. These sediment bodies are used as a geomorphic record to reveal changes in the balance between sediment flux and discharge. Dating these fluvial terraces by OSL provides the burial ages of the sediments indicating periods of sedimentation. The remains of those periods are far from equally distributed and mark the time of local conditions for sedimentation as especially the close neighbourhood of most of the terraces from the two youngest periods demonstrate. Precise measurements of the heights of the dated terraces with respect to the present river level based on relative kinematic GPS quantify the total vertical incision of the river subsequent to the sedimentation and abandonment. Incision rates

  12. The fibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor {alpha}-mediated superoxide dismutase induction in HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xianguang; An, Zhengzhe; Song, Hye Jin; Kim, Won Dong; Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of); Jang, Seong Soon [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Yu, Jae Ran [Konkuk University College of Medicine, Chungju (Korea, Republic of)


    The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) {alpha} and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofi brate (FF). Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. In HeLa cells total SOD activity was increased with increasing FF doses up to 30 {mu}M. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, PPAR{alpha} and PPAR{gamma} were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and PPAR{alpha} were not increased with FF. However, the mRNA of PPAR{gamma} was increased with FF. FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with PPAR{alpha}.

  13. Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling. (United States)

    Amith, Schammim Ray; Jayanth, Preethi; Franchuk, Susan; Finlay, Trisha; Seyrantepe, Volkan; Beyaert, Rudi; Pshezhetsky, Alexey V; Szewczuk, Myron R


    The ectodomain of TOLL-like receptors (TLR) is highly glycosylated with several N-linked gylcosylation sites located in the inner concave surface. The precise role of these sugar N-glycans in TLR receptor activation is unknown. Recently, we have shown that Neu1 sialidase and not Neu2, -3 and -4 forms a complex with TLR-2, -3 and -4 receptors on the cell-surface membrane of naïve and activated macrophage cells (Glycoconj J DOI 10.1007/s10719-009-9239-8). Activation of Neu1 is induced by TLR ligands binding to their respective receptors. Here, we show that endotoxin lipopolysaccharide (LPS)-induced MyD88/TLR4 complex formation and subsequent NFkappaB activation is dependent on the removal of alpha-2,3-sialyl residue linked to beta-galactoside of TLR4 by the Neu1 activity associated with LPS-stimulated live primary macrophage cells, macrophage and dendritic cell lines but not with primary Neu1-deficient macrophage cells. Exogenous alpha-2,3 sialyl specific neuraminidase (Streptoccocus pneumoniae) and wild-type T. cruzi trans-sialidase (TS) but not the catalytically inactive mutant TSAsp98-Glu mediate TLR4 dimerization to facilitate MyD88/TLR4 complex formation and NFkappaB activation similar to those responses seen with LPS. These same TLR ligand-induced NFkappaB responses are not observed in TLR deficient HEK293 cells, but are re-established in HEK293 cells stably transfected with TLR4/MD2, and are significantly inhibited by alpha-2,3-sialyl specific Maackia amurensis (MAL-2) lectin, alpha-2,3-sialyl specific galectin-1 and neuraminidase inhibitor Tamiflu but not by alpha-2,6-sialyl specific Sambucus nigra lectin (SNA). Taken together, the findings suggest that Neu1 desialylation of alpha-2,3-sialyl residues of TLR receptors enables in removing a steric hinderance to receptor association for TLR activation and cellular signaling. PMID:19796680

  14. Search for alpha-driven BAE modes in TFTR

    International Nuclear Information System (INIS)

    A search for alpha-driven beta-induced Alfven eigenmodes (BAE modes) was conducted in low current (1.0--1.6 MA) TFTR supershots. Stable high-beta deuterium-tritium (DT) discharges were obtained with Bρ = 2.4 and central alpha beta of 0.1%. Instabilities between 75--200 kHz were observed by magnetic probes in many DT discharges, but the activity was also present in deuterium-deuterium (DD) comparison discharges, indicating that these modes are not destabilized (principally) by the alpha-particle population. Losses of fusion products are also similar in the two sets of discharges

  15. Carbene vs olefin products of C-H activation on ruthenium via competing alpha- and beta-H elimination. (United States)

    Kuznetsov, Vladimir F; Abdur-Rashid, Kamaluddin; Lough, Alan J; Gusev, Dmitry G


    Bulky pincer complexes of ruthenium are capable of C-H activation and H-elimination from the pincer ligand backbone to produce mixtures of olefin and carbene products. To characterize the products and determine the mechanisms of the C-H cleavage, reactions of [RuCl(2)(p-cymene)](2) with N,N'-bis(di-tert-butylphosphino)-1,3-diaminopropane (L1) and 1,3-bis(di-tert-butylphosphinomethyl)cyclohexane (L2) were studied using a combination of X-ray crystallography, NMR spectroscopy, and DFT computational techniques. The reaction of L1 afforded a mixture of an alkylidene, a Fischer carbene, and two olefin isomers of the 16-e monohydride RuHCl[(t)Bu(2)PNHC(3)H(4)NHPBu(t)(2)] (2), whereas the reaction of L2 gave two olefin and two alkylidene isomers of 16-e RuHCl[2,6-(CH(2)PBu(t)(2))(2)C(6)H(8)] (3), all resulting from dehydrogenations of the ligand backbone of L1 and L2. The key intermediates implicated in the C-H activation reactions were identified as 14-electron paramagnetic species RuCl(PCP), where PCP = cyclometalated L1 or L2. Thus the alpha- and beta-H elimination reactions of RuCl(PCP) involved spin change and were formally spin-forbidden. Hydrogenation of 2 and 3 afforded 16-electron dihydrides RuH(2)Cl(PCP) distinguished by a large quantum exchange coupling between the hydrides. PMID:17076513

  16. Gastroprotective effect of alpha-pinene and its correlation with antiulcerogenic activity of essential oils obtained from Hyptis species

    Directory of Open Access Journals (Sweden)

    Marcelo de Almeida Pinheiro


    Full Text Available Background: Alpha-pinene (α-pinene is a monoterpene commonly found in essential oils with gastroprotective activity obtained from diverse medicinal plants, including Hyptis species. The genus Hyptis (lamiaceae consists of almost 400 species widespread in tropical and temperate regions of America. In the north and northeastern Brazil, some Hyptis species are used in traditional medicine to treat gastrointestinal disturbances. Objective: The present study has investigated the gastoprotective effect of purified α-pinene in experimental gastric ulcer induced by ethanol and indomethacin in mice. Materials and Methods: Gastric ulcers were induced in male Swiss mice (20-30 g by oral administration of absolute ethanol or indomethacin 45 min after oral pretreatment with vehicle, standard control drugs or α-pinene (10, 30, and 100 mg/kg. One hour after the ulcerative challenges, the stomach were removed, and gastric lesions areas measured. The effects of α-pinene on the gastric juice acidity were determined by pylorus ligation model. The gastrointestinal motility and mucus depletion were determined by measuring the gastric levels of phenol red and alcian blue, respectively. Hematoxylin and eosin stained sections of gastric mucosa of the experimental groups were used for histology analysis. Results: α-pinene pretreatment inhibited ethanol-induced gastric lesions, reduced volume and acidity of the gastric juice and increased gastric wall mucus (P < 0.05. Furthermore, we showed an interesting correlation between concentration of α-pinene and gastroprotective effect of Hyptis species (P Pearson = 0.98. Conclusion: Our data showed that the α-pinene exhibited significant antiulcerogenic activity and a great correlation between concentration of α-pinene and gastroprotective effect of Hyptis species was also observed.

  17. The Effect of Nigella Sativa Extract on Alpha-ketoglutarate Activity and Histopathologic Changes on Rat Liver Induced by Monosodium Glutamate

    Directory of Open Access Journals (Sweden)

    Ala Sh Emhemed Eshami


    Full Text Available Monosodium glutamate (MSG is a commonly used food additive and found in most soups, fish, and processed meat. The use of MSG in food is growing. However, the fear of consuming MSG has increased in the last few years due to the adverse reactions and toxicity in the liver. Nigella sativa (NS is used as traditional medicine for the treatment of many diseases. It has been extensively investigated in recent years due to its notable pharmacological properties such as inhibit oxidative stress. The present study was undertaken to investigate the effect of different doses of Nigella Sativa on alpha KGDH activity and liver histology of MSG-induced rats. The animals (n=30 were grouped into A (control, B (treated with MSG 1g/ , C (treated with MSG 1g/ and NS 0.1 g/, D (treated with MSG 1g/ and NS 0.2 g/, E (treated with MSG 1g/ and NS 0.4 g/ and F (given a daily NS extract 0.2 g/ Alpha KGDH activity was investigated using ELISA method and liver histopathology by light microscope. The MSG treatment increased Alpha KGDH activity and disturbed liver architecture, hemorrhage in the central veins, areas of necrosis, vacuolation and increased inflammatory cells infiltration. The condition was normalized by treatment NS on dose 0.2 and 0.4 g/ The findings showed that the administration of MSG increases alpha KGDH and induces damage in liver tissue. Nigella sativa extract can reduce alpha KGDH and prevent liver damage caused by MSG.

  18. The Antioxidant Activity and the Effects of Convolvulus Aucheri (Convolvulaceae Extract on Biochemical Indices in Rats

    Directory of Open Access Journals (Sweden)



    Full Text Available Convolvulus L., the second largest genus of the family Convolvulaceae, has about 250 species distributed mainly in the temperate and tropical regions of the world, with a cosmopolitan distribution. According to recent studies, this genus is represented in Turkey by 33 species, 9 of which are endemic. Convolvulus species are extensively used in traditional medicine for various purposes as in ulcer treatment, diabetes, and tension. The aim of this study was to investigate the antioxidant activity and the effects of Convolvulus aucheri extract on biochemical indices in rats.The antioxidant activities of various solvent extracts (methanol, ethanol, acetone and benzene obtained from C. aucheri were evaluated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH and β-carotene-linoleic acid assays. In addition, total phenolic contents in all the extracts of C. aucheri were determined as gallic acid equivalents. As for the biochemical assay, the extracts of the plant at the concentrations of 0.5 and 1 ml/100 g body weight/day were administered orally to the experimental groups for 36 days. Blood samples were taken by cardiac venipuncture on the 2nd and 4th weeks after the initial treatment. Aspartate aminotransferase (AST, alanine aminotransferase (ALT, gamma-glutamyltransferase (GGT and blood urea nitrogen (BUN were measured for the determination of liver function.Among all the extracts, the ethanolic extracts of C. aucheri showed the highest antioxidant activity (66.88 ± 0.8%. The highest free radical scavenging activity (59.50 ± 1.2% was recorded on the ethanolic extracts. The phenolic contents of the ethanolic extracts are higher than the other types of extracts (23.03 mg/g GAE. In biochemical assay, it was found a significant increase in the levels of serum ALT, AST and decrease the serum GGT levels in the experimental groups when compared to the controls (p<0.05. On the other hand, we found significant increase in the level of BUN.


    Directory of Open Access Journals (Sweden)

    Elena I. Danilina


    Full Text Available The assessment of the local government performance, as any other serious work, is improved and undergone major changes every year. The objective of this article-is the research of the methodological aspects of forming the system of indicators, which reflect the local government performance. The difficulties with which the constituent entities of the Russian Federation face while making assessment according to the procedure accepted on the federal level have been exposed. Some imperfections of the currently used procedure of the integrated assessment have been stated. The author concludes that the existing problems of acquiring the official and timely information from the statistical bodies, the absence of accounting the budgetary efficiency of costs and the financial status of certain municipal units, the difference in the approaches and methods of holding the opinion polls of the constituent entities of the Russian Federation, call into a question the issue of fairness of the assessment results. The conducted study has allowed the author to identify the possible opportunities for the further studies. Although the methods do not require making the assessment of the performance targets approved in the strategies of the municipalities, it would be worthwhile to consider these indicators over time. While assessing the local government performance, it is recommended to use two approaches. One of them-which is obligatory for all (according to the procedure accepted on the federal level. Another approach-is holding own secondary monitoring, involving self-assessment of the activity on the effective territory management, while paying attention to the determination of the areas requiring the priority attention of the local governments. Municipalities are recommended to study the available foreign practices and the Russian achievements in the field of assessing the public body performance, which could include, for example, the European model of CAF.

  20. On-Going Frontal Alpha Rhythms Are Dominant in Passive State and Desynchronize in Active State in Adult Gray Mouse Lemurs. (United States)

    Infarinato, Francesco; Rahman, Anisur; Del Percio, Claudio; Lamberty, Yves; Bordet, Regis; Richardson, Jill C; Forloni, Gianluigi; Drinkenburg, Wilhelmus; Lopez, Susanna; Aujard, Fabienne; Babiloni, Claudio; Pifferi, Fabien


    The gray mouse lemur (Microcebus murinus) is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009,, we tested the hypothesis that spectral electroencephalographic (EEG) markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8-12 Hz) in humans. To this aim, EEG (bipolar electrodes in frontal cortex) and electromyographic (EMG; bipolar electrodes sutured in neck muscles) data were recorded in 13 male adult (about 3 years) lemurs. Artifact-free EEG segments during active state (gross movements, exploratory movements or locomotor activity) and awake passive state (no sleep) were selected on the basis of instrumental measures of animal behavior, and were used as an input for EEG power density analysis. Results showed a clear peak of EEG power density at alpha range (7-9 Hz) during passive state. During active state, there was a reduction in alpha power density (8-12 Hz) and an increase of power density at slow frequencies (1-4 Hz). Relative EMG activity was related to EEG power density at 2-4 Hz (positive correlation) and at 8-12 Hz (negative correlation). These results suggest for the first time that the primate gray mouse lemurs and humans may share basic neurophysiologic mechanisms of synchronization of frontal alpha rhythms in awake passive state and their desynchronization during motor and locomotor activity. These EEG markers may be an ideal experimental model for translational basic (motor science) and applied (pharmacological and non-pharmacological interventions) research in Neurophysiology. PMID:26618512

  1. On-Going Frontal Alpha Rhythms Are Dominant in Passive State and Desynchronize in Active State in Adult Gray Mouse Lemurs.

    Directory of Open Access Journals (Sweden)

    Francesco Infarinato

    Full Text Available The gray mouse lemur (Microcebus murinus is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009,, we tested the hypothesis that spectral electroencephalographic (EEG markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8-12 Hz in humans. To this aim, EEG (bipolar electrodes in frontal cortex and electromyographic (EMG; bipolar electrodes sutured in neck muscles data were recorded in 13 male adult (about 3 years lemurs. Artifact-free EEG segments during active state (gross movements, exploratory movements or locomotor activity and awake passive state (no sleep were selected on the basis of instrumental measures of animal behavior, and were used as an input for EEG power density analysis. Results showed a clear peak of EEG power density at alpha range (7-9 Hz during passive state. During active state, there was a reduction in alpha power density (8-12 Hz and an increase of power density at slow frequencies (1-4 Hz. Relative EMG activity was related to EEG power density at 2-4 Hz (positive correlation and at 8-12 Hz (negative correlation. These results suggest for the first time that the primate gray mouse lemurs and humans may share basic neurophysiologic mechanisms of synchronization of frontal alpha rhythms in awake passive state and their desynchronization during motor and locomotor activity. These EEG markers may be an ideal experimental model for translational basic (motor science and applied (pharmacological and non-pharmacological interventions research in Neurophysiology.

  2. Removal of an endocrine disrupting chemical (17 alpha-ethinyloestradiol) from wastewater effluent by activated carbon adsorption: Effects of activated carbon type and competitive adsorption

    Energy Technology Data Exchange (ETDEWEB)

    Ifelebuegu, A.O.; Lester, J.N.; Churchley, J.; Cartmell, E. [Cranfield University, Cranfield (United Kingdom). School of Water Science


    Granular activated carbon has been extensively used for the adsorption of organic micropollutants for potable water production. In this study the removal of an endocrine disrupting chemical from wastewater final effluent by three types of granular activated carbon (wood, coconut and coal based) has been investigated in batch adsorption experiments and correlated with the removal of chemical oxygen demand (COD), total organic carbon (TOC) and ultraviolet absorbance (UV). The results obtained demonstrated 17 alpha-ethinyloestradiol (EE2) removals of 98.6%, 99.3%, and 96.4% were achieved by the coal based (ACo), coconut based (ACn) and wood based (AWd) carbons respectively at the lowest dose of carbon (0.1 gl{sup -1}). The other adsorbates investigated all exhibited good removal. At an equilibrium concentration of 7 mgl{sup -1} the COD adsorption capacities were 3.16 mg g{sup -1}, 4.8 mg g{sup -1} and 7.1 mg g{sup -1} for the wood, coconut and coal based carbons respectively. Overall, the order of removal efficiency of EE2 and the other adsorbates for the three activated carbons was ACn {gt} ACo {gt} AWd. The adsorption capacities of the carbons were found to be reduced by the effects of other competing adsorbates in the wastewater effluent.

  3. A Statistical Analysis of Solar Surface Indices Through the Solar Activity Cycles 21-23

    CERN Document Server

    Goker, Umit Deniz; Nutku, Ferhat; Priyal, Muthu


    Variations of total solar irradiance (TSI), magnetic field, Ca II K-flux, faculae and plage areas due to the number and the type of sunspots/sunspot groups (SGs) are well established by using ground based data from various centers such as Solar Irradiance Platform, Stanford Data (SFO), Kodaikanal data (KKL) and National Geographical Data Center (NGDC) Homepage, respectively. We applied time series analysis for extracting the data over the descending phases of solar activity cycles (SACs) 21, 22 and 23, and the ascending phases 22 and 23 of SACs, and analyzed the selected data using the Python programming language. Our detailed analysis results suggest that there is a stronger correlation between solar surface indices and the changes in the relative portion of the small and large SGs. This somewhat unexpected finding suggest that plage regions decreased in a lower values in spite of the higher number of large SGs in SAC 23 while Ca II K-flux did not decrease by large amount or it was comparable with SAC 22 for...

  4. In situ hydrogen consumption kinetics as an indicator of subsurface microbial activity (United States)

    Harris, S.H.; Smith, R.L.; Suflita, J.M.


    There are few methods available for broadly assessing microbial community metabolism directly within a groundwater environment. In this study, hydrogen consumption rates were estimated from in situ injection/withdrawal tests conducted in two geochemically varying, contaminated aquifers as an approach towards developing such a method. The hydrogen consumption first-order rates varied from 0.002 nM h-1 for an uncontaminated, aerobic site to 2.5 nM h-1 for a contaminated site where sulfate reduction was a predominant process. The method could accommodate the over three orders of magnitude range in rates that existed between subsurface sites. In a denitrifying zone, the hydrogen consumption rate (0.02 nM h-1) was immediately abolished in the presence of air or an antibiotic mixture, suggesting that such measurements may also be sensitive to the effects of environmental perturbations on field microbial activities. Comparable laboratory determinations with sediment slurries exhibited hydrogen consumption kinetics that differed substantially from the field estimates. Because anaerobic degradation of organic matter relies on the rapid consumption of hydrogen and subsequent maintenance at low levels, such in situ measures of hydrogen turnover can serve as a key indicator of the functioning of microbial food webs and may be more reliable than laboratory determinations. ?? 2007 Federation of European Microbiological Societies.

  5. Staphylococcal superantigen-like 5 activates platelets and supports platelet adhesion under flow conditions, which involves glycoprotein Ib alpha and alpha(IIb)beta(3)

    NARCIS (Netherlands)

    De Haas, C. J. C.; Weeterings, C.; Vughs, M. M.; De Groot, P. G.; Van Strijp, J. A.; Lisman, T.


    Objectives: Staphylococcal superantigen-like 5 (SSL5) is an exoprotein secreted by Staphylococcus aureus that has been shown to inhibit neutrophil rolling over activated endothelial cells via a direct interaction with P-selectin glycoprotein ligand 1 (PSGL-1). Methods and Results: When purified reco

  6. Selective activation of p38alpha and p38gamma by hypoxia. Role in regulation of cyclin D1 by hypoxia in PC12 cells. (United States)

    Conrad, P W; Rust, R T; Han, J; Millhorn, D E; Beitner-Johnson, D


    Hypoxic/ischemic trauma is a primary factor in the pathology of a multitude of disease states. The effects of hypoxia on the stress- and mitogen-activated protein kinase signaling pathways were studied in PC12 cells. Exposure to moderate hypoxia (5% O(2)) progressively stimulated phosphorylation and activation of p38gamma in particular, and also p38alpha, two stress-activated protein kinases. In contrast, hypoxia had no effect on enzyme activity of p38beta, p38beta(2), p38delta, or on c-Jun N-terminal kinase, another stress-activated protein kinase. Prolonged hypoxia also induced phosphorylation and activation of p42/p44 mitogen-activated protein kinase, although this activation was modest compared with nerve growth factor- and ultraviolet light-induced activation. Hypoxia also dramatically down-regulated immunoreactivity of cyclin D1, a gene that is known to be regulated negatively by p38 at the level of gene expression (Lavoie, J. N., L'Allemain, G., Brunet, A., Muller, R., and Pouyssegur, J. (1996) J. Biol. Chem. 271, 20608-20616). This effect was partially blocked by SB203580, an inhibitor of p38alpha but not p38gamma. Overexpression of a kinase-inactive form of p38gamma was also able to reverse in part the effect of hypoxia on cyclin D1 levels, suggesting that p38alpha and p38gamma converge to regulate cyclin D1 during hypoxia. These studies demonstrate that an extremely typical physiological stress (hypoxia) causes selective activation of specific p38 signaling elements; and they also identify a downstream target of these pathways. PMID:10438538

  7. Comparing Prescription Sales, Google Trends and CDC Data as Flu Activity Indicators (United States)

    Patwardhan, Avinash; Lorber, David


    Objective To examine if the prescription sales data from a large retail pharmacy chain in the US were comparable to Google Flu trends and CDC’s US ILI Network data as flu activity indicator. Introduction In a 2007 survey of public health officials in the United States, International Society for Disease Surveillance found that only 7% used pharmacy prescription sales data for surveillance (1). There have been many reports suggesting effective use of prescription sales data in syndromic surveillance (2, 3, 4, 5). Community pharmacies can provide a valuable supplementary tool for syndromic surveillance of infectious diseases. Methods We extracted five years of de-identified prescription sales data from the proprietary pharmacy computer system of a large retail pharmacy chain in the United States. The prescriptions were written for the common drugs for the treatment of influenza: Amantadine, Os-eltamivir, Rimantadine, and Zanamivir. We acquired Google Flu trends national aggregate counts data that represented the estimates of the ILI cases per 100,000 physician visits. We acquired CDC ILINET data for 2007. We calculated Pearson ‘r’ between our data and Google and CDC data. We also created comparable trends graphs after converting the counts of the influenza scripts and the counts of the Google estimated ILI cases to logarithmic scale. Results The Pearson ‘r’ between the aggregate counts of scripts for all the four drugs and the Google estimates of the ILI cases for years 2007, 2008, 2009, 2010, and 2011 were 0.85 (95% CI, 0.75–0.91), 0.92 (95% CI, 0.86–0.95), 0.91(95% CI, 0.85–0.95), 0.88 (95% CI, 0.80–0.93), and 0.87 (95% CI, 0.78–0.92) and 0.92 (95% CI, 0.90–0.94) for years 2007 through 2011 together. The Pearson ‘r’ between the aggregate counts of scripts and the CDC % unweighted ILI (2007) was 0.97 (95% CI, 0.95–0.98). Conclusions A strong to very strong correlation between prescription sales data and Google Flu trends and CDC’s ILI

  8. Synthesis and biological activity of new (E)-alpha-(Methoxyimino)benzeneacetate derivatives containing a substituted pyrazole ring. (United States)

    Li, Miao; Liu, Chang-Ling; Yang, Ji-Chun; Zhang, Jin-Bo; Li, Zhi-Nian; Zhang, Hong; Li, Zheng-Ming


    Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin analogues with high activity, a series of new strobilurin derivatives containing a substituted pyrazole in the side chain were synthesized and their biological activities were tested. The compounds were identified by (1)H nuclear magnetic resonance, infrared, and elemental analysis. The test results indicated that the compounds exhibited strong fungicidal activities against Pyricularia oryzae , Phytophthora infestans , Pseudoperonospora cubensis , and Erysiphe graminis . The relationship between structure and biological activity is discussed in terms of the effects of the substituents on the pyrazole ring. The present work demonstrates that strobilurin analogues with a 3-(substituted phenyl)-1H-pyrazol-5-oxy side chain can be used as possible lead compounds for the development of potential agrochemicals. PMID:19961182

  9. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    Directory of Open Access Journals (Sweden)

    Jintao Xu


    Full Text Available Anti-tumor necrosis factor alpha (anti-TNF-α therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance.

  10. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection (United States)

    Xu, Jintao; Eastman, Alison J.; Flaczyk, Adam; Neal, Lori M.; Zhao, Guolei; Carolan, Jacob; Malachowski, Antoni N.; Stolberg, Valerie R.; Yosri, Mohammed; Chensue, Stephen W.; Curtis, Jeffrey L.; Osterholzer, John J.


    ABSTRACT Anti-tumor necrosis factor alpha (anti-TNF-α) therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN) of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC) in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance. PMID:27406560

  11. Evaluation of long-lived Alpha (llα) activity associated with respirable dust in the underground Narwapahar uranium mine in India

    International Nuclear Information System (INIS)

    Uranium mining activities, in general, produce dust particle of different size in and around the location of operations being actually carried out. The most prominent being that of respirable size. Meticulously, the airborne uranium ore dust in underground uranium mines contains long-lived alpha (llα) emitters of the natural uranium decay chain. The main mining operations such as drilling, blasting, mucking, loading-dumping etc. generate ore dust of different particle size which becomes dispersed in the mine environment and gives rise to an inhalation hazard. The present work has been done in underground U mine at Narwapahar (ore grade about 0.043 % U3O8). The objective of the present study is to estimate the long lived alpha activity associated with the airborne respirable particulate in the underground mine at Narwapahar

  12. Synthesis and activity of (R)-(-)-m-trimethylacetoxy-alpha-[(methylamino)methyl]benzyl alcohol hydrochloride: a prodrug form of (R)-(-)-phenylephrine. (United States)

    Yuan, S S; Bador, N


    Optically pure (R)-(-)-m-trimethylacetoxy-alpha-[(methylamino)methyl]benzyl alcohol hydrochloride was synthesized by the following sequence: (R)-(-)-phenylephrine was condensed with acetone in the presence of calcium carbide to give an oxazolidine derivative and then treated with thallous ethoxide in ether followed by trimethylacetyl chloride to yield the phenolic ester. Finally, the oxazolidine ring was cleaved by one equivalent of hydrogen chloride in ethanol. Condensation of phenylephrine with benzaldehyde, with or without solvents, gave either 1,1,2-trimethyl-4,6-dihydroxy-1,2,3,4-tetrahydroisoquinoline or a mixture of side-chain oxazolidine and the tetrahydroisoquinoline. Condensation of epinephrine with opianic acid in pyridine also gave a tetrahydroisoquinoline only. When applied on rabbit eyes, the prodrug (R)-(-)-m-trimethylacetoxy-alpha[(methylamino)methyl]benzyl alcohol hydrochloride exhibited an unexpected, three times higher mydriatic activity than the corresponding racemic prodrug and was 15 times more active than the parent, (R)-(-)-phenylephrine.

  13. Transgenic up-regulation of alpha-CaMKII in forebrain leads to increased anxiety-like behaviors and aggression

    Directory of Open Access Journals (Sweden)

    Hasegawa Shunsuke


    Full Text Available Abstract Background Previous studies have demonstrated essential roles for alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII in learning, memory and long-term potentiation (LTP. However, previous studies have also shown that alpha-CaMKII (+/- heterozygous knockout mice display a dramatic decrease in anxiety-like and fearful behaviors, and an increase in defensive aggression. These findings indicated that alpha-CaMKII is important not only for learning and memory but also for emotional behaviors. In this study, to understand the roles of alpha-CaMKII in emotional behavior, we generated transgenic mice overexpressing alpha-CaMKII in the forebrain and analyzed their behavioral phenotypes. Results We generated transgenic mice overexpressing alpha-CaMKII in the forebrain under the control of the alpha-CaMKII promoter. In contrast to alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in anxiety-like behaviors in open field, elevated zero maze, light-dark transition and social interaction tests, and a decrease in locomotor activity in their home cages and novel environments; these phenotypes were the opposite to those observed in alpha-CaMKII (+/- heterozygous knockout mice. In addition, similarly with alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in aggression. However, in contrast to the increase in defensive aggression observed in alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in offensive aggression. Conclusion Up-regulation of alpha-CaMKII expression in the forebrain leads to an increase in anxiety-like behaviors and offensive aggression. From the comparisons with previous findings, we suggest that the expression levels of alpha-CaMKII are associated with the state of emotion; the expression level of alpha-CaMKII positively correlates with the anxiety state and strongly affects

  14. On-Going Frontal Alpha Rhythms Are Dominant in Passive State and Desynchronize in Active State in Adult Gray Mouse Lemurs


    Francesco Infarinato; Anisur Rahman; Claudio Del Percio; Yves Lamberty; Regis Bordet; Richardson, Jill C.; Gianluigi Forloni; Wilhelmus Drinkenburg; Susanna Lopez; Fabienne Aujard; Claudio Babiloni; Fabien Pifferi


    The gray mouse lemur (Microcebus murinus) is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009,, we tested the hypothesis that spectral electroencephalographic (EEG) markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8-12 Hz) in humans. To this aim, EEG (bipolar electrodes in frontal cortex) and electromyographi...

  15. Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death


    Keatinge, Marcus; Bui, Hai; Menke, Aswin; Chen, Yu-Chia; Sokol, Anna M.; Bai, Qing; Ellett, Felix; Da Costa, Marc; Burke, Derek; Gegg, Matthew; Trollope, Lisa; Payne, Thomas; McTighe, Aimee; Mortiboys, Heather; de Jager, Sarah


    Autosomal recessively inherited glucocerebrosidase 1 (GBA1) mutations cause the lysosomal storage disorder Gaucher's disease (GD). Heterozygous GBA1 mutations (GBA1 +/−) are the most common risk factor for Parkinson's disease (PD). Previous studies typically focused on the interaction between the reduction of glucocerebrosidase (enzymatic) activity in GBA1 +/− carriers and alpha-synuclein-mediated neurotoxicity. However, it is unclear whether other mechanisms also contribute to the increased ...

  16. Structure-activity relationships in cinnamamides. 1. Synthesis and pharmacological evaluation of some (E)- and (Z)-N-alkyl-alpha,beta-dimethylcinnamamides. (United States)

    Balsamo, A; Barili, P L; Crotti, P; Macchia, D; Macchia, F; Pecchia, A; Cuttica, A; Passerini, N


    Two series of (E)- and (Z)-N-alkyl-alpha,beta-dimethylcinnamamide derivatives were prepared and the biological activity of these compounds was investigated in a series of pharmacological tests. All compounds tested had clear activity on the CNS; generally, this was depressant with E isomers, while Z isomers always caused marked stimulation (tremors and convulsions). Some of the E isomers also had a clear-cut anticonvulsant activity as shown by the antagonistic effect on pentylenetetrazole-induced seizures in the mouse. The NMR spectra of these compounds, which confirm their configurations, are discussed. PMID:1159703

  17. Activation analysis of hair as an indicator of contamination of man by environmental trace element pollutants

    International Nuclear Information System (INIS)

    The burning of fossil fuel, discharges from metallurgical and chemical plants, the wide use of chemicals, and other human activities, result in releasing into the biosphere large quantities of elements which are found in relatively low concentrations in the human organism. The pollution of the biosphere by such trace elements, and in particular heavy metals, has reached such proportions that on the scale of significance of the factors causing the 'stressed' state of the environment of heavy metals occupy the second place and, according to forecasts, may in the future move on to the first. In the problem of pollution of the biosphere, man himself undoubtedly occupies the central position as a target. The pollution of air, soil and water, the contamination of micro-organisms, plants and animals are certainly growing into a serious threat and leading to heavy losses. However, it would be a real disaster if man himself became contaminated to levels giving rise to large scale harmful somatic or genetic effects. It is therefore an urgent problem today to determine the initial levels of trace elements in man and the extent of his contamination in areas where these elements are expected to show anomalous concentrations. Attention should be paid in the first place to those trace elements which probably play no physiological role, are particularly abundant in the environment, and have high toxicity (arsenic, mercury, lead, cadmium, etc.). Moreover, it should be born in mind that in anomalously high concentrations even the physiologically necessary trace elements (copper, zinc, manganese, fluorine, etc.) cause harmful effects. This paper justifies the use of hair samples as a biological indicator of environmental pollutants from physiological and morphological aspect and recommends on sample preparation and analysis methods

  18. A Growth-rate Indicator for Compton-thick Active Galactic Nuclei (United States)

    Brightman, M.; Masini, A.; Ballantyne, D. R.; Baloković, M.; Brandt, W. N.; Chen, C.-T.; Comastri, A.; Farrah, D.; Gandhi, P.; Harrison, F. A.; Ricci, C.; Stern, D.; Walton, D. J.


    Due to their heavily obscured central engines, the growth rate of Compton-thick (CT) active galactic nuclei (AGNs) is difficult to measure. A statistically significant correlation between the Eddington ratio, λ Edd, and the X-ray power-law index, Γ, observed in unobscured AGNs offers an estimate of their growth rate from X-ray spectroscopy (albeit with large scatter). However, since X-rays undergo reprocessing by Compton scattering and photoelectric absorption when the line of sight to the central engine is heavily obscured, the recovery of the intrinsic Γ is challenging. Here we study a sample of local, predominantly CT megamaser AGNs, where the black hole mass, and thus Eddington luminosity, are well known. We compile results of the X-ray spectral fitting of these sources with sensitive high-energy (E > 10 keV) NuSTAR data, where X-ray torus models, which take into account the reprocessing effects have been used to recover the intrinsic Γ values and X-ray luminosities, L X. With a simple bolometric correction to L X to calculate λ Edd, we find a statistically significant correlation between Γ and λ Edd (p = 0.007). A linear fit to the data yields Γ = (0.41 ± 0.18)log10 λ Edd + (2.38 ± 0.20), which is statistically consistent with results for unobscured AGNs. This result implies that torus modeling successfully recovers the intrinsic AGN parameters. Since the megamasers have low-mass black holes (M BH ≈ 106-107 M ⊙) and are highly inclined, our results extend the Γ-λ Edd relationship to lower masses and argue against strong orientation effects in the corona, in support of AGN unification. Finally this result supports the use of Γ as a growth-rate indicator for accreting black holes, even for CT AGNs.

  19. Evaluation of flurbiprofen urinary ratios as in vivo indices for CYP2C9 activity (United States)

    Zgheib, N K; Frye, R F; Tracy, T S; Romkes, M; Branch, R A


    Aims We investigated flurbiprofen pharmacokinetics in 12 volunteers to develop a phenotypic trait measure that correlates with the fractional clearance to 4′-hydroxyflurbiprofen. The effect of the CYP2C9 inhibitor fluconazole on flurbiprofen metabolism was also evaluated. Methods Flurbiprofen pharmacokinetics were evaluated before and after the first and seventh doses of fluconazole. The urinary recovery ratio was calculated as FLRR = 4′-OHF/ [4′-OHF + Ftot] and the urinary metabolic ratio was calculated as FLMR = 4′-OHF/Ftot, where 4′-OHF and Ftot represent total (conjugated and unconjugated) amounts recovered in urine. Results There was a statistically significant relationship between the 4′-OHF formation clearance (4OHCLf) and both the 8-h FLRR and the 8-h FLMR with and without administration of fluconazole. The flurbiprofen apparent oral clearance (CL/F) was decreased by 53% [90% confidence interval (CI) −58, −48] and 64% (90% CI −69, −59), respectively, after administration of one and seven doses of fluconazole when compared with administration of flurbiprofen alone; similarly, the 4OHCLf decreased by 69% (90% CI −74, −64) and 78% (90% CI −83, −73), the 8-h FLRR decreased by 35% (90% CI −41, −29) and 40% (90% CI −46, −35) and the 8-h FLMR decreased by 61% (90% CI −65, −58) and 67% (90% CI −70, −63). The magnitude of decrease in CL/F and 4OHCLf was greater after seven doses compared with after one dose of fluconazole (P < 0.005). Conclusions This study provides strong evidence that both the 8-h FLRR and the 8-h FLMR are suitable phenotypic indices for CYP2C9 activity. PMID:17054666

  20. PDGFR alpha signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90(RSK) and AKT signaling pathways

    DEFF Research Database (Denmark)

    Clement, Ditte L.; Mally, Sabine; Stock, Christian;


    In fibroblasts, platelet-derived growth factor receptor alpha (PDGFR alpha) is upregulated during growth arrest and compartmentalized to the primary cilium. PDGF-AA mediated activation of the dimerized ciliary receptor produces a phosphorylation cascade through the PI3K-AKT and MEK1/2-ERK1/2 path...

  1. Deletion of Asn{sup 281} in the {alpha}-subunit of the human insulin receptor causes constitutive activation of the receptor and insulin desensitization

    Energy Technology Data Exchange (ETDEWEB)

    Desbois-Mouthon, C.; Sert-Langeron, C.; Magre, J.; Blivet, M.J. [INSERM, Paris (France)] [and others


    We studied the structure and function of the insulin receptor (IR) in two sisters with leprechaunism. The patients had inherited alterations in the IR gene and were compound heterozygotes. Their paternal IR allele carried a major deletion, including exons 10-13, which shifted the reading frame and introduced a premature chain termination codon in the IR sequence. This allele was expressed at a very low level in cultured fibroblasts (<10% of total IR messenger ribonucleic acid content) and encoded a truncated protein lacking transmembrane and tyrosine kinase domains. The maternal IR allele was deleted of 3 bp in exon 3, causing the loss of Asn{sup 281} in the {alpha}-subunit. This allele generated levels of IR messenger ribonucleic acid and cell surface receptors similar to those seen in control fibroblasts. However, IRs from patients` cells had impaired insulin binding and exhibited in vivo and in vitro constitutive activation of autophosphorylation and tyrosine kinase activity. As a result of this IR-preactivated state, the cells were desensitized to insulin stimulation of glycogen and DNA syntheses. These findings strongly suggest that Asn{sup 281} of the IR {alpha}-subunit plays a critical role in the inhibitory constraint exerted by the extracellular {alpha}-subunit over the intracellular kinase activity. 59 refs., 6 figs.

  2. PGC-1alpha Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis

    Directory of Open Access Journals (Sweden)

    Leone Teresa C


    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha-/- mice. With age, the PGC-1alpha-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  3. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis.

    Directory of Open Access Journals (Sweden)

    Teresa C Leone


    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha(-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha(-/- mice. With age, the PGC-1alpha(-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha(-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  4. (210)Po in drinking water, its potential health effects, and inadequacy of the gross alpha activity MCL. (United States)

    Seiler, Ralph


    Polonium-210 ((210)Po) is a naturally-occurring, carcinogenic member of the (238)U decay series and the granddaughter of (210)Pb. It has a half life of 138.4days and is rarely found in drinking water at levels exceeding 5mBq/L because it strongly binds to aquifer sediment. When the current US Maximum Contaminant Level (MCL) covering (210)Po was promulgated in December 2000, very little was known about its occurrence and the processes responsible for mobilizing it. More is now known about the processes that mobilize (210)Po from sediments and a review of recent occurrence data show that it may not be as rare in the US as the US Environmental Protection Agency (USEPA) thought in 2000. Worldwide, only about 2200 analyses for (210)Po in drinking water were identified, with activities exceeding 500mBq/L being found only in Finland, India, Sweden, and the US. The median of 400 (210)Po analyses from the US is 4.75mBq/L and >10% of the samples exceed 500mBq/L. Current compliance-monitoring regulations in the US essentially guarantee that (210)Po contamination will not be detected except in very contaminated wells. Major problems with the US Gross Alpha Activity MCL include the volatility of (210)Po and extended holding times and sample-compositing methods that can allow the majority of (210)Po in a sample bottle to decay before analysis. In light of new information, the radionuclide rule should be changed and direct measurements of (210)Po should be made in all public-water supply wells to rule out its presence. Much of the important biological and toxicological research on (210)Po is more than four decades old and new laboratory research using modern tools is needed. Biological and epidemiological investigations of known contaminated areas are needed to assess the effect (210)Po exposure is having on animals and humans consuming the water. PMID:27369089

  5. $\\alpha_s$ review (2016)

    CERN Document Server

    d'Enterria, David


    The current world-average of the strong coupling at the Z pole mass, $\\alpha_s(m^2_{Z}) = 0.1181 \\pm 0.0013$, is obtained from a comparison of perturbative QCD calculations computed, at least, at next-to-next-to-leading-order accuracy, to a set of 6 groups of experimental observables: (i) lattice QCD "data", (ii) $\\tau$ hadronic decays, (iii) proton structure functions, (iv) event shapes and jet rates in $e^+e^-$ collisions, (v) Z boson hadronic decays, and (vi) top-quark cross sections in p-p collisions. In addition, at least 8 other $\\alpha_s$ extractions, usually with a lower level of theoretical and/or experimental precision today, have been proposed: pion, $\\Upsilon$, W hadronic decays; soft and hard fragmentation functions; jets cross sections in pp, e-p and $\\gamma$-p collisions; and photon F$_2$ structure function in $\\gamma\\,\\gamma$ collisions. These 14 $\\alpha_s$ determinations are reviewed, and the perspectives of reduction of their present uncertainties are discussed.

  6. Objective assessment and modification of physical activity and health indices in adolescent females



    non-peer-reviewed The following literature review describes the benefits of being physically active in childhood and adulthood and also the dangers that accompany inactivity. The benefits of being physically activity as a young person can affect future health and future physical activity levels and this link will be considered as a rationale for promoting physical activity in adolescence. The negative consequences of obesity in childhood and adulthood are also considered. The relationship ...

  7. Indications for an influence of Hot Jupiters on the rotation and activity of their host stars


    Poppenhaeger, K.; Wolk, S. J.


    The magnetic activity of planet-hosting stars is an important factor to estimate the atmospheric stability of close-in exoplanets and the age of their host stars. It has long been speculated that close-in exoplanets can influence the stellar activity level. However, testing for tidal or magnetic interaction effects in samples of planet-hosting stars is difficult because stellar activity hinders exoplanet detection, so that stellar samples with detected exoplanets show a bias towards low activ...

  8. Differential in vitro inhibitory activity against HIV-1 of alpha-(1-3- and alpha-(1-6-D-mannose specific plant lectins : Implication for microbicide development

    Directory of Open Access Journals (Sweden)

    Balzarini Jan


    Full Text Available Abstract Background Plant lectins such as Galanthus nivalis agglutinin (GNA and Hippeastrum hybrid agglutinin (HHA are natural proteins able to link mannose residues, and therefore inhibit HIV-target cell interactions. Plant lectins are candidate for microbicide development. Objective To evaluate the activity against HIV of the mannose-specific plant lectins HHA and GNA at the cellular membrane level of epithelial cells and monocyte-derived dendritic cells (MDDC, two potential target cells of HIV at the genital mucosal level. Methods The inhibitory effects of HHA and GNA were evaluated on HIV adsorption to genital epithelial HEC-1A cell line, on HIV transcytosis throughout a monolayer of polarized epithelial HEC-1A cells, on HIV adsorption to MDDC and on transfer of HIV from MDDC to autologous T lymphocytes. Results HHA faintly inhibited attachment to HEC-1A cells of the R5-tropic HIV-1Ba-L strain, in a dose-dependent manner, whereas GNA moderately inhibited HIV adsorption in the same context, but only at high drug doses. Only HHA, but not GNA, inhibited HIV-1JR-CSF transcytosis in a dose-dependent manner. By confocal microscopy, HHA, but not GNA, was adsorbed at the epithelial cell surface, suggesting that HHA interacts specifically with receptors mediating HIV-1 transcytosis. Both plant lectins partially inhibited HIV attachment to MDDC. HHA inhibited more efficiently the transfer of HIV from MDDC to T cell, than GNA. Both HHA and GNA lacked toxicity below 200 μg/ml irrespective the cellular system used and do not disturb the monolayer integrity of epithelial cells. Conclusion These observations demonstrate higher inhibitory activities of the lectin plant HHA by comparison to GNA, on HIV adsorption to HEC-1A cell line, HIV transcytosis through HEC-1A cell line monolayer, HIV adsorption to MDDC and HIV transfer from MDDC to T cells, highlighting the potential interest of HHA as effective microbicide against HIV.

  9. DOSEmanPRO - active electronic online personal air sampler for detection of radon progeny long lived alpha nuclides

    International Nuclear Information System (INIS)

    Full text: Using the micro system - technology we developed a online personal air sampler not bigger than a mobile phone, to open a new dimension in personal dosimetry of inhaled radioactive aerosols. The DOSEman PRO containing an internal pump with a continuous air flow of 0.15 I/min sample the radon progeny or other nuclides on a millipore filter with excellent spectroscopic resolution. A 1.5 cm2 light protected ion-implanted silicon detector analyses the alpha radiation at the filter. This small detector head contains also the pre amplification and pulse processing. The alpha radiation of the radon progeny and the long lived alpha nuclides is analyzed by a 60 channel spectrometer. The energy resolution of the online analyzed filter spectra is in the order of 150 keV. Mechanical and electronic design enables one to distinguish the long lived alpha nuclides from the radon and thoron progeny very easily. Using a special algorithm we correct the influence of the tailing of the radon progeny to the long lived alpha nuclides and take into consideration possible interference in determining the long lived alpha nuclides. Because of the air sampling volume of nearly 10 I/h, the system has a high efficiency. The detection limit by 2 hours sampling time is 0.05 Bq/m3 alpha nuclide concentration. In a modified device for air sampling especially of long-lived alpha nuclides like uranium, radium or plutonium, the flow rate is increased to 0,3 1/min e.g. during a 10 h sampling period we can detect 0.005 Bq/m3 in a low radon atmosphere. Assuming increased radon progeny concentration, the statistical error for the long lived alpha nuclides will be higher, but in most of the cases for use in nuclear facilities low radon concentrations are ambient conditions. This concept of an electronic personal air sampler with an alpha spectroscopy offers some outstanding advantages compared to passive dosimeters or off-line alpha air filters: The dose value and the nuclide concentration is

  10. Soil microbial activities in Mediterranean environment as desertification indicators along a pluviometric gradient. (United States)

    Novosadova, I.; Zahora, J.; Ruiz Sinoga, J. D.


    In the Mediterranean areas of Southern Spain, unsuitable agricultural practices with adverse environmental conditions (López Bermúdez and Albaladejo, 1990), have led to a permanent degradation and loss of soil fertility. This includes deterioration of the natural plant cover, which protects against erosion by contributing organic matter, the main prerequisite of ecosystem sustainability (Grace et al., 1994). Physico-chemical, microbiological and biochemical soil properties are very responsive and provide immediate and precise information on small changes occurring in soil (Dick and Tabatabai, 1993). There is increasing evidence that such parameters are also sensitive indicators of ecology stress suffered by a soil and its recovery, since microbial activity has a direct influence on the stability and fertility of ecosystems (Smith and Papendick, 1993). One method for recovering degraded soils of such semiarid regions, with their low organic matter content, is to enhance primary productivity and carbon sequestration without any additional nitrogen fertilization and preferably without incorporation of leguminous plants (Martinez Mena et al., 2008). Carbon rich materials can sustain microbial activity and growth, thus enhancing biogeochemical nutrient cycles (Pascual et al., 1997). The present study is focused in the role of physico-chemical and microbial soil properties in Mediterranean environment, in terms of in situ and ex situ microbial transformation of soil carbon and nitrogen, in order to characterise the key soil microbial activities which could strongly affect carbon and nitrogen turnover in soil and hereby soil fertility and soil organic matter "quality". These microbial activities could at unsuitable agricultural practices with adverse environmental conditions induce unfavourable hydrologycal tempo-spatial response. The final results shown modifications in the soil properties studied with the increasing of the aridity. Such changes suppose the soil

  11. Primary structure of human alpha 2-macroglobulin. V. The complete structure

    DEFF Research Database (Denmark)

    Sottrup-Jensen, Lars; Stepanik, Terrence M; Kristensen, Torsten;


    in the activation cleavage area (the "bait" region) are located in the sequence: -Arg681-Val-Gly-Phe-Tyr-Glu-. The molecular weight of the unmodified alpha 2-macroglobulin subunit is 160,837 and approximately 179,000, including the carbohydrate groups. The presence of possible internal homologies within the alpha 2......-macroglobulin subunit is discussed. A comparison of stretches of sequences from alpha 2-macroglobulin with partial sequence data for complement components C3 and C4 indicates that these proteins are evolutionary related. The properties of alpha 2-macroglobulin are discussed within the context of proteolytically...

  12. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. (United States)

    Heijnen, H F; Schiel, A E; Fijnheer, R; Geuze, H J; Sixma, J J


    Platelet activation leads to secretion of granule contents and to the formation of microvesicles by shedding of membranes from the cell surface. Recently, we have described small internal vesicles in multivesicular bodies (MVBs) and alpha-granules, and suggested that these vesicles are secreted during platelet activation, analogous to the secretion of vesicles termed exosomes by other cell types. In the present study we report that two different types of membrane vesicles are released after stimulation of platelets with thrombin receptor agonist peptide SFLLRN (TRAP) or alpha-thrombin: microvesicles of 100 nm to 1 microm, and exosomes measuring 40 to 100 nm in diameter, similar in size as the internal vesicles in MVBs and alpha-granules. Microvesicles could be detected by flow cytometry but not the exosomes, probably because of the small size of the latter. Western blot analysis showed that isolated exosomes were selectively enriched in the tetraspan protein CD63. Whole-mount immuno-electron microscopy (IEM) confirmed this observation. Membrane proteins such as the integrin chains alpha(IIb)-beta(3) and beta(1), GPIbalpha, and P-selectin were predominantly present on the microvesicles. IEM of platelet aggregates showed CD63(+) internal vesicles in fusion profiles of MVBs, and in the extracellular space between platelet extensions. Annexin-V binding was mainly restricted to the microvesicles and to a low extent to exosomes. Binding of factor X and prothrombin was observed to the microvesicles but not to exosomes. These observations and the selective presence of CD63 suggest that released platelet exosomes may have an extracellular function other than the procoagulant activity, attributed to platelet microvesicles.

  13. The Structure and Function of an Arabinan-specific [alpha]-1,2-Arabinofuranosidase Identified from Screening the Activities of Bacterial GH43 Glycoside Hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Cartmell, Alan; McKee, Lauren S.; Pena, Maria J.; Larsbrink, Johan; Brumer, Harry; Kaneko, Satoshi; Ichinose, Hitomi; Lewis, Richard J.; Vikso-Nielsen, Anders; Gilbert, Harry; Marles-Wright, Jon (Newcastle); (National Food Research Institute); (Novozymes A/S); (RITS); (Georgia)


    Reflecting the diverse chemistry of plant cell walls, microorganisms that degrade these composite structures synthesize an array of glycoside hydrolases. These enzymes are organized into sequence-, mechanism-, and structure-based families. Genomic data have shown that several organisms that degrade the plant cell wall contain a large number of genes encoding family 43 (GH43) glycoside hydrolases. Here we report the biochemical properties of the GH43 enzymes of a saprophytic soil bacterium, Cellvibrio japonicus, and a human colonic symbiont, Bacteroides thetaiotaomicron. The data show that C. japonicus uses predominantly exo-acting enzymes to degrade arabinan into arabinose, whereas B. thetaiotaomicron deploys a combination of endo- and side chain-cleaving glycoside hydrolases. Both organisms, however, utilize an arabinan-specific {alpha}-1,2-arabinofuranosidase in the degradative process, an activity that has not previously been reported. The enzyme can cleave {alpha}-1,2-arabinofuranose decorations in single or double substitutions, the latter being recalcitrant to the action of other arabinofuranosidases. The crystal structure of the C. japonicus arabinan-specific {alpha}-1,2-arabinofuranosidase, CjAbf43A, displays a five-bladed {beta}-propeller fold. The specificity of the enzyme for arabinan is conferred by a surface cleft that is complementary to the helical backbone of the polysaccharide. The specificity of CjAbf43A for {alpha}-1,2-L-arabinofuranose side chains is conferred by a polar residue that orientates the arabinan backbone such that O2 arabinose decorations are directed into the active site pocket. A shelflike structure adjacent to the active site pocket accommodates O3 arabinose side chains, explaining how the enzyme can target O2 linkages that are components of single or double substitutions.

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

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


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

  15. Constructing coincident indices of economic activity for the Latin American economy

    Directory of Open Access Journals (Sweden)

    João Victor Issler


    Full Text Available This paper has three main contributions. The first is to propose an individual coincident indicator for the following Latin American countries: Argentina, Brazil, Chile, Colombia and Mexico. In order to obtain similar series to those traditionally used in business-cycle research in constructing coincident indices (output, sales, income and employment we were forced to back-cast several individual country series which were not available in a long time-series span. The second contribution is to establish a chronology of recessions for these countries, covering the period from 1980 to 2012 on a monthly basis. Based on this chronology, the countries are compared in several respects. The final contribution is to propose an aggregate coincident indicator for the Latin American economy, which weights individual-country composite indices. Finally, this indicator is compared with the coincident indicator (The Conference Board - TCB of the U.S. economy. We find that the U.S. indicator Granger-causes the Latin American indicator in statistical tests

  16. Calibration of sources for alpha spectroscopy systems

    International Nuclear Information System (INIS)

    This paper describes the calibration methodology for measuring the total alpha activity of plane and thin sources with the Alpha Spectrometer for Silicon Detector in the Nuclear Measures and Dosimetry laboratory at IEAv/CTA. (author)

  17. Getting the Most from Pi Sigma Alpha Chapters: Exploring the Chapter Activity Grant Program and Its Multiplier Effects (United States)

    Alexander, Robert M.


    The political science honor society, Pi Sigma Alpha, has chapters in nearly 700 institutions across the United States. The organization sponsors many programs that can contribute a great deal to students of political science; however, many students are unaware of these opportunities. This article encourages chapter advisors to make use of these…

  18. Interrelationships among biological activity, disulfide bonds, secondary structure, and metal ion binding for a chemically synthesized 34-amino-acid peptide derived from alpha-fetoprotein. (United States)

    MacColl, R; Eisele, L E; Stack, R F; Hauer, C; Vakharia, D D; Benno, A; Kelly, W C; Mizejewski, G J


    A 34-amino-acid peptide has been chemically synthesized based on a sequence from human alpha-fetoprotein. The purified peptide is active in anti-growth assays when freshly prepared in pH 7.4 buffer at 0.20 g/l, but this peptide slowly becomes inactive. This functional change is proven by mass spectrometry to be triggered by the formation of an intrapeptide disulfide bond between the two cysteine residues on the peptide. Interpeptide cross-linking does not occur. The active and inactive forms of the peptide have almost identical secondary structures as shown by circular dichroism (CD). Zinc ions bind to the active peptide and completely prevents formation of the inactive form. Cobalt(II) ions also bind to the peptide, and the UV-Vis absorption spectrum of the cobalt-peptide complex shows that: (1) a near-UV sulfur-to-metal-ion charge-transfer band had a molar extinction coefficient consistent with two thiolate bonds to Co(II); (2) the lowest-energy visible d-d transition maximum at 659 nm, also, demonstrated that the two cysteine residues are ligands for the metal ion; (3) the d-d molar extinction coefficient showed that the metal ion-ligand complex was in a distorted tetrahedral symmetry. The peptide has two cysteines, and it is speculated that the other two metal ion ligands might be the two histidines. The Zn(II)- and Co(II)-peptide complexes had similar peptide conformations as indicated by their ultraviolet CD spectra, which differed very slightly from that of the free peptide. Surprisingly, the cobalt ions acted in the reverse of the zinc ions in that, instead of stabilizing anti-growth form of the peptide, they catalyzed its loss. Metal ion control of peptide function is a saliently interesting concept. Calcium ions, in the conditions studied, apparently do not bind to the peptide. Trifluoroethanol and temperature (60 degrees C) affected the secondary structure of the peptide, and the peptide was found capable of assuming various conformations in solution

  19. Crosstalk between the peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and the vitamin D receptor (VDR) in human breast cancer cells: PPAR{gamma} binds to VDR and inhibits 1{alpha},25-dihydroxyvitamin D{sub 3} mediated transactivation

    Energy Technology Data Exchange (ETDEWEB)

    Alimirah, Fatouma; Peng, Xinjian; Yuan, Liang; Mehta, Rajeshwari R. [Cancer Biology Division, IIT Research Institute, 10 West 35th Street, Chicago, IL 60616 (United States); Knethen, Andreas von [Institute of Biochemistry, Johann Wolfgang Goethe University, Frankfurt (Germany); Choubey, Divaker [Department of Environmental Health, University of Cincinnati, 3223 Eden Avenue, P.O. Box 670056, Cincinnati, OH 45267 (United States); Mehta, Rajendra G., E-mail: [Cancer Biology Division, IIT Research Institute, 10 West 35th Street, Chicago, IL 60616 (United States)


    Heterodimerization and cross-talk between nuclear hormone receptors often occurs. For example, estrogen receptor alpha (ER{alpha}) physically binds to peroxisome proliferator-activated receptor gamma (PPAR{gamma}) and inhibits its transcriptional activity. The interaction between PPAR{gamma} and the vitamin D receptor (VDR) however, is unknown. Here, we elucidate the molecular mechanisms linking PPAR{gamma} and VDR signaling, and for the first time we show that PPAR{gamma} physically associates with VDR in human breast cancer cells. We found that overexpression of PPAR{gamma} decreased 1{alpha},25-dihydroxyvitamin D{sub 3} (1,25D{sub 3}) mediated transcriptional activity of the vitamin D target gene, CYP24A1, by 49% and the activity of VDRE-luc, a vitamin D responsive reporter, by 75% in T47D human breast cancer cells. Deletion mutation experiments illustrated that helices 1 and 4 of PPAR{gamma}'s hinge and ligand binding domains, respectively, governed this suppressive function. Additionally, abrogation of PPAR{gamma}'s AF2 domain attenuated its repressive action on 1,25D{sub 3} transactivation, indicating that this domain is integral in inhibiting VDR signaling. PPAR{gamma} was also found to compete with VDR for their binding partner retinoid X receptor alpha (RXR{alpha}). Overexpression of RXR{alpha} blocked PPAR{gamma}'s suppressive effect on 1,25D{sub 3} action, enhancing VDR signaling. In conclusion, these observations uncover molecular mechanisms connecting the PPAR{gamma} and VDR pathways. -- Highlights: PPAR{gamma}'s role on 1{alpha},25-dihydroxyvitamin D{sub 3} transcriptional activity is examined. Black-Right-Pointing-Pointer PPAR{gamma} physically binds to VDR and inhibits 1{alpha},25-dihydroxyvitamin D{sub 3} action. Black-Right-Pointing-Pointer PPAR{gamma}'s hinge and ligand binding domains are important for this inhibitory effect. Black-Right-Pointing-Pointer PPAR{gamma} competes with VDR for the availability of their binding

  20. Alpha- and Gammaproteobacterial Methanotrophs Codominate the Active Methane-Oxidizing Communities in an Acidic Boreal Peat Bog. (United States)

    Esson, Kaitlin C; Lin, Xueju; Kumaresan, Deepak; Chanton, Jeffrey P; Murrell, J Colin; Kostka, Joel E


    The objective of this study was to characterize metabolically active, aerobic methanotrophs in an ombrotrophic peatland in the Marcell Experimental Forest, in Minnesota. Methanotrophs were investigated in the field and in laboratory incubations using DNA-stable isotope probing (SIP), expression studies on particulate methane monooxygenase (pmoA) genes, and amplicon sequencing of 16S rRNA genes. Potential rates of oxidation ranged from 14 to 17 μmol of CH4g dry weight soil(-1)day(-1) Within DNA-SIP incubations, the relative abundance of methanotrophs increased from 4%in situto 25 to 36% after 8 to 14 days. Phylogenetic analysis of the(13)C-enriched DNA fractions revealed that the active methanotrophs were dominated by the generaMethylocystis(type II;Alphaproteobacteria),Methylomonas, andMethylovulum(both, type I;Gammaproteobacteria). In field samples, a transcript-to-gene ratio of 1 to 2 was observed forpmoAin surface peat layers, which attenuated rapidly with depth, indicating that the highest methane consumption was associated with a depth of 0 to 10 cm. Metagenomes and sequencing of cDNApmoAamplicons from field samples confirmed that the dominant active methanotrophs wereMethylocystisandMethylomonas Although type II methanotrophs have long been shown to mediate methane consumption in peatlands, our results indicate that members of the generaMethylomonasandMethylovulum(type I) can significantly contribute to aerobic methane oxidation in these ecosystems. PMID:26873322