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Sample records for alpha activity indicator

  1. Alpha activity measurement with lsc

    International Nuclear Information System (INIS)

    Dobrin, R. I.; Dulama, C. N.; Ciocirlan, C. N.; Toma, A.; Stoica, S. M.; Valeca, M.

    2013-01-01

    Recently, we showed that the alpha activity in liquid samples can be measured using a liquid scintillation analyzer without alpha/beta discrimination capability. The purpose of this work was to evaluate the performances of the method and to optimize the procedure of the sample preparation. A series of tests was performed to validate the procedure of alpha emitting radionuclides extraction in aqueous samples with Actinide Resin, especially regarding to the contact time required to extract all alpha nuclides. The main conclusions were that a minimum 18 hours stirring time is needed to achieve a percent recovery of the alpha nuclides grater than 90% and that the counting efficiency of alphas measurements with LSC is nearly 100%. (authors)

  2. Determination of total alpha activity index in samples of radioactive wastes; Determinacion del indice de actividad alfa total en muestras de desechos radiactivos

    Energy Technology Data Exchange (ETDEWEB)

    Galicia C, F. J.

    2015-07-01

    This study aimed to develop a methodology of preparation and quantification of samples containing radionuclides beta and/or alpha emitters, to determine the rates of alpha and beta total activity of radioactive waste samples. For this, a device of planchettes preparer was designed, to assist the planchettes preparation in a controlled environment and free of corrosive vapors. Planchettes were prepared in three means: nitrate, carbonate and sulfate, to different mass thickness, natural uranium (alpha and beta emitter) and in case of Sr-90 (beta emitter pure) only in half nitrate; and these planchettes were quantified in an alpha/beta counter, in order to construct the self-absorption curves for alpha and beta particles. These curves are necessary to determine the rate of alpha-beta activity of any sample because they provide the self-absorption correction factor to be applied in calculating the index. Samples with U were prepared with the help of the device of planchettes preparer and subsequently were analyzed in the proportional counter Mpc-100 Pic brand. Samples with Sr-90 were prepared without the device to see if there was a different behavior with respect to obtaining mass thickness. Similarly they were calcined and carried out count in the Mpc-100. To perform the count, first the parameters of counter operating were determined: operating voltages for alpha and beta particles 630 and 1500 V respectively, a count routine was generated where the time and count type were adjusted, and counting efficiencies for alpha and beta particles, with the aid of calibration sources of {sup 210}Po for alphas and {sup 90}Sr for betas. According to the results, the counts per minute will decrease as increasing the mass thickness of the sample (self-absorption curve), adjusting this behavior to an exponential function in all cases studied. The minor self-absorption of alpha and beta particles in the case of U was obtained in sulfate medium. The self-absorption curves of Sr-90

  3. Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

    Energy Technology Data Exchange (ETDEWEB)

    Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J

    1998-06-29

    Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

  4. Cortical Alpha Activity in Schizoaffective Patients

    Directory of Open Access Journals (Sweden)

    Mahdi Moeini

    2017-02-01

    Full Text Available Objective: Electrophysiological studies have identified abnormal oscillatory activities in the cerebral cortex in schizophrenia and mood disorders. Biological and pathophysiological evidence suggests specific deficits in serotonin (5-HT receptor function in schizoaffective disorder (SA, a clinical syndrome with characteristics of both schizophrenia and bipolar disorder. This study investigated alpha oscillations in patients with SA.Method: Electroencephalography was used to measure ongoing and evoked alpha oscillations in 38 adults meeting Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition (DSM–IV criteria for SA, and in 39 healthy controls.Results: Spontaneous alpha power of the participants with SA was significantly lower than that of healthy participants [F (1, 75 = 8.81, P < 0.01]. Evoked alpha activity was also decreased in SA compared to controls [F (1, 75 = 5.67, P = 0.025].Conclusion: A strong reduction of alpha power in the posterior regions may reflect abnormality in the thalamocortical circuits. It is shown that hypoxia and reduced cerebral blood flow is associated with reduced alpha activity among different regions of the brain. Therefore, it can be concluded that greatly decreased alpha activity, particularly in centro-parietal and occipital regions, is related to SA symptoms such as hallucinations.

  5. 5alphaDH-DOC (5alpha-dihydro-deoxycorticosterone) activates androgen receptor in castration-resistant prostate cancer.

    Science.gov (United States)

    Uemura, Motohide; Honma, Seijiro; Chung, Suyoun; Takata, Ryo; Furihata, Mutsuo; Nishimura, Kazuo; Nonomura, Norio; Nasu, Yasutomo; Miki, Tsuneharu; Shuin, Taro; Fujioka, Tomoaki; Okuyama, Akihiko; Nakamura, Yusuke; Nakagawa, Hidewaki

    2010-08-01

    Prostate cancer often relapses during androgen-depletion therapy, even under the castration condition in which circulating androgens are drastically reduced. High expressions of androgen receptor (AR) and genes involved in androgen metabolism indicate a continued role for AR in castration-resistant prostate cancers (CRPCs). There is increasing evidence that some amounts of 5alpha-dihydrotestosterone (DHT) and other androgens are present sufficiently to activate AR within CRPC tissues, and enzymes involved in the androgen and steroid metabolism, such as 5alpha-steroid reductases, are activated in CRPCs. In this report, we screened eight natural 5alphaDH-steroids to search for novel products of 5alpha-steroid reductases, and identified 11-deoxycorticosterone (DOC) as a novel substrate for 5alpha-steroid reductases in CRPCs. 11-Deoxycorticosterone (DOC) and 5alpha-dihydro-deoxycorticosterone (5alphaDH-DOC) could promote prostate cancer cell proliferation through AR activation, and type 1 5alpha-steroid reductase (SRD5A1) could convert from DOC to 5alphaDH-DOC. Sensitive liquid chromatography-tandem mass spectrometric analysis detected 5alphaDH-DOC in some clinical CRPC tissues. These findings implicated that under an extremely low level of DHT, 5alphaDH-DOC and other products of 5alpha-steroid reductases within CRPC tissues might activate the AR pathway for prostate cancer cell proliferation and survival under castration.

  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: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

    2011-04-22

    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. Activity monitoring of alpha-bearing wastes

    International Nuclear Information System (INIS)

    Birkhoff, G.; Bondar, L.

    1980-01-01

    The paper aims at the survey on the actual situation in activity monitoring of alpha-bearing wastes. Homogeneous materials such as liquid-, gaseous- and homogeneous solid wastes are amenable to destructive analyses of representative samples. Available destructive analyses methods are sensitive and precise enough to cope with all requirements in alpha-waste monitoring. The more difficult problems are encountered with alpha-contaminated solids, when representative sampling is not practicable. Non-destructive analysis techniques are applied for monitoring this category of solid wastes. The techniques for nondestructive analysis of alpha-bearing wastes are based on the detection of gamma and/or neutron-emission of actinides. Principles and a theory of non-destructive radiometric assay of plutonium contaminated solid waste streams are explained. Guidelines for the calibration of instruments and interpretation of experimental data are given. Current theoretical and experimental development work in this problem area is reviewed. Evaluations concerning capabilities and limitations of monitoring systems for alpha-bearing solid wastes are very complex and out of the scope of this paper

  8. Activator protein 2alpha mediates parathyroid TGF-alpha self-induction in secondary hyperparathyroidism.

    Science.gov (United States)

    Arcidiacono, Maria Vittoria; Cozzolino, Mario; Spiegel, Noah; Tokumoto, Masanori; Yang, Jing; Lu, Yan; Sato, Tetsuhiko; Lomonte, Carlo; Basile, Carlo; Slatopolsky, Eduardo; Dusso, Adriana S

    2008-10-01

    In secondary hyperparathyroidism, enhanced expression of TGF-alpha in the parathyroid leads to its own upregulation, generating a feed-forward loop for TGF-alpha activation of its receptor, EGFR receptor (EGFR), which promotes parathyroid hyperplasia. These studies examined the role of activator protein 2alpha (AP2), an inducer of TGF-alpha gene transcription, in the upregulation of parathyroid TGF-alpha in secondary hyperparathyroidism. In rat and human secondary hyperparathyroidism, parathyroid AP2 expression strongly correlated with TGF-alpha levels and with the rate of parathyroid growth, as expected. Furthermore, the increases in rat parathyroid content of AP2 and its binding to a consensus AP2 DNA sequence preceded the increase in TGF-alpha induced by high dietary phosphate. More significant, in A431 cells, which provide a model of enhanced TGF-alpha and TGF-alpha self-induction, mutating the core AP2 site of the human TGF-alpha promoter markedly impaired promoter activity induced by endogenous or exogenous TGF-alpha. Important for therapy, in five-sixths nephrectomized rats fed high-phosphate diets, inhibition of parathyroid TGF-alpha self-induction using erlotinib, a highly specific inhibitor of TGF-alpha/EGFR-driven signals, reduced AP2 expression dosage dependently. This suggests that the increases in parathyroid AP2 occur downstream of EGFR activation by TGF-alpha and are required for TGF-alpha self-induction. Indeed, in A431 cells, erlotinib inhibition of TGF-alpha self-induction caused parallel reductions in AP2 expression and nuclear localization, as well as TGF-alpha mRNA and protein levels. In summary, increased AP2 expression and transcriptional activity at the TGF-alpha promoter determine the severity of the hyperplasia driven by parathyroid TGF-alpha self-upregulation in secondary hyperparathyroidism.

  9. Lucid dreaming and alpha activity: a preliminary report.

    Science.gov (United States)

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

    1982-12-01

    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. Predictive value of cord blood hematological indices and hemoglobin Barts for the detection of heterozygous alpha-thalassemia-2 in an African-Caribbean population

    NARCIS (Netherlands)

    van der Dijs, FPL; Volmer, M; van Gijssel-Wiersma, DG; Smit, JW; van Veen, R; Muskiet, FAJ

    Background: Cord blood hemoglobin Barts (HbBarts) and hemocytometric indices may be used for classification of newborns into those without alpha-thalassemia-2 (alpha alpha/alpha alpha) and with heterozygous alpha-thalassemia-2 (-alpha(3.7)/ alpha alpha). We investigated by logistic regression

  11. 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.

    2013-07-01

    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)

  12. Performance indicators of work activity.

    Science.gov (United States)

    Lahoz, Manoela de Assis; Camarotto, João Alberto

    2012-01-01

    The measurement of performance is a current topic in the management of people in companies, used as a parameter of effectiveness of processes and operations of production. The methods and models of the indicators of current use in the production have concentrated in the assessment of people's performance as determinative resource of the organizational success in the search for the competitiveness. Associated with the classic indicators of performance assessment of the production proceeding, other indicators are used in the assessment of risks and hazards, however with methods focused in the tasks, without connection with the real work activity. The present article explores literature on the models of performance measurement in use in companies and a field research to understand how companies interpret and use indicators that relate health and work, to direct future studies on the subject. Regarding the literature review, one can see that health indicators can be basically divided into two major groups: the legal and managerial indicators. When conducting case studies, it can be realized that companies do not have precisely the concept of health indicator, or were unable to define which of the indicators could be considered indicators of health, considering that absenteeism was the indicator mentioned by the four companies.

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

    Directory of Open Access Journals (Sweden)

    Marie-Pierre eDeiber

    2012-08-01

    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. 

  14. 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)

    2014-04-01

    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.)

  15. Identification of a novel bean alpha-amylase inhibitor with chitinolytic activity.

    Science.gov (United States)

    Dayler, Charles S A; Mendes, Paulo A M; Prates, Maura V; Bloch, Carlos; Franco, Octavio L; Grossi-de-Sá, Maria F

    2005-10-24

    Zabrotes subfasciatus is a devastating starch-dependent storage bean pest. In this study, we attempted to identify novel alpha-amylase inhibitors from wild bean seeds, with efficiency toward pest alpha-amylases. An inhibitor named Phaseolus vulgaris chitinolytic alpha-amylase inhibitor (PvCAI) was purified and mass spectrometry analyses showed a protein with 33330 Da with the ability to form dimers. Purified PvCAI showed significant inhibitory activity against larval Z. subfasciatus alpha-amylases with no activity against mammalian enzymes. N-terminal sequence analyses showed an unexpected high identity to plant chitinases from the glycoside hydrolase family 18. Furthermore, their chitinolytic activity was also detected. Our data provides compelling evidence that PvCAI also possessed chitinolytic activity, indicating the emergence of a novel alpha-amylase inhibitor class.

  16. Cortical alpha activity predicts the confidence in an impending action

    Science.gov (United States)

    Kubanek, Jan; Hill, N. Jeremy; Snyder, Lawrence H.; Schalk, Gerwin

    2015-01-01

    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 and independent of the sensory input modeled as a decision variable. Furthermore, the effect is not due to a general cognitive state, such as 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 an ensuing button press choice. In sum, alpha activity in human cortex provides a window into the commitment to make a hand movement. PMID:26283892

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

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Haglund, Elin

    2009-01-01

    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....

  18. Increased 5. cap alpha. -reductase activity in idiopathic hirsutism

    Energy Technology Data Exchange (ETDEWEB)

    Serafini, P.; Lobo, R.A.

    1985-01-01

    In vitro, genital skin 5..cap alpha..-reductase activity (5..cap alpha..-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5..cap alpha..-RA. In vitro 5..cap alpha..-RA was assessed by incubations of skin with /sup 14/C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5..cap alpha..-androstane 3..cap alpha..-17..beta..-estradiol (3..cap alpha..-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3..cap alpha..-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3..cap alpha..-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5..cap alpha..-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5..cap alpha..-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5..cap alpha..-RA.

  19. Structural basis of alpha-amylase activation by chloride

    OpenAIRE

    Aghajari, N.; Feller, Georges; Gerday, Charles; Haser, R.

    2002-01-01

    To further investigate the mechanism and function of allosteric activation by chloride in some alpha-amylases, the structure of the bacterial alpha-amylase from the psychrophilic micro-organism Pseudoalteromonas haloplanktis in complex with nitrate has been solved at 2.1 Angstrom, as well as the structure of the mutants Lys300Gln (2.5 Angstrom) and Lys300Arg (2.25 Angstrom). Nitrate binds strongly to alpha-amylase but is a weak activator. Mutation of the critical chloride ligand Lys300 into G...

  20. 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: nobu@kais.kyoto-u.ac.jp [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)

    2011-06-24

    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.

  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.

    2011-07-01

    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. Short term integrative meditation improves resting alpha activity and stroop performance.

    Science.gov (United States)

    Fan, Yaxin; Tang, Yi-Yuan; Tang, Rongxiang; Posner, Michael I

    2014-12-01

    Our previous research showed that short term meditation training reduces the time to resolve conflict in the flanker task. Studies also show that resting alpha increases with long term meditation practice. The aim of this study is to determine whether short term meditation training both increases resting alpha activity and reduces the time to resolve conflict in the Stroop task and whether these two effects are related. Forty-three Chinese undergraduates were randomly assigned an experiment group given 5 days meditation training using integrative body-mind training (IBMT) and a relaxation training control. After training, only the IBMT group showed decreased conflict reaction time (RT), and increased resting mean alpha power. Moreover, the higher the enhancement of resting alpha power, the stronger the improvement of conflict RT. The results indicate that short term meditation diffusely enhances alpha and improves the ability to deal with conflict and moreover these two effects are positively related.

  3. Which radionuclide, carrier molecule and clinical indication for alpha-immunotherapy?

    Science.gov (United States)

    Guerard, F; Barbet, J; Chatal, J F; Kraeber-Bodere, F; Cherel, M; Haddad, F

    2015-06-01

    Beta-emitting radionuclides are not able to kill isolated tumor cells disseminated in the body, even if a high density of radiolabeled molecules can be targeted at the surface of these cells because the vast majority of emitted electrons deliver their energy outside the targeted cells. Alpha-particle emitting radionuclides may overcome this limitation. It is thus of primary importance to test and validate the radionuclide of choice, the most appropriate carrier molecule and the most promising clinical indication. Four α-particle emitting radionuclides have been or are clinically tested in phase I studies namely 213Bi, 225Ac, 212Pb and 211At. Clinical safety has been documented and encouraging efficacy has been shown for some of them (213Bi and 211At). 211At has been the most studied and could be the most promising radionuclide but 225Ac and 212Pb are also of potential great interest. Any carrier molecule that has been labeled with β-emitting radionuclides could be labeled with alpha particle-emitting radionuclide using, for some of them, the same chelating agents. However, the physical half-life of the radionuclide should match the biological half-life of the radioconjugate or its catabolites. Finally everybody agrees, based on the quite short range of alpha particles, on the fact that the clinical indications for alpha-immunotherapy should be limited to the situation of disseminated minimal residual diseases made of small clusters of malignant cells or isolated tumor cells.

  4. Critical indices for reversible gamma-alpha phase transformation in metallic cerium

    Science.gov (United States)

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

    1980-08-01

    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.

  5. Sensitivity of EEG upper alpha activity to cognitive and affective creativity interventions.

    Science.gov (United States)

    Fink, Andreas; Schwab, Daniela; Papousek, Ilona

    2011-12-01

    We investigated whether creative cognition can be improved by means of cognitive and affective stimulation and whether these interventions are associated with changes of EEG alpha activity. Participants were required to generate original uses of conventional objects (Alternative Uses task, AU) while the EEG was recorded. In the cognitive stimulation condition, participants worked on the AU task subsequent to the exposure to other people's ideas. In the affective stimulation condition, they had to think creatively in positive affective states, induced via emotionally contagious sound clips. Creative cognition generally elicited alpha synchronization, most prominent in the prefrontal cortex and in the right hemisphere. The interventions were associated with stronger prefrontal alpha activity in the upper alpha band (10-12 Hz) than the control condition (no intervention), possibly indicating a state of heightened internal awareness, which might have a beneficial impact on creativity. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Alpha-amylase activity in wheat flour and breadmaking properties in relation to different climatic conditions

    Directory of Open Access Journals (Sweden)

    Rakita Slađana M.

    2015-01-01

    Full Text Available The aim of the present paper was to evaluate the influence of different climatic conditions on the activity of alpha-amylase in wheat samples and bread quality parameters. Three wheat varieties grown in three different localities in three years were chosen for this study. Commonly used methods for estimation of alpha-amylase activity in wheat grain were employed. The obtained results indicated that harvest year 2013, which was characterized with the excessive amount of rainfall, exhibited the highest level of alpha-amylase activity and the lowest values of the peak viscosity. The lowest alpha-amylase level and the highest peak viscosity and FN value were observed for samples harvested in 2012 which was characterized with the greatest number of days with an average daily temperature above 30 and 35°C. In addition, a decrease in Mixolab parameter torque C3 and specific bread loaf volume, as well as increase in the breakdown torque (C3-C4 of samples harvested in 2013 were observed, which could be attributed to rainy weather influencing increase in alpha-amylase activity. It is found that specific bread loaf volume of wheat samples is highest in 2012. Moreover, a negative correlation between alpha-amylase activity and specific bread volume for all the samples grown in three years was determined.

  7. Glucocorticoid receptor (GR) {beta} has intrinsic, GR{alpha}-independent transcriptional activity

    Energy Technology Data Exchange (ETDEWEB)

    Kino, Tomoshige, E-mail: kinot@mail.nih.gov [Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bldg. 10, CRC, Rm. 1-3140, 10 Center Drive MSC 1109, Bethesda, MD 20892-1109 (United States); Manoli, Irini [Laboratory of Clinical Investigation, National Center for Complementary and Alternative Medicine (United States); First Department of Pediatrics, Athens University Medical School (United States); Kelkar, Sujata [Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bldg. 10, CRC, Rm. 1-3140, 10 Center Drive MSC 1109, Bethesda, MD 20892-1109 (United States); Wang, Yonghong [Clinical Molecular Profiling Core, Advanced Technology Center, National Cancer Institute (United States); Su, Yan A. [Department of Biochemistry and Molecular Biology, The Catherine Birch McCormick Genomics Center, George Washington University School of Medicine and Health Sciences (United States); Chrousos, George P. [First Department of Pediatrics, Athens University Medical School (United States)

    2009-04-17

    The human glucocorticoid receptor (GR) gene produces C-terminal GR{beta} and GR{alpha} isoforms through alternative use of specific exons 9{beta} and {alpha}, respectively. We explored the transcriptional activity of GR{beta} on endogenous genes by developing HeLa cells stably expressing EGFP-GR{beta} or EGFP. Microarray analyses revealed that GR{beta} had intrinsic gene-specific transcriptional activity, regulating mRNA expression of a large number of genes negatively or positively. Majority of GR{beta}-responsive genes was distinct from those modulated by GR{alpha}, while GR{beta} and GR{alpha} mutually modulated each other's transcriptional activity in a subpopulation of genes. We did not observe in HCT116 cells nuclear translocation of GR{beta} and activation of this receptor by RU 486, a synthetic steroid previously reported to bind GR{beta} and to induce nuclear translocation. Our results indicate that GR{beta} has intrinsic, GR{alpha}-independent, gene-specific transcriptional activity, in addition to its previously reported dominant negative effect on GR{alpha}-induced transactivation of GRE-driven promoters.

  8. Gross alpha and beta activities in Tunisian mineral water

    International Nuclear Information System (INIS)

    Hamrouni Benbelgacem, Samar

    2011-01-01

    The quality of natural mineral water is a universal health problem seeing its vital importance. This problem is related to the presence of the radionuclides since this water is coming from underground, during their circulation it dissolves and conveys the radionuclides which are present in the earth's crust. This problem which leads to the contamination of the mineral water urged the World Health Organization to set standards and to recommend the respect of the median values of the activities alpha and beta within the framework of the man protection against this internal exhibition. Concerning the radiological quality of Tunisian mineral water studied in this project, we showed, by using the gross alpha and beta activities counting, that this water is specific to human consumption since their gross alpha and beta activities do not forward any risk on health.

  9. H-alpha response to geomagnetic disturbed activity at Arecibo.

    Science.gov (United States)

    Santos, Pedrina; Kerr, R.; Noto, J.; Brum, Christiano; Gonzalez, Sixto

    Configured with a spectral resolution of 0.0086 nm at 6563A, the low resolution Fabry-Perot Interferometer (FPI) installed at Arecibo Observatory sampled the geocoronal Balmer-alpha emission for sixty nights during new moon periods from September 2006 to September 2007. In this work two of these periods are analyzed according to the variability with the geomagnetic activity. With this purpose, the effect of the shadow height, local time and solar flux depen-dencies were found and isolated and only the possible variations due the geomagnetic activity were evaluated. The residuos of the relative H-alpha intensity and temperature are analyzed.

  10. Calcineurin mediates alpha-adrenergic stimulation of Na+,K(+)-ATPase activity in renal tubule cells.

    Science.gov (United States)

    Aperia, A; Ibarra, F; Svensson, L B; Klee, C; Greengard, P

    1992-01-01

    The alpha-adrenergic agonist oxymetazoline increased Na+,K(+)-ATPase activity of single proximal convoluted tubules dissected from rat kidney. Activation of the enzyme by oxymetazoline was prevented by either the alpha 1-adrenergic antagonist prazosin or the alpha 2-adrenergic antagonist yohimbine and was mimicked by the calcium ionophore A23187. The effect of oxymetazoline on Na+,K(+)-ATPase activity was prevented by a specific peptide inhibitor of calcineurin, as well as by FK 506, an immunosuppressant agent known to inhibit calcineurin; these results indicate that the action of oxymetazoline is mediated via activation of calcineurin (a calcium/calmodulin-dependent protein phosphatase). Activation of the Na+,K(+)-ATPase by either oxymetazoline or A23187 was associated with a greater than 2-fold increase in its affinity for Na+. The results provide a biochemical mechanism by which norepinephrine, released from renal nerve terminals, stimulates Na+ retention. PMID:1380157

  11. Activity of (-)alpha-bisabolol against Leishmania infantum promastigotes.

    Science.gov (United States)

    Morales-Yuste, M; Morillas-Márquez, F; Martín-Sánchez, J; Valero-López, A; Navarro-Moll, M C

    2010-03-01

    Many of the drugs used to treat leishmaniasis are associated with numerous adverse effects. Agents of natural origin have shown activity against different parasites. With this background, an in vitro study was conducted on the activity of (-)alpha-bisabolol, the principal component of Chamomilla recutita essential oil, against Leishmania infantum promastigotes, the main species responsible for human leishmaniasis in Spain. At the two highest concentrations tested (1000 and 500mug/ml), (-)alpha-bisabolol and pentamidine (control agent) achieved 100% inhibition of L. infantum promastigote. These in vitro data can be considered promising in support of the therapeutic use of (-)alpha-bisabolol preparations to treat leishmaniasis caused by L. infantum species. Copyright 2009 Elsevier GmbH. All rights reserved.

  12. Alpha-Glucosidase Inhibitory and Antioxidant Activity of Solvent ...

    African Journals Online (AJOL)

    Alpha-Glucosidase Inhibitory and Antioxidant Activity of Solvent Extracts and Fractions of Typha domingensis (Typhaceae) Fruit. Tsun-Thai Chai, Mei-Jee Chiam, Chi-Hou Lau, Nor Ismaliza Mohd Ismail, Hean-Chooi Ong, Fazilah Abd Manan, Fai-Chu Wong ...

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    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. Synthesis of high specific activity 17{alpha}-cyanomethyl-17{beta} -hydroxy-[14{alpha}, 15{alpha}-{sup 3}H]estra-4,9-dien-3-one

    Energy Technology Data Exchange (ETDEWEB)

    Droescher, P. [VEB Jenapharm, Jena (Germany); Roemer, J. [Forschungszentrum Rossendorf e.V. (FZR), Dresden (Germany)

    1995-02-01

    An improved synthesis of the tritium labelled form of the new pharmacon DIENOGEST is described. The [14{alpha}, 15{alpha}-{sup 3}H]DIENOGEST was obtained with a specific activity of 51 Ci/mmol and a radiochemical purity > 98%. (Author).

  15. Is there any relationship between the Modified Ashworth Scale scores and alpha motoneuron excitability indicators?

    Science.gov (United States)

    Ghotbi, N; Olyaei, G R; Hadian, M R; Ansari, N N; Bagheri, H

    2006-09-01

    The purpose of this study was to investigate the relationship between the modified Ashworth scale (MAS) scores and alpha motoneuron excitability indicators. Thirty-one post-stroke patients were assessed for this object. The main outcome measures were the MAS and electro physiologic assessments. The latter was performed using both conventional (Hmax/Mmax) and new (Hslope/Mslope) measures of spinal excitability. Data on thirty-one adult subjects with hemiplegia (twenty-five men and six women) were analysed. The soleus Hmax/Mmax ratio appeared to correlate directly with the MAS scores (r = 0.36; P 0.05). In seventeen patients whose H-reflex could be evoked bilaterally, spinal excitability indicators showed significant difference between the affected and non-affected sides (P < 0.05). Based on the results of this study, there is no relationship between the MAS scores and the preferred measure of alpha motoneuron excitability. This research suggests that the MAS could not distinguish between the reflexive and non-reflexive components of the hypertonicity in ankle plantar flexors.

  16. Immunomodulatory activities of alpha-mangostin on peripheral blood mononuclear cells.

    Science.gov (United States)

    Kasemwattanaroj, Pimolkan; Moongkarndi, Primchanien; Pattanapanyasat, Kovit; Mangmool, Supachoke; Rodpai, Ekkarat; Samer, Jutima; Konlata, Julaporn; Sukapirom, Kasama

    2013-09-01

    Mangosteen (Garcinia mangostana L.) a tropical fruit, has been used in traditional medicine. A frequently used part of mangosteen is the pericarp, containing a high content of xanthones. alpha-Mangostin, one of the major xanthone derivatives, exhibits a variety of actions, including antimicrobial, antioxidant, cytotoxic and antitumor; however, its function on the immune system is still equivocal. This study aimed to examine the immunomodulatory activities of alpha-mangostin on lymphocyte lineage and cytokine production in human peripheral blood mononuclear cells (PBMCs). The cytotoxic activity of alpha-mangostin was measured by MTT assay. The concentration of alpha-mangostin at 5.55 microg/mL resulted in a 50% survival of PBMCs, which was as potent a cytotoxic activity as that of paclitaxel. After 24 h of PBMCs culture, the percentages of T cells (CD3+), B cells (CD19+) and NK cells (CD3-CD16+CD56+) were not significantly changed by treatment with 1, 2 and 4 microg/mL of alpha-mangostin compared with untreated-PBMCs; in addition, the percentages of these lymphocytes treated with the combination of alpha-mangostin (1, 2 and 4 microg/mL) and the mitogen concanavalin A (ConA) was not significantly different from that of ConA-treated PBMCs. For cytokine secretion, alpha-mangostin (1, 2 and 4 microg/mL) did not significantly induce either proinflammatory cytokines (i.e., TNF-alpha and IL-1beta) or cytokine of adaptive immunity (i.e., IL-2). The combination of alpha-mangostin (1, 2 and 4 microg/mL) and ConA did not significantly alter the relative difference of TNF-alpha and IL-1beta compared with ConA-treated PBMCs; however, these combinations could significantly decrease the relative difference of IL-2 compared with ConA-treated PBMCs. These data indicated that alpha-mangostin was able to inhibit IL-2 release without interfering with human immune cells; therefore, further studies are necessary to investigate its effect on IL-2 production.

  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

    2010-06-01

    Full Text Available 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.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.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 plays a key role in regulating the response of Müller glia to hypoxia.

  18. Frontal EEG alpha activity and obsessive-compulsive behaviors in nonclinical young adults: A pilot study

    Directory of Open Access Journals (Sweden)

    Michael eWong

    2015-09-01

    Full Text Available Previous studies have shown that the resting electroencephalogram (EEG alpha patterns of nonclinical participants who score high on measures of negative affect, such as depression and shyness, are different from those who score low. However, we know relatively little about patterns of resting EEG alpha patterns in a nonclinical sample of individuals with high levels of obsessive-compulsive behaviors indicative of OCD. Here we measured resting EEG alpha activity in frontal and parietal regions of nonclinical participants who scored high and low on the Padua-R, a measure of the severity of OCD-related behaviors. We found that participants who scored high on the Padua-R exhibited decreased overall activity in frontal regions relative to individuals who scored low on the measure. We speculate that frontal hypoactivity may be a possible marker and/or index of risk for OCD.

  19. Fusion alpha loss diagnostic for ITER using activation technique

    Czech Academy of Sciences Publication Activity Database

    Bonheure, G.; Hult, M.; González de Orduña, R.; Vermaercke, P.; Murari, A.; Popovichev, S.; Mlynář, Jan

    2011-01-01

    Roč. 86, 6-8 (2011), s. 1298-1301 ISSN 0920-3796. [Symposium on Fusion Technology (SOFT) /26th./. Port o, 27.09.2010-01.10.2010] Institutional research plan: CEZ:AV0Z20430508 Keywords : ITER * fusion product * burning plasma diagnostics * alpha losses * activation technique Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 1.490, year: 2011 http://www.sciencedirect.com/science/article/pii/S0920379611002778

  20. 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: swkullma@ncsu.edu [Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695 (United States)

    2010-07-01

    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.

  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 ant...iviral activity? PubmedID 15283983 Title What is disrupting IFN-alpha's antiviral activity? Authors Mbow ML,

  2. Selection of the appropriate radionuclide source for the efficiency calibration in methods of determining gross alpha activity in water

    International Nuclear Information System (INIS)

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

    2016-01-01

    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. - Highlights: • Gross alpha activity in a water sample is a rapid way of determining if its consumption imply a TID greater than reference limit. • There is considerable variability in the selection of the most suitable radioactive reference standard. • A reference radionuclide to use as standards in determining gross alpha activities in natural waters is proposed.

  3. Activation of protein kinase C-alpha is essential for stimulation of cell proliferation by ceramide 1-phosphate.

    Science.gov (United States)

    Gangoiti, Patricia; Granado, Maria H; Arana, Lide; Ouro, Alberto; Gomez-Muñoz, Antonio

    2010-02-05

    We previously demonstrated that ceramide-1-phosphate (C1P) stimulates fibroblast and macrophage proliferation, but the mechanisms involved in this action have only been partially described. Here we demonstrate that C1P induces translocation of protein kinase C-alpha (PKC-alpha) from the soluble to the membrane fraction of bone marrow-derived macrophages. Translocation of this enzyme was accompanied by its phosphorylation on Ser 657 residue. Activation of PKC-alpha was independent of prior stimulation of phosphatidylinositol-dependent or phosphatidylcholine-dependent phospholipase C activities, but required activation of sphingomyelin synthesis. Inhibition of PKC-alpha activation also blocked C1P-stimulated macrophage proliferation indicating that this enzyme is essential for the mitogenic effect of C1P. 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. Alpha emitters activity measurement using the defined solid angle method

    International Nuclear Information System (INIS)

    Blanchis, P.

    1983-01-01

    The defined solid angle counting method can reach a very high accuracy, specially for heavy ions as alpha particles emitted by a radioactive source. The activity measurement of such sources with a relative uncertainty of the order of 0.01% is investigated. Such an accuracy is available only under suitable conditions: the radiation emitted by the source must be isotropic and all the particles emitted in the effective solid angle must be detected. The efficiency detection value must be equal to unity and phenomena such as absorption or scattering must be null. It is shown that corrections often become necessary. All parameters which can influence the measurements are studied [fr

  5. Automation of a measurement systems of waste drum alpha activity

    International Nuclear Information System (INIS)

    Labarre, S.; Bardy, N.

    1985-10-01

    The alpha radiator activity in the two-hundred liter waste drums is found by an IN96, computerized analyzer of the society Intertechnique, from data delivered by a gamma detector (GeHP) and by neutron detection blocks (He counter). This computerized analyzer manages not only the drum rotation and position in front of the detector, but also the experimental data monitoring and their processing from specific programs (background noise, calibration, drum measurements). Thanks to this automation, the measurement number and their reliability are optimized [fr

  6. Expression and functional importance of collagen-binding integrins, alpha 1 beta 1 and alpha 2 beta 1, on virus-activated T cells

    DEFF Research Database (Denmark)

    Andreasen, Susanne Ø; Thomsen, Allan R; Koteliansky, Victor E

    2003-01-01

    decreased responses were seen upon transfer of alpha(1)-deficient activated/memory T cells. Thus, expression of alpha(1)beta(1) and alpha(2)beta(1) integrins on activated T cells is directly functionally important for generation of inflammatory responses within tissues. Finally, the inhibitory effect......Adhesive interactions are crucial to cell migration into inflammatory sites. Using murine lymphocytic choriomeningitis virus as an Ag model system, we have investigated expression and function of collagen-binding integrins, alpha(1)beta(1) and alpha(2)beta(1), on activated and memory T cells. Using...... this system and MHC tetramers to define Ag-specific T cells, we demonstrate that contrary to being VLAs, expression of alpha(1)beta(1) and alpha(2)beta(1) can be rapidly induced on acutely activated T cells, that expression of alpha(1)beta(1) remains elevated on memory T cells, and that expression of alpha(1...

  7. Nutrient Content, Phytonutrient Composition, Alpha Amylase, Alpha Glucosidase Inhibition Activity and Antioxidant Activity of the Stoechospermum Marginatum Collected in Pre Monsoon Season

    Directory of Open Access Journals (Sweden)

    Reka Palanivel

    2017-03-01

    Full Text Available The objective of this study was to investigate the nutrient content, phytonutrient composition, physicochemical properties, alpha amylase and alpha glucosidase inhibition activity and antioxidant activity of the brown algae Stoechospermum marginatum collected from Gulf of Mannar, Tamil Nadu, India in pre monsoon season (June- September, 2015. Six and eight hours of ethanol and aqueous extract of Stoechospermum marginatum were used for phytonutrient screening, alpha amylase, alpha glucosidase inhibition activity and antioxidant activity. From the results of the study it is understood that Stoechospermum marginatum contain a high amount of carbohydrate, protein, crude fiber and phytonutrients like tannin, flavonoid, saponin, alkaloid, terpenoids, steroid and total phenolic content. The physicochemical properties namely Water absorption and Swelling power were very promising. Alpha amylase and alpha glucosidase inhibition activity was recorded to be high in both aqueous and ethanol extracts of eight hour extraction than in extracts taken from six hours extraction. Antioxidant activity was detected using DPPH, FRAP, beta carotene scavenging and H2O2 assay and found to have a high radical scavenging activity. Stoechospermum marginatum possess a valuable amount of total phenolic content and other phytonutrients and physicochemical properties, it may the reason for the potential inhibition of alpha amylase, alpha glucosidase and antioxidant activity. It is concluded from the study that the brown algae may be incorporated into foods to enhance their nutritional and therapeutic value.

  8. CD8 beta chain influences CD8 alpha chain-associated Lck kinase activity

    OpenAIRE

    1995-01-01

    The CD8 molecule plays an important role in the differentiation of CD8+ T cells in the thymus and in their normal function in the periphery. CD8 exists on the cell surface in two forms, the alpha alpha homodimer and the alpha beta heterodimer. Recent studies indicate an important role for the CD8 beta chain in thymic development of CD8+ T cells and suggest that signaling via CD8 alpha beta may be distinct from CD8 alpha alpha. To better understand these differences, we introduced the CD8 beta...

  9. Paroxysmal alpha activity in Rett syndrome: a case report.

    Science.gov (United States)

    Whitney, Robyn; Moharir, Mahendranath; Allen, Anita; Cortez, Miguel A

    2014-09-01

    Rett syndrome is a severe neurodevelopmental disorder that primarily affects females. Classically the disorder is characterized by early normal development, followed by a period of regression and later recovery or stagnation. Typical features include a loss of purposeful hand skills, development of hand stereotypies, loss of spoken language, gait abnormalities, and acquired microcephaly. Epilepsy affects between 70% and 90% of individuals with Rett syndrome. A number of stereotypical electroencephalography findings have been reported in Rett syndrome. We report a 9-year-old girl with Rett syndrome and epilepsy with a unique electroencephalography finding consisting of intermittent paroxysms of alpha activity in both wakefulness and sleep without clinical signs. This unique electroencephalography signature has not previously been reported in the English literature. Knowledge of this unique electroencephalography pattern of diffuse paroxysmal alpha activity represents an additional distinct feature of the electroencephalogram in Rett syndrome and expands the spectrum of electroencephalography abnormalities in Rett syndrome. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  10. Urinary alpha 1-microglobulin as an indicator protein of renal tubular dysfunction caused by environmental cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Tohyama, C.; Kobayashi, E.; Saito, H.; Sugihara, N.; Nakano, A.; Mitane, Y.

    1986-06-01

    An epidemiologic investigation was carried out to clarify the significance of the urinary excretion of alpha 1-microglobulin (alpha 1-MG) in people aged 50 years and over living in a Cd-polluted area in Japan. Approximately 80% of the population participated in the health examination. The urinary and serum levels and the relative clearance of alpha 1-MG to creatinine clearance were compared with various parameters (age, urinary beta 2-microglobulin (beta 2-MG), total protein, Cd, Cu and Zn, serum beta 2-MG, creatinine and blood urea nitrogen and relative clearances of alpha 1-MG, beta 2-MG, inorganic phosphate and uric acid). It was found that the urinary excretion of alpha 1-MG is closely associated with the urinary Cd and Cu and with the indices of renal dysfunction listed above. These results suggest that the urinary alpha 1-MG level markedly reflects a degree of proximal tubular dysfunction and that it may be useful as one of the screening measures for proximal tubular dysfunction caused by environmental Cd exposure.

  11. Vitamin D and estrogen receptor-alpha genotype and indices of bone mass and bone turnover in Danish girls

    DEFF Research Database (Denmark)

    Cusack, S.; Mølgaard, C.; Michaelsen, K. F.

    2006-01-01

    (VDR) (FokI, TaqI) and estrogen receptor-alpha (ER alpha) (PvuII, XbaI), and bone mineral density (BMD), bone mineral content (BMC), and markers of bone turnover in 224 Danish girls aged 11-12 years. BMD and BMC were measured by dual-energy X-ray absorptiometry. Serum osteocalcin, 25(OH......)D, and parathyroid hormone (PTH) were measured by ELISA assays and urinary pyridinium cross-links by HPLC. Physical activity, dietary calcium, and Tanner stage were assessed by questionnaire. In general, there were no significant differences in anthropometrical variables, physical activity, dietary calcium, serum 25......(OH)D, or PTH among genotype groups. BMD or BMC of lumbar spine or whole body (adjusted for body and bone size and pubertal status) were not associated with VDR or ER alpha genotypes or the combination of these genotypes. This lack of association remained even after adjustment for dietary...

  12. Treatment of alpha active organic liquid scintillator waste with ion exchange resins-column studies

    International Nuclear Information System (INIS)

    Venugopal Chetty, K.; Vaidya, V.N.; Venugopal, V.; Rao, P.R.V.

    2002-01-01

    The distribution ratios and percentage extraction for americium and total alpha due to plutonium and americium were determined using mixture of resins from the simulated alpha active organic liquid scintillator waste solution. Macroporous Bifunctional Phosphinic Acid (MPBPA) resin along with Amberlite IR-120 or AG 50WX8 in the ratios 1 : 1 to 1 : 6 were studied and the percentage extraction of better than 97% and distribution ratio of more than 480 were obtained. The data indicated the usefulness of these resins to remove alpha activity from these organic waste solutions. The column experiments were carried out using the active organic liquid scintillator waste with and without dilution with alcohol, and only alcoholic waste generated in the laboratory during the washing of the used liquid scintillator vials. The column containing either single MPBPA resin or with additional resin bed of Amberlite IR-120 were used for the treatment of the wastes. In the case of alcoholic waste after removal of activity it was reused for rinsing of the used vials. (author)

  13. Sources of variability in the determination by evaporation method of gross alpha activity in water samples

    International Nuclear Information System (INIS)

    Baeza, A.; Corbacho, J.A.

    2013-01-01

    Determining the gross alpha activity concentration of water samples is one way to screen for waters whose radionuclide content is so high that its consumption could imply surpassing the Total Indicative Dose as defined in European Directive 98/83/EC. One of the most commonly used methods to prepare the sources to measure gross alpha activity in water samples is desiccation. Its main advantages are the simplicity of the procedure, the low cost of source preparation, and the possibility of simultaneously determining the gross beta activity. The preparation of the source, the construction of the calibration curves, and the measurement procedure itself involve, however, various factors that may introduce sufficient variability into the results to significantly affect the screening process. We here identify the main sources of this variability, and propose specific procedures to follow in the desiccation process that will reduce the uncertainties, and ensure that the result is indeed representative of the sum of the activities of the alpha emitters present in the sample. (orig.)

  14. Gross alpha and beta activities in drinking water from Goias State, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Mingote, Raquel M. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN), Belo Horizonte, MG (Brazil); Nogueira, Regina A.; Costa, Heliana F. da, E-mail: raquel.mingote@cdtn.br, E-mail: rnogueira@cnen.gov.br, E-mail: heliana@cnen.gov.br [Centro Regional de Ciencias Nucleares do Centro-Oeste (CRCN-CO/CNEN), Abadia de Goias, GO (Brazil). Parque Estadual Telma Ortegal

    2017-07-01

    Detection of gross alpha and beta radioactivity is important for a quick surveying of both natural and anthropogenic radioactivity in water. Furthermore, gross alpha and gross beta parameters are included in Brazilian legislation on quality of drinking water. In this work, a low background liquid scintillation spectrometer was used to simultaneously determine gross alpha and gross beta in samples of the public water supplies in the state of Goias, Brazil, during 2010-2015. Sample preparation involved evaporation to concentrate the sample ten-fold. The results indicate that the water meets the radioactivity standards required by the regulations MS 2914/2011 of the Brazilian Department of Health. Concerning the high level of censored observations, a statistical treatment of data was conducted by using analysis methods of censored data to provide a reference value of the gross alpha and beta radioactivity in drinking water from the state of Goias. The estimated typical activities are very low, 0.030 Bq•L{sup -1} and 0.058 Bq•L{sup -1}, respectively. (author)

  15. The effect of alpha-thalassemia on cord blood red cell indices and interaction with sickle cell gene

    International Nuclear Information System (INIS)

    Quadri, Mohammad I.; Islam, Sherief I.A.M.; Nasserullah, Z.

    2000-01-01

    Alpha-thalassemia is known to be prevalent in the Eastern region of Saudi Arabia. There are no large scale reports regarding the effect of alpha-thalassemia on red cell indices of cord blood from Saudi Arabia. Similarly, there are reports regarding the interaction of alpha-thalassemia and the sickle-cell gene in relation to red cell indices in cord blood. To address these issues, we undertook a study on neonatal cold blood samples. In a prospective study, cord blood samples from 504 neonates from the Qatif area of the Eastern Province of Saudi Arabia were analyzed for complete blood counts (CBC) and cellulose acetate Hb electrophoresis. Hb S was confirmed by citrate agar Hb electrophoresis. There were 243 case samples with normal Hb electrophoresis (Hb A 27.2+- 7% and Hb F 72.6+-7.7%). Their mean Hb (g/dL), RBC (x10/L), Hct (%), MCV (pg), MCHC (g/dL), RDW-SD (fl) and RDW-CV (%) were 15.05+-1.6, 4.5+-0.5, 47.4+-5.3, 106+-8, 33.6+-2.3, 31.8+-1.7, 69.2+-9.5 and 17.9+-1.7, respectively. There were 136 cases with alpha-thalassemia trait (alphaTT), 57 cases with sickle cell trait (SCT) and 50 cases of sickle cell trait with alplha-thalassemia trait (SCT/ alphaTT). There were ten cases of Hb H disease (6 definite), including one with sickle cell disease (SCD) and two with SCT, Hb Bart's 23.9%-43.6%; four probable with Hb Bart's 10.9%-16.1% and one with SCT. The effect on red cell parameters in Hb H disease were most pronounced. In addition, there seven cases of SCD, four of whom had coexistent alpha-thalassemia trait (SCD/alphaTT). The prevalence of alpha-thalassemia in this cohort of Saudi population was 39.99%. Hb H disease appeared as common as SCD. Sickle cell gene was seen in 23.4% of neonatal samples. Apha-thalassemia gene significantly reduces MCH, MCV, RDW-SD, Hct, Hb and increase RBC count in both normal or sickle cell trait neonates. Generally, the variation of red cell parameters is directly proportional to the amount of Hb Bart's in the cord blood. Sickle cell

  16. Alpha attenuation soon after closing the eyes as an objective indicator of sleepiness.

    Science.gov (United States)

    Putilov, Arcady A; Donskaya, Olga G

    2014-12-01

    Attenuation of alpha rhythm in occipital derivation serves as a reliable electroencephalographic (EEG) marker of sleep onset. If such attenuation not only coincides with but also anticipates sleep onset, objective evaluation of sleepiness of permanently waking individuals might be facilitated by probing alpha attenuation immediately after closing eyes. We tested whether alpha-based EEG indexes reflect self-scored sleepiness and objectively measured waking ability. A total of 15 young adults self-scored their sleepiness before and after recording of their resting EEG with a 2-h interval in the course of 43-61-h wakefulness. For each EEG record, power spectra were calculated on 2-min intervals of the eyes open section and on five following 1-min intervals of the eyes closed section. Aking ability was assessed as latency to sleep onset marked by zero-crossing decline of such EEG indexes as alpha-theta power difference in occipital derivation and scores on the second principal component of the EEG spectrum in frontal and occipital derivations. Alpha attenuation during the first minute with eyes closed was found to be significantly related to the levels of subjective sleepiness and waking ability. The relationship between alpha attenuation and subjective sleepiness was confirmed by analysing 1-min eyes closed EEG recordings obtained with a 3-h interval in the course of 24-h sustained wakefulness of 130 adolescents and adults. We concluded that such 1-min eyes closed EEG recordings might be used for simple and quick measurements of sleepiness and waking ability in experimental and field studies of permanently waking individuals. © 2014 Wiley Publishing Asia Pty Ltd.

  17. Calcineurin mediates alpha-adrenergic stimulation of Na+,K(+)-ATPase activity in renal tubule cells.

    OpenAIRE

    Aperia, A; Ibarra, F; Svensson, L B; Klee, C; Greengard, P

    1992-01-01

    The alpha-adrenergic agonist oxymetazoline increased Na+,K(+)-ATPase activity of single proximal convoluted tubules dissected from rat kidney. Activation of the enzyme by oxymetazoline was prevented by either the alpha 1-adrenergic antagonist prazosin or the alpha 2-adrenergic antagonist yohimbine and was mimicked by the calcium ionophore A23187. The effect of oxymetazoline on Na+,K(+)-ATPase activity was prevented by a specific peptide inhibitor of calcineurin, as well as by FK 506, an immun...

  18. Adrenal scan in 17-alpha-hydroxylase deficiency: false indication of adrenal adenoma

    International Nuclear Information System (INIS)

    Shore, R.M.; Lieberman, L.M.; Newman, T.J.; Friedman, A.; Bargman, G.J.

    1981-01-01

    A patient who was thought to have testicular feminization syndrome and primary aldosteronism had an adrenal scan that suggested an adrenal adenoma. After later diagnosis of 17-alpha-hydroxylase deficiency, she was treated with glucocorticoids rather than surgery. Her clinical course and a repeat adrenal scan confirmed she did not have a tumor

  19. Correlation between phosphatidylinositol labeling and contraction in rabbit aorta: effect of alpha-1 adrenergic activation

    Energy Technology Data Exchange (ETDEWEB)

    Villalobos-Molina, R.; Uc, M.; Hong, E.; Garcia-Sainz, J.A.

    1982-07-01

    Activation of rabbit aortic strips with alpha adrenergic agonists increased the labeling (with (/sup 32/P)Pi) of phosphatidylinositol (PI) and phosphatidic acid and contracted the vascular preparations in dose-related fashion. Epinephrine, norepinephrine and methoxamine produced maximal effects, whereas clonidine behaved as partial agonist and B-HT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazole-(5,4-d) azepin dihydrochloride) was almost without activity in the two experimental models used. Phenylephrine was a full agonist in producing contraction, but failed to elicit the maximal increase in PI labeling. The EC50 values to produce contraction of aortic strips were lower for all agonists than those required to increase the incorporation of radioactive phosphate into PI, but there was a good correlation between the two sets of data. The increased PI labeling and contraction of aortic strips induced by epinephrine were antagonized by prazosin and yohimbine in dose-related fashion, but the first alpha blocker was about three orders of magnitude more potent than the second in antagonizing the two effects. The present results indicate that both stimulation of PI labeling and contraction are mediated through activation of alpha-1 adrenoceptors in rabbit aorta.

  20. Correlation between phosphatidylinositol labeling and contraction in rabbit aorta: effect of alpha-1 adrenergic activation

    International Nuclear Information System (INIS)

    Villalobos-Molina, R.; Uc, M.; Hong, E.; Garcia-Sainz, J.A.

    1982-01-01

    Activation of rabbit aortic strips with alpha adrenergic agonists increased the labeling (with [ 32 P]Pi) of phosphatidylinositol (PI) and phosphatidic acid and contracted the vascular preparations in dose-related fashion. Epinephrine, norepinephrine and methoxamine produced maximal effects, whereas clonidine behaved as partial agonist and B-HT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazole-[5,4-d] azepin dihydrochloride) was almost without activity in the two experimental models used. Phenylephrine was a full agonist in producing contraction, but failed to elicit the maximal increase in PI labeling. The EC50 values to produce contraction of aortic strips were lower for all agonists than those required to increase the incorporation of radioactive phosphate into PI, but there was a good correlation between the two sets of data. The increased PI labeling and contraction of aortic strips induced by epinephrine were antagonized by prazosin and yohimbine in dose-related fashion, but the first alpha blocker was about three orders of magnitude more potent than the second in antagonizing the two effects. The present results indicate that both stimulation of PI labeling and contraction are mediated through activation of alpha-1 adrenoceptors in rabbit aorta

  1. The activation energy for insertion of transmembrane alpha-helices is dependent on membrane composition.

    Science.gov (United States)

    Meijberg, Wim; Booth, Paula J

    2002-06-07

    The physical mechanisms that govern the folding and assembly of integral membrane proteins are poorly understood. It appears that certain properties of the lipid bilayer affect membrane protein folding in vitro, either by modulating helix insertion or packing. In order to begin to understand the origin of this effect, we investigate the effect of lipid forces on the insertion of a transmembrane alpha-helix using a water-soluble, alanine-based peptide, KKAAAIAAAAAIAAWAAIAAAKKKK-amide. This peptide binds to preformed 1,2-dioleoyl-l-alpha-phosphatidylcholine (DOPC) vesicles at neutral pH, but spontaneous transmembrane helix insertion directly from the aqueous phase only occurs at high pH when the Lys residues are de-protonated. These results suggest that the translocation of charge is a major determinant of the activation energy for insertion. Time-resolved measurements of the insertion process at high pH indicate biphasic kinetics with time constants of ca 30 and 430 seconds. The slower phase seems to correlate with formation of a predominantly transmembrane alpha-helical conformation, as determined from the transfer of the tryptophan residue to the hydrocarbon region of the membrane. Temperature-dependent measurements showed that insertion can proceed only above a certain threshold temperature and that the Arrhenius activation energy is of the order of 90 kJ mol(-1). The kinetics, threshold temperature and the activation energy change with the mole fraction of 1,2-dioleoyl-l-alpha-phosphatidylethanolamine (DOPE) introduced into the DOPC membrane. The activation energy increases with increasing DOPE content, which could reflect the fact that this lipid drives the bilayer towards a non-bilayer transition and increases the lateral pressure in the lipid chain region. This suggests that folding events involving the insertion of helical segments across the bilayer can be controlled by lipid forces. (c) 2002 Elsevier Science Ltd.

  2. SENESCENCE-ASSOCIATED DECLINE IN HEPATIC PEROXISOMAL ENZYME ACTIVITIES CORRESPONDS WITH DIMINISHED LEVELS OF RETINOID X RECEPTOR ALPHA, BUT NOT PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA1

    Science.gov (United States)

    AbstractAging is associated with alterations in hepatic peroxisomal metabolism and susceptibility to hepatocarcinogenecity produced by agonists of peroxisome proliferator-activated receptor alpha (PPARa). Mechanisms involved in these effects are not well understood. Howev...

  3. Novel tricyclic-alpha-alkyloxyphenylpropionic acids: dual PPARalpha/gamma agonists with hypolipidemic and antidiabetic activity.

    Science.gov (United States)

    Sauerberg, Per; Pettersson, Ingrid; Jeppesen, Lone; Bury, Paul S; Mogensen, John P; Wassermann, Karsten; Brand, Christian L; Sturis, Jeppe; Wöldike, Helle F; Fleckner, Jan; Andersen, Anne-Sofie T; Mortensen, Steen B; Svensson, L Anders; Rasmussen, Hanne B; Lehmann, Søren V; Polivka, Zdenek; Sindelar, Karel; Panajotova, Vladimira; Ynddal, Lars; Wulff, Erik M

    2002-02-14

    Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC(50) = 0.36 microM) and PPARgamma (EC(50) = 0.17 microM) activity in vitro. Ten days treatment of db/db mice with 3q improved the insulin sensitivity, as measured by OGTT, better than that seen with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha activity. Investigations of the pharmacokinetics of selected compounds suggested that extended drug exposure improved the in vivo activity of in vitro active compounds.

  4. Analysis of ESCO activities using country indicators

    Energy Technology Data Exchange (ETDEWEB)

    Okay, Nesrin [Department of Management, Financial Engineering Program, Bogazici University, Bebek, 34342 Istanbul (Turkey); Akman, Ugur [Department of Chemical Engineering, Bogazici University, Bebek, 34342 Istanbul (Turkey)

    2010-12-15

    Energy Service Companies (ESCOs) are private-sector instruments that offer energy-/emission-improvement (energy saving, energy efficiency, energy conservation and emission reduction) projects, or renewable-energy projects, in the developed and in some developing countries. There has been an increased interest for the provision of such energy services, driven by a restructuring of the gas and electricity sectors, and the push to mainstream sustainable forms of energy into the market. ESCOs are destined to deliver sustainable-energy solutions, especially in emerging markets. Literature reveals that energy/emission improvements of countries may be related to their innovation- and R and D-activity levels. In this work, we use a literature data on the activities and the sectors targeted by ESCOs in 38 countries, summarized in terms of the age of ESCO market (AEM), number of ESCO companies (NE), and total value of ESCO projects (VE). Along with the Global Innovation Index (GII) data of the countries, we investigate the relationships among the ESCO Indicators (EIs: AEM, NE, VE, sectors targeted by ESCOs), and the Country Indicators (CIs: GII and per-capita GDP, energy consumption, CO{sub 2} emission). We observe noteworthy dependencies between the EIs and CIs. Using the simple trend equations we estimate the missing VEs in the original data. We also project, as a hint for the size and orientation of the upcoming Turkish ESCO market, the set of EIs and the distribution of the sectors that are likely to be targeted by ESCOs in Turkey. (author)

  5. Activated endothelial cells elicit paracrine induction of epithelial chloride secretion. 6-Keto-PGF1alpha is an epithelial secretagogue.

    Science.gov (United States)

    Blume, E D; Taylor, C T; Lennon, P F; Stahl, G L; Colgan, S P

    1998-09-15

    Endothelial cells play a central role in the coordination of the inflammatory response. In mucosal tissue, such as the lung and intestine, endothelia are anatomically positioned in close proximity to epithelia, providing the potential for cell-cell crosstalk. Thus, in this study endothelial-epithelial biochemical crosstalk pathways were studied using a human intestinal crypt cell line (T84) grown in noncontact coculture with human umbilical vein endothelia. Exposure of such cocultures to endothelial-specific agonists (LPS) resulted in activation of epithelial electrogenic Cl- secretion and vectorial fluid transport. Subsequent experiments revealed that in response to diverse stimuli (LPS, IL-1alpha, TNF-alpha, hypoxia), endothelia produce and secrete a small, stable epithelial secretagogue into conditioned media supernatants. Further experiments identified this secretagogue as 6-keto-PGF1alpha, a stable hydrolysis product of prostacyclin (PGI2). Results obtained with synthetic prostanoids indicated that 6-keto-PGF1alpha (EC50 = 80 nM) and PGI2 stable analogues (EC50 = 280 nM) activate the same basolaterally polarized, Ca2+-coupled epithelial receptor. In summary, these findings reveal a previously unappreciated 6-keto-PGF1alpha receptor on intestinal epithelia, the ligation of which results in activation of electrogenic Cl- secretion. In addition, these data reveal a novel action for the prostacyclin hydrolysis product 6-keto-PGF1alpha and provide a potential endothelial- epithelial crosstalk pathway in mucosal tissue.

  6. The relationship between the level of salivary alpha amylase activity and pain severity in patients with symptomatic irreversible pulpitis

    Directory of Open Access Journals (Sweden)

    Fatemeh Ahmadi-Motamayel

    2013-08-01

    Full Text Available 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 Methods Thirty-six patients (20 females and 16 males with severe tooth pain due to symptomatic irreversible pulpitis were selected. The visual analogue scale (VAS score was used to assess the pain severity in each patient. Unstimulated whole saliva was collected, and the level of alpha amylase activity was assessed by the spectrophotometric method. Statistical analysis was performed using SPSS 13. Results The level of alpha amylase was significantly increased in the saliva in association with pain severity assessed by VAS. The salivary alpha amylase was also elevated with increased age and in males. Conclusions There was a significant correlation between the VAS pain scale and salivary alpha amylase level, which indicates this biomarker may be a good index for the objective assessment of pain intensity.

  7. Active site studies of bovine alpha1-->3-galactosyltransferase and its secondary structure prediction.

    Science.gov (United States)

    Shah, P S; Bizik, F; Dukor, R K; Qasba, P K

    2000-07-14

    The catalytic domain of bovine alpha1-->3-galactosyltransferase (alpha3GalT), residues 80-368, have been cloned and expressed, in Escherichia coli. Using a sequential purification protocol involving a Ni(2+) affinity column followed by a UDP-hexanolamine affinity column, we have obtained a pure and active protein from the soluble fraction which catalyzes the transfer of galactose (Gal) from UDP-Gal to N-acetyllactosamine (LacNAc) with a specific activity of 0.69 pmol/min/ng. The secondary structural content of alpha3GalT protein was analyzed by Fourier transform infrared (FTIR) spectroscopy, which shows that the enzyme has about 35% beta-sheet and 22% alpha-helix. This predicted secondary structure content by FTIR spectroscopy was used in the protein sequence analysis algorithm, developed by the Biomolecular Engineering Research Center at Boston University and Tasc Inc., for the assignment of secondary structural elements to the amino acid sequence of alpha3GalT. The enzyme appears to have three major and three minor helices and five sheet-like structures. The studies on the acceptor substrate specificity of the enzyme, alpha3GalT, show that in addition to LacNAc, which is the natural substrate, the enzyme accepts various other disaccharides as substrates such as lactose and Gal derivatives, beta-O-methylgalactose and beta-D-thiogalactopyranoside, albeit with lower specific activities. There is an absolute requirement for Gal to be at the non-reducing end of the acceptor molecule which has to be beta1-->4-linked to a second residue that can be more diverse in structure. The kinetic parameters for four acceptor molecules were determined. Lactose binds and functions in a similar way as LacNAc. However, beta-O-methylgalactose and Gal do not bind as tightly as LacNAc or lactose, as their K(ia) and K(A) values indicate, suggesting that the second monosaccharide is critical for holding the acceptor molecule in place. The 2' and 4' hydroxyl groups of the receiving Gal

  8. Active trafficking of alpha 1 antitrypsin across the lung endothelium.

    Directory of Open Access Journals (Sweden)

    Angelia D Lockett

    Full Text Available The homeostatic lung protective effects of alpha-1 antitrypsin (A1AT may require the transport of circulating proteinase inhibitor across an intact lung endothelial barrier. We hypothesized that uninjured pulmonary endothelial cells transport A1AT to lung epithelial cells. Purified human A1AT was rapidly taken up by confluent primary rat pulmonary endothelial cell monolayers, was secreted extracellularly, both apically and basolaterally, and was taken up by adjacent rat lung epithelial cells co-cultured on polarized transwells. Similarly, polarized primary human lung epithelial cells took up basolaterally-, but not apically-supplied A1AT, followed by apical secretion. Evidence of A1AT transcytosis across lung microcirculation was confirmed in vivo by two-photon intravital microscopy in mice. Time-lapse confocal microscopy indicated that A1AT co-localized with Golgi in the endothelium whilst inhibition of the classical secretory pathway with tunicamycin significantly increased intracellular retention of A1AT. However, inhibition of Golgi secretion promoted non-classical A1AT secretion, associated with microparticle release. Polymerized A1AT or A1AT supplied to endothelial cells exposed to soluble cigarette smoke extract had decreased transcytosis. These results suggest previously unappreciated pathways of A1AT bidirectional uptake and secretion from lung endothelial cells towards the alveolar epithelium and airspaces. A1AT trafficking may determine its functional bioavailablity in the lung, which could be impaired in individuals exposed to smoking or in those with A1AT deficiency.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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.

  10. Parieto-occipital sources account for the increase in alpha activity with working memory load

    NARCIS (Netherlands)

    Tuladhar, A.M.; Huurne, N.P. ter; Schoffelen, J.M.; Maris, E.G.G.; Oostenveld, R.; Jensen, O.

    2007-01-01

    The role of oscillatory alpha activity (8-13 Hz) in cognitive processing remains an open question. It has been debated whether alpha activity plays a direct role in the neuronal processing required for a given task or whether it reflects idling and/or functional inhibition. Recent

  11. Alpha-Amylase Activity in Blood Increases after Pharmacological, But Not Psychological, Activation of the Adrenergic System.

    Directory of Open Access Journals (Sweden)

    Urs M Nater

    Full Text Available 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 separate studies.In study 1, healthy subjects were examined in a placebo-controlled, double-blind paradigm using yohimbine, an alpha2-adrenergic antagonist. In study 2, subjects were examined in a standardized rest-controlled psychosocial stress protocol. Alpha-amylase activity in blood was repeatedly measured in both studies.Results of study 1 showed that alpha-amylase in blood is subject to stronger increases after injection of yohimbine compared to placebo. In study 2, results showed that there was no significant effect of psychological stress compared to rest.Alpha-amylase in blood increases after pharmacological activation of the adrenergic pathways suggesting that sympathetic receptors are responsible for these changes. Psychological stress, however, does not seem to have an impact on alpha-amylase in blood. Our findings provide insight into the mechanisms underlying activity changes in alpha-amylase in blood in healthy individuals.

  12. 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

    1996-01-01

    /EBP alpha expression vector into 3T3-L1 cells with a series of 5' truncated ob gene promoter constructs activated reporter gene expression with all constructs containing the proximal C/EBP binding site (nucleotides -55 to -47). Mutation of this site blocked transactivation by C/EBP alpha. Taken together......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...... gene contains several consensus C/EBP binding sites, only one of these sites appears to be functional. DNase I cleavage inhibition patterns (footprinting) of the ob gene promoter revealed that recombinant C/EBP alpha, as well as a nuclear factor present in fully differentiated 3T3-L1 adipocytes...

  13. 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

    2010-01-01

    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......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...... preclinical evaluation of alpha(7) nAChR activation. It is therefore important to consider the translational power of the animal models used before entering into a clinical evaluation of the pro-cognitive effects of alpha(7) nAChR activation....

  14. Measurement and analysis of $\\alpha$ particle induced reactions on yttrium

    CERN Document Server

    Singh, N L; Chintalapudi, S N

    2000-01-01

    Excitation functions for /sup 89/Y[( alpha ,3n); ( alpha ,4n); ( alpha , p3n); ( alpha , alpha n); ( alpha , alpha 2n)] reactions were measured up to 50 MeV using stacked foil activation technique and HPGe gamma ray spectroscopy method. The experimental data were compared with calculations considering equilibrium as well as preequilibrium reactions according to the hybrid model of Blann (ALICE/90). For ( alpha , xnyp) type of reactions, the precompound contributions are described by the model. There seems to be indications of direct inelastic scattering effects in ( alpha , alpha xn) type of reactions. To the best of our knowledge, the excitation functions for ( alpha ,4n), ( alpha , p3n), ( alpha , alpha n) and ( alpha , alpha 2n) reactions were measured for the first time. (23 refs).

  15. Measurement and analysis of alpha particle induced reactions on yttrium

    Energy Technology Data Exchange (ETDEWEB)

    Singh, N.L.; Gadkari, M.S. [Baroda Univ. (India). Dept. of Physics; Chintalapudi, S.N. [IUC-DAEF Calcutta Centre, Calcutta (India)

    2000-05-01

    Excitation functions for {sup 89}Y[({alpha},3n);({alpha},4n);({alpha},p3n);({alpha},{alpha}n);({alpha},{alpha}2n)] reactions were measured up to 50 MeV using stacked foil activation technique and HPGe gamma ray spectroscopy method. The experimental data were compared with calculations considering equilibrium as well as preequilibrium reactions according to the hybrid model of Blann (ALICE/90). For ({alpha},xnyp) type of reactions, the precompound contributions are described by the model. There seems to be indications of direct inelastic scattering effects in ({alpha},{alpha}xn) type of reactions. To the best of our knowledge, the excitation functions for ({alpha},4n), ({alpha},p3n), ({alpha},{alpha}n) and ({alpha},{alpha}2n) reactions were measured for the first time. (orig.)

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

    International Nuclear Information System (INIS)

    Shirazi, S.P.; Pakula, J.; Young, I.J.; Crayton, J.W.; Konopka, L.M.; Rybak, M.

    2002-01-01

    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

  17. Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline.

    Science.gov (United States)

    Haenisch, Britta; Walstab, Jutta; Herberhold, Stephan; Bootz, Friedrich; Tschaikin, Marion; Ramseger, René; Bönisch, Heinz

    2010-12-01

    Oxymetazoline and xylometazoline are both used as nasal mucosa decongesting α-adrenoceptor agonists during a common cold. However, it is largely unknown which of the six α-adrenoceptor subtypes are actually present in human nasal mucosa, which are activated by the two alpha-adrenoceptor agonists and to what extent. Therefore, mRNA expression in human nasal mucosa of the six α-adrenoceptor subtypes was studied. Furthermore, the affinity and potency of the imidazolines oxymetazoline and xylometazoline at these α-adrenoceptor subtypes were examined in transfected HEK293 cells. The rank order of mRNA levels of α-adrenoceptor subtypes in human nasal mucosa was: α(2A) > α(1A) ≥ α(2B) > α(1D) ≥ α(2C) > α(1B) . Oxymetazoline and xylometazoline exhibited in radioligand competition studies higher affinities than the catecholamines adrenaline and noradrenaline at most α-adrenoceptor subtypes. Compared to xylometazoline, oxymetazoline exhibited a significantly higher affinity at α(1A) - but a lower affinity at α(2B) -adrenoceptors. In functional studies in which adrenoceptor-mediated Ca(2+) signals were measured, both, oxymetazoline and xylometazoline behaved at α(2B) -adrenoceptors as full agonists but oxymetazoline was significantly more potent than xylometazoline. Furthermore, oxymetazoline was also a partial agonist at α(1A) -adrenoceptors; however, its potency was relatively low and it was much lower than its affinity. The higher potency at α(2B) -adrenoceptors, i.e. at receptors highly expressed at the mRNA level in human nasal mucosa, could eventually explain why in nasal decongestants oxymetazoline can be used in lower concentrations than xylometazoline.

  18. p38 mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease.

    Science.gov (United States)

    Waetzig, Georg H; Seegert, Dirk; Rosenstiel, Philip; Nikolaus, Susanna; Schreiber, Stefan

    2002-05-15

    Inflammatory bowel diseases (IBD)--Crohn's disease and ulcerative colitis--are relapsing chronic inflammatory disorders which involve genetic, immunological, and environmental factors. The regulation of TNF-alpha, a key mediator in the inflammatory process in IBD, is interconnected with mitogen-activated protein kinase pathways. The aim of this study was to characterize the activity and expression of the four p38 subtypes (p38alpha-delta), c-Jun N-terminal kinases (JNKs), and the extracellular signal-regulated kinases (ERK)1/2 in the inflamed intestinal mucosa. Western blot analysis revealed that p38alpha, JNKs, and ERK1/2 were significantly activated in IBD, with p38alpha showing the most pronounced increase in kinase activity. Protein expression of p38 and JNK was only moderately altered in IBD patients compared with normal controls, whereas ERK1/2 protein was significantly down-regulated. Immunohistochemical analysis of inflamed mucosal biopsies localized the main expression of p38alpha to lamina propria macrophages and neutrophils. ELISA screening of the supernatants of Crohn's disease mucosal biopsy cultures showed that incubation with the p38 inhibitor SB 203580 significantly reduced secretion of TNF-alpha. In vivo inhibition of TNF-alpha by a single infusion of anti-TNF-alpha Ab (infliximab) resulted in a highly significant transient increase of p38alpha activity during the first 48 h after infusion. A significant infliximab-dependent p38alpha activation was also observed in THP-1 myelomonocytic cells. In human monocytes, infliximab enhanced TNF-alpha gene expression, which could be inhibited by SB 203580. In conclusion, p38alpha signaling is involved in the pathophysiology of IBD.

  19. Alpha contamination assessment for D ampersand D activities: Technology overview

    International Nuclear Information System (INIS)

    Conaway, J.G.; Rawool-Sullivan, M.W.; MacArthur, D.W.

    1996-02-01

    Instruments based on the principle of Long-Range Alpha Detection (LRAD) detect the ions created in ambient air by Ionizing radiation, particularly alpha radiation, interacting with air molecules. Using either an electrostatic field or forced convection, these ions can be transported to a detection grid where the ions produce a small current that is measured with a sensitive electrometer. LRAD-based instruments can give separate, simultaneous measurements of alpha-emitting solids and inert radioactive gases such as radon. LRAD-based instruments assess surface contamination on an entire object or large surface area in a single, rapid measurement, including relatively inaccessible areas such as interior surfaces of pipes and process equipment. The LRAD concept is well proven and has been developed into a range of different radiation detection devices. This paper presents an overview of the technology, while several associated papers explore specific applications in greater detail

  20. Effect of neohesperidin dihydrochalcone on the activity and stability of alpha-amylase: a comparative study on bacterial, fungal, and mammalian enzymes.

    Science.gov (United States)

    Kashani-Amin, Elaheh; Ebrahim-Habibi, Azadeh; Larijani, Bagher; Moosavi-Movahedi, Ali Akbar

    2015-10-01

    Neohesperidin dihydrochalcone (NHDC) was recently introduced as an activator of mammalian alpha-amylase. In the current study, the effect of NHDC has been investigated on bacterial and fungal alpha-amylases. Enzyme assays and kinetic analysis demonstrated the capability of NHDC to significantly activate both tested alpha-amylases. The ligand activation pattern was found to be more similar between the fungal and mammalian enzyme in comparison with the bacterial one. Further, thermostability experiments indicated a stability increase in the presence of NHDC for the bacterial enzyme. In silico (docking) test locates a putative binding site for NHDC on alpha-amylase surface in domain B. This domain shows differences in various alpha-amylase types, and the different behavior of the ligand toward the studied enzymes may be attributed to this fact. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Measurement of very low alpha activity in water

    International Nuclear Information System (INIS)

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

    1987-01-01

    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

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    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...

  3. Anti-inflammatory activity of some novel alpha-amino naphthalene derivatives.

    Science.gov (United States)

    Sharma, Shalabh; Srivastava, Virendra Kishore; Kumar, Ashok

    2003-01-01

    alpha-Acetylamino naphthalene (1) was reacted with different aromatic aldehydes and with primary or secondary amines to give alpha-aminonaphthylsubstitutedaryl chalkones (2-5) and alpha-(substituted aminoethyl)-amidonaphthalenes (14-25), respectively. These substituted chalkones were treated with hydrazinehydrate and hydroxylamine hydrochloride to give 1-acetyl-5-substitutedaryl-3-(alpha-aminonaphthyl)-2-pyrazolines (6-9) and alpha-(2-substitutedaryl-isoxazolin-4-yl)-aminonaphthalenes (10-13), respectively. Their chemical structures were confirmed by IR and 1H-NMR spectral data and elemental analysis. Studies of the anti-inflammatory and ulcerogenic activities and acute toxicity of these newly synthesized compounds were performed in vivo and compared with the standard drug, phenylbutazone (CAS 50-33-9). Some of these compounds showed potent anti-inflammatory activity and less ulcerogenic effects than phenylbutazone.

  4. Analysis of ESCO Activities Using Country Indicators

    OpenAIRE

    Okay, Nesrin; Akman, Ugur

    2009-01-01

    Energy Service Companies (ESCOs) are private sector instruments that offer energy-/emission-improvement (energy saving, energy efficiency, energy conservation, emission reduction) projects in the developed and in some developing countries. Literature reveals that energy-/emission-improvements of countries may be related to their innovation- and R&D-activity levels. In this work, we use a literature data on the activities and the sectors targeted by ESCOs in 38 countries, summarized in terms o...

  5. Optical indicators of plant physiolgical activity

    Czech Academy of Sciences Publication Activity Database

    Kováč, Daniel; Ač, Alexander; Šigut, Ladislav; Klem, Karel; Urban, Otmar

    2012-01-01

    Roč. 60, č. 3 (2012), s. 101-110 ISSN 1211-8516 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0073; GA MŽP(CZ) SP/2D1/70/08 Institutional support: RVO:67179843 Keywords : Picea abies * refl ectance * vegetation indices * photosynthesis * ecophysiology Subject RIV: EH - Ecology, Behaviour

  6. Functional localization and effective connectivity of cortical theta and alpha oscillatory activity during an attention task

    Directory of Open Access Journals (Sweden)

    Yuichi Kitaura

    Full Text Available Objectives: The aim of this paper is to investigate cortical electric neuronal activity as an indicator of brain function, in a mental arithmetic task that requires sustained attention, as compared to the resting state condition. The two questions of interest are the cortical localization of different oscillatory activities, and the directional effective flow of oscillatory activity between regions of interest, in the task condition compared to resting state. In particular, theta and alpha activity are of interest here, due to their important role in attention processing. Methods: We adapted mental arithmetic as an attention ask in this study. Eyes closed 61-channel EEG was recorded in 14 participants during resting and in a mental arithmetic task (“serial sevens subtraction”. Functional localization and connectivity analyses were based on cortical signals of electric neuronal activity estimated with sLORETA (standardized low resolution electromagnetic tomography. Functional localization was based on the comparison of the cortical distributions of the generators of oscillatory activity between task and resting conditions. Assessment of effective connectivity was based on the iCoh (isolated effective coherence method, which provides an appropriate frequency decomposition of the directional flow of oscillatory activity between brain regions. Nine regions of interest comprising nodes from the dorsal and ventral attention networks were selected for the connectivity analysis. Results: Cortical spectral density distribution comparing task minus rest showed significant activity increase in medial prefrontal areas and decreased activity in left parietal lobe for the theta band, and decreased activity in parietal-occipital regions for the alpha1 band. At a global level, connections among right hemispheric nodes were predominantly decreased during the task condition, while connections among left hemispheric nodes were predominantly increased. At more

  7. Daily and seasonal variations of outdoor alpha-activity concentration in Salzburg city/Austria

    International Nuclear Information System (INIS)

    Lettner, H.; Hubmer, A.K.; Rolle, R.; Winkler, R.; Steinhaeusler, F.

    1996-01-01

    Long-term continuous measurements of the atmospheric outdoor alpha-activity concentration have been performed by using a radioaerosol-monitor, roof-mounted 20 m above ground. The alpha-activity concentration was identified to be predominantly attributed to radon progeny. The total alpha-activity covers a range of two orders of magnitude. Three different components of variations could be identified with regard to temporal variations: Short-term diurnal component (daily variation), mid-term component (days to weeks) and long-term component (seasonal variation). Continuous measurements have been recorded since the end of 1993. The results of continuous measurements of the outdoor alpha-activity concentration over a time span from January 1994 to June 1995 are presented. (author)

  8. Transcranial alternating current stimulation enhances individual alpha activity in human EEG.

    Directory of Open Access Journals (Sweden)

    Tino Zaehle

    Full Text Available Non-invasive electrical stimulation of the human cortex by means of transcranial direct current stimulation (tDCS has been instrumental in a number of important discoveries in the field of human cortical function and has become a well-established method for evaluating brain function in healthy human participants. Recently, transcranial alternating current stimulation (tACS has been introduced to directly modulate the ongoing rhythmic brain activity by the application of oscillatory currents on the human scalp. Until now the efficiency of tACS in modulating rhythmic brain activity has been indicated only by inference from perceptual and behavioural consequences of electrical stimulation. No direct electrophysiological evidence of tACS has been reported. We delivered tACS over the occipital cortex of 10 healthy participants to entrain the neuronal oscillatory activity in their individual alpha frequency range and compared results with those from a separate group of participants receiving sham stimulation. The tACS but not the sham stimulation elevated the endogenous alpha power in parieto-central electrodes of the electroencephalogram. Additionally, in a network of spiking neurons, we simulated how tACS can be affected even after the end of stimulation. The results show that spike-timing-dependent plasticity (STDP selectively modulates synapses depending on the resonance frequencies of the neural circuits that they belong to. Thus, tACS influences STDP which in turn results in aftereffects upon neural activity.The present findings are the first direct electrophysiological evidence of an interaction of tACS and ongoing oscillatory activity in the human cortex. The data demonstrate the ability of tACS to specifically modulate oscillatory brain activity and show its potential both at fostering knowledge on the functional significance of brain oscillations and for therapeutic application.

  9. Chrysophanic Acid Suppresses Adipogenesis and Induces Thermogenesis by Activating AMP-activated Protein Kinase Alpha in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Hara Lim

    2016-12-01

    Full Text Available Chrysophanic acid (CA is a member of the anthraquinone family abundant in rhubarb, a widely used herb for obesity treatment in Traditional Korean Medicine. Though several studies have indicated numerous features of CA, no study has yet reported the effect of CA on obesity. In this study, we tried to identify the anti-obesity effects of CA. By using 3T3-L1 adipocytes and primary cultured brown adipocytes as in vitro models, high-fat diet (HFD-induced obese mice, and zebrafish as in vivo models, we determined the anti-obesity effects of CA. CA reduced weight gain in HFD-induced obese mice. They also decreased lipid accumulation and the expressions of adipogenesis factors including peroxisome proliferator-activated receptor gamma (PPARγ and CCAAT/enhancer-binding protein alpha (C/EBPα in 3T3-L1 adipocytes. In addition, uncoupling protein 1 (UCP1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α, the brown fat specific thermogenic genes, were up-regulated in brown adipocytes by CA treatment. Furthermore, when co-treated with Compound C, the AMP-activated protein kinase (AMPK inhibitor, CA was able to restore the activation of AMPKα in both types of adipocytes, indicating the multi-controlling effect of CA was partially via the AMPKα pathway. Given all together, these results indicate that CA can ameliorate obesity by controlling the adipogenic and thermogenic pathway at the same time. On these bases we suggest the new potential of CA as an anti-obese pharmacotherapy.

  10. Structure-activity relationships of 2alpha-substituted androstenedione analogs as aromatase inhibitors and their aromatization reactions.

    Science.gov (United States)

    Numazawa, Mitsuteru; Handa, Wakako; Hasegawa, Chie; Takahashi, Madoka

    2005-12-01

    Aromatase catalyzes the conversion of androstenedione (1a, AD) to estrone through three sequential oxygenations of the 19-methyl group. To gain insight into the spatial nature of the AD binding (active) site of aromatase in relation to the catalytic function of the enzyme, we tested for the ability of 2alpha-substituted (halogeno, alkyl, hydroxy, and alkoxy) ADs (1b-1i) to inhibit aromatase in human placental microsomes as well as their ability to serve as a substrate for the enzyme. All of the steroids inhibited the enzyme in a competitive manner with the apparent K(i)'s ranging from 45 to 1150 nM. 2alpha-Halogeno (F, Cl, and Br) and 2alpha-alkyl (CH3 and CH2CH3) steroids 1b-1f were powerful to good inhibitors (Ki=45-171 nM) whereas steroids 1g-1i, having an oxygen function (hydroxy or alkoxy) at C-2alpha, were poor inhibitors (Ki=670-1150 nM). Aromatization of some of the steroids with placental microsomes was analyzed by gas chromatography-mass spectrometry, indicating that the aromatization rate of the bromide 1d was about two-fold that of the natural substrate AD and that of 2alpha-methoxide 1h was similar to that of AD. Kinetic analysis of the aromatization of androgens revealed that a good substrate was not essentially a good inhibitor for aromatase.

  11. 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.

    1990-01-01

    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

  12. Measurement of natural radioactivity in chemical fertilizer and agricultural soil: evidence of high alpha activity.

    Science.gov (United States)

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

    2008-02-01

    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.

  13. Staphylococcus aureus alpha-hemolysin activates the NLRP3-inflammasome in human and mouse monocytic cells.

    Directory of Open Access Journals (Sweden)

    Robin R Craven

    Full Text Available Community Acquired Methicillin Resistant Staphylococcus aureus (CA-MRSA causes severe necrotizing infections of the skin, soft tissues, and lungs. Staphylococcal alpha-hemolysin is an essential virulence factor in mouse models of CA-MRSA necrotizing pneumonia. S. aureus alpha-hemolysin has long been known to induce inflammatory signaling and cell death in host organisms, however the mechanism underlying these signaling events were not well understood. Using highly purified recombinant alpha-hemolysin, we now demonstrate that alpha-hemolysin activates the Nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 protein (NLRP3-inflammasome, a host inflammatory signaling complex involved in responses to pathogens and endogenous danger signals. Non-cytolytic mutant alpha-hemolysin molecules fail to elicit NLRP3-inflammasome signaling, demonstrating that the responses are not due to non-specific activation of this innate immune signaling system by bacterially derived proteins. In monocyte-derived cells from humans and mice, inflammasome assembly in response to alpha-hemolysin results in activation of the cysteine proteinase, caspase-1. We also show that inflammasome activation by alpha-hemolysin works in conjunction with signaling by other CA-MRSA-derived Pathogen Associated Molecular Patterns (PAMPs to induce secretion of pro-inflammatory cytokines IL-1beta and IL-18. Additionally, alpha-hemolysin induces cell death in these cells through an NLRP3-dependent program of cellular necrosis, resulting in the release of endogenous pro-inflammatory molecules, like the chromatin-associated protein, High-mobility group box 1 (HMGB1. These studies link the activity of a major S. aureus virulence factor to a specific host signaling pathway. The cellular events linked to inflammasome activity have clear relevance to the disease processes associated with CA-MRSA including tissue necrosis and inflammation.

  14. Staphylococcus aureus alpha-hemolysin activates the NLRP3-inflammasome in human and mouse monocytic cells.

    Science.gov (United States)

    Craven, Robin R; Gao, Xi; Allen, Irving C; Gris, Denis; Bubeck Wardenburg, Juliane; McElvania-Tekippe, Erin; Ting, Jenny P; Duncan, Joseph A

    2009-10-14

    Community Acquired Methicillin Resistant Staphylococcus aureus (CA-MRSA) causes severe necrotizing infections of the skin, soft tissues, and lungs. Staphylococcal alpha-hemolysin is an essential virulence factor in mouse models of CA-MRSA necrotizing pneumonia. S. aureus alpha-hemolysin has long been known to induce inflammatory signaling and cell death in host organisms, however the mechanism underlying these signaling events were not well understood. Using highly purified recombinant alpha-hemolysin, we now demonstrate that alpha-hemolysin activates the Nucleotide-binding domain and leucine-rich repeat containing gene family, pyrin domain containing 3 protein (NLRP3)-inflammasome, a host inflammatory signaling complex involved in responses to pathogens and endogenous danger signals. Non-cytolytic mutant alpha-hemolysin molecules fail to elicit NLRP3-inflammasome signaling, demonstrating that the responses are not due to non-specific activation of this innate immune signaling system by bacterially derived proteins. In monocyte-derived cells from humans and mice, inflammasome assembly in response to alpha-hemolysin results in activation of the cysteine proteinase, caspase-1. We also show that inflammasome activation by alpha-hemolysin works in conjunction with signaling by other CA-MRSA-derived Pathogen Associated Molecular Patterns (PAMPs) to induce secretion of pro-inflammatory cytokines IL-1beta and IL-18. Additionally, alpha-hemolysin induces cell death in these cells through an NLRP3-dependent program of cellular necrosis, resulting in the release of endogenous pro-inflammatory molecules, like the chromatin-associated protein, High-mobility group box 1 (HMGB1). These studies link the activity of a major S. aureus virulence factor to a specific host signaling pathway. The cellular events linked to inflammasome activity have clear relevance to the disease processes associated with CA-MRSA including tissue necrosis and inflammation.

  15. A tubulin alpha 8 mouse knockout model indicates a likely role in spermatogenesis but not in brain development.

    Directory of Open Access Journals (Sweden)

    Christine P Diggle

    Full Text Available Tubulin alpha 8 (Tuba8 is the most divergent member of the highly conserved alpha tubulin family, and uniquely lacks two key post-translational modification sites. It is abundantly expressed in testis and muscle, with lower levels in the brain. We previously identified homozygous hypomorphic TUBA8 mutations in human subjects with a polymicrogyria (PMG syndrome, suggesting its involvement in development of the cerebral cortex. We have now generated and characterized a Tuba8 knockout mouse model. Homozygous mice were confirmed to lack Tuba8 protein in the testis, but did not display PMG and appeared to be neurologically normal. In response to this finding, we re-analyzed the human PMG subjects using whole exome sequencing. This resulted in identification of an additional homozygous loss-of-function mutation in SNAP29, suggesting that SNAP29 deficiency, rather than TUBA8 deficiency, may underlie most or all of the neurodevelopmental anomalies in these subjects. Nonetheless, in the mouse brain, Tuba8 specifically localised to the cerebellar Purkinje cells, suggesting that the human mutations may affect or modify motor control. In the testis, Tuba8 localisation was cell-type specific. It was restricted to spermiogenesis with a strong acrosomal localization that was gradually replaced by cytoplasmic distribution and was absent from spermatozoa. Although the knockout mice were fertile, the localisation pattern indicated that Tuba8 may have a role in spermatid development during spermatogenesis, rather than as a component of the mature microtubule-rich flagellum itself.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    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...... 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...

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

    International Nuclear Information System (INIS)

    Tobias, C.C.B.

    1982-01-01

    The absolute activity of U-235 contained in a UO 2 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) [pt

  18. 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

    2010-01-01

    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......, as measured by c-Fos immunoreactivity, a marker of neuronal activation. Selective depletion of these cholinergic neurons abolishes the SSR180711-induced activation of the mPFC but not the ACCshell, demonstrating their critical importance for alpha(7) nAChR-dependent activation of the mPFC. Contrarily......, selective depletion of dopaminergic neurons in the ventral tegmental area abolishes the SSR180711-induced activation of the ACCshell but not the mPFC or HDB. These results demonstrate 2 distinct neural pathways activated by SSR180711. The BF and mPFC are important for attentional function and may subserve...

  19. The Alpha consensus meeting on cryopreservation key performance indicators and benchmarks: proceedings of an expert meeting.

    Science.gov (United States)

    2012-08-01

    This proceedings report presents the outcomes from an international workshop designed to establish consensus on: definitions for key performance indicators (KPIs) for oocyte and embryo cryopreservation, using either slow freezing or vitrification; minimum performance level values for each KPI, representing basic competency; and aspirational benchmark values for each KPI, representing best practice goals. This report includes general presentations about current practice and factors for consideration in the development of KPIs. A total of 14 KPIs were recommended and benchmarks for each are presented. No recommendations were made regarding specific cryopreservation techniques or devices, or whether vitrification is 'better' than slow freezing, or vice versa, for any particular stage or application, as this was considered to be outside the scope of this workshop. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  20. Determination of alpha activity produced by Indian tea samples using solid state nuclear track detection technique

    International Nuclear Information System (INIS)

    Azam, Ameer; Naqvi, A.H.; Srivastava, D.S.

    2001-01-01

    India has first place in the world in the production, consumption and export of tea. The average production of tea in India is about 780 million kg annually. Indian population uses tea as a favourite beverage specially with the breakfast. Tea leaves are perennial plants and they have extension root system spread over deeper layers in the soil. Soil contains uranium as trace element. Hence, uranium is transferred to the leaves as a result of uptake from the soil over the years. Since many of the decay products of uranium are alpha emitters hence tea is a source of alpha radioactivity and can cause damaging effects. Therefore, data on alpha activity of tea samples will be useful in estimating these harmful effects at least qualitatively. In the present study the alpha activity produced by thirteen samples of tea available in the local market was measured

  1. An Alpha spectrometer for measuring radon daughter individual activity concentration

    International Nuclear Information System (INIS)

    Berico, M.; Formignani, M.; Mariotti, F.

    2001-01-01

    In the frame of the program of the Institute for Radiation Protection of ENEA, related to the evaluation of dose from radon and thoron progeny, an alpha spectrometer for the continuous air monitoring (CAM type) of radon and thoron has been realized. The constructive characteristics of the device are here presented together with energy and efficiency calibration. The device allows, by means of a screen type diffusion battery and a filter, to determinate the single radioactivity of each radionuclide of the progeny selecting them in relation to their diffusive behaviour (dichotomous particle size selection). The three-count filter method has been employed to measure the concentrations of 218 Po, 214 Pb and 214 Bi in air. Radon and thoron effective doses using a dosimetric, instead of an epidemiologic approach, will be then evaluated [it

  2. Brassinolide activities of 2alpha,3alpha-diols versus 3alpha,4alpha-diols in the bean second internode bioassay: Explanation by molecular modeling methods

    Czech Academy of Sciences Publication Activity Database

    Šíša, Miroslav; Vilaplana-Polo, M.; Ballesteros, C. B.; Kohout, Ladislav

    2007-01-01

    Roč. 72, 11/12 (2007), s. 740-750 ISSN 0039-128X R&D Projects: GA AV ČR 1QS510680561; GA MŠk 1M06030 Institutional research plan: CEZ:AV0Z40550506 Keywords : 3D-SAR * 3D-QSAR * biologically active steroids * brassinosteroids Subject RIV: CC - Organic Chemistry Impact factor: 2.143, year: 2007

  3. Activation of Peroxisome Proliferator-Activated Receptor Alpha Improves Aged and UV-Irradiated Skin by Catalase Induction.

    Science.gov (United States)

    Shin, Mi Hee; Lee, Se-Rah; Kim, Min-Kyoung; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

    2016-01-01

    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.

  4. 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)

    1991-01-01

    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).

  5. [Antiviral activity of recombinant interferon-alpha-2b in combination with certain antioxidant].

    Science.gov (United States)

    Vasil'ev, A N; Deriabin, P G; Galegov, G A

    2011-01-01

    In vitro activity of interferon-alpha-2b in combination with various antioxidants against the influenza virus and Herpes simplex was studied. The standard strains and a clinical strain of Herpes simplex isolated from a patient with resistance to acyclovir were used. The in vitro studie showed that antioxidants, such as alpho-tocoferol acetate (vitamin E), Unithiol and ascorbic acid had a significant antiinfluenzae and antiherpetic action on the influenza virus A/H5N1 and Herpes simplex variants. They protected up to 100% of the cell monolayer from the virus cytopathic effect. The taurin solutions had no antiviral activity irrespective of the infection dose. Combinations of interferon-alpha-2b with alpha-tocopherol acetate (vitamin E), Unithiol or ascorbic acid showed a significant synergistic effect: the antiviral activity of interferon increased several times. The antiinfluenza activity of interferon-a-2b in the presence of various concentrations of taurin did not change.

  6. 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

    1996-01-01

    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......, but present at a much lower level in preadipocytes, protects the same region between nucleotides -58 and -42 relative to the transcriptional start site. Electrophoretic mobility-shift analysis using nuclear extracts from adipose tissue or 3T3-L1 adipocytes and an oligonucleotide probe corresponding...... to a consensus C/EBP binding site at nucleotides -55 to -47 generated a specific protein-oligonucleotide complex that was supershifted by antibody against C/EBP alpha. Probes corresponding to two upstream consensus C/EBP binding sites failed to generate protein-oligonucleotide complexes. Cotransfection of a C...

  7. alpha-MSH activates immediate defense responses to UV-induced oxidative stress in human melanocytes.

    Science.gov (United States)

    Song, Xiuzu; Mosby, Nicole; Yang, Jennifer; Xu, Aie; Abdel-Malek, Zalfa; Kadekaro, Ana Luisa

    2009-12-01

    Exposure of cultured human melanocytes to ultraviolet radiation (UV) results in DNA damage. In melanoma, UV-signature mutations resulting from unrepaired photoproducts are rare, suggesting the possible involvement of oxidative DNA damage in melanocyte malignant transformation. Here we present data demonstrating immediate dose-dependent generation of hydrogen peroxide in UV-irradiated melanocytes, which correlated directly with a decrease in catalase activity. Pretreatment of melanocytes with alpha-melanocortin (alpha-MSH) reduced the UV-induced generation of 7,8-dihydro-8-oxyguanine (8-oxodG), a major form of oxidative DNA damage. Pretreatment with alpha-MSH also increased the protein levels of catalase and ferritin. The effect of alpha-MSH on 8-oxodG induction was mediated by activation of the melanocortin 1 receptor (MC1R), as it was absent in melanocytes expressing loss-of-function MC1R, and blocked by concomitant treatment with an analog of agouti signaling protein (ASIP), ASIP-YY. This study provides unequivocal evidence for induction of oxidative DNA damage by UV in human melanocytes and reduction of this damage by alpha-MSH. Our data unravel some mechanisms by which alpha-MSH protects melanocytes from oxidative DNA damage, which partially explain the strong association of loss-of-function MC1R with melanoma.

  8. A review of alpha activity in integrative brain function: fundamental physiology, sensory coding, cognition and pathology.

    Science.gov (United States)

    Başar, Erol

    2012-10-01

    Questions related to the genesis and functional correlates of the brain's alpha oscillations around 10Hz (Alpha) are one of the fundamental research areas in neuroscience. In recent decades, analysis of this activity has been not only the focus of interest for description of sensory-cognitive processes, but has also led to trials for establishing new hypotheses. The present review and the companion review aim to constitute an ensemble of "reasonings and suggestions" to understand alpha oscillations based on a wide range of accumulated findings rather than a trial to launch a new "alpha theory". The review starts with descriptions of earlier extracellular recordings, field potentials and also considers earlier alpha hypotheses. Analytical descriptions of evoked and event-related responses, event-related desynchronization, the relationship between spontaneous activity and evoked potentials, aging brain, pathology and alpha response in cognitive impairment are in the content of this review. In essence, the gamut of the survey includes a multiplicity of evidence on functional correlates in sensory processing, cognition, memory and vegetative system, including the spinal cord and heart. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Graham, J.M. Jr.; Krakow, D.; Smith, A.K.; Lachman, R.S.

    2001-01-01

    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.)

  10. Psychosocial Stress Increases Salivary Alpha-Amylase Activity Independently from Plasma Noradrenaline Levels.

    Directory of Open Access Journals (Sweden)

    Liubov Petrakova

    Full Text Available Salivary alpha-amylase activity (sAA and plasma noradrenaline (NA concentrations are often considered to be surrogate markers of sympathetic activation in response to stress. However, despite accumulating evidence for a close association between sAA and noradrenaline and other indicators of sympathetic activity, reliability and generality of this relation remains unclear. We employed the Trier Social Stress Test (TSST in order to directly compare the responses in sAA and NA to psychological stress in healthy volunteers (n = 23. The TSST significantly increased sAA and NA plasma levels with no significant differences in females and males. However, when subjects were divided according to their NA responses into low versus high responders, both groups did not significantly differ in their sAA before, during or after stress exposure. These data suggest that in response to acute psychological stress both plasma NA levels and sAA reflect sympathetic activity, however seemed to increase independently from each other.

  11. Alpha-amylase inhibitory activities of ascidians in the treatment of diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Antonyraj Selva Prabhu

    2014-12-01

    Full Text Available Extracts of ten selected ascidians with a reputation of usefulness in treating diabetes were examined for alpha-amylase inhibition using an in vitro model. The extract with the highest activity was selected for further characterization. From the results ethyl acetate showed predominant amylase inhibition activity for all species and the maximum level of inhibition was recorded in Phallusia mammillata (68% at 300 µg/mL and the lowest activity was noted in Microcosmus squamiger (12% at 200 µg/mL. After preliminary results, the methanolic extract of P. mammallita were further assayed for confirmation of enzyme inhibition and the maximum results (82% were obtained at 250 µg/mL and the IC50 value of P. mammillata were evidenced at 145.0 ± 0.4 µg/g. In the present study, P. mammillata indicated the maximum α-amylase activity without toxic effects. Similarly, α-glucosidase and α-amylase inhibitor bromophenol, C6H5BrO was produced by P. mammillata.

  12. 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.

    2008-01-01

    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

  13. Prestimulus alpha and mu activity predicts failure to inhibit motor responses.

    NARCIS (Netherlands)

    Mazaheri, A.; Nieuwenhuis, I.L.C.; Dijk, H.P. van; Jensen, O.

    2009-01-01

    Do certain brain states predispose humans to commit errors in monotonous tasks? We used MEG to investigate how oscillatory brain activity indexes the brain state in subjects performing a Go-noGo task. Elevated occipital alpha and sensorimotor mu activity just prior to the presentation of the stimuli

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

    Directory of Open Access Journals (Sweden)

    Hironori eNakatani

    2013-05-01

    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.

  15. Monitoring of gross alpha, gross beta and tritium activities in portuguese drinking waters

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, I.; Madruga, M.J.; Ferrador, G.O.; Sequeira, M.M.; Oliveira, E.J.; Gomes, A.R.; Rodrigues, F.D.; Carvalho, F.P. [Nuclear and Technological Institute/Dep. of Radiological Protection and Nuclear Safety (Portugal)

    2006-07-01

    The gross bend tritium activities in the forty Portuguese drinking waters analyzed using the ISO standard methods (Portuguese Guidelines) are below the guidance levels proposed in the Portuguese Drinking Water Quality Guidelines. In what concerns the gross alpha activity only 18% exceeded the recommended level. In general, it can be concluded that the ingestion of these drinking waters does not create a radiological hazard to the human consumption, however, more detailed analyses will be necessary mainly the determinations of the individual alpha emitters radionuclide concentrations. The minimum gross alpha and gross beta detectable activities by L.S.C. methodology are higher than for the proportional counting technique (ISO method). Higher concentration factors will be needed to reach lower required detection limits. (authors)

  16. Monitoring of gross alpha, gross beta and tritium activities in portuguese drinking waters

    International Nuclear Information System (INIS)

    Lopes, I.; Madruga, M.J.; Ferrador, G.O.; Sequeira, M.M.; Oliveira, E.J.; Gomes, A.R.; Rodrigues, F.D.; Carvalho, F.P.

    2006-01-01

    The gross beta and tritium activities in the forty Portuguese drinking waters analyzed using the ISO standard methods (Portuguese Guidelines) are below the guidance levels proposed in the Portuguese Drinking Water Quality Guidelines. In what concerns the gross alpha activity only 18% exceeded the recommended level. In general, it can be concluded that the ingestion of these drinking waters does not create a radiological hazard to the human consumption, however, more detailed analyses will be necessary mainly the determinations of the individual alpha emitters radionuclide concentrations. The minimum gross alpha and gross beta detectable activities by L.S.C. methodology are higher than for the proportional counting technique (ISO method). Higher concentration factors will be needed to reach lower required detection limits. (authors)

  17. The determination of plutonium alpha activity in urine, faeces and biological materials

    International Nuclear Information System (INIS)

    Bains, M.E.D.

    1963-07-01

    Methods have been developed for the determination of plutonium alpha activity in urine, faeces and biological materials. The chemical stages involved give practically complete separation of all extraneous material from the plutonium, which is electrodeposited on to a 0.5 inch stainless steel disc to produce a thin high resolution source. The limit of detection is 0.025 μμc/sample (sixteen-hour count) when the sources are counted in a small scintillator counter, but is lowest when counted in a counter which counts particles of energy 5.05-5.25 MeV only, and which therefore discriminates against small quantities of α-active materials introduced with the reagents in the final electrodeposition stage of the process. (Any such alpha activity may readily be identified by alpha pulse height analysis). (author)

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

    International Nuclear Information System (INIS)

    Kraljevic, P.; Emanovic, D.; Simpraga, M.; Nejedli, S.; Stojevic, Z.

    1996-01-01

    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 32 P 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 32 P. 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)

  19. Traditionally used plants in diabetes therapy: phytotherapeutics as inhibitors of alpha-amylase activity

    Directory of Open Access Journals (Sweden)

    Ingrid Funke

    Full Text Available Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycaemia. There are many and diverse therapeutic strategies in the management of Type 2 diabetes. The inhibition of alpha-amylase activity is only one possibility to lower postprandial blood glucose levels. In our in-vitro studies we could demonstrate that different plants, mostly traditionally used in common diabetic therapy in Africa or Europe, are able to inhibit alpha-amylase, which is responsible for the breakdown of oligosaccharides into monosaccharides which are absorbed. An inhibition of alpha-amylase activity of 90% was seen with the extract of the leaves of Tamarindus indica. To quantify inhibtion rates, acarbose was used (IC50: 23.2 µM. Highest inhibition level of acarbose in our testmodel was about 85%. Additionally tests with pure polyphenolic compounds might explain the biological activity of the selected plants.

  20. Blocking of irrelevant memories by posterior alpha activity boosts memory encoding.

    Science.gov (United States)

    Park, Hyojin; Lee, Dong Soo; Kang, Eunjoo; Kang, Hyejin; Hahm, Jarang; Kim, June Sic; Chung, Chun Kee; Jensen, Ole

    2014-08-01

    In our daily lives, we are confronted with a large amount of information. Because only a small fraction can be encoded in long-term memory, the brain must rely on powerful mechanisms to filter out irrelevant information. To understand the neuronal mechanisms underlying the gating of information into long-term memory, we employed a paradigm where the encoding was directed by a "Remember" or a "No-Remember" cue. We found that posterior alpha activity increased prior to the "No-Remember" stimuli, whereas it decreased prior to the "Remember" stimuli. The sources were localized in the parietal cortex included in the dorsal attention network. Subjects with a larger cue-modulation of the alpha activity had better memory for the to-be-remembered items. Interestingly, alpha activity reflecting successful inhibition following the "No-Remember" cue was observed in the frontal midline structures suggesting preparatory inhibition was mediated by anterior parts of the dorsal attention network. During the presentation of the memory items, there was more gamma activity for the "Remember" compared to the "No-Remember" items in the same regions. Importantly, the anticipatory alpha power during cue predicted the gamma power during item. Our findings suggest that top-down controlled alpha activity reflects attentional inhibition of sensory processing in the dorsal attention network, which then finally gates information to long-term memory. This gating is achieved by inhibiting the processing of visual information reflected by neuronal synchronization in the gamma band. In conclusion, the functional architecture revealed by region-specific changes in the alpha activity reflects attentional modulation which has consequences for long-term memory encoding. Copyright © 2014 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Paul eSauseng

    2011-10-01

    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.

  2. 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: byhwang@chungbuk.ac.kr [College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763 (Korea, Republic of); Lee, Sung-Joon, E-mail: junelee@korea.ac.kr [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)

    2012-06-15

    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.

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

    Directory of Open Access Journals (Sweden)

    Sugawara A.M.

    2001-01-01

    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.

  4. Inhibitory Effect of Heracleum persicum and Ziziphus jujuba on Activity of Alpha-Amylase

    Directory of Open Access Journals (Sweden)

    Reza Afrisham

    2015-01-01

    Full Text Available Postprandial hyperglycemia plays an important role in the development of type 2 diabetes. Inhibition of alpha-amylase was led to a delay in breaks down of starch and glycogen and prevented a rapid rise in blood sugar. Alpha-amylase was isolated by gel filtration chromatography Sephadex G-75 from bovine pancreas. Then, total methanolic extracts of plants were prepared and IC50 values of extracts on alpha-amylase were obtained and compared with acarbose IC50. The polyphenolic content of extracts and antioxidant capacity were determined by Folin-Ciocalteu test and DPPH test, respectively. The specific activity of alpha-amylase was 48.2 U/mg. For inhibition of alpha-amylase, IC50 values of H. persicum, Z. jujuba, and acarbose were 307, 827, and 113 μg/ml, respectively. For inhibition of DPPH radical, IC50 values of extracts were 235 and 701 μg/ml. Total phenolic contents of methanol extracts were 73.8±3.2 and 44.2±1.8 μg tannic acid equivalent/mg extract. Acarbose causes gastrointestinal symptoms and liver toxicity, but H. persicum and Z. jujuba decrease these side effects and prevent gastrointestinal disorders. Due to the high polyphenolic content and antioxidant capacity of these plants and significant inhibitory effect of the plants on alpha-amylase, these plants can be proposed for treatment of diabetic patients.

  5. Expression of triplicated and quadruplicated alpha globin genes in sheep.

    Science.gov (United States)

    Vestri, R; Pieragostini, E; Yang, F; di Gregorio, P; Rando, A; Masina, P

    1991-01-01

    In the sheep alpha alpha alpha globin gene haplotype, the three genes display from the 5' to the 3' end the percentage efficiencies of about 30:14:6, as indicated by the amounts of the three types of alpha chain produced in the alpha alpha alpha/alpha alpha alpha homozygotes. The 3' gene in the alpha alpha alpha alpha haplotype appears to have an efficiency around 1%, as suggested by analysis of one quadruple alpha homozygote. Moreover, the total outputs of the alpha alpha alpha as well as of the alpha alpha alpha alpha haplotypes do not substantially differ from that of the common alpha alpha haplotype.

  6. HNF1 alpha activates the aminopeptidase N promoter in intestinal (Caco-2) cells

    DEFF Research Database (Denmark)

    Olsen, Jørgen; Laustsen, Lotte; Troelsen, J

    1994-01-01

    The importance of HNF1 binding proteins for intestinal aminopeptidase N expression was investigated using the Caco-2 cell-line. Aminopeptidase N promoter activity in Caco-2 cells depends on the HNF1 element (positions -85 to -58) and co-transfection with an HNF1 alpha expression vector demonstrates...... a direct activation of the promoter by HNF1 alpha through this element. Electrophoretic mobility shift assays using nuclear extracts from Caco-2 cells show the presence of high amounts of HNF1 binding proteins irrespective of their state of differentiation....

  7. The effect of carbohydrates on alpha-amylase activity measurements

    NARCIS (Netherlands)

    Baks, T.; Janssen, A.E.M.; Boom, R.M.

    2006-01-01

    The Ceralpha method can be used for ¿-amylase activity measurements during the hydrolysis of starch at high substrate concentrations (>40 wt.%). However, the results are affected by the carbohydrates present in the samples. The effect of carbohydrates on the Ceralpha ¿-amylase activity

  8. 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

    2012-01-01

    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...

  9. Development of embryos in superovulated guinea pigs following active immunization against the inhibin alpha-subunit.

    Science.gov (United States)

    Shi, F; Mochida, K; Suzuki, O; Matsuda, J; Ogura, A; Tsonis, C G; Watanabe, G; Suzuki, A K; Taya, K

    2000-08-01

    Embryo recovery and subsequent embryonic development from guinea pigs treated with or without inhibin vaccines were compared to determine the effect of active immunization against the inhibin alpha-subunit. Twenty female guinea pigs of the Hartley strain were injected 3 times either with 1 ml inhibin vaccine (recombinant ovine inhibin a-subunit in oil emulsion: 50 microg/ml, inhibin-immunized group), or 1 ml placebo (saline in oil emulsion; control group) at 4 week intervals. After one estrous cycle following the last injection, females were naturally mated and embryos were collected at 11:00 hr of day 6 of pregnancy (Day 1: sperm in the vaginal smear) for culture in vitro. Active immunization increased the number of corpora lutea (12.6+/-3.0 vs. 4.6+/-0.2, P0.05). During subsequent 8 day culture in vitro, most of the recovered embryos formed trophoblast outgrowth; 100% (14/14) and 88.2% (15/17) in control and immunized groups, respectively. High levels of inhibin antibody titers were sustained in the inhibin-immunized guinea pigs at least for 5 months after the last injection while no antibody titer was detected in the control animals. These results indicate that active immunization against the inhibin a-subunit is a long-acting and efficient method to induce superovulation with normal embryonic development in the guinea pig.

  10. Determination of total alpha activity index in samples of radioactive wastes

    International Nuclear Information System (INIS)

    Galicia C, F. J.

    2015-01-01

    This study aimed to develop a methodology of preparation and quantification of samples containing radionuclides beta and/or alpha emitters, to determine the rates of alpha and beta total activity of radioactive waste samples. For this, a device of planchettes preparer was designed, to assist the planchettes preparation in a controlled environment and free of corrosive vapors. Planchettes were prepared in three means: nitrate, carbonate and sulfate, to different mass thickness, natural uranium (alpha and beta emitter) and in case of Sr-90 (beta emitter pure) only in half nitrate; and these planchettes were quantified in an alpha/beta counter, in order to construct the self-absorption curves for alpha and beta particles. These curves are necessary to determine the rate of alpha-beta activity of any sample because they provide the self-absorption correction factor to be applied in calculating the index. Samples with U were prepared with the help of the device of planchettes preparer and subsequently were analyzed in the proportional counter Mpc-100 Pic brand. Samples with Sr-90 were prepared without the device to see if there was a different behavior with respect to obtaining mass thickness. Similarly they were calcined and carried out count in the Mpc-100. To perform the count, first the parameters of counter operating were determined: operating voltages for alpha and beta particles 630 and 1500 V respectively, a count routine was generated where the time and count type were adjusted, and counting efficiencies for alpha and beta particles, with the aid of calibration sources of 210 Po for alphas and 90 Sr for betas. According to the results, the counts per minute will decrease as increasing the mass thickness of the sample (self-absorption curve), adjusting this behavior to an exponential function in all cases studied. The minor self-absorption of alpha and beta particles in the case of U was obtained in sulfate medium. The self-absorption curves of Sr-90 follow the

  11. Innovative procedure for the determination of gross-alpha/gross-beta activities in drinking water

    International Nuclear Information System (INIS)

    Wisser, S.; Frenzel, E.; Dittmer, M.

    2006-01-01

    An alternative sample preparation method for the determination of gross-alpha/beta activity concentrations in drinking water is introduced in this paper. After the freeze-drying of tap water samples, determination by liquid scintillation counting can be applied utilizing alpha/beta separation. It has been shown that there is no adsorption or loss of solid radionuclides during the freeze-drying procedure. However, the samples have to be measured quickly after the preparation since the ingrowth of daughter isotopes negatively effects the measurement. The limits of detection for gross-alpha and gross-beta activity are in the range 25-210 mBq/l, respectively, for a measurement time of only 8-9 h

  12. Prediction of Active Site and Distal Residues in E. coli DNA Polymerase III alpha Polymerase Activity.

    Science.gov (United States)

    Parasuram, Ramya; Coulther, Timothy A; Hollander, Judith M; Keston-Smith, Elise; Ondrechen, Mary Jo; Beuning, Penny J

    2018-02-20

    The process of DNA replication is carried out with high efficiency and accuracy by DNA polymerases. The replicative polymerase in E. coli is DNA Pol III, which is a complex of 10 different subunits that coordinates simultaneous replication on the leading and lagging strands. The 1160-residue Pol III alpha subunit is responsible for the polymerase activity and copies DNA accurately, making one error per 10 5 nucleotide incorporations. The goal of this research is to determine the residues that contribute to the activity of the polymerase subunit. Homology modeling and the computational methods of THEMATICS and POOL were used to predict functionally important amino acid residues through their computed chemical properties. Site-directed mutagenesis and biochemical assays were used to validate these predictions. Primer extension, steady-state single-nucleotide incorporation kinetics, and thermal denaturation assays were performed to understand the contribution of these residues to the function of the polymerase. This work shows that the top 15 residues predicted by POOL, a set that includes the three previously known catalytic aspartate residues, seven remote residues, plus five previously unexplored first-layer residues, are important for function. Six previously unidentified residues, R362, D405, K553, Y686, E688, and H760, are each essential to Pol III activity; three additional residues, Y340, R390, and K758, play important roles in activity.

  13. Topographic distribution of EEG alpha activity during ethanol-induced intoxication in women.

    Science.gov (United States)

    Lukas, S E; Mendelson, J H; Woods, B T; Mello, N K; Teoh, S K

    1989-03-01

    Topographic maps of brain electrical activity from scalp EEG electrodes were obtained from healthy adult female volunteers using a Brain Electrical Activity Mapping (BEAM) system. Each woman received both ethanol (0.7 g/kg, p.o.) and placebo in a counterbalanced order under double-blind conditions at an interval of 1-6 days. Subjective reports of intoxication were obtained continuously via an instrumental joystick device. Subjects reported when they detected ethanol and qualitatively pleasant (i.e., euphoric) or unpleasant (i.e., dysphoric) effects. All subjects reliably discriminated ethanol from placebo. Pronounced increases in EEG alpha activity occurred during ethanol-induced intoxication in all subjects. Analysis of topographic maps revealed that the distribution of high-amplitude, fast-frequency EEG alpha activity extended further frontally to the central sulcus and temporally during ethanol intoxication than during control sessions or after placebo administration. Area analysis and significant probability mapping techniques were used to quantify the increased alpha activity and to monitor changes during the process of intoxication in each individual. One woman, with a positive family history of alcoholism, experienced only a mild degree of ethanol intoxication. This behavioral response was accompanied by a slight decrease or no change in both slow- and fast-frequency alpha activity. This finding in a single subject provides additional evidence that a possible genetic predisposition for ethanol-related effects on behavior may be reflected in measures of brain electrical activity. Overall, these data also suggest that ethanol induces rapid and widespread increases in EEG alpha activity which may be associated with the reinforcing properties of ethanol.

  14. Stabilization of the activated alphaMbeta2 integrin by a small molecule inhibits leukocyte migration and recruitment.

    Science.gov (United States)

    Björklund, Mikael; Aitio, Olli; Stefanidakis, Michael; Suojanen, Juho; Salo, Tuula; Sorsa, Timo; Koivunen, Erkki

    2006-03-07

    Integrins are potential targets for the development of antiinflammatory agents. Here we develop a novel high-throughput assay by allowing a chemical library to compete with phage display peptide binding and identify a novel small-molecule ligand to the leukocyte-specific alpha(M)beta(2) integrin. The identified thioxothiazolidine-containing compound, IMB-10, had an unexpected activity in that it stabilized binding of alpha(M)beta(2) to its endogenous ligands proMMP-9 and fibrinogen. Single amino acid substitutions in the activity-regulating C-terminal helix and the underlying region in the ligand-binding I domain of the integrin suppressed the effect of IMB-10. A computational model indicated that IMB-10 occupies a distinct cavity present only in the activated form of the integrin I domain. IMB-10 inhibited alpha(M)beta(2)-dependent migration in vitro and inflammation-induced neutrophil emigration in vivo. Stabilization of integrin-mediated adhesion by a small molecule is a novel means to inhibit cell migration and may have a utility in treatment of inflammatory diseases involving leukocyte recruitment.

  15. Kinesthetic and vestibular information modulate alpha activity during spatial navigation: a mobile EEG study.

    Science.gov (United States)

    Ehinger, Benedikt V; Fischer, Petra; Gert, Anna L; Kaufhold, Lilli; Weber, Felix; Pipa, Gordon; König, Peter

    2014-01-01

    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 2 × 2 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. Kinesthetic and Vestibular Information Modulate Alpha Activity during Spatial Navigation: A Mobile EEG Study

    Directory of Open Access Journals (Sweden)

    Benedikt Valerian Ehinger

    2014-02-01

    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.

  17. Increased event-related potentials and alpha-, beta- and gamma-activity associated with intentional actions

    Directory of Open Access Journals (Sweden)

    Susanne eKarch

    2016-01-01

    Full Text Available Objective: Internally guided actions are defined as being purposeful, self-generated and offering choices between alternatives. Intentional actions are essential to reach individual goals. In previous empirical studies, internally guided actions were predominantly related to functional responses in frontal and parietal areas. The aim of the present study was to distinguish event-related potentials and oscillatory responses of intentional actions and externally guided actions. In addition, we compared neurobiological findings of the decision which action to perform with those referring to the decision whether or not to perform an action. Methods: Twenty-eight subjects participated in adapted go/nogo paradigms, including a voluntary selection condition allowing participants to [1] freely decide whether to press the response button or [2] to decide whether they wanted to press the response button with the right index finger or the left index finger. Results: The reaction times were increased when participants freely decided whether and how they wanted to respond compared to the go condition. Intentional processes were associated with a fronto-centrally located N2 and P3 potential. N2 and P3 amplitudes were increased during intentional actions compared to instructed responses (go. In addition, increased activity in the alpha-, beta- and gamma-frequency range was shown during voluntary behaviour rather than during externally-guided responses. Conclusion: These results may indicate that an additional cognitive process is needed for intentional actions compared to instructed behaviour. However, the neural responses were comparatively independent of the kind of decision that was made (1. decision which action to perform; 2. decision whether or not to perform an action. Significance: The study demonstrates the importance of fronto-central alpha-, beta- and gamma oscillations for voluntary behaviour.

  18. rTMS induced tinnitus relief is related to an increase in auditory cortical alpha activity.

    Directory of Open Access Journals (Sweden)

    Nadia Müller

    Full Text Available Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom. A promising approach for the treatment of tinnitus is repetitive transcranial magnetic stimulation (rTMS as this directly affects tinnitus-related brain activity. Several studies indeed show tinnitus relief after rTMS, however effects are moderate and vary strongly across patients. This may be due to a lack of knowledge regarding how rTMS affects oscillatory activity in tinnitus sufferers and which modulations are associated with tinnitus relief. In the present study we examined the effects of five different stimulation protocols (including sham by measuring tinnitus loudness and tinnitus-related brain activity with Magnetoencephalography before and after rTMS. Changes in oscillatory activity were analysed for the stimulated auditory cortex as well as for the entire brain regarding certain frequency bands of interest (delta, theta, alpha, gamma. In line with the literature the effects of rTMS on tinnitus loudness varied strongly across patients. This variability was also reflected in the rTMS effects on oscillatory activity. Importantly, strong reductions in tinnitus loudness were associated with increases in alpha power in the stimulated auditory cortex, while an unspecific decrease in gamma and alpha power, particularly in left frontal regions, was linked to an increase in tinnitus loudness. The identification of alpha power increase as main correlate for tinnitus reduction sheds further light on the pathophysiology of tinnitus. This will hopefully stimulate the development of more effective therapy approaches.

  19. rTMS Induced Tinnitus Relief Is Related to an Increase in Auditory Cortical Alpha Activity

    Science.gov (United States)

    Müller, Nadia; Lorenz, Isabel; Langguth, Berthold; Weisz, Nathan

    2013-01-01

    Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom. A promising approach for the treatment of tinnitus is repetitive transcranial magnetic stimulation (rTMS) as this directly affects tinnitus-related brain activity. Several studies indeed show tinnitus relief after rTMS, however effects are moderate and vary strongly across patients. This may be due to a lack of knowledge regarding how rTMS affects oscillatory activity in tinnitus sufferers and which modulations are associated with tinnitus relief. In the present study we examined the effects of five different stimulation protocols (including sham) by measuring tinnitus loudness and tinnitus-related brain activity with Magnetoencephalography before and after rTMS. Changes in oscillatory activity were analysed for the stimulated auditory cortex as well as for the entire brain regarding certain frequency bands of interest (delta, theta, alpha, gamma). In line with the literature the effects of rTMS on tinnitus loudness varied strongly across patients. This variability was also reflected in the rTMS effects on oscillatory activity. Importantly, strong reductions in tinnitus loudness were associated with increases in alpha power in the stimulated auditory cortex, while an unspecific decrease in gamma and alpha power, particularly in left frontal regions, was linked to an increase in tinnitus loudness. The identification of alpha power increase as main correlate for tinnitus reduction sheds further light on the pathophysiology of tinnitus. This will hopefully stimulate the development of more effective therapy approaches. PMID:23390539

  20. Alpha-L-Fucosidase Serves as a Prognostic Indicator for Intrahepatic Cholangiocarcinoma and Inhibits Its Invasion Capacity

    Directory of Open Access Journals (Sweden)

    Zeyu Shuang

    2018-01-01

    Full Text Available Alpha-L-fucosidase (AFU has been reported to be a predictor of survival in patients with several cancers, but it is unclear whether AFU is associated with prognosis in patients with intrahepatic cholangiocarcinoma (iCCA. In this study, we used receiver operating characteristic (ROC analysis to generate the cutoff point of AFU for overall survival (OS. The prognostic influence of the AFU level in serum on OS was studied using Kaplan-Meier curves. Moreover, invasion assays and Western blotting were performed to explore the effects of AFU on iCCA invasion in vitro. We found that higher AFU levels (≥20.85 U/L were significantly associated with favorable median OS (44.3 months versus 20.1 months; P=0.022 in iCCA patients. Cox regression models’ analyses showed that the AFU level was an independent predictor for OS (P=0.006. Moreover, our results revealed that the AFU could impair the invasion capability of the iCCA cells, HuH28, and also downregulated the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. In conclusion, our results indicate that AFU is a significantly favorable prognostic factor in iCCA patients.

  1. Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha.

    Science.gov (United States)

    Li, Guolin; Brocker, Chad N; Yan, Tingting; Xie, Cen; Krausz, Kristopher W; Xiang, Rong; Gonzalez, Frank J

    2018-01-01

    Peroxisome proliferator-activated receptor alpha (PPARA) is a major regulator of fatty acid oxidation and severe hepatic steatosis occurs during acute fasting in Ppara-null mice. Thus, PPARA is considered an important mediator of the fasting response; however, its role in other fasting regiments such as every-other-day fasting (EODF) has not been investigated. Mice were pre-conditioned using either a diet containing the potent PPARA agonist Wy-14643 or an EODF regimen prior to acute fasting. Ppara-null mice were used to assess the contribution of PPARA activation during the metabolic response to EODF. Livers were collected for histological, biochemical, qRT-PCR, and Western blot analysis. Acute fasting activated PPARA and led to steatosis, whereas EODF protected against fasting-induced hepatic steatosis without affecting PPARA signaling. In contrast, pretreatment with Wy-14,643 did activate PPARA signaling but did not ameliorate acute fasting-induced steatosis and unexpectedly promoted liver injury. Ppara ablation exacerbated acute fasting-induced hypoglycemia, hepatic steatosis, and liver injury in mice, whereas these detrimental effects were absent in response to EODF, which promoted PPARA-independent fatty acid metabolism and normalized serum lipids. These findings indicate that PPARA activation prior to acute fasting cannot ameliorate fasting-induced hepatic steatosis, whereas EODF induced metabolic adaptations to protect against fasting-induced steatosis without altering PPARA signaling. Therefore, PPARA activation does not mediate the metabolic adaptation to fasting, at least in preventing acute fasting-induced steatosis. Published by Elsevier GmbH.

  2. Purification and characterization of neutral alpha-mannosidase from hen oviduct: studies on the activation mechanism of Co2+.

    Science.gov (United States)

    Yamashiro, K; Itoh, H; Yamagishi, M; Natsuka, S; Mega, T; Hase, S

    1997-12-01

    Neutral alpha-mannosidase was purified to homogeneity from hen oviduct. The molecular mass of the enzyme was 480 kDa on gel filtration, and the 110-kDa band on SDS-PAGE in the presence of 2-mercaptoethanol indicated that it is composed of four subunits. The activated enzyme hydrolyzed both p-nitrophenyl alpha-D-mannoside and high mannose-type sugar chains. This substrate specificity is almost the same as that reported for the neutral a-mannosidase from Japanese quail oviduct [Oku and Hase (1991) J. Biochem. 110, 982-989]. Manalpha1-6(Manalpha1-3)Manalpha1-6(Manalpha1-3) Manbeta1-4GlcNAc (Km =0.44 mM) was hydrolyzed four times faster than Manalpha1-6(Manalpha1-3)Manalpha1-6(Manalpha1-3) Manbeta1-4GIcNAcbeta1-4GlcNAc, and Manalpha1-6(Manalpha1-2Manalpha1-2Manalpha1-3)++ +Manbeta1-4GlcNAc was obtained as the end product from Man9GlcNAc on digestion with the activated alpha-mannosidase. The enzyme was activated 24-fold on preincubation with Co2+. The activation with other metal ions, like Mn2+, Ca2+, Fe2+, Fe3+, and Sr2+, was less than 5-fold, and Zn2+, Cu2+, and Hg2+ inhibited the enzyme activity. The optimum pHs for both the enzyme activity and activation with Co2+ were around 7. The cobalt ion contents of the purified, EDTA-treated, and Co2+-activated enzymes were 1.5, 0.0, and 3.9, respectively, per molecule. Since the Co2+-activated enzyme gradually lost its activity on incubation with EDTA and the activity was restored promptly on the addition of Co2+, the binding of Co2+ to the enzyme seems to be essential for its activation. The results obtained with protease inhibitors together with those of the SDS-PAGE before and after activation, showed that the proteolytic cleavage reported for the activation of monkey brain alpha-mannosidase seems not to be involved.

  3. Nonenzymatic palmitoylation at Cys 3 causes extra-activation of the alpha-subunit of the stimulatory GTP-binding protein Gs.

    Science.gov (United States)

    Mollner, S; Ferreira, P; Beck, K; Pfeuffer, T

    1998-10-01

    Treatment of crude stimulatory GTP-binding protein of adenylyl cyclase (Gs) from turkey erythrocyte membranes with hydroxylamine results in twofold enhancement of adenylyl cyclase activity following reconstitution with adenylyl cyclase type V expressed in Spodoptera frugiperda cells (Sf9) cells. Enhancement by hydroxylamine of immunoaffinity purified Gs was still 1.5-fold, while that of Gs purified according to the multiple-step procedure by Northup, J. K., Sternweis, P. C., Smigel, M. D., Schleifer, L. S., Ross, E. M. & Gilman, A. G. (Proc. Natl Acad. Sci. USA 78, 6516-6520, 1980) was close to unity. The alpha-subunit of the stimulatory GTP-binding protein expressed in Escherichia coli (r(alpha)s), likewise, failed to show an effect by hydroxylamine. Surprisingly, guanosine 5'-O-(3-thiotriphosphate) (GTP[S])-liganded r(alpha)s, treated with palmitoyl-CoA for 14 h at 4 degrees C resulted in sixfold enhancement of reconstitutive activity. In contrast, that of the GDP-liganded r(alpha)s(beta)gamma heterotrimer was not improved by palmitoylation and consecutive activation with GTP[S], although incorporation of [3H]palmitate into momomer and heterotrimer was identical. While adenylyl cyclase type-V activity reconstituted by r(alpha)s x GTP[S] was not influenced by betagamma-subunits, that activated by palmitoylated r(alpha)s x GTP[S] was considerably inhibited, suggesting a higher affinity of palmitoylated r(alpha)s for betagamma-subunits. On treatment of either form with the proteinase Lys-C, less than 25% of the label was found in a stable M(r) 38000 fragment with intact C terminus, but lacking the N-terminal portion. Absence of the latter did not affect activation by r(alpha)s, but caused a >90% loss of extra-activation by palmitoylated r(alpha)s. The results also indicate that nonenzymatic, much in the same way as physiological enzymatic, palmitoylation of alpha(s) occurs predominantly on Cys 3.

  4. Microhemodynamic indices to evaluate the effectiveness of herbal medicine in diabetes: A comparison between alpha-mangostin and curcumin in the retina of type 2 diabetic rats.

    Science.gov (United States)

    Jariyapongskul, Amporn; Areebambud, Chonticha; Hideyuki, Niimi

    2018-01-10

    This study was aimed to develop microhemodynamic indices to evaluate the effectiveness of herbal medicine in diabetic tissues. Male Sprague-Dawley rats were divided into four groups: normal control rats (Control), type 2 diabetic rats without (DM2) and with supplementation of alpha mangostin (DM2-MG) or curcumin (DM2-CUR). Alpha-mangostin or curcumin (200 mg/kg BW) were fed followed by i.p. injection of streptozotocin (STZ). Mean arterial pressure (MAP) and retinal blood flow (RBF) were measured and retinal flow resistance (RFR) was calculated. Three indices were developed to evaluate the effectiveness of herbal medicines in RFR-MAP diagram based on experimental data of MAP and RFR in type 2 diabetic rats. These indices are α, β, and γ where α is a ratio of reduction in MAP, β is a ratio of reduction in RFR increasing with MAP increase, and γ indicates a ratio of reduction in RFR. The elevated MAP and RFR and decreased RBF were observed in DM2 rats.Interestingly, alpha-mangostin or curcumin supplementation significantly increased RBF while decreased MAP and RFR. Using α, β and γ indices, it was found that alpha-mangostin is more effective than curcumin in type 2 diabetic retina. These microhemodynamic indices may be useful to compare various herbal medicines in different tissues.

  5. Alpha contamination assessment for D ampersand D activities: Monitoring pipe interiors

    International Nuclear Information System (INIS)

    Rawool-Sullivan, M.W.; Conaway, J.G.; MacArthur, D.W.; Vaccarella, J.

    1996-02-01

    We have developed a prototype instrument capable of assessing alpha-emitting contamination on interior surfaces of ducts, pipes, tanks, and other enclosed volumes without inserting a probe. Air is drawn through the potentially contaminated volume and then through a detection grid, where ions created in the air by alpha particles are collected and the resulting charge measured with a sensitive electrometer. A filter at the intake end of the contaminated volume excludes externally created ions, so only ions generated inside the volume are detected. We have studied the response of this prototype in initial experiments using calibrated alpha sources with various pipe diameters and configurations, air flows, and source locations in the pipes. The results of these experiments indicate that this method can be an effective approach to assessing internal contamination

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

    International Nuclear Information System (INIS)

    Garcia-Torano, E.; Acena, M.L.

    1989-01-01

    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)

  7. Synthesis of a structurally constrained endoperoxide having antimalarial activity from alpha-santonin

    CSIR Research Space (South Africa)

    Van der Westhuyzen, CW

    2005-01-01

    Full Text Available Alpha-Santonin 3 was successfully converted into a biologically active compound 5b containing an endoperoxide group through a photo-oxygenation approach as a single isomer. It was found that the singlet oxygen afforded the isomer produced by attack...

  8. changes in the composition of the pulp, alpha-amylase activity and ...

    African Journals Online (AJOL)

    DJFLEX

    The laboratory rotting of Egusi Fruits was completed in 120 hours. At this stage pulp became soft and the seeds were extracted easily with the fingers. The changes in the composition of the pulp, alpha-amylase activity and titratable acidity during the controlled rotting of egusi fruit (Colocynthis citrullus L.) for the harvesting of ...

  9. Changes in the composition of the pulp, alpha-amylase activity and ...

    African Journals Online (AJOL)

    The laboratory rotting of Egusi Fruits was completed in 120 hours. At this stage pulp became soft and the seeds were extracted easily with the fingers. The changes in the composition of the pulp, alpha-amylase activity and titratable acidity during the controlled rotting of egusi fruit (Colocynthis citrullus L.) for the harvesting of ...

  10. Drotrecogin alpha (activated) in two patients with the hantavirus cardiopulmonary syndrome

    OpenAIRE

    McDermid, Robert C; Gibney, RT Noel; Brisebois, Ronald J; Skjodt, Neil M

    2006-01-01

    Hantavirus cardiopulmonary syndrome (HCPS) is associated with rapid cardiopulmonary collapse from endothelial injury, resulting in massive capillary leak, shock and severe hypoxemic respiratory failure. To date, treatment remains supportive and includes mechanical ventilation, vasopressors and extracorporeal membrane oxygenation, with mortality approaching 50%. Two HCPS survivors initially given drotrecogin alpha (activated) (DAA) for presumed bacterial septic shock are described. Vasoactive ...

  11. An alpha-glucosidase inhibitory activity of thermostable lectin ...

    African Journals Online (AJOL)

    A novel GI lectin was enriched from the seeds of the Djenkol bean, A. jiringa, to apparent homogeneity by 90% saturation ammonium sulfate precipitation and Con A-Sepharose affinity column chromatography. This lectin had an IC50 value for GI activity of 0.031 „b 0.02 mg/ml, an estimated molecular mass of 35.7 kDa, ...

  12. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor suppressor in hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Rui; Zhang, Haiyang; Zhang, Yan; Li, Shuang; Wang, Xinyi; Wang, Xia; Wang, Cheng; Liu, Bin; Zen, Ke; Zhang, Chen-Yu; Zhang, Chunni; Ba, Yi

    2017-04-01

    Peroxisome proliferator-activated receptor gamma coactivator-1 alpha plays a crucial role in regulating the biosynthesis of mitochondria, which is closely linked to the energy metabolism in various tumors. This study investigated the regulatory role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha in the pathogenesis of hepatocellular carcinoma. In this study, the changes of peroxisome proliferator-activated receptor gamma coactivator-1 alpha messenger RNA levels between normal human liver and hepatocellular carcinoma tissue were examined by quantitative reverse transcription polymerase chain reaction. Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by RNA interference in the human liver cell line L02, while overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha complementary DNA in the human hepatocarcinoma cell line HepG2. Cellular morphological changes were observed via optical and electron microscopy. Cellular apoptosis was determined by Hoechst 33258 staining. In addition, the expression levels of 21,400 genes in tissues and cells were detected by microarray. It was shown that peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression was significantly downregulated in hepatocellular carcinoma compared with normal liver tissues. After knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression in L02 cells, cells reverted to immature and dedifferentiated morphology exhibiting cancerous tendency. Apoptosis occurred in the HepG2 cells after transfection by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Microarray analysis showed consistent results. The results suggest that peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor

  13. Activation of alpha6-containing GABAA receptors by pentobarbital occurs through a different mechanism than activation by GABA.

    Science.gov (United States)

    Fisher, Matthew T; Fisher, Janet L

    2010-03-08

    The GABA(A) receptors are ligand-gated chloride channels which are the targets for many clinically used sedatives, including the barbiturates. The barbiturate pentobarbital acts through multiple sites on the GABA(A) receptor. At low concentrations (muM), it acts as a positive allosteric modulator while at higher concentrations it can directly activate the receptor. This agonist action is influenced by the subunit composition of the receptor, and pentobarbital is a more effective agonist than GABA only at receptors containing an alpha6 subunit. The conformational change that translates GABA binding into channel opening is known to involve a lysine residue located in an extracellular domain between the 2nd and 3rd transmembrane domains. Mutations of this residue disrupt activation of the channel by GABA and have been linked to inherited epilepsy. Pentobarbital binds to the receptor at a different agonist site than GABA, but could use a common signal transduction mechanism to gate the channel. To address this question, we compared the effect of a mutating the homologous lysine residue in the alpha1 or alpha6 subunits (K278 or K277, respectively) to methionine on direct activation of recombinant GABA(A) receptors by GABA or pentobarbital. We found that this mutation reduced GABA sensitivity for both alpha1 and alpha6 subunits, but affected pentobarbital sensitivity only for the alpha1 subunit. This suggests that pentobarbital acts through a distinct signal transduction pathway at the alpha6 subunit, which may account for its greater efficacy compared to GABA at receptors containing this subunit.

  14. Geomagnetic Activity Indicates Large Amplitude for Sunspot Cycle 24

    Science.gov (United States)

    Hathaway, David H.

    2006-01-01

    The level of geomagnetic activity near the time of solar activity minimum has been shown to be a reliable indicator for the amplitude of the following solar activity maximum. The geomagnetic activity index aa can be split into two components: one associated with solar flares, prominence eruptions, and coronal mass ejections which follows the solar activity cycle and a second component associated with recurrent high speed solar wind streams which is out of phase with the solar activity cycle. This second component often peaks before solar activity minimum and has been one of the most reliable indicators for the amplitude of the following maximum. The size of the recent maximum in this second component indicates that solar activity cycle 24 will be much higher than average - similar in size to cycles 21 and 22 with a peak smoothed sunspot number of 160 plus or minus 25.

  15. Low level alpha activity measurements with pulse shape discrimination

    International Nuclear Information System (INIS)

    Noguchi, Masayasu; Satoh, Kaneaki; Higuchi, Hideo.

    1984-01-01

    Pulse shape discrimination of α and β rays with liquid scintillation counting was investigated for the purpose of low level α activity measurements. Various liquid scintillators for pulse shape discrimination were examined by means of pulse rise time analysis. A new scintillator of low cost and of superior characteristics was found. The figure of merits better than 3.5 in risetime spectrum and the energy resolution better than 9% were obtained for carefully prepared samples. The background counting rate for a sample of 10 ml was reduced to 0.013 cpm/MeV in the range of α ray energy 5 to 7 MeV. (author)

  16. A study of excess H-alpha emission in chromospherically active M dwarf

    International Nuclear Information System (INIS)

    Young, A.; Skumanich, A.; Stauffer, J.R.; Harlan, E.; Bopp, B.W.

    1989-01-01

    Spectroscopic observations from three observatories are combined to study the properties of the excess H-alpha emission which characterizes the most chromospherically active subset of the M dwarf stars, known as the dMe stars. It is demonstrated that the excess H-alpha luminosity from these stars is a monotonically decreasing function of their (R-I) color, and evidence is presented which suggests that the product of the mean surface brightness and the mean filling factor of the emissive regions is essentially constant with color. Another significant result of the study is a linear correlation between the excess luminosity in H-alpha and the coronal X-ray luminosity. 39 refs

  17. Low level alpha activity measurements with pulse shape discrimination

    International Nuclear Information System (INIS)

    Satoh, Kaneaki; Higuchi, Hideo; Kitamura, Kiyoshi; Noguchi, Masayasu.

    1984-01-01

    Liquid scintillation counting of α rays with pulse shape discrimination was applied to the analysis of 226 Ra and 239+240 Pu in environmental samples and of α-emitters in/on a filter paper. The instrument used in this study was either a specially designed detector or a commercial liquid scintillation counter with an automatic sample changer, both of which were connected to the pulse shape discrimination circuit. The background counting rate in α energy region of 5-7 MeV was 0.01 or 0.04 cpm/MeV, respectively. The figure of merit indicating the resolving power for α- and β-particles in time spectrum was found to be 5.7 for the commercial liquid scintillation counter. (author)

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

    International Nuclear Information System (INIS)

    Mason, C.F.V.; Allander, K.S.; Bounds, J.A.; Garner, S.E.; Walter, K.J.

    1994-01-01

    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

  19. Activated astrocytes induce nitric oxide synthase-2 in cerebral endothelium via tumor necrosis factor alpha.

    Science.gov (United States)

    Shafer, R A; Murphy, S

    1997-12-01

    Astrocytes under pathological conditions become activated and produce a variety of cytokines and low molecular weight signal molecules. Previously we demonstrated that activated astrocytes release nitric oxide which can downregulate the expression of nitric oxide synthase (NOS)-2 in co-cultured cerebral endothelium, and also release a transcriptionally regulated factor that can induce NOS-2 expression in endothelium (Borgerding and Murphy: J Neurochem 65:1342, 1995). The activity of this NOS-2-inducing factor was impeded by inhibitors of tyrosine kinases and NF-kappaB activation. Tumor necrosis factor (TNF alpha) alone, or in combination with IL-6, induced NOS-2 expression in endothelial cells. A neutralizing antibody against TNF alpha attenuated the NOS-2 expression in endothelial cells exposed to activated astrocytes. These results imply that cytokine-activated astrocytes release TNF alpha which can induce NOS-2 expression in endothelium and suggest that activated astrocytes within the CNS may induce expression of NOS-2 in cells of the adjacent microvasculature. The ensuing alterations in blood-brain barrier properties may be either beneficial or detrimental.

  20. Role of the alpha-adrenergic blocking effect in the acute hypotensive effect of beta-adrenergic blocking drugs with alpha-blocking activities in conscious SHR.

    Science.gov (United States)

    Nakahara, H; Nakazawa, M; Takeda, K; Imai, S

    1985-12-01

    Acute hypotensive effects and the mechanisms of three beta-adrenergic blocking drugs with alpha-blocking activity were studied in comparison with those of prazosin, propranolol and hydralazine in the conscious spontaneously hypertensive rat (SHR). Prazosin lowered the blood pressure dose-dependently and inhibited the pressor response to phenylephrine. Three beta-adrenergic blocking drugs with alpha-blocking activity, labetalol (30 mg/kg), arotinolol (100 mg/kg) and nipradilol (100 mg/kg) also lowered the blood pressure to the same extent as prazosin (0.3 mg/kg), but the inhibition of the pressor response to phenylephrine produced by them was disproportionately slight. Propranolol (100 mg/kg) did not lower the blood pressure. These results suggest that the acute hypotensive effects of three beta-adrenergic blocking drugs with alpha-blocking activity were attributable only partially to the alpha-adrenergic blocking effect; a mechanism or mechanisms other than the alpha-adrenergic blocking effect must be invoked to explain the acute hypotensive effect produced by lower doses of these drugs in the conscious SHR.

  1. Cholylglycine hydrolase and 7alpha-dehydroxylase optimum assay conditions in vitro and caecal enzyme activities ex vivo.

    Science.gov (United States)

    Thomas, L A; King, A; French, G L; Murphy, G M; Dowling, R H

    1997-12-10

    Increasing evidence implicates deoxycholic acid (DCA) in the pathogenesis of cholesterol-rich gallbladder stones. However, relatively little is known about the activities of the two intestinal bacterial enzymes (cholylglycine hydrolase and cholic acid 7alpha-dehydroxylase) responsible for the deconjugation and subsequent dehydroxylation of conjugated cholic acid (CA), to form DCA. We, therefore, established optimal reaction conditions for measuring the activities of these two enzymes in vitro, and applied these conditions to the determination of the enzymes in caecal aspirates from six subjects undergoing clinically-indicated colonoscopy. With respect to cholylglycine hydrolase activity: zero order kinetics were found over 20 min at 37 degrees C (pH optimum 4.0), with Km and Vmax values of 1.66 mmol/l and 0.90 mmol CA min(-1) mg prot(-1), respectively. For cholic acid 7alpha-dehydroxylation: zero order kinetics were found over 7.5 min at 37 degrees C, under anaerobic conditions (pH optimum 8.0), with Km and Vmax values of 5.23 x 10(-8) mol/l and 1.88 x 10(-7) mol DCA min(-1) mg prot(-1), respectively. Applying these reaction conditions to the caecal aspirates, endogenous cholylglycine hydrolase activities ranged from 0.49 to 2.43 units (mg protein[-1] min[-1]) and CA 7alpha-dehydroxylase activities from 1.75 to 5.82 x 10(-7) units (mg protein[-1] min[-1]). This study is unique in assaying quantitatively both the deconjugation and dehydroxylation enzyme activities in human caecal samples--an essential first step to further studies of intestinal bacterial enzymes in the pathogenesis of cholesterol gallstone disease.

  2. Brain oscillatory activity during motor preparation: Effect of directional uncertainty on beta, but not alpha, frequency band

    Directory of Open Access Journals (Sweden)

    Charidimos eTzagarakis

    2015-07-01

    Full Text Available In time-constraint activities, such as sports, it is advantageous to be prepared to act even before knowing precisely what action will be needed. Here, we studied the relation between neural oscillations during motor preparation and amount of uncertainty about the direction of the upcoming target. Ten right-handed volunteers participated in a cued center-out task. A brief visual cue identified the region of space in which the target would appear. Three cue sizes were used to vary the amount of information about the direction of the upcoming target. The target appeared at a random location within the region indicated by the cue, and the participants moved a joystick-controlled cursor towards it. Time-frequency analyses showed phasic increases of power in low (delta/theta: 30 Hz frequency-bands in relation to the onset of visual stimuli and of the motor response. More importantly in regard to motor preparation, there was a tonic reduction of power in the alpha (8-12 Hz and beta (14-30 Hz bands during the period between cue presentation and target onset. During motor preparation, the main source of change of power of the alpha band was localized over the contralateral sensorimotor region and both parietal cortices, whereas for the beta-band the main source was the contralateral sensorimotor region. During cue presentation, the reduction of power of the alpha-band in the occipital lobe showed a brief differentiation of condition: the wider the visual cue, the more the power of the alpha-band decreased. However during motor preparation, only the power of the beta-band was dependent on directional uncertainty: the less the directional uncertainty, the more the power of the beta-band decreased. In conclusion, the results indicate that the power in the alpha-band is associated briefly with cue size, but is otherwise an undifferentiated indication of neural activation, whereas the power of the beta-band reflects the level of motor preparation.

  3. Structure-activity relationship of benzoxazinones and related compounds with respect to the growth inhibition and alpha-amylase activity in cress seedlings.

    Science.gov (United States)

    Kato-Noguchi, Hisashi; Macías, Francisco A; Molinillo, José M G

    2010-10-15

    Benzoxazinones and their degradation compounds inhibited root growth and alpha-amylase activity in cress seedlings. The inhibitory activity of these compounds was divided into three groups: the high active group; 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one, 2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one, 4-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one, 4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one, the moderate active group; 7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one, (2H)-1,4-benzoxazin-3(4H)-one, 6-methoxy-benzoxazolin-2(3H)-one, benzoxazolin-2(3H)-one and 2-amino-phenoxazine-3-one, and the low active group; 2-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one, 2-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one, 2-amino-7-hydroxyphenoxazine-3-one and 2-amino-7-methoxyphenoxazine-3-one. The structure-activity of these compounds suggests that compounds that have benzoxazinone skeletons are the most active structure, and a hydroxyl group at position C-2 on the benzoxazinone skeleton may not affect inhibitory activity, whereas a hydroxyl group at position N-4 on the skeleton is essential for inhibitory activity. However, the concentration-response curves of these compounds and the I(50) values (the concentrations required for 50% inhibition) for root growth and alpha-amylase indicated that root growth was positively correlated with the alpha-amylase activity in the seedlings. alpha-Amylase is required not only for seed germination, but also subsequent seedling growth until photosynthesis is sufficient to support seedling growth. Therefore, these results suggest that the compounds studied here may inhibit the root growth of cress seedlings by inhibiting alpha-amylase activity. Copyright (c) 2010 Elsevier GmbH. All rights reserved.

  4. The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene.

    Science.gov (United States)

    Barbier, Olivier; Villeneuve, Lyne; Bocher, Virginie; Fontaine, Coralie; Torra, Ines Pineda; Duhem, Christian; Kosykh, Vladimir; Fruchart, Jean-Charles; Guillemette, Chantal; Staels, Bart

    2003-04-18

    Peroxisome proliferator-activated receptor (PPAR) alpha and gamma are ligand-activated transcription factors belonging to the nuclear receptor family. PPAR alpha mediates the hypolipidemic action of the fibrates, whereas PPAR gamma is a receptor for the antidiabetic glitazones. In the present study, the UDP-glucuronosyltransferase (UGT) 1A9 enzyme is identified as a PPAR alpha and PPAR gamma target gene. UGTs catalyze the glucuronidation reaction, which is a major pathway in the catabolism and elimination of numerous endo- and xenobiotics. Among the UGT1A family enzymes, UGT1A9 metabolizes endogenous compounds, including catecholestrogens, and xenobiotics, such as fibrates and to a lesser extent troglitazone. Treatment of human hepatocytes and macrophages and murine adipocytes with activators of PPAR alpha or PPAR gamma resulted in an enhanced UGT1A9 expression and activity. In addition, disruption of the PPAR alpha gene in mice completely abolished the PPAR alpha agonist-induced UGT1A9 mRNA and activity levels. A PPAR response element was identified in the promoter of UGT1A9 at positions -719 to -706 bp by transient transfection and electromobility shift assays. Considering the role of UGT1A9 in catecholestrogen metabolism, PPAR alpha and PPAR gamma activation may contribute to the protection against genotoxic catecholestrogens by stimulating their inactivation in glucuronide derivatives. Furthermore, since UGT1A9 is involved in the catabolism of fibrates, these results suggest that PPAR alpha and PPAR gamma may control the intracellular level of active fibrates.

  5. Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4{alpha}.

    Science.gov (United States)

    Hertz, Rachel; Kalderon, Bella; Byk, Tamara; Berman, Ina; Za'tara, Ghadeer; Mayer, Raphael; Bar-Tana, Jacob

    2005-07-01

    Hepatocyte nuclear factor-4alpha (HNF-4alpha) activity is modulated by natural and xenobiotic fatty acid and fatty acyl-CoA ligands as a function of their chain length, unsaturation, and substitutions. The acyl-CoA site of HNF-4alpha is reported here to consist of the E-F domain, to bind long-chain acyl-CoAs but not the respective free acids, and to catalyze the hydrolysis of bound fatty acyl-CoAs. The free acid pocket, previously reported in the x-ray structure of HNF-4alpha E-domain, entraps fatty acids but excludes acyl-CoAs. The acyl-CoA and free acid sites are distinctive and noncongruent. Free fatty acid products of HNF-4alpha thioesterase may exchange with free acids entrapped in the fatty acid pocket of HNF-4alpha. Cross-talk between the acyl-CoA and free fatty acid binding sites is abrogated by high affinity, nonhydrolyzable acyl-CoA ligands of HNF-4alpha that inhibit its thioesterase activity. Hence, HNF-4alpha transcriptional activity is controlled by its two interrelated acyl ligands and two binding sites interphased in tandem by the thioesterase activity. The acyl-CoA/free-acid and receptor/enzyme duality of HNF-4alpha extends the paradigm of nuclear receptors.

  6. New Method of Inhibition of Activity of Tumor Necrosis Factor Alpha In Patients with Psoriasis.

    Science.gov (United States)

    Gerasun, Borys A

    2016-01-01

    A new method of reduction of tumor necrosis factor alpha activity via intradermal immunization with inactivated autoleukocytes (patent UA97493 (2015) [1]) has been presented in the article. New patents from various countries have been analyzed [2-7]. Patients with psoriasis (24) with high level of tumor necrosis factor alpha in their blood (. 30pg/ml) were immunized with autoleukocytes. Leukocytes were isolated by centrifuging plasma, obtained after precipitation of a patient's heparinized peripheral venous blood. Precipitate was suspended in 1.0 - 1.5ml of a patient's blood serum and 0.1ml of blood was injected into the skin of the back. For determination of autoleukocyte immunization efficacy, concentration of tumor necrosis factor alpha in a patient's blood was compared prior to immunization and at different periods after immunization. In 30 days after single immunization, a considerable decrease in cytokine concentration was observed in all patients (100%); it reduced to zero in 16 out of 24 of immunized individuals (66.7%). The degree of reduction and duration of the achieved effect were individual, thus, if necessary the immunization was repeated several times. The procedure was well tolerated, and general condition of patients was improved. The method of reduction of tumor necrosis factor alpha activity is recommended for implementation into clinical practice.

  7. Effects of tobacco smoke condensate on estrogen receptor-alpha gene expression and activity.

    Science.gov (United States)

    Martin, Mary Beth; Reiter, Ronald; Johnson, Michael; Shah, Mansi S; Iann, Mary C; Singh, Baljit; Richards, Julie Kate; Wang, Antai; Stoica, Adriana

    2007-10-01

    Metallo-estrogens are a new class of potent environmental estrogens. This study investigates whether tobacco smoke condensate (TSC), which contains metals and metalloids, elicits estrogen-like effects at environmentally relevant doses. Treatment of human breast cancer cells, MCF-7, with 40 microg/ml TSC resulted in a 2.5-fold stimulation of cell growth. TSC decreased the concentration of estrogen receptor (ER)-alpha protein and mRNA (63 and 62%, respectively), and increased the expression of the estrogen-regulated genes, progesterone receptor and pS2 (5- and 2-fold, respectively). In addition, TSC activated ER-alpha in COS-1 or CHO cells transiently transfected with wild-type ER-alpha and an ERE-CAT or an ERE-luciferase reporter gene (11- and 6-fold, respectively). TSC also activated a chimeric receptor (GAL-ER) containing the hormone binding domain of ER-alpha (3.5-fold). It blocked the binding of estradiol to the receptor without altering the affinity of estradiol (K(d) = 2.2-6.8 x 10(-10) m). Transfection assays with ER-alpha mutants identified C381, C447, H524, N532, E523, and D538 in the hormone binding domain as important for activation by TSC. In ovariectomized rats, low doses of TSC [10 or 20 mg/kg body weight (bw)] increased uterine wet weight (1.7- and 2.1-fold), and induced the expression of progesterone receptor and complement C3 in the uterus (2- and 26-fold) and mammary gland (4.4- and 15-fold). Both the in vitro and in vivo TSC effects were blocked by the antiestrogen ICI 182,780, suggesting the involvement of ER. Collectively, these results provide strong evidence that low doses of TSC, acting through the hormone binding domain, exert estrogen-like effects in cell culture and animals.

  8. Biomechanical and functional indicators in male semiprofessional soccer players with increased hip alpha angles vs. amateur soccer players.

    Science.gov (United States)

    Lahner, Matthias; von Schulze Pellengahr, Christoph; Walter, Philipp Alexander; Lukas, Carsten; Falarzik, Andreas; Daniilidis, Kiriakos; von Engelhardt, Lars Victor; Abraham, Christoph; Hennig, Ewald M; Hagen, Marco

    2014-03-16

    Femoroacetabular impingement (FAI) is predominant in young male athletes, but not much is known about gait differences in cases of increased hip alpha angles. In our study, the hip alpha angle of Nötzli of soccer players was quantified on the basis of magnetic resonance imaging (MRI) with axial oblique sequences. The aim of the current study was to compare the rearfoot motion and plantar pressure in male semiprofessional soccer players with increased alpha angles to age-matched amateur soccer players. In a prospective analysis, male semiprofessional and amateur soccer players had an MRI of the right hip to measure the alpha angle of Nötzli. In a biomechanical laboratory setting, 14 of these participants in each group ran in two shoe conditions. Simultaneously in-shoe pressure distribution, tibial acceleration, and rearfoot motion measurements of the right foot were performed. In the semiprofessional soccer group, the mean value of the alpha angle of group was 55.1 ± 6.58° (range 43.2-76.6°) and 51.6 ± 4.43° (range 41.9-58.8°) in the amateur group. In both shoe conditions, we found a significant difference between the two groups concerning the ground reaction forces, tibial acceleration, rearfoot motion and plantar pressure parameters (P amateur group in both shoe conditions. This study confirmed that semiprofessional soccer players with increased alpha angles showed differences in gait kinematics compared to the amateur group. These findings support the need for a screening program for competitive soccer players. In cases of a conspicuous gait analysis and symptomatic hip pain, FAI must be ruled out by further diagnostic tests.

  9. Activation of nicotinic ACh receptors with alpha4 subunits induces adenosine release at the rat carotid body.

    Science.gov (United States)

    Conde, Sílvia V; Monteiro, Emília C

    2006-04-01

    The effect of ACh on the release of adenosine was studied in rat whole carotid bodies, and the nicotinic ACh receptors involved in the stimulation of this release were characterized. ACh and nicotinic ACh receptor agonists, cytisine, DMPP and nicotine, caused a concentration-dependent increase in adenosine production during normoxia, with nicotine being more potent and efficient in stimulating adenosine release from rat CB than cytisine and DMPP. D-Tubocurarine, mecamylamine, DHbetaE and alpha-bungarotoxin, nicotinic ACh receptor antagonists, caused a concentration-dependent reduction in the release of adenosine evoked by hypoxia. The rank order of potency for nicotinic ACh receptor antagonists that inhibit adenosine release was DHbetaE>mecamylamine>D-tubocurarine>alpha-bungarotoxin. The effect of the endogenous agonist, ACh, which was mimicked by nicotine, was antagonized by DHbetaE, a selective nicotinic receptor antagonist. The ecto-5'-nucleotidase inhibitor AOPCP produces a 72% inhibition in the release of adenosine from CB evoked by nicotine. Taken together, these data indicate that ACh induced the production of adenosine, mainly from extracellular ATP catabolism at the CB through a mechanism that involves the activation of nicotinic receptors with alpha4 and beta2 receptor subunits.

  10. Immunotoxicity of perfluorooctanoic acid and perfluorooctane sulfonate and the role of peroxisome proliferator-activated receptor alpha

    Science.gov (United States)

    Peroxisome proliferators, including perfluorooctanoic acid (PFOA), are environmentally widespread and persistent and multiple toxicities have been reported in experimental animals and humans. These compounds trigger biological activity via activation of the alpha isotype of pero...

  11. Distribution of Gs-alpha activating mutations in human thyroid tumors measured by subcloning.

    Science.gov (United States)

    Gorelov, V N; Gyenes, M; Neser, F; Röher, H D; Goretzki, P E

    1996-01-01

    In the search for the prevalence and distribution pattern of Gs-alpha gene mutations in differentiated thyroid tumors we examined 66 tumor tissue samples for the presence of mutations at "hot-spot" codons 201 and 227 using methods based on the polymerase chain reaction, subcloning and sequencing. The prevailing type of single-base substitution at codon 201 (71.4%) corresponded to the replacement of the wild-type sequence CGT (Arg) with TGT (Cys). The fragments of the Gs-alpha gene, including codon 201 or 227 from five follicular carcinomas and one follicular adenoma, were subcloned in Escherichia coli and it was found that the proportion of alleles with mutated codon 201 varied from 3.2% to 43%. Sequencing of the corresponding region has confirmed preliminary data indicating that the single-base changes CGT (Arg) to TGT (Cys) or CGT to CAT (His) occurred. There was only a weak correlation between the prevalence of cells bearing a mutation in the Gs-alpha gene and the level of Gs-alpha protein expression in the corresponding thyroid tumors.

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

    International Nuclear Information System (INIS)

    Warburton, W.K.

    2005-01-01

    processor we 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/cm 2 /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 cm 2 electrode into 4 square segments, each 625 cm 2 and demonstrating that signal noise on individual channels reduced as expected. Because the Phase II counter with a 1 m 2 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

  13. Energy-sensing Factors Coactivator Peroxisome Proliferator-activated Receptor gamma Coactivator 1-alpha (PGC-1 alpha) and AMP-activated Protein Kinase Control Expression of Inflammatory Mediators in Liver INDUCTION OF INTERLEUKIN 1 RECEPTOR ANTAGONIST

    NARCIS (Netherlands)

    Buler, M.; Aatsinki, S.M.; Skoumal, R.; Komka, Z.; Toth, M.; Kerkela, R.; Georgiadi, A.; Kersten, A.H.; Hakkola, J.

    2012-01-01

    Obesity and insulin resistance are associated with chronic, low grade inflammation. Moreover, regulation of energy metabolism and immunity are highly integrated. We hypothesized that energy-sensitive coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha) and

  14. Nitric oxide increases cyclic GMP levels, AMP-activated protein kinase (AMPK)alpha1-specific activity and glucose transport in human skeletal muscle

    DEFF Research Database (Denmark)

    Deshmukh, A S; Long, Y C; de Castro Barbosa, T

    2010-01-01

    an insulin-independent signalling mechanism. Consistent with this, spermine NONOate increased AMP-activated protein kinase (AMPK)-alpha1-associated activity (1.7-fold, p .... CONCLUSIONS/INTERPRETATION: Pharmacological treatment of skeletal muscle with spermine NONOate increases glucose transport via insulin-independent signalling pathways involving increased intracellular cGMP levels and AMPK-alpha1-associated activity....

  15. Brain correlates underlying creative thinking: EEG alpha activity in professional vs. novice dancers.

    Science.gov (United States)

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

    2009-07-01

    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.

  16. Study on influences of experimental factors on energy and absolute activity measurements of alpha-emitters

    International Nuclear Information System (INIS)

    Terini, R.A.

    1991-01-01

    This work presents firstly a review of the fundamental results and conclusions obtained through alpha-spectrometry and alpha-counting, and the influence of energy straggling, energy loss, self-absorption and backscattering, on the determination of the energy and the absolute activity of alpha samples. Is is shown that the techniques of source fabrication and the methods of measurements play a capital influence on the obtained results. Moreover, measurements made by us, with a silicon surface barrier detector, show that the peak-asymmetry and peak-shift of an alpha-spectrum increases with the angle of emission, and that the magnitude of this effect depends on the thickness and homogeneity of the sample, as well as on the geometry of the measuring system. Through an analysis of the angular distribution of the emitted particles, the degree of isotropy of some thin Am sup(241) sources was measured and the influence of source backing and the geometry was analysed. We can conclude that, in general, there is a larger precision in measurements made under very small solid angles around the normal to the sample, and we enphasize the necessary cares required on the production of the source and on the set up of the measuring system. (author)

  17. 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.

    2010-01-01

    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.

  18. A role for 5alpha-reductase activity in the development of male homosexuality?

    Science.gov (United States)

    Alias, A G

    2004-12-01

    Higher body hair with lower mesmorphism ratings were observed in Caucasian homosexual men compared with the general male population, reflecting elevated 5alpha-reductase (5alphaR) activity, and higher dihydrotestosterone-to-testosterone (DHT-to-T) ratio, in sharp contrast to 46,XY 5alphaR 2 deficiency subjects, who are often born with ambiguous, or female genitalia, but tend to grow up to be muscular, heterosexual men with very little body hair, or beard. One study also showed them scoring around dull normal IQs. A greater prevalence of liberal body hair growth in men with higher IQs and/or educational levels was also observed in several samples. The exceptions to this statistical trend are too unsettling, however. Nevertheless, the results of a number of published studies, including one showing higher DHT-to-T ratio in homosexual men, done with different objectives over a span of 80 years, together strongly support these findings. Furthermore, in an animal model, "cognitive-enhancing effects" of "5alpha-reduced androgen [metabolites]" were recently demonstrated.

  19. Alpha-amylase Inhibition and Antioxidant Activity of Marine Green Algae and its Possible Role in Diabetes Management.

    Science.gov (United States)

    Unnikrishnan, P S; Suthindhiran, K; Jayasri, M A

    2015-10-01

    In the continuing search for safe and efficient antidiabetic drug, marine algae become important source which provide several compounds of immense therapeutic potential. Alpha-amylase, alpha-glucosidase inhibitors, and antioxidant compounds are known to manage diabetes and have received much attention recently. In the present study, four green algae (Chaetomorpha aerea, Enteromorpha intestinalis, Chlorodesmis, and Cladophora rupestris) were chosen to evaluate alpha-amylase, alpha-glucosidase inhibitory, and antioxidant activity in vitro. The phytochemical constituents of all the extracts were qualitatively determined. Antidiabetic activity was evaluated by inhibitory potential of extracts against alpha-amylase and alpha-glucosidase by spectrophotometric assays. Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide (H2O2), and nitric oxide scavenging assay. Gas chromatography-mass spectrometry (GC-MS) analysis was carried out to determine the major compound responsible for its antidiabetic action. Among the various extracts screened, chloroform extract of C. aerea (IC50 - 408.9 μg/ml) and methanol extract of Chlorodesmis (IC50 - 147.6 μg/ml) showed effective inhibition against alpha-amylase. The extracts were also evaluated for alpha-glucosidase inhibition, and no observed activity was found. Methanol extract of C. rupestris showed notable free radical scavenging activity (IC50 - 666.3 μg/ml), followed by H2O2 (34%) and nitric oxide (49%). Further, chemical profiling by GC-MS revealed the presence of major bioactive compounds. Phenol, 2,4-bis (1,1-dimethylethyl) and z, z-6,28-heptatriactontadien-2-one were predominantly found in the methanol extract of C. rupestris and chloroform extract of C. aerea. Our results demonstrate that the selected algae exhibit notable alpha-amylase inhibition and antioxidant activity. Therefore, characterization of active compounds and its in vivo assays will be noteworthy. Four green algae were

  20. First synthesis and antimicrobial activity Of N- and S-alpha-L-arabinopyranosyl-1,2,4-triazoles.

    Science.gov (United States)

    Khalil, Nasser S A M

    2007-01-01

    Arabinosylation of some 4-amino- and 4-arylideneamino-5-(pyridin-3-yl)-2,4-dihydro-[1,2,4]-triazole-3-thiones with 2,3,4-tri-O-acetyl-beta-L-arabinopyranosyl bromide led to an efficient synthetic approach to the corresponding N-and S-alpha-L-arabinopyranosides. Structure assignment of these two regiosiomers was based on chemical and spectroscopic evidences. Antimicrobial activities of two selected regioisomeric N-and S-alpha-L-arabinopyranosides were compared. The N-alpha-L-arabinopyranoside showed higher inhibitory effect than its regioisomeric S-alpha-L-arabinopyranoside against Aspergillus fumigatus, Penicillium italicum, Staphylococcus aureus, and Pseudomonas aeruginosa.

  1. H(alpha) Proxies for EIT Crinkles: Further Evidence for Preflare "Breakout"-Type Activity in an Ejective Solar Eruption

    Science.gov (United States)

    Sterling, Alphonse C.; Qiu, Jiong; Wang, Haimin; Moore, Ronald L.

    2001-01-01

    We present H(alpha) observations from Big Bear Solar Observatory of an eruptive flare in NOAA Active Region 8210, occurring near 22:30 UT on 1998 May 1. Previously, using the Extreme Ultraviolet Imaging Telescope (EIT) on the Solar and Heliospheric Observatory (SOHO) spacecraft, we found that a pattern of transient, localized brightenings, which we call 'EIT crinkles,' appears in the neighborhood of the eruption near the time of flare onset. These EIT crinkles occur at a location in the active region well separated from the sheared core magnetic fields, which is where the most intense features of the eruption are concentrated. We also previously found that high-cadence images from the Soft X-ray Telescope (SXT) on Yohkoh indicate that soft X-ray intensity enhancements in the core begin after the start of the EIT crinkles. With the H(alpha) data, we find remote flare brightening counterparts to the EIT crinkles. Light curves as functions of time of various areas of the active region show that several of the remote flare brightenings undergo intensity increases prior to the onset of principal brightenings in the core region, consistent with our earlier findings from EIT and SXT data. These timing relationships are consistent with the eruption onset mechanism known as the breakout model, introduced by Antiochos and colleagues, which proposes that eruptions begin with reconnection at a magnetic null high above the core region. Our observations are also consistent with other proposed mechanisms that do not involve early reconnection in the core region. As a corollary, our observations are not consistent with the so-called tether-cutting models, which say that the eruption begins with reconnection in the core. The H(alpha) data further show that a filament in the core region becomes activated near the time of EIT crinkle onset, but little if any of the filament actually erupts, despite the presence of a halo coronal mass ejection (CME) associated with this event.

  2. Caffeine as an indicator of estrogenic activity in source water.

    Science.gov (United States)

    Montagner, C C; Umbuzeiro, G A; Pasquini, C; Jardim, W F

    2014-08-01

    Caffeine has already been used as an indicator of anthropogenic impacts, especially the ones related to the disposal of sewage in water bodies. In this work, the presence of caffeine has been correlated with the estrogenic activity of water samples measured using the BLYES assay. After testing 96 surface water samples, it was concluded that caffeine can be used to prioritize samples to be tested for estrogenic activity in water quality programs evaluating emerging contaminants with endocrine disruptor activity.

  3. UV-Activated Luminescence/Colourimetric O2 Indicator

    Directory of Open Access Journals (Sweden)

    Andrew Mills

    2008-01-01

    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.

  4. Testosterone 5alpha-reductase inhibitory active constituents of Piper nigrum leaf.

    Science.gov (United States)

    Hirata, Noriko; Tokunaga, Masashi; Naruto, Shunsuke; Iinuma, Munekazu; Matsuda, Hideaki

    2007-12-01

    Previously we reported that Piper nigrum leaf extract showed a potent stimulation effect on melanogenesis and that (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2) were isolated as active constituents. As a part of our continuous studies on Piper species for the development of cosmetic hair-care agents, testosterone 5alpha-reductase inhibitory activity of aqueous ethanolic extracts obtained from several different parts of six Piper species, namely Piper nigrum, P. methysticum, P. betle, P. kadsura, P. longum, and P. cubeba, were examined. Among them, the extracts of P. nigrum leaf, P. nigrum fruit and P. cubeba fruit showed potent inhibitory activity. Activity-guided fractionation of P. nigrum leaf extract led to the isolation of 1 and 2. Fruits of P. cubeba contain 1 as a major lignan, thus inhibitory activity of the fruit may be attributable to 1. As a result of further assay on other known constituents of the cited Piper species, it was found that piperine, a major alkaloid amide of P. nigrum fruit, showed potent inhibitory activity, thus a part of the inhibitory activity of P. nigrum fruit may depend on piperine. The 5alpha-reductase inhibitory activities of 1 and piperine were found for the first time. In addition, the P. nigrum leaf extract showed in vivo anti-androgenic activity using the hair regrowth assay in testosterone sensitive male C57Black/6CrSlc strain mice.

  5. Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha

    OpenAIRE

    Li, Guolin; Brocker, Chad N.; Yan, Tingting; Xie, Cen; Krausz, Kristopher W.; Xiang, Rong; Gonzalez, Frank J.

    2017-01-01

    Background: Peroxisome proliferator-activated receptor alpha (PPARA) is a major regulator of fatty acid oxidation and severe hepatic steatosis occurs during acute fasting in Ppara-null mice. Thus, PPARA is considered an important mediator of the fasting response; however, its role in other fasting regiments such as every-other-day fasting (EODF) has not been investigated. Methods: Mice were pre-conditioned using either a diet containing the potent PPARA agonist Wy-14643 or an EODF regimen ...

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

    Science.gov (United States)

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

    1979-01-01

    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.

  7. Alpha-amylase inhibitory activity and phytochemical study of Zhumeria majdae Rech. f. and Wendelbo

    OpenAIRE

    Mirshafie, Behnaz; Mokhber-Dezfouli, Najmeh; Manayi, Azadeh; Saeidnia, Soodabeh; Ajani, Yousef; Gohari, Ahmad Reza

    2015-01-01

    Background: Zhumeria majdae (Lamiaceae) is an endemic species growing in the South parts of Iran especially Hormozgan province. The plant is so-called Mohrekhosh locally and widely used for medicinal purposes including stomachache and dysmenorrhea. Objective: In order to separation and identification of the main flavonoid glycosides of the plant (aerial parts including leaves, stems, flowers, and fruits were used) and evaluation of its alpha-amylase inhibitory (AAI) activity, methanolic extra...

  8. Activation of the Torpedo nicotinic acetylcholine receptor. The contribution of residues alphaArg55 and gammaGlu93.

    Science.gov (United States)

    Kapur, Ankur; Davies, Martin; Dryden, William F; Dunn, Susan M J

    2006-03-01

    The Torpedo nicotinic acetylcholine receptor is a heteropentamer (alpha2betagammadelta) in which structurally homologous subunits assemble to form a central ion pore. Viewed from the synaptic cleft, the likely arrangement of these subunits is alpha-gamma-alpha-delta-beta lying in an anticlockwise orientation. High affinity binding sites for agonists and competitive antagonists have been localized to the alpha-gamma and alpha-delta subunit interfaces. We investigated the involvement of amino acids lying at an adjacent interface (gamma-alpha) in receptor properties. Recombinant Torpedo receptors, expressed in Xenopus oocytes, were used to investigate the consequences of mutating alphaArg55 and gammaGlu93, residues that are conserved in most species of the peripheral nicotinic receptors. Based on homology modeling, these residues are predicted to lie in close proximity to one another and it has been suggested that they may form a salt bridge in the receptor's three-dimensional structure (Sine et al. 2002 J Biol Chem277, 29 210-29 223). Although substitution of alphaR55 by phenylalanine or tryptophan resulted in approximately a six-fold increase in the EC50 value for acetylcholine activation, the charge reversal mutation (alphaR55E) had no significant effect. In contrast, the replacement of gammaE93 by an arginine conferred an eight-fold increase in the potency for acetylcholine-induced receptor activation. In the receptor carrying the double mutations, alphaR55E-gammaE93R or alphaR55F-gammaE93R, the potency for acetylcholine activation was partially restored to that of the wild-type. The results suggest that, although individually these residues influence receptor activation, direct interactions between them are unlikely to play a major role in the stabilization of different conformational states of the receptor.

  9. The continuous monitoring of the artificial beta aerosol activity by measuring the alpha and beta activity in aerosol simultaneously

    International Nuclear Information System (INIS)

    Hayakawa, Hironobu; Oonishi, Masaki; Matsuura, Hiroyuki

    1990-01-01

    We have constructed the system to monitor the artificial beta aerosol activity around the nuclear power plants continuously in real time. The smaller releases of artificial radionuclides from the nuclear power plants can be lost in the fluctuations of the natural background of the beta aerosol activity, when only the beta activity of the aerosol is measured. This method to discriminate the artificial and the natural beta activity of the aerosol is based on the fact that the ratio of the natural alpha and beta activities of the aerosol is almost constant. The detection limit of this system is below 3 Bq/m 3 . (author)

  10. Fatty Acid Amide Hydrolase (FAAH) Inhibition Enhances Memory Acquisition through Activation of PPAR-alpha Nuclear Receptors

    Science.gov (United States)

    Mazzola, Carmen; Medalie, Julie; Scherma, Maria; Panlilio, Leigh V.; Solinas, Marcello; Tanda, Gianluigi; Drago, Filippo; Cadet, Jean Lud; Goldberg, Steven R.; Yasar, Sevil

    2009-01-01

    Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB[subscript 1]-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain.…

  11. Orientation of the calcium channel beta relative to the alpha(12.2 subunit is critical for its regulation of channel activity.

    Directory of Open Access Journals (Sweden)

    Iuliia Vitko

    Full Text Available BACKGROUND: The Ca(vbeta subunits of high voltage-activated Ca(2+ channels control the trafficking and biophysical properties of the alpha(1 subunit. The Ca(vbeta-alpha(1 interaction site has been mapped by crystallographic studies. Nevertheless, how this interaction leads to channel regulation has not been determined. One hypothesis is that betas regulate channel gating by modulating movements of IS6. A key requirement for this direct-coupling model is that the linker connecting IS6 to the alpha-interaction domain (AID be a rigid structure. METHODOLOGY/PRINCIPAL FINDINGS: The present study tests this hypothesis by altering the flexibility and orientation of this region in alpha(12.2, then testing for Ca(vbeta regulation using whole cell patch clamp electrophysiology. Flexibility was induced by replacement of the middle six amino acids of the IS6-AID linker with glycine (PG6. This mutation abolished beta2a and beta3 subunits ability to shift the voltage dependence of activation and inactivation, and the ability of beta2a to produce non-inactivating currents. Orientation of Ca(vbeta with respect to alpha(12.2 was altered by deletion of 1, 2, or 3 amino acids from the IS6-AID linker (Bdel1, Bdel2, Bdel3, respectively. Again, the ability of Ca(vbeta subunits to regulate these biophysical properties were totally abolished in the Bdel1 and Bdel3 mutants. Functional regulation by Ca(vbeta subunits was rescued in the Bdel2 mutant, indicating that this part of the linker forms beta-sheet. The orientation of beta with respect to alpha was confirmed by the bimolecular fluorescence complementation assay. CONCLUSIONS/SIGNIFICANCE: These results show that the orientation of the Ca(vbeta subunit relative to the alpha(12.2 subunit is critical, and suggests additional points of contact between these subunits are required for Ca(vbeta to regulate channel activity.

  12. A Role for Protein Phosphatase 2A in Regulating p38 Mitogen Activated Protein Kinase Activation and Tumor Necrosis Factor-Alpha Expression during Influenza Virus Infection

    Directory of Open Access Journals (Sweden)

    Anna H. Y. Law

    2013-04-01

    Full Text Available Influenza viruses of avian origin continue to pose pandemic threats to human health. Some of the H5N1 and H9N2 virus subtypes induce markedly elevated cytokine levels when compared with the seasonal H1N1 virus. We previously showed that H5N1/97 hyperinduces tumor necrosis factor (TNF-alpha through p38 mitogen activated protein kinase (MAPK. However, the detailed mechanisms of p38MAPK activation and TNF-alpha hyperinduction following influenza virus infections are not known. Negative feedback regulations of cytokine expression play important roles in avoiding overwhelming production of proinflammatory cytokines. Here we hypothesize that protein phosphatases are involved in the regulation of cytokine expressions during influenza virus infection. We investigated the roles of protein phosphatases including MAPK phosphatase-1 (MKP-1 and protein phosphatase type 2A (PP2A in modulating p38MAPK activation and downstream TNF-alpha expressions in primary human monocyte-derived macrophages (PBMac infected with H9N2/G1 or H1N1 influenza virus. We demonstrate that H9N2/G1 virus activated p38MAPK and hyperinduced TNF-alpha production in PBMac when compared with H1N1 virus. H9N2/G1 induced PP2A activity in PBMac and, with the treatment of a PP2A inhibitor, p38MAPK phosphorylation and TNF-alpha production were further increased in the virus-infected macrophages. However, H9N2/G1 did not induce the expression of PP2A indicating that the activation of PP2A is not mediated by p38MAPK in virus-infected PBMac. On the other hand, PP2A may not be the targets of H9N2/G1 in the upstream of p38MAPK signaling pathways since H1N1 also induced PP2A activation in primary macrophages. Our results may provide new insights into the control of cytokine dysregulation.

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

    Directory of Open Access Journals (Sweden)

    Schmidt Nico M

    2011-05-01

    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.

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

    Science.gov (United States)

    Treder, Matthias S; Bahramisharif, Ali; Schmidt, Nico M; van Gerven, Marcel A J; Blankertz, Benjamin

    2011-05-05

    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. 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). 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.

  15. The peroxisome proliferator-activated receptor alpha-selective activator ciprofibrate upregulates expression of genes encoding fatty acid oxidation and ketogenesis enzymes in rat brain.

    Science.gov (United States)

    Cullingford, Tim E; Dolphin, Colin T; Sato, Hitoshi

    2002-04-01

    Activated peroxisome proliferator activated receptor alpha (PPAR alpha) protects against the cellular inflammatory response, and is central to fatty acid-mediated upregulation of the gene encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS). We have previously demonstrated both PPAR alpha and mHS expression in brain, implying that brain-targeted PPAR alpha activators may likewise up-regulate mHS expression in brain. Thus, to attempt pharmacological activation of brain PPAR alpha in vivo, we have administered to rats two drugs with previously defined actions in rat brain, namely the PPAR alpha-selective activator ciprofibrate and the pan-PPAR activator valproate. Using the sensitive and discriminatory RNase protection co-assay, we demonstrate that both ciprofibrate and valproate induce mHS expression in liver, the archetypal PPAR alpha-expressing organ. Furthermore, ciprofibrate potently increases mHS mRNA abundance in rat brain, together with lesser increases in two other PPAR alpha-regulated mRNAs. Thus we demonstrate, for the first time, up-regulation of expression of PPAR alpha-dependent genes including mHS in brain, with implications in the increased elimination of neuro-inflammatory lipids and concomitant increased production of neuro-protective ketone bodies.

  16. 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

    2008-01-01

    and adult rat forebrain using two markers, activity-regulated cytoskeleton-associated protein (Arc) and c-Fos, to map neuronal activity. Acute administration of A-582941 (1, 3, 10 mg/kg) induced a dose-dependent increase in Arc mRNA expression in the medial prefrontal cortex (mPFC) and the ventral....../lateral orbitofrontal (VO/LO) cortex of juvenile, but not adult rats. This effect was mitigated by the alpha7 nAChR antagonist methyllycaconitine. A-582941 also increased c-Fos mRNA expression in the mPFC of juvenile, but not adult rats. Furthermore, A-582941 increased the number of Arc and c-Fos immunopositive cells...... in the mPFC, VO/LO, and shell of the nucleus accumbens, in both juvenile and adult rats. The A-582941-induced c-Fos protein expression was significantly greater in the mPFC and VO/LO of juvenile compared with adult rats. These data indicate that A-582941-induced alpha7 nAChR stimulation activates brain...

  17. Temporal Courses in EEG Theta and Alpha Activity in the Dynamic Health Qigong Techniques Wu Qin Xi and Liu Zi Jue.

    Science.gov (United States)

    Henz, Diana; Schöllhorn, Wolfgang I

    2017-01-01

    Health Qigong is a common technique of Traditional Chinese Medicine applied to strengthen mental and physical health. Several studies report increases in EEG theta and alpha activity after meditative Qigong techniques indicating a relaxed state of mind. To date, little is known on the effects of dynamic Health Qigong techniques that comprise bodily movements on brain activity. In the current study, we compared effects of two dynamic Health Qigong techniques on EEG brain activity. Subjects performed the techniques Wu Qin Xi (five animals play) and Liu Zi Jue (six healing sounds) in a within-subjects design. Eyes-open and eyes-closed resting EEG was recorded before and immediately after each 15-min practice block. Additionally, the Profile of Mood States (POMS) questionnaire was administered at pretest, and after each 15-min practice block. Results show a decrease in alpha activity after 15 min, followed by an increase after 30 min in the Health Qigong technique Liu Zi Jue . Theta activity was decreased after 15 min, followed by an increase after 30 min in the technique Wu Qin Xi . Results of the POMS indicated an increased vigor-activity level with decreased fatigue and tension-anxiety levels in both techniques after 30 min of practice. Our results demonstrate different temporal dynamics in EEG theta and alpha activity for the Health Qigong techniques Wu Qin Xi and Liu Zi Jue . We hypothesize that the found brain activation patterns result from different attentional focusing styles and breathing techniques performed during the investigated Health Qigong techniques.

  18. Peroxisome Proliferator-Activated Receptor-alpha Gene Level Differently Affects Lipid Metabolism and Inflammation in Apolipoprotein E2 Knock-In Mice

    NARCIS (Netherlands)

    Lalloyer, Fanny; Wouters, Kristiaan; Baron, Morgane; Caron, Sandrine; Vallez, Emmanuelle; Vanhoutte, Jonathan; Bauge, Eric; Shiri-Sverdlov, Ronit; Hofker, Marten; Staels, Bart; Tailleux, Anne

    Objective-Peroxisome proliferator-activated receptor-alpha (PPAR alpha) is a ligand-activated transcription factor that controls lipid metabolism and inflammation. PPAR alpha is activated by fibrates, hypolipidemic drugs used in the treatment of dyslipidemia. Previous studies assessing the influence

  19. Targeted deficiency of the transcriptional activator Hnf1alpha alters subnuclear positioning of its genomic targets.

    Directory of Open Access Journals (Sweden)

    Reini F Luco

    2008-05-01

    Full Text Available DNA binding transcriptional activators play a central role in gene-selective regulation. In part, this is mediated by targeting local covalent modifications of histone tails. Transcriptional regulation has also been associated with the positioning of genes within the nucleus. We have now examined the role of a transcriptional activator in regulating the positioning of target genes. This was carried out with primary beta-cells and hepatocytes freshly isolated from mice lacking Hnf1alpha, an activator encoded by the most frequently mutated gene in human monogenic diabetes (MODY3. We show that in Hnf1a-/- cells inactive endogenous Hnf1alpha-target genes exhibit increased trimethylated histone H3-Lys27 and reduced methylated H3-Lys4. Inactive Hnf1alpha-targets in Hnf1a-/- cells are also preferentially located in peripheral subnuclear domains enriched in trimethylated H3-Lys27, whereas active targets in wild-type cells are positioned in more central domains enriched in methylated H3-Lys4 and RNA polymerase II. We demonstrate that this differential positioning involves the decondensation of target chromatin, and show that it is spatially restricted rather than a reflection of non-specific changes in the nuclear organization of Hnf1a-deficient cells. This study, therefore, provides genetic evidence that a single transcriptional activator can influence the subnuclear location of its endogenous genomic targets in primary cells, and links activator-dependent changes in local chromatin structure to the spatial organization of the genome. We have also revealed a defect in subnuclear gene positioning in a model of a human transcription factor disease.

  20. Caffeine As An Indicator Of Estrogenic Activity In Source Water.

    OpenAIRE

    Montagner, C C; Umbuzeiro, G A; Pasquini, C; Jardim, W F

    2015-01-01

    Caffeine has already been used as an indicator of anthropogenic impacts, especially the ones related to the disposal of sewage in water bodies. In this work, the presence of caffeine has been correlated with the estrogenic activity of water samples measured using the BLYES assay. After testing 96 surface water samples, it was concluded that caffeine can be used to prioritize samples to be tested for estrogenic activity in water quality programs evaluating emerging contaminants with endocrine ...

  1. Proteinaceous alpha-araylase inhibitors

    DEFF Research Database (Denmark)

    Svensson, Birte; Fukuda, Kenji; Nielsen, P.K.

    2004-01-01

    Proteins that inhibit alpha-amylases have been isolated from plants and microorganisms. These inhibitors can have natural roles in the control of endogenous a-amylase activity or in defence against pathogens and pests; certain inhibitors are reported to be antinutritional factors. The alpha-amylase...... inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha-amylases...... in complex with inhibitors from five families. These structures indicate major diversity but also some similarity in the structural basis of alpha-amylase inhibition. Mutational analysis of the mechanism of inhibition was performed in a few cases and various protein engineering and biotechnological...

  2. Physical Activity, Dietary Intake and Anthropometric Indices of a ...

    African Journals Online (AJOL)

    This study explores the interrelationships among the physical activity level, dietary pattern and anthropometric indices of some pre-clinical undergraduates in a university in southeastern Nigeria. One hundred and twenty-one (121) consecutively-recruited volunteers (57 male and 64 female), aged 19-29 years, who were ...

  3. Fibroblast activation protein alpha expression identifies activated fibroblasts after myocardial infarction.

    Science.gov (United States)

    Tillmanns, Jochen; Hoffmann, Daniel; Habbaba, Yasmin; Schmitto, Jan D; Sedding, Daniel; Fraccarollo, Daniela; Galuppo, Paolo; Bauersachs, Johann

    2015-10-01

    Fibroblast activation protein α (FAP) is a membrane-bound serine protease expressed by activated fibroblasts during wound healing in the skin. Expression of FAP after myocardial infarction (MI) and potential effects on cardiac wound healing are largely unknown. MI was induced in rats and FAP expression was analyzed at 3, 7 and 28 days post-MI by microarray, Western blot and immunohistochemistry. In human hearts after MI, a FAP(+) fibroblast population was identified, and characterized by immunohistochemistry for prolyl-4-hydroxylase β, α-smooth muscle actin, Thy-1 and vimentin. Signaling pathways leading to FAP expression were studied in human cardiac fibroblasts by Western blot and ELISA using TGFβ1, TGF-beta type I-receptor (TGFbR1)-inhibitor SB431542 or the MAPK-inhibitor U0126 as well as siRNA targeting SMAD2 and SMAD3. Finally, fibroblasts were assayed for FAP-dependent migration (modified Boyden-chamber), proliferation (BrdU-assay) and gelatinolytic activity by gelatin zymography. In rats, FAP expression was increased after MI especially in the peri-infarct area peaking at 7 days post-MI. Co-localization analysis identified the majority of FAP(+) cells as activated proto-myofibroblasts and myofibroblasts. Concordantly, FAP(+) fibroblasts were abundant in ischemic tissue of human hearts after MI, but not in healthy control hearts. In vitro, FAP was induced by TGFβ1 via the canonical SMAD2/SMAD3 pathway. Depletion of FAP in fibroblasts reduced migratory capacity, while proliferation was not affected. Gelatin zymography revealed gelatinase activity by fibroblast-derived FAP. In this study, we show for the first time the expression of FAP in activated fibroblasts after MI and its activation by TGFβ1. Effects of FAP on fibroblast migration and gelatinolytic activity indicate a potential role in cardiac wound healing and remodeling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Suppression of interleukin-1[beta] and tumour necrosis factor-[alpha] biosynthesis by cadmium in in vitro activated human peripheral blood mononuclear cells

    Energy Technology Data Exchange (ETDEWEB)

    Theocharis, S.E. (Dept. of Experimental Pharmacology, School of Medicine, Univ. of Athens (Greece) First Dept. of Internal Medicine, School of Medicine, Univ. of Athens, Laikon Hospital (Greece)); Panayiotidis, P.G. (First Dept. of Internal Medicine, School of Medicine, Univ. of Athens, Laikon Hospital (Greece)); Souliotis, V.L. (National Hellenic Research Foundation, Inst. of Biological Research and Biotechnology, Athens (Greece))

    1994-12-01

    Cadmium is a highly toxic element responsible for acute and chronic toxicity in man. There is evidence that cadmium induces pathophysiological effects by modulating components of the immune system. Cytokines are being increasingly recognized as essential mediators of normal and pathologic immune responses. Cadmium at concentrations varying from 1.0x10[sup -4] to 3.3x10[sup -6] M inhibited the phytohemagglutinin induced production of interleukin-1[beta] and tumour necrosis factor-[alpha], in in vitro activated human peripheral blood mononuclear cells. The messenger RNA levels of interleukin-1[beta] and tumour necrosis factor-[alpha] were examined during a 24-h culture period, at different time points. The decreased messenger RNA levels at the time points of the maximum expression of interleukin-1[beta] and tumour necrosis factor-[alpha] indicate that cadmium suppresses their production at the transcriptional level. (orig.)

  5. Selectivity of the imidazoline alpha-adrenoceptor agonists (oxymetazoline and cirazoline) for human cloned alpha 1-adrenoceptor subtypes.

    Science.gov (United States)

    Horie, K.; Obika, K.; Foglar, R.; Tsujimoto, G.

    1995-01-01

    1. To investigate the structure-activity relationships of alpha-adrenoceptor agonists for the alpha 1-adrenoceptor subtypes, we have compared the imidazoline class of compounds, oxymetazoline and cirazoline, with the phenethylamine, noradrenaline, in their affinities and also in their intrinsic activities in Chinese hamster ovary (CHO) cells stably expressing the cloned human alpha 1-adrenoceptor subtypes (alpha 1a-, alpha 1b-, and alpha 1d-subtypes). 2. Radioligand binding studies with [125I]-HEAT showed that cirazoline and oxymetazoline had higher affinities at alpha 1a-subtype than at alpha 1b- and alpha 1d-subtypes, while noradrenaline had higher affinity at the alpha 1d-subtype than at alpha 1a- and alpha 1b-subtypes. 3. In functional studies, cirazoline caused transients of cytosolic Ca2+ concentrations ([Ca2+]i response) in a concentration-dependent manner and developed a maximal response similar to that to noradrenaline in CHO cells expressing the alpha 1a-subtype, while it acted as a partial agonist at alpha 1b- and alpha 1d-adrenoceptors. Oxymetazoline, on the other hand, was a weak agonist at alpha 1a-adrenoceptors, and has no intrinsic activity at the other subtypes. 4. Using the phenoxybenzamine inactivation method, the relationships between receptor occupancy and noradrenaline-induced [Ca2+]i response for alpha 1a- and alpha 1d-subtypes were found to be linear, whereas it was moderately hyperbolic for the alpha 1b-subtype, indicating the absence of receptor reserves in CHO cells expressing alpha 1a- and alpha 1d-subtypes while there exists a small receptor reserve for CHO cells expressing the alpha 1b-subtype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8564227

  6. Imidazoline2 (I2) receptor- and alpha2-adrenoceptor-mediated modulation of hypothalamic-pituitary-adrenal axis activity in control and acute restraint stressed rats.

    Science.gov (United States)

    Finn, David P; Hudson, Alan L; Kinoshita, Hiroshi; Coventry, Toni L; Jessop, David S; Nutt, David J; Harbuz, Michael S

    2004-03-01

    Central noradrenaline regulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the neuroendocrine response to stress. alpha2-adrenoceptors and imidazoline2 (I2) receptors modulate the activity of the central noradrenergic system. The present set of experiments investigated the role of alpha2-adrenoceptors and I2 receptors in the regulation of HPA axis activity under basal conditions and during exposure to the acute psychological stress of restraint. Three separate experiments were carried out in which rats were given an i.p. injection of either saline vehicle, the combined alpha2-adrenoceptor antagonist and I2 receptor ligand idazoxan (10 mg/kg), the selective I2 receptor ligand BU224 (2.5 or 10 mg/kg) or the selective alpha2-adrenoceptor antagonist RX821002 (2.5 mg/kg) with or without restraint stress. Drugs were administered immediately prior to restraint of 60 min duration. Blood was sampled pre-injection, 30, 60 and 240 min post-injection and plasma corticosterone was measured by radioimmunoassay. In experiment 1, idazoxan increased plasma corticosterone levels in naive animals and potentiated the corticosterone response to acute restraint stress. In experiment 2, BU224 administration increased plasma corticosterone levels in a dose-related manner in naive rats. The results of experiment 3 indicated that RX821002 also elevated plasma corticosterone levels in naive rats, however, only BU224 potentiated the corticosterone response to restraint stress. These studies suggest that both alpha2-adrenoceptors and I2 receptors play a role in modulating basal HPA axis activity and that I2 receptors may play a more important role than alpha2-adrenoceptors in modulating the HPA axis response to the acute psychological stress of restraint.

  7. 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.

  8. Inhibitory effect of leaf extract of Newbouldia laevis on the metabolic activities of alpha-glucosidase and alpha-amylase

    Directory of Open Access Journals (Sweden)

    Oyetunji T. Kolawole

    2013-12-01

    Full Text Available In this study, the effect of ethanol extract of the leaves of Newbouldia laevis on the activity of α-amylase and α-glucosidase was investigated. Inhibitory effect of N. laevis extract on α-glucosidase was tested in vitro using baker’s yeast α-glucosidase and rat intestinal α-glucosidase while α-amylase inhibitory effect was assayed using rat pancreatic α-amylase. α-Glucosidase inhibitory effect of the extract was also tested in vivo in diabetic and non-diabetic rats. N. laevis extract exhibited good α-glucosidase inhibitory activity in vitro with IC50 values of 2.2 µg/mL and 43.5 µg/mL for baker’s yeast and rat intestinal α-glucosidase respectively. The extract also inhibited rat pancreatic α-amylase activity with IC50 value of 58.7 µg/mL. In both diabetic and non-diabetic rats, N. laevis extract caused a significant reduction in postprandial blood glucose level after oral sucrose load. The results of this study indicate that N. laevis extract exerts its glucose-lowering effect through inhibition of α-glucosidase and α-amylase.

  9. Enzyme activities by indicator of quality in organic soil

    Science.gov (United States)

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

    2016-04-01

    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

  10. Using the Statistical Indicators for the General Insurances Activity

    Directory of Open Access Journals (Sweden)

    Ion Partachi

    2007-04-01

    Full Text Available The statistics of the general insurances activity is largely used in the actuarial calculations. The actuarial analysis are achieved exclusively on the basis of primary and derived indicators, which are drawn up by various statistical methods. The statistical indicators which are used in this respect are obtained on the basis of the factors and conditions allowing the compensation cases to occur.The actuarial analysis is performed over the time as well, by using the chronological which allow the decomposition of the phenomenon being studied by its factors of influence.In this article, after briefly presenting a number of point of view regarding the utilization of the statistical indicators in the actuarial analysis, we have analyzed, successively, a series of issues, such as: the statistical indicators as regards the general insurances fund forming, expressed in physical and value units, or as absolute, relative and average volumes; the statistical indicators of the utilization of the general insurances funds (with the same diversified form of expression and the statistical indicators of the outcomes of the general insurances activity.A particular accent went to the underlying of certain methodological aspects regarding the calculation of the above mentioned indicators, emphasizing certain particular characteristics concerning their utilization in the frame of the actuarial analysis.The article is stressing the clarification of the fact that these indicators are used in the actuarial analysis as a real system. The respective proportions are enumerated, by underlying the concrete possibilities of computation, which secure the possibility of performing the necessary analysis involved by a decisional process.

  11. Production of {alpha}-glucosidases by Bacillus sp. strains

    Energy Technology Data Exchange (ETDEWEB)

    Castro, G.R. [Univ. Nacional de Tucuman, Facultad de Bioquimica, Quimica y Farmacia, Catedra de Microbiologia Superior, PROIMI-MIRCEN, Tucuman (Argentina); Baigori, M.D. [Univ. Nacional de Tucuman, Facultad de Bioquimica, Quimica y Farmacia, Catedra de Microbiologia Superior, PROIMI-MIRCEN, Tucuman (Argentina); Sineriz, F. [Univ. Nacional de Tucuman, Facultad de Bioquimica, Quimica y Farmacia, Catedra de Microbiologia Superior, PROIMI-MIRCEN, Tucuman (Argentina)

    1995-12-31

    {alpha}-Glucosidase was detected in four wild-type amylolytic production strains belonging to the Bacillus genus. The strains showed {alpha}-glucosidase activity in extracellular and membrane-bound fractions. Kinetic studies of the {alpha}-glucosidase synthesis in the batch cultures of four strains of the Bacillus genus showed two profiles: partially and totally growth-linked synthesis. The presence of different activities and production profiles of {alpha}-glucosidase in the strains at high or low glucose concentrations in the medium would indicate that {alpha}-glucosidase may have a role in the regulation of the metabolism of {alpha}-polysaccharides. (orig.)

  12. Anti-rhinovirus-specific activity of the alpha-sympathomimetic oxymetazoline.

    Science.gov (United States)

    Koelsch, Stephan; Tschaikin, Marion; Sacher, Fritz

    2007-01-01

    Oxymetazoline (CAS 2315-02-8, OMZ, Nasivin) known as the active ingredient in nose drops and sprays demonstrates excellent efficacy in the treatment of rhinitis symptoms that are mainly caused by Rhinovirus infections. To elucidate possible modes of action, the antiviral activity of OMZ was studied in vitro on human pathogenic viruses. No in vitro effects were detected against enveloped RNA viruses, Parainfluenza Virus and Respiratory Syncytial Virus and against Adenovirus, a non-enveloped DNA-virus. In contrast, OMZ showed a specific inhibition of Human Rhinovirus (HRV). Analysis of production of HRV-14 and HRV-39 after treatment of infected HeLa cells using plaque-reduction assay and virus titration showed a strong dose-dependent antiviral activity of OMZ. Additional data demonstrated that OMZ did also directly affect HRV-14 infectivity in a dose-dependent manner. Analysis of a cell-protective effect of OMZ showed that pre-treatment of HeLa cells decreased virus adsorption as well as virus replication. Furthermore, OMZ induced a down-regulation of ICAM-1 expression on Tumor Necrosis Factor-alpha (TNF-alpha)-stimulated HeLa cells and human umbilical vein endothelial cells. Taken together, these results show that OMZ besides its vasoconstrictive action also possesses potent antiviral and anti-inflammatory activities. Therefore, OMZ does not only reduce rhinitis symptoms but additionally offers a causal therapeutic approach.

  13. Dual Effects of Alpha-Arbutin on Monophenolase and Diphenolase Activities of Mushroom Tyrosinase

    Science.gov (United States)

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

    2014-01-01

    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. PMID:25303458

  14. 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.

    2011-07-01

    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.

  15. Pressor effect for ethanol and absence of its. cap alpha. -blocking activity in the SHR

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Rahman, A.R.A.; Iams, S.G.; Wooles, V.R.

    1986-03-01

    In a previous study the authors have suggested ethanol (ETOH) has an ..cap alpha..-blocking activity in anesthetized Sprague Dawley (SD) rats. The present investigation shows that ETOH (1 g/Kg, i.v.) has a pressor and tachycardic effect in SHR, SD and Wistar Kyoto (WKY) rats. However, quantitative differences existed between ..delta.. MAP, but not ..delta.. HR, among the 3 strains; the biggest rise occurred in the SHR and the least in SD. It is not yet clear whether the significantly higher MAP in the SHR contributes to the significantly larger ..delta.. MAP in response to ETOH. Nonetheless, MAP was similar in WKY and SD in spite of a larger ..delta.. MAP after ETOH in the former. Furthermore, both SD and WKY rats showed a significant and parallel rightward shift of the phenylephrine (PE) pressor response curve after ETOH (more in SD than WKY) suggesting an ..cap alpha..-blocking activity for ethanol and confirming their previous findings in SD rats. This suggestion was further supported by the absence of any shift in the angiotensin II (AII) dose-response curves. On the other hand, neither PE nor AII pressor responsiveness was influenced by ETOH in the SHR suggesting an absence of ..cap alpha..-blocking activity for ETOH in this strain. Finally, no change occurred in the baroreflex control of HR in SHR as compared to an impairment of this function in WKY and SD rats. This may relate at least in part, to the already depressed baroreflex function in the SHR.

  16. Direct activation of protein kinase C by 1 alpha,25-dihydroxyvitamin D3.

    Science.gov (United States)

    Slater, S J; Kelly, M B; Taddeo, F J; Larkin, J D; Yeager, M D; McLane, J A; Ho, C; Stubbs, C D

    1995-03-24

    The key metabolite of vitamin D3, 1 alpha,25-dihydroxyvitamin D3 (1,25-D3), induces rapid cellular responses that constitute a so-called "non-genomic" response. This effect is distinguished from its "classic" genomic role in calcium homeostasis involving the nuclear 1,25-D3 receptor. Evidence is presented that protein kinase C (PKC) is directly activated by 1,25-D3 at physiological concentrations (EC50 = 16 +/- 1 nM). The effect was demonstrable with single PKC-alpha, -gamma, and -epsilon isoform preparations, assayed in a system containing only purified enzyme, substrate, co-factors, and lipid vesicles, from which it is inferred that a direct interaction with the enzyme is involved. The finding that calcium-independent isoform PKC-epsilon was also activated by 1,25-D3 shows that the calcium binding C2 domain is not required. The level of 1,25-D3-induced activation, paired with either diacylglycerol or 4 beta-12-O-tetradecanoylphorbol-13-acetate, was greater than that achievable by any individual activator alone, each at a saturating concentration, a result that implies two distinct activator sites on the PKC molecule. Phosphatidylethanolamine present in the lipid vesicles potentiated 4 beta-12-O-tetradecanoylphorbol-13-acetate- and diacylglycerol-induced PKC activities, whereas 1,25-D3-induced activity decreased, consistent with 1,25-D3-activated PKC possessing a distinct conformation. The results suggest that PKC is a "membrane-bound receptor" for 1,25-D3 and that it could be important in the control of non-genomic cellular responses to the hormone.

  17. Modification of the activity of an alpha-amylase from Bacillus licheniformis by several surfactants

    OpenAIRE

    Bravo Rodríguez,Vicente; Jurado Alameda,Encarnación; Martínez Gallegos,Juan Francisco; Reyes Requena,Antonia; García López,Ana Isabel; Sampaio Cabral,Joaquim Manuel; Fernandes,Pedro; Pina da Fonseca,Luis Joaquim

    2006-01-01

    The influence of different commercial surfactants on the enzymatic activity of a commercial alpha-amylase from Bacillus licheniformis (Termamyl 300 L) has been studied. As non-ionic surfactants, alkyl polyglycosides (Glucopon® 215, Glucopon® 600 and Glucopon® 650) were studied, as were fatty alcohol ethoxylates (Findet 1214N/23 and Findet 10/15), and nonyl phenol ethoxylate (Findet 9Q/21.5NF). Also, an anionic surfactant, linear alkyl benzene sulfonate (LAS) was assayed. In general, none of t...

  18. 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

    2007-08-29

    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.

  19. Elimination of double strand nuclease activity from S1 nuclease prepared from crude alpha amylase.

    Science.gov (United States)

    Hahn, W E; Van Ness, J

    1976-01-01

    Single strand-specific s1 nuclease prepared as previously described from crude alpha amylase by DEAE-cellulose chromatography also contains nuclease which degrades double strand nucleic acid. The double strand activity can be removed by repeating the DEAE-cellulose chromatography procedure at least two additional times. S1 nuclease prepared by this procedure does not degrade double strand sheared DNA as measured by Sephadex chromatography. Under the same conditions single strand DNA is completely degraded. Thus, S1 nuclease prepared by this procedure is suitable for use in removing single strand regions in DNA/DNA duplexes and DNA/RNA hybrids. PMID:940774

  20. AATR an ionospheric activity indicator specifically based on GNSS measurements

    Science.gov (United States)

    Juan, José Miguel; Sanz, Jaume; Rovira-Garcia, Adrià; González-Casado, Guillermo; Ibáñez, D.; Perez, R. Orus

    2018-03-01

    This work reviews an ionospheric activity indicator useful for identifying disturbed periods affecting the performance of Global Navigation Satellite System (GNSS). This index is based in the Along Arc TEC Rate (AATR) and can be easily computed from dual-frequency GNSS measurements. The AATR indicator has been assessed over more than one Solar Cycle (2002-2017) involving about 140 receivers distributed world-wide. Results show that it is well correlated with the ionospheric activity and, unlike other global indicators linked to the geomagnetic activity (i.e. DST or Ap), it is sensitive to the regional behaviour of the ionosphere and identifies specific effects on GNSS users. Moreover, from a devoted analysis of different Satellite Based Augmentation System (SBAS) performances in different ionospheric conditions, it follows that the AATR indicator is a very suitable mean to reveal whether SBAS service availability anomalies are linked to the ionosphere. On this account, the AATR indicator has been selected as the metric to characterise the ionosphere operational conditions in the frame of the European Space Agency activities on the European Geostationary Navigation Overlay System (EGNOS). The AATR index has been adopted as a standard tool by the International Civil Aviation Organization (ICAO) for joint ionospheric studies in SBAS. In this work we explain how the AATR is computed, paying special attention to the cycle-slip detection, which is one of the key issues in the AATR computation, not fully addressed in other indicators such as the Rate Of change of the TEC Index (ROTI). After this explanation we present some of the main conclusions about the ionospheric activity that can extracted from the AATR values during the above mentioned long-term study. These conclusions are: (a) the different spatial correlation related with the MOdified DIP (MODIP) which allows to clearly separate high, mid and low latitude regions, (b) the large spatial correlation in mid

  1. AATR an ionospheric activity indicator specifically based on GNSS measurements

    Directory of Open Access Journals (Sweden)

    Juan José Miguel

    2018-01-01

    Full Text Available This work reviews an ionospheric activity indicator useful for identifying disturbed periods affecting the performance of Global Navigation Satellite System (GNSS. This index is based in the Along Arc TEC Rate (AATR and can be easily computed from dual-frequency GNSS measurements. The AATR indicator has been assessed over more than one Solar Cycle (2002–2017 involving about 140 receivers distributed world-wide. Results show that it is well correlated with the ionospheric activity and, unlike other global indicators linked to the geomagnetic activity (i.e. DST or Ap, it is sensitive to the regional behaviour of the ionosphere and identifies specific effects on GNSS users. Moreover, from a devoted analysis of different Satellite Based Augmentation System (SBAS performances in different ionospheric conditions, it follows that the AATR indicator is a very suitable mean to reveal whether SBAS service availability anomalies are linked to the ionosphere. On this account, the AATR indicator has been selected as the metric to characterise the ionosphere operational conditions in the frame of the European Space Agency activities on the European Geostationary Navigation Overlay System (EGNOS. The AATR index has been adopted as a standard tool by the International Civil Aviation Organization (ICAO for joint ionospheric studies in SBAS. In this work we explain how the AATR is computed, paying special attention to the cycle-slip detection, which is one of the key issues in the AATR computation, not fully addressed in other indicators such as the Rate Of change of the TEC Index (ROTI. After this explanation we present some of the main conclusions about the ionospheric activity that can extracted from the AATR values during the above mentioned long-term study. These conclusions are: (a the different spatial correlation related with the MOdified DIP (MODIP which allows to clearly separate high, mid and low latitude regions, (b the large spatial correlation in

  2. [Effect of pectin substances on activity of human pancreatic alpha-amylase in vitro].

    Science.gov (United States)

    Chelpanova, T I; Vitiazev, F V; Mikhaleva, N Ia; Efimtseva, É A

    2012-06-01

    Pectin substances were extracted from food plants: sweet pepper Capsicum annuum L., carrot sowing Daucus sativus L., bulb onion Allium cepa L., white cabbage Brassica oleracea L. by two methods with acid solutions similar to gastric environment. The pectins that were extracted were characterized by Monosaccharide composition and quantitative contents of uronic acids, neutral monosaccharides, methoxy groups, protein. The inhibitory effect of all extracted pectin-protein complexes on activity of pharmaceutical drugs of human pancreatic alpha-amylase was detected. It was found that the inhibitory effect of isolated pectin substances was dependent upon the species of plant source, the manner of pectin substance extraction, the chemical composition and acting concentrations. The ability of pectin substances to suppress enzyme activity was found in a range of pectin concentrations from 0.5 up to 1.5 %. It was revealed that extracted pectin substances from bulb onion and white cabbage by acid solution with pepsin had a 2.4-3.4 times greater inhibiting effect on the human pancreatic alpha-amylase activity in comparison with pectin substances extracted by solution without pepsin from the same plant sources in high concentrations.

  3. Locus coeruleus alpha-adrenergic-mediated activation of cortical astrocytes in vivo.

    Science.gov (United States)

    Bekar, Lane K; He, Wei; Nedergaard, Maiken

    2008-12-01

    The locus coeruleus (LC) provides the sole source of norepinephrine (NE) to the cortex for modulation of cortical synaptic activity in response to salient sensory information. NE has been shown to improve signal-to-noise ratios, sharpen receptive fields and function in learning, memory, and cognitive performance. Although LC-mediated effects on neurons have been addressed, involvement of astrocytes has thus far not been demonstrated in these neuromodulatory functions. Here we show for the 1st time in live mice, that astrocytes exhibit rapid Ca(2+) increases in response to electrical stimulation of the LC. Additionally, robust peripheral stimulation known to result in phasic LC activity leads to Ca(2+) responses in astrocytes throughout sensory cortex that are independent of sensory-driven glutamate-dependent pathways. Furthermore, the astrocytic Ca(2+) transients are competitively modulated by alpha(2)-specific agonist/antagonist combinations known to impact LC output, are sensitive to the LC-specific neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, and are inhibited locally by an alpha-adrenergic antagonist. Future investigations of LC function must therefore consider the possibility that LC neuromodulatory effects are in part derived from activation of astrocytes.

  4. alpha-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption.

    Science.gov (United States)

    Torielli, Lucia; Tivodar, Simona; Montella, Rosa Chiara; Iacone, Roberto; Padoani, Gloria; Tarsini, Paolo; Russo, Ornella; Sarnataro, Daniela; Strazzullo, Pasquale; Ferrari, Patrizia; Bianchi, Giuseppe; Zurzolo, Chiara

    2008-08-01

    Genetic variation in alpha-adducin cytoskeletal protein is implicated in the polymerization and bundling of actin and alteration of the Na/K pump, resulting in abnormal renal sodium transport and hypertension in Milan hypertensive rats and humans. To investigate the molecular involvement of alpha-adducin in controlling Na/K pump activity, wild-type or mutated rat and human alpha-adducin forms were, respectively, transfected into several renal cell lines. Through multiple experimental approaches (microscopy, enzymatic assays, coimmunoprecipitation), we showed that rat and human mutated forms increased Na/K pump activity and the number of pump units; moreover, both variants coimmunoprecipitate with Na/K pump. The increased Na/K pump activity was not due to changes in its basolateral localization, but to an alteration of Na/K pump residential time on the plasma membrane. Indeed, both rat and human mutated variants reduced constitutive Na/K pump endocytosis and similarly affected transferrin receptor trafficking and fluid-phase endocytosis. In fact, alpha-adducin was detected in clathrin-coated vesicles and coimmunoprecipitated with clathrin. These results indicate that adducin, besides its modulatory effects on actin cytoskeleton dynamics, might play a direct role in clathrin-dependent endocytosis. The constitutive reduction of the Na/K pump endocytic rate induced by mutated adducin variants may be relevant in Na-dependent hypertension.

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

    Directory of Open Access Journals (Sweden)

    Navarrete Erika

    2005-07-01

    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

  6. 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: serge@iem.sp.ru [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: app@iem.sp.ru [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)

    2010-07-23

    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.

  7. PROMETHEE: An Alpha Low Level Waste Assay System Using Passive and Active Neutron Measurement Methods

    International Nuclear Information System (INIS)

    Passard, Christian; Mariani, Alain; Jallu, Fanny; Romeyer-Dherbey, Jacques; Recroix, Herve; Rodriguez, Michel; Loridon, Joel; Denis, Caroline; Toubon, Herve

    2002-01-01

    The development of a passive-active neutron assay system for alpha low level waste characterization at the French Atomic Energy Commission is discussed. Less than 50 Bq[α] (about 50 μg Pu) per gram of crude waste must be measured in 118-l 'European' drums in order to reach the requirements for incinerating wastes. Detection limits of about 0.12 mg of effective 239 Pu in total active neutron counting, and 0.08 mg of effective 239 Pu coincident active neutron counting, may currently be detected (empty cavity, measurement time of 15 min, neutron generator emission of 1.6 x 10 8 s -1 [4π]). The most limiting parameters in terms of performances are the matrix of the drum - its composition (H, Cl...), its density, and its heterogeneity degree - and the localization and self-shielding properties of the contaminant

  8. Code Betal to calculation Alpha/Beta activities in environmental samples

    International Nuclear Information System (INIS)

    Romero, L.; Travesi, A.

    1983-01-01

    A codes, BETAL, was developed, written in FORTRAN IV, to automatize calculations and presentations of the result of the total alpha-beta activities measurements in environmental samples. This code performs the necessary calculations for transformation the activities measured in total counts, to pCi/1., bearing in mind the efficiency of the detector used and the other necessary parameters. Further more, it appraise the standard deviation of the result, and calculus the Lower limit of detection for each measurement. This code is written in iterative way by screen-operator dialogue, and asking the necessary data to perform the calculation of the activity in each case by a screen label. The code could be executed through any screen and keyboard terminal, (whose computer accepts Fortran IV) with a printer connected to the said computer. (Author) 5 refs

  9. Characterization of large area ZnS(Ag) detector for gross alpha and beta activity measurements in tap water plants

    Energy Technology Data Exchange (ETDEWEB)

    Lunardon, M.; Cester, D.; Mistura, G.; Moretto, S.; Stevanato, L.; Viesti, G. [Department of Physics and Astronomy ' Galileo Galilei' , University of Padova, (Italy); Schotanus, P.; Bodewits, E. [SCIONIX Holland BV, (Netherlands)

    2015-07-01

    In this work we present the characterization of a large area 200 x 200 mm{sup 2} EJ-444 scintillation detector to be used for monitoring gross alpha and beta activity in tap water plants. Specific tests were performed to determine the best setup to readout the light from the detector side in order to have the possibility to stack many detectors and get a compact device with total active area of the order of 1 m{sup 2}. Alpha/Beta discrimination, efficiency and homogeneity tests were carried out with alpha and beta sources. Background from ambient radioactivity was measured as well. Alpha/beta real-time monitoring in drinking water is a goal of the EU project TAWARA{sub R}TM. (authors)

  10. Activation of peroxisome proliferator-activated receptor-alpha and -gamma in auricular tissue from heart failure patients.

    Science.gov (United States)

    Gómez-Garre, Dulcenombre; Herraíz, Marta; González-Rubio, Ma Luisa; Bernal, Rosa; Aragoncillo, Paloma; Carbonell, Amparo; Rufilanchas, Juan José; Fernández-Cruz, Arturo

    2006-03-01

    Peroxisome proliferator-activated receptors (PPARs), key transcriptional regulators of lipid and energy metabolism in cardiomyocytes, have recently been proposed to modulate cardiovascular pathophysiological responses in experimental models. However, there is little information about the functional activity of PPARs in human heart failure. To investigate PPAR-alpha and -gamma expression and activity, and the association with ET-1 production and fibrosis, in cardiac biopsies from patients with end-stage heart failure due to ischemic cardiomyopathy (ICM) in comparison and from non-failing donor hearts. All samples were obtained during cardiac transplantation. Morphological analysis (by Masson trichrome and image analysis) did not detect fibrosis in the left atrium from non-failing donors (NFLA) or from ICM patients (FLA). However, left ventricles from failing hearts (FLV) contained a greater number of fibrotic areas (NFLA: 3.21+/-1.15, FLA: 1.63+/-0.83, FLV: 14.5+/-3.45%; n = 9, PPPAP-gamma mRNA (by RT-PCR) and protein (by Western blot) levels were higher in the ventricles from failing hearts compared with the atrium from failing and non-failing hearts. Electrophoretic mobility shift assays showed that PPAR-alpha and PPAP-gamma were not activated in the ventricles (NFLA: 1.00+/-0.11, FLA: 1.89+/-0.24, FLV: 0.95+/-0.07; n = 9, PPPAP-gamma are selectively activated in the atria from ICM patients and might be functionally important in the maintenance of atrial morphology.

  11. The effect of individual upper alpha band enhancing neurofeedbac kon reaction-time as an indicator of short-term memory in women employee’s

    Directory of Open Access Journals (Sweden)

    Mersedeh Jahanseir

    2014-11-01

    Full Text Available Background: In neurofeedback systems, people are able to reinforce or hinder their basic EEG rhythms according to operant conditioninin recent studies the effect of neurofeedback training on improvement of working memory has been shown on the healthy subjects. Disadvantage of neurofeedback is the high number of training sessions and high cost. In previous studies, alpha band power within (8-12 Hz has been considered for all subjects. Previous research reached the conclusion that by using individual upper alpha in neurofeedback, learning rate will increase, so the training sessions and the cost of training will be reduced. Material and Methods: In this study, all participants were female, 10 adults (10 women, mean age 33.8 years, SD=3.56 years. Randomly assigned to control and test group, five in test group and five in control group. Each subject performed the memory test four times, two times before the start of the first neurofeedback training and two times after the end of the last neurofeedback session. Eight training sessions were held, each session had three trials. Results: Discriminate response to the color of the drawing, as well as reaction time hadsignificant effects for test group (p0.05. Before and after eight training sessions by individual upper alpha power neurofeedback, reaction time of discriminate response to the color of the drawing for test group decreased and had significant effects (p0.05. Conclusion: Increasing relative individual upper alpha power, caused by neurofeedback training during eight sessions, indicated that this method increases the memory of women employees, and improves the ability of discriminative response to the color (red & green of the drawing as well as reducing reaction time.

  12. Activation cross sections of longer-lived radionuclides produced in germanium by alpha particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Takács, S., E-mail: stakacs@atomki.hu [Institute for Nuclear Research, Hungarian Academy of Sciences, Atomki, 4026 Debrecen (Hungary); Takács, M.P.; Ditrói, F. [Institute for Nuclear Research, Hungarian Academy of Sciences, Atomki, 4026 Debrecen (Hungary); Aikawa, M. [Faculty of Science, Hokkaido University, Sapporo 060-0810 (Japan); Haba, H.; Komori, Y. [Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan)

    2016-09-15

    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 {sup nat}Ti(α,x){sup 51}Cr reaction. The irradiations were done with E{sub α} = 20.7 and E{sub α} = 51.25 MeV, I{sub α} = 50 nA alpha particle beams for about 1 h. Direct or cumulative activation cross sections were determined for production of the {sup 72,73,75}Se, {sup 71,72,74,76,78}As, and {sup 69}Ge 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.

  13. Molecular Basis of Prodrug Activation by Human Valacyclovirase, an [alpha]-Amino Acid Ester Hydrolase

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Longsheng; Xu, Zhaohui; Zhou, Jiahai; Lee, Kyung-Dall; Amidon, Gordon L. (Michigan)

    2008-07-08

    Chemical modification to improve biopharmaceutical properties, especially oral absorption and bioavailability, is a common strategy employed by pharmaceutical chemists. The approach often employs a simple structural modification and utilizes ubiquitous endogenous esterases as activation enzymes, although such enzymes are often unidentified. This report describes the crystal structure and specificity of a novel activating enzyme for valacyclovir and valganciclovir. Our structural insights show that human valacyclovirase has a unique binding mode and specificity for amino acid esters. Biochemical data demonstrate that the enzyme hydrolyzes esters of {alpha}-amino acids exclusively and displays a broad specificity spectrum for the aminoacyl moiety similar to tricorn-interacting aminopeptidase F1. Crystal structures of the enzyme, two mechanistic mutants, and a complex with a product analogue, when combined with biochemical analysis, reveal the key determinants for substrate recognition; that is, a flexible and mostly hydrophobic acyl pocket, a localized negative electrostatic potential, a large open leaving group-accommodating groove, and a pivotal acidic residue, Asp-123, after the nucleophile Ser-122. This is the first time that a residue immediately after the nucleophile has been found to have its side chain directed into the substrate binding pocket and play an essential role in substrate discrimination in serine hydrolases. These results as well as a phylogenetic analysis establish that the enzyme functions as a specific {alpha}-amino acid ester hydrolase. Valacyclovirase is a valuable target for amino acid ester prodrug-based oral drug delivery enhancement strategies.

  14. The Determination of Gross Alpha And Beta Activity of Drinking Water in Turkey

    International Nuclear Information System (INIS)

    Dilaver, A.T.; Cifter, C.; Altay, T.

    2002-01-01

    Man and his environment must be protected from the adverse effects of pesticides, radiation, noise and other forms of pollutions. Radioactive materials occur naturally in the environment (for example uranium, thorium and potassium). Same radioactive compounds arise from human activities (for example from medical or industrial uses of radioactivity). Drinking water should be safe to use and aesthetically pleasing. World Health Organisation (WHO) and Turkish Standards (TSE) have established maximum contaminant levels for gross alpha and gross beta. The purpose of these study is to determine the level of gross alpha and gross beta activities of samples collected from the different Regional Directories of The State Hydraulic Works (DSI)). After that compare the results versus permissible values of World Health Organisation and Turkish Standards. Collected samples from 14 Regional Directories of The State Hydraulic Works (DSI), have completed. All the analyses results suitable for WHO and TSE. We will give all the research our final report after completed the other Regional Directories' s analyses

  15. CR-39 as an alpha spectrometer: analysis of the activity of a fossil from Presidente Prudente region, SP, Brazil

    International Nuclear Information System (INIS)

    Novaes, Felipe P.; Tello Saenz, Carlos A.; Balan, Ana Maria Osorio A.; Dias, Airton N.C.; Soares, Cleber J.; Oliveira, Roger D.; Barra, Beatriz C.

    2007-01-01

    In this work, CR-39 (a commercial polymer) was used as an alpha spectrometer, based on the relationship between the diameter and the trace gray scale with the energy of the incident alpha particle. A rock from Presidente Prudente region (SP, Brazil), containing a fossil, was analysed and a comparison of the activities in the areas with and without the fossil sample have been compared

  16. Trypanosoma cruzi: activities of lapachol and alpha- and beta-lapachone derivatives against epimastigote and trypomastigote forms.

    Science.gov (United States)

    Salas, Cristian; Tapia, Ricardo A; Ciudad, Karina; Armstrong, Verónica; Orellana, Myriam; Kemmerling, Ulrike; Ferreira, Jorge; Maya, Juan Diego; Morello, Antonio

    2008-01-15

    Derivatives of natural quinones with biological activities, such as lapachol, alpha- and beta-lapachones, have been synthesized and their trypanocidal activity evaluated in vitro in Trypanosoma cruzi cells. All tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity as compared with current trypanocidal drugs, nifurtimox and benznidazole. The results presented here show that the anti-T. cruzi activity of the alpha-lapachone derivatives can be increased by the replacement of the benzene ring by a pyridine moiety. Free radical production and consequently oxidative stress through redox cycling or production of electrophilic metabolites are the potential biological mechanism of action for these synthetic quinones.

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

    International Nuclear Information System (INIS)

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

    1995-11-01

    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

  18. Fuel performance review at TAPS 1 and 2 with respect to reactor coolant crud and alpha activity

    International Nuclear Information System (INIS)

    Papachan, Deepa; Kharat, P.B.; Panda, A.K.; Maskey, S.M.; Joshi, M.

    2015-01-01

    Tarapur Atomic Power Station -1 and 2 (TAPS-1 and 2) consists of twin unit of BWR in India. The reactors were commissioned during 1969-1970. Present rated capacity of each reactor is 530 MWth. Each reactor core has 284 fuel assemblies. Fuel reliability is of highest importance for any nuclear reactor operator to prevent or minimise radioactive release from a reactor. Fuel performance monitoring at TAPS 1 and 2 is carried out throughout the fuel cycle with the help of thermal parameters and radiochemistry parameters. Thermal parameters like Peak Heat Flux (PHF), Minimum Critical Heat Flux Ratio (MCHFR) etc. are calculated on monthly basis with the help of tracing of neutron flux at 52 nodes evenly distributed over entire core of the reactor. Radiochemistry parameters are determined by analysis of reactor coolant and air ejector off gas. Reactor coolant is analysed for the gross gamma activity, activities of different Iodine isotopes and other element like Cesium, Technicium, Molybdenum and Neptunium. Air ejector off gas is analysed for FPNG, mainly Xenon and Krypton isotopes. An increase in these parameters beyond certain limits is indicative of fuel failures. A comparative analysis of all these parameters helps in identifying the time of fuel failure occurrence, assessing the extent of fuel failure growth and determining the contribution of tramp uranium towards fuel performance evaluation. This feedback of fuel performance during the fuel cycle increases the confidence level of detecting leaky fuel bundle by wet sipping method. In order to achieve high fuel integrity one has to compare oneself with the global trend of fuel performance. FRI of WANO performance indicator is one of the indices of fuel performance of a reactor which is based on the FPNG release. Apart from the above mentioned parameters, there exists another indicator of fuel performance which is based on presence of alpha activity in reactor coolant and fuel pool water. This paper compares the trend

  19. The Role of Alpha Activity in Spatial and Feature-Based Attention

    NARCIS (Netherlands)

    van Diepen, Rosanne M.; Miller, Lee M.; Mazaheri, Ali; Geng, Joy J.

    2016-01-01

    Modulations in alpha oscillations (∼10 Hz) are typically studied in the context of anticipating upcoming stimuli. Alpha power decreases in sensory regions processing upcoming targets compared to regions processing distracting input, thereby likely facilitating processing of relevant information

  20. A survey of gross alpha and gross beta activity in soil samples in Kinta District, Perak, Malaysia

    International Nuclear Information System (INIS)

    Lee, Siak Kuan; Wagiran, Husin; Ramli, Ahmad Termizi

    2014-01-01

    The objective of this study was to determine the gross alpha and gross beta activity concentrations from the different soil types found in the Kinta District, Perak, Malaysia. A total of 128 soil samples were collected and their dose rates were measured 1 m above the ground. Gross alpha and gross beta activity measurements were carried out using gas flow proportional counter, Tennelec Series 5 LB5500 Automatic Low Background Counting System. The alpha activity concentration ranged from 15 to 9634 Bq kg -1 with a mean value of 1558±121 Bq kg -1 . The beta activity concentration ranged from 142 to 6173 Bq kg -1 with a mean value of 1112±32 Bq kg -1 . High alpha and beta activity concentrations are from the same soil type. The results of the analysis show a strong correlation between the gross alpha activity concentration and dose rate (R = 0.92). The data obtained can be used as a database for each soil type. (authors)

  1. 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

    2005-11-11

    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

  2. A single amino acid residue, Ala 105, confers 16alpha-hydroxylase activity to human cytochrome P450 17alpha-hydroxylase/17,20 lyase.

    Science.gov (United States)

    Swart, Amanda C; Storbeck, Karl-Heinz; Swart, Pieter

    2010-04-01

    In adrenal steroidogenesis, CYP17 catalyses the 17alpha-hydroxylation of pregnenolone and progesterone and the subsequent 17,20-lyase reaction, yielding adrenal androgens. The enzyme exhibits distinctly different selectivities towards these substrates in various species. CYP17 has also been shown to exhibit 16alpha-hydroxylase activity towards progesterone in some species, with only human and chimp CYP17 catalysing the biosynthesis of substantial amounts of 16-OHprogesterone. The 16alpha-hydroxylase activity was investigated by introducing an Ala105Leu substitution into human CYP17. The converse mutation, Leu105Ala was introduced into the baboon, goat and pig enzymes. Wt human CYP17 converted approximately 30% progesterone to 16-OHprogesterone while the Ala105Leu mutant converted negligible amounts to 16-OHprogesterone ( approximately 9%), comparable to wt CYP17 of the other three species when expressed in COS-1 cells. The ratio of 17-hydroxylated products to 16-OHprogesterone of human CYP17 was 2.7 and that of the mutant human construct 10.5. Similar ratios were observed for human and goat CYP17 with the corresponding Ala or Leu residues. Although the Leu105Ala mutation of both baboon and pig CYP17 exhibited the same trend regarding the ratios, the rate of progesterone conversion was reduced. Coexpression with cytochrome b(5) significantly decreased the ratio of 17-hydroxylated products to 16-OHprogesterone in the Leu105 constructs, while effects were negligible with Ala at this position. Homology models show that Ala105 faces towards the active pocket in the predicted B'-C domain of CYP17. The smaller residue allows more flexibility of movement in the active pocket than Leu, presenting both the C16 and C17 of progesterone to the iron-oxy complex. 2010 Elsevier Ltd. All rights reserved.

  3. 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: jbarbosa@ltf.ufpb.br [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Biologia Molecular

    2012-07-01

    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)

  4. Modifications of the alpha,beta-double bond in chalcones only marginally affect the antiprotozoal activities

    DEFF Research Database (Denmark)

    Nielsen, S F; Kharazmi, A; Christensen, S B

    1998-01-01

    Methods for selective alkylation of chalcones in the alpha- or beta-position and for selective reduction of the alpha,beta-double bond have been developed. The antiparasitic potencies of the alpha,beta-double bond modified chalcones only differ marginally from the potencies of the parent chalcones...

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    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...... of SDF-1alpha in basophils are unknown....

  6. Alpha contamination assessment for D ampersand D activities: Monitoring inside glove boxes and vessels

    International Nuclear Information System (INIS)

    Rawool-Sullivan, M.W.; Bolton, R.D.; Conaway, J.G.; MacArthur, D.W.

    1996-02-01

    We have developed a new approach to glove box monitoring that involves drawing air out of one glove port through a detection grid that collects ions created in the air inside the glove box by ionizing radiation, especially alpha radiation. The charge deposited on the detection grid by the ions is measured with a sensitive electrometer. The air can be circulated back to the glove box through the other glove port, preventing contamination from leaving the glove box and detector system. Initial experiments using a mock-up constructed of sheet metal indicate that this technology provides the measurement technique needed to perform a defensible, non-invasive measurement of alpha contamination inside glove boxes destined for waste disposal. This can result in an enormous cost savings if a given glove box can be shown to fall into the catagory of Low-Level Waste rather than Trans-Uranic Waste. Considering that hundreds of glove boxes contaminated with plutonium will be taken out of service at various nuclear facilities over the next few years, the potential cost savings associated with disposal as LLW rather than TRU waste are substantial

  7. Correlated alpha activity with the facial expression processing network in a simultaneous EEG-fMRI experiment.

    Science.gov (United States)

    Simoes, Marco; Direito, Bruno; Lima, Joao; Castelhano, Joao; Ferreira, Carlos; Couceiro, Ricardo; Carvalho, Paulo; Castelo-Branco, Miguel

    2017-07-01

    The relationship between EEG and fMRI data is poorly covered in the literature. Extensive work has been conducted in resting-state and epileptic activity, highlighting a negative correlation between the alpha power band of the EEG and the BOLD activity in the default-mode-network. The identification of an appropriate task-specific relationship between fMRI and EEG data for predefined regions-of-interest, would allow the transfer of interventional paradigms (such as BOLD-based neurofeedback sessions) from fMRI to EEG, enhancing its application range by lowering its costs and improving its flexibility. In this study, we present an analysis of the correlation between task-specific alpha band fluctuations and BOLD activity in the facial expressions processing network. We characterized the network ROIs through a stringent localizer and identified two clusters on the scalp (one frontal, one parietal-occipital) with marked alpha fluctuations, related to the task. We then check whether such power variations throughout the time correlate with the BOLD activity in the network. Our results show statistically significant negative correlations between the alpha power in both clusters and for all the ROIs of the network. The correlation levels have still not met the requirements for transferring the protocol to an EEG setup, but they pave the way towards a better understand on how frontal and parietal-occipital alpha relates to the activity of the facial expressions processing network.

  8. 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)

    2008-09-20

    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)

  9. A semi-automated system for the X-ray diffractometry of alpha-active specimens

    International Nuclear Information System (INIS)

    Benedict, U.; Dufour, C.

    1978-01-01

    Several automation steps were introduced into a standard X-ray diffractometry system. The system is mainly used for the study of nuclear fuel materials and higher actinide compounds which require containment due to their strong alpha-radioactivity. Automatic sample changers for the alpha-active specimens were constructed. An electrochemical device changes automatically the pulse rate measuring range of the recorder. Digital storage of the pulse rate signals was achieved by using a step scanning device together with a tape punch and a specially developed interface between the detector electronics and the tape punch. The punched tape is used as an input to program HEKUBA. This program calculates peak positions and peak heights and scans the peaks for the compounds present in nuclear fuels, for some hexagonal actinide compounds, and for any cubic structure that may be present. It calculates the lattice parameters of these structures and the proportions of (U,Pu) 2 C 3 and (U,Pu)O 2 phases in carbide fuels

  10. Structural (operational) synchrony of EEG alpha activity during an auditory memory task.

    Science.gov (United States)

    Fingelkurts, Andrew; Fingelkurts, Alexander; Krause, Christina; Kaplan, Alexander; Borisov, Sergei; Sams, Mikko

    2003-09-01

    Memory paradigms are often used in psycho-physiological experiments in order to understand the neural basis underlying cognitive processes. One of the fundamental problems encountered in memory research is how specific and complementary cortical structures interact with each other during episodic encoding and retrieval. A key aspect of the research described below was estimating the coupling of rapid transition processes (in terms of EEG description) which occur in separate cortical areas rather than estimating the routine phase-frequency synchrony in terms of correlation and coherency. It is assumed that these rapid transition processes in the EEG amplitude correspond to the "switching on/off" of brain elemental operations. By making a quantitative estimate of the EEG structural synchrony of alpha-band power between different EEG channels, it was shown that short-term memory has the emergent property of a multiregional neuronal network, and is not the product of strictly hierarchical processing based on convergence through association regions. Moreover, it was demonstrated that the dynamic temporal structure of alpha activity is strongly correlated to the dynamic structure of working memory.

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

    International Nuclear Information System (INIS)

    Tobias, C.C.B.

    1987-01-01

    The absolute activity of U-235 contained in a U 3 O 8 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 1 1/2'' 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) [pt

  12. Evaluation of Acute Phase Reactants As Indicators of Activity in Leprosy

    Directory of Open Access Journals (Sweden)

    A P Jain

    1985-01-01

    Full Text Available Acute phase reactants i. e. ESR, C-reactive proteins, alpha 1 antitrypsin, complement (C3 and circulation immune complexes were evaluated in relation with the activity of the disease in leprosy. Levels of all the acute phase reactants were significantly raised during the active plase (LL and ENL, while these were normal during the arrested phase of the disease. Appearance of, circulating immune complexes also followed the same pattern. It is concluded that raised levels of ESR (C-reactive proteins, alpha-1 antitrypsin, complement (C3 and circulating immune complexes suggest active phase (LL ENL of the disease in leprosy.

  13. Screening of endophytic fungi having ability for antioxidative and alpha-glucosidase inhibitor activities isolated from Taxus sumatrana.

    Science.gov (United States)

    Artanti, N; Tachibana, S; Kardono, L B S; Sukiman, H

    2011-11-15

    Endophytic microbes are considered as an important source of natural products. They show antibiotic, anticancer, antioxidative and antidiabetic activities. Therefore, there are many reports on the isolation and bioactivity screening of endophytic fungi from various plants including Taxus species. Taxus sumatrana (Miq.) de Laub is found in Indonesia. The objective of this study is to conduct an in vitro screening of 14 endophytic fungi isolated from Taxus sumatrana having antioxidative and alpha-glucosidase inhibitor activities. Each endophytic fungus was cultured for 7 days and the fungal mycelium and medium were extracted with methanol and ethyl acetate, respectively, to produce each extract. The antioxidative activity of each extract was tested by DPPH free radical scavenging activity and beta-carotene bleaching assays, whereas antidiabetic activity was tested based on alpha-glucosidase inhibitor activity. The screening results showed that fungal mycelia of TSC 13 had the best alpha-glucosidase inhibitor activity and TSC 24 had the best antioxidative activity. Isolation of bioactive compounds from TSC 13 and TSC 24 is being conducted. This is the first report that endophytic fungi isolated from T. sumatrana exhibited anti alpha-glucosidase inhibitory and anti oxidative activities.

  14. Optogenetic monitoring of synaptic activity with genetically encoded voltage indicators

    Directory of Open Access Journals (Sweden)

    Ryuichi Nakajima

    2016-08-01

    Full Text Available The age of genetically encoded voltage indicators 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 (ie., 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 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.

  15. 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

    2008-01-01

    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.

  16. Suppression of cardiac myocyte hypertrophy by conjugated linoleic acid: role of peroxisome proliferator-activated receptors alpha and gamma.

    Science.gov (United States)

    Alibin, Caroline P; Kopilas, Melanie A; Anderson, Hope D I

    2008-04-18

    Conjugated linoleic acid (CLA) refers to a naturally occurring mixture of positional and geometric isomers of linoleic acid. Evidence suggests that CLA is a dietary constituent and nutraceutical with anti-cancer, insulin-sensitizing, immunomodulatory, weight-partitioning, and cardioprotective properties. The aim of this study was to evaluate the effects of intervention with CLA on cardiac hypertrophy. In vitro, CLA prevented indicators of cardiomyocyte hypertrophy elicited by endothelin-1, including cell size augmentation, protein synthesis, and fetal gene activation. Similar anti-hypertrophic effects of CLA were observed in hypertrophy induced by angiotensin II, fibroblast growth factor, and mechanical strain. CLA may inhibit hypertrophy through activation of peroxisome proliferator-activated receptors (PPARs). CLA stimulated PPAR activity in cardiomyocytes, and the anti-hypertrophic effects of CLA were blocked by genetic and pharmacological inhibitors of PPAR isoforms alpha and gamma. CLA may disrupt hypertrophic signaling by stimulating diacylglycerol kinase zeta, which decreases availability of diacylglycerol and thereby inhibits the protein kinase Cepsilon pathway. In vivo, dietary CLA supplementation significantly reduced blood pressure and cardiac hypertrophy in spontaneously hypertensive heart failure rats. These data suggest that dietary supplementation with CLA may be a viable strategy to prevent pathological cardiac hypertrophy, a major risk factor for heart failure.

  17. Mechanisms of activation of muscle branched-chain alpha-keto acid dehydrogenase during exercise in man

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; MacLean, D A; Saltin, B

    1996-01-01

    1. Exercise leads to activation (dephosphorylation) of the branched-chain alpha-keto acid dehydrogenase (BCKADH). Here we investigate the effect of low pre-exercise muscle glycogen content and of branched-chain amino acid (BCAA) ingestion on the activity of BCKADH at rest and after 90 min of one...

  18. Maltose effects on barley malt diastatic power enzyme activity and thermostability at high isothermal mashing temperature: II. Alpha-amylase

    Science.gov (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 ...

  19. Soluble alpha-APP (sAPPalpha regulates CDK5 expression and activity in neurons.

    Directory of Open Access Journals (Sweden)

    Daniela Hartl

    Full Text Available A growing body of evidence suggests a role for soluble alpha-amyloid precursor protein (sAPPalpha in pathomechanisms of Alzheimer disease (AD. This cleavage product of APP was identified to have neurotrophic properties. However, it remained enigmatic what proteins, targeted by sAPPalpha, might be involved in such neuroprotective actions. Here, we used high-resolution two-dimensional polyacrylamide gel electrophoresis to analyze proteome changes downstream of sAPPalpha in neurons. We present evidence that sAPPalpha regulates expression and activity of CDK5, a kinase that plays an important role in AD pathology. We also identified the cytoprotective chaperone ORP150 to be induced by sAPPalpha as part of this protective response. Finally, we present functional evidence that the sAPPalpha receptor SORLA is essential to mediate such molecular functions of sAPPalpha in neurons.

  20. Drotrecogin Alpha (Activated in Two Patients with the Hantavirus Cardiopulmonary Syndrome

    Directory of Open Access Journals (Sweden)

    Robert C McDermid

    2006-01-01

    Full Text Available Hantavirus cardiopulmonary syndrome (HCPS is associated with rapid cardiopulmonary collapse from endothelial injury, resulting in massive capillary leak, shock and severe hypoxemic respiratory failure. To date, treatment remains supportive and includes mechanical ventilation, vasopressors and extracorporeal membrane oxygenation, with mortality approaching 50%. Two HCPS survivors initially given drotrecogin alpha (activated (DAA for presumed bacterial septic shock are described. Vasoactive medications were required for a maximum of 52 h, whereas creatinine levels and platelet counts normalized within seven to nine days. Given the similar presentations of HCPS and bacterial septic shock, empirical DAA therapy will likely be initiated before a definitive diagnosis of HCPS is made. Further observations of DAA in HCPS seem warranted.

  1. Induction of antibacterial activity by alpha-d-oligogalacturonides in Nephrolepis sp. (pteridophyta).

    Science.gov (United States)

    Basile, A; Spagnuolo, V; Giordano, S; Sorrentino, C; Lavitola, A; Castaldo-Cobianchi, R

    1997-03-01

    This paper presents data on the induction by alpha-d-oligogalacturonides (OG) of antibiotic activity in vitro by the fern Nephrolepis sp. The extracts from the fern grown aseptically, partly in a medium containing a mixture of OG and partly in a medium lacking OG, as control, were tested against several bacterial strains. The results show that the OG mixture promotes the production of antibiotic compounds. Comparing the present results with those on the antimicrobial properties of the same fern grown in a greenhouse, we discuss the hypothesis that the production of antibiotic substances can be elicited by different factors, such as products of synthesis or degradation of the biotic component of the soil or by OG (in axenic culture) that can mimic the effect of natural elicitors.

  2. In vitro evaluation of chitosan-coated liposome containing both coenzyme Q10 and alpha-lipoic acid: Cytotoxicity, antioxidant activity, and antimicrobial activity.

    Science.gov (United States)

    Zhao, Guodong; Hu, Caibiao; Xue, Ying

    2018-04-01

    Chitosan-coated liposome containing both coenzyme Q10 and alpha-lipoic acid (CCAL) was a novel multifunctional nano delivery system exhibited long-term stability at room temperature and high encapsulation efficiency. Which containing two kinds of antioxidants (coenzyme Q10 and alpha-lipoic acid) and two antibacterial agents (chitosan and alpha-lipoic acid). However, the further biocompatibility, such as cytotoxicity and antioxidant activity, and antimicrobial activity of CCAL, has not been systematically evaluated. This study aims to evaluate the cytotoxicity, antioxidant activity and antimicrobial activity of CCAL. This article evaluated the in vitro cytotoxicity and antioxidant activity of CCAL by CCK8 assay, and antimicrobial activity on Staphylococcus aureus and Escherichia coli was investigated. For antioxidant activity study, CCAL displayed significant antioxidant effect when compared with control group (Pcytotoxicity and artificial preservatives free. © 2017 Wiley Periodicals, Inc.

  3. BIOLOGICAL ACTIVITIES AFFORDED BY THE EXTRACT FROM RARU BARK TO INHIBIT ACTION OF ALPHA- GLUCOSIDASE ENZYMES

    Directory of Open Access Journals (Sweden)

    Gunawan Pasaribu

    2011-06-01

    Full Text Available Raru (Shoreabalanocarpoides Sym signifies one of the tree species that grows widespread in Sumatra Island.  Its bark portion is commonly used by local villagers as additional ingredient mixed to nira (sugar palm juice.  This addition is intended to make the juice more durable and also to enrich its taste after the juice is previously fermented to become traditional toddy beverage or the so-call “tuak”.  Local villagers believe that raru bark can reduce the level of blood sugar. As the relevance, the research was conducted to confirm that the extract from raru bark could afford its biological activities to inhibit alpha-glucosidase enzyme through its characterization, quantification, and isolation of its boactive compound. The extraction was performed using two methods (i.e.reflux and maceration techniques. Result revealed that the bark extract obtained from both techniques contained polyphenol compounds: flavonoid, saponin and tannin. Further, raru-bark extract from the reflux and maceration techniques could inhibit the action of alpha glucosidase enzymes on carbohydrate substrate ( i.e. p -nitrophenil-α-D-glucopyranose, at respectively 90.67% and 97.33%. Meanwhile, the inhibition activities afforded by the patented drug as a control (i.e. glucobay equaled to 97.05%.  Assesment using UV-VIS spectroscopy, showed that the maximum spectrum of bioactive compound in the extract was at the wave length of 288.6 nm. Scrutiny using FTIR spectroscopy could identif y the presence of aromatic groups in the compound, containing -OH, C-H, C=C, C-O and C-H bond types. Analysis using GC-MS exhibited that the compound had molecular weight of 390 with molecular structure as C20H22O8. Ultimately, data analysis scrutiny with the aid of NMR judged the most plausible compound as bioactive was 4-Glucosyl-3, 4’, 5-trihydroxystilbene.

  4. Temporal Courses in EEG Theta and Alpha Activity in the Dynamic Health Qigong Techniques Wu Qin Xi and Liu Zi Jue

    Directory of Open Access Journals (Sweden)

    Diana Henz

    2018-01-01

    Full Text Available Health Qigong is a common technique of Traditional Chinese Medicine applied to strengthen mental and physical health. Several studies report increases in EEG theta and alpha activity after meditative Qigong techniques indicating a relaxed state of mind. To date, little is known on the effects of dynamic Health Qigong techniques that comprise bodily movements on brain activity. In the current study, we compared effects of two dynamic Health Qigong techniques on EEG brain activity. Subjects performed the techniques Wu Qin Xi (five animals play and Liu Zi Jue (six healing sounds in a within-subjects design. Eyes-open and eyes-closed resting EEG was recorded before and immediately after each 15-min practice block. Additionally, the Profile of Mood States (POMS questionnaire was administered at pretest, and after each 15-min practice block. Results show a decrease in alpha activity after 15 min, followed by an increase after 30 min in the Health Qigong technique Liu Zi Jue. Theta activity was decreased after 15 min, followed by an increase after 30 min in the technique Wu Qin Xi. Results of the POMS indicated an increased vigor-activity level with decreased fatigue and tension-anxiety levels in both techniques after 30 min of practice. Our results demonstrate different temporal dynamics in EEG theta and alpha activity for the Health Qigong techniques Wu Qin Xi and Liu Zi Jue. We hypothesize that the found brain activation patterns result from different attentional focusing styles and breathing techniques performed during the investigated Health Qigong techniques.

  5. 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.

    Science.gov (United States)

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

    2009-08-01

    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.

  6. Technical Publications as Indicators for Nuclear Fuel Cycle Declarable Activities

    International Nuclear Information System (INIS)

    Schuler, R.; El Gebaly, A.; Feldman, Y.; Gagne, D.; Schot, P.-M.; Ferguson, M.

    2015-01-01

    The Department of Safeguards aims to provide credible assurances to the international community that States are fulfiling their safeguards obligations in that all nuclear material remains in peaceful use. It does so in part by developing and implementing methodologies for early detection of undeclared activities or misuse of nuclear material or technology, based on large and diverse sources of information. Analyzing scientific, technical and patent information allows analysts in the Department to understand the technology available to a State, to forecast possible technical developments, to map collaborative research activities within and across States, and compare that information with declarations received by the State for completeness and correctness. Furthermore, with regard to patent information, scientists or companies want to make sure their intellectual property is protected; accordingly, patents are frequently filed before the information is published elsewhere, making patent information also an early indicator of relevant activities. Dealing with such large information sources requires the use of an innovative methodology conducting analysis. The Department has recently begun to examine the efficacy of link analysis tools to help carry out its mission. Using the link analysis platform Palantir, the authors conducted several case studies with the aim of deriving sound analytical results from large amounts of technical information within a reasonable time frame. The authors used data sets of bibliographic references from the IAEA International Nuclear Information System (INIS),Web of Science, Science Direct and data on worldwide patents from the European Patent Office (EPO). Based on these case studies, the authors are developing methodologies for the efficient application of link analysis to scientific and technical information, thus strengthening the Department's information collection and analysis capabilities and the overall process of State

  7. Spectral Analysis of Geomagnetic Activity Indices and Solar Wind Parameters

    Directory of Open Access Journals (Sweden)

    Jung-Hee Kim

    2014-06-01

    Full Text Available Solar variability is widely known to affect the interplanetary space and in turn the Earth’s electromagnetical environment on the basis of common periodicities in the solar and geomagnetic activity indices. The goal of this study is twofold. Firstly, we attempt to associate modes by comparing a temporal behavior of the power of geomagnetic activity parameters since it is barely sufficient searching for common peaks with a similar periodicity in order to causally correlate geomagnetic activity parameters. As a result of the wavelet transform analysis we are able to obtain information on the temporal behavior of the power in the velocity of the solar wind, the number density of protons in the solar wind, the AE index, the Dst index, the interplanetary magnetic field, B and its three components of the GSM coordinate system, BX, BY, BZ. Secondly, we also attempt to search for any signatures of influence on the space environment near the Earth by inner planets orbiting around the Sun. Our main findings are as follows: (1 Parameters we have investigated show periodicities of ~ 27 days, ~ 13.5 days, ~ 9 days. (2 The peaks in the power spectrum of BZ appear to be split due to an unknown agent. (3 For some modes powers are not present all the time and intervals showing high powers do not always coincide. (4 Noticeable peaks do not emerge at those frequencies corresponding to the synodic and/or sidereal periods of Mercury and Venus, which leads us to conclude that the Earth’s space environment is not subject to the shadow of the inner planets as suggested earlier.

  8. delta-Atracotoxins from australian funnel-web spiders compete with scorpion alpha-toxin binding but differentially modulate alkaloid toxin activation of voltage-gated sodium channels.

    Science.gov (United States)

    Little, M J; Zappia, C; Gilles, N; Connor, M; Tyler, M I; Martin-Eauclaire, M F; Gordon, D; Nicholson, G M

    1998-10-16

    delta-Atracotoxins from the venom of Australian funnel-web spiders are a unique group of peptide toxins that slow sodium current inactivation in a manner similar to scorpion alpha-toxins. To analyze their interaction with known sodium channel neurotoxin receptor sites, we studied their effect on [3H]batrachotoxin and 125I-Lqh II (where Lqh is alpha-toxin II from the venom of the scorpion Leiurus quinquestriatus hebraeus) binding and on alkaloid toxin-stimulated 22Na+ uptake in rat brain synaptosomes. delta-Atracotoxins significantly increased [3H]batrachotoxin binding yet decreased maximal batrachotoxin-activated 22Na+ uptake by 70-80%, the latter in marked contrast to the effect of scorpion alpha-toxins. Unlike the inhibition of batrachotoxin-activated 22Na+ uptake, delta-atracotoxins increased veratridine-stimulated 22Na+ uptake by converting veratridine from a partial to a full agonist, analogous to scorpion alpha-toxins. Hence, delta-atracotoxins are able to differentiate between the open state of the sodium channel stabilized by batrachotoxin and veratridine and suggest a distinct sub-conductance state stabilized by delta-atracotoxins. Despite these actions, low concentrations of delta-atracotoxins completely inhibited the binding of the scorpion alpha-toxin, 125I-Lqh II, indicating that they bind to similar, or partially overlapping, receptor sites. The apparent uncoupling between the increase in binding but inhibition of the effect of batrachotoxin induced by delta-atracotoxins suggests that the binding and action of certain alkaloid toxins may represent at least two distinguishable steps. These results further contribute to the understanding of the complex dynamic interactions between neurotoxin receptor site areas related to sodium channel gating.

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

    LENUS (Irish Health Repository)

    Carroll, Tomás P

    2010-04-15

    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.

  10. Reward bias and lateralization in gambling behavior: behavioral activation system and alpha band analysis.

    Science.gov (United States)

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

    2014-11-30

    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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Activity of interferon alpha, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells.

    Science.gov (United States)

    McCormick, C; Freshney, R I; Speirs, V

    1995-02-01

    The differentiation of A549, a human tumour cell line from type II pneumocytes, can be induced by a crude fibroblast-derived factor (FDF) isolated from the conditioned medium of glucocorticoid-treated lung fibroblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of growth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-alpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a half-life of 1 week. Transforming growth factor alpha and beta, IL-1 alpha and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lung fibroblast-conditioned medium it seems an unlikely candidate for FDF. Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the absence of DX. This suggests that differentiation-inducing activity may be present in several paracrine factors, but that so far a candidate for FDF has not been identified.

  12. 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.

  13. Alpha-hemolysin is required for the activation of the autophagic pathway in Staphylococcus aureus-infected cells.

    Science.gov (United States)

    Mestre, María Belén; Fader, Claudio M; Sola, Claudia; Colombo, María Isabel

    2010-01-01

    Staphylococcus aureus is a pathogen that causes serious infectious diseases eventually leading to septic and toxic shock. Classically S. aureus has been considered an extracellular pathogen, but cumulative evidence indicates that it invades cells and replicates intracellularly leading to staphylococcal persistence and chronic disease. It has been previously shown that this pathogen localizes to LC3-labeled compartments and subverts the autophagy pathway. One of the key features of S. aureus infection is the production of a series of virulence factors, including secreted enzymes and toxins. In the present report we present evidence that the pore-forming toxin alpha-hemolysin (Hla) is a S. aureus secreted factor which participates in the activation of the autophagic pathway. In addition, our results indicate that although the toxin elicits an autophagic response this pathway is dysfunctional as indicated by the accumulation of the LC3-II form in cell lysates obtained from intoxicated cells. In addition, not only the purified Hla toxin but also the toxin-secreting pathogen prevented the maturation of autophagosomes. Interestingly, in cells infected with the wild-type strain of S. aureus the bacteria-containing compartments which recruited LC3 onto the limiting membrane did not accumulate the acidotropic probe LysoTracker. In contrast, those phagosomes containing the Hla(-) mutant (unable to produce the toxin) localized in an acidic compartment unlabeled by LC3. These results suggest that the LC3 protein is recruited only to those damaged vacuoles (i.e., perforated by the toxin), perhaps as an attempt to protect the cells. Furthermore, we have demonstrated that the toxin-dependent activation of autophagy (although it is regulated by calcium and requires Atg5) is independent of both PI3Kinase activity and Beclin 1 suggesting the involvement of a non-canonical autophagy pathway.

  14. Statistical Properties of Geomagnetic Activity Indices and Solar Wind Parameters

    Directory of Open Access Journals (Sweden)

    Jung-Hee Kim

    2014-06-01

    Full Text Available As the prediction of geomagnetic storms is becoming an important and practical problem, conditions in the Earth’s magnetosphere have been studied rigorously in terms of those in the interplanetary space. Another approach to space weather forecast is to deal with it as a probabilistic geomagnetic storm forecasting problem. In this study, we carry out detailed statistical analysis of solar wind parameters and geomagnetic indices examining the dependence of the distribution on the solar cycle and annual variations. Our main findings are as follows: (1 The distribution of parameters obtained via the superimposed epoch method follows the Gaussian distribution. (2 When solar activity is at its maximum the mean value of the distribution is shifted to the direction indicating the intense environment. Furthermore, the width of the distribution becomes wider at its maximum than at its minimum so that more extreme case can be expected. (3 The distribution of some certain heliospheric parameters is less sensitive to the phase of the solar cycle and annual variations. (4 The distribution of the eastward component of the interplanetary electric field BV and the solar wind driving function BV2, however, appears to be all dependent on the solar maximum/minimum, the descending/ascending phases of the solar cycle and the equinoxes/solstices. (5 The distribution of the AE index and the Dst index shares statistical features closely with BV and BV2 compared with other heliospheric parameters. In this sense, BV and BV2 are more robust proxies of the geomagnetic storm. We conclude by pointing out that our results allow us to step forward in providing the occurrence probability of geomagnetic storms for space weather and physical modeling.

  15. 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

    2008-01-01

    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...

  16. Alpha-Band Activity Reveals Spontaneous Representations of Spatial Position in Visual Working Memory.

    Science.gov (United States)

    Foster, Joshua J; Bsales, Emma M; Jaffe, Russell J; Awh, Edward

    2017-10-23

    An emerging view suggests that spatial position is an integral component of working memory (WM), such that non-spatial features are bound to locations regardless of whether space is relevant [1, 2]. For instance, past work has shown that stimulus position is spontaneously remembered when non-spatial features are stored. Item recognition is enhanced when memoranda appear at the same location where they were encoded [3-5], and accessing non-spatial information elicits shifts of spatial attention to the original position of the stimulus [6, 7]. However, these findings do not establish that a persistent, active representation of stimulus position is maintained in WM because similar effects have also been documented following storage in long-term memory [8, 9]. Here we show that the spatial position of the memorandum is actively coded by persistent neural activity during a non-spatial WM task. We used a spatial encoding model in conjunction with electroencephalogram (EEG) measurements of oscillatory alpha-band (8-12 Hz) activity to track active representations of spatial position. The position of the stimulus varied trial to trial but was wholly irrelevant to the tasks. We nevertheless observed active neural representations of the original stimulus position that persisted throughout the retention interval. Further experiments established that these spatial representations are dependent on the volitional storage of non-spatial features rather than being a lingering effect of sensory energy or initial encoding demands. These findings provide strong evidence that online spatial representations are spontaneously maintained in WM-regardless of task relevance-during the storage of non-spatial features. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Salivary alpha amylase activity in human beings of different age groups subjected to psychological stress.

    Science.gov (United States)

    Sahu, Gopal K; Upadhyay, Seema; Panna, Shradha M

    2014-10-01

    Salivary alpha-amylase (sAA) has been proposed as a sensitive non-invasive biomarker for stress-induced changes in the body that reflect the activity of the sympathetic nervous system. Though several experiments have been conducted to determine the validity of this salivary component as a reliable stress marker in human subjects, the effect of stress induced changes on sAA level in different age groups is least studied. This article reports the activity of sAA in human subjects of different age groups subjected to psychological stress induced through stressful video clip. Differences in sAA level based on sex of different age groups under stress have also been studied. A total of 112 subjects consisting of both the male and female subjects, divided into two groups on basis of age were viewed a video clip of corneal transplant surgery as stressor. Activity of sAA from saliva samples of the stressed subjects were measured and compared with the activity of the samples collected from the subjects before viewing the clip. The age ranges of subjects were 18-25 and 40-60 years. The sAA level increased significantly in both the groups after viewing the stressful video. The increase was more pronounced in the younger subjects. The level of sAA was comparatively more in males than females in the respective groups. No significant change in sAA activity was observed after viewing the soothed video clip. Significant increase of sAA level in response to psychological stress suggests that it might act as a reliable sympathetic activity biochemical marker in different stages of human beings.

  18. 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

    2005-07-01

    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.

  19. 2-Azido-( sup 32 P)NAD+, a photoactivatable probe for G-protein structure: Evidence for holotransducin oligomers in which the ADP-ribosylated carboxyl terminus of alpha interacts with both alpha and gamma subunits

    Energy Technology Data Exchange (ETDEWEB)

    Vaillancourt, R.R.; Dhanasekaran, N.; Johnson, G.L.; Ruoho, A.E. (Univ. of Wisconsin Medical School, Madison (USA))

    1990-05-01

    A radioactive and photoactivatable derivative of NAD+, 2-azido-(adenylate-32P)NAD+, has been synthesized and used with pertussis toxin to ADP-ribosylate Cys347 of the alpha subunit (alpha T) of GT, the retinal guanine nucleotide-binding protein. ADP-ribosylation of alpha T followed by light activation of the azide moiety of 2-azido-(adenylate-32P)ADP-ribose produced four crosslinked species involving the alpha and gamma subunits of the GT heterotrimer: an alpha trimer (alpha-alpha-alpha), and alpha-alpha-gamma crosslink, an alpha dimer (alpha-alpha), and an alpha-gamma crosslink. The alpha trimer, alpha-alpha-gamma complex, alpha dimer, and alpha-gamma complexes were immunoreactive with alpha T antibodies. The alpha-alpha-gamma and the alpha-gamma complexes were immunoreactive with antisera recognizing gamma subunits. No evidence was found for crosslinking of alpha T to beta T subunits. Hydrolysis of the thioglycosidic bond between Cys347 and 2-azido-(adenylate-32P)ADP-ribose using mercuric acetate resulted in the transfer of radiolabel from Cys347 of alpha T in the crosslinked oligomers to alpha monomers, indicative of intermolecular photocrosslinking, and to gamma monomers, indicative of either intermolecular crosslinked complexes (between heterotrimers) or intramolecular crosslinked complexes (within the heterotrimer). These results demonstrate that GT exists as an oligomer and that ADP-ribosylated Cys347, which is four residues from the alpha T-carboxyl terminus, is oriented toward and in close proximity to the gamma subunit.

  20. 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.

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

    International Nuclear Information System (INIS)

    Fillies, Thomas; Werkmeister, Richard; Diest, Paul J van; Brandt, Burkhard; Joos, Ulrich; Buerger, Horst

    2005-01-01

    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

  2. Differential effects of triclosan on the activation of mouse and human peroxisome proliferator-activated receptor alpha.

    Science.gov (United States)

    Wu, Yuanfeng; Wu, Qiangen; Beland, Frederick A; Ge, Peter; Manjanatha, Mugimane G; Fang, Jia-Long

    2014-11-18

    Triclosan is an anti-bacterial agent used in many personal care products, household items, medical devices, and clinical settings. Liver tumors occur in mice exposed to triclosan, a response attributed to peroxisome proliferator-activated receptor alpha (PPARα) activation; however, the effects of triclosan on mouse and human PPARα have not been fully evaluated. We compared the effects of triclosan on mouse and human PPARα using PPARα reporter assays and on downstream events of PPARα activation using mouse hepatoma Hepa1c1c7 cells and human hepatoma HepG2 cells. PPARα transcriptional activity was increased by triclosan in a mouse PPARα reporter assay and decreased in a human PPARα reporter assay. Concentrations of triclosan inhibiting 50% cell growth were similar in both human and mouse hepatoma cells. Western blotting analysis showed that triclosan increased acyl-coenzyme A oxidase (ACOX1), a PPARα target, in Hepa1c1c7 cells but decreased the level in HepG2 cells. Treatment of Hepa1c1c7 cells with triclosan enhanced DNA synthesis and suppressed transforming growth factor beta-mediated apoptosis. This did not occur in HepG2 cells. These data demonstrate that triclosan had similar cytotoxicity in Hepa1c1c7 and HepG2 cells, but differential effects on the activation of PPARα, the expression of ACOX1, and downstream events including DNA synthesis and apoptosis. Published by Elsevier Ireland Ltd.

  3. Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha

    Directory of Open Access Journals (Sweden)

    Guolin Li

    2018-01-01

    Conclusions: These findings indicate that PPARA activation prior to acute fasting cannot ameliorate fasting-induced hepatic steatosis, whereas EODF induced metabolic adaptations to protect against fasting-induced steatosis without altering PPARA signaling. Therefore, PPARA activation does not mediate the metabolic adaptation to fasting, at least in preventing acute fasting-induced steatosis.

  4. Does potentized HgCl2 (Mercurius corrosivus) affect the activity of diastase and alpha-amylase?

    Science.gov (United States)

    Witt, Claudia M; Bluth, Michael; Hinderlich, Stephan; Albrecht, Henning; Lüdtke, Rainer; Weisshuhn, Thorolf E R; Willich, Stefan N

    2006-05-01

    Homeopathic drugs even with dilutions beyond 10(23) (high potencies) are frequently used, although their working mechanism is still unknown. Curative information preserved in solvent structure is postulated to exert biologic effects. The objective was to test for a stimulating or inhibiting effect of high potencies of the homeopathic remedy HgCl2 (Mercurius corrosivus) on two sugar hydrolases. High potencies were produced using stepwise dilution plus shaking. Controls included potentized solvent (aqua bidestillata), equimolar dilutions without shaking, and enzyme-free references. Tested were potencies with dilution factors 1:200 (CC) on diastase extract from winter barley, and 1:100 (C) on alpha-amylase from hog pancreas. Enzyme activity was colorimetrically determined by Lugol's iodine-starch reaction. An inhibiting effect of HgCl2 on enzyme activities was observed only in low potencies and dilutions. Statistically significant differences between potencies and controls were not found in randomized and blinded experiments. This experimental design provided independent reproducible results of cell-free in vitro assays. However, it did not indicate an effect of potentized HgCl2 on hydrolases. Demonstrating potency effects may require additional experimental features.

  5. In parkinsonian substantia nigra, alpha-synuclein is modified by acrolein, a lipid-peroxidation product, and accumulates in the dopamine neurons with inhibition of proteasome activity.

    Science.gov (United States)

    Shamoto-Nagai, M; Maruyama, W; Hashizume, Y; Yoshida, M; Osawa, T; Riederer, P; Naoi, M

    2007-01-01

    alpha-Synuclein (alphaSYN) plays a central role in the neural degeneration of Parkinson's disease (PD) through its conformational change. In PD, alphaSYN, released from the membrane, accumulates in the cytoplasm and forms Lewy body. However, the mechanism behind the translocation and conformational change of alphaSYN leading to the cell death has not been well elucidated. This paper reports that in the dopamine neurons of the substantia nigra containing neuromelanin from PD patients, alphaSYN was modified with acrolein (ACR), an aldehyde product of lipid peroxidation. Histopathological observation confirmed the co-localization of protein immunoreactive to anti-alphaSYN and ACR antibody. By Western blot analyses of samples precipitated with either anti-alphaSYN or anti-ACR antibody, increase in ACR-modified alphaSYN was confirmed in PD brain. Modification of recombinant alphaSYN by ACR enhanced its oligomerization, and at higher ACR concentrations alphaSYN was fragmented and polymerized forming a smear pattern in SDS-PAGE. ACR reduced 20S proteasome activity through the direct modification of the proteasome proteins and the production of polymerized ACR-modified proteins, which inhibited proteasome activity in vitro. These results suggest that ACR may initiate vicious cycle of modification and aggregation of proteins, including alphaSYN, and impaired proteolysis system, to cause neuronal death in PD.

  6. Alpha 1 Antitrypsin Inhibits Dendritic Cell Activation and Attenuates Nephritis in a Mouse Model of Lupus.

    Directory of Open Access Journals (Sweden)

    Ahmed S Elshikha

    Full Text Available 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.

  7. Anti-TNF-alpha antibody attenuates subarachnoid hemorrhage-induced apoptosis in the hypothalamus by inhibiting the activation of Erk

    Directory of Open Access Journals (Sweden)

    Ma L

    2018-02-01

    -induced apoptosis in the hypothalamus. Moreover, we found that Erk activation was necessary for apoptosis after SAH and that the microinfusion of anti-TNF-α antibody could inhibit apoptosis by suppressing the increase of p-Erk in the hypothalamus. Finally, our data indicated that the infusion of anti-TNF-α antibody could improve anxiety-like behavior. Conclusion: Collectively, our data demonstrate that anti-TNF-α antibody attenuates apoptosis in the hypothalamus by inhibiting the activation of Erk, which plays an important role in the treatment of SAH. Keywords: apoptosis, subarachnoid hemorrhage, hypothalamus, tumor necrosis factor-alpha, Erk

  8. Active MMPs captured by alpha2Macroglobulin as a marker of disease activity in rheumatoid arthritis

    NARCIS (Netherlands)

    Tchetverikov, I.; Verzijl, N.; Huizinga, T.W.J.; TeKoppele, J.M.; Hanemaaijer, R.; Groot, J. de

    2003-01-01

    Objective. The aim of the present study was to analyze α2Macroglobulin/MMP (α2M/MMP) complex formation and to investigate whether MMP activity in α2M/MMP complexes in serum can be used as a disease marker in rheumatoid arthritis (RA). Methods. High and low molecular weight (H/LMW) substrates and

  9. Modelling the electrical activity of pancreatic alpha-cells based on experimental data from intact mouse islets

    DEFF Research Database (Denmark)

    Diderichsen, Paul Matthias; Gopel, S.O.

    2006-01-01

    + current, a KATP conductance, and an unspecific leak current. Tolbutamide closes KATP channels in the alpha-cell, leading to a reduction of the resting conductance from 1.1 nS to 0.4 nS. This causes the alpha-cell to depolarise from -76 mV to 33 mV. When the basal membrane potential passes the range...... between -60 and -35 mV, the alpha-cell generates action potentials. At higher voltages, the alpha-cell enters a stable depolarised state and the electrical activity ceases. The effects of tolbutamide are simulated by gradually reducing the KATP conductance (g (K,ATP) ) from 500 pS to 0 pS. When g (K......,ATP) is between 72 nS and 303 nS, the model generates action potentials in the same voltage range as the alpha-cell. When g (K,ATP) is lower than 72 nS, the model enters a stable depolarised state, and firing of action potentials is inhibited due to voltage-dependent inactivation of the Na+ and T-type Ca2...

  10. The effect of alpha2-adrenergic drugs on the activity of neurons in the rat nucleus raphe magnus in vitro.

    Science.gov (United States)

    Kanda, T; Ohta, Y; Kida, A; Kemmotsu, O

    1999-02-01

    The nucleus raphe magnus (NRM) is an important descending inhibitory system for pain transmission. We tested whether clonidine, an alpha2-adrenergic agonist, and yohimbine, an alpha2-adrenergic antagonist, modulate the activity of NRM neurons using extracellular recording in a rat brainstem slice preparation. Clonidine 1-20 microM increased firing frequencies (FF) in 22 (37%) and decreased FF in 6 (10%) spontaneously active neurons. Correlation between the concentrations of clonidine and FF changes was unremarkable. Eight spontaneously active neurons (13%) showed increases followed by decreases in FF with increasing doses of clonidine. The remaining 24 neurons (40%) showed no change in FF. Yohimbine 1 microM decreased FF in 38 spontaneously active neurons (58%), whereas the remaining 27 neurons (42%) showed no change in FF. In some neurons, yohimbine antagonized the increase or decrease in FF by application of clonidine. In three silent neurons (25%), clonidine (5 or 10 microM) induced firing activity, which stopped or decreased with the increasing doses of clonidine. In the remaining nine neurons (75%), clonidine did not induce firing activity. We conclude that activation and inhibition of alpha2-adrenergic receptors of NRM neurons augments and suppresses output of the descending inhibitory pain pathway. The nucleus raphe magnus is implicated in descending control of the nociceptive processes. We found that clonidine and yohimbine increased and decreased, respectively, the firing activity of a substantial number of nucleus raphe magnus neurons. Clonidine and may facilitate and yohimbine may reduce the outflow of the descending inhibitory pathway.

  11. Effect of domestic cooking on the starch digestibility, predicted glycemic indices, polyphenol contents and alpha amylase inhibitory properties of beans (Phaseolis vulgaris) and breadfruit (Treculia africana).

    Science.gov (United States)

    Chinedum, E; Sanni, S; Theressa, N; Ebere, A

    2018-01-01

    The effect of processing on starch digestibility, predicted glycemic indices (pGI), polyphenol contents and alpha amylase inhibitory properties of beans (Phaseolis vulgaris) and breadfruit (Treculia africana) was studied. Total starch ranged from 4.3 to 68.3g/100g, digestible starch ranged from 4.3 to 59.2 to 65.7g/100g for the raw and processed legumes; Resistance starch was not detected in most of the legumes except in fried breadfruit and the starches in both the raw and processed breadfruit were more rapidly digested than those from raw and cooked beans. Raw and processed breadfruit had higher hydrolysis curves than raw and processed beans with the amylolysis level in raw breadfruit close to that of white bread. Raw beans had a low glycemic index (GI); boiled beans and breadfruit had intermediate glycemic indices respectively while raw and fried breadfruit had high glycemic indices. Aqueous extracts of the food samples had weak α-amylase inhibition compared to acarbose. The raw and processed legumes contained considerable amounts of dietary phenols and flavonoids. The significant correlation (r=0.626) between α-amylase inhibitory actions of the legumes versus their total phenolic contents suggests the contribution of the phenolic compounds in these legumes to their α-amylase inhibitory properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Monitoring of gross alpha, gross beta and actinides activities in exhaust air released from the waste isolation pilot plant.

    Science.gov (United States)

    Thakur, P; Mulholland, G P

    2011-09-01

    The simultaneous measurements of gross alpha and beta activities is one of the simplest radioanalytical technique used as a method for screening samples of both high and low activities of alpha and beta emitting radionuclides in environmental and bioassay samples. Such measurements are of great interest from both a radiological, waste disposal viewpoint, and to establish a trend of radioactivity based on long term monitoring. At the WIPP (Waste Isolation Pilot Plant) site, unfiltered exhaust air from the underground repository is the most important effluent. As part of its monitoring program, the particulates from WIPP exhaust air are collected everyday at a location typically called the Fixed Air Sampler (FAS) site or Station A, this site is located at the release point for aerosol effluents from the underground to the environment. The measurements of gross alpha and beta activity on air filter samples were performed using an ultra low level counter, PIC-MPC 9604-α/β, from Protean Instrument Corporation. The high sensitivity of the gross alpha and beta instrument enables detection of low value activity from the air filters. In 2009, the values of gross alpha and beta activity concentrations ranged from

  13. 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

    2005-01-01

    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...... related to this syndrome. The variant was examined, using PCR-RFLP, in the DanMONICA cohort comprising a population-based sample of 2349 subjects. MS was defined using the National Cholesterol Education Program -- Adult Treatment Panel III (NCEP-ATPIII) criteria. The allelic frequency of the Ser482 allele...... and insulin secretion, 24-ambulatory blood pressure or left ventricular mass index. In conclusion, the Gly482Ser polymorphism of the PGC-1alpha gene is not associated with the metabolic syndrome, related quantitative traits or cardiac hypertrophy among Danish Caucasian subjects...

  14. Real-time Neural Network predictions of geomagnetic activity indices

    Science.gov (United States)

    Bala, R.; Reiff, P. H.

    2009-12-01

    The Boyle potential or the Boyle Index (BI), Φ (kV)=10-4 (V/(km/s))2 + 11.7 (B/nT) sin3(θ/2), is an empirically-derived formula that can characterize the Earth's polar cap potential, which is readily derivable in real time using the solar wind data from ACE (Advanced Composition Explorer). The BI has a simplistic form that utilizes a non-magnetic "viscous" and a magnetic "merging" component to characterize the magnetospheric behavior in response to the solar wind. We have investigated its correlation with two of conventional geomagnetic activity indices in Kp and the AE index. We have shown that the logarithms of both 3-hr and 1-hr averages of the BI correlate well with the subsequent Kp: Kp = 8.93 log10(BI) - 12.55 along with 1-hr BI correlating with the subsequent log10(AE): log10(AE) = 1.78 log10(BI) - 3.6. We have developed a new set of algorithms based on Artificial Neural Networks (ANNs) suitable for short term space weather forecasts with an enhanced lead-time and better accuracy in predicting Kp and AE over some leading models; the algorithms omit the time history of its targets to utilize only the solar wind data. Inputs to our ANN models benefit from the BI and its proven record as a forecasting parameter since its initiation in October, 2003. We have also performed time-sensitivity tests using cross-correlation analysis to demonstrate that our models are as efficient as those that incorporates the time history of the target indices in their inputs. Our algorithms can predict the upcoming full 3-hr Kp, purely from the solar wind data and achieve a linear correlation coefficient of 0.840, which means that it predicts the upcoming Kp value on average to within 1.3 step, which is approximately the resolution of the real-time Kp estimate. Our success in predicting Kp during a recent unexpected event (22 July ’09) is shown in the figure. Also, when predicting an equivalent "one hour Kp'', the correlation coefficient is 0.86, meaning on average a prediction

  15. 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.

    2010-10-21

    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.

  16. Fijiolides A and B, inhibitors of TNF-alpha-induced NFkappaB activation, from a marine-derived sediment bacterium of the genus Nocardiopsis.

    Science.gov (United States)

    Nam, Sang-Jip; Gaudêncio, Susana P; Kauffman, Christopher A; Jensen, Paul R; Kondratyuk, Tamara P; Marler, Laura E; Pezzuto, John M; Fenical, William

    2010-06-25

    Fijiolide A, a potent inhibitor of TNF-alpha-induced NFkappaB activation, along with fijiolide B, were isolated from a marine-derived bacterium of the genus Nocardiopsis. The planar structures of fijiolides A (1) and B (2) were elucidated by interpretation of 2D NMR spectroscopic data, while the absolute configurations of these compounds were defined by interpretation of circular dichroism and 2D NMR data combined with application of the advanced Mosher's method. Fijiolides A and B are related to several recently isolated chloroaromatic compounds, which appear to be the Bergman cyclization products of enediyne precursors. Fijiolide A reduced TNF-alpha-induced NFkappaB activation by 70.3%, with an IC(50) value of 0.57 micro-M. Fijiolide B demonstrated less inhibition, only 46.5%, without dose dependence. The same pattern was also observed with quinone reductase (QR) activity: fijiolide A was found to induce quinone reductase-1 (QR1) with an induction ratio of 3.5 at a concentration of 20 microg/mL (28.4 microM). The concentration required to double the activity was 1.8 microM. Fijiolide B did not affect QR1 activity, indicating the importance of the nitrogen substitution pattern for biological activity. On the basis of these data, fijiolide A is viewed as a promising lead for more advanced anticancer testing.

  17. Deletion of N-terminal amino acids from human lecithin:cholesterol acyltransferase differentially affects enzyme activity toward alpha- and beta-substrate lipoproteins.

    Science.gov (United States)

    Vickaryous, Nicola K; Teh, Evelyn M; Stewart, Bruce; Dolphin, Peter J; Too, Catherine K L; McLeod, Roger S

    2003-03-21

    Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for generation of the majority of the cholesteryl esters (CE) in human plasma. Although most plasma cholesterol esterification occurs on high-density lipoprotein (HDL), via alpha-LCAT activity, esterification also occurs on low-density lipoprotein (LDL) via the beta-activity of the enzyme. Computer threading techniques have provided a three-dimensional model for use in the structure-function analysis of the core and catalytic site of the LCAT protein, but the model does not extend to the N-terminal region of the enzyme, which may mediate LCAT interaction with lipoprotein substrates. In the present study, we have examined the functional consequences of deletion of the highly conserved hydrophobic N-terminal amino acids (residues 1-5) of human LCAT. Western blot analysis showed that the mutant proteins (Delta 1-Delta 5) were synthesized and secreted from transfected COS-7 cells at levels approximately equivalent to those of wild-type hLCAT. The secreted proteins had apparent molecular weights of 67 kDa, indicating that they were correctly processed and glycosylated during cellular transit. However, deletion of the first residue of the mature LCAT protein (Delta 1 mutant) resulted in a dramatic loss of alpha-LCAT activity (5% of wild type using reconstituted HDL substrate, rHDL), although this mutant retained full beta-LCAT activity (108% of wild-type using human LDL substrate). Removal of residues 1 and 2 (Delta 2 mutant) abolished alpha-LCAT activity and reduced beta-LCAT activity to 12% of wild type. Nevertheless, LCAT Delta 1 and Delta 2 mutants retained their ability to bind to rHDL and LDL lipoprotein substrates. The dramatic loss of enzyme activity suggests that the N-terminal residues of LCAT may be involved in maintaining the conformation of the lid domain and influence activation by the alpha-LCAT cofactor apoA-I (in Delta 1) and/or loss of enzyme activity (in Delta 1-Delta 5). Since the

  18. The Contribution of Peroxisome Proliferator-Activated Receptor Alpha to the Relationship Between Toxicokinetics and Toxicodynamics of Trichloroethylene

    OpenAIRE

    Yoo, Hong Sik; Cichocki, Joseph A.; Kim, Sungkyoon; Venkatratnam, Abhishek; Iwata, Yasuhiro; Kosyk, Oksana; Bodnar, Wanda; Sweet, Stephen; Knap, Anthony; Wade, Terry; Campbell, Jerry; Clewell, Harvey J.; Melnyk, Stepan B.; Chiu, Weihsueh A.; Rusyn, Ivan

    2015-01-01

    Exposure to the ubiquitous environmental contaminant trichloroethylene (TCE) is associated with cancer and non-cancer toxicity in both humans and rodents. Peroxisome proliferator-activated receptor-alpha (PPARα) is thought to be playing a role in liver toxicity in rodents through activation of the receptor by the TCE metabolite trichloroacetic acid (TCA). However, most studies using genetically altered mice have not assessed the potential for PPARα to alter TCE toxicokinetics, which may lead ...

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

    International Nuclear Information System (INIS)

    Gasco, C.; Anton, M.P.

    1996-12-01

    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

  20. Dual PPAR-alpha and -gamma activators derived from novel benzoxazinone containing thiazolidinediones having antidiabetic and hypolipidemic potential.

    Science.gov (United States)

    Madhavan, Gurram R; Chakrabarti, Ranjan; Reddy, K Anantha; Rajesh, B M; Balraju, V; Rao, P Bheema; Rajagopalan, R; Iqbal, Javed

    2006-01-15

    2,4-Thiazolidinedione derivatives of 1,3-benzoxazinone were synthesized and evaluated for their PPAR-alpha and -gamma dual activation. DRF-2519, a compound obtained through SAR of TZD derivatives of benzoxazinone, has shown potent dual PPAR activation. In ob/ob mice, it showed better efficacy than the comparator molecules. In fat fed rat model, it showed significant improvement in lipid parameters, which was better than fibrates.

  1. Investigation of activation cross-sections of alpha-induced nuclear reactions on natural cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Khandaker, Mayeen Uddin [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Department of Physics, University of Malaya, 50603 Kuala Lumpur (Malaysia); Kim, Kwangsoo [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Lee, Manwoo [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Research Center, Dongnam Institute of Radiological and Medical Science, Busan 619-953 (Korea, Republic of); Kim, Guinyun, E-mail: gnkim@knu.ac.kr [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2014-08-15

    We measured production cross-sections of Sn, In, and Cd radionuclides from alpha-induced reactions on {sup nat}Cd from their respective threshold to 45 MeV by using a stacked-foil activation technique at the MC-50 cyclotron of the Korea Institute of Radiological and Medical Sciences. The results were compared with the earlier measurements as well as with the theoretical values obtained from the TENDL-2012 library based on the TALYS 1.4 code. Our measurements for the {sup 110,113g,117m}Sn, {sup 108m,108g,109g,110m,110g,111g,113m,114m,115m,116m,117m,117g}In, and {sup 111m,115g}Cd radionuclides in the energy region from the threshold energy to 45 MeV are in general good agreement with the other experimental data and calculated results. The integral yields for thick target were also deduced using the measured cross-sections and the stopping power of natural cadmium target and found in agreement with the directly measured yields available in the literature. The measured cross-sections find importance in various practical applications including nuclear medicine and improvement of nuclear model calculations.

  2. Investigation of activation cross-sections of alpha-induced nuclear reactions on natural cadmium

    International Nuclear Information System (INIS)

    Khandaker, Mayeen Uddin; Kim, Kwangsoo; Lee, Manwoo; Kim, Guinyun

    2014-01-01

    We measured production cross-sections of Sn, In, and Cd radionuclides from alpha-induced reactions on nat Cd from their respective threshold to 45 MeV by using a stacked-foil activation technique at the MC-50 cyclotron of the Korea Institute of Radiological and Medical Sciences. The results were compared with the earlier measurements as well as with the theoretical values obtained from the TENDL-2012 library based on the TALYS 1.4 code. Our measurements for the 110,113g,117m Sn, 108m,108g,109g,110m,110g,111g,113m,114m,115m,116m,117m,117g In, and 111m,115g Cd radionuclides in the energy region from the threshold energy to 45 MeV are in general good agreement with the other experimental data and calculated results. The integral yields for thick target were also deduced using the measured cross-sections and the stopping power of natural cadmium target and found in agreement with the directly measured yields available in the literature. The measured cross-sections find importance in various practical applications including nuclear medicine and improvement of nuclear model calculations

  3. AMPK alpha1 activation is required for stimulation of glucose uptake by twitch contraction, but not by H2O2, in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Schjerling, Peter; Viollet, Benoit

    2008-01-01

    into muscle by certain stimuli. In contrast, no clear function has yet been determined for alpha(1) AMPK in skeletal muscle, possibly due to alpha-AMPK isoform signaling redundancy. By applying low-intensity twitch-contraction and H(2)O(2) stimulation to activate alpha(1) AMPK, but not alpha(2) AMPK......, in wildtype and alpha-AMPK transgenic mouse muscles, this study aimed to define conditions where alpha(1) AMPK is required to increase muscle glucose uptake. METHODOLOGY/PRINCIPAL FINDINGS: Following stimulation with H(2)O(2) (3 mM, 20 min) or twitch-contraction (0.1 ms pulse, 2 Hz, 2 min), signaling and 2......-deoxyglucose uptake were measured in incubated soleus muscles from wildtype and muscle-specific kinase-dead AMPK (KD), alpha(1) AMPK knockout or alpha(2) AMPK knockout mice. H(2)O(2) increased the activity of both alpha(1) and alpha(2) AMPK in addition to Akt phosphorylation, and H(2)O(2)-stimulated glucose...

  4. Geomorphic Indices in the Assessment of Tectonic Activity in Forearc of the Active Mexican Subduction Zone

    Science.gov (United States)

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

    2015-12-01

    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.

  5. Measuring physical activity-related environmental factors: reliability and predictive validity of the European environmental questionnaire ALPHA

    Directory of Open Access Journals (Sweden)

    Oppert Jean-Michel

    2010-05-01

    Full Text Available Abstract Background A questionnaire to assess physical activity related environmental factors in the European population (a 49-item and an 11-item version was created as part of the framework of the EU-funded project "Instruments for Assessing Levels of PHysical Activity and fitness (ALPHA". This paper reports on the development and assessment of the questionnaire's test-retest stability, predictive validity, and applicability to European adults. Methods The first pilot test was conducted in Belgium, France and the UK. In total 190 adults completed both forms of the ALPHA questionnaire twice with a one-week interval. Physical activity was concurrently measured (i by administration of the long version of the International Physical Activity Questionnaire (IPAQ by interview and (ii by accelerometry (Actigraph™ device. After adaptations, the second field test took place in Belgium, the UK and Austria; 166 adults completed the adapted questionnaire at two time points, with minimum one-week interval. In both field studies intraclass correlation coefficients (ICC and proportion of agreement were computed to assess the stability of the two test scores. Predictive validity was examined in the first field test by correlating the results of the questionnaires with physical activity data from accelerometry and long IPAQ-last 7 days. Results The reliability scores of the ALPHA questionnaire were moderate-to good in the first field testing (ICC range 0.66 - 0.86 and good in the second field testing (ICC range 0.71 - 0.87. The proportion of agreement for the ALPHA short increased significantly from the first (range 50 - 83% to the second field testing (range 85 - 95%. Environmental scales from both versions of the ALPHA questionnaire were significantly associated with self-reported minutes of transport-related walking, and objectively measured low intensity physical activity levels, particularly in women. Both versions were easily administered with an

  6. Psychological stress-induced changes in salivary alpha-amylase and adrenergic activity.

    Science.gov (United States)

    Kang, Younhee

    2010-12-01

    The aim of the study was to examine the relationships among salivary alpha-amylase, plasma catecholamines, blood pressure, and heart rate during psychological stress. This study used a pretest-post-test experimental design with a control group, using repeated measures. A total of 33 participants was divided into the experimental group (n = 16) that underwent a college academic final test as the psychological stress and the control group (n = 17) that did not undergo the test. The levels of salivary alpha-amylase and plasma catecholamines, blood pressure, and heart rate were measured seven times and stress and anxiety were measured once and twice, respectively, as subjective stress markers. Significant changes in the level of salivary alpha-amylase were found in response to psychological stress. However, the correlations of salivary alpha-amylase with the plasma catecholamines, blood pressure, and heart rate were only partially found to be statistically significant. In conclusion, it was shown that salivary alpha-amylase was sensitive to stress throughout this study. Thus, salivary alpha-amylase may be used to measure stress uninvasively in both clinical settings and nursing research where the effects of stress might be scrutinized. Furthermore, the mechanisms of illnesses that are induced by stress could be explored. © 2010 Blackwell Publishing Asia Pty Ltd.

  7. Association of apoptosis with the inhibition of extracellular signal-regulated protein kinase activity in the tumor necrosis factor alpha-resistant ovarian carcinoma cell line UCI 101.

    Science.gov (United States)

    Yazlovitskaya, E M; Pelling, J C; Persons, D L

    1999-05-01

    Tumor necrosis factor-alpha (TNF alpha) can function as both an autocrine and a paracrine growth factor and may therefore play a role in ovarian tumor progression. TNF alpha initiates multiple cellular responses, many of which are mediated through the mitogen-activated protein kinase pathways, which transduce signals from the TNF alpha receptors through the cytoplasm to the nucleus, resulting in regulation of gene expression. We examined the role of c-jun N-terminal kinase 1 (JNK1) and extracellular signal-regulated protein kinase (ERK) 1 and 2 in the cellular growth response to TNF alpha in the ovarian carcinoma cell line UCI 101. JNK1 activity was increased to a maximum level ninefold above the basal level after 10-20 min of treatment with 10 ng/mL TNF alpha. A maximum threefold induction of ERK1/2 activity was observed after 1 min of treatment. At concentrations up to 100 ng/mL, TNF alpha had neither a stimulatory nor an inhibitory effect on growth of UCI 101 cells. However, inhibition of TNF alpha-induced ERK1/2 activity by the MAP/ERK kinase 1 inhibitor PD 98059 resulted in 60% inhibition of cell growth in TNF alpha-treated UCI 101 cells. This decrease in cell growth was accompanied by apoptosis, as demonstrated by the presence of a 180-bp DNA ladder. Thus, the inhibition of TNF alpha-induced ERK1/2 activity was associated with induction of apoptosis in the TNF alpha-resistant cell line UCI 101. Inhibition of TNF alpha-induced ERK1/2 activity was accompanied by a subsequent transient increase in TNF alpha-induced JNK1 activity. The significance of this increase with respect to apoptosis induction remains to be determined. These findings demonstrated that ERK1/2 activity can modulate cellular sensitivity to TNF alpha and suggested that the balance between the levels of ERK1/2 and JNK1 activation may be critical in the cellular growth response to TNF alpha.

  8. 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.

    1984-07-01

    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.

  9. Monitoring population disability: Evaluation of a new Global Activity Limitation Indicator (GALI)

    NARCIS (Netherlands)

    Oyen, H. van; Heyden, J.; Perenboom, R.; Jagger, C.

    2006-01-01

    Objective: To evaluate a single item instrument, the Global Activity Limitation Indicator (GALI), to measure long-standing health related activity limitations, against several health indicators: a composite morbidity indicator, instruments measuring mental health (SCL-90R, GHQ-12), physical

  10. Influence of alpha-linked glucose on jejunal sodium-glucose co-transport activity in ruminants.

    Science.gov (United States)

    Bauer, M L; Harmon, D L; McLeod, K R; Huntington, G B

    2001-06-01

    Eight steers and 12 lambs were used in a completely randomized experimental design to determine the effect of partial alpha-amylase starch hydrolysate (SH) on small intestinal sodium-dependent glucose transport activity. Starch hydrolysate was delivered ruminally or abomasally to steers (960 g/day) and sheep (144 g/day) for 7 days. On day 7, the steers were rendered unconscious, exsanguinated and eviscerated. A 1-m section of jejunum was collected starting at the duodenojejunal flexure. Sheep were anaesthetized with pentobarbital and the second meter of small intestine (jejunum) was collected. Brush-border membrane vesicles were prepared and sodium-dependent glucose uptake activity was measured using the rapid uptake/filtration technique. Alkaline phosphatase and maltase activity was enriched by 8.2+/-0.5- and 8.4+/-1.2-fold in the vesicle preparation, respectively, and was not different between treatments. Abomasal SH increased (P=0.03) the Na/glucose co-transport approximately two-fold in both cattle (47.2-114.0+/-31.5 pmol/mgxsec) and sheep (77.4-152.0+/-25.7 pmol mg(-1) s(-1)). We conclude that Na/glucose co-transport activity by enterocytes responds to luminal alpha-linked glucose (from abomasal infusion) in ruminants, compared with controls. Intestinal maltase-specific activity does not respond to alpha-linked glucose in cattle, and decreases slightly in sheep.

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

    DEFF Research Database (Denmark)

    Hendriksen, Niels Bohse; Winding, Anne

    2012-01-01

    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...... awareness of the threats to soil and the ecosystem services has fostered the need for a thorough understanding of soil functions and activities. Soils are very species-rich and show great functional heterogeneity. While molecular analysis of gene expression is developing, simple and inexpensive indicators......, recycling of nutrients and waste, soil remediation, plant growth support and regulation of above ground biodiversity, resilience, and soil suppressiveness. As such, soil ecosystem services are beneficial and vital for human life and at the same time threatened by anthropogenic activities. Increasing...

  12. Characterization of alpha-amylase and pullulanase activities of Clostridium thermohydrosulfuricum. Evidence for a novel thermostable amylase.

    OpenAIRE

    Melasniemi, H

    1987-01-01

    Thermostable extracellular alpha-amylase and pullulanase activities of Clostridium thermohydrosulfuricum E 101-69 were characterized in a crude enzyme preparation. The activities responded similarly to temperature and pH, with optima at 85-90 degrees C and pH 5.6. The activities were stable at 65 degrees C, but were inactivated gradually in an identical manner at higher temperatures in the absence of Ca2+ and substrate. Ca2+ stabilized both activities similarly at high temperatures. Ca2+ also...

  13. 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

    2008-01-01

    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-terminal......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...... 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...

  14. Enzymatic activity and immunoreactivity of Aca s 4, an alpha-amylase allergen from the storage mite Acarus siro

    Directory of Open Access Journals (Sweden)

    Pytelková Jana

    2012-01-01

    Full Text Available Abstract Background Enzymatic allergens of storage mites that contaminate stored food products are poorly characterized. We describe biochemical and immunological properties of the native alpha-amylase allergen Aca s 4 from Acarus siro, a medically important storage mite. Results A. siro produced a high level of alpha-amylase activity attributed to Aca s 4. This enzyme was purified and identified by protein sequencing and LC-MS/MS analysis. Aca s 4 showed a distinct inhibition pattern and an unusual alpha-amylolytic activity with low sensitivity to activation by chloride ions. Homology modeling of Aca s 4 revealed a structural change in the chloride-binding site that may account for this activation pattern. Aca s 4 was recognized by IgE from house dust mite-sensitive patients, and potential epitopes for cross-reactivity with house dust mite group 4 allergens were found. Conclusions We present the first protein-level characterization of a group 4 allergen from storage mites. Due to its high production and IgE reactivity, Aca s 4 is potentially relevant to allergic hypersensitivity.

  15. Expression and role of fibroblast activation protein-alpha in microinvasive breast carcinoma

    Directory of Open Access Journals (Sweden)

    Hua Xing

    2011-11-01

    Full Text Available Abstract Background Diagnosis of ductal carcinoma in situ (DCIS in breast cancer cases is challenging for pathologist due to a variety of in situ patterns and artefacts, which could be misinterpreted as stromal invasion. Microinvasion is detected by the presence of cytologically malignant cells outside the confines of the basement membrane and myoepithelium. When malignant cells invade the stroma, there is tissue remodeling induced by perturbed stromal-epithelial interactions. Carcinoma-associated fibroblasts (CAFs are main cells in the microenvironment of the remodeled tumor-host interface. They are characterized by the expression of the specific fibroblast activation protein-alpha (FAP-α, and differ from that of normal fibroblasts exhibiting an immunophenotype of CD34. We hypothesized that staining for FAP-α may be helpful in determining whether DCIS has microinvasion. Methods 349 excised breast specimens were immunostained for smooth muscle actin SMA, CD34, FAP-α, and Calponin. Study material was divided into 5 groups: group 1: normal mammary tissues of healthy women after plastic surgery; group 2: usual ductal hyperplasia (UDH; group 3: DCIS without microinvasion on H & E stain; group 4: DCIS with microinvasion on H & E stain (DCIS-MI, and group 5: invasive ductal carcinoma (IDC. A comparative evaluation of the four immunostains was conducted. Results Our results demonstrated that using FAP-α and Calponin adjunctively improved the sensitivity of pathological diagnosis of DCIS-MI by 11.29%, whereas the adjunctive use of FAP-α and Calponin improved the sensitivity of pathological diagnosis of DCIS by 13.6%. Conclusions This study provides the first evidence that immunostaining with FAP-α and Calponin can serve as a novel marker for pathologically diagnosing whether DCIS has microinvasion.

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

    Directory of Open Access Journals (Sweden)

    Naoki Matsuo

    2009-09-01

    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.

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

    Science.gov (United States)

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

    2015-05-17

    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. Evolutionary analyses revealed that the ω value of Pparα of the ancestral lineage of hibernating bats in both Yinpterochiroptera and Yangochiroptera was lower than that of non-hibernating bats in Yinpterochiroptera, suggesting that a higher selective pressure acts on Pparα in hibernating bats. PPARα expression was found to be increased at both mRNA and protein levels in distantly related bats (Rhinolophus ferrumequinum and Hipposideros armiger in Yinpterochiroptera and Myotis ricketti in Yangochiroptera) during their torpid episodes. Transcription factors such as FOXL1, NFYA, NFYB, SP1, TBP, and ERG were bioinformatically determined to have a higher binding affinity to the potential regulatory regions of Pparα in hibernating than in non-hibernating mammals. Genome-wide bioinformatic analyses of 64 mammalian species showed that PPARα has more potential target genes and higher binding affinity to these genes in hibernating than in non-hibernating mammals. We conclude that PPARα is adapted to hibernation in bats based on the observations that Pparα has a more stringent functional constraint in the ancestral lineage of hibernating bats and a higher level of expression in hibernating than in non-hibernating bats. We also conclude that PPARα plays a very important role in hibernation as hibernators have more PPARα target genes than non-hibernators, and PPARα in hibernators has a higher binding affinity for its target genes than in non-hibernators.

  18. Active and intelligent packaging: The indication of quality and safety.

    Science.gov (United States)

    Janjarasskul, Theeranun; Suppakul, Panuwat

    2018-03-24

    The food industry has been under growing pressure to feed an exponentially increasing world population and challenged to meet rigorous food safety law and regulation. The plethora of media consumption has provoked consumer demand for safe, sustainable, organic, and wholesome products with "clean" labels. The application of active and intelligent packaging has been commercially adopted by food and pharmaceutical industries as a solution for the future for extending shelf life and simplifying production processes; facilitating complex distribution logistics; reducing, if not eliminating the need for preservatives in food formulations; enabling restricted food packaging applications; providing convenience, improving quality, variety and marketing features; as well as providing essential information to ensure consumer safety. This chapter reviews innovations of active and intelligent packaging which advance packaging technology through both scavenging and releasing systems for shelf life extension, and through diagnostic and identification systems for communicating quality, tracking and brand protection.

  19. Activities promoting the achievement of high nuclear fuel performance indicators

    International Nuclear Information System (INIS)

    Naev, I.; Tomov, A.

    2011-01-01

    This presentation begins with brief general information about Kozloduy Nuclear Power Plant and organization activities about fresh fuel delivery assurance. The TVSA implementation, fuel cycle, fresh fuel standard entrance inspection and additional fresh fuel inspection are briefly described. Activities concerning core refueling, radiochemistry analysis, control rods drop time, measurement of the distance between the reactor flange and PTU flange, specific items for core unloading and a comparison between the two variants for operations scope with full and without full core unloading are presented. The core unloading - results and next steps, final core design (Unit 6, 2010), preparing for core loading (Unit 6, 2010) , core loading (Unit 6, 2010), after loading core inspection (Unit 6, 2010), core inspection, reactor assembling (Unit 6, 2010), fuel control during reactor startup, fuel control during operation period and fuel assembly data base are also discussed

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

    DEFF Research Database (Denmark)

    Hendriksen, Niels Bohse; Winding, Anne

    2012-01-01

    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......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......, experimental conditions of extraction of enzymes from soils, buffer and pH, substrate concentration, temperature and the necessary controls were optimized and standardized. This has resulted in an optimized standard operating procedure of EEA, which are being tested as an indicator of soil functional diversity...

  1. Alpha 1-adrenergic receptor-mediated phosphoinositide hydrolysis and prostaglandin E2 formation in Madin-Darby canine kidney cells. Possible parallel activation of phospholipase C and phospholipase A2

    International Nuclear Information System (INIS)

    Slivka, S.R.; Insel, P.A.

    1987-01-01

    alpha 1-Adrenergic receptors mediate two effects on phospholipid metabolism in Madin-Darby canine kidney (MDCK-D1) cells: hydrolysis of phosphoinositides and arachidonic acid release with generation of prostaglandin E2 (PGE2). The similarity in concentration dependence for the agonist (-)-epinephrine in eliciting these two responses implies that they are mediated by a single population of alpha 1-adrenergic receptors. However, we find that the kinetics of the two responses are quite different, PGE2 production occurring more rapidly and transiently than the hydrolysis of phosphoinositides. The antibiotic neomycin selectively decreases alpha 1-receptor-mediated phosphatidylinositol 4,5-bisphosphate hydrolysis without decreasing alpha 1-receptor-mediated arachidonic acid release and PGE2 generation. In addition, receptor-mediated inositol trisphosphate formation is independent of extracellular calcium, whereas release of labeled arachidonic acid is largely calcium-dependent. Moreover, based on studies obtained with labeled arachidonic acid, receptor-mediated generation of arachidonic acid cannot be accounted for by breakdown of phosphatidylinositol monophosphate, phosphatidylinositol bisphosphate, or phosphatidic acid. Further studies indicate that epinephrine produces changes in formation or turnover of several classes of membrane phospholipids in MDCK cells. We conclude that alpha 1-adrenergic receptors in MDCK cells appear to regulate phospholipid metabolism by the parallel activation of phospholipase C and phospholipase A2. This parallel activation of phospholipases contrasts with models described in other systems which imply sequential activation of phospholipase C and diacylglycerol lipase or phospholipase A2

  2. Salivary alpha-amylase: More than an enzyme Investigating confounders of stress-induced and basal amylase activity

    OpenAIRE

    Strahler, Jana

    2010-01-01

    Summary: Salivary alpha-amylase: More than an enzyme - Investigating confounders of stress-induced and basal amylase activity (Dipl.-Psych. Jana Strahler) The hypothalamus-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) are two of the major systems playing a role in the adaptation of organisms to developmental changes that threaten homeostasis. The HPA system involves the secretion of glucocorticoids, including cortisol, into the circulatory system. Numerous studies hav...

  3. 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.

    2009-07-01

    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)

  4. Alpha-hemolysin from Escherichia coli uses endogenous amplification through P2X receptor activation to induce hemolysis

    DEFF Research Database (Denmark)

    Skals, Marianne; Jørgensen, Niklas Rye; Leipziger, Jens

    2009-01-01

    frequently produce virulence factors such as alpha-hemolysin (HlyA), which causes hemolysis by forming pores in the erythrocyte membrane. The present study reveals that this pore formation triggers purinergic receptor activation to mediate the full hemolytic action. Non-selective ATP-receptor (P2...... augment hemolysis induced by the bacterial toxin, HlyA. These findings potentially have clinical perspectives as P2 antagonists may ameliorate symptoms during sepsis with hemolytic bacteria....

  5. Aqueous humor tyrosinase activity is indicative of iris melanocyte toxicity.

    Science.gov (United States)

    Mahanty, Sarmistha; Kawali, Ankush A; Dakappa, Shruthi Shirur; Mahendradas, Padmamalini; Kurian, Mathew; Kharbanda, Varun; Shetty, Rohit; Setty, Subba Rao Gangi

    2017-09-01

    Antibiotics such as fluoroquinolones (FQLs) are commonly used to treat ocular infections but are also known to cause dermal melanocyte toxicity. The release of dispersed pigments from the iris into the aqueous humor has been considered a possible ocular side effect of the systemic administration of FQLs such as Moxifloxacin, and this condition is known as bilateral acute iris transillumination (BAIT). Bilateral acute depigmentation of iris (BADI) is a similar condition, with iris pigment released into the aqueous, but it has not been reported as a side effect of FQL. Iris pigments are synthesized by the melanogenic enzyme tyrosinase (TYR) and can be detected but not quantified by using slit-lamp biomicroscopy. The correlation between dispersed pigments in the aqueous and the extent of melanocyte toxicity due to topical antibiotics in vivo is not well studied. Here, we aimed to study the effect of topical FQLs on iris tissue, the pigment release in the aqueous humor and the development of clinically evident iris atrophic changes. We evaluated this process by measuring the activity of TYR in the aqueous humor of 82 healthy eyes undergoing cataract surgery following topical application of FQLs such as Moxifloxacin (27 eyes, preservative-free) or Ciprofloxacin (29 eyes, with preservative) or the application of non-FQL Tobramycin (26 eyes, with preservative) as a control. In addition, the patients were questioned and examined for ocular side effects in pre- and post-operative periods. Our data showed a significantly higher mean TYR activity in the aqueous humor of Ciprofloxacin-treated eyes compared to Moxifloxacin- (preservative free, p humor from both Ciprofloxacin- and Moxifloxacin-treated eyes showed the presence of soluble TYR enzyme, thus reflecting its toxicity to iris melanocytes and corresponding to its activity in the aqueous humor. Intriguingly, none of these patients developed any clinically appreciable ocular side effects characteristic of BAIT or BADI

  6. Autoradiographic measurement of low concentrations of alpha-active nuclides using CR-39 track detectors

    International Nuclear Information System (INIS)

    Freyer, K.; Dietze, K.; Weisse, S.; Kummer, G.

    1991-01-01

    An autoradiographic method for the determination of alpha emission rates from plastic packaging materials for VLSI silicon memory devices based on long-time exposure of the samples on CR-39 detectors has been tested. The lower limit of detection will be strongly influenced by the background of the detector material and amounts at times to 0.002 alpha particles cm -2 h -1 after 200 days exposure. A mathematical method for the interpretation of very low track densities is discussed. The first results of its application are presented. (author)

  7. Voting frequentia as an indicator of political activity

    Directory of Open Access Journals (Sweden)

    V. V. Kryvoshein

    2017-07-01

    Found that the amount of voting frequentia depends on the political regime, the form of government and the level elections. Determined that democracies characterized by an autonomous form of voting frequentia and for undemocratic – mobilizational form of voting frequentia. Followed that the highest rate of participation in voting observed in countries with a parliamentary form of government and proportional electoral system, more than 2/3 of the voting frequentia observed in countries with a parliamentary form of government and majoritarian electoral systems, lowest level of voting frequentia observed in countries with a presidential form of government. It also notes that increased voting frequentia observed in countries where compulsory voting is set. Observed trend of dependency and level elections: electoral activity of elections on the local, regional and supra-national representative authority is much lower than in the presidential and parliamentary elections. Attention is drawn to in explaining the voting frequentia considered rational and irrational factors, since voting is a two-tiered process: active, politically defined part of the voters voted party ideologically and politically unbiased – rationally.

  8. 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: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

    2012-08-17

    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.

  9. OPERATIONAL LIMITATIONS FOR DEMOLITION OF A HIGHLY ALPHA CONTAMINATED BUILDING MODLES VERSUS MEASURED AIR & SURFACE ACTIVITY CONCENTRATIONS

    Energy Technology Data Exchange (ETDEWEB)

    LLOYD, E.R.

    2006-11-02

    The demolition of a facility historically used for processing and handling transuranic materials is considered. Residual alpha emitting radionuclide contamination poses an exposure hazard if released to the local environment during the demolition. The process of planning for the demolition of this highly alpha contaminated building, 232-Z, included a predemolition modeling analysis of potential exposures. Estimated emission rates were used as input to an air dispersion model to estimate frequencies of occurrence of peak air and surface exposures. Postdemolition modeling was also conducted, based on the actual demolition schedule and conditions. The modeling results indicated that downwind deposition is the main operational limitation for demolition of a highly alpha-contaminated building. During the demolition of 232-Z, airborne radiation and surface contamination were monitored. The resultant non-detect monitoring results indicate a significant level of conservatism in the modeled results. This comparison supports the use of more realistic assumption in the estimating emission rates. The resultant reduction in modeled levels of potential exposures has significant implications in terms of the projected costs of demolition of such structures.

  10. OPERATIONAL LIMITATIONS FOR DEMOLITION OF A HIGHLY ALPHA-CONTAMINATED BUILDING- MODELED VERSUS MEASURED AIR and SURFACE ACTIVITY CONCENTRATIONS

    International Nuclear Information System (INIS)

    LLOYD, E.R.

    2006-01-01

    The demolition of a facility historically used for processing and handling transuranic materials is considered. Residual alpha emitting radionuclide contamination poses an exposure hazard if released to the local environment during the demolition. The process of planning for the demolition of this highly alpha contaminated building, 232-Z, included a predemolition modeling analysis of potential exposures. Estimated emission rates were used as input to an air dispersion model to estimate frequencies of occurrence of peak air and surface exposures. Postdemolition modeling was also conducted, based on the actual demolition schedule and conditions. The modeling results indicated that downwind deposition is the main operational limitation for demolition of a highly alpha-contaminated building. During the demolition of 232-Z, airborne radiation and surface contamination were monitored. The resultant non-detect monitoring results indicate a significant level of conservatism in the modeled results. This comparison supports the use of more realistic assumption in the estimating emission rates. The resultant reduction in modeled levels of potential exposures has significant implications in terms of the projected costs of demolition of such structures

  11. Endothelial monocyte activating polypeptide-II modulates endothelial cell responses by degrading hypoxia-inducible factor-1alpha through interaction with PSMA7, a component of the proteasome

    Energy Technology Data Exchange (ETDEWEB)

    Tandle, Anita T. [Tumor Angiogenesis Section, Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892 (United States); Calvani, Maura; Uranchimeg, Badarch [DTP-Tumor Hypoxia Laboratory, SAIC Frederick, Inc., National Cancer Institute, Frederick, Maryland 21702 (United States); Zahavi, David [Tumor Angiogenesis Section, Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892 (United States); Melillo, Giovanni [DTP-Tumor Hypoxia Laboratory, SAIC Frederick, Inc., National Cancer Institute, Frederick, Maryland 21702 (United States); Libutti, Steven K., E-mail: slibutti@montefiore.org [Department of Surgery, Montefiore-Einstein Center for Cancer Care, Albert Einstein College of Medicine, Greene Medical Arts Pavilion, 4th Floor 3400, Bainbridge Avenue, Bronx, New York 10467 (United States)

    2009-07-01

    The majority of human tumors are angiogenesis dependent. Understanding the specific mechanisms that contribute to angiogenesis may offer the best approach to develop therapies to inhibit angiogenesis in cancer. Endothelial monocyte activating polypeptide-II (EMAP-II) is an anti-angiogenic cytokine with potent effects on endothelial cells (ECs). It inhibits EC proliferation and cord formation, and it suppresses primary and metastatic tumor growth in-vivo. However, very little is known about the molecular mechanisms behind the anti-angiogenic activity of EMAP-II. In the present study, we explored the molecular mechanism behind the anti-angiogenic activity exerted by this protein on ECs. Our results demonstrate that EMAP-II binds to the cell surface {alpha}5{beta}1 integrin receptor. The cell surface binding of EMAP-II results in its internalization into the cytoplasmic compartment where it interacts with its cytoplasmic partner PSMA7, a component of the proteasome degradation pathway. This interaction increases hypoxia-inducible factor 1-alpha (HIF-1{alpha}) degradation under hypoxic conditions. The degradation results in the inhibition of HIF-1{alpha} mediated transcriptional activity as well as HIF-1{alpha} mediated angiogenic sprouting of ECs. HIF-1{alpha} plays a critical role in angiogenesis by activating a variety of angiogenic growth factors. Our results suggest that one of the major anti-angiogenic functions of EMAP-II is exerted through its inhibition of the HIF-1{alpha} activities.

  12. 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

    2001-01-01

    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...... the venom of Calloselasma rhodostoma, induces platelet activation that can be blocked by monoclonal antibodies against alpha(2)beta(1) integrin. This finding suggested that clustering of alpha(2)beta(1) integrin by rhodocytin is sufficient to induce platelet activation and led to the hypothesis...

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

    Science.gov (United States)

    Zeqiraj, Elton; Filippi, Beatrice Maria; Goldie, Simon; Navratilova, Iva; Boudeau, Jérôme; Deak, Maria; Alessi, Dario R; van Aalten, Daan M F

    2009-06-09

    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.

  14. 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

    2009-06-01

    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.

  15. 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: btprabha@uic.edu [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)

    2009-09-18

    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.

  16. 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.

    2011-01-01

    During a series of smog chamber experiments, the effects of chemical and photochemical aging on the ability of organic aerosols generated from ozonolysis of alpha-pinene to act as cloud condensation nuclei (CCN) were investigated. In particular, the study focused on the relation between oxygenation...

  17. 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

    2006-01-01

    The goldfish odorant receptor 5.24 is a member of family C of G protein-coupled receptors and is closely related to the human receptor GPRC6A. Receptor 5.24 has previously been shown to have binding affinity for L-alpha-amino acids, especially the basic amino acids arginine and lysine. Here we...

  18. Production of Active Bacillus licheniformis Alpha-Amylase in Tobacco and its Application in Starch Liquefaction

    NARCIS (Netherlands)

    Pen, J; MOLENDIJK, L; Quax, Wim J.; SIJMONS, PC; VANOOYEN, AJJ; VANDENELZEN, PJM; RIETVELD, K; HOEKEMA, A

    As a first example of the feasibility of producing industrial bulk enzymes in plants, we have expressed Bacillus licheniformis alpha-amylase in transgenic tobacco, and applied the seeds directly in starch liquification. The enzyme was properly secreted into the intercellular space, and maximum

  19. Expression of biologically active human interferon alpha 2 in aloe vera

    Science.gov (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...

  20. 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.

    1987-07-01

    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.

  1. ACTIVATION ASSAY FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR- ALPHA (PPARÁ) BY PERFLUOROALKYL ACIDS (PFAAS) IN COS-1 CELLS

    Science.gov (United States)

    PFAAs have been found to elicit various physiological effects including peroxisome proliferation, indicating the mechanism of action for these chemicals could involve PPAR. This study investigates the ability of PFAAs to bind and activate mouse and human PPARα in COS-1 cell...

  2. Role of alpha1- and alpha2-adrenoceptors in the regulation of locomotion and spatial behavior in the active place avoidance task: A dose–response study

    Czech Academy of Sciences Publication Activity Database

    Stuchlík, Aleš; Valeš, Karel

    2008-01-01

    Roč. 433, č. 3 (2008), s. 235-240 ISSN 0304-3940 R&D Projects: GA ČR(CZ) GA309/07/0341; GA MZd(CZ) NR9178; GA MŠk(CZ) 1M0517; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : alpha1- alpha2 adrenoceptors * avoidance * memory Subject RIV: FH - Neurology Impact factor: 2.200, year: 2008

  3. Chemical bonding and quadrupole splittings of {sup 57}Fe Moessbauer spectrum in active sites of oxyhemoglobin as calculated by X{sub {alpha}}-discrete variation method

    Energy Technology Data Exchange (ETDEWEB)

    Yuryeva, E. I., E-mail: yuryeva@ihim.uran.ru [Institute of Solid State Chemistry of the Ural Branch of the Russian Academy of Sciences (Russian Federation)

    2008-07-15

    Results of quantum-chemical X{sub {alpha}}-discrete variation method (X{sub {alpha}}-DVM) calculations of interaction parameters between iron (II) and oxygen molecule in active sites of {alpha}- and {beta}-subunits of oxyhemoglobin are presented within three models: without extra electron and in spin-unrestricted mode (model I); without extra electron and in spin-restricted mode (model II); with extra electrons in spin-unrestricted mode (model III). The electronic structure and {sup 57}Fe quadrupole splitting {Delta}E{sub Q} for the active site of {alpha}- and {beta}-subunits (within model I) and only of the {alpha}-subunit (within models II and III) of oxyhemoglobin are calculated. The differences in {Delta}E{sub Q} values for these three models are discussed.

  4. Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity.

    Science.gov (United States)

    Kim, Minji; Suh, Jaehong; Romano, Donna; Truong, Mimy H; Mullin, Kristina; Hooli, Basavaraj; Norton, David; Tesco, Giuseppina; Elliott, Kathy; Wagner, Steven L; Moir, Robert D; Becker, K David; Tanzi, Rudolph E

    2009-10-15

    ADAM10, a member of a disintegrin and metalloprotease family, is an alpha-secretase capable of anti-amyloidogenic proteolysis of the amyloid precursor protein. Here, we present evidence for genetic association of ADAM10 with Alzheimer's disease (AD) as well as two rare potentially disease-associated non-synonymous mutations, Q170H and R181G, in the ADAM10 prodomain. These mutations were found in 11 of 16 affected individuals (average onset age 69.5 years) from seven late-onset AD families. Each mutation was also found in one unaffected subject implying incomplete penetrance. Functionally, both mutations significantly attenuated alpha-secretase activity of ADAM10 (>70% decrease), and elevated Abeta levels (1.5-3.5-fold) in cell-based studies. In summary, we provide the first evidence of ADAM10 as a candidate AD susceptibility gene, and report two potentially pathogenic mutations with incomplete penetrance for late-onset familial AD.

  5. Indolo[3,2-b]quinoline Derivatives Suppressed the Hemolytic Activity of Beta-Pore Forming Toxins, Aerolysin-Like Hemolysin Produced by Aeromonas sobria and Alpha-Hemolysin Produced by Staphylococcus aureus.

    Science.gov (United States)

    Takahashi, Eizo; Fujinami, Chiaki; Kuroda, Teruo; Takeuchi, Yasuo; Miyoshi, Shin-Ichi; Arimoto, Sakae; Negishi, Tomoe; Okamoto, Keinosuke

    2016-01-01

    In an attempt to discover inhibitory compounds against pore-forming toxins, some of the major toxins produced by bacteria, we herein examined the effects of four kinds of indolo[3,2-b]quinoline derivatives on hemolysis induced by the aerolysin-like hemolysin (ALH) of Aeromonas sobria and also by the alpha-hemolysin of Staphylococcus aureus. The results showed that hemolysis induced by ALH was significantly reduced by every derivative, while that induced by alpha-hemolysis was significantly reduced by three out of the four derivatives. However, the degrees of reduction induced by these derivatives were not uniform. Each derivative exhibited its own activity to inhibit the respective hemolysin. Compounds 1 and 2, which possessed the amino group bonding the naphthalene moiety at the C-11 position of indolo[3,2-b]quinoline, had strong inhibitory effects on the activity of ALH. Compound 4 which consisted of benzofuran and quinoline had strong inhibitory effects on the activity of alpha-hemolysin. These results indicated that the amino group bonding the naphthalene moiety of compounds 1 and 2 assisted in their ability to inhibit ALH activity, while the oxygen atom at the 10 position of compound 4 strengthened its interaction with alpha-hemolysin. These compounds also suppressed the hemolytic activity of the supernatant of A. sobria or A. hydrophila, suggesting that these compounds were effective at the site of infection of these bacteria.

  6. 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

    2012-03-01

    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

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

    Science.gov (United States)

    Li, Jin-Lian; Wang, Qiao-Yun; Luan, Hai-Yun; Kang, Ze-Chun; Wang, Chun-Bo

    2012-03-21

    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. 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. 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. Taken together, our findings suggest that L-carnitine could protect HL7702 cells against oxidative stress through the

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

    International Nuclear Information System (INIS)

    Turner, A.D.; Worrall, G.; Dalton, J.T.

    1987-04-01

    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.)

  9. Aspirin and PPAR-alpha activators inhibit monocyte chemoattractant protein-1 expression induced by high glucose concentration in human endothelial cells.

    Science.gov (United States)

    Dragomir, Elena; Tircol, Magdalena; Manduteanu, Ileana; Voinea, Manuela; Simionescu, Maya

    2006-06-01

    Activated endothelial cells express monocyte chemoattractant protein-1 (MCP-1), a chemokine which is reportedly involved in the recruitment of plasma monocytes in the early stages of atherosclerosis. Since accelerated atherosclerosis is the main complication of diabetes and both diseases encompass an inflammatory reaction, we hypothesized that the anti-inflammatory drugs, aspirin and peroxisome proliferator-activated receptor (PPAR-alpha) activators (fenofibrate and clofibrate), could have an effect on the high glucose-induced MCP-1 expression in endothelial cells. To test this assumption, as well as the possible mechanisms involved, the MCP-1 expression and secretion, the reactive oxygen species levels, nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) expression were determined in human endothelial cells exposed to high glucose concentrations in the presence of aspirin, fenofibrate and clofibrate. Human endothelial cells kept in normal glucose concentration in the absence of drugs were used as control. The results showed that (i) aspirin, fenofibrate and clofibrate decrease significantly the MCP-1 expression and secretion in human endothelial cells; (ii) the high glucose up-regulated expression of MCP-1 in endothelial cells was significantly reduced by inhibitors of NF-kB and reactive oxygen species; (iii) all drugs notably decrease the level of the reactive oxygen species and activation of NF-kB and AP-1. Together, the findings indicate that in endothelial cells aspirin and PPAR-alpha activators reduce the high glucose-increased expression of MCP-1 by a mechanism that includes the inhibition of reactive oxygen species, and decrease of AP-1 and NF-kB activation.

  10. 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: k-ooishi@aist.go.jp [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)

    2010-10-15

    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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    is dependent on the length and position of the lipid element(s). The resulting lead compound, Pam-(Lys-beta NSpe)(6)-NH2, blocks LPS-induced cytokine secretion with a potency comparable to that of polymyxin B. The mode of action of this HDP mimic appears not to involve direct LPS interaction since it......, 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....

  12. 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

    2009-01-01

    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......, and administration of the NMDA-antagonist phencyclidine (PCP) in rodents is a well validated model of such cognitive deficits. Here we show that repeated PCP treatment (10 mg/kg/day for 10 days) decreased the expression of parvalbumin and synaptophysin mRNA in the mouse PFC, which corresponds to changes seen....... Importantly, repeated co-administration of SSR180711 (3 mg/kg) with PCP prevented both the changes in parvalbumin, synaptophysin, and Arc mRNA expression in the PFC, and the behavioral impairment induced by PCP. These results are the first to demonstrate prevention of the deleterious effects induced...

  13. Procedures and findings of examination of air contamination by alpha-active plutonium aerosols: primary and secondary products of Chernobyl accident

    International Nuclear Information System (INIS)

    Gaziev, Ya.I.; Petrenko, G.I.; Chumichyev, V.B.; Valetova, N.K.; Shkuro, V.N.; Polukhina, A.M.

    1991-01-01

    Atmospheric contamination pattern by Pu-radionuclides over a 30 km zone of the Chernobyl nuclear power plant in 1987-1988 has been examined. Aerosol samples were analyzed for isotopic composition by using gamma- and alpha-spectrometric, and radiochemical methods. Preliminary analysis of isotopic and fractional composition of aerosols carried out earlier indicated that over the first few months after the Chernobyl accident the relative contribution of 238,239,240 Pu to air contamination was lowered as compared with beta-active products. At present, however, alpha-active plutonium isotopes became the dominant radioactive contaminants of the atmosphere and the concentrations of 238,239,240 Pu inhaled fractions turned out to be lower than the limiting permissible values based on the USSR radiation safety standards for radioactive contamination of the atmosphere for the limited part of population exposed to radionuclides. Nevertheless, it is necessary to know even moderate levels of atmospheric contamination by Pu-radionuclides, since their long impacts on the personnel operating in the 30 km zone of the Chernobyl NPP and population residing in the adjavent regions have not been studied properly. So, the risks for population health of such impacts cannot be generally excluded from consideration. (author) 4 refs.; 5 tabs

  14. Xalpha-DVM investigation of double water molecule interactions with active sites of alpha- and beta-subunits of hemoglobin

    Science.gov (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.

  15. 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

    2003-01-01

    In mammals, there are MHC class II molecules with distinctive sequence features, such as the classical isotypes DR, DQ and DP. These particular isotypes have not been reported in non-mammalian vertebrates. We have isolated the class II (B-L) alpha chain from outbred chickens as the basis...... 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...... for the cloning and sequencing of the cDNA. We found only one class II alpha chain transcript, which bears the major features of a classical class II alpha sequence, including the critical peptide-binding residues. The chicken sequence is more similar to human DR than to the DQ, DP, DO or DM isotypes, most...

  16. Alpha mangostin Inhibits Hepatic Stellate Cells Activation Through TGF-β/Smad and Akt Signaling Pathways: An in vitro Study in LX2.

    Science.gov (United States)

    Rahmaniah, Rahmaniah; Yuyuntia, Yuyuntia; Soetikno, Vivian; Arozal, Wawaimuli; Antarianto, Radiana Dhewayani; Louisa, Melva

    2018-03-01

    Alpha mangostin has been reported to have activity for the treatment of liver fibrosis in the rats. However, the mechanisms of action are poorly understood. This study was aimed to investigate the effect of alpha mangostin on hepatic stellate cells (HSC) activation and proliferation through TGF-β/Smad and Akt signaling pathways. Immortalized HSC, LX2 cells, were incubated with TGF-β with or without alpha mangostin (5 or 10 μM). Sorafenib 10 µM was used as positive control. LX2 viability was counted using trypan blue exclusion method. The effect of alpha mangostin on TGF-β concentrations, and the expressions of proliferation and fibrogenic markers were evaluated. Alpha mangostin treatment resulted in a reduced proliferation of HSC, decreased Ki-67 and p-Akt expressions. These findings were followed with decreased concentrations of TGF-β in the medium of cells treated with alpha mangostin, decreased expressions of COL1A1, TIMP1, PAI1, α-SMA, and p-Smad3 as fibrogenic markers. These effects were shown to be dose-dependent. Alpha mangostin inhibits hepatic stellate cells proliferation and activation through TGF-β/Smad and Akt signaling pathways in dose dependent manner. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Decreased succinate dehydrogenase activity of gamma and alpha motoneurons in mouse spinal cords following 13 weeks of exposure to microgravity.

    Science.gov (United States)

    Ishihara, Akihiko; Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Ohira, Yoshinobu

    2013-10-01

    Cell body size and succinate dehydrogenase activity of motoneurons in the dorsolateral region of the ventral horn in the lumbar and cervical segments of the mouse spinal cord were assessed after long-term exposure to microgravity and compared with those of ground-based controls. Mice were housed in a mouse drawer system on the International Space Station for 13 weeks. The mice were transported to the International Space Station by the Space Shuttle Discovery and returned to Earth by the Space Shuttle Atlantis. No changes in the cell body size of motoneurons were observed in either segment after exposure to microgravity, but succinate dehydrogenase activity of small-sized (700 μm(2)) alpha motoneurons, in both segments was lower than that of ground-based controls. We concluded that exposure to microgravity for longer than 3 months induced decreased succinate dehydrogenase activity of both gamma and slow-type alpha motoneurons. In particular, the decreased succinate dehydrogenase activity of gamma motoneurons was observed only after long-term exposure to microgravity.

  18. Synergisms in Alpha-glucosidase Inhibition and Antioxidant Activity of Camellia sinensis L. Kuntze and Eugenia uniflora L. Ethanolic Extracts

    Science.gov (United States)

    Vinholes, Juliana; Vizzotto, Márcia

    2017-01-01

    Background: Camellia sinensis, the most consumed and popular beverages worldwide, and Eugenia uniflora, a Brazilian native species, have been already confirmed to have beneficial effects in the treatment of diabetes mellitus. However, their potential acting together against an enzyme linked to this pathology has never been exploited. Objective: The aim of this study was to evaluate the inhibitory properties of individual and combined ethanolic extracts of the leaves of C. sinensis and E. uniflora over alpha-glucosidase, a key digestive enzyme used on the Type 2 diabetes mellitus (T2DM) control. In addition, their inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) and peroxyl radicals was also assayed. Materials and Methods: Enzyme inhibition and antioxidant potential were assessed based on in vitro assays. Total phenolic compounds, carotenoids, and chlorophylls A and B were achieved using spectrophotometric methods. Results: E. uniflora was almost 40 times more active on alpha-glucosidase than C. sinensis and combined extracts showed a significant synergistic effect with an obtained IC50 value almost 5 times lower than the theoretical value. C. sinensis extract was twice more active than E. uniflora concerning DPPH•, in contrast, E. uniflora was almost 10 times more effective than C. sinensis on inhibition of peroxyl radicals with a significant synergistic effect for combined extracts. The extracts activities may be related with their phytochemicals, mainly phenolic compounds, and chlorophylls. Conclusion: Combined C. sinensis and E. uniflora ethanolic extracts showed synergistic effect against alpha-glucosidase and lipid peroxidation. These herbal combinations can be used to control postprandial hyperglycemia and can also provide antioxidant defenses to patients with T2DM. SUMMARY Alfa-glucosidase and antioxidant Interaction between Camellia sinensis L. Kuntze and Eugenia uniflora L. ethanolic extracts was investigated.Extracts showed

  19. Alpha-PVP induces the rewarding effect via activating dopaminergic neuron.

    Science.gov (United States)

    Hataoka, Kyoko; Kaizaki-Mitsumoto, Asuka; Numazawa, Satoshi

    2017-01-01

    A synthetic cathinone, 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP), was occasionally found in the "bath salt" type of designer drugs, as an active ingredient. It has been reported that drivers who consumed α-PVP were in an excited state and incapable of controlling their behavior, causing traffic accidents. Despite its acute excitatory effects, there is no information on the psychological dependency elicited by α-PVP use. The purpose of the present study was to clarify whether the reward pathway is activated with repeated doses of α-PVP in experimental animals. Treatment of male C57BL/6j mice with α-PVP (25 mg/kg, i.p.), once a day, for 3 days significantly increased the conditioned place preference scores. Therefore, repeated doses of α-PVP were shown to induce palatability in mice. α-PVP increases extracellular dopamine levels in the nucleus accumbens shell immediately after administration. The number of cells immunopositive for phosphorylated cAMP-regulatory element binding protein (CREB) was significantly increased in the α-PVP-treated mice in our study. These results indicate that the administration of α-PVP activates the phosphorylation of CREB in the nucleus accumbens shell. Our results suggest that α-PVP stimulates the reward pathway by increasing the extracellular dopamine levels and CREB phosphorylation in the nucleus accumbens shell, eventually causing positive reinforcement in mice.

  20. Radon Progenies as a Source of Gross Alpha-beta Activities in Drinking Water in Vinaninkarena, Antsirabe-Madagascar

    International Nuclear Information System (INIS)

    Raoelina Andriambololona; Rabesiranana, N.; Rasolonirina, M.; Rakotomanga, H.

    2004-01-01

    The village of Vinaninkarena, Antsirabe, Madagascar is located in a high radioactivity area. With the aim of assessing the health impact of radioactivity pollution, a survey was conducted around an abandoned radium mining. Waters from 24 sampling points, including 5 wells and 13 springs were sampled. The water radioactivity was measured using a portable Triathler LSC, model 425-034 from Hidex Turku. Each sample is counted more than 3 times: less than 2h after sampling, 4h to few days and more than 3 weeks after when 226 Ra attains equilibrium with 222 Rn and its short-lived daughters. Combination of water non miscible, radon extractive LS cocktail and water miscible one is used to reveal contribution of radium, radon and its short lived progenies to the gross alpha-beta activities. Maximum activity values found are : 3.6±0.3 Bq.L -1 for 226 Ra, 554±9 Bq.L -1 for the excess of radon, and 408±8 Bq.L -1 for the excess of radon progenies. Based on these data, a daily consumption of 2 L of these waters by a standard person would produce an annual 226 Ra ingestion well above the annual intake limit for 226 Ra. Moreover, the increasing gross alpha-beta activity resulting from radon progenies raises the issue of health effects. The potential for rapid spring-to-mouth delivery, which is frequent in rural area, may expose the water consumer to the short-lived alpha particle emitters.

  1. Convulxin binds to native, human glycoprotein Ib alpha.

    Science.gov (United States)

    Kanaji, Sachiko; Kanaji, Taisuke; Furihata, Kenichi; Kato, Kazunobu; Ware, Jerry L; Kunicki, Thomas J

    2003-10-10

    Convulxin (CVX), a C-type snake protein from Crotalus durissus terrificus venom, is the quintessential agonist for studies of the collagen receptor, glycoprotein VI (GPVI) and its role in platelet adhesion to collagens. In this study, CVX, purified from venom, behaves as expected, i.e. it binds to platelet GPVI and recombinant human GPVI, induces platelet aggregation and platelet prothrombinase activity, and binds uniquely to GPVI in ligand blots of SDS-denatured proteins. Nonetheless, we find that CVX has a dual specificity for both GPVI and native but not denatured human GPIb alpha. First, CVX binds to human GPIb alpha expressed on the surface of CHO cells. Second, CVX binds weakly to murine platelet GPIb alpha but more strongly to human platelet GPIb alpha, as evidenced by comparative binding to wild-type, GPVI(-/-), FcR gamma (-/-), and human GPIb transgenic mice. Third, the binding of CVX to human GPIb alpha is inhibited by soluble, recombinant human GPVI. Fourth, CVX binding to GPIb alpha is disrupted by phenylalanine substitutions at GPIb alpha tyrosine-276, tyrosine-278, and tyrosine-279, which also disrupts von Willebrand factor and alpha-thrombin binding to GPIb alpha. Fifth, CVX binding to GPIb alpha on Chinese hamster ovary cell transfectants is inhibited by function-blocking murine monoclonal anti-GPIb alpha antibodies. Lastly, CVX fails to bind to denatured GPIb alpha in detergent extracts of platelets. Three separate preparations of CVX (two purified by the authors; one obtained commercially) produced equivalent results. These results indicate that CVX exhibits dual specificity for both native GPIb alpha and GPVI. Furthermore, the binding site on GPIb alpha for CVX may be close to that for von Willebrand factor. Therefore, a contribution of GPIb alpha to CVX-induced platelet responses needs to be carefully re-evaluated.

  2. L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance.

    Science.gov (United States)

    Kelly, Simon P; Gomez-Ramirez, Manuel; Montesi, Jennifer L; Foxe, John J

    2008-08-01

    Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on brain state. The bulk of this research has focused on either L-theanine or caffeine ingested alone (mostly the latter) and has been limited to behavioral testing, subjective rating, or neurophysiological assessments during resting. Here, we investigated the effects of both L-theanine and caffeine, ingested separately or together, on behavioral and electrophysiological indices of tonic (background) and phasic (event-related) visuospatial attentional deployment. Subjects underwent 4 d of testing, ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or these treatments combined. The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative stimulus requiring discrimination. In addition to behavioral measures, we examined overall, tonic attentional focus as well as phasic, cue-dependent anticipatory attentional biasing, as indexed by scalp-recorded alpha-band (8-14 Hz) activity. We found an increase in hit rate and target discriminability (d') for the combined treatment relative to placebo, and an increase in d' but not hit rate for caffeine alone, whereas no effects were detected for L-theanine alone. Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment, similar to previous findings at a larger dosage of L-theanine alone. This may signify a more generalized tonic deployment of attentional resources to the visual modality and may underlie the facilitated behavioral performance on the combined ingestion of these 2 major constituents of tea.

  3. Human platelets activation by convulxin is accompanied by tyrosyl-phosphorylation of PLCgamma2 and occurs independently of integrin alphaIIbbeta3.

    Science.gov (United States)

    Francischetti, I M; Carlini, C R; Guimàraes, J A

    1998-01-01

    In the present report we show that convulxin (Cvx), a C-type lectin from Crotalus durissus terrificus venom, induces platelet agregation and phospholipase C (PLC) activation by a protein tyrosine kinase (PTK)-dependent pathway. In addition, Cvx stimulates a rapid increase in tyrosine phosphorylation of human platelet proteins with molecular masses of 40, 72/74, 78/80 and 120 kDa, followed by dephosphorylation of some proteins. However, platelet aggregation was accompanied by the phosphorylation of a 105-kDa molecular mass protein. Furthermore, Cvx stimulates a rapid-tyrosyl phosphorylation of a 145-kDa protein that was identified as PLC gamma 2. Protein tyrose phosphatase (PTP) induced by Cvx was not blocked when platelets were stimulated in the presence of indomethacin, apyrase, EDTA or RGDS peptide, but inhibited by staurosporine and genistein. These results indicate that PTP is chronologically proximal to Cvx binding to platelets, and it is independent of platelet aggregation or fibrinogen binding to integrin alphaIIbbeta3. On the other hand, the phosphorylation step, and the phosphorylation of the 105-kDa protein, were both inhibited by RGDS and EDTA, which suggests that the integrin alphaIIbbeta3 beta is involved in these steps. Our results, taken together, show that Cvx induces platelet IIb 3 aggregation in a similar manner as collagen and collagen-related peptides that also trigger platelet aggregation by a PTK-dependent pathway, and stimulate tyrosyl-phosphorylation of PLC gamma 2. However, Cvx is unique among platelet receptor agonists, because under test-tube stirring conditions it induces a PTP profile independently of integrin alphaIIbbeta3.

  4. LaaA, a novel high-active alkalophilic alpha-amylase from deep-sea bacterium Luteimonas abyssi XH031(T).

    Science.gov (United States)

    Song, Qinghao; Wang, Yan; Yin, Chong; Zhang, Xiao-Hua

    2016-08-01

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Tumor necrosis factor-alpha activates signal transduction in hypothalamus and modulates the expression of pro-inflammatory proteins and orexigenic/anorexigenic neurotransmitters.

    Science.gov (United States)

    Amaral, Maria E; Barbuio, Raquel; Milanski, Marciane; Romanatto, Talita; Barbosa, Helena C; Nadruz, Wilson; Bertolo, Manoel B; Boschero, Antonio C; Saad, Mario J A; Franchini, Kleber G; Velloso, Licio A

    2006-07-01

    Tumor necrosis factor-alpha (TNF-alpha) is known to participate in the wastage syndrome that accompanies cancer and severe infectious diseases. More recently, a role for TNF-alpha in the pathogenesis of type 2 diabetes mellitus and obesity has been shown. Much of the regulatory action exerted by TNF-alpha upon the control of energy stores depends on its action on the hypothalamus. In this study, we show that TNF-alpha activates canonical pro-inflammatory signal transduction pathways in the hypothalamus of rats. These signaling events lead to the transcriptional activation of an early responsive gene and to the induction of expression of cytokines and a cytokine responsive protein such as interleukin-1beta, interleukin-6, interleukin-10 and suppressor of cytokine signalling-3, respectively. In addition, TNF-alpha induces the expression of neurotransmitters involved in the control of feeding and thermogenesis. Thus, TNF-alpha may act directly in the hypothalamus inducing a pro-inflammatory response and the modulation of expression of neurotransmitters involved in energy homeostasis.

  6. Blockade of alcohol's amnestic activity in humans by an alpha5 subtype benzodiazepine receptor inverse agonist.

    Science.gov (United States)

    Nutt, David J; Besson, Marie; Wilson, Susan J; Dawson, Gerard R; Lingford-Hughes, Anne R

    2007-12-01

    Alcohol produces many subjective and objective effects in man including pleasure, sedation, anxiolysis, plus impaired eye movements and memory. In human volunteers we have used a newly available GABA-A/benzodiazepine receptor inverse agonist that is selective for the alpha5 subtype (a5IA) to evaluate the role of this subtype in mediating these effects of alcohol on the brain. After pre-treatment with a5IA, we found almost complete blockade of the marked impairment caused by alcohol (mean breath concentration 150mg/100ml) of word list learning and partial but non-significant reversal of subjective sedation without effects on other measures such as intoxication, liking, and slowing of eye movements. This action was not due to alterations in alcohol kinetics and so provides the first proof of concept that selectively decreasing GABA-A receptor function at a specific receptor subtype can offset some actions of alcohol in humans. It also supports growing evidence for a key role of the alpha5 subtype in memory. Inverse agonists at other GABA-A receptor subtypes may prove able to reverse other actions of alcohol, and so offer a new approach to understanding the actions of alcohol in the human brain and in the treatment of alcohol related disorders in humans.

  7. SSNTD study of the probable influence of alpha activity on the mass distribution of sup 2 sup 5 sup 2 Cf fission fragments

    CERN Document Server

    Paul, D; Sastri, R C; Ghose, D

    1999-01-01

    The SSNTD has come a long way in its application for the study of nuclear phenomena. Spontaneous fission of transuranic elements is one such phenomena wherein use of SSNTD offers easy registration of the signature of the fission fragments. The object of the present study is to explore whether any one of the track parameters such as the diameter can be used to estimate the atomic mass ratios of the spontaneous fission fragments. The spontaneous fission data from sup 2 sup 5 sup 2 Cf recorded almost at the end of one and four half-life periods for alpha decay are analysed, taking a plot of the number of tracks versus the track diameter. From these plots it is seen that initially, when significant alpha activity of sup 2 sup 5 sup 2 Cf persists, the fission fragments appear to cluster into two predominant groups as indicated by two peaks. The ratio of the diameters at these peak positions appear to be related to the ratio of average mass numbers of the light and heavy groups of fission fragments. However, absenc...

  8. Characterization of a Large Area ZnS(Ag) Detector for Gross Alpha and Beta Activity Measurements in Tap Water Plants

    Science.gov (United States)

    Bodewits, E.; Cester, D.; Lunardon, M.; Moretto, S.; Schotanus, P.; Stevanato, L.; Viesti, G.

    2016-06-01

    In this work we present the characterization of a large area 200 mm ×200 mm EJ-444 scintillation detector to be used for monitoring gross alpha and beta activity in tap water plants. Specific tests were performed in order to determine the best setup to read-out the light from the detector side. The possibility to stack many detectors and get a compact device with total active area of the order of 1 m2 has been explored. Alpha/beta discrimination, efficiency and homogeneity tests were carried out with alpha and beta sources. Background from ambient radioactivity was measured as well. Alpha/beta real-time monitoring in drinking water is a goal of the EU project TAWARA_RTM.

  9. Alpha-glucosidase inhibitory and antioxidant activities of Vietnamese edible plants and their relationships with polyphenol contents.

    Science.gov (United States)

    Mai, Truong Tuyet; Thu, Nghiem Nguyet; Tien, Pham Gia; Van Chuyen, Nguyen

    2007-06-01

    The prevention and treatment of non-communicable diseases by using the beneficial biological effects of polyphenolic plants have attracted increasing interest from nutritional scientists. The a-glucosidase inhibitory and antioxidant activities of aqueous and methanolic extracts from 28 common Vietnamese edible plants, comprising 4 groups (plants used for making drinks, edible wild vegetables, herbs, and dark green vegetables), were investigated in vitro. The polyphenol contents of these extracts were determined by the Folin-Ciocalteu method and calculated as catechin equivalents. The extracts from plants used for making drinks showed the highest activities for both a-glucosidase inhibition and as antioxidants, followed by edible wild vegetables, herbs, and dark green vegetables. Positive relationships among alpha-glucosidase inhibitory activities, antioxidant activities and polyphenol contents of these 28 edible plants were found in both aqueous and methanolic extracts. Four new promising materials that are similar to or better than guava leaf extract, including Syzygium zeylanicum, Cleistocalyx operculatus, Horsfieldia amygdalina and Careya arborea demonstrated high alpha-glucosidase inhibitory activity (93, 76, 68 and 67%, respectively) at the final concentration of 0.8 mg lyophilized material/mL solution and antioxidant activity (85, 87, 78 and 80%, respectively) at the final concentration of 30 pg lyophilized material/mL solution. These four edible plants contained significantly high polyphenol contents (equivalent to 251.7, 146.6, 136.6 and 168.6 mg of catechin/g dry weight, respectively). Thus, these four materials might be possible new sources of a-glucosidase inhibition and antioxidants suitable for use as functional foods in the future.

  10. Gross alpha and beta activity analyses in urine-a routine laboratory method for internal human radioactivity detection.

    Science.gov (United States)

    Chen, Xiaowen; Zhao, Luqian; Qin, Hongran; Zhao, Meijia; Zhou, Yirui; Yang, Shuqiang; Su, Xu; Xu, Xiaohua

    2014-05-01

    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.

  11. Alpha-mangostin induces apoptosis through activation of reactive oxygen species and ASK1/p38 signaling pathway in cervical cancer cells

    OpenAIRE

    Lee, Chien-Hsing; Ying, Tsung-Ho; Chiou, Hui-Ling; Hsieh, Shu-Ching; Wen, Shiua-Hua; Chou, Ruey-Hwang; Hsieh, Yi-Hsien

    2017-01-01

    Alpha-mangostin, a natural xanthonoid, has been reported to possess the anti-cancer property in various types of human cancer. However, its effects and mechanism of ?-mangostin in cervical cancer remain unclear. We found that ?-mangostin effectively inhibited cell viability, resulted in loss of mitochondrial membrane potential (MMP), release of cytochrome C, increase of Bax, decrease of Bcl-2, and activation of caspase-9/caspase-3 cascade in cervical cancer cells. Alpha-mangostin elevated the...

  12. 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

    2002-01-01

    , 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...... in human islets and exocrine cells is primarily mediated by the P2 promoter. Furthermore, we describe a G --> A mutation in a conserved nucleotide position of the HNF-1alpha binding site of the P2 promoter, which cosegregates with MODY. The mutation results in decreased affinity for HNF-1alpha...

  13. Thermally induced disintegration of the oligomeric structure of alphaB-crystallin mutant F28S is associated with diminished chaperone activity.

    Science.gov (United States)

    Kelley, Patrick B; Abraham, Edathara C

    2003-10-01

    alphaB-crystallin, a member of the small heat-shock protein (hsp) family of proteins, is able to function as a molecular chaperone by protecting other proteins from stress-induced aggregation by recognizing and binding to partially unfolded species of damaged proteins. The present work has investigated the role of phenylalanine-28 (F28) of the 22RLFDQFF28 region of alphaB-crystallin in maintaining chaperone function and oligomeric structure under physiological condition and under thermal stress. Bovine alphaB-crystallin was cloned for the first time and the cDNA sequence revealed greater than 90% homology to that of human, rat and mouse alphaB-crystallins. F28 was mutated to a serine followed by expression of the mutant F28S and the wild-type alphaB (alphaB-wt) in E. coli and subsequent purification of the protein by size-exclusion chromatography. Secondary and tertiary structure analyses showed some structural changes in the mutant. Chaperone activity and oligomeric size of the mutant was unchanged at 37 degrees C whereas at 58 degrees C the chaperone activity was significantly decreased and the oligomeric size ranged from low molecular weight to high molecular weight showing disintegration of the oligomeric structure. The data support the idea that the participation of large oligomeric structure rather than smaller units is required to have optimal chaperone activity and the hydrophobic F28 residue is needed for maintaining the native oligomeric structure under thermal stress.

  14. Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans.

    Science.gov (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

    2016-07-01

    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. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  15. Lipid profile of rheumatoid arthritis patients treated with anti-tumor necrosis factor-alpha drugs changes according to disease activity and predicts clinical response.

    Science.gov (United States)

    Cacciapaglia, Fabio; Anelli, Maria Grazia; Rinaldi, Angela; Serafino, Lucia; Covelli, Michele; Scioscia, Crescenzio; Iannone, Florenzo; Lapadula, Giovanni

    2014-11-01

    Patients with active rheumatoid arthritis (RA) frequently show an atherogenic lipid profile, which has been linked with the inflammatory reaction. Inflammatory cytokines, and particularly tumor necrosis factor-alpha (TNF-α), are implicated in the pathogenesis of both atherosclerosis and RA, and also involved in the development of the impaired lipid profile detected in active RA. Although anti-TNF-α agents have been proven effective in controlling joint damage and systemic inflammation, controversy remains about the effect of these drugs on the lipid profile; therefore, the aim of our study was to investigate the effect of anti-TNF-α treatment, in combination with disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroid therapy, on the lipid profile of patients with active RA. Our data suggest that the combination anti-TNF-α/DMARDs/steroids do not significantly interfere with the lipid profile of RA patients. However, analysis of clinical response data showed that patients achieving low disease activity or remission seem to have a protective lipid profile, suggesting that better control of inflammation and disease activity can affect lipid metabolism. The available evidence indicates that high inflammation interferes with lipid metabolism, whereas good control of the chronic inflammatory state may positively influence the lipid profile and cardiovascular risk. Low cholesterol levels at baseline could predict a favorable outcome with anti-TNF-α treatment, but these data need to be confirmed by large prospective studies with long-term follow-up. © 2014 Wiley Periodicals, Inc.

  16. 3-[2,4-Dimethoxybenzylidene]anabaseine (DMXB) selectively activates rat alpha7 receptors and improves memory-related behaviors in a mecamylamine-sensitive manner.

    Science.gov (United States)

    Meyer, E M; Tay, E T; Papke, R L; Meyers, C; Huang, G L; de Fiebre, C M

    1997-09-12

    The alpha7 nicotinic receptor agonist 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB; GTS-21) was investigated for its ability to: (1) activate a variety of nicotinic receptor subtypes in Xenopus oocytes; (2) improve passive avoidance and spatial Morris water task performances in mecamylamine-sensitive manners in bilaterally nucleus basalis lesioned rats; and (3) elevate high-affinity [3H]acetylcholine (ACh) and high-affinity alpha-[125I]bungarotoxin binding in rat neocortex following 2 weeks of daily injections. DMXB (100 microM) activated alpha7 homo-oligomeric receptors, without significant activity at alpha2-, alpha3- and alpha4-containing subtypes. Mecamylamine blocked rat alpha7 receptors weakly if co-administered with agonist, but much more potently when pre-applied. Bilateral ibotenic acid lesions of the nucleus basalis interfered with passive avoidance and spatial memory-related behaviors. DMXB (0.5 mg/kg, i.p.) improved passive avoidance behavior in lesioned animals in a mecamylamine-sensitive manner. DMXB (0.5 mg/kg 15 min before each session) also improved performance in the training and probe components of the Morris water task. DMXB-induced improvement in the probe component but not the training phase was mecamylamine-sensitive. [3H]ACh binding was elevated after 14 days of daily i.p. injections with 0.2 mg/kg nicotine but not after 1 mg/kg DMXB. Neither drug elevated high-affinity alpha-[125I]bungarorotoxin binding over this interval.

  17. Alpha Theta Meditation: Phenomenological, neurophysiologic ...

    African Journals Online (AJOL)

    Alpha Theta Meditation: Phenomenological, neurophysiologic, mindfulness, mood, health and sport implications. ... the single alpha theta meditation was associated with elevated alpha and theta activity, as well as decrease in negative mood perceptions, especially with regard to anxiety, sadness and confusion scores.

  18. Electrophysiological impact of multiple concussions in asymptomatic athletes: A re-analysis based on alpha activity during a visual-spatial attention task.

    Science.gov (United States)

    Guay, Samuel; De Beaumont, Louis; Drisdelle, Brandi Lee; Lina, Jean-Marc; Jolicoeur, Pierre

    2018-01-08

    Most EEG studies used event-related potentials to assess long-term and cumulative effects of sport-related concussions on brain activity. Time-frequency methods provide another approach that allows the detection of subtle shifts in types and patterns of brain oscillations. We sought to discover whether event-related alpha activity would be significantly affected in asymptomatic multi-concussed athletes. We measured the amplitude of alpha activity (8-12Hz) from the EEG recorded during a visual-spatial attention task to compare event-related alpha perturbations in 13 multi-concussed athletes and 14 age-equivalent, non-concussed teammates. Relative to non-concussed athletes, multi-concussed athletes showed significantly less event-related perturbations time-locked to stimulus presentation. Alpha activity alterations were closely related to the number of concussions sustained. Event-related alpha activity differed in asymptomatic multi-concussed athletes when compared to controls. Our study suggests that low-level neurophysiological underpinnings of the deployment of visual-spatial attention are affected in multi-concussed athletes even though their last concussion occurred on average 30 months prior to testing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. 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

    2007-01-01

    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...

  20. Adhesion and activation of human platelets induced by convulxin involve glycoprotein VI and integrin alpha2beta1.

    Science.gov (United States)

    Jandrot-Perrus, M; Lagrue, A H; Okuma, M; Bon, C

    1997-10-24

    We analyzed the interaction of convulxin (Cvx), a 72-kDa protein isolated from the venom of Crotalus durissus terrificus, with human platelets. Cvx is a potent platelet agonist that induces an increase in the intracellular Ca2+ concentration ([Ca2+]i), granule exocytosis and aggregation. 125I-Labeled Cvx binds specifically and rapidly to platelets at binding sites of high and moderate affinity. Platelets adhere to immobilized Cvx in a time-dependent but cation-independent manner. Platelet exocytosis and aggregation induced by Cvx were inhibited by an anti-integrin alpha2beta1 monoclonal antibody (6F1) and by the Fab fragments of a polyclonal anti-glycoprotein VI (GPVI) antibody. Both the adhesion of platelets to Cvx and the Cvx-induced increase in [Ca2+]i were inhibited by anti-GPVI Fab fragments but not by 6F1. Ligand blotting assay showed that 125I-Cvx binds to a 57-kDa platelet protein with an electrophoretic mobility identical to that of GPVI. In addition, we observed the following: (i) 125I-Cvx binds to GPVI immunoprecipitated by the anti-GPVI antibody from a platelet lysate, and (ii) Cvx inhibits the binding of anti-GPVI IgG to GPVI. Taken together, these results demonstrate that GPVI behaves as a Cvx receptor and that the alpha2beta1 integrin appears to be involved in the later stages of Cvx-induced platelet activation, i.e. exocytosis and aggregation.

  1. Antiulcerogenic activity of fractions and 3,15-dioxo-21alpha-hydroxy friedelane isolated from Maytenus robusta (Celastraceae).

    Science.gov (United States)

    de Andrade, Sérgio Faloni; Comunello, Eros; Noldin, Vânia Floriani; Monache, Franco Delle; Cechinel Filho, Valdir; Niero, Rivaldo

    2008-01-01

    The hexane, chloroform, ethyl acetate and aqueous-soluble fractions from leaves of Maytenus robusta (Celastraceae) were evaluated for their protective actions against ethanol-induced gastric lesions in rats. The treatment with all fractions (150 mg/kg) and omeprazol (30 mg/kg) significantly reduced the lesion index, the total lesion area, and the percentage of lesion, in comparison with the control group (p<0.05). Since the ethyl acetate-soluble fraction was found to be most active in the pylorus ligated model, this fraction was further investigated and resulted in the isolation of triterpene 3,15-dioxo-21alpha-hydroxy friedelane. The triterpene was evaluated in the HCl/ethanol-induced ulcer model in mice. In this assay, both the groups treated with 3,15-dioxo-21alpha-hydroxy friedelane and omeprazol, at a dose of 30 mg/kg, presented a significant reduction in lesion index, total lesion area, and in the percentage of the lesion, when compared with the control group (p<0.05). The result suggests that the antiulcer effect observed in the extract and fractions may be attributed, at least in part, to this compound. Further experiments are underway to determine which antiulcer mechanisms involved in gastroprotection.

  2. [Effect of alpha-tocopherol on the activity of the liver glutathione antioxidative system and the activity of serum aminotransferase in rats during tetrachloromethane poisoning].

    Science.gov (United States)

    Gubskiĭ, Iu I; Khmelevskiĭ, Iu V; Sil'chenko, N A

    1983-01-01

    The activities of glutathione peroxidase, glutathione reductase in the liver as well as of glutamate-pyruvate, and glutamate-oxaloacetate transaminase in blood serum were studied in rats which were injected tetrachloromethane in a dose of 1.04 mmol per 100 g mass for seven days. Tetrachloromethane poisoning is accompanied by a considerable decrease in the glutathione peroxidase activity in the liver and an increase in the aminotransferase activity in the blood serum. Additional administration of 20 and 30 mg of L-tocopherol per 100 g of mass prevents a tetrachloromethane-induced decrease in the activity of glutathione peroxidase in the liver and somewhat normalizes the activity of glutamate-pyruvate and glutamate-oxaloacetate transaminase in the blood serum. Possible mechanisms of the alpha-tocoferol protective action are under discussion.

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

    Directory of Open Access Journals (Sweden)

    Ivanova T.

    2013-01-01

    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.

  4. Prevotella intermedia lipopolysaccharide stimulates release of tumor necrosis factor-alpha through mitogen-activated protein kinase signaling pathways in monocyte-derived macrophages.

    Science.gov (United States)

    Kim, Sung-Jo; Choi, Eun-Young; Kim, Eun Gyung; Shin, Su-Hwa; Lee, Ju-Youn; Choi, Jeom-Il; Choi, In-Soon

    2007-11-01

    The purpose of this study was to investigate the effects of lipopolysaccharide from Prevotella intermedia, a major cause of inflammatory periodontal disease, on the production of tumor necrosis factor (TNF)-alpha and the expression of TNF-alpha mRNA in differentiated THP-1 cells, a human monocytic cell line. The potential involvement of the three main mitogen-activated protein kinase (MAPK) signaling pathways in the induction of TNF-alpha production was also investigated. Lipopolysaccharide from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. It was found that P. intermedia lipopolysaccharide can induce TNF-alpha mRNA expression and stimulate the release of TNF-alpha in differentiated THP-1 cells without additional stimuli. Treatment of the cells with P. intermedia lipopolysaccharide resulted in a simultaneous activation of three MAPKs [extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2) and p38]. Pretreatment of the cells with MAPK inhibitors effectively suppressed P. intermedia lipopolysaccharide-induced TNF-alpha production without affecting the expression of TNF-alpha mRNA. These data thus provided good evidence that the MAPK signaling pathways are required for the regulation of P. intermedia lipopolysaccharide-induced TNF-alpha synthesis at the level of translation more than at the transcriptional level.

  5. Hepatitis B spliced protein (HBSP) promotes the carcinogenic effects of benzo [alpha] pyrene by interacting with microsomal epoxide hydrolase and enhancing its hydrolysis activity

    International Nuclear Information System (INIS)

    Chen, Jin-Yan; Chen, Wan-Nan; Jiao, Bo-Yan; Lin, Wan-Song; Wu, Yun-Li; Liu, Ling-Ling; Lin, Xu

    2014-01-01

    The risk of hepatocellular carcinoma (HCC) increases in chronic hepatitis B surface antigen (HBsAg) carriers who often have concomitant increase in the levels of benzo[alpha]pyrene-7,8-diol-9,10-epoxide(±) (BPDE)-DNA adduct in liver tissues, suggesting a possible co-carcinogenesis of Hepatitis B virus (HBV) and benzo[alpha]pyrene in HCC; however the exact mechanisms involved are unclear. The interaction between hepatitis B spliced protein (HBSP) and microsomal epoxide hydrolase (mEH) was confirmed using GST pull-down, co-immunoprecipitation and mammalian two-hybrid assay; the effects of HBSP on mEH-mediated B[alpha]P metabolism was examined by high performance liquid chromatography (HPLC); and the influences of HBSP on B[alpha]P carcinogenicity were evaluated by bromodeoxyuridine cell proliferation, anchorage-independent growth and tumor xenograft. HBSP could interact with mEH in vitro and in vivo, and this interaction was mediated by the N terminal 47 amino acid residues of HBSP. HBSP could greatly enhance the hydrolysis activity of mEH in cell-free mouse liver microsomes, thus accelerating the metabolism of benzo[alpha]pyrene to produce more ultimate carcinnogen, BPDE, and this effect of HBSP requires the intact HBSP molecule. Expression of HBSP significantly increased the formation of BPDE-DNA adduct in benzo[alpha]pyrene-treated Huh-7 hepatoma cells, and this enhancement was blocked by knockdown of mEH. HBSP could enhance the cell proliferation, accelerate the G1/S transition, and promote cell transformation and tumorigenesis of B[alpha]P-treated Huh-7 hepatoma cells. Our results demonstrated that HBSP could promote carcinogenic effects of B[alpha]P by interacting with mEH and enhancing its hydrolysis activity

  6. Active immunization with a synthetic fragment of pig inhibin alpha-subunit increases ovulation rate and embryo production in superovulated ewes but season affects its efficiency.

    Science.gov (United States)

    D'Alessandro, A; Martemucci, G; Iaffaldano, N

    1999-01-01

    Two experiments were designed to determine the effects of active immunization against one of two synthetic peptides from humans (inhibin-like peptide) or pigs (inhibin alpha-subunit) on antibody titres, ovulation rate and embryo production in ewes superovulated with 16 U ovine FSH. In Expt 1, during the breeding season, 30 ewes were subdivided into three groups: group I served as the non-immunized control; group II was immunized against inhibin-like peptide (100 micrograms inhibin-like peptide equivalent, followed by three booster injections); group III was immunized against pig inhibin alpha-subunit conjugated to human serum albumin (96 micrograms for the primary administration and 46 micrograms for the booster). In Expt 2, the efficiency of immunization against pig inhibin alpha-subunit on ovarian response and embryo production was evaluated during the non-breeding season in two groups of ewes (n = 12): group IV was a non-immunized control; Group V was immunized against pig inhibin alpha-subunit. During the breeding season, the ewes immunized against pig inhibin alpha-subunit showed higher antibody titres compared with the group immunized against inhibin-like peptide (P immunized group (3.1; P Immunization against pig inhibin alpha-subunit increased transferable embryo yield 4.5-fold (6.7 versus 1.5; P immunization against pig inhibin alpha-subunit enhanced ovulation rate from 2.6 in the controls to 9.4 (P 0.05) and significantly lowered their quality (54.1 versus 100%; P active immunization against pig inhibin alpha-subunit can improve superovulatory response during the breeding season, while it appears to be unable to increase embryo yield during the seasonal anoestrus.

  7. Insulin secretagogue, alpha-glucosidase and antioxidant activity of some selected spices in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Patil, Swapnil Balasaheb; Ghadyale, Varsha Adhikrao; Taklikar, Shreehari Subhash; Kulkarni, Chaitanya Ramesh; Arvindekar, Akalpita Umesh

    2011-03-01

    Spices are extensively used to enhance the taste and flavor of foods and are known to possess several medicinal properties. Myristica fragrans, Parmelia perlata, Illicium verum, Trachyspermum copticum and Myristica malabarica, the commonly used spices in India were assessed for antidiabetic activity in streptozotocin induced diabetic rats. In the in vitro insulin secretion studies on isolated islets of Langerhans, M. fragrans, T. copticum and M. malabarica showed dose dependent insulin secretion. At 1 mg/ml, P. perlata showed significant in vitro alpha-glucosidase inhibitory activity with IC(50) value of 0.14 mg/ml followed by M. malabarica (0.64 mg/ml), I. verum (0.67 mg/ml), M. fragrans (0.85 mg/ml) and T. copticum (0.92 mg/ml). The DPPH free radical scavenging activity of the extracts at a concentration of 1 mg/ml was as M. malabarica (90.45%), M. fragrans (89.89%), I. verum (87.22%), P. perlata (76.70%) and T. copticum (38.14%). P. perlata showed the highest phenolic content (i.e., 118.5 mg gallic acid equivalents/g) followed by M. malabarica (84.13 mg gallic acid equivalents/g). M. malabarica showed the highest flavonoid content (i.e., 38.35 mg quercetin equivalents/g). Regular use of these spices may prevent postprandial rise in glucose levels through inhibition of intestinal alpha-glucosidase and may maintain blood glucose level through insulin secretagogue action.

  8. Evidence for activation of both adrenergic and cholinergic nervous pathways by yohimbine, an alpha 2-adrenoceptor antagonist.

    Science.gov (United States)

    Bagheri, H; Chale, J J; Guyen, L N; Tran, M A; Berlan, M; Montastruc, J L

    1995-01-01

    Adrenoceptors are involved in the control of the activity of the autonomic nervous system and especially the sympathetic nervous system. Activation of alpha 2-adrenoceptors decreases sympathetic tone whereas their blockade has an opposite effect. However, previous investigations have shown that yohimbine (a potent alpha 2-adrenoceptor antagonist) increases salivary secretion through activation of cholinergic pathways. The aim of the present experiment was to investigate the involvement of both the sympathetic and the parasympathetic system in several pharmacological effects of yohimbine. For this purpose, salivary secretion and various endocrino-metabolic parameters (noradrenaline and insulin secretions, lipomobilization) were evaluated in conscious fasting dogs before and after blockade of either the sympathetic (with the beta-adrenoceptor antagonist agent nadolol) or the parasympathetic (with the anticholinergic agent atropine) systems. Yohimbine alone (0.4 mg.kg-1, i.v.) increased within 5-15 minutes, plasma noradrenaline (600%), insulin levels (300%), free-fatty acids (79%) and salivary secretion (143%). Atropine (0.2 mg.kg-1, i.v.) suppressed yohimbine-induced salivary secretion (90%) but did not significantly modify the yohimbine induced changes in noradrenaline (312%), insulin (277%) and free-fatty acids (102%) plasma levels. Administration of nadolol (1 mg.kg-1, i.v.) did not change the magnitude of the increase in both noradrenaline plasma levels (550%) and salivary secretion (300%) induced by yohimbine. However, nadolol totally blunted the increase in insulin (15%) and free-fatty acids (4%) plasma levels. These results show that yohimbine-induced increase in salivary secretion is a cholinergic effect whereas the increase in insulin and free fatty acids can be explained by an increase in sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. 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

    2009-01-01

    of a recognizable p63-binding motif, suggesting that it acts through interactions with other transcription factors (TFs). Distinct PPARalpha transcripts are differentially regulated by p63, indicating a bimodal action in promoter and/or transcription start specification. PPARalpha repression is consistent with lack...... of expression in the interfollicular epidermis under physiological conditions. Furthermore, we show that PPARalpha is a negative regulator of DeltaNp63alpha levels and that it also binds to a functional region of the DeltaNp63 promoter that lacks PPRE motifs. Therefore, the reciprocal regulation is exerted...... either through binding to non-consensus sites or through interactions with other DNA-bound TFs. In conclusion, our data establish a link between two TFs intimately involved in the maintenance of skin homeostatic conditions.Journal of Investigative Dermatology advance online publication, 21 May 2009; doi...

  10. Major water-soluble polyphenols, proanthocyanidins, in leaves of persimmon (Diospyros kaki) and their alpha-amylase inhibitory activity.

    Science.gov (United States)

    Kawakami, Kayoko; Aketa, Saiko; Nakanami, Mitsuhiro; Iizuka, Shinzo; Hirayama, Masao

    2010-01-01

    The amounts and compositions of polyphenol in persimmon leaves and persimmon leaf tea were investigated. The predominant polyphenols in fresh leaves were water-soluble, and the contents reached a maximum (2.40% w/w) in June, and then gradually decreased. Separation of them followed by thiolytic degradation revealed that the major components were unique proanthocyanidin oligomers consisting of four heterogeneous extension units, including epigallocatechin-3-O-gallate. Persimmon leaf tea also contained similar proanthocyanidins with similar compositional units. Oral administration of starch with polyphenol concentrate of persimmon leaf tea resulted in a significant and dose-dependent decrease in the blood glucose level in Wistar rats. This effect is considered to be due to inhibition of pancreas alpha-amylase. These results indicate that persimmon leaf tea containing peculiar proanthocyanidins has a significant role in suppressing blood glucose elevation after starch intake, and that the best harvest time is June.

  11. The Biological Activity of alpha-Mangostin, a Larvicidal Botanic Mosquito Sterol Carrier Protein-2 Inhibitor

    Science.gov (United States)

    2010-01-01

    consider- ingG.mangostana is a tropical evergreen that ismainly found in India , Myanmar, Sri Lanka, and Thailand (Jung et al. 2006). Almost a decade...unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 ferase ( GST ) activities (Bullangpoti et al...Thermo ScientiÞc, Rockford, IL). The esterase activity was expressed as mol/mg protein/min substrate hydrolyzed. GST Activity. GST activity samples

  12. The role and regulation of the peroxisome proliferator activated receptor alpha in human liver

    NARCIS (Netherlands)

    Kersten, Sander; Stienstra, Rinke

    2017-01-01

    The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is abundantly expressed in liver. PPARα is activated by fatty acids and various other lipid species, as well as by a class of chemicals referred to as peroxisome proliferators. Studies in mice

  13. Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-alpha and -delta, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening

    NARCIS (Netherlands)

    Ratziu, V.; Harrison, S.A.; Francque, S.; Bedossa, P.; Lehert, P.; Serfaty, L.; Romero-Gomez, M.; Boursier, J.; Abdelmalek, M.; Caldwell, S.; Drenth, J.P.; Anstee, Q.M.; Hum, D.; Hanf, R.; Roudot, A.; Megnien, S.; Staels, B.; Sanyal, A.

    2016-01-01

    BACKGROUND & AIMS: Elafibranor is an agonist of the peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-delta. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. We assessed the safety and efficacy

  14. 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

    1989-01-01

    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. The p...

  15. Observing and Understanding an On-Line Learning Activity: A Model-Based Approach for Activity Indicator Engineering

    Science.gov (United States)

    Djouad, Tarek; Mille, Alain

    2018-01-01

    Although learning indicators are now properly studied and published, it is still very difficult to manage them freely within most distance learning platforms. As all activity indicators need to collect and analyze properly traces of the learning activity, we propose to use these traces as a starting point for a platform independent Trace…

  16. Synthesis and development of new 2-substituted 1-[3-(4-arylpiperazin-1-yl)propyl]-pyrrolidin-2-one derivatives with antiarrhythmic, hypotensive, and alpha-adrenolytic activity.

    Science.gov (United States)

    Malawska, Barbara; Kulig, Katarzyna; Gippert, Annika; Filipek, Barbara; Sapa, Jacek; Maciag, Dorota

    2005-10-01

    A series of new 1-[3-(4-arylpiperazinyl-1-yl)-2-(N-alkylcarbamoyloxy)propyl]-pyrrolidin-2-one derivatives (4a-12a) were synthesised and tested for their electrocardiographic, antiarrhythmic and antihypertensive activity, as well as for the alpha1- and alpha2-adrenoceptor binding affinities. Of the newly synthesised derivatives, 1-{2-(N-2-methylethylcarbamoiloxy)-3-[4-(2-methoxyphenyl)piperazin-1-yl)]propyl}pyrrolidin-2-one dihydrochloride (10a) was the most active in prophylactic antiarrhythmic tests, its ED50 value equalling 2.7 mg kg(-1), and the therapeutic index being 75.2; moreover, compound 10a was also found to possess hypotensive activity. A preliminary molecular modelling study suggested that the selected alpha1-AR antagonist distances and angles between pharmacophoric features, estimated for the tested compounds, were in good agreement with the parameters evaluated for ligands.

  17. Correlation of Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) and Retinoid X Receptor-alpha (RXR-alpha) expression with clinical risk factors in patients with advanced carotid atherosclerosis.

    Science.gov (United States)

    Giaginis, Constantinos; Klonaris, Christos; Katsargyris, Athanassios; Kouraklis, Gregorios; Spiliopoulou, Chara; Theocharis, Stamatios

    2011-07-01

    Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its nuclear partners, the Retinoid X Receptors (RXRs), have been recognized as crucial players in the pathogenesis of atherosclerosis. The present study aimed to assess the clinical significance of PPAR-gamma and RXR-alpha expression in different cellular populations localized within advanced carotid atherosclerosis lesions. PPAR-gamma and RXR-alpha expression was assessed by immunohistochemistry in 134 carotid atherosclerotic plaques obtained from an equal number of patients that underwent endarterectomy procedure for vascular repair, and was correlated with patients' medical history, risk factors and medication intake. Increased incidence of low PPAR-gamma expression in both macrophages and smooth muscle cells was noted in patients presenting coronary artery disease (p=0.032 and p=0.046, respectively). PPAR-gamma expression in smooth muscle cells was borderline down-regulated in symptomatic compared to asymptomatic patients (p=0.061), reaching statistical significance when analyzing groups of patients with specific cerebrovascular events; amaurosis fugax (p=0.008), amaurosis fugax/stroke (p=0.020) or amaurosis fugax/transient ischemic attack patients (p=0.028) compared to asymptomatic patients. Low RXR-alpha expression in macrophages was more frequently observed in hypertensive (p=0.048) and hyperlipidemic patients (p=0.049). Increased incidence of low RXR-alpha expression in smooth muscle cells was also noted in patients presenting advanced carotid stenosis grade (p=0.015). PPAR-gamma and RXR-alpha expression down-regulation in macrophages and smooth muscle cells was associated with a more pronounced disease progression in patients with advanced carotid atherosclerotic lesions.

  18. Receptor protein tyrosine phosphatase alpha activates Src-family kinases and controls integrin-mediated responses in fibroblasts

    DEFF Research Database (Denmark)

    Su, J; Muranjan, M; Sap, J

    1999-01-01

    BACKGROUND: Fyn and c-Src are two of the most widely expressed Src-family kinases. Both are strongly implicated in the control of cytoskeletal organization and in the generation of integrin-dependent signalling responses in fibroblasts. These proteins are representative of a large family...... of tyrosine kinases, the activity of which is tightly controlled by inhibitory phosphorylation of a carboxyterminal tyrosine residue (Tyr527 in chicken c-Src); this phosphorylation induces the kinases to form an inactive conformation. Whereas the identity of such inhibitory Tyr527 kinases has been well...... established, no corresponding phosphatases have been identified that, under physiological conditions, function as positive regulators of c-Src and Fyn in fibroblasts. RESULTS: Receptor protein tyrosine phosphatase alpha (RPTPalpha) was inactivated by homologous recombination. Fibroblasts derived from...

  19. Temperature dependence of decay time and intensity of alpha pulses in pure and thallium-activated cesium iodide

    Science.gov (United States)

    Senftle, F.E.; Martinez, P.; Alekna, V.P.

    1962-01-01

    The intensity and decay time of Po210 ?? particle scintillations produced in pure and thallium-activated cesium iodide have been measured with a fast electronic system as a function of temperature down to 77??K. Three modes of decay due to alpha excitation have been observed for CsI(Tl), and two for CsI. Other than the 7- and 0.55-??sec modes (at room temperature) reported in the literature for CsI(Tl), an additional temperature-independent mode of about 1.3 ??sec has been detected between 77 and 150??K. In CsI a fast temperature-dependent mode of decay (???100 nsec) was observed between 100-200??K in addition to the known principal mode. ?? 1962 The American Institute of Physics.

  20. Minimum detectable activity and false alarm rate relationships for alpha continuous air monitors

    International Nuclear Information System (INIS)

    Hoover, M.D.; Newton, G.J.

    1994-01-01

    The U.S. Department of Energy rule for Occupational Radiation Protection (10 CFR Part 835, December 1993) and the DOE Radiological Control Manual (the RCM) (DOE/EH-0256T, Rev. 1, April 1994) require the use of continuous air monitors (CAMs) in normally occupied areas where an individual is likely to be exposed to a concentration of airborne radioactivity exceeding the derived air concentration (DAC) or where there is a need to alert potentially exposed individuals to unexpected increases in airborne radioactivity levels. The DAC is the airborne concentration that equals the annual limit on intake divided by the volume of air breathed by an average worker for a working year of 2000 h (assuming a breathing volume of 2400 m 3 ). It is equivalent to the airborne concentration to which a worker could be exposed for an entire working year (2000 h) without exceeding the allowable annual limit on intake. The rule and the RCM further require that real-time air monitors have an alarm capability and sufficient sensitivity to alert potentially exposed individuals that immediate action is necessary in order to minimize or terminate inhalation exposures. The RCM also recommends that real-time air monitors should be capable of measuring 1 DAC when averaged over 8 h (8 DAC-h) under laboratory conditions. In response to these recommendations, we are developing procedures for determining the basic sensitivity of alpha CAMs under laboratory conditions and for documenting practical alarm set points for routine use of CAMs under a range of radon and thoron concentrations

  1. Demystifying AlphaGo Zero as AlphaGo GAN

    OpenAIRE

    Dong, Xiao; Wu, Jiasong; Zhou, Ling

    2017-01-01

    The astonishing success of AlphaGo Zero\\cite{Silver_AlphaGo} invokes a worldwide discussion of the future of our human society with a mixed mood of hope, anxiousness, excitement and fear. We try to dymystify AlphaGo Zero by a qualitative analysis to indicate that AlphaGo Zero can be understood as a specially structured GAN system which is expected to possess an inherent good convergence property. Thus we deduct the success of AlphaGo Zero may not be a sign of a new generation of AI.

  2. [Leptin and activity of tumor necrosis factor alpha relations with parameters of the trophologic status and digestion in patients with chronic obstructive pulmonary disease].

    Science.gov (United States)

    2011-01-01

    To study effects of leptin regulation of energy and activity of TNF-alpha on the trophologic status and digestion of main nutrients in patients with stable chronic obstructive pulmonary disease (COPD). Somatometric methods were used to examine trophologic status in 93 patients with stable COPD. Of them, 22 had stage I, 36 - stage II, 35 patients - stage III. Serum leptin was measured with enzyme immunoassay (EIA) using DSL kit (USA), TNF-alpha and receptors sTNF-R55 and -R75 with EIA (kits BioSource, Belgium). The absorption was assessed biochemically and with radionuclide investigation. Body fat was estimated by bioelectric impedance (OmRon BF-302, Japan). The level of circulating leptin decreased with progression of COPD and correlated with body fat depletion (r = 0.88 +/- 0.12). Activation of the TNF-alpha system was detected in the presence and progression of trophologic insufficiency (TI) in patients with COPD stage II and III. A correlation was found between an elevated level of circulating TNF-alpha and enhanced fat and 131-I-albumin excretion, subnormal excretion of D-xylose. Low blood serum leptin concentration in patients with moderate and severe stable COPD correlates with fat tissue depletion reflecting reduced energetic potential of adipocytes. High TNF-alpha concentration in the serum was seen only in TI and its progression. This evidences for cytokine involvement in induction of metabolic disorders in COPD patients. Elevated concentration of circulating TNF-alpha closely correlated with excretion of higher quantities of fats, protein, low excretion of D-xylose and proves its involvement in TI development in COPD patients. Activation of TNF-alpha system in COPD does not influence leptin concentration in blood serum as it functions as an independent physiological system.

  3. Alpha-2 adrenergic activity of bromocriptine and quinpirole in chicken pineal gland. Effects on melatonin synthesis and [3H]rauwolscine binding

    International Nuclear Information System (INIS)

    Zawilska, J.; Iuvone, P.M.

    1990-01-01

    In the pineal gland and retina of chickens, serotonin N-acetyl-transferase (NAT) activity and melatonin content are modulated by different receptors, alpha-2 adrenergic receptors in pineal gland and D2-dopamine receptors in retina. The effect of two D2-dopamine receptor agonists, bromocriptine and quinpirole (LY 171555), on melatonin synthesis in these tissues was investigated. Systemic administrations of bromocriptine and quinpirole decreased nocturnal NAT activity and melatonin content of both pineal gland and retina. Bromocriptine was equipotent in the two tissues, whereas quinpirole was approximately 100-fold more potent in retina than in pineal gland. In pineal gland, the suppressive effects of bromocriptine and quinpirole on NAT activity were blocked by yohimbine, a selective alpha-2 adrenergic receptor antagonist, but not by spiperone, a D2-dopamine receptor antagonist. In contrast, bromocriptine- and quinpirole-induced decreases of the enzyme activity in retina were antagonized by spiperone, and not affected by yohimbine. The nocturnal increase of NAT activity of pineal glands in vitro was inhibited with an order of potency clonidine greater than bromocriptine greater than quinpirole. Additionally, bromocriptine and quinpirole displaced the specific binding of [3H]rauwolscine, an alpha-2 adrenergic receptor antagonist, to membranes from chicken pineal gland, with potencies comparable to those observed for inhibition of NAT activity in vitro. It is suggested that bromocriptine and quinpirole, in addition to their D2-dopaminergic activity, can stimulate alpha-2 adrenergic receptors in pineal gland of chicken

  4. Molecular basis of arabinobio-hydrolase activity in phytopathogenic fungi: crystal structure and catalytic mechanism of Fusarium graminearum GH93 exo-alpha-L-arabinanase.

    Science.gov (United States)

    Carapito, Raphaël; Imberty, Anne; Jeltsch, Jean-Marc; Byrns, Simon C; Tam, Pui-Hang; Lowary, Todd L; Varrot, Annabelle; Phalip, Vincent

    2009-05-01

    The phytopathogenic fungus Fusarium graminearum secretes a very diverse pool of glycoside hydrolases (GHs) aimed at degrading plant cell walls. alpha-l-Arabinanases are essential GHs participating in the complete hydrolysis of hemicellulose, a natural resource for various industrial processes, such as bioethanol or pharmaceuticals production. Arb93A, the exo-1,5-alpha-l-arabinanase of F. graminearum encoded by the gene fg03054.1, belongs to the GH93 family, for which no structural data exists. The enzyme is highly active (1065 units/mg) and displays a strict substrate specificity for linear alpha-1,5-l-arabinan. Biochemical assays and NMR experiments demonstrated that the enzyme releases alpha-1,5-l-arabinobiose from the nonreducing end of the polysaccharide. We determined the crystal structure of the native enzyme and its complex with alpha-1,5-l-arabinobiose, a degradation product of alpha-Me-1,5-l-arabinotetraose, at 1.85 and 2.05A resolution, respectively. Arb93A is a monomeric enzyme, which presents the six-bladed beta-propeller fold characteristic of sialidases of clan GHE. The configuration of the bound arabinobiose is consistent with the retaining mechanism proposed for the GH93 family. Catalytic residues were proposed from the structural analysis, and site-directed mutagenesis was used to validate their role. They are significantly different from those observed for GHE sialidases.

  5. 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.

  6. Differences in genotoxic activity of alpha-Ni3S2 on human lymphocytes from nickel-hypersensitized and nickel-unsensitized donors.

    Science.gov (United States)

    Arrouijal, F Z; Marzin, D; Hildebrand, H F; Pestel, J; Haguenoer, J M

    1992-05-01

    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.

  7. The Na,K-ATPase alpha 2 isoform is expressed in neurons, and its absence disrupts neuronal activity in newborn mice.

    Science.gov (United States)

    Moseley, Amy E; Lieske, Steve P; Wetzel, Randall K; James, Paul F; He, Suiwen; Shelly, Daniel A; Paul, Richard J; Boivin, Gregory P; Witte, David P; Ramirez, Jan Marino; Sweadner, Kathleen J; Lingrel, Jerry B

    2003-02-14

    Na,K-ATPase is an ion transporter that impacts neural and glial physiology by direct electrogenic activity and the modulation of ion gradients. Its three isoforms in brain have cell-type and development-specific expression patterns. Interestingly, our studies demonstrate that in late gestation, the alpha2 isoform is widely expressed in neurons, unlike in the adult brain, in which alpha2 has been shown to be expressed primarily in astrocytes. This unexpected distribution of alpha2 isoform expression in neurons is interesting in light of our examination of mice lacking the alpha2 isoform which fail to survive after birth. These animals showed no movement; however, defects in gross brain development, muscle contractility, neuromuscular transmission, and lung development were ruled out. Akinesia suggests a primary neuronal defect and electrophysiological recordings in the pre-Bötzinger complex, the brainstem breathing center, showed reduction of respiratory rhythm activity, with less regular and smaller population bursts. These data demonstrate that the Na,K-ATPase alpha2 isoform could be important in the modulation of neuronal activity in the neonate.

  8. Prediction for the high-level alpha-active waste to be generated by nuclear power stations in the Member States of the European Communities

    International Nuclear Information System (INIS)

    Schmidt, E.

    1977-04-01

    Starting with a forecast for the nuclear power generating capacity to be installed in the Member States of the European Communities before the end of this century, a prediction is made of the annual production of high-level alpha-active waste from reprocessing plants and the corresponding accumulation up to the year 2000. The isotopic composition of the alpha-active waste from individual reactor types was calculated and an estimation of the influence of recycling plutonium through light water reactors on the produced quantity of higher actinides is made

  9. The effect of alpha-ketoglutaric acid on tyrosinase activity and conformation: Kinetics and molecular dynamics simulation study.

    Science.gov (United States)

    Gou, Lin; Lee, Jinhyuk; Yang, Jun-Mo; Park, Yong-Doo; Zhou, Hai-Meng; Zhan, Yi; Lü, Zhi-Rong

    2017-12-01

    Alpha-ketoglutaric acid (AKG) is naturally found in organisms and is a well-known intermediate in the production of ATP or GTP in the Krebs cycle. We elucidated the effects of AKG on tyrosinase activity and conformation via methods of inhibition kinetics integrated with molecular dynamics (MD) simulations. AKG was found to be a reversible inhibitor of tyrosinase (IC 50 =15±0.5mM) and induced parabolic slope mixed-type inhibition. Based on our newly established equation, the dissociation constant (K islope ) was determined to be 7.93±0.31mM. The spectrofluorimetry studies showed that AKG mainly induced regional changes in the active site of tyrosinase, which reflects the flexibility of the active site. The computational docking and molecular dynamics (MD) simulations further demonstrated that AKG could interact with several residues near the substrate-binding site located in the tyrosinase active site pocket. Our study provides insight into the mechanism by which energy-producing intermediates such as AKG inhibit tyrosinase through its ketone groups. Also, AKG could be a potential natural antipigmentation agent due to its non-toxic property. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Interleukin 2 and 15 activate Stat3alpha in human T lymphocytes

    DEFF Research Database (Denmark)

    Nielsen, M; Nordahl, M; Svejgaard, A

    1998-01-01

    in response to interleukin (IL)-2 and IL-15. Here, cytokine-induced activation of Stat3 in previously activated CD4(+) human T cells was examined using Stat3 antibodies directed against different regions of Stat3. As determined by tyrosine phosphorylation, nuclear translocation and binding to an h...

  11. Dimerization inhibits the activity of receptor-like protein-tyrosine phosphatase-alpha

    DEFF Research Database (Denmark)

    Jiang, G; den Hertog, J; Su, J

    1999-01-01

    that dimerization can negatively regulate activity, through the interaction of an inhibitory 'wedge' on one monomer with the catalytic cleft of domain 1 in the other monomer. Here we show that dimerization inhibits the activity of a full-length RPTP in vivo. We generated stable disulphide-bonded full...

  12. ON THE ACTIVITY OF alpha-AMYLASE IN SOME SPECIES OF ASIAN CYPRINIDS

    Directory of Open Access Journals (Sweden)

    Gabriela Vasile

    2006-08-01

    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.

  13. Functional expression of four PDH-E(1)alpha recombinant histidine mutants in a human fibroblast cell line with zero endogenous PDH complex activity.

    Science.gov (United States)

    Seyda, A; Robinson, B H

    2000-04-21

    Conserved histidine residues have been implicated in the geometry and catalytic mechanism of the E(1)alpha proteins of the PDH complex. We constructed and expressed a series of PDH-E(1)alpha histidine mutants (H63, H84, H92, and H263) in a cell line with zero PDH complex activity due to a null E(1)alpha allele. Based on immunoblot and enzyme activity analyses, all introduced histidine mutations, with the exception of H92, affected the specific activity of the PDH complex. We showed that H63 and H263 are essential for the activity since mutations introduced at those sites produced a PDH complex with near-zero activity. Mutations introduced at H84 only partially reduced activity, implying that H84 may play a less critical role in the PDH complex. Mutations introduced at H92 caused the absence of immunoreactive material for both the E(1)alpha and E(1)beta subunits and may have impaired import or assembly of precursor peptides into the mature PDH complex. Copyright 2000 Academic Press.

  14. Elevated levels of serum alpha(2) macroglobulin in wild black bears during hibernation.

    Science.gov (United States)

    Sheikh, Ashfaq M; Chauhan, Ved; Tsiouris, John A; Mehta, Pankaj D; Burguess, Kelcey; Fenko, Michael D; Spivack, Warren; Vaughan, Michael; Malik, Mazhar

    2003-10-01

    Bear serum alpha(2) macroglobulin (alpha(2)M) was purified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and partially characterized by tryptic digestion of alpha(2)M and analysis of the peptides by peptide mass fingerprinting. The molecular weight of bear serum alpha(2)M was 181 kDa, same as for human serum alpha(2)M, on SDS-PAGE. However, the MALDI mass spectrum of the tryptic digested bear serum alpha(2)M showed that it is different from human alpha(2)M or other data bank proteins. Liquid chromatography (LC)/mass spectrometry (MS)/MS of the proteolytic products of bear serum alpha(2)M showed eight peptides that had similarities to human alpha(2)M suggesting that the protein of interest was indeed alpha(2)M of bear. The polyclonal antibody against bear serum alpha(2)M recognized only one protein from the western blot of bear serum proteins. It also recognized human alpha(2)M. The levels of serum alpha(2)M were significantly increased during hibernating state as compared to active state of bears indicating its protective role from the consequences of the metabolic depression during hibernation.

  15. Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Vanesa Sanchez-Guajardo

    Full Text Available Post-mortem analysis of brains from Parkinson's disease (PD patients strongly supports microglia activation and adaptive immunity as factors contributing to disease progression. Such responses may be triggered by alpha-synuclein (alpha-syn, which is known to be the main constituent of the aggregated proteins found in Lewy bodies in the brains of PD patients. To investigate this we used a recombinant viral vector to express human alpha-syn in rat midbrain at levels that induced neuronal pathology either in the absence or the presence of dopaminergic cell death, thereby mimicking early or late stages of the disease. Microglia activation was assessed by stereological quantification of Mac1+ cells, as well as the expression patterns of CD68 and MCH II. In our study, when alpha-syn induced neuronal pathology but not cell death, a fast transient increase in microglia cell numbers resulted in the long-term induction of MHC II+ microglia, denoting antigen-presenting ability. On the other hand, when alpha-syn induced both neuronal pathology and cell death, there was a delayed increase in microglia cell numbers, which correlated with long-lasting CD68 expression and a morphology reminiscent of peripheral macrophages. In addition T-lymphocyte infiltration, as judged by the presence of CD4+ and CD8+ cells, showed distinct kinetics depending on the degree of neurodegeneration, and was significantly higher when cell death occurred. We have thus for the first time shown that the microglial response differs depending on whether alpha-syn expression results on cell death or not, suggesting that microglia may play different roles during disease progression. Furthermore, our data suggest that the microglial response is modulated by early events related to alpha-syn expression in substantia nigra and persists at the long term.

  16. Effect of the glass transition temperature on alpha-amylase activity in a starch matrix.

    Science.gov (United States)

    Chaudhary, Vinita; Panyoyai, Naksit; Small, Darryl M; Shanks, Robert A; Kasapis, Stefan

    2017-02-10

    This study optimises a protocol for the estimation of α-amylase activity in a condensed starch matrix in the vicinity of the glass transition region. Enzymatic activity on the vitrified starch system was compared with that of a reference substrate, maltodextrin. The activity was assayed as the rate of release of reducing sugar using a dinitrosalicylic acid procedure. The condensed carbohydrate matrices served the dual purpose of acting as a substrate as well as producing a pronounced effect on the ability to enzymatic hydrolysis. Activation energies were estimated throughout the glass transition region of condensed carbohydrate preparations based on the concept of the spectroscopic shift factor. Results were used to demonstrate a considerable moderation by the mechanical glass transition temperature, beyond the expected linear effect of the temperature dependence, on the reaction rate of starch hydrolysis by α-amylase in comparison with the low-molecular weight chain of maltodextrin. Copyright © 2016. Published by Elsevier Ltd.

  17. PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer

    DEFF Research Database (Denmark)

    Koefoed Petersen, Rasmus; Benzon Larsen, Signe; Jensen, Ditte Marie

    2012-01-01

    Alcohol is a risk factor for postmenopausal breast cancer. One of several proposed mechanisms is that alcohol-related breast cancer is caused by increased sex hormone levels. PPARγ inhibits aromatase transcription in breast adipocytes. We reproduced previously found allele-specific effects...... 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....

  18. Interactions of a new alpha-aminophosphinic derivative inside the active site of TLN (thermolysin): a model for zinc-metalloendopeptidase inhibition.

    Science.gov (United States)

    Selkti, Mohamed; Tomas, Alain; Gaucher, Jean-François; Prangé, Thierry; Fournié-Zaluski, Marie-Claude; Chen, Huixiong; Roques, Bernard-Pierre

    2003-07-01

    A new alpha-aminophosphinic compound able to inhibit both zinc-containing exopeptidases and endopeptidases has been crystallized with TLN as a model in order to investigate the mode of zinc recognition by the phosphinic moiety and to evaluate the potential role of the free alpha-amino group in the formation of enzyme-inhibitor complexes. In addition to the main interactions between the backbone of the inhibitor and the enzyme active site, it is observed that the phosphinic group acts as a distorted bidentate ligand for the zinc ion, while the free alpha-amino function does not directly participate in interactions within the active site. Association of the present data and the K(i) values of various analogues of the inhibitor towards TLN and neprilysin suggests differences in the hydrophobicity of the S(1)-S(2) domains of the enzymes. This could be taken into account in the design of selective inhibitors.

  19. 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

    2005-01-01

    running (90 min), and in recovery. Running increased a1-AMPK kinase activity, phosphorylation (P) of AMPK, and acetyl-CoA carboxylase (ACC)ß in a2-WT and a2-KO muscles and increased a2-AMPK kinase activity in a2-WT. In a2-KO muscles, AMPK-P and ACCß-P were markedly lower compared with a2-WT. However, in a...

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

    NARCIS (Netherlands)

    Chang Liao, Mei-Ling; de Boer, Teun P|info:eu-repo/dai/nl/30481878X; 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|info:eu-repo/dai/nl/229701310; Morlock, Michael M; Knöpfel, Thomas; Zimmermann, Wolfram-Hubertus

    2015-01-01

    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

  1. STUDY OF INDICATORS OF AMYLOLYTIC ACTIVITY OF MOUTH FLUID OF DENTAL HEALTHCARE WORKERS UNDER VARIOUS CONDITIONS OF PROFESSIONAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    S. V. Melnikova

    2014-06-01

    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.

  2. Synthesis and serotonin transporter activity of sulphur-substituted alpha-alkyl phenethylamines as a new class of anticancer agents

    DEFF Research Database (Denmark)

    Cloonan, Suzanne M.; Keating, John J.; Butler, Stephen G.

    2009-01-01

    The discovery that some serotonin reuptake transporter (SERT) ligands have the potential to act as pro-apoptotic agents in the treatment of cancer adds greatly to their diverse pharmacological application. 4-Methylthioamphetamine (MTA) is a selective ligand for SERT over other monoamine transport......The discovery that some serotonin reuptake transporter (SERT) ligands have the potential to act as pro-apoptotic agents in the treatment of cancer adds greatly to their diverse pharmacological application. 4-Methylthioamphetamine (MTA) is a selective ligand for SERT over other monoamine...... transporters. In this study, a novel library of structurally diverse 4-MTA analogues were synthesised with or without N-alkyl and/or C-alpha methyl or ethyl groups so that their potential SERT-dependent antiproliferative activity could be assessed. Many of the compounds displayed SERT-binding activity as well...... as cytotoxic activity. While there was no direct correlation between these two effects, a number of derivatives displayed anti-tumour effects in lymphoma, leukaemia and breast cancer cell lines, showing further potential to be developed as possible chemotherapeutic agents. (C) 2009 Elsevier Masson SAS. All...

  3. Hepatocyte nuclear factor 1alpha is an accessory factor required for activation of glucose-6-phosphatase gene transcription by glucocorticoids.

    Science.gov (United States)

    Lin, B; Morris, D W; Chou, J Y

    1998-11-01

    Deficiency of glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis, causes glycogen storage disease type 1a (GSD-1a), also know as von Gierke disease. Expression of the G6Pase gene is regulated by multiple hormones, including glucocorticoids. The synthetic glucocorticoid dexamethasone increased G6Pase mRNA abundance and gene transcription in H4-IIE hepatoma cells. Transient transfection assays demonstrated that the G6Pase promoter was active in H4-IIE cells only in the presence of dexamethasone. The minimal G6Pase promoter was contained within nucleotides -234/+3, which has two putative glucocorticoid response elements (GREs) at nucleotides -178/-164 (site 1) and -154/-140 (site 2). Electromobility shift and transient transfection assays showed that only GRE site 1 was required for glucocorticoid-activated transcription from the G6Pase promoter. Deletion analysis demonstrated that the DNA elements absolutely essential for glucocorticoid-stimulated transcription from the G6Pase promoter were contained within nucleotides -234/-212, encompassing binding motifs for hepatocyte nuclear factors (HNFs) 1 (-226/-212) and 4 (-231/-220). Electromobility shift and cotransfection assays showed that HNF1alpha bound to its cognate site and mediated transcription activation of the G6Pase gene by glucocorticoids.

  4. Interferon-alpha administration enhances CD8+ T cell activation in HIV infection.

    Directory of Open Access Journals (Sweden)

    Maura Manion

    Full Text Available 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.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.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.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.

  5. Ligand structure-dependent activation of estrogen receptor alpha/Sp by estrogens and xenoestrogens.

    Science.gov (United States)

    Wu, Fei; Khan, Shaheen; Wu, Qian; Barhoumi, Rola; Burghardt, Robert; Safe, Stephen

    2008-05-01

    This study investigated the effects of E2, diethylstilbestrol (DES), antiestrogens, the phytoestrogen resveratrol, and the xenoestrogens octylphenol (OP), nonylphenol (NP), endosulfan, kepone, 2,3,4,5-tetrachlorobiphenyl-4-ol (HO-PCB-Cl(4)), bisphenol-A (BPA), and 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on induction of luciferase activity in breast cancer cells transfected with a construct (pSp1(3)) containing three tandem GC-rich Sp binding sites linked to luciferase and wild-type or variant ERalpha. The results showed that induction of luciferase activity was highly structure-dependent in both MCF-7 and MDA-MB-231 cells. Moreover, RNA interference assays using small inhibitory RNAs for Sp1, Sp3 and Sp4 also demonstrated structure-dependent differences in activation of ERalpha/Sp1, ERalpha/Sp3 and ERalpha/Sp4. These results demonstrate for the first time that various structural classes of ER ligands differentially activate wild-type and variant ERalpha/Sp-dependent transactivation, selectively use different Sp proteins, and exhibit selective ER modulator (SERM)-like activity.

  6. PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise

    DEFF Research Database (Denmark)

    Pilegaard, Henriette; Birk, Jesper Bratz; Sacchetti, Massimo

    2006-01-01

    extensor exercise at moderate intensity. During the 4-h resting period, activity of PDH in the active form (PDHa) did not change in either trial, yet phosphorylation of PDH-E1a site 1 (PDH-P1) and site 2 (PDH-P2) was elevated in the intralipid compared with the control trial. PDHa activity increased during...... exercise similarly in the two trials. After 3 h of exercise, PDHa activity remained elevated in the intralipid trial but returned to resting levels in the control trial. Accordingly, in both trials PDH-P1 and PDH-P2 decreased during exercise, and the decrease was more marked during intralipid infusion....... Phosphorylation had returned to resting levels at 3 h of exercise only in the control trial. Thus, an inverse association between PDH-E1a phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1a phosphorylation, but exercise overrules this effect of FFA on PDH-E1a...

  7. Predominant alpha2/beta2/gamma3 AMPK activation during exercise in human skeletal muscle

    DEFF Research Database (Denmark)

    Birk, Jesper Bratz; Wojtaszewski, Jørgen

    2006-01-01

    -Thr-172 AMPK phosphorylation (r2 = 0.84, P important actor in exercise-regulated AMPK signalling in human skeletal muscle, probably mediating phosphorylation of ACCß.......5'AMP-activated protein kinase (AMPK) is a key regulator of cellular metabolism and is regulated in muscle during exercise. We have previously established that only three of 12 possible AMPK a/ß/¿-heterotrimers are present in human skeletal muscle. Previous studies describe discrepancies between...... total AMPK activity and regulation of its target acetyl-CoA-carboxylase (ACC)ß. Also, exercise training decreases expression of the regulatory ¿3 AMPK subunit and attenuates a2 AMPK activity during exercise. We hypothesize that these observations reflect a differential regulation of the AMPK...

  8. The radiological evaluation of a prototype posting-in hatch under conditions of high alpha activity

    International Nuclear Information System (INIS)

    Smith, D.I.; Hollick, R.C.

    1987-07-01

    A prototype posting-in hatch, mounted vertically in the top panel of a highly active glovebox has been radiologically evaluated in the Fuels Laboratory, AEEW. This simple, air-lock type system of 100 mm diameter has pneumatically operated and interlocked lids and a low velocity, inward purge, supplied by the glovebox depression. The hatch proved extremely reliable and very easy to operate. More than 1200 simulated posting movements were carried out and a > 8 order of magnitude reduction in aerosol concentration was recorded from the active glovebox to the monitoring environment. (author)

  9. [Voluntary alpha-power increasing training impact on the heart rate variability].

    Science.gov (United States)

    Bazanova, O M; Balioz, N V; Muravleva, K B; Skoraia, M V

    2013-01-01

    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

  10. Melatonin suppresses activation of hepatic stellate cells through ROR alpha-mediated inhibition of 5-lipoxygenase

    NARCIS (Netherlands)

    Shajari, Shiva; Laliena, Almudena; Heegsma, Janette; Jesus Tunon, Maria; Moshage, Han; Faber, Klaas Nico

    2015-01-01

    Liver fibrosis is scar tissue resulting from an uncontrolled wound-healing process in response to chronic liver injury. Liver damage generates an inflammatory reaction that activates hepatic stellate cells (HSC) that transdifferentiate from quiescent cells that control retinol metabolism to

  11. Decreased TNF-alpha and NK activity in obsessive-compulsive disorder

    NARCIS (Netherlands)

    Denys, Damiaan; Fluitman, Sjoerd; Kavelaars, Annemieke; Heijnen, Cobi; Westenberg, Herman

    2004-01-01

    BACKGROUND: Accumulating evidence points towards the involvement of autoimmune mechanisms in the pathophysiology of some subgroups of obsessive-compulsive disorder (OCD). This study was carried out to investigate whether obsessive-compulsive disorder is associated with altered activity of the immune

  12. Effects of sleep deprivation on event-related fields and alpha activity during rhythmic force production

    NARCIS (Netherlands)

    Boonstra, T.W.; Daffertshofer, A.; Beek, P.J.

    2005-01-01

    The influence of sleep deprivation (SD) on event-related fields and the distribution of power over the scalp of MEG imaged brain activity was studied during acoustically paced rhythmic force production. At the behavioral level, SD resulted in a reduction of the lag (negative asynchrony) between

  13. Solvated States of Poly-L-alanine alpha-Helix Explored by Raman Optical Activity

    Czech Academy of Sciences Publication Activity Database

    Yamamoto, S.; Furukawa, T.; Bouř, Petr; Ozaki, Y.

    2014-01-01

    Roč. 118, č. 20 (2014), s. 3655-3662 ISSN 1089-5639 R&D Projects: GA ČR GAP208/11/0105 Grant - others:AV ČR(CZ) M200550902 Institutional support: RVO:61388963 Keywords : molecular property tensors * nuclear magnetic resonance * activity spectra Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.693, year: 2014

  14. Effects of ultrasonication variables on the activity and properties of alpha amylase preparation.

    Science.gov (United States)

    Tran, Thi Thu Tra; Nguyen, Khanh Tien; Le, Van Viet Man

    2018-01-18

    Recently, ultrasound was demonstrated to increase enzyme activity in food industry. In most studies, an enzyme-substrate mixture was ultrasonicated. Very little is reported on the ultrasonication of enzyme preparation; the effects of ultrasonication variables on the enzyme activity and properties remained unclear. In this study, an α-amylase preparation was ultrasonicated under different conditions. At the ultrasonic frequency, power, temperature, and time of 20 kHz, 25 W/mL, 30°C, and 75 s, respectively, the secondary structure of the α-amylase was changed and that improved the catalytic activity by 47% over the control. The optimal temperature and pH of the α-amylase preparation did not change under the ultrasonic treatment. In addition, ultrasonic treatment increased kinetic parameters of the α-amylase including maximal velocity V max , Michaelis constant K m , turnover number K cat , and catalytic specificity constant K cat /K m . Nevertheless, the ultrasonicated α-amylase had lower thermal inactivation rate constant and half-life value than the nonultrasonicated enzyme. Ultrasonic treatment can be considered as a novel solution for improvement in enzyme activity. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

  15. Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells

    Science.gov (United States)

    Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in “BPA-free” products. We have compared estrogeni...

  16. The role and regulation of the peroxisome proliferator activated receptor alpha in human liver.

    Science.gov (United States)

    Kersten, Sander; Stienstra, Rinke

    2017-05-01

    The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is abundantly expressed in liver. PPARα is activated by fatty acids and various other lipid species, as well as by a class of chemicals referred to as peroxisome proliferators. Studies in mice have shown that PPARα serves as the master regulator of hepatic lipid metabolism during fasting. In addition, PPARα suppresses inflammation and the acute phase response. Comparatively little is known about PPARα in human liver. Here, an overview is provided of the role and regulation of PPARα in human liver. The main outcomes are: 1) the level of PPARA mRNA expression in human and mouse liver is similar. 2) Expression of PPARA in human liver is reduced in patients with non-alcoholic steatohepatitis or infected with the hepatitis C virus. 3) PPARα in human liver is able to effectively induce the expression of numerous genes involved in numerous lipid metabolic pathways, including microsomal, peroxisomal and mitochondrial fatty acid oxidation, fatty acid binding and activation, fatty acid elongation and desaturation, synthesis and breakdown of triglycerides and lipid droplets, lipoprotein metabolism, gluconeogenesis, bile acid metabolism, and various other metabolic pathways and genes. 4) PPARα activation in human liver causes the down-regulation of a large number of genes involved in various immunity-related pathways. 5) Peroxisome proliferators do not promote tumour formation in human liver as opposed to mouse liver because of structural and functional differences between human and mouse PPARα. 6) In addition to helping to correct dyslipidemia, PPARα agonists may hold promise as a therapy for patients with cholestatic liver diseases, non-alcoholic fatty liver disease, and/or type 2 diabetes. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  17. Effect of estradiol on estrogen receptor-alpha gene expression and activity can be modulated by the ErbB2/PI 3-K/Akt pathway.

    Science.gov (United States)

    Stoica, Gerald E; Franke, Thomas F; Moroni, Maria; Mueller, Susette; Morgan, Elisha; Iann, Mary C; Winder, Abigail D; Reiter, Ronald; Wellstein, Anton; Martin, Mary Beth; Stoica, Adriana

    2003-09-11

    Epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and heregulin-beta1 (HRG-beta1), can modulate the expression and activity of the estrogen receptor-alpha (ER-alpha) via the phosphatidylinositol 3-kinase (PI 3-K)/Akt pathway in the ER-alpha-positive breast cancer cell line, MCF-7. Estradiol can also rapidly activate PI 3-K/Akt in these cells (nongenomic effect). The recent study examines whether Akt is involved in the ER-alpha regulation by estradiol (genomic effect). Stable transfection of parental MCF-7 cells with a dominant-negative Akt mutant, as well as the PI 3-K inhibitors wortmannin and LY 294,002, blocked the effect of estradiol on ER-alpha expression and activity by 70-80 and 55-63%, respectively. Stable transfection of MCF-7 cells with a constitutively active Akt mimicked the effect of estradiol. The changes in ER-alpha expression and activity were abrogated in response to estradiol by an arginine to cysteine mutation in the pleckstrin homology (PH) domain of Akt (R25C), suggesting the involvement of this amino acid in the interaction between Akt and ER-alpha. Experiments employing selective ErbB inhibitors demonstrate that the effect of estradiol on ER-alpha expression and activity is mediated by ErbB2 and not by EGFR. Moreover, anchorage-dependent and -independent growth assays, cell cycle and membrane ruffling analyses showed that Akt exerts estrogen-like activity on cell growth and membrane ruffling and that a selective ErbB2 inhibitor, but not anti-ErbB2 antibodies directed to the extracellular domain, can block these effects. In the presence of constitutively active Akt, tamoxifen only partially inhibits cell growth. In contrast, in cells stably transfected with either a dominant-negative Akt or with R25C-Akt, as well as in parental cells in the presence of a selective ErbB2 inhibitor, the effect of estradiol on anchorage-dependent and -independent cell growth was inhibited by 50-75 and 100%, respectively. Dominant-negative Akt

  18. Patterns of physical activity and obesity indices among white-collar men in Taiwan.

    Science.gov (United States)

    Liou, Yiing Mei

    2007-06-01

    The purposes of this study were to identify patterns of physical activity among white-collar men in Taiwan and to analyze the relationships between physical activity patterns and obesity indices. This cross-sectional survey included 350 subjects (between 21 and 75 years old). The Monitoring Trends and Determinants of Cardiovascular Disease Optional Study of Physical Activity Questionnaire (MOSPA-Q), developed and published by the World Health Organization (WHO) was used to measure subjects' daily energy expenditures attributed to physical activity. Obesity indices included body weight, body mass index (BMI), waist/hip ratio (WHR), body fat percentage, total cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Three patterns of physical activity, namely work-oriented, active, and light-active lifestyles, were identified through cluster analysis. The work-oriented group reported spending the most amount of time on work-related activities (10.5 hours/week). The active group spent the most time (1 hour/day) of the three groups on leisure activities. The light-active group spent the most time (7 hours/day) of the three groups on light activities. Referencing the 150 minutes/week of moderate- intensity physical activity recommended by the US Centers for Disease Control and prevention (CDC) for health gain as a cut-off point, 1.1%, 15.2%, and 29.1% of subjects in the active, light-active and work-oriented groups, respectively, failed to achieve this minimal level. Those in the work-oriented group categorized in high work-overload and prevalent inactivity situations returned the worst obesity indices (Body weight, BMI, WHR, and body fat percentages) adjusted by age.

  19. EEG and dementia indicators in AIDS patients' Rorschach test

    Directory of Open Access Journals (Sweden)

    G. Fernandes do Prado

    1994-09-01

    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.

  20. 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

  1. Triclocarban Mediates Induction of Xenobiotic Metabolism through Activation of the Constitutive Androstane Receptor and the Estrogen Receptor Alpha

    Science.gov (United States)

    Yueh, Mei-Fei; Li, Tao; Evans, Ronald M.; Hammock, Bruce; Tukey, Robert H.

    2012-01-01

    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 potential human

  2. Measurement of the absolute activity of alpha or beta emitters by measuring product nuclei (daughter) activity increase or by studing its radioactive decay

    International Nuclear Information System (INIS)

    Campos, L.C. de.

    1981-01-01

    A new method for determining absolute activity of alpha or beta emitters by measuring daughter product radioactive decay is presented. The separation method of UX from hexahydrated uranyl nitrate UO 2 (NO 3 ) 2 6H 2 O based on its dissolution in ethyl ether is described and the accuracy of this method is shown. The factors which accuate on total efficiency of a Geiger Mueller detector for beta particles are determined. The possibility to determine the mass of precursor element by daughter nuclei activity is shown. The results are compared with the one obtained by direct measurement of the mass (or number of atoms) of precursor radioactive substance and with theoretical values calculated for isotopes in secular equilibrium. (Author) [pt

  3. Effect of diclofenac alone or in combination with alpha-tocopherol on the oxidative activity of polymorphonuclear leukocytes in healthy and osteoartheritic individuals

    International Nuclear Information System (INIS)

    Al-Arfaj, Abdurahman S.; Alballa, Sulaiman R.; Mustafa, Ali A.; Al-Tuwajiri, Ali S.; Al-Humayyad, M.S.; Al-Dalaan, Abdullah N.

    2004-01-01

    To ivestigate the effects of diclofenac alone or when combined with alpha-tocopherol on the oxidative activity of polymorphonuclear leukocytes (PMNs) in healthy and osteoartheritic (OA) patients. The study was carried out at the College of Medicine, King Saud University, Riyadh, KIgdom of Saudi Arabia, over the period 1999 to 2000. 12 healthy controls and 12 osteoartheritic patients were recruited to the study. They were given diclofenac 50mg thricedaily orally, initially for 5 days then alpha-tocopherol at 200mg thrice daily orally, was added for another 5 days. Blood samples were drawn before the start of study and at 5 days following treatmentwith diclofenac alone and 10 days following treatment with diclophenac and alpha-tocopherol. Chemiluminescence (CL)reponse was measured for wohle blood and isolated (PMNs) on all samples. Diclofenac enhanced CL response of whole blood and PMNs of healthy controls when stimulated with phorbol myristate acetate (PMA) and opsonized zymosan (OPZ). Cotreatment with alpha-tocopherol resulted in no appreciable change in the CL response of whole blood when stimulated with PMA or OPZ but a further significant enhancement of CL response of isolated PMNs when these cells were stimulated by either PMA or OPZ. In osteoartheritic patients, diclofenac alone and when combined with alpha-tocopherol showed no significant change in CL response of the whole blood.The CL response of PMNs from OA patients was decreased by diclofenac alone. However the inhibitory effect was not observed when alpha-tocopherol was used together with diclofenac. The effect of diclofenac alone or in combination with alpha-tocopherol did not produce a consistent effect on the CL response of whole blood or isolated PMNs of healthy or osteoartheritic patients. (author)

  4. THE EFFECT OF SOME ALPHA-ADRENOCEPTOR ANTAGONISTS ON SPONTANEOUS MYOGENIC ACTIVITY IN THE RAT PORTAL-VEIN AND THE PUTATIVE INVOLVEMENT OF ATP-SENSITIVE K+ CHANNELS

    NARCIS (Netherlands)

    SCHWIETERT, R; WILHELM, D; WILFFERT, B; VANZWIETEN, PA

    1992-01-01

    In the present study we showed that the alpha-adrenoceptor antagonists phentolamine, yohimbine, prazosin, corynanthine and idazoxan, when cumulatively applied in high concentrations (1-100-mu-mol/l), can increase spontaneous myogenic activity in the rat portal vein. 5-Methyl-urapidil and rauwolscine

  5. Thorium: one of the analytical techniques in neutronic activation and alpha spectrometry of the CDTN (Brazilian Nuclear Technology Development Center) in the last three decades

    International Nuclear Information System (INIS)

    Menezes, M.A.B.C.; Sabino, C.V.S.

    1994-01-01

    For long years, the CDTN (Brazilian Nuclear Technology Development Center ) has applied several analytical techniques in the thorium determination. This work is about the evolution of the neutronic activation in the thorium 232 analysis from the 1960's to now. The importance of the analysis request and alpha spectrometry for the thorium 228 and thorium 232 determination is emphasized. (J.A.M.M.)

  6. Inhibitory Effect of Capparis spinosa Extract on Pancreatic Alpha-Amylase Activity

    Directory of Open Access Journals (Sweden)

    Mostafa Selfayan

    2016-04-01

    Full Text Available Background Diabetes mellitus is a metabolic disorder characterized by high blood glucose level caused due to deficiency of insulin secretion or insulin function. The inhibition of carbohydrate hydrolyzing enzymes such as α-amylase can be an important strategy for decrease postprandial blood glucose level in patients with type II diabetes. Plants contains different chemical constituents with potential for inhibition of α-amylase and hence maybe used as therapeutic. Objectives The aim of the present study is to investigate the effect of the ethanolic extract of Capparis spinosa on pancreatic α-amylase activities to find out the relevance of the plant in controlling blood sugar. Materials and Methods In this experimental study, root and leaves of C. spinosa were tested for α-amylase inhibition. Different concentrations (1.56, 3.12, 6.25, 12.5 and 25 mg/mL of extracts were incubated with enzyme substrate solution and the spectrometric method used for measure enzyme activity. Also acarbose was used as the standard inhibitor. Results Both root and leaves extracts showed inhibition of α-amylase (root = 97.31% and leaves = 98.92%. The root and leaves extracts of C. spinosa exhibited appreciable α-amylase inhibitory activity with an IC50 values 5.93 mg/mL and 3.89 mg/mL respectively, when compared with acarbose (IC50 value 0.038 mg/mL. Conclusions This study supports that root and leaves extracts of C. spinosa exhibit considerable α-amylase inhibitory activities. These results could be useful for developing functional foods by combination of plant-based foods for treatment of diabetes mellitus.

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

    Directory of Open Access Journals (Sweden)

    Zhuk Mykola O.

    2014-01-01

    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.

  8. The use of starch azure for measurement of alpha-amylase activity.

    Science.gov (United States)

    Lehoczki, Gábor; Kandra, Lili; Gyémánt, Gyöngyi

    2018-03-01

    Despite being widely used, there is no standard protocol for α-amylase activity measurement with starch azure substrate. Boiling pre-treatment of starch azure suspension increased the reaction rate of hydrolysis catalysed by human salivary α-amylase (HSA) or porcine pancreatic α-amylase (PPA) and the sensitivity of spectrophotometric activity measurement has been improved. Kinetic constants, K M , and v max , obtained from parallel isothermal titration calorimetric (ITC) measurements on natural and starch azure revealed, that the blue starch derivative does not differ significantly from its natural counterpart from kinetic point of view. Interestingly, substrate inhibition was observed in starch azure hydrolysis characterised by dissociation constants 49 mg/mL and 16.4 mg/mL for HSA and PPA, respectively. In this work a new protocol has been suggested for α-amylase activity measurement using boiled insoluble starch azure as substrate at 5 mg/mL concentration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Amino acid-dependent activation of liver estrogen receptor alpha integrates metabolic and reproductive functions via IGF-1.

    Science.gov (United States)

    Della Torre, Sara; Rando, Gianpaolo; Meda, Clara; Stell, Alessia; Chambon, Pierre; Krust, Andrée; Ibarra, Cristian; Magni, Paolo; Ciana, Paolo; Maggi, Adriana

    2011-02-02

    Throughout evolution, organisms have devised strategies to limit fertility in case of prolonged starvation. In mammals, the liver plays a central role in the orchestration of mechanisms allowing for the maintenance of energy homeostasis. We here demonstrate that dietary amino acids regulate the transcriptional activity of hepatic estrogen receptor alpha (ERα) through an mTOR-dependent mechanism. As a result of ERα activation, hepatic IGF-1 mRNA and blood IGF-1 are increased. Conversely, calorie restriction or selective ablation of ERα in the liver decrease blood IGF-1 to levels inadequate for the correct proliferation of the lumen epithelium in the uterus and the progression of the estrous cycle. We propose that the liver acts as critical mediator of energetic and reproductive functions responsible for the blockade of the estrous cycle in case of protein scarcity. Our findings may provide novel insights to understand the cause of selected forms of infertility and metabolic alterations in women after menopause. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Effect of 17alpha-ethinylestradiol on activity of rat liver enzymes for synthesis and hydrolysis of cholesterol esters

    International Nuclear Information System (INIS)

    Nikitin, Yu.P.; Dushkin, M.I.; Dolgov, A.V.; Gordienko, I.A.

    1987-01-01

    Administration of estrogens is known to lower the concentration of cholesterol esters in the blood vessel wall and may delay the development of arteriosclerosis. It is also known that under the influence of estrogens the redistribution of concentrations of free cholesterol and cholesterol esters takes place in rats between the blood and liver as a result of the intensification of receptor-dependent uptake of low-density lipoproteins by the hepatocytes. The mechanisms of this intracellular redistribution, however, have been inadequately studied. The purpose of this paper is to study the effects of 17alpha-ethinylestradiol on the activity of lysosomal and cytoplasmic cholesterol esterases, acyl-CoA-cholesterol-O-acyltransferase, lysosomal acid phosphatase, and beta-D-galactosidase. The activity was measured by using cholesterol [1-C 14]-oleate as the substrate. The influence of the estradiol is found to be based on cholesterol redistribution between the blood and liver. Accumulation of free cholesterol in the liver under these conditions stimulates bile acid formation. Depression of cholesterol ester synthesis as a result of direct inhibition of the acyltransferase by the estradiol is found to possibly contribute to the fall in the cholesterol level in the body. Liquid scintillation counting was used to measure distribution and accumulation

  11. Elevated second-trimester maternal serum β-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome.

    Science.gov (United States)

    Alvarez-Nava, Francisco; Soto, Marisol; Lanes, Roberto; Pons, Hector; Morales-Machin, Alisandra; Bracho, Ana

    2015-12-01

    The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median ≥3.5 for β-subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free β-subunit (fβ)-hCG were not different to those of the control group, AFP, unconjugated estriol and β-hCG concentrations were significantly different in the study group (P < 0.05), when compared to those of unaffected pregnancies. Levels of β-hCG in pregnancies with hydrops fetalis were significantly higher than in those with cystic hygroma (P <0.0001), as were AF-AFP concentrations (P <0.0015). In addition, abnormalities in both maternal serum β-hCG and AF-AFP predicted fetal death. The relative risk of adverse obstetric outcome was 10.667 (P = 0.0004; 95% confidence interval [CI]: 1.554-73.203) for β-hCG and 2.19 (P = 0.0256; 95% CI: 1.001 to 4.779), for AF-AFP. Maternal serum β-hCG and AF-AFP levels may preferentially identify those Turner syndrome pregnancies with the highest risk of fetal death. © 2015 Japan Society of Obstetrics and Gynecology.

  12. Fibrates suppress bile acid synthesis via peroxisome proliferator-activated receptor-alpha-mediated downregulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase expression

    NARCIS (Netherlands)

    Post, SM; Duez, H; Gervois, PP; Staels, B; Kuipers, F; Princen, HMG

    2001-01-01

    Fibrates are hypolipidemic drugs that affect the expression of genes involved in lipid metabolism by activating peroxisome proliferator-activated receptors (PPARs). Fibrate treatment causes adverse changes in biliary lipid composition and decreases bile acid excretion, leading to an increased

  13. Activity Level in the Lab: Overlap with Shyness Indicates It is More than Pure Motoric Activity

    Science.gov (United States)

    Frazier-Wood, Alexis C.; Saudino, Kimberly J.

    2017-01-01

    The observation that children's activity level (AL) differs between novel and familiar situations is well established. What influences individual differences in how AL is different across these situations is less well understood. Drawing on animal literature, which links rats' AL when 1st placed in a novel setting with novelty seeking phenotypes,…

  14. Proposed development programme for a temporary containment system for alpha active decommissioning

    International Nuclear Information System (INIS)

    Pengelly, M.G.A.; Burnett, R.C.

    1983-06-01

    This report makes a proposal to design, develop and test a containment of modular construction under plutonium active conditions. While this proposal contemplates work with plutonium, the system, when fully developed, has obvious applications wherever a temporary containment of radioactive or toxic materials is required. The fundamental feature of the proposal is that strippable coatings are used to prevent the inner surfaces of the working area from becoming contaminated. It is envisaged that this method of protecting the surfaces will enable the modular containment structure to be disassembled and re-used. (author)

  15. Monoclonal antibody fragment from combinatorial phage display library neutralizes alpha-latrotoxin activity and abolishes black widow spider venom lethality, in mice.

    Science.gov (United States)

    Bugli, Francesca; Graffeo, Rosalia; Paroni Sterbini, Francesco; Torelli, Riccardo; Masucci, Luca; Sali, Michela; Grasso, Alfonso; Rufini, Stefano; Ricci, Enzo; Fadda, Giovanni; Pescatori, Mario

    2008-03-15

    Alpha-latrotoxin (alpha-ltx), a component of the venom of black widow spiders (BWSV), binds to higher vertebrates presynaptic nerve terminals, stimulating massive neurotransmitter release. This neurotoxic protein is responsible for most of the symptoms elicited in men by the bite of black widow spider (BWS), i.e. a neurological syndrome named latrodectism. By reasoning that targeting this single component would abrogate most of the effect of BWS envenomation, we took advantage of the antibody phage display technology to generate monoclonal Fab fragments able to bind and neutralize the alpha-ltx. To this aim, we immunized Balb/c mice with purified toxin and cloned their antibody repertoire in the pCombIII phage display vector. By combining a high-stringency affinity selection with a sensitive 45Ca(2+) uptake assay, we isolated a Fab fragment (FM1) able to bind the alpha-ltx in the low nM range and neutralize its ionophore activity, in vitro and in vivo. After the onset of overt symptomatology, administration of FM1 to experimentally envenomed mice induced remission of symptoms and prevented lethality. Since alpha-ltx is the only molecule responsible for the great toxicity of BWS bites in mammals, the FM1 Fab, highly effective in neutralizing the toxin in vivo, represents a promising immunotherapy reagent for treating latrodectic patients.

  16. Designed low amphipathic peptides with alpha-helical propensity exhibiting antimicrobial activity via a lipid domain formation mechanism.

    Science.gov (United States)

    Yamamoto, Naoki; Tamura, Atsuo

    2010-05-01

    Although several low amphipathic peptides have been known to exhibit antimicrobial activity, their mode of action has not been completely elucidated. In this study, using designed low amphipathic peptides that retain different alpha-helical content and hydrophobicity, we attempted to investigate the mechanism of these properties. Calorimetric and thermodynamic analyses demonstrated that the peptides induce formation of two lipid domains in an anionic liposome at a high peptide-to-lipid ratio. On the other hand, even at a low peptide-to-lipid ratio, they caused minimal membrane damage, such as flip-flop of membrane lipids or leakage of calcein molecules from liposomes, and never translocated across membranes. Interaction energies between the peptides and anionic liposomes showed good correlation with antimicrobial activity for both Escherichia coli and Bacillus subtilis. We thus propose that the domain formation mechanism in which antimicrobial peptides exhibit activity solely by forming lipid domains without membrane damage is a major determinant of the antimicrobial activity of low amphipathic peptides. These peptides appear to stiffen the membrane such that it is deprived of the fluidity necessary for biological functions. We also showed that to construct the lipid domains, peptides need not form stable and cooperative structures. Rather, it is essential for peptides to only interact tightly with the membrane interface via strong electrostatic interactions, and slight differences in binding strength are invoked by differences in hydrophobicity. The peptides thus designed might pave the way for "clean" antimicrobial reagents that never cause release of membrane elements and efflux of their inner components. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  17. 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.

    1995-12-31

    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.

  18. Working life and physical activity in ankylosing spondylitis pre and post anti-tumor necrosis factor-alpha therapy.

    Science.gov (United States)

    Prince, David S; McGuigan, Louis E; McGirr, Ellen E

    2014-02-01

    To assess effects of ankylosing spondylitis (AS) on working life and physical activity in Australia; to quantify changes in working life and physical activity that occur after anti-tumor necrosis factor-alpha (TNF-α) treatment; and to assess efficacy of anti-TNF-α therapy for AS in an Australian context. This is a multi-centre observational study of people with AS on anti-TNF-α therapy. All participants satisfied the New York Modified Criteria and had active and refractory disease at anti-TNF-α therapy commencement. Participation involved a standardized interview, a metrology assessment, assessment of disease remission and medical record review. Interviews and patients' records were used to compare working life (employment, sick leave and productivity) and physical activity (participation rate, hours/week, and physical intensity) between the pre-AS, post-AS and post-anti-TNF-α therapy periods. Fifty-two patients took part. Participants were on average 44.8 years old, predominately male (86.5%) and had been on anti-TNF-α therapy for 29 months; 39% were in partial remission and 75% had 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Responders to anti-TNF-α therapy were 10.5 years younger than non-responders (P = 0.004). Post-anti-TNF-α therapy participants gained 6.6 h/week of work (P = 0.02), and productivity improved 31% (P treatment. Physical activity participation increased from 71% to 85% (P = 0.039) and activity intensity increased by 33% (P = 0.002) post-treatment. Participants gained 1.8 h/week of sport (P = 0.001) and 2.2 h/week of recreational physical activity (P Treatment with anti-TNF-α therapy results in significant improvement in these parameters. © 2012 The Authors International Journal of Rheumatic Diseases © 2012 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  19. Alpha-synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation

    DEFF Research Database (Denmark)

    Betzer, Cristine; Lassen, Louise Berkhoudt; Olsen, Anders

    2018-01-01

    cytosolic Ca2+levels followed by a later Ca2+increase. Aggregated but not monomeric α-synuclein binds to and activates SERCAin vitro, and proximity ligation assays confirm this interaction in cells. The SERCA inhibitor cyclopiazonic acid (CPA) normalises both the initial reduction and the later increase......Aggregation of α-synuclein is a hallmark of Parkinson's disease and dementia with Lewy bodies. We here investigate the relationship between cytosolic Ca2+and α-synuclein aggregation. Analyses of cell lines and primary culture models of α-synuclein cytopathology reveal an early phase with reduced...... in cytosolic Ca2+CPA protects the cells against α-synuclein-aggregate stress and improves viability in cell models and inCaenorhabditis elegans in vivoProximity ligation assays also reveal an increased interaction between α-synuclein aggregates and SERCA in human brains affected by dementia with Lewy bodies...

  20. Electrochemistry of cyclic alpha-imino carboxylates and their metal complexes: correlation with physiological activity.

    Science.gov (United States)

    Kovacic, P; Popp, W J; Timberlake, J W; Ryan, M D

    1989-01-01

    Cyclic voltammetry data were obtained for delta 1-pyrroline-2-carboxylate, delta 3-thiazoline-4-carboxylate, delta 2-thiazoline-2-carboxylate and their complexes with Cu(II), Fe(III), and Fe(II). The free ligands were reduced at about -0.35 V and were oxidized in the range of 0.42-0.52 V. Complexing the imine carboxylates with metal ions produces reduction and oxidation in the ranges of 0.05-0.37 V and 0.52-0.74 V, respectively. Prior reports show that these ligands take part in various biological functions. We propose that electron transfer may be involved in some aspects of the physiological activity. The captodative effect can be applied.

  1. 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

    2015-01-01

    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....

  2. 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: bart.staels@pasteur-lille.fr [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)

    2009-08-28

    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.

  3. Assessment of heavy metals and alpha activity in Indian phosphate fertilizer: possible environmental implications

    International Nuclear Information System (INIS)

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

    2007-01-01

    The study of radioactivity and heavy metals in phosphate fertilizers are very important from environmental point of view. Inorganic phosphate fertilizers may contain radionuclides, heavy metals and fluorine. The present work is the continuation of our study on radioactivity of phosphate fertilizers. Here we have determined the concentrations of heavy metals (Cu, Cr, Zn, Pb, and Mn) in phosphate fertilizers by atomic absorption spectrometer (AAS) in order to estimate the effect of the use of phosphate fertilizers on human health. Also we have measured the concentrations of heavy metals in nonphosphate fertilizers and compared with the phosphate fertilizers. An attempt has been made to establish the correlation between radioactivity and heavy metals in phosphate fertilizers. The sampling sites were randomly selected in the cultivated area in Midnapore district, West Bengal, where phosphate fertilizers are widely used for large agricultural production of mainly potato. Measured data indicates that the concentration of Pb is higher than that of other heavy metals present in phosphate and nonphosphate fertilizer samples. These data might help us to calculate the environmental toxicity of heavy metals on human health due to the direct application of phosphate fertilizers. (author)

  4. Histologic scoring indices for evaluation of disease activity in ulcerative colitis.

    Science.gov (United States)

    Mosli, Mahmoud H; Parker, Claire E; Nelson, Sigrid A; Baker, Kenneth A; MacDonald, John K; Zou, G Y; Feagan, Brian G; Khanna, Reena; Levesque, Barrett G; Jairath, Vipul

    2017-05-25

    Disease activity can be determined using clinical, endoscopic or histologic criteria in patients with ulcerative colitis (UC). Persistent disease activity is associated with poor outcomes. Histologic disease activity has been shown to be associated with relapse, colectomy and colorectal cancer. The ability to objectively evaluate microscopic disease activity using histology is important for both clinical practice and clinical trials. However, the operating properties of the currently available histologic indices remain unclear. A systematic review was undertaken to identify and evaluate the development and operating characteristics of histologic disease activity indices used to assess disease activity in people with ulcerative colitis. We searched MEDLINE, EMBASE, PubMed, CENTRAL and the Cochrane IBD Review Group Specialized Trials Register from inception to 2 December 2016 for applicable studies. There were no language or document type restrictions. Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated a histologic index in patients with UC were considered for inclusion. Eligible patients were adults (> 18 years), diagnosed with UC using conventional clinical, radiographic, endoscopic and histologic criteria. Two authors (MHM and CEP) independently reviewed the titles and abstracts of the studies identified from the literature search. A standardized form was used to assess eligibility of trials for inclusion and for data extraction.Two authors (MHM and CEP) independently extracted and recorded data, which included the number of patients enrolled, number of patients per treatment arm, patient characteristics including age and gender distribution, and the name of the histologic index. Outcomes (i.e. intra-rater reliability, inter-rater reliability, internal consistency, content validity, criterion validity, construct validity, responsiveness, and feasibility) were recorded for each trial. In total, 126 reports describing 30

  5. Increased expression of fibroblast activation protein-alpha in keloid fibroblasts: implications for development of a novel treatment option.

    Science.gov (United States)

    Dienus, Kirstin; Bayat, Ardeshir; Gilmore, Brendan F; Seifert, Oliver

    2010-12-01

    Keloid scars are common benign fibroproliferative reticular dermal lesions with unknown etiology and ill-defined management with high rate of recurrence post surgery. The progression of keloids is characterized by increased deposition of extracellular matrix proteins, invasion into the surrounding healthy skin and inflammation. Fibroblasts are considered to be the key cellular mediators of fibrogenesis in keloid scars. Fibroblast activation protein alpha (FAP-α) and dipeptidyl peptidase IV (DPPIV) are proteases located at the plasma membrane promoting cell invasiveness and tumor growth and have been previously associated with keloid scars. Therefore, in this study we analyzed in further detail the expression of FAP-α in keloid fibroblasts compared to control skin fibroblasts. Dermal fibroblasts were obtained from punch-biopsies from the active margin of four keloids and four control skin samples. Flow cytometry was used to analyze FAP-α expression and the CytoSelect 24-Well Collagen I Cell Invasion Assay was applied to study fibroblast invasion. Secretion of extracellular matrix (ECM) proteins was investigated by multiplexed particle-based flow cytometric assay and enzyme-linked immunosorbent assay. We found an increased expression of FAP-α in keloid fibroblasts compared to control skin fibroblasts (p fibroblasts (p fibroblast growth factor or vascular endothelial growth factor, (c) on the expression of the proinflammatory cytokines interleukin-6 (IL-6), interleukin 8 (IL-8) or monocyte chemotactic protein-1. These results suggest a potential role for FAP-α and DPPIV in the invasive behavior of keloids. FAP-α and DPPIV may increase the invasive capacity of keloid fibroblasts rather than by modulating inflammation or ECM production. Since FAP-α expression is restricted to reactive fibroblasts in wound healing and normal adult tissues are generally FAP-α negative, inhibiting FAP-α/DPPIV activity may be a novel treatment option to prevent keloid progression.

  6. Obesity reversibly depletes the basal cell population and enhances mammary epithelial cell estrogen receptor alpha expression and progenitor activity.

    Science.gov (United States)

    Chamberlin, Tamara; D'Amato, Joseph V; Arendt, Lisa M

    2017-11-29

    Obesity is correlated with an increased risk for developing postmenopausal breast cancer. Since obesity rates continue to rise worldwide, it is important to understand how the obese microenvironment influences normal mammary tissue to increase breast cancer risk. We hypothesized that obesity increases the proportion of luminal progenitor cells, which are thought to be the cells of origin for the most common types of breast cancer, potentially leading to an increased risk for breast cancer. To study the obese microenvironment within the mammary gland, we used a high-fat diet mouse model of obesity and human breast tissue from reduction mammoplasty surgery. We identified changes in breast epithelial cell populations using flow cytometry for cell surface markers, in vitro functional assays and expression of markers on breast tissue sections. In both obese female mice and women, mammary epithelial cell populations demonstrated significant decreases in basal/myoepithelial cells, using either flow cytometry or cell-type-specific markers (SMA and p63). Estrogen receptor alpha (ERα) expression was significantly increased in luminal cells in obese mammary tissue, compared with control mice or breast tissue from lean women. Functional assays demonstrated significantly enhanced mammary epithelial progenitor activity in obese mammary epithelial cells and elevated numbers of ERα-positive epithelial cells that were co-labeled with markers of proliferation. Weight loss in a group of obese mice reversed increases in progenitor activity and ERα expression observed in obese mammary tissue. Obesity enhances ERα-positive epithelial cells, reduces the number of basal/myoepithelial cells, and increases stem/progenitor activity within normal mammary tissue in both women and female mice. These changes in epithelial cell populations induced by obesity are reversible with weight loss. Our findings support further studies to examine how obesity-induced changes in stem/progenitor cells

  7. Metabolomics: An Essential Tool to Understand the Function of Peroxisome Proliferator–Activated Receptor Alpha

    Science.gov (United States)

    Montanez, Jessica E.; Peters, Jeffrey M.; Correll, Jared B.; Gonzalez, Frank J.; Patterson, Andrew D.

    2013-01-01

    The peroxisome proliferator–activated receptor (PPAR) family of nuclear hormone transcription factors (PPARα, PPARβ/δ, and PPARγ) is regulated by a wide array of ligands including natural and synthetic chemicals. PPARs have important roles in control of energy metabolism and are known to influence inflammation, differentiation, carcinogenesis, and chemical toxicity. As such, PPARs have been targeted as therapy for common disorders such as cancer, metabolic syndrome, obesity, and diabetes. The recent application of metabolomics, or the global, unbiased measurement of small molecules found in biofluids, or extracts from cells, tissues, or organisms, has advanced our understanding of the varied and important roles that the PPARs have in normal physiology as well as in pathophysiological processes. Continued development and refinement of analytical platforms, and the application of new bioinformatics strategies, have accelerated the widespread use of metabolomics and have allowed further integration of small molecules into systems biology. Recent studies using metabolomics to understand PPARα function, as well as to identify PPARα biomarkers associated with drug efficacy/toxicity and drug-induced liver injury, will be discussed. PMID:23197196

  8. Longitudinal and Immediate Effect of Kundalini Yoga on Salivary Levels of Cortisol and Activity of Alpha-Amylase and Its Effect on Perceived Stress.

    Science.gov (United States)

    García-Sesnich, Jocelyn N; Flores, Mauricio Garrido; Ríos, Marcela Hernández; Aravena, Jorge Gamonal

    2017-01-01

    Stress is defined as an alteration of an organism's balance in response to a demand perceived from the environment. Diverse methods exist to evaluate physiological response. A noninvasive method is salivary measurement of cortisol and alpha-amylase. A growing body of evidence suggests that the regular practice of Yoga would be an effective treatment for stress. To determine the Kundalini Yoga (KY) effect, immediate and after 3 months of regular practice, on the perception of psychological stress and the salivary levels of cortisol and alpha-amylase activity. To determine the psychological perceived stress, levels of cortisol and alpha-amylase activity in saliva, and compare between the participants to KY classes performed for 3 months and a group that does not practice any type of yoga. The total sample consisted of 26 people between 18 and 45-year-old; 13 taking part in KY classes given at the Faculty of Dentistry, University of Chile and 13 controls. Salivary samples were collected, enzyme-linked immunosorbent assay was performed to quantify cortisol and kinetic reaction test was made to determine alpha-amylase activity. Perceived Stress Scale was applied at the beginning and at the end of the intervention. Statistical analysis was applied using Stata v11.1 software. Shapiro-Wilk test was used to determine data distribution. The paired analysis was fulfilled by t -test or Wilcoxon signed-rank test. T -test or Mann-Whitney's test was applied to compare longitudinal data. A statistical significance was considered when P effect on salivary cortisol. The activity of alpha-amylase did not show significant changes. A significant decrease of perceived stress in the study group was found. KY practice shows an immediate effect on salivary cortisol levels and on perceived stress after 3 months of practice.

  9. sup. alpha. N-acetyl derivatives of. beta. -endorphin-(1-31) and -(1-27) regulate the supraspinal antinociceptive activity of different opioids in mice

    Energy Technology Data Exchange (ETDEWEB)

    Garzon, J.; Sanchez-Blazquez, P. (Cajal Institute, Madrid (Spain))

    1991-01-01

    {sup {alpha}}N-acetyl human {beta}-endorphin(1-31) injected icv to mice antagonized the analgesic activity of {beta}-endorphin-(1-31) and morphine whereas the analgesia evoked by DADLE and DAGO was enhanced by this treatment. The modulatory activity of {sup {alpha}}N-acetyl {beta}-endorphin-(1-31) was exhibited at remarkable low doses (fmols) reaching a maximum that persisted even though the dose was increased 100,000 times. The regulatory effect of a single dose of the acetylated neuropeptide lasted for 24h. The activity of {sup {alpha}}N-acetyl human {beta}-endorphin(1-31) was partially retained by the shorter peptide {sup {alpha}}N-acetyl human {beta}-endorphin-(1-27) and to a lesser extent by {beta}-endorphin-(1-27), {beta}-endorphin-(1-31) lacked this regulatory activity on opioid analgesia. Acetylated {beta}-endorphin-(1-31) displayed a biphasic curve when competing with 5 pM ({sup 125}I)-Tyr{sup 27} human {beta}-endorphin-(1-31) specific binding, the first step was abolished with an apparent IC{sub 50} of 0.35 nM, and the rest with an IC{sub 50} of 200 nM. It is suggested that {sup {alpha}}N-acetyl {beta}-endorphin-(1-31) changed the efficiency of the opioid analgesics by acting upon a specific substrate that is functionally coupled to the opioid receptor, presumably the guanine nucleotide binding regulatory proteins G{sub i}/G{sub 0}.

  10. Chemical stimulation of the ST36 acupoint reduces both formalin-induced nociceptive behaviors and spinal astrocyte activation via spinal alpha-2 adrenoceptors.

    Science.gov (United States)

    Kang, Suk-Yun; Kim, Chi-Young; Roh, Dae-Hyun; Yoon, Seo-Yeon; Park, Ji-Ho; Lee, Hye-Jung; Beitz, Alvin J; Lee, Jang-Hern

    2011-11-25

    Spinal astrocytes have emerged as important mechanistic contributors to pathological and chronic pain. Recently, we have demonstrated that injection of diluted bee venom (DBV) into the Zusanli (ST36) acupoint produces a potent anti-nociceptive effect via the activation of spinal alpha-2 adrenoceptors. However, it is unclear if this anti-nociceptive effect is associated with alterations in spinal astrocytes. Thus, the present study was designed to determine: (1) whether DBV's anti-nociceptive effect in the formalin test involves suppression of spinal astrocyte activation; (2) whether DBV-induced astrocyte inhibition is mediated by spinal alpha-2 adrenoceptors; and (3) whether this glial modulation is potentiated by intrathecal administration of the glial metabolic inhibitor, fluorocitrate (FC) in combination with DBV injection. DBV was injected directly into the ST36 acupoint, and spinal expression of the astrocytic marker, glial fibrillary acidic protein (GFAP), was assessed together with effects on formalin-induced nociception. DBV treatment reduced pain responses in the late phase of the formalin test and significantly blocked the formalin-evoked increase in spinal GFAP expression. These effects of DBV were prevented by intrathecal pretreatment with selective alpha-2A and alpha-2C adrenoceptor antagonists. Moreover, low dose intrathecal injection of FC in conjunction with low dose DBV injection into the ST36 acupoint synergistically suppressed pain responses and GFAP expression. These results demonstrate that DBV stimulation of the ST36 acupoint inhibits the formalin-induced activation of spinal astrocytes and nociceptive behaviors in this inflammatory pain model and this inhibition is associated with the activation of spinal alpha-2 adrenoceptors. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Longitudinal and immediate effect of Kundalini Yoga on salivary levels of cortisol and activity of alpha-amylase and its effect on perceived stress

    Directory of Open Access Journals (Sweden)

    Jocelyn N García-Sesnich

    2017-01-01

    Full Text Available Context: Stress is defined as an alteration of an organism's balance in response to a demand perceived from the environment. Diverse methods exist to evaluate physiological response. A noninvasive method is salivary measurement of cortisol and alpha-amylase. A growing body of evidence suggests that the regular practice of Yoga would be an effective treatment for stress. Aims: To determine the Kundalini Yoga (KY effect, immediate and after 3 months of regular practice, on the perception of psychological stress and the salivary levels of cortisol and alpha-amylase activity. Settings and Design: To determine the psychological perceived stress, levels of cortisol and alpha-amylase activity in saliva, and compare between the participants to KY classes performed for 3 months and a group that does not practice any type of yoga. Subjects and Methods: The total sample consisted of 26 people between 18 and 45-year-old; 13 taking part in KY classes given at the Faculty of Dentistry, University of Chile and 13 controls. Salivary samples were collected, enzyme-linked immunosorbent assay was performed to quantify cortisol and kinetic reaction test was made to determine alpha-amylase activity. Perceived Stress Scale was applied at the beginning and at the end of the intervention. Statistical Analysis Used: Statistical analysis was applied using Stata v11.1 software. Shapiro–Wilk test was used to determine data distribution. The paired analysis was fulfilled by t-test or Wilcoxon signed-rank test. T-test or Mann–Whitney's test was applied to compare longitudinal data. A statistical significance was considered when P< 0.05. Results: KY practice had an immediate effect on salivary cortisol. The activity of alpha-amylase did not show significant changes. A significant decrease of perceived stress in the study group was found. Conclusions: KY practice shows an immediate effect on salivary cortisol levels and on perceived stress after 3 months of practice.

  12. B-Cell-Activating Factor Affects the Occurrence of Thyroid Autoimmunity in Chronic Hepatitis C Patients Treated with Interferon Alpha

    Directory of Open Access Journals (Sweden)

    Yusuke Kajiyama

    2012-01-01

    Full Text Available Chronic hepatitis C (CHC patients frequently suffer from thyroid disorders during interferon therapy. However, the mechanism remains unclear. In this study, we investigated the association between serum B-cell-activating factor belonging to the TNF family (BAFF levels and the presence of antithyroid peroxidase antibody (anti-TPO in CHC patients treated with pegylated interferon alpha and ribavirin combination therapy. Six months after the therapy, anti-TPO antibody was detected in 10 (males, 1; females, 9 of 50 patients. The mean age of these patients was higher than that of the anti-TPO-negative patients (61 yr versus 55 yr. Before treatment, the serum BAFF levels of the anti-TPO-positive patients were higher than those of the anti-TPO-negative patients. After starting therapy, the serum BAFF levels of both the anti-TPO-positive and -negative patient groups were elevated. Our findings suggest that the serum BAFF concentration before therapy can predict the risk of thyroid autoimmunity in elderly female patients with CHC.

  13. Food does not affect the pharmacokinetics of tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist.

    Science.gov (United States)

    Samuelsson, S; Johansson, S; Halldórsdóttir, S; Stenhoff, H; Ohman, K P

    2006-09-01

    Tesaglitazar is a dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist in development to treat lipid and glucose abnormalities associated with type 2 diabetes. This study evaluated the effects of food on tesaglitazar pharmacokinetics. In an open, randomized, 2-way crossover study, 20 healthy men received tesaglitazar 1 mg during fasting and after a high-fat, high-calorie breakfast. Blood samples were taken to assess pharmacokinetic variables. Systemic exposure to tesaglitazar was unaffected by food intake. Estimated ratios were 0.99 (90% confidence interval [CI], 0.94-1.04) for fed/fasted area under plasma concentration-time curve and 0.82 (90% CI, 0.78-0.86) for fed/fasted maximum plasma concentration (C(max)). Mean C(max) was approximately 18% lower (0.41 [95% CI, 0.38-0.43] versus 0.50 [95% CI, 0.47-0.53] mumol/L), and median time to C(max) was increased (2.00 vs 0.75 h) in fed versus fasted state. The median difference of t(max) was 1.25 h (P = .0001, signed-rank test). Tesaglitazar was well tolerated. Tesaglitazar pharmacokinetics is unaffected by food intake, allowing once-daily administration of tesaglitazar with or without food in clinical practice.

  14. Blood coagulation parameters and activity indices in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    A. A. Arshinov

    2005-01-01

    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.

  15. Palladium alpha-lipoic acid complex formulation enhances activities of Krebs cycle dehydrogenases and respiratory complexes I-IV in the heart of aged rats.

    Science.gov (United States)

    Sudheesh, N P; Ajith, T A; Janardhanan, K K; Krishnan, C V

    2009-08-01

    Age-related decline in the capacity to withstand stress, such as ischemia and reperfusion, results in congestive heart failure. Though the mechanisms underlying cardiac decay are not clear, age dependent somatic damages to mitochondrial DNA (mtDNA), loss of mitochondrial function, and a resultant increase in oxidative stress in heart muscle cells may be responsible for the increased risk for cardiovascular diseases. The effect of a safe nutritional supplement, POLY-MVA, containing the active ingredient palladium alpha-lipoic acid complex, was evaluated on the activities of the Krebs cycle enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, II, III, and IV in heart mitochondria of aged male albino rats of Wistar strain. Administration of 0.05 ml/kg of POLY-MVA (which is equivalent to 0.38 mg complexed alpha-lipoic acid/kg, p.o), once daily for 30 days, was significantly (pKrebs cycle dehydrogenases, and mitochondrial electron transport chain complexes. The unique electronic and redox properties of palladium alpha-lipoic acid complex appear to be a key to this physiological effectiveness. The results strongly suggest that this formulation might be effective to protect the aging associated risk of cardiovascular and neurodegenerative diseases.

  16. Endothelial-monocyte activating polypeptide II alters fibronectin based endothelial cell adhesion and matrix assembly via alpha5 beta1 integrin

    International Nuclear Information System (INIS)

    Schwarz, Margaret A.; Zheng, Hiahua; Liu, Jie; Corbett, Siobhan; Schwarz, Roderich E.

    2005-01-01

    Mature Endothelial-Monocyte Activating Polypeptide (mEMAP) II functions as a potent antiangiogenic peptide. Although the anti-tumor effect of mEMAP II has been described, little is known regarding its mechanism of action. Observations that mEMAP II induced apoptosis only in a subset of migrating and proliferating endothelial cells (EC) suggests a targeted effect on cells engaged in angiogenic activities which are known to rely upon cell adhesion and migration. Indeed, we demonstrate that mEMAP II inhibited fibronectin (FN) dependent microvascular EC (MEC) adhesion and spreading and we show that this depends upon the alpha5 beta1 integrin. Immunofluorescence analysis demonstrated that mEMAP II-dependent blockade of FN-alpha5 beta1 interactions was associated with disassembly of both actin stress fiber networks and FN matrix. These findings suggest that mEMAP II blocks MEC adhesion and spreading on fibronectin, via a direct interaction with the integrin alpha5 beta1, thus implicating that alpha5 integrin may be a mediator of mEMAP II's antiangiogenic function

  17. Molecular identification of four different alpha-amylase inhibitors from baru (Dipteryx alata) seeds with activity toward insect enzymes.

    Science.gov (United States)

    Bonavides, Krishna B; Pelegrini, Patrícia B; Laumann, Raúl A; Grossi-de-Sá, Maria F; Bloch, Carlos; Melo, Jorge A T; Quirino, Betania F; Noronha, Eliane F; Franco, Octávio L

    2007-07-31

    The endophytic bruchid pest Callosobruchus maculatus causes severe damage to storage cowpea seeds, leading to economical losses. For this reason the use of alpha-amylase inhibitors to interfere with the pest digestion process has been an interesting alternative to control bruchids. With this aim, alpha-amylase inhibitors from baru seeds (Dipteryx alata) were isolated by affinity chromatographic procedures, causing enhanced inhibition of C. maculatus and Anthonomus grandis alpha-amylases. To attempt further purification, this fraction was applied onto a reversed-phase HPLC column, generating four peaks with remarkable inhibition toward C. maculatus alpha-amylases. SDS-PAGE and MALDI-ToF analysis identified major proteins of approximately 5.0, 11.0, 20.0 and 55 kDa that showed alpha-amylase inhibition. Results of in vivo bioassays using artificial seeds containing 1.0% (w/w) of baru crude extract revealed 40% cowpea weevil larvae mortality. These results provide evidence that several alpha-amylase inhibitors classes, with biotechnological potential, can be isolated from a single plant species.

  18. Appraisal of active tectonics in Hindu Kush: Insights from DEM derived geomorphic indices and drainage analysis

    Directory of Open Access Journals (Sweden)

    Syed Amer Mahmood

    2012-07-01

    The results obtained from these indices were combined to yield an index of relative active tectonics (IRAT using GIS. The average of the seven measured geomorphic indices was used to evaluate the distribution of relative tectonic activity in the study area. We defined four classes to define the degree of relative tectonic activity: class 1__very high (1.0 ≤ IRAT < 1.3; class 2__high (1.3 ≥ IRAT < 1.5; class 3—moderate (1.5 ≥ IRAT < 1.8; and class 4—low (1.8 ≥ IRAT. In view of the results, we conclude that this combined approach allows the identification of the highly deformed areas related to active tectonics. Landsat imagery and field observations also evidence the presence of active tectonics based on the deflected streams, deformed landforms, active mountain fronts and triangular facets. The indicative values of IRAT are consistent with the areas of known relative uplift rates, landforms and geology.

  19. 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-Against-Beta...... in publicly traded stocks versus wholly-owned private companies, we find that the former performs the best, suggesting that Buffett's returns are more due to stock selection than to his effect on management. These results have broad implications for market efficiency and the implementability of academic...

  20. 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

    2015-04-01

    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 neuro